USMLE STEP 1

PLATINUM NOTES
The Complete Preparatory Guide
Second Edition

Ashfaq UI Hassan

MBBS MS
Consultant Anatomy
SKIMS Medical College
Bemina, Srinagar, Jammu and Kashmir, India

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USMLE Step 1 Platinum Notes
First Edition: 2013
Second Edition: 2016
ISBN: 978-93-5250-171-7
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Contributors
Ashfaq UI Hassan
MBBS MS

ConsultantAnatomy
SKIMS Medical College
Bemina, Srinagar, Jammu and Kashmir, India

Prof. Showkat A Zargar

MD DM (Gastroenterology)

Director and Principal

Sher-i-Kashmir Institute of Medical Sciences (SKIMS)
Srinagar, Jammu and Kashmir, India

Prof. Naseer Mir

MS (Orthopedics)

Professor and Head Orthopedics

Sher-i-Kashmir Institute of Medical Sciences (SKIMS)
Srinagar, Jammu and Kashmir, India

Dr Sheikh Manzoor Ahamed

MD (Dermatology)

Associate Professor and HeadDermatology

Sher-i-Kashmir Institute of Medical Sciences (SKIMS)
Srinagar, Jammu and Kashmir, India

Preface to the Second Edition

I am extremely obliged to the Almighty Allah and no words would be enough to express my thanks to his holiness for
guiding me.
This book USMLE Step 1 Platinum Notes consists of complete revision material for the preparation of the USMLE
examinations with important latest questions asked in these examinations and most of the students do not fare well with
these questions, thus significantly lowering their scores.
The book is for complete revision with special focus on the most common and most important cases asked. It covers
special and important topics which are most frequently asked by the examiners.
The prime focus for the students to go through the most important points and recapitulating these at the end is
important for any examination and special focus for the same has been given for their benefit.
Like the other series of books for the USMLE examinations being authored by me, which have had a tremendous
success, I hope this effort of mine again would be helpful for the students throughout the world in their pursuit of academic
excellence along with the important fact of getting a very good score in the examinations.
I hope the book proves to be useful for our students to the fullest.
I would encourage any aspiring student to join me for his/her contribution.

Ashfaq Ul Hassan
ashhassan@rediffmail.com

Preface to the First Edition

It gives me a great pleasure to introduce Platinum Notes for USMLE Step 1 and Step 2.
A need was felt by most of the students for a comprehensive book for USMLE for preparing extensively and
simultaneously getting a very good score.
My efforts are directed to benefit the students to the maximum.
For a student preparing, revising, forgetting and consulting different books is a part of the game. In this journey some
students tend to get nervous and anxious and I thought of putting all my best efforts into one book which would make the
preparation simpler, interesting, more lucid and palatable.
High yield points, important topics, clinical correlations, in-depth focus on subjects, easy retention and quick revision
are the points on which I have focused taking into account the latest trends of the examinations.
The matter in the book is highly concentrated, needs multiple revisions and deep concentration for retention.
The book has been framed to simulate the study pattern of USMLE examinations to its best.
The questions in the text and after every subject are almost similar to the questions put in the actual USMLE examination
which gives a student a good chance to understand the standard of USMLE as well as to prepare for the examinations in a
better way.
I feel that the students would be benefitted through my effort and a feedback from the students would be highly
appreciated at ashhassan@rediffmail.com
I wish you good luck for your academic pursuits.

Ashfaq Ul Hassan
ashhassan@rediffmail.com

Acknowledgments
No words would be enough to express my regards to Prof. Showkat A Zargar, Director, Sher-i-Kashmir Institute of Medical
Sciences (SKIMS), Srinagar, Jammu and Kashmir, India for his constant encouragement.
I am also thankful to my father Prof. Ghulam Hassan for his constant encouragement in all my academic pursuits and
guiding me throughout the process of the completion of this book.
I convey my sincere thanks to Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India for their efforts and
suggestions, especially Shri Jitendar P Vij (Group Chairman), Ms Chetna Vohra (Associate Director), and Ms Payal Bharti
(Project Manager) for helping me through my idea.

Abbreviations
1

Primary

bid

Twice a day

Secondary

BMR

Basal metabolic rate

Fracture

BP

Blood pressure

ACE

Angiotensin converting enzyme

BPH

Benign prostatic hypertrophy

ACE-I

Angiotensin converting enzyme inhibitor

BUN

Blood urea nitrogen

ACTH

Adrenocorticotropic hormone

B/L

Bilateral

ACh Acetylcholine

BM

Bone marrow, basement membrane

Adr Adrenaline

b/n or b/w

Between

AD

Autosomal dominant

C/S

Culture and sensitivity

ADH

Anti-diuretic hormone

Ca Calcium

AF

Atrial fibrillation

CABG

Coronary artery bypass graft

AFB

Acid-fast bacilli

CAD

Coronary artery disease

AFP Alpha-fetoprotein

CCF

Congestive cardiac failure

A.k.a

Also known as

CT

Computerized tomography

ALL

Acute lymphocytic leukemia

CHF

Congestive heart failure

AML

Acute myelogenous leukemia

CHO Carbohydrate

ANA

Antinuclear antibody

CML

ANS

Autonomic nervous system

CMV Cytomegalovirus

2+

Chronic myelogenous leukemia

AP Anteroposterior

CN

Cranial nerves

AR

Autosomal recessive

CNS

Central nervous system

ARDS

Acute respiratory distress syndrome

CO

Cardiac output

ARF

Acute renal failure

C/O

Complaining of

AS

Aortic stenosis

COLD

Chronic obstructive lung disease

ATP

Adenosine triphosphate

COPD

Chronic obstructive pulmonary disease

ASD

Atrial septal defect

CPK

Creatine phosphokinase

AV Atrioventricular

CRF

Chronic renal failure

A/E

All except

CRP

C-reactive protein

Acc/ to

According to

CSF

Cerebrospinal fluid

Ad/E, ad/e

Adverse effects

CVA

Cerebrovascular accident

A/W or a/w

Associated with

CVP

Central venous pressure

BBB

Bundle branch block

CVS

Cardiovascular system

xii

USMLE Step 1 Platinum Notes

FTT

Failure to thrive

Ca Carcinoma/Cancer

FVC

Forced vital capacity

C/c

Complication

FA

Fatty acid

CT

Chemotherapy

FFA

Free fatty acid

C/I

Contraindication

GFR

Glomerular filtration rate

CI/f

Clinical features

GH

Growth hormone

CTD

Connective tissue disease

GIT

Gastrointestinal tract

Cont./L

Contralateral

GTT

Glucose tolerance test

Cx

Cervix

GU Genitourinary

D and C

Dilation and curettage

HAV

Hepatitis A virus

DI

Diabetes insipidus

HCG

Human chorionic gonadotropin

DIC

Disseminated intravascular coagulopathy

HDL

High density lipoprotein

DIP

Distal interphalangeal joint

Hb Hemoglobin

DKA

Diabetic ketoacidosis

HIV

Human immunodeficiency virus

dL Deciliter

HLA

Histocompatibility locus antigen

DM

Diabetes mellitus

H/O

History of

DTR

Deep tendon reflexes

HR

Heart rate

DVT

Deep venous thrombosis

HSV

Herpes simplex virus

d/to

Due to

HTN Hypertension

D/g

Diagnosis

HS

Hereditary spherocytosis

DOC

Drug of choice

HCC

Hepato cellular carcinoma

Ds, d/s

Disease, disease

HD

Hodgkins disease

DM

Diabetes mellitus

I and D

Incision and drainage

ECG Electrocardiogram

IDDM

Insulin dependent diabetes mellitus

ECT

Ig Immunoglobulin

CXR

Chest X-ray

Electroconvulsive therapy

ECHO Echocardiography

IM Intramuscular

EMG Electromyogram

INR

International normalized ratio

EOM

Extraocular muscles

ITP

Idiopathic thrombocytopenic purpura

ESR

Erythrocyte sedimentation rate

IV Intravenous

ERCP

Endoscopic retrograde cholangioPancreatography

IVP

Intravenous pyelogram

IVU

Intravenous urogram

EUA

Examination under anesthesia

ICT

Intracranial tension

FBS

Fasting blood sugar

IOC

Investigation of choice

FEV

Forced expiratory volume

ILD

Interstitial lung disease

FFP

Fresh frozen plasma

IOT

Intraocular tension

FRC

Functional residual capacity

Ipsi/L

Ipsilateral

Abbreviations
JVP

Jugular venous pressure

K Potassium
+

xiii

PT

Prothrombin time, or physical therapy

PTCA

Percutaenous transluminal coronary

angioplasty

K/as

Known as

LAE

Left atrial enlargement

PTH

Parathyroid hormone

LBBB

Left bundle branch block

PTT

Partial thromboplastin time

LDH

Lactate dehydrogenase

P/g

Prognosis

LMN

Lower motor neuron

Px

Prophylaxis

LE

Lupus erythematosus

PBC

Primary bilary cirrhosis

LP

Lumbar puncture

RA

Rheumatoid arthritis

LV

Left ventricle

RBBB

Right bundle branch block

LVH

Left ventricular hypertrophy

RBC

Red blood cell

LN

Lymph node

RIA Radioimmunoassay

MAO

Monoamine oxidase

RNA

Ribonucleic acid

MEN

Multiple endocrine neoplasia

RTA

Renal tubular acidosis

MI

Myocardial infarction or mitral

insufficiency

RVH

Right ventricular hypertrophy

Rx Treatment

mL Milliliter

R, or T/t

Treatment

MMR

Measles, mumps, rubella

RT

Radiotherapy

MRI

Magnetic resonance imaging

SBE

Subacute bacterial endocarditis

MRSA

Methicillin resistant staph aureus

SGOT

Serum glutamic-oxaloacetic transaminase

MG

Myasthenia gravis

SGPT

Serum glutamic-pyruvic transaminase

Mc or MC

Most common

SIADH

MN

Malnutrition

Syndrome of inappropriate antidiuretic

hormone

M/m

Management

SLE

Systemic lupus erythematous

Ms, m/s

Muscle

SCLC

Small cell lung carcinoma

Na Sodium

SM

Smooth muscle

NIDDM

Non-insulin dependent diabetes mellitus

Supf.

Superficial

NSAID

Non-steroidal anti-inflammatory drugs

SqCC

Squamous cell carcinoma

n.or nv

Nerve

TIBC

Total iron binding capacity

NHL

Non-Hodgkins lymphoma

tid

Three times a day

OCG

Oral cholecystogram

TSH

Thyroid stimulating hormone

PA Posteroanterior

TT

Thrombin time

PDA

Patent ductus arteriosus

TTP

Thrombotic thrombocytopenic purpura

PMN

Polymorphonuclear leukocyte
(neutrophil)

TURP

Transurethral resection of prostate

TOC

Treatment of choice

Patient profile

UC

Ulcerative colitis

PP

xiv

USMLE Step 1 Platinum Notes

UMN

Upper motor neuron

V/s

Vessel

URI

Upper respiratory infection

Vs

Versus (= against)

US, U/S Ultrasound

WBC

White blood cell

UTI

Urinary tract infection

WPW Wolff-Parkinson-White

UVA

Ultraviolet A light

WG

Wegners granulomatosis

U/L

Unilateral

WT

Wilms tumor

VF

Ventricular fibrillation

XLR

X linked recessive

VDRL

Venereal disease research laboratory

Yr Year

(test for syphilis)

Zn Zinc

V/Q Ventrilation-perfusion

ZES

Zollinger Ellison Syndrome

VT

Ventricular tachycardia

Reaction block by, inhibited by

vWD

von Willebrands virus

Denotes heading

VZV

Varicella zoster virus

! Increase

Contents
1. Anatomy

2. Physiology

115

3. Biochemistry

183

4. Microbiology

237

5. Pathology

333

6. Pharmacology

451

7. Biostatistics

549

ANATOMY

Anatomy

EMBRYOGENESIS
Important Events and Their Time Sequence: (Days)
Implantation occurs at

6 days

Uteroplacental circulation establishes at

1112 days

Primitive streak appears on

Formed from: ectoderm

1315th day

Angiogenesis

15th day

Closure of anterior neuropore

24 days

Embryo develops by

8 week

Fetus is

> 8 weeks

Common Signaling Pathways Used during Development

The differentiation of many different cell types is regulated through a relatively restricted set of molecular signaling pathways:
Morphogens: These are diffusible molecules that specify which cell type will be generated at a specific anatomic location and
direct the migration of cells and their processes to their final destination
These Include
Retinoic acid
Transforming growth factor bone morphogenetic proteins (BMPs) and
The hedgehog and the Wnt family proteins
Notch/Delta: This pathway often specifies which cell fate precursor cells will adopt
Transcription factors: This set of evolutionarily conserved proteins activates or represses downstream genes that are essential
for many different cellular processes. Many transcription factors are members of the homeobox or helix-loop-helix (HLH) families.
Their activity can be regulated by all of the other pathways described in this chapter
Receptor tyrosine kinases (RTKs): Many growth factors signal by binding to and activating membrane-bound RTKs. These
kinases are essential for the regulation of cellular proliferation, apoptosis and migration as well as processes such as the growth of
new blood vessels and axonal processes in the nervous system.

Fetal Landmarks (Weeks)

Within 1 week

Implantation

Within 2 week

Bilaminar disk

Within 3 week

Trilaminar disk Gastrulation

Within 3 week

Primitive streak begins to form

Notochord forms

Within 38 week

Organogenesis
Teratogen susceptibility maximum

Week 10

Genitalia with male and female characters

USMLE Step 1 Platinum Notes

Stem Cells (USMLE Favorite)

Stem cells must be able to:
Divide to produce sufficient cells
Differentiate into the cell types needed
Survive after transplant
Mesh into the surrounding tissues
Function properly for long enough to extend the recipients life or to improve it significantly
Avoid harming the recipient

Karyotyping
In 1961 an international meeting was held at the University of Colorado Medical School in Denver, Colorado to standardize the format for
a normal human karyotype. The format that evolved is known as the Denver System.
Each chromosome has its own individuality as shown by its size, shape, and position of its kinetochore. Using the Denver System, the
chromosomes are put into similar groups designated by letters. Then numbers are used to subdivide the chromosomes within the groups
designated by numbers based on the position of the kinetochore and the length of the chromatids. The homologous chromosomes are
paired based on their banding.

X Chromosome belongs to group C

Y Chromosome belongs to group G
Group A

Ch 1, 2, 3

Group B

Ch 4, 5

Group C

Ch 6, 7, 8, 9, 10, 11, 12, X

Group D

Ch 13, 14, 15

Group E

Ch 16, 17, 18

Group F

Ch 19, 20

Group G

Ch 21, 22, Y

Important Embryological Structures: High Yield Points for USMLE

Meckels Diverticulum
This true diverticulum is a remnant of the vitelline duct and often contains ectopic gastric mucosa which can cause bleeding and
perforation.
The Ductus Venosus
It is a shunt that bypasses the liver and carries blood from the umbilical vein directly to the IVC. Its remnant is the ligamentum
venosum.
The Ductus Arteriosus
It is a shunt that bypasses the lungs to carry blood from the pulmonary artery to the aortic arch. Its remnant is the ligamentum
arteriosum.
The Urachus
Becomes the Median umbilical ligament
The 2 umbilical arteries becomes the Medial umbilical ligaments
Urachal fistula from persistent allantois
The Vitelline Duct
It is a connection with the yolk stalk and bowel, but normally obliterates during week 7 of development.

Anatomy
Fetal Structure

Adult Remnant

Right and left umbilical artery

Medial umbilical ligament

Left umbilical vein

Ligamentum teres

Ductus venosus

Ligamentum venosum

Foramen ovale

Fossa ovalis

Ductus arteriosus

Ligamentum arteriosum

Embryology of Umbilical Cord: (USMLE Favorite )

Connects fetus and placenta
It is rich in Whartons jelly
Has Two arteries and one vein
Rt umbilical vein disappears, left is left
In case of single artery only, congenital anomalies should be excluded
Umbilical arteries carry deoxygenated blood
Umbilical arteries do not possess internal elastic lamina
Vas vasorum are absent in cases of umbilical vessels

Female Gametogenesis
Oogonia are derived from yolk sac
Germ cells are derived from yolk sac
Polar bodies are formed during oogenesis
Polar bodies are extruded 24 hours prior to ovulation

Male Gametogenesis
Spermatogenesis occurs at temperature lower than body temperature
Y chromosome is ACROCENTRIC
In absence of Y chromosome ovaries develop
Sperms are stored in epididymis
Length of mature human sperm is 5060 microns

Chromosomal Configuration of Important Cells in Gonads

Number of Chromosomes in Cells During Gametogenesis
Primordial germ cell, oogonia, spermatogonia

46, 2N

Primary oocyte, primary spermatocyte

46, 4N

Secondary oocyte, secondary spermatocyte

23, 2N

Oocyte, spermatid, sperm

23, 1N

Placentation: (USMLE Favorite)

Abnormalities of Placenta
Biscoidal placenta: Placenta has two disks
Lobed placenta: Placenta divides into lobes
Diffuse placenta: Chorionic villi persist all around the blastocys.
Placenta succenturiate: Small part of placenta separated from the rest

USMLE Step 1 Platinum Notes

Fenestrated: Placenta has hole in center

Circumvallate: Edge of placenta covered by circular fold of deciduous
According to umbilical cord attachment:
Marginal: Marginal as well as battledore placenta refers to placenta with cord attached to margins
Furcate: Blood vessels divide before reaching the placenta
Velemantous insertion: Blood vessels are attached to amnion where they ramify before reaching the placenta
Oligohydramnios: Low level of amniotic fluid (< 400 ml) in renal agenesis
Polyhydramnios: High level of amniotic fluid (>2000 ml)
In the fourth intrauterine month the fetus begins to swallow amniotic fluid (25 to 40% of the volume) and absorbs the fluid from
the upper gastrointestinal tract
The fluid is urinated back out into the amniotic pool by the fetal kidneys and a functioning bladder. Although there are maternal
causes of polyhydramnios (cardiac failure, renal failure, other causes of fluid retention) and some idiopathic cases, many instances
are related to the presence of fetal anomalies. These include:
Central nervous system problems such as anencephaly, which prevents normal swallowing, and any high alimentary tract
obstruction that blocks the passage of the amniotic fluid and prevents its absorption such as:
Esophageal atresia
Pyloric atresia
Duodenal atresia
Maternal diabetes
Amniotic band syndrome: When bands of amniotic membrane encircle and constrict parts of fetus causing limb amputations
and Craniofacial anomalies

USMLE Case Scenario

Polyhydramnios is not seen in one of the following conditions:
1. Esophageal atresia
2. Duodenal atresia
3. Pyloric atresia
4. Hirschsprungs disease
5. Congenital diaphragmatic hernia
Ans. 4. Hirschsprungs disease

Derivatives of Germ Layers: (USMLE Favorite)

Derivatives of Ectoderm

Skin and most of appendages

Lens of eye
Epithelial linning of Lower half of anal canal
Epithelial lining of external auditory meatus
Epithelial lining of distal part of male urethra
Adenohypophysis

Derivatives of Mesoderm

Musculoskeletal system
Cardiovascular system
Kidney, ureter
Trigone of bladder (mesonephric duct absorption)

Anatomy

Posterior wall of female urethra

Posterior wall of prostatic part of male urethra
Reproductive tract except labia majora, minora and major part of prostate
Mesothelium of pleural, pericardial and peritoneal cavities
Dentine of teeth
Cornea, sclera, choroid, ciliary body and iris of eye
Somites from paraxial mesoderm

Derivatives of Endoderm

Epithelial lining of GIT

Epithelial lining of Biliary tract
Epithelial lining of Respiratory tract
Epithelial lining of vagina
Epithelial lining of auditory tube, middle ear

Development of Lungs

Glandular stage
Cannalicular stage
Terminal sac stage
Alveolar stage

517 weeks
1625 weeks
24 Weeksbirth
Birth-8 years

Respiration not possible

Respiratory bronchioles and terminal sacs form
Type I and II Pneumocytes present
Respiratory bronchioles, terminal sacs, alveolar duct, alveoli

Embryology of Heart: (USMLE Favorite)

Embryonic Structure

Adult Structure

Truncus arteriosus

Aorta
Pulmonary trunk

Bulbus cordis

Smooth part of R ventricle

Smooth part of L ventricle

Development of heart

USMLE Step 1 Platinum Notes

Primitive ventricle

Rough part of R ventricle

Rough part of L ventricle

Primitive atrium

Rough part of R ventricle

Rough part of Latrium

Sinus venosus

Smooth part of Ratrium

Coronary sinus (Lt horn of sinus venosus)
Oblique vein of left atrium

Embryology of Thoracic Vessels

Embryonic Structure

Adult Structure

Aortic arch 1
Aortic arch 2
Aortic arch 3

Common carotid artery

Internal carotid artery (proximal part)

Aortic arch 4

Rt. Subclavian artery (proximal part)

Part of aortic arch
Persistence leads to double aortic arch

Aortic arch 5

Regresses

Aortic arch 6

Pulmonary artery
Ductus arteriosus

Remember
Ventral mesogastrium

Lesser omentum, hepatoduodenal, hepatogastric, falciform, coronary and triangular

ligament of liver

Dorsal mesogastrium

Greater omentum, mesentry of small intestine, mesoappendix, sigmoid mesocolon,

transverse mesocolon

Embryology of Urinary Tract: (USMLE Favorite)

Embryo

Adult structure

Ureteric Bud

Collecting duct
Major/Minor Calyx
Renal pelvis
Ureter
Epithelium of ureter from mesonephros

Metanephric Mesoderm

Renal glomerulus
Bowmans capsule
PCT
DCT
Loop of Henle
Connecting tubule

Anatomy

Embryology of Genital Tract

Gonads

Ovary

Testis

Paramesonephric duct or Mullerian duct

Appendix testis

Mesonephric duct or Wollfian duct

Appendix vesiculosa
Duct of Garnier

Epididymis
ductus deferens
Seminal vesicles
Ejaculatory ducts
Appendix epididymis

Mesonephric tubules

Epoophoron
Paroophoron

Efferent ductules
Paradidymis

Phallus

Clitoris

Glans penis

Urethral folds

Labia minora

Genital swellings

Labia majora

Uterine tubes
Uterus
Cervix
Hydatid of morgagni

Scrotum

USMLE Favorite
Embryonic Structure

Genital ridge
Genital swelling
Genital fold
Genital tubercle

Female

Male

Ovary
L majora
L minora
Clitoris

Testis
Scrotum
Ventral aspect of penis
Glans penis

Testicular Descent
Iliac fossa

3rd month

Deep inguinal ring

7th month

Pass through inguinal canal

7th month

At superficial inguinal ring

8th month

Enter scrotum

9th month

Derivatives of Neural Crest

Neurons of spinal posterior nerve root ganglia
Neurons of sensory ganglia
Neurons of autonomic ganglia (sympathetic ganglia)
Schwann cells
Melanocytes
Piamater and arachnoid matter
Mesenchyme of dental papillae
Cartilage cells of branchial arches
Chromaffin tissue

10

USMLE Step 1 Platinum Notes

Defective Migration of Neural Crest Cells Results in

Albinism
Melanoma
Hirschsprungs disease
Oropharyngeal teratoma
Neurocristopathies (Cleft Lip, Cleft palate, Digeorges syndrome, Waarden burgs syndrome, Charge syndrome

Tumors of Neural Crest Origin

Neuroblastoma
Pheochromacytoma
Carcinoid tumor
Neurofibromatosis
Medullary carcinoma thyroid

USMLE Case Scenario

A newborn boy does not pass meconium until 45 hours after his birth. Several weeks later his well educated mother complains
that he has not been passing stool regularly. Anorectal manometry reveals increased internal anal sphincter pressure on
rectal distention with a balloon. The patients disorder maybe attributed to distention with a balloon. The patients disorder
maybe attributed to:
1. Defective recanalization of the colon
2. Failure of neural crest cells to migrate
3. Herniation of abdominal contents into the umbilical cord
4. Persistence of the proximal end of the yolk stalk
5. Persistence of processus vaginalis
6. Failure of gastrulation
Ans. 2. Failure of neural crest cells to migrate

Pharyngeal Apparatus (USMLE Favorite)

Pharyngeal Arches are derived from Mesoderm
Pharyngeal clefts are derived from Ectoderm
Pharyngeal Pouches are derived from Endoderm

Five pharyngeal arches

Anatomy

Pharyngeal Arch 1 Derivatives

Meckels Cartilage:
Mandible
Malleus
Incus
Sphenomandibular ligament
Muscles: Muscles of mastication (Medial pterygoid and lateral pterygoid, masseter, temporalis)
Two Tensors (Tensor tympani, tensor palati)
Mylohyoid, anterior belly of digastrics

Pharyngeal Arch 2 Derivatives (Word S)

Reicherts Cartilage:
Stapes
Styloid process
Smaller cornu of Hyoid Bone
Superior surface of Hyoid Bone
Stylohyoid ligament
Muscles of facial expression, Stapedius, Stylohyoid, Posterior Belly of Digastric
Platysma

Pharyngeal Arch 3 Derivatives

Greater cornu of Hyoid Bone
Stylopharyngeus muscle
Think of Stylopharyngeus when thinking about Glossopharyngeal Nerve

Pharyngeal arch 4 and 6 Derivatives

Cartilages of larynx
Intrinsic muscles of larynx and pharynx

PHARYNGEAL ARCH 5 DOES NOT CONTRIBUTE TO DEVELOPMENT

Nerve Supply of Pharyngeal arches is: My Father gave me Some Rupees

Mandibular nerve Ist arch

Facial nerve 2nd arch
Glossopharyngeal nerve 3rd arch
Superior laryngeal nerve 4th arch
Reccurent laryngeal nerve 6th arch

Treacher-Collins syndrome/Mandibulofacial dysostosis

Abnormal formation of pharyngeal arch
Faulty migration of neural crest cells

11

12

USMLE Step 1 Platinum Notes

Patients are mostly characterized by the following abnormalities

Hypoplasia of the facial bones: An underdeveloped mandibular and zygomatic bone leading to a small and malformed jaw
Ear anomalies: Consist small, rotated or even absent ears with or without bilateral stenosis or atresia of the external auditory
canals
Eye problems: Varying from colobomata of the lower eyelids and aplasia of lid lashes to short, downslanting palpebral fissures and
missing eyelashes. Vision loss can occur and is associated with strabismus, refractive errors, and anisometropia
Cleft palate
Airway problems: Which are often results of mandibular hypoplasia
Dental anomalies: Consist in tooth agenesis, enamel disformaties and malplacement of the maxillary first molars.

Less Frequent Defects

Nasal deformity
High-arched palate
Coloboma of the upper lid
Ocular hypertelorism
Choanal atresia
Macrostomia
Preauricular hair displacement
Pharyngeal Pouch

Adult Structure

Pharyngeal Pouch 1

Epithelial linning of Auditory tube/Middle ear

Pharyngeal Pouch 2

Palatine tonsil

Pharyngeal Pouch 3

Inferior parathyroid and Thymus

Pharyngeal Pouch 4

Superior parathyroid and Ultimobranchial body

Para follicular cells are derived from ultimobranchial body

Pharyngeal Cleft/Groove

Adult Structure

External linning of External auditory meatus

2, 3, 4

Obliterated

Cleft Lip and Cleft Palate: (USMLE Favorite)

Cleft Lip:
Failure of Fusion of Maxillary and Medial Nasal Process
Usually associated with cleft palate. (Commonest)
Midline cleft lip is due to failure of fusion of two medial nasal processes
Cleft Palate: Failure of fusion of lateral palatine process, nasal septum and median palatine process (occasional)

Cleft Lip and Cleft Palate (Detailed Overview)

Unilateral cleft lip. Also called Harelip

Failure of fusion of medial nasal process with maxillary process

Midline defect of upper lip

Defect in development of lowermost part of frontonasal process

Midline defect of lower lip

Defective fusion of mandibular processes

Anatomy
Microstomia

Excessive fusion of maxillary and mandibular processes

Macrostomia

Inadequate fusion of maxillary and mandibular processes

Oblique facial cleft

Non fusion of maxillary and lateral nasal process

Tongue Development
1st pharyngeal arch forms ant 2/3
3 rd and 4 th arch forms post 1/3
Muscles of tongue develop from occipital myotomes
Muscles of tongue are both smooth and skeletal muscles
Muscles of tongue are supplied by hypoglossal nerve
Safety muscle of tongue is genioglossus

Genioglossus

Tip of tongue drains to submental lymph nodes

Posterior 1/3 of tongue is supplied by glossopharyngeal nerve
Pain of cancer base of tongue is also reffered to ear through glossopharyngeal nerve
Circumvallate pappilae of tongue are supplied by glossopharyngeal nerve

Development of tongue

13

14

USMLE Step 1 Platinum Notes

General Features of Tongue

Anterior 2/3 of tongue develops from lingual swellings and tuberculum impar
Anterior 2/3 of tongue is supplied by chorda tympani (FACIAL) (taste)
Anterior 2/3 of tongue is supplied by lingual nerve (general)
Anterior 2/3 of tongue drains into submandibular lymph nodes
Posterior 1/3 of tongue develops from hypobranchial eminence
Posterior 1/3 of tongue is supplied by glossopharyngeal nerve (taste)
Posterior 1/3 of tongue is supplied by glossopharyngeal nerve (general)
Posterior 1/3 of tongue drains into jugulo omohyoid lymph nodes
Tip drains into submental lymph nodes

Tonsil: (USMLE Favorite)

Has nonkeratinized squamous epithelium

It is an endodermal structure
Rests on superior constrictor muscle of pharynx
Vagus supplies tonsil
Main nerve supply is the glossopharyngeal nerve
Lymph drains into jugulo digastric nodes
Arterial supply:
Ascending palatine
Descending palatine and
Ascending pharyngeal artery supply tonsils

Diaphragm Development

Septum transversum
Pleuroperitoneal folds
Body wall
Dorsal mesentry of esophagus

Development of Intra-abdominal Organs Frequently Asked

Spleen
It is unique in respect to its development within the gut. While most of the gut viscera are endodermally derived (with the exception
of the neural-crest derived suprarenal gland), the spleen is derived from mesenchymal tissue. Specifically, the spleen forms within,
and from, the dorsal mesentery.
Pancreas
The pancreas develops between the layers of the mesentery from dorsal and ventral pancreatic buds of endodermal cells, which
arise from the caudal or dorsal part of the foregut. Most of the pancreas is derived from the dorsal pancreatic bud. The larger dorsal
pancreatic bud appears first and develops a slight distance cranial to the ventral bud.
The liver, gallbladder and the biliary duct system arise as a ventral outgrowth (hepatic diverticulum) from the caudal foregut in the
4th week
This hepatic diverticulum extends into septum transversum, a mass of splanchnic mesoderm between the developing heart and
the midgut
The septum transversum forms the ventral mesentery in this region. This double-layered membrane gives rise to the lesser
omentum and the falciform ligament
The superior layers of the coronary and left triangular ligaments meet and continue as a ventral mesentery attached to the
ventrosuperior aspect of the liver
Gallbladder arises from pars cystica (from the hepatic bud)

Anatomy

15

Embryology of Nervous System

The nervous system develops from the neural plate which appears at the beginning of the third week as thickening of the
ectoderm
Its lateral edges soon elevate to form the neural folds
With further development, the neural folds continue to elevate, and form a tube known as neural tube
The neural tube has an enlarged cranial part that forms the brain, and a narrow caudal part that becomes the spinal cord
The wall of the neural tube at first has a single layer of cells. They multiply and form three layers- ependymal, mantle and marginal
layer
Neural tube closure begins at cephalic end
The mantle layer divides into a
Ventral part, the basal lamina and
Dorsal part, the alar lamina, separated by a groove, the sulcus limitans
Alar plate gives rise to sensory areas of the spinal cord and the sensory nuclei
Basal plate forms the motor areas of the spinal cord and motor nuclei
The cerebellum and its nuclei develop from the dorsal parts of the alar plate
Inferior olivary and Substantia nigra are sensory nuclei and thus derived from the alar plate
Hypoglossal is a motor nuclei and develops from the basal plate

The Wall of the Spinal Cord

Neuroepithelial Layer

Mantle Layer

Marginal Layer

These cells extend over the Once the neural tube closes,
entire thickness of the wall and
neuroepithelial cells begin to give rise
form a thick PSEUDOSTRATIFIED
to another cell type.
EPITHELIUM

The outermost layer of the spinal cord,

the marginal layer, contains nerve
fibers emerging from neuroblasts in the
mantle layer.

Junctional complexes at the These cells are characterized by

lumen connect them
a large round nucleus with pale
nucleoplasm and a dark- staining
nucleolus. These are primitive nerve
cells, or NEUROBLASTS.

As a result of myelination of nerve fibers,

this layer takes on a white appearance
and therefore is called the white matter
of the spinal cord.

After closure of neural tube,

they divide rapidly, producing
more and more neuroepithelial
cells

They form the mantle layer, a zone

around the neuroepithelial layer.
The mantle layer later forms the gray
matter of the spinal cord.

Remember
Forebrain
(Prosencephalon)

Telencephalon

Cerebral hemispheres

Diencephalon

Thalamus
Hypothalamus
Posterior Pituitary
Pineal body

No division

Tectum

Metancephalon
Cerebellum

Pons

Myelencephalon

Medulla

No division

Spinal cord

Midbrain
(Mesencephalon)
Hindbrain
(Rhombencephalon)

Remainder of neural tube

16

USMLE Step 1 Platinum Notes

Development of brain
3rd ventricle develops from diencephalon
4th ventricle develops from rhombencephalon

Myelination
Myelin is formed in the central nervous system by oligodendrocytes
There are no myelinated fibers in the CNS before the end of the fifth fetal month
There is no myelination of the forebrain until the seventh fetal month. Most myelination in the telencephalon occurs in the third
trimester and postnatally
The first neurones to acquire myelin sheaths are the olfactory, optic and acoustic cortical areas and the motor cortex
(pyramidal cells)
The last to be myelinated are the projection commissure and association neurons of the cerebral hemispheres
Myelination is a critical process for the development of the brain because it enhances the speed of neural communication. It occurs
most rapidly during the first 2 years of life, but continues until early adulthood

In CNS Myelin is produced by Oligodendrocyte

A single oligodendrocyte myelinates as many as 20 or 30 different CNS axonal segments, each over a length of 1 mm or less
Oligodendrocyte membrane extensions wrap around the axons in a concentric fashion to form the myelin sheath. Myelin proteins
include proteolipid protein, myelin basic protein, myelin-associated glycoprotein, and a number of less abundant proteins detectable
by electrophoretic separation
Active myelin synthesis starts in utero and continues for the first 2 years of life; slower synthesis continues during childhood and
adolescence.

High Yield USMLE Points Lately Asked

Developmental Anomalies of Lungs
Lobe of Azygos Vein: This lobe appears especially in the right lung in approximately 1% of people. It develops when the apical
bronchus grows superiorly, medial to the arch of the azygos vein and produces a linear marking on a radiograph of the lungs
Sequestration of lung: Lung tissue getting trapped in the core of a lobe is called as intralobar sequestration. Lung tissue
completely separated from tracheobronchial tree replacing complete lobe is lobar sequestration
Potters Syndrome: It is pulmonary Hypoplasia with renal agenesis.

Anatomy

17

Developmental Anomalies of Thyroid

Thyroglossal Duct Cysts and Sinus: Normally, the thyroglossal duct atrophies and disappears, but a remnant of it may persist and
form a cyst in the tongue or in the anterior part of the neck, usually just inferior to the hyoid bone.
Most thyroglossal duct cysts are observed by the age of 5 years. The swelling produced by a thyroglossal duct cyst usually develops
as a painless, progressively enlarging, movable mass. The cyst may contain some thyroid tissue.
After infection of a cyst, a perforation of the skin occurs, forming a thyroglossal duct sinus that usually opens in the median plane
of the neck, anterior to the laryngeal cartilages.
Ectopic Thyroid Gland: An ectopic thyroid gland is usually located along the course of the thyroglossal duct. Lingual thyroid
tissue is the most common of ectopic thyroid tissues. Other sites:
Larynx
Trachea
Esophagus
Pericardium
Pleura
Ovaries
Struma Ovary:
It is a rare ovarian tumor defined by the presence of thyroid tissue
Most commonly, they occur as part of a teratoma, but may occasionally be encountered with serous or mucinous cystadenomas
Benign strumosis is a rare version of mature thyroid tissue implants throughout the peritoneal cavity

Teratoma (ovary)
A 10-year-old girl with round 1 cm mass in midline of neck moving with Throglossal duct cyst
movement of tongue
A 15-year-old girl with round 1 cm on side of neck beneath and in front of Branchial cyst
sternocleidomastoid.
A 6-year-old with fluid filled translucent mass in supraclavicular area

Cystic hygroma

Developmental Anomalies of Tongue

Ankyloglossia: The lingual frenulum normally connects the inferior surface of the tongue to the floor of the mouth. Sometimes
the frenulum is short and extends to the tip of the tongue. This interferes with its free protrusion and may make breastfeeding
difficult. A short frenulum usually stretches with time, making surgical correction of the anomaly unnecessary.
Macroglossia: An excessively large tongue is not common. Amyloidosis is associated with Macroglossia
Microglossia: An abnormally small tongue is extremely rare and is usually associated with micrognathia (underdeveloped
mandible and recession of the chin) and limb defects (Hanharts syndrome)
Bifid Tongue
Fissured tongue

18

USMLE Step 1 Platinum Notes

Developmental Anomalies of Larynx

Laryngeal Atresia: This anomaly results from failure of recanalization of the larynx, which causes obstruction of the upper fetal
airway. Distal to the region of atresia (blockage) or stenosis (narrowing), the airways become dilated, the lungs are enlarged and
echogenic
Laryngeal web: Results from incomplete recanalization of the larynx during the 10th week. A membranous web forms at the level
of the vocal folds, partially obstructing the airway
Laryngoptosis: Larynx is situated lower down in neck
Laryngeocele: Excessive enlargement of saccule of larynx.

Developmental Anomalies of Trachea

Tracheoesophageal Fistula:
A fistula between the trachea and esophagus
Most affected infants are males
In more than 85% of cases, the tracheoesophageal fistula (TEF) is associated with esophageal atresia
A TEF results from incomplete division of the cranial part of the foregut into respiratory and esophageal parts during the
fourth week
Incomplete fusion of the tracheoesophageal folds results in a defective tracheoesophageal septum and a TEF between the
trachea and esophagus
Polyhydramnios is often associated with esophageal atresia. The excess amniotic fluid develops because fluid cannot pass to the
stomach and intestines for absorption and subsequent transfer through the placenta to the mothers blood

Developmental Anomalies of Cardiovascular System

Ectopia cordis: Non union of sternal plates exposing the heart to surface
Dextrocardia: If the heart tube bends to the left instead of to the right, the heart is displaced to the right and there is transposition
the heart and its vessels are reversed left to right as in a mirror image. Dextrocardia is the most frequent positional abnormality
of the heart. In isolated dextrocardia, the abnormal position of the heart is not accompanied by displacement of other viscera
Maybe associated with
Situs Inversus/ Kartageners Syndrome/Immotile Cilia Syndrome
Atrial Septal Defects: An atrial septal defect (ASD) is a common congenital heart anomaly and occurs more frequently in females
than in males. The most common form of ASD is patent oval foramen. A small isolated patent oval foramen is of no hemodynamic
significance; however, if there are other defects (e.g. pulmonary stenosis or atresia), blood is shunted through the oval foramen
into the left atrium and produces cyanosis.
Ventricular Septal Defects: VSDs are the most common type of CHD, accounting for approximately 25% of defects. VSDs occur
more frequently in males than in females. VSDs may occur in any part of the IV septum but membranous VSD is the most common
type frequently, small VSDs close spontaneously. Most people with a large VSD have massive left-to-right shunting of blood.
Muscular VSD is a less common type of defect and may appear anywhere in the muscular part of the interventricular septum.
Sometimes there are multiple small defects, producing what is sometimes called the Swiss cheese VSD.
Cor biloculare: Two chambered heart
Cor Triloculare: Three chambered heart
L. Cor triloculare biatriatum: (Two atria, one ventricle): Absence of the IV septum-single ventricle or common ventricle-resulting
from failure of the IV septum to form is extremely rare and results in a three-chambered heart (L. cor triloculare biatriatum).
Transposition of the Great Arteries: TGA is the most common cause of cyanotic heart disease in newborn infants. TGA is often
associated with other cardiac anomalies (e.g. ASD and VSD).
In typical cases, the aorta lies anterior and to the right of the pulmonary trunk and arises from the morphologic right ventricle, whereas
the pulmonary trunk arises from the morphologic left ventricle. The aorticopulmonary septum fails to pursue a spiral course during
partitioning of the bulbus cordis and TA
This defect is thought to result from failure of the conus arteriosus to develop normally during incorporation of the bulbus cordis into
the ventricles
Recent studies suggest that defective migration of neural crest cells may also be involved.

Anatomy

19

Tetralogy of Fallot: This classic group of four cardiac defects

Pulmonary stenosis (Obstruction of right ventricular outflow)
VSD
Dextroposition of aorta (Overriding or straddling aorta)
Right ventricular hypertrophy
Coarctation of the Aorta: Aortic coarctation (constriction) occurs in approximately 10% of children and an adult with CHDs.
Coarctation is characterized by an aortic constriction of varying length. Most coarctations occur distal to the origin of the left
subclavian artery at the entrance of the DA (juxtaductal coarctation). The classification into preductal and postductal coarctations
is commonly used. Coarctation of the aorta occurs twice as often in males as in females and is associated with a bicuspid aortic
valve in 70% of cases.

Developmental Anomalies of Lymphatic System

Cystic hygroma: Large swellings usually appear in the inferolateral part of the neck and consist of large single or multilocular,
fluid-filled cavities. Hygromas maybe present at birth, but they often enlarge and become evident during infancy. Most hygromas
appear to be derived from abnormal transformation of the jugular lymph sacs
Represents lymphatic venous anastamotic failure
Located usually in the neck at lower in posterior triangle
Brilliantly translucent

Developmental Anomalies of GIT

Esophageal Atresia: Esophageal atresia is associated with tracheoesophageal fistula in more than 85% of cases. Atresia may
occur as a separate anomaly, but this is less common. Esophageal atresia results from deviation of the tracheoesophageal septum
in a posterior direction as a result there is incomplete separation of the esophagus from the laryngotracheal tube. A fetus with
esophageal atresia is unable to swallow amniotic fluid; consequently, this fluid cannot pass to the intestine for absorption and
transfer through the placenta to the maternal blood for disposal. This results in polyhydramnios

Tracheoesophageal fistula
Esophageal Stenosis: Narrowing of the lumen of the esophagus can be anywhere along the esophagus, but it usually occurs in its
distal third, either as a web or as a long segment of esophagus with a thread like lumen. Stenosis usually results from incomplete
recanalization of the esophagus.
Short Esophagus (Congenital Hiatal Hernia): Initially the esophagus is very short. Its failure to elongate sufficiently as the neck
and thorax develop results in displacement of part of the stomach superiorly through the esophageal hiatus into the thoraxcongenital hiatal hernia. Most hiatal hernias occur long after birth, usually in middle-aged people.

20

USMLE Step 1 Platinum Notes

Dysphagia Lusoria: Abberant vessels compressing esophagus leading to dysphagia. Usually Abnormal right subclavian artery is
implicated.
Duodenal Atresia: Complete occlusion of the lumen of the duodenum. If recanalization of the lumen fails to occur a short segment
of the duodenum is occluded. The blockage occurs nearly always at the junction of the bile and pancreatic ducts (hepatopancreatic
ampulla) but occasionally involves the horizontal (third) part of the duodenum.
In infants with duodenal atresia, vomiting begins a few hours after birth. The vomitus almost always contains bile; duodenal
atresia may occur as an isolated anomaly, but other congenital anomalies are often associated with it, e.g. anular pancreas
cardiovascular abnormalities, anorectal anomalies, and malrotation. Importantly, approximately one third of affected infants
have Down syndrome and an additional 20% are premature. Duodenal atresia is associated with bilious emesis (vomiting of bile)
because the blockage occurs distal to the opening of the bile duct. Polyhydramnios also occurs because duodenal atresia prevents
normal intestinal absorption of swallowed amniotic fluid. The diagnosis of duodenal atresia is suggested by the presence of a
double bubble sign on plain radiographs or ultrasound scans. This appearance is caused by a distended, gas-filled stomach and
proximal duodenum.
Riedels Lobe: A tongue like extension of right lobe of liver.
Phrygian cap: Fundus of the gallbladder folded upon itself giving rise to an appearance of cap worn by people of an ancient
Asian community of Phrygia.
Moynihans Hump: Normally the arterial supply of gallbladder is from cystic artery which is a branch of Right hepatic artery.
Sometimes an accessory cystic artery is also seen to arise from either Gastroduodenal or right hepatic artery
The Right hepatic artery takes a tortuous course called caterpillar turn or Moynihans hump. This can be a source of profuse
bleeding.
Intrahepatic gallbladder is one of the ectopic locations of the gallbladder. The gallbladder is usually intrahepatic during
its embryologic period and becomes extrahepatic later on in its development. In adults approximately 60% of intrahepatic
gallbladders are associated with gallstones
Double and Triple gallbladders have been reported, the latter being extremely rare. Double gallbladders may share a common
cystic duct and be completely separated, or they maybe divided by a septum. When they do not share a common outlet, the cystic
ducts of double or triple gallbladders open separately into the common bile duct or, less commonly, into the right hepatic duct
Choledochal Cyst: Choledochal cysts are congenital cystic dilatations of the extrahepatic and/or intrahepatic biliary tree. They
are rare. Originally, they were described as cystic dilatations of the extrahepatic duct system. Subsequently this classification was
extended to include the frequent association with cystic dilatation of the duct system within the liver, a condition described in
1958 and now known as Carolis disease.
Extrahepatic Biliary Atresia: This is the most serious anomaly of the extrahepatic biliary system and occurs in one in 10,000 to
15,000 live births
The most common form of extrahepatic biliary atresia is obliteration of the bile ducts at or superior to the porta hepatis
Biliary atresia could result from a failure of the remodeling process at the hepatic hilum or from infections or immunologic reactions
during late fetal development
Jaundice occurs soon after birth and stools are acholic (clay colored).
Accessory Pancreatic Tissue: Accessory pancreatic tissue is most often located in
The wall of the stomach
Wall of duodenum
In an ileal diverticulum a/Meckel diverticulum
Anular Pancreas:
May cause duodenal obstruction
The ring like or anular part of the pancreas consists of a thin, flat band of pancreatic tissue surrounding the descending or
second part of the duodenum.
An anular pancreas may cause obstruction of the duodenum either shortly after birth or later. Infants present with symptoms
of complete or partial bowel obstruction. An anular pancreas maybe associated with
Down syndrome
Intestinal atresia
Imperforate anus
Pancreatitis
Malrotation

Anatomy

21

Congenital Omphalocele: This anomaly is a persistence of the herniation of abdominal contents into the proximal part of the
umbilical cord. Herniation of intestines and herniation of liver and intestines occurs
Infants with these large omphaloceles often suffer from pulmonary and thoracic hypoplasia and a delayed closure is a better
clinical decision. The covering of the omphalocele is by amnion and peritoneum.
Umbilical Hernia: When the intestines return to the abdominal cavity during the 10th week and then herniate through an
imperfectly closed umbilicus, an umbilical hernia forms. This common type of hernia is different from an omphalocele. In an
umbilical hernia, the protruding mass (usually the greater omentum and part of the small intestine) is covered by subcutaneous
tissue and skin. The defect through which the hernia occurs is in the linea alba. The hernia protrudes during crying, straining, or
coughing and can be easily reduced through the fibrous ring at the umbilicus. Surgery is not usually performed unless the hernia
persists to the age of 3 to 5 years.
Gastroschisis: This anomaly is a relatively uncommon congenital abdominal wall defect. Gastroschisis results from a defect lateral
to the median plane of the anterior abdominal wall. The linear defect permits extrusion of the abdominal viscera without
involving the umbilical cord. The viscera protrude into the amniotic cavity and are bathed by amniotic fluid.

Anomalies of the Midgut

Nonrotation occurs when the intestine does not rotate as it re-enters the abdomen. As a result, the caudal limb of the midgut loop
returns to the abdomen first and the small intestines lie on the right side of the abdomen and the entire large intestine is on the left
and the cecum lies just inferior to the pylorus of the stomach. The cecum is fixed to the posterolateral abdominal wall by peritoneal
bands that pass over the duodenum. These bands and the volvulus (twisting) of the intestines cause duodenal obstruction.
When midgut volvulus occurs, the superior mesenteric artery maybe obstructed, resulting in infarction and gangrene of
the intestine supplied by it. Infants with intestinal malrotation are prone to volvulus and present with bilious emesis.
Reversed Rotation: In very unusual cases, the midgut loop rotates in a clockwise rather than a counterclockwise direction. As
a result, the duodenum lies anterior to the superior mesenteric artery rather than posterior to it, and the transverse colon lies
posterior instead of anterior to it. In these infants, the transverse colon maybe obstructed by pressure from the superior mesenteric
artery.

Development of gut
Congenital Megacolon or Hirschsprung Disease:
Infants with congenital megacolon or Hirschsprungs disease lack autonomic ganglion cells in the myenteric plexus distal to the
dilated segment of colon
(Hirschsprungs disease is the congenital absence of enteric neurons in the submucosal and myenteric plexuses, due to an
arrest of the embryonic caudal migration of the enteric neurons along the gut. The aganglionic segment remains contracted,
dilating the proximal normal bowel
The severity of symptoms and the age at diagnosis are related to the length of the aganglionic segment. Involvement of the
rectum or additional parts of the colon results in constipation or obstipation in infancy, requiring emergent resection of the a
ganglionic bowel and a pull-through anastomosis to the anus.)

22

USMLE Step 1 Platinum Notes

Imperforate Anus and Anorectal Anomalies: Imperforate anus occurs approximately once in every 5000 newborn infants
and is more common in males. Most anorectal anomalies result from abnormal development of the urorectal septum, resulting
in incomplete separation of the cloaca into urogenital and anorectal portions. There is normally a temporary communication
between the rectum and anal canal dorsally from the bladder and urethra ventrally but it closes when the urorectal septum fuses
with the cloacal membrane.
Anal Agenesis, with or without a Fistula: The anal canal may end blindly or there maybe an ectopic anus or an anoperineal fistula
that opens into the perineum. The abnormal canal may, however, open into the vagina in females or the urethra in males.
Anal Stenosis: The anus is in the normal position, but the anus and anal canal are narrow. This anomaly is probably caused by a
slight dorsal deviation of the urorectal septum as it grows caudally to fuse with the cloacal membrane. As a result, the anal canal
and anal membrane are small.

USMLE Case Scenario

Embryologically, The Gut rotates and the rotation occurs in a way that:
1. The large intestine rotates in a clockwise manner around the axis of the celiac trunk
2. The large intestine rotates in a clockwise manner around the axis of the superior mesenteric artery
3. The large intestine rotates in a clockwise manner around the axis of the inferior mesenteric artery
4. The large intestine rotates in a counterclockwise manner around the axis of the celiac trunk
5. The large intestine rotates in a counterclockwise manner around the axis of the superior mesenteric artery
6. The large intestine rotates in a counterclockwise manner around the axis of the inferior mesenteric artery
Ans. 5. The large intestine rotates in a counterclockwise manner around the axis of the superior mesenteric artery

Derivatives of fore, mid and hindgut

Developmental Anomalies of Urinary Tract

Horseshoe Kidney: In 0. 2% of the populations, the poles of the kidneys are fused; usually the inferior poles fuse. The large
U-shaped kidney usually lies in the hypogastrium, anterior to the inferior lumbar vertebrae. Normal Persons with Turners
syndrome have horseshoe kidneys.
Ectopic Ureter: An ectopic ureter does not enter the urinary bladder. In males, ectopic ureters usually open into the neck of the
bladder or into the prostatic part of the urethra, but they may enter the ductus deferens, prostatic utricle, or seminal gland. In
females, ectopic ureters may open into the
Bladder neck
Urethra
Vagina
Vestibule of the vagina

Anatomy

23

An ectopic ureter: Results when the ureter is not incorporated into the trigone in the posterior part of the urinary bladder. Instead
it is carried caudally with the mesonephric duct and is incorporated into the middle pelvic portion of the vesical part of the
urogenital sinus.
Cystic Kidney Diseases
In autosomal recessive polycystic kidney disease, diagnosed at birth or in utero by ultrasonography, both kidneys contain
many hundreds of small cysts which result in renal insufficiency.
Multicystic dysplastic kidney disease results from dysmorphology during development of the renal system. The outcome for
children with multicystic dysplastic kidney disease is generally good because the disease is unilateral in 75% of the cases. In
multicystic dysplastic kidney disease, fewer cysts are seen than in autosomal recessive polycystic kidney disease and they range in
size from a few millimeters to many centimeters in the same kidney.
Congenital Adrenal Hyperplasia (CAH): An abnormal increase in the cells of the suprarenal cortex results in excessive androgen
production during the fetal period. In females, this usually causes masculinization of the external genitalia. Affected male infants
have normal external genitalia, and the syndrome may go undetected in early infancy. Later in childhood in both sexes, androgen
excess leads to rapid growth and accelerated skeletal maturation. CAH is a group of autosomal recessive disorders that result in
virilization of female fetuses.

Developmental Anomalies of Genital System

Mesonephric Duct Remnants in Males
The cranial end of the mesonephric duct may persist as an appendix of the epididymis, which is usually attached to the head of the
epididymis Caudal to the efferent ductules, some mesonephric tubules may persist as a small body, the paradidymis. It forms
Epididymis
Ductus deferens
Seminal vesicles
Ejaculatory ducts
Appendix epididymis
Mesonephric Duct Remnants in Females
The cranial end of the mesonephric duct may persist as an appendix vesiculosa. A few blind tubules and a duct, the epoophoron,
correspond to the efferent ductules and duct of the epididymis in the male. The epoophoron may persist in the mesovarium between
the ovary and uterine tube. Closer to the uterus, some rudimentary tubules may persist as the paroophoron. Parts of the mesonephric
duct, corresponding to the ductus deferens and ejaculatory duct, may persist as Gartners duct cysts between the layers of the broad
ligament along the lateral wall of the uterus and in the wall of the vagina.
Paramesonephric Duct Remnants in Males
The cranial end of the paramesonephric duct may persist as a vesicular appendix of the testis, which is attached to the superior pole
of the testis
The prostatic utricle, a small saclike structure that opens into the prostatic urethra, is homologous to the vagina.
Paramesonephric Duct Remnants in Females
Part of the cranial end of the paramesonephric duct that does not contribute to the infundibulum of the uterine tube may persist
as a vesicular appendage it forms
Uterus
Cervix
Uterine tubes
Hydatid of morgagni

24

USMLE Step 1 Platinum Notes

Appendages around testis

Cryptorchidism or Undescended Testes
The term cryptorchidism (Greek cryptos = hidden, orchis = testis) should be reserved for impalpable, usually abdominal, testes
There is a higher incidence of undescended testes in premature than in full-term babies
Two-thirds of undescended testes in newborn infants will descend, usually by 6 weeks in term and 3 months in preterm babies
There is an increased incidence of cryptorchidism in anencephalics and other cerebral anomalies.
Ectopic Testes: After traversing the inguinal canal, the testis may deviate from its usual path of descent and lodge in various
abnormal locations
Interstitial (external to aponeurosis of external oblique muscle)
In the proximal part of the medial thigh
Dorsal to the Penis
On the opposite side (crossed ectopia)
Exstrophy of the bladder results from a rare ventral body wall defect through which the posterior wall of the urinary bladder
protrudes onto the abdominal wall. Epispadias is a common associated anomaly in males; the urethra opens on the dorsum
of the penis.

Developmental Anomalies of CNS

Spina Bifida: The original defect lies in the vertebrae when their laminae fail to cover the spinal cord dorsally. Spina bifida maybe
simple or complicated. Complicated Spina bifida is associated with involvement of the cord and its membranes
Rarely do the two halves of the vertebral body fail to fuse and the spinal cord protrudes anteriorly through the gap. This rarity is
called as anterior spina bifida
Spina bifida occulta: Here the spinal cord is normal. The defect is not manifest externally and usually a tuft of hair is present
on the skin over the affected area
Meningocele: The Arachnoid and the Piamater covering the spinal cord protrude through the opening of the bifid spine and
form a cystic swelling
Meningomyelocele: Here the spinal cord along with its meninges and the spinal nerves are seen to protrude. It is a more
serious condition owing to development of infection of the cord itself
This condition is associated with displacement of medulla and a part of cerebellum which cause obstruction of the
foramen magnum producing hydrocephalus. An association of hydrocephalus and Meningomyelocele is called Arnold Chiari
malformation
Syringomyelia: Once the central canal of the spinal cord is distended with excessive fluid it is called Syringomyelia
Myelomalacia: Abnormal softening of spinal cord. Usually seen after trauma to spinal cord

Anatomy

25

Syringomyelia
In Syringomyelia there is softening of the spinal cord and the central canal becomes very wide at lesion in this position will
interrupt the pain and temperature fibers which pass in front of the central canal as they cross from one side to another
Syringomyelia usually occurs in the lower cervical and the upper thoracic regions of the spinal cord and the loss of pain and
temperature
Only the fibers of the pain and temperature which pass in front of the central canal are injured: the lateral spinothalamic tracts
themselves remain normal and there is no loss of pain and temperature in the lower limbs
Touch can be felt in the area of the skin in which pain and temperature are lost: this condition in which pain and temperature is lost
while touch is nearly normal called Dissociated sensory loss.

USMLE Case Scenario

Which of the following embryonic structures gives rise to the adrenal cortex?
1. Ectoderm
2. Endoderm
3. Mesoderm
4. Mesonephros
Ans. 3. Mesoderm

Types of Neurons Based on Poles

Unipolar Neurons
They have only one pole
Both Axon and Dendrons arise by a common stem.

Present in
Fetal life
Posterior root ganglion
Sensory nucleus of the fifth cranial nerve

Bipolar Neurons
They have two poles
Axon and Dendron lie at opposite poles

Present in

Cochlear ganglion of the eight nerves

Vestibular ganglion of the eight nerves
Retina
Olfactory nerve

Multipolar Neurons
They have multiple poles
The Axon and all other Dendrons form multiple poles

Present in
The spinal cord
Cerebral cortex
Cortex of cerebellum

26

USMLE Step 1 Platinum Notes

Important Changes in Phases of Cell Cycle

Leptotene: Chromosomes become visible

Zygotene: Pairing of chromosomes
Pachytene: Tetrad formation, crossing over, chiasmata formation
Diplotene: Chromosomes break
Metaphase: Spindle formation
Anaphase: Chromosomes move from equator to poles
Telophase: Chromosomes move completely to opposite sides

Sex Chromatin or Barr body

Of the two X-chromosomes in a Female only one is functionally active. The other (Inactive) X-chromosome forms a mass
of heterochromatin that lies just under the nuclear membrane. This mass of heterochromatin can be identified in suitable
preparations and can be useful in determining whether a particular tissue belongs to a male or a female. Because of this
association with sex this mass of heterochromatin is called the SEX CHROMATING. It is also called a BARR-BODY after the name
of the scientist who first discovered it.

Sex chromatin
In NEURONS it forms a rounded mass lying very close to the nucleolus and is therefore called a NUCLEOLAR SATELLITE.
In NEUTROPHIL LEUCOCYTES it may appear as an isolated round mass attached to the rest of the nucleus by a narrow band, thus
resembling the appearance of a DRUM-STICK. Rarely, some individuals may have more than two X-chromosomes. In these cases
only one X-chromosome is active (and hence euchromatic) while others are represented by masses of heterochromatin.
In normal females XX

There is one barr body

In normal males XY

There is no barr body

In Turners Syndrome XO

There is no barr body

In males with Klienfilters syndrome XXY

There is one barr body

In super female XXX

There are two barr bodies

The number of Barr bodies is (X-1)

Cell Division
The number of chromosomes found in somatic cells is constant and is termed the diploid (2n) number. Each gamete, however, has only
half the diploid number and is said to be haploid (n). In order to maintain this regularity, two types of cell division occur: mitosis, which
is the cell division occurring in somatic tissues during growth and repair, and meiosis, which is the specialized form of cell division
occurring when gametes form.

Mitosis
The function of mitosis is to distribute and maintain the continuity of the genetic material in every cell of the body. This process
consists of a number of different phases, which results in an equal distribution of the chromosomes to the two daughter cells. The cell
cycle has four stages: mitosis (M), gap1 (G1), synthesis (S), and gap2 (G2). The G1 phase follows mitosis, during which RNA and
protein synthesis occurs. S is the period during which DNA replication takes place and the DNA content of the cell doubles, and G2 is
the period during which energy requirements for cell division are built-up and any repair of errors in DNA synthesis takes place.

Anatomy

27

Meiosis
This process occurs only during the formation of the gametes and results in four daughter cells, each with the haploid number of
chromosomes. In males each primary spermatocyte forms four functional spermatids that develop into sperm, while in females each
oocyte forms only one ovum, the remaining products of meiosis being nonfunctional polar bodies.
Lyonization
In females, the sex chromosomes are identical in size and are genetically homologous chromosomes (as in the case of autosomes);
however, in the normal diploid interphase cell, one of the Xs forms a condensed heterochromatic body called the Barr body. These
condensations, together with evidence from coat color pattern in mice, led Lyon to hypothesize X-inactivation.
She Stated
In each somatic cell there is inactivation of all but one of the X-chromosomes;
This process occurs early in development and is random with respect to maternally or paternally derived X-chromosomes in
different cells; and
Once a particular X is inactive, it is inactive in all daughter cells.

Important Points about Skin

1.
2.
3.
4.

The Skin has stratified squamous epithelium

Classically epidermis has four layers
Normal turn over of epidermis is 4 weeks
Skin doubling time is 4 weeks
Stratum Germinativium composed of stratum Basale and Stratum Spinosum
Stratum Granulosum (Granular cell layer)
Stratum Lucidum (Clear cell layer)
Stratum Corneum (horny cell layer)

1. Stratum Germinativium is also called as Malphigian layer composed of

(a) Basal cell layer
(b) Prickle cell layer (stratum spinosum)
The Basal cell layer is composed of single layer of columnar cells resting on a clear wavy basement membrane From the basal borders
of these cells Cytoplasmic processes extend anchoring the epidermis to dermis Melanocytes are present here.
Acantholytic cells are present here
Dermatophytes are present here
It is underdeveloped in VLBW infants
The prickle cell layer (stratum spinosum) consists of 46 layers of cells which are polygonal and connected together by tonofilaments
giving them a prickly appearance.
2. Stratum Granulosum
Consists of 34 layers of flattened cells rich in keratohyaline granules
The keratohyaline granules eventually fill much of the cell, and it is these granules which give the cells of the stratum
Granulosum its granular appearance
The keratohyaline granules contain a protein called filaggrin, the function of which appears to be to bind the tonofibrils
together, converting them into keratin
3. Stratum Lucidum
Consists of few layers of dead, non nucleated cells without cell boundaries
These cells are rich in Eleidin granules
4. Stratum Corneum
It is the most superficial layer of epidermis
It is made of flat, dead cornified cells which have horny scales
They are continuously shed from the surface and replaced by newer cells

28

USMLE Step 1 Platinum Notes

The Dermis is formed of CT present beneath the epidermis. It is made of two layers continuous with each other
The Papillary layer or the loose connective tissue layer
The Reticular layer or the deeper layer
The Hypodermis is continuous with the dermis. It is formed of loose CT rich in blood vessels, loose CT, nerve endings.

Cells in Skin are

Langerhans Cells
Are located primarily in the stratum spinosum
They function in the immune system as antigen presenting cells
They stain selectively with gold chloride and contain numerous rod like or racket-shaped Cytoplasmic granules (Birbecks
granules)

Merkel Cells
Are located in the stratum basale
They contain granules which contain catecholamines
The base of a Merkel cell makes contact with the expanded terminal disk of a nerve fiber, forming a special receptor which functions
as a mechanoreceptor (detection of touch)

Dendritic Cells
Are found throughout the epidermis
They are antigen presenting cells

EPITHELIUM
Simple Squamous Epithelium
Alveoli of lungs
Mesothelium of pleura, peritoneum and pericardium
Endothelium of heart and blood vessels

Simple Cuboidal Epithelium

Lining of the thyroid follicles
Germinal epithelium of ovary
Anterior surface of lens of eye

Simple Columnar Epithelium

The lining of stomach
Intestines
Gallbladder

Simple Columnar Ciliated

Fallopian tubes and the uterus
Central canal of spinal cord
Osseous part of eustachian tube

Anatomy

29

Pseudostratified Columnar (Pseudo: False, Stratified: Layered)

It is a simple type of columnar cells resting on a clear wavy basement membrane. The cells are crowded over each other and appear
multilayered. The nuclei are arranged at different levels, some situated basal and others centrally as a result of which a false impression
of multilayered cells is created. However, most of the cells reach the basement membrane. The cells maybe ciliated or nonciliated
With cilia
Nasal cavity, nasal air sinuses, nasopharynx, larynx, trachea and bronchi
Eustachian tube in its cartilaginous parts
Without cilia
Vas deferens
Part of male urethra

Stratified Squamous Epithelium

The surface of the cells maybe keratinized (Protective function) as in case of
Epidermis of skin
External ear
External nose
The surface of the cells maybe without keratin called Nonkeratinized as in case of
Esophagus
Tongue
True vocal cords
Cornea
Tonsil

Stratified Columnar Epithelium

Conjunctival fornicies
Penile part of male urethra
Anorectal junction

Transitional Epithelium

It is a type of epithelium composed of multiple cell layers

They have extra reserve of cell membrane
The top cell layers are broader
The intermediate cell layers are polyhedral without intercellular bridges separated by mucus like substance. The cells can
undergo transition in relaxed and contracted state. In the relaxed state the number of layers is 68 while as in the contracted state
it is 23 layers
The basal cell layers are cuboidal.

It is present in

Calyces
Ureter
Urinary bladder
UV junction
Male urethra

30

USMLE Step 1 Platinum Notes

Salivary Glands
Gland

Duct

Type of Gland

Duct opening

Parotid

Stensens duct

Serous

Vestibule of mouth opposite second upper molar

S u b m a n d i - Whartons duct
bular

Mixed but
predominantly serous

On the floor of mouth on summit of sublingual papilla

at the side of frenulum of tongue

Sublingual

Mixed but
predominantly mucus

On the floor of mouth on summit of sublingual papilla

Bartholins duct

Structures within Parotid Gland

External carotid artery
Retromandibular vein
Facial nerve

Questions Frequenly asked from Histology of Liver

Classic Hepatic Lobule: This model is based on the direction of blood flow. In sections, liver substructure exhibits a pattern of
interlocking hexagons; each of these is a classic lobule. Whereas lobules in pigs are defined by a sheath of connective tissue, there
is less connective tissue in humans and the lobule boundaries are indistinct. The central vein at its center and the alternating
hepatocyte plates and sinusoids that lie between them.
Portal Canal/triad: One triad occupies a potential space (portal space) at each of the 6 corners of the lobule. Each triad contains
3 main elements surrounded by connective tissue: a portal venule (a branch of the portal vein), a hepatic arteriole (a branch of
the hepatic artery) and a bile ductule (a tributary of the larger bile ducts). A lymphatic vessel may also be seen. In the portal canal
blood vessels and bile ductules are separated by a space called as Space of Mall
Portallobule: This model is based mainly on the direction of bile flow, which is opposite to that of blood. From this perspective,
the liver parenchyma is divided into interlocking triangles, each of which has a portal triad at the center and a central vein at each
of its 3 comers
Hepatic lobule: It is the structural unit of liver. It has a central vein. A single vein marks the center of each lobule. This vessel is easily
distinguished from those in the portal triad by its larger opening and lack of a connective tissue investment.
Kuffercells are Reticuloendothelial cells of liver
Itto cells are fat storing cells in liver
'Space of Dissie and Space of Mall are seen in Liver

Important Histological Features: (USMLE Favorite)

Hassals corpuscles

Thymus

Corpora amaylacea

Prostate

Corpora atretica

Ovary

Germinal center

Lymph node

Corpora aranacea

Pineal gland

Herring bodies

Pituitary gland

Cords of Billiroth

Spleen

Cells of Stomach
The Mucus neck cells
Called so as they are present in the necks of glands
They secrete mucin which serves as a protective layer against HCL

Anatomy

31

They appear pale because of dissolved mucin

They are low columnar with basal flat nuclei
The Chief cells (The Peptic cells or the Zymogen cells)
Called as chief because they line the main part of the body of the gland
They are low columnar with basal round nuclei
They secrete pepsinogen
Oxyntic Cells (Parietal Cells)
They are scattered in between peptic cells
They are highly acidophilic
Intrinsic factor of Castle is secreted by parietal cells
They secrete HCL
They contain secretory canaliculi and are rounded
The Argentaffin Cells
They are chromaffin positive and stain positive with Silver salts
They also contain acidophilic granules and are oval in shape

Cells of Intestine
Simple Columnar Cells
Line the villi and crypts
Have free brush border due to presence of microvilli to increase surface area
Goblet Cells
Are also present in the villi and crypts
They are unicellular glands
They are flask shaped
They secrete mucin
Paneth Cells
Are acidophilic
Secrete intestinal enzymes
Rich in Rough ER
Argentaffin cells
These are cells with silver staining properties
They secrete serotonin

Diffuse Lymphatic Tissue, Isolated Lymphatic Nodules

The diffuse lymphatic tissue is a collection of lymphatic tissue in:
Alimentary tract
Respiratory tract
Genitourinary tract
The lymphoid tissue is deposited randomly in the subepithelial layers and placed strategically so as to detect and destroy the
pathogenic agents instantaneously and effectively. Located in adventitia
Functioning in close collaboration is other set of localized concretions of lymphocytes in the form of follicles and nodules such as:
Pharyngeal tonsils
Palatine tonsils
Lingual tonsils
Peyers patches in the small intestine especially in the ileum
Lymphoid follicles in appendix/abdominal tonsil

32

USMLE Step 1 Platinum Notes

In the alimentary canal the diffuse and the local lymphatic systems combine synergistically to form the GUT ASSOCIATED LYMPHOID
TISSUE (GALT). The main function of this system is to act along with the main lymphatic organs.

Remember frequently asked Terms in USMLE

Eponyms

Description

Bowmans capsule

Glomerular capsule of the kidney seen on histology slides

Bowmans membrane

Layer in the cornea below epithelium seen on histology slides

Brunners glands

Glands in the duodenum seen on histology slides

Bundle of His

Atrioventricular bundle

Cords of Billroth

Splenic cords of the spleen seen on histology slides

Crypts of Lieberkuhn

Epithelial glands in the small intestine seen on histology slides

Descemets membrane

Limiting layer of the cornea seen on histology slides

Ducts of Bellini

Papillary duct of the kidney seen on histology slides

Ducts of Luschka

Small ducts found in the connective tissue between the gallbladder and the liver

Golgi aparatus

Intracellular organelle

Golgi tendon organ

Sensory nerve ending embedded in a tendon for proprioception

Graafian follicle

Tertiary follicle of an ovary seen on a histology slide

Haversian canal

Central canal of an osteon of bone seen on a histology slide

Haversian system

Osteon of bone seen on a histology slide

Islets of Langerhans

Pancreatic islets of the pancreas seen on histology slides

Leydig cells

Interstitial cells of the testis

Loop of Henle

U shaped loop in the nephron of the kidney

Krause end bulbs

Cylindrical/oval sensory receptor

Malpighian corpuscle

Renal corpuscle of the kidney seen on histology slides

Meissners corpuscle

Mechanoreceptor

Meissner s plexus

Submucosal plexus

Merkels disk

Tactile receptor

Molls gland

Glands of the conjunctiva

Nissl bodies

Rough endoplasmic reticulum of a neuron

Node of Ranvier

Area between two Schwann cells covering nerve fibers with axon which is not covered
by myelin

Organ of Corti

Small organ of sound transduction; spiral organ

Pacinian corpuscle

Lamellar corpuscle

Peyers patches

Aggregates of lymphatic tissue in the ileum seen on histology slides

Purkinje fibers

Part of the conducting system of the heart

Renal columns of Bertin

Renal columns seen on histology slides

Ruffinis corpuscle

Sensory receptor

Space of Disse

Perisinosoidal space of the liver seen on histology slides

Volkmanns canals

Perforating canals of bone

Whartons jelly

Mucous connective tissue seen in umbilical cord

Anatomy

HIGH YIELD CLINICAL ANATOMY

Upper Limb
Brachial Plexus
C5 and C6 roots join to form the upper trunk
C7 root alone forms the middle trunk
C8 and T1 roots join to form the lower trunk
Each trunk divides into an anterior and posterior division:
All the posterior divisions join to form the posterior cord
The upper two anterior divisions join to form the lateral cord
The lowest anterior division alone forms the medial cord

Branches of the Brachial Plexus

Branches from the roots
Nerve to serratus anterior (C5,C6,C7)
Dorsal scapular nerve (C5)
Muscular branches to the 3 scalene muscles
Branches from the trunks
Suprascapular nerve (C5,C6)
Subclavius nerve (C5,C6)
Branches from the cords
Medial cord
Medial head of median nerve (C8, T1)
Medial pectoral (C8, T1)
Ulnar nerve (C8, T1)
Median cutaneous nerve of forearm (C8, T1)
Medial cutaneous nerve of arm (T1)
Lateral cord
Lateral pectoral (C5, C6, C7)
Lateral head of median (C5, C6, C7)
Musculocutaneous (C5, C6, C7)
Posterior cord

Radial (C5, C6, C7, C8, T1)

Axillary (C5, C6)
Nerve to latissimus dorsi (C6, C7, C8)
Subscapular Upper (C5, C6)
Subscapular lower

Upper trunk deformity is called

Erbs palsy or policemans
Waiters tip
Porter tip deformity
Lower trunk deformity is called Klumpkes palsy

33

34

USMLE Step 1 Platinum Notes

Questions frequently asked from Nerves of Upper Limb

Ulnar nerve Musicians Nerve
Ulnar nerve supplies medial 1/3 of palm. (Hypothenar area)
Ulnar nerve in hand supplies:
3, 4 Lumbricals
Palmar and dorsal interosei
Adductor pollicis
Hypothenar muscles
Ulnar nerve in hand supplies flexor carpi ulnaris and medial half of flexor digitorum profundus
Lesion of ulnar nerve causes:
Weakness of ulnar deviation
Weakness of wrist flexion
Adductor pollicis paralysis with loss of thumb adduction

In Ulnar Nerve Palsy there is

Positive card test
Positive book test/Froment sign
Positive Egawas test
Ulnar claw hand

Median nerve: Laborers nerve, Eye of hand

Does not supply arm
Supplies all flexors except flexor carpi ulnaris and medial half of flexor digitorum profundus in forearm
Supplies thenar eminence
Lumbrical 1 and 2
Opponens pollicis
Abductor pollicis brevis
Flexor pollicis brevis in hand. (LOAF)
Implicated in:
Lunate dislocation
Ape thumb deformity
Carpal tunnel syndrome
Pointing index
Pen test is positive in median nerve injury
Loss of opposition and abduction of thumb

Carpal Tunnel Syndrome

Affects the median nerve. Patients often note a tingling, a loss of sensation, or diminished sensation in the digits. There is also often
a loss of coordination and strength in the thumb, because the median nerve also sends fibers to the abductor pollicis brevis, flexor
pollicis brevis, and the opponens pollicis. A final function of the median nerve distal to the carpal tunnel is control of the first and
second lumbricals which function to flex digits two and three at the metacarpophalangeal joints and extend interphalangeal joints of
the same digits.

Anatomy

35

Radial Nerve
Supplies:
Extensor compartment of arm, forearm
Triceps
Anconeus and extensors of forearm. Extension of MCP joint
Injury to RN Causes
Wrist drop
Saturday night palsy/crutch palsy
Commonly injured in Radial groove

USMLE Case Scenario

A 43-year-old man suffered an injury in his left upper limb. His radial nerve was injured. The radial nerve is at greatest risk for
injury with:
1. Fracture of the surgical neck of the humerus
2. Fracture of the shaft of the humerus
3. Supracondylar fracture of the humerus
4. Olecranon fractures
Ans. 2. Fracture of the shaft of the humerus

Remember
The radial nerve lies in proximity to the humerus as it courses laterally at the junction of the middle and distal thirds of the shaft
of the humerus. Therefore, it is at greatest risk of injury in shaft fractures.

Common Questions in Surgical Anatomy (Hot Questions)

In supracondylar fracture of humerus triangular relationship of three bony prominences is not disturbed. In elbow
dislocation it is disturbed
The shoulder joint is the most commonly dislocated major joint in the body
MC dislocation is inferior
In subacromial bursitis, person feels pain when arm is abducted. Dawbarns sign is seen in subacromial bursitis
PIN (Posterior interosseous nerve) is a branch of radial nerve. No wrist drop is seen in injury to PIN
If posterior medial aspect of elbow is banged against a hard object, it mat cause temporary ulnar nerve damage. This may result in
painful tingling sensations along ulnar aspect of forearm and hand. Because of these sensations, this area of elbow is called Funny
bone/Crazy bone
Eye of hand: median nerve. Enables the individual to feelthinness and texture of cloth
Pronator syndrome: compression of Median nerve between two heads of pronator teres
Infection of pulp spaces is Felon/Whitlow

REMEMBER
USMLE Favorite
Important Nerves Involved in

Wrist drop
Foot drop
Meralgia parasthetica
Winging of scapula
Erbs Palsy
Klumpkes palsy
Sluders neuralgia

Radial nerve palsy

Common peroneal nerve palsy
Lateral cutaneous nerve of thigh
Long thoracic nerve of bell
Upper trunk of brachial plexus
Lower trunk of brachial plexus
Middle turbinate pressing anterior ethmoidal nerve

36

USMLE Step 1 Platinum Notes

The Axillary Nerve

The Axillary nerve is a branch of the posterior cord of the brachial plexus
It is particularly susceptible to the injury in shoulder dislocations that displace the humeral head or in fracture of the surgical neck
of the humerus
A poorly placed crutch (Crutch Palsy) may also damage this nerve causing paralysis of the Teres minor and Deltoid muscles
Arm abduction is impaired and there is associated loss of sensation over the lower half of the deltoid
When the head of the humerus dislocates from the glenohumeral joint, it exits inferiorly, where the joint capsule is the
weakest. Immediately inferior to the glenohumeral joint, the axillary nerve exits from the axilla by passing through the
quadrangular space. At this location, the downward movement of the head of the humerus can stretch the axillary nerve.
The axillary nerve innervates the deltoid muscle after leaving the axilla.
The Lower Subscapular nerve innervates the Teres major, which is responsible for adducting and medially rotating the arm, it
is a branch of the posterior chord (C5 C6) of the brachial plexus.
The Suprascapular nerve innervates the Supraspinatus and Infraspinatus muscle that are responsible for abduction and
lateral rotation of the arm. The nerve is derivated from the C5 and C6 nerve roots
In shoulder abduction:
Humerus elevates
Clavicle rotates
Lateral rotation of scapula occurs along with acromioclavicular joint movement.
The Throacodorsal nerve innervates the latissimus dorsi muscle that is responsible from adduction and extension of the arm.
The nerve arises from the posterior chord (C5, C6, C7) of the brachial plexus
Musculocutaneous nerve supplies (BBC) biceps, bracialis and corocabrachialis.
Brachioradialis is supplied by radial nerve.

Effects caused by Injuries of Important Nerves of Upper Limb

Musculocutaneous
nerve

Muscles of anterior compartment of arm

Median nerve

Muscles of anterior compartment of forearm

Supplies Biceps, corocabrachialis, brachialis

Injury causes loss of elbow flexion and weakness in
supination.
Injury to median nerve at wrist causes:
Ape thumb deformity
Pen test for abductor pollicis brevis
Inability to count on fingers with thumb

Axillary nerve

Deltoid and teres minor

Injury causes
Loss of abduction of shoulder
Rounded contour of shoulder is lost
Sensory loss over lower half of deltoid

Radial nerve

Posterior muscles of arm and forearm

Injury causes
Saturday night palsy
Crutch palsy
Wrist drop

Fracture surgical neck of humerus

dislocation of shoulder

Fracture of humeral shaft

Anatomy

37

USMLE Case Scenario

Deltoid is a thick muscle. It arises from the anterior border and superior surface of the lateral third of the clavicle. Which of the
following nerves innervates the deltoid?
1. Radial
2. Musculocutaneous
3. Ulnar
4. Anterior interosseous c nerve
5. Cranial nerve XI
6. Subscapular
7. Axillary
Ans. 7. Axillary Nerve

Action of Various Muscles of Upper Limb

Flexors of forearm: Biceps, brachialis, brachioradialis
Extensors of arm: Triceps, Anconeus
Muscles attached to greater tubercle: Supraspinatus, infraspinatus, teres minor
Muscles attached to lesser tubercle: subscapularis
Muscles attached to coracoid process: biceps, short head of biceps
Abductors of shoulder joint: Deltoid, serratus anterior, trapezius
Adductors of shoulder joint: pectoralis major, lattismus dorsi

Cleidocranial Dysostosis
Defective intramembranous ossification
Agenesis of clavicle and deformity of skull cap

Four Rotator Cuff Muscles are

Supraspinatus
Infraspinatus
Teres minor
Subscapularis

Remember: Clinical Anatomy (USMLE Favorite)

Frozen shoulder
Dropped shoulder
Chronic supraspinatus tendinitis
Tennis elbow
Golfers elbow
Base pitchers elbow
De quevarians disease
Trigger finger
Mallet finger

Is adhesive capsulitis or periarthritis

Paralysis of trapezius
Is painful arc syndrome
Is lateral epicondylitis
Is medial epicondylitis
Is damage to soft tissues/bones around elbow
Is tenosynovitis of Extensor pollicis brevis and abductor pollicis longus
Is thickening of tendon sheaths at metacarpophalyngeal joint
Is avulsion of extensor tendon of distal interphalangeal joint

38

USMLE Step 1 Platinum Notes

The Anatomical Snuffbox

Triangular depression formed on the posterolateral side of the wrist and metacarpal I by the extensor tendons passing into the
thumb
Historically, ground tobacco (snuff ) was placed in this depression before being inhaled into the nose
The base of the triangle is at the wrist and the apex is directed into the thumb. The impression is most apparent when the thumb
is extended:
The lateral border is formed by the tendons of the abductor pollicis longus and extensor pollicis brevis;
The medial border is formed by the tendon of the extensor pollicis longus;
The floor of the impression is formed by the scaphoid and trapezium and distal ends of the tendons of the extensor carpi radialis
longus and extensor carpi radialis brevis. Structures inside:
Remember essentially:
The radial artery passes obliquely through the anatomical snuffbox
Terminal parts of the superficial branch of the radial nerve pass subcutaneously over the snuffbox
Origin of the cephalic vein from the dorsal venous arch of the hand

Volkmans Ischemic Contracture (Features) (P)

Pallor
Pain (Most important sign)
Paralysis
Parasthesias
Pulselessness

Median nerve mostly involved with Deformity: Flexion of wrist, Extension of Fingers at MCP, Flexion at IP and Pronation of forearm.
Flexor digitorum profundus and Flexor Pollicis Longus are muscles damaged.

Dupuytrens contracture
Progressive, Painless, Puckeringor fibrosis of skin of Palmar Fascia with flexion of MCP joints of ring and little fingers

Colles Fracture
Fall on outstretched hands, Common in elderly women
Distal fragment displaced dorsally, Angulated dorsally, supinated and is also called as Dinner Fork Deformity

De Quervain syndrome
Also known as washerwomans sprain or mothers wrist is a tendinosis of the sheath or tunnel that surrounds two tendons that
control movement of the thumb. (Extensor pollicis brevis and abductor pollicis longus muscles). De Quervain is potentially more
common in women; the speculative rationale for this is that women have a greater styloid process angle of the radius. Symptoms are
pain, tenderness, and swelling over the thumb side of the wrist, and difficulty gripping. Finkelsteins test is used to diagnose
de Quervain syndrome in people who have wrist pain.

Scaphoid Fracture
Scaphoid is one of the Carpal bones which undergo fracture commonly as well as avascular necrosis. Avascular necrosis of
proximal fragment is seen
Injury occurs by fall on outstretched hands. MC site of injury is Waist
Tenderness in Anatomical snuff box maybe seen. Best Radiological view is Oblique view
In absence of Radiological findings, suspect scaphoid fracture. Most common site is between proximal 1/3 and distal 2/3.

Anatomy

39

Action of Various Muscles of Lower Limb

Hip joint
Medial rotator of thigh:
Gracilis
Lateral rotators of femur are:
Obturator internus, Obturator externus
Sartorius, Pyriformis
Superior gemellus, inferior gemellus
Abductors of the hip include the gluteus medius and gluteus maximus
Adductors of the hip include the adductors longus, brevis and magnus
Extensors of hip include gluteus maximus
Internal (medial) rotators of the hip include gluteus medius, minimus, Tensor facia lata
Lateral rotators: quadriceps femoris (rectus femoris, vastus lateralis, medialis and intermedius)
Iliopsoas is flexor of hip
Remember:
Tensor fascia lata is extensor of knee, Abductor and medial rotator of hip. (Imp) TEAM
Ilio tibial tract is flexor, external rotator, abductor of hip. (Imp)
Knee Joint
Extensor of knee: quadriceps femoris
Flexion of knee: long head of biceps femoris. Semimembranosus, semitendonosus, ischial head of adductor magnus
Medial rotation: Semimembranosus, semitendonosus, popliteus
Lateral rotation: biceps femoris

Important Points: (USMLE Favorite)

Meralgia Parasthetica Lateral cutaneous nerve of thigh
Anterior Tarsal Tunnel Syndrome: Deep peroneal nerve
Tarsal Tunnel syndrome: Tibial nerve
Joggers Foot: Medial plantar nerve
Hip Pointer: Iliac Crest
Tennis Leg: Gastrocnemius Soleus strain

Hip Joint

Ileo femoral ligament is ligament of Bigelow

It is the strongest ligament
It prevents hyperextension of hip
Pain of hip is referred to knee joint

Knee

Coronary ligament is present between menisci and tibial condyle

There is other Coronary ligament in liver
Posterior dislocation of Femur is prevented by anterior cruciate ligament
Posterior cruciate ligament prevents posterior dislocation of Tibia
Ligament of Humphery and Wrisberg are anterior and posterior meniscofemoral ligaments

40

USMLE Step 1 Platinum Notes

MENISCAL TEAR
Medial meniscus is 20 times more prone to injury than lateral meniscus. The medial meniscus is firmly adherent to the
deep part of tibial collateral ligament. In forceful strains (adduction and lateral rotation of the femur over the tibia with
the foot firmly placed on the ground) the medial meniscus gets torn. It is because:
The medial collateral ligament does not allow the meniscus to move away from under the femoral condyle
It gets compressed crushed between femoral and tibial condyles that are moving with great force
Part of torn cartilage may get displaced. This small piece floats in the joint cavity. It may get lodged between femoral and
tibial condyles causing locking of knee joint in flexed position

Arterial Supply of Hip Joint

Obturator artery
Medial circumflex artery
Lateral circumflex artery
Superior gluteal artery
Inferior gluteal artery

In Fracture Neck of femur, Blood supply is from these vessels.

USMLE Case Scenario

A 88-year-old osteoporotic female who was a chronic smoker stumbled and fell. The right leg is shortened and externally
rotated with marked loss of range of movements at hip joint
The most likely cause is: Fracture Neck of femur

Nerve Supply of Hip Joint

Femoral nerve through nerve to rectus femoris

Anterior division of obturator nerve
Nerve to quadrates femoris
Superior gluteal nerve

Arterial Supply of Knee Joint

Genicular branches of popliteal artery

Genicular branches of femoral artery
Genicular branches of lateral circumflex femoral artery
Branches of anterior tibial artery
Branches of posterior tibial artery

Nerve Supply of Knee Joint

Femoral nerve through nerve to vasti
Posterior division of obturator nerve
Sciatic nerve through tibial and common peroneal nerves

Nerves Related to Lower Limb Compartments: (USMLE Favorite)

Adductor compartment of thigh: Obturator nerve

Flexor compartment of thigh: Femoral nerve
Posterior compartment of thigh (hamstrings); tibial part of sciatic nerve
Gluteal region: superior and inferior gluteal nerves

Anatomy

41

Anterior compartment of leg: Deep peroneal nerve

Lateral compartment of leg: Superficial peroneal nerve
Posterior compartment of leg: Tibial nerve

Nerves of Lower Limb

Femoral nerve (posterior division of L2, L3, L4)

Anterior compartment of high

Obturator nerve (anterior division of L2, L3, L4)

Medial compartment of thigh

Tibial nerve

Posterior compartment of thigh

Posterior compartment of leg

Common peroneal nerve

Short head of biceps femoris

Superficial peroneal nerve

Lateral compartment of leg

Injury causes loss of eversion of foot

Deep peroneal nerve

Anterior compartment of leg

Injury causes foot drop

Superior gluteal nerve

(Very Important)

Gluteus minimus, gluteus medius, tensor fascia lata NOT Gluteus maximus. Injury Causes
loss of abduction of limb
Impairment of gait
Patient cannot keep pelvis level when standing on one leg. Tredlenburgs sign +

Inferior gluteal nerve

Gluteus maximus. Injury causes:

Weakened hip flexion
Difficulty rising from sitting position.

Q angle: Quadriceps angle is formed by line of pull of quadriceps femoris muscle and that of ligamentum patellae as they intersect
at center of patella. more pronunced in females
Genu valgum (knock knee) angle < 165
Genu varum (bow legs) angle > 180
The Common Peroneal Nerve
Branches into the superficial and deep peroneal nerves, which supply the muscles of the anterior compartment of the leg and
cutaneous areas of the distal anterior leg, dorsum of the foot, and most of the digit
The Tibial Nerve
Supplies all the muscles in the posterior compartment of the leg (e.g. tibialis posterior, flexor digitorum longus, gastrocnemius, and
soleus)

Movements at Different Joints

Ankle: Dorsiflexion, Plantar flexion
Subtalar joint: Inversion, eversion
Mid tarsal joint: Forefoot adduction and abduction

Muscles Involved in Various Movements

Plantar flexion

Gastrocnemius, soleus

Dorsiflexion

Tibialis anterior

Inversion

Tibialis anterior, tibialis posterior

Eversion

Peroneus longus, peroneus brevis

42

USMLE Step 1 Platinum Notes

Common Peroneal Nerve

It is related to the neck of fibula and winds around it
It is the smaller terminal branch of Sciatic nerve
It pierces peroneus longus
It divides into superficial and deep peroneal nerves and supplies the anterior and lateral compartments of leg
Injury to CPN produces foot drop
It is subcutaneous
It is the most common nerve in lower limb to get injured

Ankle Joint
Dorsiflexion

Tibialis anterior
Extensor digitorum longus
Extensor hallucis longus
Peroneus tertius

Plantar flexion

Gastrocneimus
Soleus
Plantaris
Tibialis posterior
Flexor hallucis longus
Flexor digitorum longus

Inversion

Tibialis posterior
Flexor hallucis longus
Flexor digitorum longus

Eversion

Peroneus longus
Peroneus brevis
Peroneus tertius

Reflexes
Biceps

C5, C6

Supinator

C5, C6

Pronator

C5, C6

Triceps

C6, C7

Cremaster

L1, L2

Knee

L2, L3, L4

Plantar

L5 S1

Ankle

S1, S2

Anal, Bulbocavernous

S3, S4

Important Points about Anatomy of Breast

The protuberant part of the human breast is generally described as overlying the 2nd to the 6th ribs, and extending from the
lateral border of the sternum to the anterior axillary line. Actually, a thin layer of mammary tissue extends considerably farther
from the clavicle above to the 7th or 8th ribs below, and from the midline to the edge of latissimus dorsi posteriorly.
The Axillary tail of Spence in the breast is of considerable surgical importance. In some normal cases it is palpable, and in a few it
can be seen premenstrually or during lactation. A well-developed axillary tail is sometimes mistaken for a mass of enlarged lymph
nodes or a lipoma.

Anatomy

43

Axillary tail
The lobule is the basic structural unit of the mammary gland. The number and size of the lobules vary enormously: they are
most numerous in young women. From 10 to over 100 lobules empty via ductules into a lactiferous duct of which there are
from 15 to 20. Each lactiferous duct is lined by a spiral arrangement of contractile myoepithelial cells and is provided with a
terminal ampulla a reservoir for milk or abnormal discharges.
The ligaments of Cooper are hollow conical projections of fibrous tissue filled with breast tissue, the apices of the cones being
attached firmly to the superficial fascia and thereby to the skin overlying the breast. These ligaments account for the dimpling of
the skin overlying a carcinoma.
The areola contains involuntary muscle arranged in concentric rings as well as radially in the subcutaneous tissue. The areolar
epithelium contains numerous sweat glands and sebaceous glands, the latter of which enlarge during pregnancy and serve to
lubricate the nipple during lactation (Montgomerys tubercles).
The nipple is covered by thick skin with corrugations. Near its apex lie the orifices of the lactiferous ducts. The nipple contains
smooth muscle fibers arranged concentrically and longitudinally; thus is an erectile structure which points outwards. Lymphatics
of the breast drain predominantly into the axillary and internal mammary lymph nodes. The axillary nodes receive approximately
75 percent of the drainage and are arranged in the following groups.

Blood Supply is via

Internal thoracic artery
Intercostal artery
Lateral thoracic artery

Lymph nodes of Breast

Lateral, along the axillary vein
Anterior, along the lateral thoracic vessels
Posterior, along the subscapular vessels
Central embedded in fat in the center of the axilla
Interpectoral, a few nodes lying between the pectoralis major and minor muscles
Apical, which lie above the level of the pectoralis minor tendon in continuity with the lateral nodes and receive the efferents of all
the other groups
The apical nodes are also in continuity with the supraclavicular nodes and drain into the subclavian lymph trunk which enters the
great veins directly or via the thoracic duct or jugular trunk. The sentinal node is that lymph node designated as the first axillary node
draining the breast.
The internal mammary nodes are fewer in number and lie along the internal mammary vessels deep to the plane of the costal cartilages
Mondors disease is thrombophlebitis of the superficial veins of the breast and anterior chest wall (although it has also been
encountered in the arm).
Familial breast cancer Recent developments in molecular genetics and the identification of a number of breast cancer predisposition
genes (BRCA1, BRCA2 and TPS3). These women have a risk of developing breast cancer two to 10 times above baseline.

44

USMLE Step 1 Platinum Notes

Lymph nodes below Pectoralis Minor Level 1

Lymph nodes behind Pectoralis Minor Level 2
Lymph nodes above Pectoralis Minor Level 3
The principal nodes which drain the breast are: Axillary Group of Lymph nodes
About 70 -75% of lymph from breast drains into Axillary group of Lymph nodes, 20% into internal mammary group of Lymph
nodes and 5% into posterior intercostal group of lymph nodes
Among the Axillary Group Chief is the Anterior group
Rotters nodes are interpectoral nodes
Absence of sternal head of pectoralis major: Polands syndrome

Openings of Diaphragm: (USMLE Favorite)

Vena caval opening:
Thoracic 8 level
Inferior vena cava
Rt phrenic nerve
Esophageal opening:
Thoracic 10 level
Esophagus
Vagus nerves
Esophageal branch of it gastric artery
Aortic opening:
Thoracic 12 level
Aorta
Thoracic duct
Azygous vein

CONTENTS OF IMPORTANT STRUCTURES

Contents of Spermatic Cord: (USMLE Favorite)

The ducts deferens

Testicular and cremastric arteries
Artery of vas
The pampiniform plexus of veins
Lymph vessels from testis
Genital branch of Genitofemoral nerve
Remains of processus vaginalis

Contents of Rectus Sheath: (USMLE Favorite)

Rectus abdominis and pyramidalis muscle

Superior epigastric artery and inferior epigastric artery
Superior epigastric vein and inferior epigastric vein
Lower five intercostal nerves and subcostal nerve

Contents of Broad Ligament: (USMLE Favorite)

Uterine tube
Round ligament of uterus, ligament of ovary
Uterine vessels, ovarian diseases
Uterovaginal, ovarian nerve plexus
Epoophoron, Paroophoron
Lymph vessels, lymph nodes

Anatomy

Contents of Ischiorectal Fossa: (USMLE Favorite)

Perianal space
Ischiorectal space
Lunate fascia
Pudendal canal

Contents of Adductor Canal are: (USMLE Favorite)

Femoral artery
Saphanous nerve
Nerve to vastus medialis

Esophageal opening lies in muscular part of diaphragm

Vena caval lies in central tendon of diaphragm
Aortic opening is not a true opening but an osseo aponeurotic opening
Greater and lesser splanchnic nerves pierces each crus of diaphragm
Lt crus is also pierced by hemi azygous vein
Sympathetic chain passes behind medial arcuate ligament
Subcostal nerves vessels pass behind lateral arcuate ligament
Superior epigastric vessels and lymphatics pass through Foramen of Morgagni (Larrys space)
Musculophrenic vessels pierce the diaphragm
Hernia does not occur through vena caval opening
Bochaldeks hernia occurs through posterolateral part of diaphragm
Morgagni hernia occurs anteriorly on right usually
Remember Accessory phrenic nerve is commonly a branch from the nerve to subclavius

Sites of Esophageal Constrictions

Distance from Incisor

Landmark

6 inches

Pharyngoesophageal junction

9 inches

Aortic arch crossing

11 inches

Left bronchus

15 inches

Pierces diaphragm

Esophagus

Length 25 cm
Commences at lower end of cricoid
Has squamous epithelium
Toughest layer is muscularis
No serosa

THORAX
Heart
Right coronary artery arises from anterior aortic cusp
Left coronary arises from posterior aortic cusp
Posterior interventricular artery determines coronary dominance

45

46

USMLE Step 1 Platinum Notes

In case it arises from right coronary artery, right dominance

In case it arises from left coronary, left dominance
Right Coronary artery mostly supplies SA node, AV node, AV bundle
The SA node is usually supplied by Right coronary artery and Right Vagus
The AV node is usually supplied by Right coronary artery and Left vagus
Sympathetic innervation is by T2-T6
Maximum (90%) of venous drainage of Heart goes to Coronary Sinus
In fetal life left sided svc drains into coronary sinus
Great Cardiac Vein follows Anterior Interventricular artery
Middle Cardiac Vein follows Posterior Interventricular artery
Small Cardiac Vein follows Rt Marginal artery
Inferior surface of heart is formed by Rt and Lt ventricle
Base of heart is formed by Rt and Lt atrium
Part of heart lying close to esophagus: Lt atrium
Structures Present In:
Musculi pectinati: Atria of heart
Trabeculae cornea: Rt ventricle of heart
Moderator band/Septomarginal trabeculae: right ventricle
Coronary sinus, SVC, IVC: open in Right atrium
SA node is located in: Rt Atrium
Whole of conducting system is mostly supplied by rt coronary artery except Right bundle branch (supplied by left coronary
artery)
Holmes heart: single ventricle

Coronary Sinus
It is the largest venous channel of the heart about 3 cms. It located in left posterior coronary sulcus
It is a remnant of left horn of sinus venosus = while the right horn gets incorporated into right atrium
It opens into the right atrium of the heart through an orifice of coronary sinus and has a valve called the Thebesian valve. It receives:
Great cardiac vein
Middle cardiac vein
Small cardiac vein
Right marginal vein
Oblique vein of left atrium
Right marginal vein

Thoracic Duct

Also called as Pecquets duct

Beaded in appearance
18 inches in length
It is the largest lymphatic pathway in body
The duct commences in the abdomen as an elongated lymph sac of the cisterna chylli is: Thoracic duct
Begins from cisterna chyli at the level of T12 vertebrae
Injury to thoracic duct by trauma leads to chylothorax

Anatomy

47

LUNGS
Bronchopulmonary Segment

Vascular segment
Independent
Bronchial artery supplies till respiratory bronchiole
Largest subdivision of lobe

Remember
Because the right main bronchus is wider and more vertical than the left, foreign objects are more likely to be aspirated into the
right main bronchus. The superior segmental bronchus of the lower lobar bronchus is the only segmental bronchus that exits from
the posterior wall of the lobar bronchi. Therefore, if a patient is supine at the time of aspiration, the object is most likely to enter the
superior segmental bronchus of the lower lobe.

Peculiarities of Blood Supply of Lung

Smallest functional unit of lung is lobule
Blood supply of lung tissue proper is by Bronchial arteries
Bronchial arteries are branches of descending: Thoracic Aorta
They supply nutrition to bronchial tree and pulmonary tissue up to respiratory bronchiole
Segments distal to respiratory bronchiole are supplied by branches from pulmonary vessels
On the right side there is only one BA arising indirectly from descending Thoracic Aorta
On the Left side there are two BA arising directly from descending Thoracic Aorta
Bronchial arteries are responsible for Hemoptysis
Pulmonary arteries carry deoxygenated blood
Pulmonary veins carry oxygenated blood
Sequestered segments are supplied by systemic circulation

AZYGOS Lobe of Lung

Azygos means unpaired. Azygos lobe maybe seen on the right lung
It is seen as a result of developmental anomaly related to lung bud and posterior cardinal vein
The posterior cardinal vein (future azygos vein) gets embedded in the substance of lung which passes as lung bud below the arch
formed by posterior cardinal vein
The part of lung medial to the vein forms the azygos lobe

GEMS ABOUT INTRA-ABDOMINAL ORGANS

The Spleen
It is a hemolymphatic organ:
The second largest organ of the reticuloendothelial system
It is located in the posterior left upper quadrant of the abdomen (left hypochondrium) where its relationships to the diaphragm,
stomach, pancreas, left kidney, and splenic flexure of the colon are maintained by suspensory ligaments. The splenophrenic,
splenorenal, and splenocolic ligaments are usually relatively avascular and their transection allows the spleen to be displaced
medially and anteriorly
The Gastrosplenic ligament extends from the greater curvature of the body and fundus of the stomach to the spleen, contains
the short gastric arteries and veins
The Splenorenal ligament (Lienorenal) and attached to the spleen at the hilum: Splenic artery and vein, lymphatic structures,
and often the tail of the pancreas

48

USMLE Step 1 Platinum Notes

The arterial supply to the spleen is derived from the celiac artery from both the splenic artery and the short gastric arteries,
which usually arise as branches of the gastroepiploic or the splenic arteries
The splenic vein is formed by a coalescence of polar veins in the splenic hilum and courses with the splenic artery along the dorsal
surface of the pancreas to enter the portal system.

The Stomach
Starts from gastroesophageal junction to the pylorus
It is bounded on the left by the spleen and on the right by the liver
The blood supply to the stomach is extensive
Left gastric artery, which supplies the upper lesser curvature of the stomach from celiac trunk
The right gastric artery branches off the hepatic artery, which originates from the celiac axis; it supplies blood to the distal lesser
curvature
The left gastroepiploic artery is a branch off the short gastric vessels; it comes from the splenic and therefore originally from the
celiac axis
The right gastroepiploic artery branches off the gastroduodenal artery, which comes originally from the hepatic artery and
therefore from the celiac axis
The venous drainage of the stomach empties in a variety of directions, including venous tributaries along the esophagus, veins that
flow with the short gastrics to the splenic vein, and venous drainage that is carried toward the duodenum and toward the portal vein
Nerve supply is predominantly by the vagus
An anterior (left) and posterior (right) vagus nerve courses with the esophagus until the gastroesophageal junction
The criminal nerve of Grassi is the first branch of the posterior vagal nerve innervating the greater curvature fundus. At the junction
of the fundus and the antrum of the stomach, the vagal nerves branch and innervate the antrum. This vagal branch point is called the
crows foot
The lesser sac is bounded ventrally by the stomach and is an important location during operation, in that it is a frequent space for
fluid collection and is an important plane for the exposure of gastric anatomy.

Duodenum
The duodenum extends from the pylorus about 20 to 30 cm and ends at the ligament of Treitz, which is where the jejunum
begins. This is marked by adhesive bands between the duodenal-jejunal junction and the retroperitoneum on the left side of the
abdomen
The duodenum is divided into four anatomic regions:
The first portion, or the cap or bulb
The second portion, or the descending duodenum
The third, or transverse, portion; and the
Fourth, or ascending, portion

Gems about Duodenum

The duodenal cap lies just beyond the pylorus. Ninety percent of ulcers occur in the duodenal cap region.
The gastroduodenal artery lies directly behind the duodenal cap, and penetrating ulcers into the pancreas initially erode through
the gastroduodenal artery, accounting for the massive bleeding that occurs with these ulcers.
The second (descending) portion of the duodenum: The ampulla of Vater and the minor papilla both enter into the duodenum
in this portion. The second portion of the duodenum is approximately 10 cm in length.
The third and fourth portions of the duodenum (transverse and ascending portions) are mostly retroperitoneal.
The third portion is attached to the uncinate process and crosses the abdomen and over the aorta.
Compression of the junction of the third and fourth portions of the duodenum by the angle of the SMA and the aorta is called
the SMA syndrome.

Anatomy

49

The fourth portion of the duodenum blends into the jejunum at the ligament of Treitz, which attaches this junction to the
retroperitoneum. Mobilization of the ligament of Treitz is necessary in duodenal resections. The ligament is often composed of small
strands of striated muscle that eventually extend to the crus of the diaphragm.
Kerckrings folds The mucosal surface of the small intestine contains numerous circular mucosal folds called the plicae
circulares (valvulae conniventes, or valves of Kerckring) of the duodenum begin just beyond the cap and continue throughout
the duodenum. The concentric folds of Kerckring are approximately 1 to 2 mm thick and 2 to 4 mm high. They are taller and more
numerous in the distal duodenum and proximal jejunum, becoming shorter and fewer distally.

Difference between Small and Large Intestine

Small intestine

Large intestine

About 6 -7 meters in length

About 180 cms in length

Small diameter

Larger diameter

Mucosa has villi and crypts

Mucosa hascrypts but no villi

Paneth cells present

Paneth cells absent

Less goblet cells

More goblet cells

Brunners glands in duodenum present

Peyers patches in ileum present

Both absent

Sacculations absent

Sacculations present

Appendices epiploicae absent

Appendices epiploicae present

Tenia absent

Tenia present

Celiac Trunk
LEFT GASTRIC ARTERY Esophageal branch, gastric branch
COMMON HEPATIC ARTERY Right hepatic, left hepatic, Gastroduodenal artery supraduodenal, right gastroepiploic, superior
pancreaticoduodenal artery
SPLEENIC ARTERY Short gastric, left gastroepiploic, pancreatic branches

Meckels Diverticulum
A Meckels diverticulum, a true congenital diverticulum
It is a vestigial remnant of the omphalomesenteric duct (also called the vitelline duct) and is the most frequent malformation
of the gastrointestinal tract
Meckels diverticulum is located in the distal ileum, usually within about 60-100 cm of the ileocecal valve
It is typically 3-5 cm long, runs antimesenterically and has its own blood supply
It is a remnant of the connection from the umbilical cord to the small intestine present during embryonic development

A Memory Aid is the Rule of 2s

2% (of the population)
2 feet (from the ileocecal valve)
2 inches (in length)
2% are symptomatic
2 types of common ectopic tissue (gastric and pancreatic)
Most common age at clinical presentation is 2
Males are 2 times as likely to be affected

50

USMLE Step 1 Platinum Notes

Anal canal above Dentate Line

Anal Canal Below Dentate Line

Endodermal

Ectodermal

Cuboidal epithelium

Stratified squamous

Superior Rectal Artery

Inferior Rectal Artery

Superior Rectal Vein

Inferior Rectal Vein

Internal Iliac group of lymph nodes

Superficial inguinal group of lymph nodes

Pain insensitive

Pain sensitive

The liver
Lies in the right upper quadrant of the abdomen
It is the largest gland in the body, it weighs approximately 1500 gm
The gallbladder lies on the dorsal surface of the liver in a transpyloric plane
A peritoneal membrane (Glissons capsule) covers the liver
The superior surface of the liver conforms to the undersurface of the right diaphragm. The relations of the inferior surface of
the liver are the duodenum, colon, kidney, adrenal gland, esophagus, and stomach. Peritoneum invests the entire liver except for a
bare area under the diaphragm on the posterosuperior surface adjacent to the inferior vena cava and hepatic vein.

Ligaments of Liver
The falciform ligament, which attaches the liver to the anterior abdominal wall from the diaphragm to umbilicus and incorporates
the ligamentum teres hepaticus
The anterior and posterior right and left coronary ligaments, which in continuity with the falciform ligament connect the
diaphragm to the liver. The lateral aspects of the anterior and posterior leaves of the coronary ligaments fuse to form the right and
left triangular ligaments
The gastrohepatic and hepatoduodenal ligaments, which consist of the anterior layer of lesser omentum and are continuous
with the left triangular ligament. The hepatoduodenal ligament contains the hepatic arteries, portal vein, and extrahepatic bile
ducts. It forms the anterior boundary of the epiploic foramen of Winslow and the communication between the greater and lesser
peritoneal cavities.

Four Lobes of the Liver are Commonly Described

Right
Left
Quadrate
Caudate

Portal Vein
The portal vein provides about three fourths of the livers blood supply
The combination of the superior mesenteric and splenic veins forms the portal vein, behind the neck of the pancreas
The portal vein then passes superiorly, posterior to the first part of the duodenum at the level of the second lumbar vertebra
Portal vein is 1 to 3 cm in diameter and 5 to 8 cm in length before dividing into right and left branches at the portal hepatis
The portal vein usually passes behind the bile duct and hepatic artery in the hepatoduodenal ligament
The portal trunk divides into left and right hepatic branches in the portal fissure. The left branch of the portal vein is longer
The portal vein divides into small veins and venules, which finally enter hepatic sinusoids
The portal vein has no valves

Anatomy

51

Portocaval Anastomosis
Numerous tributaries of the portal vein connect outside the liver with the systemic venous system. Under normal circumstances
these communications have little physiologic significance. However, if portal hypertension develops, these rudimentary
portosystemic communications develop into large channels with increased collateral flow.

Sites of Portosystemic Anastomoses Include

The submucosal veins of the proximal stomach and distal esophagus, which can receive blood from the coronary and short gastric
veins to drain into the azygous veins (high blood flow through this pathway produces gastric varices, esophageal varices, or
both)
Umbilical and periumbilical veins, recanalized from the obliterated umbilical vein in the ligamentum teres hepaticus, and which
may cause caput medusae or the loud Cruveilhier-Baumgarten bruit
Tributaries of the inferior mesenteric vein, which include the superior hemorrhoidal veins that communicate with the middle and
inferior hemorrhoidal veins of the systemic circulation and may cause large hemorrhoids; and
Other retroperitoneal communications, including connections to the renal and adrenal veins.

Sphincter of Oddi
The circular smooth muscle fibers in the ampulla of Vater area constitute the sphincter of Oddi, which regulates the flow of bile from
the liver into the duodenum
The three principal parts of the sphincter of Oddi are:
1. The sphincter of the choledochus (i.e. the circular muscle fibers surrounding the intramural and submucosal bile duct);
2. The pancreatic sphincter, which consists of a muscular septum between the bile and pancreatic ducts;
3. Ampullary sphincter: The ampullary sphincter, the most important component of the sphincter of Oddi, includes a layer of
longitudinal muscle fibers that help prevent reflux of intestinal contents into the ampulla
Relaxation of the ampullary sphincter may promote reflux into the pancreatic duct.

Gallbladder
The gallbladder, a pear-shaped (pyriform), distensible appendage of the extrahepatic biliary system
Capacity: 30 to 50 ml of bile
Parts: It has a fundus, body, and neck
The duct of gallbladder cystic duct varies in length and usually contains spiral valves of Heister that regulate bile flow
Enlargement of the neck of the gallbladder such as from a stone may form a pouch (Hartmanns pouch)
The triangle bounded by the cystic duct, common hepatic duct, and inferior border of the liver is the Triangle of Calot
The gallbladder receives its blood supply from the cystic artery, which originates from the right hepatic artery
Venous drainage of the gallbladder enters principally into the portal vein
The lymphatics drain into cystic duct nodes near the superior aspect of the cystic duct. (Cystic Lymph node of Lund)

The Triangle of Calot

It is a surgical landmark used to identify important structures during cholecystectomy, is bounded by the cystic duct, the
common hepatic duct, and the inferior border of the liver
The right hepatic and cystic arteries are located within it and anomalous structures often pass through it
Moynihans Hump: An abnormal bend in the course of the right hepatic artery, throwing it into the configuration of a caterpillar
hump, (Moynihans hump) invites injury unless it is carefully dissected free

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USMLE Step 1 Platinum Notes

The Pancreas (Pan: All creas Flesh)

It is a retroperitoneal organ, lying posterior to the stomach and lesser omentum
It extends from the duodenal C loop to the hilum of the spleen
The gland has a distinctive yellow/tan/pink color and is multilobulated
The pancreas is covered by peritoneum anteriorly and posteriorly it lies in proximity to the inferior vena cava, right renal vein, aorta
at the level of the first lumbar vertebra, superior mesenteric vessels, and splenic vein.
The gland is divided into four portions:
a. The head (which includes the uncinate process)
b. The neck
c. The body and
d. The tail
The head of the gland extends to the right of the neck, lying within the confines of the duodenal C loop; it includes the posteroinferior
extension arising from the ventral primordium, designated the uncinate process. The uncinate process extends posterior to the
superior mesenteric vein, ending at the right margin of the superior mesenteric artery. The body of the pancreas lies immediately
to the left of the neck; the tail of the pancreas extends to the left of the body into the splenic hilum.
The head of the pancreas is intimately associated with the second portion of the duodenum, and these two structures are jointly
supplied by two arterial arcades known as the anterior and posterior pancreaticoduodenal arteries. These arteries originate
from the superior and inferior pancreaticoduodenal vessels as branches of the celiac axis and superior mesenteric artery,
respectively. The distal body and tail of the pancreas are supplied by short branches of the splenic and left gastroepiploic arteries.
Within the posterosuperior and posteroinferior aspects of the body of the pancreas lie the superior and inferior pancreatic arteries,
respectively.
Veins draining the pancreatic parenchyma eventually terminate in the portal vein, which arises posterior to the neck of the
pancreas at the junction of the splenic and superior mesenteric veins
Multiple lymph node groups drain the pancreas
From the head of the gland, nodes in the pancreaticoduodenal groove communicate with subpyloric, portal, mesocolic,
mesenteric, and aortocaval nodes
Lymphatics in the body and tail of the pancreas drain to retroperitoneal nodes in the splenic hilum or to celiac, aortocaval,
mesocolic or mesenteric nodes

The Kidneys
Bean shaped
Retroperitoneal
Right kidney is lower than left (but right suprarenal is higher than left.)
Each kidney is 9 to 15 cm long, 4 to 5 cm wide and approximately 3 cm thick. They are located on each side of the vertebral
column between the parietal perineum and the fascia and musculature of the posterior abdominal wall and are embedded in a
variable amount of fat and surrounded by a layer of fascia (Gerotas fascia)
They lie on the side of the psoas muscle
They are not parallel, with the upper poles being approximately 2 cm from the midline and the lower poles approximately 3.5 cm
from the midline
Coverings of Kidney (From inside to out)
Fibrous capsule
Perinephric fat
Renal fascia with 2 layers
-- Anterior layer of Toldts Fascia
-- Posterior layer of fascia of Zuckerkandl
Pararenal Fat

Anatomy

53

Posterior Relations of Kidney

3 parts of diaphragm: Medial arcuate ligament, Lateral arcuate ligament, Diaphragm

3 muscles: Psoas major, quadrates lumborum, transverses abdominis
3 nerves: Subcostal, iliohypogastric, ilioinguinal nerves
Right kidney: 12th rib
Left kidney: 11th and 12th rib

Ureter
25 cm long (PGI)
Totally retroperitoneal
It enters true pelvis after crossing iliac vessel

Important Points about Ureter

Starts at the hilum

Changes its direction at the ischial spine
Penetrates the bladder wall without any valve
Enters the bladder at the lateral angle of the trigone
Enters pelvis in front of bifurcation of common iliac artery

The Suprarenals or the Adrenal Glands

Are bilateral retroperitoneal organs located on the superior medial aspect of the upper pole of each kidney
Each gland weighs approximately 4 gm. The left adrenal is larger and flatter
The normal adrenal cortex is bright yellow and thicker than the red-brown medulla.

Blood Supply of Suprarenals

Superior suprarenal artery: branch of inferior phrenic artery
Middle suprarenal artery: branch of abdominal aorta
Inferior suprarenal artery: branch of renal artery

Venous Drainage
The left adrenal vein empties primarily into the left renal vein but may occasionally drain directly to the vena cava
Lymphatic plexuses within the subcapsular portion of the adrenal cortex and the adrenal medulla drain to the adjacent para-aortic
subdiaphragmatic and renal lymph nodes.

Important Anatomical Relations

Relations at hilum of kidney (Anterior to Posterior) VAP
Renal vein
Renal artery
Renal pelvis
Relations at Femoral Triangle (From Medial to Lateral) 'VAN
Femoral vein
Femoral artery
Femoral nerve

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USMLE Step 1 Platinum Notes

Intercostal space (From Above Downwards) VAN

Intercostal vein
Intercostal artery
Intercostal nerve
Cubital Fossa (From Medial to lateral side). MBBR
Median nerve (Medial aspect)
Brachial artery
Biceps tendon
Radial nerve
Lateral boundary by brachioradialis muscle.

MALE REPRODUCTIVE TRACT

Testes

It is male gonad
Two oval structures are average 4 to 5 cm in length and 2.5 to 3.5 cm in width in the normal adult male
1015 gms in weight (Indians average)
Testis arises from the genital ridge

Covered by
Tunica vaginalis
Tunica albugenia
Tunica vasculosa
Blood supply is by testicular artery which is a branch of abdominal aorta
Venous drainage of the testis is through the pampiniform plexus to the spermatic vein, which is usually single and emerges
from the upper end of the cord and then follows the internal spermatic artery through the retroperitoneum. On the right the
spermatic vein empties into the vena cava below the right renal vein, whereas on the left the spermatic vein empties into
the main renal vein. Increased hydrostatic pressure, particularly on the left, may result in dilatation of the pampiniform venous
plexus, producing a varicocele
The lymphatic drainage of the testis is through the spermatic cord and the inguinal canal and then to the common iliac and
preaortic and paraortic nodes, with the latter communicating across the midline at the level of the kidneys and also with the
mediastinal and supraclavicular chains
Histologically, there are two principal portions of the testis: The seminiferous tubules, which are responsible along with the
Sertoli cells for spermatogenesis, and the interstitial or Leydig cells, which elaborate androgenic hormones, predominantly
testosterone

Testicular Descent
Iliac Fossa: 3rd month
Deep Inguinal Ring: 7th month
Pass through Inguinal Canal: 7th month
At Superficial Inguinal ring: 8th month
Enter Scrotum: 9th month

Anatomy

55

Epididymis
Are coiled structures each containing a single epididymal tubule 12 to 19 feet long and attached to the posterolateral surface of each testis
Remember:
From the tails of the epididymi sperm are transmitted into the vasa deferentia, which are direct continuations of the duct of the
epididymi passing up the spermatic cord, across the inguinal canal, and then retroperitoneally to the ampulla of the seminal vesicles,
with which they conjoin to form an ejaculatory duct on each side. The ejaculatory duct then empties directly into the prostatic
urethra.
The principal blood supply for the epididymis is from the internal spermatic artery. Venous drainage corresponds to the arterial supply,
and the lymphatic drainage of the epididymis parallels that of the testis. The prime function of the epididymis is not only as a conduit
for spermatozoa but also for biochemical and functional maturation and ultimate storage.
Ductus deferens/Vas Deferens
It is 18 inches in length. The vas deferens is an easily discernible structure within the scrotum and spermatic cord because it is a
heavily muscled tubular structure
Spermatic Cord
The spermatic cord, suspending each testis and its attached epididymis, is composed of the vas deferens, the internal spermatic
artery, the external spermatic artery, the pampiniform plexus of veins, the lymphatic drainage system of the contents of the
scrotum, and the autonomic nerve supply to the testis. In addition, the cord is surrounded by fibers of the cremasteric muscle,
which assist by contraction and relaxation in the maintenance of optimal testicular temperature and provide for testicular
retraction with sexual excitation or in the primitive fright reaction.

Contents of Spermatic Cord

The ducts deferens

Testicular and cremastric arteries
Artery of vas
The pampiniform plexus of veins
Lymph vessels from testis
Genital branch of genitofemoral nerve
Remains of processus vaginalis

Scrotum
The scrotal sac, consisting of two lateral compartments fused in the midline encloses the testes, epididymi, and terminal
portions of the spermatic cords. The dartos, consisting of elastic fibers, connective tissue, and smooth muscle fibers, is attached
to the corrugated skin of the scrotum, rich in sebaceous glands, and provides for muscular contraction of the scrotal sac in response
to temperature changes or sexual excitation. The principal function of the scrotum is to aid in temperature control of the testes
for optimal spermatogenesis, which takes place at temperatures several degrees lower than those in the intra-abdominal cavity
The blood supply of the scrotum comes from the deep pudendal branches of the femoral artery and branches of the internal
pudendal artery
The lymphatics of the scrotal halves anastomose freely, surround the penis, and drain to the inguinal and femoral nodes. There are
no connections between the lymphatics of the scrotum and the testes; the scrotal lymphatics do not accompany the pudendal
vessels.

Seminal Vesicles
Are paired, monotubular, convoluted structures lying beneath the base of the bladder and trigone. Posteriorly they are
invested by Denonvilliers fascia, which separates them from the anterior wall of the rectum
The two seminal vesicles fuse immediately with the ampullae of the vasa, forming the ejaculatory ducts, which open into
the prostatic urethra at the level of the verumontanum. The seminal vesicles secrete a mucoid vehicle for the spermatozoa and
also elaborate the bodys only source of fructose, which is used as an essential nutrient for maintenance of spermatozoal viability.

56

USMLE Step 1 Platinum Notes

Prostate Gland
It is a fibromuscular, glandular organ that surrounds the neck of the urinary bladder and the proximal portion of the male
urethra. The gland is supported anteriorly by the puboprostatic ligaments, inferiorly by the genitourinary diaphragm (external
urinary sphincter), and posteriorly by the rectal wall, which is separated from the prostate by an obliterated pelvic reflection of
the peritoneum called Denonvilliers fascia.
The prostate consisting of two portions: an anterior (inner) group of glands intimately associated with the urethra and a posterior
(outer) portion of more fibromuscular character
Arterial supply: The inferior vesical and internal pudendal arteries provide the blood supply to the prostate, entering the gland
posterolaterally at the vesical neck
Venous drainage of the prostate is complex and diffuse, with plexuses over the anterior and lateral portions of the gland that
drain into the internal iliac veins
Intercommunicating lymphatics of the prostate, bladder, seminal vesicles, vasa deferentia, and rectum provide drainage into
both the internal and external iliac systems as well as the sacral promontory nodes
Zones of Prostate:
These zones have physiologic and surgical significance because Benign enlargement of the prostate (BHP) occurs in the
transition or periurethral zone and Malignancy develops in the majority of cases in the Peripheral zone.

Urethra
18-20 cms in length with 3 parts
Prostatic (3 cms semilunar)
Membranous (2 cms stellate)
Spongy/penile (15 cms slit shaped)
Prostatic part is widest and more dilatable part
Contains:
Veru montanum (urethral crest)
Colliculus seminalis
Prostatic sinuses
Prostatic utricle (analogous to uterus/vagina of females)
Cowpers Glands: (Bulbourethral glands of Cowper) are small, paired glands lying between the layers of the urogenital diaphragm at
the junction of the bulbous and membranous portions of the urethra. The ducts of the glands empty distally into the bulbous urethra
traversing the corpus spongiosum. The secretions from this gland not only act as a lubricant but may also have factors that aid in
seminal fluid coagulation after ejaculation.

Penile Tissue
Organ of copulation and excretion of urine
It consists of two parallel erectile tissues as the corpora cavernosa, which are situated dorsolaterally, and the corpus spongiosum,
which invests the urethra ventrally, terminating distally in the erectile glans penis
Each corpus cavernosum and the corpus spongiosum are enveloped in fascial sheaths, and all three corpora are surrounded by
Bucks fascia
The blood supply of the penis is through the dorsal arteries derived from the internal pudendal arteries, which are branches
of the internal iliac artery
The venous drainage is through the dorsal veins, with the superficial dorsal vein emptying into the saphenous vein, and the
deep dorsal vein emptying into the prostatic plexus known as the plexus of Santorini
Penile erection is induced by the engorgement of the erectile tissues of the corpora, principally the corpora cavernosa
Lymphatic drainage of the penis is abundant. The lymphatics from the shaft of the penis, the corpora cavernosa, and the skin pass
through the superficial and deep inguinal nodes, communicating with the iliac nodes.

Anatomy

57

Lymphatic drainage of the glans penis drains into deep inguinal nodes and rest of the penis drains into superficial inguinal
nodes
The skin of the penis differs considerably from other skin of the body in its paucity of sebaceous glands, its elasticity, and its
extensive blood supply.

REMEMBER
High Yield Points

The bulbourethral glands secrete mucus for lubrication

The epididymis concentrates and stores sperm for ejaculation
The prostate gland secretes alkaline fluid to neutralize vaginal pH and induces clotting of the semen
The seminal vesicles produce fructose, citric acid, prostaglandins, and fibrinogen. These comprise about 60% of the volume of
semen
The ampulla is the end of the vas deferens
The bulbourethral glands secrete mucus for lubrication
The epididymis concentrates and stores sperm for ejaculation
The prostate gland secretes alkaline fluid to neutralize vaginal pH and induces clotting of the semen

The seminal vesicles produce fructose, citric acid, prostaglandins, and fibrinogen. These comprise about 60% of the volume of semen.

FEMALE REPRODUCTIVE TRACT

The Vagina
The vagina is a female copulatory organ. It is a muscular tube lined with stratified squamous epithelium. The adult vagina measures
12 to 13 cm in-depth. In virgin lower end of vagina is closed partially by annular fold of mucus membrane called hymen which gets
distorted after intercourse forming rounded elevations called caruncle hymenale.

The Cervix
It is the lower cylindrical portion of the uterus
The cervix, is a fibromuscular organ covered with stratified squamous epithelium. The walls of cervix show mucosal folds called
arbor vitae
The squamocolumnar junction is the most common site of origin of squamous cell carcinoma
The endocervical canal is lined by columnar epithelium, and racemose glands, lined with similar epithelium, are found in the
fibromuscular stroma. Such glands, if obstructed, may form nabothian cysts on the cervical surface
The nulliparous cervical os is round.

The Uterus
The uterus is a hollow, fibromuscular-walled organ between the bladder
The normal position of uterus is anteverted and anteflexed
Angle of anteversion is 90
Angle of anteflexion is 120
The organ is pear shaped and in nonpregnant women measures approximately 8 cm in length and weighs 30 to 100 gm
The fallopian tubes and the cervical canal communicate with the uterine cavity, which is lined by the endometrium
The uterine fundus is covered by peritoneum except in the lower anterior portion, where the bladder is contiguous with the lower
uterine segment and the peritoneum is reflected, and laterally where the folds of the broad ligament are attached. The uterus is
supported by condensations of endopelvic fascia and fibromuscular tissue laterally at the base of the broad ligaments
Blood supply of uterus is by uterine artery which is tortuous and branch of anterior division of internal iliac artery lying on the
lateral aspect of uterus in the broad ligament.

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USMLE Step 1 Platinum Notes

Uterine Prolapse, or Procidentia and Uterine Descensus

Occurs when the uterus and its adjoining structures herniate through the vaginal canal
Prolapse is described as first, second, or third degree in severity, the last being protrusion of the entire uterus from the vagina, with
the entire vagina everted as a consequence.
Although congenital weakness of the supporting tissues may occasionally cause uterine prolapse, the most frequent cause is
childbirth. The signs of uterine prolapse are protrusion of the cervix or uterus through the introitus. Prolapse is frequently associated
with cystocele or rectocele, and these defects may cause presenting symptoms. Symptoms include backache, significant pelvic
pressure, and ulceration or bleeding of the prolapsed structures.

The Fallopian Tubes

Tortous ducts about 10 cms in length:
Arise from the superior portion of the lateral borders of the uterus, superior to the attachment of the round ligaments, and are
patent. The distal ends, the fimbriae, open into the abdominal cavity and the proximal ends open into the uterine cavity. It is
divided into interstitial, isthmic, ampullar, and fimbriated portions
The wall is thin with two muscular layers and an outer layer of peritoneum within the upper borders of the broad ligament.

The Ovaries
Lie in the ovarian fossa. Ovaries are almond-shaped structure measuring 2 3 3 cm and is located on the posterior surface of
the broad ligament and inferior to the fallopian tube. The ovary has a cortex and a medulla. Germinal epithelium, a single layer
of cuboidal cells, covers condensed fibrous tissue called the tunica albuginea. Follicles originate within the ovarian cortex and are
composed of the basic embryonic complement; no new follicles are formed after birth
Mesovarium is a fold of peritoneum by which ovary is connected to the broad ligament
The Arterial blood supply is predominantly by ovarian artery a branch of Abdominal aorta
Venous drainage is by Pampiniform plexus. The left ovarian vein empties into the left renal vein; the right ovarian vein empties
into the vena cava just inferior to the renal vein.

The Adult Inguinal Canal

It is approximately 4 cm in length
Extends between the internal (deep inguinal) ring and the external (superficial inguinal) ring opening
The inguinal canal contains either the spermatic cord or the round ligament of the uterus
The inguinal canal is bounded superficially by the external oblique aponeurosis
The superior wall is composed of internal oblique muscle, transversus abdominis muscle, and the aponeuroses of these muscles
The inferior wall of the inguinal canal is formed by the inguinal ligament and lacunar ligament
The posterior wall (floor) of the inguinal canal is formed by the transversalis fascia and the aponeurosis of the transversus
abdominis muscle
Hesselbachs triangle: The inferior epigastric vessels serve as the superolateral border of Hesselbachs triangle. The medial border
of the triangle is formed by the rectus sheath, and the inguinal ligament serves as its inferior border
Hernias occurring within Hesselbachs triangle are considered direct hernias, whereas hernias occurring lateral to the triangle are
indirect hernias.

THE HEAD AND NECK AND CNS

The Scalp
The SCALP has five layers:
S Skin
C Connective tissue

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59

A Aponeurosis -galea aponeurotica

L Loose connective tissue
P Pericranium
The scalp receives a rich vascular supply. This arises from both the external and internal carotid arteries with the vessels lying in the
dense connective tissue layer.
The anterior part of the scalp is supplied by the supratrochlear and supraorbital arteries, and branches of the internal carotid via the
ophthalmic artery
The lateral and posterior part of the scalp is supplied by the superficial temporal, posterior auricular and occipital arteries, and
branches of the external carotid
The sensory nerves run with the arteries and are derived from the trigeminal nerve at the front and sides
The posterior aspect is supplied by the greater and lesser occipital nerves with motor supply to the occipitofrontalis muscle by the
facial nerve
Venous drainage of the face and anterior scalp is via the facial vein. The lateral and posterior aspects are drained by the external
jugular vein and the vertebral venous plexus, respectively. The veins of the scalp and face communicate directly with the intracranial
venous sinuses via emissary veins, hence infections in the nasal region have the potential to cause cavernous sinus thrombosis
Lymph drainage from the scalp is to the preauricular and occipital lymph nodes
The loose areolar tissue under the galea aponeurotica is a Dangerous zone for infections. Pus can spread freely in this layer and
reach the intracranial sinuses through the emissary veins
Abscesses and hematomas under the pericranium are limited to the area of one bone because the pericranium is firmly adherent to
the sutures between the skull bones
Osteomyelitis of the skull is associated with a subperiosteal swelling and edema of the scalp referred to as Ports puffy tumor

Fractures of Facial Skeleton

The Le Fort I fracture separates the alveolus and palate from the facial skeleton above
The fracture line runs through points of weakness from the pyriform aperture, through the lateral and medial wall of the maxillary
sinus running posteriorly to include the lower part of the pterygoid plates
The Le Fort II fracture is pyramidal in shape. The fracture involves the orbit, running through the bridge of the nose, and the ethmoids
whose cribriform plate maybe fractured, leading to a dural tear and CSF leak. It continues to the medial part of the infraorbital rim,
through the infraorbital foramen and through the infraorbital fissure. The orbital floor is always involved
The Le Fort III fracture effectively separates the facial skeleton from the base of the skull The fracture lines run high through the
nasal bridge, septum and ethmoids, again with the potential for dural tear and CSF leak, and irregularly through the bones of the orbit
to the frontozygomatic suture. The zygomatic arch fractures, and the facial skeleton is separated from the bones above at a high level
through the lateral wall of the maxillary sinus and the pterygoid plates.

Various Important Areas of Cerebrum

Motor area
Premotor area
Brocas area
Sensory area
Visual area
Werneckies area

Precentral gyrus
Anterior to motor area
Motor speech area (Inferior frontal gyrus)
Postcentral gyrus
Occipital lobe
Superior temporal lobe

Important Points about Functional Anatomy of Cerebral Cortex

Frontal
lobe

Primary motor area

(concerned with initiation of
Precentral cortex voluntary movements and speech)
(Post Part)
Premotor area

Supplementary motor area

Area 4 center for movement

Area 4S suppressor area. Inhibits movements initiated by
area 4.
Area 6 concerned with coordination of movements
initiated by area 4.
Area 8 frontal eye field.
Area 44 and 45 (brocas area) motor area for speech.
Concerned with coordinated skilled movements.

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USMLE Step 1 Platinum Notes

Prefrontal cortex Silent area or association area
(Ant Part)
Center for higher functions
emotion, learning, memory

Area 1 concerned with sensory perception

Area 2 and 3 integration of these sensations. Spatial
recognition. Recognition of intensity, similarities and diff.
B/W stimuli
Concerned with perception of sensation.

Somesthetic area I
Parizetal
lobe

Somesthetic area II
Somesthetic association area

Synthesis of various sensations perceived by S. Area-I.

Stereognosis

Primary auditory area

Area 41, 42 and wernickes area concerned with

perception of auditory impulses, analysis of pitch,
determination of intensity and source of sound
Superior part of temporal gyrus.

Auditopsychic area
Area of equilibrium
Primary visual area

Area 22 Interpretation of auditory sensation

Maintenance of equilibrium
Area 17 Perception of visual impulse
Lines of Gernari seen.
Area 18 - Interpretation of visual impulses
Area 19 - Movements of eye

Temporal
lobe

Occipital
lobe

Area 9 to 14, 23, 24, 29 and 32. Center for planned action
Seat of intelligence. Personality of individual

Visual association area

Occipital eye field

Lemniscus
Lemniscus, tract and sensation

Thalamic nucleus

Part of the internal capsule Sensory areas of the cerebral

cortex

Medial lemniscus
(Proprioception and fine touch)
Spinal lemniscus
(Pain, temperature and crude touch)

PLVNT

SENSORY RADIATION

Trigeminal lemniscus
(Pain, temperature, touch and
proprioception from the head, taste)

PMVNT

In posterior of postlimb of Lower 1/3 of sensory area in

internal capsule (IC)
post-central gyrus (Face region).

Lateral lemniscus
(hearing)

Medial geniculate body AUDITORY RADIATION

[MGB]
in sublentiform part of IC

Upper 1/3 of sensory area in

post-central gyrus (Arm and leg
region).

Auditory area in Heschls gyrus in

temporal lobe (area 41 and 42).

Internal Capsule
Part of internal capsule

Types of fibers in it

Anterior limb

Fibers from and to the prefrontal area of the cortex

Genu (MOTOR)

Corticobulbar fibers
Sensory fibers from thalamus to brain

Ant of posterior limb (MOTOR)

Corticospinal fibers

Post of posterior limb (SENSORY)

SENSORY radiation
(From PLVNT and PMVNT to main sensory area in post central gyrus)

Retrolentiform part (VISION)

OPTIC radiation
(From LGB to visual sensory area 17)

Sublentiform part (HEARING)

AUDITORY radiation
(From MGB to auditory area in temporal lobe)

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61

Remember: M-M (medial geniculate body/hearing (music)

Lateral L-L Lateral geniculate body/light)

Arrows show geniculate bodies

A small lesion at the level of internal capsule can result in a clinical scenario with widespread manifestations and most of them lethal
depending on what part of internal capsule is damaged.
The internal capsule maybe damaged by a cerebrovascular lesion mostly by Hemorrhage (rupture of Charcots artery) leading to
Hemiplegia on the opposite side of the body.
In this type of Hemiplegia motor functions are effected mostly and sensory functions later or not at all because motor fibers lie laterally
and the arterial supply is more laterally as a result of which are motor fibers likely to be effected more.

Summary of the Lesion in Brown Sequard Syndrome

On the same side of the lesion
Pyramidal tract damage results in: UMNL and motor paralysis below the injury (spastic paralysis, hyperactive reflexes, loss of
superficial reflexes and Babinski sign)
Proprioceptive tracts damage (gracile and cuneate) results in: loss of sense of position, sense of passive movement, sense of
vibration and touch discrimination below the injury. These are the signs of sensory ataxia.
On the opposite side of the lesion:
Lateral spinothalamic tract damage results in: loss of pain and temperature sensation beginning one or two dermatomes below
the lesion
Ventral spinothalamic tract damage results in: little or No change in the sense of simple touch.

Remember
Midbrain: Usually the fibers of the third (oculomotor) nerve are affected alternating oculomotor hemiplegia, this means;
Hemiplegia on opposite half of the body (UMNL)
Signs of oculomotor nerve paralysis on the same side (LMNL)
Pons: Usually the fibers of the sixth (abducent) nerve are affected alternating abducent hemiplegia, this means:
Hemiplegia on opposite half of the body (UMNL)
Signs of abducent nerve paralysis on the same side (LMN)
Medulla: Usually the fibers of the hypoglossal nerve are affected alternating hypoglossal hemiplegia, this means
Hemiplegia on opposite half of the body (UMNL)
Signs of hypoglossal nerve paralysis on the same side (LMNL)

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USMLE Step 1 Platinum Notes

Brown sequard syndrome

Arterial Territories and Important Points in Blood Supply of Brain

Left middle cerebral artery: Blockage of this vessel would cause, among other effects, right-sided hemiplegia and sensory deficits
mainly of the face and arms, a right visual field defect with inability to gaze to the right, and aphasia.

Anatomy

63

Right middle cerebral artery: Blockage of this vessel would cause, among other things, left-sided hemiplegia and sensory deficits
mainly of the face and arms and left visual field neglect with inability to gaze to the left. In addition, there maybe neglect of the
left side.
Left anterior cerebral artery: This vessel supplies the medial aspects of the left hemisphere. Blockage may cause a weak, numb
right leg (and possibly arm symptoms in milder forms). The face is typically spared.
Right anterior cerebral artery: This vessel supplies the medial aspects of the right hemisphere. Blockage may cause a weak,
numb left leg (and possibly arm symptoms in milder forms). The face is typically spared.
Left posterior cerebral artery: This lesion presents as a right-sided visual field deficit, alexia without agraphia (if the corpus
callosum is spared), and possible defects in naming colors.
Right posterior cerebral artery: This lesion typically presents as a left-sided visual field deficit along with left-sided sensory loss
if the thalamus is affected. There may also be left-sided neglect
Visual cortex is supplied by posterior + middle cerebral artery.
Left posterior inferior cerebellar artery: This lesion would cause infarction of the lateral medulla and inferior cerebellar surface,
causing vertigo with vomiting, dysphagia, and dysarthria. In addition, there would be nystagmus looking toward the left, leftsided
Horners syndrome, and loss of pinprick sensation on the left side of the face and on the right side of the trunk and extremities. This
condition is also known as Wallenbergs syndrome.

Blood supply of brain

Right posterior inferior cerebellar artery: This lesion would cause infarction of the lateral medulla and inferior cerebellar
surface, causing vertigo with vomiting, dysphagia, and dysarthria. In addition, there would be nystagmus looking toward the
right, rightsided Horners syndrome, and loss of pinprick sensation on the right side of the face and on the left side of the trunk
and extremities. This condition is also known as Wallenbergs syndrome.

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USMLE Step 1 Platinum Notes

MOVEMENT DISORDERS AND THEIR NUCLEI

Cranial Nerves: (USMLE Favorite)

Optic nerve is not only a cranial nerve. It is a tract and direct extension of CNS
This nerve is about 4 cm long
The optic nerve is enclosed in 3 sheaths covering with meninges
It is crossed by ophthalmic artery
Trigeminal nerve is the largest cranial nerve
Abducent nerve has the longest course
Trochlear nerve has the longest intracranial course. Thinnest as well
Cranial nerve 3 and 4 have their nuclei in midbrain
Cranial nerve 5, 6, 7, 8 have their nuclei in pons
Cranial nerve 9, 10, 11, 12 have their nuclei in medulla

Cranial nerve emerging from dorsal aspect of brain: Trochlear

MC nerve involved in intracranial aneurysms: Occulomotor
Common nucleus for VII, IX, X nerves is Nucleus Tractus Solitarius. (NTS)
Trochlear nerve has the longest intracranial course

Summary of Distribution of Cranial Nerves: (USMLE Favorite)

No.

Nerve

Type

Function

1.

Olfactory

Sensory

smell

2.

Optic

Sensory

vision

3.

Oculomotor

Motor

To all muscles of the eye except two: (superior oblique and lateral rectus)

4.

Trochlear

Motor

To one eye muscle (superior oblique)

5.

Trigeminal

Mixed
Sensory to
mainly sensory with small
Mouth
motor part
Face
Ant of scalp

6.

Abducent

Motor

To one eye muscle (lateral rectus)

7.

Facial

Mixed
Motor Sensory
Parasympathetic

(a) Motor to muscles of the face

(b) Sensory: taste to anterior 2/3 of tongue
(c) Parasym
(d) Pathetic to certain glands.

8.

Vestibulocochlear

Sensory

(a) Hearing (cochlear part)

(b) Equilibrium (Vestibular part)

9.

Glossopharyngeal

Mixed
Motor Sensory
Parasympathetic

Sensory for pharynx and tongue

Motor to: One muscle of pharynx (stylophar ngeus)
Parasympathetic to parotid gland

10.

Vagus
(Including Cranial
accessory)

Mixed
Motor Sensory
Parasympathetic

Motor to: Muscles of pharynx, larynx and palate

Parasympathetic and sensory to:
The structures in the thorax and abdomen

11.

Spinal Accessory

Motor

To two important muscles of the neck:

1. Sternomastoid
2. Trapezius

12

Hypoglossal

Motor

To all muscles of the tongue (except one)

Anatomy

65

Cranial Nerve
The First (Olfactory) Nerve Palsy
The chief function of the 1st cranial nerve (olfactory nerve) is concerned with the sense of smell. Cells of origin are located in the nasal
mucosa. Nerve filaments group and pass through the cranium at cribriform plate and end in olfactory bulb. The olfactory nerve is
composed exclusively of somatic afferent fibers.
The olfactory nerve branches penetrate through the cribriform plate, and collect in the olfactory bulb and nerve which passes under
the frontal lobe to the temporal lobe and other centers
EXAMINATION
Each nostril is examined separately. One nostril is closed while the patient sniffs with the other. Mild aromatic substances such as
orange, coffee, or tobacco should be used as strong irritant smells stimulate the sensory endings of the fifth nerve. The result of
affection will be loss of smell or anosmia.

The Third (Oculomotor) Nerve Palsy

It supplies all extraocular muscles except the superior oblique and the lateral rectus
Complete paralysis results in:
External ophthalmoplegia: In a complete lesion inability to move the eye upward, inward and downward
External Squint: The eye is deviated laterally and downwards due to the unopposed action of the lateral rectus and superior
oblique
Diplopia: A person sees double
Ptosis: Drooping of the upper eyelids due to paralysis of levator palpabrea superioris
Dilated nonreactive pupil due to paralysis of the sphincter pupillae. The pupil also shows no reaction to light (direct or consensual),
or to accommodation.

The Fourth (Trochlear) Nerve Palsy

There is weakness or paralysis of the superior oblique muscle which normally moves the eye downwards and inwards
Result: Defective depression of the adducted eye. The patient is unable to look at his shoulder
Symptom presentation: DIPLOPIA (double vision), when looking downwards, e.g. when reading or descending the stairs. The
head may tilt to the opposite side to minimize the diplopia.

The Sixth (Abducent) Nerve Palsy

The sixth nerve supplies the lateral rectus which normally rotates the eye laterally. Its paralysis causes:
Internal Squint: The eyeball is turned inwards due to unopposed adduction of the medial rectus
Diplopia, which is maximum on looking outwards.

The Fifth (Trigeminal) Nerve Palsy

The sensory fibers are divided into three divisions:
1. Ophthalmic Division
2. Maxillary Division
3. Mandibular Division
Sensation
Sensation is tested in the distribution of the 3 divisions of the nerve. Routinely, it is sufficient to test the sensation at three Sites: on the
forehead, the cheek and over the lower jaw, together with anterior two-thirds of the tongue
Motor Functions
A. Masseters And Temporalis:
Any wasting of the temporalis
The degree of contraction of the temporalis and masseter by palpation while asking the patient to bite hard.

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USMLE Step 1 Platinum Notes

The Seventh (Facial) Nerve Palsy

Weakness in the facial muscles may result from:
Upper motor neuron lesion:
Here only the muscles of the lower part of face are affected. The eye closure is normal
This is because the muscles of the lower part (unlike those of the lower part) are activated through the upper motor neuron fibers of
both sides
Spontaneous emotional expression is unaffected
Lower motor neuron lesion:
All the muscles of the face (upper and lower) are affected on the same side
Facial nerve passes through parotid gland but does not supply it
Facial nerve supplies submandibular and lacrimal glands
Arterial supply to facial nerve: ascending pharyngeal artery.
Facial Nerve has:
The longest intraosseous course
It is the Mc paralyzed cranial nerve
Muscles supplied by facial nerve:
Platysma
Stylohyoid
Muscles of facial expression
Buccinator
Stapedius
Posterior belly of digastric
Submandibular, Lacrimal, nasal gland
Supplies gustatory sensation to soft palate
Kindly never forget that despite the fact that facial nerve traverses the substance of parotid but does not supply it. (keeps
it high and dry)
Facial nerve is related to
Pterygopalatine ganglion
Geniculate ganglion submandibular ganglion
Submandibular

The Eight (Vestibulocochlear) Nerve Palsy

The eighth nerve consists of two parts which have different functions Cochlear and vestibular nerves
The cochlear part is concerned with hearing. An affection results is tinnitus and deafness
The vestibular part is concerned with equilibrium. Its affection may result in vertigo.

The Ninth (Glossopharyngeal) Nerve Palsy

Paralysis of Glossopharyngeal nerve causes:
Anesthesia of the pharynx
Loss of taste on the posterior third of the tongue
Glossopharyngeal nerve is involved in:
Jugular foramen syndrome: Involving IX, X, XI cranial nerves
Collet Sicard Syndrome: Involving IX, X, XI, XII cranial nerves (Extracranially)
Villaret Synrome: Lesion in retropharyngeal space involving IX, X, XI, XII cranial nerves

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67

The Tenth (Vagus) Nerve Palsy

Paralysis of vagus nerve causes:
Ipsilateral paralysis of the palate,
Ipsilateral paralysis of the pharynx and
Ipsilateral paralysis of the larynx with anesthesia of the larynx on the affected side
Remember: The Recurrent Laryngeal nerve arises from vagus. On the Right side it winds around the subclavian artery and on
the Left side it winds around the aortic arch behind ligamentum arteriosum.

The Eleventh (Accessory) Nerve Palsy

As a Result of damage to the Accessory nerve
Sternomastoids
Unilateral
Apparent wasting
The muscle does not stand out on testing
Bilateral
Wasting of the neck which appears like that of a chicken
Falling of head backwards
Trapezius
Unilateral paralysis
Drooping of the shoulder when arm is hanging
Weak movements on testing
Supplies all palatal muscles except Tensor palate
Spasmodic torticollis is due to central irritation of this nerve (cranial part)

The Twelfth (Hypoglossal) Nerve Palsy

Lesion of one hypoglossal nerve results in deviation of the tongue towards the paralyzed side. If you ask the patient to
protrude his tongue the muscles of the same side of the lesion become paralyzed and begin to atrophy (lower motor neuron lesion)
Safety muscle of tongue is geniglossus supplied by hypoglossal nerve.

GEMS NEVER TO BE FORGOTTEN

The Pituitary Gland
Also known as Hypophysis cerebri. Pineal is Epiphysis cerebri
The average adult pituitary measures 11 15 5 mm
The gland is oval, bilaterally symmetrical, and brownish red
The pituitary is approximately 20% larger in females than in males and it enlarges about in females during pregnancy
It lies within the sella turcica (Turkish saddle)
This fossa is bordered anteriorly, posteriorly, and inferiorly by the sphenoid bone and laterally by the cavernous sinus
The floor of the sella forms the roof of the sphenoidal sinus
The diaphragma sellae, a thick reflection of dura mater, covers the roof of the sella and closely encircles the pituitary stalk in 50% of
individuals
The arterial supply to the hypothalamic-pituitary region is complex and arises from three sources
a. The inferior hypophyseal artery, a branch of the carotid artery, supplies the posterior pituitary.
b. The superior hypophyseal arteries branch from the circle of Willis to supply the median eminence
c. The middle hypophyseal arteries are of variable origin and supply the pituitary stalk
Capillary portions of the superior hypophyseal arteries drain from the hypothalamus, the median eminence, and the superior portions
of the pituitary stalk. These vessels drain into the hypophyseal portal system, which forms a secondary venous plexus in the anterior
pituitary and ultimately empties into the cavernous sinus. This portal venous system constitutes the principal blood supply to the
anterior pituitary and serves as the medium through which releasing hormones from the hypothalamus reach the pituitary.

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USMLE Step 1 Platinum Notes

The pituitary has dual embryonic origin

The Anterior pituitary arises from embryonic ectoderm (Rathkes pouch) and includes the pars distalis, pars intermedia
(vestigial in humans), and pars tuberalis
The Posterior pituitary of the gland arises from the diencephalon and includes the neural stalk, infundibulum, and posterior lobe
Embryonic defects in invagination and obliteration of the pharyngeal extent of Rathkes pouch may lead to craniopharyngiomas
or hormonally active ectopic pituitary adenomas.

Cavernous Sinus

Paralysis of 3, 4, 6 cranial nerves indicates lesion of cavernous sinus

Occulomotor, trochlear and ophthalmic nerves lie in lateral wall of cavernous sinus
Abducent nerve is a direct content of cavernous sinus
Infections from dangerous area of face can spread to cavernous sinus

Remember
The pituitary gland is located in the pituitary fossa within the skull. The floor of this fossa is formed by the sella turcica. The
lateral walls of the fossa are formed by the cavernous sinuses. The abducens nerve passes through the cavernous sinus along
with the internal carotid artery. As the tumor expands laterally, the first nerve that will be encountered is the abducens nerve,
producing lateral rectus palsy.

Sympathetic and Parasympathetic Systems

Organ

Sympathetic

Parasympathetic

Pupil

Dilates

Constricts

Lacrimal and salivary glands

Stops secretion

Produces secretion

Heart

Accelerates

Slows

Bronchioles

Dilates

Constricts

Alimentary canal

Dilates

Contracts

Urinary bladder

Dilates

Contracts

Penis

Causes erection
[For this reason the pelvic nerve was called the nervus erigens].

Limbic System

Subcallosal Gyri
Cingulate Gyri
Hippocampal formation comprising of Hippocampal Gyrus, Parahippocampal Gyrus and Dentate gyrus
Amygdaloidal nucleus
Mammillary bodies
Anterior thalamic nucleus

Briefly Functions of the Limbic System can be summarized by Five Fs

Feeding
Flight
Feeling
Fighting and
Fun {sex}

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SKULL FORAMINA AND CONTENTS (USMLE FAVORITE)

What Passes through What
Foramen

Contents

Optic canal

Optic (II) Nerve and ophthalmic artery

Superior orbital fissure

III, IV, VI and ophthalmic division of V cranial nerves, sympathetic nerves and ophthalmic veins

Stylomastoid foramen

VII cranial nerve

Foramen Rotundum

Maxillary division of V

Foramen ovale

Mandibular division of V and accessory meningeal artery

Foramen spinosum

Middle meningeal artery, meningeal branch of the mandibular nerve

Foramen magnum

Accessory (XI) nerve, vertebral and spinal arteries. NOT SPINAL CORD

Foramen lacerum

Internal carotid artery, lesser petrosal

Nerve (branch of IX), greater petrosal
Nerve (branch of VII), deep petrosal

Jugular foramen

Inferior petrosal sinus (anterior part)

Internal jugular vein and IX, X, XI cranial nerves

Hypoglossal foramen

XII cranial nerve, meningeal branch of ascending pharyngeal artery

Internal auditory meatus

Dorellos canal

VII and VIII cranial nerves, labyrinthine (internal auditory) artery

Abducent nerve.

Cerebrospinal Fluid (CSF)

Clear fluid
Colorless fluid
Choroid Plexus (formed by)
Chloride content
Cells minimal
Cushions the brain

Circulus arteriosus (branches) supply choroids plexus

CSF is principally secreted by choroid plexus
Choroid plexus is absent in anterior horn of lateral ventricle
Total volume of CSF 150 ml
Normal adult CSF pressure: 6 12 mm Hg
pH of CSF is: 7.33
Epidural space is devoid of CSF
Rate of CSF absorption is the main factor controlling CSF Pressure
Persistent leakage can cause headache
No neutrophils in normal state seen

ARTERIAL TERITORIES IN HEAD AND NECK AND CLINICAL CORRELATION

(USMLE Favorite)
* Occlusion of the vertebral artery may cause Medial Medullary Syndrome which is characterized by:
Paralysis or atrophy of tongue on the side of lesion (XII nerve involvement)
Paralysis of arm and leg on opposite side
Impaired tactile and proprioceptive sense on opposite side. (Involvement of pyramidal tract and medial lemniscus)

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USMLE Step 1 Platinum Notes

* The posterior inferior cerebellar artery:

It is the largest and main branch of the vertebral artery
It has a tortuous S-shaped course. Immediately after it arises from the vertebral artery, it runs backwards around the lower
end of the olive passing through the rootless of the hypoglossal nerve, it then turns round the inferior cerebellar peduncle
and finally divides into two terminal branches which supply: (a) the inferior vermis (b) the posterior part of the inferior
surface of the cerebellum.
Impaired pain and temperature sense on opposite side
Nystagmus (involvement of vestibular nucleus)
Dysphagia (involvement of nucleus ambigus)
Nystagmus (involvement of cerebellum)
Horners syndrome (involvement of sympathetic pathway)

Occlusion of the Anterior Spinal Artery May Cause

Loss of motor function below the level of the lesion (due to damage to the corticospinal tracts)
Loss of pain and temperature Sensation below the level of the lesion (due to damage to the spinothalamic tracts)
Weakness of limbs (due to damage of the anterior grey horns in the cervical or lumbar regions of the cord)
Loss of bowel and bladder control (due to damage of the descending autonomic tracts)

Occlusion of the Posterior Spinal Artery May Cause

Loss of position sense, vibration sense and light touch due to damage of the posterior white columns

Larynx
Larynx has three paired and three unpaired cartilages
Extends from C3-C6
Anatomic basis of stridor is in larynx
The larynx serves as the sounding source for speech. A fundamental tone is produced by the movement of the vocal cords, which is
brought about by the flow of exhaled air past lightly approximated vocal cords
The internal laryngeal nerve is sensory to larynx above vocal cords
The recurrent laryngeal nerve is sensory to larynx below vocal cords
All muscles of larynx except cricothyroid are supplied by recurrent laryngeal nerve
Cricothyroid supplied by External laryngeal nerve

Muscles of Larynx and their Action

Abductor of vocal cords: Posterior Cricoarytenoid
Adductor of vocal cords:
Lateral cricoarytenoid
Transverse arytenoids
Cricothyroid
Thyroarytenoid
Tensor of vocal cords: Cricothyroid
Relaxor of vocal cords:
Thyroarytenoids
Vocalis

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71

Muscles Acting at Temporomandibular Joint

Depression: Lateral Pterygoid

Elevation: Temporalis, Massetter, Medial Pterygoid
Protrusion: Pterygoids
Retraction: Posterior fibers of Temporalis
Lateral movements: Pterygoids
Buccinator: Nota muscle of mastication

In Simple Terms

The backward movement step is accomplished by the posterior fibers of the temporalis muscle
The digastric helps to depress the lower jaw during chewing
The lateral pterygoid helps to move the lower jaw forward during chewing
The medial pterygoid helps to elevate the lower jaw during chewing
The mylohyoid helps to depress the lower jaw during chewing

Ansa Cervicalis
Ansa cervicalis is a thin nerve loop that lies in the anterior wall of carotid sheath
Superior root is a continuation of descending branch of hypoglossal (XII) Cranial nerve. Superior root supplies Superior belly of
omohyoid. Its fibers are derived from first cervical nerve
Inferior root is derived from spinal nerves C2 and C3
Loop of Ansa supplies:
Inferior belly of omohyoid
Sternothyroid
Sternohyoid

Dangerous Areas: (USMLE Favorite)

Dangerous area of face: Lowerpart of nose and upper lip
Dangerous area of scalp: Loose areolar tissue layer of scalp
Dangerous zone of eye: Ciliary body

Commonest Sites

Commonest site of BHP: Periurethral zone

Commonest site of cancer prostate: peripheral zone
Commonest site of varicocele: Left side
Commonest position of appendix: Retrocecal
Commonest site of internal hemorrhoids: 3, 7 and 11 Oclock

Superficial Cutaneous Reflexes

Center spinal
segment involved

Reflex

Stimulus

Response

Scapular

Irritation of skin at the interscapular space

Contraction of scapular muscles and C5 to T1

drawing in of scapula

Upper
abdominal

Stroking the abdominal wall below the Ipsilateral contraction of abdominal T6 to T9

costal margin
muscle and movement of umbilicus
towards the site of stroke

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USMLE Step 1 Platinum Notes

Lower abdominal Stroking the abdominal wall at umbilical Ipsilateral contraction of abdominal T10 to T12
and iliac level
muscle and movement of umbilicus
towards the site of stroke
Cremasteric

Stroking the skin at upper and inner aspect Elevation of testicles

of thigh

L1, L2

Gluteal

Stroking the skin over glutei

Contraction of glutei

L4 to S1, S2

Plantar

Stroking the sole

Plantar flexion and adduction of toes

L5 to S2

Bulbocavernous

Stroking the dorsum of glans penis

Contraction of bulbocavernous

S3, S4

Anal

Stroking the perianal region

Contraction of anal sphincter

S4, S5

Functions of Limbic System

Emotion
Memory
Higher functions
Consolidation of long-term memory occurs in hippocampus
Processing of short term memory to long term occurs in hippocampus
Amygdala is the window of limbic system
Damage to amygdala causes Kluver Bluck syndrome
Reward center is in medial forebrain bundle.

Herniations
Uncal or transtentorial herniation. The herniated uncus will compress the oculomotor nerve, the posterior cerebral artery, and
the brainstem. The pathophysiologic consequences include oculomotor paralysis (manifesting with fixed and dilated pupil on
the same side), ipsilateral infarction of the occipital lobe, and hemorrhages within the midbrain and pons. The latter may result in
respiratory paralysis and death
Cerebellar tonsillar herniation refers to downward displacement of the cerebellar tonsils through the foramen of magnum. This
results from space-occupying lesions in the infratentorial compartment, such as bleeding and tumors. It leads to compression of
the medulla and death by cardiorespiratory arrest
Subfalcine (cingulate) herniation describes the lateral displacement of the cingulate gyrus beneath the falx cerebri. This
event is caused by space-occupying masses in the cerebral hemisphere. It leads to compression of the anterior cerebral artery and
infarction of dependent cerebral territories (mostly the medial portion of the frontal and parietal lobes)
Reverse cerebellar herniation is a rare form of herniation due to midbrain lesions (again, hemorrhages and tumors) that push
the midbrain upward through the incisura of the tentorium
Transcalvarial herniation may develop in open (i.e. accompanied by calvarial bone fractures) head injuries if brain
parenchyma is displaced outside the cranial cavity through a calvarial defect
Split brain syndrome: Disconnection syndrome of cerebral cortex resulting from transection or congenital absence of cerebral
cortex.

Types of Fibers in CNS

Association fibers: Connecting different areas of same cerebral hemisphere
Superior longitudinal fasiculus
Inferior longitudinal fasiculus
Cingulum
Uncinate fasiculus

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73

Projection fibers: Connecting cerebral cortex to other parts of CNS

Corticospinal tract
Internal capsule
Commisural fibers: connecting corresponding parts of two cerebral hemispheres
Corpus callosum
Anterior commisure
Posterior commisure
Hippocampal commisure
Habenular commisure
Hypothalmic commisure

Clinical
observation

Effects

Upper motor neuron

Lower motor neuron lesion

Muscle tone

Hypertonic

Hypotonic

Paralysis

Spastic type of paralysis

Flaccid type of paralysis

Wastage of muscle

No wastage

Present

Superficial reflexes

Lost

Lost

Plantar reflex

Abnormal babinskis sign

Absent

Deep reflexes

Exaggerated

Lost

Clonus

Present

Lost

Anatomy of Eye: (USMLE Favorite)

The Extroter of Eye ball is Inferior Oblique and Inferior Rectus
The Introter of Eye ball is Superior Oblique and Superior Rectus.
Action of Superior oblique is Abduction, Intorsion and depression
Dilator Pupillae dilates pupil and is supplied by Sympathetics
Sphincter Pupillae constricts pupil and is supplied by Parasympathetics
LR6S04
Lateral rectus is supplied by 6th Cranial Nerve (Abducent)
Superior oblique is supplied by 4th Cranial Nerve (Trochlear)
Rest other ocular muscles are supplied by 3rd Cranial Nerve (Occulomotor)
Muscle attached to posterior tarsal margin: Mullers muscle
Ligament of Lockwood is found in Orbit.

Structures passing through Superior Orbital Fissure are

Live Free To See No Insult at All
Lacrimal Nerve
Frontal Nerve
Trochlear Nerve
Superior Ophthalmic Vein
Nasociliary Nerve
Inferior Ophthlamic Vein
Abducent Nerve

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USMLE Step 1 Platinum Notes

Structures Passing Through Inferior Orbital Fissure are

Maxillary nerve
Zygomatic nerve
Infraorbital vessels
Orbital branch of pterygoplatine ganglion

Lesions and Effects of (Visual Pathway)

Central scotoma ~ macula

Ipsilateral blindness ~ optic nerve
Bitemporal hemianopia ~ optic chiasm
Homonymous hemianopia ~ optic tract
Upper homonymous quadrantanopia ~ temporal optic radiations
Lower homonymous quadrantanopia ~ parietal optic radiations
Also, cortical lesions produce defects similar to those of the optic radiations, but may spare the macula.

Spinal Cord

Spinal cord in adults ends at L1- L2

Spinal cord in infant sends at L3
Thoracic and sacral curves are concave anteriorly
Subarachnoid space/Subdural space ends at S2
Dural sheath ends at S2
Filum terminale and piamater extend up to tip of coccyx
Number of spinal nerve pairs: 31.

Cauda Equina Syndrome

It is a serious neurologic condition in which there is acute loss of function of the lumbar plexus, neurologic elements (nerve roots)
of the spinal canal below the conus of the spinal cord
After the conus, the canal contains a mass of nerves (the cauda equina or horse-tail) that branches off the lower end of the spinal
cord and contains the nerve roots from L1-5 and S1-5. The nerve roots from L4-S4 join in the sacral plexus which affects the sciatic
nerve, which travels caudally (toward the feet)

End of spinal cord

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75

Vertebrae and Corresponding Spinal Level

Cervical region

C1-C7 Add1

Upper Thoracic Lesion

T1 T6 Add 2

Lower Thoracic Lesion

T7-T9 Add 3

T 10

Corresponds to L1-L2

T12-L1

Corresponds to L5-S1

Ascending Tracts of Spinal Cord

Situation

Tract

Function

Anterior white funiculus

Anterior spinothalamic tract

Crude touch sensation

Lateral spinothalamic tract

Pain and temperature sensation

Ventral spinocerebellar tract

Subconscious kinesthetic sensations

Dorsal spinocerebellar tract

Subconscious kinesthetic sensations

Spinotectal tract

Concerned with spinovisual reflex

Fasiculus dorsolateralis

Pain and temperature sensations

Spinoreticular tract

Conciousness and awareness

Spino olivary tract

Proprioception

Spinovestibular tract

Proprioception

Fasciculus gracilis

Tactile sensation

Fasciculus cuneatus

Tactile localization
Tactile discrimination
Vibratory sensation
Conscious kinesthetic sensation
Stereognosis

Lateral white funiculus

Posterior white funiculus

Descending Tracts of Spinal Cord

Situation

Tract

Function

Pyramidal
tracts

Anterior corticospinal tract

Control voluntary, skilled movements

Lateral corticospinal tract

Forms upper motor neurons

Medial longitudinal fasciculus

Coordination of reflex ocular movement

Integration of movements of eyes and neck

Extra
Pyramidal
tracts

Anterior vestibulospinal tract

Maintenance of muscle tone and posture

Lateral vestibulospinal tract

Maintenance of position of head and body during acceleration

Reticulospinal tract

Coordination of voluntary and reflex movements

Control of muscle tone
Control of respiration and blood vessels

Tectospinal tract

Control of movement of head in response to visual and auditory impulses

Rubrospinal tract

Facilitatory influence on flexor muscle tone

Olivospinal tract

Control of movements due to proprioception

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USMLE Step 1 Platinum Notes

Important Stains used in Histology

Hand E Stain (Hematoxylin and Eosin): Hematoxylin, a natural dye product, acts as a basic dye that stains blue or black. Nuclear
heterochromatin stains blue and the cytoplasm of cells rich in ribonucleoprotein also stains blue
The aniline dye, Eosin, is an acid dye that stains cytoplasm, muscle, and connective tissues various shades of pink and orange. This
difference in staining intensity is useful in differentiating one tissue from another
Vital Stain: Such as Neutral red, Trypan blue are used for staining living cells such as Reticuloendothelial cells
Metachromatic Stains are used for staining mast cells with Toluidine blue. The stains react with granules of mast cells
(metachromasia) to give a new color to the cells
Periodic Acid-Schiff Method (PAS): Principally used to demonstrate structures rich in carbohydrate macromolecules such as
glycogen, glycoprotein, and proteoglycans found in ground substance of connective tissues, basement membranes and mucus
Phosphotungstic Acid Hematoxylin (PTAH): This is an ideal stain for the demonstration of striated muscle fibers and
mitochondria, which stain blue
Silver Stains: Certain tissue components called Argyrophilic have a natural affinity for silver salts. Reticular fibers and the
granules in diffuse endocrine cells are argyrophilic
Sudan Stains: Sudan dyes are used to stain lipids. The Sudan dyes, e.g. Sudan IV, dissolve in droplets containing triglycerides and
color them intensely.

Important Points about Vessels: (USMLE Favorite)

Umbilical arteries carry venous blood

Pulmonary vasculature also follows reverse pattern
Coronary arteries have three elastic lamina: Internal, middle and external
Umbilical arteries have no elastic lamina
The arteries of lower limb have more developed muscular tissue than those of upperlimb

IMPORTANT POINTS ABOUT SKULL BONES Skull

Scaphocephaly

Boat shaped skull due to premature union of saggital suture

Acrocephaly/Oxycephaly

Pointed skull due to premature union of coronal suture

Plagiocephaly

Twisted skull due to assymetrical union of sutures

Trigonocephaly

Triangular prominence of forehead due to premature fusion of metopic suture

Brachycephaly

Short and broad skull

Seen in Cleidocranial dysostosis
Seen in Downs Syndrome
Seen in Achondroplasia

Dolicocephaly

Long and thin skull

Seen in Marfans syndrome

Anencephaly

Vault of skull not developed resulting in the absence of a major portion of the brain, skull, and scalp

Pneumatic Bones: (USMLE Favorite)

Contain air spaces. Usually present in skull
Make the skull light in weight
Act as air conditioners
Maxilla
Sphenoid
Ethmoid
Mastoid Bones

Anatomy

Sesamoid Bones
Patella
Pisiform
Fabella

Bones Ossified at Birth

Lower end of femur
Upper end of tibia
Calcaneum

Important Points about Muscles

Anti rape muscle/muscle virgineous: Gracilis
Cheating muscle: Superior oblique of eye
Safety muscle of tongue: Genioglossus
Tailors muscle: Sartorius
Thermostat of testis cremaster
Bladder muscles in whorls detrusor

Hybrid/Composite Muscles

Adductor magnus
Biceps Femoris
Pectineus
Digastric
Flexor digitorum superficialis

Digastric Muscles
Digastric: Anterior belly, posterior belly
Omohyoid: Superior belly, inferior belly
Occipitofrontalis: Occipital belly, frontal belly
Gastrocnemius: Lateral head, medial head
Ligament of Treitz: Skeletal part, smooth part

Important Lymph Nodes (USMLE Favorite)

Glans Penis and clitoris

Cloquets node

Rest of Penis

Superficial inguinal node

Labium majus
Testis
Ovaries
Palatine tonsil

Superficial inguinal node

Preaortic/Para aortic nodes
Preaortic/Para aortic nodes
Jugulo digastric nodes

Tip of Tongue

Submental nodes

Anal canal above pectinate line

Internal iliac nodes

Anal canal below pectinate line

Superficial inguinal nodes

Delphic nodes

Pretracheal

Spongiform urethra

Deep inguinal nodes

77

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USMLE Step 1 Platinum Notes

Lymph node of lund: cystic lymph node of gallbladder

Cloquets node/Rossenmullers node
Mucocutaneous lymph node syndrome
Sister mary josephs node
Virchows node
Rotters lymph nodes are small interpectoral lymph nodes located between the pectoralis major and pectoralis minor muscles.
They receive lymphatic fluid from the muscles and the mammary gland, and deliver lymphatic fluid to the axillary lymphatic plexus.

Thoracic duct

Thoracic duct starts as continuation of cisterna chylii

Crosses from right to left at four level
Passes through aortic opening of diaphragm
The right lymphatic duct drains the right arm, the right side of the chest, and the right side of the head. The thoracic duct drains
the rest of the body. Both the right lymphatic duct and the thoracic duct dump into the large venous channels at the base of the
neck. Occlusion of this drainage cans produce intractable edema in sites feeding these ducts.

Primary lymphoid organs are Thymus and Bone marrow

Lymphatics are absent in

Epidermis
Eye
Cornea
Lens
Articular cartilage
Placenta
Bone marrow
Glottis

Eponym Nerves: (USMLE Favorite)

Arnolds nerve/Aldermans nerve auricular branch of vagus
Nerve of Bell long thoracic nerve

Buffer nerve carotid sinus and vagal fibers from aortic arch
Saphenous nerve longest/largest cutaneous branch of femoral nerve
Herrings nerve branch of glossopharyngeal nerve to carotid sinus
Exners nerve from pharyngeal plexus to cricothyroid membrane
Vidian nerve Greater pertrosal + deep pertrosal nerve (N of Pterygoid canal)
Nerve of Wrisberg: (2 nerves) Nervus intermedius (branch of Facial nerve), medial cutaneous nerve of forearm

Freys syndrome/Baillargers Syndrome

Due to abnormal and inappropriate regeneration Auriculotemporal branch of trigeminal nerve there is rednesss, sweating especially
on cheeks while eating, talking (gustatory sweating)

Important Points about Veins

Great cerebral vein of Galen is formed by union of internal cerebral veins

Great cerebral vein of Galendrains into straight sinus
Facial vein communicates to cavernous sinus via: Superior ophthalmic vein, inferior ophthalmic vein, deep facial vein
Long saphenous vein is the largest and longest superficial vein of lower limb formed on medial side of dorsal venous arch
Injury to great saphenous vein corresponds to area of femoral nerve distribution.

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79

The portal vein begins at the level of the second lumbar vertebra and is formed from the convergence of the superior
mesenteric and splenic veins. It is 3. 8 cm long and lies anterior to the inferior vena cava and posterior to the neck of the
pancreas. It lies obliquely to the right and ascends behind the first part of the duodenum, the common bile duct and
gastroduodenal artery. At this point it is directly anterior to the inferior vena cava. It enters the right border of the lesser
omentum, and ascends anterior to the epiploic foramen to reach the right end of the porta hepatis. It then divides into
right and left main branches which accompany the corresponding branches of the hepatic artery into the liver
Portal vein is formed behind the neck of pancreas by union of superior mesentric and spleenic vein
Normal pressure is 510 mm Hg
Portal venous system is valveless.

Left suprarenal drains into left renal vein

Left testicular vein drains into left renal vein
Left ovarian vein drains into left renal vein
Batesons vertebral venous plexus is valveless

Varicose Veins
Are dilated, tortuous veins and are very common; they may either give no symptoms or cause aching and discomfort in the legs.
Varices are recognized as tortuous dilated veins in the leg, a varicose vein is one which permits reverse flow through its faulty valves.
Occasionally complications of varicose veins may develop. These include:
Thrombosis: Which is referred to as superficial thrombophlebitis
Sometimes thrombosis extends into the deep venous system to cause Deep vein thrombosis, although this is infrequent
Hemorrhage: Can occur when large superficial varices are damaged
The most serious problem is venous ulceration which complicates varicose veins.

Excepts in Anatomy
All muscles are mesodermal in origin except muscles of Iris (Sphincter pupillae and dilator pupillae) which are ectodermal
All Pharyngeal arches persist except fifth which disappears
All intrinsic muscles of Larynx are supplied by recurrent laryngeal nerve except cricothyroid which is supplied by external laryngeal
nerve
All major salivary gland are supplied by facial nerve except Parotid gland (Although passes through the substance of parotid)
All divisions of Trigeminal nerve except Mandibular division lie in lateral wall of Cavernous sinus
All muscles of pharynx are supplied by pharyngeal plexus except stylopharyngeus which is supplied by Glossopharyngeal nerve.
All muscles of soft palate are supplied by pharyngeal plexus except tensor palate which is supplied by Nerve to medial pterygoid
All muscles of tongue are supplied by hypoglossal nerve except palatoglossus which is supplied by pharyngeal plexus.

Important Vessels and Source of Bleeding: (USMLE Favorite )

Hemoptysis: Bronchial artery

Duodenal ulcer: Gastroduodenal artery
Gastric ulcer: Left Gastric artery
SDH: Bridging veins
EDH: Middle meningeal artery
Tonsillectomy: Paratonsillar vein
Menstruation: Spiral arteries

Duodenal ulcer: The duodenal cap lies just beyond the pylorus. Externally, the cap has attachments to the hepatoduodenal
ligament in the pancreatic head. Most of the ulcers occur in the duodenal cap region. The gastroduodenal artery lies directly
behind the duodenal cap, and penetrating ulcers into the pancreas initially erode through the gastroduodenal artery,
accounting for the massive bleeding that occurs with these ulcers
Extradural hemorrhage: Usually follows arterial hemorrhage between the skull and the dura. Most frequently, acute epidural
hematomas occur in the temporal or temporoparietal region as a consequence of hemorrhage from one of the branches of
the middle meningeal artery.

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USMLE Step 1 Platinum Notes

Eponym Ducts
Parotid duct: Stensons duct
Submandibular duct: Whartons duct
Pancreatic duct: Wirsungs duct
Accessory pancreatic duct: Santoniris duct
Gartners duct: Remanant of Mesonephric duct (WOLLFIAN)
Thoracic duct: Pecquet duct

Important Membranes in Body: (USMLE Favorite)

Huxles Membrane

Inner layer of cells of root sheath of hair

Henles Membrane

Outer layer of cells of root sheath of hair

Bowmans Membrane

'Anterior limiting membrane of Cornea

Decemets Membrane

Posterior limiting membrane of Cornea

Bruchs Membrane

Pigment membrane in Retina

Elschings Membrane

Astroglial membrane covering Optic Disk

Heusers Membrane

Exocelomic Membrane

Sharpnells Membrane

Pars Flaccida of the tympanic membrane

Important Cells in Histology (USMLE Favorite)

Bergmann Cells

Glial cells of Cerebellum

Gitter Cells

Microglia

Interstitial Cells of Cajal

Nerve cells of superficial layers of cerebral cortex

Supporting Cells of Claudius

Cells in floor of Cochlear canal of inner ear

Dieters Cells

Outer hair cells of organ of Corti

Hensens Cells

Supporting cells in organ of Corti external to Dieters cells

Houfbauers Cells

Ellipsoidal cells in chorionic villi of placenta

JG Cells

Smooth muscle cells of afferent arteriole. (kidney)

Ito Cells

Stellate cells in liver

Langerhans Cells

Antigen presenting epithelial dendritic cells

Langhans Cells

Cytotrophoblastic cells of chorionic villi

Basket Cells

Myoepithelial cells in salivary/mammary/sweat glands

Gitter Cells

Microglia of brain

Basket Cells of Cerebellum

Neurons of molecular layer of Cerebellum

Merkel Cells

Sensory nerve endings

Mullers Cells

Neuroglial cells in Retina

Hilus Cells

Rare cells found in Medulla of Ovary at Hilum of Ovary

Lacis Cells

Extra glomerular Mesengial Cells outside Glomerulus

Peg Cells

Secretory cells in mucosa of uterine tube

Glomus Cells

Present in Carotid Bodies

Anatomy

81

Abnormal cells
Reed Sternberg cell
These cells characteristically are neoplastic giant cells with a bilobed mirror-image nucleus that may have large (owl-eyes)
nucleoli surrounded by a clear halo. Most commonly, these cells are associated with Hodgkins disease.
The Langhans cell
It is a giant cell with peripherally arranged nuclei found in granulomas
The LE cell
It is a degenerating neutrophil seen in lupus erythematosus in in vitro preparations
The Mott cell
It is a constipated plasma cell filled with immunoglobulins, producing a grape-cluster appearance to the cell. Mott cells are
seen in multiple myeloma and some parasitic infestations
The Touton giant cell
Has distributed nuclei and is found in tumors other than Hodgkins lymphoma

Diaphragms of Body (USMLE Favorite)

Diaphragm of oral cavity: Mylohyoid
Diaphragm of Superior thoracic aperture: Sibsons Fascia

Sibsons fascia
Pelvic diaphragm: Levator ani and coccygeus
Urogenital diaphragm: Deep transverse perinea and sphincter urethrae, perineal mermbrane
Diaphragm sella: Fold of duramater overlying pituitary fossa
Iris diaphragm: In eye

Eponym Fascias (USMLE Favorite)

Toldts fascia

Anterior renal fascia

Zuckerland fascia

Posterior renal fascia

Bucks fascia

Deep fascia of penis

Denonvillers fascia

Fascia separating rectum from prostate

Waldeyers fascia

Fascia separating rectum from coccyx

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USMLE Step 1 Platinum Notes

Campers fascia

Fatty layer of superficial fascia

Scarpas fascia

Deep membranous layer of Superficial fascia

Fascia Colli

Investing layer of deep cervical fascia of neck

Fascia transversalis

Forms anterior wall of femoral sheath

Fascia iliaca

Forms posterior wall of femoral sheath

Pelvic fascia

Forms hypogastric sheath

USMLE Case Scenario

The Fascial layer separating the rectum from the coccyx is:
1. Waldeyers Fascia
2. Fascia Coli
3. Denonveliers Fascia
4. Gerotas Fascia
5. Cruveilhiers Fascia
6. Campers Fascia
7. Colles Fascia
8. Scarpas Fascia
Ans. 1. Waldeyers Fascia

Bursitis
Bursitis is inflammation of a bursa, which is a thin-walled sac lined with synovial tissue
The function of the bursa is to facilitate movement of tendons and muscles over bony prominences:
Subacromial bursitis (subdeltoid bursitis) is the most common form of bursitis. Trochanteric bursitis involves the bursa around
the insertion of the gluteus medius onto the greater trochanter of the femur.
Olecranon bursitis occurs over the posterior elbow, and when the area is acutely inflamed, infection should be excluded by
aspirating and culturing fluid from the bursa. Achilles bursitis involves the bursa located above the insertion of the tendon to the
calcaneus and results from overuse and wearing tight shoes.
Retrocalcaneal bursitis involves the bursa that is located between the calcaneus and posterior surface of the Achilles tendon.
Ischial bursitis (weavers bottom) affects the bursa separating the gluteus medius from the ischial tuberosity and develops from
prolonged sitting and pivoting on hard surfaces.
Iliopsoas bursitis affects the bursa that lies between the iliopsoas muscle and hip joint and is lateral to the femoral vessels.
Anserine bursitis is an inflammation of the sartorius bursa located over the medial side of the tibia just below the knee and under
the conjoint tendon and is manifested by pain on climbing stairs.
Prepatellarbursitis (housemaids knee) occurs in the bursa situated between the patella and overlying skin and is caused by
kneeling on hard surfaces. Treatment of bursitis consists of prevention of the aggravating situation, rest of the involved part,
administration of a nonsteroidal anti-inflammatory drug (NSAID), or local glucocorticoid injection.

Bursitis of Knee Joint

Housemaids knee is the result of inflammation of Prepatellar bursa
Miners beat knee is the result of inflammation of Prepatellar bursa
Clergymans knee is the result of inflammation of subcutaneous infrapatellar bursa

Important Nutrient Arteries

Nutrient artery of clavicle

Suprascapular artery

Nutrient artery of humerus

Profunda brachii artery

Anatomy

83

Nutrient artery of femur

Second perforating artery. Sometimes by first and third perforating arteries

Nutrient artery of tibia. Largestin body

Posterior tibial artery

Nutrient artery of fibula

Peroneal artery

Axis Arteries
Axis artery of upper limb: seventh cervical intersemental artery persisting as:
Axillary
Brachial
Anterior interosseous artery and
Deep palmar arch
Axis artery of lower limb: fifth lumbar intersemental artery persisting as:
Inferior gluteal artery
Companion artery of sciatic nerve
Popliteal artery
Peroneal artery and
Plantar arch

Important Vessels (USMLE Favorite)

The Marginal artery of Drummond is also known as the Marginal artery of the colon.
The anastomoses of the terminal branches of the ileocolic, right colic and middle colic arteries of the continuous arterial circle or
arcade along the inner border of the colon known as the marginal artery of Drummond.
Components
Ileocolic artery - colic branch
Right colic artery ascending and descending branches
Middle colic artery right and left branches
Left colic artery ascending and descending branches
Sigmoid arteries unnamed terminal branches
From this marginal artery, straight vessels (known as vasa recta) pass to the colon
The marginal artery is an important connection between the SMA and IMA, and provides collateral flow in the event of
occlusion or significant stenosis. The junction of the SMA and IMA territories is at the:
-- Superior mesentric artery (SMA), and of the left colic and sigmoid branches of the IMA, form a splenic flexure. Anastomoses
here are often weak or absent, hence the marginal artery at this point (known as Griffiths point) is often focally small or
discontinuous. For this reason, the splenic flexure is a watershed area prone to ischemia and infarction
-- One of the commonest area of colonic ischemia is called Sudecks point.

Charcots Artery
Charcots Artery: lenticulostriate arteries which arise at the commencement of the middle cerebral artery supply blood to part of
the basal ganglia and posterior limb of the internal capsule. The lenticulostriate perforators are end arteries. The name of these arteries
is derived from some of the structures it supplies: the lenticular nucleus and the striatum.

Heubners Artery
Heubners artery: A branch of anterior Cerebral artery, supplies the anteromedial part of the head of the caudate and anteroinferior
internal capsule Its vascular territory is the anteromedial section of the caudate nucleus and the anteroinferior section of the internal capsule.

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USMLE Step 1 Platinum Notes

Artery of Adamkiewicz
Artery of Adamkiewicz: Arteria Radicularis Magna, Great radicular artery of Adamkiewicz. Provides the major blood supply to the
lumbar and sacral cord. When damaged or obstructed, it can result in anterior spinal artery syndrome, with loss of urinary and fecal
continence and impaired motor function of the legs; sensory function is often preserved to a degree. It is important to identify the
location of the artery when treating a thoracic aortic aneurysm or a thoracoabdominal aortic aneurysm.

The Dorsalis Pedis Artery

The dorsalis pedis artery is the continuation of the anterior tibial artery after the artery anterior tibial artery crosses the ankle
to reach the dorsum of the foot
Its pulse is the most distal palpable pulse in the lower limb and therefore is useful for evaluating the arterial supply to the limb
On the dorsum of the foot, the pulse maybe felt as the artery passes over the navicular bone between the extensor hallucis longus
tendon and the extensor digitorum longus tendon.

Batsons Vertebral Venous Plexus

Batsons vertebral venous plexus: The valveless vertebral venous veins that communicate with the prostatic venous plexus and
explain the readiness with which carcinoma of the prostate spreads to the pelvic bones and vertebrae.
Tortuous Arteries
Facial artery
Splenic artery
Uterine artery
Vaginal artery
Ophthalmic artery
Lingual artery
PICA (Post Inferior Cerebellar Artery)

USMLE Case Scenario

A 66-year-old male patient from Florida complains of loss of pain and temperature sensation over the left side body ipsilateral
dysphagia, hoarseness, and diminished gag reflex with vertigo and diplopia of two months duration. Most likely tortuous
vessel affected is:
1. AICA
2. PICA
3. Common carotid
4. Internal carotid
5. Arch of aorta
Ans. 2. PICA: The condition itself is Lateral Medullary (Wallenburgs Syndrome)

End Arteries

Central artery of retina

Central branches of cerebral artery
Coronary artery
Segmental branches of renal/splenic artery

Important Arteries and Their Branches: (USMLE Favorite)

Axillary Artery
It is continuation of subclavian artery
Pectoralis minor divides it into three Branches

Anatomy

Ist part:
Superior thoracic artery
2nd part:
Thoracoacromial artery
Lateral thoracic artery
3rd part:
Subscapular artery
Anterior circumflex humeral artery
Posterior circumflex humeral artery

Internal Carotid Artery

No Branches in Neck
Caroticotympanic
Pterygoid

Cavernous branch to trigeminal ganglion

Superior and inferior hypophyseal
Ophthalmic
Anterior cerebral
Middle cerebral
Posterior communicating
Anterior choridal

External Carotid Artery

Superior thyroid
Lingual
Facial
Occipital
Posterior auricular
Ascending pharyngeal
Maxillary
Superficial temporal

Subclavian Artery

Vertebral artery
Internal thoracic artery
Thyrocervical trunk (Inferior thyroid, suprascapular, superficial cervical)
Costocervical trunk (Superior intercostal, Deep cervical)

Vertebral Artery

Spinal
Muscular
Meningeal
Anterior spinal
Posterior spinal
Posterior inferior cerebellar
Medullary

85

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USMLE Step 1 Platinum Notes

Basilar Artery

Formed by Union of Two Vertebral Arteries:

Posterior cerebral arteries
Superior cerebellar
Pontine
Labyrinthine
Anteroinferior cerebellar

Internal Iliac Artery

It is smaller terminal branch of common iliac artery
It is about one and half inches long (33.5 cn)
It begins in front of sacroiliac joint
It divides into ant and post Divisions at upper margin of greater sciatic notch
Branches from Anterior Division: (Six in males and seven in females.)
Superior vesical artery
Inf vesical
Obturator
Middle rectal
Inf Gluteal
Internal pudendal
In females, inferior vesical is replaced by vaginal artery
Uterine artery is the 7th branch in females
Branches from Posterior Division
Superior gluteal
IIio lumbar
Lateral sacral

Questions asked in USMLE Examinations

Inferior thyroid artery is a branch of: Thyrocervical trunk
Ascending pharyngeal artery is a branch of external carotid artery
Internal pudendal artery in females is a branch of internal iliac artery
Left gastroepiploic artery is a branch of splenic artery
Splenic artery is a branch of celiac trunk
Uterine artery is a branch of internal iliac artery
Cystic artery is a branch of right hepatic artery
Cilio retinal artery is a branch of choridal artery
Middle meningeal artery is a branch of maxillary artery
Anterior spinal artery is a branch of vertebral artery
Ophthalmic artery is a branch of internal carotid artery

Structures Pasing between/Piercing

Structure passing between two heads of gastrocnemius: Sural nerve
Structure passing between two heads of lateral pterygoid: Maxillary artery
Structure passing between pronator teres: Median nerve

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87

Structure passing between two plains of fibers of supinator: Posterior interosseous nerve
Structure passing through tarsal tunnel: Posterior tibial nerve
Structure passing through choroid fissure of eye: Hyaloids artery
Structure passing through foramen of Vesalius: Emissary vein
Structure passing through carotid sheath: Internal carotid/common carotid artery, internal jugular vein, vagus nerve. External
carotid is External to sheath
Structure piercing corocabrachialis: Musculocutaneous nerve
Structure piercing clavipectoral fascia (encloses subclavius): Lateral pectoral nerve, thoracoacromial vesses Cephalic vein
Structure piercing thyrohyoid membrane: Internal laryngeal nerve

Important Structures Accompanying (USMLE Favorite)

Axillary nerve accompanies posterior humeral circumflex artery
Radial nerve accompanies profunda brachii vessels
Short saphenous vein accompanies sural nerve
Great saphenous vein accompanies saphenous nerve
Superior thyroid vessels accompany external laryngeal nerve
Superior laryngeal vessels accompany internal laryngeal nerve
Inferior laryngeal vessels accompany recurrent laryngeal nerve

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USMLE Step 1 Platinum Notes

USMLE Case Scenario

Stroking the skin of the medial side of the thigh evokes a reflex contraction of the muscle, the cremasteric reflex, which
is most, pronounced in children. It may represent a protective reflex, and the cremaster may also have a role in testicular
thermoregulation. Cremaster consists of loosely arranged muscle fasciculi lying along the spermatic cord. It is variable in
thickness and is thickest in young men. It may form an incomplete coating around the cord, known as the cremasteric fascia,
which extends around the testis but lies within the external spermatic fascia. Cremaster is innervated by:
1. The terminal branches of the subcostal nerve
2. The terminal branches of the iliohypogastric nerve
3. The terminal branches of the ilioinguinal nerve
4. The genital branch of the genitofemoral nerve
5. The femoral branch of the genitofemoral nerve
Ans. 4. The genital branch of the genitofemoral nerve

USMLE Case Scenario

A 45-year-old man is evaluated by a neurologist because of a gait disorder. When the physician passively moves the patients
right great toe upward or downward, the patient cannot accurately report the direction of motion. This finding can best be
explained by a lesion of which of the following structures?
1. Right fasciculus cuneatus
2. Right fasciculus gracilis
3. Right lateral lemniscus
4. Right medial lemniscus
Ans: 2. Right fasciculus gracilis

USMLE Case Scenario

As part of a complete neurological examination, a medical student takes a cotton-tipped applicator and touches the patients
left eye with a thin wisp of cotton as the patient looks to the right. The patient closes both of his eyelids in response. Which of
the following cranial nerves is responsible for the motor limb of this reflex?
1. Abducens
2. Facial
3. Optic
4. Trigeminal
Ans. 2. Facial

USMLE Case Scenario

The Epithelium of the Bronchi contains:
1. Simple ciliated columnar cells, basal cells, and goblet cells
2. Simple ciliated columnar cells, basal cells, but not goblet cells
3. Non ciliated columnar cells, basal cells, and goblet cells
4. Stratified ciliated columnar cells, basal cells, and goblet cells
Ans. 4. Stratified ciliated columnar cells, basal cells, and goblet cells

USMLE Case Scenario

The Dandy-Walker malformation is a developmental abnormality in which:
1. In which the roof of the third ventricle fails to perforate with concomitant hyperplasia of the cerebellar vermis
2. In which the roof of the fourth ventricle fails to perforate with concomitant hyperplasia of the cerebellar vermis
3. In which the roof of the third ventricle fails to perforate with concomitant hypoplasia of the cerebellar vermis
4. In which the roof of the fourth ventricle fails to perforate with concomitant hypoplasia of the cerebellar vermis
Ans. 4. In which the roof of the fourth ventricle fails to perforate with concomitant hypoplasia of the cerebellar vermis.

Anatomy

89

The Dandy-Walker malformation is a developmental abnormality in which the roof of the fourth ventricle fails to perforate to form the
foramen of Magendie. The resultant cystic dilatation of the fourth ventricle expands the posterior fossa, elevating the tentorium and
causing hydrocephalus because of obstruction of the aqueduct of Sylvius, with concomitant hypoplasia of the cerebellar vermis.

USMLE Case Scenario

The kidneys and ureter arise from:
1. The pronephros and a diverticulum from the wolffian duct
2. The mesonephros and a diverticulum from the wolffian duct
3. The metanephros and a diverticulum from the wolffian duct
4. The pronephros and a diverticulum from the gartners duct
5. The mesonephros and a diverticulum from the gartners duct
6. The metanephros and a diverticulum from the gartners duct
Ans. 2. The mesonephros and a diverticulum from the wolffian duct.

USMLE Case Scenario

From its origin, the uterine artery crosses the ureter anteriorly in the broad ligament before branching at the level of the
uterus. One major branch ascends the uterus tortuously within the broad ligament until it reaches the region of the ovarian
hilum where it anastomoses with branches of the ovarian artery. The uterine artery arises as a branch of:
1. The anterior division of the internal iliac artery
2. The anterior division of the external iliac artery
3. The posterior division of the internal iliac artery
4. The posterior division of the external iliac artery
5. The common iliac artery
Ans. 1. The anterior division of the internal iliac artery

USMLE Case Scenario

A 34-year-old patient arrives in the emergency room after having suffered severe head trauma in a accident. Radiographic
studies of the head reveal a basilar skull fracture in the region of the foramen ovale. Which of the following nerve passes
through this foramen:
1. Maxillary
2. Mandibular
3. Ophthalmic
4. Occulomotor
Ans. 2. Mandibular

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USMLE Step 1 Platinum Notes

USMLE Case Scenario

A Lecturer in Florida is demonstrating a thick fibrous band that runs on the visceral surface of the liver. It is attached on one
end to the inferior vena cava and on the other end to the left branch of the portal vein. In the Adult the structure corresponds to:
1. Ductus venosus
2. Ligamentum teres
3. Ligamentum venosum
4. Umbilical arteries
5. Ligamentum arteriosum
6. Ligamentum nucha
7. Ligament of Treitz
Ans. 3. Ligamentum venosum

USMLE Case Scenario

A Lecturer in Florida is demonstrating a fibrous band that runs on the visceral surface of the liver. It is attached on one end
to the inferior vena cava and on the other end to the left branch of the portal vein. In the embryo structure corresponds to:
1. Ductus venosus
2. Ligamentum teres
3. Ligamentum venosum
4. Umbilical arteries
Ans. 1. Ductus venosus

USMLE Case Scenario

A 66-year-old driver suffers a stroke while driving on highway. He has a history of hypertension, is a heavy smoker, and drinks
beer every weekend A right upper motor neuron paralysis of the facial nerve is noted; the other cranial nerves are normal. He
has a hemiplegia on the right side, with equal paralysis of the arm and leg. His lesion most likely involves the:
1. Left internal capsule
2. Left midbrain
3. Left pons
4. Left medulla
Ans. 1. Left internal capsule
Remember:
The anterior limb of the internal capsule conveys frontopontine fibers, the genu conducts corticobulbar fibers, and the posterior limb
of the internal capsule conveys corticospinal fibers to the contralateral arm and leg. Hemorrhage of the left internal capsule results in
right-sided dense hemiplegia in which paralysis of the arm and leg are of the same intensity.

USMLE Case Scenario

A structure is caused by failure of obliteration of the vitellointestinal duct. It is classically located in the distal ileum within 30
cm of the ileocecal valve, and the structure is a true diverticulum. The anatomist is talking about:
1. Ligament of Trietz
2. Meckels diverticulum
3. Appendicis epiploicae
4. Sacculations
Ans. 2. Meckels diverticulum

USMLE Case Scenario

A newborn boy does not pass meconium until 48 hours after his birth. Several weeks later his mother complains that he has not
been passing stool regularly. Anorectal manometry reveals increased internal anal sphincter pressure on rectal distention with
a balloon. The patients disorder maybe attributed to distention with a balloon. The patients disorder maybe attributed to:
1. Defective recanalization of the colon

Anatomy

91

2. Failure of neural crest cells to migrate

3. Herniation of abdominal contents into the umbilical cord
4. Persistence of the proximal end of the yolk stalk
Ans. 2. Failure of neural crest cells to migrate

USMLE Case Scenario

The vagina is a muscular tube lined with:
1. Non stratified squamous epithelium that is histologically similar to the mucosa of the cervix and vulva
2. Stratified squamous epithelium that is histologically similar to the mucosa of the cervix and vulva
3. Stratified cuboidal epithelium that is not histologically similar to the mucosa of the cervix and vulva
4. Stratified cuboidal epithelium that is histologically similar to the mucosa of the cervix and vulva
Ans. 2. Stratified squamous epithelium that is histologically similar to the mucosa of the cervix and vulva.

USMLE Case Scenario

A 5-year-old child aspirates a peanut. Following bronchopulmonary segments would this foreign object most likely enter.
1. Superior segment of the right lower lobes
2. Inferior segment of the right lower lobe
3. Superior segment of the left lower lobe
4. Superior segment of the left lower lobe
Ans. 1. Superior segment of the right lower lobe
Because the right main bronchus is wider and more vertical than the left, foreign objects are more likely to be aspirated into the
right main bronchus. The superior segmental bronchus of the lower lobar bronchus is the only segmental bronchus that exits from
the posterior wall of the lobar bronchi. Therefore, if a patient is supine at the time of aspiration, the object is most likely to enter the
superior segmental bronchus of the lower lobe.

USMLE Case Scenario

Fracture of neck of Fibula produces foot drop due to injury of:
1. Common peroneal nerve
2. Tibial nerve
3. Obturator nerve
4. Femoral nerve
Ans: 1. Common peroneal nerv

USMLE Case Scenario

Which of the following embryonic structures gives rise to the adrenal cortex?
1. Ectoderm
2. Endoderm
3. Mesoderm
4. Mesonephros
Ans. 3. Mesoderm

USMLE Case Scenario

The modified structures at the border of the epithelium are villi which are immotile in a patient. Which of the following would
be a consequence of this lack of motility?
1. Implantation failure
2. Kartageners syndrome

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USMLE Step 1 Platinum Notes

3. Increased gut motility

4. Decreased protein absorption
Ans. 2. Kartageners syndrome

USMLE Case Scenario

The arterial blood supply to the palatine tonsil is derived from branches of the external carotid artery. The principal artery is
the tonsillar artery, which is a branch of the:
1. Facial artery
2. Lingual artery
3. Superficial temporal artery
4. Maxillary artery
5. Superior thyroid artery
Ans. 1. Facial artery

USMLE Case Scenario

Occlusion of which artery would result in insufficient perfusion of the urinary bladder:
1. Internal iliac
2. External iliac
3. Renal
4. Suprarenal
Ans. 1. Internal iliac

USMLE Case Scenario

Statement True about Esophagus is:
1. The upper 2/3 of the esophagus contains striated muscle and is innervated by the vagus nerve (CNX). The lower 1/3 contains
smooth muscle from splanchnic mesoderm and is innervated by the splanchnic plexus
2. The lower 2/3 of the esophagus contains striated muscle and is innervated by the vagus nerve (CNX). The upper 1/3 contains
smooth muscle from splanchnic mesoderm and is innervated by the splanchnic plexus
3. The upper 2/3 of the esophagus contains smooth muscle and is innervated by the vagus nerve (CNX). The lower 1/3 contains
skeletal muscle from splanchnic mesoderm and is innervated by the splanchnic plexus
4. The upper 2/3 of the esophagus contains striated muscle and is innervated by the splanchnic plexus. The lower 1/3 contains
smooth muscle from splanchnic mesoderm and is innervated by the vagus nerve
Ans. 1. The upper 2/3 of the esophagus contains striated muscle and is innervated by the vagus nerve (CNX). The lower 1/3
contains smooth muscle from splanchnic mesoderm and is innervated by the splanchnic plexus.

USMLE Case Scenario

The mesentery, a large fold of peritoneum, suspends the small intestine from the posterior abdominal wall. The base of the
mesentery attaches to the posterior abdominal wall:
1. To the right of the third lumbar vertebra and passes obliquely to the left and inferiorly to the right sacroiliac joint
2. To the left of the third lumbar vertebra and passes obliquely to the left and inferiorly to the right sacroiliac joint
3. To the right of the second lumbar vertebra and passes obliquely to the left and inferiorly to the right sacroiliac joint
4. To the left of the second lumbar vertebra and passes obliquely to the right and inferiorly to the right sacroiliac joint
Ans. 4. To the left of the second lumbar vertebra and passes obliquely to the right and inferiorly to the right sacroiliac joint.
The mesentery contains blood vessels, nerves, lymphatics, and lymph nodes, as well as considerable fat. It attaches to the small
intestine along the length of one side, the mesenteric border, leaving the remainder of the surface of the bowel covered by its visceral
peritoneum, the serosa. The broad-based attachment of the mesenteric base stabilizes the small bowel and prevents it from twisting
upon its blood supply.

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93

USMLE Case Scenario

A 33-year-old person from Toledo is hit by a car has been said to develop extradural hematom1. Most likely vessel to bleed is:
1. Ophthalmic artery
2. Subdural veins
3. Occipital artery
4. Middle meningeal artery
Ans. 4. Middle meningeal artery

USMLE Case Scenario

During an abdomino pelvic surgery a big, tortuous vessel was seen by a gynecologist on the lateral side of uterus. The vessel
was found to be a branch of internal iliac artery. Most likely the vessel found by the gynecologists was:
1. Splenic artery
2. Ovarian artery
3. Vaginal artery
4. Uterine artery
Ans. 4. Uterine artery

USMLE Case Scenario

A surgeon wishes to perform a splenectomy on a 77-year-old patient who has been in an automobile accident. Before
removing the spleen, the splenic artery and splenic vein are ligated. Within which of the following peritoneal structures are
the splenic artery and vein found?
1. Gastrocolic ligament
2. Gastrosplenic ligament
3. Lesser omentum
4. Splenorenal ligament
Ans. 4. Splenorenal ligament

USMLE Case Scenario

A 44-year-old has a normal thyroid gland which normally moves with swallowing because the thyroid gland is enclosed by
which of the following fascia?
1. Carotid sheath
2. Investing layer of the deep cervical fascia
3. Pretracheal fascia
4. Prevertebral fascia
Ans. 3. Pretracheal fascia

USMLE Case Scenario

A 15-year-old typist from ilinos comes to the health clinic because of recurrent episodes of wheezing during basketball
practices. His activity has been hampered by shortness of breath shortly after beginning practice and during games. The
symptoms are accompanied by a nonproductive cough and chest tightness. He denies any symptoms at rest. The symptoms
occur whether the practices are indoors or outdoors. On physical examination, he is comfortable and denies any symptoms.
His physical examination is unremarkable. Which of the following cells are most likely to mediate his symptoms?
1. Eosinophils
2. Lymphocytes
3. Mast cells
4. Monocytes

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USMLE Step 1 Platinum Notes

5. Neutrophils
Ans. 3. Mast cells
This patient has symptoms of exercise-induced asthma. The symptoms of exercise-induced asthma are due to mast cell release of
histamines, which degranulate with the initiation of exercise.

USMLE Case Scenario

Carotid Sheath is an important structure. It contains a cranial nerve. The cranial nerve is:
1. IX
2. X
3. XI
4. XII
Ans. 2. X

USMLE Case Scenario

The cranial nerve passing through the substance of parotid gland is:
1. Abducens
2. Facial
3. Optic
4. Trigeminal
5. Glossopharyngeal
6. Vagus
Ans. 2. Facial

USMLE Case Scenario

A feature of Sharipos Syndrome is agenesis of:
1. Corpus callosum
2. Anterior commisure
3. Posterior commisure
4. Hippocampal commisure
Ans. 1. Corpus callosum

USMLE Case Scenario

During cranial nerve examination, a neurologist asks her 33-year-old patient to protrude his tongue. On doing so, her tongue
deviates to the right side. This finding results from paralysis of tongue muscle namely:
1. Genioglossus
2. Styloglossus
3. Palatoglossus
4. Hyoglossus
Ans. 1. Genioglossus
The genioglossus muscle is innervated by the hypoglossal nerve. The function of the genioglossus muscle is to pull the tongue
forward (protrude) and toward the opposite side. When the right genioglossus muscle is paralyzed, the left genioglossus muscle pulls
the tongue forward and to the right.

USMLE Case Scenario

Bells Palsy is a LMNL of a cranial nerve. The cranial nerve most commonly involved is:
1. Abducens
2. Facial
3. Optic
4. Trigeminal
Ans. 2. Facial

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95

USMLE Case Scenario

An inflammatory process in the temporal bone has resulted in a swelling of the facial nerve within the facial canal. Which
muscle maybe paralyzed as a result of this compression?
1. Anterior belly of the digastrics
2. Geniohyoid
3. Stapedius
4. Stylopharyngeus
Ans. 3. Stapedius
The stapedius muscle is innervated by the facial nerve. This muscle is located in the middle ear and attaches to the neck of the stapes.
Contraction of the Stapedius reduces the amplitude of oscillation of the stapes and thus reduces the perceived loudness of a sound.
Paralysis of this muscle may result in hyperacusis.

USMLE Case Scenario

A 34-year-old male smoker notices loss of taste sensation in his anterior part of tongue. He reports to a physician who tells him
that one of his nerves maybe damaged which supplies taste sensation to this part of his tongue. The nerve specifically most
likely to be damaged is:
1. Glossopharyngeal
2. Lingual
3. Chorda tympani
4. Vagus
Ans. 3. Chorda tympani

USMLE Case Scenario

The neck of the pancreas links the head and body. It is often the most anterior portion of the gland. The lower part of the
neck lies anterior to the superior mesenteric vein. This is important during surgery for pancreatic cancer since malignant
involvement of these vessels may make resection impossible. The anterior surface of the neck is covered with peritoneum. The
posterior surface of neck is closely related to:
1. Pylorus of stomach
2. Aorta
3. Internal iliac vein
4. External iliac vein
5. Common iliac vein
6. Portal vein
Ans. 6. Portal vein
The neck of the pancreas is defined as that portion of the pancreas which lies anterior to the portal vein, and is closely related to the upper
posterior surface. The lower part of the neck lies anterior to the superior mesenteric vein just before the formation of the portal vein.

USMLE Case Scenario

An ENT surgeon plainly tells his patient from North Carolina that he has got hyperacusis and that one of his important nerve
is damaged. The nerve most likely to be damaged is:
1. Auriculotemporal
2. Greater Auricular
3. Auricular branch of Vagus
4. Nerve to Stapedius
Ans. 4. Nerve to Stapedius

USMLE Case Scenario

A 66-year-old patient from Ohio has a large meningioma involving the parasagittal region and falx cerebri neurologic deficits
expected to be produced by mass lesion in this region is:
1. Lower limb paralysis

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USMLE Step 1 Platinum Notes

2. Upper limb paralysis

3. Motor aphasia
4. Sensory aphasia
Ans. 1. Lower limb paralysis
A meningioma of the parasagittal region and the falx cerebri would be located superiorly, between the two hemispheres. In this
position, it could compress the sensory (postcentral gyrus) or motor cortex (precentral gyrus) supplying the lower extremities and
cause lower limb paralysis.

USMLE Case Scenario

A 66-year-old man working in a bar complains of trouble swallowing and hoarseness. On physical exam, he is noted to have
ptosis and a constricted pupil on the left, and a diminished gag reflex. Neurological examination shows decreased pain and
temperature sensation on the left side of his face and on the right side of his body. Which vessel is most likely occluded?
1. Spinal artery
2. PICA
3. AICA
4. Vertebral artery
Ans. 2. PICA
The signs and symptoms in this patient are consistent with occlusion of the posterior inferior cerebellar artery (PICA). PICA
is a branch of the vertebral artery (which is itself a branch of the subclavian artery). Occlusion of PICA causes a lateral medullary
syndrome characterized by deficits in pain and temperature sensation over the contralateral body (spinothalamic tract dysfunction);
ipsilateral dysphagia, hoarseness, and diminished gag reflex (interruption of the vagal and glossopharyngeal pathways);
vertigo, diplopia, nystagmus and vomiting (vestibular dysfunction); ipsilateral Horners syndrome (disruption of descending
sympathetic fibers); and ipsilateral loss of pain and temperature sensation of the face (lesion of the spinal tract and nucleus of the
trigeminal nerve).

USMLE Case Scenario

Vessel lying within cavernous sinus is:
1. Internal carotid
2. External carotid
3. Common carotid
4. External jugular vein
Ans. 1. Internal carotid

USMLE Case Scenario

A 55-year-old male received a hit on left hypochondriac region. Spleen was found to be lacerated. On operation, a large
tortuous vessel was found to be seen. Doctor reported it as splenic artery. It is a branch of:
1. Celiac trunk
2. Superior mesenteric artery
3. Inferior mesenteric artery
4. Thoracic aorta
Ans. 1. Celiac trunk

USMLE Case Scenario

A 55-year-old male had a surgery. His leino renal ligament was seen to contain an artery. Most likely the artery was:
1. Short gastric artery
2. Splenic artery
3. Pancreatic artery
4. Renal artery
Ans. 2. Splenic artery

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USMLE Case Scenario

A 55-year-old is to be operated for inguinal hernia. An antomist while discussing the hernia describes one artery as a land
mark for differentiating direct and indirect inguinal hernias. The artery most likely is:
1. Superior epigastric artery
2. Inferior epigastric artery
3. Umbilical artery
4. Obliterated umbilical artery
Ans. 2. Inferior epigastric artery
Remember:
Indirect inguinal hernias lie lateral to the inferior epigastric artery, whereas direct inguinal hernias lie medial to these vessels.

USMLE Case Scenario

The superficial perineal fascia is a continuation into the perineum of the membranous fascia from the anterior abdominal
wall. The superficial perineal fascia is called as:
1. Colles fascia
2. Fascia colli
3. Campers fascia
4. Waldeyers fascia
5. Thoraco lumbar fascia
Ans. 1. Colles fascia

USMLE Case Scenario

An aneurysm of the axillary artery within the axilla is most likely to compress which of the following neural structures?
1. Axillary nerve
2. Long thoracic nerve
3. Lower trunk of the brachial plexus
4. Medial cord of the brachial plexus
Ans. 4. Medial cord of the brachial plexus
Remember:
Within the axilla, the axillary artery is within the axillary sheath and is surrounded by the three cords of the brachial plexus, which are
also within the axillary sheath. An aneurysm of the axillary artery may compress any of the three cords.

USMLE Case Scenario

Physical examination of 32-year-old medical graduate from kansas reveals a winged left scapula and an inability to raise his
left arm above the horizontal. Which of the following nerves is most likely affected?
1. Axillary nerve
2. Long thoracic nerve
3. Lower subscapular
4. Suprascapular nerve
Ans. 2. Long thoracic nerve
Remember:
The serratus anterior, innervated by the long thoracic nerve, is responsible for stabilization of the scapula during abduction of the arm
from 90 to 180 degrees. When the long thoracic nerve is damaged, it is difficult to elevate the arm above the horizontal. This nerve
arises from C5, 6, and 7. Remember: winged scapula is a classic clue for long thoracic nerve injury.

USMLE Case Scenario

Waldeyers ring is a circumpharyngeal ring of mucosa-associated lymphoid tissue which surrounds the openings into the
digestive and respiratory tracts. It is made-up:
1. Posterosuperiorly by the lingual tonsil

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USMLE Step 1 Platinum Notes

2. Anterosuperiorly by the lingual tonsil

3. Posteroinferiorly by the lingual tonsil
4. Anteroinferiorly by the lingual tonsil
Ans. 4. Anteroinferiorly by the lingual tonsil
Waldeyers Ring: Anteroinferiorly by the lingual tonsil, laterally by the palatine and tubal tonsils, and posterosuperiorly by the
nasopharyngeal tonsil

USMLE Case Scenario

A 33-year-old female engineer complains to her orthopedician that her thumb does not work right. The physician notes
weakness of the thumb in extension, although rotation, flexion, abduction, adduction, and opposition are normal. Which of
the following nerves is most likely involved?
1. Ulnar
2. Radial
3. Median
4. Axillary
Ans. 2. Radial
Redial extension is provided by the extensors pollicis longus and brevis, which are innervated by the radial nerve
The median nerve supplies the thenar group, which allows the thumb to oppose, flex, abduct, and rotate
The ulnar nerve supplies the adductor pollicis, which adducts the thumb
Axillary nerve supplies Teres Minor and Deltoid.

USMLE Case Scenario

A branch of the posterior cord of the brachial plexus particularly susceptible to injury in shoulder dislocations that displace
the humeral head with impaired Arm abduction and loss of sensation over the lower half of the deltoid. The nerve involved is:
1. Ulnar
2. Radial
3. Median
4. Axillary
Ans. 4. Axillary

USMLE Case Scenario

A nerve innervates the muscle of the anterior compartment of the arm but does not innervate any muscle in the hand is:
1. Ulnar
2. Radial
3. Musculocutaneous
4. Median
Ans. 3. Musculocutaneous

USMLE Case Scenario

A 36-year-old Acromegaly patient complains of a tingling sensation in the 1st, 2nd, and 3rd digits of the right hand and loss
of coordination and strength of the right thumb. The condition is most likely to be:
1. Claw hand
2. Carpal tunnel syndrome
3. Ape hand deformity
4. Dupynterns contracture
Ans. 2. Carpal tunnel syndrome
Overgrowth in the wrist area has compressed the carpal tunnel, thereby impinging on the median nerve. The median nerve (root C5T1) provides motor innervation to the forearm flexors, thenar muscles, and radial lumbricals. It provides sensory innervation to the
radial 2/3 of the palm, volar surfaces of the thumb, 2nd and 3rd digits, and radial 1/2 of the 4th digit.

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USMLE Case Scenario

A 55-year-old suffered trauma to his penis. His Dorsal artery of penis got damaged. The said vessel is a branch of:
1. Anterior division of internal iliac artery
2. Posterior division of internal iliac artery
3. Anterior division of external iliac artery
4. Posterior division of external iliac artery
Ans. 1. Anterior division of internal iliac artery
The internal pudendal is a branch of the anterior division of the internal iliac artery. It gives rise to the inferior rectal artery, perineal
artery, artery of the bulb in men, urethral artery, deep artery of the penis and dorsal artery of the penis.

USMLE Case Scenario

A 66-year-old reports pain in his left upper extremity and tingling and numbness in his 4th and 5th digits of his left hand.
There is mild swelling of the left hand. The man reports most of his pain and numbness occurs when he is doing electric work
with his arms overhead. X-ray reveals the presence of a cervical rib. The artery liable to be compressed is:
1. Axillary
2. Radial
3. Brachial
4. Subclavian
Ans. 4. Subclavian
The subclavian artery passes laterally over the upper surface of the first rib and lies posterior to the scalenus anterior. In the case of
thoracic outlet syndrome, this artery is usually compressed between the scalenus anterior and a cervical rib. Thoracic outlet syndrome
is a broad term for a group of disorders in which there is compression of certain neurovascular bundles. The presence of a cervical rib
adds to the compression, and repetitive motion and poor posture are other predisposing factors. When the neurovascular bundle is
entrapped, the patient presents with neurological and/or circulatory changes in the upper extremity on the involved side.

USMLE Case Scenario

A 44-year-old complains of Galactorrhea and Amonorrhea. CT Scan was done. Image shows a pituitary tumor compressing
optic chiasma. Hemianopia produced would be of type:
1. Bitemporal hemianopia
2. Binasal hemianopia
3. Unilateral hemianopia
4. Superior quadrant unilateral hemianopia
Ans. 1. Bitemporal hemianopia

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USMLE Step 1 Platinum Notes

Parkinsons disease

USMLE Case Scenario

The person shown in figure has features as identified in figure. Most likely he is suffering from a disease that affects which
part of CNS.
1. Cerebellum
2. Substantia nigra
3. Nucleus basalis
4. Frontal lobe
Ans. 2. Substantia nigra

Midbrain

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101

USMLE Case Scenario

The chorda tympani nerve of is a branch of cranial nerve. The cranial nerve is:
1. Abducens
2. Facial
3. Optic
4. Trigeminal
Ans. 2. Facial

USMLE Case Scenario

A 45-year-old from India notices swelling in his groin. He is reported to have an abscess after further investigations reveal
tuberculosis of spine. The abscess is found along sheath of a muscle whose function is: to flex the thigh at the hip. The muscle
involved is:
1. Gluteus maximus
2. Psoas
3. Gluteus minimus
4. Sartorius
Ans. 2. Psoas

USMLE Case Scenario

Pyramidalis is a triangular muscle that lies in front of the lower part of rectus abdominis within the rectus sheath. It is attached
by tendinous fibers to the front of the pubis and to the ligamentous fibers in front of the symphysis. The muscle diminishes
in size as it runs upwards, and ends in a pointed apex that is attached medially to the linea alba. This attachment usually lies
midway between the umbilicus and pubis, but may occur higher. The pyramidalis is supplied by:
1. The terminal branches of the subcostal nerve
2. The terminal branches of the iliohypogastric nerve
3. The terminal branches of the ilioinguinal nerve
4. The terminal branches of the genitofemoral nerve
Ans. 1. The terminal branches of the subcostal nerve

USMLE Case Scenario

The muscles of the pharynx with the exception of one muscle are supplied from the pharyngeal plexus by the pharyngeal
branch of the vagus. The exception is:
1. Palatopharyngeus
2. Stylopharyngeus
3. Salpingopharyngeus
4. Inferior constrictor
Ans. 2. Stylopharyngeus
The muscles of the pharynx-with the exception of stylopharyngeus, which is supplied by the glossopharyngeal nerve are supplied
from the pharyngeal plexus by the pharyngeal branch of the vagus. This branch emerges from the upper part of the inferior vagal
ganglion.

USMLE Case Scenario

The paired renal arteries supply the kidneys through a number of subdivisions described sequentially as segmental, lobar,
interlobar, and arcuate arteries. These are end arteries with no anastomoses. The renal arteries branch laterally from the:
1. Iliac vessels just below the origin of the superior mesenteric artery
2. Iliac vessels just above the origin of the superior mesenteric artery
3. Aorta just below the origin of the superior mesenteric artery

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USMLE Step 1 Platinum Notes

4. Aorta just above the origin of the superior mesenteric artery

Ans. 3. Aorta just below the origin of the superior mesenteric artery
The renal arteries branch laterally from the aorta just below the origin of the superior mesenteric artery. Both cross the corresponding
crus of the diaphragm at right angles to the aorta. The right renal artery is longer and often higher, passing posterior to the inferior
vena cava, right renal vein, head of the pancreas and descending part of the duodenum. The left renal artery is a little lower and passes
behind the left renal vein, the body of the pancreas and splenic vein.

USMLE Case Scenario

The aortic aperture is the lowest and most posterior of the large openings. It is at the level of the lower border of the twelfth
thoracic vertebra and the thoracolumbar intervertebral disk, slightly to the left of the midline. It is an osseoaponeurotic
opening defined by the diaphragmatic crura laterally, the vertebral column posteriorly and the diaphragm anteriorly. Strictly
speaking, it lies behind the diaphragm and its median arcuate ligament. The aortic opening transmits:
1. The aorta, thoracic duct, azygos veins
2. The inferior vena cava, thoracic duct, azygos veins
3. Esophagus, thoracic duct, azygos veins
4. The phrenic nerve, thoracic duct, azygos veins
Ans. 1. The aorta, thoracic duct, azygos veins

USMLE Case Scenario

The epithelial lining of the trachea is composed of:
1. Pseudostratified columnar nonciliated cells, goblet cells and basal cells
2. Pseudostratified columnar ciliated cells, goblet cells and basal cells
3. Stratified columnar nonciliated cells, goblet cells and basal cells
4. Stratified noncolumnar ciliated cells, goblet cells and basal cells
Ans. 2. Pseudostratified columnar ciliated cells, goblet cells and basal cells

USMLE Case Scenario

Kidney is surrounded by a special layer of fascia called:
1. Waldeyers fascia
2. Fascia coli
3. Denonveliers fascia
4. Gerotas fascia
5. Cruveilhiers fascia
6. Campers fascia
7. Colles fascia
8. Scarpas fascia
Ans. 4. Gerotas fascia

USMLE Case Scenario

The ovarian vessels follow a downward course and pass between the layers of the infundibulopelvic ligament and the broad
ligament to reach the ovary. The true statement regarding blood supply of ovary is:
1. The ovarian arteries arise from aorta, the left ovarian vein and the right ovarian vein empties into the vena cava
2. The ovarian arteries arise from aorta and the left ovarian vein empties into the left renal vein; the right ovarian vein empties
into the vena cava
3. The ovarian arteries arise from uterine artery and the right ovarian vein empties into the left renal vein; the left ovarian vein
empties into the vena cava
4. The ovarian arteries arise from uterine artery and the left ovarian vein empties into the left renal vein; the right ovarian vein
empties into the vena cava
Ans. 2. The ovarian arteries arise from aorta and the left ovarian vein empties into the left renal vein; the right ovarian vein
empties into the vena cava.

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103

USMLE Case Scenario

A 44-year-old suffers fracture of surgical neck of humerus. Most likely effected nerve is:
1. Radial
2. Musculocutaneous
3. Ulnar
4. Anterior interosseous c nerve
5. Cranial nerve XI
6. Subscapular
7. Axillary nerve
Ans. 7. Axillary nerve

USMLE Case Scenario

Valves of Kerckring are seen in:
1. Appendix
2. Small intestine
3. Cecum
4. Sigmoid colon
5. Rectum
6. Anal canal
Ans. 2. Small intestine
The mucosal surface of the small intestine contains numerous circular mucosal folds called the plicae circulares (valvulae conniventes,
or valves of Kerckring). These folds are 3 to 10 mm in height; they are taller and more numerous in the distal duodenum and proximal
jejunum, becoming shorter and fewer distally. Intestinal villi barely visible to the naked eye resemble tiny finger-like processes
projecting into the intestinal lumen.

USMLE Case Scenario

A nerve innervates the anconeus muscle of the arm. Most likely nerve supply of anconeus is:
1. Ulnar
2. Radial nerve
3. Musculocutaneous
4. Median
Ans. 2. Radial nerve

USMLE Case Scenario

The cranial nerves lying in the cavernous sinus are:
1. VII , IX
2. X , XI
3. XII, VI
4. Divisions of V nerve
5. Divisions of VII nerve
Ans. 4. Divisions of V nerve

USMLE Case Scenario

Annular bronchial cartilage is congenitally absent, leading to bronchomalacia and Bronchiectasis is termed as:
1. Cystic fibrosis syndrome
2. Ehlers-Danlos syndrome
3. Mounier-Kuhn syndrome
4. Kartageners syndrome
5. Immotile cilia syndrome
6. Williams-Campbell syndrome
Ans. 6. Williams-Campbell syndrome

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USMLE Step 1 Platinum Notes

USMLE Case Scenario

Fold of serous pericardium surrounding right and left pulmonary veins are connected by an irregular pericardial reflection
creates a space termed the:
1. Oblique sinus
2. Transverse sinus
3. Coronary sinus
Ans. 1. Oblique sinus

USMLE Case Scenario

After a fight a sharp instrument passed through the superior orbital fissure of a 45-year-old man. It would most likely damage the:
1. Abducens nerve
2. Facial nerve
3. Mandibular nerve
4. Maxillary nerve
5. Middle meningeal artery
6. Ophthalmic artery
7. Optic nerve
Ans. 1. Abducens nerve
Almost everything that innervates the eye, other than the optic nerve, passes through this fissure. This includes the oculomotor nerve
(CN III), the trochlear nerve (CN IV), the ophthalmic nerve (V1), and the abducens nerve (CN VI).

USMLE Case Scenario

Meckels Diverticulitis is persistence of:
1. Portion of the vitelline duct on the mesenteric border of the distal ileum, may produce bleeding, intestinal obstruction
2. Portion of the vitelline duct on the mesenteric border of the proximal ileum, may produce bleeding, intestinal obstruction
3. Portion of the vitelline duct on the antimesenteric border of the proximal ileum, may produce bleeding, intestinal obstruction
4. Portion of the vitelline duct on the antimesenteric border of the distal ileum, may produce bleeding, intestinal obstruction
Ans. 4. Portion of the vitelline duct on the antimesenteric border of the distal ileum, may produce bleeding, intestinal
obstruction

USMLE Case Scenario

A 27-year-old woman presents with hyperthyroidism, and subtotal thyroidectomy is successfully performed, but following
the surgery, the woman is extremely hoarse, and can barely speak above a whisper. This hoarseness is most probably related
to damage to a nerve which is a branch of CRANIAL NERVE:
1. IX
2. X
3. XI
4. XII
Ans. 2. X

USMLE Case Scenario

A physician is performing a cranial nerve examination on a patient. While testing the gag reflex, it is noted that when the
right side of the pharyngeal mucosa is touched, the patients uvula deviates to the right. When the left side of the pharyngeal
mucosa is touched, the patient does not gag. Which of the following is the most likely location of his lesion?
1. Left glossopharyngeal nerve and left vagus nerve
2. Right glossopharyngeal nerve and left vagus nerve
3. Left glossopharyngeal nerve and Right vagus nerve
4. Right glossopharyngeal nerve and Right vagus nerve
Ans. 1. Left glossopharyngeal nerve and left vagus nerve

Anatomy

105

USMLE Case Scenario

A cranial nerve innervates the stylopharyngeus muscle and the parotid gland. Visceral afferents supply the carotid sinus
baroreceptors and carotid body chemoreceptors, and mediate taste from the posterior one-third of the tongue. Somatosensory
fibers supply pain, temperature, and touch information from the posterior one-third of the tongue, upper pharynx, middle
ear and eustachian tube. The cranial nerve mentioned is:
1. IX
2. X
3. XI
4. XII
Ans. 1. IX

USMLE Case Scenario

An injury to the lateral portion of the dorsal columns would most likely damage:
1. Fine motor control of fingers
2. Motor control of the contralateral foot
3. Sweating of the ipsilateral face
4. Proprioception from the ipsilateral leg
5. Vibratory sense from the ipsilateral arm
6. Vibratory sense from the contralateral arm
7. Sensory control of the contralateral foot
Ans. 5. Vibratory sense from the ipsilateral arm

USMLE Case Scenario

Atresia (blockage) of this canal results from failure of the meatal plug to canalize. Usually the deep part of the meatus is open,
but the superficial part is blocked by bone or fibrous tissue. Most cases are associated with the:
1. First arch syndrome
2. Second arch syndrome
3. Third arch syndrome
4. Fifth arch syndrome
Ans. 1. First arch syndrome

USMLE Case Scenario

The tensor tympani muscle, attached to the malleus, is derived from mesenchyme in the first pharyngeal arch and is innervated by:
1. CN V, the nerve of this arch
2. CN VI, the nerve of this arch
3. CN VII, the nerve of this arch
4. CN VIII, the nerve of this arch
Ans. 1.CN V, the nerve of this arch

USMLE Case Scenario

Fine motor control of the fingers would be carried principally by the:
1. Contralateral lateral corticospinal tract
2. Ipsilateral lateral corticospinal tract
3. Ipsilateral rubrospinal tract
4. Ipsilateral Tectospinal tract
5. Ipsilateral vestibulospinal tract
Ans. 2. Ipsilateral lateral corticospinal tract

106

USMLE Step 1 Platinum Notes

USMLE Case Scenario

The rectum is separated from the prostate by:
1. Waldeyers fascia
2. Fascia coli
3. Denonveliers fascia
4. Gerotas fascia
5. Cruveilhiers fascia
6. Campers fascia
7. Colles fascia
8. Scarpas fascia
Ans. 3. Denonveliers fascia

USMLE Case Scenario

An 89 years old elderly patient suffering from Picks disease also had multiple small strokes. During her stay in the nursing
home on multiple occasions she aspirated food, and neurological examination reveals that her gag reflex is absent. These
findings suggest involvement of the nucleus of which of the following cranial nerves?
1. Facial (VII)
2. Glossopharyngeal (IX)
3. Hypoglossal (XII)
4. Spinal accessory (XI)
5. Vestibulocochlear (VIII)
Ans. 2. Glossopharyngeal (IX)
Cranial nerve IX is the glossopharyngeal nerve, which has a nucleus in the medulla and is necessary for the gag reflex

USMLE Case Scenario

The esophagus begins at the lower border of the cricoid cartilage at the level of C6 vertebra. It is about 25 cm (10 inches) long.
The intra-abdominal part of the esophagus varies in length according to the tone of its muscle and the degree of distension
of the stomach. It passes through the diaphragm at the level of:
1. T6 vertebra
2. T8 vertebra
3. T10 vertebra
4. T12 vertebra
Ans. 3. T10 vertebra

USMLE Case Scenario

The upper part of the anal canal above the pectinate line is endodermal, and the lower part is derived from the ectoderm.
The upper half of the canal is lined by columnar epithelium and the lower half with stratified squamous epithelium. True
statement would be:
1. A carcinoma of the lower canal is usually an adenocarcinoma, while that arising from the upper part would be a squamous cell
carcinoma
2. A carcinoma of the upper canal is usually an adenocarcinoma, while that arising from the lower part would also be an
adenocarcinoma
3. A carcinoma of the upper canal is usually a squamous cell carcinoma, while that arising from the lower part would also be a
squamous cell carcinoma
4. A carcinoma of the upper canal is usually an adenocarcinoma, while that arising from the lower part would be a squamous cell
carcinoma
Ans. 4. A carcinoma of the upper canal is usually an adenocarcinoma, while that arising from the lower part would be a
squamous cell carcinoma

Anatomy

107

USMLE Case Scenario

The cranial nerve carrying the pain sensations from tip of tongue is:
1. VI
2. V2
3. V3
4. VII
5. IX
6. X
7. XI
8. XII
Ans. 3. V3
The mandibular division of the trigeminal nerve (V3) carries general somatic sensation from the anterior two-thirds of the
tongue.

USMLE Case Scenario

Which of the following eye muscles rotates the eye downward and away from midline?
1. Inferior oblique
2. Superior oblique
3. Inferior rectus
4. Superior rectus
Ans. 2. Superior oblique

USMLE Case Scenario

A 44-year-old engineer noticed that he has an eye that is persistent directed toward his nose. A lesion of which of the following
nerves could produce this finding?
1. CN II
2. CN IV
3. CN V
4. CN VI
Ans. 4. CN VI

USMLE Case Scenario

The Fascial layer separating the rectum from the coccyx is:
1. Waldeyers fascia
2. Fascia coli
3. Denonveliers fascia
4. Gerotas fascia
5. Cruveilhiers fascia
6. Campers fascia
7. Colles fascia
8. Scarpas fascia
Ans. 1. Waldeyers fascia

USMLE Case Scenario

Carotid Sheath is an important structure. It contains:
1. Facial nerve and internal carotid artery
2. Facial nerve and external carotid artery
3. Facial artery and external carotid artery
4. Vagus nerve and external carotid artery
5. Vagus nerve and internal carotid artery
Ans. 5. Vagus nerve and internal carotid artery

108

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Meckels ganglion is related to a cranial nerve. The cranial nerve is:
1. Abducens
2. Facial
3. Optic
4. Trigeminal
Ans. 4. Trigeminal

USMLE Case Scenario

The cranial nerve supplying the Trapezius muscle is:
1. VII
2. IX
3. X
4. XI
5. XII
Ans. 4. XI

USMLE Case Scenario

A Nerve innervating the muscles of the Posterior compartment of the arm is:
1. Ulnar
2. Radial
3. Musculocutaneous
4. Median
Ans. 2. Radial

USMLE Case Scenario

Physical examination of 36-year-old medical graduate from Texas reveals a winged left scapula and an inability to raise his left
arm above the horizontal. Which of the following muscles is most likely affected?
1. Serratus posterior
2. Serratus anterior
3. Deltoid
4. Scalenus anterior
5. Scalenus medius
6. Scalenus posterior
7. Levator scapulae
8. Sternomastoid
9. Rhombidius minor
Ans. 2. Serratus anterior
Remember:
The serratus anterior, innervated by the long thoracic nerve, is responsible for stabilization of the scapula during abduction of the arm
from 90 to 180 degree.

USMLE Case Scenario

A Newborn boy does not pass meconium until 55 hours after his birth. Several weeks later his mother complains that he has
not been passing stool regularly. Anorectal manometry reveals increased internal anal sphincter pressure on rectal distention
with a balloon. The patients disorder is:
1. Intussusception
2. Hirschsprungs disease
3. Exomphalos
4. Dysphagia lusoria

Anatomy

109

5. Anal atresia
6. Malrotation of gut
Ans. 2. Hirschsprungs disease

USMLE Case Scenario

A physician during cranial nerve examination asks her patient to protrude his tongue. On doing so, her tongue deviates to the
right side. This finding results from paralysis of tongue muscle. The likely nerve paralyzed is:
1. Facial
2. Vagus
3. Hypoglossal
4. Glossopharyngeal
5. Chorda tympani
6. Lingual
Ans. 3. Hypoglossal
The genioglossus muscle is innervated by the hypoglossal nerve. The function of the genioglossus muscle is to pull the tongue
forward (protrude) and toward the opposite side. When the right genioglossus muscle is paralyzed, the left genioglossus muscle pulls
the tongue forward and to the right.

Tongue deviation

USMLE Case Scenario

As part of a complete neurological examination, a medical student takes a cotton-tipped applicator and touches the patients
left eye with a thin wisp of cotton as the patient looks to the right. The patient closes both of his eyelids in response. Which of
the following cranial nerves is responsible for the sensory limb of this reflex?
1. Abducens
2. Facial
3. Optic
4. Trigeminal
Ans. 4. Trigeminal

USMLE Case Scenario

A 34-year-old patient arrives in the emergency room after having suffered severe head trauma in a accident. Radiographic
studies of the head reveal a basilar skull fracture in the region of the foramen ovale. Which of the following nerve passes
through this foramen:
1. Maxillary

110

USMLE Step 1 Platinum Notes

2. Mandibular
3. Ophthalmic
4. Occulomotor
Ans. 2. Mandibular

USMLE Case Scenario

Annular pancreas is a condition that results when normal pancreatic tissue completely or partially encircles the duodenum.
Annular pancreas is thought to arise from failure of normal clockwise rotation of the ventral pancreatic bud. In children,
there is a common association with other serious congenital anomalies such as intracardiac defects, Downs syndrome, and
intestinal malrotation. It commonly encircles:
1. First part of duodenum
2. Second part of duodenum
3. Third part of duodenum
4. Fourth part of duodenum
5. Jujenum
6. Ileum
Ans. 2. Second part of duodenum

USMLE Case Scenario

Pancreas is a mixed gland divided into four portions: the head, the neck, the body, and the tail. It is a retroperitoneal organ.
The structure related to the head of the pancreas is:
1. Hilum of spleen
2. Uncinate process
3. Portal vein
4. Tuber omentale
5. Pappilary process
6. Foramen of Winslow
7. Ligament of Treitz
8. Linea semilunaris
Ans. 2. Uncinate process

USMLE Case Scenario

The Distal portion of the gallbladder has the appearance of a diverticulum, which is called:
1. Morrisons pouch
2. Zenkers diverticulum
3. Meckels diverticulum
4. Spiral valve of Heister
5. Hartmanns pouch
6. Uncinate process
7. Tuber omentale
8. Pappilary process
9. Foramen of Winslow
Ans. 5. Hartmanns pouch

USMLE Case Scenario

Pancreas is a mixed gland divided into four portions: the head, the neck, the body, and the tail. It is a retroperitoneal organ.
The endocrine portion of pancreatic function is served by the structures termed the islets of Langerhans. The islets are nearly
spherical collections of cells scattered throughout the pancreatic parenchyma and is composed of several distinctive cell
types. True statement is:
1. The insulin-producing alpha cells compose the majority of the islet population
2. The insulin-producing beta cells compose the minority of the islet population

Anatomy

111

3. The insulin-producing beta cells compose the majority of the islet population
4. The insulin-producing alpha cells compose the minority of the islet population
Ans. 3. The insulin-producing beta cells compose the majority of the islet population

USMLE Case Scenario

Embryologically, the gut rotates and the rotation occurs in a way that:
1. The large intestine rotates in a clockwise manner around the axis of the celiac trunk
2. The large intestine rotates in a clockwise manner around the axis of the superior mesenteric artery
3. The large intestine rotates in a clockwise manner around the axis of the inferior mesenteric artery
4. The large intestine rotates in a counterclockwise manner around the axis of the celiac trunk
5. The large intestine rotates in a counterclockwise manner around the axis of the superior mesenteric artery
6. The large intestine rotates in a counterclockwise manner around the axis of the inferior mesenteric artery
Ans. 5. The large intestine rotates in a counterclockwise manner around the axis of the superior mesenteric artery

USMLE Case Scenario

The ligaments that should be carefully considered during mobilization of the splenic flexure to avoid injury to the spleen are:
1. Leinorenal and splenocolic attachments
2. Phrenocolic and leinorenal attachments
3. Phrenocolic and splenocolic attachments
4. Greater omentum and splenocolic attachments
5. Lesser omentum and leinorenal attachments
Ans. 3. Phrenocolic and splenocolic attachments
The large intestine rotates in a counterclockwise manner around the axis of the superior mesenteric artery

USMLE Case Scenario

The anastomosis between the superior and inferior mesenteric vessels is known as the:
1. Marginal artery of Drumond
2. Sudecks point
3. Batesons Plexus
4. Vasa recta
5. Anastomosis of Riolan
Ans. 5. Anastomosis of Riolan

USMLE Case Scenario

As Per the anatomical knowledge of a student, which is not true about pain:
1. A sudden burning pain in the epigastric region suggests a perforated viscus
2. Severe intermittent cramping pain with short pain-free intervals favors small bowel obstruction
3. Sudden excruciating tearing pain maybe associated with a ruptured aneurysm
4. Pain of acute cholecystitis frequently radiates around the right costal margin to the right scapula and to the shoulder
5. Pain in acute pancreatitis is usually epigastric in origin, with subsequent radiation along both costal margins to the back
6. Ureteral calculi causes pain radiating to the groin
7. Pain of stomach is referred to perineum
Ans. 7. Pain of stomach is referred to perineum

USMLE Case Scenario

Maximal tenderness in the right lower quadrant over Mcburneys point is suggestive of an inflammation of an organ. The
characteristic feature of the organ implicated is:
1. It is rich in blood supply with rich anastomosis

112

USMLE Step 1 Platinum Notes

2. It is not covered by peritoneum

3. It is rich in lymphatic tissue
4. It is a derivative of foregut
5. It has a fixed location
6. It has a wide lumen
Ans. 3. It is rich in lymphatic tissue

USMLE Case Scenario

The arterial supply to the hypothalamic-pituitary region is complex and arises from three sources. The inferior hypophyseal
artery, the superior hypophyseal arteries and the middle hypophyseal arteries. These vessels drain into the hypophyseal
portal system, which forms a secondary venous plexus in the anterior pituitary and ultimately empties into the cavernous
sinus. The inferior hypophyseal artery is:
1. A branch of the internal carotid artery
2. A branch of the external carotid artery
3. A branch of the common carotid artery
4. A branch of the vertebral artery
5. A branch of the subclavian artery
Ans. 1. A branch of the internal carotid artery

USMLE Case Scenario

Oxyphil cells are a feature of:
1. Spleen
2. Pituitary
3. Adrenals
4. Prostate
5. Lens of eye
6. Cochlea
7. Thymus
8. Thyroid
9. Parathyroid
Ans. 9. Parathyroid

USMLE Case Scenario

The superior parathyroid glands are usually located on the posterior surface of the upper portion of the thyroid lobe. The lower
parathyroid glands are more ventral, close to the lower pole of the thyroid gland. True statement about the development of
parathyroids is:
1. The superior parathyroids arise from the second pharyngeal pouch and the inferior parathyroids arise from the third
pharyngeal pouch
2. The superior parathyroids arise from the second pharyngeal pouch and the inferior parathyroids arise from the fourth
pharyngeal pouch
3. The superior parathyroids arise from the third pharyngeal pouch and the inferior parathyroids arise from the fourth
pharyngeal pouch
4. The superior parathyroids arise from the fourth pharyngeal pouch and the inferior parathyroids arise from the third
pharyngeal pouch
Ans. 4. The superior parathyroids arise from the fourth pharyngeal pouch and the inferior parathyroids arise from the third
pharyngeal pouch

USMLE Case Scenario

The transition between the oblique fibers of the thyropharyngeus muscle and the transverse fibers of the cricopharyngeus
muscle creates a point of potential weakness in the pharyngoesophageal segment, which is the site of origin of:
1. Rathkes pouch

Anatomy

113

2. Foramen of morgagni
3. Pharyngoesophageal diverticulum
4. Laryngocele
Ans. 3. Pharyngoesophageal diverticulum

USMLE Case Scenario

The esophagus is a hollow tube of muscle that is approximately 25 cm in length and extends from the pharynx to the stomach.
It is arbitrarily divided into four segments: pharyngoesophageal, cervical, thoracic, and abdominal.
True statement about esophagus is that:
1. The esophagus is a nonmucosal-lined muscular tube that has a serosa
2. The esophagus is a nonmucosal-lined muscular tube that lacks a serosa
3. The esophagus is a mucosal-lined muscular tube that has a serosa
4. The esophagus is a mucosal-lined muscular tube that lacks a serosa
Ans. 4. The esophagus is a mucosal-lined muscular tube that lacks a serosa

USMLE Case Scenario

Throughout the fat of the breast, coursing from the overlying skin to the underlying deep fascia, strands of dense connective
tissue provide shape and hold the breast upward. These strands, devoid of epithelial elements, are called:
1. Montogmerys tubercles
2. Sappys Plexus
3. Axillary tail of spence
4. Coopers ligaments
5. Milk line
6. Pectoral fascia
Ans. 4. Coopers ligaments

USMLE Case Scenario

Retropubic space is named after:
1. Fallopius
2. Meckel
3. Camillo golgi
4. Hunter
5. Scarpa
6. Retzius
7. Tredlenburg
Ans. 6. Retzius

USMLE Case Scenario

In the cochlear pathway, the axons terminate in the dorsal and ventral cochlear nuclei in the medulla and the pathway to the
auditory cortex consists of at least four orders of neurons and includes the superior olivary complexes, the lateral lemnisci,
the inferior colliculi, and the medial geniculate bodies. The auditory cortex:
1. Lies in the posterior portion of the Inferior temporal gyrus
2. Lies in the posterior portion of the superior temporal gyrus
3. Lies in the posterior portion of the superior frontal gyrus
4. Lies in the posterior portion of the middle frontal gyrus
5. Lies in the posterior portion of the inferior frontal gyrus
Ans. 2. Lies in the posterior portion of the superior temporal gyrus

114

USMLE Step 1 Platinum Notes

USMLE Case Scenario

The primordia of the principal respiratory organs appear as a medial longitudinal groove in the ventral wall of the pharynx by
the fourth week of gestation. True statement is:
1. The tube is lined with ectoderm, from which the epithelium of the respiratory tract develops
2. The tube is lined with mesoderm, from which the epithelium of the respiratory tract develops
3. The tube is lined with endoderm, from which the epithelium of the respiratory tract develops
4. The tube is lined with endothelium, from which the epithelium of the respiratory tract develops
5. The tube is lined with mesothelium, from which the epithelium of the respiratory tract develops
Ans. 3. The tube is lined with endoderm, from which the epithelium of the respiratory tract develops

USMLE Case Scenario

Folds of serous pericardium surrounding the entrance of the right and left pulmonary veins are connected by an irregular
pericardial reflection that creates a space called as:
1. Transverse sinus
2. Oblique sinus
3. Occipital sinus
4. Maxillary sinus
5. Coronary sinus
6. Sinus of morgagni
7. Sinus venosus
Ans. 2. Oblique sinus

USMLE Case Scenario

The Mullerian ducts develop into the:
1. Ovaries, uterus, cervix, and lower vagina
2. Ovaries, uterus, cervix, and upper vagina
3. Cervix, and upper vagina only
4. Uterus, cervix, and upper vagina
5. Fallopian tubes, uterus, cervix, and upper vagina
6. Ovaries, fallopian tubes, uterus, cervix, and upper vagina
Ans. 5. Fallopian tubes, uterus, cervix, and upper vagina

USMLE Case Scenario

A semicircular line which is about halfway between the umbilicus and pubic symphysis is named as line of:
1. Mc Burney
2. Nelaton
3. Rion
4. Douglas
5. Waldeyer
6. Morrison
7. Heister
8. Scarpa
9. Zuckderkand
Ans. 4. Douglas

USMLE Case Scenario

Lymphatics from the gallbladder drain into the lymph node, located near the superior aspect of the junction of the
infundibulum of the gallbladder and the cystic duct. It is known as:
1. Lymph node of Rossenmller
2. Lymph node of Cloquet
3. Delphic node
4. Lymph node of lund
Ans. 4. Lymph node of lund

PHYSIOLOGY

Physiology

Basics of Physiology
Na+ K+ ATPase Pump
Two ions are responsible: sodium (Na+) and potassium (K+). An unequal distribution of these two ions occurs on the two
sides of a nerve cell membrane because carriers actively transport these two ions: sodium from the inside to the outside and
potassium from the outside to the inside. As a result of this active transport mechanism (commonly referred to as the sodiumpotassium pump), there is a higher concentration of sodium on the outside than the inside and a higher concentration of
potassium on the inside than the outside.
Na K ATPase Pump is an active, electrogenic pump moving three sodium ions outside and in place two potassium ions inside
utilizing ATP. It helps in intrusion of K+
It accounts for 20% of energy utilized by cells
Thus its coupling ratio is 3:2
Extracellular binding site is Ouabain
Its activity is inhibited by Ouabain and related cardiac glycosides
It is a P type ATPase (super family of cation transporters)
Also called E1/E2 Type ATPase responsible for carrying ions across cell membranes
Type: Heterodimer Heterogeneous
It is an example of active transport
RMP (Resting Membrane Potential)
Resting membrane potential of a skeletal muscle is 90 mV
Resting membrane potential of a smooth muscle is 50 to 75 mV
Resting membrane potential of a cardiac muscle is 85 to 95 mV
The resting membrane potential in the nerve fiber is 70 mV
The resting membrane potential in the rods is 40 mV
The resting membrane potential of inner ear cell is 60 mV

The Action Potential

Neurons transmit information as action potentials

An action potential is a temporary change in the membrane potential
Usually initiated in the cell body
Travels in one direction normally
Action potential is conducted in an all-or-none fashion
If the stimulus is too low there is no action potential
If the stimulus is above a threshold the action potential is always the same size

118

USMLE Step 1 Platinum Notes

Action potential
Electrical changes during action potential
Membrane potential depolarizes (becomes more positive)
After the peak of the spike the membrane repolarises (becomes more negative)
The potential becomes more negative than the resting potential (negative after potential)
It then returns to normal
The action potentials of most nerves last 510 milli seconds
Action potentials are initiated by many different types of stimuli
Sensory nerves respond to stimuli of many types including chemicals, light, electricity, pressure, touch and stretch
In the central nervous system most nerves are stimulated by chemical activity at synapses
Stimuli must be above a threshold level to initiate an action potential
After a nerve has fired there is a period of time during which it cannot be stimulated again
This is known as the refractory period

Concepts
Resting Membrane Potential is due to: K+
Resting Membrane Potential is close to isoelectric potential of: Cl
IPSP is due to Cl influx
EPSP is due to K+ influx
For action potential; threshold stimulus is required
Nerve conduction follows All or None phenomenon
Axon has the lowest threshold potential in a nerve fiber
Nerve impulse travels in one direction only at synapse

Physiology

RMP is close to isoelectric potential of chloride

RMP is due to pottasium
IPSP is due to chloride
Amplitude is due to chloride

Most of pottasium is intracellular

Mx pottasium is found in skeletal muscles
In response to tissue injury intracellular pottasium shifts to extracellular space

The Cell Membrane: (USMLE Favorite)

Main constituent is the protein

Lipids are regular but assymetrically arranged
Membrane lipids are amphiphatic
Are arranged as a bilayer
Signal transduction and enzyme activation are the functions of phospholipid part
The fluidity of cell membrane is increased by Polyunsaturated fatty acids
Lipids and proteins intract by hydrogen bonds
RBC Membrane is specially having spectrin (maintains integrity) and glycophyrin
Lipid bilayer is most permeable to urea
Lipid bilayer acts as a gel
Protein: lipid ratio is 2:1

Basement Membrane

Contains laminin
Nidogenin
Enactin
Type IV collagen
Degeneration mediated by metalloproteineases

Functions of Organalles Commonly Asked: (USMLE Favorite)

Synthesis of lipids occurs in Agranular Endoplasmic Reticulum

Synthesis of proteins occurs in Rough ER
Intracellular sorting and packing is done in Golgi complex
Cell shape and motility are a function of Microtubules
Catabolism of H2O2 is a function of Peroxisomes
Site of ATP synthesis is Mitochondria

Marker of
Plasma membrane: adenyl cyclase, 5 nucleotidase
Golgi bodies: galactosyl transferase
Mitochondria: Glutamic dehydrogenase

Fluids and Electrolytes: (USMLE Favorite)

Water constitutes between 50% and 70% of total body weight
The water of the body is divided into three functional compartments

119

120

USMLE Step 1 Platinum Notes

The intracellular water, represents between 30% and 40% of body weight
The extracellular water represents approximately 20% of body weight and is divided between intravascular fluid, or plasma (5%
of body weight), and interstitial, or extravascular, extracellular fluid (15% of body weight)
Intracellular Fluid: Measurement of intracellular fluid (ICF) is determined indirectly by subtraction of the measured extracellular
fluid (ECF) from the measured total body water. The intracellular water is between 30% and 40% of body weight, with the
largest proportion in the skeletal muscle mass. Because of the smaller muscle mass in the female, the percentage of intracellular
water is lower than in the male. The chemical composition of ICF with potassium and magnesium the principal cations, and
phosphates and proteins the principal anions
Extracellular Fluid: The total ECF volume represents approximately 20% of body weight. The ECF compartment has two major
subdivisions. The plasma volume is approximately 5% of body weight in the normal adult. The interstitial, or extravascular,
ECF volume, obtained by subtracting the plasma volume from the measured total ECF volume, accounts for approximately 15%
of body weight
The interstitial fluid is further complicated by having a rapidly equilibrating or functional component as well as several more
slowly equilibrating, or relatively nonfunctioning, components. The nonfunctioning components include connective tissue water
as well as transcellular water, which includes cerebrospinal and joint fluids. This nonfunctional component normally represents
only 10% of interstitial fluid volume (1 to 2% of body weight) and is not to be confused with the relatively nonfunctional ECF, often
called a third space, found in burns and soft tissue injuries
The normal constituents of ECF are with sodium the principal cation and chloride and bicarbonate the principal anions.
Electrolyte

Function

Distribution

Sodium (Na )

Essential role in fluid and electrolyte balance Represents about 90% of extracellular cations
accounts for half the osmolarity of ECF
Level in blood controlled by aldosterone, ANP and
Role in generation of action potentials
ADH

Potassium (K+)

Establishes resting membrane potential and Most abundant intracellular cation

essential in the repolarization phase of action Blood serum level controlled by aldosterone.
potentials in nervous and muscle tissue
Aids maintenance of fluid volume in cells
Helps regulate pH.

Calcium (Ca2+)

Roles in blood clotting, neurotransmitter release, Most abundant mineral in the body due to bone
maintenance of muscle tone, and excitability of content
nervous and muscle tissue
Principally extracellular
Blood level controlled chiefly by Parathyroid hormone
(PTH)

Chloride (Cl)

Helps balance anions in different fluid

compartments.

Most prevalent extracellular anion

Diffuses easily between interstitial space and ICF
Level controlled indirectly by aldosterone due to
relationship with sodium

Bicarbonate (HCO3) Major buffer of H+ in plasma

Second most prevalent anions in extracellular fluid
Helps maintain correct balance of anions and A small amount found in intracellular fluid
cations in ECF and ICF
Blood level controlled by kidneys which can both form
and excrete bicarbonate

Remember
If an isotonic salt solution is added to or lost from the body fluids, only the volume of the ECF is changed. The acute loss of an
isotonic extracellular solution, such as intestinal juice, is followed by a significant decrease in ECF volume and little, if any, change
in ICF volume. Fluid is not transferred from the intracellular space to refill the depleted extracellular space as long as the osmolality
remains the same in the two compartments.

Physiology

121

If water alone is added to or lost from the ECF, the concentration of osmotically active particles changes. Sodium ions account
for most of the osmotically active particles in ECF and generally reflect the tonicity of other body fluid compartments. If ECF is
depleted of sodium, water passes into the intracellular space until osmolality is again equal in the two compartments
The concentration of most other ions within the ECF compartment can be altered without significant change in the total number of
osmotically active particles, thus producing only a compositional change. For instance, a rise of the serum potassium concentration
from four to eight mEq per liter would have a significant effect on the myocardium, but it would not significantly change the effective
osmotic pressure of the ECF compartment. Normally functioning kidneys minimize these changes considerably, particularly if the
addition or loss of solute or water is gradual
An internal loss of ECF into a nonfunctional space, such as the sequestration of isotonic fluid in a burn, peritonitis, ascites, or
muscle trauma, is termed a distributional change. This transfer or functional loss of ECF internally maybe extracellular (e.g. as in
peritonitis) or intracellular (e.g. as in hemorrhagic shock). In any event, all distributional shifts or losses cause a contraction of the
functional ECF space.

Regulation of Fluid Transfer among Compartments

The transfer of fluid between vascular and interstitial compartments occurs at the capillary level and is governed by the
balance between hydrostatic pressure gradients and plasma oncotic pressure gradients
This relation is stated by the Starling equation:
Jv = Kf (DP Dp)
Where:
Jv is rate of fluid transfer between vascular and interstitial compartments, Kf is the water permeability of the capillary bed
DP is the hydrostatic pressure difference between capillary and interstitium, and
Dp is the oncotic pressure difference between capillary and interstitial fluids
Under normal circumstances, interstitial tissue pressure is low, and the DP term in the Starling equation represents the integrated
hydrostatic pressure gradient from arteriolar to venular ends of a capillary. Since interstitial fluid is protein poor, the Dp term in the
Starling equation represents the oncotic pressure of plasma proteins, principally albumin; five grams of albumin per deciliter of plasma
exerts an oncotic pressure of about 15 mm Hg.

Osmolal gap
It is the difference between measured serum osmolality and calculated serum osmolality. It is typically calculated as: OG = measured
serum osmolality (2 serum sodium + serum glucose + serum urea) Where: 2 serum sodium + serum glucose + serum urea = the
calculated serum osmolality and all measures are in mmol/L. OG = Osmolal gap. In US customary units the calculated osmolarity is:
(2 sodium) + glucose/18 + BUN/2.8
Causes of an Elevated Osmolal Gap are numerous
Ethanol intoxication
Methanol ingestion
Isopropanol ingestion
Ethylene glycol ingestion

Acidosis and Alkalosis: (USMLE Favorite)

Refer to the mechanism by which a given acid base disturbance is reached
Primary refers to the initiating process of acid base disturbance, while secondary refers to a compensatory process
Mixed acid base disturbances are combinations of two or more primary acid base disturbances
The pH of arterial blood and interstitial fluid normally ranges between 7.38 and 7.42 despite wide variations in dietary intake of acids
or alkali
The arterial pH range over which cardiac function, metabolic activity and CNS function can be maintained is narrow; the widest range
of pH values compatible with life is from 6.8 to 7.8, or an interval of one pH unit.

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USMLE Step 1 Platinum Notes

The major buffer system in ECF is the bicarbonate-carbonic acid pair. The relation between pH, bicarbonate and carbonic acid
concentrations in ECF maybe expressed according to the familiar Henderson-Hasselbalch equation:
pH = pK + log HCO3/ H2CO3
Where pK is the carbonic acid dissociation constant, HCO3 is the plasma bicarbonate concentration and H2CO3 is the plasma carbonic
acid concentration. The H2CO3 concentration is given by a PaCO2, where is the CO2 solubility constant and has a value of 0.0301, and
PaCO2 is the arterial carbon dioxide tension. Therefore, the Henderson-Hasselbalch equation becomes
pH = 6.1 + log HCO3/0.03 PCO2
Primary changes in the numerator (blood bicarbonate concentration) refer to primary metabolic changes, while primary changes in
the denominator (blood carbon dioxide tension) refer to primary respiratory changes
Proton shifts: Between the ECF and ICF stabilize the plasma pH against acute fluctuations. But the ultimate maintenance of pH
balance requires that input of acid or base into the body be matched by output of acid or base so that the HCO3/H2CO3 ratio and the
total bicarbonate content in the ECF remain constant. The cardinal systems involved in these external processes are the kidneys for
bicarbonate balance, and the lungs for CO2 balance.

The Serum Anion Gap

Sodium is the principal cation in extracellular fluids. The sum of plasma chloride plus bicarbonate concentrations is less than the serum
sodium concentration; the remaining anions required for electroneutrality, generally not reported with routine serum electrolyte
measurements, are referred to as unmeasured anions, or as the serum anion gap. A convenient formula for calculating the serum
anion gap is the following:
Serum anion gap = Na+ (Cl + HCO3)
Where Na+, Cl and HCO3 are the serum sodium, chloride and bicarbonate concentrations, respectively
The anion serum gap includes primarily phosphates and sulfates derived from tissue metabolism, lactate and keto acids arising from
incomplete combustion of carbohydrates and fatty acids, and negatively charged protein molecules, principally albumin. The normal
value for unmeasured anions, or the serum anion gap, is 10 to 12 mEq per liter; albumin and other proteins normally account for about
half the anion gap
An increased serum anion gap generally indicates the presence of metabolic acidosis
A reduced serum anion gap provides an index to certain other disorders
The anion gap will be reduced if the sodium concentration falls while the chloride plus bicarbonate concentrations are unchanged
or, in other words, when the concentration of another cation in serum is increased while the serum osmolality remains normal. This
may occur in multiple myeloma of the immunoglobulin G (IgG) variety if the myeloma proteins are cationic at pH 7.4. Hyperviscosity
syndromes also may result in a reduced anion gap.

The Urinary Anion Gap

The urinary anion gap, defined as:
Urinary anion gap = (Na+ + K+) Cl
It is useful in evaluating patients with hyperchloremic acidosis. The test provides an approximate index to urinary NH4+ excretion, as
measured by a negative urinary anion gap, that is, urinary (Na+ + K+) is less than urinary Cl. Thus, in hyperchloremic metabolic acidosis,
a normal renal response would be a negative urinary anion gap, generally in the range of 30 to 50 mEq per liter. In such an instance,
the hyperchloremic acidosis is probably due to gastrointestinal losses rather than a renal lesion. In contrast, a positive urinary anion
gap implies a renal tubular disorder.

Remember
Water constitutes roughly 60% of body weight
Na, Cl, HCO3 are predominantly in ECF
K, P, Mg are predominantly in ICF

Measurement of Body Fluids

Total Body water
ICF
ECF

About 60% of body weight

40%
20%

Physiology
Total body water
ECF
Plasma volume

Tritrated water, Deuterium Oxide, Antipyrine

Inulin, Mannitol
Evans Blue, radiolabelled albumin

ECF is rich in: Na+

ICF is rich in: K+
Endolymph is rich in: K+

Anion Gap: (Repeat)

Anion gap = unmeasured ions in plasma

Normal cations in plasma: Na+, K+, Ca++, Mg++
Normal anions in plasma: Cl, HCO3, albumin, phosphate, lactate
Sum of positive and negative charges is equal
Anion gap = (Na+ + K+ ) (Cl + HCO3)
Normal AG = 1012 mmol/l

Terms Frequently Asked

Endocytosis: Substance transported into cell by infoldings of cell membrane around substance and internalizing it
Pinocytosis: Engulfing liquid substances by enfolding of cell membrane
Phagocytosis: Engulfing soild substances by enfolding of cell membrane
Exocytosis: Reverse of endocytosis
Emiocytosis: Excretion of specific hormones and granules by cell is emiocytosis
Requires calcium
Transcytosis: Vesicular transport within cell. (epithelial cells of intestine)

Proteins in Vesicular Transport

AP 1 clathirin: Involved in transportation from Golgi bodies to lysosomes
AP 2 clathirin: Involved in transportation to endosomes
CO PI: Coating proteins in vesicles for transportation between endoplasmic reticulum and Golgi apparatus
CO PII: Coating proteins in vesicles for transportation between endoplasmic reticulum and Golgi apparatus
Dynamin: Vesicle formation from Golgi complex and cell membrane
Docking protein: V snare protein and T snare proteins present on target cells

Cutaneous Vascular Responses

White reaction:
Appearance of pale stroke line when pointed object is drawn lightly over skin
Due to precapillary sphincter contraction
Triple response:
1. Red reaction: Red line appearing at site of injury
Due to dilatation of precapillary sphincter. (histamine and bradykinin)
2. Flare: Diffuse irregular outside red reaction due to dilatation of arteriole and precapillary sphincter
3. Wheal: Swelling or localized edema within area of flare
Due to increased capillary permeability
Dermatographia: Striking triple response on touching the skin

123

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USMLE Step 1 Platinum Notes

Muscle Contraction
The skeletal muscle fibers are cylindrical in shape.
The length varies from 1 mm to 15 cm. The width varies from 10 microns to 80 microns.
Each muscle fiber has a thick sarcolemma
The cytoplasm is acidophilic and granular and is composed of Actin, Myosin and Tropomyosin.
The Cytoplasm contains longitudinal Myo fibrils or Sarcostyles which are striated transversely.
Each Myofibril or Sarcostyles is formed of smaller filaments called as Myofilaments.
The Myofilaments are of two types:
Thin or Actin Filaments
Thick or Myosin Filaments
The Transverse striations are due to presence of dark and light bands
The Sarcomere is the unit of contraction
It is formed of Actin and Myosin
Actin is present in light band and Myosin is present in the dark band

Remember

A: Anisotropic; broad, dark; remains constant in width despite degree of contraction

I: Isotropic; broad, light; only thin filaments (no thick); narrows during contraction
Z: (Zwischenscheiben) bisects I band; drawn together during contraction
H: (Heller) light band bisects A band; only thick filaments (no thin); narrows during contraction
M: (Mittelscheibe) denser band bisects H band.

Heads of Myosin contain actin binding site and possess ATPase activity
Tropomyosin is a relaxing protein
Troponin I inhibits interaction of myosin with actin
Troponin T binds other troponins to tropomyosin
Troponin C has binding sites for calcium which initiates contraction
Tropomyosin covers the active sites of actin
RMP of skeletal and cardiac muscle is 90 mV
Repolarization is due to pottasium efflux
Depolarization is due to sodium influx
Treppe or stair case phenomenon is due to increased availability of Calcium for binding to troponin C
Rheobase is the minimum amount of current to cause excitation
Chronaxie is the shortest duration for a stimulation to excite tissue with a current strength twice the rheobase
Newborns have longer chronaxies
Skeletal muscles have shorter chronaxies
Cold lenthens chronaxie
Vagal stimulation shortens chronaxie
For smooth muscle contraction presence of cellular calcium is essential to cause contraction
Force of muscle contraction is independent of amplitude of action potential
Nerve fibers and anesthesia:
SUSCEPTIBILITY: Type C > Type B > Type A
Nerve fibers and pressure
SUSCEPTIBILITY: Type C < Type B < Type A

Physiology

125

Golgi Tendon Organ

It is an encapsulated sensory receptor

Detects muscle tension
Involved in inverse stretch reflex
325 muscle fibers on an average are attached to golgi tendon organ
Impulses are transmitted by type nerve fibers
It is inhibitory and protective
Golgi tendon reflex is bisynaptic.

Muscle Spindle
312 mm long structure containing intrafusal muscle fibers enclosed in capsule of connective tissue
It is a receptor for myotactic or stretch reflex
Central zone has no actin and myosin
Peripheral zone has actin and myosin
Are of two types:
Intrafusal
Extrafusal
Intrafusal are of two types:
Nuclear bag and
Nuclear chain fibers
Two types of sensory nerve endings are
Primary annulospiral endings
Secondary flower spray endings

Neurapraxia : No anatomic disruption

Axonometesis : Axon and myelin disruption
Neurontemesis : Complete division of nerve
Degeneration distal to cut end : Wallerian degeneration

The skeletal muscle fibers are two types: Red Fibers and white fibers
Red Fibers

White Fibers

Have irregular striations

Have regular striations

Have central nuclei

Have peripheral nuclei

Have rich vascular supply

Have poorer blood supply

Nonfatiguable

Are fatiguable

Are poor in mitochondria, Myoglobin, fats

Are rich in Myoglobin, fats

Example : Skeletal muscle

Examples: diaphragm, muscles of eye, mastication
They react quickly, with brief, forceful contractions, Their contraction in response to nervous stimulation is slow
but cannot sustain contraction for long periods
and steady, resulting in their designation as slow fibers
They are thus termed fast fibers

Red Blood Cell

Mature Red cell is 8 micrometer in diameter
Mature Red cell is anucleate

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USMLE Step 1 Platinum Notes

Mature Red cell is discoid in shape

Mature Red cell is pliable
Average life of red cell is 100120 days
Hematopoiesis is the process by which formed elements of the blood are produced
In the BM (Bone Marrow) first morphologically recognizable precursor is the PRO normoblast Erythropoietin is produced by the
peritubular cells within the kidney
There is daily replacement of 0.81% of all circulating red cells
Hematopoiesis is the process by which formed elements of the blood are produced. Stem cells are capable of producing all classes
of cells
In the BM (Bone Marrow) first morphologically recognizable precursor is the PRO normoblast. This cell can undergo 45 cell divisions
that result in production of 1632 mature red cells
Erythropoietin (EPO) is produced by the peritubular cells within the kidney. These cells are specialized epithelial cells. A small
amount of EPO is also produced by Hepatocytes.

Cardiovascular Physiology
Artery/Arteriole Resistance Vessel
Capillary (Mx Surface area) Exchange Vessel
Vein Capacitance Vessel
BP = Cardiac output x Peripheral resistance
BP measured by sphygmomanometer is less than arterial BP actually
Small cuff = High BP
Thick walled vessels = High BP
Obesity = High BP
Pulse Pressure = Systolic pressure Diastolic Pressure
Mean Arterial Pressure = Diastolic Pressure +1/3 of Pulse Pressure
Ventricular End Diastolic Volume: Volume of blood in ventricular cavity at the end of atrial contraction (n) = 120 ml. Determines
Preload
Ventricular End Systolic Volume: Volume of blood in ventricular cavity at the end of ejection (n) = 40 ml
Stroke Volume: Volume of blood ejected with each heart beat. CO/HR (n) = 70 80 ml
Ejection Fraction: Ratio of stroke volume to End Diastolic Volume (SV/EDV) (n) = 50 70%
Cardiac Output: Volume of blood expelled from one side of heart per minute
Can be detected by:
Ficks principle
Echocardiography
Thermodilution
Cardiac index = CO/Body surface area
Normal cardiac index IS 3.2

FrankStarling Law
This principle illustrates the relationship between cardiac output and left ventricular end diastolic volume (or the relationship
between stroke volume and right atrial pressure.)

Physiology

127

Determinant of cardiac output

The Frank-Starling principle is based on the length-tension relationship within the ventricle. If ventricular end diastolic volume
(preload) is increased it follows that the ventricular fiber length is also increased, resulting in an increased tension of the muscle
In this way, cardiac output is directly related to venous return the most important determining factor of preload. When heart rate
is constant, cardiac output is directly related to preload (up to a certain point.)
An increase in preload will increase the cardiac output until very high end diastolic volumes are reached. At this point cardiac
output will not increase with any further increase in preload, and may even decrease after a certain preload is reached
Also, any increase or decrease in the contractility of the cardiac muscle for a given end diastolic volume will act to shift the curve
up or down, respectively.

Frank-starling curve

Regional Blood Flow

Blood flow is controlled mainly by arterioles
Velocity of blood is maximum in large veins

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USMLE Step 1 Platinum Notes

Blood flow of liver > kidney > brain > heart

Carbon dioxide produces vasodilation in brain
Exercise produces venoconstriction in splanchnic circulation
Exercise produces increase in coronary circulation
Hypoxia produces vasoconstriction in pulmonary circulation
PGE1, PGI2 produce renal vasodilation.

Myocardial Action Potential

Phases of myocardial action potential

Phase 0 rapid depolarization
Rapid sodium influx
These channels automatically deactivate after a few ms
Phase 1 early repolarization
Efflux of potassium
Phase 2 plateau
Slow influx of calcium
Phase 3 final repolarization
Efflux of potassium
Phase 4 restoration of ionic concentrations
Resting potential is restored by Na+/K+ ATPase
There is slow entry of Na+ into the cell decreasing the potential difference until the threshold potential is reached, triggering a
new action potential

Physiology

129

Ventricular Muscle

Phase 0
Phase 1
Phase 2
Phase 3

Membrane Depolarization
Rapid Repolarization
Slow Repolarization
Rapid Repolarization

permeability to Na
permeability to Na, permeability to K
permeability to Ca
Inactivation of Ca channels, permeability to K

Pacemaker Cells

Slow upstroke Action Potential

Smaller magnitude of Action Potential
No Fast Sodium channels
Spontaneous Depolarization

Inotropic State: (Myocardial Contractility)

A number of factors determine the level of ventricular performance at any given ventricular end-diastolic volume
Adrenergic Nerve Activity: The quantity of norepinephrine released by adrenergic nerve endings in the heart is determined by
the adrenergic nerve impulse traffic. This mechanism is the most important one that acutely modifies myocardial contractility
under physiologic conditions
Circulating Catecholamines: When stimulated by adrenergic nerve impulse, the adrenal medulla releases catecholamines, which,
when they reach the heart, augment both heart rate and myocardial contractility
The Force-Frequency Relation: The position of the myocardial force-velocity curve is also influenced by the rate and rhythm of
cardiac contraction; e.g. ventricular extrasystoles result in postextrasystolic potentiation, presumably by increasing the quantity
of Ca2+ that enters the cardiac cell. The contractility of the normal (but not of the failing) heart is augmented by an increase in
frequency of contraction
Exogenously Administered Inotropic Agents: Isoproterenol, dopamine, dobutamine, and other sympathomimetic agents,
cardiac glycosides, Ca2+, amrinone, milrinone, and other phosphodiesterase inhibitors all improve the myocardial forcevelocity relation and therefore maybe used to stimulate ventricular performance
Physiologic Depressants: Included among these are severe myocardial hypoxia, ischemia, and acidosis. Acting either singly
or in combination, these influences depress the myocardial force-velocity curve and left ventricular work at any given ventricular
end-diastolic volume
Pharmacologic Depressants: These include many antiarrhythmic drugs such as procainamide and disopyramide; calcium
antagonists such as verapamil; beta blockers; and large doses of barbiturates, alcohol, and general anesthetics as well as
many other drugs
Loss of Myocytes: When a sufficiently large portion of ventricular myocardium becomes nonfunctional or necrotic, as occurs
transiently during ischemia and permanently in myocardial infarction total ventricular performance at any given level of enddiastolic volume becomes depressed.

Exercise: Physiological Change

Blood pressure
Systolic increases, diastolic decreases
Leads to increased pulse pressure
In healthy young people the increase in MABP is only slight
Cardiac output
Increase in cardiac output maybe 35-fold
Results from venous constriction, vasodilation and increased myocardial contractibility, as well as from the maintenance of right
atrial pressure by an increase in venous return
Heart rate up to 3-fold increase
Stroke volume
Up to 1.5-fold increase

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USMLE Step 1 Platinum Notes

Central Venous Pressure

Normal Pressure: 2 cm H2O to 12 cm H2O
Causes of CVP: Noncardiogenic shock
Causes of CVP: Heart Failure, Expansion of Blood volume, PEEP

Isometric Contraction
Mitral and tricuspid valve close (c-c)
Aortic and pulmonary valve open

Isometric Relaxation
Mitral and tricuspid valve open
Aortic and pulmonary valve close

Normal coronary blood flow is 250 ml at rest

It is 5% of cardiac output
Blood flow to left ventricle is twice that of right ventricle
Atrial blood flow is half of ventricular flow
Most of coronary blood flow occurs in diastole

Chrontropic effect
Ionotropic effect
Dromotropic effect
Bathmotropic effect

Effect on heart rate

Effect on force of contraction
Effect on conduction of impulses through heart
Effect on excitability of heart

ECG and JVP

Physiology
SA node discharges most rapidly
SA node is located sub epicardially
Pacemaker cells are present in SA node
AP of SA and AV node are due to calcium
RMP of myocardial fibers is 90 mV
Depolarization is from endocardium to epicardium
Repolarization is also from endocardium to epicardium
Speed of conduction is fastest in Purkinje fibers
Speed of conduction is least in AV node

Waves of normal ECG

Normal ECG
Wave/Segment

Cause

Duration (Second)

P wave

FromTo

Atrial depolarization

0.1

QRS complex

Ventricular Depolarization

0.08 0.10

T wave

Ventricular Repolarization

0.2

P R interval

Onset of P wave to onset of Q wave

0.18 (0.12 to 0.2)

Q T interval

Onset of Q wave and end of T wave

0.4 0.42

Intervals in ECG

131

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USMLE Step 1 Platinum Notes

The 12 conventional ECG leads record the difference in potential between electrodes placed on the surface of the body
These leads are divided into two groups:
Six extremity (limb) leads and six chest (precordial) leads. The extremity leads record potentials transmitted onto the frontal plane
and the chest leads record potentials transmitted onto the horizontal plane
The six extremity leads are further subdivided into three bipolar leads (I, II and III) and three unipolar leads (aVR, aVL and aVF)
Each bipolar lead measures the difference in potential between electrodes at two extremities:
Lead I left arm-right arm voltages
Lead II left leg-right arm, and
Lead III left leg-left arm
The six chest leads are unipolar recordings obtained by electrodes in the following positions:
Lead V1, fourth intercostal space, just to the right of the sternum;
Lead V2, fourth intercostal space, just to the left of the sternum;
Lead V3, midway between V2 and V4;
Lead V4, midclavicular line, fifth intercostal space;
Lead V5, anterior axillary line, same level as V4; and
Lead V6, midaxillary line, same level as V4 and V5.

Remember
First-degree AV block, more properly termed prolonged AV conduction, is classically characterized by a PR interval > 0.20s
Second-degree heart block (intermittent AV block) is present when some atrial impulses fail to conduct to the ventricles
Mobitz type I second-degree AV block
(AV Wenckebach block)
It is characterized by progressive PR interval prolongation prior to block of an atrial impulse
This type of block is almost always localized to the AV node and associated with a normal QRS duration, although bundle
branch block may be present
In Mobitz type II second-degree AV block
Conduction fails suddenly and unexpectedly without a preceding change in PR intervals
It is generally due to disease of the His-Purkinje system and
It is most often associated with a prolonged QRS duration
Third-degree AV block
It is present when no atrial impulse propagates to the ventricles
If the QRS complex of the escape rhythm is of normal duration, occurs at a rate of 40 to 55 beats per minute, and increases with
atropine or exercise, AV nodal block is probable
Congenital complete AV block is usually localized to the AV node
Refractoriness is a property of cardiac cells that defines the period of recovery that cells require after being discharged before
they can be reexcited by a stimulus.
The absolute refractory period is defined by that portion of the actionpotential during which no stimulus, regardless of its
strength, can evoke another response.
The effective refractory period is that part of the action potential during which a stimulus can evoke only a local, nonpropagated
response.
The relative refractory period extends from the end of the effective refractory period to the time that the tissue is fully recovered.
During this time, a stimulus of greater than threshold strength is required to evoke a response, which is propagated more slowly
than normal.

Physiology

133

Heart Sounds
Heart sounds

Occurs during

Cause

Characteristics

First

Isometric contraction and ejection Closure of AV valves (Mitral Tricuspid)

period

Second

Protodiastole and part of isometric Closure of semilunar valves (Aortic, Short, sharp and high pitched.
relaxation
Pulmonary)
Resembles the word DUBB

Long, soft and low pitched. Resembles

the word LUBB

Third Heart Sound is due to Rapid Ventricular filling

Fourth Heart sound
It is due to ventricular distension caused by forceful atrial contraction
Heard during ventricular filling phase
Correlates with second filling phase

Waves in JVP

JVP waves

a wave First positive wave and its due to atrial systole

x wave Fall of pressure in atrium, coincides with atrial diastole
c wave It is due to rise in atrial pressure during isometric contraction during which the AV valves bulges into atrium
x1 wave Occurs during ejection period, when AV ring is pulled towards ventricles causing distension of atria
v wave Occurs during isometric relaxation period or during atrial diastole
y wave Due to opening of AV valve and emptying of blood into ventricle.

Pathological CVP Wave forms:

In atrial fibrillation, a waves will be absent, and in atrioventricular disassociation, a waves will be dramatically increased
(cannon waves) as the atrium contracts against a closed tricuspid valve
In tricuspid regurgitation, the c wave and x descent will be replaced by a large positive wave of regurgitation as the blood
flows back into the right atrium during ventricular contraction. This can elevate the mean central venous pressure, but it is not an
accurate measurement. A better way of estimating CVP in this case would be to look at the pressured between the regurgitation
waves for a more accurate mean
In cardiac tamponade, all pressure will be elevated, and the y descent will be nearly absent.

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USMLE Step 1 Platinum Notes

Reflexes
The Bainbridge reflex, also called the atrial reflex
It is an increase in heart rate due to an increase in central venous pressure
Increased blood volume is detected by stretch receptors located in both atria at the venoatrial junctions
The Bainbridge reflex and the Baroreceptor reflex act antagonistically to control heart rate
The baroreceptor reflex acts to decrease heart rate when blood pressure rises
When blood volume is increased, the Bainbridge reflex is dominant
When blood volume is decreased, the Baroreceptor reflex is dominant
The oculocardiac reflex
Also known as Aschner phenomenon
It is a decrease in pulse rate associated with traction applied to extraocular muscles and/or compression of the eyeball
The reflex is mediated by nerve connections between the trigeminal cranial nerve and the vagus nerve of the parasympathetic
nervous system.

Respiratory Physiology
Number of alveoli in man: 300 million
Carbon dioxide is primarily transported in arterial blood as bicarbonate
Oxygen delivery to tissues depends on
Cardiac output
Hb
Affinity of Hb for oxygen
Normal value of PO2 is: 80 mm Hg
Arterial CO2 Level is: 40 mm Hg

Physiology of Respiration

During inspiration intrapleural pressure becomes more negative

Respiration stops in late expiration because of dynamic compression of airways
Total lung capacity depends on compliance
Nitrogen wash out method detects functional residual capacity
FRC is not estimated by spirometry
Slow and deep breathing are the most economical way of breathing.

The Respiratory neurons of the medulla are responsible for the main neural control of breathing. This control center is composed of
two groups of respiratory neurons:
The dorsal respiratory group (DRG) that consists primarily of inspiratory neurons that connect with phrenic motor neurons; and
The ventral respiratory group (VRG) that contains a mixture of both I neurons and expiratory (E) neurons.
Selective electrical stimulation of either I or E neurons in the ventral group will result in inspiration or expiration, respectively. The VRG,
however, is especially important in sending expiratory signals to the abdominal group of muscles to increase pulmonary ventilation
during times of increased respiratory drive. The basic medullary pattern of breathing can be modified by efferent activity arising in the
apneustic and pneumotaxic centers of the pons, as well as by motor impulses originating in the cerebral cortex
Transection of various brainstem structures and transection of the vagus nerves reveals information about the neural control
of breathing
Transection of the brainstem at the caudal end of the pons allows spontaneous respiration to continue, but the pattern of
breathing is irregular. This indicates that the rhythmic, automatic control of breathing originates at some point inferior to the pons
Transection of the brainstem below the medulla causes an immediate halt in breathing, reinforcing the concept of medullary
control as the primary stimulus for ventilation.

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135

Transection of the brainstem rostral to the pons results in normal breathing whereas transection at the caudal border of the
pons causes irregular breathing. This finding indicates that the pons exhibits a modifying influence on the medulla. In fact, if the
pontine pneumotaxic center (composed of the medial parabrachial and the Klliker-Fuse nuclei) is damaged, respiration becomes
slower and the tidal volume becomes greater. These nuclei contain both inspiratory and expiratory neurons that modify the
medulla. If both vagi are cut, the depth of inspiration is markedly increased. This occurs because stretching of the lungs during
inflation normally stimulates afferent pulmonary vagal fibers
These afferent impulses limit inspiratory impulses to slow inspiration. Without intact vagi, prolonged inspiration occurs.

Lung volumes

The All Important Respiratory Volumes

Measurement

Value (Male/Female)

Calculation

Description

Total lung capacity = 6.0/4.7 L

(TLC)

= IRV + Vt + ERV + RV

The volume of air contained in the lung at the end of

maximal inspiration
Depends on lung compliance

Vital capacity (VC)

= IRV + Vt + ERV

The amount of air that can be forced out of the lungs after
a maximal inspiration. (Rohtak 97)

= 4.8/3.6 L

Forced vital capacity = 4.8/3.7 L

(FVC)

The amount of air that can be maximally forced out of the

lungs after a maximal inspiration. Emphasis on speed.

Tidal volume (Vt)

= 500/390 mL IC-IRV

Residual volume (RV)

= 1.2/0.93 L

Expiratory reserve volume (ERV)

= 1.2/0.93 L

Inspiratory reserve volume (IRV)

= 3.3/2.3 L

Functional residual capacity (FRC) = 2.4/1.9 L

Inspiratory capacity (IC)
= 3.8/2.7 L

Measured IRV =
VC - (TV + ERV)
= ERV + RV
= TV + IRV

The amount of air breathed in or out during normal

respiration. The volume of air an individual is normally
breathing in and out.
The amount of air left in the lungs after a maximal
exhalation
The amount of air that is always in the lungs and can never
be expired (i.e. the amount of air that stays in the lungs after
maximum expiration).
The amount of additional air that can be pushed out after
the end expiratory level of normal breathing. (At the end of
a normal breath, the lungs contain the residual volume plus
the expiratory reserve volume, or around 2.4 liters. If one then
goes on and exhales as much as possible, only the residual
volume of 1.2 liters remains).
The additional air that can be inhaled after a normal tidal
breath in. The maximum volume of air that can be inspired in
addition to the tidal volume.
The amount of air left in the lungs after normal expiration.
The maximal volume that can be inspired following a
normal expiration.

136

USMLE Step 1 Platinum Notes

Anatomical dead space

= 150/120 mL

Physiologic dead volume

= 155/120 mL

The volume of the conducting airways. Measured with

Fowler method.
The anatomic dead space + alveolar dead space
Under normal conditions equal to anatomic dead space.

Lung volumes

Intra-alveolar Pressure during Inspiration and Expiration

As the external intercostals and diaphragm contract, the lungs expand. The expansion of the lungs causes the pressure in
the lungs (and alveoli) to become slightly negative relative to atmospheric pressure. As a result, air moves from an area of
higher pressure (the air) to an area of lower pressure (our lungs and alveoli). During expiration, the respiration muscles relax
and lung volume descreases. This causes pressure in the lungs (and alveoli) to become slight positive relative to atmospheric
pressure. As a result, air leaves the lungs.

Spirometry
Conventionally, a spirometer is a device used to measure timed expired and inspired volumes, and from these we can calculate how
effectively and how quickly the lungs can be emptied and filled. The measurements that are usually made are as follows:
VC (vital capacity) is the maximum volume of air which can be exhaled or inspired during either a forced (FVC) or a slow (VC)
maneuver
FEV1 (forced expired volume in one second) is the volume expired in the first second of maximal expiration after a maximal
inspiration and is a useful measure of how quickly full lungs can be emptied
FEV1/VC is the FEV1 expressed as a percentage of the VC or FVC (whichever volume is larger) and gives a clinically useful index of
airflow limitation
FEF 2575% is the average expired flow over the middle half of the FVC maneuver and is regarded as a more sensitive measure of
small airways narrowing than FEV1
PEF (Peak expiratory flow) is the maximal expiratory flow rate achieved and this occurs very early in the forced expiratory maneuver.
Ventilation Perfusion Ratio

Ideally Ventilation = Perfusion, i.e. V/Q = 1

Apex of Lung V > Q Wasted Ventilation
Base of Lung V < Q Wasted Perfusion
With exercise V/Q approaches zero

Pulmonary Circulation
It is a Low Resistance
High Compliance Bed
Hypoxia produces pulmonary vasoconstriction. (unique feature)

Physiology

137

Response to High Altitude

Ventilation (EARLIEST CHANGE)

Sensitivity of central receptors
Response of carotid bodies
Erythropoietin
2 3 DPG
Mitochondria
Renal excretion of Bicarbonate
Respiratory alkalosis
Pulmonary edema when occurs is due to increased pulmonary capillary pressure

A number of physiologic changes occur in a person living at high altitude. The diminished barometric pressure at high altitude
causes alveolar hypoxia and arterial hypoxia. Pulmonary vasoconstriction occurs in response to alveolar hypoxia; therefore,
the diameter of the pulmonary vessels would be greater in the brother living at sea level. Increased erythropoietin production
(choice B), caused by arterial hypoxia, leads to increases in hematocrit in people living at high altitude
Mitochondrial density increases in people chronically exposed to the hypoxemia caused by living at high altitude
At high altitudes, the ventilation rate increases, causing a respiratory alkalosis. The kidney then compensates by increasing
the excretion of HCO3
Increasing the rate of respiration is a very useful adaptation to the hypoxic conditions of high altitude. The primary
stimulus is the hypoxic stimulation of peripheral chemoreceptors.
Type I cells or type I pneumocytes
These are squamous epithelial cells that make-up 97% of the alveolar surfaces
They are specialized to serve as very thin (often only 25 nm in width) gas-permeable components of the blood-air barrier
Type II cells
Are also called type II alveolar cells, type II pneumocytes, great alveolar cells, and alveolar septal cells, cover the
remaining 3% of the alveolar surface
They are interspersed among the type I cells, to which they attach by desmosomes and occluding junctions
Type II cells are roughly cuboidal with round nuclei
Type II cells are secretory cells secreting pulmonary surfactant.
Alveolar macrophages
Known also as dust cells, these large monocyte-derived representatives of the mononuclear phagocyte system are found
both on the surface of alveolar septa and in the interstitium
They also phagocytose blood cells that enter the alveoli as a result of heart failure
These alveolar macrophages, which stain positively for iron pigment (hemosiderin), are thus designated heart failure cells
Clara cells
Are nonmucous and nonciliated secretory cells found in the primary bronchioles of the lungs
Main functions of Clara cells are to protect the bronchiolar epithelium by secreting a small variety of products, including
Clara cell secretory protein (CCSP) and a component of the lung surfactant
They are also responsible for detoxifying harmful substances inhaled into the lungs.
Surfactant

It is (Dipalmitoyl Lecithin)
It is secreted by Type II Pneumocyte
Synthesis begins at 1618 weeks of gestation
Maintains alveolar integrity
Breaks structure of water in alveoli
Deficiency causes Hyaline Membrane Disease

138

USMLE Step 1 Platinum Notes

Smoking surfactant production

Surfactant:
Surface Tension
Compliance
Prevents pulmonary edema
Glucocorticoids accelerate surfactant production
It is used therapeutically nowadays
Deficiency Causes
IRDS
HMD
Patchy atelectasis
Pulmonary alveolar proteinosis

Nernest Equation/Chloride shift

Bicarbonate diffuses intoplasma and same quantity of chloride diffuses into RBC in venous circulation
In place of bicarbonate chloride moves into RBC from plasma
Occurs in one second
Bohr Effect
Affinity of Oxygen for Hb decreases with fall in pH
Haldane effect
It is reverse of Bohr effect
Binding of Oxygen with hemoglobin displaces carbon dioxide from blood
Deoxygenated Hb binds more H+ than oxy hemoglobin
Hering-Bruer reflex: Overinflation of lung causes stretch receptors in bronchi and bronchioles to send inhibitory signals to
inspiratory center through vagus. (Distension of lung causes slowing of respiratory rate.)
Heads Reflex Inflation of lungs induces more inflation
Heads Reflex is due to irritant receptors in lungs
J receptor reflex: J receptors are present in close association with pulmonary capillaries
On stimulation of j receptors, apnea followed by hyperapnea, bradycardia and hypotension occurs. Bronchospasm also occurs.
Davenport diagram is used to determine type and severity of Acidosis/Alkalosis
Siggard-Anderson Nomogram is used for calculating abnormalities of acid base balance. (Plasma Bicarbonate)

Control of Respiration

Inspiratory center
Expiratory center
Pneumotaxic center
Apneustic center

Dorsal respiratory group of Neurons: Inspiration

Ventral respiratory group of Neurons: Expiration
Peripheral chemoreceptors are located in Carotid and Aortic bodies
Transection of brainstem produces irregular and gasping respiration. (Less smooth respiration)
Damage to pneumotaxic center causes slow and deep respiration
Damage to vagi nerves causes increase in depth of inspiration
Only hypercapnia not Hypocapnia stimulates receptors
Respiratory center is inhibited during swallowing and vomiting.

Dorsal Medulla
Ventral Medulla
Pons (DORSAL)
Pons

Physiology

Oxygen Hb Dissociation Curve

Oxygen Hb dissociation curve

Oxygen Hb dissociation curve is S shape or sigmoid shape

Factors influencing oxygen - Hb dissociation

139

140

USMLE Step 1 Platinum Notes

To left ()

To right ()

CO
HbF
PCO2
2, 3-DPG
Temp

[H+] , pH
Temp
PCO2
2, 3-DPG

Additional
Shift to left

Shift to right

Increase pH

Decrease pH

Decrease in temp

Increase in temp

Fetal blood
Oxygen affinity of Hb

Excess of 2, 3 DPG

Increase PCO2 (Bohr effect)

Sickle cell Hb
Shock
RDS
CHF

In anemia 2, 3 DPG concentration increases

2, 3 DPG unloads oxygen to tissues

In a healthy adult, 24 hour production of CO2 is about 330 liters

Diffusion capacity for carbon dioxide as compared to that of O2 is 20 times
Average area of the alveolar walls in contact with capillaries in both lungs is about 70 sq m
Diffusion capacity of lungs for CO2 is 10 30 ml/min/mm Hg
Normal composition of venous blood is PO2 40 mm Hg, PCO2 46 mm Hg and Hb saturation 75%
Peak expiratory flow rate is 400 500 L/mt
The presence of Hb increases the O2 carrying capacity of the blood by 70 fold
Intrapleural pressure (recoil pressure) required to prevent collapse of the lung 4 mm Hg in presence of surfactant
Intrapleural pressure at the end of deep inspiration is 4 mm Hg
Intrapleural pressure during expiration is 2 mm Hg
Hypoxia causes pulmonary vasoconstriction but cerebral vasodilation.
In lungs Angiotensin I is converted into Angiotensin II
Transport of CO2 is maximum in the form of bicarbonate.

Never to be Forgotten
Respiratory Acidosis
Respiratory Alkalosis
Metabolic Acidosis
Metabolic Alkalosis

CO2

No change
No change

pH

HCO3

PCO2 is the most important variable in regulation of ventilation

Central chemoreceptors respond to changes in [H+]
Peripheral chemoreceptors respond to changes in PO2, PCO2, H+ conc. of arterial blood

Physiology

141

Clinically Important
Cheyne-Stokes breathing is characterized by irregular pattern of respiratory dysfunction (apnea and hyper apnea) suggests
that central respiratory mechanism are no longer functioning adequately
Opium poisoning, uremia, CCF, Hypoxia.
Apneustic breathing is seen after head trauma and is characterized by inspiratory breath holding that lasts many seconds,
followed by brief exhalations.
Biots breathing is seen in some patients with CNS disease (e.g. meningitis). It consists of periods of normal breathing interrupted
suddenly by periods of apnea.
Hysterical breathing may produce hyperventilation, i.e. rapid, intense breathing that causes the PaCO2 to decrease
Kussmaul breathing occurs in diabetic coma and consists of continuous, rapid, deep breathing seen in Diabetic ketoacidosis,
uremia
Ondines curse loss of automatic respiratory control
Apnea: Cessation of respiration

Cyanosis

Reduced Hb > 4 gm/dl

Oxygen saturation < 85%
Methemoglobin > 1.5 gm/dl
Sulfhemoglobin > 0.5 gm/dl

Difference in Hb and myoglobin

Shift to right

Difference between Obstructive Lung Disease and Restrictive Lung Disease

Obstructive lung disease

Restrictive lung disease

TLC

TLC

RV

RV

TV

TV

VC

VC

FEV1

FEV1

FVC

FVC

FEV1/FVC

FEV1/FVC

PaCO2

PaCO2 (N )or

142

USMLE Step 1 Platinum Notes

Carbon Monoxide Poisoning Causes: (USMLE Favorite)

Carbon monoxide has approximately 240 times the affinity for hemoglobin than does oxygen. In a sense, the hemoglobinCO dissociation curve is shifted very far to the left compared to the hemoglobin-O2 dissociation curve. This means that the
binding of hemoglobin to carbon monoxide is virtually irreversible. (The carbon monoxide that cigarette smokers inhale
is cleared only when senescent red cells are phagocytized in the spleen and the hemoglobin is degraded.) In addition, the
carbon monoxide shifts the hemoglobin-O2 dissociation curve to the left, making the unloading of O2 to the tissues very
difficult. When too much hemoglobin is tied up with carbon monoxide, the person dies. The carbon monoxide-hemoglobin
complex has a bright red color; a distinctive feature of carbon monoxide poisoning that can be helpful either at autopsy or in
living patients is that this color makes the skin and organs also appear bright cherry red
Normal PO2
Oxygen saturation
Metabolic Acidosis
Cherry red skin discoloration
CO has 210 times more affinity for oxygen than hemoglobin
Form of Hypoxia produced is anemic hypoxia
Oxygen dissociation curve shifts to left

Hypoxia

Hypoxic Hypoxia: High altitude, Respiratory diseases Test by: PaO2

Anemic Hypoxia: Anemia, CO Poisoning: Test by Oxygen content (HB%)
Stagnant Hypoxia: Cardiogenic shock: Test by A-V difference of O2
Histotoxic Hypoxia: Cyanide poisoning: Test by A-V difference/ PO2 of venous blood

Low arterial PO2

Oxygen affinity also decreases
Response to oxygen is good
Hypoxic hypoxia is the mc type
Causes rise in pulmonary arterial pressure
Carbon dioxide is the most potent stimulus for respiration
Carbon dioxide affects respiratory center by influence on H+ concentration in CSF
CO2 causes:
CNS Depression
Ventilation
Sensory acuity
Confusion, coma, death

Oxygen Toxicity Causes

CNS Effects (Bert Effect)
Hyper irritability
Muscular twitching
Convulsions
Dizziness, Irritability, disorientation
Pulmonary effects (Smith Effect)
Tracheobronchial irritation
Pulmonary edema
Congestion and atelectasis

Physiology

143

Retinal effects:
Retrolental fibroplasia
Retinal damage
Burnt out Tissue
Due to metabolic rates and excess heat production with tissue damage

Mountain Sickness
Adverse effects of Hypoxia at High Altitude
Develops 824 hours after arrival and lasts 48 days
Low PO2 stimulation is the main cause leading to ventilation blowing of CO2 which inhibits respiratory center causing respiratory
distress
Expansion of gases in GIT occurs Nausea, Vomiting
Pulmonary edema (Permeability) Breathlessness
Cerebral edema (Cerebral vasodilation) Headache, Irritability, Insomnias, Weakness
Acclimatization is by:
Hyperventilation
Hb
Polycythemia
Mitochondria
Cardiac Output
2, 3 DPG
Diffusion capacity
Reticulocytosis
Erythropoietin

Renal Physiology
Role of Kidneys: Primarily regulation or homeostasis
Regulation of blood plasma and interstitial fluid composition (homeostasis), especially inorganic ions (e.g. Na+, K+, Cl, Ca2+)
and osmolality (osmotic activity of dissolved particles)
Regulation of body fluid volume fluid balance
Regulation of blood plasma and interstitial fluid pH
Excretion of (nonvolatile) metabolic end products (e.g. urea, uric acid, creatinine, NH4+) and foreign solutes (e.g. some
drugs)
Endocrine organ, secreting
a. Renin, for regulation of Na+, ECF (extracellular fluid) volume, vascular resistance
b. Erythropoietin, for regulation of erythrocyte production
c. Calcitriol, related to calcium regulation
Metabolic functions e.g. peptide degradation, synthesis of NH3 and H+

RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
Adrenal Cortex
Zona Glomerulosa (on outside) Mineralocorticoids mainly aldosterone
Zona Fasciculata (middle) Glucocorticoids mainly cortisol
Zona Reticularis (on inside) Androgens mainly dehydroepiandrosterone (DHEA)

144

USMLE Step 1 Platinum Notes

Kidneys
Each kidney contains about one million nephrons
Juxtra medullary nephrons constitute only 15% of nephrons
Filtration barrier of kidneys is formed by:
Podocytes
Endothelial cells
Basement membrane

Renin
It is released by JG cells in kidney in response to reduced renal perfusion, low Na+
Converts angiotensinogen to angiotensin I
Factors stimulating renin secretion
Low BP
Hyponatremiae
Sympathetic nerve stimulation
Catecholamines
Erect posture

Angiotensin

ACE in lung converts angiotensin I angiotensin II

Produced in liver
Vasoconstriction leads to raised BP
Stimulates thirst
Stimulates aldosterone and ADH release

Aldosterone

Released by zona glomerulosa

Causes retention of Na+ in exchange for K+/H+ in distal tubule
Aldosterone is produced in zona glomerulosa of adrenal glands
It binds to MR (Mineralocorticoid receptors) in renal tubular cells

It Causes

Increased Na reabsorption
Increased potassium excretion
Increased hydrogen secretion
Increased ammonia excretion
Increased magnesium excretion

Renin Aldosterone

Renovascular Hypertension
Fibromuscular Dysplasia
Diuretic use
Malignant Hypertension
Reninoma

Physiology
Sites of action of hormones

Aldosterone: Cortical ducts and distal tubules

Angiotensin II: Afferent arteriole constriction reduces GFR
ADH: Medullary collecting duct
ANP: Collecting duct

Commonly asked and Repeated Questions in Renal Physiology

Major part of glomerular filtrate is absorbed in PCT

Substances completely reabsorbed in PCT
Glucose
Proteins, amino acids, vitamins, acetoacetate
Bicarbonate
Water
In prescence of vasopressin mx reabsorption of water occurs in PCT
Substances partially absorbed in PCTNa, K, Cl (7/8 reabsorbed in PCT)
Maximum water absorption occurs at PCT
Glucose transport occurs with sodium
Substances secreted in PCT: H+, PAH (para amino hippurate). Creatinine
H+ are actively secreted in proximal tubules, distal tubules, collecting ducts
Hyperosmilality in the interstitum is the prerequisite for excretion of concentrated urine
Urea is reabsorbed from inner medullary collecting ducts only in presence of ADH
K+ is actively secreted in Late Distal tubules and Collecting ducts
Macula densa is the epithelial cells of the distal tubule that comes to contact with the arterioles
Tubuloglomerular feedback is mediated by sensing NaCl in macula densa
Juxtaglomerular cells produce renin
Are smooth muscle cells of afferent arteriole
Lies in relation to glomerulus
Consists of macula densa
Renin acts on angiotensinogen and convert it into angiotensin I.

Loop of henle does not handle urea

Urea has no T m value

Effect of angiotensin, aldosterone

145

146

USMLE Step 1 Platinum Notes

Site of Action of Diuretics

Thiazides
Chlorthiazide

Distal tubule

Hydrochlorthiazide

Distal tubule

Chlorthalidone

Distal tubule

Indapamide

Distal tubule

Metolazone

Proximal and distal tubules

Loop diuretics
Frusemide

Loop of Henle

Bumetanide

Loop of Henle

Ethacrynic acid

Loop of Henle

Carbonic anhydrase inhibitors

Acetazolamide

Proximal tubule

Potassium sparing diuretics

Spironolactone

Distal tubule and collecting duct

Triamterene

Distal tubule and collecting duct

Amiloride

Distal tubule and collecting duct

Remember
Filtration fraction = GFR/RPF = 20%
Clearance = Urine concentration x flow rate/Plasma Concentration
If Clearance < GFR, there is net tubular reabsorption
If Clearance > GFR, there is net tubular secretion
If Clearance = GFR, there is no net secretion/reabsorption
GFR = insulin clearance NOT Insulin = 125 ml/min
RPF = PAH Clearance = 500800
Normal creatinine levels: 0.61.2 mg%
Urea clearance: 88 ml/minute.
Excretion rate = Clearance Plasma concentration
or
Clearance [C] = Excretion excretion rate/Plasma concentration [P]
Excretion rate = Urine concentration[U] Volume[V] of urine formed per unit time
so
Cx = Ux V/Px
Cx = Clearance of substance x
Ux = Concentration of x in urine
Px = Concentration of x in blood plasma
V = Rate of urine formation
Determination of GFR (Glomerular filtration rate): If a substance is filtered but not reabsorbed or secreted (nor metabolized or
synthesized) by the kidney, then its clearance must equal GFR. Substances which are only filtered include insulin and (more-or-less)
creatinine
Determination of RPF (Renal plasma flow): If a substance is completely cleared from the renal blood (combination of filtration
and secretion) in one pass through the kidney, then its clearance is equal to RPF. A substance which fulfills this criteria is PAH (Para
Amino Hippuric acid), as long at TmPAH Is not exceeded.
Determination of tubular transport: If the clearance of a filtered substance is less than GFR, then that substance must be
reabsorbed. If the clearance of a substance is greater than GFR, then that substance must be secreted.

Physiology

147

Determination of fraction excreted: For substances filtered and reabsorbed, the fraction of the amount filtered (called the
filtered load) that is excreted is given by the ratio of CX/GFR.

Clearance

Demonstrating: Relationship between arterial pressure and renal blood flow

At low systemic arterial pressure, renal blood flow is reduced, compromising renal function and even kidney vitality.

Important Enzyme Deficiencies

21 Hydroxylase deficiency

Hypotension, Hyponatremia, Hyperkalemia

17 Hydroxylase deficiency

Hypertension, Ambigious genitalia

5 Reductase deficiency

Testosterone Feminization

GIT Physiology
Substance

Site of absorption

Duodeneum
Jejunum
Jejunum
Terminal ileum
Terminal ileum

Iron
Calcium
Folate
Vit B 12
Bile salts

148

USMLE Step 1 Platinum Notes

Oxyntic cells of gastric gland contain receptors for PGE2, M3, H2, Somatostatin
Chief cells/Zymogen cells secrete Pepsinogen
Oxyntic/Parietal Cells secrete Intrinsic Factor and HCl

Remember: Other Important cells of GIT, Hormones and their Function

Hormone

Source of Secretion

Actions

Gastrin

G cells of stomach; duodenum, jejunum, Stimulates the secretion of gastric juice

Ant Pituitary, Pancreas and Brain
Increase the gastric motility
Stimulates the release of pancreatic hormones.

Secretin

S cells of duodenum, jejunum and ileum

Stimulates secretion of watery, alkaline and pancreatic

secretions
Inhibits gastric secretion
Causes contraction of pyloric sphincter
Most potent stimulus is acidic chyme.

Cholecytokinin

I cells in duodenum, jejunum and ileum

Stimulates contraction of gallbladder

Activates secretin;
Inhibits gastric motility;
Increases secretion of enterokinase and intestinal
motility
Protein stimulates CCK section.

Gastric inhibitory peptide (GIP)

K cells in duodenum and jejunum

Inhibits secretion of gastric juice, gastric motility and

increase insulin secretion.

Ingestion causing release

Gastric Secretion
Stimulated by:
Stomach distension
Acetylcholine
Gastrin
Histamine
Decreased by:
H2 blockers
Secretin
Gastric emptying:
Stimulated by gastrin and distension of stomach
Decreased by cholecystokinin.

Physiology

149

Motilin
Motilin is a polypeptide secreted by enterochromaffin cells
It acts on G protein coupled receptors. Motilin is a 22 amino acid polypeptide hormone which in humans is encoded by the MLN
gene
Motilin secreted by endocrine M cells (these are not the same M cells that are in Peyers patches) that are numerous in crypts of the
small intestine, especially in the duodenum and jejunum
Based on amino acid sequence, motilin is unrelated to other hormones. Because of its ability to stimulate gastric activity, it was
named Motilin.
Its circulating level increases at approximately 100 minutes in interdigestive state and is the major regulator of MMCs that
control GIT motility in between meals
Erythromycin binds to these motilin receptors and is used for treating gastric hypomotility.
Pacemaker of small intestine is in second part of duodenum.
Cephalic phase of gastric secretion is mediated by: parasympathetics
Gastric phase of gastric secretions is mediated by hormones
Intestinal motility is stimulated by:
Distension
Ach Cholecystokinin
Gastrocolic reflex is a mass reflex
Enterogastric reflex: chyme entering intestines inhibits gastric motility
Stimulated by:
Duodenal distension
Acidity of duodenal chyme
Osmolarity of chyme
Protein/fat breakdown products

Sites of Absorption

Iron is actively absorbed in duodenum

Fat is maximally absorbed in jejunum
Vitamin B12 is absorbed in ileum
Calcium is maximally absorbed in ileum
Maximum absorption of bile is seen in ileum
Electrolytes are absorbed in colon

Dietary Fiber

Increases bulk of stools

metabolism of sugar in GIT
Decreases stool transit time
Prevent against colonic cancer
Examples:
Pectin
Cellulose
Hemicellulose

Fat
Fat is the largest reserve of energy in body
Fat is maximally absorbed in jejunum

150

USMLE Step 1 Platinum Notes

Short chain Fatty acids are maximally absorbed in Colon

Digestion of fats occurs by:
Gastric lipase
Collipase
Bile salts
Pancreatic lipase
Fat in stool > 6 gms/day is indicative of malabsorption
Bile absorption is maximum in ileum

Leptin
Associated with puberty
Secreted from adipose tissue
Decreased hunger

Physiology of Bile

Secreted by hepatocytes
Most potent stimulant for bile secretion is bile salts
Composed of water, Bile salts, Cholesterol
Bile salts are amphipathic
Primary Bile Acids: Cholic acid, Chenodeoxycholic acid
Secondary Bile Acids: Deoxycholic acid, Lithocholic acid
Cholagogues are substances causing gallbladder contraction
CCK
Fatty acids
Amino acids
Cholerectics are substances increasing secretion of bile
Secretin
Bile salts
Vagal stimulation

Insulin
Insulin acts through activation of receptor tyrosine kinase activity
Insulin receptor has two subunits:
1. Alpha subunit: which is extracellular and binds to insulin
2. Beta subunit: which is transmembranous and has tyrosine kinase activity functioning in signal transduction
Insulin Increases
Glucose uptake
Glycogen synthesis
Protein synthesis
Fat synthesis
Insulin Decreases
Gluconeogenesis
Glycogenolysis
Lipolysis

Physiology

151

Insulin is a polypeptide Hormone

Insulin is an anabolic hormone
It is a hypoglycemic hormone
Insulin is secreted by Beta cells of Pancreas
Secreted along with Cpeptide in 1: 1 ratio
In fetus secretion begins by 3 month
Insulin Secretion is stimulated by increased blood glucose
Insulin Secretion is inhibited by epinephrine
Insulin is prepared on a large scale by recombinant DNA technology from mRNA
Pork insulin differs from human insulin by one amino acid only
Insulin DOES NOT cross placenta

Alpha cell Glucagon

Beta cells Insulin
Delta cells Somatostatin
F or PP cells Pancreatic polypeptide

Hormones
Hormones can be divided into five major classes:
1. Amino acid derivatives such as:
Dopamine
Catecholamines, and
Thyroid hormone
2. Small neuropeptides such as:
Gonadotropin-releasing hormone (GnRH)
Thyrotropin-releasing hormone (TRH)
Somatostatin and
Vasopressin
3. Large proteins such as:
Insulin
Luteinizing hormone (LH), and
PTH produced by classic endocrine glands;
4. Steroid hormones such as:
Cortisol and
Estrogen that are synthesized from cholesterol-based precursors
5. Vitamin derivatives such as:
Retinoids (vitamin A) and
Vitamin D
A variety of peptide growth factors, most of which act locally, share actions with hormones
As a rule, amino acid derivatives and peptide hormone interact with cell-surface membrane receptors
Steroids, thyroid hormones, vitamin D and retinoids are lipid-soluble and interact with intracellular nuclear receptors.

Remember the Latest Source and Nature of Hormones

Hormone

Structure

Source

FGF-23 (phosphatonin)

Protein

Bone

Osteocalcin

Peptide

152

USMLE Step 1 Platinum Notes

Glucocorticoids (e.g. cortisol)

Steroids

Mineralocorticoids (e.g. aldosterone)

Steroids

Androgens (e.g. testosterone)

Steroids

Adrenaline (epinephrine)

Tyrosine derivative

Noradrenaline (norepinephrine)

Tyrosine derivative

Estrogens (e.g. estradiol)

Steroid

Ovarian follicle

Progesterone

Steroid

Corpus luteum and placenta

Human chorionic gonadotropin (HCG)

Protein

Trophoblast and placenta

Androgens (e.g. testosterone)

Steroid

Testes

Erythropoietin (EPO)

Protein

Kidney

Calcitriol

Steroid derivative

Calciferol (Vitamin D3)

Steroid derivative

Skin

Atrial-natriuretic peptide (ANP)

Peptides

Heart

Incretins

Peptides

Stomach and intestine

Somatostatin

Peptides

Neuropeptide Y

Peptide

Ghrelin

Peptide

PYY3-36

Peptide

Serotonin

Tryptophan derivative

Leptin

Protein

Retinol Binding Protein 4

Protein

Adiponectin

Protein

Secondary Messengers
cAMP
DAG

IP 3
Ca++
Protein kinase
NO acts as cellular signalling molecule

C AMP mediates action of

PTH
LH
FSH, HCG
ADH
Calcitonin
Glucagon
C GMP mediates action of
ANF
NO
Insulin acts through tyrosine kinase

Adrenal cortex

Adrenal medulla

Fat cells (adipocytes)

Physiology

153

Ca++, Phosphatidyl inophosphate mediates action of

Ach
Angiotensin II
Oxytocin

Thyroid hormones act on intracellular receptors

Retinoic acid, act on intracellular receptors
(Steroids) act on intracellular receptors
Androgens, estrogen, progesterone, glucocorticoids, mineralocorticoids act on intracellular receptors
Vitamin D3 and thyroid belong to steroid receptor family

Calcium Metabolism
Parathormone:
Stimulates osteoclastic activity, thereby increasing bone resorption by mobilizing calcium and phosphate;
Increases the reabsorption of calcium by the renal tubules, thus reducing the urinary excretion of calcium;
Augments the absorption of calcium from the gut;
Calcium reabsorption takes place from proximal small intestine
Reduces the renal tubular reabsorption of phosphate, thus promoting phosphaturia.
Calcitonin:
It is secreted by the Parafollicular cells of the Thyroid (thyrocalcitonin)
It lowers the serum calcium and affects calcium storage in bones; quite the opposite action of parathormone
Acts by decreasing bone absorption
That means inhibits osteoclastic activity.
Parathyroid hormone-related protein (PTH-rP):
It is a hypercalcemic factor with similar bioactivity to that of parathyroid hormone
Low calcium levels stimulate its secretion
Since its isolation from cancer cell lines and carcinoma of the breast, strong evidence has emerged that it is an important hormonal
mediator of cancer-associated hypercalcemia in patients with solid tumors.
PARATHYROID HORMONE MECHANISMS OF ACTION
PTH binds to a plasma membrane receptor; the PTH receptor then causes a rise of cyclic 3, 5-adenosine monophosphate (cAMP)
and other second messengers in the cytoplasm of its target cells. The consequence is rapid effects of PTH on the target cells in
bone and
kidney. A different peptide, termed parathyroid hormone-related peptide, with homology to PTH at the amino terminus, is secreted
by many cancers, causing hypercalcemia through its interactions with PTH receptors
PARATHYROID HORMONE ACTION IN BONE
PTH in bone stimulates osteoblasts and osteoclasts. The effects on osteoclasts are indirect because these cells lack receptors for PTH.
Very high PTH levels result in clear excess of bone resorption over bone formation. Controversy exists over whether mild PTH excess
might have a net anabolic effect selectively in trabecular bone
PARATHYROID HORMONE ACTION IN KIDNEY
PTH acts in the kidney to stimulate the synthesis of 1, 25 (OH) 2D by increasing the activity of 25OHD3 1a-hydroxylase in the proximal
tubules. PTH acts in the distal portions of the nephron to increase tubular reabsorption of calcium. In addition, PTH inhibits phosphate
reabsorption in the distal, and perhaps also the proximal, tubules. PTH also inhibits bicarbonate reabsorption
PARATHYROID HORMONE ACTION ON INTESTINE
PTH has no important direct action on the intestine. However, the direct renal effect of PTH to increase serum 1, 25 (OH) 2D causes
highly important secondary effects in the intestine

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USMLE Step 1 Platinum Notes

Calcium
Calcium is absorbed in proximal small intestine
Absorption is increased by acidic pH, proteins
Absorption is decreased by phosphates and oxalates
Ionized form is the active form of calcium
A decrease in the concentration of free calcium ions in plasma results in
Increased neuromuscular irritability and tetany
Peripheral and perioral paresthesia
Carpal spasm
Pedal spasm, anxiety, seizures
Bronchospasm, laryngospasm
Chvosteks sign
Trousseaus sign
Erbs sign
Lengthening of the QT interval of the electrocardiogram
Substance

Serum calcium

Serum phosphate

Vitamin D

PTH

Calcitonin

Pituitary Gland
The anterior pituitary is often referred to as the master gland
Called Hypophysis cerebri
Remember Epiphysis cerebri is Pineal Gland
The anterior pituitary gland produces six major hormones:
Prolactin (PRL)
Growth hormone (GH)
Adrenocorticotropin hormone (ACTH)
Luteinizing hormone (LH)
Follicle-stimulating hormone (FSH), and
Thyroid-stimulating hormone (TSH)
Pituitary hormones are secreted in a pulsatile manner
The pituitary gland weighs ~600 mg
It is located within the sella turcica ventral to the diaphragm sella
The hypothalamic-pituitary portal plexus provides the major blood source for the anterior pituitary
The posterior pituitary is supplied by the inferior hypophyseal arteries
The Posterior Lobe is directly innervated by hypothalamic neurons (supraopticohypophyseal and tuberohypophyseal nerve tracts)
via the pituitary stalk
Thus, posterior pituitary production of vasopressin (antidiuretic hormone; ADH) and oxytocin
It is particularly sensitive to neuronal damage by lesions that affect the pituitary stalk or hypothalamus
Vasopressin and oxytocin are typical Neural Hormones. They are secreted into the circulation by nerve cells
The term neurosecretion is classic for these two hormones
B oth are synthesized in Para ventricular and Supraoptic nuclei and transported via hypothalmoneurohypophyseal tracts to
posterior pituitary
Posterior lobe of pituitary is important in their formation and they are synthesized as a part of large precursor molecule

Physiology

155

Both vasopressin and oxytocin have a characteristic neurophysin attached with them. In the granules of the neurons that secrete
them
Neurophysin I in case of oxytocin and Neurophysin II in case of Vasopressin
These neurophysins were initially thought to be binding molecules but now they are thought to be parts of precursor molecule
The vasopressin and Neurophysin II after being secreted forms secretory granules called Herrings bodies.

Reproductive Physiology
Potency: Dihydrotestosterone > Testosterone > Androstenendione
Testosterone is converted to DHT by enzyme 5 reductase
Testosterone is converted into estrogen and estrodial by aromatase

FSH stimulates formation of Secondary follicle to Graffian Follicle

Estrogen is responsible for Proliferative phase
LH stimulates ovulation
LH maintains corpus luteum
FSH receptors are present on granulosa cells
Progesterone is responsible for Secretory phase

Male sex hormones are called the androgens (secreted by leydig cells); testosterone, dihydro testosterone and androstenedione
Mullerian ducts gives rise to female accessory sex organs such as vagina, uterus and fallopian tube
Wolffian duct gives rise to male accessory sex organs such as epididymis, vas deferens and seminal vesicles
Fetal testes begin to secrete the testosterone at about 2nd to 4th month of embryonic life
The secretion from seminal vesicles contains fructose, phosphorylcholine, fibrinogen, ascorbic acid, citric acid, pepsinogen, acid
phosphatase and prostaglandin
Fructose and citrate acts as fuel for the spermatozoa
Prostatic secretion is rich in enzymes, zinc and citrate
Androgen appears to be essential for spermatogenesis. Whereas FSH is required for spermatic maturation

Menopause Causes HAVOC

Hot flushes
Atrophy vagina
Osteoporosis
Coronary artery disease
Features
Estrogen
FSHLH
GnRH
Prolactin increases Dopamine Synthesis
Dopamine inhibits Prolactin Synthesis
Dopamine agonists (Bromocriptine) inhibit Prolactin synthesis

Important Points in Reproductive Physiology

Spermatogenesis occurs at lower temperatures at about 32 C
Spermatozoa acquire motility in epididymis

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USMLE Step 1 Platinum Notes

Capacitation (Fertilization capabilities) occurs in female genital tract

Sperms move at a speed of 13 mm/min
Semen contains high concentration of prostaglandins
Sperms reach uterine tubes in 3060 minutes after copulation
In female genital tract do not survive for more than 48 hours
Estrogen content of fluid in Rete Testis is high
Spermatozoa contain a special enzyme Germinal Angiotensin II Converting enzyme
Testosterone is produced from pregnanalone
Testosterone is produced by Leyding cells
CART WHEEL appearance of nucleus is seen in sertoli cells
Blood testis barrier is formed by sertoli cells
Receptors for FSH are present in sertoli cells
Inhibin is secreted by sertoli cells

Thyroid Hormones
The thyroid gland produces two related hormones, thyroxine (T4) and triiodothyronine (T3) Thyroid hormones act through
nuclear hormone receptors to modulate gene expression
TSH, secreted by the thyrotrope cells of the anterior pituitary serves as the most useful physiologic marker of thyroid
hormone action
Thyroid hormones feedback negatively to inhibit TRH and TSH production
Thyroid hormones are derived from a large iodinated glycoprotein
Iodide uptake is a critical first step in thyroid hormone synthesis
Iodide uptake is mediated by the Na+/I symporter (NIS), which is expressed at the basolateral membrane of thyroid follicular
cells, followed by Organification, Coupling, Storage, Release
TSH is the dominant hormonal regulator of thyroid gland growth and function
Excess iodide transiently inhibits thyroid iodide organification, a phenomenon known as the Wolff-Chaikoff effect
T4 is secreted from the thyroid gland in at least 20-fold excess over T3
Both hormones circulate bound to plasma proteins, including thyroxine-binding globulin (TBG), transthyretin (TTR, formerly
known as thyroxine-binding prealbumin, or TBPA) and albumin
Thyroid hormones act by binding to nuclear receptors, termed thyroid hormone receptors (TRs) a and b.

Effects
Brain Maturation
Bone Growth
BMR
Beta adrenergic effects
Wolf Chaikoff effect is Iodine itself inhibits organic binding.

Hypertrophy of Zona Glomerulosa Conns Syndrome

Hypertrophy of Zona Fasiculata Cushings Syndrome
Adrenal Cortical Atrophy Addisons Disease
Hypertrophic Adrenal Medulla Pheochromocytoma
Hypertrophic Adrenal Medulla Neuroblastoma

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157

Hormones in Stress
Adrenaline
Vasopressin
Cortisol
Glucagon
Epinephrine
Insulin is not increased

Melatonin
It is a pineal hormone
It is serotegenic
It is secreted predominantly at night in both day- and night-active species
Exogenous melatonin increases sleepiness and may potentiate sleep when administered to good sleepers attempting to sleep
during daylight hours at a time when endogenous melatonin levels are low
Increased serotonin N acetyl transferase activity occurs in darkness.

Sleep

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USMLE Step 1 Platinum Notes

EEG waves are called Berger rhythm

Normal EEG is bilaterally symmetrical
Alpha waves: 813 Hz seen in awake patient with eyes closed
Beta waves: 14 Hz seen in awake with eyes open
Theta waves: 47 Hz seen in hippocampus
Delta waves: 35 Hz seen in deep sleep
DTAB is order of increasing frequency. (Digest TAB)

Sleep stages
REM Sleep:
Light phase with difficult arrousal
Called paradoxical sleep
Disorders of REM sleep:
Nightmares (remembered)
Narcolepsy
Nocturnal penile trumescene

NREM Sleep
BP
HR
Disorders of NREM sleep:
Sleep walking
Sleep talking
Night terror
Bruxism
Nocturnal enuresis

Iron Metabolism

The major role of iron is to carry O2 as part of the heme

O2 also is bound by a heme protein in muscle, myoglobin
Iron also is a critical element in iron-containing enzymes, including the cytochrome system in mitochondria
Iron absorbed from the diet or released from stores circulates in the plasma bound to transferrin, the iron transport protein
In a normal individual, the average red cell life span is 120 days

The balance of iron metabolism in the organism is tightly controlled and designed to conserve iron for reutilization
There is no excretory pathway for iron, and the only mechanisms by which iron is lost from the body are blood loss (via
gastrointestinal bleeding, menses, or other forms of bleeding) and the loss of epidermal cells from the skin and gut
Iron absorption takes place largely in the proximal small intestine

Physiology

Factors influencing iron absorption

Hemoglobin

Hb A
Hb F
Hb A 2
Hb H
Hb S
Hb Barts

Alpha 2, Beta 2
Alpha 2, Gamma 2
Alpha 2, Delta 2
Beta 4
Beta 6 val- glu
Gamma 4

Blood Coagulation Factors

1, 2, 5, 7, 9, 10
2, 7, 8, 9, 10
2, 7, 9, 10
5, 8
5, 10

Produced in liver
Levels increased with oral contraceptives
Vitamin K required
Unstable in stored blood
Good for growth of hemophilus organisms

Physiology of Eye

Rods are responsible for dim light or night vision or scotopic vision. (Electric Rods are used at night)
Cones are responsible for color vision, sensitive to day light and acuity of vision
Rhodopsin is the photosensitive pigment of rods cells
Hemholtz Theory states that there are three kinds of cones in retina corresponding to three colors
Most sensitive in Green light and least sensitive in Red light
Photosensitive pigment in cones are:
Porpyropsin Red
Iodopsin Green
Cyanopsin Blue
Test for visual acuity Snells chart (distant vision) and Jaegers chart (near vision)
Test for color blindness Ishiharas color chart
Mapping of visual field Perimetry
Nearest point at which the object is seen clearly is about 7 to 40 cm
Farthest point is infinite
Protanomoly refers to defect in red cones
Deutranomoly refers to defect in green cones
Trianamoly refers to defect in blue cones

159

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USMLE Step 1 Platinum Notes

Cell Adhesion Molecules

Cells are attached to Basal Lamina and each other by cell adhesion molecules (CAMs)
They are:
Integrins
Adhesion molecules of IgG Superfamily
Cadherins
Selectins

Nitric Oxide
Nitric oxide is NO
It is also called as EDRF (Endothelial derived relaxing factor)
It is produced from arginine by enzyme NO synthetase
NO has a short t (4 seconds)
It acts via c GMP pathway
It relaxes smooth muscles specifically
It prevents platelet aggregation
It functions as a neurotransmitter
It mediates bactericidal actions of macrophages
Acts as:
Free radical
Vasodilator
Oxidizing agent
Catalyst
NO, ANP, BNP act through c GMP
Remember:
Calmodulin is Ca Dependent
Calmodulin acts through Protein Kinase

Inflammatory Mediators

Histamine is present in mast cells, basophils, enterochromaffin cells

Has three types of receptors H1, H2, H3
Formed by decarboxylation of histidine
Alter venular permeability
Mediates triple response

Natriuretic Peptides
Atrial distention and/or a sodium load cause release into the circulation of atrial natriuretic peptide (ANP), a polypeptide; a highmolecular-weight precursor of ANP is stored in secretory granules within atrial myocytes.
Release of ANP causes
Excretion of sodium and water by augmenting glomerular filtration rate
Inhibiting sodium reabsorption in the proximal tubule, and
Inhibiting release of renin and aldosterone; and
Arteriolar and venous dilatation by antagonizing the vasoconstrictors
Thus, ANP has the capacity to oppose sodium retention and arterial pressure elevation in hypervolemic states
The closely related brain natriuretic peptide (BNP) is stored primarily in cardiac ventricular myocardium and is released when ventricular
diastolic pressure rises.

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161

Its actions are similar to those of ANP

Circulating levels of ANP and BNP are elevated in congestive heart failure but not sufficient to prevent edema formation
In addition, in edematous states (particularly heart failure), there is abnormal resistance to the actions of natriuretic peptide
increase the concentrations of cyclic GMP in the kidney, adrenal glomerulose, vascular smooth muscle and platelets. Elevated circulating
concentrations of ANP and particularly BNP correlate with a poor prognosis in heart failure:
Natriuretric substance
Promotes sodium excretion
Decreases blood pressure
Acts by c GMP Pathway
The 'Encapsulated'mechanoreceptors include:
Pacinian corpuscles in skin and connective tissues that sense (rapidly adapting touch) pressure and vibration. They look like
onion bulbs
Meissners corpuscles in dermal papillae of non-hair bearing skin of hands, feet, genitalia, nipples and mouth that provide tactile
discrimination. They look like nutmegs
Ruffinis corpuscles in skin and joints that respond to stretch and pressure
Golgi tendon organs located where muscle inserts into tendon sense stretch for proprioception
Muscle spindles in skeletal muscles are composed of nerve endings in association with specialized intrafusal muscle fibers that
function to detect stretch for reflexes
The Nonencapsulated endings include:
Peritricial nerve endings around hair follicles that detect touch through movement of hair
Merkels disks on nonhair bearing skin such as the hands that perceive touch. It is present in epidermis.

Important Regions of CNS

The Locus Ceruleus is adense collection of neuromelanincontaining cells in the rostralpons. It appears blue-black in unstained
brain tissue. These cells contain norepinephrine
The Basal nucleus of Meynert is one of the structures that degenerates in Alzheimers disease
The Caudate nucleus degenerate in Huntingtons disease (GABAergeic) neurons
The Substantianigra contains the nigrostriatal neurons that are the source of striat aldopamine. This cell group degenerates in
Parkinsons disease
The Ventral Tegmentalarea is located in the midbrain and is an important source of dopamine for the limbic and cortical areas.
Over activity of this cell group is a popular theory of the etiology of Schizophrenia
Aphasia should be diagnosed only when there are deficits in the formal aspects of language such as naming, word choice,
comprehension, spelling and syntax
Dysarthria and mutism do not, by themselves, lead to a diagnosis of aphasia
In approximately 90% of right handers and 60% of left handers, aphasia occurs only after lesions of the left hemisphere
A language disturbance occurring after a right hemisphere lesion in a right hander is called crossed aphasia

Wernickes Aphasia
Damage: Comprehension is impaired for spoken and written language
Language output is fluent
The tendency for paraphasic errors maybe so pronounced that it leads to strings of neologisms, which form the basis of what is
known as jargon aphasia.

Brocas Aphasia
Brocas area is present in inferior frontal gyrus
Concerned with word formation

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USMLE Step 1 Platinum Notes

Damage: Speech is nonfluent, labored, interrupted by many word finding pauses and usually dysarthric
Brocas: Broken Speech

Global Aphasia
Speech output is nonfluent and comprehension of spoken language is severely impaired. Naming, repetition, reading and writing
are also impaired
This syndrome represents the combined dysfunction of Brocas and Wernickes areas and usually results from strokes that
involve the entire middle cerebral artery distribution in the left hemisphere.

Conduction Aphasia
Speech output is fluent but paraphasic, comprehension of spoken language is intact, and repetition is severely impaired. Naming
and writing are also impaired.

Anomic Aphasia
This form of aphasia maybe considered the minimal dysfunction syndrome of the language network. Articulation, comprehension,
and repetition are intact, but confrontation naming, word finding and spelling are impaired.

Main Hypothalamic Nuclei and Their Functions

Thirst and water balance

Supraoptic nucleus
Supraoptic nucleus controls ADH secretion

Hunger

Lateral nucleus

Satiety

Ventromedial nucleus

Regulation of Autonomic Nervous system

Anterior Hypothalamus

Circadian Rhythm

Suprachiasmatic nucleus

Heat production

Posterior hypothalamus

Cooling

Anterior hypothalamus

Sexual functions

Septate nucleus

Control of anterior pituitary

By releasing factors

Control of posterior pituitary

By hormones produced in hypothalamic nuclei

Functions of Hypothalamus
Food intake
Temperature control
Hypophyseal control
Nonshivering thermogenesis is because of noradrenaline
Nonshivering thermogens are secreted by heart, liver small intestine
Nonshivering thermogenesis is mediated by 3 receptors
Heat loss depends mostly on environmental temperature

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163

Ascending Tracts of Spinal Cord

Situation

Tract

Function

Anterior white funiculus

Anterior spinothalamic tract

Crude touch sensation

Lateral white funiculus

Lateral spinothalamic tract

Pain and temperature sensation

Ventral spino cerebellar tract

Subconscious kinesthetic sensations

Dorsal spino cerebellar tract

Subconscious kinesthetic sensations

Spinotectal tract

Concerned with spinovisual reflex

Fasiculus dorsolateralis

Pain and temperature sensations

Spinoreticular tract

Conciousness and awareness

Spinoolivary tract

Proprioception

Spinovestibular tract

Proprioception

Fasciculus gracilis
Fasciculus cuneatus

Posterior white funiculus

Tactile sensation
Tactile localization
Tactile discrimination
Vibratory sensation
Conscious kinesthetic sensation
Stereognosis

Descending Tracts of Spinal Cord

Situation

Tract

Function

Pyramidal tracts

Anterior corticospinal tract

Lateral corticospinal tract

Control voluntary, skilled movements

Forms upper motor neurons
Forms pyramids

Extra Pyramidal
tracts

Medial longitudinal fasciculus

Coordination of reflex ocular movement

Integration of movements of eyes and neck

Anterior vestibulospinal tract

Maintenance of muscle tone and posture

Maintenance of position of head and body during acceleration

Lateral vestibulospinal tract

Reticulospinal tract

Coordination of voluntary and reflex movements

Control of muscle tone
Control of respiration and blood vessels.

Tectospinal tract

Control of movement of head in response to visual and auditory impulses.

Rubrospinal tract

Facilitatory influence on flexor muscle tone

Olivospinal tract

Control of movements due to proprioception

Main excitatory neurotransmitter in CNS is: Glutamate

Main inhibitory neurotransmitter in CNS is GABA

Action of Sympathetic and Parasympathetic Divisions of ANS

Effector Organ
Eye

Sympathetic Division

Parasympathetic Division

Ciliary muscle

Relaxation

Contraction

Pupil

Dilatation

Constriction

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USMLE Step 1 Platinum Notes

Effector Organ

Sympathetic Division

Parasympathetic Division

Lacrimal secretion

Decrease

Increase

Salivary secretion

Decrease in secretion and vasoconstriction

Increase in secretion and vasoconstriction

Motility

Inhibition

Acceleration

Secretion

Decrease

Increase

Sphincters

Constriction

Relaxation

Relaxation

Contraction

Detrusor muscle

Relaxation

Contraction

Internal sphincter

Constriction

Relaxation

Sweat glands

Increase in secretion

Heart rate and force

Increase

Decrease

Blood vessels

Constriction of all blood vessels except Dilatation

those in heart and skeletal muscle

Bronchioles

Dilatation

GIT

Gallbladder
Urinary bladder

Constriction

Flight or Fright response is seen in Sympathetic stimulation. Example of seeing a lion and subsequent body respone
BMR: To runaway
Vasodilation of vessels of heart and skeletal muscle
Dilatation of Pupils: To increase field of vision to escape not to frighten the lion
Urinary and fecal spincters need to close. No need of micturating/defecating at this stage
Increase heart rate
Increase blood pressure
Increase total peripheral resistance

Cerebellum
Purkinje cells are the largest neurons in the body
The axons of Purkinje cells are the only output from cerebellar cortex and these pass to deep nuclei
From the cerebellar nuclei they project to other parts (Thalamus, Brainstem)
Layers of Cerebellum
Molecular layer
Purkinje layer
Granular layer
Nuclei of Cerebellum
Dentate
Emboliform
Globoose
Fastigial
Types of Neurons in Cerebellum
Golgi cells
Basket cells
Granule cells
Stellate cells
Purkinje cells (end in cerebellar nuclei)

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165

Remember

The Cerebellum is not a Sensory Organ

Removal of cerebellum does not result in loss of any sensation
The Cerebellum Is not a motor Organ
Stimulation of cerebellum does not produce movement
The function of cerebellum is
It coordinates and smoothens the action of different muscle groups
It times their contraction properly
In this way it produces smooth and accurate movements

Diseases of the Cerebellum

Diseases of the cerebellum result in inability to do movements smoothly and accurately. This condition is called cerebellar ataxia
or cerebellar asynergia
Disturbance of Gait: Gait is similar to that of as drunken person; Lesion in one cerebellar hemisphere results in a tendency to
fall towards that side. {Right Side of Body is under control of Right Cerebellar hemisphere}. Lesions of cerebellar ataxia are not
corrected by vision
Decomposition of movements: A movement is broken into components i.e. the Shoulder, elbow and the wrists move separately
and not in a synchronized way
Dysmetria: Inability to stop a movement at a desired point, i.e. overshooting, past pointing, etc.
Dysadiadochokinesia: Inability to stop one movement and immediately to follow it up with other movement of opposite nature,
i.e. rapid pronation and supination
Scanning speech: Due to lack of synergy of muscles used in speaking, the spacing of sounds is irregular with pauses at wrong
places
Hypotonia
Decreased tendon reflexes
Intention tremor
Sometimes Nystagmus

Basal Nuclei or Basal Ganglia

Subcortical
Intracerebral
Grey matter masses
They are concerned with planning and programming of movements
They include:
Caudate nucleus + Lentiform nuclei (Corpus Straitum)
Amygdaloidal nucleus
Claustrum
Functions:
The basal ganglia are concerned with the control of skilled movements, coordinated movements as well as involuntary movements
and regulation of reflex and muscular activity
As a result disease processes effecting basal ganglia can lead to diseases which can be:
More Movements (Hyper kinetic), Less Movement (Hypo kinetic)
Movement Disorders and their nuclei:
Parkinsonism: Lesion of Globus Pallidus

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USMLE Step 1 Platinum Notes

Chorea: Lesion of Caudate Nucleus

Athetosis: Lesion of Putamen
Hemiballismus: Lesion of Subthalamic nucleus

Parkinson's disease

Parkinsonism Patient
1. Acalculia: A selective impairment of mathematical ability
2. Achalasia: Condition in which food accumulates in the esophagus and the organ becomes highly diluted. It is due to increased
resting lower esophageal sphincter tension and incomplete relaxation of this sphincter on swallowing.
3. Ageusia: Absence of the sense of taste
4. Agnosia: Inability to recognize objects by a particular sensory modality even though the sensory modality itself is intact. Lesions
producing these defects are generally in the parietal lobe.
5. Akinesia: Difficulty in initiating movements and decreased spontaneous movement.
6. Ataxia: In coordination due to errors in the rate, range, force and direction of movement.

Superficial Reflexes- Mucus Membrane Reflexes

Reflex
Corneal reflex

Stimulus
Irritation of cornea

Response
Blinking of eye
(closure of eyelids)

Afferent Nerve
V Cranial nerve

Center
Pons

Efferent Nerve
VII Cranial nerve

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167

Conjunctival reflex

Irritation of
conjunctiva

Blinking of eye

V Cranial nerve

Pons

VII Cranial nerve

Nasal reflex
(sneezing reflex)

Irritation of nasal
mucus membrane

Sneezing

V Cranial nerve

Motor nucleus of
V Cranial nerve

X Cranial nerve and

upper cervical nerves

Pharyngeal reflex
mucus membrane

Irritation of
Retching or of
pharyngeal gagging mouth
opening

IX Cranial nerve
X Cranial

Nuclei of nerve

X Cranial nerve

IX Cranial nerve
X Cranial

Nuclei of nerve

X Cranial nerve

Uvular reflex (while Irritation of uvula

talking)

Raising of uvula

Superficial Reflexes- Cutaneous Reflexes

Reflexes

Stimulus

Response

Center-Segments of Spinal
Cord Involved

Scapular reflex

Irritation of skin at the interscapular Contraction of scapular muscles C5 to T1

space
and drawing in of scapula

Upper abdominal
reflex

Stroking the abdominal wall below Ipsilateral contraction of abdominal T6,7,8,9

the costal margin
muscle and movement of umbilicus
towards the site of stroke

Lower abdominal
reflex

Stroking the abdominal wall at Ipsilateral contraction of abdominal T10,11,12

umbilical and iliac level
muscle and movement of umbilicus
towards the site of stroke

Cremasteric reflex

Stroking the skin at upper and inner Elevation of testicles

aspect of thigh

L1,2

Gluteal reflex

Stroking the skin over glutei

Contraction of glutei

L4,5 S1,2

Bulbocavernous reflex

Stroking the dorsum of glans penis

Contraction of bulbocavernous

S3,4

Anal reflex

Stroking the perianal region

Contraction of anal sphincter

S4,5

Deep Reflexes
Reflex

Stimulus

Response

Center-Spinal
Segments Involved

Jaw Jerk

Tapping the middle of the chin Closure of mouth

with slightly opened mouth

Pons V Cranial
nerve

Biceps Jerk

Percussion of biceps tendon

Flexion of forearm

C 5, 6

Triceps Jerk

Percussion of triceps tendon

Extension of forearm

C 6, 7,8

Supinator Jerk or radial periosteal

reflex

Percussion of tendons over distal Supination

end (styloid process) of radius
forearm

and

flexion

of C7, 8

Wrist tendon or finger flexion reflex Percussion of wrist tendons

Flexion of corresponding finger

C 8, T1

Knee Jerk or patellar tendon reflex

Extension of leg

L2,3,4

Planter flexion of foot

L5 S1S2

Percussion of patellar ligament

Ankle Jerk or Achilles tendon reflex Percussion of Achilles tendon

Susceptibility of Nerve Fibers

Pressure

Type A

Hypoxia

Type B

Anesthesia

Type C

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USMLE Step 1 Platinum Notes

Type A have largest diameter, Highest conduction velocity, function in Proprioception

Type A and B are Myelinated
Type C has least diameter, least conduction velocity, unmyelinated
Nerve conduction velocity is more in upper limbs than in lower limbs

Neurotransmission

Chemical Classification of Neurotransmitters

Acetylcholine
Biogenic Amines
Catecholamines: Dopamine, norepinephrine (NE) and epinephrine
Indolamines
Serotonin and histamine (5-Hydroxytryptamine or 5-HT)
Amino Acids
GABAGamma (-aminobutyric acid)
Glycine
Aspartate
Glutamate
Neuropeptides
Substance P
Endorphins and Enkephalins
Somatostatin, gastrin, cholecystokinin, oxytocin, vasopressin, Leutinizing hormone releasing hormone (LHRH)
Purines
Adenosine
ATP

Physiology
Gases and Lipids
Nitric Oxide (NO)
Carbonmonooxide (CO)
Cannabinoids

Acetylcholine (Ach)
Acetylcholine (Ach) was the first neurotransmitter to be identified. It is the most abundant neurotransmitter in the brain
Released at neuromuscular junctions and some ANS neurons
Synthesized by enzyme choline acetyltransferase
Degraded by the enzyme acetylcholinesterase (AChE)

Catecholamines
Catecholamines-Dopamine, norepinephrine (NE), and epinephrine are synthesized from Tyrosine
It is involved in reward-pleasure and learning
Dopamine is the principle neurotransmitter involved in Addiction pathway

Serotonin
Broadly distributed in the brain, derived from Tryptophan
Involved in sleep, dreaming, hunger and arousal
Play roles in emotional behaviors and the biological clock
Depletion of serotonin in brain leads to depression

GABA
GABAGamma (-aminobutyric acid) is the major inhibitory neurotransmitter in CNS
Synthesized from decarboxylation of Glutamate
Involved in regulating anxiety
Maybe related to eating or sleep disorders

Endorphins, Enkephalins and Substance P

Substance P is the mediator of pain signals
Endorphins and Enkephalins act as natural opiates; reduce pain perception
They also depress physical functions like breathing and may produce physical dependence

Purines such as ATP

Purines such as ATP
Act in both the CNS and PNS
Produce fast or slow responses
Induce Ca2+ influx in astrocytes
Provoke pain sensation

169

170

USMLE Step 1 Platinum Notes

Nitric Oxide (NO)

Synthesized on demand
Activates the intracellular receptor guanylyl cyclase to cyclic GMP
Involved in learning and memory

Endocannabinoids
Lipid soluble; synthesized on demand from membrane lipids
Bind with G proteincoupled receptors in the brain
Involved in learning and memory

Blood Brain Barrier

It is formed by
Capillary Endothelium
Basement Membrane
Foot Processes of Astrocytes

Features
It is a selective barrier, only certain substances can pass across the barrier
The permeability of the barrier is inversely related to the size of the molecules
The permeability of the barrier is directly related to the lipid solubility of the substance
The barrier is more permeable to certain substances in the newborn than in the adults. It is because of the fact that it is under
developed in the newborn and especially in the preterm fetuses
The barrier undergoes breakdown in case of direct injury to brain or secondary to toxin/chemical induced damage
The Tight Junction between the endothelial cells is responsible for the Blood Brain Barrier
The Blood Brain Barrier is deficient at some regions in the CNS, e.g. in next table

Area Postrema
Organum Vasculosum of the lamina terminalis
Subfornical organ
The posterior pituitary

These areas are called Circum Ventricular Organs

Important Molecules

P53
bcl2
fas
c myc
ras
Caspaces

Tumor suppressor gene

Negative regulator of Apoptosis
Activator of apoptosis
Transcription factor which commits cells to mitosis
G protein. Most commonly mutated gene in Solid Tumors
Activates Apoptosis

Changes in Exercise
Oxygen uptake
Left shift of oxygen Hb Dissociation curve.

Physiology

171

ventilation
CO2 Excretion
PaO2
HR
CO
RR
BP
Blood flow To brain unaltered
Insulin Sensitivity
Causes Hyperkalemia
Endorphin levels (Relieves depression)

Changes in Aging

Vital capacity decreases

Glucose tolerance decreases
GFR decreases
Colonic motility decreases
Bone mass decreases
BP increases
Prostate size usually increases
Brain atrophies
Vaginal mucosa atrophies
Hematocrit remains same

Some Laws of Physiology: (Frequently Asked)

1. Laplaces Law
For a globular structure, P = 2T / r
Where P: transmural force
T: wall tension
r : Radius of the globular structure
2. Frank-Starlings Law: The force of contraction is directly proportional to the initial length of muscle fiber.
3. All or None Law: The action potential fails to occur if the stimulus is subthreshold in magnitude, and it occurs with constant amplitude
and from regardless of the strength of the stimulus, if the stimulus is at or above threshold intensity.
4. Bell- Magendie Law: In the spinal cord, the dorsal roots are sensory and the ventral roots are motor.
5. Landsteiners Law:
a. Where an agglutinogen is present on the membrane of RBC, the corresponding agglutinin must be absent in the plasma
of that person
b. Where, in an individual, the RBCs are devoid of an agglutinogen, plasma shall contain the corresponding agglutinin.
6. Ficks Law
This law states: Vg = A / T D (P1 P2)
Where Vg = volume of the gas diffusing through the membrane per min
A = total surface area of alveolo-capillary membrane of the two lungs taken together
T = thickness of alveolo-capillary membrane
D = diffusion constant of the gas
P1 P2 = pressure of the gas in the alveoli and within the capillary blood

172

USMLE Step 1 Platinum Notes

7. Dermatomal Rule: When pain is referred, it is usually to a structure that developed from the same embryonic segment or
dermatome as the structure in which the pain originates.
8. Monro- Kellie Doctrine: Brain tissue and spinal fluid are essentially incompressible; hence the volume of blood, spinal fluid and
brain in the cranium at anytime must be relatively constant.
9. Weber Fechner Law
It states that the magnitude of the sensation felt is proportionate to the log of the intensity of the stimulus
In other words: R = KSA
Where R = sensation felt
S = intensity of the stimulus and for any specific sensory modality
K and A = are constants
10. Law of Projection: No matter where a particular sensory pathway is stimulated along its course to the cortex, the conscious
sensation produced is referred to the location of the receptor. This principle is called Law of Projection
Involved in phantom limb sensation
11. Size principle: In general, slow muscle units are innervated by small, slowly conducting motor neurons and fast units by large,
rapidly conducting motor neurons

Sites of Important Receptors

Hearing
Rotational acceleration
Linear acceleration
Arterial BP
Arterial PO2 and PCO2

Hair cells of organ of Corti

Hair cells of semicircular canals
Hair cells of utricle and saccule
Stretch receptors in Carotid sinus/Aortic arch
Glomus cells of Aortic and Carotid Bodies

Carotid body

Important Substances and their Role: (USMLE Favorite)

Bradykinin: stimulation of visceral smooth muscle
Nitric oxide: vasodilator
Clathirin: receptor mediated endocytosis

Physiology

173

Natriuretic Peptides: (USMLE Favorite)

Atrial distention and/or a sodium load cause release into the circulation of atrial natriuretic peptide (ANP), a polypeptide; a highmolecular-weight precursor of ANP is stored in secretory granules within atrial myocytes
Release of ANP causes
Excretion of sodium and water by augmenting glomerular filtration rate
Inhibiting sodium reabsorption in the proximal tubule, and
Inhibiting release of renin and aldosterone; and
Arteriolar and venous dilatation by antagonizing the vasoconstrictors
Thus, ANP has the capacity to oppose sodium retention and arterial pressure elevation in hypervolemic states
The closely related brain natriuretic peptide (BNP) is stored primarily in cardiac ventricular myocardium and is released when
ventricular diastolic pressure rises
Its actions are similar to those of ANP
Circulating levels of ANP and BNP are elevated in congestive heart failure but not sufficient to prevent edema formation
In addition, in edematous states (particularly heart failure), there is abnormal resistance to the actions of natriuretic
peptide increase the concentrations of cyclic GMP in the kidney, adrenal glomerulose, vascular smooth muscle, and platelets.
Elevated circulating concentrations of ANP and particularly BNP correlate with a poor prognosis in heart failure
Natriuretric substance
Promotes sodium excretion
Decreases blood pressure
Acts by c GMP Pathway
Cell Adhesion Molecules
Cells are attached to Basal Lamina and each other by cell adhesion molecules (CAMs)
They are:
Integrins
Adhesion molecules of IgG Superfamily
Cadherins
Selectins

Nitric Oxide: (USMLE Favorite)

Nitric oxide is NO
It is also called as EDRF (Endothelial derived relaxing factor)
It is produced from arginine by enzyme NO synthetase
NO has a short t (4 seconds)
It acts via c GMP pathway
It relaxes smooth muscles specifically
It prevents platelet aggregation
It functions as a neurotransmitter
It mediates bactericidal actions of macrophages
Acts as:
Free radical
Vasodilator
Oxidizing agent
Catalyst
NO, ANP, BNP act through cGMP

174

USMLE Step 1 Platinum Notes

REMEMBER
Somatomedins: (USMLE Favorite)
Are polypeptide growth factors secreted by liver, and other tissues, which mediate the growth-promoting effects of GH
Somatomedins exhibit sequence homology with insulin and proinsulin, they belong to the insulin family
Because of their resemblance to insulin, they can bind to insulin receptors and elicit insulin-like effects
At least four somatomedins have isolated, but by far the most important of these is somatomedin C (also called IGF-I)
The somatomedins, have characteristics:
Regulation of their concentration in serum by growth hormone
Stimulation of sulfate incorporation into the cartilage proteoglycan chondroitin sulfate
Insulin- like effects on both adipose and muscle tissue, and
Mitogenicity for fibroblasts

Effects of IGF-I

Ubiquitin

Ubiquitin is itself a protein that degrades other proteins i.e. unfriendly, for proteins
It is a highly conserved protein
Degradation by Ubiquitin occurs in Proteosomes by a process which is ATP dependent
Before degradation proteins are bound to binding proteins
Ubiquitin tags proteins for degradation.

Physiology

175

USMLE Case Scenario

A matrix glycoprotein inhibits the cell adhesion effect of fibronectin and permits cells to detach from the matrix and migrate.
The appearance of this glycoprotein in the wound matrix correlates with the initiation of epithelial and mesenchymal cell
migration. The matrix glycoprotein is:
1. Tenascin
2. Laminin
3. Brabykinin
4. Heparin
5. Incertin
6. Fibronectin
Ans. 1. Tenascin

USMLE Case Scenario

Maximum absorption of the water occurs at:
1. Proximal convoluted tubule
2. Distal convoluted tubule
3. Collecting duct
4. Loop of henle
Ans. 1. Proximal convoluted tubule

USMLE Case Scenario

Ghrelin is secreted from:
1. Endocrinal cells of the pancreas
2. Epithelium of the fundus
3. Epithelium of the antrum
4. Epithelial cells of the jejunum
Ans. 2. Epithelium of the fundus

USMLE Case Scenario

During embryological development, hematopoiesis occurs in different organs at different times. Which of the following are
the correct organs, in the correct sequence, at which hematopoiesis occurs embryologically?
1. Amnion, yolk sac, placenta, bone marrow
2. Placenta, liver and spleen, yolk sac, bone marrow
3. Placenta, spleen and lymphatic organs, bone marrow
4. Yolk sac, bone marrow, liver and spleen
5. Yolk sac, liver, spleen and lymphatic organs, bone marrow
Ans. 5. Yolk sac, liver, spleen and lymphatic organs, bone marrow
By the third week of development, hematopoiesis begins in the blood islands of the yolk sac. Beginning at 1 month of age
and continuing until 7 months of age, blood elements are also formed in the liver. Hematopoiesis occurs in the spleen and
lymphatic organs between 2 and 4 months, and in the bone marrow after 4 months.

USMLE Case Scenario

Calcitonin is secreted by:
1. Thyroid gland
2. Parathyroid gland
3. Adrenal glands
4. Ovaries
Ans. 1. Thyroid gland

176

USMLE Step 1 Platinum Notes

USMLE Case Scenario

QRS complex is due to:
1. Ventricular repolarization
2. Ventricular depolarization
3. Atrial repolarization
4. Atrial depolarization
Ans. 2. Ventricular depolarization

USMLE Case Scenario

GABA is produced from:
1. Alanine
2. Glycine
3. Glutamate
4. Glutamine
Ans. 3. Glutamate

USMLE Case Scenario

Brocas area is concerned with:
1. Word formation
2. Comprehension
3. Repetition
4. Reading
Ans. 1. Word formation

USMLE Case Scenario

Agranular endoplasmic reticulum is involved in the synthesis of:
1. Protein
2. Lipid
3. Carbohydrate
4. Vitamin D
Ans. 2. Lipid

USMLE Case Scenario

CO2 is primarily transported in the arterial blood as:
1. Dissolved CO2
2. Carbonic Acid
3. Carbamino-hemoglobin
4. Bicarbonate
Ans. 4. Bicarbonate

USMLE Case Scenario

The enzyme associated with the conversion of androgen to estrogen in the growing ovarian follicle is:
1. Desmolase
2. Isomerase

Physiology

177

3. Aromatase
4. Hydroxylase
Ans. 3. Aromatase

USMLE Case Scenario

Respiratory acidosis is compensated by:
1. Renal excretion of bicarbonate and excretion of base
2. Renal excretion of bicarbonate and excretion of acid
3. Renal retention of bicarbonate and excretion of acid
4. Renal retention of bicarbonate and excretion of base
Ans. 3. Renal retention of bicarbonate and excretion of acid

USMLE Case Scenario

Cortisol is secreted by:
1. Zona glomerulosa
2. Zona fasciculata
3. Zona reticularis
4. Zona medulla
Ans. 2. Zona fasciculata

USMLE Case Scenario

Brocas area situated in:
1. Superior temporal gyrus
2. Inferior temporal gyrus
3. Superior frontal gyrus
4. Inferior frontal gyrus
Ans. 4. Inferior frontal gyrus

USMLE Case Scenario

The extracellular matrix is the complex, cross-linked structure of proteins and polysaccharides that surrounds cells and
organizes the geometry of tissues. Collagen is the principal component of the extracellular matrix. The rate-limiting enzyme
in collagen synthesis is:
1. Lysyl hydroxylase
2. Prolyl hydroxylase
3. Lysyl oxidase
4. Prolyl oxidase
Ans. 2. Prolyl hydroxylase

USMLE Case Scenario

A 50-year-old drug addict man was brought to the emergency room in a stuporous state. Blood pressure is
100/50 mm Hg, heart rate 110 beats/min, respiratory rate 34/min, and his temperature is 103F. Below are his lab results:
Sodium 152 mEq/L (135145)
Potassium 2.4 mEq/L (3.55.0)
Chloride 108 mEq/L (95105)
Bicarbonate 11 mEq/L (2426)

178

USMLE Step 1 Platinum Notes

pH 7.2 (7.357.45)
PCO2 25 mm Hg (3545)
It implies an acid base status suggestive of:
1. Metabolic acidosis and metabolic alkalosis
2. Metabolic acidosis with partial respiratory compensation
3. Respiratory acidosis and partial metabolic compensation
4. Respiratory acidosis
Ans. 2. Metabolic acidosis with partial respiratory compensation

USMLE Case Scenario

A 55-year-old man is brought to the emergency room by his son in a stuporous and obtunded condition. Physical examination
reveals BP 120/70 and pulse 90 (supine); and BP 90/50 and pulse 120 (standing).
Serum chemistries are:
Na+ = 141 mEq/L
Cl = 87 mEq/L
K+ = 2.9 mEq/L
HCO3 = 42 mEq/L
Arterial pH = 7.53
PCO2 = 50 mm Hg
The disease process that best accounts for this problem:
1. Ethylene glycol poisoning
2. Chronic obstructive pulmonary disease
3. Congestive heart failure
4. Lactic acidosis
5. Vomiting
6. Chronic renal failure
Ans. 5. Vomiting

USMLE Case Scenario

Capacitance of sperm is attained in:
1. Epididymis
2. Genital tract
3. Vagina
4. Fallopian tube
Ans. 4. Fallopian tube

USMLE Case Scenario

Neuroendocrine responses contributes to meeting the enhanced energy demands during exercise is:
1. Glucagon stimulation of hepatic glycogen synthesis
2. Epinephrine stimulation of hepatic glycogenolysis
3. Epinephrine inhibition of hepatic glycogenolysis
4. Norepinephrine-induced stimulation of insulin release
5. Cortisol inhibition of gluconeogenesis
Ans. 2. Epinephrine stimulation of hepatic glycogenolysis

USMLE Case Scenario

Elevated fasting plasma glucose levels in pregnant women with no history of diabetes maybe related to:
1. Increased estrogen production
2. Decreased progesterone clearance

Physiology

179

3. Increased h PL/GH production

4. Increased insulin degradation
5. Decreased prolactin levels
Ans. 3. Increased hPL/GH production

USMLE Case Scenario

Testosterone production is mainly contributed by:
1. Leydig cells
2. Sertolie cells
3. Seminiferous tubules
4. Epididymis
Ans. 1. Leydig cells

USMLE Case Scenario

The processing of short-term memory to long-term memory is done in:
1. Prefrontal cortex
2. Hippocampus
3. Neocortex
4. Amygdala
Ans. 2. Hippocampus

USMLE Case Scenario

Basal ganglia is involved primarily in:
1. Planning and programming of voluntary movements
2. Processing of cognitive functions
3. Sensory-motor integration
4. Language function
Ans. 1. Planning and programming of voluntary movements

USMLE Case Scenario

Which of the following can be present in hyperosmolar coma in a diabetic patient?
1. Low plasma glucose
2. Low plasma potassium
3. High plasma pH
4. High plasma ketones
Ans. 4. High plasma ketones

USMLE Case Scenario

A 88-year-old woman from Mexico is admitted to the hospital following about of severe vomiting and generalized weakness.
Initial laboratory values reveal elevated Ca2 levels. The referring physician tells you that she has breast cancer and her bone
scan indicates metastasis to bone. The most likely cause of hypercalcemia is:
1. Increased PTH production
2. Increased responsiveness of the PTH receptor 1
3. Increased PTHrP production
4. Decreased responsiveness to calcitonin
Ans. 3. Increased PTHrP productions

180

USMLE Step 1 Platinum Notes

USMLE Case Scenario

FIGLU excretion in the urine, is an index of the deficiency of:
1. Thiamine
2. Niacin
3. Pyridoxine
4. Folate
Ans. 4. Folate

USMLE Case Scenario

In a 55-year-old anion gap needs to be calculated. The anion gap is calculated as:
1. [K+] + [HCO3 + Cl]
2. [Na+] + [Cl + HCO3]
3. [Na+] [HCO3 + Cl]
4. [Mg] + [HCO3 + Cl]
5. [Mg] + [HCO3 + Cl]
Ans. 3. [Na+] [HCO3 Cl]

USMLE Case Scenario

Intrinsic Factor of Castle is secreted by which of the following cells in gastric glands:
1. Chief cells
2. Parietal cells
3. Enterochromaffin cells
4. cells
Ans. 2. Parietal cells

USMLE Case Scenario

A 25-year-old man from New Jersy after a fight incurs blunt trauma to his upper outer arm. On physical examination, there is
a 2 3 cm contusion. He bleeds but the initial soft tissue bleeding stops in a few minutes and the size of the bruise does not
increase. Which of the following chemical mediators is most important in this episode of hemostasis?
1. Leukotriene
2. Neurokinin
3. Bradykinin
4. Prostaglandin
5. Prostacyclin
6. Plasminogen
7. Thromboxane
Ans. 7. Thromboxane
It is released by platelets to promote formation of a stable secondary plug to achieve hemostasis

USMLE Case Scenario

A 55-year-old man has severe chest pain for the past 6 hours. Laboratory studies show an elevated serum troponin I. A
coronary angiogram is performed emergently and reveals >85 % occlusion of the left anterior descending artery (LAD). An
irreversible injury to myocardial fibers will have occurred when?
1. Cellukar swelling
2. Fat stores are depleted+
3. Glycogen stores are depleted

Physiology

181

4. Cytoplasmic sodium increases

5. Karyorrhexis
6. Intracellular pH
7. Blebs form on cell membranes
Ans. 1. Cellukar swelling

USMLE Case Scenario

Ovulation is primarily caused by preovulatory surge of:
1. Estradiol
2. Luteinizing hormone
3. Progesterone
4. Follicle stimulating hormone
Ans. 2. Luteinizing hormone

USMLE Case Scenario

The parvocellular pathway, from the lateral geniculate nucleus to the visual cortex, carries signals for the detection of:
1. Movement, depth and flicker
2. Color vision, shape and fine details
3. Temporal frequency
4. Luminance contrast
Ans. 2. Color vision, shape and fine details

USMLE Case Scenario

A single-breath carbon monoxide diffusion capacity (DLCO) is done in a 33-year-old patient. In this test, the patient is required
to inhale low, nontoxic concentrations of carbon monoxide, hold the breath for 10 seconds, and then exhale. This test is rapid,
simple, safe and painless. DLCO is an estimate of:
1. Pulmonary capillary surface area
2. Respiratory reserve
3. Elastic recoil
4. Airway resistance
Ans. 1. Pulmonary capillary surface area

USMLE Case Scenario

The supraoptic nucleus of the hypothalamus is believed to control secretion of which of the following hormones?
1. Serotonin
2. Oxytocin
3. Growth hormone
4. Adrenocorticotropic hormone
Ans. 2. Oxytocin

USMLE Case Scenario

Central Chemoreceptors are most sensitive to following changes in blood:
1. PCO2
2. PCO2
3. H+
4. PO2
Ans. 1. PCO2

182

USMLE Step 1 Platinum Notes

USMLE Case Scenario

The Hyperkinetic features of the Huntingtons disease are due to the loss of:
1. Nigrostriatal dopaminergic system
2. Intrastriatal cholinergic system
3. GABA-ergic and cholinergic system
4. Intrastriatal GABA-ergic and cholinergic system
Ans. 3. GABA-ergic and cholinergic system

USMLE Case Scenario

The Myelin sheath is formed around the nerve fibers in the central nervous system by:
1. Astrocytes
2. Microglia
3. Oligodendrocytes
4. Protoplasmic astrocytes
Ans. 3. Oligodendrocytes

BIOCHEMISTRY

Biochemistry

DNA: (HIGH YIELD POINTS FOR USMLE)

Deoxyribonucleic acid (DNA) is the hereditary material of the cell
Important points about Structure of DNA
DNA consists of two strands of nucleotides wrapped around each other to form a complex double helix
The building blocks of each strand are deoxyribonucleotides, which consist of one of four basesadenine (A), guanine (G),
cytosine (C), and thymine (T)a sugar-deoxyribose, and a covalently joined phosphate group
The deoxyribose molecules are linked by phosphates to form the backbone of DNA
The double helix is held together by the hydrogen bonds that form between the bases on the two complementary strands
oriented in antiparallel directions
RNA is similar to DNA except that the deoxyribose sugar of DNA is replaced by a ribose moiety in RNA, and instead of Thymine T,
RNA uracil (U)
Transcription results in the production of a precursor messenger RNA (pre-mRNA) that contains both intron and exon
sequences
The introns are excised
Exons are ligated together in a two-stage splicing process that results in a mature mRNA that can be exported from the nucleus and
translated to produce the desired protein
While still in the nucleus, the spliced mRNA undergoes further processing
The 5 end of the RNA is capped by a guanosine derivative
A string of adenylic acid residues (polyA) is added to its 3end to stabilize the transcript for transit within the cellular environment
Watson and Crick theory pertains to DNA
Human genome contains 3 x 109 base pairs
Histones are proteins present in DNA
New DNA synthesis occurs in interphase

High Yield Points

Most DNA occurs as Right Handed Double Helical called B DNA.
Rare Left Handed Double Helical called Z DNA
Negative super coiling occurs if DNA is wound loosely
Positive super coiling occurs if DNA is wound Tightly
Topoisomerases are enzymes that change amount of supercoiling in DNA molecules
DNA Topoisomerase II can induce negative supercoiling or Remove Positive super coils
DNA Topoisomerase I can relax supercoiling
Heterochromatin

Euchromatin

Highly condensed
Inactive

Loosely condensed
Active

186

USMLE Step 1 Platinum Notes

Prokaryotes have single origin of Replication

Eukaryotes have multiple origin of Replication

Remember
New synthesized strand is made in 5 3 direction
Template is scanned in 3 5direction
New synthesized strand is complimentary and antiparallel
Daunorubicin and Doxorubicin exert their effect by intercalating between bases of DNA and thereby interfering with activity of
Topoisomerase II
Cisplatin on the other hand binds tightly to DNA causing structural Distortion

Important Points about DNA and RNA (Repeated in USMLE Frequently)

DNA repair: Single
strand

DNA/RNA/ protein
synthesis direction
Types of RNA

Polymerases: RNA

Start and Stop

codons

Promoter
Enhancer

Single strand, excision-repair-specific glycosylase recognizes and removes damaged base

Endonuclease makes a break several bases to the 5 side
Exonuclease removes short stretch of nucleotides. DNA polymerase fills gap
DNA ligase seals
DNA and RNA are both synthesized in 53 direction
Protein synthesis also proceeds in the 5 3 direction
mRNA is largest type of RNA
rRNA is the most abundant type of RNA
tRNA is the smallest type of RNA
Eukaryotes:
RNA polymerase I make rRNA
RNA polymerase II makes mRNA
RNA polymerase III makes t RNA
No proofreading function. RNA polymerase II opens DNA at promoter site (A-T-rich upstream sequenceTATA and CAAT)
-amanitin inhibits RNA polymerase II
Prokaryotes:
RNA polymerase makes all three kinds of RNA
AUG (or rarely GUG) is the initiation codon
AUG codes for methionine, which may be removed before translation is completed. In prokaryotes the initial
AUG codes for a formyl-methionine (f-met)
Stop codons: UGA, UAA, UAG
Site where RNA polymerase and multiple other transcription factors bind to DNA upstream from gene locus
Stretch of DNA that alters gene expression by binding transcription factors. May be close to, far from, or even
within (in an intron) the gene whose expression it regulates

Transcription and translation

Biochemistry

187

Functions of Different Types of DNA Polymerases

In Eukaryotes
DNA Polymerase synthesizes leading strand
DNA Polymerase synthesizes lagging strand
DNA Polymerase replicates mitochondrial DNA
DNA Polymerase , DNA polymerase participate in DNA Repair

Functions of Different Enzymes (Remember Thoroughly)

Site

Prokaryotic

Eukaryotic

Recognition of origin of replication

DNA A Protein

Unwinding of DNA Helix

Helicase

Helicase

Stabilization of unwound Template strand

Single stranded binding protein (SSB)

Single stranded binding protein (SSB)

Synthesis of RNA Primers

Primase

Primase

Synthesis of DNA
Leading strand+ Proof reading
Lagging strand

DNA Polymerase III

DNA Polymerase

DNA Polymerase III

DNA Polymerase

Removal of RNA Primers

DNA Polymerase I

Joining of Okazaki Fragments

DNA ligase

DNA ligase

Removal of Positive super coils

DNA Topoisomerase II
(DNA gyrase)

DNA Topoisomerase II

RNA Polymerase
In bacteria RNA polymerase synthesizes almost all of the RNA
RNA polymerase is a multi subunit enzyme
One component of RNA polymerase is the sigma subunit which enables RNA Polymerase to recognize promoter regions on the
DNA
Other component is the rho factor or termination factor which enables RNA Polymerase to recognize termination regions on
the DNA

Mitochondrial DNA: (Cases asked in USMLE)

Thirteen out of 100 polypeptides required for oxidative phosphorylation are coded by mitochondrial DNA
Defects in oxidative phosphorylation are most likely as a result of alterations in mitochondrial DNA as it has a mutation rate
about ten times greater than nuclear DNA
This is because there are no introns and a mutation invaribly strikes a coding sequence (axon)
Tissues with greatest ATP requirement (CNS, Skeletal muscle, Heart muscle, Kidney, Liver) are most affected
Mitochondrial DNA is maternally inherited because mitochondria from sperms do not enter the fertilized egg
Mitochondrial DNA is closed and circular and 16.5 kb in length
MELAS (Mitochondrial Encephalopathy, Lactic Acidosis and Stroke like episodes) are attributed to mitochondrial mutations. Other
diseases associated with mitochondrial DNA are:
Lebers Hereditary Optic Neuropathy
MELAS (Mitochondrial encephalopathy with lactic acidosis and stroke like episodes)
Myopathy

188

USMLE Step 1 Platinum Notes

MERRF Syndrome: (Myoclonic epilepsy and ragged red fibers.)

Cardiomyopathy
Strokes
Lactic acidosis
External Ophthalmoplegia
Optic atrophy
NARP (Neuropathy, ataxia and retinitis pigmentosa)
Pearsons syndrome
Sensorineural deafness
Diabetes mellitus

Hereditary DNA Repair Disorders

Xeroderma pigmentosum:
Hypersensitivity to sunlight/UV, resulting in increased skin cancer
Incidence and premature aging
Cockayne syndrome:
Hypersensitivity to UV and chemical agents
Trichothiodystrophy:
Sensitive skin, brittle hair and nails
Werners syndrome:
Premature aging and retarded growth
Blooms syndrome:
Sunlight hypersensitivity, high incidence of malignancies
(Especially leukemias)
Ataxia telangiectasia:
Sensitivity to ionizing radiation and some chemical agents
All of the above diseases are often called segmental progerias (accelerated aging diseases) because their victims appear elderly
and suffer from aging-related diseases at an abnormally young age
Other diseases associated with reduced DNA repair function include
Fanconis anemia
Hereditary breast cancer and
Hereditary colon cancer

Xeroderma pigmentosa: (Repeated in USMLE)

Extreme UV sensitivity
Exposure of cell to UV light can result in the covalent joining of two adjacent pyrimidines (Usually Thymines) producing a dimer
These Thymine dimmers prevent DNA polymerase from replicating the DNA strands
Pyrimidine dimmers can be formed in the skin cells of humans exposed to unfiltered sunlight
In Xeroderma Pigmentosa, the cells cannot repair the damaged DNA, resulting in accumulation of mutations and skin cancers
The most common form is produced by absence of enzyme UV specific Exonuclease/Endonuclease
Excessive freckling
Multiple skin cancers
Corneal ulcers

Biochemistry

189

Transposons
Are pieces of DNA that move readily from the one site to another either within or between the DNAs of bacteria, plasmids and
bacteriophages
They are also known as Jumping Genes
They can code for drug resistance, enzyme, toxin or a variety of metabolic enzymes
They can either cause mutation in the gene into which they insert or alter the expression of nearby genes
In contrast to plasmids or bacterial viruses, transposons are not capable of independent replication
They replicate as a part of recipient DNA

Prions
Prions are proteins which are normally found in the body. Prions become infectious or pathogenic due to misfolding of the proteins
Prions are normally present in human. The prion protein, endogenous to the human is PrP (which is a glycoprotein rich in b sheets)
PrPsc is the infectious form of the Prion. (It is formed due to mutation in PrP)
The key to become infectious lies in changes in three dimensional conformation of PrP, i.e. there is abnormality in protein folding
(the a helical secondary structure of PrP changes to b sheets in PrPsc)
So, PrPsc is a misfolded PrP and this conformational difference cause PrPsc to resist proteolytic degradation
Misfolded proteins are quite dangerous for the body because they possess a remarkable property that they can cause other
normally folded prions to distort into the same misfolded state. Thus, misfolded proteins, i.e. prions are able to replicate and
spread throughout tissue without using either DNA or RNA
The infective agent is thus an altered version of a normal protein which acts as a template for converting more normal protein
to the pathogenic conformation

Enzymology

Enzymes do not alter Energy of Reaction

Enzymes lower Energy of Activation
Vmax = Maximum velocity with specified amount of enzyme
Km = Concentration of substrate required to produce half V max

Competitive Inhibition
It is reversible
Substrate and inhibitor resemble each other
V max is same, Km is increased
Substrate affinity to enzyme is lowered

Noncompetitive Inhibition

It is reversible or irreversible
Substrate and inhibitor do not resemble each other
V max is decreased, Km is unaltered
Substrate affinity to enzyme is not lowered

Allosteric Inhibition
Here inhibitor binds to enzyme at a site different than active site

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USMLE Step 1 Platinum Notes

Does not follow Michaelis Menten Kinetics

Follows sigmoid kinetics
Km is raised but V max is unchanged in some allosteric inhibition reactions
Substances that reduce the activity of an enzyme are called inhibitors
Reversible inhibitors bind to an enzyme but rapidly dissociate from it in contrast to irreversible inhibitors which bind tightly and
dissociate very slowly from the enzyme
There are several types of reversible inhibitors:
Competitive inhibitors usually resemble the substrate and compete with it for binding at the active site

Thus, increasing the concentration of substrate will decrease the percent inhibition of the enzyme. The Vmax is unchanged, but the
Km is increased

A noncompetitive inhibitor binds with equal affinity to both enzyme and enzyme-substrate complex

This binding leads to a distortion of the substrate binding site, so new substrate cannot bind and/or the product cannot be
released. In this kind of inhibition, the Vmax is decreased but the Km is not altered

An uncompetitive inhibitor does not bind to free enzyme, but binds to the enzyme-substrate complex at a site other than
the catalytic site. Once bound by the inhibitor, the enzyme is trapped in the enzyme-substrate complex state until the inhibitor
dissociates. In this kind of inhibition, the slope of the reaction (which is the ratio Km/Vmax) remains the same, but both Vmax and
Km are reduced.

Remember
Michaelis Menten (Km) reflects the affinity of enzymes to that substrate
It is equal to the substrate concentration at which reaction velocity is half of V max
Low Km reflects high affinity of enzyme
High Km reflects low affinity of enzyme

Metabolic Processes and their Sites

Processes occurring in cytosol:
Glycolysis
Glycogenolysis
Glycogenesis
HMP Shunt (Pentose phosphate synthesis)
Fatty acid synthesis
Bile acid synthesis
Cholesterol synthesis
Processes occurring in Mitochondria:
Fatty acid oxidation(Beta)
Electron transport chain
Krebs/TCA Cycle
Oxidative phosphorylation
Processes occurring in both mitochondria and cytosol:
Urea synthesis
Gluconeogenesis

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191

Sites of metabolic processes

Sites of
Protein synthesis: RER
Steroid synthesis: Smooth ER
Sorting of Proteins: Golgi bodies (Dictyosome)

Medically Important Enzymes Frequently asked

Reverse Transcriptase:
It is an RNA dependent DNA polymerase that requires an RNA Template to direct the synthesis of new DNA
AZT, ddC, ddI (Antiretrovirals) act on reverse transcriptase
Restriction Endonucleases:
Are Bacterial enzymes that cleave double stranded DNA into smaller fragments
Each enzyme cleaves DNA at a specific 46 base long nucleotide sequence producing DNA segments called restriction fragments
These enzymes form either sticky ends or blunt ends on the DNA
The DNA sequence recognized by a restriction enzyme is called a restriction site
Telomerase
Is an enzyme that completes replication of Telomers
Telomeres are repetitive sequences at ends of DNA

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USMLE Step 1 Platinum Notes

Telomerase is present in embryonic cells, stem cells and cancer cells

DNA polymerase is unable to replicate the end of a DNA chain completely, resulting in loss of DNA with each replication. This
problem has been solved by a mechanism that replicates tandem repeats of a six-nucleotide sequence (GGGTTA) to the ends
of each chromosome. These repeated sequences are called telomeres and are replicated through an RNA-dependent DNA
polymerase called telomerase
Normal somatic cells do not express telomerase, and the replicative lifetime of such cells is limited to approximately 30 cell
divisions due to the progressive loss of telomere repeats; the limit imposed on somatic cell division is called the Hayflick limit, at
which time replicative senescence occurs
Germ cells express telomerase and have a long (possibly unlimited) replicative lifetime
Cancer cells express telomerase and in cancer cells is thought to be a component of the neoplastic process, assuring that the cell
will be able to undergo many divisions without inducing senescence or genetic catastrophe. Inhibition of telomerase activity in
cancer cells could have antitumor effects
Human pluripotential stem cells express high levels of telomerase, an enzyme that is essential for allowing repeated replication
of the ends of eukaryotic chromosomes
The capacity to divide indefinitely is provided by activation of telomerase, which allows continued replication of chromosomes
by addressing the unique need of chromosome ends to be continually renewed to a proper length to allow normal mitosis
The capacity to invade and metastasize is conveyed by elaboration of matrix metalloproteases and plasminogen activators
and the capacity to recruit host stromal cells at the site of invasion through tumor-induced angiogenesis.

Classification of Enzymes
Class 1

Oxidoreductases: Transfer of hydrogen or addition of oxygen; e.g. Lactate dehydrogenase (NAD);

Glucose-6-phosphate dehydrogenase (NADP); Succinate dehydrogenase (FAD); di-oxygenases

Class 2

Transferases: Transfer of groups other than hydrogen

Example, Aminotransferase. (Subclass: Kinase, transfer of phosphoryl group from ATP, e.g. Hexokinase)

Class 3

Hydrolases: Cleave bond and add water, e.g. Acetyl choline esterase; Trypsin

Class 4

Lyases: Cleave without adding water, e.g. Aldolase; HMG CoA lyase; ATP Citrate lyase. (Subclass:
Hydratase; add water to a double bond)

Class 5

Isomerases: Intramolecular transfers. They include racemases and epimerases. Examples, Triose
phosphate isomerase

Class 6

Ligases: ATP dependent condensation of two molecules, e.g. Acetyl CoA carboxylase; Glutamine
synthetase; PRPP synthetase

USMLE Case Scenario

The lack of chromosomal shortening allows the malignant cells to undergo many more divisions than the normal cells. Which
of the following enzymes is most likely to have this effect?
1. Reverse transcriptase
2. DNA polymerase
3. Isomerase
4. Phosphodiesterase
5. Telomerase
6. Protein kinase
7. Topoisomerase
Ans. 5. Telomerase

Mutations
Transistion: A point mutation that replaces purine-pyrimidine base pair with different purine-pyrimidine base pair
Transversion: A point mutation that replaces purine-pyrimidine base pair with different pyrimidine-purine base pair

Biochemistry
Mutation

193

Effect on Protein

Silent

New codon specifies same amino acid

None

Missense

New codon specifies new amino acid

Decrease in function

Non sense

New codon is Stop codon

Usually non functional

Frameshift

Deletion/addition of base

Usually non functional

USMLE Case Scenario

A 2-month-old, breastfed baby that was normal at birth begins to develop GI problems and cirrhosis of the liver. Molecular
analysis indicates a normal amount of galactose-1-phosphate uridyl transferase (GALT) mRNA, but no observable enzyme
activity. Which of the following would be the best possible explanation for this?
1. Gene deletion
2. Nonsense mutation
3. Premature transcription termination sequence in the DNA
4. Promoter mutation
5. RNA splicing mutation
Ans. 2. Nonsense mutation
It is a mutation in the DNA that leads to a premature stop codon when the mRNA is being translated into protein. The mRNA would
be transcribed correctly, but when the protein was being translated, it would be stopped prematurely, leading to a truncated protein.

Collagen

Collagen formation begins with transcription of mRNA from appropriate

DNA genes in the nucleus. While still within the nucleus, the mRNA is spliced
It is then transported through the cytoplasm to the ribosomes on the rough endoplasmic reticulum
Individual chains are translated on the ribosomes, with the ends feeding into the endoplasmic reticulum lumen. Within the lumen,
glycosylation of the individual chains occurs
The material then moves toward the Golgi bodies (whose lumens are connected to the endoplasmic reticulum) where the triple
helices of procollagen form
The procollagen is then secreted into the extracellular space, where cleavage of pro-peptides and cross- linking of different
triplehelices occurs, maturing the collagen
The extracellular space is the site of procollagen cleavage and cross- linking
The nucleus is the site of mRNA transcription and splicing
The rough endoplasmic reticulum is the site of chain translation and glycosylation

Disorders of Collagen Synthesis

Scurvy

Deficient hydroxylation secondary to Ascorbate deficiency

Osteogenesis imperfecta

Mutations in collagen genes

Ehler Danhlos syndrome

Mutations in collagen genes, Lysine and Hydroxylase genes

Menkes disease

Deficent cross linking secondary to Cu deficiency

Scurvy [USMLE CASE]

A 72-year-old retired engineer alcoholic male who lives alone is admitted to the hospital for evaluation of wounds on limbs that
are not healing well
On physical examination, multiple ecchymoses are noted on the posterior aspect of his thighs and front of arm. Careful
examination of his skin reveals minute hemorrhages around hair follicles and splinter hemorrhages in the nail beds.
Laboratory examination is remarkable for hemoglobin of 9 (normal 1418 g/dL); no other hematologic abnormalities are
noted. He is most probably suffering from Scurvy.

194

USMLE Step 1 Platinum Notes

USMLE High Yield Points

Vitamin C deficiency causes scurvy
Seen primarily among poor and elderly people and alcoholics who consume <10 mg/d of vitamin C. Symptoms of scurvy primarily
reflect impaired formation of mature connective tissue and include bleeding into skin (petechiae, ecchymoses, perifollicular
hemorrhages);
Absence of vitamin C leads to impaired hydroxylation of proline residues in the nascent procollagen chains, leading to weakness
of blood vessel walls
Clinical Features:
It is characterized by perifollicular hemorrhages, fragmentation of hairs, purpura, ecchymoses
Splinter hemorrhages, and hemorrhages into muscle. In patients with normal dentition, gum changes
(Swelling, bleeding, loosening of teeth) are also noted
Without supplementation with vitamin C
Death may eventually occur
Other generalized symptoms include weakness, fatigue, and depression
In children, vitamin C deficiency may cause impaired bone growth
Laboratory diagnosis of vitamin C deficiency is made on the basis of low plasma or leukocyte levels
Administration of vitamin C (200 mg/d) results in marked improvement in the symptoms of scurvy in a matter of several days

Osteogenesis Imperfecta (OI): (USMLE Case Scenario)

A 5-month-old infant has fracture clavicle, fracture left radius, fracture right clavicle. Fractures are in different stages of healing. X-ray
reveals thin bones with thin cortices. There is no evidence of child abuse
The child has most likely: Osteogenesis imperfect.

USMLE High Yield Points

OI is also called as Brittle bone disease or Lobstein syndrome

Basic defect is in Collagen Type 1
It is transmitted either as AD or AR Inheritance
Type 1 OI is THE MOST COMMON TYPE
OI is inherited as autosomal dominant trait mostly
Blue sclera is present in several types of OI But not all
Grey sclera is a feature as well. Other ocular features of OI are:
-

Saturn ring, Arcus juvenilis, Hypermetropia and Retinal Detachment are seen

The sclera is normal in some types of OI

Feature of OI is generalized osteopenia with recurrent fractures and skeletal deformity. Fracture healing however is normal.
Fracture in utero may be seen. Laxity of joint ligaments leads to hypermobility
Some people have associated dentogenesis imperfecta: small fragile and discolored teeth
Dermis may be abnormally thin and skin is susceptible to easy bruising
Hearing loss due to involvement of inner and middle ear bones may produce deafness
Wormian bones are a feature
Pop corn calcification and whorls of radiodensities are a radiographic feature
Treatment is largely supportive

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195

Ehler Danlos Syndrome

Defect in normal synthesis and processing of collagen
Thin skin with easy bruising
Arterial intestinal or uterine rupture can occur

Menkes Disease: USMLE HighYield Points

Menkes disease also known as kinky hair disease, is an X-linked neurodegenerative disease of impaired copper transport
Named after noting the similarity of kinky hair to the brittle wool of Australian sheep raised in areas with copper-deficient soil,
he demonstrated abnormal levels of copper and ceruloplasmin in these patients
In Menkes disease, transport of dietary copper from intestinal cells is impaired, leading to the low serum copper levels. Abnormal
copper transport in other cells leads to paradoxical copper accumulation in duodenal cells, kidney, pancreas, skeletal muscle, and
placenta.
Hair changes: Abnormal kinky hair, eyebrows, and eyelashes. Often lightly or abnormally pigmented; can be white, silver, or gray
Associated are abnormal facies, Progressive cerebral degeneration and connective-tissue abnormalities. Loose skin at the
nape of the neck and over the trunk
Joint hyper mobility, Polypoid masses, which can be multiple, in the gastrointestinal tract, umbilical and inguinal hernias,
which can be bilateral, Bladder diverticula, Dilated ureters, Emphysema, Arterial rupture Brachial, lumbar, and iliac artery
aneurysms, Internal jugular vein aneurysms.
Menkes Kinky hair syndrome is associated with the defecive functioning of several copper-dependent enzymes due to impaired
copper absorption, transport, or metabolism. Lysyl oxidase is a copper-requiring enzyme that catalyzes the oxidative deamination
of lysyl residues linking two adjacent chains of tropoelastin polypeptides into an insoluble network.
Decreased lysyl oxidase (LO) activity accounts for the connective-tissue fragility and vascular abnormalities in Menkes disease

Vitamins
Important Vitamin Deficiencies: (Repeated in USMLE)
Vitamin

Enzyme

Deficiency State

Thiamine (B1)

Pyruvate dehydrogenase
Ketoglutarate dehydrogenase
Transketolase

Wernicke Korsakoff Syndrome

Wet Beriberi
Dry Beriberi

Biotin

Pyruvate carboxylase
Acetyl CoA carboxylase
Propionyl CoA carboxylase

Consumption of eggs containing avidin

Alopecia, Muscle pains

Pyridoxine

Aminotransferases

Riboflavin

Dehydrogenases

Corneal neovascularization
Chielosis/stomatitis
Magenta tongue

Niacin

Dehydrogenases

Pellagra
Diarrhea, Dementia, Dermatitis, Death

Pantothenic

Fatty acid Synthase

Fatty acyl CoA synthase

Rare
Burning foot syndrome

Isoniazid therapy
Sidderoblastic anemia
Chielosis/stomatitis
Convulsions

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USMLE Step 1 Platinum Notes

Folic Acid

Thymidylate synthase

Alcholics and pregnancy

Homocystenemia
Macrocytic anemia
Neural tube defects

Vitamin B12
Extrinsic factor of castle

Homocysteine methyltransferase
Methyl malonyl CoA mutase

Pernicious anemia
Megaloblastic anemia
Neuropathy
SACD
Methyl malonic aciduria

Vitamin C
post translation modifier

Propyl and Lysyl hydroxylase

Dopamine hydroxylase

Diet deficient in citrus

Scurvy

Fat Soluble Vitamins

Vitamin A (acts as hormone)

Night blindness
Xerophthalmia
Follicular Hyperkeratosis

Vitamin D

Rickets
Osteomalacia

Vitamin E
Prevents lipid peroxidation

Hemolysis
Retinitis pigmentosa
Neurological problems

Vitamin K
(Gamma carboxylation)
Post translation modifier

Bleeding tendency with PT normal BT

Deficiency of vitamin K produces a clotting disorder characterized by an elevated prothrombin
time and easy bleeding, particularly in neonates (hemorrhagic disease of the newborn).
The biochemical basis for this hemorrhagic tendency is that glutamate residues on Factors II
(Thrombin), VII, IX, and X must be converted to gamma-carboxyglutamate residues (in a vitamin
K-requiring reaction) for optimal activity.

Synthesis of vitamin D

Vitamin K Deficiency
The symptoms of vitamin K deficiency are due to hemorrhage, and newborns are particularly susceptible because of low fat stores,
low breast milk levels of vitamin K, sterility of the infantile intestinal tract, liver immaturity, and poor placental transport. Intracranial
bleeding, as well as gastrointestinal and skin bleeding, can occur in vitamin Kdeficient infants 17 days after birth. Thus, vitamin K
(1 mg IM) is given prophylactically at the time of delivery.

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197

USMLE Clinical Scenario

A child has cystic fibrosis. His parents report a history of recurrent respiratory tract infections and bulky, foul-smelling stools. After
assessment of his respiratory tract illness, the practitioner should also look for signs of which vitamin deficiency.
Fat soluble vitamin deficiency (A, D, E, K)

Remember: Conversions: Vitamins are required for

The conversion of homocysteine to methionine requires vitamin B12

Conversion of methylmalonyl CoA to succinyl CoA requires vitamin B12
Degradation of cystathionine requires vitamin B6
Hydroxylation of proline requires vitamin C

Vitamin A is necessary for formation of retinal pigments (deficiency can cause night blindness) and for appropriate differentiation
of epithelial tissues (including hair follicles, mucous membranes, skin, bone, and adrenal cortex)
Vitamin C is necessary for collagen synthesis
Vitamin D is important in calcium absorption and metabolism
Vitamin E is important in the stabilization of cell membranes
Vitamin K is necessary for normal blood coagulation

Hypervitaminosis (A): USMLE Favorite

Acute toxicity
It is manifest by increased intracranial pressure, vertigo, diplopia, bulging fontanels in children, seizures, and exfoliative dermatitis; it
may result in death
Chronic vitamin A intoxication has
Manifestations Include:
Dry skin, cheilosis, glossitis, vomiting, alopecia, bone pain, hypercalcemia, lymph node enlargement, hyperlipidemia, amenorrhea,
and features of:
Pseudotumor cerebri with increased intracranial pressure and papilledema
Congenital malformations, spontaneous abortions, craniofacial abnormalities, and valvular heart disease

USMLE Clinical Scenario

A chronic alcoholic develops severe memory loss with marked confabulation. Deficiency of which of the vitamins would be
most likely to contribute to the neurologic damage?
Wernicke-Korsakoff syndrome refers to the constellation of neurologic symptoms caused by thiamine deficiency
A severe memory deficit, which the patient may attempt to cover by making up bizarre explanations (confabulation), is prominent
Anatomical damage to the mamillary bodies and periventricular structures has been postulated as the cause
In the US severe thiamine deficiency is seen most commonly in chronic alcoholics
Thiamine deficiency can also damage peripheral nerves (dry beriberi) and the heart (wet beriberi).

High Yield Facts

Folic acid deficiency produces megaloblastic anemia without neurologic symptoms

Niacin deficiency produces pellagra, characterized by depigmenting, dermatitis, chronic diarrhea, and death
Riboflavin deficiency produces ariboflavinosis, characterized by glossitis, corneal opacities, dermatitis, and erythroid hyperplasia
Vitamin B12 deficiency produces megaloblastic anemia accompanied by degeneration of the posterolateral spinal cord

198

USMLE Step 1 Platinum Notes

Substance Accumulation in Different Diseases

Accumulation of galactocerebrocide occurs in Krabbe disease, which is due to galactocerebrocide deficiency
Accumulation of glucocerebroside occurs in Gaucher disease, which is due to defects in -glucocerebrosidase. The
reticuloendothelial cells and CNS are affected
Accumulation of GM2 ganglioside occurs in Tay
Sachs disease because of hexosaminidase deficiency. The swollen ganglion cells of the retina contribute to a classic sign of TaySachsthe macular cherry-red spot
Accumulation of sphingomyelin in a variety of organs occurs in Niemann-Pick disease, which is due to a defect in sphingomyelinase
Accumulation of sulfatide occurs in Metachromatic leukodystrophy, caused by aryl sulfatase A deficiency

USMLE Case Scenario

A 3-year-old retarded child is seen by a specialist. The childs history is significant for failure to thrive and progressive
neurologic deterioration, including deafness and blindness. Physical examination is remarkable for hepatosplenomegaly, as
well as a cherry-red spot on funduscopic examination. These symptoms are consistent with a diagnosis of:
Tay-sachs Disease

Lysosomal Storage Disease

Fabrys
Disease

Lysosomal
Storage Disease

X-Linked Recessive
Angiokeratomas (skin lesions) over lower
Alpha-Galactosidase A deficiencybuild up of trunk, fever, severe burning pain in extremities,
cardiovascular and cerebrovascular involvement.
ceramide trihexoside in body tissues

Hunters
Syndrome

Lysosomal
Storage Disease

X-Linked Recessive. L-iduronosulfate sulfatase Similar to but less severe than Hurler Syndeficiencybuild up of mucopolysaccharides drome. No corneal clouding. Hepatospleno(heparan sulfate and dermatan sulfate)
megaly, micrognathia, retinal degeneration, joint
stiffness, mild retardation, cardiac lesions

Hurlers
Syndrome

Lysosomal
Storage Disease

Autosomal Recessive. -L-iduronidase deficiency - Gargoyle-like facies, progressive mental

accumulation of mucopolysaccharides (heparan deterioration, stubby fingers, death by age 10.
sulfate, dermatan sulfate) in heart, brain, liver, Similar to Hunters Syndrome
other organs

MPS IV (Morquio Syndrome)

Characterized by severe skeletal diseases that resemble the spondyloepiphyseal dysplasias
There is extreme shortening of the trunk due to multiple vertebral collapses
The long bones are relatively spared
Joint laxity can lead to osteoarthritis-like destruction of the joints
Upper cervical spinal cord compression due to atlanto axial instability predisposes to subluxation and paralysis
Many patients have mitral valve insufficiency that can be functionally significant

I Cell Disease

USMLE Case Scenario

A Child with large tongue, coarse facial features and club foot is seen by a pediatrician. You hear the doctor talking to his
colleague that the child has a problem with Phosphorylation of their mannose residues. The most likely possibility is a disease
called I-cell disease.

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199

It is an inborn error that led to the discovery of how enzymes are imprinted to reside in lysosomes. Patients with I-cell disease
have inherited defects in the recognition markers required to direct enzymes to the endocytic receptor of plasma membrane
and to its capture in the acidic milieu of the lysosome. Patients lack all cellular lysosomal enzymes. Instead cells are filled with
inclusion bodies (hence I-cell). The misdirected lysosomal enzymes are secreted and are present in excess in plasma but are
missing from cells. These extracellular enzymes were found to lack mannose 6-phosphate residues and lead to importance
of the post-translational mechanisms by which enzymes are directed to the lysosome by adding phosphorylated mannose.
Individuals with I-cell disease lack this phosphotransferase activity.
Lysosomal enzymes are glycosylated and modified
In the Golgi complex specific mannose residues are phosphorylated
This phosphorylation directs them towards lysosomes. In absence of Phosphorylation of their mannose residues, these enzymes
are (not directed to lysosomes) but to extracellular space and inclusions accumulate in cell
Specifically, the Golgi apparatus incells of these patients has an abnormal N-acetyl-glucosaminotransferase (N-acetylglucosamine1-phosphotransferase), and is not able to add the necessary recognition marker mannose phosphate to enzymes usually destined
to enter lysosomes. A complete deficiency of this enzyme (type I form of I cell disease) causes death early in life; partial deficiencies
(Type III form) produce milder disease (pseudo-Hurler syndrome) with survival to adulthood
Features:
Coarse facial features
Macroglossia, Gingival hyperplasia
Club foot, club hand
Cardiorespiratory failure

USMLE Case Scenario

A child with coarse facies, corneal clouding, joint stiffness and mental retardation is found to have a partial defect in
N-acetylglucosaminotransferase. Damage to this enzyme directly affects which of the following biochemical functions?
Targeting of enzymes for lysosomes: N-acetylglucosamine-1-phosphotransferase to add the recognition marker mannose
phosphate to enzymes destined to enter lysosomes. Consequently, there is a generalized defect in lysosome function.

Glycolysis
Glycolysis is conversion of glucose to pyruvate under aerobic condition
Glycolysis is conversion of glucose to lactate under anerobic condition
Mature RBC do not contain enzymes of TCA cycle
Glycolysis occurs in cytosol
Cancer cells derive energy by glycolysis
Sodium fluoride is used as an anticoagulant for estimating blood glucose to prevent glycolysis
Flouride inhibits enolase
Glycolysis is regulated at three steps involving irreversible reactions catalysed by enzymes namely
Hexokinase
Phosphofructokinase
Pyruvate kinase

Citric Acid Cycle

Also called Krebs cycle
First substrate is pyruvate

200

USMLE Step 1 Platinum Notes

ATP is produced in steps catalyzed by:

Isocitrate dehydrogenase
Succinate dehydrogenase
Succinate thiokinase
Malate dehydrogenase
Pyruvate dehydrogenase contains:
Decarboxylase
Transacetylase
Dehydrogenase
Substrate level phosphorylation occurs in reaction catalyzed by: Succinyl Co A thiokinase

Glycogen Synthesis
Insulin is produced in the beta cells of the pancreatic islets
It is initially synthesized as a single-chain 86-amino-acid precursor polypeptide, preproinsulin.
The mature insulin molecule and C peptide are stored together and cosecreted from secretory granules in the beta cells
Human insulin is now produced by recombinant DNA technology
Glucose is the key regulator of insulin secretion by the pancreatic beta cell, although amino acids, ketones, various nutrients,
gastrointestinal peptides, and neurotransmitters also influence insulin secretion
Glucose stimulates insulin secretion through a series of regulatory steps that begin with transport into the beta cell by the GLUT2
glucose transporter
Glucose phosphorylation by glucokinase is the rate-limiting step that controls glucose-regulated insulin secretion
Insulin binding to the receptor stimulates intrinsic tyrosine kinase activity, leading to receptor autophosphorylation
In the fasting state, low insulin levels promote hepatic gluconeogenesis and glycogenolysis to prevent hypoglycemia
Low insulin levels decrease glycogen synthesis, reduce glucose uptake in insulin-sensitive tissues, and promote mobilization of
stored precursors
Reduced insulin levels are also permissive in allowing glucagon to stimulate glycogenolysis and gluconeogenesis by the liver and
renal medulla
These processes are of critical importance to ensure an adequate glucose supply for the brain

REGULATION
Glycogen Synthesis
(Glycogen synthetase)
Activated by

Insulin
Glucose

Inhibited by

Glucagon
Epinephrine

Glycogen Breakdown
(Glycogen Phosphorylase)
Activated by

Glucagon
Epinephrine

Inhibited by

Insulin
Glucose

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201

Gluconeogenesis

Occurs from glycerol, alanine, lactate

Major contributor is alanine
Gluconeogenic capability is determined by fructose 1, 6 biphosphate
Enzyme common to gluconeogenesis and glycolysis is phosphofructokinase

Enzymes Controlling

Fructose 1,6 Biphosphate

Pyruvate carboxylase
Phosphoenol pyruvate carboxykinase
Glucose 6 phosphatase

Well Fed State

Ingestion of glucose.blood glucoseinsulin releasephosphatase activityfructose 2,6 biphosphatase

Fasting State
Ingestion of glucose.blood glucoseglucagon releasecAMPProtein kinase fructose 2,6 biphosphatase

Remember: High Yield Points about Important Enzymes

The Three irreversible steps of glycolysis are catalyzed by hexokinase,phosphofructokinase-1 and pyruvate kinase
Fructose-1,6-bisphosphatase is the enzyme that splits fructose-1,6-bisphosphate into fructose-6-phosphate and inorganic
phosphate. It is required for gluconeogenesis
Glucose-6-phosphatase is a liver enzyme that hydrolyzes glucose-6-phosphate to glucose. A deficiency of this enzyme leads to
von Gierke disease, also known as glycogen storage
Pyruvate dehydrogenase is a mitochondrial enzyme that converts pyruvate to acetyl CoA. This enzyme requires thiamine
pyrophosphate, lipoamide, and FAD as cofactors
Glucokinase is a liver enzyme that converts glucose to glucose-6-phosphate. Unlike hexokinase, it is specific for glucose and is
unresponsive to the level of glucose-6-phosphate. Its function is to store excess glucose so it has a very high Km (i.e. a low affinity)
for glucose, becoming active only when the concentration of glucose is very high.

202

USMLE Step 1 Platinum Notes

Pyruvate kinase catalyzes the conversion of phosphoenol pyruvate to pyruvate in the glycolytic pathway. It is activated by
fructose-1, 6-biphosphate, the product of the committed step of glycolysis, and is allosterically inhibited by ATP, alanine, and
acetyl CoA
Glycogen synthase is involved in the synthesis of glycogen. Glucagon (and epinephrine) stimulates the phosphorylation and
inactivation of glycogen synthase
Pyruvate kinase catalyzes the last reaction of glycolysis. It is inhibited by glucagon (thus decreasing the amount of glucose
consumption). Glucagon promotes the phosphorylation of pyruvate kinase, which renders it inactive.

Glucose 6 Phosphate Dehydrogenase Deficiency

A child who develops hemoglobinuria following a meal of beans

It is X linked Recessive
Most common enzyme deficiency
Causes episodic hemolytic anemia because of decreased ability of RBCS to withstand oxidative stress
G6PD is the first and rate limiting step of HMP shunt responsible for NADPH production
NADPH is the cofactor for production for glutathione reductase forming reduced glutathione which is a potent antioxidant
In its absence H2O2 accumulates in RBC causing cell membrane damage leading to hemolysis.
Pallor, Hemoglobinuria, Jaundice, Heinz bodies, Bite Cells are seen.
Oxidized hemoglobin denatures and precipitates in the form of Heinz bodies.

Pyruvate Kinase Deficiency

Pyruvate kinase is a glycolytic enzyme; pyruvate kinase deficiency is an autosomal recessive disorder, affecting males and females
approximately equally.
If this enzyme is deficient, red cells have trouble producing enough ATP to maintain the Na+/K+ pump on the plasma membrane,
secondarily causing swelling and lysis.

HMP Shunt
Present in cytoplasm and also known as Pentose phosphate pathway
No ATP is directly produced or consumed in this cycle
Particularly important in liver and mammary glands

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203

Generates
NADPH
Ribose 5 P for Nucleotide synthesis
Xylulose 5 phosphate
6 Phosphogluconolactone
Glyceraldehydes 3 phosphate
Seodoheptulose 7 phosphate

NADPH is used for

Fatty acid synthesis

Steroid synthesis
Drug metabolism
Glutathione reduction
Generation of superoxide in phagocytes by NADPH oxidase
Uronic acid pathway

ATP Yield

Anaerobic glycolysis: 2 ATP per glucose molecule

Aerobic glycolysis: 8 ATP per glucose molecule
Krebbs cycle: 12 ATP per acetyl co A
HMP Shunt: O
Palitic acid oxidation:129ATP
Stearic acid oxidation: 146 ATP

Remember
Brain, liver, muscles uses glucose as primary fuel
Heart uses fatty acids as primary fuel
In starvation brain and heart use ketone bodies as fuel

Glycogen Storage Diseases

1. von Gierkes
Disease

Glucose-6-phosphatase Protruding abdomen because of marked hepatomegaly, hypotrophic

deficiency
muscles, truncal obesity, a rounded doll face
Severe symptomatic hypoglycemia is frequent, often occurring during the
night or after even short periods of reduced caloric intake
Even minor delays or reduction of carbohydrate intake may provoke
hypoglycemic attacks that are accompanied by lactic acidosis

2. Pompe Disease

Lysosomal alpha-1,
Profound muscle hypotonia, weakness, hyporeflexia, glossomegaly,
4-glucosidase
massive cardiomyopathy without murmurs but no hepatomegaly except
deficiency
with cardiac failure
Acid maltase deficiency The ECG shows a huge QRS complex, left or biventricular hypertrophy and
(AMD),
shortened PR interval

3. Cori Disease

Debranching enzyme

4. Andersons Disease Branching enzyme

Mild Hypoglycemia, Hepatomegaly

Infantile Hypotonia, cirrhosis

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USMLE Step 1 Platinum Notes

5. Mc Ardle Disease

Muscle Phosphorylase

Increasing intolerance for strenuous exercise

Strenuous muscle activity is accompanied by severe cramps and may be
followed by myoglobinuria, which can precipitate anuria and renal failure

6. Hers Disease

Liver phosphorylase

Pronounced hepatomegaly, without splenomegaly

Protuberant abdomen due to muscle hypotonia are the most striking
features

7. Tauris Disease

Phosphofructokinase
Deficency

USMLE Case Scenario

A 3-month-old boy is evaluated for failure to thrive, seizure. Examination Shows truncal obesity, hepatomegaly. Serum
chemistries demonstrate severe hypoglycemia, hyperlipidemia, lactic acidosis, and ketosis. Which of the following diseases
best accounts for this presentation?
Von Gierkes Disease

USMLE Case Scenario

A 23-year-old engineer to a physician with complaints of severe muscle cramps and weakness with even mild exercise. Muscle
biopsy demonstrates glycogen accumulation, but hepatic biopsy is unremarkable. Which of the following is the most likely
diagnosis?
Mc Ardles Disease

Galactosemia
Galactosemia occurs in two very different clinical forms
Deficiency of galactokinase produces very mild disease with the only significant complication being cataract formation. In contrast,
homozygous deficiency of galactose-1-phosphate uridyltransferase produces severe disease culminating in death in infancy.
In addition to galactosemia and galactosuria, these patients have impaired renal tubular resorption leading to aminoaciduria,
gastrointestinal symptoms, hepatosplenomegaly, cataracts, bleeding diathesis, hypoglycemia, and mental retardation
Pathologically, the CNS shows neuronal loss and gliosis and the liver shows fatty change progressing to cirrhosis.
Three enzyme deficiencies implicated
GPUT Deficiency( Galactose 1 Po4 uridyl transferase) most common
UDP galactose 4 epimerase deficiency
Galactokinase deficiency
AR condition
Newborn presents with failure to thrive, vomiting, diarrhea and Jaundice
Hepatomegaly, Cataract (oil drop cataract), Mental retardation, E.coli sepsis
Cataract because of accumulation of galactilol
Reducing sugar seen in urine
Rapid diagnosis and rapid removal of galactose from diet

Essential Fructosuria

Fructokinase deficiency
AR Condition
Benign, asymptomatic
Fructose accumulates in urine

Biochemistry
Hereditary Fructose Intolerance:
Aldolase B deficiency
Sever hypoglycemia, vomiting, hepatomegaly and hyperuricemia
Hepatic failure and death if not treated

Electron Transport Chain

Electron transport chain is located in inner mitochondrial membrane
Internal respiration is exorgenic and catabolic
Mitochondrial membrane protein contain transporter of NADH, NADPH and ATP
In electron transport chain FADH gives 2 ATP
In electron transport chain NADH gives 3 ATP
Cyanide inhibits cytochrome oxidase
Cyanide inhibits Complex IV
Carbon monoxide, cyanide and azide inhibit cytochrome oxidase
Dinitrophenol is uncoupler of oxidation and phosphorylation
Uncouplers of oxidative phosphorylation are:
Snake venom, Serum bilirubin, T 4, Free fatty acids
Electron Transport Inhibitors
Rotenone, amobarbital, chlorpromazine (complex I)
Antimycin A, BAL, phenformin (complex II)
Cyanide, azide, CO, H2S (complex III)
ATP ase Inhibitors
Oligomycin, atractyloside, bongregate
Uncoupling agents
2, 4 Dinitrophenol

Fatty Acids
Saturated fatty acids:
Butyric acid
Palmitic acid
Stearic acid
Monounsaturated fatty acids:
Oleic acid
Elaidic acid
Polyunsaturated fatty acids PUFA:
Linoleic Acid
Linolenic Acid
Arachdonic Acid

Essential Fatty Acids are

Linoleic acid
Linolenic acid
Ecosopantanoic acid
Docosa Hexanoic acid
Arachidonic acid

205

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USMLE Step 1 Platinum Notes

Fatty Acid Synthesis

Occurs in cytoplasm
Most fatty acids are synthesized in the liver.
Fatty acids to a lesser extent are also synthesized in Lactating breast, adipose tissue and kidney
Fatty acids are synthesized in cytosol.
Carbon atoms needed for fatty acid synthesis are provided by acetyl COA
Energy for fatty acid synthesis is provided by ATP
Reducing equivalents for fatty acid synthesis are provided by NADPH
The regulated step in fatty acid synthesis is catalyzed by acetyl COA carboxylase which requires Biotin
Citrate is the allosteric activator of enzyme acetyl CO A carboxylase and long chain fatty acyl COA is the inhibitor
Insulin also activates the enzyme
Epinephrine and glucagon inactivate the enzyme
Acetyl co A carboxylase containing Biotin is the rate limiting step
It is activated by insulin (Promotes fatty acid synthesis)
Fatty acid synthetase is a large multi enzyme complex containing Acyl carrier protein, Pantothenic acid.
Ketosis results from a marked increase in free fatty acid release from adipocytes, with a resulting shift toward ketone body synthesis
in the liver. Reduced insulin levels, in combination with elevations in catecholamines and growth hormone, lead to an increase in
lipolysis and release of free fatty acids
In Diabetic Keto Acidiosis, the ketone body, b-hydroxybutyrate, is synthesized at a threefold greater rate than acetoacetate
Ketone body formation occurs in Liver
Ketone bodies are by products of fatty metabolism
Ketone bodies are normally produced from Acetyl CoA
Normal excretion of ketone bodies daily is 1 mg
Ketone bodies are utilized by conversion of acetoactetate to acetoacetyl COA
Ketone body formation without glycosuria is a feature of starvation

Bile
Major components of bile by weight include water (82%), bile acids (12%), lecithin and other phospholipids (4%), and unesterified
cholesterol (0.7)
The primary bile acids, cholic acid and chenodeoxycholic acid (CDCA), are synthesized from cholesterol in the liver
Are conjugated with glycine or taurine
Are excreted into the bile
Secondary bile acids, including deoxycholate and lithocholate, are formed in the colon as bacterial metabolites of the primary
bile acids
In normal bile, the ratio of glycine to taurine conjugates is about 3:1
Bile acids are detergents that in aqueous solutions and above a critical concentration of about 2 mM form molecular aggregates
called micelles
Cholesterol alone is poorly soluble in aqueous environments, and its solubility in bile depends on both the total lipid concentration
and the relative molar percentages of bile acids and lecithin
Normal ratios of these constituents favor the formation of solubilizing mixed micelles, while abnormal ratios promote the
precipitation of cholesterol crystals in bile
Lipoproteins and their clinical significance
Lipoproteins are spherical particles made-up of lipid and protein molecules
The major lipids of the lipoproteins are cholesterol, triglycerides, and phospholipids

Biochemistry

207

Triglycerides and the esterified form of cholesterol (cholesteryl esters) are nonpolar lipids that are insoluble in aqueous
environments (hydrophobic) and comprise the core of the lipoproteins.
Phospholipids and a small quantity of free (unesterified) cholesterol, which are soluble in both lipid and aqueous environments
(amphipathic), cover the surface of the particles, where they act as the interface between the plasma and core components.
Apolipoproteins also occupies the surface of the lipoproteins; the apolipoproteins play crucial roles in the regulation of lipid
transport and lipoprotein metabolism.
Lipoproteins have been classified on the basis of their densities into five major classes:
Chylomicrons
Very low density lipoproteins (VLDL)
Intermediate-density lipoproteins (IDL)
LDL
High-density lipoproteins (HDL)
Chylomicrons

Transports dietary cholesterol/ TG from intestine to tissues(Apo B)

Apo B 48
Apo C II
Apo E

VLDL

Transports TG from Liver to Tissues

Apo B 100
Apo C II
Apo E

LDL

Delivers cholesterol to cells

Apo B 100

IDL
HDL

Apo E
Picks up cholesterol from blood vessels

Apo A1

APOLIPOPROTEINS The apolipoproteins (apos) provide structural stability to the lipoproteins and determine the metabolic fate of
the particles upon which they reside

Important Points to be remembered

LDL has only one apoprotein B100

LDL has the highest Cholesterol content and is most atherogenic

Chylomicrons have highest triglyceride content
Chylomicrons contain Apo A, Apo B, Apo C, Apo E
LDL delivers cholesterol to extrahepatic tissues (Cells)
LDL has scavenging action

LDL receptors are widely present on cell membranes, liver and extrahepatic tissues
After binding with receptors LDL is taken in by endocytosis
A rise of intracellular cholesterol inhibits the synthesis of new LDL receptors
HDL is good as it scavenges body cholesterol and transports cholesterol from liver to tissues. (reverse cholesterol transport)

Secondary Hyperlipidemias
Disease
Diabetes
Nephritic syndrome
Hypothyroidism
Biliary obstruction

Serum cholesterol
Increased
Increased
Increased
Increased

Serum triglyceride
Increased
Increased
Increased
Normal
Contd...

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USMLE Step 1 Platinum Notes

Contd...

Disease
Pregnancy
Alcoholism
Oral contraceptives

Serum cholesterol
Normal
Normal
Normal

Serum triglyceride
Increased
Increased
Increased

Familial Hypercholesterolemia

FH is due to mutations in the gene for the LDL receptor and is genetically heterogeneous
Plasma levels of LDL cholesterol are elevated at birth and remain so throughout life
In untreated adults, total cholesterol levels range from (275 to 500 mg/dL)
Plasma triglyceride levels are typically normal, and
HDL cholesterol levels are normal or reduced

As would be expected of a disorder with decreased numbers of LDL receptors, the fractional clearance of LDL apo B is reduced
LDL production is increased because the liver secretes more VLDL and IDL and more IDL particles are converted to LDL rather
than taken up by the hepatic LDL receptors
FH heterozygotes usually develop severe atherosclerosis in early or middle age
Tendon xanthomas, which are due to both intracellular and extracellular deposits of cholesterol, most commonly involve the
Achilles tendons and the extensor tendons of the knuckles
Tuberous xanthomas, which are softer, painless nodules on the elbows and buttocks,
Xanthelasmas, which are barely elevated deposits of cholesterol on the eyelids, are common
Successful therapy should be aimed at increasing Apo B 100 receptor gene products in hepatocyte cell membranes
Type II Familial Hyper cholestrolemia is due to defective LDL receptors with high LDL and cholesterol levels
Type I Familial Hyperlipoproteinemia is due to deficiency of lipoprotein lipase or Apo C II with increased chylomicrons and
triglycerides
Familial hypercholesterolemia, which is due to defective function of the LDL receptor
More than 200 mutations in the gene for the LDL receptor have been identified. The gene has 5 general domains and 18 exons.
Defects near exons 7 to 14 are in the region of homology with epidermal growth factor receptor precursor. This region of the molecule
is needed for dissociation of LDL from the receptor in the endosome. Receptors with a defect in this area (sometimes called class II
mutations) also have trouble being initially transported to the Golgi complex (transport-deficiency alleles) and become trapped in
endoplasmic reticulum.

Familial Lipoprotein Lipase Deficiency

Autosomal recessive disorder:
It is due to the severe impairment or absence of LPL, leading to massive accumulation of chylomicrons in plasma
Manifestations begin in infancy and include pancreatitis, eruptive xanthomas, hepatomegaly, splenomegaly, foam cell
infiltration of the bone marrow and when the level of triglycerides is (1000 mg/dL), lipemia retinalis. Atherosclerosis is not
accelerated
The diagnosis is suspected by finding a creamy layer (chylomicrons) at the top of plasma that has incubated overnight;

Abetalipoproteinemia

It is AR disease
Defective synthesis or secretion of Apo B with
Low levels of chylomicrons, VLDL and LDL
Low levels of Cholesterol and Triglycerides

Biochemistry

209

Clinical features include:

Fat Malabsorption
Failure to thrive
Neuropathy
Spinocerebellar degeneration
Retinitis pigmentosa
Acantholysis
Treatment is with low fat, High calorie diet
Chylomicrons are Lipoproteins lowest in density
Chylomicrons are Lipoproteins largest in size
Chylomicrons are Lipoproteins with highest percentage of lipid
Chylomicrons are Lipoproteins lowest percentage of protein
Lipid Metabolism Disease

Deficiency

Fabrys

Alpha galactoside- A (Ceramide trihexoside accumulates)

Niemann- Picks

Sphingomyelinase (RBC appear as foam cells)

Tay- Sachs

Hexosaminidase A

Sandhoff disease

Hexosaminidase A and B

Krabbe Leukodystrophy

Galacto Cerebrosidase

Metachromatic Leukodystrophy

Arylsulfatase A

Gaucher disease

Gluco Cerebrosidase

Tangier Disease

Lipid Metabolism Disturbed (Low Alpha lipoprotein)

Gauchers Cells
Glucocerebrosides accumulate in massive amounts within phagocytic cells throughout the body in all forms of Gaucher disease. The
distended phagocytic cells, known as Gaucher cells, are found in the spleen, liver, bone marrow, lymph nodes, tonsils, thymus, and
Peyer patches. Similar cells may be found in both the alveolar septa and the air spaces in the lung.

Tangiers Disease

lpha lipoprotein (HDL)deficiency

HDL,
LDL,
Apo A because of high catabolic rates; abnormal cholesterol uptake into and/or efflux from macrophages; increased apo AI
clearance
Large orange tonsils
Corneal opacities
Relapsing polyneuropathy
No premature atherosclerosis
It is a rare familial disorder characterized by alpha-lipoprotein deficiency, which leads to very low high-density lipoprotein
(HDL), recurrent polyneuropathy, lymphadenopathy, and hepatosplenomegaly due to storage of cholesterol esters in
reticuloendothelial cells. The association of orange-yellow tonsillar hyperplasia (due to the cholesterol ester deposition there as
well) with Tangier disease is a sufficiently distinctive clue in physical diagnosis to be worth remembering.

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USMLE Step 1 Platinum Notes

Lecithin: cholesterol acyltransferase (LCAT) deficiency (Fish-eye disease)

Decreased LCAT activity in plasma leads to accumulation of excess unesterified cholesterol in plasma and body tissues
Total plasma cholesterol level variable with
Decrease in esterified cholesterol and
Increase in unesterified cholesterol
Elevated VLDL level; structure of all lipoproteins is abnormal
Corneal opacities, hemolytic anemia, renal insufficiency, premature atherosclerosis

Wolmans Disease
AR disorder
Lipid storage disease
Lysosomal acid lipase deficiency causes accumulation of triglycerides,cholestrylesters and other fats within the cells of affected
individuals
Lipids accumulate in various organs
Calcification of adrenals
Hepatospleenomegaly, poor weight gain, anemia, jaundice, and features of severe malnutrition occur
Lipid Mobilization:
Adipose Tissue breakdown yields Fatty acids plus Glycerol
Hormone sensitive lipase is responsible
Hormone sensitive lipase is activated by:
Epinephrine
Insulin
Cortisol
Sphingolipids
Sphingomyelin: Phosphorylcholine
Cerebrosides: Galactose or glucose
Gangliosides: N acetyl neuraminic acid
Disease

Enzyme deficiency

Substance Accumulated

Symptoms

Tay sachs

Hexosaminidase

Ganglioside

Cherry red spot in macula

Psychomotor retardation

Gauchers

Glucocerebrosidase

Glucocerebroside

Erosion of bones
Hepatosplenomegaly
Crumpled paper inclusions in macrophages

Niemann Picks

Sphingomyelinase

Sphingomyelin

Cherry red spot in macula

Mental
Retardation
Zebra body inclusions
Foamy Macrophages

Tay-Sachs Disease
An autosomal recessive disorder caused by the deficiency of hexosaminidase A, which leads to the accumulation of
ganglioside GM2 in neurons, producing a degenerative neurologic disease. Children appear normal at birth, but then begin to
suffer from diminished responsiveness, deafness, blindness, loss of neurologic function, and seizures. A cherry-red spot on the

Biochemistry

211

macula may be seen by ophthalmoscopic examination. The incidence is higher among Jews of Eastern European descent. Since
the parents must be heterozygotes for the mutant hexosaminidase. A allele, they would be expected to have diminished levels of
the enzyme.

Ketoacidosis
Occurs In type I IDDM
Urinary Acetoacetate, Hydroxy butyrate
Urinary Nitroprusside test Positive
The hyperglycemia of DKA results from increased hepatic glucose production (gluconeogenesis and glycogenolysis) and
impaired peripheral glucose utilization
The decreased ratio of insulin to glucagon promotes gluconeogenesis, glycogenolysis, and ketone body formation in the
liver, as well as increasing substrate delivery from fat and muscle (free fatty acids, amino acids) to the liver
Insulin deficiency also reduces levels of the GLUT4 glucose transporter, which impairs glucose uptake into skeletal muscle
and fat and reduces intracellular glucose metabolism

Amino Acid Metabolic Defects

Phenylketonuria:

Phenylalanine Hydroxylase

Mental retardation, seizures, hyperactivity

Tremor

Mousy odor of urine

Microcephaly, Hypopigmentation
Failure to grow are features
Musty urine
Alkaptonuria:

Homogentisate oxidase

Urine darkens on standing

Pigmentation of the sclerae and ears
Generalized darkening of the concha, anthelix and
helix of the ear are typical
Arthritis
Pigmentation of heart valves, larynx, tympanic
membranes, and skin
Arthritis

Maple syrup urine disease (MSUD)

Branched chain Ketoacid Valine, Leucine, Isoleucine defect

dehydrogenase
Maple syrup urine
Lethargic baby, Loses weight, Ketosis, Coma

Homocystinuria

Cystathionine synthetase

Mental retardation, MI, Osteoporosis

Dislocation of lens

(Abnormal methionine metabolism)

It is inherited as AR triat
Patients can be responsive to Vitamin B6
(Pyridoxine)
Albinism

Tyrosinase

White hair
Photosensitivity
Strabismus
Nystagmus
Photophobia

212

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 10-year-old girl is seen by a doctor for removal of multiple squamous cell carcinomas of the skin. The patient has nearly
white hair, pink irises, very pale skin, and a history of burning easily when exposed to the sun. This patients condition is
albinism
The most common form of albinism is caused by a deficiency of copper-dependent tyrosinase (tyrosine hydroxylase), blocking the
production of melanin
From the aromatic amino acid tyrosine. Affected individuals lack melanin pigment in skin, hair, and eyes, and are prone to develop
sun-induced skin cancers, including both squamous cell carcinomas and melanomas
This question is simple if you know that tyrosinase is an enzyme in the
Biosynthetic pathway for melanin formation from tyrosine. A lack of tyrosinase causes one form of albinism; a second form is
caused by defective tyrosine uptake
Patients with albinism are:
Vulnerable to developing cancers of the skin of all types, including basal cell carcinoma, squamous cell carcinoma, and
melanoma. The melanomas are unusual in that they are non-pigmented (amelanotic) rather than black, since the patients
cannot form melanin.

Albinism
It is an example of an inborn error in which the pathophysiologic mechanism is directly related to the lack of an end
product. Tyrosine is converted by the action of a cytosolic tyrosinase first to dopa and then dopamine.
Dopamine can then be converted either to the red-yellow pigment phenomelanin or to the black-brown pigment
eumelanin. These reactions occur in the melanosomes produced in the melanocytes and exported to the keratinocytes.
Color of skin is an inherited factor that depends on several genes and is a function of the intensity of the pigment in
the skin and not the number of melanocytes, which is constant for all humans. Although skin color is a polygenic trait,
single genes can have a profound effect on this color, as evidenced by the albino phenotype. In humans, oculocutaneous
albinism (OCA) is inherited as an autosomal recessive trait.
An X-linked and autosomal recessive form of ocular albinism also exists. Individuals with OCA are classified as either
tyrosinase-negative or positive for tyrosine activity in hair bulbs. Tyrosinase-negative individuals form no pigment, and
prenatal monitoring for tyrosinase activity in cultured amniocytes is possible.
A tyrosinase-positive OCA has been associated with an autosomal recessive gene located on chromosome 15q11-13 (the
P gene). A wide variation in phenotypic expression of OCA is reported from very severe neurologic deficiency with ocular
and sarcomatous skin cancers to mild cosmetic problems.

Amino Acid Transport Defects

Cystinuria
Defective transport of Basic amino acids (COAL: Cystine, Ornithine, Arginine, Lysine)
Cystine calculi and cystine crystals in urine
Cyanide Nitrosoprusside Test positive

Hartnups Disease
Defective renal and intestinal transport of Tryptophan
Malabsorption, Ataxia, Pellagrous rash

USMLE Case Scenario

A 10-year-old child is suspected of having pellagra because of chronic symptoms including diarrhea, a red scaly rash, and mild
cerebellar ataxia. However, his diet is not deficient in protein and he appears to be ingesting adequate amounts of niacin.
A sister has a similar problem. Chemical analysis of his urine demonstrates large amounts of free amino acids. Which of the
following is the most likely diagnosis?

Biochemistry

213

1. Alkaptonuria
2. Carcinoid syndrome
3. Ehlers-Danlos syndrome
4. Hartnups disease
5. Scurvy
Ans. 4. Hartnups disease
The child has Hartnups disease. This condition clinically resembles pellagra (diarrhea, dementia, and dermatitis), and may
be misdiagnosed as this nutritional (niacin) deficiency. In fact, niacin therapy may actually be helpful in controlling the
symptoms. The underlying problem is a defect in the epithelial transport of neutral amino acids, including tryptophan, which
can act as a precursor of niacin. The defective amino acid transport leads to poor absorption of dietary amino acids as well as
excess amino acid secretion in the urine.

Fanconis Syndrome
Generalized Tubular damage
Aminoaciduria, Glycosuria, Phosphaturia (AGP)
Renal Tubular disorders, Progressive Renal Failure
Exopeptidases:
Carboxypeptidases
Aminopeptidase
Prolidase
Endopeptidases:
Elastase
Trypsin
Chymotrypsin
Collagenase

Urea Cycle

Takes place in liver and brain

1st two reactions occur in mitochondria
1st two reactions are rate controlling reactions
Combination of Hyperammonemia+ Blood Glutamine+Blood urea suggests defect in Urea Cycle. Lethargy, vomiting, coma
are associated

Genetic Defects in Urea Synthesis

Carbomyl Phosphate Synthetase
Ammonia +Blood Glutamine+Blood urea

Ornithine Transcarbomylase
Ammonia +Blood Glutamine+Blood urea

No increase in Uracil or orotic acid

Increase in Uracil or orotic acid

Urea Cycle Disorders

Diseases
Hyperammonemia
type 1
Hyperammonemia
type 2

Enzyme deficit
CPS-I
(OTC) Ornithine
transcarbamoylase

Features
Very high NH3 level levels in blood. Autosomal recessive
Mental retardation
Ammonia level high in blood
Increased glutamine in blood, CSF and urine
Orotic aciduria due to the channelling of carbamoyl phosphate into Pyrimidine
synthesis
Xlinked
Contd...

214

USMLE Step 1 Platinum Notes

Contd...

Diseases
Hyperornithinemia

Enzyme deficit
Defective ornithine
transporter protein

Features
Failure to import ornithine from cytoplasm to mitochondria
Defect in ORNT1 gene
Hyperornithinemia, hyperammonemia and homocitrullinuria is seen (HHH
syndrome)
Decreased urea in blood
Autosomal recessive condition.

Citrullinemia

Argininosuccinate
synthetase

Autosomal recessive inheritance. High blood levels of ammonia amd citrulline.

Citrullinuria (12 g/day).

Argininosuccinic
aciduria

Argininosuccinate
lyase

Argininosuccinate in blood and urine. Friable brittle tufted hair (Trichorrhexis

nodosa).

Hyperargininemia

Arginase

Arginine increased in blood and CSF. Instead of arginine, cysteine and lysine
are lost in urine.

Ammonia is Generated

From amino acids: by Aminotransferase and Glutamate dehydrogenase

From urea by urease
From amines by amine oxidase
From glutamine by glutaminase

Defects of Purine and Pyrimidine Metabolism

Orotic Aciduria

Orotic acid
phosphoribosyltransferase/
OMP decarboxylase

Autosomal recessive
A newborne with Megaloblastic anemia
Lack of pyrimidine synthesis with orotic acid crystals in urine
needed for hematopoesis

Lesch Nyhan
Syndrome

Deficiency of HGPRT

X linked recessive

A child with cerebral palsy,repeated self

biting and needle shaped crystals in urine
with hyperuricemia

Autosomal recessive

A boy with severe immunodeficiency with

B and T cells

Severe combined
Adenosine deaminase
immunodeficiency deficency
SCID

USMLE Case Scenario

A baby that was apparently normal at birth begins to show a delay in motor development by 6 months of age. At three year
of age, the child begins to develop spasticity and writhing movements. At age four, compulsive biting of fingers and lips
and head-banging appear. At puberty, the child develops arthritis, and death from renal failure occurs at age 21
The patient has a classical case of Lesch-Nyhan syndrome, an X-linked disorder due to severe deficiency of the purine
salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). This defect is associated with excessive de
novo purine synthesis, hyperuricemia, and the clinical signs and symptoms described. The biochemical basis of the often
striking self-mutilatory behavior. Treatment with allopurinol inhibits xanthine oxidase and reduces gouty arthritis, urate
stone formation, and urate nephropathy
A Partial deficiency of HPRT, the Kelley-Seegmiller syndrome, is associated with hyperuricemia but no central nervous system
manifestations

Allopurinol
Allopurinol and its metabolite, oxipurinol (alloxanthine), decrease the production of uric acid by inhibiting the action of xanthine
oxidase, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid.

Biochemistry

215

Allopurinol thereby decreases uric acid concentrations in both serum and urine
Also, allopurinol increases reutilization of hypoxanthine and xanthine for nucleotide and nucleic acid synthesis via an action
involving the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase)
The resultant increase in nucleotide concentration leads to feedback inhibition of de novo purine synthesis.

Hyperuricemia

Increased Purine synthesis: Lesch Nyhan Syndrome,Type I glycogen storage disease

Increased Purine Turnover: High purine diet, Myeloproliferative disorders, Exfoliative diseases (Psoriasis)
Decresed uric acid excretion: Primary gout, Renal failure, alcohol, starvation
Drugs:
Thiazides
Loop diuretics
Pyrimidine
Ethambutol
Salicylates
Cytotoxic agents

USMLE Case Scenario

A 47-year-old male patient presents with painful arthritis in the right big toe and uric acid renal stones. He has been
taking allopurinol for his condition. He is suffering from Gout
This patient has gout, characterized by painful joints due to the precipitation of uric acid crystals caused by excessive
production of uric acid (a minority of cases are associated with underexcretion of uric acid)
Kidney disease is also seen due to accumulation of uric acid in the tubules. The disease mostly affects males, and is
frequently treated with allopurinol, an inhibitor of xanthine oxidase. Xanthine oxidase catalyzes the sequential oxidation
of hypoxanthine to xanthine to uric acid.

Important Molecules/Substances Frequently asked In Examinations

Glycoproteins
Glycoproteins are also called mucoproteins
Glycoproteins are proteins that have oligosaccharide side chains covalently attached to their polypeptide back bones
Most of the plasma proteins in humans except albumin are glycoproteins
Certain hormones (HCG, TSH) are also glycoproteins
Glycoproteins contain N terminal signal sequences which direct the growing polypeptide chain to ER (Endoplasmic Reticulum
and Golgi Complex) where Carbohydrates are added and Proteins are sorted to their proper destination.
Functions of glycoproteins:
Cell surface recognition
Cell surface antigenicity
Components of extracellular matrix
Composition of globular proteins in plasma

Glycosaminoglycans
(GAG) Glycosaminoglycans are large complexes of negatively charged, unbranched heteropolysaccharide chains usually
composed of repeating disaccharide units
They produce gel like matrix and hold large quantities of water
They are also called as mucopolysaccharides

216

USMLE Step 1 Platinum Notes

They are synthesized in Golgi bodies

They are degraded by lysosomal hydrolases
Deficency of lysosomal hydrolases results in accumulation of GAG causing mucopolysaccharidoss. Examples are:
Chondritin 4 sulfate
Chondritin 6 sulfate
Heparin
Heparin sulfate
Keratin sulfate
Dermatin sulfate
Hyaluronic acid

Glutathione
Glutathione is a tripeptide (Glutamyl-cysteinyl-glycine) present in most cells. It serves as an important reducing agent along
with ascorbate, vitamin E and beta carotene
It detoxifies hydrogen peroxide. This reaction catalyzed by selenium requiring glutathione peroxidase forms oxidized glutathione
After this cells regenerate the essential glutathione in a reaction catalyzed by glutathione reductase
Glutathione also helps in transport of certain amino acids into the cell
It has electron donating properties and functions as an intracellular reducing agent (antioxidant effects).
Reduced glutathione detoxifies hydrogen peroxide
It acts as a carrier of amino acids in kidney
It helps in conjugation reactions and detoxification of xenobiotics
Following an acute ingestion of Acetaminophen, sulfate and glucuronide pathways become saturated, resulting in an increased
fraction and amount of acetaminophen metabolized to NAPQI and eventual glutathione depletion when this occurs, free NAPQI
binds covalently to hepatocytes and causes their lysis (centrilobular necrosis). Less often, hepatotoxicity develops following the chronic
ingestion of therapeutic or slightly greater amounts in conditions associated with decreased glutathione reserves (e.g. alcoholism,
childhood, acute starvation, chronic malnutrition).

Other Antioxidants

Vitamin A
Vitamin E
Vitamin C
Catalase
Superoxide dismutase
NADPH

PAF
PAF is a potent Glycerophospholipid and a phospholipid activator and mediator of leucocyte functions such as inflammation,
platelet aggregation, anaphylaxis
Neutrophils, basophils, platelets and endothelial cells produce PAF
PAF Mediates bronchoconstriction
PAF Causes platelet aggregation

Prostaglandins
LTA4:
Produced in leucocytes, platelets, mast cells, vascular tissue

Biochemistry

217

LTC4, LTD4, LTE4:

Contraction of smooth muscle
Bronchoconstriction
Vasoconstriction
vascular permeability
Components of SRSA
LTB4:
Chemotaxis
Adhesion of WBC
Release of lysosomal enzymes
Thromboxanes:
Produced mainly in platelets
Promotes platelet aggregation
Vasoconstriction
Smooth muscle contraction
Prostacyclins:
Produced by endothelium of vessels
Vasodilation
Inhibits platelet aggregation
Cortisol inhibits Phospholipase A2
Aspirin, Indomethacin, Phenylbutazone inhibit Both COX 1 and COX 2
Coxibs are selective COX 2 inhibitors (Celecoxib)

Ionophores
Ionophores are organic molecules synthesized by microbes to facilitate movement of ions across membranes
Their properties are because of lipophilic nature and penetrate lipid membranes
They have hydrophilic core and hydrophobic periphery
Valinomycin is an ionophore
Representative ionophores (with the ion(s) they act upon)
1. 2, 4 - Dinitrophenol (H+)
2. Beauvericin (Ca2+, Ba2+)
3. Gramicidin A (H+, Na+, K+)
4. Ionomycin (Ca2+)
5. Monensin (Na+, H+)
6. Nigericin (K+, H+, Pb2+)
7. Salinomycin (K+)
8. Valinomycin (K+)

Zellwegers Syndrome
Peroxisomes are single membrane organalles that are responsible for oxidation of fatty chains. Deficiency of Peroxisomes causes
Zellwegers syndrome with accumulation of long chain fatty acids.

Rate Limiting Steps

Cholesterol synthesis
Ketone body synthesis
Fatty acid synthesis
Bile acid synthesis

HMG CoA reductase

HMG CoA Synthetase
Acteyl Co A Carboxylase
7 hydroxylase

218

USMLE Step 1 Platinum Notes

Important Inhibitors of Medically Important Enzymes

Xanthine oxidase:
Folate reductase:
Lactate Dehyrogenase:
Dihydrofolate reductase:
Vitamin K synthesis:

Allopurinol
Methotrexate
Oxamates
Amethroptin
Dicumarol

Diagnostic Techniques
Blot Type

Material Analyzed

Southern blot
ASO titer

DNA
DNA

Northern blot
Microarray

RNA
RNA or c DNA

Western blot
ELISA
Proteomics

Protein
Protein/antibodies
Proteins

Dot Blot

DNA, RNA or Protein

Proteomics: Study of all proteins expressed in a genome, including their abundance, distribution, post translational modification,
function and interaction with other molecules.
DNA library: Collection of cloned restriction fragments of DNA of an organism
Genomic library: It is a collection of fragments of double stranded DNA obtained by digestion of total DNA of an organism with
restriction endonucleases and subsequent ligation to appropriate vector.
Probe: It is a single stranded piece of DNA usually labeled with radio isotope that has nucleotide sequence complimentary to DNA
molecule of interest
Nucleotide sequence of a probe is complimentary to DNA of interest called Target DNA
Vector is a molecule of DNA to which fragment of DNA to be joined is attached.

Polymerase Chain Reaction

The polymerase chain reaction (PCR) is now the most frequently used technique in molecular biology.
Used to study a specific area of DNA using short complementary sequences of DNA (oligonucleotides) from both the 3 and the 5
ends of the DNA to be studied.
These oligonucleotides build copies of the DNA (amplifies) using a heat stable polymerase (Taq 1).
It is then possible to heat the mixture and the DNA strands will separate.
On cooling, the DNA can once more be duplicated and the process repeated again and again leading to an exponential increase
in the copies of the two fragments.
The main advantages of this technique are that it is very quick, highly sensitive and very robust and it can be used to study
mRNA as well as DNA.
It can also be used to study very small amounts of almost any tissue, e.g. the blood spots on a Guthrie card or the cells found in a
mouth wash sample.
The technique is widely used in molecular diagnosis of genetic disease. It is also being used in infectious disease to confirm the
presence of infectious agents and in immunology to identify the human leukocyte antigen (HLA) haplotype.

Biochemistry

219

Ion-exchange Chromatography
Process in which exchange of ions in solution form with that on to surface form occurs in is Ion exchange:
Ion-exchange chromatography is a process that allows the separation of ions and polar molecules based on their charge.
It can be used for almost any kind of charged molecule including large proteins, small nucleotides and amino acids. The solution
to be injected is usually called a sample, and the individually separated components are called analytes.
It is often used in protein purification, water analysis, and quality control. Ion exchange chromatography retains analyte molecules
on the column based on coulombic (ionic) interactions.
The stationary phase surface displays ionic functional groups (R-X) that interact with analyte ions of opposite charge. This type of
chromatography is further subdivided into cation exchange chromatography and anion exchange chromatography.
The ionic compound consisting of the cationic species M+ and the anionic species B-can is retained by the stationary phase.
Cation exchange chromatography retains positively charged cations because the stationary phase displays a negatively charged
functional group.

Salting out

Proteins are purified using differences in protein solubility in varying salt concentrations
The solubility of proteins varies according to the ionic strength of the solution and hence according to the salt concentration
Two distinct effects are observed
At low salt concentrations, the solubility of the protein increases with increasing salt concentration (increasing ionic strength),
and effect termed salting in
As the salt concentration (ionic strength) is increased further, the solubility of the protein begins to decrease
At high ionic strength, the protein will be almost completely precipitated from the solution (salting out)
Since proteins differ markedly in their solubilities at high ionic strength, salting-out is a very useful procedure to assist in the
purification of a given protein. The commonly used salt is Ammonium sulfate, as it is very water soluble
The ammonium sulfate concentration is increased stepwise, and the precipitated protein is recovered at each stage
The precipitated protein is then removed by centrifugation and then the ammonium sulfate concentration is increased to a value
that will precipitate most of the protein of interest whilst leaving the maximum amount of protein contaminants still in solution
This technique is useful to quickly remove large amounts of contaminant proteins, as a first step in many purification schemes. It is
also often employed during the later stages of purification to concentrate protein from dilute solution following procedures such
as gel filtration.

Restriction Fragment Length Polymorphism (RFLP)

It is a difference in homologous DNA sequences that can be detected by the presence of fragments of different lengths after
digestion of the DNA samples in question with specific restriction endonucleases
It is a DNA Variation sequence
RELP, as a molecular marker, is specific to a single clone/restriction enzyme combination
An RFLP probe is a labeled DNA sequence that hybridizes with one or more fragments of the digested DNA sample after
they were separated by gel electrophoresis, thus revealing a unique blotting pattern characteristic to a specific genotype at a
specific locus. Short, single-or-low-copy genomic DNA or cDNA clones are typically used as RFLP probes
RFLPs are visualized by digesting DNA from different individuals with restriction enzyme, followed by gel electrophoresis
to separate fragments according to size, then blotting and hybridization to a labeled probe that identifies the locus under
investigation. An RFLP is demonstrated when ever the Southern blot pattern obtained with one individual is different from the one
obtained with another individual
RFLP is an important tool in
Genome mapping
Localization of genes from genetic disorders
Determination of risk for diseases, and paternity testing
Test which uses oligomer with single base pair substitution: RFLP

220

USMLE Step 1 Platinum Notes

Paper Chromatography
Technique for identification and determination of amino acids
The Principle: A small amount of solvent is put at the bottom of a jar. A strip of absorptive paper, with a concentrated spot of the
mixed amino acids near the bottom, is suspended in the jar so that its end dips into the solvent. The solvent moves slowly up the
strip of paper, carrying the amino acids with it. As the amino acids travel at different speeds, they separate from one another. The
paper is then treated with a reagent which strains the amino acids so they can be detected and identified. The location reagent
used for amino acids is ninhydrin
Chromatography paper contains about 1520% water, held to the paper fibers. This water acts as the stationary phase in paper
chromatography. Amino acids are separated according to their solubility in the water and in an organic solvent (the mobile
phase) moving up the paper. The most non-polar amino acids migrate the furthest, due to their greater solubility in the organic
solvent
Paper also acts as an adsorbent, having an affinity for polar groups.

Amino Acids
Phenylalanine and Tyrosine are precursors of Cathecolamines.
Tryptophan is precursor for Serotonin, Niacin.
Valine and isoleucine are branched chain amino acids whose metabolism is abnormal in MSUD. (Maple Syrup Urine Disease).
Proline has an imino group.
Essential AA: Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine.
Histidine is a buffer at normal pH. It can protonate or deprotonate.
Glycine is the smallest and simplest AA.
Glycine is responsible for flexibility of proteins.
Hydrophilic AA are present on outer surface of membrane.
Hydrophobic AA are present in transmembrane region
Most of the amino acids do not absorb visible light and hence are colorless
Aromatic amino acids are the only amino acids that absorb light. They are:
Tryptophan (contains indole ring)
Tyrosine
Phenylalanine
Histidine
Tryptophan is the major amino acid contributing to ability to absorb light in the range of 250290 nm.

Biochemistry

221

Glucogenic amino acids are:

Alanine, Arginine, Asparagine, Aspartate
Cysteine
Glutamate, Glutamine, Glycine
Methionine, Theronine, Valine
Ketogenic Amino acids are:
Leucine, Lysine

Mechanism Pathway of Important Enzymes

Pathway

G protein

Protein Kinase

Examples

c AMP

Adenyl cyclase

Protein Kinase A

Glucagon
Epinephrine

PIP2

Phospholipase

Protein Kinase B

Vasopressin

C GMP

Guanyl cyclase

Protein Kinase C

ANF
NO

Proteins
1o Structure specific order of Amino Acids in peptide chain
2o Structure spatial relationship of neighboring Amino Acid residues, e.g. Helix
3o Structure spatial relationship of distant Amino Acid residues by arrangement of secondary structure
4o Structure spatial relationship between individual Polypeptide chains

Alpha Helix, Beta Sheet and Beta Bends are Secondary Structures
Alpha helix can be composed of more than one polypeptide chains. It is a spiral structure with polypeptide backbone and side
chains of amino acids
It is stabilized by hydrogen bonds
Each turn of the helix has 3.6 amino acids
Proline disrupts alpha helix because of geometric incompatibility of imino group of proline
Beta sheets are secondary structures in which all peptide bonds are involved in hydrogen bonding
Beat sheets are both parallel and anti parallel
Beta bends are also called reverse turns
Beta bends often contain glycine
Proline can also be present
Motifs are super secondary structures
Domains are a type of tertiary structure

222

USMLE Step 1 Platinum Notes

Levels of protein structure

Hydroxylation of proline in fibroblasts generates the modified amino acid hydroxyproline. This is an example of post-translational
modification.
Hydroxyproline is involved in stabilizing the three-dimensional triple helix structure of collagen.
Cysteine is unique in its ability to form a covalent disulfide bond with another cysteine residue elsewhere in the protein molecule,
thereby forming a cystine residue.
Such strong disulfide bonds stabilize the three-dimensional structure of the protein.
Glycine is abundant in fibroblasts since it constitutes every third amino acid in the primary sequence of collagen. However, glycine
is not hydroxylated.
Serine tyrosine and threonine can all be phosphorylated post-translationally to form phosphoserine, phosphotyrosine, and
phosphothreonine, respectively. These phosphorylated amino acids are believed to play a role in signal transduction.
Primary structure: Peptide bonds
Secondary structure: hydrogen bonds
Tertiary structure: disulfide bonds

Important Elements

Magnesium: Kinases, Phosphatases, Ribonuclease, Adenyl cyclase, Transketolase

Copper: Cytochrome Oxidase, Tyrosinase, Superoxide dismutase
Zinc: Carboxy peptidase
Molybedenum: Xanthine Oxidase
Manganese: Pyruvate Carboxylase

Effects of Mineral Deficiencies

Arsenic (Impaired growth, infertility)
Boron (Impaired energy metabolism, Impaired brain function)
Nickel (Impaired-growth and reproduction)
Silicon (Impaired growth) and
Vanadium (Impaired skeletal formation)

Biochemistry
Zn is a cofactor in many enzymes. Some of the important ones are:
Carbonic anhydrase
Lactate/Alcohol Dehyrogenase
DNA polymerase
RNA polymerase
Alkaline phosphatase

Globulins
Alpha 1 globulins: AFP, 1 AT, Trypsin
Alpha 2 globulins: Cerruloplasmin, Haptoglobin
Beta globulin: Transferrin, CRP, Hemopexin

Important Tests in Biochemistry

Zwengers test: Cholesterol
Fouchets test bile pigments
Hays sulfur test bile salts
Xanthoproteic test: Proteins
Selivanoffs test: Fructose in urine
Rotheras test: Ketone bodies
Gerhardts test: Ketosis
Molishs test: Color test for sugar
Guthries test: Phenylketonuria
Exton Rose test: Glucose Tolerance test
Cyanide nitroprusside test: Phenyl ketonuria
Benedicts test: Glucose in urine
Sulkowitz test: Urinary calcium
Biurate test: protein

Heme Protein
1. Cytochrome
2. Hemoglobin
3. Myoglobin
4. Catalase
Heme proteins are specialized proteins containing Heme as a prosthetic group
Heme itself is a complex of Protoporphyrin IX and Ferrous iron
Hemoglobin binds four molecules of oxygen
Hemoglobin exists in two forms Deoxygenated form or (T) Taut form and
Oxygenated form or (R) relaxed form
Oxygen dissociation curve of Hb is sigmoidal

223

224

USMLE Step 1 Platinum Notes

Myoglobin binds one molecule of oxygen

Oxygen dissociation curve of Myoglobin is Hyperbolic

Gems about Hemoglobin

Earliest Hemoglobin

Hb Gowers
Hb Fetal
Hb Adult
Hb A2

22
22
22
22

Configuration of Hemoglobins

Most common Hb is: HbA

Adult Hb is HbA is: 22
Fetal Hb is Hb F is: 22
Minor Adult Hb is HbA2 is: 22

Clinically Important Points About

Methemoglobin

Form of oxidized HB
(Fe2+ replaced by Fe3+)
Oxygen carrying capacity
Phenacetin, Primaquine, Sulfonamides, Nitrites, Nitrates cause Methemoglobinemia.

Carboxy Hemoglobin
Hb combines with CO (Carbon Monoxide NOT Dioxide) to form Carboxy Hemoglobin
Affinity of Hb for CO is 200 times more than that of O2, hence CO displaces O2

Glycosylated Hemoglobin

Adult Hb binds with glucose during 120 day life cycle of RBC
It is an irreversible reaction
Normally up to 9% of adult Hb is Glycosylated
In diabetes >9 % Hb is glycosylated
It is useful for providing picture of long-term state of diabetic control

Important Inhibitors of Medically Important Enzymes

Xanthine oxidase
Folate reductase
Lactate Dehyrogenase
Dihydrofolate reductase
Vitamin K synthesis

Allopurinol
Methotrexate
Oxamates
Amethroptin
Dicumarol

Biochemistry

Aconitase
Citrate
ketoglutarate dehydrogenase arsenate
Succinate dehydrogenase
Enolase
Glyceraldehydes 3 phosphate

Flouroacetate
Flouroacetate
Malonate
Fluoride
Iodoacetate

Metabolic Functions of Subcellular Organelles

Organelle
Nucleus
Endoplasmic
Reticulum

Golgi body
Lysosome
Mitochondria

Cytosol

Function
DNA replication, transcription
Biosynthesis of proteins, glycoproteins, lipoproteins
Drug metabolism
Ethanol oxidation
Synthesis of cholesterol (partial)
Maturation of synthesized protein
Degradation of proteins, carbohydrates, lipids and nucleotides
Electron transport chain
ATP generation
TCA cycle
Beta oxidation of fatty acids
Ketone body production
Urea synthesis (part)
Heme synthesis (part)
Gluconeogenesis (part)
Pyrimidine synthesis (part)
Protein synthesis
Glycolysis
Glycogen metabolism
HMP shunt pathway, transaminations, fatty acid synthesis
Cholesterol synthesis, heme synthesis (part), urea synthesis (part)
Pyrimidine synthesis (part), purine synthesis

Enzymes used for Diagnostic Purpose

Enzyme
Urease
Uricase
Glucose oxidase
Peroxidase
Hexokinase
Cholesterol oxidase
Lipase
Horse radish peroxidase
Alkaline phosphatase
Restriction endonuclease
Reverse transcriptase

Used for Testing

Urea
Uric acid
Glucose
Glucose; Cholesterol
Glucose
Cholesterol
Triglycerides
ELISA
ELISA
Southern blot; RFLP
Polymerase chain reaction (RT = PCR)

225

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USMLE Step 1 Platinum Notes

Nonfunctional Plasma Enzymes used in Clinical Diagnosis

Serum Enzymes

Diagnostic use

Amylase and lipase

Acute pancreatitis

Aminotransferases

Myocardial infarction

Aspartate aminotransferase (AST or SGOT)

Alanine aminotransferase (ALT or SGPT)

Viral hepatitis

Acid Phosphatase

Prostate cancer

Alkaline phosphatase

Obstructive liver diseases, bone diseases and hyperparathyroidism

Creatine kinase

Muscle disorders and Myocardial infarction

Ceruloplasmin

Wilsons disease

Gamma-glutamyl transpeptidase

Liver diseases

Lactate dehydrogenase

Myocardial infarction

Sub cellular Organelle

Marker enzyme

Inner membrane:
ATP Synthase
Cathepsin
Galactosyl transferase
Glucose-6-phosphatase
Lactate dehydrogenase

Mitochondria
Lysosome
Golgi complex
Microsomes
Cytoplasm

Key Enzymes under Well Fed Conditions, Fasting and Starvation

Enzyme
Glucokinase
Phosphofructokinase 1
Fructose 1,6 biphosphatase
Pyruvate carboxylase
PEPCK
Glycogen phosphorylase
Glycogen synthase
Carnitine acyl transferase
Acetyl CoA carboxylase
Hormone sensitive lipase

Fed
Increase
Increase
Decrease
Decrease
Decrease
Decrease
Increase
Increase
Decrease

Fasting
Decrease
Decrease
Increase
Increase
Increase
Increase
Decrease
Increase
Decrease
Increase

Starvation
Decrease
Decrease
Increase
Increase
Increase
Decrease
Increase
Decrease
Increase

PEPCK = phospho enol pyruvate carboxy kinase; F-6-P = fructose-6-phosphate; F-2, 6-bisP=fructose-2,
6-biphosphate; G-6-P = glucose-6-phosphate.

Enzyme Deficiencies in Porphyrias

Erythropoetic porphyria
Heridetary Porphyria
Vaiegate Porphyria
Acute Intermittent porphyria
Porphyria cutanea Tarda
Congenital Erythropoetic porphyria

Ferrochelatase
Coproporphynogen Oxidase
Protoporphyrinogen Oxidase
Porphobilinogen Deaminase
URO Decarboxylase
URO III cosynthetase

Biochemistry

Important Biochemical Tests

Barfoeds test

Differentiates monosaccharides disaccharides

Mucic acid test

Detects galactose

Biuret test

Detects proteins

Xanthopretic test

Detects phenylalanine, tyrosine, tryptophan

Millions test

Detects tyrosine

Sullivan reaction

Detects cysteine

Acrolein test

Detects triglycerides

Leiberman Burchard reaction

Salkowskys reaction

Detects cholesterol

Rothera test
Legals test
Gerhardts test

Detects ketone bodies

Biochemically useful Competitive Inhibitors

Drug

Enzyme Inhibited

Allopurinol

Xanthine oxidase

6-mercapto-purine

Adenylosuccinate synthetase

5-fluorouracil

Thymidylate synthase

Azaserine

Phosphoribosyl-amidotransferase

Cytosine arabinoside

DNA polymerase

Acyclovir

DNAP of virus

Neostigmine

ACh-esterase

Alpha-methyl dopa

Dopa-decarboxylase

Lovastatin

HMGCoA-lowering

Oseltamiver

Neuraminidase

Dicoumarol

Vit.K-epoxide-reductase

Penicillin

Transpeptidase

Sulphonamide

Pteroid synthetase

Trimethoprim

FH2-reductase

Pyrimethamine

FH2-reductase

Methotrexate

FH2-reductase

227

228

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Tangier disease is a rare familial disorder characterized by deficiency of an enzyme, which leads to very low high density
lipoprotein (HDL), recurrent polyneuropathy, lymphadenopathy, and hepatosplenomegaly due to storage of cholesterol
esters in reticuloendothelial cells. The enzyme deficency is:
1. G6 Phosphatase
2. Pyruvate kinase
3. alpha-lipoprotein deficiency
4. Urea cycle enzyme deficiency
5. Multiple carboxylase deficiency
Ans. 3. Alpha-lipoprotein deficiency

USMLE Case Scenario

A baby presents with refusal to feed, skin lesions, seizures, ketosis organic acids in urine with normal ammonia; likely
diagnosis is:
1. Proprionic aciduria
2. Multiple carboxylase deficiency
3. Maple syrup urine disease
4. Urea cycle enzyme deficiency
Ans. 2. Multiple carboxylase deficiency

USMLE Case Scenario

The primary role of chaperones is to help in:
1. Protein synthesis
2. Protein degradation
3. Protein denaturation
4. Protein folding
Ans. 4. Protein Folding

USMLE Case Scenario

A young man finds that everytime he eats dairy products he feels very uncomfortable. His stomach becomes distended. He
develops gas and diarrhea frequently. These symptoms do not appear when he eats foods other than dairy products. Which of
the following is the most likely enzyme in which this young man is deficient?
1. a-amylase
2. b-galactosidase
3. a-glucosidase
4. Sucrase
Ans. 4. Sucrase

USMLE Case Scenario

A child with large tongue, coarse facial features and club foot is seen by a pediatrician. You hear the doctor talking to his colleague
that the child has a problem with Phosphorylation of their mannose residues. The most likely possibility is a disease called:
1. Fabrys disease
2. Gauchers disease
3. Mc Ardles disease
4. Forbes disease
5. I-cell disease
Ans. 5. I-cell disease

Biochemistry

229

USMLE Case Scenario

Proteins targeted for destruction in eukaryotes are covalently linked to:
1. Clathrin
2. Pepsin
3. Laminin
4. Ubiquitin
Ans. 4. Ubiquitin

USMLE Case Scenario

The defect in sickle cell anemia is amino acid substitution/s but the globin chain is still made. The gene may less commonly
be present in some Mediterranean and eastern Arabian populations. There is enough fetal hemoglobin at birth to prevent
sickling with sickle cell disease. Sickle cell disease represents:
1. Missense mutations involve a change in many amino acids
2. Missense mutations involve a change in a single amino acid (valine for glutamic acid)
3. Missense mutations involve a change in a single amino acid (glutamic acid for valine)
4. Nonsense mutations involve a change in a single amino acid (valine for glutamic acid)
5. Nonsense mutations involve a change in a single amino acid (glutamic acid for valine)
Ans. 2. Missense mutations involve a change in a single amino acid (valine for glutamic acid)

USMLE Case Scenario

Northern blot test is used for:
1. DNA analysis
2. RNA analysis
3. Analysis of proteins
4. Enzyme analysis
Ans. 2. RNA analysis

USMLE Case Scenario

Which Apoprotein helps in the transport of chylomicrons from intestine to liver?
1. Apoprotein B
2. Apoprotein A
3. Apoprotein C
4. Apoprotein E
Ans. 1. Apoprotein B

USMLE Case Scenario

True about G protein coupled receptors is:
1. G proteins bind to hormones on the cell surface
2. All the three subunits alpha, beta and gamma should bind to each other for G protein to act
3. G proteins act as inhibitory and excitatory because of difference in alpha subunit
4. G protein is bound to GTP in resting state
Ans. 3. G proteins act as inhibitory and excitatory because of difference in alpha subunit

230

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Collagen of which type is found in hyaline cartilage:
1. Type I
2. Type II
3. Type III
4. Type IV
Ans. 2. Type II

USMLE Case Scenario

A 34-year-old male patient presents with pain in the right big toe and uric acid renal stones. He has been taking allopurinol
for his condition. What biochemical defect would likely be found in this patient?
1. A defect in fatty acid synthesis
2. An abnormality of the purine degradation pathway
3. An inability to synthesize essential amino acids
4. Defective topoisomerases
5. Increased levels of leukotrienes
Ans. 2. An abnormality of the purine degradation pathway
This patient has gout, characterized by painful joints due to the precipitation of uric acid crystals caused by excessive
production of uric acid (a minority of cases are associated with underexcretion of uric acid). Kidney disease is also seen due
to accumulation of uric acid in the tubules. The disease mostly affects males, and is frequently treated with allopurinol, an
inhibitor of xanthine oxidase. Xanthine oxidase catalyzes the sequential oxidation of hypoxanthine to xanthine to uric acid.

USMLE Case Scenario

Vitamin K is required for:
1. Hydroxylation
2. Chelation
3. Transamination
4. Carboxylation
Ans. 4. Carboxylation

USMLE Case Scenario

NO is synthesized from:
1. Uracil
2. Aspartate
3. Guanosine
4. Arginine
5. Alanine
Ans. 4. Arginine

USMLE Case Scenario

A one and a half year-old retarded childs history is significant for failure to thrive and progressive neurologic deterioration,
including deafness and blindness. Physical examination is remarkable for hepatosplenomegaly, as well as a cherry-red spot
on funduscopic examination. The most likely diagnosis is:
1. Fabrys Disease
2. Mcardles Disease

Biochemistry

231

3. Hunter syndrome
4. Niemann-Pick disease
5. Pompes disease
6. Tyrosinosis
7. Cystinosis
8. Von Gierkes disease
Ans. 4. Niemann-Pick disease
It is due to a deficiency of sphingomyelinase, leading to an accumulation of sphingomyelin. The cherry-red spot is also a
characteristic of Tay-Sachs disease, but hepatosplenomegaly suggests Niemann-Pick disease rather than Tay-Sachs.

USMLE Case Scenario

Vitamin A intoxication causes injury to:
1. Lysosomes
2. Mitochondria
3. Endoplasmic reticulum
4. Microtubules
Ans. 1. Lysosomes

USMLE Case Scenario

A 23-year-old engineer to a physician with complaints of severe muscle cramps and weakness with even mild exercise. Muscle
biopsy demonstrates glycogen accumulation, but hepatic biopsy is unremarkable. Which of the following is the most likely
diagnosis?
1. Fabrys Disease
2. Hunter syndrome
3. Niemann-Pick disease
4. Pompes disease
5. Tyrosinosis
6. Cystinosis
7. Von Gierkes disease
8. Mcardles Disease
Ans. 8. Mcardles Disease

USMLE Case Scenario

Lead inhibits incorporation of iron into heme. The diminished heme synthesis leads to a hypochromic, microcytic anemia, and
there may be mild hemolysis. Basophilic stippling can be an indicator of toxic injury to RBCs. Lead poisoning is characterized by:
1. Elevated zinc protoporphyrin and decreased free erythrocyte protoporphyrin
2. Decreased zinc protoporphyrin and elevated free erythrocyte protoporphyrin
3. Decreased zinc protoporphyrin and decreased free erythrocyte protoporphyrin
4. Elevated zinc protoporphyrin and elevated free erythrocyte protoporphyrin
Ans. 4. Elevated zinc protoporphyrin and elevated free erythrocyte protoporphyrin

USMLE Case Scenario

The Similarity between Vit C and Vit K is:
1. Both help in conversion of proline to hydroxy-proline
2. Both help in post-translational modification
3. Both have anti infective activity
4. Both are involved in coagulation cascade
Ans. 2. Both help in post-translational modification

232

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A patient was diagnosed with isolated increase in LDL. His father and brother had the same disease with increased cholesterol.
The likely diagnosis is:
1. Familial type III hyperlipoproteinemia
2. Abetalipoproteinemia
3. Familial lipoprotein lipase deficiency (type I)
4. LDL receptor mutation
Ans. 4. LDL Receptor Mutation

USMLE Case Scenario

The gaps between segments of DNA on the lagging strand produced by restriction enzymes are rejoined/sealed by:
1. DNA Ligases
2. DNA Helicase
3. DNA topoisomerase
4. DNA phosphorylase
Ans. 1. DNA Ligases

USMLE Case Scenario

Intron is not found in:
1. Nuclear DNA
2. Mitochondrial DNA
3. B DNA
4. Z DNA
Ans. 2. Mitochondrial DNA

USMLE Case Scenario

Agranular cytoplasmic reticulum is involved in the synthesis of:
1. Protein
2. Lipid
3. Vitamin
4. Carbohydrate
Ans. 2. Lipid

USMLE Case Scenario

A 45-year-old obese female from Mexico presents to her dermatologist. She noticed that her hair is falling out. On questioning,
she reports having followed a strict fat-free diet. Her alopecia is probably related to a deficiency of which of the following
vitamins?
1. Vitamin A
2. Vitamin C
3. Vitamin D
4. Vitamin E
5. Vitamin K
Ans. 1. Vitamin A
Vitamin A is necessary for formation of retinal pigments (deficiency can cause night blindness) and for appropriate
differentiation of epithelial tissues (including hair follicles, mucous membranes, skin, bone and adrenal cortex).

Biochemistry

233

USMLE Case Scenario

Coenzyme responsible for carboxylation reaction is:
1. Biotin
2. FAD
3. NADH
4. Thiamine pyrophosphate
Ans. 1. Biotin

USMLE Case Scenario

Xeroderma pigmentation is caused due to a group of closely related abnormalities in:
1. Mismatch repair
2. Base excision repair
3. Nucleotide excision repair
4. Phagosomes
Ans. 3. Nucleotide excision repair

USMLE Case Scenario

If cellular proteins do not fold into a specific conformation, their functions are affected. Certain disorders arise, if specific
proteins are misfolded. Which of the following disorders arises due to conformational isomerization?
1. Familial fatal insomnia
2. Hepatitis delta
3. Pernicious anemia
4. Lesch-Nyhan syndrome
Ans. 1. Familial fatal insomnia

USMLE Case Scenario

Fluoride, used in the collection of blood samples for glucose estimation, inhibits the enzyme:
1. Glucokinase
2. Hexokinase
3. Enolase
4. Glucose-6-phosphatase
Ans. 3. Enolase

USMLE Case Scenario

During replication of DNA, which one of the following enzymes polymerizes the Okazaki fragments?
1. DNA Polymerase I
2. DNA Polymerase II
3. DNA Polymerase III
4. RNA Polymerase I
Ans. 3. DNA Polymerase III

USMLE Case Scenario

In an experiment, biologic characteristics of neoplastic and non-neoplastic cells are analyzed in culture. The biochemical
experts report that it is observed that cell division in cells derived from malignant neoplasms, but not in normal cells, is aided
by the presence of an enzyme which repairs progressive chromosomal shortening. The lack of chromosomal shortening
allows the malignant cells to undergo many more divisions than the normal cells. Which of the following enzymes is most
likely to have this effect?
1. Reverse transcriptase
2. DNA polymerase

234

USMLE Step 1 Platinum Notes

3. Isomerase
4. Phosphodiesterase
5. Telomerase
6. Protein kinase
7. Topoisomerase
Ans. 5. Telomerase

USMLE Case Scenario

Refsums disease is due to deficiency of:
1. Malonate dehydrogenase
2. Thiophorase
3. Succinate thiokinase
4. Phytanic alpha oxidase
5. HGPRT
6. Telomerase
7. Galactokinase
Ans. 4. Phytanic alpha oxidase

USMLE Case Scenario

A 10-year-old girl is seen by a doctor for removal of multiple squamous cell carcinomas of the skin. The patient has nearly
white hair, pink irises, very pale skin, and a history of burning easily when exposed to the sun. This patients condition is due
to deficency of:
1. Malonate dehydrogenase
2. Thiophorase
3. Succinate thiokinase
4. Phytanic alpha oxidase
5. HGPRT
6. Tyrosine hydoxylase
7. Galactokinase
Ans. 6. Tyrosine hydoxylase
The disease is albinism. The most common form of albinism is caused by a deficiency of copper-dependent tyrosinase (tyrosine
hydroxylase), blocking the production of melanin from the aromatic amino acid tyrosine. Affected individuals lack melanin
pigment in skin, hair, and eyes, and are prone to develop sun-induced skin cancers, including both squamous cell carcinomas
and melanomas.

USMLE Case Scenario

The molecule, which is the intiator of cataract formation in the eye lens is:
1. Sorbitol
2. Mannitol
3. Inositol
4. Galacticol
Ans. 4. Galacticol

USMLE Case Scenario

A newborn infant refuses breast milk since the 2nd day of birth, vomits on force-feeding but accepts glucose-water, develops
diarrhea on the third day, by 5th day she is jaundiced with liver enlargement and eyes show signs of cataract. Urinary
reducing sugar was positive but blood glucose estimated by glucose oxidation method was found low. The most likely cause
is deficiency of:
1. Galactose-1-phosphate uridyl transferase

Biochemistry

235

2. Beta galactosidase
3. Glucose-6-phosphatase
4. Galactokinase
Ans. 1. Galactose-1-phosphate uridyl transferase

USMLE Case Scenario

Excessive ultraviolet radiation is harmful to life. The damage caused to the biological systems by ultraviolet radiation is by:
1. Inhibition of DNA synthesis
2. Formation of thymidine dimmers
3. Ionization
4. DNA fragmentation
Ans. 2. Formation of thymidine dimmers

USMLE Case Scenario

Euchromatin is the region of DNA that is relatively:
1. Uncondensed
2. Condensed
3. Overcondensed
4. Partially condensed
Ans. 1. Uncondensed

USMLE Case Scenario

Proteins are linear polymers of amino acids. They fold into compact structures. Sometimes, these folded structures associate
to form homo-or hetero-dimers. Which one of the following refers to this associated form?
1. Denatured state
2. Molecular aggregation
3. Precipitation
4. Quaternary structure
Ans. 4. Quaternary structure

USMLE Case Scenario

Basement membrane degeneration is mediated by:
1. Metalloproteinases
2. Oxidases
3. Elastases
4. Hydroxylases
Ans. 1. Metalloproteinases

USMLE Case Scenario

A ten year old child with aggressive behavior and poor concentration is brought with presenting complaints of joint pain and
reduced urinary output. Mother gives history of self mutilitative behavior stating that he tends to mutilate his fingers. Which
of the following enzymes is likely to be deficient in this child?
1. HGPRT
2. Adenosine Deaminase
3. Galactokinase
4. Acid Maltase
5. Hydroxylase
Ans. 1. HGPRT

236

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A child presents with massive hepatomegaly and hypoglycemia. There is no improvement in blood glucose on administration
of Glucagon. The probable diagnosis is:
1. von Gierke disease
2. McArdle disease
3. Coris disease
4. Forbes disease
Ans. 1. von Gierke Disease

USMLE Case Scenario

A 2-month-old, breastfed baby that was normal at birth begins to develop GI problems and cirrhosis of the liver. Molecular
analysis indicates a normal amount of galactose-1-phosphate uridyl transferase (GALT) mRNA, but no observable enzyme
activity. Which of the following would be the best possible explanation for this?
1. Gene deletion
2. Nonsense mutation
3. Premature transcription termination sequence in the DNA
4. Promoter mutation
5. RNA splicing mutation
Ans. 2. Nonsense Mutation
A nonsense mutation is a mutation in the DNA that leads to a premature stop codon when the mRNA is being translated
into protein. The mRNA would be transcribed correctly, but when the protein was being translated, it would be stopped
prematurely, leading to a truncated protein.

USMLE Case Scenario

A child has cystic fibrosis. His parents report a history of recurrent respiratory tract infections and bulky, foul-smelling stools.
After assessment of his respiratory tract illness, the practitioner should also look for signs of which vitamin deficiency.
1. Vitamin C
2. Vitamin A
3. Vitamin B1
4. Vitamin B6
Ans. 2. Vitamin A

USMLE Case Scenario

A 10-year-old child is suspected of having pellagra because of chronic symptoms including diarrhea, a red scaly rash, and mild
cerebellar ataxia. However, his diet is not deficient in protein and he appears to be ingesting adequate amounts of niacin.
A sister has a similar problem. Chemical analysis of his urine demonstrates large amounts of free amino acids. Which of the
following is the most likely diagnosis?
1. Alkaptonuria
2. Carcinoid syndrome
3. Ehlers-Danlos syndrome
4. Hartnups disease
5. Scurvy
Ans. 4. Hartnups Disease

MICROBIOLOGY

Microbiology

HIGH YIELD USMLE POINTS

Prokaryotes

Absence of nuclear membrane

Absence of nucleolus
Absence of DNA
Absence of cytoplasmic organalles
Absence of sterols/muramic acid
Bacteria are prokaryotes

Eukaryotes

Presence of nuclear membrane

Presence of nucleolus
Presence of DNA
Presence of cytoplasmic organalles
Presence of sterols/ muramic acid

USMLE Case Scenario

After a skin infection in the nail, A Pathologist is talking about a nonmotile organism is found to be eukaryotic, with both RNA
and DNA present. Ribosomes are 80 S and reproduction occurs by budding. Most likely the organism is:
1. Virus
2. Bacteria
3. Fungus
4. Viroid
Ans. 3. Fungus

Characteristics of Different Organisms

Characteristics

Viruses

Bacteria

Fungi

Nucleic acid

Either DNA/RNA

Both Present

Both Present

Nucleus

Absent

Prokaryotic

Eukaryotic

Ribosomes

Absent

70 S

80 S

Mitochondria

Absent

Absent

Present

Motility

Nil

Present

Nil

Binary fission

Budding

Reproduction

240

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Lipopolysaccharide is an important component of:
1. Gram-positive cells
2. Gram-negative cells
3. Neither gram-positive nor gram-negative cells
4. Both gram-positive and gram-negative cells
Ans. 2. Gram-negative cells

Difference between Gram-Positive and Gram-Negative Cells

Component

Gram-Positive Cells

Gram-Negative Cells

Peptidoglycan

Thick

Thin

Teichoic acid

Present

Absent

Periplasmic space

Absent

Present

Lipopolysaccharide

Absent

Present

USMLE Case Scenario

Which of the following structures is found only in gram-negative microorganisms:
1. Cell envelope
2. Exotoxin
3. Peptidoglycan
4. Periplasmic space
Ans. 4. Periplasmic space

FUNCTIONS OF DIFFERENT COMPONENTS OF CELL ENVELOPE

(USMLE High Yield Points)
Capsule: Antiphagocytic and immunogenic
Capsulated organisms:
Pneumococus
Anthrax bacillus
Bordetella
Meningococci

Klebsiella
Cryptococcus, H. influenza
Bacteroids
V. parahemolyticus

Teichoic acid: Attachment to epithelial surfaces and immunogenic

Cell wall: Rigid support, protection from osmotic damage
Cytoplasmic membrane: Membranous matrix for respiratory pathways and cell wall synthesis
Porin proteins: Passive transport of aqeous materials
Perplasmic space: Extracellular enzymes, osmotic pressure
Inner membrane: Matrix for enzymes of respiratory pathways and cell wall synthesis

Detection Techniques

Flagella are detected by Dark ground microscopy

Fimbriae are detected by Hemagglutination
Spores are detected by Acid fast (ZN staining)
Capsules are detected by India ink/Quelling reaction

Microbiology

241

Phases of Bacterial Growth Cycle

Lag Phase

Nutrients incorporated

Log Phase

Rapid cell division

Stationary Phase

Cell Death = Cell formation

Death Phase

Cell death > Cell formation

Phases of bacterial growth

USMLE Case Scenario

An antibiotic, such as penicillin, which modifies cell wall synthesis, tends to be most effective during which phase of bacterial
growth in a closed system?
Ans. Log phase

BACTERIAL CONJUGATION: (USMLE FAVORITE)

Bacterial conjugation is the transfer of genetic material between bacteria through direct cell-to-cell contact.
Discovered in 1946 by Joshua Lederberg and Edward Tatum.
Conjugation is a mechanism of horizontal gene transfer
The prototype for conjugative plasmids is the F-plasmid, also called the F-factor.The F-plasmid is an episome (a plasmid that can integrate
itself into the bacterial chromosome by genetic recombination) of about 100 kb length.The host bacterium is called F-positive or F-plus(d
enoted F+). Strains that lack F plasmids are called F-negative or F-minus (F-).
Bacterial conjugation is often incorrectly regarded as the bacterial equivalent of sexual reproduction or mating.
It is merely the transfer of genetic information from a donor cell to a recipient.

Transduction
Transduction is the process by which DNA is transferred from one bacterium to another by a virus
It also refers to the process whereby foreign DNA is introduced into another cell via a viral vector
This is a common tool used by molecular biologists to stably introduce a foreign gene into a host cells genome.
When bacteriophages (viruses that infect bacteria) infect a bacterial cell, their normal mode of reproduction is to harness the
replicational, transcriptional, and translation machinery of the host bacterial cell to make numerous virions, or complete viral particles,
including the viral DNA or RNA and the protein coat.

242

USMLE Step 1 Platinum Notes

Bacterial Transformation
Bacteria transformation maybe referred to as a stable genetic change brought about by taking up naked DNA (DNA without
associated cells or proteins), and competence refers to the state of being able to take up exogenous DNA from the environment.
Procedure

Process

DNA Transferrred

Conjugation

Bacterium to Bacterium

Chromosomal/Plasmid

Transduction

By Virus

Any Gene

Transformation

DNA taken Directly

Any DNA

Plasmids: (USMLE Favorite)

Extrachromosomal genetic material
Generally have covalently, closed, circular DNA (ccc)
One class of plasmids, Episomes maybe integrated into bacterial DNA
Plasmids carry genetic material for variety of genes, (Fertility genes, antibiotic resistance, exotoxins)
Involved in multi drug resistance transfer.

Bacteriophage
Viral DNA maybe inserted into bacterial chromosome as prophage by a temperate virus which directs the synthesis of a virulence
factor making bacterium more pathogenic.

Transposons

Mobile genetic elements that can move themselves from one DNA to other
Jumping genes
Create additional mutations
Have sequences of indirect repeats of bases at each end

According to Shape Bacteria are Classified into

Cocci: Spherical shaped bacteria

Bacilli: Rod shaped cell
Vibrio: Comma shaped cells
Spirilla: Rigid spiral forms
Spirochetes: Flexuous spiral forms
Actinimycetes: Branching filamentous form
Mycoplasma: Lacks cell wall, hence do not possess stable morphology

USMLE Case Scenario

An intravenous drug abuser is found to have infective endocarditis. Most common organism in Acute Endocarditis: Staph
aureus. The organism is:
1. A Gram-positive coccocus
2. A Gram-negative rod
3. A Gram-positive coccus
4. A Gram-positive rod
Ans. 3. A Gram-positive coccus

Microbiology

243

USMLE Case Scenario

Among the following which is an obligate intracellular organism:
1. Nocardia
2. Chlamydia
3. Bacillus
4. Legionella
Ans. 2. Chlamydia

USMLE Case Scenario

A 26-year-old male complains of a severe headache and weakness. His condition rapidly deteriorates over a period of hours. A
lumbar puncture is performed and a Grams stain of spinal fluid reveals Neisseria meningococcus. The organism is:
1. Gram-negative diplococci
2. Gram-positive cocci
3. Gram-positive bacillus
4. Obligate intracellular organism
Ans. 1. Gram-Negative Diplococci

CLASSIFICATION: FREQUENTLY ASKED IN USMLE

Gram-Positive Cocci:
Streptococcus
Staphylococcus
Gram-Positive Spore forming Bacilli:
Bacillus Anthraxus (Aerobic)
Clostridium (Anaerobic)
Gram-Positive Nonspore forming Bacilli:
Corynebacterium diphtheriae
Listeria
Actinomyces
Nocardia
Gram-Negative Cocci:
Neisseria gonococcus, meningococcus
Gram-negative Rods:
Hemophilus
Bordetella
Legionella
E coli
Serratia
Klebsiella
Salmonella
Shigella
Vibrio
Pseudomonas

244

USMLE Step 1 Platinum Notes

Obligate intracellular parasites:

Rickettsia
Chlamydia
Thin walled spirochetes:
Treponema
Borrelia
Leptospira
Wall less:
Mycoplasma

USMLE Case Scenario

A 33-year-old Indian reported in New York and is found to have chronic weight loss, pyrexia and easy fatiguibility. A chest
X-ray reveals miliary form of tuberculosis. The feature of the organism causing the disease is:
1. Aerobe
2. Obligate aerobe
3. Anaerobe
4. Obligate anaerobe
Ans. 2. Obligate aerobe

USMLE Case Scenario

Gastric ulcers are associated with malignancy, and therefore biopsy should be performed when they are discovered. This
association with malignancy is not found with duodenal ulcers. The increased risk for malignancy with gastric ulcers is a good
reason to test patients for H pylori and initiate treatment if it is found. H pylori is a:
1. Aerobe
2. Anaerobe
3. Obligate aerobe
4. Microaerophilic
Ans. 4. Microaerophilic
Obligate aerobes
Use oxygen dependent mechanisms to generate ATP
Examples
Pseudomonas aeruginosa
Mycobacterium tuberculosis
Nocardia
Obligate anaerobes
Lack catalase and superoxide dismutase
Examples (ABC)
Actinomyces
Bacteroids
Clostridium

Microaerophilic
Campylobacter
H pylori

Microbiology

245

USMLE Case Scenario

An organism causing otitis media in children and pneumonia in adults. With a peculiar growth requirement, requiring factor
X (hematin) and factor V (NAD). The most likely organism is:
1. H. influenza
2. B. pertusis
3. M. tuberculosis
4. Klebsiella
Ans. 1. H. Influenza

Remember Bacterial Cultures: (High Yield for USMLE)

Smith noguchi medium: Spirochetes
Selenite F Broth: Salmonella, shigella
Dorset egg medium: Mycobacterium
Noguchi medium : Borellia
BYCE medium: Legionella
Lofflers serum slope: Corynebacterium diphtheria
Tellurite media: Corynebacterium diphtheria
Thayer martin media: N.gonorrhea
Korthof media: Leptospira
Staurts media: Leptospira
Fletcher media: Leptospira
Chocolate agar: H.influenza
Bordet gengou: B.pertusis
Lownstein Johnson: M.tuberculosis
Sabourdars media: Fungi
Skirrows media: Campylobacter Jejuni

USMLE Favorite
EXOTOXIN

ENDOTOXIN

Mostly Gram-positive bacteria

Gram-negative bacteria

Polypeptides

Lipopolysaccharides

Highly toxic

Low toxicity

Highly antigenic

Poorly antigenic

Toxoids used as vaccines

No toxoids, no vaccines

Heat sensitive

Heat stable

Secreted from cell

Not secreted from cell

Antiphagocytic Structures (CAMP)

Capsule
Pilli of Neisseria Gonorrhea
M protein of streptococcus pyogenes
A protein of staph aureus

246

USMLE Step 1 Platinum Notes

Pathogenesis of shock

Capsulated Organisms

Streptococcus Pneumoniae
Klebsiella Pneumoniae
Hemophilus influenza
Pseudomonas Aeruginosa
Neisseria meningitidis
Cryptococcus neoformans

USMLE Case Scenario

Cryptococcus is nondimorphic yeast, meaning that it exists only in the yeast form and it reproduces by budding. It is found
worldwide in bird droppings (think pigeons). It can also cause transient pulmonary illness in otherwise healthy individuals.
The feature of Cryptococcus is that:
1. It is capsulated so takes India ink stain
2. It is noncapsulated so takes India ink stain
3. It is capsulated so does not take India ink stain
4. It is noncapsulated so does not take India ink stain
Ans. 1. It is capsulated so takes India ink stain

Understanding Toxins Commonly asked in USMLE Examination

Pseudomonas alpha toxin, which is responsible for the tissue damage, inhibits Protein synthesis by acting on EF-2 with a
primary target cell in the liver
The diphtheria toxin has a similar action, although its target cells are heart and nerve
Anthrax toxin is an Adenylate cyclase that causes fluid loss from cells
Botulinum toxin is a neurotoxin that decreases acetylcholine synthesis
Cholera toxin acts to increase adenylate cyclase activity by ribosylation of GTP-binding protein
Clostridium perfringens alpha toxin is a lecithinase
Escherichia coli labile toxin works in a fashion similar to the cholera toxin
Pertussis toxin causes fluid loss by ribosylating Gi
Shiga toxin decreases protein synthesis by inhibiting the 60S ribosomal subunit
Streptococcal erythrogenic toxins act similarly to the diphtheria toxin, but do so by increasing cytokine production
Tetanus toxin is a neurotoxin that inhibits the inhibitory neurotransmitters glycine and GABA
TSST-1 is a superantigen that acts by increasing cytokine production and decreasing liver clearance. A superantigen, such as
TSST- 1 or staphylococcal enterotoxin, cross-links the variable domain of the TCR b chain to the MHC class II molecule and
specifically induces massive T cell activation.

Microbiology

247

REMEMBER
Clostridial Associations in USMLE

USMLE Case Scenario

Among the following organisms would most likely cause infection after a sterilization procedure that killed vegetative cells
but did not kill spores?
1. Chlamydia
2. Clostridium
3. Pseudomonas
4. Streptococcus
Ans. 2. Clostridium
Clostridium botulinum spores (found in honey) in the babys gastrointestinal tract. Patients improve when honey is removed
from the diet. This disorder is most common in children under the age of six months; older children and adults do not appear to be
vulnerable to this form of botulism, but are susceptible to botulism caused by ingestion of preformed toxin
Clostridium difficile causes pseudomembranous colitis, especially after antibiotic therapy
Clostridium perfringens causes gas gangrene and gastroenteritis, and it is not associated with ingestion of honey
Clostridium tetani causes tetanus, and does not cause a foodborne illness in infants.

Important Bacterial Toxins: (USMLE Favorite)

Corynebacterium Diphtheria

Diphtheria

Inactivates EF2: shuts down protein synthesis

Clostridium tetani

Tetanus

Blocks release of Glycine

Clostridium boutilinium

Boutilism

Blocks release of Acetyl choline

Clostridium difficile

Pseudomembranous colitis

Exotoxin BCytotoxin disaggregates actin filaments

Clostridium perfringens

Gas gangrene

Alpha toxin acting as lecithinase

Bacillus anthraxus

Anthrax

Edema factor, Lethal factor

Staph aureus

TSS

Superantigen binding directly to MHC II

Stret pyogenes

Scarlet fever

Superantigen

E coli

Watery diarrhea

Stimulates adenylate cyclase (Gs)

Vibrio cholera

Cholera

Stimulates adenylate cyclase (Gs)

Bordetella Pertussis

Whooping cough

Stimulates adenylate cyclase (Gi)

Main toxins

USMLE Case Scenario

Pseudomembranous colitis occurs as a result of treatment with clindamycin or ampicillin. You would confirm your suspicion
by sending a stool culture to be tested for the presence of the:
1. Toxin
2. Flagella

248

USMLE Step 1 Platinum Notes

3. Bacteria
4. Virus
Ans. 1. Toxin

USMLE Case Scenario

An injection of a substance from gram-negative bacteria into the vascular system will rapidly produce myocardial dysfunction,
hypotension, disseminated intravascular coagulation and coma resembling septic shock. The substance is most likely:
1. Lipopolysaccharide
2. Protein only
3. Saccharide
4. Hapten
Ans. 1. Lipopolysaccharide

USMLE Case Scenario

A 18-year-old, ill-appearing woman comes OPD with a fever. She notes the recent development of nausea, diarrhea, and a
rash. Her last menstrual period began 3 days ago. Physical examination is remarkable for blood pressure of 90/40 mm Hg and
heart rate of 120 beats per minute. A diffuse erythematous rash with desquamation over feet is noted. Infection with which of
the following toxin is the most likely cause of these signs and symptoms?
1. Clostridium perfringens toxin
2. Shigella dysenteriae toxin
3. Staphylococcus aureus toxin
4. Staphylococcus epidermidis toxin
Ans. 3. Staphylococcus aureus toxin

Toxins c AMP levels (PACE)

Pertusis toxin
Anthrax toxin
Cholera toxin
E coli toxin (labile)

Site

Important organism

Skin

Staph Epidermidis

Nose

Staph Aureus

Mouth

Strept Viridians

Dental plaque

Strept Mutans

Vagina

Lactobacillus, E coli, Group B Strept

Colon

Bacteroids, E coli

Throat

Strept Viridians

USMLE Case Scenario

Bacillus anthracis is found in many animal species, and humans can acquire the organism either through contact with the
animals or from locally contaminated soiL Feature of colonies of Anthrax bacillus is:
1. Swimming Growth
2. Swarm of Gnats or Fish in Stream
3. Stalactite Growth
4. Medusa Head
Ans. 4. Medusa Head

Microbiology

249

Colony Appearances
Colony Appearance in culture

Organism

1. Draughtsman (Concentric Rings)

Pneumococci

Medusa Head
Frosted Glass
Inverted Fir Tree in Stab Culture
String of pearls

B Anthracis

2. Swimming Growth (Fishy or Seminal Smell)

Proteus

3. Swarm of Gnats or Fish in Stream

V Cholerae

4. Stalactite growth

Yersinia Pestis

5. Thumb print appearance, Bisected pearls or mercury drops, B Pertussis

Aluminium Paint appearance
6. Cigar bundle (globi) appearance

M Leprae

7. Fried egg

Mycoplasma

8. Bread crumb

Actinomyces israelii

9. Oil Paint

Staphylococci

10. School of Red fish

H ducreyi

11. Stately Motility

Clostrida

Gram-Positive Bacilli
Corynebacterium Diphtheriae

Aerobic
Catalase +
Nonhemolytic
Toxin production

Diphtheria

Listeria monocytogenes

Aerobic
Hemolytic

Meningoencephalitis in neonates, immunocompromised

Bacillus anthracis
Bacillus cereus
Bacillus anthracis

Aerobic spore
forming

Anthrax
Food poisoning (reheated rice)
Most common form: cutaneous (hide porters disease)
Most fatal form: pulmonary (wool sorters disease)

Anaerobic, spore
forming

Food poisoning, gas gangrene

Gas gangrene
Tetanus
Botulism
Pseudomembranous colitis

Aerobic, rod shaped

Tuberculosis

Clostridium welchii
Clostridium septicum
Clostridium tetani
Clostridium botulinium
Clostridium difficile

Mycobacterium tuberculosis
M aviumintercellulare
M leprae

Cervical LAP
Cannot be
cultured
Acid fast rods
Cooler parts of
body
Do not follow
kochs postulates

Leprosy

250

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A gram-positive spore-forming rod that is associated with food poisoning outbreaks following the ingestion of fried rice. The
organism survives the boiling of the rice because it is a spore-former. It germinates as the rice cools, grows, and elaborates an
enterotoxin that is responsible for the nausea and vomiting characteristic of the disease. The most likely organism is:
1. Bacillus anthracis
2. Bacillus cereus
3. Staph aureus
4. Salmonella
Ans. 2. Bacillus cereus

USMLE Case Scenario

A 33-year-old cave digger who has been excavating acave develops a pustule on his hand. The pustule then ruptures to form
a black eschar surrounded by expanding brawny edema. Which of the following gram-positive organisms is the most likely
cause of this condition:
1. Clostridium welchii
2. Clostridium tetani
3. Bacillus anthracis
4. Clostridium botulinium
Ans. 3. Bacillus anthracis

USMLE Case Scenario

A 58-year-old has developed thick, erythematous nodules on her ears and nose with significant associated sensory loss. The
nodules have grown slowly over the course of many years. Biopsy of the lesions shows dermal granulomas with giant cells
but no acid-fast bacteria. Culture on blood agar and Lowenstein-Jensen medium shows no growth. The disease is identified
as leprosy. The organism is:
1. Gram-positive, acid fast rod
2. Gram-positive, nonacid fast rod
3. Gram-negative, acid fast rod
4. Gram-negative, nonacid fast rod
Ans. 1. Gram-positive, acid fast rod
Hansens disease: A key feature in the description is the fact that the organism is acid-fast. Both of the mycobacteria,
M avium-intracellulare and M leprae are strongly acid-fast, that is they retain the carbol fuchsin dye in the face of acidalcohol decolorization. M leprae has a predilection for the skin and cutaneous nerves, thereby producing the symptoms of
depigmentation and anesthetic cutaneous lesions. This loss of peripheral nerve function leads to many of the disfiguring
features of the disease; because the patients do not have normal pain sensation, they sustain repeated injuries. In addition,
the organism attacks cartilage and causes granuloma formation in the skin, leading to some of the facial disfigurement.

Gram-Negative Bacilli: (High Yield for USMLE)

Hemophilus influenza
Hemophilus parainfluenza
Hemophilus aegyptius
Hemophilus ducreyi

Needs factor X and V, satellite

phenomenon

Koch weeks bacillus

Acute epiglottitis, meningitis in children, otitis

media
COPD Exacerbations
Conjunctivitis
Genital ulcers, chancroid

Bordetella pertusis

Cocco bacillus
Bordet Gengou media

Whooping cough

Yersenia pestis
Yersenia enterocolitica

Aerobic, bipolar staining

Bubonic plague, pneumonic plague

Gastroenteritis, Pseudoappendicitis

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251

Pasturella multicoida

Aerobic

Wound sepsis following dog bites

Vibrio cholera
Vibrio para hemolyticus

Aerobic curved motile rod

Cholera
Food poisoning (sea food) shellfish

Campylobacter

Microaerophilic

Acute diarrhea (bloody)

Gullian barre syndrome
Reactive arthritis

E coli

Aerobic, lactose fermenter, enterotoxin UTI, Peritonitis, cholecystitis, neonatal meningitis, travelers diarrhea
HUS, TTP, hemorrhagic colitis
Verocytotoxin, shiga like toxin

E coli 0157: H7

Nonsorbitol fermenting
Klebsriella pneumoniae

Aerobic, lactose fermenter

Proteus mirabilis

Shigella

Nonlactose fermenters
Nonmotile

Bacillary dysentery

Bacteroids

Anaerobic, nonsporing

Abscesses, septicemia

Fusobacterium

Anaerobic, nonsporing

Vincents angina, gingivitis

Acinetobacter

Anaerobes

Hospital acquired infections

Borrelia vincenti
Borrelia recurrentis
Borrelia duttoni
Borrelia burgdorfei

Helicobacter pylori

Swarming growth on agar

Aerobic nonlactose fermenter
Peritrichous flagella
Urease positive

Aerobic
Anaerobic
Anaerobic
Anaerobic

Pneumonia (currant jelly)

Spiral, flagellate
Microaerophilic
Urease positive
Invasive
Campys medium, Skirrows agar

UTI

Vincents angina
Relapsing fever (r-r)
Relapsing fever
Lyme disease

Peptic ulcer, gastric cancer, gastric lymphoma

Extra gastric diseases

Treponema pallidum
Treponema pertenue
Treponema carateum

Anaerobic, spiral, motile

Anaerobic
Anaerobic

Syphilis
Yaws
Pinta

Leptospira icterohemorrhagica
Leptospira canicola

Anaerobic
Anaerobic

Weils disease
Canicola fever

Obligate intracellular bacteria

Obligate intracellular bacteria

smallest free living bacteria
no cell wall
sterols in membrane

Primary atypical pneumonia

Urethritis, PID

Rickettsia prowazekii
Ricketssia mooseri
Ricketssia burnetti
Ehrlichia chaffeensis

Mycoplasma pneumonia
(Eaton agent)

Ureaplasma urealyticum
M hominis

Epidemic typhus
Endemic typhus
Q fever
Ehrlichiosis

Pyelonephritis
PID

252

USMLE Step 1 Platinum Notes

USMLE Case Scenario

An organism is causing urinary tract infections. It has ability to breakdown urea is thought to contribute to the development of
struvite kidney stones due to the elevation of urine pH by production of ammonia. The said organism is also having swarming
motility. The organism is identified as proteus species. It is a:
1. Aerobic nonlactose fermenter
2. Anaerobic nonlactose fermenter
3. Aerobic lactose fermenter
4. Anaerobic lactose fermenter
Ans. 1. Aerobic nonlactose fermenter

USMLE Case Scenario

A 33-year-old patient presents with a red macule or papule at the site of the tick bite. This lesion, called erythema chronicum
migrans, slowly expands to form a large annular lesion with a red border and central clearing. The patient also has severe
headache, stiff neck, chills, arthralgias and profound malaise and fatigue. The causative organism is:
1. Borrelia vincentii
2. Borrelia recurrentis
3. Borrelia duttonii
4. Borrelia burgdorferi
Ans. 4. Borrelia burgdorferi

USMLE Case Scenario

A child presents with chronic enteritis, failure to thrive, hypoalbuminemia, and hypokalemia. Other findings include acute
right lower quadrant abdominal pain, tenderness, nausea and vomiting. The infection mimics appendicitis or Crohns disease.
Most likely organism is:
1. Yersinia enterocolitica
2. Hemophilus aegyptius
3. Borrelia duttonii
4. Hemophilus ducreyi
Ans. 1. Yersinia enterocolitica

USMLE Case Scenario

A 66-year-old man is brought to a rural hospital. He has severe bronchopneumonia after sudden onset of chills, fever, and
headache several days ago. One day later, he coughed up blood-tinged sputum. Chest X-ray reveals patchy infiltrates and
segmental consolidation. Which organism with bipolar staining pattern is the most likely cause of this mans pneumonia?
1. Yersinia Pestis
2. Streptococcus pneumonia
3. Staph aureus
4. Leptosporia
Ans. 1. Yersinia Pestis

USMLE Case Scenario

A curved, gram-negative rod which is microaerophilic is causing enterocolitis with diarrhea and less commonly, chronic
gastritis. Most likely the organism is:
1. Vibrio cholera
2. H pylori
3. E coli
4. Campylobacter jejuni
Ans. 4. Campylobacter jejuni

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253

USMLE Case Scenario

A 8-year-old girl is bitten in the leg by a dog. She presents the next day with fever and bone pain localized to her right calf.
X-ray reveals a lytic lesion of the left femur. Results of the boneculture are pending. Infecting organism is most likely to be:
1. Pasteurella
2. Bartonella
3. Yersinia
4. Bordetella
Ans. 1. Pasteurella

USMLE Case Scenario

An infection is characterized by rapidly evolving cellulitis starting at the site of the bite. A gram-negative rod was found to be
spread via dog bites. Most likely organism is:
1. Pasteurella
2. Bartonella
3. Yersinia
4. Bordetella
Ans. 1. Pasteurella
Actinomyces israelli

Anaerobic, branching filaments, non acid fast, sulfur Actinomycosis, lumpy jaw
granules

Nocardial asteroids

Anaerobic, branching filaments, partially acid fast

Staph Aureus: USMLE High Yield

Gram-positive
Cluster-forming coccus, nonmotile, nonspore forming facultative anaerobe
Fermentation of glucose produces mainly lactic acid.+
Ferments mannitol (distinguishes from S epidermis)+
Catalase positive+
Coagulase positive +
Coagulase is responsible for pathogenecity
Golden yellow colony on agar
Normal flora of humans found on nasal passages, skin and mucous membranes
Food poisoning is due to preformed endotoxin
Occurs within 6 hours of food intake
Panton valentine leucocidin is seen in staph infections
Especially diary products involved in poisoning
CAUSES:
Acute osteomyelitis
Acute mastitis
Botromycosis
SSSS
Furunculosis, carbuncle
Acute endocarditis
Sycosis barbae
Tropical polymyositis

Nocardiosis

254

USMLE Step 1 Platinum Notes

Methicillin Resistant Staphylococcus Aureus (MRSA)

MRSA is a major nosocomial pathogen
Causes severe morbidity and mortality worldwide
40% of nosocomial Staph aureus infections are methicillin resistant
Hospital personnel maybe carriers
Spread by hand, usually of health care workers
Microbiology
Methicillin resistance is mediated by the mecA gene
Encodes a single additional penicillin binding protein PBP2a
Expression of mecA can be either constitutive or inducible
Risk factors for MRSA coloniation (USMLE Favorite)
Advanced age
Male gender
Previous hospitalization
Length of hospitalization
Stay in ICU
Chronic medical illness
Prior and prolonged antibiotic therapy
Presence and size of a wound
Exposure to colonized or infected patient
Presence of invasive indwelling device
Clinical presentations
Pneumonia
Surgical site infections
Line sepsis
Intra-abdominal infections
Osteomyelitis
Toxic shock syndrome
Infection control
Screening of patients and staff
Handwashing
Use of gowns and gloves
Topical antimicrobials
Isolation of patients
Environmental cleaning
Management
Vancomycin is used
Teicoplanin maybe used if the isolate is resistant to vancomycin
Linezolid is new class of antimicrobial agent, active against MRSA and VRE
Quinupristin/Dalfopristin are newer alternative

USMLE Case Scenario

Microbiologic studies on a gram-positive coccus isolated from a skin abscess demonstrate a positive catalase test and a
positive coagulase test. This is most consistent with which of the following organism:
1. Staph aureus
2. Streptococcus
3. Neisseria gonorrhea
4. Neisseria meningococcus
Ans. 1. Staph Aureus

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USMLE Case Scenario

A 22 -year-old, ill-appearing woman comes to the emergency room with a fever. She notes the recent development of nausea,
diarrhea, and a rash. Her last menstrual period began 2 days ago. Physical examination is remarkable for blood pressure of
88/40 mm Hg. A diffuse erythematous rash with areas of desquamation over the hands and feet is noted. Infection with which
of the following agents is the most likely cause of these signs and symptoms?
1. Streptococcus
2. Neisseria gonorrhea
3. Neisseria meningococcus
4. Staph aureus
Ans. 4. Staph Aureus

USMLE Case Scenario

A 4-year-old girl with a history of hydrocephalus is brought to the neurologist by her parents with a severe headache and
fever. The girl underwent a surgery for a ventricular-peritoneal shunt 2 months ago and the neurologist suspects that an
infection has occurred. Organisms would most likely be isolated from the shunt tubing is:
1. Staph aureus
2. Streptococcus
3. Staphylococcus epidermidis
4. Meningococcus
Ans. 3. Staphylococcus epidermidis

USMLE Case Scenario

A 56-year-old has developed acute osteomyelitis in his left tibia. The most common organism a pathologist would be thinking
about is:
1. Streptococcus
2. Staphylococcus epidermidis
3. Meningococcus
4. Staph aureus
Ans. 4. Staph aureus

Streptococci: USMLE High Yield

C carbohydrate is used for Lancfield classification
M protein is mainly responsible for pathogenecity
MC organism causing cellulitis: streptococcus pyogenes
Causes:
Erysipelas
Scarlet fever
Purpureal sepsis
Non suppurative infections: rheumatic fever, glomerulonephritis
Are usually initially speciated by their hemolytic capacity on sheep blood agar. Beta-hemolytic streptococci include groups A, B, and
D S agalactiae is the classic group B streptococcus. The non beta-hemolytic streptococci consist principally of the pneumococci and
the viridans group.

High Yield Points Repeated Often: (USMLE Favorite)

Str. agalactiae

Neonatal meningitis, neonatal sepsis

Str. Bovis

Endocarditis

Str. Pneumonia

Pneumoniae, Otitis media

256

USMLE Step 1 Platinum Notes

Str. Mutans

Dental caries

anaerobic streptococci

Purpureal sepsis

Str. Pyogenes

Erysipelas, Cellulitis
Impetigo, scarlet fever, Rheumatic fever, Acute Glomerulonephritis

Str. Viridians

Endocarditis

USMLE Case Scenario

A 1-week-old female infant with symptoms of vomiting and anorexia has a temperature of 102 F. A bulging fontanel is noted
on physical examination. The most likely coccusis:
1. Streptococcus agalactiae
2. Streptococcus pneumonia
3. Streptococcus viridians
4. Streptococcus pyogenes
Ans. 1. Streptococcus agalactiae

USMLE Case Scenario

A 55-year-old man presents with an episode of shaking chills the previous night. He has now developed right-sided pleuritic
chest pain, fever, sweats, malaise, purulent sputum, and mild hemoptysis. On examination, the patient is diaphoretic but
alert, with right basilar rales. Chest X-ray films show a right lower lobe infiltrate with blunting of the right costophrenic angle.
The causative organism implicated is:
1. Streptococcus agalactiae
2. Streptococcus pneumonia
3. Streptococcus viridians
4. Streptococcus pyogenes
Ans. 2. Streptococcus pneumonia
Streptococcus agalactiae

Group b Streptococci. Gram-positive

Beta hemolytic
Bacitracin Resistant
Hydrolyses hippurate
C AMP test positive

Acute Meningitis: Commonest Bacterial Organisms

Neonates: Group B streptococci, E coli
Adolescents and young adults: N meningitidis
Elderly: Strept Pnemoniae, Listeria Monocytogenes
Beta hemolysis is shown by:
Strep pyogenes
Strept agalataciae
Staph aureus
Listeria monocytogenes
Bacillus subtilis
Alpha hemolysis is shown by:
Strep pneumonia
Strep viridians

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Sterpt mutans
Strep sanguis
Enterococcus

USMLE High Yield

The catalase test is used to differentiate Staphylococci from Streptococci. Staphylococci are catalase positive, Streptococci are
catalase negative
The coagulase test is used to differentiate Staph aureus from the other Staph spp. Staph aureus is coagulase positive; the others
are negative
Sensitivity to novobiocin is used to differentiate Staph saprophyticus (resistant) from Staph epidermidis (sensitive)
Sensitivity to optochin is used to differentiate Strep pneumoniae (sensitive) from viridans Strep (resistant).
Catalase + ve
Coagulase + ve

Staph aureus

Catalase ve
Coagulase ve

Streptococcus

Catalase + ve
Coagulase ve

Novibocin sensitive st epidermidis

Novibocin resistant st saprophyticus

Distinguishing strept and staph

Streptococcus Bovis

The main nonenterococcal group D streptococcal species that causes human infections is S bovis
S bovis endocarditis is often associated with neoplasms of the gastrointestinal tract
3/4 Most frequently a colon carcinoma or polyp 3/4 but is also reported in association with other bowel lesions
S bovis are reliably killed by penicillin as a single agent, and penicillin is the treatment of choice for S bovis infections.

USMLE Case Scenario

A 88-year-old patient from North America with colorectal cancer develops severe septicemia complicated by bacterial type of
endocarditis among the below mentioned choices. You would expect the blood cultures to grow.
1. Streptococcus agalactiae
2. Streptococcus bovis
3. Streptococcus pneumonia
4. Streptococcus pyogenes
Ans. 2. Streptococcus bovis

Catalase Positive Organisms are

Staph aureus
Pseudomonas
Aspergillus
Candida
Citrobacter
Enterobacter
E coli
Klebsiella
Shigella
Yersinia

258

USMLE Step 1 Platinum Notes

Gems about Pneumococcus

Gram-positive
Capsulated
Most virulent: Type C
Draughtsman colonies
Quelling reaction seen
Vaccine is made from capsule
Lanceolate, flame shaped diplococcus
Bile soluble
Optochonin sensitive
Virulence is due to capsule

USMLE Case Scenario

A Eight year-old boy from California presents to the pediatrician because his mother noticed a smoky color to his urine.
The child suffered a sore throat several weeks ago that was left untreated. Physical examination reveals hypertension and
mild generalized edema. Urinalysis is significant for red blood cell casts. Which of the following accurately describes the
microorganism responsible for this childs illness?
1. Streptococcus
2. Staphylococcus
3. Gonococcus
4. Camplyobacter
Ans. 1. Streptococcus

USMLE Case Scenario

Which of the following organisms is the most common cause of community-acquired pneumonia?
1. Chlamydia pneumoniae
2. Mycoplasma pneumoniae
3. Staphylococcus aureus
4. Streptococcus pneumonia
Ans. 4. Streptococcus pneumonia

Neisseria Gonococcus USMLE High Yield

Means flow of seeds

Intracytoplasmic Gram-negative
Noncapsulated
Do not ferment maltose. Ferments glucose
Kidney shaped
Causes:
Urethritis
Cervicitis
Salpingitis
Vaginitis
Conjunctivitis
Meningitis, arthritis, endocarditis

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259

USMLE Case Scenario

A sexually active 22-year-old manfrom Kansas develop sacute epididymitis and orchitis. Needle biopsy demonstrates a
prominent leukocytic infiltrate with numerous neutrophils. Which of the following organisms is the most likely cause of this
mans infection?
1. Escherichia coli
2. Mycobacterium tuberculosis
3. Neisseria gonorrheae
4. Staphylococcus
Ans. 3. Neisseria gonorrheae

Neisseria Meningococcus

Gram-negative diplococcic
Capsulated
Carriers are a source of infection
Cause Waterhouse-Friderichsen syndrome, Meningitis
Neisseria meningitides: Capsule + Maltose Fermentation+
Neisseria gonococcus: Capsule-Maltose Fermentation

Corynebacterium Diphtheriae: USMLE High Yield

Gram-positive, nonmotile, nonsporing, noncapsulated

Babes ernest/volutin granules seen/Metachromatic granules seen
Loefflers serum slope, Tellurite media used
Eleks gel precipitation test used
Incubation period 26 days
Faucial (tonsillar) not facial diphtheria is the commonest type of diphtheria
Pseudomembrane formation is a feature
Bulls neck (cervical lymphadenopathy) occurs in diphtheria
Diphtheria toxin inhibits protein synthesis
Toxin is phage mediated
Corynebacterium parvum is used as immunomodulator
Corynebacterium pseudotuberculosis is Nocards bacillus
Corynebacterium minnusitum causes Erythrassma.

Diphtheria
Daisy head colony (C Diphtheriae) gravis
Frogs egg colony (C Diphtheriae) intermedius
Poached egg colony (C Diphtheriae) mitis

260

USMLE Step 1 Platinum Notes

Corynebacterium Minutissimum
It is a part of normal skin flora
It is lipophilic, Gram-positive, aerobic, catalase positive but nonspore forming diphtheroid
It ferments glucose, dextrose, sucrose, maltose and mannitol
Erythrassma is a chronic superficial infection of intertriginous areas
Organism causing erythrassma is Corynebacterium Minutissimum
Erythrassma produces coral red fluorescene under wood light secondary to production of porphyrins

Anthrax

USMLE Case Scenario

An organism produces cutaneous disease (malignant pustule or eschar) at the site of inoculation in handlers of animal skins.
Most likely organism is:
1. Bacilus anthracus
2. Pseudomonas Aeruginosa
3. Neisseria meningitides
4. Cryptococcus neoformans
Ans. 1. Bacilus anthracus

USMLE Case Scenario

A disease is found to produce severe hemorrhagic pneumonia in a person handling carcasses or skins. The organism causing
the disease is a gram-positive rod. Most likely organism is:
1. Yersinia
2. Francisella
3. Spirillum
4. Anthrax
Ans. 4. Anthrax

Anthrax: USMLE High Yield

It is a Zoonosis
Gram-positive, nonmotile, capsulated, sporing
Cutaneous anthrax commonest
Painless malignant pustule. (CHARBON)
Hide porters disease is cutaneous anthrax
Wool sorters disease is pulmonary anthrax
Colony woes for a student
Colony characteristics for the organism
Medusa head
Inverted fir tree appearance
Frosted glass appearance
String of pearl appearance
Mc Faydens reaction positive
PLET medium used

Gems about Clostridia

Clostridium Tetani:
Gram-positive
Anaerobic spore forming bacilli
Motile with swarming tendency
Strict anaerobe

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261

Spherical and terminal spores: (drum stick) CL tetani

Oval and terminal spores: (tennis racket) CL difficile
Central or sub terminal: (spindle) other species
Tetanospasmin is the toxin. Blocks release of inhibitory neurotransmitters glycine/GABA.
Generalized tetanus is the mc form
Most effective way of preventing tetanus is tetanus toxoid.

Clostridial Myonecrosis (Gas Gangrene)

80% of cases are caused by C perfringens
Alpha toxin is the most important toxin responsible
C novyi, C septicum, and C histolyticum cause the other cases
Typically, gasgangrene begins with the sudden onset of pain in the region of the wound, which helps to differentiate it from
spreading cellulitis
Once established, the pain increases steadily in severity but remains localized to the infected area and spreads only if the infection
spreads.

Clostridium Botulinium

The CNS is not affected by the toxin of CL botulinium

Blocks release of Ach at synapses and NM junction
Infant botulism is caused by ingestion of spores food borne botulism is due to ingestion of preformed toxin
Symmetric descending paralysis is a feature of botulinism

Clostridium Gifficile

Causes pseudomembranous colitis

It is a normal gut commensal
Almost all antibiotics even the ones used in treatment of pseudomembranous colitis can cause the disease
Metronidazole is the DOC
Vancomycin is also effective in treatment
Cytotoxin assay in stools is the best test

USMLE Case Scenario

A 6-month-old infant presents with failure to thrive, progressive muscular weakness, and poor head control Mother typically
feeds the baby food sweetened with honey. Which of the following organisms is most likely to be responsible for the childs
presentation?
1. Clostridium botulinum
2. Clostridium difficile
3. Clostridium perfringens
4. Clostridium tetani
Ans. 1. Clostridium botulinum

USMLE Case Scenario

A 10-month-old baby presents to the pediatric emergency room with a 1-day history of poor feeding and generalized
weakness. The mother states that she often feeds the baby honey to pacify her. The most likely organism is:
1. Clostridium botulinum
2. Clostridium difficile
3. Clostridium perfringens
4. Clostridium tetani
Ans. 1. Clostridium botulinum

262

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 66-year-old alcoholic man with brain and pulmonary abscess and is treated with antibiotics for last two weeks. He develops
nausea, vomiting, abdominal pain and voluminous green diarrhea. Which of the following organisms can be most likely
responsible for this patients symptoms?
1. Clostridium botulinum
2. Clostridium difficile
3. Clostridium perfringens
4. Clostridium tetani
Ans. 2. Clostridium difficile

USMLE Case Scenario

An obligate anaerobic, spore-forming, gram-positive bacillus. Which is an important cause of infection following trauma and
surgery and can cause gas gangrene and food poisoning is:
1. Clostridium botulinum
2. Clostridium difficile
3. Clostridium perfringens
4. Clostridium tetani
Ans. 3. Clostridium perfringens

USMLE Case Scenario

A 7-month-old baby presents to pediatrician with a 1-day history of poor feeding and generalized weakness. The mother states
that she often feeds the baby honey. The toxin responsible for this presentation works by which of the following mechanisms?
1. It blocks the release of acetylcholine from the nerve terminal
2. It blocks the release of inhibitory neurotransmitters such as glycine and GABA
3. It has a subunit that inactivates an elongation factor by ADP-ribosylation
4. It stimulates guanylate cyclase
Ans. 1. It blocks the release of acetylcholine from the nerve terminal

Gems about Enterobacteriaceae

E coli, Klebsiella, enterobacter: Ferments lactose
Salmonella, shigella, proteus, pseudomonas: Do not Ferment lactose
Capsular
Antigen
Flagellar antigen
Ferment glucose: E coli, Proteus, Klebsiella
Includes:
Escherichia
Klebsiella
Proteus
Enterobacter
Serratia
Citrobacter
Morganella
Providencia, and
Edwardsiella as well as the genus Actinetobacter from the family Neisseriaceae
Six distinct pathotypes of intestinal pathogenic E coli exist: (1) enterotoxigenic E coli (ETEC); (2) Shiga toxin-producing E coli (STEC)/
enterohemorrhagic E coli (EHEC); (3) enteropathogenic E coli (EPEC); (4) enteroinvasive E coli (EIEC); (5) enteroaggregative E coli
(EAEC); and (6) diffusely adherent E coli (DAEC). Organisms of these pathotypes are acquired via the fecal-oral rout.

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263

ETEC is the most common cause of travelers diarrhea

EHEC estimated 50% of all cases of HUS are caused by EHEC infection
EPEC is an important cause of infant diarrhea
EIEC shares many features with Shigella infection; however, unlike Shigella, EIEC causes disease only at a high inoculum (108 to
1010 CFU). Penetrate Hela cells in tissue culture
Sereny test in diagnosis used. Nonmotile and Noniactose fermenting
EAEC: These pathotypes have been described primarily in developing countries and mostly affect young children. These strains
may also cause some cases of travelers diarrhea. A high inoculum is required for infection. In vitro, the organisms exhibit a diffuse
or stacked-brick adherence pattern.

USMLE Case Scenario

An organism is found to be a major cause of travelers diarrhea with watery stools and is a very important pathogen in
neonates, who become infected during passage through the birth canaL The most likely organism is:
1. E coli
2. Rota virus
3. Norwalk virus
4. Campylobacter
Ans. 1. E coli

USMLE Case Scenario

A 42-year-old man from New Jersy presents to surgery department with a tender prostate gland. An acute bacterial infection
of prostate is suspected. Which of the following organisms is the most common pathogen in this setting?
1. Enterobacter
2. Escherichi
3. Klebsiella
4. Proteus
Ans. 2. Escherichi

USMLE Case Scenario

Acute pyelonephritis is an infectious disease involving the kidney parenchyma and the renal pelvis. The most common
organism causing acute pyelonephritis in an adult is:
1. E coli
2. Proteus
3. Klebsiella
4. Pseudomonas
Ans. 1. E coli

Gems about Proteus

Causes only 1 to 2% of cases of UTI in healthy women, and Proteus species cause only 5% of cases of hospital-acquired UTI
Swarming motality
Fishy/seminal odor
Urease positive
Dienes phenomenon shown
Proteus is responsible for 10 to 15% of cases of complicated UTI, primarily those associated with catheterization; in the setting of longterm catheterization. This high prevalence is due to the ability of Proteus to produce high levels of urease, which hydrolyzes urea to
ammonia and results in alkalization of the urine
This situation, in turn, leads to precipitation of organic and inorganic compounds, with the

264

USMLE Step 1 Platinum Notes

Formation of struvite and carbonate-apatite crystals

Biofilm formation on catheters, and/or the
Development of calculi
Proteus becomes associated with the stones and usually can be eradicated only by complete stone removal overtime, staghorn
calculi may form and lead to obstruction and renal failure.

USMLE Case Scenario

A 33-year-old male presents with UTI. An organism isolated is found to have swarming growth on solid media and production
of urease and hydrogen sulfide), associated with urinary tract infections and development of struvite kidney stones. The most
likely organism is:
1. E coli
2. Proteus
3. Klebsiella
4. Pseudomonas
Ans. 2. Proteus

Gems about Klebsiella

Causes only a small proportion of cases of community-acquired pneumonia
Friedlanders bacillus
This infection occurs primarily in hosts with underlying disease, such as alcoholics, diabetics, and individuals with chronic lung
disease
Presentation with earlier, less extensive infection is more common than that with the classic lobar infiltrate with a bulging fissure
Currant jelly sputum is a feature in lung infections

USMLE Case Scenario

An highly encapsulated organism is found to cause a bronchopneumonia with patchy infiltrates involving one or more lobes
with red sputum in a debilitated alcoholic. Most likely organism is:
1. E coli
2. Proteus
3. Klebsiella
4. Pseudomonas
Ans. 3. Klebsiella

Shigella: USMLE High Yield

Gram-negative
Noncapsulated
Nonmotile
Lactose nonfermenters
Ferment mannitol except S dysentrae
Subdivided on basis of Mannitol fermentation
Most virulent type is S dysentiae
Stool culture is the best test

USMLE Case Scenario

A Gram-negative, noncapsulated nonlactose fermenting organism is causing dysentery (multiple, small-volume stools with
blood, mucus and pus associated with abdominal cramps and tenesmusin a 33-year-old male. Most likely organism is:
1. Proteus
2. E coli

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265

3. Pseudomonas
4. Shigella, dysentrae
Ans. 4. Shigella dysentrae

Salmonella: USMLE High Yield

Gram-negative
Peritrichate flagella
Need tryptophan as growth factor
Selenite F is used as growth medium
Affects Payers patches in intestines
H antigen is the most immunogenic
VI agglutination detects carriers
VI antigen is not seen in normal population
Blood culture is the gold standard for diagnosis
Diazo reaction is also used for diagnosis

USMLE Case Scenario

A 26-year-old woman with a history of sickle cell disease presents with fever and severe bone pain localized to her left tibia.
X-ray reveals a lytic lesion and blood cultures reveal infection. A bone culture grows gram-negative rods. The organism
responsible is:
1. Salmonella
2. Klebsiella
3. E coli
4. Francisella
Ans. 1. Salmonella

USMLE Case Scenario

A 4-year-old boy presents with a 1-day history of loose stools, fever, abdominal cramping, headache and myalgia. He has no
blood in the stool. The incubation period is 36 hours after ingestion of contaminated food or water. Which of the following is
most likely the causative agent of his diarrhea?
1. Vibrio
2. Bacillus cereus
3. Francisella
4. Salmonella
Ans. 4. Salmonella

Vibrio Cholera: USMLE High yield

Isolated by Koch
Most cases are subclinical
Gram-negative bacilli, aerobic
Noncapsulated, comma shaped
Motile with polar flagellum
Ferments glucose, transported in alkaline medium
Toxin action is CAMP mediated
Darting motility
Cary Blair medium used

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USMLE Step 1 Platinum Notes

Venkata Raman medium used

Humans are the reservoir
Survives boiling for 30 seconds
Survives in cold temperature (ice for 46 weeks)
Causes rice water stools/ Pea soup diarrhea
Nonhalophilic

USMLE Case Scenario

A comma-shaped organism is found to be sensitive to acidic pH, is a gram-negative rod and causes severe enterotoxin-induced
diarrhea, with rice-water stools and dehydration. Most likely organism is:
1. Proteus
2. Vibrio cholera
3. Klebsiella
4. Francisella
Ans. 2. Vibrio cholera

Pseudmonas: USMLE High Yield

Pseudomonas aerugenosais a gram-negative, aerobic, motile bacillus
Cetrimide agar is the selective media for Pseudomona saerugenosa
EXOTOXIN A inhibits protein synthesis
Pseudomonas aerugenosa produces pigments
Pyocyanin
Pyoverdin
Pyorubin and
Fluorescein
Produces blue green pus
Virulence factors are:
Pilli, Elastase, Exotoxin, Endotoxin, Alkaline protease, Hemolysin Alginate
Grape like odor
Slime layer formation
Pseudomonas aerugenosagrows at 3742 C
Pseudomonas aerugenosa hydrolyses arginine to citrulline and ammonia
Pseudomonas aerugenosa oxidises indophenols
Pseudomonas aerugenosa does not ferment lactose
Piperacillin is an antipseudomonal pencillin. (p-p)

USMLE Case Scenario

A 5-year-old child with cystic fibrosis presents with chronic productive cough. On physical exam, he is febrile and lung exam
reveals intercostal retractions, wheezing, rhonchi, and rales. Chest X-ray demonstrates patchy infiltrates and atelectasis and
Grams stain of the sputum reveals slightly curved, motile gram-negative rods that grow aerobically. The microorganism
responsible for this childs pneumonia is also the most common cause of which of the following diseases?
1. Pseudomonas
2. E coli
3. Proteus
4. Klebsiella
Ans. 1. Pseudomonas

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USMLE Case Scenario

A 85-year-old man with a history of diabetes presents with left ear pain and drainage of pus from the ear canal. He has swelling
and tenderness over the left mastoid bone. Most likely organism is:
1. E coli
2. Proteus
3. Klebsiella
4. Pseudomonas
Ans. 4. Pseudomonas

USMLE Case Scenario

A 23-year-old engineer was involved in a serious accident and received second- and third-degree burns over his body. He was
placed in the burn unit and, on his twelfth day of his admission, developed a wound infection with a bluish-green exudate.
A gram-negative, motile organism was isolated that was oxidase-positive, did not ferment lactose, sucrose, or glucose, but
grew on MacConkeys agar and produced a fruity aroma on that medium. Which of the following organisms was most likely
isolated?
1. Pseudomonas
2. E coli
3. Proteus
4. Klebsiella
Ans. 1. Pseudomonas

USMLE Case Scenario

A 70-year-old diabetic patient presents with an unresolved skin lesion on his foot. The lesion began several weeks ago as a
blister and has since become a painful, erosive, expanding sore 6 cm in diameter, with a black necrotic center and raised red
edges. Most likely diagnosis is Ecthyma Gangrenosum. Disease is caused by:
1. E coli
2. Proteus
3. Klebsiella
4. Pseudomonas
Ans. 4. Pseudomonas

USMLE Case Scenario

A 2-year-old boy with an indwelling urinary catheter in place develops a urinary tract infection. Urine culture grows out a
lactose-negative, oxidase-positive, gram-negative rod. Which of the following agents is the most likely cause of this boys
urinary tract infection?
1. Escherichia coli
2. Klebsiella pneumonia
3. E Proteus mirabilis
4. Pseudomonas aeruginosa
Ans. 4. Pseudomonas aeruginosa
Pseudomonas aerugenosa causes:
Serious infections in burn patients
Shock with bullous lesions
Ecthyma gangrenosum
Shanghai fever
Hot tub folliculitis
Multi drug resistance is due to biofilm production in cornea

268

USMLE Step 1 Platinum Notes

Pseudomonas pseudomallei
Causes Meliodosis
Also called Whitmores bacillus
Great imitator disease
Pseudomonas Mallei
Causes glanders

Gems about Yersinia

Plague is an acute, febrile, zoonotic disease caused by infection with Yersinia pestis
Y pestis is a gram-negative coccobacillus in the family Enterobacteriaceae
It is microaerophilic, nonmotile, nonsporulating, oxidase and urease negative and biochemically unreactive
Bipolar staining
Safety pin appearance
Waysons staining done for identification
Stalactite growth
The organism is nonfastidious and infective for laboratory rodents. It grows well, if slowly, on routinely used microbiologic
media (e.g. sheep blood agar, brain-heart infusion broth and MacConkey agar)
The colonies are gray-white with irregular surfaces, described as having a hammered-metal appearance when viewed
microscopically
When stained with a polychromatic stain (e.g. Wayson or Giemsa), Y. pestis isolated from clinical specimens exhibits a characteristic
bipolar appearance, often resembling closed safety pins
Bubonic plague, the most common form
It is almost always caused by the bite of an infected flea but occasionally results from direct inoculation of infectious fluids
Septicemic and pneumonic plague can be either primary or secondary to metastatic spread
Because fleas often bite the legs, femoral and inguinal nodes are most commonly involved; axillary and cervical nodes are next
most commonly affected. The enlarging bubo becomes progressively painful and tender
The bubo of plague is distinguishable from lymphadenitis of most other causes, however, by its rapid onset, its extreme
tenderness, the accompanying signs of toxemia, and the absence of cellulitis or obvious ascending lymphangitis
Pneumonic plague is most infectious. pneumonic plague develops most rapidly and is most frequently fatal
Streptomycin is the drug of choice
Tetracycline is the doc for prophylaxis

Erysipelothrix rhusiopathiae is a pleomorphic, gram-negative rod that causes a localized skin infection. It is an occupational disease of
fishermen, fish handlers, butchers, meat-processing workers, poultry workers, farmers, veterinarians, abattoir workers, and housewives.

USMLE Case Scenario

A 44-year-old man from rural America is brought to a rural hospital with severe bronchopneumonia. He suffered sudden
onset of chills, fever and headache several days ago. Two-day later, he complained of chest pain and difficulty breathing and
coughed up blood-tinged sputum. Chest X-ray reveals patchy infiltrates and segmental consolidation. Which of the following
organisms is the most likely cause of this mans pneumonia?
1. Clostridium perfringens
2. Francisella tularensis
3. Listeria monocytogenes
4. Yersinia pestis
Ans. 4. Yersinia pestis

Gems about Hemophilus

Gram-negative cocco bacillus
Grows on chocolate agar
Capsulated

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269

Requires factor X and V

Satellitism is seen Chancroid is caused by H ducreyi
Shows school of fish appearance

USMLE Case Scenario

A 3-year-old boy from rural America is brought to the ENT emergency room in extreme respiratory distress, with a temperature
of 104 degrees Fahrenheit. He is drooling and has great difficulty swallowing, and on physical examination, an inspiratory
stridor is noted. An immediate lateral X-ray done shows swelling of the epiglottis. He has had no previous vaccinations. Which
of the following agents is the most likely cause of these symptoms?
1. Klebsiella pneumoniae
2. Hemophilus influenzae
3. Legionella pneumophila
4. Streptococcus
Ans. 2. Hemophilus influenzae

Gems about Bordetella

Gram-negative cocco bacillus

Capsulated
Bordet gengou media used
Causes whooping cough
Incubation period 12 weeks
Thumb printing appearance in culture films
Erythromycin prevents spread of disease in children

USMLE Case Scenario

A seven-week-old infant is brought to the emergency room with a 10-day history of coughing and choking spells. The white
blood cell count is elevated with 85% lymphocytes. The child is gasping for breath, experiencing paroxysms of coughing, and
vomits twice in the examination room. Encapsulated, gram-negative rods grow out on Bordet-Gengou media. Which of the
following microorganisms is the likely cause of these symptoms?
1. Hemophilus influenzae type b
2. Bordetella pertussis
3. Klebsiella pneumonia
4. Legionella pneumophila
Ans. 2. Bordetella pertussis

Gems about Brucellosis

It is a zoonosis
Malta fever/undulant fever/meditarrean fever
Gram-negative
Noncapsulated
Nonmotile
Nonsporing
No personperson transmission

Causative Organisms

B militensis from goat, sheep, cattle (most common)

B abortus from cattle
B suis from hogs
B canis from dogs

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USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 55-year-old veterinarian presents with a 2-month history of malaise, chills, sweats, fatigue, and weakness. He has anorexia
and has lost 5 kgs. He has intermittent fevers. A physical examination reveals mild lymphadenopathy, petechiae. What is the
most likely gram-negative etiologic agent?
1. Pseudomonas
2. Brucella
3. Vibrio
4. Klebsiella
Ans. 2. Brucella
Brucella survive in unpasteurized milk for up to 8 weeks
Brucella is transmitted most commonly through UN pasteurized milk/milk products, raw meat and bone marrow
It can also be contracted through inhalation in farm houses, slaughter houses, labs. Other routes are skin abrasion, inoculation,
conjunctival splashing
The common symptoms are fever, chills, diaphoresis, headache, myalgias, fatigue
Patient can look deceptively well with just fever
In severe cases Hepatosplenomegaly, Lymphadenopathy, arthritis, meningitis or pneumonia can occur
Rose Bengal Card test used
Milk Ring test used
Diagnosis is by culture, Phage typing, DNA Characteristics, Metabolic profiling (BACTEC)
Treatment is by combination therapy of aminoglycoside plus doxycycline for 4 weeks followed by doxycycline plus rifampin
for 4-8 weeks
In pregnancy TMP-SMZ plus rifampin for 812 weeks is given.

Gems about Mycobacterium Tuberculosis

Mycobacterium tuberculosis complex (consisting of M. tuberculosis, M. bovis, and M. africanum)

USMLE Case Scenario

Achronic meningoencephalitis, with a prolonged clinical course. Characterized pathologically by a dense granulomatous
infiltrate of the base of the brain with increased lymphocytes and slightly decreased glucose is usually caused by:
1. Mycobacterium tuberculosis
2. Neisseria meningococcus
3. Listeria
4. Bordetella
Ans. 1. Mycobacterium tuberculosis

USMLE Case Scenario

Which of the following microorganisms is an obligate aerobe?
1. Bacteroides fragilis
2. Clostridium perfringens
3. Escherichia coli
4. Mycobacterium tuberculosis
Ans. 4. Mycobacterium tuberculosis

Discovered by Robert Koch

Obligate aerobe
Acid fast
Acid fastness is due to mycolic acid and cell wall
Slightly curved rod

Microbiology

LJ Medium (Lowenstein Jonson Medium) used

Usually affects apical and posterior segments of upper lobes
Lung is the mc organ involved
Tubercular lymphadenitis is the mc extra pulmonary TB
Rapid diagnosis is by Auramine Rhodamine stain
Production of niacin is an important feature
Cord factor promotes virulence
Mycobacteium Para tuberculosis is Johnes bacillus

Caseation necrosis

Atypical Mycobacteria
Photochromogen: M kanasi
Scotochromogen: M scofulaceum
Nonchromogen: MAI
Rapid grower: M smegmatis
Buruli ulcer is caused by: M ulcerans
Swimming pool granuloma/Fish tank granuloma is caused by M marinum

Gems about M. Leprae

Gram-positive
Generation time 12 days
Acid fast bacilli. Less acid fast than M tuberculosis
Globi and cigar bundle appearance are a feature
Cultivated in Armadillo
Can be grown in foot pad of mice
Spreads by skinskin contact
Lepra cells are histiocytes

Treponema Pallidium

Causes syphilis
Gram-negative spirochete with polar flagellum
Has hylauronidase
Incubation period 9-90 days

271

272

USMLE Step 1 Platinum Notes

Primary lesion is a chancre. Painless ulcer with nontender inguinal lymphadenopathy

Condyloma lata is seen in secondary syphilis
Dark ground microscopy is used for diagnosis.104 organisms/ml are needed to be detected
Leviditti stain is used for staining
FTAABS is a specific test
VDRL is a slide flocculation test
VDRL is positive in secondary syphilis

USMLE Case Scenario

A 44-year old from New Orleans is referred to a neurologist because of ataxia. Neurological examination reveals a loss of
Proprioception and a wide-based, slapping gate. MRI reveals degeneration of the dorsal columns and dorsal roots of the
spinal cord. Organism implicated is most likely:
1. Mycobacterium leprae
2. Mycobacterium tuberculosis
3. Treponema pallidium
4. Klebsiella
Ans. 3. Treponema pallidium

USMLE Case Scenario

Aspirochete is causing a (a painless, indurated ulcer) at the site of inoculation. Most likely organism is:
1. Chlamydia
2. Mycoplasma
3. Mycobacteria
4. Treponema Pallidium
Ans. 4. Treponema Pallidium

USMLE Case scenario

An organism identified on dark ground microscopy caused testicular involvement with gumma formation, endarteritis, and/
or a prominent plasma cell infiltrate. Most likely organism is:
1. Chlamydia
2. Mycoplasma
3. Mycobacteria
4. Treponema Pallidium
Ans. 4. Treponema Pallidium

Borellia
Borrelia burgdorferi Causes Lymes disease. (erythema migrans)
Borrelia recurrentis causes relapsing fever
Kellys medium used
Lymes Disease:
Causative agent: B. burgdorferi
Vector: Ixodes tick
Features:
STAGE I: Localized disease, IP: 332 days, Erythema migrans at local site
STAGE II: Disseminated disease, Secondary skin lesions, meningitis, carditis
STAGE III: Oligoarticular arthritis, Encephalopathy, Polyneuropathy. Acrodermatitis atrophicans

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273

USMLE Case Scenario

A 44-year-old woman vacationing in US is bitten by a tick. She does not seek medical treatment and eventually develops
chronic arthritis of the knee and hip joints and paralysis of the left facial muscles. Most likely disease is:
1. Erythema migrans caused by Borrelia burgdorferi
2. Erythema migrans caused by Borrelia recurrentis
3. Erythema nodosum caused by virus
4. Erythema abigne
Ans. 1. Erythema migrans caused by Borrelia burgdorferi
Erythema chronicum migrans is usually the first sign of the illness. This is a large red patch on the buttocks or chest that slowly
expands as the center blanches. Generally, patients also have constitutional symptoms, such as fever and chills + Stiff neck
may develop, along with other signs of meningeal irritation, because of an aseptic meningitis. +Bells palsy due to involvement
of branches of the facial nerve. + Arthritis + Cardiac abnormalities in Lyme disease include pericarditis and heart block.

Leptospirosis

Spirochetal infection
Rats, rice and rain associations
Transmitted by rat urine
Seen in sewage workers
Acute renal failure and jaundice is a feature
Leptospira icterohemorrhagica causes Weils disease
Weils syndrome, the most severe form of leptospirosis, is characterized by jaundice, renal dysfunction, hemorrhagic diathesis,
and high mortality. This syndrome is frequently but not exclusively associated with infection due to icterohemorrhagiae/
copenhageni.

USMLE Case Scenario

A 39-year-old American farmer develops fever with chills, myalgias, headache, skin rash, and vomiting. He is quite ill and
is hospitalized. Blood cultures demonstrate tightly coiled, thin, flexible spirochetes. The spirochetes are easily cultured in
serum-enriched nutrient agar. Which of the following organisms should be suspected:
1. Brucella
2. Treponema
3. Leptospira
4. Pseudomonas mallei
Ans. 3. Leptospira

USMLE Case Scenario

An Spirochetal infection is caused by contact with urine from infected animals such as rats. The disease is characterized
by abrupt-onset headache (98%), fever, chills, conjunctivitis, severe muscle aches, gastrointestinal symptoms, changes in
sensorium, rash, and hypotension. This phase lasts from 3 to 7 days. Meningeal symptoms hepatic dysfunction and renal
failure develops is later.
1. Brucella
2. Treponema
3. Leptospira
4. Pseudomonas mallei
Ans. 3. Leptospira

Gems about Mycoplasma

Eaton agent
The smallest free-living organisms known
Are prokaryotes that are bounded only by a plasma membrane

274

USMLE Step 1 Platinum Notes

Their lack of a cell wall is associated with cellular pleomorphism and resistance to cell wall-active antimicrobial agents, such as
penicillins and cephalosporins
Fried egg colonies
L forms seen. (Concept has changed now)
Mycoplasma pneumoniae causes primary atypical pneumonia, upper and lower respiratory tract infections
M genitalium and Ureaplasma urealyticum are established causes of urethritis and have been implicated in other genital
conditions
M hominis and U. urealyticum are part of the complex microbial flora of bacterial vaginosis
Mycoplasma Pneumoniae
M pneumoniae causes upper and lower respiratory tract symptoms
The infection is acquired by inhalation of aerosols

USMLE Case Scenario

A 22-year-old college student from Ohiopresents to the chest clinic complaining of weakness, malaise, and a chronic cough.
He has a fever of 100 degrees F and a dry cough; no sputum can be obtained for laboratory analysis, so a bronchial lavage
is performed and the washings are submitted to the laboratory. The laboratory reports that the organism is slow-growing.
Serodiagnosis reveal sagglutinins in the patients serum. Which of the following organisms is the most likely cause of this
students illness?
1. Mycoplasma pneumonia
2. Mycobacterium tuberculosis
3. Treponema pallidium
4. Chlamydia
Ans. 1. Mycoplasma pneumonia

USMLE Case Scenario

Certain organisms are found by a pasthologist in Main Hospital New York to be susceptible to the macrolide family of antibiotics
(erythromycin). These organisms lack a cell wall, hence they are indifferent to antibiotics that interfere with peptidoglycan
synthesis, such as penicillin. The organisms are most likely:
1. Mycobacteria
2. Mycoplasma
3. Treponema
4. Leptospira
Ans. 2. Mycoplasma

Actinomyces

Gram-positive
Nonmotile
Nonsporing
Nonacid fast
Noncapsulated
Mc form cervico facial
Lumpy jaw is a feature

Growth of actinomycetes usually results in the formation of clumps called grains or sulfur granules
Oral-Cervicofacial Disease
Actinomycosis occurs most frequently at an oral, cervical, or facial site, usually as a soft tissue swelling, abscess, or mass lesion that
is often mistaken for a neoplasm
The angle of the jaw is generally involved.

Microbiology

275

USMLE Case Scenario

Pathologist in New Orleans Pathology clinic finds Organisms to be normal inhabitants of the gastrointestinal tract that grow
under anaerobic and microaerophilic conditions. They are gram-positive rods; they grow as branching filaments and have
been confused with fungi. The yellow colonies are found in abscesses. Most Likely organism is:
1. Actinomyce
2. Anthrax
3. Aspergillus
4. Blastomyce
Ans. 1. Actinomyce

Nocardia

Strict aerobe
Acid fast
Causes Nocardiosis
Paraffin bait is used for isolation
Soil is natural habitat
Pneumonia is the mc manifestation

Listeria Monocytogenes
It is a gram-positive cocobacillus in short chains
That can be isolated from soil, vegetation and many animal reservoirs
Shows tumbling motility
Survives and multiplies in phagocytes
Human disease due to L monocytogenes generally occurs in the setting of pregnancy or of immunosuppression caused by illness
or medication
Antons test used

L monocytogenes grows well in cold temperatures

L monocytogenes causes meningitis and sepsis in neonates
L monocytogenes causes meningitis and sepsis in immunocompromised patients
L monocytogenes during pregnancy can cause abortion, premature delivery or sepsis during postpartum period.

Campylobacter: (USMLE Favorite)

Are motile
Nonspore-forming, curved gram-negative rods
Microaerophilic
The principal diarrheal pathogen is c. jejuni, which accounts for 80 to 90% of all cases of recognized illness due to campylobacters
Skirrows medium is culture medium
Butzlers medium is culture medium

H pylori: (USMLE Favorite)

It is a gram-negative, spiral, flagellate bacillus

It is noninvasive, living in gastric mucus; a small proportion of the bacterial cells are adherent to the mucosa
Its spiral shape and flagellae render H pylori motile in the mucous environment
Its efficient urease protects it against acid by catalyzing urea hydrolysis to produce buffering ammonia
In vitro, H pylori is microaerophilic and slow-growing and requires complex growth media

276

USMLE Step 1 Platinum Notes

Complete genomic sequence has been studied

Causes duodenal ulcers (stronger relation)
Causes gastric ulcers
Prevalence increases with age
Transmitted from man-man, fecal orally and orogastric route

Urease Positive Organisms

S aureus
Proteus
H pylori
Klebsiella
Cryptococcus
Nocardia
Diphtheroids
Yersinia pseudotuberculosis
Yersinia enterocolitica

USMLE Case Scenario

A 32-year-old pregnant woman develops a severe flu-like illness with fever, headache, myalgia, and backpain. As a
complication she has a spontaneous abortion. Examination of the abortus demonstrates severe amnionitis. Which of the
following organisms with tumbling motility would most likely be isolated from the placental membranes?
1. Borrelia burgdorferi
2. Leptospira interrogans
3. Listeria monocytogenes
4. Group B streptococcus
Ans. 3. Listeria monocytogenes

USMLE Case Scenario

An actinomycete causes a chronic lobar pneumonia that may metastasize to the brain. It is more common in the
immunocompromised. It is found in soil and aquatic environments. Organism is:
1. H pylori
2. Nocardia
3. Leptospira
4. Blastomyce
Ans. 2. Nocardia

USMLE Case Scenario

A Gram-positive coco bacillus is causing Infection during pregnancy that may result in sepsis, abortion or premature delivery.
Infection in the neonate may produce meningitis. In immunocompromised adults, either meningitis or sepsis may occur. The
organism is:
1. H pylori
2. Legionella
3. Leptospira
4. Listeria
Ans. 4. Listeria

USMLE Case Scenario

An organism is foud to be gram-negative, spiral, flagellate bacillus with microaerophilic character. Among the choices
mentioned below the most likely organism is:
1. H pylori
2. Legionella

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277

3. Leptospira
4. Listeria
Ans. 1. H pylori

Legionellosis

Weakly gram-negative bacillus

Motile, nonencapsulated
Pleomorhic rods requiring Cysteine and Iron
Aerosols from natural reservoirs are the most common source of infection
No man to man transmission occurs
No animal reservoir occurs
Disease is limited to humans
Lungs are primarily effected
Legionellosis is an infectious disease caused by bacteria belonging to the genus Legionella
Over 90% of legionellosis cases are caused by Legionella pneumophila, a ubiquitous aquatic organism that thrives in warm
environments (25 to 45C F)

Legionellosis Takes Two Distinct Forms

Legionnaires disease, also known as Legion Fever (archaic), is the more severe form of the infection and produces pneumonia
Pontiac fever is caused by the same bacterium, but produces a milder respiratory illness without pneumonia which resembles
acute influenza
The time between the patients exposure to the bacterium and the onset of illness for Legionnaires disease is 2 to 10 days;
For Pontiac fever, it is shorter, generally a few hours to 2 days
Grown on BYCE medium (Bufferred Charcoal Yeast Extract)

USMLE Case Scenario

A pathologist reports mild walking pneumonia-like condition. The organism is motile, encapsulated and can be cultured
on a charcoal yeast extract medium, but identification is usually accomplished by immunofluorescent examination of the
pulmonary specimen. Most likely cause is:
1. Legionella
2. Leptospira
3. Listeria
4. Chlamydia
Ans. 1. Legionella

Remember: (USMLE Favorite)

Meleneys gangrene: Anaerobic bacterial synergistic gangrene is characterized by exquisite pain, redness, and swelling
followed by induration. These infections usually involve a combination of Peptostreptococcus spp. and S. aureus; the usual site
of infection is an abdominal surgical wound or the area surrounding an ulcer on an extremity
Necrotizing fasciitis, a rapidly spreading destructive disease of the fascia, is usually attributed to group A streptococci but
can also be caused by anaerobic bacteria, including Peptostreptococcus and Bacteroides spp. Gas maybe found in the tissues
Fourniers gangrene consists of cellulitis involving the scrotum, perineum, and anterior abdominal wall, with mixed anaerobic
organisms spreading along deep external fascial planes and causing extensive loss of skin.
Neutropenic enterocolitis (typhlitis) has been associated with anaerobic infection of the cecum but in the setting of
neutropenia may involve the entire bowel. The primary pathogen is thought by some authorities to be C. septicum, but other
clostridia and mixed anaerobic infections have also been implicated
Brain abscesses are frequently associated with anaerobic bacteria If optimal bacteriologic techniques are employed, as many as
85% of brain abscesses yield anaerobic bacteria most often anaerobic gram-positive cocci (especially peptostreptococci),
which are followed in frequency by Fusobacterium and Bacteroides spp.

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USMLE Step 1 Platinum Notes

Enterococci: (USMLE High Yield Facts)

Lancefield group D includes the enterococci
Enterococci are distinguished from nonenterococcal group D streptococci by their ability to grow in the presence of 6.5%
sodium chloride
Significant pathogens for humans are E faecalis and E faecium
These organisms tend to produce infection in patients who are elderly or debilitated or in whom mucosal or epithelial barriers have
been disrupted or the balance of the normal flora altered by antibiotic treatment
Urinary tract infections due to enterococci are quite common, particularly among patients who have received antibiotic
treatment or undergone instrumentation of the urinary tract
Enterococci are a frequent cause of nosocomial bacteremia in patients with intravascular catheters
These organisms account for 10 to 20% of cases of bacterial endocarditis on both native and prosthetic valves
Enterococci are frequently cultured from bile and are involved in infectious complications of biliary surgery and in liver abscesses
Moreover, enterococci are often isolated from polymicrobial infections arising from the bowel flora (e.g. intraabdominal
abscesses), from abdominal surgical wounds, and from diabetic foot ulcers.

Anaerobic Infections
Nonsporing anaerobic bacteria are:
Bacteroids fragilis
Fusobacterium
Peptostreptococcus
Actinomyces israelli

USMLE Case Scenario

A 36-year-old female in New Jersy is diagnosed with subacute bacterial endocarditis after urologic instrumentation. Organisms
causing the same are gamma-hemolytic, gram-positive cocci that grow on bile-esculin agar. Most likely organisms are:
1. Streptococci
2. Staphylococci
3. Enterococci
4. Meningococci
Ans. 3. Enterococci

Rickettsial Diseases

Rickettesia are obligate intracellular parasites

Rickettesia divide by binary fission
Rickettesial diseases are transmitted by bites of arthropods
Typical lesion is vasculitis and these organisms effect endothelial lining of vessel walls
Lab diagnosis is based on serology rather than isolation of organisms.

Rocky mountain spotted fever: The most severe of the rickettsial diseases, is caused by Rickettsia rickettsii
Mediterranean spotted fever (boutonneuse fever) and other spotted fevers: The etiologic agent of mediterranean spotted
fever, R conorii
Rickettsial pox: caused by R akari
Endemic murine typhus (flea-borne) caused by R typhi
Epidemic typhus (louse-borne): Due to infection with R prowazekii is transmitted by the human body louse (pediculus humanus
corporis), which lives on clothes and is found in poor hygienic conditions (especially in jails, where the disease it causes is called
jail fever) and usually in cold areas
Brill-zinsser disease is a recrudescent, mild form of epidemic typhus occurring years after the acute disease, probably as a result
of immunosuppression or old age.

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279

Scrub typhus caused by R tsutsugamushi

Ehrlichioses: Ehrlichiae are small, obligately intracellular bacteria with a gram-negative-type cell wall that grow in cytoplasmic
vacuoles to form clusters called morulae
Two distinct ehrlichia species cause human infections that can be severe and frequent
E chaffeensis, the agent of Human monocytotropic ehrlichiosis infects predominantly mononuclear phagocytic cells in tissues
and blood monocytes
A member of the E. phagocytophila group that infects cells of myeloid lineage is the agent of Human granulocytotropic
Ehrlichiosis
Q fever: Results from infection with C burnetii.

USMLE Case Scenario

A Disease is found to be due to reactivation of epidemic typhus infection caused by Rickettsia prowazekii. It can occur many
years after an infection that was not treated with antibiotics. The most likely disease is:
1. Human granulocytotropic Ehrlichiosis
2. Epidemic typhus
3. Brill-Zinsser disease
4. Endemic typhus
Ans. 3. Brill-Zinsser disease

USMLE Case Scenario

Organism most likely to be implicated as a cause of urethritis that persists after antibiotic therapy for gonorrhea:
1. Chlamydia
2. Rickettsia
3. Mycoplasma
4. Mycobacteria
Ans. 1. Chlamydia

USMLE Case Scenario

An obligate intracellular parasite that induces endocytosis and resides in the phagosome of infected epithelial cell is:
1. Rickettsia
2. Mycoplasma
3. Mycobacteria
4. Chlamydia
Ans. 4. Chlamydia

Chlamydia

Are obligate intracellular bacteria

Gram-negative
They possess both DNA and RNA
Have a cell wall and ribosomes
Mc Coy and HeLa cells used for detection
Multiply by binary fission

Elementary body is metabolically inert. (Extracellular)

Reticulate body is active. (Intracellular)
IDENTIFIED BY Nucleic acid amplification test NAAT
Inclusion body in conjunctivitis: HP (Halberstaedter prowazek bodies)
Inclusion bodies in LGV: Miyagawa bodies
Inclusion bodies in Psittacosis: Levinthal Colles Lille bodies

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USMLE Step 1 Platinum Notes

Pecularities

Meta chromatic staining: Corynebacterium

Lancet shaped diplococcic: Pneumococci
Bean shaped diplococcic: Neisseria
Bipolar staining: Yersenia
Gulls wing: Campylobacter

Clinical scenarios: Most Likely Organism: (USMLE Favorite)

MC cause of lobar pneumoniae in elderly

Streptococcus pneumonia

lobar pneumonia with deep red (Currant jelly) sputum

Klebsiella pneumonia

Meningitis in neonate (Gram-positive organism)

Strep Agalactiae

Meningitis in neonate (Gram-negative organism)

E coli

Meningitis in neonate (Gram-positive Rod)

Listeria monocytogenes

Joint pains, skin petechiae, fever, in young female

Gonococcal arthritis

Patient on clindamycin complaining of diarrhea

Clostridium difficile

Abdominal pain, bloody diarrhea and flask shaped ulcers

Entameba histolitica

Important Culture Media

Thayer Martinmedia

Neisseria Gonorrhea

Chocolate agar with Factor X and V

H. influenza

Bordet Gengou

Bordetella Pertussis

Lownstein Johnson

Mycobacterium Tuberculosis

Charcoal Yeast Agar

Legionella

USMLE Case Scenario

A 4-week-old infant is brought with a 6-day history of coughing and choking spells. The white blood cell count is elevated with
92 % lymphocytes. The child is gasping for breath, experiencing paroxysms of coughing. Encapsulated; gram-negative rods
grow out on Bordet-Gengou media. Which microorganism is the likely cause of these symptoms?
1. Borellia
2. Legionella
3. Bordetella pertussis
4. Listeria
Ans. 3. Bordetella pertusis

Eponyms: USMLE
Eponyms
Whitmoores bacillus

Pseudomonas pseudomallei

Eaton agent

Mycoplasma

Johnes bacillus

Mycobacterium paratuberculosis

Batteys bacillus

Mycobacterium intercellulare

Freidlanders bacillus

Klebsiella Pneumoniae

Koch weeks bacillus

Hemophilus aegipticus

Nocard bacillus

Cornyebacterium Pseudotuberculosis

Microbiology

Tests for Organisms

Ascolis thermoprecipitation test

Anthrax, Plague

Xeno Diagnosis

Rickettsia

Naeglers reaction (is due to Lecithinase)

Clostrida

Green fluorescent on media with neutral red

CL Tetani

Cholera Red reaction indole formation and

Nitrates to Nitrites

Cholera

Strauss reaction

Pseudomonas Mallei

Neil Mooser reaction (Tunica reaction)

Rickettsia Mooseri

Satellitism

H Influenza
Diphtheria
Diphtheria
Diphtheria

a. Chinese letter pattern

b. Eleks test
c. Schick test
Dick test

Streptococci/pneumococci

Schultz- charlton reaction

Streptococci

MFadyeans reaction

B Anthrax

Stormy reaction in Culture

Cl Welchii

Milk Ring test (Rose Bengal Card test)

Brucellosis

Von- Pirquet test

Tuberculosis

Kochs phenomenon

Tuberculosis

Francis test (Dick test)

Pneumococci/streptococci

String Test

V Cholerae

Typical Appearances: (USMLE Favorite)

School of fish

Hemophilus ducreyi

Satellitism

Hemophilus influenza

Fried egg colony

Mycoplasma

Draughtsman colony

Pneumococcus

Swarming growth

Proteus

Oil paint appearance

Staph

Different Motilities: (USMLE Favorite)

Darting motility

Cholera

Swarming motility

Proteus

Spinning motility

Fusobacterium

Tumbling motility

Listeria

Diagnosis of Urethritis and Causative Organism

Gram-negative diplococcic in PMNs in urethral Exudate:

Culture negative specimen with inclusion bodies:
Organisms without cell wall and urease positive:
Flagellate protozoa with motility:

Neisseria gonorrhea
Chlamydiae trachomatis
Ureaplasma Urealyticum
Trichomonas vaginalis

281

282

USMLE Step 1 Platinum Notes

Vaginal Discharge
Yellow, pH>5, clue cells, amine odor
Cottage cheese discharge, pruritis, Vulvovaginitis
Frothy, Foamy discharge and motile trophozites seen

Vaginosis
Candida
Trichomonas vaginalis

USMLE Case Scenario

A Pap smear from a 33-year-old woman demonstrates protozoal parasites. These organisms are likely to be:
1. Treponema
2. Trichomonas vaginalis
3. Vaginosis
4. Candida
Ans. 2. Trichomonas vaginalis

USMLE Case Scenario

A 33-year-old female has Sexually transmitted disease. Pear-shaped flagellated protozoal infection characterized by a
malodorous, cheesy exudate and erythema of the external genitalia is caused by:
1. Treponema
2. Trichomonas vaginalis
3. Bacterial vaginosis
4. Candida
Ans. 2. Trichomonas vaginalis

USMLE Case Scenario

Chagas disease is an important cause of cardiac failure in some Latin American countries, and Brazilian cases can be associated
with megaesophagus and megacolon. The disease is Chagas disease, which is caused by:
1. Bacteria
2. Mycoplasma
3. protozoa
4. Virus
Ans. 3. Protozoa

Virology

Viruses: Smallest infectious agent containing only one kind of nucleic acid as their genome
Virion: Extracellular infectious particle
Largest virus: Poxvirus (300 nm)
Smallest Virus: Foot and Mouth Disease Virus (20 nm)
Capsid is a protein coat surrounding nucleic acids
Capsid+nucleic acid is Nucleocapsid

Features of Virus: (USMLE Favorite)

Ribosomes absent
Mitochondria absent
Motility absent
Nucleus absent But Nucleic acid Either DNA or RNA Present. That is why some viruses are DNA Viruses and others are RNA Viruses.
(Common Sense)

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Virusoids are nucleic acids that depend on helper viruses to package the nucleic acids into virus-like particles
Viroids are simply molecules of naked, cyclical, mostly double-stranded, small RNAs and appear to be restricted to plants, in
which they spread from cell to cell and are replicated by cellular RNA polymerase II
Prions are protein molecules that can spread from cell to cell and effect changes in the structure of their normal counterparts
(cellular proteins). Prions have been implicated in neurodegenerative conditions such as Creutzfeldt-Jakob disease, Kuru, and
Gerstmann-Straussler disease. Prions have also been implicated in neurodegeneration associated with human infection with
bovine spongiform encephalopathy (mad cow disease).

Classification of Viruses
Nucleic Acid

DNA

Nucleic Acid

RNA

Capsid Symmetry

Enveloped/Naked

Family

Type of Strand

Icosahedral
Icosahedral
Icosahedral
Icosahedral
Complex

Naked
Naked
Naked
Enveloped
Complex
Coat

Parvoviridae
Papovaviridae
Adenoviridae
Herpes viridae
Pox
Hepadna

Positive strand

Capsid Symmetry

Enveloped/Naked

Family

Type of Strand

Icosahedral
Icosahedral
Icosahedral
Icosahedral

Naked
Naked
Naked
Enveloped

Picorna
Calci
Reo
Toga

Positive strand

Unknown or Complex
Unknown or Complex
Unknown or Complex
Unknown or Complex

Enveloped
Enveloped
Enveloped
Enveloped

Flavi
Areana
Corona
Retro

Positive strand

Helical

Enveloped
Enveloped
Enveloped
Enveloped

Buny
Orthomyxo
Negative strand
Paramyxo
Rhabdo

Virus with smallest genome: Parvo virus

Virus with genome having double stranded nucleic acid: Poxvirus, Reo virus
Virus with Segmented RNA: Influenza virus
Virus with split genome: Rota virus

Human Slow Virus Infections: (USMLE Favorite)

Virus/agent

Disease

Measles

Subacute sclerosing panencephalitis

Papovavarus (JC Virus)

Progressive multifocal leucoencephalopathy

HIV encephalopathy

Rubella

Progressive rubella panencephalitis

Retrovirus

Acquired Immuno Defeciency Syndrome

Prion disease

Kuru
Creutzfeldt-Jakob disease

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USMLE Step 1 Platinum Notes

Poxviruses Causing Human Disease

Smallpox
Molluscumcontagiosum
Vaccina
Cow pox
Monkey pox
Buffalo pox
Orf

Herpesvirus Group Includes

HSV 1
HSV 2
Varicella zoster virus
EBV
CMV
RK Virus

Herpes Simplex Virus

Double stranded DNA virus
Orofacial infection mc caused by HSV 1
Genital infection mc caused by HSV 2
Causes:
Gingivostomatitis
Herpetic whitlow
Corneal infection
Esophagitis
Genital herpes
Herpetic gladiatorum
Meningitis/encephalitis (HSV 1). MC cause of sporiadiac viral encephalitis
Herpes virus 1 causes Herpes labialis
Herpes virus 2 causes Genital herpes.

Varicella Zoster Infection

Caused by VZV
Reactivates and can involve eye
Remains dormant in trigeminal ganglion
Causes herpes zoster
Post herpetic neuralgia
Infectivity lasts 6 days after onset of rash

EBV
Belongs to herpes group
Binds through CD 21receptor
Diseases caused by EBV:
Oral hairy leukoplakia
Chronic fatigue syndrome
Burkitts lymphoma

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Anaplastic nasopharyngeal carcinoma

Tonsillar carcinoma
Angioimmunoblastic lymphadenopathy
Angiocentric nasal NK/T cell immuneproliferative lesions
T cell lymphoma
Thymoma
Gastric carcinoma, and
CNS lymphoma from patients with no underlying immunodeficiency
Paul bunnel test is done in infectious mononucleosis

USMLE Case Scenario

A 22-year-old college student from New York complains of a sore throat and fever. He describes feeling tired for the past few
days and reports a loss of appetite. On examination; he has pharyngitis with cervical lymphadenopathy. Blood tests reveal
lymphocytosis and the presence of heterophil antibodies. The virus responsible is:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 1. EBV

USMLE Case Scenario

An African child develops massive unilateral enlargement of his lower face in the vicinity of the mandible. Biopsy demonstrates
sheets of medium-sized blast cells with admixed larger macrophages. This type of tumor has been associated with viral
infection:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 1. EBV

USMLE Case Scenario

Encephalitis typically affects the inferomedial temporal lobes and orbitofrontal gyri. Most likely Double stranded DNA virus
implicated is:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 2. HSV

USMLE Case Scenario

A viral organism was isolated from a painful blister on the lip of a girl. The agent was found to double-stranded, linear DNA
and was enveloped. Most likely causative organism is:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 2. HSV

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USMLE Step 1 Platinum Notes

CMV

MC congenital infections
Petechiae, hepatospleenomegaly, jaundice are the mc presenting features of congenital CMV infection
Cause of heterophile negative mononucleosis. (Kindly remember). Different from infectious mononucleosis
Fifty percent of renal transplant patients with fever 14 months after transplant have CMV infection.

USMLE Case scenario

Cytomegalovirus produces neonatal infections and infections in immunocompromised patients such as AIDS patients. CD4 counts are
usually <100 cells/mm3. The most common clinical presentation is chorioretinitis producing floaters, +visual field deficits+painless loss
of vision. CMV also produces encephalitis and may produce calcifying lesions in the CNS.

USMLE Case scenario

A 29-year-old was given a renal graft after a month of hemodialysis for end-stage renal failure. Later given immunosuppressive
therapy and presented one month after with general malaise, muscle aches and IgM anti-CMV antibodies were detected
in a current serum sample accompanied by a positive PCR signal for CMV antigen. These findings indicated primary CMV
infection in the recipient due to transplantation of a CMV-positive kidney into a CMV-negative recipient. He made a complete
recovery following prompt treatment with a combination of ganciclovir (a CMV-specific drug) and CMV-specific immune
globulin.

USMLE Case Scenario

Intranuclear owls eye inclusion bodies causing, a common STD in the United States manifested by mononucleosis-likes
symptoms. Most likely organism is:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 3. CMV

Adenovirus
Nonenveloped DNA virus
Mc manifestation is URTI in children
Mc manifestation is RDS in adults
Causes:
Diarrhea
Hemorrhagic cystitis
Epidemic keratoconjunctivitis

Picarnovirus

Poliovirus
Coxsackie A
Coxsackie B
Echovirus
Enterovirus
Hepatitis A virus
Rhinovirus

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Enterovirus 70 causes: Acute hemorrhagic conjunctivitis

Enterovirus 70 causes: Acute epidemic keratoconjunctivitis
Adenovirus causes: Epidemic keratoconjunctivitis
Herpesvirus causes: Acute keratoconjunctivitis

Coxsackievirus
Herpangina
It is most commonly seen in infants and children, though can occur in adults
The incubation period lies between 3 and 5 days and fecal infectivity may last for several weeks
Local examination of the mouth will usually reveal hyperemia of the pharynx and characteristic papulovesicular lesions,
approximately 12 mm in diameter and surrounded by an erythematous ring
Most commonly the lesions are present over the tonsillar pillars, soft palate and uvula though on occasion the tongue maybe
involved
Aseptic Meningitis
It is the most common clinical manifestation and may result from infection by several different Coxsackie A virus strains
Coxsackievirus A7 is the most frequently implicated but other strains such as A9 have also been involved
Severe and fatal encephalitis has been described in only a small number of cases of Coxsackie A virus infection
Hand, foot and mouth disease (HFM)
Examination of the mouth often shows some mild ulceration over the tongue and further examination indicates the pearly
white vesicles, sometimes surrounded by a red halo, on the extremities
The lesions are mainly found over the ventral surface of the fingers and toes and have a characteristic distribution along the sides
of the feet. Some cases also show a maculopapular rash over the buttocks
Coxsackie A causes herpangina and hand-foot-and-mouth disease
Coxsackie B is seen in patients with pleurodynia, myocarditis, and pericarditis

Poliovirus
Poliovirus belongs to picarnoviradiae family and has icosahedral symmetry
Poliovirus is ether resistant
Poliovirus is a single stranded, positive sense, RNA Virus
Most common type is Type 1 Polio virus
Mc cause of epidemics: Type 1
Most difficult to eradicate: Type 1
Mc associated with paralysis: Type 1
Mc cause of vaccine induced paralysis: Type III
Most antigenic strain is Type 2
Most common manifestation is subclinical infection. (90%)
Descending assymetrical paralysis is the predominant sign
Proximal muscles are more involved than distal
No sensory loss
No autonomic disturbance
Inapparent infections mc feature transmitted by feco oral route
Spreads by both hematogeneous and neural route
Death in polio is mostly due to respiratory paralysis

Influenza Virus
Belongs to orthomyxovirus group
Enveloped RNA virus
Type A: Causes all pandemics and most epidemics

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USMLE Step 1 Platinum Notes

Type C: Causes endemics

Type B: Causes Reyes syndrome. (mc)
Hemaglutinin and Neuraminidase is strain specific
Antigenic variation seen as:
Antigenic drift (minor change) seen. Small mutations in H and N
Antigenic shift (major change) seen

The Bird Flu Virus: (USMLE Favorite)

H5N1 IS THE AVIAN FLUE INFLUENZA VIRUS ALSO CALLED AS THE BIRD FLU VIRUS.
H5N1 was previously believed to cause outbreak in birds only. (enzootic)
H5N1 is a highly pathogenic virus
Risk factor is handling of infected poultry
H stands for Hemaglutinin and N in H5N1 Stands for Neuraminidase
Virus can pass vertically from mother to fetus

Swine Flu

Occurred in Mexico in may 2009 with threat of a pandemic spreading as far as Newzeland, Australia, Asia, UK, etc
Caused by swine influenza virus (SIV)
SIV usually infects pigs
Undercooked pork is a common cause
When infection spreads to humans, it is called zoonotic flu
Clinical features: chills, fever, sore throat, headache, coughing weakness
SIV subtype: H1N1CAUSED 2009 OUTBREAK
This strain has human to human transmission
The US Centers for Disease Control and Prevention recommends the use of Tamiflu (oseltamivir) or (zanamivir) for the
treatment and/or prevention of infection with swine influenza viruses
However, the majority of people infected with the virus make a full recovery without requiring antiviral drugs
The virus isolates in the 2009 outbreak have been found resistant to amantadine and rimantadine

Measles
Paramyxovirus
Causes rubeola (measles)
Infective period 4 days before and 5 days after appearance of rash

Kopiloks spots+maculopapular rash a feature

Otitis media is the MC complication
Hechts pneumonia/primary giant cell pneumonia is seen in measles
SSPE is a late complication. (RARE)

Mumps

Paramyxovirus
Bilateral parotid enlargement seen
Orchitis is the MC complication in post pubertal males
Meningoencephalitis can precede parotitis
One attack gives life long immunity
Incubation period varies from 23 weeks
Pain and swelling of parotids (earache) is a feature

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Orchitis, ovaritis, pancreatitis, meningoencephalitis, throditis, neuritis, hepatitis and myocarditis are a feature
Mumps is leading cause of parotitis in children
Control of mumps is difficult because disease is infectious before a diagnosis is made.

Rubella
Toga virus
No carrier state
Cervical lymphadenopathy
Rubella can cause a congenital infection characterized by ocular problems (cataracts, retinopathy, microphthalmos, glaucoma),
cardiovascular problems, deafness, thrombocytopenic purpura, hepatosplenomegaly, CNS problems, and bony lesions
Congenital rubella causes: cataract+deafness+heat diseases.

Arboviruses: (USMLE Favorite)

Chikungunya

Japanese encephalitis
West nile
Yellow fever
Dengue
Kyanasaur forest disease
Sandfly fever
Rift valley fever
Hanta virus

alphavirus

flavivirus
flavivirus
flavivirus
flavivirus
flavivirus
bunyavirus
bunyavirus
bunyaviridae

Hantavirus

It is a RNA virus
Belongs to arbovirus
Causes hemorrhagic fever with nephritis
Causes hantavirus pulmonary syndrome

Rabies Virus
Rabies virus has negative polarity
Rhabdoviridae
Bullet shaped, neurotropic
Enveloped virus with ss RNA
It is Lyssavirus serotype 1
Inactivated by Phenol, UV radiation, Beta propiono lactone
Negri bodies are present inside nerve cells. Most characteristic finding in CNS is the formation of cytoplasmic inclusion bodies
called Negri Bodies (composed of fibrillary matrix and rabies virus particles) within neurons of ammons horn, Cerebral cortex,
Brainstem, Hypothalamus, Cerebellum and Dorsal spinal ganglia
Since first described by Negri in 1903, the Negri body has been regarded as a pathognomonic
Finding signifying the presence of rabies encephalitis. Negri bodies (light microscope) were found in the brain of a patient with
conclusive evidence in favor of the presence of rabies encephalitis
Brainstem encephalitis is a feature
Fluorescent stains are used for antemortem diagnosis.

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USMLE Step 1 Platinum Notes

Hepatitis A virus

It is a nonenveloped 27-nm, heat-, acid- and

Ether-resistant RNA virus
In the hepatovirus genus of the picornavirus family
Previously called enterovirus 72
No chronic course
Inactivated by boiling, formalin, uv radiation

Hepatitis B Virus: (USMLE Favorite)

It is a DNA virus
Hepadnavirus Contains DNA dependent DNA polymerase and RNA dependent reverse transcriptase
Reverse transcriptase is coded by P gene
Dane particle is HBV
HBV strain in India is Ayw, Adr
HBV has maximum perinatal transmission risk
Oncogenicity present in Hepatitis B especially after neonatal infection
Carrier state present in Hepatitis B
Hepatitis B virus may present in blood and other body fluids and excretions such as saliva, breast milk, semen, vaginal
secretions, urine, bile, etc.
Feces not known to be infectious
HBs Ag is the first viral marker to appear in blood after infection; it remains in circulation throughout icteric course of
disease. In a typical case it disappears within roughly 2 months but may last for 6 months
HBs Ag is not demonstrable in circulation but antibody, anti H-Be appear in serum a week or two after appearance of Hbs Ag
Anti-Hbe Ag is the antibody marker to be seen in blood
Serological marker of acute hep B is: HBs Ag + core antibody
Epidemological marker of Hep B is: core antibody
HBe Ag (HB envelop antigen) appears in blood concurrently with HBs Ag
Hbe Ag is an indicator of intrahepatic viral replication and its presence in blood
Indicates high infectivity
For diagnosis of HBV infection, simultaneous presence of IgM, HBC indicates recent infection
Presence of IgG; anti H-Be indicates remote infection
Hep B vaccine is cell fraction derived.

Other Hepatitis Viruses

Hepatitis C virus
Which, before its identification was labeled non-A, non-B hepatitis,
It is a linear, single-stranded, positive-sense, RNA virus; (Enveloped)
HCV belongs to family Flaviviridae
Mc cause of post transfusion hepatitis
Causes chronic hepatitis
Hepatitis D
The delta hepatitis agent, or HDV, is a defective RNA virus
Coinfects with and requires the helper function of HBV (or other hepadnaviruses) for its replication and expression
Resembles plant viruses
Hepatitis E
Previously labeled epidemic or enterically transmitted non-A, non-B hepatitis,
HEV is an enterically transmitted virus
It is a Calci virus
Mortality in pregnancy is a feature of Hep E virus

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291

Hepatic encephalopathy in pregnancy is seen

Fulminant hepatic failure can occur with Hep C in pregnancy
Hepatitis G
Also called GB virus
RNA virus
Blood borne virus
Resembles Hep C virus
Lamuvudine responsive
Spreads by fecal oral route -Hepatitis A and E
Spreads by percutaneous route -Hepatitis B, C and D
HTLV I cause adult T cell Leukemia/Lymphoma and Tropical spastic paraplegia. Other putative HTLV-I-related diseases In
areas where HTLV-I is endemic, diverse inflammatory and autoimmune diseases have been attributed to the virus, including
uveitis, dermatitis, pneumonitis, rheumatoid arthritis and polymyositis
HTLV II causes Hairy cell leukemia
HTLV III causes AIDS

USMLE Case Scenario

HTLV-1, or human T-cell lymphotrophic virus 1 can lead to T-cell leukemia 2030 years after the infection. The virus is:
1. A nonenveloped, single-stranded, RNA retrovirus
2. An enveloped, double-stranded, RNA retrovirus
3. An enveloped, single-stranded, DNA retrovirus
4. An enveloped, single-stranded, RNA retrovirus
Ans. 4. An enveloped, single-stranded, RNA retrovirus

USMLE FAVORITE
HIV virus

Positive sense, single stranded, RNA virus

Retro virus
Diploid
Attacks T helper cells and macrophages
Non segmented
Found in semen, saliva and blood

Contains two copies of ss (+) RNA, RNA dependent DNA Polymerase (Reverse Transcriptase), integrase and protease
Subtype A is most prevalent worldwide
Subtype C is most prevalent in India
Seroconversion takes 4 weeks

Heterosexual mode is the mc mode of transmission of HIV

Malefemale transmission >female-male
Accidential needle prick for health worker is 1%
RNA-DNA-RNA is the retroviral sequence in host celL
p 24 is used for early diagnosis
p 24 antigen disappears 68 weeks after HIV infection
CD 4 cells are attacked
CD 4: CD 8 ratio is reversed
Macrophages serve as reservoir of infection
Window period of AIDS: infection to appearance of antibodies in serum
Both ELISA and western blot are negative in window period.

292

USMLE Step 1 Platinum Notes

Cryptosporiodosis is the mc cause of diarrhea in AIDS

Oral ulcer in AIDS is commonly due to candida
MC cause of acute meningitis in AIDS: Cryptococcus
MC cause of tuberculosis in AIDS in tropical countries: Myc. Tuberculosis
Mc Cause of seizures in AIDS: Toxoplasmosis
Multifocal tumor of vascular origin in AIDS is: Kaposis sarcoma
MC opportunistic infection in AIDS in India is: Tuberculosis.

USMLE Case Scenario

Toxoplasmosis is a protozoan infection acquired by eating undercooked meat or by exposure to cat feces
Primary toxoplasmosis is usually asymptomatic. In patients with normal immunity, the organism can cause a heterophile-negative,
mononucleosis-like syndrome. In patients with AIDS, it causes ring-enhanced focal brain lesions and pneumonia.

STRUCTURAL GENES OF HIV VIRUS

HIV virus
Antigens
p 24
p 7p
p17

Proteins
Capsid protein
Core nucleocapsid protein
Matrix protein

Gag

Pol

Reverse transcriptase
Integrase
Protease

Produces ds DNA pro virus

Produces ds DNA integration into host DNA
Cleaves poly protein

Envelop

gp 120
gp 41

Surface protein that binds to CD4 on host cell

Transmembrane protein for cell fusion

Regulatory genes of HIV Virus

Tat: Transactivator protein: Activator of transcription
Rev: Regulator Protein: Regulator of transport of RNA to cytoplasm
Nef: Negative factor: Decrease MHC on infected T cells

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Negative sense RNA Viruses

Parainfluenza virus

Croup, common cold, bronchitis

Mumps

Parotitis, pancreatitis, orchitis, memingoencephalitis

Measles

RSV

Bronchiolitis and pneumonia in infants

Rabies virus

Bites of rabid dogs

Negri Bodies
Bullet shaped from Rhabdo viridae

Marburg virus

Acute Hemmorrhagic fever

Ebolavirus

Acute Hemorrhagic fever

Influenza virus

Lassa Fever virus

Hemorrhagic fever in Africa

Rubeola
Cough, coryza, conjunctivitis, kopliks spots
Warthin Finkeldey cells
SSPE

Segmented
Enveloped nucleocapsid
Shows minor variation: antigenic drift
Major variation: antigenic shift
Shows Von Magnus phenomenon (on serial passing progeny with high
hemagluttination titer but low infectivity
Guillain barre and Ryes Syndrome associations

USMLE Case Scenario

A 3-year-old child develops voluminous watery diarrhea and vomiting. She is brought to the pediatrician by her parents and
evaluated. Which of the following viruses is the most likely cause of the childs diarrhea?
1. Norwalk virus
2. Rotavirus
3. Influenza virus
4. Parainfluenza virus
Ans. 2. Rota virus

USMLE Case Scenario

An enveloped Rhabdovirus produces encephalitis inpersons who have recently traveled outside of the US after a bite of dog.
The organism is most likely:
1. Togavirus
2. EB
3. Rabies virus
4. Influenza virus
Ans. 3. Rabies virus

USMLE Case Scenario

The Picornaviruses are positive single-stranded RNA viruses with a naked icosahedral nucleocapsid. This family does not
include:
1. Polioviruses
2. Pappiloma viruses
3. Echoviruses
4. Coxsackieviruses
Ans. 2. Pappiloma viruses

294

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Progressive multifocal leukoencephalopathy is a rapidly progressive demyelinating disorder in which the JC virus infects
oligodendroglial cells in the brain. The Eosinophilic inclusions represent accumulations of JC virus which is a:
1. Papovavirus
2. Herpes virus
3. Retrovirus3
4. Arena virus
Ans. 1. Papova virus

USMLE Case Scenario

A 44-year-old mother brings her 4-year-old boy into the emergency room of ENT Department because he has developed a
harsh, barking cough with hoarseness. The virus responsible for this childs illness belongs to which of the following families?
1. Papovavirus
2. Paramyxovirus
3. Parvovirus
4. Picornavirus
Ans. 2. Paramyxovirus (para influenza)

USMLE Case Scenario

A paralytic disease affecting the ventral horn of the spinal cord and motor cortex, caused by RNA enterovirus is:
1. EBV
2. Poliovirus
3. Rabies virus
4. Influenza virus
Ans. 2. Polio virus

USMLE Case Scenario

A 66-year-old patient from wales presents to a physician because of pain during defecation accompanied by blood in the stool.
Physical examination demonstrates a large perianal mass. Pathologic examination of the rectal mass following resection
demonstrates a condyloma in which transformation to frank carcinoma has occurred. Which of the following viruses would
most likely be associated with these lesions?
1. EBV
2. CMV
3. HSV
4. HPV
Ans. 4. HPV
The tumor is anal carcinoma arising in a condyloma. Both condyloma and anal carcinoma are related to human papilloma
virus (HPV), which is also associated with cervical and penile condylomas and carcinomas.

USMLE Case Scenario

A Bullet shaped virus spreading along peripheral nerves to the central nervous system causing hydrophobia and copious
salivation. Most likely virus is:
1. Togavirus
2. EBV
3. Rabies virus
4. Influenza virus
Ans. 3. Rabies virus

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295

USMLE Case Scenario

A 48-year-old female presents with malaise, loss of appetite, nausea, moderate fever, and jaundice. Laboratory tests indicate
a marked increase in serum transaminases. Serology for hepatitis viruses is performed and indicates positive results for the
presence of HBsAg, HBc IgM antibody, and HCV antibody. Antibody tests for HBsAb and HAV are negative. The results indicate:
1. Hepatitis A virus infection
2. Hepatitis B virus infection
3. Hepatitis C virus infection
4. Hepatitis D virus infections
Ans. 2. Hepatitis B virus infection

USMLE Case Scenario

Dysplasia of the cervix and later carcinomas of the cervix is found to be caused by a virusin a 30-year-old woman with a history
of multiple sexual partners. Most likely virus is:
1. EBV
2. CMV
3. HSV
4. HPV
Ans. 4. HPV

USMLE Case Scenario

A 3-month-old infant presents with a 3-day history of fever, cough, and poor feeding. On examination, the baby appears ill
and has a temperature of 102 F and a respiratory rate of 32. A chest X-ray film shows bilateral patchy infiltrates in the lungs.
Which of the following is the most likely etiologic agent?
1. Influenza virus
2. Parainfluenza virus
3. EBV
4. Respiratory syncytial virus
Ans. 4. Respiratory syncytial virus

USMLE Case Scenario

Pathologist describes a pandemic caused by the ability of the virus of Reoviridae family to undergo dramatic genetic changes
of type by reassortment of its segmented RNA genome - a trait called genetic shift. Virus implicated is:
1. Rotavirus
2. Ebola virus
3. Parainfluenza virus
4. EBV
Ans. 1. Rota virus

USMLE Case Scenario

A naked, icosahedral double-stranded circular DNA virus presents with anogenital warts. Most likely virus is:
1. EBV
2. CMV
3. HSV
4. HPV
Ans. 4. HPV

296

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 14-year-old student presents to the hospital complaining of a sore throat and fever. On examination, he has pharyngitis
with cervical lymphadenopathy. Blood tests reveal lymphocytosis and the presence of heterophil antibodies. Which of the
following virus is responsible for his illness?
1. Double-stranded, enveloped DNA virus
2. Double-stranded, nonenveloped DNA virus
3. Single-stranded, enveloped RNA virus
4. Single-stranded, nonenveloped DNA virus
Ans. 1. Double stranded enveloped DNA virus

USMLE Case Scenario

Among the choices mentioned below is a member of family Herpesviridae. It is an enveloped virus with an icosahedral
nucleocapsid that contains a double-stranded linear DNA genome.
1. CMV
2. Polio
3. HPV
4. Influenza
Ans. 1. CMV

USMLE Case Scenario

A single-stranded +RNA virus, is naked (i.e. nonenveloped) and hence will not be inactivated by lipid solvents such as ether.
The live virus vaccine had colonized the intestinal tract of the infant and was still being shed 2 weeks after the earlier oral
dose. The virus is:
1. HDV
2. Polio
3. EBV
4. CMV
Ans. 2. Polio

USMLE Case Scenario

A Virus produces neonatal infections and infections in immunocompromised patients such as AIDS patients and most common
clinical presentation is producing floaters, visual field deficits, and painless loss of vision. It also produces encephalitis and
may produce calcifying lesions in the CNS. Virus most likely is:
1. CMV
2. EBV
3. HSV
4. HHV
Ans. 1. CMV

USMLE Case Scenario

Kaposi Sarcoma is caused by:
1. HHV6
2. HHV7
3. HHV8
4. HHV9
Ans. 3. HHV 8

Double Stranded RNA Viruses

Reovirus
Rotavirus

URTI
Mc cause of infantile diarrhea
Noncultiviable virus
Detected by antigen in stools

Microbiology

297

Rota Virus

Reoviridae family
Double stranded RNA virus
Group A mc causative agent
Does not grow in cell cultures (noncultiviable)
Mc cause of diarrhea in infants
Causes destruction of mature enterocytes
Detected by antigen in stools

Diarrheas are a Feature of

Rotavirus
Adenovirus
Calcivirus
Enterovirus

Hemorrhagic Fever
African hemorrhagic fever:
Hemorrhagic fever with renal syndrome:
Dengue hemorrhagic fever:

Marburg/ebola virus
Hantavirus
Flavivirus

ONCOGENIC VIRUSES: (USMLE FAVORITE)

Virus

Disease

Pox disease

Molluscum contagiosum

Hepatitis B and C

Liver Cancer

EBV

Burkitts lymphoma (in malaria infested parts of Africa), and

Other lymphomas in immunosuppression;
Nasopharyngeal carcinomas

Human papilloma virus

Warts, genital warts, cervical, vulval, penile, anal and perianal carcinoma

HTLV-1

Adult T-cell Leukemia (RNA virus)

HHV 8

Kaposis sarcoma

Adenovirus, SV40

Malignant neoplasms in mice

Polyomavirus hominis 1 and 2

Are found in the urine of some transplant recipients

Human Pappiloma Virus

Deep plantar/palmar warts: HPV 1
Common warts/Verruca Vulgaris: HPV 2
Plane warts: HPV 3
Laryngeal Papillomas: HPV 6,11, 30
Anogenital warts (Condyloma accuminata): HPV 6,11
Butchers warts: HPV 7
Koilocytes are a feature of HPV infections
High oncogenic potential is with: HPV16, 18, 31, 33
Low oncogenic potential is with: HPV6,11, 42, 43

298

USMLE Step 1 Platinum Notes

Viruses and CNS: (USMLE Favorite)

Acute viral meningitis is most commonly due to enterovirus.
Fungal meningitis is mostly due to Candida, Aspergillus, Mucor and Cryptococcus.
Viral Encephalitis shows:
Perivascular cuffs
Microglial nodules
Neuronophagia
HSV1 particularly effects Temporal lobes, causes hemmorhagic necrosis of temporal lobes
Aspergillus and Mucor causes vasculitis with hemorrhage
Cryptococcus invades brain via Virchow Robins spaces with soap bubble lesions
Toxoplasmosis presents with ring enhancing lesions

Kaposis sarcoma

Kaposis sarcoma is common in homosexuals

KS arises from cells linning lymph vessels or blood vessels
KS is associated with HIV, immunosuppression, organ transplants
On skin Kaposis lesions are red/purple blotches which are asymptomatic or tender
GIT, liver, lung lesions can prove dangerous
Treatment of HIV with HAART reduces KS as well
Associated with HHV 8 virus
Common sites: Skin, GIT, Lymph nodes, Lungs
Classic KS as originally described was a relatively indolent disease affecting elderly men from the Mediterranean region, or of
Eastern European descent
Endemic KS was described later in young African people, mainly from sub-Saharan Africa, as a more aggressive disease which
infiltrated the skin extensively, especially on the lower limbs. This, it should be noted, is unrelated to HIV infection
Transplant Related KS had been described, but only rarely until the advent of calcineurin inhibitors (such as ciclosporin,
which are inhibitors of T-cell function) for transplant patients.

Erythema Infectiosum: (Fifth disease, Slapped cheek disease)

Erythema infectiosum is caused by parvovirus B19 (human parvovirus), a small, single-stranded DNA virus
In children the first sign of infection is usually marked erythema of the cheeks or slapped cheek appearance often with
relative circumoral pallor
Then 14 days after the slapped cheeks an itchy, erythematous, maculopapular rash develops on the trunk and limbs
As the rash on the limbs clears it leaves a lacy, reticular pattern. The rash may fluctuate over the next 13 weeks and a hot bath,
for example, may lead to recrudescence of an evanescent rash
Complications
Arthritis or arthralgia is more common in adults, but certainly can occur in children. It usually appears 16 days after the rash
but there maybe no history of rash at all
Arthritis is characteristically transient and asymmetrical, affecting wrists, knees, ankles, elbows and fingers, though it may
persist for weeks or even months
Children with sickle cell anemia, thalassemia major, hereditary spherocytosis or other hemolytic anemias, may have severe
aplastic crises with hemoglobin levels falling as low as 12 g/dl and no reticulocytes
Infection during pregnancy can result in hydrops fetalis due to fetal anemia, which maybe fatal, but no congenital syndrome
has been described in babies of infected mothers who delivered at term
The diagnosis can be made serologically by demonstrating parvovirus B19-specific IgM on an acute serum sample Treatment
Arthritis may require salicylates or nonsteroidal antiinflammatory agents
Children with aplastic crises may require blood transfusion until the red cell aplasia resolves spontaneously after 12 weeks.

Microbiology

299

Parvoviruses
Are small single-stranded DNA viruses, of which only serotype B19 is pathogenic for humans. This virus causes three distinct syndromes:
A childhood febrile rash known as erythema infectiosum (Fifth disease);
Aplastic crisis in individuals with chronic hemolytic diseases (sickle cell anemia, thalassemia, etc.); and congenital infections that
can present as stillbirth,
Hydrops fetalis (analogous to severe Rh incompatibility), or severe anemia.
Herpesvirus 6 (HHV-6) is the main causative agent for Roseola infantum
A common disease of infancy, characterized by fever and the appearance of an erythematous maculopapular rash as the fever
defervesces. It is generally benign.

Viral Hemorrhagic Fever

Lassa fever
Rift valley fever
Hf with renal syndrome
Hantavirus pulmonary syndrome
Yellow fever
Dengue hemorrhagic fever/dengue shock syndrome

Slow Viruses Diseases: (USMLE Favorite)

Group A
MaedI
Visna
Group B
Prion diseases
Caused By prion Protein
Prions are proteins
They are infectious
Most common infectious prion disease in humans
CJD
Kuru
Gerstmann Straussler disease
Fatal familial insomnia
Group C
SSPE
PML
SSPE
Subacute sclerosing panencephalitis (SSPE), a rare degenerative central nervous system (CNS) disease characterized by behavioral
and intellectual deterioration and convulsions, is a result of a persistent measles virus infection that develops years after the original
infection
PML
JC virus, a human papilloma virus the etiologic agent of progressive multifocal leukoencephalopathy (PML), is an important
opportunistic pathogen in patients with AIDS

Remember: (USMLE Favorite)

Nagleria

Primary amebic meningoencephalitis

Acanthamoeba

Keratitis
Granulomatous amebic encephalitis

300

USMLE Step 1 Platinum Notes

Entamoeba histolytica

Amebiasis with flask shaped ulcers

Giardia lamblia

Giardiasis (malabsorption)
Habitat: duodenum, jejunum
Falling leaf motility
Tennis racket shape
Trophozites and cysts seen in man
Associated with common variable immunodeficiency
May cause travelers diarrhea

Cryptosporidium

Diarrhea in immunocompromised

Trichomonas vaginalis

Trichomoniasis (frothy vaginal discharge)

Balantidium coli

Dysentery

Malaria
Plasmodium vivax

Benign tertian malariae

Plasmodium ovale

Benign tertian malariae

Plasmodium malaria

Quartan malaria

Plasmodium falciparum

Malignant malaria

Malarial Parasites
Species Identification
Mauriers clefts: P falciparium
Schuffners dots: P vivax
Zeimmans dots: P malariae
James dots: P ovale
Urban Malaria is caused by Anopheles Culcifacies
Type of malaria not seen in India is ovale
Size of RBC is increased in vivaxmalaria
The infective agent of malaria is sporozoite
Gametocytes are seen in PBF of falciparum malaria
Shizont is not seen in PBF
Relapse of malaria is seen in P ovale and P malariae

Important Features of P Falciparum

Splenic rupture is commonest with P falciparum
Parasitemia is highest with P falciparum
Most virulent form P falciparum
Exoerythrocytic stage is absent in P falciparum
Multiple infection of RBCS is seen in P falciparum
Most Virulent plasmodium species is P falciparum

Microbiology

301

KALA-AZAR: (USMLE FAVORITE)

L donovani
L tropica
L major
L braziliens

Visceral Leishmaniasis
Cutaneous Leishmaniasis
Cutaneous Leishmaniasis
Mucocutaneous Leishmaniasis

Splenomegaly is a feature
NNN (Novy, mc Neal, Nicolle) medium used
Aldehyde test + in 12 weeks
KALA-AZAR (Visceral Leishmaniasis; Dumdum Fever)
Kala-azar occurs in India, China, southern USSR, Africa, the Mediterranean basin, and several South and Central American
countries.
Children and young adults are particularly susceptible.
The protozoa (L donovani) invade the bloodstream and localize in the reticuloendothelial system, causing fever, pronounced
hepatosplenomegaly, emaciation, and pancytopenia.
The fever is seldom sustained and recurs irregularly.
Hypergammaglobulinemia is present.
The parasite maybe found in needle biopsy of the liver, spleen, bone marrow, skin lesions, or lymph nodes or in cultures from these
tissues or from blood.
Pentavalent antimony compounds and pentamidine are the drugs of choice.
Sodium stibogluconate (sodium antimony gluconate) is given once daily, slowly IV or IM in distilled water.
Trypanosoma cruzi

Chagas disease (American Trypanosomiasis)

Vector: reduvid bug
Romana sign +(Swelling around eyelids)
Megacolon, Megaesophagus, Cardiomyopathy are complications
Nifurtimox used in treatment

Trypanosoma brucei

Sleeping sickness (African Trypanosomiasis)

Tse tse fly transmits it
Posterior cervical lymphadenopathy (Winter Bottom sign seen)
Suramin and Melarsoprol used in treatment

Babesia microti

Babeiosis
Seen in immunocompromised/splenectomized patients
Resides in RBC

Toxoplasma gondii

Toxoplasmosis
Cat: definitive host
Oocyst found in cat
Intracerebral calcifications, chorioretinitis, microcephaly
Sabin Feld man test +
Pyremethamine + sulfadiazine used in treatment
Frenkels test+

USMLE Case Scenario

Chagas disease is characterized by facial edema and nodules, fever, lymphadenopathy, and hepatosplenomegaly. It affects
cardiac muscle most severely. It is most prevalent in Central and South America; with rare cases in the southern US. The
causative organism is:
1. Trypanosoma cruzi
2. Trypanosoma brucei

302

USMLE Step 1 Platinum Notes

3. Toxoplasma gondii
4. Babesia microti
Ans. 1. Trypanosoma cruzi
Onchocerca volvolus

River blindness

Wucheria bancrofti

Lymphadenitis
Elephantiasis

Genus

Disease produced

Tenia solium

Cysticercosis and enteritis

Tenia saginata

Enteritis

Entrobius Vermicularis

Pruritis ani

Ascaris lumbricoides

Enteritis, cholangitis

Ent. histolytica

Amebiasis

Naegleria and Acanthameba

Meningitis

Cryptosporidium Parvum

Cryptosporidiosis

Giardia lamblia

Giardiasis

Toxoplasma gondi

Intrauterine infection

USMLE Case Scenario

An organism inhibits the large intestine migrates at night into the perianal region to lay eggs, and can be identified by placing
cellophane tape on the perianal skin and then looking at the tape with a microscope. The most likely cause is:
Ans. Entrobius vermicularis

USMLE Case Scenario

A newborn has developed the classic triad of chorioretinitis (at birth), hydrocephalus, and cerebral calcifications. It is found
that Humans become infected with it by ingesting cysts in contaminated food or through contact with cat feces Most likely
organism is:
Ans. Toxoplasma gondii

USMLE Case Scenario

An organism occurs in the immunocompromised population and may cause severe diarrhea. The organism presents as minute
(25 mm) intracellular spheres or arc-shaped merozoites under normal mucosa, Most likely organism is:
Ans. Cryptosporum parvum

Common Names
Fish Tapeworm: Diphyllobotherium latum
Beef Tapeworm: Tenia saginata
Pork Tapeworm: Tenia solium
Dwarf Tapeworm: H. nana
Rat Tapeworm: H. diminuta
Dog Tapeworm: Echinococcus granulosus

Microbiology
Clonorchis sinesis

Chinese liver fluke

Fasciola hepatica

Sheep liver fluke

Fasciola buski

Giant intestinal fluke

Paragonimus westermanii

Lung fluke

Echinococcus granulosus

Hydatid cyst disease

Echinococcus multilocularis

Alveolar hydatid

303

USMLE Case Scenario

A fluke is producing obstruction of the biliary tract or pancreatic duct and are associated with an increased risk of
cholangiocarcinoma. Most likely organism is:
Clonorchis sinesis

Parasites Causing Autoinfection

Tenia solium
Strongyloides stercolis
Hymenolepsis nana
Enterobius vermicularis
Cryptosporidium parvum
Capillaria philippinesis

Loa Loa causes Calabar swellings

Wucheria bancrofti causes Lymphatic Filariasis
Strongyloides stercolis Larva currens
Toxocaria canis causes Visceral Larva migrans
Strongyloides stercolis causes cutaneous larva migrans

Filariasis

Wucheria bancrofti causes Filariasis

Habitat is lymph vessels and lymph nodes
Man is the definitive host
Innoculation is through bite of mosquito

Infective form is third stage larvae

Notice the difference in classic Filariasis and occult Filariasis
Classic Filariasis

Occult Filariasis (Meyer Kouwenaar Syndrome)

Caused by adult worms

Caused by microfilariae

Epitheloid granuloma is basic lesion

Eosinophilic granuloma is basic lesion

Lymphatic system involved

Lymphatic system
Liver
Lungs involved

Microfilaria present in blood

Microfilaria in tissues

Complement Fixation test insensitive

CFT Sensitive

304

USMLE Step 1 Platinum Notes

Tenia Solium
Cysticercosis in muscles
Cysticerci can develop in any voluntary muscle in humans. Invasion of muscle by cysticerci can cause myositis, with fever, eosinophilia,
and muscular pseudohypertrophy, which initiate with muscle swelling and later progress to atrophy and fibrosis. In most cases, it
is asymptomatic since the cysticerci die and become calcified.
Neurocysticercosis
Neurocysticercosis presents in many forms, depending on the localization of the cysts and disease activity. Sixty percent of the patients
with cysticerci are found to have them in the brain. These cysts increase and slowly leak their antigen into the subarachnoid CSF
producing meningitis and can further develop into arachnoiditis, which may lead to obstructive hydrocephalus, cranial nerve
involvement, intracranial hypertension, arterial thrombosis and stroke. In intraventricular cysticercosis, the cysts occur in the
lateral, third or fourth ventricles which maybe asymptomatic or if they block the flow of CSF, they may cause increased intracranial
pressure.
Ophthalmic Cysticercosis
In some cases, cysticerci maybe found in the globe, subconjunctiva, and extraocular muscles. Depending on the location, they may
cause visual difficulties that fluctuate with eye position, retinal edema, hemorrhage, a decreased vision or even a visual loss.
Subcutaneous Cysticercosis
Subcutaneous cysts are in the form of firm, mobile nodules, occurring mainly on the trunk and extremities. Subcutaneous nodules are
sometimes painful

Echinococcosis
It is also known as hydatid disease. (Echinococcus granulosus)
Hydatid cyst is a parasitic infection of humans by the tapeworm of genus echinococcus
It is a zoonosis
Echinococcus granulosus causes Cystic Echinococcuosis
Echinococcus multilocularis causing Alveolar Echinococcuosis
Echinococcus vogeli causes Polycystic disease
Echinococcus granulosus:
The liver is the most common organ effected followed by lungs, muscles, bones and kidneys.
Passage of hydatid membrane in emesis is called hydatid emesia.
Passage of hydatid membrane in stools is called hydatid enterica.
Echinococcosis is caused by larval stages of parasite
Man is an accidential intermediate host. Other intermediate hosts are sheep and cattle
The dog is the definitive host. (D-D)
Serological assay (Weinberg reaction) is specific example of Complement fixation test used in detection
ELISA is also sensitive
ARA C 5 is used in diagnosis.

Entamoeba Histolytica
Amebiasis is an infection with the intestinal protozoan Entamoeba histolytica
About 90% of infections are asymptomatic, and the remaining 10% produce a spectrum of clinical syndromes ranging from
dysentery to abscesses of the liver or other organs
E histolytica is acquired by ingestion of viable cysts from fecally contaminated water, food, or hands
Both trophozoites and cysts are found in the intestinal lumen, but only trophozoites of E histolytica invade tissue
Cyst has glycogen mass, chromidial bars, eccentric nucleus
Liver abscesses are always preceded by intestinal colonization, which maybe asymptomatic
The most common type of amebic infection is asymptomatic cyst passage
Amebic Liver Abscess Extraintestinal infection by E histolytica most often involves the liver
Pleuropulmonary involvement, which is reported in 20 to 30% of patients, is the most frequent complication of amebic liver
abscess.

Microbiology

Microscopic feature

305

Sites of abscess

USMLE Case Scenario

Patients typically present with diarrhea (often bloody) + right lower quadrant abdominal pain+fever. Amebic abscesses in the
liver are a complication due to invasion of the portal venous system by the ameba.
Primary amebic encephalitis: Naegleria fowleria
Fulminant amebic meningoencephalitis: Naegleria fowleria
Granulomatous amebic encephalitis: Balamuthia mandrillaris

Paracapillaria Philippinensis
It has long been known that the nematode Capillaria hepatica can cause a visceral larva migrans-like syndrome in people
who have eaten meat (e.g. infected liver) or sand containing the eggs of the worm
These children exhibit such symptoms as fever, eosinophilia, abdominal pain and hepatomegaly, with large numbers of typical
eggs being found in the liver on histological examination.
P philippinensis is a parasite of the small intestine and it is believed to be a zoonotic infection involving birds and freshwater
fish. Humans become infected by ingestion of eggs or infected raw fish, the usual intermediate host, and loads within the host
may increase as a result of autoinfection
Diagnosis of capillariasis is based upon histology or finding eggs and larvae in feces
These eggs are like those of Trichuris, but the polar plugs are inset and the shells are striated or pitted
Treatment for capillariasis is tiabendazole 25 mg/kg per day for 30 days or longer. Side effects and relapses are, however, common.
Mebendazole and albendazole are also reported to be effective for the treatment of capillariasis.

Gems Never to be forgotten

Pneumoniae after exposure to parrots

Chlamydiae psittaci

Pregnant women with cats

Toxoplasmosis gondii

Muscle pain and eosinophilia

Trichinosis (Trichinella spiralis)

Slaughter house worker with fever

Brucellosis

Gardener stuck with a thorn

Sporothrix schenckii

Aplastic anemia in Sickle cell Disease

Parvo virus B 19

Fungus Ball

Aspergillus

306

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A patient (pigeon handler) presents with interstitial pneumonitis accompanied by headache, backache, and a dry, hacking
cough. A pale, macular rash is also found on the trunk (Horders spots). Likely organism is:
1. Histoplasma
2. Chlamydiae
3. Mycoplasma
4. Aspergillus
Ans. 2. Chlamydiae

USMLE Case Scenario

A nematode infection is caused by taking undercooked Pork with symptoms of diarrhea, periorbital edema, myositis, fever
and eosinophilia. Most likely organism is:
1. Tenia solium
2. Tenia saginata
3. Trichinella
4. Fasciola
Ans. 3. Trichinella

USMLE Case Scenario

An organism is found to be a pleomorphic, gram-negative rod that causes a localized skin infection and seems to be a cause
of an occupational disease of fishermen, fish handlers, and butchers. Most likely organism is:
1. Erysipelothrix
2. Brucella
3. Salmonella
4. Leptospira
Ans. 1. Erysipelothrix

NEVER TO BE FORGOTTEN: (USMLE FAVORITE)

Swollen jaw with sulfur granules

Actinomyces israelii

Necrotizing fasciitis

Sterptococcus pyogenes

Diaper rash with hyphae and yeast on microscopy

Candida

Burnt tissue with blue greenpus, grape like odor

Pseudomonas aeruginosa

Denuded superficial area of large skin area: SSS

Staph aureus

Pink umblicate warts with central debris

Molluscum contagiosum

Virus latent in sensory ganglia with unilateral reactivation

Varicella zoster virus

Virus latent in trigeminal ganglia

Herpes simplex virus 1, VZV

Virus latent in S2, S3

Herpes simplex virus 2

Conjunctivitis on first day of life

Chemical conjunctivitis

Purulent Conjunctivitis on day 1-4

Gonococcal conjunctivitis

Conjunctivitis on 3-10 days with inclusion bodies

Chlamydiae trachomatis

Follicular conjunctivitis with inturned eye lashes, Corneal scarring

Chlamydiae trachomatis

Chorioretinitis in immunocompromised

Toxoplasma gondii

Microbiology

Gram-positive cocci in clusters

Pear shaped trophozoites
Budding yeasts forming germ tubes
Yeast within macrophages
BLOODY E coli
Scotch tape test positive organism

Cholera toxin: Stimulates Gs

E coli heat labile toxin: stimulates Gs
Pertussis toxin: inhibits Gi
Diphtheria Toxin: acts on EF: Shuts down protein synthesis
Pseudomonas aeruginosa: acts on EF: Shuts down protein synthesis

307

Staph aureus
Giardia lamblia
Candida albicans
Histoplasma capsulatum
E coli 0157: H7
Entrobius vermicularis

CAUSATIVE ORGANISMS OF COMMONLY ASKED DISEASES: (USMLE FAVORITE)

Progressive postoperative Bacterial synergistic gangrene
Malignant Otitis externa

Microaerophillic, nonhemolytic Streptococci plus

staphylococci
Pseudomonas

Scleroma

Klebsiella rhinoscleromatosis

Sudoku

Spirillum minus

Botryomycosis

Staph aureus

Chicleros ulcer

Leishmania Mexicana

Espundia

L Braziliensis

Favus

Tricophyton Schonleneii

Erysipeloid

Erysipelothrix rhusiopathia

Important Causative Agents: (USMLE Favorite)

Necrotizing fasciitis: Group A streptococci

Purpureal sepsis: Group B streptococci
Sweaty tennis shoe syndrome: Pseudomonas
Fish handlers disease: Erysipelothrix rhusiopathiae
Granuloma infantisepticum: Listeria
Gay bowel syndrome: Shigella flexiniri
Human monocytic ehrilichiosis: E chaffeensis
Human granulocytic ehrilichiosis: E equi
Rat bite fever: Spirillum minus
Medittarenean spotted fever: Ricketssia conorii
Cat scratch disease: Bartonella hensla
Typhilitis: Pseudomonas aeruginosa
Red leg disease: Aeromonas

USMLE Case Scenario

A gram-negative rod that is a zoonotic agent causingan undulating febrile disease with malaise, lymphadenopathy and
hepatosplenomegaly. The normal route of exposure is via ingestion of the organism. Most likely organism is:
1. Borrelia
2. Brucella
3. Legionella3
4. Leptospira
Ans. 2. Brucella

308

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A5-year-old child is bitten by a rat. Three days later, the child develops a rash characterized by discrete erythematous 24 mm
macules on the lower extremities and face, most obvious on the palms and soles. Most likely organism is:
1. Yersinia Pestis
2. Streptobacillus moniliformis
3. Pasturella
4. Yersinia enterocolitica
Ans. 2. Streptobacillus moniliformis

USMLE Case Scenario

Infection in AIDS Patient from New York is characterized by firm a nodule that often becomes umbilicated. Cause is found to
be viral most likely organism is:
1. HSV
2. HPV
3. Poxvirus
4. EBV
Ans. 3. Poxvirus

USMLE Case Scenario

A small, pleomorphic, gram-negative rod that a cause (rabbit fever) with bacteremia, splenomegaly, rash, pneumonia is most
likely caused by:
1. Francisella
2. Listeria
3. Leptospira
4. Brucella
Ans. 1. Francisella

USMLE Case Scenario

A gram-negative bacterium causing a local, chronic lymphadenitis, proliferation of blood and lymphatic vessels causing a
characteristic mulberry lesion in the skin and subcutaneous tissues of the afflicted individual and bacillary angiomatosis is:
1. Brucella
2. Bartonella
3. Legionella
4. Leptospira
Ans. 2. Bartonella

USMLE Case Scenario

A gram-positive spore-forming anaerobic rod causing (a spastic paralysis caused by toxin which blocks the release of the
inhibitory neurotransmitters glycine and gamma-aminobutyric acid [GABA]) is most likely:
1. Clostridium tetani
2. Clostridium difficile
3. Clostridium welchi
4. Bacillus anthracus
Ans. 1. Clostridium tetani

Generalizations asked in USMLE

First disease: Rubeola, (measles, kopliks spots)
Second disease: Scarlet fever, (circumoral pallor, pastias lines, strawberry tongue)
Third disease: Rubella, (Forschmiers spots, posterior cervical lymphadenopathy)

Microbiology
Fourth disease: SSSS, (Nikolskys sign)
Fifth disease: Erythema infectiosum (parvovirus b 19, slapped cheek appearance)
Sixth disease: Exanthem subitum, Roseola infantum
Ankylostoma duodenale:
Babesia:
Diphyllobithirum latum:

Iron deficiency anemia

Hemolytic anemia
Megaloblastic anemia

Microbiology of Sexually Transmitted/Genital Diseases

Syphilis: painless ulcer with painless Lymphadenopathy
Chancroid: (soft chancre) painful ulcer with painful lymphadenopathy.
LGV: un noticed painless papule with suppurative lymphadenopathy. Groove sign
Donovaniosis (Granuloma inguinale): painless subcutaneous nodules without lymphadenopathy with pseudobuboes.
Herpes genitalis: painful papule, with inguinal Lymphadenopathy
The chancre of CHANCROID IS PAINFUL IN CONTRAST TO SYPHILIS WHICH IS PAINLESS. Ducreyi makes you cry
Never forget the lines about Features of Chancroid:
Lesions are multiple in number in the form of ulcers which are painful with undermined and ragged edges
Accompanied by Tender and suppurative lymphadenopathy in the form of inguinal buboes.

Important Microbiological Tests

Dick Test

Scarlet Fever

Freis Test

Lymphogranuloma venereum

Kahns Test

Syphilis

Kveims Test

Sarcoidosis

Mono spot/ Paul Bunnel Test

Infectious Mononucleosis

Rose waaler Test

Rheumatoid Arthritis

Sweat Test

Cystic Fibrosis

Weil Felix Test

Rickettsial infection

Rumpel leed test (Capillary Fragility Test)

Scurvy

USMLE Clinical Case Scenarios

Frequent Repititions
Vomiting 16 hours after eating fried rice: Bacillus Cereus
Vomiting and Diarrhea 16 hours after eating contaminated food (Creams): Staph aureus
Diarrhea after ingestion of raw shell fish: Vibrio parahemolyticus
Watery Diarrhea with or without vomiting after travel in developing countries: ETEC
Diarrhea with rapid Fluid loss and Dehydration: V. cholera
Acute endocarditis: Staph aureus
Endocarditis in IV Drug abusers: Staph aureus
Megaloblastic Anemia with history of fish ingestion: Diphyllobothrium latum

309

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USMLE Step 1 Platinum Notes

Vibrio vulnificus is an extremely invasive organism, producing a septicemia in patients after eating raw shellfish, or causing
wound infections, cellulitis, fasciitis, and myositis after exposure to seawater or after cleaning shellfish. Patients at high-risk
for septicemia include those with liver disease, congestive heart failure, diabetes mellitus, renal failure, hemochromatosis,
and immunosuppression.

Vibrio diarrhea

USMLE Repeated Favorites

Sporothrix schenckii. This organism is responsible for rose gardeners disease, known technically as sporotrichosis. The organism
enters through skin breaks in the fingers or hands, causing a chancre, papule, or subcutaneous nodule with erythema and
fluctuance. Ulcerating lesions appear along lymphatic channels, but the lymph nodes are not commonly infected. Potassium iodide
is the treatment for the subcutaneous manifestations.
Tularemia, which maybe spread by handling rabbits or rabbit skins, or by bites from ticks that feed on the blood of wild rabbits. The
causative organism is Francisella tularensis, a gram-negative coccobacillus. The disease begins as a rupturing pustule followed
by an ulcer, with involvement of regional lymph nodes. More serious cases can be complicated by bacteremia, splenomegaly, rash,
pneumonia, or endotoxemic shock.
Borrelia spp. causes relapsing fever (transmitted by ticks and lice) and Lyme disease (transmitted by ticks).
Brucella causes brucellosis after ingestion of contaminated milk or contact with Infected livestock.
Leptospira causes leptospirosis and Weils disease; the organism is acquired by ingestion of water contaminated with animal
urine.
Listeria causes listeriosis after contact with contaminated milk, vegetables, or with transplacental transmission.

Fungi: (USMLE Favorite)

Characteristics

Fungi

Nucleic Acid

Both

Nucleus

Eukaryotic

Ribosomes

80S

Mitochondria

Present

Motality

Nil

Reproduction

Budding

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311

Dimorphic (having two forms) because they are spherical in tissue but grow like molds when cultured at room temperature
Histoplasmosis
Blastomycosis
Sporotrichosis
Coccidioidomycosis
Paracoccidioidomycosis
Penicillin marfenii

Fungi are Eukaryotic organisms

Fungal cell wall contains Chitin.(Chitin is a polysaccharide of long chains of N acetyl glucosamine.)
Fungal Cell membrane contains Ergosterol in contrast to human cell membrane which contains cholesteroL
STAINED by PAS
Most fungi reproduce asexually by forming asexual spores conidia
Fungi without sexual stage: fungi imperfectii
Fungi are culture in Saboubards medium
NON Culturable fungus: Rhinosporodium
Candida species other than Candida glabrata appear in tissue as both budding yeasts and tubular elements called pseudohyphae
Pneumocystis carinii is closer to fungi than to parasites by ribosomal sequences

Monomorphic, Hyphal fungi with dichotomus branching hyphae at acute angles: Aspergillus fumigates
Yeasts with pseudohyphae and true hyphae: Candida albicans
Monomorphic yeast with polysaccharide capsule: Cryptococcus
Non septate filamentous fungi: Mucor, Rhizopus, Absidia
Yeast with broadbased bud and double retractile cell wall: Blastomyces Dermatitidis
Fungus with Endospores and spherules: Coccidomyces immitis
Filamentous fungi with Tuberculate Macronidia: Histoplasma capsulatum

USMLE Case Scenario

A disease is seen mainly in the desert parts of the Southwest US. In the lungs, spherules containing endospores are seen. Most
likely disease is:
1. Coccidioidomycosis
2. Sporotrichosis
3. Paracoccidioidomycosis
4. Blastomycosis
Ans. 1. Coccidioidomycosis

USMLE Case Scenario

A Disease producing a localized cutaneous infection, following inoculation occurring in association with minor skin trauma
during gardening is:
1. Coccidioidomycosis
2. Sporotrichosis
3. Paracoccidioidomycosis
4. Blastomycosis
Ans. 2. Sporotrichosis

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USMLE Step 1 Platinum Notes

USMLE Case Scenario

A disease is endemic in Latin America, especially in Brazil. The infected cells show a typical pilots wheel appearance due to
multiple yeasts sprouting out of a single parent cell. Most likely the disease is:
1. Coccidioidomycosis
2. Sporotrichosis
3. Blastomycosis
4. Paracoccidioidomycosis
Ans. 4. Paracoccidioidomycosis
Mycotoxicosis: Ingestion of fungal toxins produced in foodmost notably aflatoxin in pea nuts
Mycetismus: Illness from toxic ingestion of toxic mushrooms
Fungemia: Sever disseminated fungal infections in immunocompromised patients
Sick building syndrome: Inhalation of volatile fungal toxins which aggreviates allergies

Candida
Candidiasis, commonly called yeast infection or thrush, also known as Candidosis, Moniliasis, and Oidiomycosis is a fungal
infection (mycosis) of any of the Candida species, of which Candida albicans is the most common
It is an endogeneous infection
In immunocompetent persons, candidiasis is usually a very localized infection of the skin or mucosal membranes, including the
oral cavity (thrush), the pharynx or esophagus, the gastrointestinal tract, the urinary bladder, or the genitalia (vagina, penis)
MC fungal infection in neutropenic patients
Candidiasis is a very common cause of vaginal irritation, or vaginitis, and can also occur on the male genitals
In immunocompromised patients, Candida infections can affect the esophagus with the potential of becoming systemic, causing
a much more serious condition, a fungemia called candidemia
Shows Reynolds Braude phenomenon- ability to form germ tubes within 2 hours of incubation.
Candida shows Reynolds Braude Phenomenon (ability to form germ tubes within two hours when incubated in human serum
at 37oC).
Hepatosplenic candidiasis manifests as Bulls Eye Lesion.

USMLE Case Scenario

A 44-year-old woman in Mexicopresents to her gynecologist because of vaginal itchiness and discharge. Pelvic examination
demonstrates abundant white, curdy material in the vagina. Microscopic examination of the material demonstrates fungal
hyphae and yeast forms. Fungal Organism is:
1. Aspergillus
2. Trichomonas
3. Tinea
4. Candida
Ans. 4. Candida

USMLE Case Scenario

A lesion appears as creamy, white patches of exudate that can be scraped off an inflamed tongue or buccal mucosa of an AIDS
patient from Suburban America. Organisms appear as very large, gram-positive, spherical-to-ovoid organisms with budding
daughter cells in Gram-stained preparations. Most likely organism is:
1. EBV
2. HSV
3. Candida
4. CMV
Ans. 3. Candida

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USMLE Case Scenario

A 33-year-old HIV-positive male from New York complains of pain on swallowing. Physical examination is remarkable for white
plaque-like material on his tongue and buccal mucosa, which is scraped and sent to the laboratory. The man is diagnosed with
acquired immunodeficiency syndrome (AIDS). With which of the following agents is the man most likely infected?
1. EBV
2. HSV
3. Candida
4. CMV
Ans. 3. Candida
Types of Dermatophyte Infections
Dermatophytes infect: skin, nails, hair
Athletes foot or tinea pedis T rubrum, T mentagrophytes, E floculossum
Jock itch or tinea cruris T rubrum, T mentagrophytes, E floculossum
Ringworm of the body or tinea corpora
Facial ringworm or tinea faciei
Blackdot ringworm or tinea capitis
MC agent: T tonsurans
Favus is other manifestation. Caused by T schoneilenni
Kerion is caused by T mentagrophytes and T verrucosum
Ringworm of the hands or tinea manuum
In most cases of tinea manuum, only one hand is involved. Frequently both feet are involved concurrently,
Thus the saying one hand, two feet
Ringworm of the nail, Onychomycosis, or tinea unguium

Mycetoma

Chronic granulomatous involvement of subcutaneous and deep tissues

Commonly effecting foot
Usually presents with ulcer on leg, indurated margins and discharging sinuses
Destruction of bone occurs
Actinomycetoma is caused by bacteria: nocardia, actinomadura, streptomyces, actinomyces
Eumycetoma is caused by fungus: madurella, pseudallescheria boydii, philphora

Cryptococcus

Cryptococcus is MonomorphicYeast
Has a Polysaccharide capsule
The environmental source is soil enriched with pigeon droppings
Prediliction for brain

Acute pulmonary infections are common in pigeon breeders

Cryptococcal meningitis is dominant in AIDS patients and patients with cancers
Latex particle agglutination test for capsular polysaccharide in CSF is rapid and sensitive
It is urease positive yeast
Microscopy on India ink wet mount is also used for diagnosis

Late infections (> 6 months after kidney transplantation) include CMV retinitis and a variety of CNS complications. Patients
(particularly those whose immunosuppression has been increased) are at risk for subacute meningitis due to Cryptococcus
neoformans. Cryptococcal disease may present in an insidious manner (sometimes as a skin infection before the development of
clear CNS findings).

314

USMLE Step 1 Platinum Notes

Cryptococcal Meningitis is the mc cause of acute meningitis in AIDS

Cryptococcal infections of the lung can be seen in patients with AIDS. Patients with pulmonary cryptococcal disease present with
fever, cough, dyspnea, and in some cases, hemoptysis. A focal or diffuse interstitial infiltrate is seen on chest X-ray in >90% of
patients. In addition, one may see lobar disease, cavitary disease, pleural effusions, and hilar or mediastinal adenopathy.
Indium In 111-labeled leukocyte scans have become useful as an adjunct to other diagnostic procedures in the detection of
gastrointestinal and central nervous system (CNS) infections, such as focal encephalitis, cryptococcal meningitis, and cytomegalovirus
encephalitis, in acquired immunodeficiency syndrome (AIDS) patients.

Coccidioides Immitis
Grows as a white fluffy mold on most culture media and as a nonbudding spherical form (a spherule) in host tissue or under
special conditions
The organism reproduces in host tissue by forming small endospores within mature spherules
After rupture of the spherule, the released endospores enlarge, become spherules, and repeat the cycle. The fungus is identified by
its appearance and by the formation of thick-walled, barrel-shaped spores, called arthrospores, in the hyphae of the mold form
Causes: Valley fever/Desert Rheumatism.

Histoplasma Capsulatum
It is a dimorphic fungus
Hyphae bear both large and small spores, which are used for identification
H capsulatum grows as small budding yeast in host tissue and on enriched agar, such as blood cysteine glucose, at 37C
The fungus is unencapsulated
Grows in bird/bat enriched soil
Coculture of isolates with opposite mating types can produce different sporulating structures in which genetic recombination
occurs
When these structures, referred to as a teleomorph or the perfect state, are seen in culture, the name Ajellomyces capsulatus is
used
Causes: Histoplasmosis

USMLE Case Scenario

A 55-year-old HIV-positive male from Toledo complains of headache and blurred vision. Physical exam reveals papilledema
and ataxia. Head CT is normal but CSF obtained by lumbar puncture reveals encapsulated organisms observable with India
ink. Which is the organism implicated?
1. Cryptococcus
2. Histoplasmosis
3. Chromoblastomycosis
4. Blastomycosis
Ans. 1. Cryptococcus

USMLE Case Scenario

A 66-year-old farmer from rural area presents with chronic cough. Chest X-ray demonstrates a mass lesion with hilar
lymphadenopathy. Biopsy of the mass demonstrates multiple, tiny yeast forms within macrophages. Which of the following
is the most likely diagnosis?
1. Histoplasmosis
2. Chromoblastomycosis
3. Blastomycosis
4. Mucormycosis
Ans. 1. Histoplasmosis

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315

Blastomyces Dermatitidis
It is a dimorphic fungus
Seen as broad, based, and budding, round yeast like cells with thick wall
Causes:
Blastomycosis
Have an indolent onset and a chronically progressive course. Fever, cough, weight loss, lassitude, skin lesions, and
chest ache are common
Skin lesions favor exposed areas and enlarge over many weeks from pimples to well-circumscribed, verrucous, crusted,
or ulcerated lesions
Pain and regional lymphadenopathy are minimal large chronic lesions may undergo central healing with scarring and
contracture. Mucous membrane lesions resemble squamous cell carcinoma
Chest X-ray findings are abnormal in two-thirds of patients, with one or more pneumonic or nodular infiltrate
Remember: Blasts skin, lungs.

USMLE Case Scenario

A pathogen is found to be present in the respiratory tract of a 36-year-old patient from Honduras as an opportunistic
pathogen; Fungus balls are also seen. Patient previously had Tuberculosis. Most likely organism is.
1. Blastomyces dermatitidis
2. Pneumocystis carinii
3. Aspergillus
4. Mycobacterium tuberculosis
Ans. 3. Aspergillus

Aspergillus: (USMLE Favorite)

It is the most common cause of aspergillosis, but A flavus, A niger, and several other species can also cause disease
Has branching hyphae. (septate)
Mc disease caused: otomycosis
Aspergillus is a mold with septate hyphae about 2 to 4 mm in diameter
Portal of entry is lungs
Aspergillus can colonize the damaged bronchial tree, pulmonary cysts, or cavities of patients with underlying lung disease
Causes:
Aspergillomas: Balls of hyphae within cysts or cavities usually in the upper lobe, may reach several centimeters in
diameter and maybe visible on chest X-ray. Tissue invasion does not occur
Allergic bronchopulmonary aspergillosis denotes the condition of patients with pre-existing asthma who have
eosinophilia, IgE antibody to Aspergillus and fleeting pulmonary infiltrates from bronchial plugging.

Mucormycosis: (USMLE Favorite)

Species of Rhizopus, Rhizomucor, are the most common causes of mucormycosis
It is angio invasive

Zygomycosis is a term that includes mucormycosis and entomophthoromycosis

Rhizopus and Rhizomucor species are ubiquitous, appearing on decaying vegetation, dung, and foods of high sugar content
Mucormycosis is uncommon and is largely confined to patients with serious pre existing diseases. (Diabetic ketoacidosis)
Mucormycosis originating in the paranasal sinuses and nose predominantly affects patients with poorly controlled diabetes
mellitus
Patients who have undergone organ transplantation, who have a hematologic malignancy, or who are receiving long-term
deferoxamine therapy are predisposed to mucormycosis of either sinus or lung
Gastrointestinal mucormycosis occurs in a variety of conditions, including uremia, severe malnutrition, and diarrheal diseases
Pulmonary mucormycosis manifests as progressive severe pneumonia accompanied by high fever and toxicity. The necrotic
center of large infiltrates may cavitate.

316

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A fungal infection begins in the nasal passages, extends into the paranasal sinuses and spreads through the cribiform plate
to the frontal lobes of the brain. Patients typically complain of headache, facial pain and orbital swelling. Most likely cause is:
1. Chromoblastomycosis
2. Aspergillus
3. Mucormycosis
4. Blastomycosis
Ans. 3. Mucormycosis

USMLE Case Scenario

A mold with septate hyphae in immunocompromised patients, aspergillosis presenting with acute pneumonia with
cavitation is:
1. Chromoblastomycosis
2. Aspergillus
3. Mucormycosis
4. Blastomycosis
Ans. 2. Aspergillus

USMLE Case Scenario

An 85-year-old diabetic woman, on dialysis for chronic renal failure, develops bilateral orbital and facial pain, headache, and
sudden loss of vision in the right eye. When examined 2 days later, she is found to have the right eyelids red and swollen, and
she has complete loss of vision and motion on the right eye and partial loss of vision on the left eye. The mucosa of the nasal
passages is swollen and necrotic, with a black discoloration. MRI shows soft-tissue swelling of the nasal mucosa, sinuses, and
orbital tissues, with no evidence of cavernous sinus thrombosis or retro-orbital cellulitis. Biopsy of the temporal artery is
negative for giant cell arteritis. Biopsy of the nasal and sinuses mucosa demonstrates thrombosed vessels and multiple broad
nonseptate hyphae with right-angle branches. Which of the following is the most appropriate treatment?
1. Amphotericin B and surgical debridement
2. Corticosteroids
3. Heparin anticoagulation
4. Metronidazole and drainage of the paranasal sinuses
5. Surgical decompression of both orbits
Ans. 1. Amphotericin B and surgical debridement

Chromoblastomycosis
Chronic subcutaneous mycosis, presents as a verrucoid, ulcerated, or crusted skin lesion
Cladosporium is causative organism
The disease follows the introduction of any of several fungi into subcutaneous tissue by thorns or bits of vegetation
The appearance of thick-walled, dark-colored, rounded forms (copper pennies) in histopathologic section is diagnostic. Sclerotic
bodies
Surgical excision is the treatment of choice.

USMLE Case Scenario

A 66-years-old AIDS patient with pneumonia has a bronchoalveolar lavage that demonstrates small, hat-shaped structures
in alveoli that are about the size of an erythrocyte and stain with silver stains. The microorganism involved is most likely which
of the following?
1. Blastomyces dermatitidis
2. Mycobacterium avium
3. Mycobacterium tuberculosis
4. Pneumocystis carinii
Ans. 4. Pneumocystis carinii

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USMLE Case Scenario

A 44-year-old HIV-positive mancomes to Immunology clinic complaining of dyspnea mild cough and fever. Physical
examination is remarkable for oral thrush and a few small, nontender cervical lymphnodes. A chest X-ray film reveals bilateral
interstitial infiltrates, and bronchoalveolar lavage reveals small silver-staining cysts. Most likely organism is:
1. Blastomyces dermatitidis
2. Pneumocystis carinii
3. Mycobacterium avium
4. Mycobacterium tuberculosis
Ans. 2. Pneumocystis carinii

Pneumocystis Carinii: (USMLE Favorite)

Obligate extracellular fungus
Present in patients with defects in cell-mediated immunity as with hematologic malignancies, lymphoproliferative diseases,
cancer chemotherapy, and AIDS
Causes interstitial pneumonia
Traditional stains have included reagents such as methenamine silver, toluidine blue, and cresyl violet, which selectively stain
the wall of P carinii cysts, and reagents such as Wright-Giemsa, which stain the nuclei of all developmental stages. Other reagents
include nonspecific fluorochrome stains (calcofluor white) and Papanicolaous stain.

Clinical Case Scenarios of USMLE (Important Guiding Features)

An organism is found to be a pleomorphic, gram-negative rod that causes a localized skin Erysipelothrix
infection and seems to be a cause of an occupational disease of fishermen, fish handlers, and
butchers. Most likely disease is caused by:
A nematode infection is caused by taking undercooked Pork with symptoms of diarrhea, periorbital Trichinella
edema, myositis, fever, and eosinophilia. Most likely organism is:
An organism occurs in the immunocompromised population and may cause severe diarrhea. Cryptosporodiosis
The organism presents as minute (2-5 mm) intracellular spheres or arc-shaped merozoites
under normal mucosa. Most likely disease is
A 44-year-old patient presents with facial edema and nodules, fever, lymphadenopathy, and Chagas disease
hepatosplenomegaly. The disease also affects cardiac muscle most severely. It is most prevalent
in Central and South America; with rare cases in the southern US. The disease is:
A 35-year-old female says she had a protozoan infection and used to eat undercooked Toxoplasmosis
meat and had exposure to cat feces. The organisms can also cause a heterophile-negative,
mononucleosis-like syndrome. In patients with AIDS, it causes ring-enhanced focal brain
lesions and pneumonia. Most likely the disease is
An African child develops massive unilateral enlargement of his lower face in the vicinity of Burkitts Lymphoma
the mandible. Biopsy demonstrates sheets of medium-sized blast cells with admixed larger
macrophages. This type of tumor has been associated with viral infection. Most likely
disease is
A Disease is found to be due to reactivation of epidemic typhus infection caused by Rickettsia Brill Zinsser disease
prowazekii. It can occur many years after an infection that was not treated with antibiotics.
The most likely disease is:
A gram-positive coco bacillus is causing Infection during pregnancy that may result in Listerosis
sepsis, abortion or premature delivery. Infection in the neonate may produce meningitis. In
immunocompromised adults, either meningitis or sepsis may occur. The organism is
A 3-year-old boy from rural America is brought to the ENT emergency room in extreme Epiglottitis
respiratory distress, with a temperature of 104 degrees Fahrenheit. He is drooling and
has great difficulty swallowing, and on physical examination, an inspiratory stridoris noted.
An immediate lateral X-ray done shows swelling of the epiglottis. He has had no previous
vaccinations. Most likely disease is

318

USMLE Step 1 Platinum Notes

An highly encapsulated organism is found to cause a bronchopneumonia with patchy infiltrates Klebsiella pneumoniae
involving one or more lobes with red sputum in a debilitated alcoholic. Most likely disease is:
A 8-year-old girl is bitten in the leg by a dog. She presents the next day with fever and bone Pasteurella
pain localized to her right calf. X-ray reveals a lytic lesion of the left femur. Results of the bone
culture are pending. Infecting organism is most likely to be:
An organism is causing urinary tract infections. It has ability to breakdown urea and is thought to Proteus species.
contribute to the development of struvite kidney stones due to the elevation of urine pH by production
of ammonia. The said organism is also having swarming motility. The organism is identified
A 44-year-old man from rural Indian village is brought to a rural hospital with severe Plague
bronchopneumonia. He suffered sudden onset of chills, fever, and headache several days ago.
Two day later, he complained of chest pain and difficulty breathing, and coughed up bloodtinged sputum. Chest X-ray reveals patchy infiltrates and segmental consolidation. The most
likely cause of this mans pneumonia and the disease itself is due to yersinia. Disease itself is:
A disease is caused the organism enters through skin breaks in the fingers or hands, causing Sporotrichosis
a chancre, papule, or subcutaneous nodule with erythema and fluctuance. Ulcerating lesions
appear along lymphatic channels, but the lymph nodes are not commonly infected. Potassium
iodide isused for the treatment for the subcutaneous manifestations. The disease is common in
gardeners. Most likely disease is:
A 66-year-old alcoholic man with brain and pulmonary abscess and is treated with antibiotics Clostridium difficile
for last two weeks. He develops nausea, vomiting, abdominal pain, and voluminous green
diarrhea. The condition is diarrhea due to:
An organism identified on dark ground microscopy caused testicular involvement with gumma Syphilis
formation, endarteritis, and/or a prominent plasma cell infiltrate. Most likely disease is:
A disease which maybe spread by handling rabbits or rabbit skins, or by bites from ticks that feed Tularemia
on the blood of wild rabbits, a gram-negative coccobacillus. The disease begins as a rupturing
pustule followed by an ulcer, with involvement of regional lymph nodes. More serious cases
can be complicated by bacteremia, splenomegaly, rash, pneumonia, or endotoxemic shock.
Most likely disease is:
A gram-positive spore-forming anaerobic rod causing (a spastic paralysis caused by toxin Tetanus caused by clostridia
which blocks the release of the inhibitory neurotransmitters glycine and gamma-aminobutyric tetani
acid [GABA]) is most likely:
A gram-negative rod that is a zoonotic agent causing an undulating febrile disease with Brucellosis
malaise, lymphadenopathy and hepatosplenomegaly. The normal route of exposure is via
ingestion of the organism. Most likely disease is:

Microbiology

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USMLE Case Scenario

A minority of cases of infective endocarditis are caused by a number of normal commensals in the oral cavity, i.e. the HACEK
group. Hacek Means.
1. Hemophilus, Actinobacillus, Corynebacterium, Eikenella, and Kingella
2. Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Klebsiella
3. Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella
4. Hemophilus, Actinobacillus, Cardiobacterium, E coli, and Kingella
Ans. 3. Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella

USMLE Case Scenario

ADP-ribosylation of an elongation factor is a mechanism of action of:
1. Pseudomonas exotoxins
2. Clostrodial toxin
3. Streptococcal toxin
4. Staphylococcal toxin
Ans.1. Pseudomonas exotoxins

USMLE Case Scenario

An organism is found to be a pleomorphic, gram-negative rod that causes a localized skin infection and seems to be a cause
of an occupational disease of fishermen, fish handlers and butchers. Most likely organism is:
1. Erysipelothrix
2. Brucella
3. Salmonella
4. Leptospira
Ans. 1. Erysipelothrix

USMLE Case Scenario

Stalacite growth is a feature of:
1. Hemophilus
2. Pasteurella
3. Corynebacterium
4. Mycoplasma
5. Klebsiella
6. Pseudomonas
Ans. 2. Pasteurella

USMLE Case Scenario

A Virus produces neonatal infections and infections in immunocompromised patients such as AIDS patients and most common
clinical presentation is producing floaters, visual field deficits, and painless loss of vision. It also produces encephalitis and
may produce calcifying lesions in the CNS. Virus most likely is:
1. CMV
2. EBV
3. HSV
4. HHV
Ans. 1. CMV

320

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Staphylococcus aureus is present in mayonnaise. The patient presents with nausea, vomiting, and abdominal pain, followed
by diarrhea beginning 16 hours after ingestion of the toxin. The toxin is:
1. Not a Preformed enterotoxin
2. Preformed enterotoxin
3. Preformed non enterotoxin
4. Non Preformed non enterotoxin
Ans. 2. Preformed enterotoxin

USMLE Case Scenario

An obligate intracellular parasite that induces endocytosis and resides in the phagosome of infected epithelial cell is:
1. Rickettsia
2. Mycoplasma
3. Mycobacteria
4. Chlamydia
Ans. 4. Chlamydia

USMLE Case Scenario

Lucio phenomenon is a widespread diffuse infiltration of the skin with secondary alopecia of the hair, eyebrows and eyelashes,
and generalized sensory loss. The patients are systemically ill with fever, chills, malaise, arthralgias, myalgias, and tender
cutaneous lesions that are responsive to steroids but not to thalidomide. Lucio phenomenon is usually associated with:
1. Mycoplasma
2. Chlamydia
3. Mycobacterium avium
4. Mycobacterium africanum
5. Mycobacterium tuberculosis
6. Mycobacterium leprae
Ans. 6. Mycobacterium leprae

USMLE Case Scenario

Overall, 3040% of all infections contracted in the post renal transplant period are viral. The most common viral infections
are by:
1. DNA viruses
2. RNA Viruses
3. Retroviruses
4. Arboviruses
Ans. 1. DNA viruses
The most common viral infections are DNA viruses of the herpes virus family and include cytomegalovirus (CMV), Epstein-Barr
virus, herpes simplex virus, and varicella zoster virus.

USMLE Case Scenario

An 66-years-old AIDS patient with pneumonia has a bronchoalveolar lavage that demonstrates small, hat- shaped structures
in alveoli that are about the size of an erythrocyte and stain with silver stains. The microorganism involved is most likely which
of the following?
1. Blastomyces dermatitidis
2. Mycobacterium avium
3. Mycobacterium tuberculosis
4. Pneumocystis carinii
Ans. 4. Pneumocystis carinii

Microbiology

321

USMLE Case Scenario

An 85-year-old diabetic woman from Chicago develops orbital and facial pain, headache. When examined 2 days later, she is
found to have the right eyelids red and swollen, and she has complete loss of vision and motion on the right eye. The mucosa
of the nasal passages is swollen and necrotic, with a black discoloration. Biopsy of the temporal artery is negative for giant cell
arteritis. Biopsy of the nasal and sinuses mucosa demonstrates thrombosed vessels and multiple broad nonseptate hyphae
with right-angle branches. Most likely cause is:
1. Histoplasmosis
2. Blastomycosis
3. Mucormycosis
4. Aspergellosis
Ans. 3. Mucormycosis

USMLE Case Scenario

A child after playing with a pet injured while playing with a pet has a local abscess. A gram-negative rod that is normal flora
of the oral cavity of dogs and cats is found to be causative. Most likely organism is:
1. Pasteurella
2. Pseudomonas
3. Francisella
4. Bartonella
Ans. 1. Pasteurella

USMLE Case Scenario

Visceral larva migrans is due to:
1. Ascariasis
2. Toxocaria
3. Schistosomiasis
4. Clonorchis
5. Trichomonas
6. Plasmodium
Ans. 2. Toxocaria

USMLE Case Scenario

An organism is causing urinary tract infections. It has ability to breakdown urea and is thought to contribute to the
development of struvite kidney stones due to the elevation of urine pH by production of ammonia. The said organim is also
having swarming motility. The organism is identified as:
1. Brucella
2. Proteus
3. Pseudomonas
4. Anthrax bacillus
5. Clostridia
Ans. 2. Proteus

USMLE Case Scenario

Botulin toxin acts by:
1. Secretion of Ach
2. Synthesis of Ach
3. Muscle nerve block
4. Inhibits Ach release
Ans. 4. Inhibits Ach release

322

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 33-year-old HIV-positive male from New York complains of pain on swallowing. Physical examination is remarkable for white
plaque-like material on his tongue and buccal mucosa, which is scraped and sent to the laboratory. The man is diagnosed with
acquired immunodeficiency syndrome (AIDS). With which of the following agents is the man most likely infected?
1. EBV
2. HSV
3. Candida
4. CMV
Ans. 3. Candida

USMLE Case Scenario

A 55-year-old man presents with an episode of shaking chills the previous night. He has now developed right-sided pleuritic
chest pain, fever, sweats, malaise, purulent sputum, and mild hemoptysis. On examination, the patient is diaphoretic but
alert, with right basilar rales. Chest X-ray films show a right lower lobe infiltrate with blunting of the right costophrenic angle.
The causative organism implicated is:
1. Streptococcus agalactiae
2. Streptococcus pneumonia
3. Streptococcus viridians
4. Streptococcus pyogenes
Ans. 2. Streptococcus pneumonia

USMLE Case Scenario

A 22-year-old veterinary surgeon presents with a 2 week history of high fevers, night sweats. He also had dry cough, and
myalgia. On examination, the patient had a palpable splenic tip. Blood films for malaria parasites were negative. Liver function
tests showed a raised serum alkaline phosphatase, raised serum aspartate aminotransferase concentration, serum bilirubin
concentration. Likely cause is:
1. Salmonella
2. Chlamydia
3. Bartonella
4. Francisella
5. Mycoplasma
6. Brucella
7. Legionella
Ans. 6. Brucella

USMLE Case Scenario

Erythema infectiosum is caused by:
1. Parvovirus B19
2. Papova virus
3. Human herpes virus type 8
4. Measles virus
Ans. 1. Parvovirus B19

USMLE Case Scenario

A Virus produces neonatal infections and infections in immunocompromised patients such as AIDS patients and most common
clinical presentation is producing floaters, visual field deficits, and painless loss of vision. It also produces encephalitis and
may produce calcifying lesions in the CNS. Virus most likely is:
1. CMV
2. EBV

Microbiology

323

3. HSV
4. HHV
Ans. 1. CMV

USMLE Case Scenario

Lipopolysaccharide is an important component of:
1. Gram-positive cells
2. Gram-negative cells
3. Neither Gram-positive nor Gram-negative cells
4. Both Gram-positive and Gram-negative cells
Ans. 2. Gram-negative cells

USMLE Case Scenario

Encephalitis typically affects the inferomedial temporal lobes and orbitofrontal gyri. Most likely double stranded DNA virus
implicated is:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 2. HSV

USMLE Case Scenario

Chagas disease is characterized by facial edema and nodules, fever, lymphadenopathy, and hepatosplenomegaly. It affects
cardiac muscle most severely. It is most prevalent in Central and South America; with rare cases in the southern US. The
causative organism is:
1. Trypanosoma cruzi
2. Trypanosoma brucei
3. Toxoplasma gondii
4. Babesia microti
Ans. 1. Trypanosoma cruzi

USMLE Case Scenario

Epidemic keratocojunctivitis is caused by:
1. Coronavirus
2. Epstien-Barr virus
3. Picornavirus
4. Adenovirus
Ans. 4. Adenovirus

USMLE Case Scenario

A pregnant 18-year-old woman came to the clinic with a low-grade fever, malaise and headache. Few days later she presented
with a macular rash on her trunk, arms, hands, and feet. Further examination revealed that 1 month previously, she had a
painless ulcer on her vagina that healed spontaneously. Most likely diagnosis is:
1. Lyme disease
2. Lymphogranuloma venereum
3. Behcets disease
4. Endocarditis
5. Syphilis by treponema
Ans. 5. Syphilis by treponema

324

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Madura foot is caused by:
1. Blastomycosis
2. Nocardia
3. Candida albicans
4. Tenia versicolor
Ans. 2. Nocardia

USMLE Case Scenario

A Bullet shaped virus spreading along peripheral nerves to the central nervous system causing hydrophobia and copious
salivation. Most likely virus is:
1. Toga virus
2. EBV
3. Rabies virus
4. Influenza virus
Ans. 3. Rabies virus

USMLE Case Scenario

A 18-year-old, ill-appearing woman comes OPD with a fever. She notes the recent development of nausea, diarrhea, and a
rash. Her last menstrual period began 3 days ago. Physical examination is remarkable for blood pressure of 90/40 mm Hg and
heart rate of 120 beats per minute. A diffuse erythematous rash with desquamation over feet is noted. Infection with which of
the following toxin is the most likely cause of these signs and symptoms?
1. Clostridium perfringens toxin
2. Shigella dysenteriae toxin
3. Staphylococcus aureus toxin
4. Staphylococcus epidermidis toxin
Ans. 3. Staphylococcus aureus toxin

USMLE Case Scenario

A 26-year-old male complains of a severe headache and weakness. His condition rapidly deteriorates over a period of hours. A
lumbar puncture is performed and a Grams stain of spinal fluid reveals Neisseria meningococcus. The organism is:
1. Gram-negative diplococci
2. Gram-positive cocci
3. Gram-positive bacillus
4. Obligate intracellular organism
Ans. 1. Gram-negative diplococci

USMLE Case Scenario

HTLV-1, or human T-cell lymphotrophic virus 1 can lead to T-cell leukemia 2030 years after the infection. The virus is:
1. A nonenveloped, single-stranded, RNA retrovirus
2. An enveloped, double-stranded, RNA retrovirus
3. An enveloped, single-stranded, DNA retrovirus
4. An enveloped, single-stranded, RNA retrovirus
Ans. 4. An enveloped, single-stranded, RNA retrovirus

USMLE Case Scenario

A 64-year-old man from New Jersy presents with severe hemoptysis. An organism is isolated and found that it has a tendency
to invade pre-existing pulmonary cavities and form a rounded necrotic mass of matted hyphae, fibrin, and inflammatory cells.
A filamentous organism with coarse, septate, fragmented hyphae is isolated. Most likely organism is:

Microbiology

325

1. Cryptococcus neoformans
2. Candida albicans
3. Blastomyces dermatitidis
4. Paracoccidioides brasiliensis
5. Coccidioidomycosis
6. Aspergillus fumigatus
Ans. 6. Aspergillus fumigatus

USMLE Case Scenario

HTLV-1, or human T-cell lymphotrophic virus 1 can lead to T-cell leukemia 2030 years after the infection. The virus is:
1. A nonenveloped, single-stranded, RNA retrovirus
2. An enveloped, double-stranded, RNA retrovirus
3. An enveloped, single-stranded, DNA retrovirus
4. An enveloped, single-stranded, RNA retrovirus
Ans. 4. An enveloped, single-stranded, RNA retrovirus

USMLE Case Scenario

A 40-year-old man has been to Malaysia for 6 months. He has an erythematous, serpiginous, pruritic, cutaneous eruption on
the medial side of the ankle. What is the diagnosis?
1. Lyme disease
2. Cutaneous larval migrans
3. Leishmaniasis
4. Sarcoidosis
5. Tuberculosis
Ans. 2. Cutaneous larval migrans
Cutaneous larva migrans is caused by the penetration through intact skin of larval animal hookworms

USMLE Case Scenario

A 44-year-old man from rural Indian village is brought to a rural hospital with severe bronchopneumonia. He suffered sudden
onset of chills, fever, and headache several days ago. Two day later, he complained of chest pain and difficulty breathing, and
coughed up blood-tinged sputum. Chest X-ray reveals patchy infiltrates and segmental consolidation. The most likely cause
of this mans pneumonia and the disease itself is due to yersinia. Disease itself is:
1. Leprosy
2. Tuberculosis
3. Listerosis
4. Legionella pneumoniae
5. Tularemia
6. Psittacosis
7. Plague
Ans. 7. Plague

USMLE Case Scenario

The sulfur granules in the wound are diagnostic of:
1. Nocardia
2. Actinomyces
3. Clostridium welchii
4. Aspergillus flavusm
Ans. 2. Actinomyces

326

USMLE Step 1 Platinum Notes

USMLE Case Scenario

An organism inhabits the large intestine migrates at night into the perianal region to lay eggs, and can be identified by placing
cellophane tape on the perianal skin and then looking at the tape with a microscope. The most likely cause is:
1. Tenia solium
2. Tenia saginatum
3. H nana
4. F hepatica
5. T vaginalis
6. Enterobius vermicularis
Ans. 6. Enterobius vermicularis

USMLE Case Scenario

A 66-year-old patient from wales presents to a physician because of pain during defecation accompanied by blood in the stool.
Physical examination demonstrates a large perianal mass. Pathologic examination of the rectal mass following resection
demonstrates a condyloma in which transformation to frank carcinoma has occurred. Which of the following viruses would
most likely be associated with these lesions?
1. EBV
2. CMV
3. HSV
4. HPV
Ans. 4. HPV

USMLE Case Scenario

Which virus reactive and involves the eyes?
1. Herpes-Zoster
2. CMV
3. EB virus
4. Enterovirus-70
Ans. 1. Herpes-Zoster

USMLE Case Scenario

A pathogen is found to be present in the respiratory tract of a 36-year-old patient from Honduras as an opportunistic pathogen;
Fungus balls are also seen. Patient previously had Tuberculosis. Most likely organism is:
1. Blastomyces dermatitidis
2. Pneumocystis carinii
3. Aspergillus
4. Mycobacterium tuberculosis
Ans. 3. Aspergillus

USMLE Case Scenario

A 36-year-old female from Washington presents with a 2-day history of fever, chills, chest pain, and cough productive of rusty
sputum. Past medical history includes a splenectomy 1 year ago. A chest X-ray film indicates consolidation of the right lower
lobe. Blood cultures are positive for and alpha; hemolytic gram-positive diplococcic. Most likely organism is:
1. Pneumococcus
2. Meningococcus
3. Staphylococcus
4. Gonococcus
Ans. 1. Pneumococcus

Microbiology

327

USMLE Case Scenario

A 24-year-old AIDS patient develops chronic abdominal pain, low-grade fever, diarrhea, and malabsorption. Oocysts are
demonstrated in the stool. Which of the following organisms is most likely to be the cause of the patients diarrhea?
1. Diphyllobothrium latum
2. Entamoeba histolytica
3. Giardia lamblia
4. Isospora belli
5. Microsporidia
Ans. 4. Isospora belli

USMLE Case Scenario

Friable Nasal polyps and subcutaneous nodules are characteristically associated with the infection of:
1. Histoplasma
2. Sporothrix
3. Rhinosporidium
4. Cryptococcus
Ans. 3. Rhinosporidium

USMLE Case Scenario

Gastric ulcers are associated with malignancy, and therefore biopsy should be performed when they are discovered. This
association with malignancy is not found with duodenal ulcers. The increased risk for malignancy with gastric ulcers is a good
reason to test patients for H pylori and initiate treatment if it is found. H pylori is a:
1. Aerobe
2. Anaerobe
3. Obligate aerobe
4. Microaerophilic
Ans. 4. Microaerophilic

USMLE Case Scenario

A 66-year-old farmer from rural area presents with chronic cough. Chest X-ray demonstrates a mass lesion with hilar
lymphadenopathy. Biopsy of the mass demonstrates multiple, tiny yeast forms within macrophages. Which of the following
is the most likely diagnosis?
1. Histoplasmosis
2. Chromoblastomycosis
3. Blastomycosis
4. Mucormycosis
Ans. 1. Histoplasmosis

USMLE Case Scenario

A child presents with chronic enteritis, failure to thrive, hypoalbuminemia, and hypokalemia. Other findings include acute
right lower quadrant abdominal pain, tenderness, nausea, and vomiting. The infection mimics appendicitis or Crohns disease.
Most likely organism is:
1. Yersinia enterocolitica
2. Haemophilus aegyptius
3. Borrelia duttonii
4. Haemophilus ducreyi
Ans. 1. Yersinia enterocolitica

328

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Torres bodies are seen in:
1. Kala-Azar
2. Q-fever
3. Yellow fever
4. LGV
5. Malaria
6. Hepatitis
7. Babeiosis
Ans. 3. Yellow fever

USMLE Case Scenario

An organism produces cutaneous disease (malignant pustule or eschar) at the site of inoculation in handlers of animal skins.
Most likely organism is:
1. Bacillus anthracus
2. Pseudomonas Aeruginosa
3. Neisseria meningitides
4. Cryptococcus neoformans
Ans. 1. Bacillus anthracus

USMLE Case Scenario

A viral organism was isolated from a painful blister on the lip of a girl. The agent was found to double-stranded, linear DNA
and was enveloped. Most likely causative organism is:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 2. HSV

USMLE Case Scenario

Donovan bodies are:
1. Leukocytes that contain the organism, Calymmatobacterium granulomatis
2. Eosinophils that contain the organism, Calymmatobacterium granulomatis
3. Monocytes that contain the organism, Hemophilus influenza
4. Monocytes that contain the organism, Calymmatobacterium granulomatis
Ans. 4. Monocytes that contain the organism, Calymmatobacterium granulomatis

USMLE Case Scenario

Chagas disease is an important cause of cardiac failure in some Latin American countries, and Brazilian cases can be associated
with megaesophagus and megacolon. The disease is Chagas disease, which is caused by:
1. Bacteria
2. Mycoplasma
3. Protozoa
4. Virus
Ans. 3. Protozoa

Microbiology

329

USMLE Case Scenario

A 55-year-old HIV-positive male from Toledo complains of headache and blurred vision. Physical exam reveals papilledema
and ataxia. Head CT is normal but CSF obtained by lumbar puncture reveals encapsulated organisms observable with India
ink. Which is the organism implicated?
1. Cryptococcus
2. Histoplasmosis
3. Chromoblastomycosis
4. Blastomycosis
Ans. 1. Cryptococcus

USMLE Case Scenario

A 4 year-old girl with a history of hydrocephalus is brought to the neurologist by her parents with a severe headache and
fever. The girl underwent a surgery for a ventricular-peritoneal shunt 2 months ago and the neurologist suspects that an
infection has occurred. Organisms would most likely be isolated from the shunt tubing is:
1. Staph aureus
2. Streptococcus
3. Staphylococcus epidermidis
4. Meningococcus
Ans. 3. Staphylococcus epidermidis

USMLE Case Scenario

A disease is seen mainly in the desert parts of the Southwest US. In the lungs, spherules containing endospores are seen. Most
likely disease is:
1. Coccidioidomycosis
2. Sporotrichosis
3. Paracoccidioidomycosis
4. Blastomycosis
Ans. 1. Coccidioidomycosis

USMLE Case Scenario

Among the choices mentioned below is a member of family Herpes viridae. It is an enveloped virus with an icosahedral
nucleocapsid that contains a double-stranded linear DNA genome.
1. CMV
2. Polio
3. HPV
4. Influenza
Ans. 1. CMV

USMLE Case Scenario

A 33-year-old woman in New Jersy presented with a 1 day history of fever and chills. On examination, she was febrile with
a blood pressure of 70/40 mm Hg. Over several hours, a widespread erythrodermic rash developed. The female collapses.
Further questioning revealed that the patient had removed a tampon shortly before presentation, as she had just ceased
menstruating.
1. Streptoccus Bovis infection
2. Hemolytic uremic syndrome
3. E coli sepsis
4. Fungal infection
5. Toxic shock syndrome
6. Meningococcal septicemia

330

USMLE Step 1 Platinum Notes

7. Staph epidermis infection

8. Pseudomonas induced shock
Ans. 5. Toxic shock syndrome
Toxic shock syndrome is due to toxin-1 (TSST-1), a protein secreted by S aureus or streptococci, was the first of many toxins
associated with the syndrome to be identified.

USMLE Case Scenario

Pinta is caused by:
1. Treponema pertenue
2. Treponema cerateum
3. Treponema pallidum
4. Treponema endemicum
Ans. 2. Treponema cerateum

USMLE Case Scenario

The organism that is strongly urease positive:
1. Proteus species
2. Klebsiella species
3. Helicobacter pylori
4. Staphylococcus
Ans. 1. Proteus species

USMLE Case Scenario

A 34 years old person has rapidly developing cough, dyspnea, expectoration and blood-tinged sputum. He is febrile, cyanosed,
and toxic. Chest examination reveals crepitations and ronchi. The most likely diagnosis is:
1. Legionella
2. Pneumonic plague
3. Septicemic plague
4. Pulmonary tuberculosis
Ans. 2. Pneumonic plague

USMLE Case Scenario

Satellitism is seen in cultures of:
1. Hamophilus
2. Streptococcus
3. Klebsiella
4. Proteus
5. Salmonella
Ans. 1. Hamophilus

USMLE Case Scenario

A patient (pigeon handler) presents with interstitial pneumonitis accompanied by headache, backache and a dry, hacking
cough. A pale, macular rash is also found on the trunk (Horders spots). Likely organism is:
1. Histoplasma
2. Chlamydiae
3. Mycoplasma
4. Aspergillus
Ans. 2. Chlamydiae

Microbiology

331

USMLE Case Scenario

In a 40-year-old man following tooth extraction developed oral local infection with draining discharge, which on examination
showed Gram-positive branching roads and leucocytes. Anaerobic growth was absent. The most likely organism responsible
for this is:
1. Fusobacterium
2. Nocardia
3. Bacteroids fragilis
4. Actinomyces
Ans. 4. Actinomyces

USMLE Case Scenario

A-65-year-old man presents to the hospital unwell with diarrhea. He has a BP of 110/70, heart rate 120 and Temp 38C. A
diastolic murmur is heard in aortic area. Which organism is likely to grow in the blood cultures?
1. MRSA
2. Listeria
3. Streptococcus mitis
4. Staphylococcus aureus
5. Streptococcus bovis
6. Escherichia coli
7. Brucella melitensis
Ans. 5. Streptococcus bovis usually enters the bloodstream via the gastrointestinal tract. There is also an association with
malignancy of the GI tract

USMLE Case Scenario

In a poultry farm, many chickens developed diarrhea, emaciation and mucopurulent discharge. After about 2 hours the farmer
developed fever, chills, headache, and Breathlessness. The most likely diagnosis is:
1. Anthrax b
2. Q fever
3. Relapsing fever
4. Ornithosis
Ans. 4. Ornithosis

USMLE Case Scenario

Fungal meningitis in an immunocompromised individual is most commonly caused by:
1. Candida albicans
2. Cryptococcus neoformans
3. Penicillium
4. Aspergillus
Ans. 2. Cryptococcus neoformans

USMLE Case Scenario

Transplacental transfer of antibodies from immunized mother to her newborn is:
1. Natural active immunity
2. Natural passive immunity
3. Acquired active immunity
4. Acquired passive immunity
Ans. 2. Natural passive immunity

332

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A severely ill 44 years old HIV affected patient from New york has evidence of destruction of myelin at multiple sites in the CNS
pointing to a diagnosis of progressive multifocal leukoencephalopathy (PML). PML is caused by:
1. JC virus which is a papovavirus
2. JC virus which is a parvovirus
3. HTLV1 virus which is a Rhabdovirus
4. HTLV2 virus which is a papovavirus
Ans. 1. JC virus which is a papovavirus

USMLE Case Scenario

A farmer developed a swelling in the inguinal region which later ulcerated. What stain can be used to detect bipolar stained
organisms?
1. Alberts stain
2. Waysons stain
3. Ziehl neelsen stain
4. Nigrosin stain
Ans. 2. Wayson stain

PATHOLOGY

Pathology

CELL INJURY/CELL DEATH

Terminology frequently asked in USMLE
Hypertrophy: Increased cell and organ size, often in response to increased workload; induced by mechanical stress and by growth
factors; occurs in tissues incapable of cell division
Hyperplasia: Increased cell numbers in response to hormones and other growth factors; occurs in tissues whose cells are able
to divide
Atrophy: Decreased cell and organ size, as a result of decreased nutrient supply or disuse; associated with decreased synthesis
and increased proteolytic breakdown of cellular organelles
Metaplasia: Change in phenotype of differentiated cells, often a response to chronic irritation that makes cells better able to
withstand the stress; usually induced by altered differentiation pathway of tissue stem cells; may result in reduced functions or
increased propensity for malignant transformation.

Different Cell Types: (Commonly asked)

Cell proliferation is regulated by cyclins that, when complexed with cyclin-dependent kinases, regulate the phosphorylation of
proteins involved in cell cycle progression leading to DNA replication and mitosis
The cell cycle is tightly regulated by stimulators and inhibitors, and contains intrinsic checkpoint controls to prevent replication of
abnormal cells
Tissues are divided into labile, stable and permanent, according to the proliferative capacity of their cells
Continuously dividing tissues (labile tissues) contain stem cells that differentiate to replenish lost cells and maintain tissue
homeostasis

High Yield USMLE Points

Labile cells
Stable cells
Permanent cells
Totipotent cells
Pleuropotent cells

Regenerate throughout life. (Surface Epithelial Cells, Stem cells, Blood Cells)
Replicate at low levels. (Hepatocytes, Proximal tubule Cells)
Dont Replicate (Neurons)
They can develop into any cell type, e.g. Germ cells
They are primitive cells and can develop into multiple cell types

Growth Factors
Growth Factors, Receptors and Signal Transduction Polypeptide growth factors act in autocrine, paracrine, or endocrine manner
Growth factors are produced transiently in response to an external stimulus and act by binding to cellular receptors
Different classes of growth factor receptors include receptors with intrinsic kinase activity, G-protein-coupled receptors and
receptors without intrinsic kinase activity
Growth factors such as EGF and HGF bind to receptors with intrinsic kinase activity, and trigger a cascade of phosphorylating
events through MAP kinases, which culminate in transcription factor activation and DNA replication
Cytokines generally bind to receptors without kinase activity; such receptors interact with cytoplasmic transcription factors that
move into the nucleus
Most growth factors have multiple effects, such as cell migration, differentiation, stimulation of angiogenesis and fibrogenesis in
addition to cell proliferation.

336

USMLE Step 1 Platinum Notes

Difference in Calcifications: (High Yield Topic)

Dystrophic calcification

Metastatic calcification

Occurs in Dying tissues

Occurs in Normal tissues

Serum calcium levels are usually Normal

Serum calcium levels are usually elevated

Seen in
Atherosclerosis
Damaged heart valves
Psammoma bodies

Seen in
Kidneys
Lungs
Gastric mucosa

An elevated calcium phosphate product, as in secondary hyperparathyroidism, can lead to nodules of metastatic calcinosis cutis,
which tend to be subcutaneous and periarticular. This form is often accompanied by calcification of muscular arteries and subsequent
ischemic necrosis (calciphylaxis).

Types of Infarcts
Red Infarct

Pale Infarct

Hemorraghic infarct

White Infarct

Seen in venous occlusion

Occurs in arterial occlusion

Area of infarct usually has double blood supply

Area of infarct usually has single blood supply

Seen in
Brain
Gut
Liver

Seen in
Kidney
Myocardium
Spleen

Septic Infarctions
Occur when bacterial vegetations from a heart valve embolize or when microbes seed an area of necrotic tissue. In these cases the
infarct is converted into an abscess, with a correspondingly greater inflammatory response.

INFLAMMATION
Positive Acute Phase Reactants
CRP
Mannose binding protein
Complement factors
Ferritin
Cerruloplasmin
Serum amyloid A
Haptoglobin
Alpha 1 antitrypsin
Alpha 2 macroglobulin

Negative Acute Phase Reactants

Albumin
Transferrin
Transthyretin
Transcortin
Retinol Binding Protein

Pathology

337

Types of Necrosis: (Very Important Topic)

Coagulation Necrosis

Liquefaction Necrosis

Fat Necrosis

Caseous Necrosis

Gangrenous Necrosis

Most Common Type

(Kerala 96)

Seen in Brain

Seen in adipose
Tissues

Combination of
Coagulation and
Liquefaction

Due to Ischemia
especially to Lower Limb

Severe ischemia Predisposes

Due to Hydrolytic
enzymes

Due to Lipases

Cottage cheese
appearance

Examples:
Thermal injury
Myocardial infarction
Tuberculosis

Bacterial infections

Acute Pancreatic
Necrosis
Trauma to Breast
Retroperitoneal fat

Seen in centre of
Tuberculous Lesions

More of coagulation leads

to Dry gangrene
More of Liquefaction
leads to Wet Gangrene

Reversible Cell Injury

Cellular swelling
Loss of microvilli
Formation of cytoplasmic blebs
ER swelling
Ribosomal detachment
Myelin figures
Clumping of nuclear chromatin

Irreversible Cell Injury

Flocculent, amorphous densities in mitochondria
Swelling and disruption of lysosomes
Plasma membrane damage
Nuclear changes:
Pyknosis (nuclear condensation)
Karryorex his (nuclear fragmentation)
Karyolysis (nuclear dissolution)

Mechanisms of Cell Injury

ATP depletion: Failure of energy-dependent functions reversible injury necrosis Mitochondrial damage: ATP
depletion failure of energy-dependent cellular functions ultimately, necrosis; under some conditions, leakage of
proteins that cause apoptosis
Influx of calcium: activation of enzymes that damage cellular components and may also trigger apoptosis
Accumulation of reactive oxygen species: covalent modification of cellular proteins, lipids, nucleic acids
Increased permeability of cellular membranes: may affect plasma membrane, lysosomal membranes, mitochondrial
membranes; typically culminates in necrosis. Accumulation of damaged DNA and misfolded proteins: triggers apoptosis.

USMLE Case Scenario

Earliest transient change following tissue injury will be:
1. Neutropenia
2. Neutrophilia
3. Monocytosis
4. Lymphocytosis
Ans. 2. Neutrophilia

338

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Oxygen dependent killing is done through:
1. NADPH oxidase
2. Superoxide dismutase
3. Catalase
4. Glutathione peroxidase
Ans. 1. NADPH oxidase

USMLE Case Scenario

Reactive oxygen intermediates are released by:
1. Catalase
2. NADPH oxidase
3. Glutathione peroxidase
4. Superoxide dismutase
Ans. 2. NADPH oxidase

USMLE Case Scenario

The epitheloid cell and multinucleated gaint cells of Granulomatous inflammation are derived from:
1. Basophils
2. Eosinophils
3. CD4-T lymphocytes
4. Monocytes Macrophages
Ans. 4. Monocytes Macrophages

USMLE Case Scenario

Degeneration of the basement membrane is mediated by:
1. Oxidases
2. Elastases
3. Hydroxylases
4. Metallo proteinase
5. Protease
Ans. 4. Metallo proteinase

USMLE Case Scenario

Most characteristic feature of acute inflammation is:
1. Vasoconstriction
2. Vascular stasis
3. Vasodilatation and Increased vascular permeability
4. Vasoconstriction and decreased vascular permeability
5. Margination of Leucocytes
Ans. 3. Vasodilatation and Increased vascular permeability

USMLE Case scenario

Most effective bactericidal system within phagocytes is:
1. Lysozyme mediated
2. Lactoferrin mediated
3. Reactive oxygen metabolite mediated
4. Cationic basic protein mediated
Ans. 3. Reactive oxygen metabolite mediated

Pathology

339

Apoptosis: (USMLE Favorite)

Regulated mechanism of cell death that serves to eliminate unwanted and irreparably damaged cells, with the least
possible host reaction
Characterized by: enzymatic degradation of proteins and DNA, initiated by caspases; and recognition and removal of dead
cells by phagocytes
Initiated by two major pathways:
1. Mitochondrial (intrinsic) pathway is triggered by loss of survival signals, DNA damage and accumulation of misfolded
proteins (ER stress); associated with leakage of pro-apoptotic proteins from mitochondrial membrane into the cytoplasm,
where they trigger caspase activation; inhibited by anti-apoptotic members of the Bcl family, which are induced by survival
signals including growth factors
2. Death receptor (extrinsic) pathway is responsible for elimination of self-reactive lymphocytes and damage by cytotoxic
T-lymphocytes; is initiated by engagement of death receptors (members of the TNF receptor family) by ligands on adjacent
cells.

Nutshell of Programmed Cell Death

Lack of Inflammation
Cell shrinkage
Condensation of nuclear chromatin followed by fragmentation
Intranucleosomal cleavage of DNA is characteristic
Formation of cytoplasmic/Membrane blebs
Cytoplasmic chromophilia is a feature
Apoptotic bodies
bcl2 inhibits Phagocytosis
p53 stimulates phagocytosis

Proapoptotic Factors

Apaf 1
Cytochrome C
AIF
p53
Caspaces
TNFRI
FAS (CD 95)

Apoptosis inhibiting gene is: bcl2

Detection of Apoptosis is by:
DNA fragmentation analysis
Capsase activity assays
Annexin V Assay
Propium Iodide assay

USMLE Case Scenario

Which of the following organelles plays a pivotal role in Apoptosis:
1. Mitochondria
2. Endoplasmic Reticulum
3. Nucleus
4. Golgi Apparatus
Ans. 1. Mitochondria

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USMLE Step 1 Platinum Notes

USMLE Case Scenario

Caspases are involved in:
1. Cell division
2. Necrosis
3. Apoptosis
4. Inflammation
Ans. 3. Apoptosis

USMLE Case Scenario

Irreversible cell injury is indicated by:
1. Accumulation of calcium in mitochondria
2. Myelin figures
3. ATP depletion
4. Shifting of ribosomes
Ans. 1. Accumulation of calcium in mitochondria

USMLE Case Scenario

Wound contraction is mediated by:
1. Myofibroblasts
2. Epithelial cells
3. Collagen
4. Elastin
Ans. 1. Myofibroblasts

USMLE Case Scenario

Gene inhibiting apoptosis is:
1. bcl2
2. p53
3. ras
4. n-myc
Ans. 1. bcl2

Systemic Effects of Inflammation

Fever: cytokines (TNF, IL-1) stimulate production of prostaglandins in hypothalamus
Production of acute-phase proteins: C-reactive protein, others; synthesis stimulated by cytokines (IL-6, others) acting on
liver cells
Leukocytosis: cytokines (colony-stimulating factors) stimulate production of leukocytes from precursors in the bone
marrow
In some severe infections, septic shock: fall in blood pressure, disseminated intravascular coagulation, metabolic
abnormalities; induced by high levels of TNF.

Sepsis, Severe Sepsis, Septic Shock, Systemic Inflammatory Response Syndrome (SIRS)
The hosts reaction to invading microbes involves a rapidly amplifying polyphony of signals and responses that may spread beyond
the invaded tissue. Fever or hypothermia, tachypnea, and tachycardia often herald the onset of sepsis.
The systemic response to microbial invasion. When counter regulatory control mechanisms are overwhelmed, homeostasis may fail,
and dysfunction of major organs may supervene (severe sepsis).

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Further regulatory imbalance leads to septic shock, which is characterized by hypotension as well as organ dysfunction. As sepsis
progresses to septic shock, the risk of dying increases substantially. Sepsis is usually reversible, whereas patients with septic shock
often succumb despite aggressive therapy.
Systemic inflammatory response syndrome (SIRS):
Temp > 38C or < 36C
HR > 90 bpm
RR > 20 breaths/min
WBC > 12000 cells/mm3 or < 4000 cells/mm3

Monocytes-Macrophages: (USMLE Favorite)

Monocytes arise from precursor cells within bone marrow and circulate with a half-life ranging from 1 to 3 days
Common locations where tissue macrophages (and certain of their specialized forms) are found are lymph node, spleen, bone
marrow, perivascular connective tissue, serous cavities such as the peritoneum, pleura, skin connective tissue, lung (alveolar
macrophage),
Liver (Kupffer cell)
Bone (osteoclast)
Central nervous system (microglia)
And synovium (type A lining cell)

Specific Cell Types

Lymphocytes are the mediators of adaptive immunity and the only cells that produce specific and diverse receptors for antigens
T (Thymus-derived) lymphocytes express antigen receptors called T cell receptors (TCRs) that recognize peptide fragments of
protein antigens that are displayed by MHC molecules on the surface of antigen-presenting cells
B (Bone marrow-derived) lymphocytes express membrane-bound antibodies that recognize a wide variety of antigens. B cells
are activated to become plasma cells, which secrete antibodies
Natural killer (NK) cells kill cells that are infected by some microbes, or are stressed and damaged beyond repair. NK cells express
inhibitory receptors that recognize MHC molecules that are normally expressed on healthy cells, and are thus prevented from
killing normal cells
Antigen-presenting cells (APCs) capture microbes and other antigens, transport them to lymphoid organs, and display them
for recognition by lymphocytes. The most efficient APCs are dendritic cells, which live in epithelia and most tissues. The cells of
the immune system are organized in tissues, some of which are the sites of production of mature lymphocytes (the generative
lymphoid organs, the bone marrow and thymus), and others are the sites of immune responses (the peripheral lymphoid organs,
including lymph nodes, spleen, and mucosal lymphoid tissues).

Types of immunity

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USMLE Step 1 Platinum Notes

Dendritic/Langerhans Cells

Dendritic/Langerhans cells are bone marrow-derived

They generally lack the standard T, B, NK, and monocyte cell markers but do express CD83
CD 1 is the marker
Dendritic cells are referred to as Langerhans cells when they are present in the skin and beneath the mucosal surface.

Mediators of Shock
Clinical finding

Mediator

Fever

Interleukin 1

Hypotension

Bradykinin, Nitric Oxide

Inflammation

C3a, C5a

DIC

Hageman Factor

Remember Bradykinin also causes pain, Vasodilation and cough

CVC Lungs: Brown induration of lungs
CVC Liver: Nut meg liver
CVC Spleen: Gamma Gandy bodies

Cytokines
Cytokines are soluble proteins produced by a wide variety of hematopoietic and nonhematopoietic cell types
Cytokines are involved in the regulation of the growth, development, and activation of immune system cells and in the mediation of
the inflammatory response
Immunoregulatory cytokines involved in the activation, growth, and differentiation of lymphocytes and monocytes, e.g. IL-2,
IL-4, IL-10 and transforming growth factor (TGF)
Proinflammatory cytokines produced predominantly by mononuclear phagocytes in response to infectious agents (e.g. IL1, TNF- and IL-6) and the chemokine family of inflammatory cytokines, within which are included IL-8, monocyte chemotactic
protein (MCP)-1, MCP-2, MCP-3, macrophage inflammatory protein and regulation-upon-activation, normal T expressed and
secreted (RANTES)
Cytokines that regulate immature leukocyte growth and differentiation, e.g. IL-3, IL-7, and GM-CSF.

Prostaglandins: (USMLE Favorite)

LTA4:
Produced in leucocytes, platelets, mast cells, vascular tissue
LTC4, LTD4, LTE4:
Contraction of smooth muscle
Bronchoconstriction
Vasoconstriction
vascular permeability
Components of SRSA
LTB4:
Chemotaxis
Adhesion of WBC
Release of lysosomal enzymes
Thromboxanes:
Produced mainly in platelets
Promotes platelet aggregation

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343

Vasoconstriction
Smooth muscle contraction
Prostacyclins:
Produced by endothelium of vessels
Vasodilation
Inhibits platelet aggregation
Cortisol inhibits Phospholipase A2
Aspirin, Indomethacin, Phenylbutazone inhibit Both COX 1 and COX 2
Coxibs are selective COX 2 inhibitors (Celecoxib)

USMLE Case Scenario

Which of the following cells play a crucial role in the pathogenesis of alveolar-capillary damage in adults respiratory distress
syndrome (ARDS)?
1. Basophils
2. CD4-positive lymphocytes
3. CD8-positive lymphocytes
4. Eosinophils
5. Mast cells
6. Neutrophils
Ans. 6. Neutrophils
Neutrophils release chemokines that attract histiocytes and produce oxygen radicals, prostaglandins, and proteases that damage
alveolar epithelium. Formation of hyaline membranes is due to a combination of plasma fluid extravasation and alveolar cell necrosis.

Procoagulant States

Factor V (Leidein mutation)

Protein C deficiency
Protein S deficiency
Homocystenemia
Antiphospholipid antibody

Thrombus Development
Depends on the relative contribution of the components of Virchows triad:
Endothelial injury (e.g. by toxins, hypertension, inflammation, or metabolic products)
Abnormal blood flow stasis or turbulence (e.g. due to aneurysms, atherosclerotic plaque)
Hypercoagulability, which can be either primary (e.g. factor V Leiden, increased prothrombin synthesis, antithrombin III
deficiency) or secondary (e.g. bed rest, tissue damage, malignancy)
Thrombi may propagate, resolve, become organized, or embolize. Thrombosis causes tissue injury by local vascular occlusion or by
distal embolization.

Anticoagulant Factors

Antithrombin III
Protein C
Protein S
Prostacyclin
Nitric oxide

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USMLE Step 1 Platinum Notes

Hyperviscosity
Multiple myeloma
Cryoglobinemia
Myeloproliferative disorders

Remember: Virchows Triad

Endothelial injury
Alteration in blood flow
Hypercoagulability

Stains
Von kossa: calcium
Toluidine blue: mast cells
Alician blue: mucins
Congo red: amyloid
Masons trichome: collagen, connective tissue
Orcein: elastic fibers

USMLE Case Scenario

Which one of the following stains is specific for Amyloid?
1. Periodic Acid schif (PAS)
2. Alzerian red
3. Congo red
4. Von-Kossa
Ans. 3 Congo red

Major Histocompatibility Complex

The human major histocompatibility complex (MHC), commonly called the human leukocyte antigen (HLA) complex, is a 4-megabase
(Mb) region on chromosome 6
Class I MHC
They are glycoproteins
Present on surface of all nucleated cells
Presents antigen to CD 8 positive cells
Have only one chain encoded by MHC locus
Antigen binding site on MHC I is proximal end of alpha subunit of one and two
Class II MHC
They are glycoproteins present on the surface of Macrophages, B cells, dendritic cells of spleen and Langerhans cells
Presents antigen to CD 4 positive cells
Not Present on surface of nucleated cells
Have both chains encoded by MHC locus

Important HLA Associations: (Frequently asked)

A3 Hemachromatosis
B5 Behcets Disease
B 27 Ankylosing Spondylitis, Rieters Syndrome, Psoriatic Arthritis

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345

DR 2 Multiple Sclerosis, Narcolepsy

DR 3 Dermatitis Herpetiformis, Sjogrens Syndrome, Myasthenia Gravis, Iddm
DR 4 Iddm, Rheumatoid Arthritis
DR 5 Pernicious Anemia
DR 7 Coeliac Disease

HLA B-27 associations

USMLE Case Scenario

Rheumatoid arthritis is characterized by Rheumatoid nodules which develop in 20 to 30 percent of patients, usually on or
around joints, on extensor surfaces, or on other areas subjected to mechanical trauma. The most important HLA association
is with:
1. HLA-DR2
2. HLA-DR3
3. HLA-DR4
4. HLA B 27
Ans. 3. HLA-DR4

USMLE Case Scenario

A 24-year-old man presented to an ophthalmologist with a severe painful left eye for 38 hours. There is redness around the
cornea which developed into a iritis. Three days later the right eye also became involved. One week after the onset of the eye
symptoms, the patient complained of dysuria. No chlamydia, viruses or bacteria were isolated from this discharge. He was
treated with oxytetracycline and his eye signs gradually cleared. At about this time, however, his right first metatarsophalangeal
joint became inflamed and, subsequently, several joints were similarly involved. He was found to be HLA-B27-positive. Most
likely diagnosis would be:
1. Behcets Disease
2. Ankylosing Spondylitis
3. Reiters Disease
4. Gonococcal arthritis
5. Rheumatoid arthritis
6. Gouty Arthritis
Ans. 3. Reiters Disease

Natural Killer Cells

Are part of innate immunity
Are large granular lymphocytes
Lack T cell receptor, surface IgM and IgD

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USMLE Step 1 Platinum Notes

Express CD 16 and CD 56
The classic NK cells are CD2+, CD3+, CD4+, CD56+, and CD16+
Thymus is not required for their development
Activity not enhanced by prior sensitization. NK cells do not require sensitization to express the killer function
NK cells constitute 2 to 10% of normal peripheral blood lymphocytes
Contain Azurophilic granules
Kill virus infected cells and cancer cells
Kill by producing perforins, granzymes

Killing is non specific

NK cells are not MHC-restrictedthey will kill certain autologous, allogeneic, and even xenogeneic tumor cells whether or not
these targets express MHC
NK cells do not use the TCR, CD3 complex to recognize target cells
Killing is not dependent on foreign antigen presentation. (MHC Independent)

Graft Rejection
The graft rejection response is initiated mainly by host T cells that recognize the foreign HLA antigens of the graft, either directly (on
APCs in the graft) or indirectly (after uptake and presentation by host APCs)
Types and mechanisms of rejection:
Hyperacute rejection. Preformed antidonor antibodies bind to graft endothelium immediately after transplantation, leading to
thrombosis, ischemic damage, and rapid graft failure
Acute cellular rejection. T-cells destroy graft parenchyma by cytotoxicity and DTH reaction
Acute vascular rejection. T-cells and antibodies damage graft vasculature
Chronic rejection. Dominated by arteriosclerosis, this type is probably caused by T-cell reaction and secretion of cytokines that
induce proliferation of vascular smooth muscle cells, associated with parenchymal fibrosis.

Molecular Basis of Carcinogenesis

Self-sufficiency in growth signals

Insensitivity to growth-inhibitory signals
Evasion of apoptosis
Limitless replicative potential, (i.e. overcoming cellular senescence and avoiding mitotic catastrophe)
Development of sustained angiogenesis
Ability to invade and metastasize
Genomic instability resulting from defects in DNA repair

Oncogenes that Promote Unregulated Proliferation (Self-sufficiency in Growth Signals)

Proto-oncogenes: normal cellular genes whose products promote cell proliferation
Oncogenes: mutant versions of proto-oncogenes that function autonomously without a requirement for normal growthpromoting signals.

Insensitivity to Growth-Inhibitory Signals

Tumor suppressor genes encode proteins that inhibit cellular proliferation by regulating the cell cycle. Unlike oncogenes,
both copies of the gene must be lost for tumor development, leading to loss of heterozygosity at the gene locus. In cases
with familial predisposition to develop tumors, the affected individuals inherit one defective (nonfunctional) copy of a tumor
suppressor gene and lose the second one through somatic mutation. In sporadic cases both copies are lost through somatic
mutations.

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347

USMLE Case Scenario

An example of a tumor suppressor gene is:
1. myc
2. fos
3. ras
4. Rb
Ans. 4. Rb

Oncogenic Organisms
HPV has been associated with benign warts, as well as cervical cancer.The oncogenic ability of HPV is related to the expression of
two viral oncoproteins, E6 and E7; they bind to RB and p53, respectively, neutralizing their function; they also activate cyclins
E6 and E7 from high-risk HPV (that give rise to cancers) have higher affinity for their targets than E6 and E7 from low-risk HPV (that give
rise to low-grade tumors).
EBV has been implicated in the pathogenesis of Burkitt lymphomas, lymphomas in immunosuppressed individuals with
HIV infection or organ transplantation, some forms of Hodgkin lymphoma, and nasopharyngeal carcinoma. All except the
nasopharyngeal cancers are B-cell tumors.
The oncogenic effects of HBV and HCV are multifactorial, but the dominant effect seems to be immunologically mediated chronic
inflammation, hepatocellular injury, stimulation of hepatocyte proliferation, and production of reactive oxygen species that can
damage DNA. The HBx protein of HBV and the HCV core protein can activate a variety of signal transduction pathways that may
also contribute to carcinogenesis.
H pylori infection has been implicated in both gastric adenocarcinoma and MALT lymphoma. The mechanism of H pylori-induced
gastric cancers is multifactorial, including immunologically mediated chronic inflammation, stimulation of gastric cell proliferation,
and production of reactive oxygen species that damage DNA. H pylori pathogenicity genes, such as CagA, may also contribute by
stimulating growth factor pathways. It is thought that H pylori infection leads to polyclonal B-cell proliferations and that eventually a
monoclonal B-cell tumor (MALT lymphoma) emerges as a result of accumulation of mutations.

Important Translocations: (USMLE Favorite)

t(8;14) Burkitts Lymphoma
t(9;22) CML
t(15;17) AML
t(11;22) Ewings sarcoma
t(X;18) Synovial cell Ca

USMLE Case Scenario

A sarcoma appears like a malignant melanoma, which arises in the soft tissue. It usually is found on the tendons of extremities
of young patients. Histologically, the cells can have pigment or clear cytoplasm. It is associated with t(12,22). The sarcoma is:
1. Synovial cell sarcoma
2. Clear Cell sarcoma
3. Leiomyosarcoma
4. Rhabdomyosarcoma
Ans. 2. Clear Cell sarcoma
Burkitts Lympohoma is associated with:
1. t (8:14)
2. t (11:14)
3. t (15:17)
4. t (14:18)
Ans. 1. t (8:14)

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USMLE Step 1 Platinum Notes

Atrophy: Decreae in cell size/function

Hypertrophy: Increase in cell size/function
Hyperplasia: Increase in number of cells in tissues/organs
Metaplasia: Reversible change of epithelial transformation
Anaplasia: Hallmark of malignant transformation
Dysplasia: Reversible abnormal proliferation of cells. Intact basement membrane

Premalignant forms of SCC: (USMLE Favorite)

Actinic keratosis, or solar keratoses

Actinic cheilitis
Bowens disease
Erythroplasia of Queyrat
DLE
Xeroderma Pigmentosa
UV Radiation UV B
Hypertrophic lichen planus

Actinic keratoses and cheilitis are hyperkeratotic papules and plaques that occur on sun-exposed areas. While the potential for
malignant degeneration is low in any individual lesion, the risk of SCC increases with larger numbers of lesions
Bowens disease presents as a scaling, erythematous plaque, which may develop into invasive SCC in up to 20% of cases. Treatment
of premalignant and in situ lesions reduces the subsequent risk of invasive disease.

The following oral lesions are Premalignant Lesions

Leucoplakia
Erythroplakia
Chronic hyperplastic candidiasis
Oral submucous fibrosis
Syphilitic glossitis
Sideropenic dysphagia
Cancer Type Environmental Risk Factor
Lung: Smoking, Asbestos, Nickel, Radon, Coal, Arsenic, Chromium, Uranium
Mesothilioma: Asbestos
Bladder Ca: Smoking, Aniline dyes, Schistomiasis
Skin Ca: UV light exposure, coal, Tar, Arsenic
Liver: Alcohol, Vinyl chloride, Aflatoxins
Pancreas: Smoking
Renal Cell Carcinoma: Smoking
Stomach: Alcohol, Nitrosamines

Chemical Carcinogens
Chemical carcinogens have highly reactive eletrophile groups that directly damage DNA, leading to mutations and eventually
cancer
Direct-acting agents do not require metabolic conversion to become carcinogenic, while indirect-acting agents are not active until
converted to an ultimate carcinogen by endogenous metabolic pathways.

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349

Hence polymorphisms of endogenous enzymes like cytochrome P-450 may influence carcinogenesis. Following exposure of a
cell to a mutagen or an initiator; tumorigenesis can be enhanced by exposure to promoters, which stimulate proliferation of the
mutated cells
Examples of human carcinogens include direct-acting (e.g. alkylating agents used for chemotherapy), indirect-acting (e.g.
benzopyrene, azo dyes, and aflatoxin), and promoters/agents that cause pathologic hyperplasias of liver, endometrium.

Immune Surveillance
Tumor cells can be recognized by the immune system as nonself and destroyed. Antitumor activity is mediated by
predominantly cell-mediated mechanisms. Tumor antigens are presented on the cell surface by MHC class I molecules and are
recognized by CD8+ CTLs
The different classes of tumor antigens include products of mutated proto-oncogenes, tumor suppressor genes, overexpressed or
aberrantly expressed proteins, tumor antigens produced by oncogenic viruses, oncofetal antigens, altered glycolipids and glycoproteins,
and cell type-specific differentiation antigens. Immunosuppressed patients have an increased risk of cancer. In immunocompetent
patients, tumors may avoid the immune system by several mechanisms, including selective outgrowth of antigennegative variants,
loss or reduced expression of histocompatibility antigens, and immunosuppression mediated by secretion of factors (e.g. TGF-) from
the tumor.

Hereditary DNA Repair Disorders: (USMLE Favorite)

Xeroderma pigmentosum:
Hypersensitivity to sunlight/UV, resulting in increased skin cancer
Incidence and premature aging
Cockayne syndrome:
Hypersensitivity to UV and chemical agents
Trichothiodystrophy:
Sensitive skin, brittle hair and nails
Werners syndrome:
Premature aging and retarded growth
Blooms syndrome:
Sunlight hypersensitivity, high incidence of malignancies (especially leukemias)
Ataxia telangiectasia:
Sensitivity to ionizing radiation and some chemical agents.
All of the above diseases are often called segmental progerias (accelerated aging diseases) because their victims appear elderly
and suffer from aging-related diseases at an abnormally young age
Other diseases associated with reduced DNA repair function include:
Fanconis anemia
Hereditary breast cancer and
Hereditary colon cancer

Important Tumor Markers

Alpha fetoprotein

Hepato cellular carcinoma

Endodermal sinus tumor

PSA

Prostate cancer

Neuron specific enolase

Small cell lung cancer, Neuroblastoma

LDH

Lymphoma

Cathecolamines

Pheochromocytoma

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USMLE Step 1 Platinum Notes

Beta 2 microglobulin

Multiple Myeloma
Lymphoma

Gastrin

Pancreatic neuroendocrine tumors

Bladder Tumor Antigen

Bladder Tumor, UTI, Renal Calculi

CA 27.29

Breast Cancer

CA 72.4

Ovarian and Pancreatic Cancer

LASA P (Lipid Associated Sialic Acid)

Ovarian Cancer

Keratin

Ca cervix

NMP 22

Bladder Cancer

HCG

Gestational Trophoblastic Disorders

CA 125

Ovarian Cancer

Placental Alkaline Phosphatase

Seminoma

S100

Melanoma, Neural Tumors

APUD omas: (CAPITALS)

C- Carcinoid tumor
A- Adrenal pheochromocytoma
P- Pancreatic endocrine tumors
I- Islet-cell tumor
T- Thyroid medullary carcinoma
A- Additional: Ganglioblastoma, neuroblastoma, paragangliomas
L- Lung: Small-cell carcinoma
S- Skin: Melanoma

USMLE Case Scenario

Serous papillary cystadenocarcinomas of the ovaries express:
1. CA-125
2. CA-19
3. CEA
4. AFP
Ans. 1. CA-125

USMLE Case Scenario

A 25-year-old man has a testicular mass, which on orchiectomy shows a malignant tumor with yolk sac differentiation. Which
of the following tumor markers would probably be most useful in monitoring the patient for recurrent or metastatic disease?
1. Alpha-fetoprotein
2. Carcinoembryonic antigen (CEA)
3. Prostate-specific antigen (PSA)
4. S-100
Ans. 1. Alpha-fetoprotein
Serum alpha-fetoprotein is a fetal serum protein produced by the yolk sac and liver. Increased serum levels in adults are seen
in tumors (hepatocellular carcinoma, neuroblastomas and teratoma) and acute hepatitis and colitis. In patients with tumors,
serum levels often correlate with tumor size. Resection is usually associated with a fall in serum levels. Serum levels are useful
in assessing response to treatment.

Pathology

Mesenchymal Tumors
Endothelial tumors
Melanoma
Fibrohistiocytic tumors
Muscle tumors

HYPERSENSITIVITY REACTIONS: (USMLE FAVORITE)

Type I Hypersensitivity reactions: IgE Mediated
Theobald phenomenon
Prusnitz reaction (PK)
Casonis Test
Anaphylaxis
Local: Asthma, Hay fever, Angioedema, Eczema, Urticaria

Type II Hypersensitivity reactions: IgG or IgM Mediated

Graves disease (ALSO TYPE V)
Goodpastures Syndrome
Myasthenia Gravis
Blood transfusion reactions
Immune hemolytic anemia
Immune Thrombocytopenic purpura

Type III Hypersensitivity Reactions: Immune Complex Mediated

Arthus reaction
Serum Sickness
SLE
Schiks test
Post Streptococcal Glomerulonephritis

Type IV Hypersensitivity Reactions: Delayed Hypersensitivity

Tuberculin test
Lepromin Test
Contact dermatitis
Pernicious anemia

Immune-Complex-Dependent Reactions/Serum Sickness

Serum sickness is produced by circulating immune complexes and is characterized by:
Fever
Arthritis
Nephritis
Neuritis
Edema, and an Urticarial, papular, or purpuric rash
Serum sickness was first described following administration of foreign sera, but drugs are now the usual cause

351

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USMLE Step 1 Platinum Notes

TYPE III hypersensitivity reaction

Drugs that produce serum sickness include the
Penicillins
Sulfonamides
Thiouracils
Cholecystographic dyes
Phenytoin, aminosalicylic acid
Heparin and antilymphocyte globulin
In classic serum sickness, symptoms develop 6 days or more after exposure to a drug, the latent period representing the time
needed to synthesize antibody. The antibodies responsible for immune-complex-dependent drug reactions are largely of the IgG
or IgM class
Vasculitis, may also be a result of immune complex deposition.

Collagen
Collagen is the main protein of connective tissue in animals and
The most abundant protein in mammals, making up about 25 to 35% of the whole-body protein content
In muscle tissue it serves as a major component of Endomysiun.
Type I
This is the most abundant collagen of the human body
It is present in scar tissue, the end product when tissue heals by repair. It is found in
Tendons
Skin
Artery walls
The endomysium of myofibrils
Fibrocartilage and the organic part of bones and teeth.
Type II
Hyaline cartilage makes up 50% of all cartilage protein
Vitreous humor of the eye.
Type III
This is the collagen of granulation tissue, and is produced quickly by young fibroblasts before the tougher type I collagen is synthesized.
Also found in:
Artery walls
Skin
Intestines and the
Uterus
Reticular fiber.
Type IV
Present in
Basal lamina
Eye lens
Filtration system in capillaries and the
Glomeruli of nephron in the kidney.

Amyloidosis: (USMLE Favorite)

Amyloidosis is a disorder characterized by the extracellular deposits of misfolded proteins that aggregate to form insoluble
fibrils. The deposition of these proteins may result from: excessive production of proteins that are prone to misfolding and
aggregation; mutations that produce proteins that cannot fold properly and tend to aggregate; defective or incomplete
proteolytic degradation of extracellular proteins
Amyloidosis maybe localized or systemic.

Pathology

Remember the type of Amyloidosis and the Protein type associated

Type of Amyloidosis

Amyloid protein

Primary Amyloidosis, Myeloma

AL

Secondary Amyloidosis
Tuberculosis
Rheumatoid arthritis
Hodgkins lymphoma

AA

Familial Medittarean Fever

AA

Hemodialysis associated Amyloidosis

A2M

Cerebral (Alzhiemers) Amyloidosis

Cardiac Amyloidosis

ATTR

Amyloidosis is deposition of an extracellular protein

Individual subunits form pleated sheets.
Kidney followed by liver is the commonest sites involved
Deposits stain red with Congo red
Apple green birefrigerence is seen on Congo red stain under polarized light
Amyloid is composed of fibrillary protein, amyloid P Component and Glycosaminoglycans
Thyroid cancer with amyloid stroma: MTC (Medullary ca thyroid)
Rectal biopsy is the best diagnostic method.

On light microscopy: Eosinophilic amorphous substance

Congo red in ordinary light: Pink color
Congo red on polarizing microscope: Yellow green birefringence
Electron microscopy: Nonbranching fibrils
X-ray crystallography: Crossed pleated configuration

Pathology and Genetics: (USMLE Favorite)

The following conditions are inherited as
Asked innumerable times in
Autosomal Dominant

Autosomal Recessive

Huntingtons disease
Marfans syndrome
Adult polycystic kidney disease
Familial hypercholestremia
Osteogenesis imperfecta
Neurofibromatosis
Achondroplasia
Myotonic dystrophy
Von Willebrands disease
HNPCC
BRCA1, BRCA2 Breast cancer
Otosclerosis
Tuberous sclerosis
MC group of mendelian disorders

Cystic fibrosis
Ataxia telengectasia
Freidrechs ataxia
Infantile polycystic kidney disease
Wilsons disease
Alkaptonuria
Hemochromatosis
Sickle cell anemia
phenyl ketonuria
beta thalessemia
alpha 1 antitrypsin deficency

X-linked recessive
Becker
Colour blindness
Duchenne muscular dystrophy
Fabrys disease
G6PD deficiency
Hemophilia A, B
Hunters disease
Lesch-Nyhan syndrome
Nephrogenic diabetes insipidus
Ocular albinism
Retinitis pigmentosa
Testicular feminization syndrome
Wiskott-Aldrich syndrome
Color blindness
Affects males more

353

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USMLE Step 1 Platinum Notes

Autosomal Dominant Traits

Are fully manifest in the presence of a gene in the heterozygous state, i.e. when only one abnormal gene (mutant allele) is present and
the corresponding partner allele on the homologous chromosome is normal. The following features are characteristic:
Each affected individual has an affected parent (unless the condition arose by a new mutation in a germ cell that formed
the individual);
An affected individual usually bears an equal number of affected and unaffected offspring;
Males and females are affected in equal numbers;
Each gender can transmit the trait to male and female;
Normal children of an affected individual have only normal off spring;
When the trait does not impair viability or reproductive capacity, vertical transmission of the trait occurs through
successive generations. Three or more generations of male-to-male transmission argues against X-linkage of a rare gene.

Autosomal Recessive Traits

Autosomal recessive conditions are clinically apparent only in the homozygous state, i.e. when both alleles at a particular
genetic locus are mutant alleles. The following features are characteristic:
The parents are clinically normal
Only siblings are affected
Males and females are affected in equal proportions
If an affected individual marries a homozygous normal person, none of the children is affected but all are heterozygous carriers
If an affected individual marries a heterozygous carrier, one half of the children are affected, and the pedigree pattern superficially
suggests a dominant trait
If two individuals who are homozygous for the same mutant gene marry, all of their children are affected
If both parents are heterozygous at the same genetic locus, one fourth of their children are homozygous affected, on average one
fourth are homozygous normal, and one half are heterozygous carriers of the same mutant gene; and
The less frequent the mutant gene is in the population, the greater the likelihood that the affected individual is the product of
consanguineous parents.

X-Linked Recessive Traits

Diseases or traits that result from genes located on the X chromosome are termed X-linked. Because the female has two
X chromosomes, she maybe either heterozygous or homozygous for the mutant gene, and the trait may exhibit recessive or
dominant expression. The terms X-linked dominant and X-linked recessive refer only to expression of the trait in females. The
male has only one X chromosome and therefore is hemizygous for X-linked traits. Males can be expected to express X-linked traits
regardless of their recessive or dominant behavior in the female. This accounts for the large numbers of X-linked diseases.
Males transmit their X chromosome to all of their daughters, making them all obligate carriers of an X-linked disease trait
Affected males do not transmit an X chromosome to their sons; thus, an important feature of X-linked inheritance is the
absence of male-to-male transmission.

X-Linked Dominant Traits

This mode of inheritance is uncommon. Its characteristic features are as follows:
Females are affected about twice as often as males;
Heterozygous females transmit the trait to both genders with a frequency of 50%;
Hemizygous affected males transmit the trait to all of their daughters and none of their sons; and
The expression is more variable and generally less severe in heterozygous females than in hemizygous affected males. Examples
of X-linked dominant inheritance include the vitamin D-resistant (hypophosphatemic) rickets and pseudohypoparathyroidism.

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USMLE Case Scenario

The BRCA-1 gene associated with breast cancer and ovarian cancer, is located on:
1. 17q
2. 17 p
3. 22q
4. 18q
Ans. 1. 17q
The NF-1 gene is, associated with neurofibromatosis type I, is on 17q
The NF-2 gene associated with neurofibromatosis type II, is on 22q
The p53 gene associated with many cancers, is on 17p
The DCC oncogene located on the long arm of chromosome 18q

USMLE Case Scenario

Ophthalmoscopic examination of a 7-year-old child from Washington DC demonstrates a retinal angioma. This finding should
raise the possibility of which of the following syndromes?
1. Neurofibromatosis type I
2. Neurofibromatosis type II
3. Tuberous sclerosis
4. von Hippel-Lindau disease
Ans. 4. von Hippel-Lindau disease

USMLE Case Scenario

Subependymal giant cell astrocytoma is a peculiar astrocytic tumor that grows from the walls of the lateral ventricles. It is
caused by mutations of TS1 or TS2 genes. It is usually seen in:
1. von Hippel-Lindau syndrome
2. Neurofibromatosis 1
3. Neurofibromatosis 2
4. Tuberous Sclerosis
Ans. 4. Tuberous Sclerosis

USMLE Case Scenario

Kinky hair disease is a disorder where an affected child has peculiar white stubby hair, does not grow, brain degenration is
seen and dies by age of two years. A lady is hesitant about having children because her two sisters had sons who had died
from kinky hair disease. Her mothers brother also died of the same condition. Which of the following is the possible mode of
inheritence in her family?
1. X-linked recessive
2. X-linked dominant
3. Autosomal recessive
4. Autosomal dominant
Ans. 1. X-linked recessive

USMLE Case Scenario

The chances of having an unaffected baby, when both parents have achondroplasia, are:
1. 0%
2. 25%
3. 50%
4. 100%
Ans. 2. 25%

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USMLE Step 1 Platinum Notes

X-Linked Dominant
Hypophosphatemic type of vitamin D resistant rickets
Incontenentia pigmentii
Orofaciodigital syndrome
Hereditary spherocytosis is AD
Achondroplasia is AD
Familial hypercholestrelemia is AD
Retinoblastoma is AD
von Villebrands disease is AD
Homocystinuria is AR

Y-Linked Disorders
Only a few genes are known on the Y chromosome
One such gene, the sex-region determining Y factor (SRY), or testis-determining factor (TDF), is crucial for normal male
development
Men with oligospermia/azoospermia frequently have microdeletions on the long arm of the Y chromosome that involve one or
more of the azoospermia factor (AZF) genes.

Trinucleotide Repeat Disorders

A number of diseases are caused by a mutation that is an expansion of a repetitive sequence of three nucleotides
which is genetically unstable
When repeat length increases from one generation to the next, disease manifestations may worsen or be observed atan earlier
age; this phenomenon is referred to as anticipation
Conditions Include:
Huntingtons disease
Myotonic dystrophy
Fragile X Syndrome
Kennedys Syndrome
Some forms of Spino cerebellar Ataxia
Huntingtons disease is transmitted in an autosomal dominant fashion. The age at which the patient becomes symptomatic
is variable and has no effect on the probability of transmitting the disease. The defect underlying this degenerative disease
is an abnormal expansion of a region of chromosome 4 containing a triplicate repeat (CAG) sequence. Normal individuals
have between 6 and 34 copies of this CAG section; patients with Huntingtons disease may have from 37 to more than 100
repeats. Once expanded beyond 40 copies, the repeats are unstable and may further increase as they are passed on from one
generation to the next. An increased number of repeats leads to a phenomenon known as anticipation, by which successive
generations have earlier disease onset.

Fragile X-Syndrome: (USMLE Favorite)

Pathologic amplification of trinucleotide repeats causes loss-of-function (fragile X-syndrome) or gain-of-function mutations
(Huntington disease). Most such mutations produce neurodegenerative disorders. Fragile X-syndrome results from loss of
FMR1 gene function and is characterized by mental retardation, macroorchidism, and abnormal facial features. In the normal
population there are about 29 CGG repeats in the FMR1 gene. Carrier males and females carry permutations with 52 to 200
CGG repeats that can expand to 4000 repeats (full mutations) during oogenesis. When full mutations are transmitted to
progeny, fragile X-syndrome occurs.

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Genomic Imprinting
Imprinting involves transcriptional silencing of the paternal or maternal copies of certain genes during gametogenesis. For such genes
only one functional copy exists in the individual. Loss of the functional allele (not imprinted) by deletions gives rise to diseases
Prader-Willi syndrome results from deletion of paternal chromosome 15q12 and is characterized by mental retardation, short stature,
hypotonia, obesity and hypogonadism
Angelman syndrome results from deletion of maternal chromosome 15q12 and is characterized by mental retardation, ataxia,
seizures and inappropriate laughter.

Mitochondrial DNA/Mitochondriopathies: (USMLE Favorite)

Mutation rate about ten times greater than nuclear DNA
This is because there are no introns and a mutation invariably strikes a coding sequence (axon)
Tissues with greatest ATP requirement (CNS, Skeletal muscle, Heart muscle, Kidney, Liver) are most affected
Mitochondrial DNA is maternally inherited because mitochondria from sperms do not enter the fertilized egg
Mitochondrial DNA is Closed and circular and 16.5 kb in length
MELAS (Mitochondrial Encephalopathy, Lactic Acidosis and Stroke like episodes) are attributed to
Mitochondrial mutations. Other diseases associated with mt DNA are:
Lebers Hereditary Optic Neuropathy
MELAS (mitochondrial encephalopathy with lactic acidosis and stroke like episodes)
Myopathy
MERRF Syndrome: (myoclonic epilepsy and ragged red fibers.)
Cardiomyopathy
Strokes
Lactic acidosis
External Ophthalmoplegia
Optic atrophy
NARP (Neuropathy, ataxia and retinitis pigmentosa)
Pearsons syndrome
Sensorineural deafness
Diabetes mellitus

Gene Frequency
The distribution of a mutant gene in the general population maybe calculated on the basis of the Hardy-Weinberg equation. If the
frequency of a particular gene A is p, then that of its alternative allele is (1 p) = q. Three genotypes are found in the population:
Those who are homozygous AA
Those who are heterozygous Aa and
Those who are homozygous aa
In a randomly mating population, the frequencies of these genotypes are in the proportion p2 (AA), 2 pq (Aa), and q2 (aa)
An important consequence of this distribution is that irrespective of the initial frequency of the genes A and a in the
population, the proportion of the three genotypes tends to remain constant in succeeding generations, provided that
there is no difference in biologic fitness of any of the genotypes. If viability or fertility among the three genotypes is
unequal, if individuals migrate into or out of the population, or if mating is not random, the frequency calculations require
considerable correction. In small populations major changes in gene frequency can occur on the basis of chance alone
If the frequency of a recessive disease in a particular population is known, the frequency of heterozygous carriers and
of the abnormal gene can be calculated. Thus for a recessively inherited disease aa (q2) with a frequency of 1 per 10,000
(e.g. albinism), the frequency of the gene a (q) is 1 per 100, and that of heterozygous carriers is 2 p q = 2 99/100 1/100
= approximately 1 in 50

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USMLE Step 1 Platinum Notes

Commonly asked Terminology: (USMLE Favorite)

Allelic Heterogeneityrefers to the fact that different mutations in the same genetic locus can cause an identical or similar
phenotype. For example, many different mutations of the b-globin locus can cause b-thalassemia.
Phenotypic Heterogeneityoccurs when more than one phenotype is caused by allelic mutations (e.g. different mutations
in the same gene). e.g. Similarly, identical mutations in the FGFR2 gene can result in very distinct phenotypes: Crouzon syndrome
(craniofacial synostosis), or Pfeiffer syndrome (acrocephalo polysyndactyly).
Locus or Nonallelic Heterogeneity and Phenocopies: Refers to the situation in which a similar disease phenotype results
from mutations at different genetic loci. For example, osteogenesis imperfecta can arise from mutations in two different
procollagen genes (COL1A1 or COL1A2) that are located on different chromosomes.
Variable Expressivity and Incomplete Penetrance: The same genetic mutation causes a phenotypic spectrum illustrating
the phenomenon of variable expressivity. MEN-1 illustrates several of these features. Families with this autosomal dominant
disorder develop tumors of the parathyroid gland, endocrine pancreas, and the pituitary gland. However, the pattern of tumors
in the different glands, the age at which tumors develop, and the types of hormones produced vary among affected individuals,
even within a given family.
Penetrance: It is the probability of expressing the phenotype given a defined genotype; it can be complete or incomplete. For
example, hypertrophic obstructive cardiomyopathy (HOCM) caused by mutations in the myosin heavy chain b gene is a dominant
disorder with clinical features in only a subset of patients who carry the mutation. Patients who have the mutation but no
evidence of the disease can still transmit the disorder to subsequent generations. In this situation, the disorder is said to be
nonpenetrant or incompletely penetrant.

USMLE Case Scenario

Differential expression of same gene depending on parent of origin is referred to as:
1. Genomic imprinting
2. Mosaicism
3. Anticipation
4. Nonpenetrance
Ans. 1. Genomic imprinting

USMLE Case Scenario

Males are more commonly affected than females in:
1. Autosomal Dominant
2. Autosomal Recessive
3. X- Linked Dominant
4. X- Linked recessive
Ans. 4. X- Linked recessive

Cluster Designation (CD) Markers

CD 3
CD 10
CD 19
CD 20, 21, 22
CD 16 and CD 56

Pan T-cell marker

Immature B-cell marker
Pan B-cell marker
B-cell markers
NK-cells

USMLE Case Scenario

Which of the following markers is specific for Gastrointestinal stromal tumors (GIST):
1. CD 117
2. CD 34

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359

3. CD 23
4. S 100
Ans. 1. CD 117

USMLE Case Scenario

Which of the following are characteristic markers for Hodgkins Lymphoma?
1. CD15 and CD30
2. CD15 and CD45
3. CD30 and CD68
4. CD15 and CD3
Ans. 1. CD15 and CD30

USMLE Case Scenario

Which of the following is a marker for Langerhans cell histiocytosis:
1. CD 1a
2. CD 10
3. CD 30
4. CD 56
Ans. 1. CD 1a

Chromosomal Involvements: (USMLE Favorite)

Chromosome 1

Neuroblastoma

Chromosome 2

Cystinuria

Chromosome 3

RCC

Chromosome 4

Huntingtons Chorea

Chromosome 5

FAP, Cri Du Chat

Chromosome 6

HLA/MHC Antigens

Chromosome 7

Cystic Fibrosis

Chromosome 8

Osteopetrosis

Chromosome 9

Freidreichs Ataxia

Chromosome 11

Wilms Tumor

Chromosome 13

Retinoblastoma

The c-Ki-ras and the c-myc genes are the oncogenes most frequently altered in colorectal cancer
Antigen presenting cells (APC) gene, a tumor suppressor gene located on chromosome 5q, is a inactivated by a point mutation
in FAP
The p53 gene is also implicated in colorectal cancer. It checks the integrity of the genome prior to mitosis
BRCA1 gene is associated with familial breast cancer.

USMLE Case Scenario

Familial polyposis coli is a rare condition inherited as autosomal dominant, with equal sex incidence. Hundreds of adenomas
develop throughout the colon and rectum. The gene responsible for FAP is:
1. On the short arm of chromosome 5
2. On the long arm of chromosome 5
3. On the short arm of chromosome 15
4. On the long arm of chromosome 15
Ans. 1. On the short arm of chromosome 5

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USMLE Step 1 Platinum Notes

USMLE Case Scenario

Cowden syndrome is due to:
1. Mutations of a gene on chromosome 9
2. Mutations of a gene on chromosome 10
3. Mutations of a gene on chromosome 11
4. Mutations of a gene on chromosome 12
Ans. 2. Mutations of a gene on chromosome 10

Remember

Gene for Major Histocompatibility is carried on chromosome 6

Gene for Folate carrier protein is carried on chromosome 21
Cystic fibrosis transmembrane conductance regulator gene is carried onchromosome 7
Short arm of chromosome is p arm
Long arm of chromosome is q arm
Genes regulating morphogenesis: homeobox genes (HOX)
APC gene is located on chromosome 5
BRCA 1 gene is located on chromosome 17

Important Points about Antibodies

Immunoglobulin
IgM
The first Ab formed after primary immunization (exposure to new Ag)
Exists in a monomeric or pentameric form and protects the intravascular space from disease.
The large IgM molecules readily activate complement and serve as opsonizers and agglutinators to assist the phagocytic system
to eliminate many kinds of microorganisms
Fixes complement
Isohemagglutinins and many Abs to gram-negative organisms are IgM.

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361

IgG
The most prevalent type of Ab is found in plasma and extravascular spaces; it is produced when IgM titers begin to decrease after
primary immunization.
IgG is the major Ig produced after reimmunization (the memory immune response or secondary immune response).
IgG is the prime mediator of the memory response and protects the tissues from bacteria, viruses and toxins.
It is the only Ig that crosses the placenta.
IgG subclasses neutralize bacterial toxins, activate complement and enhance phagocytosis by opsonization.
Commercial gamma globulin is almost entirely IgG, with small amounts of other Igs.
IgA (secretory Ab)
It is found in mucous secretions (saliva, tears, respiratory, GU and GI tracts, and colostrum), where it provides an early
antibacterial and antiviral defense.
Secretory IgA is synthesized in the subepithelial regions of the GI and respiratory tracts and is present in combination with locally
produced secretory component (SC).
IgD
It is not known to have much biologic activity. Present in serum in extremely low concentrations, it appears on the surface of
developing B cells and maybe important in their growth and development.
IgE
(Reaginic, skin-sensitizing, or anaphylactic Ab), like IgA, is found primarily in respiratory and GI mucous secretions.
In serum, IgE is present in very low concentrations
IgE is elevated in atopic diseases (e.g. allergic asthma, hay fever and atopic dermatitis), parasitic diseases, far-advanced
Hodgkins disease, and IgE-monoclonal myeloma
IgE may also have a beneficial role in the defense against parasites.
IgE -mediates reagenic hypersensitivity
IgG
IgG: This is major serum immunoglobulin
IgG: It is only maternal immunoglobulin that is normally transported across the placenta and provides natural passive immunity
in newborn
IgA: It is the second most abundant class of immunoglobulin seen in body fluids such as colostrums, saliva and tears
IgM: It is called millionaire molecule. It is not transported across the placenta hence presence of IgM in the fetus or newborn
indicates diagnosis of congenital infection such as syphilis, rubella, HIV and toxoplasmosis
IgM: Antibodies are short lived; hence their presence in serum indicates recent infection
IgE: Greatly elevated in atopic (Type I allergy) conditions such as asthma, hay fever, eczema, and also in children having high
load of intestinal parasites.

Interferons
IFN-alpha
Produced by leucocytes
Antiviral action
Useful in hepatitis B and C, Kaposis sarcoma, metastatic renal cell cancer, hairy cell leukemia

IFN-beta
Produced by fibroblasts
Antiviral action
Reduces the frequency of exacerbations in patients with relapsing-remitting MS

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USMLE Step 1 Platinum Notes

IFN-gamma
Produced by T-lymphocytes and NK-cells
Weaker antiviral action, more of a role in immunomodulation particularly macrophage activation
Maybe useful in Chronic granulomatous disease.

Interleukins: (USMLE Favorite)

IL1 causes Fever
IL2T cell stimulation
IL3 Bone Marrow stimulation
IL4IgE Stimulation
IL5IgA Stimulation

Functions of Different Complement Components

Opsonization (C3b)
Chemotaxis (C5a)
Anaphylotoxin (C3a, C4a, C5a)
Cytolysis (insertion of C5b, 6,7,8,9 into the cell membrane)
Enhancement of antibody production (C3b)

Oncogenes
Oncogenes are regulatory genes
Activity is abnormally increased after a genetic alteration
Oncogene activation may occur after
Chromosomal translocation
Gene amplification
Mutation within coding sequence of oncogene
Oncogenes act in a dominant fashion
Examples of oncogenes include:
Ras on chromosome 11 mediates signal transduction
ErbB2 on chromosome 7 growth factor receptor
Src on chromosome 20 tyrosine kinase
Myc on chromosome 8 transcription factor.

Tumor Suppressor Genes

Code for inhibitory proteins

Normal function is to prevent cell growth
In cancer, suppressor function is lost
Most tumor suppressor genes are recessive
Inactivation of tumor suppressor genes can occur by
Gene mutation causing loss of gene product
Prevention of binding of a gene product to its target site
Inactivation by other proteins

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Examples of tumor suppressor genes include

Rb on chromosome 13 control of cell cycle
p53 on chromosome 17 DNA repair and apoptosis
Bcl2 on chromosome 18 apoptosis
APC on chromosome 5 regulation of co-transcriptional activators
Mutation of tumor suppressor genes is seen in many familial cancers
Rb childhood retinoblastoma
p53 Li-Fraumeni syndrome
APC familial colon cancer
BRCA1/2 familial breast cancer

Tumor Suppressor Genes: (Nutshell)

Tumor suppressor gene
VHL
WT 1 and 2
Rb
P53 (Guardian of genome)
BRCA1
BRCA2
APC
DCC
NF1 and NF2

Tumors
von Hippel-Lindau disease
Wilms tumor
Retinoblastoma, Osteosarcoma
Lung, colon, breat Ca
Hereditary breast and ovarian Ca
Hereditary breast Ca
Adenomatous polyps and colon Ca
Colon Ca
Neurofibromas

Protein 53: (USMLE Favorite)

p53 also known as protein 53 or tumor protein 53 is a transcription factor which in humans is encoded by the TP53 gene.
p53 is important in multicellular organisms, where it regulates the cell cycle and thus functions as a tumor suppressor that is
involved in preventing cancer
Acts at G1 S Phase.
As such, p53 has been described as
The guardian of the genome,
The guardian angel gene, and the
Master watchman, referring to its role in conserving stability by preventing genome mutation.
The name p53 is in reference to its apparent molecular mass: it runs as a 53 kilodalton (kDa) protein on SDS-PAGE.
In humans, p53 is encoded by the TP53 gene (guardian of the cell) located on the short arm of chromosome 17 (17p13.1).
p53 has many anti-cancer mechanisms:
It can activate DNA repair proteins when DNA has sustained damage.
It can induce growth arrest by holding the cell cycle at the G1/S regulation point on DNA damage recognition
(if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to
continue the cell cycle.)
It can initiate apoptosis, the programmed cell death, if the DNA damage proves to be irreparable.

Oncogenes: (USMLE Favorite)

RAS:
K-RAS: colon, lung, pancreatic tumors
N-RAS: melanoma, AML
H-RAS: Bladder, kidney tumors

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USMLE Step 1 Platinum Notes

ABL
MYC
C-MYC: Burkitts lymphoma
N-MYC: Neuroblastoma
L-MYC: Small cell lung cancer
WNT 1
ERB B2
FOS
JUN
AKTI, AKT2
BRAF

Immunology: (USMLE Favorite)

Primary immunodeficiency disorders maybe classified according to which component of the immune system they affect:
Neutrophil disorders
Chronic granulomatous disease
Chediak-Higashi syndrome
Leukocyte adhesion deficiency
B-cell disorders
Common variable immunodeficiency
Brutons congenital agammaglobulinemia
IgA deficiency
T-cell disorders
Di George syndrome (Thymic and Parathroid aplasia)
Combined B-and T-cell disorders
Severe combined immunodeficiency
Ataxic telangiectasia
Wiskott-Aldrich syndrome

Jobs Syndrome/Hyperimmunoglobulin E-recurrent Infection Syndrome

The hyperimmunoglobulin E-recurrent infection (HIE) syndrome or Jobs syndrome
It is a rare multisystem disease in which the immune system, bone, teeth, lung and skin are affected. Abnormal chemotaxis is a
variable feature
The cold abscesses have been considered a reflection of impaired chemotaxis with too few phagocytes arriving too late, perhaps
due to a lymphocyte factor inhibiting chemotaxis
Serum IgE elevated. Other immunoglobulins normal.

ABNORMAL NEUTROPHIL FUNCTION

Disorders of Adhesion (Leukocyte adhesion deficiency (LAD))
Two types of leukocyte adhesion deficiency (LAD) have been described
Both are autosomal recessive traits and result in the inability of neutrophils to exit the circulation to sites of infection, leading
to leukocytosis and increased susceptibility to infection Neutrophils (and monocytes) from patients with LAD 1 adhere poorly to
endothelial cells and protein-coated surfaces and exhibit defective spreading, aggregation and chemotaxis
LAD 1 Patients have recurrent bacterial and fungal infections involving skin, oral and genital mucosa, and respiratory and intestinal
tracts; persistent leukocytosis (neutrophil counts of 15,000 to 20,000/uL) because cells do not marginate; and in severe cases
A history of delayed separation of the umbilical stump
Infections, especially of the skin, may become necrotic with progressively enlarging borders

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Slow healing and development of dysplastic scars

The most common bacteria are Staphylococcus aureus and enteric gram-negative bacteria
LAD 2 is caused by an abnormality of CD15, the ligand on neutrophils that interacts with selectins on endothelial cells.

Disorders of Neutrophil Granules

The most common neutrophil defect is Myeloperoxidase deficiency, a primary granule defect inherited as an autosomal
recessive trait
Microbicidal activity of neutrophils is delayed but not absent
Myeloperoxidase deficiency may make other acquired host defense defects more serious
An acquired form of myeloperoxidase deficiency occurs in myelomonocytic leukemia and acute myeloid leukemia.

Chediak-Higashi Syndrome (CHS)

Autosomal recessive inheritance due to defects in the lysosomal transport protein LYST, encoded by the gene CHS1 at 1q42.
This protein is required for normal packaging and disbursement of granules
Neutrophils (and all cells containing lysosomes) from patients with CHS characteristically have large granules Patients with CHS
have an increased number of infections resulting from many agents
CHS neutrophils and monocytes have impaired chemotaxis and abnormal rates of microbial killing due to slow rates of
fusion of the lysosomal granules with phagosomes
NK cell function is also impaired
Specific granule deficiency is a rare autosomal recessive disease in which the production of secondary granules and their contents,
as well as primary granule component defensins, is defective
The defect in bacterial killing leads to severe bacterial infections.

Chronic Granulomatous Disease

Disorders of granulocyte and monocyte oxidative metabolism
There is defective neutrophil oxidative metabolism
Most often CGD is inherited as an X-linked recessive trait; 30% of patients inherit the disease in an autosomal recessive pattern
Leukocytes from patients with CGD have severely diminished hydrogen peroxide production
Patients with CGD characteristically have increased numbers of infections due to catalase-positive microorganisms (organisms
that destroy their own hydrogen peroxide)
When patients with CGD become infected, they often have extensive inflammatory reactions, and lymph node suppuration is
common despite the administration of appropriate antibiotics.
Persistent Neutrophilia with cell counts of 30,000 to 50,000/microliter or higher is called Leukemoid reaction
In leukemoid reaction the circulating neutrophils are mature and not clonally derived.
Cyclic Neutropenia:
It is decrease in neutrophils counts at intervals of 3 weeks (1345) days with normal periods in between
Patients develop overwhelming infections
It is inherited as Autosomal Dominant trait
It is due to Neutrophil elastase gene defect.
Hereditary neutropenias:
Are rare and may manifest in early childhood as a profound constant neutropenia or agranulocytosis
Congenital forms of neutropenia include:
Kostmanns syndrome (neutrophil count <100/uL), which is often fatal; more benign chronic idiopathic neutropenia (neutrophil
count of 300 to 1500/uL);

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USMLE Step 1 Platinum Notes

Cartilage-hair hypoplasia syndrome; Shwachmans syndrome associated with pancreatic insufficiency; myelokathexis, a
congenital disorder characterized by neutrophil degeneration, hypersegmentation, and myeloid hyperplasia in the marrow
associated with decreased expression of bcl-XL in myeloid precursors and accelerated apoptosis
Neutropenias associated with other immune defects (X-linked agammaglobulinemia, ataxia telangiectasia, IgA deficiency)
The presence of immunoglobulin directed toward neutrophils is seen in Feltys syndrome: a triad of rheumatoid arthritis,
splenomegaly and Neutropenia.

Vessel Disorders: (USMLE Favorite)

Large Vessel Arteritis
Giant cell arteritis
Takayasus arteritis

Medium Sized Vessel Arteritis

Poly arteritis nodosa
Kawasaki disease

Small Sized Vessel Arteritis

Essential cryoglobinemia
Churg strauss syndrome
HSP
Microscopic poly angitis
Wegners Granulomatosis

Takayasus Arteritis
Also called as Pulseless Disease or Aortic Arch Syndrome
It is a vasculitis common in Asia especially in young and middle aged females, affecting medium to large size arteries including
Aorta and its branches
Characterized by granulomatous Inflammation leading to arterial thrombosis, stenosis or aneurysm
Clinical features are:
Loss of pulse in upper extremities. (Radial Pulse not felt)
Systemic features: fever, weight loss, arthalgias, fatigue
Anemia and increased ESR
Visual loss or field defects, retinal hemorrhages
Neurological abnormalities like Headache, plus Chest Pain, Hypertension

Polymyositis/Dermatomyositis
A systemic connective tissue disease characterized by inflammatory and degenerative changes in the muscles (polymyositis) and
frequently also in the skin (dermatomyositis), leading to symmetric weakness and some degree of muscle atrophy, principally
of the limb girdles.

USMLE Case Scenario

A 32-year-old woman with a past history of ulcerative colitis (quiescent for the last 7 years), presented with a dry cough.
Increasing dyspnea, myalgia and arthralgia. A clinical diagnosis of fibrosing alveolitis was made and confirmed by
transbronchial biopsy. She had a severe proximal myopathy. Serum creatine kinase was found to be very high and a muscle
biopsy showed necrosis and a cellular infiltrate. She had a circulating autoantibody to Jo1 antigen
Ans. Diagnosis is: Polymyositis

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367

Reiters Syndrome (RS)

Arthritis associated with nonbacterial urethritis or cervicitis, conjunctivitis and mucocutaneous lesions
RS is classified with the seronegative spondyloarthropathies
Joint involvement generally is asymmetric and polyarticular, occurring in the large joints of the lower extremities as well as the
toes. Back pain may occur, usually with more severe disease
Enthesopathy (inflammation at tendinous insertion into bone) is common in RS and other seronegative arthritides, e.g. plantar
fasciitis, digital periostitis, Achilles tendinitis
Mucocutaneous lesionssmall, painless superficial ulcersare commonly seen on the oral mucosa, tongue, and glans penis
(balanitis circinata)
Patients may also develop hyperkeratotic skin lesions of the palms and soles and around the nails (keratoderma blennorrhagica)
Cardiovascular involvement with aortitis, aortic insufficiency and conduction defects occurs rarely.

Temporal Arteritis
(Giant Cell Arteritis; Cranial Arteritis)
A chronic inflammatory disease of large blood vessels, particularly those with a prominent elastica, occurring primarily in the elderly
Giant cell arteritis most often involves arteries of the carotid system, particularly the cranial arteries
Segments of the aorta, its branches, the coronary arteries, and the peripheral arteries may also be affected
The disease has a predilection for arteries containing elastic tissue; it is rarely seen in veins
The histologic reaction is a granulomatous inflammation of the intima and inner part of the media
Presentations are diverse, depending on the distribution of the arteritis, but typically include:
Severe headache (especially temporal and occipital)
Scalp tenderness
Visual disturbances (amaurosis fugax, diplopia, scotomata, ptosis and vision blurring)
Claudication of the masseter, temporalis and tongue muscles are characteristic
Blindness due to ischemic optic neuropathy probably occurs in < = 20% of patients but is infrequent after high dose corticosteroid
treatment. On physical examination, there maybe swelling and tenderness with nodularity over the temporal arteries and bruits
over the large vessels
ESR is usually markedly elevated (often > 100 mm/h, Westergren) during the active phase, but is normal in about 1% of patients
Normochromic and normocytic anemia is often present and, at times, profound. Alkaline phosphatase maybe elevated. Other
nonspecific findings include polyclonal hyperglobulinemia and leukocytosis.

High Yield USMLE

Wegners granulomatosis: necrotizing lesions in upper respiratory tract and kidney
Henon scholein purpura: IgA deposits with vasculitis
Churg strauss syndrome: asthma plus blood eosinophilia
Kawasakis disease: in children
Takayasus arteritis: in young patients
Giant cell arteritis: in older patients

USMLE Case Scenario

Giant cell arteritis involves the cranial arteries (branches of the carotid system). Biopsying 2 cm lengths of each temporal
artery are indicated because the process can be patchy. Biopsy can reveal.
1. Granulomatous inflammation
2. Fibrinoid necrosis
3. Hyperplastic necrosis
4. Leukocytoclastic vasculitis
Ans. 1. Granulomatous inflammation

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USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 48-year-old male from Ohio presents with sinus pain and drainage, bloody nasal discharge and nasal mucosal ulceration.
On laboratory examination, the man is found to have hematuria, and red blood cell casts. A biopsy of the upper airway tissue
reveals granulomatous inflammation with necrosis. Blood tests show the presence of antineutrophil cytoplasmic antibodies
(c-ANCA). Most likely diagnosis is:
1. Goodpastures syndrome
2. Noninfectious granulomatous disease
3. Wegeners granulomatosis
4. Bergers Disease
Ans. 3. Wegeners granulomatosis

Atherosclerosis
Complicated lesions indicate advanced atherosclerotic disease. They arise in atherosclerotic plaques, and render them more
susceptible to sudden occlusion and acute infarction of the supplied tissues. Commonly, the plaque ulcerates or ruptures, and
the exposed surfaces, being highly thrombogenic, precipitate thrombus formation
Thrombi are typified by the lines of Zahn, alternating layers of platelets and fibrin (the pale lines) and layers of blood (the dark lines).
Beyond thrombus formation, other features of a complicated plaque include hemorrhage into the lesion itself, and microembolism
by cholesterol crystals or calcified debris. Furthermore, the weakened media underlying the plaque may develop an aneurysmal
dilatation. In general, the clinical significance of atherosclerosis is related to the consequences of complicated lesions.

Aneurysms
Pseudoaneurysm also known as false aneurysm is usually as a result of trauma to all the three layers of the artery resulting in hematoma
This hematoma must communicate with artery to be considered as a pseudoaneurysm
Pseudoaneurysm differs from true aneurysm in that it does not contain any vessel wall
Penetrating trauma is the most common cause of pseudoaneurysm.

Other Causes are

Marfans syndrome
Fibromuscular Dysplasia
Vasculitis

Pulsatile mass is the most common manifestation. Locations of Pseudoaneurysms

Femoral artery
Left Ventricular Pseudoaneurysm
Abdominal Aorta Pseudoaneurysm
Carotid Pseudoaneurysm

Important Points about Aneurysms

The most common type of true aneurysm is fusiform type

The most common site of arterial aneurysm is Infrarenal part of Abdominal Aorta
Popliteal Aneurysms are the most common Peripheral aneurysms
The most common site for dissecting aneurysms is Ascending Aorta
Cirsoid aneurysms are common in superficial temporal artery
Atherosclerosis is the mc cause of Abdominal aneurysms
Atherosclerosis is the mc cause of any aneurysm.

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Types of aneurysms:
Berry aneurysm: occurs in circle of willis
Microaneurysms: seen in Diabetes and Hypertension
Mycotic aneurysms: are seen in bacterial infections
Aortic dissecting Aneurysms: Due to degeneration of tunica media
Occur in Marfans Syndrome and Hypertension
Syphilitic aneurysms or Luetic aneurysms: involve ascending Aorta
Tree bark calcification is seen in syphilis.

Developmental or Berry, Aneurysms

Occur in cerebral vessels. These are small, spherical dilatations typically in the circle of Willis; when ruptured, they can causes fatal
intracerebral hemorrhage.
Arteriovenous fistulas
Are abnormal, typically small, direct connections between arteries and veins that bypass the intervening capillaries. They occur most
commonly as developmental defects but can also result from rupture of an arterial aneurysm into the adjacent vein, from penetrating
injuries that pierce arteries and veins or from inflammatory necrosis of adjacent vessels; intentionally created arteriovenous fistulas are
used to provide vascular access for chronic hemodialysis. When arteriovenous fistulas are large or extensive, they can become clinically
significant by shunting blood from the arterial to the venous circulations. This forces the heart to pump additional volume, and highoutput cardiac failure can ensue.
Fibromuscular dysplasia
It is a focal irregular thickening of the walls of medium and large muscular arteries, including renal, carotid, splanchnic and vertebral
vessels. The cause is developmental. Segments of the vessel wall are focally thickened by some combination of irregular medial and
intimal hyperplasia and fibrosis; this results in luminal stenosis and in the renal arteries maybe a cause of renovascular hypertension.

Aortic Dissection
In the vast majority of spontaneous dissections, the intimal tear marking the point of origin of the dissection is found in the
ascending aorta, usually within 10 cm of the aortic valve
The dissection can extend along the aorta retrograde toward the heart as well as distally, sometimes all the way into the
iliac and femoral arteries. The dissecting hematoma spreads characteristically along the laminar planes of the aorta, usually
approximately between the middle and outer thirds
It often ruptures out through the adventitia, causing massive hemorrhage. In some instances, the dissecting hematoma reenters
the lumen of the aorta, producing a second distal intimal tear and a new vascular channel within the media of the aortic wall (and
resulting in a double-barreled aorta with a false channel). This averts a fatal extra-aortic hemorrhage. In the course of time,
false channels may become endothelialized and can be recognized as chronic dissections.

Abnormal structural proteins produce inborn errors such as

Marfan syndrome (fibrillin)

Osteogenesis imperfecta (collagen type I)
Spondyloepiphyseal dysplasia (collagen type II), and
Sack syndrome (collagen type III)

Marfan Syndrome: (USMLE Favorite)

It is characterized by skeletal, ocular and cardiovascular abnormalities. Typically, Marfan patients are tall with very long legs and
tapering fingers. Laxity of joints is present, so that the thumb can be extended back to the wrist. Chest and spinal column deformities
maybe present as well. The most frequent cardiovascular anomalies are incompetence of the aortic valve, aortic dissection and mitral
valve prolapse (floppy valve). The latter may give rise to mitral regurgitation with the typical auscultatory phenomenon of a systolic
click followed by a murmur. The most characteristic ocular change is ectopia lentis, i.e. dislocation of the lens. Most deaths are due to
rupture of aortic dissections. The gene mutated in Marfan syndrome encodes fibrillin, a 350-kD protein that serves as scaffolding for
the deposition of elastin and formation of elastic fibers.

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USMLE Step 1 Platinum Notes

USMLE Case Scenario

It is seen that vasa vasorum of the aorta undergoes obliterative endarteritis, leading to atrophy of the muscularis and elastic
tissues of the aorta and dilatation. Linear calcifications are often seen in the ascending aorta by X-ray. The intimal wrinkling is
seen. The disease most likely represents:
1. Marfans syndrome
2. Syphilis infection
3. Aortic dissection
4. Takayasus arteritis
Ans. 2. Syphilis Infection (The intimal wrinkling or tree barking is also a common feature.)

USMLE Case Scenario

A 35-year-old tall male from New Jersey has Marfan syndrome, an autosomal dominant disorder with features of subluxated
lens of the eye, mitral valve prolapsed. The defect lies in:
1. Gene on chromosome 15 encoding fibrillin
2. Gene on chromosome 16 encoding fibrillin
3. Gene on chromosome 17 encoding fibrillin
4. Gene on chromosome 18 encoding fibrillin
Ans. 1. Gene on chromosome 15 encoding fibrillin

Rheumatic Heart Disease

Preceded by streptococcal pharyngitis

Aschoff bodies are a feature
Anitschkow cells/caterpillar cells are seen
Pancarditis
Bread and butter pericarditis
Vegitation along line of closure of valves
Sub endocardial Mc Callums patches present
Mc cause of mitral stenosis
ASLO titers used in diagnosis
Tricuspid valve is least commonly involved
MC cause of MS is rheumatic fever

Mc Callums Patch

Lesions of Mural endocardium

Deposition of Aschoff Bodies occurs here
Site of Thrombus formation

Aschoff Bodies

Present in Perivascular connective tissue

Feature of Rheumatic heart disease

Anitschkow myocytes

Modified cardiac mesenchymal cells with caterpillar nuclei, cytoplasm.

Aschoff cells

Multinucleated giant cells

USMLE Case Scenario

Aschoffs nodules are seen in:
1. Subacute bacterial endocarditis
2. Libman-Sacks endocarditis
3. Rheumatic carditis
4. Nonbacterial Thrombotic endocarditis
Ans. 3. Rheumatic carditis

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Myocarditis
Can be caused by a variety of conditions such as a virus, sarcoidosis and immune diseases (such as systemic lupus, etc.), pregnancy,
and others. The most common cause of myocarditis is infection of the heart muscle by a virus. Coxsackievirus B is the most common
culprit in the United States. Viruses capable of causing myocarditis include.
Coxsackievirus types A and B (especially type B)
Adenovirus (most commonly types 2 and 5)
Cytomegalovirus
Echovirus
Epstein-Barr virus
Hepatitis C virus
Herpes virus
Human immunodeficiency virus
Influenza and parainfluenza
Measles
Mumps, associated with endocardial fibroelastosis (EFE)
Parvovirus B19
Poliomyelitis virus
Rubella
Varicella
HIV infection: About 10 percent of people with HIV develop myocarditis
Bacterial infection: Rarely, myocarditis occurs as a complication of endocarditis, an infection of the heart valves and the lining
inside the hearts chambers caused by bacteria. Some common bacteria responsible for myocarditis include Staphylococcus aureus,
enterococci and Corynebacterium diphtheriae
Chagas disease: This infection, caused by the protozoan Trypanosoma cruzi, is transmitted by an insect bite. In the United States,
myocarditis caused by Chagas disease is most common among travelers or immigrants from Central and South America. In up to
one-third of people with Chagas disease, a form of chronic myocarditis develops many years after the initial infection. This chronic
myocarditis leads to significant destruction of heart muscle with progressive heart failure
Lyme myocarditis: Lyme disease, an infection caused by the tick-borne bacterium Borrelia burgdorferi, causes myocarditis or other
heart problems in about 10 percent of patients
Giant cell myocarditis: This rare form of myocarditis takes its name from large, abnormal giant cells that are found when a piece of
the affected heart muscle is examined under a microscope. Giant-cell myocarditis is most common among patients suffering from
thymoma, systemic lupus erythematosus (SLE or lupus), or thyrotoxicosis
Other agents: Myocarditis also can be caused by:
Alcohol, radiation, chemicals (hydrocarbons and arsenic) and drugs, including doxorubicin Adriamycin, cyclophosphamide
emetine, chloroquine and sulfonamides
Diphtheria causes myocarditis by virtue of it exotoxin. The flabby, stretched out heart muscle is characteristic of diphtheria.
Because of flabby nature of heart muscle; the myocardial pumping activity is significantly reduced as a result if which congestive
heart failure occurs within three weeks of illness.

Myxoma

Myxomas are the most common type of primary cardiac tumor in all age groups
Female predilection
Most myxomas are sporadic
NAME syndrome (nevi, atrial myxoma, myxoid neurofibroma and ephelides)
LAMB syndrome (lentigines, atrial myxoma and blue nevi)
Carney complex

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USMLE Step 1 Platinum Notes

Pathologically, myxomas are gelatinous structures consisting of myxoma cells imbedded in a stroma rich in glycosaminoglycans
The majority are solitary and located in the atria
Myxomas commonly present with obstructive, embolic, or constitutional signs and symptoms.

USMLE Case Scenario

A 68-year-old woman who is normotensive presents to hercardiac physician after several episodes of syncope. Physical
examination is remarkable for alow-pitched plopping sound during mid-systole. Two-dimensional echocardiography
demonstrates aball-valve type obstruction of the mitral valve. Which of the following would most likely be observed if the
cause of the obstruction were biopsied?
1. Benign glandular tissue
2. Myxomatous degeneration of valves
3. Dense calcification in tricuspid area
4. Densely packed smooth muscle
5. Densely packed striated muscle
6. Malignant glandular tissue
7. Scattered mesenchymal cells in a myxoid background
Ans. 7. Scattered mesenchymal cells in a myxoid background
Atrial myxoma may intermittently obstruct the mitral valve. Histologically, these tumors are composed of scattered
mesenchymal cells in a prominent myxoid background.

Myocardial Infarction

LAD is the mc artery involved

Enzyme elevated in first two hours is CPK MB
Waviness of fibers is the earliest change
Coagulation necrosis and neutrophilic infiltration is seen within 13 days
Granulation tissue is seen within 1 week
Scarring in MI is completed by 3 months
Troponin T is a marker of MI.

Hyaline arteriosclerosis: benign hypertension

Hyperplastic arteriosclerosis: malignant hypertension
MC Primary tumor of heart myxoma
Libman sacks endocarditis is found in SLE
Dresselers syndrome is autoimmune.

Respiratory Pathology

Pores of Kohn are present in Alveoli

Charcoat layden crystals: Feature of asthma
Curschmanns spirals: Feature of asthma
Creola bodies: Feature of asthma
Reid index is used for Chronic bronchitis
Blue bloaters: Chronic bronchitis
Pink puffers: Emphysema.

ARDS
In the acute phase of ARDS the lungs are dark red, firm, airless and heavy
Microscopically, there is capillary congestion, necrosis of alveolar epithelial cells, interstitial and intra-alveolar edema and hemorrhage,
and (particularly with sepsis) caollections of neutrophils in capillaries
The most characteristic finding is the presence of hyaline membranes, particularly lining the distended alveolar ducts
Such membranes consist of fibrin-rich edema fluid admixed with remnants of necrotic epithelial cells.

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Emphysema
Emphysema is defined anatomically as a permanent and destructive enlargement of airspaces distal to the terminal bronchioles
without obvious fibrosis and with loss of normal architecture
1 antitrypsin (1AT) deficency is associated with panacinar emphysema
Smoking is a cause of emphysema.
The diagnosis and classification of emphysema depend largely on the macroscopic appearance of the lung
Panacinar emphysema, when well developed, produces pale, voluminous lungs that often obscure the heart when the anterior chest
wall is removed at autopsy
With advanced disease, adjacent alveoli become confluent creating large airs paces. In addition to alveolar loss, the number of alveolar
capillaries is diminished.

Chronic Bronchitis: (USMLE Favorite)

Grossly, the mucosal lining of the larger airways is usually hyperemic and swollen by edema fluid
It is often covered by a layer of mucinous or mucopurulent secretions
The smaller bronchi and bronchioles may also be filled with similar secretions. Histologically, the diagnostic feature of chronic
bronchitis in the trachea and larger bronchi is enlargement of the mucus-secreting glands The magnitude of the increase in size is
assessed by the ratio of the thickness of the submucosal gland layer to that of the bronchial wall (Reid index; normally 0.4)
Chronic bronchiolitis (small airway disease), characterized by:
Goblet cell metaplasia
Mucus plugging
Inflammation, and
Fibrosis

Asthma
Grossly, the lungs are overdistended because of overinflation, and there maybe small areas of atelectasis. The most striking
macroscopic finding is occlusion of bronchi and bronchioles by thick, tenacious mucus plugs. Histologically, the mucus plugs
contain whorls of shed epithelium (Curschmann spirals)
Numerous eosinophils and Charcot-Leyden crystals (collections of crystalloids made-up of eosinophil proteins) are also present.

Bronchiectasis: (USMLE Favorite)

When tumors or aspiration of foreign bodies lead to bronchiectasis, involvement maybe sharply localized to a single segment of
the lungs
In the full-blown active case, an intense acute and chronic inflammatory exudate within the walls of the bronchi and bronchioles
and the desquamation of lining epithelium cause extensive areas of ulceration. In the usual case, a mixed flora can be cultured from
the involved bronchi, including staphylococci, streptococci, pneumococci, enteric organisms, anaerobic and microaerophilic
bacteria, and (particularly in children) Hemophilus influenzae and Pseudomonas aeruginosa.

Pulmonary Anthracosis
It is coal-induced pulmonary lesion in coal miners, urban dwellers and tobacco smokers. Inhaled carbon pigment is engulfed by
alveolar or interstitial macrophages, which then accumulate in the connective tissue along the lymphatics, including the pleural
lymphatics or in lymph nodes.

Coal Workers Pneumoconiosis (Cwp)

Coal dust is associated with CWP
Much of the symptomatology associated with simple CWP appears to be similar and additive to the effects of cigarette smoking
on the development of chronic bronchitis and obstructive lung disease

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USMLE Step 1 Platinum Notes

With prolonged exposure, small, rounded, regular opacities, 1 to 5 mm in diameter (nodular pattern). Calcification is generally not
seen
Complicated CWP is manifested by the appearance on the chest radiograph of nodules ranging from 1 cm in diameter to the size
of an entire lobe, generally confined to the upper half of the lungs
Particle size of 15 micrometer is dangerous dor pneumoconiosis.

Caplans Syndrome: (USMLE Favorite)

First described in coal miners but subsequently found in patients with a variety of
Pneumoconioses
Seropositive Rheumatoid arthritis with
Characteristic progressive massive fibrosis

Simple CWP
It is characterized by coal macules and the somewhat larger coal nodule
The coal macule consists of dust-laden macrophages; in addition the nodule contains small amounts of a delicate network of
collagen fibers
Although these lesions are scattered throughout the lung, the upper lobes and upper zones of the lower lobes are more
heavily involved.

Complicated CWP (PMF)

Occurs on a background of simple CWP by coalescence of coal nodules and generally requires many years to develop
It is characterized by intensely blackened scars larger than 2 cm, sometimes up to 10 cm in greatest diameter
They are usually multiple.

Beryllium may produce an acute pneumonitis or, far more commonly, a chronic interstitial pneumonitis. (BERYLLIOSIS)
Radiodense dusts include iron and iron oxides from welding or silver finishing (Siderosis)
Tin oxide used in metallurgy, color stabilization, printing, and the manufacture of porcelain, glass, and fabric (Stannosis)
And barium sulfate used as a catalyst for organic reactions, drilling mud components, and electroplating (Baritosis).

Silicosis: (USMLE Favorite)

Mc occupational disorder
Crystalline form most common cause
Upper lobes involved
Eggshell pattern
Patients with silicosis are at greater risk of acquiring Mycobacterium tuberculosis infections (silicotuberculosis) and atypical
mycobacterial infections.

Silicotic nodules are characterized grossly in their early stages by tiny, barely palpable, discrete, pale-to-blackened nodules in the
upper zones of the lungs
Microscopically, the silicotic nodule demonstrates concentrically arranged hyalinized collagen fibers surrounding an amorphous
center
The whorled appearance of the collagen fibers is quite distinctive for sometimes, thin sheets of calcification occur in the lymph
nodes and are appreciated radiographically as eggshell calcification (e.g. calcium surrounding a zone lacking calcification).

Asbestosis: (USMLE Favorite)

Asbestos is a generic term for several different mineral silicates, including chrysolite, amosite, anthophyllite and crocidolite
Asbestosis is a diffuse interstitial fibrosing disease of the lung
Physiologic studies reveal a restrictive pattern with a decrease in lung volumes

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Lower lobes affected commonly

Asbestos bodies
Ferruginous bodies
Laryngeal and colonic cancers associated
Mesotheliomas, both pleural and peritoneal, are also associated with asbestos exposure
Intense fibrosis is a pathological feature of mesotheliomas.
It is marked by diffuse pulmonary interstitial fibrosis
These changes are indistinguishable from those resulting from other causes of diffuse interstitial fibrosis, except for the presence
of asbestos bodies, which are seen as golden brown, fusiform or beaded rods with a translucent center. They consist of asbestos
fibers coated with an iron-containing proteinaceous material
Asbestosis begins in the lower lobes and subpleurally, but the middle and upper lobes of the lungs become affected as fibrosis
progresses. Pleural plaques are the most common manifestation of asbestos exposure and are well-circumscribed plaques of
dense collagen.

Sarcoidosis: (USMLE Favorite)

Noncaseating granulomas with bilateral hilar lymphadenopathy

Berylium inhalation mimicks sarcoidosis
It is an end stage lung disease
Epitheloid cells with no caseation Seen
Sarcoidosis does not involves brain
Kveim test is used for sarcoidosis
Schaumann bodies (conchlike structures)
Asteroid bodies (stellate-like structures), and
Residual bodies (refractile calcium-containing inclusions)
Two syndromes have been identified in the acute group
Lofgrens syndrome includes the complex of Erythema nodosum and X-ray findings of bilateral hilar adenopathy, often
accompanied by joint symptoms, including arthritis at the ankles, knees, wrists, or elbows
The Heerfordt-Waldenstrom syndrome describes individuals with fever, parotid enlargement, anterior uveitis and facial
nerve palsy.
Feature is the noncaseating epithelioid granuloma
This is a discrete, compact collection of epithelioid cells rimmed by an outer zone of largely CD4 + T-cells. The epithelioid cells are
derived from macrophages and are characterized by abundant eosinophilic cytoplasm and vesicular nuclei. Two other microscopic
features are sometimes seen in the granulomas: (1) Schaumann bodies: laminated concretions composed of calcium and
proteins; and (2) Asteroid bodies: stellate inclusions enclosed within giant cells
Intrathoracic hilar and paratracheal lymph nodes are enlarged 75 to 90% of patients, while a third present with peripheral
lymphadenopathy. The nodes are characteristically painless and have a firm, rubbery texture
Erythema nodosum, the hallmark of acute sarcoidosis, consists of raised, red, tender nodules on the anterior aspects of the legs.
In contrast, discrete painless subcutaneous nodules can also occur in sarcoidosis, and these usually reveal abundant noncaseating
granulomas. Another characteristic skin lesion of sarcoidosis consists of indurated plaques associated with a violaceous discoloration in
the region of the nose, cheeks and lips (lupus pernio)
Involvement of the eye and lacrimal glands occurs in about one-fifth to one-half of patients. The ocular involvement takes the
form of iritis or iridocyclitis and maybe unilateral or bilateral. The posterior uveal tract is also affected with resultant choroiditis,
retinitis and optic nerve involvement. These ocular lesions are frequently accompanied by inflammation in the lacrimal glands,
with suppression of lacrimation (sicca syndrome)
Unilateral or bilateral parotitis with painful enlargement of the parotid glands occurs in less than 10% of the individuals
with sarcoidosis; some go onto develop xerostomia (dry mouth). Combined uveoparotid involvement is designated Mikulicz
syndrome.

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USMLE Step 1 Platinum Notes

Acute Pneumonias
S pneumoniae (pneumococcus) is the most common cause of community-acquired acute pneumonia, and the distribution of
inflammation is usually lobar
Morphologically, lobar pneumonias evolve through four stages: congestion, red hepatization, gray hepatization and resolution
Other common causes of acute pneumonias in the community include H influenzae and M catarrhalis (both associated with acute
exacerbations of COPD)
S aureus (usually secondary to viral respiratory infections)
K pneumoniae (observed in chronic alcoholics)
P aeruginosa (seen in individuals with cystic fibrosis, in burn patients and in neutropenics) and L pneumophila, seen
particularly in individuals who have undergone organ transplants.

Lung Abscess: (USMLE Favorite)

Abscesses vary in diameter from a few millimeters to large cavities of 5 to 6 cm
The localization and number of abscesses depend on their mode of development
Pulmonary abscesses resulting from aspiration of infective material are much more common on the right side (more
vertical airways) than on the left and most are single
On the right side, they tend to occur in the posterior segment of the upper lobe and in the apical segments of the lower
lobe, because these locations reflect the probable course of aspirated material when the patient is recumbent
Abscesses that develop in the course of pneumonia or bronchiectasis are commonly multiple, basal and diffusely scattered. Septic
emboli and abscesses arising from hematogenous seeding are commonly multiple and may affect any region of the lungs.

Tuberculosis: (USMLE Favorite)

The initial lesion is usually a small focus of consolidation, less than 2 cm in diameter, within 1 to 2 cm of the apical pleura. Localized,
apical, secondary pulmonary tuberculosis may heal with fibrosis either spontaneously or after therapy, or the disease may progress
and extend along several different pathways:
Progressive pulmonary tuberculosis may ensue. The apical lesion enlarges with expansion of the area of caseation. Erosion into a
bronchus evacuates the caseous center, creating a ragged, irregular cavity lined by caseous material that is poorly walled off by fibrous
tissue
Erosion of blood vessels results in hemoptysis. If the treatment is inadequate, or if host defenses are impaired, the infection may
spread by direct expansion, via dissemination through airways, lymphatic channels, or the vascular system.
Miliary pulmonary disease occurs when organisms drain through lymphatics into the lymphatic ducts, which empty into the
venous return to the right side of the heart and thence into the pulmonary arteries
Miliary lesions may expand and coalesce to yield almost total consolidation of large regions or even whole lobes of the lung. With
progressive pulmonary tuberculosis, the pleural cavity is invariably involved and serous pleural effusions, tuberculous empyema,
or obliterative fibrous pleuritis may develop
Endobronchial, endotracheal and laryngeal tuberculosis may develop when infective material is spread either through
lymphatic channels or from expectorated infectious material. The mucosal lining maybe studded with minute granulomatous
lesions, sometimes apparent only on microscopic examination
Systemic miliary tuberculosis ensues when infective foci in the lungs seed the pulmonary venous return to the heart; the
organisms subsequently disseminate through the systemic arterial system. Almost every organ in the body maybe seeded. Lesions
resemble those in the lung. Miliary tuberculosis is most prominent in the liver, bone marrow, spleen, adrenals, meninges, kidneys,
fallopian tubes and epididymis
Isolated-organ tuberculosis may appear in any one of the organs or tissues seeded hematogenously and maybe the
presenting manifestation of tuberculosis. Organs typically involved include the :
Meninges (tuberculous meningitis)
Kidneys (renal tuberculosis)
Adrenals (formerly an important cause of Addison disease)
Bones (osteomyelitis), and
Fallopian tubes (salpingitis)
When the vertebrae are affected, the disease is referred to as Pott disease.

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Paraspinal cold abscesses in persons with this disorder may track along the tissue planes to present as an abdominal or
pelvic mass
Lymphadenitis is the most frequent form of extrapulmonary tuberculosis, usually occurring in the cervical region (scrofula).
In HIV-negative individuals, lymphadenopathy tends to be unifocal, and most individuals do not have evidence of ongoing
extranodal disease
Intestinal tuberculosis is more often a complication of protracted advanced secondary tuberculosis, secondary to the swallowing
of coughed-up infective material. Typically, the organisms are trapped in mucosal lymphoid aggregates of the small and large
bowel, which then undergo inflammatory enlargement with ulceration of the overlying mucosa, particularly in the ileum.

Malignant Mesotheliomas: (USMLE Favorite)

Are often preceded by extensive pleural fibrosis and plaque formation
These tumors begin in a localized area and in the course of time spread widely, either by contiguous growth or by diffusely seeding
the pleural surfaces
The neoplasm may directly invade the thoracic wall or the subpleural lung tissue. Normal mesothelial cells are biphasic, giving rise
to pleural lining cells as well as the underlying fibrous tissue.

USMLE Case Scenario

(PAS)-positive cytoplasmic granules in hepatocytes are seen in:
1. Wilsons disease
2. Hepatitis B
3. Alpha1-antitrypsin deficiency
4. Alcoholic hepatitis
Ans. 3. Alpha1-antitrypsin deficiency

USMLE Case Scenario

A 34-year-old male from Africa in New York Chest clinic as a pathology characterized by noncaseating granulomata in lungs.
The disease was discovered incidentally when chest X-ray reveals bilateral hilar adenopathy. Definitive diagnosis is based
on biopsy, which reveals noncaseating granulomata that are negative for fungi or acid-fast bacilli. The disease most likely is:
1. Cat scratch disease
2. Sarcoidosis
3. Scleroderma
4. Systemic lupus erythematosus
Ans. 2. Sarcoidosis

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USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 38-year-old man from Washington complained of breathlessness on examination, he had no clubbing and no abnormal
chest signs. A chest X-ray showed fine, diffuse radiological shadows, predominantly in the mid zones, and bilateral hilar
lymphadenopathy. Lung function tests were normal and a Mantoux test was negative. ACE levels and calcium levels are
increased. A clinical diagnosis suggests:
1. Pneumonia
2. Tuberculosis
3. Sarcoidosis
4. Cat scratch disease
5. Coal workers lung
6. Caplans syndrome
Ans. 3. Sarcoidosis

USMLE Case Scenario

A disease occurs with prolonged exposure to dust during glass production which can progress to respiratory failure and death,
and is associated with increased risk for tuberculosis. Classic X-ray findings include calcified lymph nodes that produce an
eggshell pattern. Pleural involvement creates dense fibrous plaques and adhesions that may obliterate the pleural cavities.
Most likely disease is:
1. Byssinosis
2. Berylliosis
3. Silicosis
4. Anthracosis
Ans. 3. Silicosis

USMLE Case Scenario

A 35-year-old occupational worker presents to his primary care physician complaining of dyspnea and chronic dry cough.
Chest X-ray reveals pulmonary hyperinflation with honeycombing and calcified parietal pleural plaques. The most likely
diagnosis is:
1. Anthracosis
2. Asbestosis
3. Histoplasmosis
4. Tuberculosis
5. Berylliosis
6. Byssinosis
7. Silicosis
Ans. 2. Asbestosis

GIT PATHOLOGY
Esophagus
The metaplasia of esophageal squamous epithelium to columnar epithelium (Barretts esophagus) is a complication of severe reflux
esophagitis, and it is a risk factor for esophageal adenocarcinoma
Barretts epithelium progresses through a dysplastic stage before developing into adenocarcinoma
The etiology of squamous cell esophageal cancer is related to
Excess alcohol consumption and/or cigarette smoking
Ingestion of nitrites, smoked opiates and fungal toxins in pickled vegetables, as well as mucosal damage caused by such physical
insults as long-term exposure to extremely hot tea, the ingestion of lye, radiation-induced strictures, and chronic achalasia
The presence of an esophageal web in association with glossitis and iron deficiency (i.e. Plummer-Vinson or Paterson-Kelly
syndrome) and congenital hyperkeratosis and pitting of the palms and soles (i.e. tylosis palmaris et plantaris) have each been
linked with squamous cell esophageal cancer
Dietary deficiencies of molybdenum, zinc and vitamin A
Viral Esophagitis Herpes simplex virus (HSV) type 1 occasionally causes esophagitis in immunocompetent individuals, but
either HSV type 1 or HSV type 2 may afflict patients who are immunosuppressed.

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Herpetic vesicles on the nose and lips may provide a clue to the diagnosis. Barium swallow is inadequate to detect early lesions and
cannot reliably distinguish HSV infection from other types of infections. Endoscopy shows vesicles and small, discrete, punched-out
superficial ulcerations with or without a fibrinous exudate. In later stages, a diffuse erosive esophagitis develops from enlargement
and coalescence of the ulcers. Mucosal cells from a biopsy sample taken at the edge of an ulcer or from a cytologic smear show
ballooning degeneration, ground-glass changes in the nuclei with eosinophilic intranuclear inclusions (Cowdry type A), and giant
cell formation on routine stains
Viruses causing esophagitis:
HSV1
HSV2
Varicella zoster
CMV
HIV
Varicella-zoster virus (VZV) sometimes produces esophagitis in children with chickenpox and adults with herpes zoster.
Esophageal VZV also can be the source of disseminated VZV infection without skin involvement. In an immunocompromised host,
VZV esophagitis causes vesicles and confluent ulcers and usually resolves spontaneously, but it may cause necrotizing esophagitis in
a severely compromised host.
Cytomegalovirus (CMV) infections occur only in immunocompromised patients. CMV is usually activated from a latent stage or
maybe acquired from blood product transfusions
CMV lesions initially appear as serpiginous ulcers in an otherwise normal mucosa
These may coalesce to form giant ulcers, particularly in the distal esophagus.

Barretts Esophagus: (USMLE Favorite)

May occur in a small number of patients who have gastroesophageal reflux disease (GERD). This condition is a metaplasia of
the normal squamous mucosa of the esophagus to a columnar (glandular) type of epithelium, and is usually seen as a response
to repeated acid exposure to the distal esophagus. Tobacco and alcohol use are also thought to contribute to the process. The
significance of Barretts esophagus is that it may lead to the development of low-grade dysplasia, high-grade dysplasia, or esophageal
adenocarcinoma.

H pylori
H pylori colonization induces chronic superficial gastritis, which includes both mononuclear and polymorphonuclear cell
infiltration of the mucosa
Progression to atrophy when H pylori is present
Most H pylori-colonized persons do not develop clinical sequelae
The two major disease-associated H pylori virulence factors are a vacuolating cytotoxin, VacA, and a group of genes termed the
cag pathogenicity island (cag PaI)
H pylori colonization diminishes the number of somatostatin-producing cells; somatostatin-mediated inhibition of gastrin release
leads to hypergastrinemia.

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USMLE Step 1 Platinum Notes

Gastric Carcinoma
Gastric carcinoma is classified on the basis of depth of invasion, macroscopic growth pattern and histologic subtype. The
morphologic feature having the greatest impact on clinical outcome is the depth of invasion
Early gastric carcinoma is defined as a lesion confined to the mucosa and submucosa, regardless of the presence or absence
of perigastric lymph node metastases
Advanced gastric carcinoma is a neoplasm that has extended below the submucosa into the muscular wall and has perhaps
spread more widely. Gastric mucosal dysplasia is the presumed precursor lesion of early gastric cancer, which then in turn
progresses to advanced lesions.
Sometimes a broad region of the gastric wall, or the entire stomach, is extensively infiltrated by malignancy. The rigid and
thickened stomach is termed a leather bottle stomach, or linitis plastical
The diffuse variant is composed of gastric-type mucous cells that generally do not form glands but rather permeate the
mucosa and wall as scattered individual signet-ring cells or small clusters in an infiltrative growth pattern
For obscure reasons, the earliest lymph node metastasis may sometimes involve a supraclavicular lymph node (Virchow
node)
Another somewhat unusual mode of intraperitoneal spread in females is to both the ovaries, giving rise to the so-called
Krukenberg tumor.

Gastrointestinal stromal tumor (GIST): (USMLE Favorite)

Arise from interstitial cells of Cajal
Stain positive for antibodies with: CD 117, CD 34
Increased tyrosine kinase activity
Most (5080%) GISTs arise because of a mutation in a gene called c-kit. This gene encodes a transmembrane receptor for a growth
factor termed scf (stem cell factor). The c-kit/CD117 receptor is expressed on ICCs and a large number of other cells, mainly bone
marrow cells, mast cells, melanocytes and several others. In the gut, however, a mass staining positive for CD117 is likely to be a GIST,
arising from ICC cells
The c-kit molecule comprises a long extracellular domain, a transcellular segment, and an intracellular part. Mutations generally occur
in the DNA encoding the intracellular part (exon 11), which acts as a tyrosine kinase to activate other enzymes. Mutations make c-kit
function independent of activation by scf, leading to a high cell division rate and possibly genomic instability. It is likely that additional
mutations are required for a cell with a c-kit mutation to develop into a GIST, but the c-kit mutation is probably the first step of this
process. The tyrosine kinase function of c-kit is vital in the therapy for GISTs
Carneys triad: Gastric GIST+Para ganglioma+pulmonary chondroma.

Intestinal Polyposis and Associations: (This table has been repeated in surgery for revision)
Bessauds-Hillmand-Augier Syndrome: Sexual infantilism associated with intestinal polyposis.
Carter-Horsley-Hughes Syndrome. Diffuse polyposis of the small and large intestine.
Cowdens Disease or Multiple Hamartoma Syndrome
Hamartomatous, juvenile, lipomatous, or inflammatory polyps are present mainly in the stomach and colon but are
also present in the small intestine. Benign and malignant breast and thyroid disease are also found in these patients, as well
as mucocutaneous lesions, trichilemmomas, acral keratoses and oral papillomas.
Cronkhite-Canada Syndrome. This syndrome is characterized by:
Generalized gastrointestinal polyposis and
Ectodermal defects, such as alopecia, excessive skin pigmentations and nail atrophy
In the intestinal polyps, dilated cystic glands are found in an edematous lamina propria. Loss of protein from the gut, along
with calcium, magnesium and potassium deficiencies, may occur.
Familial Polyposis of the Colon. This syndrome is customarily associated with polyps of the colon, but cases of generalized
polyposis have been recorded, with associated malignancy
Gardners Syndrome. This syndrome is generally characterized by rectal and colonic polyposis, but generalized Polyposis has
been recorded. These polyps are involved in the development of adenocarcinoma. The syndrome also includes:

Pathology

381

Cysts of the skin

Osteomas
Fibrous and fatty tumors of the skin and mesentery
Follicular odontomas
Dentigerous cysts and
Changes in the bony structures of the jaws
This syndrome is familial and is transmitted as an autosomal dominant trait

Gordons Disease. This is a protein-losing gastroenteropathy, usually manifested as Menetriers disease, which involves:
Mucosal hypertrophy
Hyperplasia of the superficial epithelium
Degeneration in the glandular layer, and
Hypoproteinemia due to leakage of proteins through the mucous membranes. A diffuse gastrointestinal polyposis associated
with protein loss has also been reported.
Juvenile Polyposis. Juvenile polyposis is most commonly found in the colon and rectum, but isolated examples of generalized
gastrointestinal polyposis have been reported with and without family history or other congenital abnormalities.

Muir-Torre Syndrome. This syndrome was described to include

Sebaceous adenomas
Epidermoid cysts, fibromas, desmoids, lipomas, fibrosarcomas and
Leiomyomas with visceral cancers

Peutz-Jeghers Syndrome. This syndrome is characterized by hamartomatous polyps of the gastrointestinal tract (stomach,
small bowel, colon) that are associated with mucocutaneous pigmentation (lips, oral mucosa, fingers, forearm, toes, umbilical
area). The skin pigmentation may fade after puberty, but that of the mucous membrane is retained.
Rendu-Osler-Weber Disease. This disease is described as telangiectasia of the nasopharynx or gastrointestinal tract.
Turcots Syndrome. Malignant brain tumors are associated with inherited intestinal adenomatous polyposis.
von Recklinghausens Disease. Generalized neurofibromatosis with caf au lait skin pigmentation may also include
neurofibromas of the gastrointestinal tract.

PATHOLOGY OF INTESTINAL DISEASES

Celiac sprue
Is gluten sensitive enteropathy or nontropical sprue
Hypersensitivity to gluten/gliadin occurs with loss of villi and Malabsorption

Genetic predisposition:
HLA B8
DR 3
DQ2

Pathology
Loss of villi
Increased intraepithelial lymphocytes
Increased plasma cells in lamina propria
Presentation: Malabsorption, abdominal distension, bloating, diarrhea, steatorrhea, weight loss
Association with dermatitis herpetiformis.

Tropical Sprue
Malabsorptive disease in tropical regions with unknown etiology
Similar features to celiac sprue and responds to antibiotics, Vitamin B12, Folate.

382

USMLE Step 1 Platinum Notes

Whipple Disease
Malabsorptive disease caused by Trophermyma whippeli
PAS positive, rod shaped bacilli fill lamina propria
Treatment is with antibiotics.

USMLE Case Scenario

A 44-year-old female developed loose stools and generalized but vague abdominal pain. On questioning, she had felt tired for
3 years and had lost about five kg in weight during the preceding 7 months despite a good appetite. Laboratory investigations
showed a macrocytic anemia only. The blood film showed many Howell-Jolly bodies. Bone marrow examination revealed
active erythropoiesis with early megaloblastic features. Her serum was positive for IgA antibodies to endomysium and she
had high levels of IgA and IgG antibodies to gliadin. The pathologists report on doing jejunal biopsy showed stunted villi,
and subtotal villous atrophy with marked increase in intraepithelial lymphocytes and chronic inflammation in the lamina
propria. The patient should be started on:
1. A high carbohydrate diet
2. A low iron diet with high gluten content
3. A high calorie diet
4. A gluten-free diet
5. Total parentral nutrition (TPN)
6. Intravenous iron only
Ans. 4. A gluten-free diet

INFLAMMATORY BOWEL DISEASES

Crohn Disease
There is gross involvement of the small intestine alone in about 30% of cases, of small intestine and colon in 40%, and of the
colon alone in about 30%. Crohn disease may involve the duodenum, stomach, esophagus and even mouth, but these sites
are distinctly uncommon
When fully developed, Crohn disease is characterized by:
Sharply delimited and typically transmural involvement of the bowel by an inflammatory process with mucosal damage
The presence of noncaseating granulomas in 40 to 60% of cases, and
Fissuring with formation of fistulae.

Ulcerative Colitis
Involves the rectum and sigmoid and may involve the entire colon
Presentation with an even higher proximal extension (pancolitis) occurs much less frequently. Colonic involvement is
continuous from the distal colon, so that skip lesions are not encountered. Active disease denotes ongoing inflammatory
destruction of the mucosa, with macroscopic hyperemia, edema and granularity with friability and easy bleeding.
Ulcerative colitis

Crohns disease

Involves rectum always

Pipe stem colon

Involves ileum mostly

May cause pancolitis

Diffuse involvement

Nondiffuse involvement
Called regional enteritis

Retrograde spread to ileum is backwash ileitis

Disease of continuity

Skip lesions

Pseudopolyps present

Pseudopolyps absent

Limited to mucosa and submucosa

Transmural inflammation

Noncaseating granulomas not seen

Noncaseating granulomas seen

Pathology
Ulcerative colitis

Crohns disease

Creeping fat not seen

Creeping fat seen

Strictures, ulcerations, fistula less frequent

Strictures, ulcerations, fistula frequent

Toxic megacolon occurs

Rare

Malignant transformation +++

Malignant transformation +

383

USMLE Case Scenario

A 52-year-old man from Nebraska presents to Gastro clinic with a complaint of nonbloody diarrhea and right lower
quadrant pain with a palpable mass and tenderness. He states that this flare-up is one of the worst he has ever experienced.
Radiographic examination reveals evidence of ulceration, stricturing, and fistula development of the colon and small bowel.
The most likely diagnosis is:
Ans. Crohns disease

USMLE Case Scenario

A 33-year-old business class woman was admitted with a 3 weeks history of increasing bloody diarrhea and abdominal
pain; she had lost 5 kg in weight. She smoked 25 cigarettes a day. On examination, she was having tenderness over the right
iliac fossa, sigmoidoscopy showed a red, granular mucosa with mucopus and contact bleeding. Ulceration of the surface
epithelium, noncaseating granulomas and skip lesions. Most likely cause is:
1. Ischemic colitis
2. Gluten enteropathy
3. Crohns disease
4. Ulcerative colitis
5. Pseudomembranous colitis
Ans. 3. Crohns disease

Typhoid Ulcer

Ulceration of Peyers patches

It is a longitudinal ulcer
Perforates
Stricture formation is rare.

Mallory bodies are composed of eosinophilic intracytoplasmic inclusions are seen in:
Alcoholism
Primary Biliary Cirrhosis
Wilsons Disease

384

USMLE Step 1 Platinum Notes

Mallory Hyaline is absent in:

Hepatitis
Secondary Biliary Cirrhosis
Fibrosis
Ito cells are a source of collagen in Cirrhosis of liver
Nutmeg Liver is due to Chronic passive congestion

Hepatitis: (You should not attempt examinations without knowing this table)
Acute infection: HBsAg+, IgM anti HBc+
Resolved infection: HBsAg, IgG anti HBc+
Vaccination: HBsAg, anti HBs+
Inactive carrier:
HBsAg + greater than 6 months
HBeAg, antiHBe+
HBV DNA < 105copies/ml
Normal liver enzymes
Chronic Hepatitis:
HBV DNA > 105copies/ml
Liver enzymes
Necro inflammation on liver biopsy.

Features of Acute Hepatitis: (USMLE Favorite)

Zonal necrosis
Bridging hepatic necrosis
Hepatic cell necrosis
liver size
liver redness
Kupffer cell hypertrophy and hyperplasia
Lobular disarray
Focal necrotic spot
Councilman/apoptotic bodies are seen in acute hepatitis.

Features of Chronic Hepatitis: (USMLE Favorite)

Chronic Active Hepatitis:
Piecemeal necrosis
Bridging necrosis
Rosette and Pseudolobule formation
Ground glass appearance of Hepatocytes
Councilman Bodies
Kupffer cell Hyperplasia.
Chronic Persistent Hepatitis:
No piecemeal necrosis
Mononuclear infiltrate confined to portal tract
Septae into parenchyma.

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385

HEPATITIS C
The Characteristic Lesion is:
Paucity of inflammation
Increase in activation of sinusoidal lining
Lymphoid aggregates
Bile duct damage in portal tracts
Most common cause of post-transfusion hepatitis
Causes chronic hepatitis.

USMLE Case Scenario

A 44-year-old lady had nephrotic syndrome. On further investigations warm sample of ladys blood serum contained a mixed
cryoglobulin, A skin biopsy showed scattered deposits of IgM, IgG and C3 in dermal blood vessels. The final diagnosis was
mixed cryoglobulinemia. It is seen in association with:
1. Perihepatitis by chlamydia
2. Hepatitis A infection
3. Chronic Hepatitis C infection
4. Lichen planus
5. Psoriasis
Ans. 3. Chronic Hepatitis C infection

HEPATITIS D

HDV is Defective because it does not have genes for its proteins
HDV can replicate in cells only infected with HBV
HDV uses surface antigen of HBV (HBsAg) as it envelop protein
HBV is a helper virus for HDV.

HDV is an enveloped virus

HDV is an RNA virus
Genome of HDV is small and encodes only one protein the delta antigen
HDV genome is a Ribozyme i.e. has ability to self-cleave and self-ligate
Infection with hepatitis D can be prevented by vaccinating susceptible persons with hepatitis B vaccine

Most common cause of sporadiac cases of hepatitis in adults: Hep E

Worst prognosis in pregnancy: Hep E
Most common route of spread of Hep E is fecooral

PRIMARY LIVER CARCINOMAS

Hepatocellular Cancer
Hepatocelluler Cancer is the most common. They, may appear grossly as:
A unifocal, usually massive
A multifocal tumor made of nodules of variable size; or
A diffusely infiltrative cancer, permeating widely and sometimes involving the entire liver, blending imperceptibly into the cirrhotic
liver background
The main etiologic agents for hepatocellular carcinoma are:
Hepatitis B and C
Alcoholic cirrhosis

386

USMLE Step 1 Platinum Notes

Hemochromatosis and
Tyrosinemia
Hepatocellular carcinomas maybe unifocal or multifocal tend to invade blood vessels, and recapitulate normal liver architecture to
varying degrees
Histologically, HCCs range from well differentiated lesions that reproduce hepatocytes arranged in cords, trabeculae or glandular
patterns to poorly differentiated lesions, often composed of large multinucleate anaplastic tumor giant cells.

Fibrolamellar Carcinoma
A distinctive clinicopathologic variant of HCC is the fibrolamellar carcinoma, which occurs in young male and female adults (20
40 years of age) with equal incidence has no association with cirrhosis or other risk factors (It usually consists of a single large,
hard scirrhous tumor with fibrous bands coursing through it, vaguely resembling focal nodular hyperplasia.
The liver is the most common site of metastatic cancers from primary tumors of the colon, lung and breast.
Angiosarcoma liver: Vinyl chloride, Aflatoxin, Thorotrast
Peliosis hepatitis: Steroids, Danazol
Hepatic vein thrombosis: OCP, cytotoxic drugs
Veno-occlusive disease: Pyrrolizidine alkaloids, cytotoxic drugs.

Causes of Splenomegaly: (USMLE Favorite)

Massive Splenomegaly (weight more than 1000 gm)
Chronic myeloproliferative disorders (chronic myeloid leukemia, myeloid metaplasia with myelofibrosis)
Chronic lymphocytic leukemia
Hairy cell leukemia
Lymphomas
Malaria
Gaucher disease
Primary tumors of the spleen
Moderate splenomegaly (weight 5001000 gm)
Chronic congestive splenomegaly (portal hypertension or splenic vein obstruction)
Acute leukemias
Hereditary spherocytosis
Thalassemia major
Autoimmune hemolytic anemia
Amyloidosis
Niemann-Pick disease
Langerhans histiocytosis
Chronic splenitis (especially with infective endocarditis)
Tuberculosis, sarcoidosis, typhoid
Metastatic carcinoma or sarcoma
Mild splenomegaly (weight < 500 gm)
Acute splenitis
Acute splenic congestion
Infectious mononucleosis
Miscellaneous acute febrile disorders, including septicemia, SLE and intraabdominal infections

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387

RENAL SYSTEM
Pathology detected on Macroscopic appearance of Kidneys
Renomegaly:
Diabetic nephropathy
Amyloidosis
Scleroderma
Polycystic kidney
Acute Glomerulonephritis
Contracted Kidney:
Chronic Glomerulonephritis
Chronic Pyelonephritis
Benign Nephrosclerosis (B/L)
Flea Bitten Kidney:
Acute Post streptococcal Glomerulonephritis
RPGN
HUS
TTP
HSP
SABE
Malignant Hypertension

USMLE Case Scenario

Kidney biopsy from a child with hemolytic uremic syndrome characteristically most likely presents features of:
1. Thrombotic microangiopathy
2. Proliferative glomerulonephritis
3. Focal segmental glomerulosclerosis
4. Minimal change disease
Ans. 1. Thrombotic microangiopathy
Nephritic syndrome

Nephrotic syndrome

Hematuria

Severe proteinuria

Hypertension

Hypoalbuminemia

Oliguria

Hyperlipidemia

Proteinuria

Glomerulopathies: (USMLE Favorite)

The most frequent cause of nephrotic syndrome in children is minimal change disease (lipoid nephrosis)
It is characterized by an absence of findings by light microscopy and
Fusion of epithelial foot processes by electron microscopy

Dense deposits are seen in type II membranoproliferative glomerulonephritis

Mesangial deposits are a prominent feature of IgA nephropathy and are seen to a lesser degree in several other glomerulonephritides
Subendothelial deposits are seen in type I membranoproliferative glomerulonephritis
Diffuse involvement is seen in PSGN
Anti GBM antibodies are seen in Goodpastures syndrome

Focal segmental glomerulosclerosis is a feature of HIV associated nephropathy

Collapsing variety of FSGS has worst prognosis
Hypertrophy and necrosis of epithelium are a feature.

388

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 34-year-old man from New Orleans presents with hemoptysis and hematuria. This is a classic case of Goodpastures
syndrome. Under immunofluorescence; there are linear deposits of IgG on alveolar and glomerular basement membranes.
Renal biopsy shows inflammation of the glomeruli. X-ray shows focal pulmonary infiltrates. The most likely cause is:
1. Wegeners granulomatosis
2. Poststreptococcal glomerulonephritis
3. Bergers disease
4. Goodpastures syndrome
Ans. 4. Goodpastures syndrome

Subepithelial humps: PSGN

Subepithelial spikes with M spike: Membranous GN
Subendothelial deposits: Lupus nephritis
Spike and dome pattern: Membranous glomeruolonephritis
Lumpy bumpy deposits: RPGN
Tram track appearance: Membranoproliferative GN
Crescents: Epithelial cells + fibrin + macrophage

Causes of Low Complement

Poststreptococcal GN (NONPERSISTENT)
Lupus nephritis
Cryoglobinemia
Bacterial endocarditis
Shunt nephritis
MP GN
Cresentric GN
Idiopathic Proliferative GN
Sepsis
Cryoglobulinemia

Alports Syndrome: (USMLE Favorite)

Hereditary Nephritis
Nerve Deafness
Eye disorders (Lens Dislocation, Corneal Dystrophy, Posterior cataracts)
Foamy cells in interstitium
Thinning of Basement membrane <100 nm
Mutation in alpha 5 chain of collagen type IV

Xanthogranulomatous Pyelonephritis
Rare type of chronic pyelonephritis
Accumulation of foamy macrophages, plasma cells, lymphocytes.

Analgesic Nephropathy

Chronic disease due to excessive use of analgesics

Pathological; lesions: Papillary Necrosis with Chronic Tubulointerstitial nephritis
But most common cause of renal papillary necrosis is Diabetes mellitus
Diabetes mellitus, Analgesics, sickle cell disease cause necrotizing pappilitis

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389

POLYCYSTIC KIDNEYS
Autosomal Dominant Polycystic Kidney Disease: (USMLE Favorite)
ADPKD-1 accounts for 90% of cases, and the gene has been localized to the short arm of chromosome 16
ADPKD-2 has been mapped to the long arm of chromosome 4
The protein products of the two genes form the Polycystin complex, which may regulate cell-cell or cell-matrix interactions

Pathology:
The kidneys are grossly enlarged, with multiple cysts studding the surface of the kidney
The cysts contain straw-colored fluid that may become hemorrhagic
The cysts are spherical, vary in size from a few millimeters to centimeters, and are distributed evenly throughout the cortex and
medulla
The remaining renal parenchyma reveals varying degrees of tubular atrophy, interstitial fibrosis and nephrosclerosis
Colonic diverticulae
Cysts in other organs
Berry aneurysm
Mitral valve prolapsed + Aortic Regurgitation.
Autosomal Recessive Polycystic Kidney Disease
The gene for ARPKD has been localized to chromosome 6
Hepatic cysts with hepatic fibrosis.

390

USMLE Step 1 Platinum Notes

Tuberous Sclerosis: (USMLE Favorite)

Patients with this multisystem disease most commonly present with skin lesions and benign tumors of the central nervous system)
Renal involvement is common
Angiomyolipomas are the most frequent abnormality and are usually bilateral
Renal cysts maybe present as well and can give an appearance similar to that of ADPKD
Histologically, the cysts are unique
The cyst lining cells are large with an eosinophilic staining cytoplasm and may form hyperplastic nodules that can fill the cyst
space.

Von Hippel-Lindau Disease

This autosomal dominant disease is characterized by
Hemangioblastomas of the retina and the central nervous system
Renal cysts occur in the majority of cases and are usually bilateral
The VHL gene is a tumor-suppressor gene and has been localized to chromosome 3. It is the same gene that is mutated in sporadic
renal cell carcinoma, which maybe found in up to 25% of patients with von Hippel-Lindau disease and is frequently multifocal.

Medullary: (Sponge Kidney)

Medullary sponge kidney (MSK) is a congenital disorder
Although some cases have apparent autosomal dominant inheritance, most are sporadic
Males and females are affected equally
The pathologic lesion is cystic dilation of the inner medullary and papillary collecting ducts, with collecting diameters
ranging from 1 to 5 mm
Bilateral renal involvement is present in 70% of cases, but not all papillae are equally affected
The dilated ducts are lined by cuboidal epithelium with areas of pseudostratified and stratified squamous epithelium
Calculi are frequently found in the dilated collecting ducts.

Juvenile Nephrophthisis/Medullary Cystic Disease

Juvenile nephrophthisis (JN) and medullary cystic disease (MCD) have similar pathologic findings but differ in inheritance pattern
and age of onset
JN is inherited as an autosomal recessive disease
MCD is an autosomal dominant disease
In both conditions
The kidneys tend to be small, with cysts throughout the medulla
The cortex and papilla rarely have cysts
The cysts originate in the collecting ducts, distal convoluted tubules and loops of Henle and range in size from 1 to 10 mm
Sclerotic glomeruli, tubule atrophy and interstitial fibrosis are frequent findings on biopsy.
Juvenile Nephronophthisis

Medullary Cystic Disease

Patients with JN present during childhood with symptoms

of polyuria, growth retardation, anemia and progressive
renal insufficiency
Most patients develop ESRD prior to the age of 20;

MCD presents in the third or fourth decade, though some

cases maybe diagnosed in the elderly population. Presenting
symptoms in MCD are the same as in JN except for growth
retardation.

JN accounts for 2 to 10% of renal failure in children

MCD does not have extrarenal abnormalities. Severe salt
wasting can be seen
Hepatic fibrosis and cerebellar ataxia has been reported
in association with JN
Other features of tubule damage are often found, including hyperkalemia and hyperchloremic metabolic acidosis. Proteinuria
JN with retinal degeneration is termed the Senior-Loken
is mild, and hematuria is rare.
syndrome.

Pathology

391

Renal Cancer
Renal cell neoplasia represents a heterogeneous group of tumors with distinct histopathologic, genetic and clinical features ranging
from benign to high-grade malignant
Categories include:
Clear cell carcinoma (MC)
Papillary
Chromophobic tumors
Oncocytomas
Collecting or Bellini duct tumors
Clear cell tumors are characterized by tumor cells with clear cytoplasm and consistently show a deletion of 3p
Papillary tumors tend to be bilateral and multifocal. Trisomy 7 and/or 17 is most frequent genetic markers
Chromophobic tumors are characterized by multiple chromosomal losses but do not exhibit 3p deletions
Oncocytomas have a characteristic morphology including a deeply eosinophilic cytoplasm, do not exhibit 3p deletions or
trisomy 7 or 17, and are considered benign neoplasms
Bellini duct carcinomas are very rare and are thought to arise from the collecting ducts within the renal medulla. They tend to
afflict younger patients and are very aggressive tumors.

Wegners Granulomatosis
Necrotizing vasculitis of small arteries and veins together with granuloma formation that can be either Intravascular or
extravascular
Lung involvement: bilateral nodular cavitary infiltrates, demonstrate necrotizing granulomatous vasculitis
The renal biopsy lesion is that of a pauci-immune necrotizing and crescentic GN
Lung, nose, kidneys involved
Anti-GBM disease commonly presents with hematuria, nephritic urinary sediment, subnephrotic proteinuria
Rapidly progressive renal failure over weeks, with or without pulmonary hemorrhage
When pulmonary hemorrhage occurs, it usually predates nephritis by weeks or months
Hemoptysis can vary from fluffy pulmonary infiltrates on Chest X-ray and mild dyspnea on exertion to life-threatening pulmonary
hemorrhage
Renal biopsy is the gold standard for diagnosis of anti-GBM nephritis
The typical morphologic pattern on light
Microscopy is diffuse proliferative glomerulonephritis, with focal necrotizing lesions and crescents in >50% of Glomeruli (crescentic
glomerulonephritis)
Immunofluorescence microscopy reveals linear ribbon-like deposition of IgG along the GBM

USMLE Case Scenario

A 62-year-old from Wales presently in US develops oliguria and peripheral edema over a period of weeks. Urinalysis reveals
hematuria and proteinuria; examination of the urinary sediment reveals red cell casts. Renal biopsy shows many glomerular
crescents. This presentation is most suggestive of which of the following conditions?
1. Rapidly progressive glomerulonephritis
2. Diabetic nephropathy
3. Hypertensive nephropathy
4. Lupus nephritis
Ans. 1. Rapidly progressive glomerulonephritis

Catheter-Associated UTIs
Bacteriuria develops in at least 10 to 15% of hospitalized patients with indwelling urethral catheters
E coli, Proteus, Pseudomonas, Klebsiella, Serratia, staphylococci, enterococci and Candida usually cause these infections
Infection occurs when bacteria reach the bladder by one of two routes: by migrating through the column of urine in the catheter lumen
(intraluminal route) or by moving up the mucous sheath outside the catheter (periurethral route).

392

USMLE Step 1 Platinum Notes

Clinically, most catheter-associated infections cause minimal symptoms and no fever and often resolve after withdrawal of the
catheter
Catheter-associated UTIs can sometimes be prevented in patients catheterized for 2 weeks by use of a sterile closed collecting
system, by attention to aseptic technique during insertion and care of the catheter and by measures to minimize crossinfection. Other preventive approaches, including
Short courses of systemic antimicrobial therapy
Topical application of periurethral antimicrobial ointments
Use of preconnected catheter-drainage tube units
Use of catheters impregnated with antimicrobial agents and
Addition of antimicrobial drugs to the drainage bag
Bilateral renal cell carcinomas can be a feature of von Hippel-Lindau disease
Kimlstein wilson lesions: feature of diabetic nephropathy.

Thyroid Pathology
Primary hyperthyroidism: TSH , T4
Secondary hyperthyroidism: TSH
Hypothyroidism: TSH

Hashimotos Thyroiditis
Mc type
Mc cause of hypothyroidism
Mc in females
Anti-TSH receptor antibodies
Anti-thyroglobulin antibodies
Anti-thyroid peroxidase antibodies
Hurthle cells seen
Grossly, the thyroid is usually diffusely and symmetrically enlarged, although more localized enlargement maybe seen in some cases
The capsule is intact, and the gland is well demarcated from adjacent structures. The cut surface is pale, gray-tan, firm and somewhat
friable. Microscopic examination reveals widespread infiltration of the parenchyma by a mononuclear inflammatory infiltrate
containing small lymphocytes, plasma cells and well-developed germinal centers
The thyroid follicles are atrophic and are lined in many areas by epithelial cells distinguished by the presence of abundant eosinophilic,
granular cytoplasm, termed Hrthle, or oxyphil, cells
Less commonly, the thyroid is small and atrophic as a result of more extensive fibrosis (fibrosing variant).

Subacute Granulomatous (De Quervain) Thyroiditis: (USMLE Favorite)

Subacute granulomatous thyroiditis, also known as de Quervain thyroiditis, is much less common than is Hashimoto disease
De Quervain thyroiditis is most common between the ages of 30 and 50 and, like other forms of thyroiditis, occurs more frequently
in women than in men
Subacute thyroiditis is believed to be caused by a viral infection or a postviral inflammatory process
The gland is firm, with an intact capsule, and maybe unilaterally or bilaterally enlarged
Histologically, there is disruption of thyroid follicles, with extravasation of colloid leading to a polymorphonuclear infiltrate, which
is replaced overtime by lymphocytes, plasma cells and macrophages.

Riedel Thyroiditis
It is a rare disorder of unknown etiology, is characterized by extensive fibrosis involving the thyroid and contiguous neck
structures
The presence of a hard and fixed thyroid mass clinically simulates a thyroid neoplasm
It maybe associated with idiopathic fibrosis in other sites in the body, such as the retroperitoneum
The presence of circulating antithyroid antibodies in most patients suggests an autoimmune etiology.

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393

Hyperthyroidism
The measurement of serum TSH concentration using sensitive assays provides the most useful single screening test for hyperthyroidism,
because TSH levels are decreased even at the earliest stages. Hyperthyroidism results predominantly from increased circulating levels
of T3 (T3 toxicosis). In these cases free T4 levels maybe decreased, and direct measurement of serum T3 maybe useful
Remember:
Once the diagnosis of thyrotoxicosis has been confirmed by a combination of TSH and free thyroid hormone assays,
measurement of radioactive iodine uptake by the thyroid gland is often valuable in determining the etiology
There maybe diffusely increased uptake in the whole gland (Graves disease), increased uptake in a solitary nodule (toxic
adenoma), or
Decreased uptake (thyroiditis).

USMLE Case Scenario

A 33-year-old nervous and anxious woman presented with a 3-month history of increased sweating and palpitations with
weight loss of 7 kg. On examination, she had a diffuse, nontender, smooth enlargement of her thyroid, over which a bruit
could be heard. She had a fine tremor of her fingers and a resting pulse rate of 159/minute. On investigation, she had serum
T3 of 5.5 nmol/l (NR 0.82.4) and a T4 of 59 nmol/l (NR 923). Measurement of her thyroid-stimulating hormone showed that
this was low normal, 0.4 mU/l (NR 0.45 mU/l). Circulating antibodies to thyroid peroxidase were detected by agglutination.
Most likely cause is:
1. Hashimotos disease
2. Wolf chaikkoff effect
3. Pendred syndrome
4. Autoimmune thyrotoxicosis
5. De quervians disease
Ans. 4. Autoimmune thyrotoxicosis

USMLE Case Scenario

A 44 year-old woman from a hilly area presented with a large, painless swelling in her neck. Thyroid function tests showed
that she was euthyroid; however, her serum contained high titre antibodies to thyroid peroxidase. Most likely cause is:
1. Hashimotos thyroiditis
2. Wolf chaikkoff effect
3. Pendred syndrome
4. Autoimmune thyrotoxicosis
5. De quervians disease
Ans. 1. Hashimotos thyroiditis

Malignant Solitary Thyroid Nodule

Male
Young
Solitary nodule
Cold on radioactive scan
Radiation exposure to head and neck

Pappilary Ca Thyroid

Mc type
Spread by lymphatics
Psommoma bodies seen
Orphan annie eyed nuclei seen
Develops in throglossal tract
Associated with dystrophic calcification

394

USMLE Step 1 Platinum Notes

Least malignant
The nuclei of papillary carcinoma cells contain very finely dispersed chromatin, which imparts an optically clear appearance, giving
rise to the designation ground-glass or Orphan Annie eye nuclei. A papillary architecture is present in many cases Concentrically
calcified structures termed psammoma bodies are often present within the papillae.

Follicular Ca Thyroid: (USMLE Favorite)

Second mc tumor of thyroid
Hematogeneous spread
Diagnosis by biopsy not FNAC
Hurhle cell ca is a variant
Microscopically, most follicular carcinomas are composed of fairly uniform cells forming small follicles, reminiscent of normal
thyroid.

Medullary Ca Thyroid: (USMLE Favorite)

Arises from parafollicular cells C cells

Secrete calcitonin
Associated with MEN II
Amyloid stroma
RET proto oncogene involved

Anaplastic Ca
Worst Prognosis

Thyroid Neoplasms
Most thyroid neoplasms present as solitary thyroid nodules; only 1% of all thyroid nodules are neoplastic
Follicular adenomas are the most common benign neoplasms, while papillary carcinoma is the most common malignancy
Multiple genetic pathways are involved in thyroid carcinogenesis. Some of the genetic abnormalities that are fairly unique to
thyroid cancers include
PAX8-PPAR1 fusion (in follicular carcinoma)
Chromosomal rearrangements involving the RET oncogene (papillary cancers)
Mutations of RET (medullary carcinomas)
Follicular adenomas and carcinomas are both composed of well-differentiated follicular epithelial cells, and are distinguished by
evidence of capsular and/or vascular invasion in the latter.

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Papillary carcinomas are recognized based on nuclear features (ground-glass nuclei, pseudo-inclusions) even in the absence of
papillae
Psammoma bodies are a characteristic feature of papillary cancers; these neoplasms typically metastasize via lymphatics but their
prognosis is excellent
Medullary cancers are nonepithelial neoplasms arising from the parafollicular C cells and can occur in either sporadic (80%) or
familial (20%) settings Amyloid deposits are a characteristic histologic finding
Anaplastic carcinomas are thought to arise by dedifferentiation of more differentiated neoplasms. They are highly aggressive,
uniformly lethal cancers.

USMLE Case Scenario

MEN II and MEN III are associated with:
1. C-myc
2. erb-B2
3. L-myc
4. Ret
Ans. 4. Ret

USMLE Case Scenario

Which of the following gene defect is associated with development of medullary carcinoma of thyroid?
1. Ret Proto Oncogene
2. FAP gene
3. Rb gene
4. BRCA 1 gene
Ans. 1. Ret Proto Oncogene

USMLE Case Scenario

The correct sequence of cell cycle is:
1. G0-G1-S-G2-M
2. G0-G1-G2-S-M
3. G0-M-G2-S-G1
4. G0-G1-S-M-G2
Ans. 1.G0-G1-S-G2-M

Struma Ovarii
It is composed of mature thyroid tissue
Usually a teratoma
May present with hyperthyroidism.

Pheochromocytoma
Sweating, tachycardia, palpitations, hypertension are features
MC site: adrenal glands
Bilaterality: 10%
Extra-adrenal: 10%
Malignant: 10%
Children: 10%
Familial: 10%

396

USMLE Step 1 Platinum Notes

Immunomarkers:
Chromogranin
Synaptophysin
S 100
Associations:
MEN I
MEN II
MEN III
Sturge weber syndrome
von Hippel-Lindau syndrome
Neurofibromatosis
Pheochromocytomas range from small, circumscribed lesions confined to the adrenal to large, hemorrhagic masses
weighing several kilograms
On cut surface, smaller pheochromocytomas are yellow-tan, well-defined lesions that compress the adjacent adrenal
larger lesions tend to be hemorrhagic, necrotic, and cystic and typically efface the adrenal gland
Incubation of the fresh tissue with potassium dichromate solutions turns the tumor a dark brown color
Microscopically, pheochromocytomas are composed of polygonal to spindle-shaped chromaffin cells and their supporting
cells, compartmentalized into small nests, or Zellballen, by a rich vascular network.

USMLE Case Scenario

Pheochromocytoma intermittently secretes epinephrine and other vasoactive amines, producing episodes of elevated blood
pressure accompanied by headache. This is the tumor to associate with the rule of the 10s:
1. It is 10% nonmalignant
2. It is 10% unilateral
3. 10% adrenal
4. 10% are familial
Ans. 4. 10% are familial

USMLE Case Scenario

A disease is associated with multiple telangiectasias which are usually small. The most likely disease is:
1. von Hippel-Lindau disease
2. Osler-Weber-Rendu disease
3. Milroys disease
4. Buergers disease
Ans. 2. Osler-Weber-Rendu disease

USMLE Case Scenario

A boy presents with a purple, flat vascular ectasia on the head and along distribution of the trigeminal nerve, mental
retardation, seizures, and hemiplegia. The most likely disease is:
1. Milroys disease
2. Osler-Weber-Rendu disease
3. Sturge-Weber syndrome
4. von Hippel-Lindau disease
Ans. 3. Sturge-Weber syndrome

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397

Hematology
Uremia
G6PD deficiency
Hemet cells

Burr cells are seen

Bite cells
Hemolytic Uremic Syndrome

Cirrhosis

Spur cells are seen

Iron depletion

Seen in Iron deficiency anemia, polycythemia vera

Thalassemia minor

Decreased osmolysis, microcytic hypochromic anemia, increased HbA2

Sickle cell anemia

Tactoids and sickling seen

Acquired spherocytosis

Schistocytes present, Coombs positive

Hereditary spherocytosis

Coombs negative

Aplastic anemia

Platelets maximum affected and last to recover, Pancytopenia present

Pernicious anemia and Folate deficiency Anisocytosis, poikilocytosis, fragmented RBC, neutrophil lobes increased,
anemia
platelets normal. Absolute reticulocyte count low.
Sideroblastic Anemia

Ring Sideroblasts present (These are Iron granules in mitochondria around

the nucleus) Microcytic, hypochromis RBC Macrocytic hypo or normochromic
RBC

Polycythemia vera

Increased RBCs, platelets and Leukocytes Splenomegaly Present

Myeloid metaplastia and Myelofibrosis

Giant Platelets Macrocytic Anemia Tear Droppoikilocytes Leukoerythroblastic

picture

Megakaryocytosis marrow seen in

Idiopathic Thrombocytopenic purpura Myeloid Metaplasia Polycythemia vera

Postsplenectomy Changes

Anisocytosis, poikilocytosis
Macrocytosis
Howell jolly bodies
Heinz bodies
Target cells
Pappenheimer bodies.

Burr cell is seen in uremia

Acanthocytes are seen in abetalipoproteinemia
Macroploycytes are seen in megaloblastic anemia
Hypersegmented neutrophils are seen in megaloblastic anemia
Spurr cells are seen in chronic liver disease.

398

USMLE Step 1 Platinum Notes

Sickle cell anemia is due to structurally abnormal Hb

Sickle cell anemia is due to replacement of glutamate by valine
Hereditary spherocytosis is due to spectrin deficiency
Proteins defective in hereditary spherocytosis are ankyrin, paladin, anion transport protein
Hereditary spherocytosis is Autosomal dominant.

Recognizing the Hematological Diseases by

Subleukemic Leukemia

Abnormal cells present White cell count normal or decreased

Aleukemic Leukemia

No abnormal cells WBC Count usually decreased below normal

Diagnosis from marrow aspiration

Hairy cell Leukemia (B-CELL)

Neutropenia, Splenomegaly, hairy cells seen

Acute nonlymphocytic Leukemia Lymphoblasts Total count usually more than 1,00,000 Macrocytic Normochromic
Myeloblasts
Anemia Severe Thrombocytopenia PAS Positive, Sudan black positive
stains with Romanowski stain
CML

All series of cells seen Myeloblasts greater than 10

Increased Basophils, eosonophils, thrombocytes

CLL (B-Cell disease)

Small lymphocytes increased Blasts are rare Auto immune hemolytic

anemia present

Prolymphocytic Leukemia

Large lymphocytes with prominent nucleolus

Eosinophilic Leukemia

Eosinophils increased

Burkits lymphoma

Starry sky appearance in Lymphnode biopsy

Causes of Aplastic Anemia

Drugs (Chloramphenicol)
Viruses
PNH
Pregnancy
Idiopathic
Fanconis anemia
Schwaman Diamond Syndrome

Pan Cytopenia with Hypocellular Marrow

Acquired aplastic anemia
Fanconis anemia
A leukemic leukemia

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399

Pan Cytopenia with Hypercellular Marrow

Myelodysplastic syndrome
PNH
Megaloblastic anemia
Myelofibrosis
Hairy cell leukemia
Myelophthisis

Splenomegaly is absent in aplastic anemia

BMT (bone marrow transplant) is the most effective treatment

USMLE Case Scenario

Microcytic, hypochromic anemia with reduced mental and physical performance is due to:
1. Iron deficiency
2. Copper deficiency
3. Calcium deficiency
Ans. 1. Iron deficiency

LEUKEMIA
Acute myeloid leukemia
Heredity: Certain syndromes with somatic cell chromosome aneuploidy, e.g. Down (chromosome 21 trisomy), Klinefelter (XXY
and variants), and Patau (chromosome 13 trisomy), are associated with an increased incidence of AML. Inherited diseases with
excessive chromatin fragility, e.g.
Fanconi anemia
Bloom syndrome
Ataxia telangiectasia and
Kostmann syndrome are also associated with AML
Radiation Survivors of the atomic bomb explosions in Japan had an increased incidence of myeloid leukemias that peaked 5
to 7 years after exposure. Therapeutic radiation alone seems to add little risk of AML but can increase the risk in people exposed
to alkylating agents
Chemical and Other Exposures Exposure to benzene, which is used as a solvent in the chemical, plastic, rubber and pharmaceutical
industries, is associated with an increased incidence of AML. Smoking and exposure to petroleum products, paint, embalming
fluids, ethylene oxide, herbicides and pesticides, have also been associated with an increased risk of AML
Drugs Anticancer drugs are the leading cause of treatment-associated AML. Alkylating agents, Topoisomerase II inhibitors,
Chloramphenicol, phenylbutazone and less commonly, chloroquine and methoxy psoralen can result in bone marrow failure
that may evolve into AML
Chloroma occurs in AML
Auer rods seen
Nonspecific esterase is positive
Nonspecific esterase is NOT positive IN M 6 Type only
AML with gum infiltration is M4
DIC is seen in APML
t (15: 17) is seen in APML
MC type is pre B-cell ALL
By definition, in AML myeloid blasts or promyelocytes make-up more than 20% of the bone marrow cellularity
Myeloblasts (precursors of granulocytes) have delicate nuclear chromatin; three to five nucleoli; and fine, azurophilic granules in
the cytoplasm
Distinctive red-staining rodlike structures (Auer rods) maybe present in myeloblasts or more differentiated cells; they are
particularly prevalent in the progranulocytes found in acute promyelocytic leukemia.

400

USMLE Step 1 Platinum Notes

Chronic Myeloid Leukemia (CML)

The diagnosis of CML is established by identifying a clonal expansion of a hematopoietic stem cell possessing a reciprocal
translocation between chromosomes 9 and 22
This translocation results in the head-to-tail fusion of the breakpoint cluster region (BCR) gene on chromosome 22q11 with the ABL
(named after the abelson murine leukemia virus) gene located on chromosome 9q34.
Basophilic leukocytosis occurs
Untreated, the disease is characterized by the inevitable transition from a chronic phase to an accelerated phase and onto blast crisis

Chronic Lymphoid Leukemia (CLL): (USMLE Favorite)

It is the most prevalent form of leukemia in western countries
It occurs most frequently in older adults and is exceedingly rare in children
CML principally affects adults between 25 and 60 years of age and accounts for 15 to 20% of all cases of leukemia
The peak incidence is in the fourth and fifth decades of life
CLL is more common in men than in women and more common in whites than in blacks
The onset of CML is usually slow, and the initial symptoms are often nonspecific (e.g. easy fatigability, weakness, and weight
loss)
Sometimes the first symptom is a dragging sensation in the abdomen, caused by the extreme splenomegaly that is
characteristic of this condition.

Acute Lymphoid Leukemias (ALL): (USMLE Favorite)

Acute lymphoid leukemias (ALLs) are predominantly cancers of children and young adults
The L3 or Burkitts leukemia occurring in children in developing countries seems to be associated with infection by the EpsteinBarr virus (EBV) in infancy
Childhood ALL occurs more often in higher socioeconomic subgroups
Children with trisomy 21 (Downs syndrome) have an increased risk for childhood acute lymphoblastic leukemia as well as acute
myeloid leukemia
Exposure to high-energy radiation in early childhood increases the risk of developing T-cell acute lymphoblastic leukemia.

FAB Classification of ALL

L 1 Lymphoblasts with uniform, round nuclei and scant cytoplasm
L 2 More variability of lymphoblasts; nuclei maybe irregular with more cytoplasm than L 1
L 3 Lymphoblasts have finer nuclear chromatin and blue-to-deep-blue cytoplasm with cytoplasmic vacuolization

FAB Classification of AML

M 1
M 2
M 3
M 4
M 5
M 6
M 7

Undifferentiated myeloblastic; no cytoplasmic granulation

Differentiated myeloblastic; a few to many cells may have sparse granulation
Promyelocytic; granulation typical of promyelocytic morphology
Myelomonoblastic; mixed myeloblastic and monocytoid morphology
Monoblastic; pure monoblastic morphology
Erythroleukemic; predominantly immature erythroblastic morphology, sometimes megaloblastic appearance
Megakaryoblastic; cells have shaggy borders that may show some budding.

B-Cell Neoplasms

CLL
Hairy cell leukemia
Promyelocytic leukemia
NHL
Mantle cell lymphomas
Burkitts lymphoma

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401

Mantle Cell Lymphoma: (USMLE Favorite)

Tumor of mature B-cells that usually presents with advanced disease involving lymph nodes, bone marrow, and extranodal sites
such as the gut
Associated with t (11; 14) translocations that result in over-expression of cyclin D1, a regulator of cell cycle progression.

Hairy Cell Leukemia

B-cell neoplasm is distinguished by the presence of leukemic cells that have fine, hairlike cytoplasmic projections
The tumor cells express pan-B-cell markers, including CD19 and CD20, surface immunoglobulin, and characteristically, CD11c
and CD103
Occurs mainly in older males, and its manifestations result largely from infiltration of bone marrow and spleen
Splenomegaly is often massive, is the most common and sometimes the only abnormal physical finding
Pancytopenia, resulting from marrow infiltration and splenic sequestration, is seen in more than half the cases
Hepatomegaly is less common and not as marked, and lymphadenopathy is distinctly rare.

Burkitt Lymphoma
Very aggressive tumor of mature B-cells that usually arises at extranodal sites
It is uniformly associated with translocations involving the c-MYC protooncogene
It is often associated with latent infection by Epstein-Barr virus (EBV).

T-Cell Neoplasms
Mediastinal lymphatic leukemia
Adult T-cell leukemia

MISCELLANEOUS NEOPLASMS
Mycosis Fungoides and Sezary Syndrome
These are composed of neoplastic CD4+ T-cells that home to the skin; as a result, they are often referred to as cutaneous T-cell
lymphomas
Usually presents as a nonspecific erythrodermic rash, which overtime tends to progress through a plaque phase to a tumor phase
Histologically, there is infiltration of the epidermis and upper dermis by neoplastic T-cells, which often have a cerebriform nucleus
characterized by marked infolding of the nuclear membrane
Sezary syndrome is a clinical variant characterized by the presence of (1) a generalized exfoliative erythroderma and (2) tumor cells
(Szary cells) in the peripheral blood.

Infectious Mononucleosis
It is the cause of heterophile-positive infectious mononucleosis (IM), which is
Characterized by:
Fever
Sore throat
Lymphadenopathy, and
Atypical lymphocytosis
The EBV receptor (CD21), present on the surface of B-cells and epithelial cells, is also the receptor for the C3d component of
complement
Lymphadenopathy most often affects the posterior cervical nodes but maybe generalized. Enlarged lymph nodes are frequently
tender and symmetric but are not fixed in place. Pharyngitis, often the most prominent sign, can be accompanied by enlargement
of the tonsils with an exudate resembling that of streptococcal pharyngitis
A morbilliform or papular rash, usually on the arms or trunk, develops in about 5% of cases. Most patients treated with ampicillin
develop a macular rash

402

USMLE Step 1 Platinum Notes

Erythema nodosum and erythema multiforme

Downey cell
Atypical lymphocytes
Paul Bunnel test+
Monospot Test +
Called Kissing Disease.

Other Diseases Associated with EBV Infection

The X-linked lymphoproliferative syndrome (Duncans disease) is a recessive disorder of young boys who have a normal response
to childhood infections but develop fatal lymphoproliferative disorders after infection with EBV
Oral hairy leukoplakia
Chronic fatigue syndrome
Burkitts lymphoma
Anaplastic nasopharyngeal carcinoma EBV has been associated with Hodgkins disease, especially the mixed-cellularity type
Tonsillar carcinoma
Angioimmunoblastic lymphadenopathy
Angiocentric nasal NK/T-cell immunoproliferative lesions
T-cell lymphoma
Thymoma
Gastric carcinoma, and
CNS lymphoma from patients with no underlying immunodeficiency.

PLASMA CELL DYSCRASIASIS: (USMLE FAVORITE)

Multiple Myeloma
Multiple myeloma:
Mc symptomatic monoclonal gammopathy
Russel bodies
Flame cells
Mott cells
Dutcher bodies
Pathological fractures with hypercalcemia with M spike with Bence jones proteins
IL 6 associated with poor prognosis
Bence Jones proteins are light chains
Ca
uric acid
urea

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403

Multiple myeloma presents most often as multifocal destructive bone lesions throughout the skeletal system
The bone resorption results from the secretion of cytokines (e.g. IL-1, tumor necrosis factor, IL-6) by myeloma cells
These cytokines stimulate production of another cytokine called RANK-ligand, which promotes the differentiation and
activation of osteoclasts.
Plasma cell lesions often lead to pathologic fractures, which occur most frequently in the vertebral column. The bone lesions
usually appear radiographically as punched-out defects
Microscopic examination of the marrow reveals an increased number of plasma cells
With progressive disease, plasma cell infiltrations of soft tissues can be encountered in the spleen, liver, kidneys, lungs and
lymph nodes.
Renal involvement, generally called myeloma nephrosis, is a distinctive feature of multiple myeloma. Proteinaceous casts are
prominent in the distal convoluted tubules and collecting ducts. Most of these casts are made-up of Bence-Jones proteins, but
they may also contain complete immunoglobulins, Tamm-Horsfall protein and albumin
Metastatic calcification as a result of bone resorption and hypercalcemia maybe encountered.
Waldenstroms macroglobunemia: Hyperviscocity with IgM
Heavy chain disease
Immune associated amyloidosis
Monoclonal gamma pathy of undetermined significance (MGUS).

Manifestations of myeloma

WALDENSTROMS MACROGLOBULINEMIA

USMLE Case Scenario

A 88-year-old woman presented with a 7 month history of weakness, malaise, exertional dyspnoea and abdominal discomfort.
She had experienced two epistaxis but did not have headaches, visual disturbances, weight loss, bone pain or recurrent
infections. On examination she was pale, with moderate axillary and cervical lymphadenopathy. Her liver and spleen were
enlarged by 5 cm
On investigation, she had an ESR of 112 mm/h and hemoglobin of 108 g/l. The total serum protein was increased to 130 g/l. Protein
electrophoresis and immunoelectrophoresis showed a dense paraprotein in the gamma region which proved to be an IgM of kappa
type. IgM was noted. Electrophoresis of concentrated urine showed no free monoclonal light chains and there were no bone
lesions on X-rays of her chest and skull
Diagnosis would be most Likely NOT Myeloma BUT Waldenstrms macroglobulinemia.

USMLE Case Scenario

A patient reports to a physician. His details are: A 77-year-old man residing in a suburban area of Mexico presented with Lumbago.
He was mildly anemic but had no lymphadenopathy and no fever. There was no hepatosplenomegaly and no abdominal masses. On
investigation, his hemoglobin was low (99 g/l). He had a normal differential white-cell count and a normal platelet count but his ESR
was 96.6 mm/h. Total serum proteins were raised at 88.9 g/l (NR 6575 g/l) and this resulted on the rouleaux seen on the blood
film.His serum albumin, creatinine and urea were normal. He had a raised serum calcium level (3.2 mmol/l), a normal alkaline
phosphatase. Serum protein electrophoresis revealed a monoclonal band in the gamma region. Skull X-ray Revealed Osteolytic
Lesions. He was having bone pains before the diagnostic evaluation
Likely Diagnosis is: Myeloma

404

USMLE Step 1 Platinum Notes

Gamma Heavy Chain Disease: (Franklins Disease)

Characterized by: lymphadenopathy, fever, anemia, malaise, hepatosplenomegaly and weakness
Most distinctive symptom is palatal edema, resulting from node involvement of Waldeyers ring, and this may progress to
produce respiratory compromise
The diagnosis depends on the demonstration of an anomalous serum M component [often < 20 g/L (< 2 g/dL)] that reacts
with anti-IgG but not anti-light chain reagents
The M component is typically present in both serum and urine
The patients may have thrombocytopenia, eosinophilia, and nondiagnostic bone marrow.

Alpha Heavy Chain Disease: (Seligmanns Disease)

This is the most common of the heavy chain diseases
It is closely related to a malignancy known as Mediterranean lymphoma, a disease that affects young people in parts of the world
where intestinal parasites are common, such as the Mediterranean, Asia and South America
The disease is characterized by an infiltration of the lamina propria of the small intestine with lymphoplasmacytoid cells that
secrete truncated alpha chains
The patients present with chronic diarrhea, weight loss, and malabsorption and have extensive mesenteric and para-aortic
adenopathy. Respiratory tract involvement occurs rarely.

Mu Heavy Chain Disease

The secretion of isolated mu heavy chains into the serum appears to occur in a very rare subset of patients with chronic
lymphocytic leukemia
The only features that may distinguish patients with mu heavy chain disease are the presence of vacuoles in the malignant
lymphocytes and the excretion of kappa light chains in the urine
The tumor cells seem to have a defect in the assembly of light and heavy chains, because they appear to contain both in their
cytoplasm.

Types of plasma cell disorders

Mantle Cell Lymphoma

Makes up ~ 6% of all non-Hodgkins lymphomas
These lymphomas have a characteristic chromosomal translocation, t(11;14)
The tumor is a B-cell lymphoma
Mantle cell lymphoma and small lymphocytic lymphoma share a characteristic expression of CD5
Present CD 20, CD 43 also
Mantle cell lymphoma usually has a slightly indented nucleus
Express bcl 1 protein called cyclin D
The most common presentation of mantle cell lymphoma is with palpable lymphadenopathy, frequently accompanied by
systemic symptoms.

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405

Hairy Cell Leukemia: (USMLE Favorite)

It is a rare disease that presents predominantly in older males
B-cell neoplasm
Typical presentation involves pancytopenia, although occasional patients will have a leukemic presentation
Splenomegaly is usual
The malignant cells appear to have hairy projections on light and electron microscopy
The cells are tartrate-resistant acid phosphatase positive (TRAP)+
Bone marrow is typically not able to be aspirated, and biopsy shows a pattern of fibrosis with diffuse infiltration by the malignant
cells
Patients with this disorder are prone to unusual infections including infection by Mycobacterium avium intracellulare, and vasculitic
syndromes have been described
Hairy cell leukemia is responsive to chemotherapy with interferon, pentostatin, or
Cladribine being the usually preferred treatment. (DOC)

Immunophenotyping

USMLE Case Scenario

A 44-year-old man was found to have an enlarged spleen on examination confirmed by USG Scan. Further Investigation
showed normal hemoglobin, raised white-cell count (14.2 x 109/l). On the blood film these cells were mainly small mononuclear
cells resembling lymphocytes, but had a hairy appearance, had B-cell markers on their surface. The cells stain positively for
tartrate-resistant acid phosphatase. (TRAP +)
Most likely diagnosis is: Hairy cell leukemia

Castlemans Disease: (USMLE Favorite)

Which can present with localized or disseminated lymphadenopathy; some patients have systemic symptoms
The disseminated form is often accompanied by anemia and polyclonal hypergammaglobulinemia, and the condition
seems to be related to an overproduction of interleukin 6, possibly produced by human herpesvirus 8.

Rosai-Dorfmans Disease: (USMLE Favorite)

Sinus histiocytosis with massive lymphadenopathy (usually presents with bulky lymphadenopathy in children or young adults.
The disease is usually nonprogressive and self-limited, but patients can manifest autoimmune hemolytic anemia.

Mycosis Fungoides: (USMLE Favorite)

Is also known as cutaneous T-cell lymphoma
Mycosis fungoides is an indolent lymphoma with patients often having several years of eczematous or dermatitic skin
lesions. The skin lesions progress from patch stage to plaque stage to cutaneous tumors.
A particular syndrome in patients with this lymphoma involves erythroderma and circulating tumor cells. This is known as Sezarys
syndrome.

406

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 58-year-old man after repeated visits to a dermatologist is referred to a physician. He presented severe keratosis on the soles
of his feet and the palms of his hands. On examination, he had characteristic exfoliative dermatitis with lymphadenopathy in
the axilla and inguinal region. Investigation showed he had a white-cell count (17 109/l). A blood film shows a considerable
increase in the number of small cleaved lymphocytes, 90% of which were T-lymphocytes. Electron microscopy of buffy coat
cells confirmed that the nuclei of these cells had multiple clefts. Most likely diagnosis is:
1. Mantle cell lymphoma
2. Glandular fever
3. Littoral cell angioma
4. Portal hypertension
5. Acute Leukemia
6. Sezary Syndrome
7. Follicular cell lymphoma
8. Hairy cell Leukemia
9. CML
Ans. 6. Sezary Syndrome

Hodgkins Disease: (USMLE Favorite)

Bimodal age distribution. (late 20 and after 50 years)

The commonest presentation of Hodgkins Lymphoma is painless enlargement of Lymph nodes
Prognosis is directly proportional to number of RS cells and inversely proportional to number of lymphocytes
Spread is to contigious to adjacent lymph nodes
Extranodal spread is uncommon
Malignant cell is Reed Stenberg Cell. (Owl eyed, bilobed nucleus with prominent nucleoli)
RS cells are positive for CD 15 and CD 30. (except Lymphocyte Predominant)
CNS involvement is uncommon.
The feature for Hodgkin lymphoma is the Reed-Stenberg (RS) cell. This is a large cell (1545 m in diameter) with an
enlarged multilobated nucleus, exceptionally prominent nucleoli, and abundant, usually slightly eosinophilic, cytoplasm
Particularly characteristic are cells with two mirror-image nuclei or nuclear lobes, each containing a large (inclusion-like)
acidophilic nucleolus surrounded by a distinctive clear zone; together they impart an owl-eye appearance. The nuclear
membrane is distinct.
As we will see, such classic RS cells are common in the mixed-cellularity subtype, uncommon in the nodular sclerosis
subtype and rare in the lymphocyte-predominance subtype; in these latter two subtypes, other characteristic RS cell
variants predominate.

Starry sky appearance: Burkitts Lymphoma

Lacunar cells are seen in nodular sclerosis type of lymphoma
Stomach is the mc site for extranodal NHL
Hilar lymphadenopathy is a feature of nodular sclerosis type.

Nodular Sclerosing HL

Most common type

Most common type in females
Mediastinal involvement common
Lacunar cell present.

Antiphospholipid Syndrome: (USMLE Favorite)

Arterial thromboses, recurrent fetal loss and thrombocytopenia
It may occur as primary disorder or secondary to other conditions, most commonly systemic lupus erythematous (SLE)
A key point for the exam is to appreciate that antiphospholipid syndrome causes a paradoxical rise in the APTT. This is due to an
ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids involved in the coagulation cascade.

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407

Features: can be assymptomatic

Venous/arterial thrombosis NOT BLEEDING
Recurrent fetal loss (2nd trimester abortions)
Live do reticularis
Thrombocytopenia
Prolonged APTT, Normal PT
Other features: Preeclampsia
Pulmonary hypertension.

USMLE Case Scenario

Lacunar cells are seen in:
1. Nodular sclerosing variant of Hodgkins disease
2. Burkitts lymphoma
3. Mixed cellularity Hodgkins
4. Normal Lymph nodes
Ans. 1. Nodular sclerosing variant of Hodgkins disease

Remember: (USMLE Favorites, Commonly asked)

Faggot cell: It is a term used for cells normally found in the hypergranular form of acute promyelocytic leukemia. This term is
applied to these blast cells because of the presence of numerous Auer rods in the cytoplasm. The accumulation of these Auer rods
gives the appearance of a bundle of sticks, from which the cells are given their name. They are also seen in AML type M3
Dohle bodies: Irregular grayish or greenish inclusions in the peripheral cytoplasm of neutrophils. They are nuclear remnants that
are often seen in association with toxic granules and vacuoles. They maybe present in association with burns, trauma, acute or
systemic infections, and maybe present with exposure to cytotoxic agents, (i.e. chemotherapy). They may also be seen during a
normal pregnancy
Toxic Granulation: Large dark blue granules in the cytoplasm, associated with severe infection, chemical poisoning, and other
toxic states
Auer Bodies (Auer Rods): Unique, pink or red rod-shaped inclusions that are seen in very immature granulocytes (blasts) in
patients with acute non-lymphocytic leukemias (i.e. Acute Myeloid Leukemia; AML)
Pelger-Huet Anamoly: Hereditary anomaly where neutrophils appear with fewer than two lobes. The nucleus is often in the shape
of a peanut or dumbbell, or may consist of two lobes connected with an obvious filament
Pseudo-Pelger-Huet anomaly: An acquired or pseudo-Pelger-Huet anomaly is seen in myelodysplastic disorders and following
drug therapy, and may accompany leukemia and certain infections
Alder-Reilly granules: Large, dark leukocyte granules that stain purple. They are indicative of mucopolysaccharidosis (an inherited
enzyme deficiency disorder, Hurlers and Hunters syndromes).

CNS Pathology
Macrophage of Brain is Microglia
Complex granular corpuscles are produced by Microglia
Cell not participating in repair after brain infarction is Fibroblast

Bacterial Meningitis is Due to: (USMLE Favorite)

In Neonates: Group B streptococci, E. Coli

Infants: H Influenza
Youg Adults: Nisseria meningitides
Elderly: Strep Pneumoniae

408

USMLE Step 1 Platinum Notes

Bacterial Meningitis Score = determined that patients had a very low risk for bacterial meningitis if all of the following were absent:
Positive CSF gram stain
CSF absolute neutrophil count (ANC) of 1000
CSF protein of 80 mg/dL
A circulating ANC of 10,000 cells/microliter (mcL) or a seizure as part of the presentation
CSF findings in Tubercular meningitis: increased protein decreased sugar, increased lymphocytes
CSF findings in pyogenic meningitis: increased protein, decreased sugar.
In acute meningitis, an exudate is evident within the leptomeninges over the surface of the brain. The meningeal vessels are
engorged and prominent
From the areas of greatest accumulation, tracts of pus can be followed along blood vessels on the brain surface
When the meningitis is fulminant, the inflammatory cells infiltrate the walls of the leptomeningeal veins and may spread into the
substance of the brain (focal cerebritis), or the inflammation may extend to the ventricles, producing ventriculitis.
Features of viral encephalitis:
Perivascular cuffing
Microglial nodules
Neuron loss
Neuronophagia
Viral Meningitis (Aseptic) is most commonly due to Enteroviruses
HSV Virus usually affects Temporal Lobes
Negri bodies in Hippocampus in Rabies.

Tuberculous Meningitis
Usually presents with generalized symptoms of headache, malaise, mental confusion and vomiting
There is only a moderate increase in cellularity of the CSF (pleiocytosis) made-up of mononuclear cells, or a mixture of
polymorphonuclear and mononuclear cells; the protein level is elevated
May also result in a well-circumscribed intraparenchymal mass (tuberculoma), which maybe associated with meningitis
Chronic tuberculous meningitis is a cause of arachnoid fibrosis, which may produce hydrocephalus
There maybe discrete white granules scattered over the leptomeninges
The infection may spread through the CSF to the choroid plexuses and ependymal surface
On microscopic examination there are mixtures of lymphocytes, plasma cells and macrophages. Florid cases show wellformed granulomas, often with caseous necrosis and giant cells, similar to the lesions of tuberculosis elsewhere in the body.
Similar findings are observed in tuberculomas within the brain.

Neurosyphilis: (USMLE Favorite)

Neurosyphilis is a tertiary stage of syphilis
The major manifestation is meningeal, called meningovascular neurosyphilis
Tabes dorsalis is another form of neurosyphilis, resulting from damage to the sensory nerves in the dorsal roots producing
impaired joint position sense and resultant ataxia (locomotor ataxia); loss of pain sensation, leading to skin and joint
damage (Charcot joints)
Other sensory disturbances, particularly characteristic lightning pains and absence of deep tendon reflexes
Cerebral gummas (mass lesions rich in plasma cells) may also occur in relation to meninges and extend into the brain.

HIV
Cerebral involvement: AIDS dementia complex
Multinucleate giant cells
Vacuolar myelopathy.

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409

Progressive Multifocal Leukoencephalopathy: (USMLE Favorite)

It is due to Polyoma JC Virus, a polyomavirus
The virus preferentially infects oligodendrocytes, so demyelination is its principal pathologic effect
The disease occurs almost invariably in immunosuppressed individuals in various clinical settings, including chronic
lymphoproliferative or myeloproliferative illnesses, immunosuppressive therapy and AIDS
Patients develop focal and relentlessly progressive neurologic symptoms and signs, and imaging studies show extensive, often
multifocal, ring-enhancing lesions in the hemispheric or cerebellar white matter
Demyelination and Astrogliosis are a feature
The lesions consist of patches of irregular, ill-defined destruction of the white matter that enlarge as the disease progresses. Each
lesion is an area of demyelination, in the center of which are scattered lipid-laden macrophages and a reduced number of axons.
At the edge of the lesion are greatly enlarged oligodendrocyte nuclei whose chromatin is replaced by glassy amphophilic viral
inclusion.

Prion Disease: (USMLE Favorite)

This group of diseases includes sporadic, familial, iatrogenic and variant forms of Creutzfeldt-Jakob disease (CJD)
Several animal diseases from this group are also known, including scrapie in sheep and goats and bovine spongiform
encephalopathy in cattle (mad cow disease)
All these disorders are associated with abnormal forms of a normal cellular protein, termed prion protein (PrPc)
The abnormal form of this protein can act as an infectious agent, since it propagates itself and injures the cells in which it is
present
Most cases of prion disease are either sporadic or associated with mutations in the gene that encodes PrPc
The unique pathogenesis of prion diseases is related to changes in the conformation of PrP from its native PrPc form to an
abnormal configuration called either PrPsc (for scrapie) or PrPres (for protease resistant)
In the abnormal conformation, the prion protein becomes resistant to protease digestion. Once formed, PrPsc can then initiate
comparable transformation of other PrPc molecules. The infectious nature of PrPsc protein comes from this ability to propagate
the pathologic conformational change.

Creutz Feldt Jackobson Disease: (USMLE Favorite)

Manifests clinically as a rapidly progressive dementia

Most common infectious prion disease in humans
On light microscopy, the pathologic hallmarks of CJD are spongiform degeneration and astrogliosis
The lack of an inflammatory response in CJD and other prion diseases is an important pathologic feature of these degenerative
disorders
Spongiform degeneration is characterized by many 1- to 5-um vacuoles in the neuropil between nerve cell bodies
In (New variant) nvCJD, a characteristic feature is the presence of florid plaques. These are composed of a central core of PrP
amyloid surrounded by vacuoles in a pattern suggesting petals on a flower.

Cerebral Toxoplasmosis: (USMLE Favorite)

Cerebral toxoplasmosis-infection with the protozoan Toxoplasma gondii
Seen in AIDS Patients
Computed tomography and magnetic resonance imaging studies can show multiple ring-enhancing lesions; however, this
radiographic appearance is not pathognomonic
Acute lesions consist of central foci of necrosis with variable petechiae surrounded by acute and chronic inflammation, macrophage
infiltration and vascular proliferation. Both free tachyzoites and encysted bradyzoites maybe found at the periphery of the necrotic foci.

Cysticercosis: (USMLE Favorite)

Cysticercosis is the consequence of an end-stage infection by the tapeworm Tenia solium
These cysts can be found throughout the body, although they are common within the brain and subarachnoid space
They typically present as a mass lesion and can cause seizures. Symptoms can intensify when the organism dies within the cyst, as
happens after therapy
The organism is encysted within a smooth lining; around the cyst, there is often a marked degree of gliosis.

410

USMLE Step 1 Platinum Notes

Diffuse Axonal Injury

Deep white matter lesion consists of widespread acute disruption, or shearing, of axons at the time of impact
Pathologically there are small areas of tissue disruption in the corpus callosum and dorsolateral pons
The presence of widespread axonal damage of both hemispheres, a state called Diffuse axonal injury, has been proposed as
the explanation of persistent coma or vegetative state, but small ischemic-hemorrhagic lesions in the midbrain and low
diencephalon are as often the cause
Only severe shearing lesions that contain blood are visualized by CT, usually in the corpus callosum and centrum semi ovale
however, within days of the injury
MRI scan demonstrates such lesions throughout the white matter, especially with the use of gradient echo MRI sequences.

CNS TUMORS: (GEMS ABOUT TUMORS) (NEVER FORGET)

High Yield USMLE Points
Astrocytoma

Oligodendroglioma

Ependymoma

Origin from oligodendrocytes

Fried Egg Appearance
Chicken wire pattern of
capillaries
Slow growing

Schwanomma

Cranipharyngioma

From Odontogenic
epithelium
Affects young/children
Calcium deposits seen

Origin from astrocytes

Most common primary brain tumor in adults
GFAP Positive
Glioblastoma multi forme is grade IV astrocytoma
Crosses midline
(Butterfly Glioma)
Pseudopallisading Necrosis
Common in white matter

Meningoma

Most common benign brain tumor

Origin from arachnoid cells
Whorled pattern
Psommoma bodies
Good prognosis

From schwann cells

Eighth cranial nerve
At CP angle
Antoni A and Antoni B areas
Verocay Bodies
S 100 positivity
Bilateral NF 2

Medulloblastomas: (USMLE Favorite)

Are primitive neuroectodermal tumors (PNET)

Arise in cerebellar vermis (midline)
Responsive to radiotherapy
These highly cellular malignant tumors are thought to arise from neural precursor cells
They are the most frequent malignant brain tumor of children
These tumors frequently disseminate along CSF pathways.

Remember
Mc primary brain tumor: glioma
Mc brain tumor in adults: astrocytoma
Mc type of glial tumor: astrocytoma
Mc site of brain tumors in children: infratentorial (cerebellar)
Mc site of brain tumor in neonates: supratentorial
Mc posterior fossa tumor in children: cerebellar astrocytoma
Second mc posterior fossa tumor in children. Medulloblastoma

Usually in ventricular system

Ependymal rosettes
Perivascular pseudorossettes
Often causes hydrocephalus

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411

Features not to be forgotten

Pseudorosettes: Neuroblastoma
Enamel like structures: Craniopharyngioma
Glial fibrillary proteins: Astrocytoma
Verocay bodies: Schwannoma
Butterfly tumor: Glioblastoma multi forme
Fried egg appearance: Oligiodendroglioma

USMLE Case Scenario

A 45-year-old male from Kansas develops a gelatinous, well-circumscribed mass in her right cerebral hemisphere. Biopsy of
the mass reveals neoplastic cells with fried egg morphology. Which of the following tumors does these patients most likely
have?
1. Choroid plexus papilloma
2. Ependymoma
3. Glioblastoma multiforme
4. Oligodendroglioma
5. Medulloblastoma
6. Hemangioma
Ans. 4. Oligodendroglioma

USMLE Case Scenario

Rosenthal fibers are corkscrew-shaped, intensely eosinophilic structures deriving from accumulation of and alpha; and beta;crystalline within astrocytic processes. They are usually found in:
1. Ependymoma
2. Glioblastoma multiforme
3. Medulloblastoma
4. Pilocytic astrocytoma
Ans. 4. Pilocytic astrocytoma

High Yield USMLE Pointson Commonly asked Diseases

Alzhiemers disease

Picks Disease

Lewy Body Disease

Parkinsonism

Neurofibrillary tangles are

intracytoplasmic filamentous
inclusions found in Alzheimer disease
and, to a lesser extent, in normal
aging brains
Granulovacuolar degeneration
Hirano Bodies: They are Specific
protein deposits associated with AGE
(Advance Glycosylation End products)
localized within soma of neurons
Amyloid Plaques: They represent
fragmented accumulations of proteins
which are normally broken down but
accumulate in Alzheimers disease
Alzhiemers Cells (Special cells)
Neurofibrillary tangles: are insoluble
twisted fibrils composed of Tau
proteins

Swollen or ballooned
neurons contain silverstaining cytoplasmic
inclusions referred to as
Pick bodies
Walnut brain
Knife blade atrophy
Balloning
degeneration

Lewy bodies are

intraneuronal
cytoplasmic inclusions
that stain with periodic
acid-Schiff and ubiquitin.
They contain epitopes
recognized by antibodies
against phosphorylated
and nonphosphorylated
neurofilament proteins,
ubiquitin, and a
presynaptic protein called
synuclein

Lewy bodies are

filamentous inclusions
that appear brightly
eosinophilic on
hematoxylin and eosin
stain and accumulate in the
cytoplasm of dopaminergic
neurons in the substantia
nigra in Parkinson disease.

412

USMLE Step 1 Platinum Notes

Marinesco bodies are also present in the dopaminergic neurons of substantia nigra. They are intranuclear. These inclusions are found
occasionally in normal brains, and their significance is unknown.

USMLE Case Scenario

Intracytoplasmic spherules composed of paired helical filaments stained with silver stains are seen infrontallobe with severe
neuronal loss and astrocytosis. The condition most likely is:
1. HSV Encephalitis
2. Picks disease
3. Alzhiemers disease
4. Parkinsons disease
Ans. 2. Picks Disease (Picks bodies)

USMLE Case Scenario

Methyl phenyl tetrahydropyridine is taken by a 25-year-old male from Calfornia complaining of uncontrollable shaking in his
hands. Most likely pathology he might have as a result of above mentioned features is:
1. Lewy bodies
2. Picks bodies
3. Negri bodies
4. Neurofibrillary tangles
Ans. 1. Lewy bodies
The patient has Parkinsonism induced methyl phenyl tetrahydropyridine (MPTP), a meperidine analog.

USMLE Case Scenario

Degenerated neurofilaments seen in patients with Alzheimers disease are:
1. Hirano bodies
2. Lipofuscin granules
3. Neurofibrillary tangles
4. Amyloid plaques
Ans. 3. Neurofibrillary tangles

USMLE Case Scenario

A dementing disorder is characterized clinically by progressive loss of memory, parkinsonism, and visual/auditory
hallucinations, and pathologically by round intracytoplasmic neuronal inclusions in the substantia nigra and neocortex. The
clinical features are suggestive of:
1. HIV encephalitis
2. Lewy body disease
3. Shy dragger syndrome
4. Parkinsonism
Ans. 2. Lewy body disease

Abnormal Protein Aggregates

Alzhiemers disease: A beta, tau

Picks disease: tau
Parkinsons disease, multiple systems atrophy: alpha synuclein
Huntigtons disease: huntingtin
Spinocerebellar ataxia: ataxin
Prion disease: prion protein

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413

Berry Aneurysm

Thin walled Saccular out pouching of Tunica intima and adventitia

Most frequent cause of SAH
Most frequent site: Anterior circle of willis
Least frequent site: posterior circulation
Association with:
Marfans syndrome
Ehler danhlos Syndrome
Adult Polycystic Kidney Disease.

Multiple Sclerosis
Multiple sclerosis (MS) is characterized by
A relapsing-remitting or progressive course and
A pathologic triad of CNS inflammation, demyelination and gliosis (scarring)
MS derives its name from the multiple scarred areas visible on macroscopic examination of the brain. These lesions, termed
plaques, are sharply demarcated gray or pink areas easily distinguished from surrounding white matter
MS is a white matter disease; abnormalities on the surface of the brain are usually restricted to those regions where
myelinated fiber tracts course superficially (brain stem and spinal cord). Affected areas show multiple, well-circumscribed,
slightly depressed, glassy, gray-tan, irregularly shaped lesions, termed plaques
The acute MS lesion, rarely found at autopsy, consists of perivenular cuffing by inflammatory mononuclear cells, predominantly
T-lymphocytes and macrophages, which also infiltrate white matter tissue and appear to orchestrate demyelination. At sites of
inflammation, the blood-brain barrier is disrupted but the vessel wall itself is preserved, distinguishing the MS lesion from vasculitis

The correspondence between number and size of plaques (Plaque burden) and the severity of clinical symptoms is imprecise
Axonal loss and cavitation are particularly prominent in the subtype of MS known as Neuromyelitis Optica or Devics syndrome.
CSF analysis in Multiple Sclerosis: USMLE asks presentations with Lab values
IgG concentration
Albumin concentration
IgG/albumin ratio
IgG index
Isoelectric focusing Oligoclonal bands present

USMLE Case Scenario

A 44-year-old woman concerned about her disease reports and presents with unusual feelings like tingling, numbness and
clumsiness of both hands for 2 week. Earlier she had experienced paraesthesia in the feet. On neurological examination,
she had absent abdominal reflexes with brisk tendon jerks and bilateral extensor plantar responses. Blood investigations
were normal, including hemoglobin, white-cell count and differential, erythrocyte sedimentation rate, vitamin B12 and folate
levels and syphilis serology. Oligoclonal IgG bands were found in CSF. The most likely diagnosis is:

414

USMLE Step 1 Platinum Notes

1. SAH
2. Gullian Barre Syndrome
3. Multiple sclerosis
4. Subacute degeneration of cord
5. Hysteria
6. Empty sella syndrome
Ans. 3. Multiple Sclerosis

BREAST PATHOLOGY: (USMLE FAVORITE)

High Yield USMLE Points

Mc disorder of breast
Mc tumor of breast
Mc carcinoma of breast
Mc bilateral tumor
Mc involved Lymph nodes are
Mc cause of breast discharge
Mc cause of bloody discharge
Mc site of metastasis of breast Ca
Mc site of breast Ca
FIRST INVESTIGATION FOR BREAST LUMP
BEST INVESTIGATION FOR BREAST LUMP
BRCA 1 gene is located on chromosome
BRCA 2 gene is located on chromosome
Marker for breast cancer

Fibroadenosis
Fibroadenoma
Ductal/Schirrous carcinoma
Lobular carcinoma of breast
Axillary group
Duct ectasia
Duct pappiloma
Bone
Upper outer quadrant
FNAC
BIOPSY
17
13
CA 15-3

Risk Factors for Breast Cancer

Race: White females

Age: elderly
Family history +
Relatives (true)
Nonbreastfeeding mothers
Fatty food intake
Nulliparity
BRCA1 and BRCA2 mutations
Cancer in other breast
Mammary dysplasia/Atypical hyperplasia/Sclerosing adenosis
Early menarche
Late menopause
Late first pregnancy

Epithelial hyperplasia: (USMLE Favorite)

Histologically, there is an almost infinite spectrum of proliferative alterations. The ducts, ductules, or lobules maybe filled with
orderly cuboidal cells, within which small gland patterns can be discerned (called fenestrations)
Sometimes the proliferating epithelium projects in multiple small papillary excrescences into the ductal lumen (ductal
papillomatosis). The degree of hyperplasia, manifested in part by the number of layers of intraductal epithelial proliferation, can
be mild, moderate, or severe
In some instances the hyperplastic cells become monomorphic with complex architectural patterns
Atypical lobular hyperplasia is the term used to describe hyperplasias that cytologically resemble lobular carcinoma in situ.
Atypical lobular hyperplasia is associated with an increased risk of invasive carcinoma.

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415

Fibrocystic Changes
Classified as nonproliferative cystic lesions or proliferative lesions
Proliferative lesions include epithelial proliferations of ducts and lobules, with or without features of atypia, and adenosis, the
proliferation of terminal ducts, sometimes associated with fibrosis (sclerosing adenosis)
Atypical hyperplasia of ductular or lobular epithelium is associated with a five-fold increase in the risk of developing carcinoma;
when associated with a family history of breast carcinoma, the risk is 10-fold.

Abscesses
Staphylococcal infections induce single or multiple abscesses accompanied by the typical clinical acute inflammatory changes
They are usually small, but when sufficiently large they may heal with residual foci of scarring that are palpable as localized areas
of induration
Streptococcal infections generally spread throughout the entire breast, causing pain, marked swelling and breast tenderness.

Galactocele: (USMLE Favorite)

It is a milk-filled cyst
Round, well circumscribed and easily movable within the breast
Usually occurs after the cessation of lactation or when feeding frequency has been curtailed significantly
Inspissated milk within a large lactiferous duct is responsible
The tumor is usually located in the central portion of the breast or under the nipple
Needle aspiration produces thick, creamy material that maybe tinged dark-green or brown. Although it appears purulent, the
fluid is sterile
The treatment is needle aspiration. Withdrawal of thick milky secretion confirms the diagnosis
Operation is reserved for those cysts that cannot be aspirated or that become super infected.

MAMMARY DUCT ECTASIA: (PERIDUCTAL OR PLASMA CELL MASTITIS)

(USMLE Favorite)
It is a nonbacterial chronic inflammation of the breast associated with inspissation of breast secretions in the main excretory
ducts
Ductal dilation with ductal rupture leads to reactive changes in the surrounding breast substance
It is an uncommon condition, usually encountered in women in their 40s and 50s who have borne children
Usually the inflammatory changes are confined to an area drained by one or several of the major excretory ducts of the
nipple.

Fibroadenoma
It is by the most common benign neoplasm of the female breast
Increase in estrogen activity is thought to contribute to its development, and indeed similar lesions may appear with fibrocystic
changes (fibroadenomatoid changes)
Fibroadenomas usually appear in young women
The peak incidence is in the third decade of life
The fibroadenoma occurs as a discrete, usually solitary, freely movable nodule, 1 to 10 cm in diameter

Intraductal Papilloma
It is a neoplastic papillary growth within a duct
Most lesions are solitary, found within the principal lactiferous ducts or sinuses
They present clinically as a result of
(1) the appearance of serous or bloody nipple discharge
(2) the presence of a small subareolar tumor a few millimeters in diameter, or
(3) rarely, nipple retraction

416

USMLE Step 1 Platinum Notes

Breast cancers are classified into those that have not penetrated the limiting basement membrane (noninvasive) and those that
have (invasive).
The chief forms of carcinoma of the breast are classified as follows:
Noninvasive
Ductal carcinoma in situ (DCIS; intraductal carcinoma)
Lobular carcinoma in situ (LCIS)
Invasive (infiltrating)
Invasive ductal carcinoma (not otherwise specified)
Invasive lobular carcinoma
Medullary carcinoma
Colloid carcinoma (mucinous carcinoma)
Tubular carcinoma
Other types
Of these, invasive ductal carcinoma is by far the most common. Because it usually has an abundant fibrous stroma, it is also
referred to as scirrhous carcinoma.

NONINVASIVE (IN SITU) CARCINOMA (INCLUDING PAGET DISEASE)

(USMLE Favorite)
There are two types of noninvasive breast carcinoma: DCIS and LCIS
Morphologic studies have shown that both usually arise from the Terminal duct lobular unit
DCIS tends to fill, distort and unfold involved lobules and thus appears to involve duct like spaces
LCIS usually expands but does not alter the underlying lobular architecture
Both are confined by a basement membrane and do not invade into stroma or lymphovascular channels
DCIS has a wide variety of histologic appearances
Architectural patterns are often mixed and include.

Solid
Comedo
Cribriform
Papillary
Micropapillary and
Clinging types

Paget Disease of the Nipple: (USMLE Favorite)

It is caused by the extension of DCIS up to the lactiferous ducts and into the contiguous skin of the nipple
The malignant cells disrupt the normal epidermal barrier, which allows extracellular fluid to be extruded onto the surface
The clinical appearance is usually of a unilateral crusting exudate over the nipple and areolar skin. In about half of cases, an
underlying invasive carcinoma will also be present
Prognosis is based on the underlying carcinoma and is not worsened by the presence of Paget disease.
LCIS, like the low-nuclear-grade DCIS and unlike high-nuclear-grade DCIS, has a uniform appearance.
Carcinomas of no special type or not otherwise specified are synonyms for ductal carcinomas.
The majority (70 to 80%) of cancers fall into this group
This type of cancer is usually associated with DCIS, but rarely LCIS is present
Most ductal carcinomas produce a desmoplastic response, which replaces normal breast fat (resulting in a mammographic density)
and forms a hard, palpable mass (Advanced cancers may cause dimpling of the skin, retraction of the nipple, or fixation to the chest
wall. About two-thirds express estrogen or progestagen receptors, and about one-third overexpress HER2/NEU.

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Inflammatory Carcinoma: (USMLE Favorite)

It is defined by the clinical presentation of an enlarged, swollen, erythematous breast, usually without a palpable mass
The underlying carcinoma is generally poorly differentiated and diffusely invades the breast parenchyma. The blockage of
numerous dermal lymphatic spaces by carcinoma results in the clinical appearance
True inflammation is minimal or absent
Most of these tumors have distant metastases, and the prognosis is extremely poor.

Invasive Lobular Carcinoma

Consists of cells morphologically identical to the cells of LCIS

Two-thirds of the cases are associated with adjacent LCIS
The cells invade individually into stroma and are often aligned in strands or chains
More frequently than ductal carcinomas, metastasize to cerebrospinal fluid, serosal surfaces, gastrointestinal tract, ovary
and uterus, and bone marrow
Lobular carcinomas are also more frequently multicentric and bilateral (10 to 20%)
Almost all of these carcinomas express hormone receptors, but HER2/NEU overexpression is very rare or absent.

Medullary Carcinoma
It is a rare subtype
Occur with increased frequency in women with BRCA1 mutations
These carcinomas uniformly lack hormone receptors and do not overexpress HER2/NEU

Colloid: (Mucinous) Carcinoma

It is a rare subtype
Tumor cells produce abundant quantities of extracellular mucin that dissects into the surrounding stroma
Grossly the tumors are usually soft and gelatinous. Most express hormone receptors and rare examples may overexpress HER2/
NEU.

Tubular Carcinomas: (USMLE Favorite)

Rarely present as palpable masses but account for 10% of invasive carcinomas smaller than 1 cm found with mammographic
screening
They usually present as irregular mammographic densities
Microscopically, the carcinomas consist of well-formed tubules with low-grade nuclei
Lymph node metastases are rare and prognosis is excellent
Virtually all tubular carcinomas express hormone receptors, but overexpression of HER2/NEU is highly unusual

Phyllodes Tumor: (USMLE Favorite)

Serocystic disease of Broide or Cystosarcoma Phyllodes

Name is misnomer as it is rarely cystic or rarely develops into sarcoma
Phyllodes: Leaf. It is a benign breast tumor. It is a stromal breast tumor
They presents as a large, massive tumor with uneven bosselated surface
They are however mobile and resemble fibroadenoma
They account for less than 1% of all breast neoplasms
This is predominantly a tumor of adult women, with very few examples reported in adolescents
Patients typically present with a firm, palpable mass
These tumors are very fast growing, and can increase in size in just a few weeks
Occurrence is most common between the ages of 40 and 50, prior to the menopause
The common treatment for phyllodes is wide local excision. Other than surgery, there is no cure for phyllodes, as chemotherapy
and radiation therapy are not effective.

418

USMLE Step 1 Platinum Notes

FEATURES COMMON TO ALL INVASIVE CANCER: (USMLE FAVORITE)

These Include
Tendency to become adherent to the pectoral muscles or deep fascia of the chest wall, with consequent fixation of the lesion
As well as adherence to the overlying skin, with retraction or dimpling of the skin or nipple. The latter is an important sign, because it
maybe the first indication of a lesion, observed by the woman herself during self-examination
Involvement of the lymphatic pathways may cause localized lymphedema. In these cases the skin becomes thickened around
exaggerated hair follicles, a change known as peau dorange.

Ovarian Tumors
Primary Epithelial Tumors 80%

Nonepithelial Tumors

Mucinous Cystadenoma or
Cystadenocarcinoma
Serous Cystadenoma or
Cystadenocarcinoma
Endometrioma or Endometriod
Carcinoma
Clear cell carcinoma
Brenner Tumor

Fibroma
Dysgerminoma
Teratoma
Gonadoblastoma
Yolk-sac tumor

Hormone-Producing Tumors
Estrogen-producing
Granulosa cell tumor
Thecoma
Androgen-producing
Sertoli-Leydig cell tumor
(Arrhenoblastoma)
Hilar cell tumor
Lipoid cell tumor (Ovoblastoma,
Musculinovoblastoma, Adrenal-like tumor)
OTHERS
Carcinoid (Seratonin-producing)
Thyroid tumor (Struma Ovarii)
Choriocarcinoma of the ovary

High Yield USMLE Points

Call Exner Bodies

Renkies Crystals
Signet ring cells
Schiller Duval bodies
Psommoma bodies
Meigs syndrome
Pseudomeigs syndrome
Walthard cell nest
Rokintansky bodies

Granulosa cell tumor

Hilus cell tumor
Krukenbergs tumor
Endodermal sinus tumor
Pappillary Serous tumors
Fibroma ovary
Brenner cell tumor
Brenner tumor
Teratoma

Remember
Rupture of mucinous tumors may result in mucinous deposits in the peritoneum; however, these typically do not result in longterm growth of tumor in the peritoneum. Implantation of mucinous tumor cells in the peritoneum with production of copious
amounts of mucin is called pseudomyxoma peritonei
They are caused by metastasis from the gastrointestinal tract, primarily the appendix
Metastasis of mucinous tumor of the gastrointestinal tract to the ovaries (the so-called Krukenberg tumor) may also mimic an
ovarian primary tumor.

Testicular Cancer: (USMLE Favorite)

Primary germ cell tumors (GCTs) of the testis constitute 95% of all testicular neoplasms. Infrequently, GCTs arise from an
extragonadal site, including the:
Mediastinum
Retroperitoneum and very rarely
Pineal gland. (Remember the sites)

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419

Cryptorchidism is associated with a several fold higher risk of GCT

Abdominal cryptorchid testes are at a higher risk than inguinal cryptorchid testes
Orchiopexy should be performed before puberty, if possible
Testicular feminization syndromes increase the risk of testicular GCT and
Klinefelters syndrome is associated with mediastinal GCT
An isochromosome of the short arm of chromosome 12 is pathognomonic for GCT
A painless testicular mass is pathognomonic for a testicular malignancy
Commonest testicular malignancy is: Seminoma
Most malignant testicular cancer is: Choriocarcinoma.

Seminoma

Has a median age in the fourth decade

Generally follows a more indolent clinical course
Seminomas are radiosensitive
Seminomas metastasize by lymphatics
Seminomas correspond to dysgerminomas of ovary

They are histologically identical to ovarian dysgerminomas and to germinomas occurring in the central nervous system and other
extragonadal sites. Seminomas are large, soft, well-demarcated, usually homogeneous, gray-white tumors that bulge from the
cut surface of the affected testis. Microscopically, seminomas are composed of large, uniform cells with distinct cell borders, clear,
glycogen-rich cytoplasm, and round nuclei with conspicuous nucleoli. The cells are often arrayed in small lobules with intervening
fibrous septa. A lymphocytic infiltrate is usually present and may, on occasion, overshadow the neoplastic cells.
Neoplasms of the Peripheral Nervous System and Familial Tumor Syndromes
Neoplasms of the peripheral nervous system may originate from
Schwann cells
Perineurial cells and
Fibroblasts
They include
Schwannoma
Neurofibroma and
Malignant peripheral nerve sheat tumor.

Familial Tumor Syndromes Include

Neurofibromatosis
Tuberous sclerosis and
von Hippel-Lindau disease

Miscellaneous Hot Topics Asked in Previous Examinations

Neurofibromatosis Type 1 (von Recklinghausens Disease)

NEUROFIBROMATOSIS
NF1
Cutaneous neurofibromas, pigmented lesions of the skin called cafe au lait spots, freckling in nonsun exposed areas such as the
axilla, hamartomas of the iris termed Lisch nodules, and pseudoarthrosis of the tibia
Neurofibromas are benign peripheral nerve tumors composed of proliferating Schwann cells and fibroblasts. They present as
multiple, palpable, rubbery, cutaneous tumors
Mutation of the NF1 gene on chromosome 17 causes von Recklinghausens disease
The NF1 gene is a tumor suppressor gene; it encodes a protein, neurofibromin, which modulates signal transduction through
the ras GTPase pathway.

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USMLE Step 1 Platinum Notes

Patients with NF1 are at increased risk of developing nervous system neoplasms, including plexiform neurofibromas, optic
gliomas, ependymomas, meningiomas, astrocytomas and pheochromocytomas
Neurofibromas may undergo secondary malignant degeneration and become sarcomas
Optic nerve glioma is the one of the mc tumor associated with NF1.
Neurofibromatosis Type 2

NF2

(USMLE Favorite)
It is characterized by the development of bilateral vestibular schwannomas in 90% of individuals who inherit the gene
Patients with NF2 also have a predisposition for the development of meningiomas, gliomas and schwannomas of cranial and
spinal nerves
In addition, a characteristic type of cataract, juvenile posterior subcapsular lenticular opacity, occurs in NF2. Multiple cafe au
lait spots and peripheral neurofibromas occur rarely
In patients with NF2, vestibular schwannomas usually present with progressive unilateral deafness early in the third decade of life
Bilateral vestibular schwannomas are generally detectable by MRI
The NF2 gene on chromosome 22q codes for a protein called neurofibromin 2, schwannomin, or merlin.
Tuberous Sclerosis (Bournevilles Disease)

(USMLE Favorite)
Is characterized by cutaneous lesions, seizures and mental retardation
The cutaneous lesions include
Adenoma sebaceum (facial angiofibromas)
Ash leaf-shaped hypopigmented macules (best seen under ultraviolet illumination with a Woods lamp)
Shagreen patches (yellowish thickenings of the skin over the lumbosacral region of the back) and
Depigmented nevi
On neuroimaging studies, the presence of subependymal nodules, which maybe calcified, is characteristic
Patients inheriting the tuberous sclerosis gene are at increased risk of developing ependymomas and childhood astrocytomas,
of which 90% are subependymal giant cell astrocytomas
Rhabdomyomas of the myocardium and angiomyomas of the kidney, liver, adrenals and pancreas may also occur
Subependymal giant cell astrocytoma is a peculiar astrocytic tumor that grows from the walls of the lateral ventricles. It is
pathognomonic of tuberous sclerosis, which is caused by mutations of TS1 or TS2 genes. Tuberous sclerosis manifests with multiple
hamartomatous lesions in the skin, CNS, and visceral organs. Cortical tubers are malformed (hamartomatous) nodules of the cortex,
probably resulting from faulty cortical development. USMLE Favorite

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VON HIPPEL-LINDAU SYNDROME

(USMLE Favorite)
This syndrome consists of retinal, cerebellar and spinal hemangioblastomas, which are slowly growing cystic tumors
Hypernephroma
Renal cell carcinoma
Pheochromocytoma, and
Cysts of the kidneys, pancreas, epididymis, or liver may also occur
Erythropoietin production by hemangioblastomas may result in polycythemia
The von Hippel-Lindau (VHL) is a tumor suppressor gene on chromosome 3p.

Sturge Weber Syndrome: (USMLE Favorite)

Port wine stain

Cavernous hemangioma
Seizures
Hemiatrophy of cerebral cortex
Rail road calcifications of cerebral cortex.

Appendegeal Tumors

Adenexal or Appendegeal tumors arise from cutaneous appendages

They may serve as markers for internal malignancies
They are mostly in the form of solitary or multiple nodules/papules
Eccrine porcoma is seen on palms and soles
Cylindroma or turban tumor is seen on forehead and scalp
Syringomas are seen in vicinity of lower eyelids
Trichoepitheliomas and Tricolemmoma arise from hair follicles and are seen on face, scalp, neck and upper trunk
Sebaceous adenoma arises from sebaceous glands
Brookes tumor from hair follicles.

Benign fibrous histiocytoma on the other hand is a benign dermal neoplasm.

Most common presentation is a dermatofibroma.
They are most common in adults with indolent behaviour and appear as tan to brown firm papules.

USMLE Case Scenario

A 3-year-old child with mental retardation, seizures and facial angiofibromas develops repeated episodes of syncope.
Echocardiogram reveals a mass in the left ventricle producing intermittent obstruction. Pathologic examination of the
resected mass demonstrates a cardiac rhabdomyoma. Which of the following lesions would this patient most likely also have?
1. Acoustic neuromas
2. Berry aneurysm
3. Cortical tubers
4. Neurofibromas
Ans. 3. Cortical tubers (The disease is tuberous sclerosis)

USMLE Case Scenario

Ophthalmoscopic examination of a 7-year-old child from Washington DC demonstrates a retinal angioma. This finding should
raise the possibility of which of the following syndromes?
1. Neurofibromatosis type I
2. Neurofibromatosis type II

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USMLE Step 1 Platinum Notes

3. Tuberous sclerosis
4. von Hippel-Lindau disease
Ans. 4. von Hippel-Lindau disease

USMLE Case Scenario

A 22-year-old male from New York presents with adenoma sebaceum of the skin and cortical tubers. The person is most
probably having:
1. Neurofibromatosis type I
2. Neurofibromatosis type II
3. Tuberous sclerosis
4. von Hippel-Lindau disease
Ans. 3. Tuberous sclerosis

Important Pathological Eponyms Related to Fruits/Vegetables

Potato Nodes: Sarcoidosis

Potato Tumor: Chemodectoma
Potato/oyster ovary: PCOD
Strawberry Cervix: Trichomonas Vaginalis
Strawberry tongue: Scarlet fever
Strawberry hemangioma: Nevus vasculosus
Barley colored fluid cyst: Spermatocele
Aple jelly nodules: Lupus Vulgaris
Apple core lesion: Ca Colon
Raspberry tumor: Umbilical adenoma
Raspberry thorn sign: Crohns disease
Peau de Orange appearance of breast: Breast Cancer
Orange Tonsils : Tangiers disease

Antibodies and Diseases: (USMLE Favorite)

Antibody Target

Disease

Nicotinic acetyl choline receptor

Myasthenia Gravis

Intrinsic factor

Pernicious Anemia

Proiteinase 3 (ANCA)

Wegners Granulomatosis

Alpha 3 chain of Collagen Type IV

Good Pasteurs Syndrome

Thyroid Peroxidase

Hashimotos Thyroiditis

ANA: SLE
Anti-Smith, anti ds DNA: Specific for SLE
Anti-Histone: Drug induced SLE
Anticentromere: CREST Syndrome
Anti-Scl-70: Scleroderma
Anti-SSA, Anti-SSB: Sjogrens syndrome
Anti-Jo-1: Polymyositis
Antimitochondrial: Primary Biliary Cirrhosis
Antiglidian, Antitransglutaminase: Celiac disease

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423

Anti-GIL: Hemolytic transfusion reactions

Anti-sacchromyces cervessiae: Crohns disease
Anti-epithelial cell: Pemphigus vulgaris
Anti-IgG: Rheumatoid Arthritis
Anti-Ri is the least common of the paraneoplastic autoantibodies. Detection of Anti-Ri antibody in serum or spinal fluid identifies an
otherwise unexplained neurological disorder as autoimmune and paraneoplastic. A positive result prompts a search for an underlying
occult malignancy. Anti-Ri antibodies are detected most commonly in postmenopausal women who usually present with signs of
midbrain, brainstem, cerebellar and/or spinal cord dysfunction. Ocular opsoclonus-myoclonus maybe a prominent symptom. Most
patients have a primary carcinoma of the breast. Lung and gynecological cancer are less frequently associated with this syndrome.
Treatment of the cancer can lead to decreased antibody titer and improvement of the neurological disorder. A negative result does
not rule out cancer
Anti-Hu is one of several antibodies detected in the serum of patients with neurologic paraneoplastic syndromes. Anti-Hu antibody
causes either a syndrome of encephalomyelitis or sensory neuropathy. The underlying cancer is usually small cell cancer of the lung
Anti-Yo polyclonal IgG autoantibody directed against Purkinjes cells and associated with paraneoplastic cerebellar degeneration in
oat cell carcinoma of the lung and cancer of the breast or ovary. Also called anti-Purkinje cell antibody.

USMLE Case Scenario

A 32-year-old female is reported with a past history of ulcerative colitis has a severe proximal myopathy. Serum creatine
kinase is found to be very high and a muscle biopsy shows necrosis and a cellular infiltrate. She had a circulating autoantibody
to Jo-1 antigen. Diagnosis is:
Ans. Polymyositis

USMLE Case Scenario

CREST syndrome (calcinosis, Raynauds phenomenon, esophageal motility syndrome, sclerodactyly and telangiectasia) which
is also called limited scleroderma. This would be associated with:
1. Anti-Ro
2. Anti-SS-B
3. Decreased ESR
4. Anti-centromere antibody
Ans. 4. Anti-centromere antibody

HIV Infection
HIV is an RNA virus whose hallmark is the reverse transcription of its genomic RNA to DNA by the enzyme reverse transcriptase
Window period is time between infection and detection of antibodies against HIV
HIV is transmitted by:
Homosexual
Heterosexual contact
Blood and blood products
Infected mothers to infants either intrapartum, perinatally, or via breast milk
HIV can be transmitted to individuals who receive HIV-tainted blood transfusions, blood products, or transplanted tissue
The hallmark of HIV disease is a profound immunodeficiency progressive quantitative and qualitative deficiency of the subset of
T-lymphocytes referred to as helper T-cells, or inducer T-cells.
AIDS related neoplasms are:
Kaposis sarcoma
B-cell non-hodgkins lymphoma
Primary lymphoma of brain

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USMLE Step 1 Platinum Notes

Important points in HIV Pathology: (USMLE Favorite)

AIDS is caused by HIV
A human retrovirus belonging to the lentivirus family
HIV-1 is the more common type associated with AIDS in the United States, Europe and Central Africa, whereas HIV-2 causes a
similar disease principally in West Africa
The viral particle is covered by a lipid bilayer derived from the host cell and studded with viral glycoproteins gp41 and gp120
Like most retroviruses, the HIV-1 virion is spherical and contains an electron-dense, cone-shaped core surrounded by a lipid
envelope derived from the host cell membrane
The virus core contains:
Major capsid protein p24
Nucleocapsid protein p7/p9
Two copies of genomic RNA and
Three viral enzymes (protease, reverse transcriptase and integrase)
p24 is the most readily detected viral antigen and is therefore the target for the antibodies used to diagnose HIV infection in blood
screening
The viral core is surrounded by a matrix protein called p17, lying beneath the virion envelope
The viral envelope itself is studded by two viral glycoproteins (gp120 and gp41), critical for HIV infection of cells
The HIV-1 proviral genome contains the gag, pol and env genes, which code for various viral proteins
In addition to these three standard retroviral genes, HIV contains several other genes (given three-letter names such as tat, rev, vif,
nef, vpr and vpu) that regulate the synthesis and assembly of infectious viral particles
The product of the tat (transactivator) gene, e.g. is critical for virus replication
The nef protein activates intracellular kinase activity (affecting T-cell activation, viral replication and viral infectivity) and reduces
surface expression of CD4 and MHC molecules on infected cells
The two major targets of HIV infection are the immune system and the CNS. The life cycle of the virus is best understood in
terms of its interactions with the immune system
The entry of HIV into cells requires the CD4 molecule, which acts as a high-affinity receptor for the virus. This explains the tropism of the
virus for CD4 + T-cells and its ability to infect other CD4 + cells, particularly macrophages and DCs
However, binding to CD4 is not sufficient for infection; the HIV envelope gp-120 must also bind to other cell surface molecules
(coreceptors) to facilitate cell entry. Two cell surface chemokine receptors, CCR5 and CXCR4, serve this role.

Kaposis Sarcoma
Kaposis sarcoma is common in homosexuals
Kaposis sarcoma (KS) is asociated with HHV 8 virus
KS arises from cells linning lymph vessels or blood vessels. KS actually arises as a cancer of lymphatic endothelium
KS is associated with HIV, immunosuppression, organ transplants
On skin Kaposis lesions are red/purple blotches which are asymptomatic or tender
GIT, liver, lung lesions are dangerous
Treatment of HIV with HAART reduces KS as well
Common sites: Skin, GIT, Lymph nodes, Lungs
Pathologically KS lesions contain tumor cells with a characteristic abnormal elongated shape, called spindle cells
The tumor is highly vascular, containing abnormally dense and irregular blood vessels, which leak red blood cells into the surrounding
tissue and give the tumor its dark color. Inflammation around the tumor may produce swelling and pain
Although KS maybe suspected from the appearance of lesions and the patients risk factors, a definite diagnosis can only be made
by biopsy and microscopic examination, which will show the presence of spindle cells
Detection of the KSHV protein LANA in tumor cells confirms the diagnosis.

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425

USMLE Case Scenario

A 45-year-old man came to see an immunologist who has noted several 1 to 2 cm reddish purple, nodular lesions present on
the skin of his right arm which have increased in size and number over the past 3 months. The lesions do not itch and are not
painful. He has had a watery diarrhea for the past month. On physical examination he has generalized lymphadenopathy and
oral thrush. Which of the following infections is most likely to be related to the appearance of these skin lesions?
1. Candida albicans
2. Human herpesvirus 8
3. Mycobacterium tuberculosis
4. Pseudomonas aeruginosa
5. Pneumocystis jiroveci
Ans. 2. Human herpesvirus 8

Histiocytosis X
This condition is rare
Cells involved are Langerhans cells
Cells contain Birbeck granules
Cells express CDI markers
LettererSiwe disease
Discrete yellowbrown papules develop on the scalp, face, upper trunk and flexures, with a distribution mimicking
seborrheic eczema. Purpura and crusting of the lesion may become evident. In some children mucous membranes are also
involved, with gingivitis and oral and genital ulceration
Signs of systemic involvement become manifest, with hepatosplenomegaly, lymphadenopathy and anemia. Chest X-ray shows
miliary shadowing and bone scans may show osteolytic areas
HandSchullerChristian disease
This is a more benign form of histiocytosis X, which usually presents within the first 5 years of life and follows a chronic nonfatal
course. The usual manifestations are radiological bone defects, exophthalmos and diabetes insipidus
Eosinophilic granuloma
This is the most benign form of histiocytosis X. It commonly presents within the first 5 years of life, and skin involvement is rare.
When it does occur, yellowish or brownish papules are found on the scalp and trunk in a distribution similar to the other forms
of histiocytosis X
Solitary lesion is commonest in skull
Spontaneous resolution usually occurs.

Pathological Conditions Related to Term X: (USMLE Favorite)

Cardiac syndrome X: occurs when a patient has all of the symptoms of angina pectoris without coronary artery disease or spasm.
These spasms can occur either at rest or with exertion. Cardiac syndrome X, the triad of
Angina pectoris
A positive exercise electrocardiogram for myocardial ischemia and
Angiographically smooth coronary arteries
The main cause of this syndrome is coronary microvascular dysfunction, as indicated by an abnormal response of coronary
microcirculation to both vasoconstrictor and vasodilatory stimuli (microvascular angina).
Syndrome X:
It is a term used to describe a constellation of metabolic derangements that includes
Insulin resistance
Hypertension
Dyslipidemia
Central or visceral obesity
Endothelial dysfunction and
Accelerated cardiovascular disease

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USMLE Step 1 Platinum Notes

X-Linked agammaglobulinemia
Males with this syndrome often begin to have recurrent bacterial infections late in the first year of life, when maternally derived
immunoglobulins have disappeared
Affected individuals have very few immunoglobulin-bearing B-lymphocytes in their circulation and lack primary and secondary
lymphoid follicles
Mutations of Brutons tyrosine kinase (Btk) gene are responsible for X-linked agammaglobulinemia
Sinopulmonary bacterial infections constitute the most frequent clinical problem
Treatment with intravenous immunoglobulin.

Fragile X Syndrome: (USMLE Favorite)

It is now recognized as the second commonest cause of mental handicap in males after Downs syndrome
Fragile X males have
A large forehead
Large head
Long nose
Prominent chin and
Long ears
Fragile X males tend to be larger at birth
Macro-orchidism is present.The size of the testes maybe considerably enlarged
There is a slight increase in the frequency of mitral valve prolapse, aortic root dilatation and hernias. More striking clinically is the
soft skin and joint hypermobility, which maybe helpful diagnostically. The range of intellectual handicap in fragile X males varies
but most are moderately to severely retarded.

THE X-LINKED LYMPHOPROLIFERATIVE SYNDROME (DUNCANS DISEASE):

(USMLE Favorite)
It is aX LINKED recessive disorder of young boys who have a normal response to childhood infections but develop fatal lympho
proliferative disorders after infection with EBV.

Enzyme Markers used in Pathology: (USMLE Favorite)

Serum Enzyme
Aminotransferases

Amylase
Cerulloplasmin
CPK
LDH
Lipase
Alkaline Phosphatase

Diagnostic Use
Viral Hepatitis (AST>ALT)
Alcoholic Hepatitis (ALT>AST)
Acute Pancreatitis
Wilsons Disease
Muscular Dystrophies, MI
MI (LDH 1>LDH2)
Acute Pancreatitis
Pagets disease (of bone)
Obstructive Liver Disease

Chromosomal Disorders: (USMLE Favorite)

Chromosome 14:
Krabbes disease
Niemann pick disease
Multiple myeloma
Alpha 1 antitrypsin deficiency
Familial HOCM
Congenital hypothyroidism

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Chromosome 15:
Albinism
Angelman syndrome
Prader willi syndrome
Tay Sachs disease
Xeroderma pigmentosum
Marfans syndrome
Bloom syndrome
Chromosome 16:
ADPKD
Alpha thalassemia
Pseudoxanthoma elasticum
Chromosome 17:
p53 gene
Neurofibromatosis 1
BRCA 1gene
Medulloblastoma
Ovarian tumor
Chromosome 18:
De Gruchy syndrome
Bipolar disorder
Chromosome 19:
Myotonia dystrophica
Malignant hyperthermia
Familial hypercholesterolemia
Peutz jeghers syndrome
Chromosome 20:
Severe combined immunodeficiency disease (SCID)
Chromosome 21:
Amyloidosis
Homocystinuria
Down syndrome
Chromosome 22:
Meningioma
Acoustic neuroma
Neurofibromatosis 2
Di George syndrome
Velocardiofacial syndrome

USMLE Case Scenario

A disease is characterized by osteolysis, producing patchwork areas of bone resorption with bizarre, large osteoclasts. In the
middle stage of the disease, secondary osteoblastic activity compensates with new bone formation, producing the mosaic
pattern. A mosaic pattern is a feature. The Pathology represents:
1. Rickets
2. Osteomalacia
3. Osteodystrophy
4. Pagets Disease
Ans. 4. Pagets Disease

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USMLE Step 1 Platinum Notes

Remember: (How to Identify Tricky Questions)

Burkitts lymphoma

Starry skin pattern

Mycosis fungoides

Pautriers abscess

Hairy cell leukemia

TRAP Positive

Histiocytosis X

Birbeck granules

Multiple Myeloma

Lytic bony lesions

Waldenstroms Macroglobunemia

Nonlytic lesions

Pathologically Important Bodies: (Viral)

Guarneri bodies

Vaccinia

Bollinger bodies

Fowlpox

Paschen bodies

Smallpox

Torres Bodies

Yellow fever

Cowdry Type A

Herpesvirus

Cowdry Type B

Adeno virus, Poliovirus

Some Other Important Bodies are

HP (Halber staedtler) bodies

Trachoma

Levinthal Colle Bodies

Psittacosis

Moosers bodies

Endemic Typhus

Miyagawa bodies

Chlamydia Trachomatis

Asteroid Bodies

Sarcoidosis

Babes Ernest Bodies

Diphtheria

Verocay Bodies

Neurilemmoma

Civatte Bodies

Lichen Planus

Donavan Bodies

Kala azar

Hassal bodies

Thymus

Zebra bodies

Metachromatic leukodystrophy

Winkler bodies

Syphilis

Ross bodies

Syphilis

Moot bodies

Multiple myeloma

Creola bodies

Asthma

Citron bodies

Clostridium septicum

Psammoma Bodies

Papillary adenocarcinoma of Thyroid

Serous Papillary cystadenocarcinoma of ovary
Meningiomas
Malignant Mesothelioma

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SRBCTS: (SMALL ROUND BLUE CELL TUMORS)

Are characterized by sheets of cells with rounded, small nuclei. They include:

Neuroblastoma
Ewings sarcoma
Rhabdomyosarcoma
Burkitts lymphoma
Lymphobalstic lymphoma
Wilms tumor
Retinoblastoma
Medulloblastoma

USMLE Case Scenario

A 58-year-old woman who is a bit nervous presents to a physician in Detriot with a 3-year history of headaches, generalized
tonic-clonic seizures and bilateral leg weakness. Skull X-ray shows areas of hyperostosis of the calvarium. Biopsy of the
responsible lesion shows a whorling pattern of the cells. Which of the following is the most likely diagnosis?
1. Medulloblastomas
2. Arachnoid cyst
3. Glioblastoma multiforme
4. Meningioma
5. Neurosarcoid
6. Metastatic breast cancer
7. Oligodendroglioma
Ans. 4. Meningioma
The most likely diagnosis is an intracranial meningioma.

USMLE Case Scenario

Embryonal rhabdomyosarcoma is the most common form of rhabdomyosarcoma. The tumor is composed predominantly of
small, round cells resembling cells found in developing muscle. The most common site for embryonal rhabdomyosarcoma is:
1. Head and neck
2. Kidneys
3. Liver
4. Lungs
Ans. 1. Head and neck

Types of Erythemas

Erythema chronicum migrans. Lymes Disease

Erythema Ab Agne: Reticulate pigmentation due to long-term heat exposure.
Erythema Gyratum Repens: Internal malignancies
Erythema Nodosum: Multisystemic disorders, e.g. sarcoidosis
Erythema multiforme: Mucosal involvement with viral, bacterial, rickettsial diseases with target lesions
Erythema toxicum neonatorum: This is a transient condition of unknown etiology occurring in up to 70% of neonates. The onset
is from birth to 14 days but most cases start between day 1 and day 4. The commonest lesions are erythematous macules and
papules but in some cases pustules appear
Erythema marginatum: Present in acute rheumatic fever, pink/red nonpruritic rash on trunk and upper limbs in associsation with
carditis
Erythema necrolyticum migrans Glucagonoma
Erythema infectiosum Parvo virus
Erythema arthriticum epidemicum Haver hill fever, streptobacillus monoliformis.

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USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 45-year-old abruptly develops an intensely itchy rash. He reports to a dermatology clinic. Physical examination demonstrates
multiple erythematous patches of the distal arms and legs. Some of the patches show central clearing with surrounding
erythematous rings. Which of the following is the most likely diagnosis?
1. Erythema nodosum
2. Erythema chronicum migrans
3. Erythema migrans chronicum
4. Erythema multiforme
Ans. 4. Erythema multiforme

Pathological Types of Common Cancers

Mc type of Stomach Ca: Adeno carcinoma

Mc type of Lung Ca: Adeno Carcinoma
Mc type of Pancreatic Ca: Ductal cell Adeno carcinoma
Mc type of Breast Ca: Intra ductal Adeno carcinoma
Mc type of Endometrial Ca: Adenocarcinoma
Mc type of cervical Ca: Squamous cell cancer
Mc type of vulval Ca: Squamous cell cancer

IMPORTANT CLINICAL SCENARIOS: (USMLE FAVORITES)

Repeated often

USMLE Case Scenario

Klinefilters Disease
Males who are
Sexually under developled with rudimentary testes and prostate glands
Sparse pubic and facial hair
Long arms and legs, and large hands and feet are likely to have the chromosome complement of: Klinefelters disease.

USMLE Case Scenario

Verrucous Carcinoma
A 72-year-old male from Texas who has been
Chewing tobacco for the past 50 years presents with a six months history of a large, fungating, soft papillary lesions in the
oral cavity
The lesion has penetrated into the mandible. Lymph nodes are not palpable
Two biopsies taken from the lesion proper show benign appearing papillomatosis with hyperkeratosis and acanthosis
infiltrating the subjacent tissues
The most likely diagnosis is Verrucous Carcinoma

USMLE Case Scenario

Clear Cell Sarcoma
A sarcoma appears
Like a malignant melanoma, which arises in the soft Tissue
It usually is found on the tendons of extremities of young Patients
Histologically, the cells can have pigment or clear cytoplasm. It is associated with t (12,22)
The sarcoma is Clear Cell sarcoma

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431

USMLE Case Scenario

Pagets Disease
A disease is characterized by osteolysis, producing patchwork areas of
Bone resorption with bizarre, large osteoclasts
In the middle stage of the disease, secondary osteoblastic activity compensates with new bone formation, producing
the mosaic pattern
Inlate Pagets, the bones are dense and osteosclerotic. A mosaic pattern is a feature
The Pathology represents Pagets Disease

USMLE Case Scenario

Picks Disease
Intracytoplasmic spherules composed of
Paired helical filaments stained with silver stains are seen in frontallobe with
Severe neuronal loss and astrocytosis
The condition most likely is Picks Disease (Picks bodies)

USMLE Case Scenario

Hairy Cell Leukemia
An elderly 77-year-old man comes to oncology clinic with:
Anemia and multiple infections
Physical examination is remarkable for marked hepatosplenomegaly
Blood counts demonstrates pancytopenia
Peripheral smear by a hematologist demonstrates rare, distinctive
Neoplastic white cells covered by fine, hairlike projections
Most likely disease is Hairy cell leukemia

USMLE Case Scenario

Crohns Disease
A 52-year-old man presents to Gastro clinic with a complaint of:
Nonbloody diarrhea and right lower quadrant pain with a palpable mass and tenderness
He states that this flare-up is one of the worst he has ever experienced
Radiographic examination reveals evidence of ulceration, stricturing, and fistula development of the colon and small
bowel
The most likely diagnosis is Crohns disease

USMLE Case Scenario

Silicosis
A disease occurs with:
Prolonged exposure to dust during glass production which can progress to respiratory failure and death, and is associated
with increased risk for tuberculosis
Classic X-ray findings include calcified lymph nodes that produce an eggshell pattern. Pleural involvement creates dense
fibrous plaques and adhesions that may obliterate the pleural cavities
Most likely disease is Silicosis

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USMLE Step 1 Platinum Notes

USMLE Case Scenario

Syphilis
It is seen that vasa vasorum of the aorta undergoes obliterative end arteritis:
Leading to atrophy of the muscularis and elastic tissues of the aorta and dilatation
Linear calcifications are often seen in the ascending aorta by X-ray
The intimal wrinkling is seen
The disease most likely represents: Syphilis infection. (The intimal wrinkling or tree barking is also a common feature.)

USMLE Case Scenario

Sturge-Weber Syndrome
A 13-year-old boy presents with a
Purple, flat vascular ectasia on the head and along distribution of the trigeminal nerve, mental retardation
Seizures and
Hemiplegia
The most likely disease is Sturge-Weber syndrome

USMLE Case Scenario

Wegeners Granulomatosis
A patient presents with:
Respiratory symptoms, i.e. cough hemoptysis and glomerulonephritis
His C-ANCA levles in serum were found to be raised
The most lkely diagnosis is Wegeners granulomatosis.

USMLE Case Scenario

Pituitary Adenoma
A 35-year-old female from New Orleans presented
With one year history of menstrual irregularity and galactorrhea
She also had off-and-on headache
Her examination revealed bitemporal superior quadrantopia
Her fundus examination showed primary optic atropy
The most likely diagnosis in this case Pituitary macroadenoma

USMLE Case Scenario

Acute Lymphoblastic Leukemia
A four-year-old boy was admitted with a history of abdominal pain and fever for two months, maculopapular rash for ten
days and dry cough, dyspnea and wheezing for three days. On examination, liver and spleen were enlarged 4 cm and 3 cm
respectively below the costal margins. His hemoglobin was 10.0 g/dl, platelet count 37 5 109/L and total leukocyte count 70
109/L, which included 80% eosinophils. Bone marrow examination revealed a cellular marrow comprising 45% blasts and 34%
Eosinophils and eosinophilic precursors. The blasts stained negative for myeloperoxidase and nonspecific esterase and were
positive for CD19, CD10, CD22 and CD20
The most likely diagnosis acutelymphoblastic leukemia with hyper eosinophilic syndrome

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USMLE Case Scenario

Hairy Cell Leukemia
CD19 positive, CD22 positive, CD103 positive monoclonal B-cells with bright kappa positivity were found to comprise 60%
of the peripheral blood lymphoid cells on flow cytometric analysis in a 55-year-old man with massive splenomegaly and a total
leucocyte count of 3.3 109/L
The most likely diagnosis is Hairy cell leukemia

USMLE Case Scenario

Syphilis
A 30-year-old male from suburban area with a history of sexual exposure comes with a painless indurated ulcer over the penis
with everted margins
The diagnosis is Syphilis

USMLE Case Scenario

Craniopharyngioma
A 6-year-old boy has been complaining of
Headache, ignoring to see the objects on the sides for four months. On examination, he is not mentally retarded, his grades at
school are good, and visual acuity is diminished in both the eyes. Visual charting showed significant field defect
CT scan of the head showed suprasellar mass with calcification
The most probable diagnosis Craniopharyngioma

USMLE Case Scenario

Tuberculosis
A 25-year-old man presented with fever and cough for two months
CT chest showed bilateral upper lobe fibrosis and mediastinal enlarged necrotic nodes with peripheral rim enhancement
The most likely diagnosis Tuberculosis

USMLE Case Scenario

Polyarteritis Nodosa
A 30-year-old male patient presents with complaints of
Weakness in right upper and both lower limbs for last 4 months
He developed digital infarcts involving 2nd and 3rd fingers on right side and 5th finger on left side. On examination, BP was
160/140 mm Hg, all peripheral pulses were palpable and there was asymmetrical neuropathy
Investigations showed Hb 12 gm%, TLC 12,000 per cu. mm, Platelets 4,30,000 and ESR 49 mm. Urine examination showed
Proteinuria and RBC-1015/hpf with no casts. The most likely diagnosis Polyarteritis nodosa

USMLE Case Scenario

Caplans Syndrome
A 45-year-old coal mine worker presents with
Cutaneous nodules, joint pain and occasional cough with dyspnea
His chest radiograph shows multiple small (14 cm) nodules in bilateral lung fields
Some of the nodules show cavitation and specks of calcification
Most likely these features are diagnostic of Caplans syndrome

434

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Crohns Disease
Two identical specimen of the intestine obtained following colectomy shows on examination hemorrhagic cobblestone
appearance one of them however, shows longitudinal grooving. it is likely to be a specimen of:
Ans. Crohns disease

USMLE Case Scenario

Adenoid Cystic Carcinoma
Salivary gland tumors having propensity for perineural spread and tendency for recurence along the nerve is most likely:
Adenoid cystic carcinoma

USMLE Case Scenario

Alpha-1 Antitrypsin Deficiency
Liver biopsy in an adolescent with cirrhosis revealed hepatocytes containing round to oval PAS distase resistant globular
inclusions. The most likely cause of cirrhosis in this patient is Alpha-1 antitrypsin deficiency.

USMLE Case Scenario

Clostridium Difficile
In a case of diarrhea with histopathological feature of intestinal mucosal clefts studded with copious thick secretions and
inflammatory cells, characteristic of pseudomembranous colitis, the likely cause is: Clostridium difficile.

USMLE Case Scenario

Good Pasteurs Syndrome
A person presents with hemoptysis and hematuria with antibasement membrane antibodies Diagnosis is Good Pasteurs
syndrome

USMLE Case Scenario

Seminoma
Testicular tumors having an increased elevation of placental alkaline phosphatase in the serum as well as a positive
immunohistochemical staining for placental alkaline phosphatase Seminoma

USMLE Case Scenario

CML: (Chronic Myeloid Leukemia)
A 60-year-old man from Cardiff presently working in New York presented with fatigue, weight loss and heaviness in left
hypochondrium for 6 months
The hemogram showed
Hb 10 gm/dL
TLC 5 lakhs/mm3
Platelet count 4 lakhs/mm3
DLC; neutrophil 55%, lymphocytes 4%, monocytes 2%, basophils 6%
metamyelocytes 10%, myelocytes 18%, promyelocytes 2% and blasta 3%
The most likely diagnosis is CML

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435

USMLE Case Scenario

Multiple Myeloma
A renal biopsy from a 66-year-old woman from Washington DC with
Progressive renal failure for the past 3 years shows glomerular and vascular deposition of pink amorphous material
It shows apple-green birefringence under polarized light after Congo red staining
These deposits are positive for lambda light chains
Likely diagnosis is Multiple myeloma

USMLE Case Scenario

Pulmonary Thromboembolism
On sectioning of an organ at the time of autopsy, a pathologist in New York Central Hospital reports
A focal, wedge-shaped firm area is seen accompanied by extensive hemorrhage, with a red appearance
The lesion has a base on the surface of the organ
This findings is typically of Lung with pulmonary thromboembolism

USMLE Case Scenario

Sarcoidosis
A young lady from Ohio presented with
Bilateral nodular lesions on shins
She was also found to have bilateral hilar lymphadenopathy on chest X-ray
Mantoux test reveals indurations of 5 mms
Skin biopsy would reveals Noncaseating Granuloma
Likely diagnosis is Sarcoidosis.

436

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 68-year-old woman who is normotensive presents to her cardiac physician after several episodes of syncope. Physical
examination is remarkable for a low-pitched plopping sound during mid-systole. Two-dimensional echocardiography
demonstrates a ball-valve type obstruction of the mitral valve. Which of the following would most likely be observed if the
cause of the obstruction were biopsied?
1. Benign glandular tissue
2. Myxomatous degeneration of valves
3. Dense calcification in tricuspid area
4. Densely packed smooth muscle
5. Densely packed striated muscle
6. Malignant glandular tissue
7. Scattered mesenchymal cells in a myxoid background
Ans. 7. Scattered mesenchymal cells in a myxoid background
Atrial myxoma may intermittently obstruct the mitral valve. Histologically, these tumors are composed of scattered
mesenchymal cells in a prominent myxoid background.

USMLE Case Scenario

A 8-year-old girl has chickenpox. A week after the onset of the rash, she begins vomiting and becomes lethargic and comatose.
Laboratory examination is significant for elevated liver enzymes and ammonia. Which of the following is the most likely
diagnosis?
1. Crigler-Najjar syndrome
2. Dubin-Johnson syndrome
3. Gilbert syndrome
4. Reye syndrome
Ans. 4. Reye Syndrome

USMLE Case Scenario

Condition resulting from incomplete separation of the cerebral hemisphere along the midline, leading, in its extreme form, to
a single midline ventricular cavity enclosed within the forebrain. Associated facial anomalies, often associated with trisomy
13 is:
1. Dandy-Walker malformation
2. Holoprosencephaly
3. Arnold-Chiari malformation
4. Myelomeningocele
Ans. 2. Holoprosencephaly

USMLE Case Scenario

Lacunar cells are seen in:
1. Nodular sclerosing variant of Hodgkins disease
2. Burkitts lymphoma
3. Mixed cellularity Hodgkins
4. Normal Lymph nodes
Ans. 1. Nodular sclerosing variant of Hodgkins disease

USMLE Case Scenario

A sarcoma appears like a malignant melanoma, which arises in the soft tissue. It usually is found on the tendons of extremities
of young patients. Histologically, the cells can have pigment or clear cytoplasm. It is associated with t(12, 22). The sarcoma is:
1. Synovial cell sarcoma
2. Clear Cell sarcoma

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437

3. Leiomyosarcoma
4. Rhabdomyosarcoma
Ans. 2. Clear Cell sarcoma

USMLE Case Scenario

A 24-year-old man presented to an ophthalmologist with a severe painful left eye for 38 hours. There is redness around the
cornea which developed into a iritis. Three days later the right eye also became involved. One week after the onset of the eye
symptoms, the patient complained of dysuria. No chlamydia, viruses or bacteria were isolated from this discharge. He was
treated with oxytetracycline and his eye signs gradually cleared. At about this time, however, his right first metatarsophalangeal
joint became inflamed and, subsequently, several joints were similarly involved. He was found to be HLA-B27-positive. Most
likely diagnosis would be:
1. Behcets Disease
2. Ankylosing Spondylitis
3. Reiters Disease
4. Gonococcal arthritis
5. Rheumatoid arthritis
6. Gouty Arthritis
Ans. 3. Reiters Disease

USMLE Case Scenario

A 45-year-old male from Kansas develops a gelatinous, well-circumscribed mass in her right cerebral hemisphere. Biopsy
of the mass reveals neoplastic cells with fried egg morphology. Which of the following tumors does this patient most likely
have?
1. Choroid plexus papilloma
2. Ependymoma
3. Glioblastoma multiforme
4. Oligodendroglioma
Ans. 4. Oligodendroglioma

USMLE Case Scenario

A 44-year-old woman who takes alcohol heavily has the sudden onset of severe abdominal pain with diffuse tenderness in all
abdominal quadrants, with marked guarding and muscular rigidity. An abdominal CT scan reveals peritoneal fluid collections
and decreased attenuation along with enlargement of the pancreas. A diagnosis of pancreatitis is made. Which of the following
cellular changes is most likely to accompany these findings?
1. Coagulative necrosis
2. Dry gangrene
3. Fat necrosis
4. Apoptosis (Programmed Cell Death)
5. Liquefactive necrosis
6. Wet gangrene
7. Hemorrhagic necrosis
Ans. 3. Fat Necrosis
The enzymes released from the pancreas with acute pancreatitis damage the surrounding fat and cause of fat necrosis.

USMLE Case Scenario

Rosenthal fibers are corkscrew-shaped, intensely eosinophilic structures deriving from accumulation of alpha and beta
crystalline within astrocytic processes. They are usually found in:
1. Ependymoma
2. Glioblastoma multiforme
3. Medulloblastoma
4. Pilocytic astrocytoma
Ans. 4. Pilocytic astrocytoma

438

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 44-year-old patient on chemotherapy for small cell carcinoma lung presents to a physician because of a markedly inflamed
and painful great toe. Physical examination additionally demonstrates small nodules on the patients external ear. Aspiration
of the metatarsal-phalangeal joint of the affected toe demonstrates needle-shaped, negatively birefringent crystals. Which of
the following are the crystals most likely composed of?
1. Bile pigments
2. Calcium pyrophosphate
3. Cystine
4. Monosodium urate
Ans. 4. Monosodium urate

USMLE Case Scenario

A 34-year-old man from New Orleans presents with hemoptysis and hematuria. This is a classic case of Goodpastures
syndrome. Under immunofluorescence, there are linear deposits of IgG on alveolar and glomerular basement membranes.
Renal biopsy shows inflammation of the glomeruli. X-ray shows focal pulmonary infiltrates. The most likely cause is:
1. Wegners granulomatosis
2. Poststreptococcal glomerulonephritis
3. Bergers disease
4. Goodpastures syndrome
Ans. 4. Goodpastures syndrome

USMLE Case Scenario

A 22-year-old tall man from Honduras presents with gynecomastia and testicular atrophy has a testicular biopsy that shows
sparse, completely hyalinized seminiferous tubules with Leydig cells present in large clumps between the hyalinized tubules.
Which of the following genetic disorders should be suspected?
1. 45, XO
2. 47, XXY
3. Trisomy 18
4. Trisomy 21
Ans. 2. 47, XXY

USMLE Case Scenario

A 48-year-old male from Ohio presents with sinus pain and drainage, bloody nasal discharge and nasal mucosal ulceration.
On laboratory examination, the man is found to have hematuria and red blood cell casts. A biopsy of the upper airway tissue
reveals granulomatous inflammation with necrosis. Blood tests show the presence of antineutrophil cytoplasmic antibodies
(c-ANCA). Most likely diagnosis is:
1. Goodpastures syndrome
2. Noninfectious granulomatous disease
3. Wegeners granulomatosis
4. Bergers Disease
Ans. 3. Wegeners granulomatosis

USMLE Case Scenario

A 45-year-old abruptly develops an intensely itchy rash. Physical examination demonstrates multiple erythematous patches
of the distal arms and legs. Some of the patches show central clearing with surrounding erythematous rings. Which of the
following is the most likely diagnosis?
1. Erythema nodosum
2. Erythema chronicum migrans
3. Erythema migrans chronicum
4. Erythema multiforme
Ans. 4. Erythema multiforme

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439

USMLE Case Scenario

Gandy-Gamma nodules are thought to be the result of organization of old hemorrhages. Seen in:
1. Hepatic cirrhosis
2. Hodgkins disease
3. Rheumatoid arthritis
4. Sickle cell anemia
Ans. 1. Hepatic cirrhosis

USMLE Case Scenario

It is seen that meninges and spinal cord herniate through a bony vertebral defect. These defects most commonly occur in
the lumbosacral region typically resulting in motor and sensory deficits in the lower extremities, and bowel and bladder
dysfunction. Deficency of which factor leads to the defect:
1. Ascorbate
2. Folate
3. Pyruvate
4. Glutamate
Ans. 2. Folate

USMLE Case Scenario

Pheochromocytoma intermittently secretes epinephrine and other vasoactive amines, producing episodes of elevated blood
pressure accompanied by headache. This is the tumor to associate with the rule of the 10s:
1. It is 10% nonmalignant
2. It is 10% unilateral
3. 10% adrenal
4. 10% are familial
Ans. 4. 10% are familial

USMLE Case Scenario

The defect in sickle cell anemia is amino acid substitution/s but the globin chain is still made. The gene may less commonly
be present in some Mediterranean and Eastern Arabian populations. There is enough fetal hemoglobin at birth to prevent
sickling with sickle cell disease. Sickle cell disease represents:
1. Missense mutations involve a change in many amino acids
2. Missense mutations involve a change in a single amino acid (valine for glutamic acid)
3. Missense mutations involve a change in a single amino acid (glutamic acid for valine)
4. Nonsense mutations involve a change in a single amino acid (valine for glutamic acid)
5. Nonsense mutations involve a change in a single amino acid (glutamic acid for valine)
Ans. 2. Missense mutations involve a change in a single amino acid (valine for glutamic acid)

USMLE Case Scenario

Ophthalmoscopic examination of a 7-year-old child from Washington DC demonstrates a retinal angioma. This finding should
raise the possibility of which of the following syndromes?
1. Neurofibromatosis type I
2. Neurofibromatosis type II
3. Tuberous sclerosis
4. von Hippel-Lindau disease
Ans. 4. von Hippel-Lindau disease

440

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 22-year-old male from New York presents with adenoma sebaceum of the skin and cortical tubers. The person is most
probably having:
1. Neurofibromatosis type I
2. Neurofibromatosis type II
3. Tuberous sclerosis
4. von Hippel-Lindau disease
Ans. 3. Tuberous sclerosis

USMLE Case Scenario

A 3-year-old child with mental retardation, seizures and facial angiofibromas develops repeated episodes of syncope.
Echocardiogram reveals a mass in the left ventricle producing intermittent obstruction. Pathologic examination of the
resected mass demonstrates a cardiac rhabdomyoma. Which of the following lesions would this patient most likely also have?
1. Acoustic neuromas
2. Berry aneurysm
3. Cortical tubers
4. Neurofibromas
Ans. 3. Cortical tubers. The disease is tuberous sclerosis

USMLE Case Scenario

A disease is characterized by osteolysis, producing patchwork areas of bone resorption with bizarre, large osteoclasts. In the
middle stage of the disease, secondary osteoblastic activity compensates with new bone formation, producing the mosaic
pattern. In late Pagets, the bones are dense and osteosclerotic. A mosaic pattern is a feature. The Pathology represents:
1. Rickets
2. Osteomalacia
3. Osteodystrophy
4. Pagets Disease
Ans. 4. Pagets Disease

USMLE Case Scenario

Cowden syndrome is due to :
1. Mutations of a gene on chromosome 9
2. Mutations of a gene on chromosome 10
3. Mutations of a gene on chromosome 11
4. Mutations of a gene on chromosome 12
Ans. 2. Mutations of a gene on chromosome 10

USMLE Case Scenario

An elderly 77-year-old man comes to oncology clinic with anemia and multiple infections. Physical examination is remarkable for
marked hepatosplenomegaly. A blood count demonstrates pancytopenia. Peripheral smear by a hematologist demonstrates
rare, distinctive, neoplastic white cells covered by fine, hairlike projections. Which of the following characteristics would likely
be associated with these cells?
1. Elevated CEA levels
2. Elevated leukocyte alkaline phosphatase
3. Philadelphia chromosome
4. Positive tartrate-resistant acid phosphatase
Ans. 4. Positive tartrate-resistant acid phosphatase

Pathology

441

USMLE Case Scenario

A pathologist from Mexico reports the presence of koilocytes in a cervical biopsy from a 22-year-old woman. Which of the
following conditions does this patient most likely have?
1. Chlamydia infection
2. Gonococcal infection
3. Herpes simplex virus infection
4. Human papilloma virus infection
Ans. 4. Human papilloma virus infection

USMLE Case Scenario

With CML there is a marked increase in the WBC count with many immature myelocytic forms, but not many blasts. In CML
1. The erythrocyte alkaline phosphatase is low
2. The erythrocyte alkaline phosphatase is high
3. The leukocyte alkaline phosphatase is low
4. The leukocyte alkaline phosphatase is high
Ans. 3. The leukocyte alkaline phosphatase is low

USMLE Case Scenario

A 25-year-old man has a testicular mass, which on orchiectomy shows a malignant tumor with yolk sac differentiation. Which
of the following tumor markers would probably be most useful in monitoring the patient for recurrent or metastatic disease?
1. Alpha-fetoprotein
2. Carcinoembryonic antigen (CEA)
3. Prostate-specific antigen (PSA)
4. S-100
Ans. 1. Alpha-fetoprotein

USMLE Case Scenario

A 45-year-old abruptly develops an intensely itchy rash. Physical examination demonstrates multiple erythematous patches
of the distal arms and legs. Some of the patches show central clearing with surrounding erythematous rings. Which of the
following is the most likely diagnosis?
1. Erythema nodosum
2. Erythema chronicum migrans
3. Erythema migrans chronicum
4. Erythema multiforme
Ans. 4. Erythema multiforme

USMLE Case Scenario

A 42-year-old female presents to New York Central Hospital with painful oral ulcers. Physical examination demonstrates
widespread erosions of her mucous membranes. Dermatological examination reveals a friable mucosa. Biopsy of perilesional
mucosa demonstrates acantholysis; Direct immunofluorescence demonstrates an intraepidermal band of IgG and C3. The
most likely diagnosis is:
1. Bullous pemphigoid
2. Dermatitis herpetiformis
3. Herpes simplex I
4. Pemphigus vulgaris
Ans. 4. Pemphigus vulgaris

442

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Cells similar to fibroblasts are seen growing in a storiform (pinwheel) pattern. This pattern of cells is characteristic of:
1. Leiomyosarcoma
2. Basal cell carcinoma
3. Keratocanthoma
4. Dermatofibrosarcoma
Ans. 4. Dermatofibrosarcoma

USMLE Case Scenario

A 58year-old woman who is a bit nervous presents with a 3-year history of headaches, generalized tonic-clonic seizures,
and bilateral leg weakness. Skull X-ray films reveal hyperostosis of the calvarium. Biopsy of the responsible lesion shows a
whorling pattern of the cells. Which of the following is the most likely diagnosis?
1. Medulloblastomsa
2. Arachnoid cyst
3. Glioblastoma multiforme
4. Meningioma
5. Neurosarcoid
6. Metastatic breast cancer
7. Oligodendroglioma
Ans. 4. Meningioma

USMLE Case Scenario

A 44-year-old male presents to the dermatologist with pain in the joints along with silvery, scaling plaques on his elbows and
knees. The most likely diagnosis is
1. Acne vulgaris
2. Pemphigus vulgaris
3. Psoriasis vulgaris
4. Pemphigoid
Ans. 3. Psoriasis vulgaris

USMLE Case Scenario

A 33-year-old female bar worker presents in a hospital in Ohio with a red, scaling, herald patch approximately 3 cm in
diameter. It is followed within days by eruption in a short-sleeve turtleneck distribution and crops of small, pink, oval patches
in a fir tree configuration on the flexural lines. The most likely disease is:
1. Pityriasis alba
2. Pityriasis rosea
3. Pemphigus vegetans
4. Pemphigus vulgaris
Ans. 2. Pityriasis rosea

USMLE Case Scenario

A 34-year-old male from Africa in New York Chest clinic has a pathology characterized by noncaseating granulomata in lungs.
The disease was discovered incidentally when chest X-ray reveals bilateral hilar adenopathy. Definitive diagnosis is based on
biopsy, which reveals non-caseating granulomata that are negative for fungi or acid-fast bacilli. The disease most likely is:
1. Cat Scratch Disease
2. Sarcoidosis
3. Scleroderma
4. Systemic lupus erythematosus
Ans. 2. Sarcoidosis

Pathology

443

USMLE Case Scenario

Embryonal rhabdomyosarcoma is the most common form of rhabdomyosarcoma. The tumor is composed predominantly of
small, round cells resembling cells found in developing muscle. The most common site for Embryonal rhabdomyosarcoma is:
1. Head and neck
2. Kidneys
3. Liver
4. Lungs
Ans. 1. Head and neck

USMLE Case Scenario

A biopsy of this mass demonstrates pleomorphic spindle cells that are cytokeratin negative, CD 45 negative and vimentin
positive. Which of the following neoplasms is he most likely to have?
1. Wilms tumor
2. Teratoma
3. Leiomyosarcoma
4. Rhabdomyosarcoma
5. Neuroblastoma
6. Ewing sarcoma
7. Malignant lymphoma
Ans. 4. Rhabdomyosarcoma

USMLE Case Scenario

A 38-year-old downtown drug addict known to be infected with HIV for the past 8 years has abdominal pain for the past
3 days. On Physical examination there is abdominal distension with diffuse tenderness and absent bowel sounds. An
abdominal CT scan reveals a mass lesion involving the small intestine after surgical excision shows an encircling mass 8.5 cm
long and 3.5 cm infiltrating the bowel. Most likely diagnosis is:
1. Metastatic disease
2. Hodgkin lymphoma
3. High-grade B-cell lymphoma
4. AML
5. CML
6. Carcinoid
7. Adenocarcinoma
Ans. 3. High-grade B-cell lymphoma

USMLE Case Scenario

An elderly 77-year-old man comes to oncology clinic with anemia and multiple infections. Physical examination is remarkable
for marked hepatosplenomegaly. Blood counts demonstrate pancytopenia. Peripheral smear by a hematologist demonstrates
rare, distinctive, neoplastic white cells covered by fine, hairlike projections. Which of the following characteristics would likely
be associated with these cells?
1. Elevated CEA levels
2. Elevated leukocyte alkaline phosphatase
3. Philadelphia chromosome
4. Positive tartrate-resistant acid phosphatase
Ans. 4. Positive tartrate-resistant acid phosphatase

USMLE Case Scenario

A 48-year-old woman who has had multiple sexual partners for the past 30 years has an abnormal Pap smear with cytologic
changes suggesting human papillomavirus infection. Without treatment, she is most likely to develop which of the following
lesions?
1. Squamous cell carcinoma

444

USMLE Step 1 Platinum Notes

2. Non-Hodgkins lymphoma
3. Kaposis sarcoma
4. Adenocarcinoma
5. Leiomyoma
Ans. 1. Squamous cell carcinoma

USMLE Case Scenario

Hypophosphatemic rickets is a condition causing abnormal regulation of vitamin D3 metabolism and defects in renal tubular
phosphate transport. Symptoms include growth retardation, osteomalacia, and rickets.It is a/an:
1. Is an X-linked recessive condition
2. Is an X-linked dominant condition
3. Is an autosomal dominant condition
4. Is an autosomalco dominant condition
Ans. 2. Is an X-linked dominant condition

USMLE Case Scenario

Hereditary hemochromatosis results from increased iron absorbtion with markedly increased iron stores. The iron
accumulation in tissues results in manifestations such as
1. Hepatomegaly, skin hypopigmentation, diabetes insipidus and hypogonadism
2. Hepatomegaly, skin hyperpigmentation, diabetes insipidus and hypogonadism
3. Hepatomegaly, skin hyperpigmentation, diabetes mellitus and hypogonadism
4. Hepatomegaly, skin hypopigmentation, diabetes mellitus and hypergonadism
Ans. 3. Hepatomegaly, skin hyperpigmentation, diabetes mellitus and hypogonadism

USMLE Case Scenario

Rheumatoid arthritis is characterized by Rheumatoid nodules which develop in 20 to 30 percent of patients, usually on or
around joints, on extensor surfaces, or on other areas subjected to mechanical trauma. The most important HLA association
is with:
1. HLA-DR2
2. HLA-DR3
3. HLA-DR4
4. HLA B 27
Ans. 3. HLA-DR4

USMLE Case Scenario

Cervical intraepithelial neoplasia (CIN) is associated with human papilloma virus (HPV) infection, particularly types 16 or 18.
These papillomaviruses produce
1. E6 and E7 proteins
2. EBNA proteins
3. E1A and E1B proteins
4. Tumor Proteins
Ans. 1. E6 and E7 proteins

USMLE Case Scenario

A patient has a pleural effusion. Which of the following conditions may lead to development of an exudate within the pleural
cavity?
1. Tubercular effusion
2. Cirrhosis of the liver
3. Congestive heart failure
4. Nephrotic syndrome

Pathology

445

5. Protein-losing enteropathy
Ans. 1. Tubercular Effusion
An exudate results from leakage of protein-rich fluid from the plasma into the interstitium. It is usually the result of increased
vascular permeability caused by inflammation.

USMLE Case Scenario

Mutagenic effects on bacterial cells in culture is tested by:
1. Rotheras test
2. Lachman Test
3. Ames test
4. Nitroblue tetrazolium test
5. Watson-Schwartz test
6. Widal test
Ans. 3. Ames test. It measures damage to DNA and correlates well with carcinogenicity in vitro

USMLE Case Scenario

A 2-year-old boy was admitted to a pediatric hospital with a 7-day history of high fever, lymphadenopathy, conjunctivitis
and an erythematous exfoliative rash affecting his trunk and extremities. On the basis of the characteristic clinical picture, a
clinical diagnosis of Kawasakis disease (also known as acute mucocutaneous lymph node syndrome). It is best described as:
1. An acute vasculitic disorder of infants affecting small and medium-sized blood vessels
2. An acute vasculitic disorder of infants affecting medium and large sized blood vessels, was made
3. A chronic nonvasculitic disorder of infants affecting small and medium-sized blood vessels was made
4. A chronic nonvasculitic disorder of infants affecting medium and large sized blood vessels, was made
Ans. 1. An acute vasculitic disorder of infants affecting small and medium-sized blood vessels

USMLE Case Scenario

TTP, as is the pentad of:
1. Fever, mental changes, renal failure, thrombocytosis and microangiopathic hemolytic anemia
2. Fever, mental changes, renal failure, thrombocytosis and microangiopathic nonhemolytic anemia
3. Fever, mental changes, renal failure, thrombocytopenia and microangiopathic hemolytic anemia
4. Fever, mental changes, renal failure, thrombocytopenia and macroangiopathic nonhemolytic anemia
Ans. 3. Fever, mental changes, renal failure, thrombocytopenia and microangiopathic hemolytic anemia

USMLE Case Scenario

Intracytoplasmic spherules composed of paired helical filaments stained with silver stains are seen infrontal lobe with severe
neuronal loss and astrocytosis. The condition most likely is:
1. HSV Encephalitis
2. Picks disease
3. Alzheimers disease
4. Parkinsons disease
Ans. 2. Picks Disease (Picks bodies)

USMLE Case Scenario

Subependymal giant cell astrocytoma is a peculiar astrocytic tumor that grows from the walls of the lateral ventricles. It is
caused by mutations of TS1 or TS2 genes. It is usually seen in:
1. von Hippel-Lindau syndrome
2. Neurofibromatosis 1
3. Neurofibromatosis 2
4. Tuberous Sclerosis
Ans. 4. Tuberous Sclerosis

446

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Microcytic, hypochromic anemia with reduced mental and physical performance is due to:
1. Iron deficiency
2. Copper deficiency
3. Calcium deficiency
4. Calcium deficiency
Ans. 1. Iron deficiency
Giant cell arteritis involves the cranial arteries (branches of the carotid system)

USMLE Case Scenario

Biopsying 2 cm lengths of each temporal artery are indicated because the process can be patchy. Biopsy can reveal
1. Granulomatous inflammation
2. Fibrinoid necrosis
3. Hyperplastic necrosis
4. Leukocytoclastic vasculitis
Ans. 1. Granulomatous inflammation

USMLE Case Scenario

A dementing disorder characterized clinically by progressive loss of memory, Parkinsonism, and visual/auditory hallucinations,
and pathologically by round intracytoplasmic neuronal inclusions in the substantia nigra and neocortex. The clinical features
are suggestive of:
1. HIV encephalitis
2. Lewy body disease
3. Shy dragger syndrome
4. Parkinsonism
Ans. 2. Lewy body disease

USMLE Case Scenario

A 32-year-old female presents to her physician with fatigue, pruritus and steatorrhea. Blood tests demonstrate an elevated
alkaline phosphatase. Patient has hypercholesterolemia and xanthomas. The most likely disease is:
1. Primary biliary cirrhosis
2. Alcoholic hepatitis
3. Bacterial Cholangitis
4. Carolis disease
Ans. 1. Primary biliary cirrhosis

USMLE Case Scenario

A 45-year-old man has easy fatiguibility for the past 12 months. On physical examination there are no abnormal findings.
Laboratory studies show his Hg is 9.5, Hct 26.9%, MCV 139 fL, platelet count 240,000/microliter, and WBC count 7200/
microliter. Which of the following morphologic findings is most likely to be present on examination of his peripheral blood
smear?
1. Tactoids
2. Hypersegmented RBCs
3. Hypersegmented neutrophils
4. Nucleated red blood cells
5. Blasts
6. Hypochromic, microcytic RBCs
7. Spherocytes

Pathology

447

8. Elliptocytes
Ans. 3. Hypersegmented neutrophils
The increased MCV points to a macrocytic anemia such as a megaloblastic anemia that can also have hypersegmented PMNs
from reduced numbers of nuclear divisions.

USMLE Case Scenario

Auer rods are formed of the cytoplasmic granules of the myeloid blasts of AML and are a typical finding with
1. ALL
2. AML
3. CML
4. CLL
5. Hodgkins disease
6. Non-hodgkins disease
Ans. 2. AML

USMLE Case Scenario

Serous papillary cystadenocarcinomas of the ovaries express:
1. CA-125
2. CA-19
3. CEA
4. AFP
Ans. 1. CA-125

USMLE Case Scenario

A Syndrome is characterized by Pancreatic neoplasm (insulinoma), Pituitary, and Parathyroid involvement. The syndrome is:
1. Polyglandular Type 1
2. Polyglangular Type 2
3. Wermer
4. Sipple
Ans. 3. Wermer

USMLE Case Scenario

Degenerated neurofilaments seen in patients with Alzheimers disease are:
1. Hirano bodies
2. Lipofuscin granules
3. Neurofibrillary tangles
4. Amyloid plaques
Ans. 3. Neurofibrillary tangles

USMLE Case Scenario

Methyl phenyl tetrahydropyridine is taken by a 25-year-old male from California complaining of uncontrollable shaking in his
hands. Most likely pathology he might have as a result of above mentioned features is:
1. Lewy bodies
2. Picks bodies
3. Negri bodies
4. Neurofibrillary tangles
Ans. 1. Lewy Bodies
The patient has parkinsonism induced methyl phenyl tetrahydropyridine (MPTP), a meperidine analog

448

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A disease is associated with multiple telangiectasias which are usually small. The most likely disease is:
1. von Hippel-Lindau disease
2. Osler-Weber-Rendu disease
3. Milroys disease
4. Buergers disease
Ans. 2. Osler-Weber-Rendu Disease

USMLE Case Scenario

A boy presents with a purple, flat vascular ectasia on the head and along distribution of the trigeminal nerve, mental
retardation, seizures and hemiplegia. The most likely disease is:
1. Milroys disease
2. Osler-Weber-Rendu disease
3. Sturge-Weber syndrome
4. von Hippel-Lindau disease
Ans. 3. Sturge-Weber syndrome

USMLE Case Scenario

A disease occurs with prolonged exposure to dust during glass production which can progress to respiratory failure and death,
and is associated with increased risk for tuberculosis. Classic X-ray findings include calcified lymph nodes that produce an
eggshell pattern. Pleural involvement creates dense fibrous plaques and adhesions that may obliterate the pleural cavities.
Most likely disease is:
1. Byssinosis
2. Berylliosis
3. Silicosis
4. Anthracosis
Ans. 3. Silicosis

USMLE Case Scenario

It is seen that vasa vasorum of the aorta undergoes obliterative endarteritis, leading to atrophy of the muscularis and elastic
tissues of the aorta and dilatation. Linear calcifications are often seen in the ascending aorta by X-ray. The intimal wrinkling is
seen. The disease most likely represents:
1. Marfans syndrome
2. Syphilis infection
3. Aortic dissection
4. Takayasus arteritis
Ans. 2. Syphilis infection (The intimal wrinkling or tree barking is also a common feature)

USMLE Case Scenario

A patient is brought to the emergency room following a seizure. Electrolytes show SIADH. CT-Scand emonstrates a lung mass.
Which of the following forms of lung cancer is most likely to cause the described electrolyte imbalance?
1. Adenocarcinoma
2. Bronchioloalveolar carcinoma
3. Large cell carcinoma
4. Small cell carcinoma
Ans. 4. Small cell carcinoma

Pathology

449

USMLE Case Scenario

The BRCA-1 gene associated with breast cancer and ovarian cancer, is located on:
1. 17 q
2. 17 p
3. 22 q
4. 18 q
Ans. 1. 17 q
The NF-1 gene is associated with neurofibromatosis type I is on 17q
The NF-2 gene associated with neurofibromatosis type II is on 22q
The p53 gene associated with many cancers, is on 17p
The DCC oncogene located on the long arm of chromosome 18q.

USMLE Case Scenario

A 35-year-old tall male from New Jersy has Marfan syndrome, an autosomal dominant disorder with features of subluxated
lens of the eye, mitral valve prolapsed. The defect lies in:
1. Gene on chromosome 15 encoding fibrillin
2. Gene on chromosome 16 encoding fibrillin
3. Gene on chromosome 17 encoding fibrillin
4. Gene on chromosome 18 encoding fibrillin
Ans. 1. Gene on chromosome 15 encoding fibrillin

USMLE Case Scenario

MEN II and MEN III are associated with
1. C-myc
2. Erb-B2
3. L-myc
4. Ret
Ans. 4. Ret

USMLE Case Scenario

A 62-year-old from Wales presently in US develops oliguria and peripheral edema over a period of weeks. Urinalysis reveals
hematuria and proteinuria; examination of the urinary sediment reveals red cell casts. Renal biopsy shows many glomerular
crescents. This presentation is most suggestive of which of the following conditions?
1. Rapidly progressive glomerulonephritis
2. Diabetic nephropathy
3. Hypertensive nephropathy
4. Lupus nephritis
Ans. 1. Rapidly progressive glomerulonephritis

USMLE Case Scenario

Touton giant cells are found in:
1. Xanthomas
2. Dermatofibromas
3. Actinic keratosis
4. Benign nevocellular nevus
Ans. 1. Xanthoma

450

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 72-year-old man from Chicago with an 76 pack year history of smoking experiences an episode of hemoptysis. On physical
examination he has puffiness of the face, some pedal edema. A chest radiograph reveals a 5.5 cm right upper lobe lung
mass.A fine needle aspirate of this mass yields cells consistent with oat cell carcinoma. A bone scan shows no metastases.
Immunohistochemical staining of the tumor cells is likely to be positive for which of the following hormones?
1. Parathormone
2. Erythropoietin
3. ACTH
4. Insulin
5. Vimentin
6. Keratin
7. Gastrin
Ans. 3. ACTH

USMLE Case Scenario

In a Teritary level Labit is observed that chronic, increased exposure to ionizing radiation results in damage to cellular DNA.
As a consequence, a protein is now absent that would arrest the cell in the G1 phase of the cell cycle. Subsequent to this, the
cell is transformed to acquire the property of unregulated growth. The absent protein is most likely the product of which of
the following genes?
1. RAS
2. VHL
3. p53
4. MYC
5. ABL
Ans. 3. p53

USMLE Case Scenario

A 55-year-old man from Chicago complains of pain in his left thigh for five months. On physical examination his thigh is
increased in size, compared to the right. A plain film radiograph reveals the presence of a 15 cm solid mass that does not
appear to arise from bone, but it does have infiltrative margins. A biopsy of this mass is taken and on microscopic examination
the mass is composed of highly pleomorphic spindle cells. Which of the following markers is most likely to be demonstrated
in the cells of this mass?
1. Cytokeratin
2. Factor VIII
3. Alpha fetoprotein
4. Lambda light chain
5. Vimentin
6. Parathormone
7. Erythropoietin
8. ACTH
9. Insulin
Ans. 5. Vimentin

USMLE Case Scenario

PAS-positive cytoplasmic granules in hepatocytes are seen in:
1. Wilsons disease
2. Hepatitis B
3. Alpha1-antitrypsin deficiency
4. Alcoholic hepatitis
Ans. 3. Alpha1-antitrypsin deficiency

PHARMACOLOGY

Pharmacology

Important Terminology in Basic Pharmacology

Affinity
Intrinsic activity (efficacy)
Agonist
Antagonist
Partial agonist
Inverse agonist

Ability of a drug to combine with receptor

Ability of drug to activate receptor
Have affinity and maximal efficacy
Have affinity and no maximal efficacy
Have affinity and sub maximal efficacy
Have affinity and opposite efficacy

Important Terminology (USMLE Favorite)

Clearance, a measure of the bodys ability to eliminate drug; Clearance is a measure of the rate at which the organs that eliminate
drug from the body remove drug from the blood
Volume of distribution, an indication of the extent to which the drug is distributed outside of the blood compartment
Bioavailability, the fraction of the administered dose that reaches the systemic circulation
Steady state is achieved when the rate of drug elimination equals the rate of drug delivery into the systemic circulation,
which, if bioavailability is complete, corresponds to the rate at which the drug dose is administered:
Therapeutic index: The ratio of the toxic dose to the therapeutic dose. LD50/ED50
If absorption is too rapid, then the resulting high concentration may cause adverse effects not observed with a more slowly available
formulation. At the other extreme, slow absorption is deliberately designed into slow-release or sustained-release drug formulations
in order to maintain plasma concentrations essentially constant during the dosage interval, because the drugs rate of elimination is
offset by an equivalent rate of absorption controlled by formulation factors
Half-Life: Half-life (t1/2) is the time that it takes for the plasma concentration or amount of drug in the body to decline by 50%
Drug Potency: Relative concentrations of two or more drugs that elicit same effect. Refers to amount of drug needed to produce
a certain response
Drug Efficacy: Maximal effect that a particular drug may elicit
More important than potency in determining choice of drug
Therapeutic window phenomenon: Optimal therapeutic response of drug is exerted only over a narrow range of plasma drug
concentration, e.g. TCA, clonidine, glipize.

Therapeutic and toxic effect

454

USMLE Step 1 Platinum Notes

Pharmacokinetics: It is quantitative study of drug movement in through and out of the body what the body does to a drug
Pharmacodynamics: It is what the drug dose to a body
Pharmacogenetics: Study of genetic basis for variability in drug response
Pharmacogenomics: Use of genetic information to guide choice of drug and dose on individual basis
Pharmacovigilance: Science and activities related to detection, assessment, understanding and prevention of adverse
effects of drug or other drug related problems.

DRUG METABOLISM
Occurs in two phases
Phase I:
Oxidation
Reduction
Hydrolysis
Cyclization, Decyclization
MFO (Mixed Function Oxidases) in Liver participate.
Phase II: Conjugation with
Glucronide
Sulfate
Glutathione, Acetylation, Methylation
Conjugation does not occur in metabolism of xenobiotics.

Factors Governing Volume of Distribution of a Drug

Lipid: water coefficient of drug
pKa: value of a drug
Degree of Plasma protein binding
Degree of blood flow
Affinity for different tissues
Fat: Lean body mass ratio
Diseases like CHF, Uremia, Cirrhosis
Pregnancy

Never Forget

Plasma protein binding occurs with many drugs

Highly plasma protein bound drugs are restricted mainly to vascular compartment
Displacement of protein bound drug plasma levels of drug
Have lower volumes of distribution
Bound fraction is not available for action
In hypoalbuminemia binding maybe reduced and high concentration of free drug maybe available
Binding sites are nonspecific and one drug can displace other.

List of Prodrugs
Enalapril: Enalaprilate
Sulfasalazine: 5 Aminosalisylic acid
Fluorouracil: Fluorouracil monophosphate

Pharmacology

455

Dipivefrine: Epinephrine
Predsnisone: Prednisolone
Levodopa: Dopamine

Other Prodrugs
Methyl dopa
Terfenadine
Zidovudine
Sulindac
Cyclophosphamide
Bacampacillin
Fluorouracil, mercaptopurine
Ticlopidine, Clopidregel

Drug Kinetics (USMLE Favorite)

1. Drugs with zero order kinetics: Phenytoin, aspirin, ethanol, theophylline, propafenone, warfarin, tolbutamide
2. Drugs with First-order kinetics, the time required to achieve steady-state levels can be predicted from the Half-life, because
accumulation is a first-order process with a half-life identical to that for elimination. Thus, accumulation reaches 90% of steadystate levels at the end of three to four half-lives.
A pharmacologist is examining a new drug with potential antipsychotic properties. He begins by analyzing the pharmacokinetic
properties of the drug. Studies of the drugs rate of elimination reveal the data below. The kinetics of drug are: This drug is exhibiting
zero-order kinetics, also known as saturation kinetics.

Drug kinetics
This means that a constant amount of drug is eliminated per unit time, regardless of the plasma concentration
This is in contrast to first-order kinetics, which implies that a constant fraction of drug is eliminated per unit time, so that drug
elimination is dependent on the plasma concentration
Drugs with zero-order kinetics and first-order kinetics can be distinguished from each other by examining a graph depicting
the time course of the disappearance of the drug from the plasma
With zero-order kinetics, the drug concentration falls linearly
With first-order kinetics, the drug declines in an exponential fashion. Therefore, when the Y-axis is plasma concentration (Linear
concentration scale), the curve shows exponential decay; when the Y-axis is the logarithm of the plasma concentration (logarithmic
concentration scale), a straight line is observed. Very few drugs actually exhibit zero-order kinetics; notable examples are:

456

USMLE Step 1 Platinum Notes

Ethanol
Phenytoin and
Salicylate

In Zero Order Reaction

A constant amount of drug is eliminated per unit time

Rate of elimination is independent of plasma concentration
Drugs with zero order elimination have no fixed half life. (t is variable)
Phenytoin, Ethanol and Salicylates show zero order kinetics.

In First Order Reaction

A Constant fraction of drug is eliminated per unit time

Rate of elimination is directly dependent on plasma concentration
Drugs with first order elimination have fixed half life. (t is constant)
Most drugs show first order kinetics.

Zero order: Elimination rate constant

t variable
First order: Elimination rate variable
t Constant
Some drugs follow first order kinetics but at higher doses follow zero order kinetics
This is actually known as Pseudo zero order. Phenytoin, Tolbutamide, Warfarin and Theophylline follows both zero as well as first
order kinetics.

Important Points: (USMLE Favorite)

In 1st t1/2E 50% drug eliminated
In 2nd t1/2

75% drug eliminated

In 3rd t1/2

87.5% drug eliminated

In 4th t1/2

93.7% drug eliminated

In 5th t1/2

97% drug eliminated

Loading dose is governed by volume of distribution

Maintainance dose is governed by clearance of drug and half life (t )

Acidic drugs ionize more at alkaline pH

Basic drugs ionize more at acidic pH
Unionized drugs are lipid soluble and diffusible
Ionized drugs are lipid insoluble and non diffusible
Ionized drugs are excreted mainly by kidney
Acidic drugs are absorbed in stomach. (are unionized in acidic medium and hence difusable)
Basic drugs are absorbed from intestine. (Proximal)

Ionized drugs poorly pass across placenta

Ionized drugs poorly pass across blood brain barrier
Ionized drugs poorly pass across renal tubules (Easily excreted).

Pharmacology

Microsomal Enzyme Inducers: (USMLE Favorite)

Barbiturates
Carbamazepine, clofibrate
DDT
Ethanol
Griseofulvin
Phenytoin, phenobarbitone
Primidone
Rifampicin, ritonavir
Phenobarbitone
Smoking, chronic alcohol intake

Microsomal Enzyme Inhibitors: (USMLE Favorite)

Quinolones
Erythromycin
Quinidine
Grape fruit juice
Cimetidine
Allopurinol
Ketocanazole
Omeprazole
Sulfonamides
MAO inhibitors

SIDE EFFECTS OF DRUGS ON IMPORTANT ORGANS

Features Related to Nephrotoxicity: (USMLE Favorite)

Most nephrotoxic cephalosporine: cephaloridine

Most nephrotoxic aminoglycoside: gentamycin
Least nephrotoxic antitubercular: rifampicin
Least nephrotoxic aminoglycoside: tobramycin
Tetracycline safe in renal failure: doxycycline

Features Related to Hepatotoxicity: (USMLE Favorite)

Causing Hepatitis
Halothane
MAO inhibitors
Anticonvulsants
Methyldopa
Rimapicin, isoniazid, pyrazinamide
Causing Intrahepatic Cholestasis
Phenothiazines
TCA
NSAIDS
Erythromycin, carbencillin, sulfonamides

457

458

USMLE Step 1 Platinum Notes

Hepatotoxins
Tetracycline
CCL4
Paracetamol
Methotrexate
Alfatoxin

Features related to Cardiotoxicity: (USMLE Favorite)

Doxarubicin
Daunorubicin
Vincristine
Halothane
Alcohol

Drugs causing Pulmonary Fibrosis

Busulfan
Bleomycin
Methotrexate
Nitrofurantoin
Sulfasalazine
Practolol
Amiodarone

Drugs with Low Safety Margin

Digoxin
Anticonvulsants
Antiarrythmics
TCA (Tricyclic antidepressants)
Lithium
Aminoglycosides

Age Related Changes in Body which Effect Drug Action

Body fat
Volume of distribution
Total body water
Lean body mass
Baroreceptor sensitivity
Renal function
Serum albumin
Hepatic blood flow

The Cytochrome P-450 Mixed-Function Oxidase System: (USMLE Favorite)

It is located on smooth endoplasmic reticulum in liver cells. This system is involved in the detoxification of some drugs and
other exogenous compounds (barbiturates, carcinogenic hydrocarbons, steroids, carbon tetrachloride, alcohol, insecticides), and its
growth can be stimulated by exposure (particularly chronic exposure) to these agents. As a consequence, cells adapted to one drug
can more rapidly metabolize the other drugs and compounds handled by the P-450 system.

Pharmacology

Drugs Produced by DNA Recombinant Technology

Human insulin
Growth hormone
Interferons
Interleukins
Monoclonal antibodies
Vaccines

Pharmacology of Autonomic Nervous System: High Yield Basic Points

Neurotransmitter in all preganglionic nerves is acetyl choline

Neurotransmitter in all ganglia is acetyl choline
Neurotransmitter in all postganglionic parasympathetic nerves is acetyl choline
Neurotransmitter in almost all postganglionic sympathetic nerves is noradrenaline except renal
Mesenteric beds and sweat glands

Botulinium inhibits Acetylcholine release.

Ach use is not possible because it is rapidly degraded.

Muscarinic Receptor Agonists

Contraction of sphincter puppilae:

Miosis

Contraction of ciliary muscle:

Accommodation

Heart:

heart rate conduction velocity

Lungs:

Bronchoconstriction

GIT:

motility, cramps

Urinary bladder:

Contraction

Glands:

Secretion

Blood vessels:

Dilatation

459

460

USMLE Step 1 Platinum Notes

Uses

Ach
Bethanechol
Methanechol
Pilocarpine

No clinical use
Treatment of ileus, urinary retention
Diagnosis of bronchial hyperreactivity
Treatment of glaucoma, xerostomia

Acetyl Cholinesterase Inhibitors

Edrophonium: Diagnosis of myasthenia gravis
Physostigmine: Tertiary amine antidote in atropine poisoning

Neostigmine/Pyridostigmine:
Treatment of ileus
Urinary retention
Reversal of NM blockade

Donepezil: Treatment of Alzhiemers disease

Organophosphates: Used as insectiscides

OP Poisoning: (Important For USMLE)

A 33-year-old farmer is rushed to a Peripheral Hospital after accidental exposure to parathion. He is in severe respiratory
distress and is bradycardia. Which of the following drugs can be given to increase the activity of his acetylcholinesterase.
Pralidoxime: PAM is an acetylcholinesterase (AChE) reactivating agent
It is only useful for counteracting AChE inhibitors which act by phosphorylating the enzyme (organophosphates). Pralidoxime can
remove the phosphate group from AChE, thus regenerating the enzyme. This must be done in a timely fashion because normally after
the phosphate group is bound to the enzyme, it undergoes a chemical reaction known as aging. Once this bond ages, pralidoxime
will nolonger be effective
Atropine is a nonselective muscarinic antagonist. Although atropine would be an appropriate agent for this patient, it acts by preventing
the excess ACh from stimulating muscarinic receptors rather than altering the activity of AChE.

Features of OP Poisoning: (DUMBBELSS)

Diarrhea
Urination
Pin point pupils
Miosis
Bradycardia
Bronchoconstriction
Excitation of muscles and CNS (Nicotinic)
Lacrimation
Salivation
Sweating

Atropine is used in OP Poisoning. (Antidote)

Atropine is also used for amantia (mushroom) poisoning
Pralidoxime is used in conjuction and reactivates cholinesterase.

Uses of Atropine
Atropine is used in OP Poisoning
Atropine is used as Mydriatic

Pharmacology

461

Atropine is used in Mushroom poisoning

Atropine is used in Preanesthetic medication
Atropine is used in treating Bradyarrhythmias

Nicotinic Receptor Antagonists

Ganglion blockers: Hexamethonium and Mecamylamine
Reduce autonomic tone
Prevent baroreceptor reflex changes in heart rate
a 1 agonists: Uses
Phenyl epherine: Nasal decongestant, Mydriatic
Methoxamine: Paroxysmal atrial tachycardia
a 2 agonists:
Clonidine and methyl dopa: used in hypertension

agonists
Isoproterenol: 1 = 2, used in bronchospasm, heart block, bradyarrhythmias
Dobutamine: 1 > 2
Selective 2 agonists:
Salmeterol, albuterol, terbutaline: Used in asthma
Ritodrine: Used in premature labor

Receptors on Which Important Drugs Act (USMLE Favorite)

Isoprenaline

1, 2

Diastolic BP, HR

Noradrenaline
Adrenaline

a1, a2, 1
a1, a2, 1, 2

Systolic BP, Diastolic BP, HR

Systolic BP, Diastolic BP, HR

Dopamine
a 1 blockers:
Prazosin
Doxazosin
Terazosin
Tamsolusin
a 2 blockers:
Yohimbine
Mirtazapine (antidepressant)

D1, D2, a1, a2, 1

Improves renal perfusion

USMLE Case Scenario

A 76-year-old patient is presenting with hypertension and signs and symptoms of benign prostatic hyperplasia (BPH) such as
nocturia, high post-void residual volume, urinary retentionTerazosin is given. Terazosin is: an alpha-adrenergic antagonist
that selectively blocks alpha-1 receptors in vascular smooth muscle producing relaxation. It is indicated for the treatment of
both hypertension and BPH.

Beta Blockers
1 blockers:
Acebutolol

462

USMLE Step 1 Platinum Notes

Atenolol
Metoprolol
Combined 1 2 blockers:
Labetalol
Carvedilol
Dilevalol

Timolol
Used mainly for glaucoma
No miosis
No accommodative spasm

Timolol can cause

AV Block
Bradycardia
Hypotension
Asthma

Contraindicated in asthma, heart block

SEROTONIN: 5HT
5HT Agonists
5HT1AAgonist: Antianxiety

Buspirone, ipsapirone, gepirone

5HT1BAgonist: Migrane

Sumitriptan

5HT4Agonist: gastric motility

Cisapride

5HT Antagonists
5HT2AAntagonist

Cyproheptadine, ketansarein

5HT2A/2 CAntagonist

Clozapine

5HT3Antagonist

Ondansetron, granisetron, tropisetron

USMLE Case Scenario

A 77-year-old patient from Chicago goes to his family doctor complaining of persistent and severe headaches with aura. His
physician diagnoses migraine headache and prescribes sumatriptan. What is the mechanism of action of this drug?
Sumatriptan is a serotonin agonist that is used to abort migraine headaches.

Antimigrane Drugs (High Yield for USMLE)

Triptans act on 5HT1B receptors. (agonists)

Sumatriptan is shortest acting triptan
Frovatriptan is longest acting triptan
Rizatriptan is fastest acting triptan
DOC for acute migrane: aspirin, paracetamol
DOC for acute severe migrane: sumatriptan

Drugs used in prophylaxis of migrane:

Beta blockers: propranolol

Pharmacology

TCA: amytriptiline
Calcium channel blockers (flunarazine)
Valproic acid, cyproheptadine
Methysergide
Papaverin

Prostaglandins

Cytoprotective for stomach

Dilate renal vasculature
Contract uterus
Maintain ductus arteriosus

PGE 1
Misoprostol: treatment of NSAID induced ulcer maintains ductus arteriosus
Alprostadil: used in male impotence

PGE 2
Dinoprostone: used in cervical ripening, abortifacient

PGF 2a
Carboprost: Abortifacient
Latanoprost: Treatment of glaucoma

PGI 2
Prostacyclin: Vasodilator, platelet stabilizer

PGE 2 and PGF 2

Mediate dysmenorrheal

Thrombaxanes
Platelet aggregator

Drugs used for Glaucoma

Acetazolamide is a carbonic anhydrase inhibitor used firstly as IV followed by Oral dose
Mannitol is also used as an IV Solution
Topical drugs to be used are:
Topical Pilocarpine 2 %
Topical Timolol
Topical Dorzolamide
Topical Brinzolamide
Anti glaucoma drugs
Binatoprost
Travoprost
Iravoprost
Unoprostone

463

464

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 66-year-old man presents to the ophthamology department in Ohio with acute onset of severe ocular pain accompanied by
blurred vision that is associated with halos around lights. On examination, the left eye is red and hard; the cornea is described
as having a steamy appearance, and mydriasis is noted. The most appropriate agent for the treatment of this patients acute
signs and symptoms is:
Acetazolamide (IV)
Acetazolamide is a carbonic anhydrase inhibitor used firstly as IV followed by Oral dose.

Aspirin
Irreversible COX Inhibitor
Antiplatelet
Analgesia
Antipyretic
Anti-inflammatory
Aspirin has an anti thrombotic effect
It inhibits TXA2 synthesis in platelets by irreversible acetylation and inhibition of COX 1
Platelets are annucleate and cannot overcome this inhibition but endothelial cells are nucleate and can overcome this
acetylation by regenerating more enzyme. (These points are gems, so try to remember not just for exams)
This is a therapeutic effect finding use of aspirin in prophylaxis for stroke and MI management.
Causes respiratory alkalosis and metabolic acidosis in high doses
GIT ulceration, bleeding, salicylism: tinnitus vertigo
Bronchoconstriction
Reyes syndrome
BT

Other NSAIDS
Nonselective COX 2 inhibitors:
Ibuprofen
Naproxen
Indomethacin
Ketorolac
Sulindac
Selective COX 2 inhibitors:
Celecoxib
Etorocoxib
Valdecoxib
Lumiracoxib
Rofecoxib
Preferential COX 2 inhibitors:
Nimesulide
Meloxicam
Nabumetone

Pharmacology

465

Acetaminophen
No antiplatelet action
No Reyes syndrome
No bronchospasm
Lesser GIT effects
Increased doses cause hepatotoxicity due to depletion of glutathione
N acetyl cysteine is used in acetaminophen toxicity

Diuretics Sites of Action

Thiazides

Chlorthiazide

Distal tubule

Hydrochlorthiazide

Distal tubule

Chlorthalidone

Distal tubule

Indapamide

Distal tubule

Metolazone

Proximal and distal tubules

Loop diuretics

Frusemide

Loop of Henle

Bumatenide

Loop of Henle

Ethacrynic acid

Loop of Henle

Carbonic anhydrase inhibitors

Acetazolamide

Proximal tubule

Potassium sparing diuretics

Spironolactone

Distal tubule and collecting duct

Triamterene

Distal tubule and collecting duct

Amiloride

Distal tubule and collecting duct

Thiazides
Chlorthalidone
Indapamide
Chlorothiazide
Inhibit Na+/Cl transporter in DCT. (Compare with loop diuretics below)
With K+ sparing diuretics are first choice treatment of essential hypertension
Thiazides are drugs used for idiopathic Hypercalciuria. (Dents Disease) But not Hypercalcemia
Uses:
CHF
Hypertension
Nephrogenic Diabetes Insipidus
Side effects/Cause:
Hyperglycemia
Hyperurecemia
Hypercalcemia
Kindly understand the point: Thiazides are used in treatment of hypercalciuria but themselves causes hypercalcemia and
renal stones.

466

USMLE Step 1 Platinum Notes

Loop Diuretics
Furoremide is basically a diuretic which acts rapidly. (High ceiling, loop diuretics) is a sulphamoyl derivative
(Furosemide, bumetanide, toresamide, ethacrynic acid.)
Furosemide acts on thick ascending limb of loop of Henle
Inhibit Na+/K+/2Cl transporter. (compare with thiazides above)
Can be used in renal failure
It is also used for: Acute Hypercalcemia
Second drug of choice after morphine for Acute Pulmonary edema
Uses:
Heart Failure
Pulmonary edema
Acute Renal Failure
Hypertension
Anion Overdose
Side effects:
Hyperuricemia
Hypocalcemia
Hyperlipidemia
Hyperglycemia
Acute saline depletion
Ethacrynic acid among the group is more ototoxic.

Spironolactone and Eplerenone

USMLE Case Scenario

A 55-year-old male presents to Medical OPD with a chief complaint of a substantial increase in the size of his breasts over
the past few months. Three months ago he was diagnosed with hypertension, and placed on antihypertensive medication.
Medications most likely prescribed was Spironolactone.
Spironolactone antagonizes the sodium retaining effect of aldosterone and is used to treat
Cirrhotic edema
Nephrotic syndrome
CHF and
Hyperaldosteronism
It also acts as a diuretic. (Pottasium sparing)
Caneronone is its active metabolite.
Spironolactone reduces potassium loss and in combination with other potassium sparing diuretics, fatal hyperkalemia can occur.
Side effects are:
Rashes
Abdominal pain
Amenorrhea
Gynecomastia

Pharmacology

Triamterene and Amiloride

Pottasium sparing diuretics
Saluretic effect is greater than thiazides
Block Na+ channels in collecting duct
Amiloride is more potent.

Acetazolamide
Carbonic anhydrase inhibitors (CA)
Acetazolamide
Dorazolamide
Brinzolamide
CA is present in renal tubular cells, gastric mucosa, exocrine pancreas, brain, RBC and ciliary body of eye
Uses:

Glaucoma
Acute mountain sickness
Epilepsy
Not given in sulfonamide sensitivity

Mannitol

Primary site of action of Mannitol is proximal tubule

Mannitol increases blood viscosity and increases perfusion
Mannitol is not metabolized
Mannitol is given parentally
On oral administration mannitol causes Osmotic diarrhea.

Uses:
Reduce ICT (Intra Cranial Tension)
Reduce IOT (Intra Ocular Tension)
Increase Urine volume in Renal Compromise
Should not be given in ATN, anuria, pulmonary edema
Toxicity:
Extracellular volume Expansion
Dehydration and Hypernatremia.

Raised ICT: Treatment

IV mannitol
Furosemide

Hyperventilation
Fluid restriction
Osmotic agents
Corticosteroids (dexamethasone) for vasogenic edema

Antidiuretics
Vasopressin
Lypressin
Terlipressin

467

468

USMLE Step 1 Platinum Notes

Desmopressin
Given intranasally
DOC for Diabetes insipidus
Lithium
Demeclocycline DOC for SIADH

Desmopressin
Desmopressin (DDAVP) is a synthetic replacement for vasopressin, the hormone that reduces urine production during sleep. It
maybe taken nasally, intravenously, or as a pill
Clinical uses
Bedwetting
Desmopressin is frequently used for treatment of bedwetting. It is usually in the form of Desmopressin acetate, DDAVP. The drug
replaces the antidiuretic hormone for a single night with no cumulative effect
Coagulation disorders
Desmopressin can be used to promote the release of von Willebrand factor and factor VIII in patients with coagulation
disorders such as type I von Willebrand disease, mild hemophilia A, and thrombocytopenia. It is not effective in the treatment of
hemophilia B or severe hemophilia A
Diabetes Insipidus
Desmopressin is also used to replace missing ADH in central diabetes.

ANTIDIABETIC DRUGS
Metformin
Glycolysis
Gluconeogenesis
Diarrhea and metallic taste in mouth are adverse features
It is particularly used in obese patients
It does not cause weight gain

Lactic acidosis is a feared complication of Metformin use

Metformin should not be used in Renal impairment
Causes Malabsorption of Vit B12
Metformin is a biguanide

Acarbose and Miglitol are alpha glucosidase inhibitor

Decreases progression of impaired glucose tolerance to overt disease. Along with (metformin, orlistat reduces fibrinogen levels
also are euglycemics. Do not cause hypoglycemia
Side effects are: GIT Discomfort, Flatulence and Diarrhea.
Also known as starch inhibitor
Potential Hepatotoxicity has been demonstrated.
Hypoglycemia occurs with sulfonylureas (Tolbutamide) and can be severe, prolonged for days and fatal especially in elderly and
in heart failure.

Thiazolidinediones
Thiazolidinediones or TZDs act by binding to PPARs (peroxisome proliferator-activated receptors), a group of receptor
molecules inside the cell nucleus, specifically PPAR (gamma)
The ligands for these receptors are free fatty acids (FFAs) and eicosanoids. When activated, the receptor migrates to the DNA,
activating transcription of a number of specific genes. By activating PPAR :
Insulin resistance is decreased
Insulin sensitivity

Pharmacology

469

Adipocyte differentiation is modified

VEGF-induced angiogenesis is inhibited
Leptin levels decrease (leading to an increased appetite)
Levels of certain interleukins (e.g. IL-6) fall
Adiponectin levels rise.
Chemically, the members of this class are derivatives of the parent compound thiazolidinedione, and include:
Rosiglitazone
Pioglitazone
Troglitazone, which was withdrawn from the market due to an increased incidence of drug-induced hepatitis
Rivoglitazone
Ciglitazone
Piaglitazone and rosiglitazone are antihyperglycemics which bind to PPAR (Peroxisome Proliferator Activating Receptors) increase
insulin sensitivity, increase insulin receptor numbers and decrease hepatic gluconeogenesis.
Side effects
Hypoglycemia, weight gain, edema

Repaglinide and Nateglinide

Stimulate insulin release from Pancreatic Beta cells
Used in Type II DM as an adjunct just before meals
Have rapid onset, short duration.

Glucagon like Peptide-Exenatide

It is an incretin released from small intestine
Glucagon like peptide. (GLP 1 analouge)
Augments insulin secretion
Degraded by enzyme dipeptidyl peptidase DPP4
Sitagliptin inhibits DPP4 and hence augments action of exenatide
It is a full agonist and used as a combination

Pramlinitide
Synthetic amylin analogue:
Reduces glucagon secretion from alpha cells of pancreas
Useful in both type 1 and type 2 DM

Glucomannan

Powdered extract from konjar

Promoted as a dietary fiber for diabetics
Dietary adjunct for diabetes
Appetite,
Serum lipids
Blood sugar
Constipation

470

USMLE Step 1 Platinum Notes

Insulin
t of insulin in blood is: 5 minutes
Insulin causes potassium entry into cell
Insulin has 51 amino acids. Human insulin differs from pork insulin by 1 amino acid
Humulin is human insulin

Insulin types
Rapid acting

Insulin aspartate
Lisproinsulin
Insulin glusuline

Short acting

Semilentene
Soluble insulin (SSS)

Intermediate acting

Insulin zinc suspension

Isophane insulin

Long acting

Protamine zinc insulin

Insulin glargine

Rapid Slow
Lispro > Regular > NPH>
Lente > Ultralente > Glargine

Types of insulin

Factors effecting insulin release

USMLE Case Scenario

An overweight 48-year-old male from Texas presents with complaints of increased thirst and frequent urination. Laboratory
examination reveals a blood glucose level of 192 mg/dL. The patients past medical history is unremarkable, except for an
anaphylactic reaction that occurred one year ago when he was given trimethoprim-sulfamethoxazole for a sinus infection. Based on
this information, which of the following agents should be prescribed?
1. Chlorpropamide
2. Glipizide
3. Glucagon
4. Metformin
5. Propranolol
Ans. 4. Metformin

The patients presentation strongly suggests Type 2 diabetes mellitus (NIDDM), which usually begins in middle or late life.
Obesity makes Metformin DOC.

USMLE Case Scenario

An obese patient presented in casualty in an unconscious state. His blood sugar measured 400 mg%, urine tested positive for
sugar and ketones; drug most useful in management is:
1. Glibenclamide
2. Troglitazone
3. Insulin
4. Chlorpropamide
Ans. 3. Insulin

Pharmacology

471

Diabetes Insipidus
Thiazides paradoxically exert an antidiuretic effect in diabetes insipidus
DRUGS USED IN DI:
Vasopressin (Neurogenic DI)
Amiloride (Lithium induced DI)
Indomethacin
Chlorpropamide
Carbamazepine
Clofibrate

Corticoids

Maximum mineralocorticoid activity: Aldosterone

Maximum glucocorticoid activity: Dexamethasone
Glucocorticoids with maximum mineralocorticoid activity: Hydrocortisone
Glucocorticoids with minimum glucocorticoid activity: Hydrocortisone

Antiandrogens

Flutamide
Biclutamide
Finasteride
Dutasteride
Danazol
Cyproterone (Androgen receptor blocker)

Important Table
Flutamide: Used in metastatic prostate cancer
Has fast action in case of BHP
Biclutamide: Longer acting and more potent analogue of flutamide
Finasteride: Selective 5 reductase type 1 inhibitor
Uses BHP, hirusitism
Male pattern baldness
Dutasteride: 5 reductase type 1 and type 2 inhibitor. Longer acting
Cyproterone: Used in PCOD, Precocious puberty
Clompihene is antiestrogen

Tamoxifen (USMLE Favorite)

Tamoxifen is an oral selective estrogen receptor modulator
FSH
It is used for the treatment of early and advanced breast cancer in both pre- and post-menopausal women
It is also approved by the FDA for the reduction of the incidence of breast cancer in women at high-risk of developing the
disease. It has been further approved for the reduction of contralateral (in the opposite breast) breast cancer
It has benefit throughout the whole spectrum of breast cancer: In the treatment of noninvasive ductal carcinoma in situ
(DCIS) it has been shown to be effective as adjuvant to surgery and radiotherapy. In early breast cancer adjuvant treatment with
tamoxifen has been shown to significantly reduce the risk of disease recurrence and death, and reduce the risk of new primary
tumors developing in the contralateral breast.

472

USMLE Step 1 Platinum Notes

These benefits appear to apply to both node-negative and node-positive disease and irrespective of the menopausal status
of the patient. Five years of treatment with tamoxifen is currently recommended in the adjuvant setting
Tamoxifen is a well-established endocrine treatment for advanced breast cancer, providing effective palliative treatment in
hormone-responsive breast cancer at all stages of the disease and irrespective of the age of the patient
Given orally once daily, it is relatively well tolerated, most side effects being of an antioestrogenic nature hot flushes, tachycardia
However, as a partial agonist the drug also displays some estrogenic properties. Whilst these can confer some benefits in
postmenopausal women, such as protection against osteoporosis and cardiovascular disease, they can also have detrimental
effects in a small number of women, notably an increase in the risk of endometrial hyperplasia and carcinoma.
Exemastine, latrazole are other hormonal agents used for breast cancer.
Latrazole is an aromatase inhibitor.
Tamoxifen is known to act as an estrogen agonist at the level of the endometrium. Numerous studies have shown that women
on tamoxifen develop changes in the endometrium including polyps, hyperplasia, and cancer. Hyperplasia runs a continuum
from cystic glandular hyperplasia to atypical hyperplasia. Patients with atypical hyperplasia are at significantly increased risk
for the eventual development of endometrial cancer. Thus, in a patient who is taking tamoxifen for breast cancer prevention
and develops atypical endometrial hyperplasia, the tamoxifen should be stopped. If there is a need to continue the tamoxifen,
then hysterectomy should be considered.

Antiasthmatics
Theophylline and Doxophylline
Mechanism of Action:
Inhibits phosphodiesterase 4 and increases cAMP concentration
Blocks adenosine receptors
Releases calcium from Sarcoplasm
BETA 2 Agonist
Mucociliary movement stimulator
Important points about metabolism:
It has low therapeutic index
At high doses kinetics changes from First order to zero order
Erythromycin inhibits metabolism of Theophylline (Increases Theophylline levels)
Crosses placenta and is secreted in milk
Smoking, phenytoin, rifampicin, phenobarbitone plasma levels of Theophylline
Erythromycin, ciprofloxacin, cimetidine, allopurinol plasma levels of theophylline

Sodium Cromoglycate

Inhibits mast cell degranulation

Ineffective in acute attack
Used for prophylaxis
Not absorbed orally, given as aerosol

Montelukast
Montelukast is a LTRA (Leukotriene receptor antagonist) used in maintenance therapy of asthma and relief of seasonal allergies
It is not useful in acute attacks. It is usually administered orally
Montelukast is a CysLT1 antagonist; that is it blocks the action of leukotriene D4 on the cysteinyl leukotriene receptor CysLT1 in
the lungs and bronchial tubes by binding to it. This reduces the bronchoconstriction otherwise caused by the leukotriene, and
results in less inflammation
Because of its method of operation, it is not useful for the treatment of acute asthma attacks. Again because of its very specific
focus of operation, it does not interact with other allergy medications such as theophylline.

Pharmacology

473

Side effects
Side effects include gastrointestinal disturbances, hypersensitivity reactions, sleep disorders and increased bleeding tendency,
aside from many other generic adverse reactions. Its use is associated with a higher incidence of Churg-Strauss syndrome
Another leukotriene receptor antagonist is zafirlukast taken once daily
5 lipo oxygenase inhibitor is Zileuton.

Beta 2 Sympathomimetic Bronchodilators

Salbutamol, Terbutaline: Short acting: Used in acute attacks

Salmeterol, bambuterol, formoterol: Long acting: used for prophylaxis
Most effective bronchodilators
No anti-inflammatory effects

Side Effects:
Hypokalemia
Hyperglycemia
Tolerance, tachyphylaxis

Ipratropium and Tiotropium

Anticholinergic bronchodilators
Bronchodilators of choice in COPD/COAD

Steroids

Are anti-inflammatory
Lipocortin levels
Block phospholipid breakdown
Not bronchodilators
Have no role in acute attacks or status asthamaticus
Reduce airway inflammation
Beclomethasone
Budesonide
Fluticasone
Flunisolide
Triamicinolone
Ciclesonide are commonly used steroids.

Effects of antiasthamatics

474

USMLE Step 1 Platinum Notes

Newer Drugs
Omalizumab
Humanized IgE antibody
Reduces frequency of Asthma exacerbations
Ciclesonide:
Inhalational steroid
Prodrug
Cilomilast, Roflumilast
PGE 4 inhibitors

Ist Generation Antihistaminics

Terfenadine is the drug listed that does not cross the blood-brain barrier and therefore does not cause sedation (a bad thing for
someone flying an airplane). Other drugs from the same class include astemizole and loratadine.
Diphenhydramine
Dimenhydrinate
Promethazine
Hydroxyzine
Meclizine
Pheniramine
Chlorpheniramine
Cyclazine

Second Generation Antihistaminics

Terfenadine
Astemizole
Loratidine
Cetrizine
Fexofenadine
Rupatidine
Azelastine
Acrivastin

Drugs Acting on GIT

Prokinetics are:
Metoclop aramide
Domperidone
Cisapride
Mozapride
Primary indication is Gastroesophageal Reflux Disease (GERD)
Antiulcer drugs
Ranitidine
Roxatidine
Famotidine

Pharmacology

475

Omeprazole
Esmoperazole
Rabeperazole
Pentoprazole
Proton pump inhibitor
Are long acting
Are long lasting
Have high first pass metabolism
Sucralfate: Ulcer protectant
H pylori gastritis responds to: Omeprazole, clarithromycin, amoxicillin, metronidazole therapies, bismuth
Triple therapy: (Lansoprazole, clarithromycin and amoxicillin)
Triple therapy: (Bismuth subsalicylate, tetracycline, and metronidazole).

Sucralfate
It is a drug that is not presently in widespread use because it is incompatible with H2 antagonists such as cimetidine, ranitidine,
famotidine and nizatidine.
Sucralfate is aluminum sucrose sulfate, a sulfated disaccharide, which polymerizes and binds to ulcerated tissue. It forms a
protective coating against acid, pepsin and bile, giving the tissue a chance to heal. Unfortunately, a low gastric pH is required for
polymerization, meaning that sucralfate is incompatible with drugs that reduce gastric acidity, such as H2 blockers and antacids.

ANTIBIOTICS
Mechanism of Action of Antibiotics
Inhibition of Cell wall Synthesis
Inhibition of cross linking (Transpeptidase): Pencillins, Cephalosporins, Vancomycin, Imipinem, Aztreonam
Inhibition of Peptidoglycan synthesis: Cycloserine, Bacitracin
Inhibition of glucan synthesis: Caspofungin

Inhibitors of Protein Synthesis

Aminoglycosides, Tetracyclines bind to 30S Ribosomal subunit
Chloramphenicol, erythromycin, clindamycin bind to 50S Ribosomal subunit

Inhibition of Nucleic Acid Synthesis

Rifampin blocks RNA Synthesis RNA polymerase
Quinolones inhibit DNA Synthesis DNA gyrase (Topoisomerase)
Sulfonamides and trimethoprim inhibit Nucleotide synthesis of tetrahydrofolic acid.

Alteration of Cell Membrane

Antibacterial Polymyxin
Antifungal Azoles (Ketoconazole, Flucoriazole, Itracanazole) inhibit ergosterol synthesis
Amphoterecin disrupts fungal cell membrane by binding to ergosterol.
Metronidazole acts as an electronic sink taking away electrons that organisms need for survival

476

USMLE Step 1 Platinum Notes

Actions of drugs

Drugs Inhibiting Cell Wall Synthesis: (USMLE Favorite)

Penicillins
Cephalosporins
Cycloserine
Vancomycin
Bacitracin

Drugs Acting on Cell Membrane: (USMLE Favorite)

Amphotercin
Nystatin
Polymyxin
Colistin

Drugs Interfering with Metabolism

Trimethoprim
Sulfonamides
Ethambutol, Pyrimethamine
PAS

Mechanism of Action of Antimicrobials

Aminoglycoside, Tetracyclines Block protein synthesis at the 30S ribosomal Subunit
Chloramphenicol Blocks protein synthesis at the 50S ribosomal subunit

Pharmacology
Clindamycin Blocks protein synthesis at the 50S ribosomal subunit
Macrolides Block protein synthesis at the 50S ribosomal subunit
Penicillin along with the cephalosporins, imipenem and actreonam, penicillin inhibits peptidoglycan cross-linking
Quinolones Block DNA topoisomerases
Rifampicin Blocks mRNA synthesis
Sulfonamides Block nucleotide synthesis
Vancomycin Blocks peptidoglycan synthesis

Drugs effecting folate metabolism

Types of drugs
Bacteriostatic drugs:
Erythromycin
Clindamycin
Chloramphenicol
Streptomycin
Tetracycline
Trimethoprim
Bacteriocidal drugs:
Penicillin
Cephalosporin
Aminoglycosides
Metronidazole

Mechanism of Action Outlined

Aminoglycosides and tetracyclines bind to 30S Ribosomal subunit
Chloramphenicol, erythromycin, clindamycin bind to 50S Ribosomal subunit
Chloramphenicol inhibits bacterial protein synthesis by blocking peptidyl transferase

Isoniazid inhibits synthesis of mycolic acid

Metronidazole acts as an electronic sink taking away electrons that organisms need for survival
Rifampicin blocks RNA polymerase
Quinolones inhibit DNA gyrase (topoisomerase)

477

478

USMLE Step 1 Platinum Notes

Sulfonamides and trimethoprim inhibit synthesis of tetrahydrofolic acid

Azoles (Ketoconazole, fluconazole, Itracanazole) inhibit ergosterol synthesis
Amphoterecin disrupts fungal cell membrane by binding to ergosterol
Vancomycin inhibits transpeptidases
Capsofungin blocks synthesis of glucan

Penicillinase-resistant penicillins are able to resist degradation by staphylococcal penicillinase

Methicillin, (Acid labile)
Nafcillin
Oxacillin
Cloxacillin
Dicloxacillin
Flucloxacillin

CEPHALOSPORINS
Ist Gen: effective against gram+ ve organisms
Cefazolin

Cephalothin

Cephapirin

Cephalexin

Cefadroxil

Cephradine

2nd Gen: effective against gram-organisms

Cefamandole, Cefuroxime, Cefoxitin, Cefotetan, Cefmetazole, Cefaclor, Cefprozil, Cefpodoxime, Loracarbef

3rd Gen: Effective against gram-enterobacteriacea

Cefotaxime

Ceftriaxone

Ceftizoxime

Ceftazidime

Cefoperazone

4th Gen
Cefepime
Cefpirome

Cefepime
The fourth-generation cephalosporin cefepime is more resistant to hydrolysis by beta-lactamases than are the thirdgeneration cephalosporins is stable against plasmid-encoded beta-lactamase and is also relatively resistant to the inducible
chromosomally encoded beta-lactamases
Penetrates rapidly into gram-negative bacteria
Targets multiple essential penicillin-binding proteins
Cefoxitine is effective against anaerobes
Cephaperazone has antipseudomonal activity
Cefepime is inactive against, methicillin-resistant staphylococci, penicillin-resistant pneumococci, most strains of Clostridium
difficile, and most strains of enterococci such as Enterococcus faecalis.

Quinupristin and Dalfopristin (USMLE Favorite)

Quinupristin and dalfopristin are used in treatment of vancomycin-resistant Enterococcus faecium (VREF)
Bind 50 S ribosome
Dalfopristin inhibits the early phase of protein synthesis in the bacterial ribosome and quinupristin inhibits the late phase of
protein synthesis
Quinupristin and dalfopristin are bacteriostatic against Enterococcus faecium and bacteriocidal against strains of methicillinsusceptible and methicillin-resistant staphylococci.

Pharmacology

479

Quinupristin and dalfopristin combination, a streptogamin antibacterial agent for intravenous administration, is a sterile
lyophilized formulation of two semisynthetic pristinamycin derivatives
Quinupristin is derived from pristinamycin I
Dalfopristin is derived from pristinamycin IIA

Drugs and Protein Synthesis

Linezolid interferes with formation of Initiation complex
Dalforpristin interferes with Amino Acid Incorporation
Quinipristine interferes with Amino Acid Incorporation
Chloramphenicol interferes with formation of Peptide bonds
Macrolides interfere with translocation
Sites of action

Carbapenams

Imipenem
Meropenem
Faropenem
Ertapenem
Effective against gram, gram-, anaerobic pathogenic bacteria
Beta lactamase resistant
Imipenem is inhibited by dehydropeptidase and hence given along with cilastatin.

Aztreonam
It is a monobactam
No activity against gram+ and anaerobes
Can be safely used in patients allergic to pencillin and related group of drugs because of lack of cross reactivity.

Linezoild
It is a synthetic antibiotic used for the treatment of serious infections caused by multi-resistant Gram-positive bacteria,
including
Streptococci
Vancomycin-resistant enterococci (VRE)
Methicillin-resistant staphylococcus aureus (MRSA)
Linezolid is a protein synthesis inhibitor:
Unlike most other protein synthesis inhibitors, which inhibit elongation, linezolid appears to work on the first step of protein
synthesis, i.e. initiation
Linezolid binds to the 23S portion of the 50S subunit (the center of peptidyl transferase activity)
Linezolid is effective against all clinically important Gram-positive bacteria, notably Enterococcus faecium and Enterococcus faecalis
(including vancomycin-resistant enterococci), Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus, MRSA),
Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes
It has almost no effect on Gram-negative bacteria.

480

USMLE Step 1 Platinum Notes

Macrolides
Three important macrolides are:
Erythromycin
Azithromycin and Chlarithromycin
Azithromycin is effective against Chlamydia, Mycoplasma, Ureaplasma, Legionella.
Mycobacterium avium intercellulare
Azithromycin is excreted by kidneys
Azithromycin does not inhibit cytochrome P450 (IS NOT AN ENZYME INHIBITOR)
Azithromycin is safe in pregnancy
Clarithromycin is most effective against H Pylori
Macrolides stimulate motilin receptors and cause GIT distress
Erythromycin estolate causes cholestatic jaundice
Erythromycin is used in penicillin allergics
In meningitis and pencillin allergy Chloramphenicol is used.

Telithromycin

It is the first ketolide antibiotic to enter clinical use

It is used to treat mild to moderate respiratory infections
Telithromycin is a semi-synthetic erythromycin derivative
Telithromycin prevents bacteria from growing, by interfering with their protein synthesis
Telithromycin binds to the subunit 50S of the bacterial ribosome, and blocks the progression of the growing polypeptide chain
Telithromycin has over 10 times higher affinity to the subunit 50S than erythromycin
Telithromycin is metabolized mainly in the liver, the main elimination route being the bile, a small portion is also excreted into the
urine.

GLYCOPEPTIDES ANTIBIOTICS: VANCOMYCIN, TEICOPLANIN

Vancomycin: (USMLE Favorite)
Inhibits bacterial cell wall
Ototoxicity, nephrotoxicity, Red man syndrome
It is DOC for MRSA infection and used for pseudomembranous colitis

Teicoplanin: (USMLE Favorite)

Teicoplanin is an antibiotic used in the prophylaxis and treatment of serious infections caused by Gram-positive bacteria, including
MRSA. Methicillin-resistant Staphylococcus aureus and Enterococcus faecalis.
It is a glycopeptide antibiotic extracted from Actinoplanes teichomyceticus, with a similar spectrum of activity to vancomycin
Its mechanism of action is to inhibit bacterial cell wall synthesis.

Clindamycin: (USMLE Favorite)

Lincosamide antibiotic
Inhibits protein synthesis
Binds to 50S ribosomal subunit
Implicated in pseudomembranous colitis
DOC for streptococcal necrotizing fasciitis

USMLE Case Scenario

Following the treatment of an oral abscess with clindamycin, a patient develops a greenish, foul-smelling watery diarrhea
with left lower quadrant pain. Other signs and symptoms include fever, leukocytosis, and lethargy. If the toxin produced by
Clostridium difficile is detected in the stool, the patient would most appropriately be treated with Metronidazole.

Pharmacology

481

Antibiotic-induced colitis (pseudomembranous colitis) is characterized by severe persistent greenish, foul-smelling diarrhea
and severe abdominal cramps, as well as fever, leukocytosis, and lethargy. This condition is caused by the toxin produced by
Clostridium difficile. This disorder is after clindamycin therapy.

Tetracyclines
Group I: Tetracycline, oxytetracycline, Chlortetracycline
Group II: Demeclocycline
Group III: Minocycline, Doxycycline are bacteriostatic
Tetracyclines bind to 30S Ribosomal subunit
Doxycycline:
All tetracyclines are nephrotoxic except Doxycycline
Doxycycline is metabolized and excreted via liver in bile.
Doxycycline is not excreted via kidneys and hence is not nephrotoxic.
All tetracyclines except doxycycline accumulate in renal failure
All tetracyclines except doxycycline enhance renal failure.
Contraindicated in pregnancy, lactation
Outdated tetracyclines cause Fanconis syndrome
Doxycycline causes photodermatitis
Are teratogenic
Cause super infections
Cause tooth discoloration
Minocycline causes pigmentation

Uses
Doxycycline is indicated for use in the treatment of chronic adult periodontitis in order to increase clinical attachment, reduce
probing depth, and reduce bleeding upon probing
Endocervical, rectal, or urethral infection, uncomplicated, caused by Chlamydia trachomatis
Epididymo-orchitis caused by C trachomatis or Neisseria gonorrheae or
Nongonococcal urethritis caused by C trachomatis or Ureaplasma urealyticum
Gonococcal infections, uncomplicated (except anorectal infections in men)
Lyme disease
Malaria prophylaxis
Syphilis (early), for penicillin-allergic patients
Syphilis (of > 1 years duration), for penicillin-allergic patients

Chloramphenicol

Binds 50S subunit

Bacteriostatic
Blocks elongation of peptide chain
Undergoes extensive enterohepatic circulation
Causes aplastic anemia
Causes grey baby syndrome

482

USMLE Step 1 Platinum Notes

Aminoglycosides

Bactericidal
Inhibit translation
Active against grambacilli
Ineffective against anaerobes
Used synergestic with pencillins
Distributed only extra cellularly
Netlimicin is least ototoxic
Framycetin, sisomycin are aminoglycosides
Streptomycin is used in treatment of plague/tularemia
Teratogenic
Ototoxic
Vestibulotoxic
Nephrotoxic
Cause neuromuscular blokade

Ototoxicity is due to damage to stereocilia

Should not be used in myasthenia gravis
Resistance is due to enzyme production
Amikacin is one of the most resistant to bacterial inactivating enzymes.

Quinolones
Ist generation:
Norfloxacin, ciprofloxacin, ofloxacin, pefloxacin
2 nd generation:
lomefloxacin, levofloxacin, sparfloxacin, gatifloxacin, moxifloxacin
Pefloxacin: Attains high CSF concentration
Levofloxacin: Highest oral bioavailability
Pefloxacin: Highest first pass metabolism
Sparfloxacin: Longest acting, phototoxic
Moxifloxacin: Most potent, active against gram-positive organisms are contraindicated in children
Cause arthopathy in children
Temafloxin: Causes immune hemolytic anemia
Trovafloxacin: Hepatotoxic

Chemoprophylactic Agents of Choice

Cholera
Plague
P carnii
Whooping cough
Diphtheria
TB
MAC
Malaria
Rheumatic fever

Tetracycline
Tetracycline
Cotrimaxozole
Erythromycin
Erythromycin
INH
Clarithromycin, azithromycin
Chloroquine
Benzathine pencillin

Pharmacology

PARASITOLOGY
Antimalarials
Treatment of
Chloroquine sensitive malaria: chloroquine
Chloroquine resistant malaria: mefloquine
Mefloquine resistant malaria: sulfadoxine+pyremethamine
Quinine
It is the DOC for cerebral malaria
Causes hypoglycemia
Can be given safely in pregnancy along with chloroquine
Primaquine
It is the only antimalarial active in exoerythrocytic stage
Primaquine is ineffective against p falciparum
Primaquine is effective for radical cure of pl vivax
Can cause G6PD deficiency
Halofantrine
It is effective against Chloroquine resistant p falciparum and p vivax
Causes prolonged QT
Artemensin derivatives
(artesunate, artemether, arteheter) are fastest acting erythrocytic schizontocides
Lumefantrine is an antimalarial
Pyronaridine is an antimalarial

Chloroquine
Chloroquine is an antimalarial drug
Chloroquine is also an immunosuppressant drug
Chloroquine is lysomotrophic (accumulates in lysosomes)
It is widely distributed in adipose tissue
It also has
Antitumor
Antiviral
DMARD Properties
It is used in treatment of SLE, Rheumatoid arthritis
Chloroquine is known to cause lots of side effects

Occular manifestations:
Keratopathy
Retinal toxicity
Blurred vision
Corneal deposits
Central serous retinopathy
Pigmentary bulls eye retinopathy
Optic atrophy
Myopathy
Retinopathy

Antifungal Drugs
Antifungal

Amphotericin B
Griseofulvin
Ketoconazole
Flucytosine

Mechanism of Action

Affinity for ergosterol, forms micropores in fungal cell membrane

Interferes with mitosis, disorients microtubules
Inhibits fungal lanosterol 14-demethylase, impairing ergosterol synthesis
Inhibits thymidilate synthetase (after being converted to active form;5-fluorouracil)

483

484

USMLE Step 1 Platinum Notes

Polyenes- amphotericin b, nystatin, hamycin, natamycin

Heterocyclic benzofuran- griseofulvin
Azole, miconazole, clotrimazole, ketoconazole.
Aspergillosis (treatment) Itraconazole is indicated in the treatment of aspergillosis caused by Aspergillus species in patients who are
intolerant of or refractory to amphotericin B therapy
Blastomycosis (treatment) Itraconazole is indicated for the treatment of pulmonary and extrapulmonary blastomycosis caused by
Blastomyces dermatiditis in immunocompromised and nonimmunocompromised patients
Candidiasis (prophylaxis) Fluconazole is indicated for the prophylaxis of candidiasis in patients undergoing bone marrow transplant
who receive cytotoxic chemotherapy and/or radiation therapy.

Amphotericin
Polyene derivative
Derived from streptomyces nodosus
Fungicidal as well as fungistatic
High affinity for ergosterol
Given IV with glucose solution
Given as lipid bound preparations
Amphotericin B lipid complex
Amphotericin B colloid suspension
Liposomal Amphotericin Decreases toxicity
It is not mixed with saline
Causes hypokalemia

Parenteral Amphotericin

Parenteral amphotericin B is indicated in the treatment of aspergillosis caused by Aspergillus fumigates

Parenteral amphotericin B is indicated in the treatment of disseminated candidiasis caused by Candida species
Parenteral amphotericin B is indicated in the treatment of coccidioidomycosis caused by Coccidioides immitis
Parenteral amphotericin B is indicated in the treatment of cryptococcosis caused by Cryptococcus neoformans
Parenteral amphotericin B is indicated in the treatment of fungal endocarditis
Parenteral and intraocular administration of amphotericin B are used in the treatment of candidal endophthalmitis
Parenteral amphotericin B is indicated in the treatment of histoplasmosis caused by Histoplasma capsulatum
Parenteral amphotericin B is indicated, with or without concurrent administration of flucytosine, in the treatment and suppression
of cryptococcal meningitis caused by Cryptococcus neoformans
Parenteral amphotericin B is also indicated in the treatment of fungal meningitis caused by organisms such as Coccidioides
immitis, Candida species, Sporothrix schenckii, and Aspergillus species
Parenteral amphotericin B is indicated in the treatment of mucormycosis (phycomycosis) caused by Mucor, Rhizopus, Absidia,
Entomophthora, and Basidiobolus organisms
Parenteral amphotericin B is indicated in the treatment of fungal septicemia
Parenteral amphotericin B is indicated in the treatment of disseminated sporotrichosis caused by Sporothrix schenckii.

Antivirals: (USMLE Favorite)

Acyclovir is a highly potent and selective inhibitor of the replication of certain herpesviruses, including herpes simplex virus (HSV)
types 1 and 2, varicella-zoster virus (VZV), and Epstein-Barr virus (EBV).
Valacyclovir
The L-valyl ester of acyclovir
It is converted almost entirely to acyclovir after oral administration
Valacyclovir has pharmacokinetic advantages over orally administered acyclovir
It exhibits significantly greater oral bioavailability

Pharmacology

485

Results in higher blood levels and

Can be given less frequently than acyclovir
Cidofovir:Cidofovir is a phosphonate nucleotide analogue of cytosine
Its major use is in CMV infections, particularly retinitis, but it is active against a broad range of herpesviruses, including HSV,
human herpesvirus (HHV) type 6, HHV-8
Fomivirsen: Fomivirsen is the first antisense oligonucleotide
Fomivirsen has been approved for intravitreal administration in the treatment of CMV retinitis in AIDS patients who have failed to
respond to other treatments or cannot tolerate them
Ganciclovir:
An analogue of acyclovir, ganciclovir is active against HSV and VZV and is markedly more active than acyclovir against CMV.
Famciclovir and Penciclovir
Foscarnet: Foscarnet (phosphonoformic acid) is a pyrophosphate-containing compound that potently inhibits herpesviruses,
including CMV.
Idoxuridine: Analogue of thymidine
Idoxuridine inhibits the replication of herpesviruses and poxviruses
Cannot be given orally
Trifluridine: Trifluridine is a pyrimidine nucleoside active against HSV-1, HSV-2, and CMV.
Vidarabine: Vidarabine is a purine nucleoside analogue with activity against HSV-1, HSV-2, VZV, and EBV.

USMLE Case Scenario

A 29-year-old female diagnosed with AIDS has been suffering from a progressive blurring of vision in her right eye. On
funduscopic examination, a small white opaque lesion is noted on the retina of her right eye. This patient is most likely
suffering from cytomegalovirus (CMV) retinitis. The best drug treatment for this infection is ganciclovir.

Other Antiviral Drugs

Lamivudine is a pyrimidine nucleoside analogue that is used primarily in combination therapy against HIV infection. It is also active
against HBV through inhibition of the viral DNA polymerase and has been approved for the treatment of chronic HBV infection.
Lobucavir is a synthetic cyclobutane nucleoside analogue with activity against a broad range of herpesviruses, HIV, and HBV.
Pleconaril is an investigational drug active in vitro against picornavirus replication, including over 90% of the most commonly
isolated enterovirus types and 80% of rhinovirus serotypes.
Interferons are cytokines that exhibit a broad spectrum of antiviral activities as well as immunomodulating and antiproliferative
properties.

Nucleoside Reverse Transcriptase Analogues

Zidovudine
Didanosine
Zalcitabine
Stavudine
Lamivudine
Abacavir

Nonnucleoside Reverse Transcriptase Inhibitors

Nevirapine
Delavirdine and
Efavirenz

486

USMLE Step 1 Platinum Notes

Nucleotide Reverse Transcriptase Inhibitors

Tenofovir

Protease Inhibitors
Saquinavir
Nelfinavir
Indinavir
Atazanavir
Ritonavir
Tipranavir

Fusion Inhibitor
Enfuvertide

Sites of action of anti HIV drugs

Side Effects Commonly Asked

Stavudine, didanosine, zalcitibine

Indinavir
Efavirenz
Zidovudine
Didanosine
Abacavir

Peripheral neuropathy
Nephrolithiasis
Rash, liver enzymes , CNS effects
Myelosuppression, Megaloblastic anemia
Pancreatitis
Severe hypersensitivity

Elvitegravir:
HIV integrase inhibitor
Interferes with HIV replication by blocking activity of virus to integrate into genetic material.
Emtricitabine: NRTI

Pharmacology

487

Lobucavir is a synthetic cyclobutane nucleoside analogue with activity against a broad range of herpesviruses, HIV and HBV. It
is currently under investigation in clinical trials. Its mechanism of action is through inhibition of viral DNA synthesis. Lobucavir
is initially phosphorylated by virus-induced kinases, and lobucavir triphosphate is a potent inhibitor of HSV, CMV, and HBV DNA
polymerases.

Raltegravir: (USMLE Favorite)

It is an antiretroviral drug, the first of a new class of HIV drugs, the integrase inhibitors, to receive such approval
Integration occurs following production of the double-stranded viral DNA by the viral RNA/DNA-dependent DNA polymerase,
reverse transcriptase
The main function of Integrase is to insert the viral DNA into the host chromosomal DNA, a step that is essential for HIV
replication
Integration is a point of no return for the cell, which becomes a permanent carrier of the viral genome (provirus)
Integration is in part responsible for the persistence of retroviral infections. After integration, the viral gene expression and particle
production may take place immediately or at some point in the future.

Bevirimat: (USMLE Favorite)

It is an anti-HIV drug believed to inhibit HIV by a novel mechanism, so-called maturation inhibition
Like protease inhibitors, bevirimat and other maturation inhibitors interfere with protease processing of newly translated HIV
polyprotein precursor, called gag
This molecule contains a number of HIV proteins in a single polypeptide which is then cleaved by the enzyme protease to produce
functional structural proteins
However, unlike the protease inhibitors, bevirimat binds the gag protein, not protease
Once bound to gag, bevirimat prevents a critical cleavage at a site called the capsid-SP1 junction
The resulting virus particles lack functional capsid protein and have structural defects, rendering them incapable of infecting other
cells.
Pleconaril is an investigational drug active in vitro against picornavirus replication including over 90% of the most commonly
isolated enterovirus types and 80% of rhinovirus serotypes.

Neuraminidase Inhibitors: (USMLE Favorite)

Neuraminidase inhibitors zanamivir and oseltamivir for both influenza A and influenza B.
Oseltamivir is indicated for the treatment of uncomplicated acute infection caused by influenza A virus in patients older than 1 year
of age
Oseltamivir is indicated for the treatment of uncomplicated acute infection caused by influenza B virus in patients older than 1 year
of age
Specific antiviral therapy is available for influenza: Amantadine and Rimantadine for influenza A

Antituberculous Drugs
First-line agents for the treatment of tuberculosis:
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol and streptomycin
Second-line drugs are used only for the treatment of patients with tuberculosis resistant to first-line drugs. Included in this group are
the injectable drugs
Kanamycin, amikacin, capreomycin and the oral agents
Ethionamide, cycloserine, and PAS, ofloxacin, levofloxacin and sparfloxacin
Other second-line drugs include clofazimine, amithiozone (thiacetazone)

488

USMLE Step 1 Platinum Notes

The treatment regimen of choice for virtually all forms of tuberculosis in both adults and children consists of a 2-month initial phase
of isoniazid, rifampicin, and pyrazinamide followed by a 4-month continuation phase of isoniazid and rifampicin
Except for patients who seem unlikely on epidemiologic grounds to be initially infected with a drug-resistant strain, ethambutol (or
streptomycin) should be included in the regimen for the first 2 months or until the results of drug susceptibility testing become
available.
Tuberculocidal* drugs

Isoniazid, Rifampicin, Pyrazinamide, Streptomycin

Tuberculostatic* drugs

Ethambutol, Thiacetazone, PAS, Ethionamide, Cycloserine

Mechanism of Action
ISONIAZID

Inhibits mycolic acid synthesis

RIFAMPICIN

Inhibits RNA polymerase

ETHAMBUTOL

Inhibits mycolic acid incorporation into cell wall

STREPTOMYCIN

Inhibits protein synthesis

SIDE EFFECTS:
INH Remember as
I - Irritation (epigastric distress)
N- Neuritis (peripheral neuritis common in slow acetylator)
H- Hepatotoxicity (Rare in children, common in elderly & alcoholics)
Rifampicin Remember as Syndromes
Respiratory syndrome
Cutaneous syndrome
Flu like syndrome
Abdominal syndrome
Pyrazinamide Remember as 3 H s
Hepatotoxicity
Hyperuricemia
Hyperglycemia
Ethambutol Most important side effect optic neuritis, blue vision
Streptomycin Vestibulotoxic Cochleotoxic
Nephrotoxic

Antitubercular drug which acts intracellularly pyrazinamide

Antitubercular drug which acts at low pH- pyrazinamide
Antitubercular drug which penetrates meninges pyrazinamide, INH, Rifampicin
Antitubercular drug which is contraindicated in renal failure- Ethambutol

FIRST-LINE ESSENTIAL DRUGS

Rifampicin
A semisynthetic derivative of Streptomyces mediterranei
Rifampicin distributes well throughout most body tissues, including inflamed meninges. The fact that rifampicin turns body fluids
(urine, saliva, sputum, tears) to a red-orange color
Has both intracellular and extracellular bactericidal activity
It blocks RNA synthesis by specifically binding and inhibiting DNA-dependent RNA polymerase
Other adverse effects of rifampicin include rash, hemolytic anemia, thrombocytopenia and immunosuppression of unknown
clinical importance. Rifampin is a potent inducer of the hepatic microsomal enzymes
Resistance to rifampicin results from spontaneous point mutations that alter the RNA polymerase (rpoB) gene.

Pharmacology

489

Isoniazid
Its mechanism of action involves inhibition of mycolic acid cell-wall synthesis via oxygen-dependent pathways such as the
catalase-peroxidase reaction
Isoniazid is bacteriostatic against resting bacilli and bactericidal against rapidly multiplying organisms, both extracellularly
and intracellularly
The two most important adverse effects of isoniazid therapy are hepatotoxicity and peripheral neuropathy
Other adverse reactions are either rare or less significant and include rash (2%), fever (1.2%), anemia, acne, arthritic symptoms, a
systemic lupus erythematosus-like syndrome, optic atrophy, seizures, and psychiatric symptoms
Isoniazid-associated hepatitis is idiosyncratic and increases in incidence with age
The risk of isoniazid-associated hepatitis is increased by daily alcohol consumption, concomitant rifampicin administration,
and slow isoniazid acetylation
Serum concentrations of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) be determined at baseline in
patients over 35 years of age who are receiving isoniazid for chemoprophylaxis, with monthly determinations thereafter
Discontinuation of isoniazid be strongly considered whenever an asymptomatic AST or ALT level exceeds 150 to 200 IU (three
to five times the upper limit of normal) in high-risk patients whose baseline values were normal
Peripheral neuritis associated with isoniazid relates to interference with pyridoxine (vitamin B6) metabolism. This can be
reduced with the prophylactic administration of 10 to 50 mg of pyridoxine daily
Almost all isoniazid-resistant strains have amino acid changes in the catalase-peroxidase gene (katG) or a two-gene locus
known as INHA.

Pyrazinamide

Bactericidal drug used in short-course therapy for tuberculosis

Levels in CSF are high
Intracellular action
Mechanism of Action Pyrazinamide is similar to isoniazid
Adverse hepatotoxicity, Hyperuricemia

USMLE Case Scenario

A 33-year-old male in US from India on isoniazid (INH) for last five months began to experience muscle fasciculations and
convulsions. Administration of which of the following vitamins might have prevented these symptoms: Pyridoxine

First-Line Supplemental Drugs

Ethambutol: Adverse effects retrobulbar optic neuritis is the most serious adverse effect; axial or central neuritis, hyperuricemia
Streptomycin: An aminoglycoside isolated from streptomyces griseus, streptomycin is available for intramuscular and intravenous
administration only.

Second-Line Drugs
Capreomycin: A complex cyclic polypeptide antibiotic derived from Streptomyces capreolus after streptomycin, capreomycin is
the injectable drug of choice for tuberculosis.
Amikacin and Kanamycin these well known aminoglycosides are bactericidal to extracellular organisms.
Para-Aminosalicylic Acid PAS, drug has a short half-life (1 h), and 80% of the dose is excreted in the urine.
Thiacetazone
Viomycin
Ethionamide
Cycloserine

490

USMLE Step 1 Platinum Notes

Newer Antituberculous Drugs

This group includes rifabutin, rifapentine
The newer fluorinated quinolones
Amoxicillin/clavulanic acid, clofazimine, clarithromycin and rifamycins KRM -1648 (Benzoxazinorifamycin).

Resistance is Due to
Isoniazid, Kat G or Inh A gene
Rifampicin, rpo B gene
Pyrazinamide, pnc A gene
Ethambutol, emb B gene
Streptomycin 16 s r RNA gene or ribosomal protein S 12 gene

Antileprotics
Multibacillary leprosy: Rifampicin, Dapsone, Clofazamine
Paucibacillary leprosy: Rifampicin, Dapsone
Rifampicin is the drug most rapidly acting and most potent against Leprosy bacilius. (R-R)
Dapsone is the drug of choice
Leprostatic
Acedapsone is repository form used as IM.

Side Effects of Dapsone

Peripheral motor weakness may occur more frequently.
Fatalities have occurred due to agranulocytosis, aplastic anemia, and other blood dyscrasias.
Serious cutaneous reactions, such as exfoliative dermatitis, toxic erythema, erythema multiforme, toxic epidermal
necrolysis, morbilliform and scarlatiniform reactions, and erythema nodosum may occur.
A dose-related hemolysis is seen in all patients, (Most common side effect) (with a slight decrease in hemoglobin and an increase
in reticulocyte count. Patients with G6PD-deficiency or a decrease in activity in glutathione reductase are more susceptible to
hemolysis.
A low level of methemoglobinemia also occurs in all patients at recommended doses
Hepatitis
Infectious mononucleosis like illness
Fixed drug eruptions

Side Effects of Clofazamine

Reddish black discoloration of skin
Acneform eruptions
Enteritis

Antiparasitic Drugs: (USMLE Favorite)

Parasites

Drug of Choice

1. Ascariasis

Albendazole

2. Capillariasis

Mebendazole

Pharmacology

491

3. Giardiasis

Metronidazole

4. Trichuris trichura

Albendazole

5. Cysticercosis (T solium)

Praziquental

6. Sheep Liver Fluke (due to Fasciola hepatica)

a. Triclabendazole-a veterinary fasciolicide is a drug of choice

b. Bithionol is alternative drug of choice
c. Pranziquantel-generally ineffective.

7. Chinese Liver Fluke (Clonorchis sinensis)

Pranziquantel

8. Intestinal Fluke (Fasciolopsiasis)

Pranziquantel

9. Lung Fluke (Paragonimus westermani)

Pranziquantel

10. Tape worms, dwarf tapeworm

Pranziquantel

11. Schistosomiasis

Pranziquantel

12. Trichomonius vaginalis

Metronidazole

13. Dracunculiasis

Metronidazole

14. Enterobiasis

Mebendazole

15. Strongyloidiasis

Ivermectin

16. Pnuemocystis carinii

Trimethoprim Sulfamethoxazole

17. a. Angiostrongyliasis
b. Cutaneous larva migrans

Thiabendazole

18. Amebic meningoencephalitis

Amphotericin B

19. Babesiosis

Quinine plus Clindamycin

20. Balantidiasis

Tetracycline

21. Filariasis

Diethyl carbamazine

22. Leishmaniasis

Stibogluconate sodium diazine

23. Toxoplasmosis

Pyrimethamine plus either trisulfamethoxazole or, sulfadiazine (Sulfonamides).

24. Trypanosomiasis
a. T cruzi (Chagas Disease)
b. T brucei (Sleeping Sickness)
1. Hemolymphatic stage
2. Late stage (CNS involvement)

Suramin
Melarsoprol

25. Onchocerciasis (River blindness)

Ivermectin

26. Hookworms
a. Ancylostoma duodenale
b. Necator americanus

Mebendazole

27. Uncomplicated Gonorrhea

Ceftriaxone

28. Nocardiasis

Trimethoprim-Sulfamethoxazole

29. Actinomycosis

Penicillin-G

ANTIHYPERTENSIVES
Beta Blockers
Half life of esmolol is 10 minutes (shortest)
Half life of nadolol is 24 hours (longest)
Esmolol is a class II antiarrhythmic.

492

USMLE Step 1 Platinum Notes

Cardioselective (beta 1antagonists) are safer to use in asthma, diabetics and peripheral vascular diseases
Celiprolol has membrane stabilizing properties
Cardioselective Beta Blockers are (B2EA2M)
Betaxolol

Bisoprolol

Esmolol

Atenolol

Acebutolol

Metoprolol.

Beta Blockers with both Alpha and Beta Blocking Properties Are
Labetalol

Dilevalol

Cardivelol

USED IN
Cardiovascular

Angina
Hypertension
Myocardial Infarction
Cardiac Tachyarrhythmias
Hepatic portal hypertension
Esophageal variceal bleeding

Endocrine
Hyperthyroidism
Pheochromocytoma

CNS
Anxiety
Migrane Prophylaxis
Essential tremor

Eye
Glaucoma (Timolol)

ACE Inhibitors

Benazepril
Captopril
Cilazapril
Enalapril
Enalaprilat
Fosinopril
Lisinopril
Moexipril
Perindopril
Quinapril
Ramipril
Trandolapril

Are used for [treatment of malignant, refractory, or accelerated hypertension, and for treatment of renovascular
hypertension (Except in patients with bilateral renal artery stenoses or renal artery stenosis in a solitary kidney)
Are also indicated, in combination with diuretics and digitalis therapy, for treatment of congestive heart failure not responding
to other measures.

Pharmacology

493

Postmyocardial infarction
Left ventricular dysfunction
Indicated for the treatment of hemodynamically stable patients within 24 hours of an acute myocardial infarction to improve
survival
Nephropathy in patients with Type 1 insulin-dependent diabetes mellitus (IDDM)
Hypertension or renal crisis in scleroderma
Cause cough because of bradykinin
Ommission of prior diuretic dose decreases risk of postural hypotension.
ACE inhibitors are used for reducing proteinuria in both diabetic as well as nondiabetics
They are however the drugs of choice for reducing proteinuria in Diabetic Renal failure
ACE Inhibitors delay ESRD in Diabetic Nephropathy. Albuminuria remains stable after ACE INH Therapy
However it should be remembered that ACE Inhibitors are contraindicated in:
Patients with Single kidney
B/L Renal artery stenosis GFR
Hyperkalemia
Pregnancy
NOT used in pheochromocytoma

(Angiotensin Receptor Blockers) (USMLE Favorite)

Action of angiotensin and aldosterone

Losartan
Eprostan
Irbesartan
Candersartan
Olmesartan
Telmisartan
These drugs have effects similar to those of ACE inhibitors
However, instead of blocking the production of angiotensin II, they competitively inhibit its binding to the angiotensin II AT1 receptor
subtype
Their utility and tolerability are similar to those of the ACE inhibitors, but they do not cause cough or angioedema.

494

USMLE Step 1 Platinum Notes

Difference in action

Malignant Hypertension
Nitroprusside is given by continuous intravenous infusion
It is the agent of choice in this condition, since it dilates both arterioles and veins
It has the advantage over the ganglionic blockers of not being associated with the development of tachyphylaxis and can be used for
days with few side effects. The dosage must be controlled with an infusion pump
Gaunylate cyclase
No central effects
NO levels along with hydralazine, nitrates
Nitroglycerin
Affects veins more than arterioles
It is particularly useful in the treatment of hypertension following coronary bypass surgery, myocardial infarction, left
ventricular failure, or unstable angina pectoris.
Diazoxide is the easiest agent to administer, for no individual titration of dosage is required. However, it is probably less effective
than the other agents. It primarily affects arteriolar and not venous tone
Inhibits labor
Intravenous labetalol maybe particularly useful in patients with a myocardial infarct or angina because it prevents an increase in
heart rate. However, it maybe ineffective in patients previously treated with beta blockers and is contraindicated in patients with
heart failure, asthma, bradycardia, or heart block
Indicated in Pregnancy
Intravenous hydralazine
Causes drug induced lupus
Hydralazine should be used with caution in patients with significant coronary artery disease and should be avoided in patients
manifesting myocardial ischemia or aortic dissection. It is effective in preeclampsia.
Esmolol, a beta blocker with an onset of action of 1 to 2 min, is particularly useful in aortic dissection and for perioperative
hypertensive crisis.
Enalaprilat, an intravenous form of the ACE inhibitor enalapril, has also proven effective, particularly in individuals with left heart
failure.
Indapamide: diuretic with vasodilator properties
Clonidine, methyl dopa, gaunabenz, gaunafacine, moxonidine, rilmenidine: central sympatholytics
Clonidine: 2 agonist
Minoxidil: potassium channel opener

Pharmacology

495

USMLE Case Scenario

A 67-year-old woman from Chicago is brought to the emergency department with complaints of persistent fever, malaise,
and the recent appearance of a malar butterfly rash on the face, as well as numerous oral ulcers. The patient states that she
is taking one medication for treatment of arrhythmias. If the antinuclear antibody test is positive and the patient is mildly
anemic, which of the following medications is she most likely taking?
1. Propafenone
2. Lidocaine
3. Amidarone
4. Mexiletine
5. Procainamide
Ans. 5. Procainamide
The patient is presenting with signs and symptoms of drug-induced lupus. This complication is associated with procainamide
and other agents, including
Hydralazine
Chlorpromazine
Isoniazid
Methyldopa and
Quinidine
Procainamide is a class IA agent, similar in action to quinidine, and is indicated for the treatment of ventricular arrhythmias.

Venodilators
Nitrates
Nitroprusside
ACE inhibitors

Arteriolar Dilators

Calcium channel blockers

Minoxidil
Hydralazine
ACE inhibitors
Nitroprusside
Alpha blockers
Fenoldapam

Phenoxybenzamine
During perioperative period, patients require medications that block the excessive amounts of noradrenaline and adrenaline that
is secreted by the tumor. A medication called Phenoxybenzamine is used to block noradrenaline activity. This medication usually
controls the hypertension and also allows an expansion of the blood volume. In patients with pheochromocytoma the blood
volume is diminished because of the effects of the catecholamines. After some periods of treatment with phenoxybenzamine, a betablocker is added to control the effects of the excessive production of adrenaline from the tumor (p-p)

Hypertension in Pregnancy
Drugs considered safe in pregnancy are:
Hydralazine and Methyldopa
The drug of choice for Hypertension in pregnancy is Methyldopa
The drug of choice for Hypertensive crisis in Pregnancy is Hydralazine

496

USMLE Step 1 Platinum Notes

The drug of choice to control seizures in pregnancy is Magnesium sulfate

ACE inhibitors are absolutely contraindicated in pregnancy.

PROLONGED QT SYNDROME (TORSADES DE POINTS)

Causes
Quinidine
Procanamide
Disopyramide
Terfenadine, Astemizole
Cisapride
Gatifloxacin
Sparfloxacin
Halofantrine
Mefloquine
TCA
Treatment is by: Beta blockers, Magnesium Sulfate.

USMLE Case Scenario

Torsades de pointes maybe caused by which one of the following drugs:
1. Quinidine
2. Digoxin
3. Phenytoin
4. Chlorthiazide
Ans. 1. Quinidine

Antiarrhythmics
Class

Example

Mechanism of action

Ia

Disopyramide, quinidine, procainamide

Block sodium channels

Ib

Lidocaine, phenytoin, mexilitene

Block sodium channels

Ic

Flecainide, encanide, propafenone

Block sodium channels

II

Propranolol, esmolol, sotalol

Beta-adrenoceptor antagonists

III

Amiodarone, bretylium, ibutilide

Block potassium channels

IV

Verapamil, dilatazem

Calcium channel blockers

Lignocaine is one of the most useful drugs for Ventricular arrhythmia

Lignocaine belongs to Class IB Antiarrhythmic
Lignocaine blocks fast Na+ channels
Lignocaine decreases APD (action potential duration)
Used in Arrhythmias due to:
Post MI
Open Heart Surgery
Digoxin Toxicity
Side Effects:
Hypotension
Convulsions
Myocardial depression

Pharmacology

497

Potassium channel blockers used in the treatment of cardiac arrhythmia are classified as class III antiarrhythmic agents.
Pottasium channel blockers are:

Dofetilide
Sotalol
Ibutilide
Azimilide
Bretylium
Clofilium
Nifekalant
Tedisamil
Sematilide

DOC for ventricular arrhythmias

DOC for AF without Heart failure
DOC for Atrial flutter without heart failure
DOC for AF with Heart failure
DOC for Atrial flutter with heart failure
DOC for PSVT
DOC for WPWS
DOC for ventricular ectopics
DOC for sinus bradycardia

Lidocaine
Beta blockers
Beta blockers
Digoxin
Digoxin
Adenosine
Procainamide
Beta blockers
Atropine

USMLE Case Scenario

An elderly 90-year-old man who has been for the past 6 years on some type of antiarrhythmic drug presents with complaints
of ringing in his ears, blurred vision. He is taking multiple medications. He has had three episodes of confused, delirious
behavior over the last few weeks. Drug responsible is:
Quinidine
The symptoms described above, tinnitus, blurred vision, and delirium, are known as cinchonism, a side effect of quinidine
toxicity. EKG changes such as prolongation of the QT and QRS intervals may also occur. Quinidine is an antiarrhythmic used
for the treatment of ventricular arrhythmias and atrial fibrillation.

USMLE Case Scenario

Drug of choice for Supraventricular tachycardia is:
1. Verapamil
2. Diltiazem
3. Digoxin
4. Phenytoin
Ans. 1. Verapamil

Amiodarone: USMLE High Yield Drug

Class III antiarrhythmic
Has class I, II, III, IV properties
Potassium channel blocker
Prevention of atrial and ventricular arrhythmia
Causes:
Pulmonary fibrosis
Hepatitis

498

USMLE Step 1 Platinum Notes

Photodermatitis
Grey blue discoloration of skin
Corneal microdeposits
Bradycardia, heart block
Hypothyroidism/hyperthyroidism

Heart Failure (HF)

The treatment of HF maybe divided into four components:
1. Removal of the precipitating cause
2. Correction of the underlying cause
3. Prevention of deterioration of cardiac function and
4. Control of the congestive HF state

AIMS of CHF treatment

Angiotensin-Converting Enzyme Inhibitors: The administration of ACE inhibitors has been shown to prevent or retard the
development of HF in patients with left ventricular dysfunction without HF, to reduce symptoms, enhance exercise performance, and
to reduce long-term mortality when they are begun in such patients shortly after acute myocardial infarction. These beneficial effects
are related only in part to the salutary hemodynamic effects, i.e. the reduction of preload and afterload. Their major effect appears to
be on inhibition of local (tissue) renin-angiotensin systems.
Lisinopril or enalapril have been shown to be useful in the management of heart failure.
Angiotensin Receptor Blockers: In patients who cannot tolerate ACE inhibitors (because of cough, angioneurotic edema, leukopenia),
an angiotensin II receptor blocker (type AT1) antagonist (e.g. losartan 50 mg qid) maybe used instead.
Aldosterone spironolactone, 25 mg/d reduces total mortality, as well as sudden death and death from pump failure. Since
spironolactone is also a useful diuretic its widespread use in systolic heart failure should be considered.
B-Adrenoceptor Blockers: Administration of gradually escalating doses of metoprolol, carvedilol, and bisoprolol have been
reported to improve the symptoms of HF and to reduce all-cause death, cardiovascular death, sudden death and pump failure death.
In patients with moderately severe HF (classes II and III), their administration of has been shown to be beneficial.

Angioedema Due to Angiotensin Converting Enzyme Inhibitors

USMLE Case Scenario

A 41-year-old female came to the emergency room (ER) with an upper lip swelling which she noted when she woke up in the
morning. She denied shortness of breath, change in her voice or wheezing. She was taking (lisinopril). The episode did not
involve any airway compromise and was treated as an out patient.
THIAZIDE DIURETICS
Thiazide diuretics are effective and useful in the treatment of HF as long as the glomerular filtration rate exceeds approximately 50%
of normal.
FUROSEMIDE DOC in acute failure
Bumetanide, ethacrynic acid, piretanide, and torsemide

Pharmacology

499

These powerful diuretics are useful in all forms of HF, particularly in patients with otherwise refractory HF and pulmonary edema.
ALDOSTERONE ANTAGONISTS
Spironolactone maybe administered
TRIAMTERENE AND AMILORIDE exert renal effects similar to those of the spironolactones

Vasodilators
Direct vasodilators maybe useful in patients with severe, acute HF who demonstrate systemic vasoconstriction despite ACE inhibitor
therapy. The combination of hydralazine (up to 300 mg qd orally) and isosorbide maybe useful for chronic oral administration.
Enhancement of Myocardial Contractility
Digitalis: The improvement of myocardial contractility by means of cardiac glycosides is useful in the control of HF.
Phosphodiesterase, inhibitors: Amrinone and milrinone, are noncatecholamine, nonglycoside agents that exert both positive
inotropic and vasodilator actions by inhibiting a specific phosphodiesterase.
Other Measures
Anticoagulants Patients with severe HF are at increased risk of pulmonary emboli secondary to venous thrombosis and of systemic
emboli secondary to intracardiac thrombi and should be treated with warfarin. Patients with HF and atrial fibrillation, previous venous
thrombosis, and pulmonary or systemic emboli are at especially high-risk and should receive heparin followed by warfarin
Assisted Circulation/Cardiac Transplantation: When patients with HF become unresponsive to a combination of all the
aforementioned therapeutic measures, are in New York Heart Association class IV, and are deemed unlikely to survive 1 year, they
should be considered for temporary assisted circulation and/or cardiac transplantation.

Nesiritide (USMLE Favorite)

Recombinant brain natriuretic peptider BNP
It acts by reducing preload
Has short half-life.
Conivaptan:
V1a and V2 (Vasopressin) receptor Treat (Acute heart failure and Hyponatremia)

Digoxin
Therapeutic level: 05 1.5 ng/ml
Toxic level > 2.4 ng/ml
Increases ventricular contractile force
Excreted by kidneys
Half-life is 40 hours
Inhibits Na/K ATPase
Contraindicated in HOCM
Digoxin Toxicity
Features: Generally unwell, lethargy, N/V, confusion, yellow-green vision, arrhythmias (e.g. AV block, bradycardia)
Precipitating factors
Renal Disease
Classically: Hypokalemia
Myocardial Ischemia
Hypomagnesemia
Hypoalbuminemia
Hypothermia
Hypothyroidism

500

USMLE Step 1 Platinum Notes

Hypercalcemia, hypernatremia
Acidosis
Drugs: amiodarone, quinidine, verapamil, spironolactone (compete for secretion in distal convoluted tubule therefore
reduce excretion)
Management
Digibind
Correct arrhythmia
Phenytoin
Monitor K+

Treatment of Acute Pulmonary Edema

It is life-threatening and must be considered a medical emergency
1. Morphine is administered intravenously repetitively, as needed, in doses from 2 to 5 mg. This drug reduces anxiety, reduces
adrenergic vasoconstrictor stimuli to the arteriolar and venous beds, and thereby helps to break a vicious cycle
2. Naloxone should be available in case respiratory depression occurs
3. Because the alveolar edema interferes with O2 diffusion resulting in arterial hypoxemia, 100% O2 should be administered,
preferably under positive pressure. The latter increases intraalveolar pressure, reduces transudation of fluid from the alveolar
capillaries, and impedes venous return to the thorax, reducing pulmonary capillary pressure
4. The patient should be maintained in the sitting position, with the legs dangling along the side of the bed, if possible, which
tends to reduce venous return
5. Intravenous loop diuretics, such as furosemide (DOC) or ethacrynic acid or bumetanide, will, by rapidly establishing a diuresis,
reduce circulating blood volume and thereby hasten the relief of pulmonary edema. In addition, when given intravenously,
furosemide also exerts a venodilator action, reduces venous return, and thereby improves pulmonary edema even before the
diuresis commences
6. Afterload reduction is achieved with intravenous sodium nitroprusside at 20 to 30 mg/min in patients whose systolic arterial
pressures exceed 100 mm Hg
7. Inotropic support should be provided by dopamine or dobutamine
8. Aminophylline (theophylline ethylenediamine), is effective in diminishing bronchoconstriction, increasing renal blood flow
and sodium excretion, and augmenting myocardial contractility
If the above-mentioned measures are not sufficient, rotating tourniquets should be applied to the extremities
After these emergency measures have been instituted and the precipitating factors treated, the diagnosis of the underlying cardiac
disorder responsible for the pulmonary edema must be established, if it is not already known.

Acute MI
Aspirin: Rapid inhibition of cyclooxygenase in platelets followed by a reduction of thromboxane A2 levels is achieved by buccal
absorption of a chewed 160 to 325 mg tablet in the emergency department. This measure should be followed by daily oral
administration of aspirin in a dose of 160 to 325 mg.
Supplemental oxygen. In patients whose arterial oxygen saturation is normal as estimated by pulse oximetry or measured
by an arterial blood gas specimen, supplemental oxygen is of limited. However, when hypoxemia is present, oxygen should be
administered by nasal prongs or face mask (2 to 4 L/min) for the first 6 to 12 h after infarction; the patient should then be reassessed
to determine if there is a continued need for such treatment.
Morphine is a very effective analgesic for the pain associated with AMI
Before morphine is administered, sublingual nitroglycerin can be given safely to most patients with AMI
Intravenous beta blockers are also useful in the control of the pain of AMI. These drugs control pain effectively in some patients,
presumably by diminishing myocardial oxygen demand and hence ischemia.
Tissue plasminogen activator (tPA), streptokinase, anisoylated plasminogen streptokinase activator complex (APSAC) and
reteplase (rPA) have been approved by the Food and Drug Administration for intravenous use in the setting of AMI. These drugs
all act by promoting the conversion of plasminogen to plasmin, which subsequently lyses fibrin thrombi
The fibrinolytic activity of streptokinase is due to its ability to bind and cleave plasminogen, producing plasmin. Plasmin
directly cleaves fibrin, both between and within the fibrin polymers, thus breaking up thrombi and potentially restoring
blood flow to ischemic cardiac muscle. This same mechanism of fibrinolysis is shared by urokinase and tissue-plasminogen
activator (tPA).

Pharmacology

501

The standard antithrombin agent used in clinical practice is unfractionated heparin (UFH)
An alternative to UFH for anticoagulation of patients with AMI that is being used with increased frequency are the low-molecularweight heparin preparations (LMWHs).
Angiotensin converting enzyme inhibitors: Angiotensin-converting enzyme (ACE) inhibitors reduce the mortality rate after AMI,
and the mortality benefits are additive to those achieved with aspirin and beta blockers
ACE inhibitors should be prescribed within 24 h to all patients with AMI.

Other Drugs Used as Maintenance

Aspirin, Clopidregel or ticlopidine as antiplatelet drugs

Beta blockers
Nicronadil as potassium channel opener:preload
Statins: for lipid lowering
Heparin, warfarin, GP IIa/IIIb inhibitors: as antithrombotic

Nitrates

Release NO
Cause vasodilation
Preload and after load
Myocardial oxygen consumption
Cause reflex tachycardia, hypotension
Long acting nitrates are not used chronically as tolerance develops (due to SH Group)
Amyl nitrite is the shortest acting nitrite
Nitriglycerine is the shortest acting nitrate
Penta erythritol tetra nitrate is longest acting nitrate
Nitrates cause vasodilation, flushing, headache, dizziness, methemoglobunemia
Molisidomine: tolerance does not develop to it.

Hypolipidemic Drugs
Statins (also known as HMG CoA reductase inhibitors). Statins are most effective at lowering the LDL(bad) cholesterol, but also have
modest effects on lowering triglycerides (blood fats) and raising HDL (good) cholesterol.

Statins Currently Used

Atorvastatin
Fluvastatin
Lovastatin
Pravastatin
Rosuvastatin
Simvastatin

LDL receptor levels

cholesterol synthesis
VLDL
HDL

Most effective hypolipidemics

Best tolerated

502

USMLE Step 1 Platinum Notes

Statins have
Antioxidant
Anti-inflammatory and
Anti proliferative properties
Rosuvastatin is longest acting, most potent, greatest HDL

USMLE Case Scenario

A 66-year-old man from Canada after sustaining a myocardial infarction and is admitted to the coronary care unit in New york.
Serum chemistries elevation of his LDL cholesterol. He is prescribed lovastatin by cardiologist, which acts by inhibiting which
enzyme?
Hydroxymethyl glutaryl-CoA reductase (HMG-CoA reductase) catalyzes the rate-limiting step in cholesterol synthesis.
Lovastatin reduces cholesterol synthesis.

Selective Cholesterol Absorption Inhibitors

Are most effective at lowering the LDL (bad) cholesterol, but may also have modest effects on lowering triglycerides (blood fats)
and raising HDL (good) cholesterol
The first medication of this class, ezetimibe.

Resins (Also known as bile acid sequestrant or bile acid-binding drugs)

This class of LDL-lowering drugs works in the intestines by promoting increased disposal of cholesterol
These medicines bind to bile, so it cannot be used during digestion
Resins currently available
Cholestyramine
Colestipol
Colesevelam Hcl

Fibrates (Fibric Acid Derivatives)

Fibrates are best at lowering triglycerides and in some cases increasing HDL (good cholesterol) levels
These drugs are not very effective in lowering LDL (bad) cholesterol
Thats why fibrates are generally used in people whose triglycerides are high or whose HDL is low, after reaching LDL goal. Fibrates
are most effective at lowering triglycerides (blood fats)
Additionally, they act to raise the levels of HDL (good) cholesterol. Fibrates maybe used in combination therapy with the statins
Gemfibrozil
Fenofibrate
Clofibrate

Niacin (Nicotinic acid)

This drug works in the liver by affecting the production of blood fats
Lower triglycerides and LDL cholesterol and raise HDL (good) cholesterol
Niacin side effects may include flushing, itching and stomach upset
Liver functions maybe closely monitored, as niacin can cause toxicity
Niacin is used cautiously in diabetic patients as it can raise blood sugar levels
Remember:
Niacin is vitamin B3
NAD and NADP are its active forms
Deficiency of niacin causes pellagra
Deficiency occurs in: Maize eaters, Carcinoid syndrome, Hartnups disease

Pharmacology

503

USMLE Case Scenario

An antilipidemic drug causing LDL reduction and HDL level elevation and generalized flushing with a sensation of warmth
is most likely:
Niacin
Drugs
Statins (HMG CoA reductase inhibitors)
Ezetimibe
Nicotinic acid
Fibrates
Anion-exchange resins

Adverse Effects
Myositis, deranged LFTs
Headache
Flushing, myositis
Myositis, pruritus cholestasis
GI side-effects

Drugs Acting on Blood

Acetylsalicylic acid acts as a platelet aggregation inhibitor by decreasing thromboxane A2 production, which under normal
circumstances causes platelet aggregation
Dipyridamole is also a platelet aggregation inhibitor that increases cAMP levels by inhibiting cyclic nucleotide phosphodiesterase
Warfarin inhibit epoxide reductase. Clotting factors II, VII, IX, and X and proteins C and S are all dependent on vitamin K, which
acts as a cofactor for carboxylation reactions
Heparin acts by potentiating the activity of antithrombin III, which is a suicide inhibitor of thrombin an factors IXa, Xa, XIa, and
XIIa
Streptokinase is a protein produced by and beta;-hemolytic streptococci that converts plasminogen to plasmin, which is
involved in digesting fibrin clots
tPA is also a thrombolytic agent used intravenously. Its mechanism of action is similar to that of streptokinase. tPA has the
advantage of not being rapidly inactivated by antibodies from a previous streptococcal infection (as streptokinase can be) because
it is a recombinant human enzyme.

Heparin
Heparin is a polysaccharide
Heparin causes alopecia
Heparin causes heparin induced thrombocytopenia HIT
Heparin causes osteoporosis
Heparin causes hyperkalemia
Heparin does not cross placenta
Protamine sulfate is used in heparin overdose
Anticoagulant of choice in HIT (heparin induced thrombocytopenia) is Argatroban
Replace warfarin by heparin prior to conception and through first trimester (organogenesis)
After is trimester replace heparin by warfarin (heparin causes osteoporosis)
Near term replace warfarin by heparin
Heparin is anticoagulant of choice in pregnancy
LMW heparins (enoxaparin, reviparin, nadroparin, ardeparin) inhibit factor Xa
LMW heparins act by inducing conformational change in AT III
LMW heparins have slight antiplatelet effect.

Warfarin

Oral anticoagulant
Causes inhibition of vitamin K dependent clotting factors. (II, VII, IX, X)
Warfarin induced skin necrosis is because of protein c deficiency
It is a racemic mixture
Monitoring is done by INR monitoring
Warfarin crosses placenta
Warfarin causes fetal warfarin syndrome
In liver diseases dose of warfarin needs to be decreased.

504

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 85-year-old woman had a mitral valve replacement in New York, and was placed on anticoagulants and prophylactic
antibiotics following her surgery. A week after her surgery, she developed a sharply demarcated, erythematous rash on her
thigh
Three days after the rash appeared, large hemorrhagic bullae began to form in the area of the rash. Drug implicated is: warfarin
The rash by warfarin resolve or progress to large, irregular, hemorrhagic bullae that can eventually lead to necrosis. The mechanism
for this reaction is related to warfarins ability to deplete protein C, which can lead to a state of hypercoagulability and thrombosis in
the cutaneous microvasculature.
Warfarin is an anticoagulant used for the prophylaxis and treatment of thromboembolic complications associated with cardiac
valve replacement and atrial fibrillation, as well as the prophylaxis and treatment of venous thrombosis and pulmonary embolism
Warfarin may cause necrosis of the skin (typically on the breasts, thighs, and buttocks) generally between the third and
tenth days of therapy
The lesions are initially sharply demarcated, erythematous, and purpuric
They may resolve or progress to large, irregular, hemorrhagic bullae that can eventually lead to necrosis. The mechanism for this
reaction is related to warfarins ability to deplete protein C, which can lead to a state of hypercoagulability and thrombosis in the
cutaneous microvasculature.

Drugs used for ITP Are

Platelet infusion maybe administered in an emergency bleeding situation in order to attempt to quickly raise the count
Removal of the spleen is sometimes undertaken, as platelets targeted for destruction will often meet their fate in the spleen.
Splenectomy is said to be successful in 60 to 65 percent of cases, less so in older patients
Romiplostim is a new treatment for stimulating platelet production. It is a thrombopoiesis stimulating Fc-peptide fusion
protein (peptibody) that is administered by subcutaneous injection
Eltrombopag is an orally-administered agent with an effect similar to that of romiplostim. It has been demonstrated to increase
platelet counts and decrease bleeding in a dose-dependent manner
Dapsone has also proved helpful as a second-line treatment for ITP
Rituximab, a chimeric monoclonal antibody against the B cell surface antigen CD20, has been shown in preliminary studies to
be an effective alternative to splenectomy in some patients
Promising results have been reported in a small phase II study of the experimental kinase inhibitor Tamatinib (R788).

Common Anticoagulants

Aspirin
Clopidogrel, ticlopidine
GP IIb, IIIa inhibitors: abciximab, eptifibatide, tirofiban
LMW Heparin: enoxaparin, dalteperin
Direct thrombin inhibitors: lepirudin, argatroban, bivaluridin, ximelagatran, melagartan
Factor X A inhibitor: Fondaparinux

Factors effecting platelet functions

Pharmacology

505

NEWER FIBRINOLYTICS: RETEPLASE, TENECTEPLASE

Treatment of Hypercalcemia
Treatment

Advantages

Hydration with saline

Forced diuresis; saline plus loop diuretic

Rehydration invariably needed

Rapid action

Bisphosphonates
1st generation: Etidronate

First available bisphosphonate; intermediate onset of action

2nd generation: Pamidronate

High potency; intermediate onset of action

Calcitonin

Rapid onset of action; useful as adjunct in severe hypercalcemia

Phosphate
Oral

Chronic management (with hypophosphatemia

Intravenous

Rapid action, highly potent but rarely used except with severe hypercalcemia
and cardiac and renal decompensation present

Glucocorticoids

Oral therapy, antitumor agent

Dialysis

Useful in renal failure; onset of effect in hours; can immediately reverse lifethreatening hypercalcemia

SERMs: (USMLE Favorite)

1. Raloxifene Hcl: A potent estrogen agonist in bone. It is approved for the prevention and treatment of osteoporosis in
postmenopausal women
2. Ormeloxifene: A potent estrogen antagonist on uterus as well as breast tissue. It is approved for the prevention and treatment of
dysfunctional uterine bleeding (DUB) in women
3. Tamoxifen Exhibits anti-estrogenic activity (on uterus and breast tissue), estrogenic activity in bone, liver and the endometrium
tissue. It is approved for the treatment and prevention of metastatic breast cancer
4. Toremifene is chemically related to Tamoxifen, and is approved for the treatment of metastatic breast cancer in postmenopausal
women
Unlike, Hormone Replacement Therapy (HRT), SERMs do not produce:
Endometrial Cancer
Breast Cancer
Uterine Cancer
Gallbladder Disease
Blood Clots/Hypertension
Undiagnosed Vaginal Bleeding

Bisphosphonates
1.
2.
3.
4.
5.
6.

Are concentrated in areas of high bone turnover and are taken up by and inhibit osteoclast action; the mechanism of action is
complex
Alter osteoclast proton pump function or impair the release of acid hydrolases into the extracellular lysosomes contiguous with
mineralized bone
Pamidronate, is a potent inhibitor of osteoclast-mediated skeletal resorption
Several additional bisphosphonates (alendronate, tiludronate, and risedronate)
Overall, second-generation bisphosphonates are now the agents of choice in severe hypercalcemia, particularly that
associated with malignancy
Zoledronate, a third-generation bisphosphonate.

Plicamycin (mithramycin), which inhibits bone resorption, has been a useful therapeutic agent but is now little used because
of the effectiveness of bisphosphonates. Plicamycin must be given intravenously, either as a bolus injection or by slow infusion.
Gallium nitrate exerts a hypocalcemic action by inhibiting bone resorption and altering the structure of bone crystals.

506

USMLE Step 1 Platinum Notes

DRUGS AND ARTHRITIS

Rhematoid Arthritis
First line Aspirin and NSAIDS are used.
Second line involves use of low dose glucocorticoids
Third line involves use of DMARDS (Disease modifying Antirheumatic drugs)
Methotrexate
Gold Compounds, (Stomatitis, dermatitis, metallic taste)
Pencillamine
Hydroxychloroquine and
Sulfasalazine
Fourth line is use of TNF alpha blockers. (Infliximab and Etarnacept)
Fifth line is use of Immunosupressants and Cytotoxic drugs
The immunosuppressive drugs
Azathioprine
Leflunomide
Cyclosporine
Cyclophosphamide

Anti TNF alpha drugs are used in treatment of: (USMLE Favorite)

Crohns disease
Rheumatoid arthritis
Juvenile rheumatoid arthritis
Psoriasis

Infliximab:
Chimeric Monoclonal antibody
Given IV
Etarnacept:
Recombinant fusion protein binding TNF
Administered SC
Anakinra:
IL1 receptor antagonist
Adminstered SC
Abatacept:
Fusion protein of CTLA4 and Fc PART of IgG
Inhibits T cell activation

GOUT: (USMLE Favorite)

Allopurinol is not given in acute gout
Drugs in acute gout: NSAIDS, colchicine, corticosteroids
Uric acid synthesis inhibitors: allopurinol
Uricosuric drugs: probencid, sulfinpyrazone
Newer drugs: Pegylated uricase
Xanthine oxidase inhibitor: Febuxostat

Pharmacology

507

Allopurinol
Decreases the production of uric acid by inhibiting the action of xanthine oxidase
Decreases uric acid concentrations in both serum and urine
By lowering both serum and urine concentrations of uric acid below its solubility limits, allopurinol prevents or decreases urate
deposition, thereby preventing the occurrence or progression of both gouty arthritis and urate nephropathy
Decreases tophi formation and chronic joint changes
Promotes resolution of existing urate crystals and deposits, and after several months of therapy, reduce the frequency of acute
gout attacks
Allopurinol inhibits hepatic microsomal enzyme activity
DOC in chronic gout
USED In Lesch Nyhan syndrome
Used in urate nephropathy
NSAIDs
Are affective in about 90% of patients, and the resolution of signs and symptoms usually occurs in 5 to 7 days. The most effective
drugs are indomethacin, ibuprofen, diclofenac.
Glucocorticoids
Such as prednisone, a single intravenous dose of methylprednisolone, betamethasone, triamcinolone acetonide have been equally
effective
ACTH as an intramuscular injection is effective in patients with acute polyarticular refractory gout or with a contraindication for
using colchicine or NSAIDs.

Colchicine
Colchicine inhibits microtubule polymerization and stabilizes tubulins in microtubules
Neither analgesic nor anti-inflammatory
Colchicine stimulates the Depolymerization of microfilaments and not polymerization
Availability of tubulin is essential to mitosis, and therefore colchicine effectively functions as a mitotic poison or spindle poison.
(metaphase arrestor)
Colchicine also inhibits neutrophil motility and activity, leading to a net anti-inflammatory effect
Colchicine can act as a cardiac glycoside
Colchicine also inhibits uric acid (urate) crystal deposition, which is enhanced by a low pH in the tissues, probably by inhibiting
oxidation of glucose and subsequent lactic acid production in leukocytes. The inhibition of uric acid crystals is a vital aspect on the
mechanism of gout treatment.

Mc side effect is diarrhea (bloody)

Causes aplastic anemia, agranulocytosis, myopathy
Hair loss
Colchicine as Medicine
It is prescribed for the treatment of gout and also for familial Mediterranean fever, secondary amyloidosis (AA), and
scleroderma
It is also used as an anti-inflammatory agent for long-term treatment of Behets disease
A combination therapy to treat constipation-predominant irritable bowel syndrome which combines colchicine with the antiinflammatory drug olsalazine
Now a developing a prodrug of colchicine, ZD6126 (also known as ANG453) as a treatment for cancer
Colchicine has a relatively low therapeutic index.

USMLE Case Scenario

A medical physician gives an antigout drug to a patient which is indicated for the treatment of chronic gout and which
functions by Inhibiting the enzyme xanthine oxidase and lowers both serum and urinary concentrations of uric acid. The drug
most likely is:
Ans. Allopurinol

508

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 66-year-old alcoholic businessman complains of 2 days of sudden, severe worsening pain with redness and swelling of his
first metatarsophalangeal joint. Drug likely be prescribed for this patient.
Ans. Colchicine

USMLE Case Scenario

A Physician decides to use an antigout agent prophylactically to reduce the severity of hyperuricemia associated with both
antineoplastic and radiation therapy. The drug most likely is:
Ans. Allopurinol

USMLE Case Scenario

A 55-year-old patient has gout, which is due to precipitation of monosodium urate crystals in joint spaces and tophi on the right
external ears. A drug is given which reduces the inflammation caused by the urate crystals by inhibiting leukocyte migration and
phagocytosis secondary to an effect on microtubule assembly. Drug with such mechanism of action is:
Ans. Colchicine

CLASSES OF ANTIDEPRESSANTS
List of TCAS
Amitriptyline
Amoxapine
Clomipramine
Desipramine
Doxepin

Tetracyclic Antidepressants (Second Generation)

Lofepramine
Maprotiline
Mianserin

SSRIS are
Fluoxetine
Fluoxamine
Paroxitene
Sertaline
Citalopram
Tricyclic overdose
Early features relate to anticholinergic properties: dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision
Features of severe poisoning include:
Arrhythmias
Seizures
Metabolic acidosis
Coma

Pharmacology

509

ECG changes include:

Sinus tachycardia
Widening of QRS
Prolongation of QT interval
Widening of QRS > 100 ms is associated with an increased risk of seizures whilst QRS > 160 ms is associated with ventricular
arrhythmias.
Management
IV bicarbonate may reduce the risk of seizures and arrhythmias in severe toxicity
Arrhythmias: Class 1a, (e.g. quinidine) and class Ic antiarrhythmics (e.g. flecainide) are contraindicated as they prolong depolarization.
Class III drugs such as amiodarone should also be avoided as they prolong the QT interval. Response to lignocaine is variable and it
should be emphasized that correction of acidosis is the first line in management of tricyclic induced arrhythmias
Dialysis is ineffective in removing tricyclics.

USMLE Case Scenario

A 55-year-old woman has a significant history of asymptomatic ventricular couplets had been placed on quinidine. She
experiences a syncopal episode and is brought to the emergency department. She is placed on a cardiac monitor and is noted
to have a transient wide complex tachycardia with waves of alternating morphology. She appears to be in torsades de pointes.
Which of the following is the most appropriate next step?
1. Check the sodium level
2. Discontinue quinidine
3. Increase the quinidine dose
4. Administer IV potassium
Ans. 2. Discontinue quinidine
This is a case of polymorphic ventricular tachycardia called torsades de pointes associated with a prolongation of the QT
interval, which could have occurred as a result of the quinidine administration. Thus, the appropriate step is to discontinue the
quinidine and observe.

Typical Antipsychotics: (USMLE Favorite)

Low-potency
Chlorpromazine
Thioridazine
Mid-potency
Trifluoperazine
Perphenazine
High potency
Haloperidol
Fluphenazine
Thiothixene
Novel antipsychotics
Clozapine
Risperidone
Olanzapine
Quetiapine
A serious side effect of long-term use of the classic antipsychotic agents is tardive dyskinesia, characterized by repetitive,
involuntary, and potentially irreversible movements of the tongue and lips (bucco-linguo-masticatory triad) and, in
approximately half of cases, choreoathetoid movements of the limbs.
Antipsychotic agents remain the cornerstone of acute and maintenance treatment of schizophrenia and are effective in the
treatment of hallucinations, delusions, and thought disorders, regardless of etiology.

510

USMLE Step 1 Platinum Notes

Older agents, such as chlorpromazine and thioridazine, are more sedating and anticholinergic and more likely to cause
orthostatic hypotension, while higher potency antipsychotics, such as haloperidol, perphenazine and thiothixene, carry a
higher risk of inducing extrapyramidal side effects.
Long-acting injectable preparations (haloperidol decanoate and fluphenazine decanoate) are considered when noncompliance
with oral therapy leads to relapses.
In treatment-resistant patients, a transition to clozapine usually results in rapid improvement, but a prolonged delay in response in
some cases necessitates a 6-to 9-month trial for maximal benefit to occur.
Antipsychotic medications can cause a broad range of side effects, including lethargy, weight gain, postural hypotension,
constipation, and dry mouth.
Rabbit syndrome: Late onset, drug induced extrapyramidal symptoms is seen.
Extrapyramidal symptoms such as dystonia, akathisia, and akinesia are also frequent with traditional agents and may contribute
to poor compliance if not specifically addressed.
Akathisia is restlessness may respond to beta blockers. (Propranolol) Haloperidol especially causes Akathisia.
In rare cases, more serious and occasionally life-threatening side effects may emerge, including ventricular arrhythmias,
gastrointestinal obstruction, retinal pigmentation, obstructive jaundice, and neuroleptic malignant syndrome (characterized by
hyperthermia, autonomic dysfunction, muscular rigidity, and elevated creatine phosphokinase levels).
The most serious adverse effects of clozapine are agranulocytosis, which has an incidence of 1%, and induction of seizures, which
has an incidence of 10%. Weekly white blood cell counts are required, particularly during the first 3 months of treatment
Extrapyramidal side effects are rare with Clozapine.
Acute dystonia occurs

Hours

After RX

Akathisia occurs

Days

After RX

Tardive dyskinesia occurs

Years

After RX

Side effects and timing

Extrapyramidal Side-Effects
1.
2.
3.
4.

Parkinsonism (Responds to Leva dopa)

Acute dystonia (e.g. torticollis, oculogyric crisis)
Akathisia (severe restlessness)
Tardive dyskinesia (late onset of choreathetoid movements, abnormal, involuntary, may occur in 40% of patients, maybe
irreversible, most common is chewing and pouting of jaw)

Antiparkinsonism Drugs

Selegeline: MAO B inhibitor

Dopamine Agonists: Bromocriptine, Lysuride, Pergolide, Pramipexole, Ropinirole, Rotigotine
Levadopa and Dopa Decarboxylase inhibitors
Antiviral: Amantidine
COMT (Cathecol O Methyl Transferase) Inhibitors: Tolcapone and Entacapone

THE ANTICHOLINERGICS/ANTIMUSCARINICS ARE USED IN PARKINSONISM

Useful in drug induced parkinsonism are:
Benzhexol
Orphenadrine
Benztropine
Procyclidine
Biperiden

Pharmacology

511

They provide moderate improvements in tremor, rigidity, sialorrhea, muscular stiffness and cramps
They are more effective as IM/IV in drug induced dystonias
Side effects include
Dry mouth, blurred vision, constipation, urinary retention, glaucoma, hallucinations, memory deficits.

Antiepileptics and Mechanism of Action

Barbiturates

Acts on GABA:BZD receptor Cl channel complex

Benzodiazepine

GABA facilitatory

Carbamazepine

Blocks Na+ channel

Ethosuximide

Blocks Ca+ mediated T current

Valproic acid

GABAergic action, by inhibiting GABA transaminase

Blocks Na+ channels (phenytoin like)
Blocks Ca + mediated T current (ethosuximide like)

GABA metabolism
Lacosamide: Amino acid related peptide used in pain syndromes and partial seizures
Inactivation of voltage gated sodium channels
Binds to collapsing response mediator protein CRMP 2
Zonisamide, Rufinamide inactivate sodium plus calcium channels
Inhibition of Na+dependent action potentials in a frequency-dependent manner (e.g. phenytoin, carbamazepine,
topiramate, zonisamide)
Decrease of glutamate release (lamotrigine)
Potentiation of GABA receptor function (benzodiazepines and barbiturates)
Increase in the availability of GABA (valproic acid, gabapentin, tiagabine)
The two most effective drugs for absence seizures, ethosuximide and valproic acid, probably act by inhibiting T-type Ca2+ channels in
thalamic neurons.
Inducers of cytochrome P450: Carbamazepine, phenytoin
Teratogenic: valproate, phenytoin, carbamazepine
Steven johnsons syndrome: phenytoin, lamotrigine, ethoxysuccimide, carbamezapine

USMLE Case Scenario

A 33-year-old woman with a history of tonic-clonic seizures complains of double vision, thickened gums, and growth of facial
hair since starting a new medication. Anticonvulsant medication most likely responsible for her symptom is:
Phenytoin

512

USMLE Step 1 Platinum Notes

USMLE Case Scenario

An antiepileptic drug is found to cause ataxia, enzyme induction, and neural tube defects. It has also been found to be useful
in treating tic douloureux. Drug most likely mentioned is:
Carbamazepine

USMLE Case Scenario

A 15-year-old boy with epilepsy on treatment with combination of valproate and phenytoin has good control of seizures. Levels of
both drugs are in the therapeutic range. Adverse effects which cannot be attributed to valproate is:
1. Weight gain of 5 kg
2. Serum alanine aminotransaminase 150 IU/L
3. Rise in serum ammonia level by 20 g/dL
4. Lymphadenopathy
Ans. 4. Lymphadenopathy

Side Effects of Phenytoin

Hypertrophy of gums
Hirusitism
Hypersensitivity
Hyperglycemia
Hydantoin syndrome
Cerebellar atrophy
Megaloblastic anemia
Osteomalacia
Ophthalmoplegia
Lymphoma
Hepatocellular damage
Phenytoin follows saturation kinetics
Depresses CNS

Carbamazepine is also used for

Grand mal epilepsy
Manic Depressive Pshycosis
Trigeminal neuralgia
Atypical pain syndromes
Epilepsy: Carbamazepine is indicated for the treatment of partial seizures with simple or complex symptomatology
(psychomotor, temporal lobe), generalized tonic-clonic seizures (grand mal); mixed seizure patterns that include the
above; or other partial or generalized seizures not absence seizures.
Carbamazepine is a first-choice anticonvulsant because of its relatively low behavioral and psychological toxicity and the rarity
of serious adverse effects.
Carbamazepine is indicated for relief of pain due to true trigeminal neuralgia (tic douloureux) and glossopharyngeal
neuralgia.
Carbamazepine is used alone or in combination with lithium and/or antidepressants or antipsychotic agents to treat patients with
manic-depressive illness who are unresponsive to, or cannot tolerate, lithium or neuroleptics alone.
Carbamazepine may also be used in some patients to relieve the lightning pains of tabes dorsalis; neuralgic pain associated
with multiple sclerosis, acute idiopathic neuritis (Guillain-Barre syndrome), peripheral diabetic neuropathy, phantom
limb, restless leg syndrome (Ekboms syndrome) and hemifacial spasm; post-traumatic neuropathy or neuralgia; and
postherpetic neuralgia.

Pharmacology

513

Carbamazepine is used alone or with other agents such as clofibrate or chlorpropamide in the treatment of partial central
diabetes insipidus.
Carbamazepine is used for the detoxification of alcoholics. It has been found to be effective in rapidly relieving anxiety and
distress of acute alcohol withdrawal and for such symptoms as seizures, hyperexcitability and sleep disturbances.
Carbamazepine has been shown to be effective in certain psychiatric disorders including schizoaffective illness, resistant
schizophrenia, and dyscontrol syndrome associated with limbic system dysfunction.

Side Effects of Carbamazepine

CNS depression
Osteomalacia
Megaloblastic anemia
Aplastic anemia
Exfoliative dermatitis
Increased ADH secretion. Hyponatremia
Teratogenecity (Spina Bifida, cleft lip and cleft palate)

Topiramate
Topiramate is used to treat epilepsy in both children and adults
Topiramate can also be used as an antidepressant. In children it is also indicated for treatment of Lennox-Gastaut syndrome
Topiramate is now frequently prescribed for, the prevention of migraines. It has been used by psychiatrists to treat bipolar
disorder
Chemically, topiramate is a sulfamate-substituted monosaccharide, related to fructose, a rather unusual chemical structure for an
anticonvulsant
Topiramate enhances GABA-activated chloride channels
In addition, topiramate inhibits excitatory neurotransmission, through actions on kainate and AMPA receptors
It is also an inhibitor of carbonic anhydrase, particularly subtypes II and IV, but this action is weak and unlikely to be related to
its anticonvulsant actions, but may account for the bad taste and the development of renal stones seen during treatment
As topiramate inhibits carbonic anhydrase, the concomitant use of other inhibitors of carbonic anhydrase (e.g. acetazolamide) may
lead to an increased risk of renal stones
Acute myopia and secondary angle closure glaucoma, in a small subset of patients who take topiramate regularly, may cause
transient (reversible), or permanent, loss of vision
Another serious side-effect is the development of osteoporosis in adults and children (bones affected break more easily) and
rickets (abnormal, deformed growth of bones) in children
In other postmarketing research, a risk of decreased sweating and hyperthermia was noticed.

DOC for Epiplepsy (USMLE Favorite)

Doc for generalized tonic lonic seizures: Valproic acid**
Doc for absence seizures: Ethoxsuccimide, valproic acid*
Doc for atonic seizures: Valproic acid**
Doc for myoclonic epilepsy: Valproic acid*
Doc for partial seizures: Carbamazepine*
Doc for status epilepticus: IV lorazepam**
Doc for febrile seizures: Rectal diazepam*
Doc for eclampsia: Magnesium sulfate*
Doc for infantile spasms: Vigabatrin/ethox succimide**

514

USMLE Step 1 Platinum Notes

Drugs and GABA

USMLE Case Scenario

A mother complains to her pediatrician that both she and her five-year-old sons teacher have noticed that the child has
become inattentive. She states that her son frequently stops what he is doing and stares blankly into space before resuming
his activities. Electroencephalography reveals a 3/second spike and slow wave pattern of discharges. Which of the following
agents would most effectively treat this childs disorder?
1. Carbamazepine
2. Diazepam
3. Ethosuximide
4. Lamotrigine
5. Methylphenidate
6. Felbemate
7. Phenytoin
Ans. 3. Ethosuximide
The child is suffering from absence (petit mal) seizures. Ethosuximide is indicated for this type

PDE Inhibitors: (Phospho Diesterase Inhibitors)

PDE1 selective inhibitors
Vinpocetine
PDE2 selective inhibitors
EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine)
Anagrelide
PDE3 Selective inhibitors
Enoximone and milrinone, used clinically for short-term treatment of cardiac failure. These drugs mimic sympathetic stimulation
and increase cardiac output
PDE4 Selective inhibitors
Mesembrine, an alkaloid from the herb Sceletium tortuosum
Rolipram, used as investigative tool in pharmacological research
Ibudilast, a neuroprotective and bronchodilator drug used mainly in the treatment of asthma and stroke. It inhibits PDE4 to the
greatest extent, but also shows significant inhibition of other PDE subtypes, and so acts as a selective PDE4 inhibitor or a nonselective phosphodiesterase inhibitor depending on the dose
Pentoxifylline, a drug that potentially enhances circulation and may have applicability in treatment of diabetes, fibrotic disorders,
peripheral nerve damage, and microvascular injuries
PDE5 Selective Inhibitors
Sildenafil, tadalafil and vardenafil, udenafil and avanafil selectively inhibit PDE5, which is cGMP-specific and responsible for
the degradation of cGMP in the corpus cavernosum. These phosphodiesterase inhibitors are used primarily as remedies for erectile
dysfunction, as well as having some other medical applications such as treatment of pulmonary hypertension
Dipyridamole also inhibits PDE5.

Other Drugs Used In Erectile Dysfunction: (ED)

Alprastadil: (PGE1) analogue. Directly injected into corpora cavernosa, powerful vasodilator
Papaverine: Nonspecific PDE inhibitor

Pharmacology
Androgens: Only used in case of associated androgen deficiency
Apomorphine: Sometimes given for ED

Drugs Causing Hyperuricemia

Pyrazinamide
Ethambutol
Cyclosporine
Alcohol
Levodopa
Low dose aspirin
Chlorthalidone
Nicotinic acid

Drugs Causing Extrapyramidal Side Effects

Haloperidol
Levodopa
Methyldopa
Metoclopramide
OCP
Phenothiazines
TCA

ONCOLOGY
Anticancer drugs acting in which phase of cell cycle

M phase: Vinblastine, vincristine, paclitaxel

G0 phase: Alkylating agents, doxarubicin, daunorubicin, nitrosoureas, cisplatin
S phase: Cytarabine, 6 MP, Methotrexate, Hydroxyurea, Etoposide
G2 phase: Bleomycin

Cell cycle and anticancer drugs

515

516

USMLE Step 1 Platinum Notes

Direct DNA-Interactive Agents (USMLE Favorite)

Formation of covalent DNA adducts occurs
Alkylating agents as a class breakdown, either spontaneously or after normal organ or tumor cell metabolism, to reactive intermediates
that covalently modify bases in DNA
This leads to cross-linkage of DNA strands or the appearance of breaks in DNA as a result of repair efforts. Broken or cross-linked DNA
is intrinsically unable to complete normal replication or cell division.

Nitrogen mustard (Mechlorethamine)

Cyclophosphamide
Ifosfamide
Chlorambucil
Nitrosoureas
Melphalan
Streptozotocin
Lomustine, carmustine, semustine
Procarbazine, altretamine
Dacarbazine
Cisplatin, carboplatin, oxaliplatin, nedaplatin

Antitumor Antibiotics and Topoisomerase Poisons

Doxorubicin
Daunorubicin
Idarubicin
Bleomycin
D-Actinomycin
Mitomycin C
Mitoxantrone
Etoposide
Camptothecin

Indirect Effectors of DNA Function: Antimetabolites

Methotrexate
5-Fluorouracil (5FU) excreted by lungs
Cytosine arabinoside (ara-C)
Gemcitabine
Fludarabine
2-Chlorodeoxyadenosine
Hydroxyurea
Purine antagonists: Mercaptopurine, azathioprine, thioguanine, fludarabine, cladarabine
Pyrimidine antagonists: 5 FU, cytosine arabinoside, gemicatibine, capecatabine
Folate antagonist: Methotrexate, premetraxate.

Mitotic Spindle Inhibitors

Microtubules are cellular structures that form the mitotic spindle and in interphase cells are responsible for the cellular
scaffolding along which various motile and secretory processes occur.

Vincristine
Vinblastine
Paclitaxel and Docetaxel
Estramustine

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517

Hormonal Agents

Glucocorticoids
Progestational agents including medroxyprogesterone acetate, androgens
Diethylstilbesterol (DES)
Aminoglutethimide or ketoconazole
Retinoids, including tretinoin

Topoisomerase and drugs

Specific Toxicities
Chronic lymphocytic leukemia (CLL) typically presents with a complaint of chronic fatigue and/or lymphadenopathy. It is primarily
used to treat chronic lymphocytic leukemia and ovarian carcinoma.

A Nitrogen Mustard

Cyclophosphamide:
Ifosfamide:
Cisplatin:
Busulfan:
Procarbazine:
Cytarabine:
5 FU:
Methotrexate, 6 MP:
Gemcitabine:

Hemorrhagic cystitis
Hemorrhagic cystitis
Nephrotoxicity, ototoxicity, vomiting (most emetogenic), peripheral neuropathy
Pulmonary fibrosis, adrenal insufficiency, hyperpigmentation
Disulfuram like reaction, secondary leukemia
Cerebellar toxicity
Nausea, vomiting, stomatitis, Diarrhea, hand foot syndrome
Hepatotoxicity
Diarrhea.

Remember
ATRA (All Trans retinoic acid) is used in APML. (ACUTE PROMYELOCYTIC LEUKEMIA)
Virinostat (histone deacylase inhibitor) is used in cutaneous T cell lymphoma
Boartezomib (proteosome inhibitor) is used in multiple myeloma

Vinca Alkaloids (Vincristine)

Vincristine is a vinca alkaloid from the Catharanthus roseus (Madagascar periwinkle)
It is a mitotic inhibitor, and is used in cancer chemotherapy
Vincristine binds to tubulin dimers, inhibiting assembly of microtubule structures. Disruption of the microtubules arrests mitosis
in metaphase.
The vinca alkaloids therefore affect all rapidly dividing cell types including cancer cells, but also intestinal epithelium and bone
marrow.
Vincristine is delivered via intravenous infusion for use in various types of chemotherapy regimens.
Its main uses are in non-Hodgkins lymphoma as part of the chemotherapy regimen CHOP, Hodgkins lymphoma as part
of MOPP, COPP, BEACOPP, or the less popular Stanford V chemotherapy regimen, in acute lymphoblastic leukemia, and in
treatment for nephroblastoma (Wilms tumor, a kidney tumor common in children).

518

USMLE Step 1 Platinum Notes

The main side-effects of vincristine are peripheral neuropathy, hyponatremia, constipation and hair loss.
Peripheral neuropathy can be severe, and hence a reason to avoid, reduce, or stop the use of vincristine. One of the first symptoms
of peripheral neuropathy is foot drop.
Accidental injection of vinca alkaloids into the spinal canal (intrathecal administration) is highly dangerous, with a mortality rate
approaching 100%.

Paclitaxel
Paclitaxel belongs to the class of medications known as antimicrotubule agents
It promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization.
Paclitaxel is indicated as first-line and subsequent therapy for treatment of advanced ovarian carcinoma. When used as firstline therapy, paclitaxel is indicated in combination with cisplatin.
Paclitaxel is indicated for the adjuvant treatment of node-positive breast cancer when administered sequentially to standard
doxorubicin-containing combination chemotherapy.
Paclitaxel is indicated as first line therapy, as a single agent or in combination with other chemotherapeutic agents, for treatment
of metastatic breast carcinoma.
Paclitaxel is also indicated for treatment of metastatic breast carcinoma after failure of combination chemotherapy or at
relapse within 6 months of adjuvant chemotherapy.
Aldesleukin: It is recombinant IL-2 used in treatment of metastatic renal cell cancer and melanoma. It is implicated in causation
of capillary leak syndrome.
Bendamustine: A purine alkylator used in treatment of CLL and relapsed indolent Non Hodgkins lymphoma.
Ixabepilone: Indicated for treatment of patients of breast cancer
Stabilizes microtubules.
Plerixafor: It is a CXCR4 chemokine receptor antagonist used in autologous transplantation in patients with NHL and Multiple
myeloma.
Temozolomide:
Oral alkylating agent
Derivative of Dacarbazine
Treatment of Brain Tumor and Metastatic Melanoma

Immunosuprressants

Cyclosporine
Sirolimus
Azathioprine
Mycophenolic acid (PRODRUG)
Tacrolimus
Thalidomide
Muromonab CD 3
Antithymocyte globulin
Hydroxychloroquine

Cyclosporin: (USMLE Favorite)

Cyclosporin is an immunosuppressant which decreases clonal proliferation of T cells by reducing IL-2 release
It acts by binding to cyclophilin forming a complex which inhibits calcineurin, a phosphotase that activates various transcription
factors in T cells
Acts on CD 4 +T cells.

Pharmacology

519

Adverse effects of cyclosporine:

Nephrotoxicity
Hepatotoxicity
Fluid retention not Dehydration
Hypertension
Hyperkalemia not Hypokalemia
Hypertrichosis not Alopecia
Hyperplasia of gum
Tremor

Indications

Crohns disease
Rheumatoid arthritis
Psoriasis (has a direct effect on keratinocytes as well as modulating T cell function)
The primary mode of action of orilistat is to inhibit pancreatic lipases, which in turn will decrease the absorption of lipids from
the intestine.

Tacrolimus

Inhibits IL-2 like cyclosporine

Acts on T cells mainly
FK 506 is Tacrolimus
Used in organ transplantation
It is a Macrolide antibiotic
Glucose intolerance is a significant side effect
Nephrotoxicity is a well established feature.

USMLE Case Scenario

A 55-year-old male patient is being treated for non-Hodgkins lymphoma with a nitrogen mustard-type antineoplastic agent
suddenly develops dysuria and frequency.

Cyclophosphamide
The patient is presenting with signs and symptoms of hemorrhagic cystitis. This condition is characterized by a sudden onset
of dysuria and frequency in the absence of bacteriuria. This disorder is most often seen in patients taking ifosfamide and
cyclophosphamide, both of which are nitrogen mustards
Hemorrhagic cystitis can be prevented in patients taking ifosfamide and cyclophosphamide by administering mesna. Mesna
reacts chemically with the urotoxic metabolites produced when both agents are metabolized. Mesna is not effective for prophylaxis
of other types of hemorrhagic cystitis.
It is metabolized to acrolein, which is excreted in the urine. If the patients urine is concentrated, the toxic metabolite may cause
severe bladder damage. Early symptoms of bladder toxicity include dysuria and frequency. This can be distinguished from a urinary
tract infection, since there is no bacteriuria with cyclophosphamide-induced bladder toxicity. However, microscopic hematuria is
often present on urinalysis. In severe hemorrhagic cystitis, large segments of the bladder mucosa maybe shed which can lead to
prolonged, gross hematuria. The incidence of cyclophosphamide-induced hemorrhagic cystitis can be decreased by ensuring that
the patient maintains a high fluid intake. Cyclophosphamide is an alkylating agent used in the treatment of breast carcinoma,
malignant lymphoma, multiple myeloma, and adenocarcinoma of the ovary, as well as various other forms of cancer. The major toxic
reactions commonly seen with this agent include mucositis, nausea, hepatotoxicity, sterile hemorrhagic and nonhemorrhagic cystitis,
leukopenia, neutropenia, and interstitial pulmonary fibrosis.

520

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Which of the following chemotherapeutic agents is specific for the M phase of the cell cycle?
1. Vincristine
2. Cytarabine
3. Daunorubicin
4. Hydroxyurea
5. Mechlorethamine
Ans. 1. Vincristine
Vincristines (and vinblastine) are Vinca alkaloids that bind to tubulin, a component of cellular microtubules. This leads to
disruption of the mitotic spindle apparatus and results in metaphase arrest since the chromosomes are unable to segregate.
Since these drugs interfere with mitosis, they are considered cell-cycle specific for the M phase
Dilated cardiomyopathy results in a diminution in the contractile function of the left, right, or even both ventricles of the heart.
Doxorubicin and daunomycin both are commonly associated with the development of congestive cardiomyopathy

IMPORTANT DRUGS ASKED AND REPEATED FREQUENTLY

Alcohol
Metabolism and Health Effects
Acute alcohol abuse causes drowsiness at blood levels of approximately 200 mg/dL. Stupor and coma develop at higher levels
Alcohol is oxidized to acetaldehyde in the liver by alcohol dehydrogenase, by the cytochrome P-450 system, and by catalase, which
is of minor importance
Acetaldehyde is converted to acetate in mitochondria and utilized in the respiratory chain. Alcohol oxidation by alcohol
dehydrogenase depletes NAD, leading to accumulation of fat in the liver and metabolic acidosis
The main effects of chronic alcohol consumption are fatty liver, alcoholic hepatitis, and cirrhosis, which causes portal hypertension
and increases the risk of development of hepatocellular carcinoma. Chronic alcohol consumption can cause bleeding from gastritis
and gastric ulcer, peripheral neuropathy associated with thiamine deficiency, and alcoholic cardiomyopathy, and increases the risk
for acute and chronic pancreatitis
Chronic alcohol consumption is a major risk factor for cancers of the oral cavity, pharynx, larynx, and esophagus. The risk is
greatly increased by concurrent smoking or use of smokeless tobacco.

Nimodipine
Vasospasm remains the leading cause of morbidity and mortality following aneurysmal SAH
Treatment with the calcium channel antagonist nimodipine (60 mg orally q6h) has been reported to be beneficial, but the effects
seem to be modest
Nimodipine can cause significant hypotension in some patients, which may worsen cerebral ischemia in patients with vasospasm.
The most widely accepted therapy for symptomatic cerebral vasospasm is to increase the cerebral perfusion pressure by raising
mean arterial pressure through plasma volume expansion and the judicious use of vasopressor agents, usually phenylephrine or
dopamin
Nimodipine is indicated for improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in
patients with subarachnoid hemorrhage from ruptured congenital intracranial aneurysms who are in good neurological
condition postictal.

Bromocriptine (USMLE Favorite)

It is indicated in the treatment of prolactin-secreting pituitary tumors in men and women considered to be the treatment of
choice for microadenomas and for macroadenomas including those with visual defects. However, surgery maybe required to
treat macroadenomas in those patients who either cannot take bromocriptine or who exhibit a poor therapeutic response to
bromocriptine inhibits prolactin secretion
Treatment of Amenorrhea, secondary, due to hyperprolactinemia
Treatment of Galactorrhea due to hyperprolactinemia
Treatment of Hypogonadism, male, due to hyperprolactinemia

Pharmacology

521

Treatment of Infertility due to hyperprolactinemia

In Acromegaly
It is indicated, usually as an adjunct to levodopa/carbidopa therapy, in the treatment of the signs and symptoms of idiopathic or
postencephalic parkinsonism
It is indicated in the treatment of some cases of acromegaly, usually as an adjunct to surgery or radiotherapy
It is sometimes used as adjunctive therapy in the treatment of neuroleptic malignant syndrome
Was used in induction of ovulation, Corpus luteum cyst.
Galactorrhea is a commonly associated with hyperprolactinemia. The secretion, occurring with galactorrhea, can occur spontaneously
or on breast examination. Hyperprolactinemia can also cause oligomenorrhea or amenorrhea. Hyperprolactinemia can be caused
by medications that affect normal pathways for dopamine and norepinephrine. Medications most commonly associated with this
disorder include
Tricyclic antidepressants such as nortriptyline
Tranquilizers
Methyldopa
Narcotics
Phenothiazines

Octreotide (USMLE Favorite)

It is indicated for palliative management of gastrointestinal endocrine tumors, such as:
Carcinoid tumors to suppress or inhibit the associated severe diarrhea and facial flushing
Vasoactive intestinal polypeptide-secreting tumors (VIPomas) for the treatment of the profuse watery diarrhea associated with
VIPomas
It is indicated to suppress secretion of growth hormone from pituitary tumors and decrease blood concentrations of insulin-like
growth factor-I (IGF-I; somatomedin C) in patients with acromegaly
It is indicated to reduce the incidence and severity of the postoperative complications of high-risk pancreatic surgery. These
complications may include abscess formation and subsequent sepsis, acute pancreatitis, pancreatic fistula, and peripancreatic
fluid collection
It is indicated in Varices, gastroesophageal, bleeding
It is indicated to reverse life-threatening hypotension due to carcinoid crisis during induction of anesthesia
It is indicated for use as palliative treatment of the symptoms resulting from hyperinsulinemia from severe refractory metastatic
insulinoma
It is indicated in AIDS patients with severe secretory diarrhea who have failed to respond to antimicrobial or antimotility agents.

Dantrolene: (USMLE Favorite)

Intravenous dantrolene is indicated to reverse the symptoms of the Malignant Hyperthermic crisis syndrome occurring during
or following surgery or anesthesia
It is also indicated for administration prior to surgery or anesthesia to prevent or attenuate the symptoms of the malignant
hyperthermic crisis syndrome in patients known or suspected to be at risk for this complication
Oral dantrolene is indicated to relieve spasticity caused by upper motor neuron disorders such as spinal cord injury,
cerebrovascular accident, cerebral palsy and multiple sclerosis
It is used to relieve the symptoms of Neuroleptic malignant syndrome, which are similar to those caused by malignant
hyperthermia
Treatment of exercise-induced pain in muscle phosphorylase deficiency
Oral dantrolene is used in the management of flexor spasms in patients who are confined to bed or a wheelchair.

Riluzole: (USMLE Favorite)

It is indicated in the treatment of Amyotrophic lateral sclerosis (ALS)
Riluzole presynaptically inhibits glutamate release in the central nervous system (CNS) and postsynaptically interferes with
the effects of excitatory amino acids.

522

USMLE Step 1 Platinum Notes

Ivermectin: (USMLE Favorite)

Binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate muscle and nerve cells
of the microfilaria. This binding causes an increase in the permeability of the cell membrane to chloride ions and results in
hyperpolarization of the cell, leading to paralysis and death of the parasite
Ivermectin also is believed to act as an agonist of the neurotransmitter gamma-aminobutyric acid (GABA), thereby disrupting
GABA-mediated central nervous system (CNS) neurosynaptic transmission
Oral agent for scabies now.

Filgrastim

It is a granulocyte colony-stimulating factor (G-CSF) analog used to stimulate the proliferation and differentiation of granulocytes
It is produced by recombinant DNA technology
Filgrastim is used to treat neutropenia stimulating the bone marrow to increase production of neutrophils
Filgrastim is also used to increase the number of hematopoietic stem cells in the blood before collection by leukapheresis for use
in hematopoietic stem cell transplantation.

Calcitonin (Lately asked in USMLE)

Inhibits bone reabsorption by osteoclasts
It is important to know that although calcitonin inhibits reabsorption of calcium and phosphate in renal tubule,
hypocalcemia which occurs, overrides this direct action by decreasing the total calcium filtered at glomerulus; urinary
calcium is actually reduced
Uses of Calcitonin:
Hypercalcemia
Osteoporosis
Pagets disease

Denosumab: (Lately asked in USMLE)

It is a fully human monoclonal antibody which is being studied in the treatment of osteoporosis, treatment induced bone loss,
bone metastases, rheumatoid arthritis, multiple myeloma and giant cell tumor of bone
Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal. In
many bone loss conditions, RANKL overwhelms the bodys natural defense against bone destruction
It was approved by FDA for use in postmenopausal women with risk of osteoporosis.

Entacapone
It is a drug that functions as a catechol-O-methyl transferase (COMT) inhibitor
It is used in the treatment of Parkinsons disease
Entacapone is a member of the class of drugs known as nitrocatechols

Letrozole
It is an oral nonsteroidal aromatase inhibitor for the treatment of hormonally-responsive breast cancer after surgery
Estrogens are produced by the conversion of androgens through the activity of the aromatase enzyme. Estrogens then bind to an
estrogen receptor, which causes cells to divide
Letrozole prevents the aromatase from producing estrogens by competitive, reversible binding to the heme of its cytochrome
P450 unit. The action is specific, and letrozole does not reduce production of mineralo or corticosteroids.

Thymosin alfa: TA1

TA1 is a synthetic polypeptide
The drug is in Phase III trials for the treatment of hepatitis C and in Phase II trials for hepatitis B. Additional possible indications
are malignant melanoma, hepatocellular carcinoma, drug-resistant tuberculosis, and Di Georges syndrome
TA1 is thought to modulate the immune system by augmenting T-cell function
TA1 may affect thymocytes by stimulating their differentiation or by converting them to active T cells.

Pharmacology

523

Bevirimat: (Lately asked in USMLE)

It is an anti-HIV drug believed to inhibit HIV by a novel mechanism, so-called maturation inhibition
Like protease inhibitors, bevirimat and other maturation inhibitors interfere with protease processing of newly translated HIV
polyprotein precursor, called gag
This molecule contains a number of HIV proteins in a single polypeptide which is then cleaved by the enzyme protease to produce
functional structural proteins
However, unlike the protease inhibitors, bevirimat binds the gag protein, not protease
Once bound to gag, bevirimat prevents a critical cleavage at a site called the capsid-SP1 junction
The resulting virus particles lack functional capsid protein and have structural defects, rendering them incapable of infecting other
cells.

Raltegravir: (Lately asked in USMLE)

It is an antiretroviral drug, the first of a new class of HIV drugs, the integrase inhibitors, to receive such approval
Integration occurs following production of the double-stranded viral DNA by the viral RNA/DNA-dependent DNA polymerase,
reverse transcriptase
The main function of Integrase is to insert the viral DNA into the host chromosomal DNA, a step that is essential for HIV
replication
Integration is a point of no return for the cell, which becomes a permanent carrier of the viral genome (provirus)
Integration is in part responsible for the persistence of retroviral infections. After integration, the viral gene expression and particle
production may take place immediately or at some point in the future.

Tigecycline: (Lately asked in USMLE)

It is a glycylcycline antibiotic was developed in response to the growing prevalence of antibiotic resistance in bacteria such as
Staphylococcus aureus and Acinetobacter baumannii
Tigecycline is bacteriostatic and is a protein synthesis inhibitor by binding to the 30S ribosomal subunit of bacteria and thereby
blocking entry of Aminoacyl-tRNA into the A site of the ribosome during prokaryotic translation
Tigecycline is active against many Gram-positive bacteria, Gram-negative bacteria and anaerobes including activity
against methicillin-resistant Staphylococcus aureus (MRSA), Stenotrophomonas maltophilia, Hemophilus influenzae, and
Neisseria gonorrheae.

Iclaprim: (Lately asked in USMLE)

It is a diaminopyrimidinedihydrofolate reductase inhibitor being developed for the treatment of complicated skin and soft tissue
infections caused by antibiotic-resistant bacteria
It is structurally related to trimethoprim intravenously-administered iclaprim was found to be as effective in skin and soft tissue
infections, many caused by methicillin-resistant Staphylococcus aureus (MRSA).

Thalidomide: (OLD Drug for New Diseases)

Thalidomide is a drug, immunomodulator but a potent teratogen as well
It is an old drug with new uses
Thalidomide is used in Multiple Myeloma due to antiangiogenic activity. (Thalidomide+Dexamethasone +Melphalan) is a very
effective therapy for MM
Thalidomide reduces production of TNF alpha and is used for Rh arthritis and Crohns disease. Serious infections including sepsis
and tuberculosis cause the level of Tumor necrosis factor-alpha (TNF) to rise. TNF is a chemical mediator in the body, and it may
enhance the wasting process in cancer patients as well. Thalidomide may reduce the levels of TNF, and it is possible that the drugs
effect on ENL is caused by this mechanism. Thalidomide also has potent anti-inflammatory effects that may help ENL patients
Thalomide, in conjunction with dexamethasone, is now standard therapy for multiple myeloma
Thalidomide is also prescribed for its anti-inflammatory effects in actinic prurigo, an autoimmune skin disease
Thalidomide also inhibits the growth of new blood vessels (angiogenesis), which maybe useful in treating macular degeneration
and other diseases. This effect helps AIDS patients with Kaposis sarcoma, although there are better and cheaper drugs to treat
the condition.

524

USMLE Step 1 Platinum Notes

Thalidomide maybe able to fight painful, debilitating aphthous lesions in the mouth and esophagus of AIDS patients which
prevent them from eating
Thalidomide is also being investigated for treating symptoms of prostate cancer, glioblastoma, lymphoma, arachnoiditis,
Behets disease, and Crohns disease
Remember:
Used in leprosy (ENL)
HIV associated ulcer
AIDS related wasting syndrome
Multiple myeloma
Crohns disease
Behets syndrome
Rheumatoid arthritis, Ankylosing spondylitis
Behets ulcer
Has teratogenicity associated with its use dietary triglycerides into absorbable fatty acids and monoglycerides
Other drugs used in obesity are:
Sibutarmine
Olestra
Fenfluramine

Gallium Citrate
It is indicated to demonstrate the presence and extent of lymphoma, bronchogenic carcinoma, [acute myelocytic leukemia],
[chronic myelocytic leukemia], [hepatoma] and [bone sarcoma]
Gallium citrate Ga 67 is indicated for the localization of focal inflammatory lesions, such as abscess, osteomyelitis, pneumonia,
pyelonephritis, and granulomatous diseases (sarcoidosis). May also be useful in the detection of active tuberculosis; and for
assessing the activity of the inflammatory process in certain interstitial pulmonary diseases, including sarcoidosis and fibrosing
alveolitis
In combination with thallous chloride Tl 201 imaging, gallium citrate Ga 67 imaging maybe useful in the diagnosis of myocardial
sarcoidosis and in predicting the response to corticosteroid therapy
Useful in the diagnosis and monitoring of Pneumocystis carinii pneumonia, tuberculosis, and other infections in acquired
immunodeficiency syndrome (AIDS) patients
It is useful as a diagnostic screening test in cases of prolonged fever (PUO), when physical examination, laboratory tests, and
other imaging studies have failed to disclose the source of the fever.

ANTI OBESITY DRUGS

Orlistat
Orlistat is an inhibitor of intestinal lipase that causes modest weight loss due to drug-induced fat Malabsorption
Orlistat is indicated for the management of obesity in persons with an initial body mass index (BMI) 30 kg per square meter of
body surface area (kg/m2), or a BMI 27 kg/m2 when other risk factors (such as hypertension, diabetes, or dyslipidemia) are present
Orlistat is a reversible inhibitor of intestinal lipases. In the lumen of the stomach and intestine, it bonds covalently with active
serine residues of gastric and pancreatic lipases, making them unavailable to hydrolyze.

NEW DRUGS: FREQUENTLY ASKED AND HIGH YIELD TOPIC

Very Important
Rituximab is anti CD 20, Used in B cell lymphomas with CHOP Regime
Trastuzumab is used in Breast Cancer
Alemtuzumab is used in CLL and T cell Lymphomas
Dacluzimab is used for Kidney transplant

Pharmacology

525

Trastuzumab: HER-2 /neu Breast Ca

Alemtuzumab: CD 25 Resistant CLL (seems you have forgotten read just two line above) (Concentration in this book is
important)
Cetuximab: EGFR Resistant Colorectal Ca, Head and neck cancer
Bevacizumab: Anti angiogenic drug (Colorectal Ca, RCC, Breast Ca)
Gemtuzumab ozoogamicin: Anti CD33, used for refractory AML.
Golimumab: Anti TNF monoclonal antibody used for psoriatic arthritis, rheumatoid arthritis and ankylosing spondylitis
Pavluzimab is used for Respiratory syncytial virus infections
Trastuzumab (Herceptin) is used in Breast Cancer. It is an important drug.
It is a humanized monoclonal antibody to HER2/neu specifically directed to target tumor cells.
HER 2 has been found to be increased in 510% of breast cancer patients.
It is associated with larger tumor size, higher tumor grade and positive lymph nodes.
HER 2 is also in ovarian, prostate, gastric and bronchial cancer.
Lepatinib is HER 2 and EGF receptor antagonist.

Imatinib
Imatinib is a magic bullet
Imatinib is effectively used as a tyrosine kinase inhibitor
Imatinib targets bcr-abl and breaks it
It is used in treatment of:
CML
GISTS (Gastrointestinal stromal tumors)
Systemic Mastocytosis
Hyper eosinophilic Syndrome
Imatinib mesylate is effective in patients with systemic mastocytosis
Drugs in same class:
Imatinib, Bastinib, nilotinib: used in CML
Sunitinib used in renal cell carcinoma
Sorafenib used in renal cell carcinoma
Gefitinib, erlotinib: used in non small cell lung cancer
Bartezomib is a proteosome inhibitor

USMLE Case Scenario

Drug of choice for Chronic myeloid Leukemia (CML) is:
1. Hydroxyurea
2. Imatinib
3. Inflliximab
4. IFN
Ans. 2. Imatinib
Leucovorin

Protects against Methotrexate toxicity

Amifostine

Prevents radiation toxicity

Dexrazoxane

Protects against anthracycline cardiac toxicity

Palifermin

Prevents mucositis

526

USMLE Step 1 Platinum Notes

DRUGS IMPLICATED IN SYNDROMES

Ebsteins Anamoly

Lithium given in pregnancy results in: Cardiac malformation

Lithium given in early pregnancy; the drug causes cardiac and vascular abnormalities
Atrialization of right ventricle is known as Ebsteins anomaly
It results into displaced and malformed tricuspid valves

Serotonin Syndrome (USMLE Favorite)

Remember Important Facts:
It is a complication of two drugs with serotonergic activity is combined together
This is often the case when tricyclic antidepressants + monoamineoxidase inhibitors
This interaction is potentially life threatening and has features similar to that of neuroleptic malignant syndrome
Wine and cheese (and many other fermented foods) contain tyramine, an indirect sympathomimetic that can trigger
excess catecholamine release and lead to a hypertensive crisis when ingested by patients taking MAO inhibitors
These include a variety of autonomic, somatic and cognitive symptoms
Symptoms include:
Rigidity+
Hyperthermia+
Autonomic instability+
Myoclonus+
Confusion+
Delirium and
Coma
Serotonin syndrome caused by:
Phenelzine
Imipramine
Fluoxetine

Fetal-Hydantoin Syndrome/Phenytoin Embryopathy: (USMLE Favorite)

Features: Growth and mental deficiency in fetal hydantoin with/without heart defects and cleft lip syndrome
Folic acid is essential for protein synthesis and growth, and since hydantoin interferes with intestinal transport of folic
acid, it has been postulated that part of the fetal hydantoin syndrome maybe due to inhibition of placental folic acid by
maternal hydantoin.

Gray Baby Syndrome (USMLE Favorite)

It is a rare but serious side effect that occurs in newborn infants (especially premature babies) following the intravenous
administration of chloramphenicol
This condition is due to a lack of glucuronidation reactions occurring in the baby, thus leading to an accumulation of toxic
chloramphenicol metabolites
The UDP-glucuronyl transferase enzyme system of infants, especially premature infants, is immature and incapable of
metabolizing the excessive drug load.

Fetal Hydantoin Syndrome (USMLE Favorite)

Also called Fetal Hydantoin Syndrome, Dilantin Embryopathy, or Phenytoin Embryopathy
About one-third of children whose mothers are taking this drug during pregnancy typically have children who have
intrauterine growth restriction with microcephaly and develop minor dysmorphic craniofacial features and limb defects
including hypoplastic nails and distal phalanges.

Pharmacology

527

Red Man Syndrome

Vancomycin can cause two types of hypersensitivity reactions, the red man syndrome and anaphylaxis
Red man syndrome has often been associated with rapid infusion of the first dose of the drug which stimulates histamine
release results in red man syndrome.

Purple-Toe Syndrome: (USMLE Favorite)

It is one of the thromboembolic complications of warfarin therapy
These problems are much less common than bleeding complications, they nevertheless demand a prompt diagnosis and
treatment.

Fetal Warfarin Syndrome: (USMLE Favorite)

Warfarin given in early pregnancy increases birth defects especially skeletons abnormalities
Fetal warfarin syndrome
Hyperplasia of nose, eye, socket, hand bones
Growth retardation
Given later in pregnancy it causes:
CNS defects
Fetal death
Accentuates neonatal hypothrombinemia

DRESS Syndrome
Drug Reaction with Eosinophilia and Systemic Symptoms
It is a syndrome, caused by exposure to certain medications, that may cause a rash, fever, inflammation of internal organs,
lymphadenopathy and characteristic hematologic abnormalities such as eosinophilia, thrombocytopenia, and atypical
lymphocytosis
Treatment consists of stopping the offending medication and providing supportive care.

Fanconi Syndrome: (USMLE Favorite)

It is a generalized defect in proximal tubule transport involving amino acids, glucose, phosphate, uric acid, sodium,
potassium, bicarbonate, and proteins
Idiopathic Fanconi syndrome maybe inherited as an autosomal dominant, autosomal recessive or X-linked trait. Sporadic
cases are also seen
A variety of inherited systemic disorders are also associated with Fanconi syndrome including Wilsons disease,
galactosemia, tyrosinemia, cystinosis, fructose intolerance, and Lowes oculocerebral syndrome. The syndrome maybe
acquired in multiple myeloma, amyloid, and heavy metal toxicity
Kindly remember to distinguish it from Fanconis Anemia which is a different entity.

MECHANISM OF ACTION OF SOME IMPORTANT DRUGS

(USMLE Favorite)
Sucralfate: Aluminum sucrose sulfate polymerizes in the acid environment of the stomach and selectively binds necrotic peptic
ulcer tissue. Acts as a barrier to acid, pepsin, and bile
Celecoxib, Rofecoxib: Selectively inhibit cyclooxygenase (COX) isoform 2, which is found in inflammatory cells and mediates
inflammation and pain; spares COX-1 which helps maintain the gastric mucosa
Cromolyn: Prevents release of mediators from mast cells. Effective only for the prophylaxis of asthma. Not effective during an
acute attack
Flutamide: It is a nonsteroidal competitive inhibitor of androgens at the testosterone receptor, used in prostate carcinoma
Ketoconazole and Spironolacton: Inhibit steroid synthesis, used in the treatment of polycystic ovarian syndrome to prevent
hirsutism.

528

USMLE Step 1 Platinum Notes

Acetaminophen: Reversibly inhibits cyclooxygenase, mostly in CNS. Inactivated peripherally

Allopurinol: Inhibits xanthine oxidase, decreasing conversion of xanthine to uric acid
Aspirin: Acetylates and irreversibly inhibits cyclooxygenase (COX I and COX II) to prevent the conversion of arachidonic acid to
prostaglandins
Clomiphene: It is a partial agonist at estrogen receptors in the pituitary gland. Prevents normal feedback inhibition and increases
release of LH and FSH from the pituitary, which stimulates ovulation
Colchicine: Depolymerizes microtubules, impairing leukocyte chemotaxis and degranulation
Cyclosporine: Binds to cyclophilins (peptidyl proline cis-trans isomerase), blocking the differentiation and activation of T cells
mainly by inhibiting the production of IL-2 and its receptor
Heparin: Heparin catalyzes the activation of antithrombin III
Mifepristone (RU486): Competitive inhibitor of progestins at progesterone receptors
Misoprostol: It is a PGE1 analog that increases the production and secretion of the gastic mucous barrier
Omeprazole, Lansoprazole: Irreversibly inhibits H+/K+ ATPase in stomach parietal cells
Probenacid: Inhibits reabsorption of uric acid
Sildenafil: Inhibits cGMP phosphodiesterase, casuing increased cGMP, smooth muscle relaxation in the corpus cavernosum,
increased blood flow, and penile erection
Alpha-glucosidase inhibitors: Inhibit intestinal bursh border Alpha-glucosidases; delayed hydrolysis of sugars and absorption of
sugars leading to decreased postprandial hyperglycemia
Glucocorticoids: Decrease the production of leukotrienes and protaglandins by inhibiting phospholipase A2 and expression of
COX-2
H2 Blockers: Reversible block of histamine H2 receptors
Thrombolytics: Directly of indirectly aid conversion of plasminogen to plasmin which cleaves thrombin and fibrin clots. (It is
claimed that tPA specifically converts fibrin-bound plasminogen to plasmin.)
Ticlopidine, Clopidogrel: Inhibits platelet aggregation by irreversibly inhibiting the ADP pathway involved in the binding of
fibrinogen
Warfarin (Coumadin): Warfarin interferes with the normal synthesis and gamma-carboxylation of vitamin K-dependent clotting
factors II, VII, IX, and X, Protein C and S via vitamin K antagonism
Azathioprine: Antimetabolite derivative of 6-mercaptopurine that interferes with the metablolism and synthesis of nucleic acid
Leuprolide: GnRH analog with agonist properties when used in pulsatile fashion and antagonist properties when used in
continuous fashion, causing a transient initial burst of LH and FSH
Tacrolimus (FK506): Similar to cyclosporine; binds to FK-binding protein, inhibiting secretion of IL-2 and other cytokines.

The Commonest Side Effects Most Frequently asked: (USMLE Favorite)

Drug(s) causing Adrenocortical Insufficiency: Glucocorticoid withdrawal

Drug(s) causing Agranulocytosis: Cloazapine, carbamazapine, colchicine, Propylthiouracil
Drug(s) causing Aplastic anemia: Chloramphenicol, benzene, NSAIDS, PTU, phenytoin
Drug(s) causing Cardiac toxicity: Daunorubicin and Doxorubicin
Drug(s) causing Cinchonism: Quinidine, quinine
Drug(s) causing Cough: ACE inhibitors
Drug(s) causing Cutaneous flushing: Niacin, Ca++ channel blockers, adenosine, vancomycin
Drug(s) causing Diabetes insipidus: Lithium
Drug(s) causing Disulfiram-like reaction: Metronidazole, certain cephalosporins, procarbazine, sulfonylureas
Drug(s) causing Drug induced Parkinsons: Haloperidol, chlorpromazine, reserpine, MPTP
Drug(s) causing Extrapyramidal side effects: Chlorpromazine, thioridazine, haloperidol
Drug(s) causing Fanconis syndrome: Tetracycline
Drug(s) causing hepatic necrosis: Halothane, Valproic acid, acetaminophen, Amantia phalloides
Drug(s) causing G6PD hemolysis: Sulfonamides, INH, ASA, Ibuprofen, primaquine, nitrofurantoin/pyrimethamine,
chloramphenicol

Pharmacology

529

Drug(s) causing Tubulointerstitial Nephritis: Sulfonamides, furosemide, methicillin, rifampin, NSAIDS

Drug(s) causing Osteoporosis: Corticosteroids, heparin
Drug(s) causing reaction: Oto and Nephrotoxicity: Aminoglycosides, loop diuretics, cisplatin
Drug(s) causing P450 induction: Barbiturates, phenytoin, carbamazipine, rifampin, griseofulvin, quinidine
Drug(s) causing P450 inhibition: Cimetidine, ketoconazole, grapefruit juice, erythromycin, INH, sulfonamides
Drug(s) causing:Photosensitivity: Tetracycline, amiodarone, sulfonamides
Drug(s) causing: Pseudomembranous colitis: Clindamycin
Drug(s) causing: Pulmonary fibrosis: Bleomycin, amiodarone, busulfan
Drug(s) causing: SLE-like syndrome: Hydralazine, Procainamide, INH, phenytoin
Drug(s) causing Stevens-Johnson syndrome: Ethosuxamide, sulfonamides, lamotrigine
Drug(s) causing Tardive dyskinesia: Antipsychotics
Drug(s) causing Tendonitis: Fluoroquinolones
Drug(s) causing Thrombotic complications: Oral Contraceptives
Drug(s) causing Torsade de pointes: Class III antiarrhythmics (sotalol), class IA (quinidine)

Latest Drugs asked in USMLE

Surfactants used for Neonatal RDS

Poractant/Beractant

VIP analogue for Erectile Dysfunction

Aviptadil

Opioid receptor antagonist for Paralytic ileus

Alvimopan

PAF antagonists for Acute Pancreatitis

Lexipafant/Apafant

Recombinant Dnase used for hydrolysing Pulmonary Secretions in Dornase Alpha

Cystic fibrosis
IL-1 antagonist used as Disease Modifier in Osteoarthritis

Diacerin

Disease modifier for osteoarthritis (COX-LOX inhibitor)

Licofelone

Used in CML

Imatinib, Dasatanib, Bastinib, nilotinib

Used in renal cell carcinoma

Sunitinib
Pazopanib

NMDA Antagonist for ALS (Amyotrophic Lateral Sclerosis)

Riluzole

NMDA Antagonist for Alzheimers Disease

Memantine

Used in non small cell lung cancer

Efitinib, erlotinib

Vasopeptidase inhibitors used for CHF treatment

Omapatrilat, sampatrilat

PDE 4 inhibitors for Asthma

Roflumilast, tofimilast, cilomilast

CD 20 directed monoclonal antibody used in Patients of CML

Ofatumumab

Kallikerin Inhibitor used in Acute attack of Hereditary Agioneurotic Ecallantide

edema
An Ach release inhibitor and Neuromuscular blocker used for Abobotulinomtoxin
Dystonias/Torticollosis
Glucagon Like Peptides used in Type 2 Diabetes Mellitus

Exenatide, Liraglutide

Anti TNF agent used in Crohns Disease/Rheumatoid arthritis

Certoluzimab

5 Lipooxygenase inhibitor for Actinic Keratosis

Mesoprocol

Fidaxomicin: As a treatment for patients with Clostridium difficile infection (CDI).

Ioflupane I 123 injection is a radiopharmaceutical indicated for striatal dopamine transporter visualization using single photon
emission computed tomography (SPECT) brain imaging to assist in the evaluation of adult patients with suspected Parkinsonian
syndromes.

530

USMLE Step 1 Platinum Notes

Tesamorelin: It is a synthetic analog of growth hormonereleasing factor A hypothalamic peptide that acts on pituitary cells
in the brain to stimulate the production and release of endogenous growth hormone. Treatment indicated to reduce excess
abdominal fat in HIV-infected patients with lipodystrophy.
Denosumab: Human monoclonal antibody which is being studied in the treatment of osteoporosis, treatment induced bone loss,
Denosumab targets RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal. In many bone loss
conditions, RANKL overwhelms the bodys natural defense against bone destruction. Used in postmenopausal women with risk
of osteoporosis.
Retapamulin: A pleuromutilin antibiotic ointment for topical treatment of impetigo.
Doripenem: A carbapenem antibiotic for intra-abdominal and urinary tract infections.
Raltegravir: An integrase inhibitor for treatment of HIV-1.
Eribulin mesylate: Unique inhibitor of microtubule dynamics binding predominantly to a small number of high affinity sites
at the plus ends of existing microtubules. Eribulin exerts its anticancer effects by triggering apoptosis of cancer cells following
prolonged and irreversible mitotic blockade. Has a role in breast cancer
Ixabepilone: A microtubule inhibitor for metastatic or advanced breast cancer
Sapropterin: An enzyme enhancer for treatment of phenylketonuria (PKU)
Fidaxomicin: As a treatment for patients with Clostridium difficile infection (CDI)
Ambrisentan: An endothelin receptor antagonist for pulmonary arterial hypertension
Ioflupane I 123 injection: It is a radiopharmaceutical indicated for striatal dopamine transporter visualization using single photon
emission computed tomography (SPECT) brain imaging to assist in the evaluation of adult patients with suspected Parkinsonian
syndromes
Rotigotine: A transdermal dopamine agonist for Parkinsons disease
Mavirocl: A CCR5 antagonist, antiretroviral for treatment of HIV-1 infection
Lanreotide: A depot injection for treatment of acromegaly
Nilotinib: A kinase inhibitor for a specific type of chronic myelogenous leukemia
Aliskiren: A direct renin inhibitor for treatment of hypertension
Temsirolimus: A kinase inhibitor for advanced renal cell carcinoma
Lisdexamfetamine A prodrug of dextroamphetamine for ADHD

Revision of Poisonings and Antidotes

Flumazenil is an antagonist at the benzodiazepine receptor

Acetylcysteine is the drug of choice for treatment of overdose of acetaminophen
Atropine is a muscarinic antagonist used in cases of acetylcholinesterase inhibitor overdoses
Calcium disodium acetate is used as a chelator in lead poisoning
Defipirone/Deferoxamine is an effective chelator for poisoning with iron salts
Ethanol is used in cases of methanol and ethylene glycol poisoning
Pralidoxime is an acetylcholinesterase reactivating agent used in cases of organophosphorus acetylcholinesterase inhibitor
overdose
Protamine sulfate is administered to reverse the anticoagulant effects of heparin overdose
Leucovorin is primarily used to prevent or diminish toxicity associated with the use of antineoplastic folic acid antagonists,
particularly methotrexate
Penicillamine is a chelating agent used to promote the renal excretion of excess copper in Wilsons disease
Sodium thiosulfate is an antidote for cyanide poisoning.

Pharmacology

531

USMLE Case Scenario

A 33-year-old male is brought to emergency with straight away diagnosis of iron poisoning. The physician wishes to give him
oral iron chelator. The drug used is:
Deferiprone

USMLE Case Scenario

A 55-year-old male on Heparin for Deep vein Thrombosis prophylaxis is said to have developed Heparin Overdosage. The drug
to be given as antidote for the condition is:
Protamine Sulfate

USMLE Case Scenario

A 26-year-old uneducated farmer from rural Mexico is rushed to a hospital emergency room after an accidental exposure to
parathion. He is in respiratory distress and is bradycardic. Which of the following drugs can be given to increase the activity
of his acetylcholinesterase?
1. Atropine
2. Deferoxamine
3. Dimercaprol
4. N-acetylcysteine
5. Physostigmine
6. Pralidoxime
Ans. 6. Pralidoxime (2-PAM) is an acetylcholinesterase (AChE) reactivating agent

USMLE Case Scenario

A 88-year-old woman with Alzheimers disease attempts suicide by ingesting a bottle full of 100 tablets of acetaminophen. Her
husband immediately rushes her to the hospital OPD. Immediate antidote given is:
Acetylcysteine
Acetylcysteine (N-acetylcysteine) is the antidote for acetaminophen overdose. It likely acts by replenishing hepatic stores of
glutathione, which become depleted in the effort to metabolize the acetaminophen. It is most effective if administered within
10 hours of acetaminophen ingestion.
Acetaminophen is metabolized in the liver, and a small percentage undergoes metabolism by cytochrome P-450 to a toxic
intermediate, NAPQI. Normally, NAPQI is conjugated to glutathione to produce a harmless by-product. In overdose situations,
the glutathione supply is exhausted and NAPQI covalently binds to liver cell components, resulting in centrilobular necrosis,
hepatic failure, and death. The estimated toxic dose of acetaminophen in children is estimated at 150 mg/kg. N-acetylcysteine
(NAC) is the antidote of choice for acetaminophen toxicity. NAC is a glutathione precursor that repletes glutathione storage,
and it reacts directly with NAPQI to prevent cellular damage. The optimal time for NAC administration is within the first 8
hours after acetaminophen ingestion. After the 8-hour postingestion period, the efficacy decreases progressively and is
determined primarily by the blood acetaminophen level.

USMLE Case Scenario

A child is brought with drowsiness, decreased deep tendon reflexes and seizures. On examination the child has a line on gums.
There is history of constipation. Which will be most appropriate drug that should be used in this child?
1. EDTA
2. DMSA
3. Acetylcysteine
4. BAL
5. Pencillamine
Ans. 1. EDTA

532

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A Proteasome inhibitor used for Multiple Myeloma is:
1. Rimonabant
2. Iloprost
3. Bartezomib
4. Conivaptan
Ans. 2. Iloprost

USMLE Case Scenario

A small molecule was subsequently found to be a potent inhibitor of ABL kinases, including the BCR-ABL fusion protein
generated as a result of the t (9;22) chromosomal translocation (Philadelphia chromosome). Most likely molecule is:
1. Paclitaxel
2. Infliximab
3. Etarnacept
4. Imatinib
5. Interferon
6. Doxarubicin
Ans. 4. Imatinib

USMLE Case Scenario

Denosumab is a fully human monoclonal antibody which is being studied in the treatment of osteoporosis, treatment induced
bone loss, bone metastases, rheumatoid arthritis, multiple myeloma and giant cell tumor of bone. Denosumab is designed to
target a protein that acts as the primary signal to promote bone removal. The target Protein is:
1. RANK ligand
2. Osteocalcinin
3. Myosin
4. Troponin
5. N-peptide
Ans. 1. RANK ligand

USMLE Case Scenario

Purple-toe syndrome is a complication of:
1. Vancomycin therapy
2. Warfarin therapy
3. Phenytoin therapy
4. Chloramphenicol therapy
5. Tetracycline therapy
Ans. 2. Warfarin therapy

USMLE Case Scenario

Rivastigmine is predominantly used in the management of:
1. Depression
2. Dissociation
3. Delusions
4. Dementia
Ans. 4. Dementia

Pharmacology

533

USMLE Case Scenario

Linezolid binds to the 23S portion of the 50S subunit (the center of peptidyl transferase activity). Linezolid is a:
1. Protease inhibitor
2. Protein synthesis inhibitor
3. Fusion inhibitor
4. Telomerase inhibitor
Ans. 2. Protein synthesis inhibitor

USMLE Case Scenario

Bevirimat is a drug used for:
1. HPV
2. HSV
3. HIV
4. CMV
Ans. 3. HIV

USMLE Case Scenario

Drug Metabolized by Hoffmans elimination is:
1. Atracurium
2. Halothane
3. Ketamine
4. Pancuronium
Ans. 1. Atracurium

USMLE Case Scenario

Lacosamide, amino acid related peptide used in treatment of:
1. Depression
2. Mania
3. Partial seizures
4. Pshycosis
5. Hypertension
6. Hypercalcemia
Ans. 3. Partial Seizures

USMLE Case Scenario

A 58-year-old lady has a painful cheek when eating. The neurologist diagnoses this pain as trigeminal neuralgia. Best
medication to prescribe is:
1. Benztropine
2. Aspirin
3. Tramadol
4. Diclofenac
5. Propanolol
6. Carbamazepine
7. Paracetamol
8. Ketrolac
Ans. 6. Carbamazepine (For Trigeminal neuralgia, carbamazepine is the first treatment of choice)

534

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 44-year-old man from Kansas has presented with pain in back, lack of interest in recreational activities, low mood, lethargy,
decreased sleep and appetite for two months. There was no history suggestive of delusions or hallucinations. He did not
suffer from any chronic medical illness. There was no family history of psychiatric illness. Routine investigations including
hamogram, renal function tests, liver function tests, electrocardiogram did not reveal any abnormality. This patient should
be treated with:
1. Haloparidol
2. Sertraline
3. Alprazolam
4. Olanzapine
Ans. 2. Sertraline

USMLE Case Scenario

A Man with alcoholic liver failure requires general anesthesia for surgery. Anesthetic agent of choice is:
1. Ether
2. Halothane
3. Methoxyflurane
4. Isoflurane
Ans. 4. Isoflurane
Alcoholism damages the liver and also induces enzymes involved in the metabolism of drugs. Hence, the response to drugs is
not always predictable in a chronic alcoholic.
Ether, Halothane and Methoxyflurane are metabolized by the liver and hence would preferably be avoided in liver failure.

USMLE Case Scenario

Which one of the following is a well known side effect of the Cyclosporine?
1. Skin necrosis
2. Hyperkalemia
3. Hypokalemia
4. Alopecia
5. Constipation
6. Gum aplasia
7. Hypotension
Ans. 2. Hyperkalemia

USMLE Case Scenario

A 44-year-old is brought to the casualty in the state of altered sensorium. He was on lithium for affective disorder and has
suffered through an attack of epileptic fits. On examination he has tremors increased DTRs and incontinence of urine. He has
also undergone an episode of severe gastroenteritis 2 days ago. The serum lithium was found to be 1.95 m moles/L. The cause
of her conditon is:
1. Drug toxicity
2. Dehydration
3. Manic episode
4. Depressive stupor
Ans. 1. Drug toxicity

USMLE Case Scenario

Inhibition of initial step of cholesterol synthesis is by:
1. Nicotinic acid
2. Sumitriptan
3. Lovostatin

Pharmacology

535

4. Probucol
5. Gemfibrozil
6. Nitric oxide
Ans. 3. Lovostatin

USMLE Case Scenario

A 33-year-old woman attempts suicide by taking an overdose of 300 iron tablets. She is rushed to the emergency department,
where the attending physician will most likely order which of the following treatments?
1. Acetylcysteine
2. Atropine
3. Bicarbonate
4. EDTA chelation
5. Deferoxamine
6. Pencillin
7. Pencillamine
8. Ethanol
9. Flumazenil
10. Physostigmine
11. Pralidoxime
12. Protamine
Ans. 5. Deferoxamine

USMLE Case Scenario

A 39-year-old woman gradually developed painful wrists over 3 months. On examination, both wrists and the
metacarpophalangeal joints of both hands were swollen and tender but not deformed. There were no nodules or vasculitic
lesions. The clinical diagnosis was rheumatoid arthritis. Effective medication would be:
1. Allopurinol
2. Paracetamol
3. Cysclosporine
4. Low-dose methotrexate
5. Carbamazepine
6. Phenytoin
Ans. 4. Low-dose methotrexate

USMLE Case Scenario

A drug causes chemical castration in men. It inhibit FSH and LH release, thereby decreasing testosterone production and can
be used in the treatment of uterine fibroids and endometriosis. The drug most likely is:
1. Methyl prednisolone
2. Clomiphene
3. Tamoxifen
4. Paclitaxel
5. Leuprolide
6. Testosteron
Ans. 5. Leuprolide

USMLE Case Scenario

Which of the following could prevent an allergen from reacting with a specific IgE molecule present on the mast cell membrane?
1. Antihistamine
2. Blocking antibody

536

USMLE Step 1 Platinum Notes

3. Cromolyn sodium
4. Epinephrine
5. Theophylline
Ans. 2. Blocking antibody

USMLE Case Scenario

A 35-year-old patient on hemodialysis for two weeks is noted by his physician in the Ward that his blood pressure is difficult
to control. He reports good compliance with his medications, which include erythropoietin, ferrous sulfate, vancomycin and
vitamin D. His blood pressure is 188/90 mm Hg. Which of the following is the most likely cause for the worsening control of
his blood pressure?
1. Erythropoietin
2. Ferrous sulfate
3. Vancomycin
4. Vitamin D
5. Uremia
Ans. 1. Erythropoietin
The patient most likely has a worsening of his blood pressure due to erythropoietin. This is seen in about 33% of dialysis
patients.

USMLE Case Scenario

Epinephrine is the mainstay of therapy in severe cases of immediate hypersensitivity (anaphylaxis). It decreases mast cell
degranulation, and causes smooth muscle dilation in the airways. Mechanism of action is:
1. Increases intracellular cyclic GMP
2. Decreases intracellular cyclic AMP
3. Increases intracellular cyclic AMP
4. Decreases intracellular cyclic AMP
Ans. 3. Increases intracellular cyclic AMP

USMLE Case Scenario

Theophylline is a drug used in Asthma. Mechanism of action is:
1. Inhibits phosphodiesterase decreasing mast cell cyclic AMP levels
2. Inhibits phosphodiesterase increasing mast cell cyclic AMP levels
3. Inhibits phospholipase increasing mast cell cyclic AMP levels
4. Inhibits phospholipase decreasing mast cell cyclic AMP levels
Ans. 2. Inhibits phosphodiesterase increasing mast cell cyclic AMP levels
Cyclic AMP is degraded in cells by the enzyme phosphodiesterase. Theophylline inhibits this enzyme, thereby increasing mast
cell cyclic AMP levels and making degranulation less likely without affecting the binding of the allergen to IgE on mast cells.

USMLE Case Scenario

A new antifungal medication is being tested in Phase I clinical trials. Examination of the pharmacokinetic properties of the
drug reveals that the half-life of the drug is 6 hours. If a continuous intravenous infusion of this drug were started on a research
subject, how long would it take to reach 75% of steady state?
1. 3 hours
2. 6 hours
3. 9 hours
4. 12 hours
5. 18 hours
Ans. 4. 12 hours

Pharmacology

537

USMLE Case Scenario

A 58-year-old woman had a mitral valve replacement, and was placed on anticoagulants and prophylactic antibiotics following
her surgery. Five days after her surgery, she developed a sharply demarcated, erythematous rash on her left thigh. Two days
after the rash appeared, large hemorrhagic bullae began to for in the area of the rash. Which of the following medications
most likely caused the patients rash?
1. Aspirin
2. Cefazolin
3. Heparin
4. Vancomycin
5. Warfarin
Ans. 5. Warfarin
It is a coumarin anticoagulant used for the prophylaxis and treatment of thromboembolic complications associated with
cardiac valve replacement and atrial fibrillation, as well as the prophylaxis and treatment of venous thrombosis and pulmonary
embolism. Warfarin may cause necrosis of the skin (typically on the breasts, thighs, and buttocks) generally between the third
and tenth days of therapy
The lesions are initially sharply demarcated, erythematous, and purpuric. They may resolve or progress to large, irregular,
hemorrhagic bullae that can eventually lead to necrosis
The mechanism for this reaction is related to warfarins ability to deplete protein C, which can lead to a state of hypercoagulability
and thrombosis in the cutaneous microvasculature.

USMLE Case Scenario

Dopamine agonist ergot derivative that stimulates D1 and D2 receptors is:
1. Levodopa
2. Amantadine
3. Pergolide
4. Selegiline
5. Trihexyphenidyl
Ans. 3. Pergolide

USMLE Case Scenario

Methyldopa has been safely used in the treatment of hypertension during pregnancy; this agent is not associated with the
development of teratogenic or other fetal abnormalities. Methyldopa is converted intraneuronally to a-methylnorepinephrine,
an alpha-2 adrenergic agonist, which is subsequently released. Basic mechanism of action is:
1. Release of methylnorepinephrine in the cortex leads to an increase in sympathetic outflow, thus lowering blood pressure
2. Release of methylnorepinephrine in the cortex leads to a decrease in sympathetic outflow, thus lowering blood pressure
3. Release of methylnorepinephrine in the medulla leads to a increase in sympathetic outflow, thus lowering blood pressure
4. Release of methylnorepinephrine in the medulla leads to a decrease in sympathetic outflow, thus lowering blood pressure
Ans. 4. Release of methylnorepinephrine in the medulla leads to a decrease in sympathetic outflow, thus lowering blood
pressure

USMLE Case Scenario

Megestrol helps to increase appetite patients with cancers. This agent is:
1. A nonsteroidal hormone with antineoplastic properties
2. An estrogenic hormone with antineoplastic properties
3. A progestational hormone with antineoplastic properties
4. A nonprogestational hormone with antineoplastic properties
Ans. 3. A progestational hormone with antineoplastic properties

538

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Bacillary angiomatosis is a disease that occurs primarily in AIDS patients and is indicative of a defect in cell-mediated immunity.
It is caused by either Bartonella henselae or Bartonella quintana. The domestic cat is the reservoir for these organisms and
they are usually transmitted to humans via a cat scratch or cat bite. Drug of choice for the infection is:
1. Levofloxacin
2. Quinipristin
3. Cefepime
4. Linezolid
5. Azithromycin
Ans. 5. Azithromycin

USMLE Case Scenario

Human papillomavirus causes warts. Infection can present as a sessile wart or as condyloma acuminatum, which are fleshy
soft growths that coalesce into large masses. When cellular immunity is depressed, as in AIDS, the condylomata acuminatum
proliferate. Warts can be treated with:
1. Theophylline
2. Doxophylline
3. Podophylline
4. Acyclovir
5. Foscarnet
Ans. 3. Podophylline

USMLE Case Scenario

A 32-year-old man from ilinos reports with lethargy and confusion after taking an overdose of beta blockers. Followed by
hypotension and bradycardia After giving IV fluids, atropine and isoproterenol his hypotension and bradycardia are not
improving. Next line of treatment is:
1. Epinephrine
2. Pacemaker
3. Glucagon
4. Albuterol
Ans. 3. Glucagon

USMLE Case Scenario

A 33-year-old divorced male man is brought to the emergency by his neighbors. He has ingested some unknown medication.
The patient is not oriented to time. His temperature is 39.5 C, blood pressure is 120/80 mm Hg, pulse is 99/min and irregular
and respirations are 25/min. The skin is flushed and dry. Dilated pupils and muscle twitching are also noted on physical
examination. ECG reveals prolonged QRS complexes. Hepatic transaminases are normal, and blood gas analysis shows a
normal pH. These findings are most likely due to intoxication by which of the following substances?
1. Acetaminophen
2. Lead
3. Organophosphorus Poison
4. Alcohol
5. Benzodiazepines
6. Nitrates
7. Clonidine
8. Monoamine oxidase (MAO) inhibitors
9. Tricyclic antidepressants
Ans. 9. Tricyclic antidepressants
This Scenario is consistent with intoxication with tricyclic antidepressants such as amitriptyline and imipramine.

Pharmacology

539

USMLE Case Scenario

Antiviral drug found to have anti-Parkinsons properties:
1. Procyclidine
2. Pergolide
3. Amantadine
4. Levodopa
5. Reserpine
Ans. 3. Amantadine

USMLE Case Scenario

A 50-year-old lady is given methotrexate for severe rheumatoid disease causing joint pains and functional limitation. She also
has to be given folinic rescue therapy. Which of the following is the mechanism by which methotrexate acts?
1. Increasing folic acid excretion
2. DNA binding
3. Binding to dihydrofolate reductase
4. Increasing nucleotide synthesis
5. Inhibiting DNA gyrase
Ans. 3. Binding to dihydrofolate reductase

USMLE Case Scenario

A 35-year-old is given excessive intravenous Benzodiazepine. She suddenly becomes agitated, combative and exhibits
involuntary movements. The anesthesiologist determines that she is having a reaction to the drug which has been given in
excess. Next step would be adminstration of:
1. Glucagon
2. Naloxone
3. Nitrite
4. Protamine
5. Flumazenil
6. Buprenorphine
7. Morphine
Ans. 5. Flumazenil

USMLE Case Scenario

A 55-year-old drug addict from california presents with euphoria, altered time perception, and conjunctival injection. There
is impairment of judgment. Most likely cause is addiction from substance:
1. Marijuana
2. Cocaine
3. Phencyclidine
4. Benzodiazepine
Ans. 1. Marijuana

USMLE Case Scenario

A 55-year-old drug addict from california presents to emergency with seizures. Before this his mother says his physician who
saw him reports with Nystagmus, euphoria, ataxia and sensory impairment. Most likely features suggest addiction from
substance:
1. Marijuana

540

USMLE Step 1 Platinum Notes

2. Cocaine
3. Phencyclidine
4. Benzodiazepine
Ans. 3. Phencyclidine

USMLE Case Scenario

An elderly housewife lost her husband who died suddenly of Myocardial infarction couple of years ago. They had been staying
alone for almost a decade with infrequent visits from her son and grandchildren. About a week after the death she heard
his voice clearly talking to her as he would in a routine manner from the next room. She went to check but saw nothing.
Subsequently she often heard his voice conversing with her and she would also discuss her daily matters with him. This
however, provoked anxiety and sadness of mood when she was preoccupied with his thought. She should be treated with:
1. Clomipramine
2. Alprazolam
3. Electroconvulsive therapy
4. Haloperidol
Ans. 4. Haloperidol

USMLE Case Scenario

A 32-year-old boy has attempted suicide with pesticides. His clothes and body are soiled with the pesticides. He has excessive
salivation, sweating. Pupils are constricted. Most appropriate next step in management of this fellow is:
1. Induce emesis
2. Give atropine immediately
3. Give PAM immediately
4. Remove clothing
Ans. 4. Remove clothing
First step is to remove source of poisoning as OP poisons can be absorbed through skin also

USMLE Case Scenario

A 30-year-old presents with nausea, weakness, headache and impaired vision and high anion gap metabolic acidosis. Most
likely cause is:
1. Methanol
2. Ethanol
3. Ethylene glycol
4. Amphetamine
Ans. 1. Methanol

USMLE Case Scenario

A 76-year philipino lady had a history of a red facial rash suffered venous eczema of legs. She was treated for acne rosacea by
her GP. On examination, she had bluish pigmentation on both the legs. What drug is likely to have caused this?
1. Amiodarone
2. Hydroxychloroquine
3. Minocycline
4. Amoxycillin
5. Tetracycline
Ans. 3. Minocycline
This patient developed skin pigmentation in her venous eczema due treatment of her acne rosacea with minocycline

Pharmacology

541

USMLE Case Scenario

A 45-year-old-man comes to emergency with dizziness. He had supraventricular beats. He is on aspirin, atenolol and quinine.
EKG reveals torsades de pointes. He should be managed by:
1. Digoxin
2. Calcium
3. Magnesium
4. Atropine
Ans. 3. Magnesium

USMLE Case Scenario

Assesment of tricyclic antidepressant toxicity is best done by:
1. Serum drug levels
2. Urine drug levels
3. QRS Duration
4. Bowel sounds
Ans. 3. QRS Duration

USMLE Case Scenario

It is known that elevated levels of a substance alter the hypothalamic-pituitary-ovarian axis in such a way that ovulation is
suppressed and menses do not. Most probably the substance is:
1. Thyroxine
2. Epinephrine
3. Progesterone
4. Estrogen
5. Prolactin
6. Bromocriptine
Ans. 5. Prolactin

USMLE Case Scenario

A 33-year-female complains of nausea and has two episodes of vomiting. The physician administers droperidol. On follow-up
evaluation, the patients neck is involuntarily flexed to one side. She is alert, oriented, and conversant and has an otherwise
normal neurologic examination. Which of the following is the most likely diagnosis?
1. Cerebral Hemorrhage
2. SAH
3. Conversion disorder
4. Dystonia
5. Munchausen syndrome
6. Seizure
Ans. 4. Dystonia
The most likely diagnosis is a dystonic reaction to the droperidol. Droperidol causes its antiemetic effect by antagonizing
dopaminergic receptors in the vomiting center (central chemoreceptor zone) of the brain. This antidopaminergic action can
produce torticollis or other dystonias.

USMLE Case Scenario

A 40-year-old lady is being considered for treatment for rheumatoid arthritis. Which of the following is a disease modifying
antirheumatic drug?
1. Mercury
2. Phenylephrine

542

USMLE Step 1 Platinum Notes

3. Silver
4. Leflunomide
5. Benzoyl peroxide
Ans. 4. Leflunomide
DMARDS include gold, chloroquine, sulfasalazine, penicillamine, methotrexate, azathioprine and leflunomide. Leflunomide
inhibits pyrimidine synthesis through inhibition of dihydro-orotate dehydrogenase.

USMLE Case Scenario

A 48-year-old man who has had a renal transplant for a long standing renal ailment is much concerned about the side effects
of cyclosporin. Which one of the following is a well known side effect of the drug?
1. Skin necrosis
2. Hyperkalemia
3. Alopecia
4. Constipation
5. Gum aplasia
6. Hypotension
Ans. 2. Hyperkalemia
Cyclosporine causes Hyperkalemia, hirsutism, tremors, hypertension

USMLE Case Scenario

A drug is a synthetic analog of growth hormonereleasing factor A hypothalamic peptide that acts on pituitary cells in
the brain to stimulate the production and release of endogenous growth hormone. Treatment indicated to reduce excess
abdominal fat in HIV-infected patients with lipodystrophy. The drug mentioned is:
1. Eribulin mesylate
2. Fidaxomicin
3. Tesamorelin
4. Xabepilon
Ans. 3. Tesamorelin

USMLE Case Scenario

Carbidopa is useful in the management of Parkinsons disease because it is an:
1. D2 agonist
2. D2 antagonist
3. M2 Agonist
4. M2 Antagonist
5. Peripheral decarboxylase inhibitor
6. Central decarboxylase inhibitor
7. Effective competitor at the GABA receptor
Ans. 5. Peripheral decarboxylase inhibitor

USMLE Case Scenario

A 30-year-old man who was recenlty started on haloperidol 30 mg/day developed hyperpyrexia, muscle rigidity, akinesia,
mutism, sweating, tachycardia and increased blood pressure. The investigations showed increased WBC count, increased
creatinine phophokinase. These are no history of any other drug intake or any signs of infection. The most likely diagnosis is:
1. Drug overdose
2. Neuroleptic malignant syndrome
3. Drug induced Parkinsonism
4. Tardive dyskinesia
Ans. 2. Neuroleptic malignant syndrome

Pharmacology

543

USMLE Case Scenario

A patient has taken few drugs simultaneously. Symptoms include:
Rigidity+ hyperthermia+ autonomic instability+ myoclonus+ confusion+ delirium and coma
Likely cause is a combination of:
1. Tricyclic antidepressants + Monoamineoxidase inhibitors
2. Tricyclic antidepressants + Phosphodiesterase inhibitiors
3. Tricyclic antidepressants + Protease inhibitors
4. Tricyclic antidepressants + Fusion inhibitors
Ans. 1. Tricyclic antidepressants + monoamineoxidase inhibitors

USMLE Case Scenario

Gray baby syndrome is a rare but serious side effect that occurs in newborn infants (especially premature babies) following
the intravenous administration of chloramphenicol. It is due to specific defective:
1. Oxidation reactions
2. Reduction reactions
3. Oxidation reactions
4. Hydroxylation reactions
5. Isomerization reactions
6. Glucoronidation reactions
Ans. 6. Glucoronidation reactions

USMLE Case Scenario

Which one of the following drug is used for CMV infections?
1. Ritonavir
2. Diadenosine
3. Raltegavir
4. Ganciclovir
5. Acyclovir
6. Zidovudine
7. Foscornet
Ans. 4. Ganciclovir

USMLE Case Scenario

Riluzole presynaptically inhibits release of a substance in the central nervous system (CNS) and postsynaptically interferes
with the effects of excitatory amino acids. It inhibits release of:
1. GABA
2. Acetylcholine
3. Substance P
4. Glutamate
5. Norepinephrine
Ans. 4. Glutamate

USMLE Case Scenario

An enzyme enhancer for treatment of phenylketonuria (PKU) is:
1. Aminopterin
2. Sapropterin
3. Retapamulin
4. Rotigotine
Ans. 2. Sapropterin

544

USMLE Step 1 Platinum Notes

USMLE Case Scenario

Papillomatous Warts can be treated with:
1. Theophylline
2. Doxophylline
3. Podophylline
4. Acyclovir
5. Foscarnet
Ans. 3. Podophylline

USMLE Case Scenario

A transdermal dopamine agonist for Parkinsons disease.
1. Aminopterin
2. Sapropterin
3. Retapamulin
4. Rotigotine
5. Maviroc
6. Lanreotide
Ans. 4. Rotigotine

USMLE Case Scenario

A kinase inhibitor for advanced renal cell carcinoma is:
1. Aminopterin
2. Sapropterin
3. Tesamorelin
4. Temsirolimus
5. Herceptin
Ans. 4. Temsirolimus

USMLE Case Scenario

A drug that functions as a catechol-O-methyl transferase (COMT) inhibitor and is used in the treatment of Parkinsons disease
is:
1. Sapropterin
2. Letrozole
3. Thymosin alfa
4. Entacapone
Ans. 4. Entacapone

USMLE Case Scenario

A 50-year-old man has presented with pain in back, lack of interest in recreational activities, low mood, lethargy, decreased
sleep and appetite for two months. There was no history suggestive of delusions or hallucinations. He did not suffer from any
chronic medical illness. There was no family history of psychiatric illness. Routine investigations including hemogram, renal
function tests, liver function tests, electrocardiogram did not reveal any abnormality. This patient should be treated with:
1. Haloparidol
2. Sertraline
3. Alprazolam
4. Olanzapine
Ans. 2. Sertraline

Pharmacology

545

USMLE Case Scenario

A diaminopyrimidine dihydrofolate reductase inhibitor being developed for the treatment of complicated skin and soft
tissue infections caused by antibiotic-resistant bacteria. It is structurally related to trimethoprim intravenously-administered
iclaprim was found to be as effective in skin and soft tissue infections, many caused by methicillin-resistant Staphylococcus
aureus (MRSA). The drug is:
1. Filgastrim
2. Methcathinone
3. Iclaprim
4. Aminopterin
5. Levofloxacin
Ans. 3. Iclaprim

USMLE Case Scenario

Alosteron is approved for treatment of patients with Severe IBS with diarrhea. (Diarrhea predominant IBS). It is:
1. 5 HT 4 agonist
2. 5 HT 4 antagonist
3. 5HT 3 agonist
4. 5HT 3 antagonist
Ans. 4. 5HT3 antagonist

USMLE Case Scenario

Oprelvekin (Recombinant IL-2) is used in treating:
1. Thrombocytosis
2. Thrombocytopenia
3. Leucopenia
4. Leucocytosis
5. Eosinophilia
6. Eosinopenia
Ans. 2. Thrombocytopenia

USMLE Case Scenario

Linezolid is a protein synthesis inhibitor; Linezolid binds to the 23S portion of the 50S subunit (the center of peptidyl
transferase activity). Unlike most other protein synthesis inhibitors, linezolid appears to work on:
1. The step of protein synthesis, i.e. initiation
2. The step of protein synthesis, i.e. elongation
3. The step of protein synthesis, i.e. termination
4. The step of protein synthesis, i.e. assembly of proteins
Ans. 1. The step of protein synthesis, i.e. initiation

USMLE Case Scenario

Glucagon Like Peptide used in treatment of Diabetes is:
1. Piaglitazone
2. Rosiglitazone
3. Exenatide
4. Acarbose
5. Glucomannan
Ans. 3. Exenatide

546

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A coumarin anticoagulant used for the prophylaxis and treatment of thromboembolic complications associated with cardiac
valve replacement and atrial fibrillation, as well as the prophylaxis and treatment of venous thrombosis and pulmonary
embolism. It may cause necrosis of the skin. The mechanism for this reaction is related to its ability to deplete protein C,
which can lead to a state of hypercoagulability and thrombosis in the cutaneous microvasculature. The most likely drug we
are talking about is:
1. Aspirin
2. Warfarin
3. Dextran
4. Streptokinase
5. Urokinase
6. Clopedrigel
Ans. 2. Warfarin

USMLE Case Scenario

Tropisteron is used for treatment of:
1. Vomiting
2. Diarrhea
3. Constipation
4. Colic
5. Dysuria
Ans. 1. Vomiting

USMLE Case Scenario

Frovatriptan is used as:
1. Hypolipidemic
2. Antimigrane
3. Antispasmodic
4. Antiheliminthic
5. Anti-inflammatory
Ans. 2. Antimigrane

USMLE Case Scenario

A 44-year-old AIDS patient from New York, is being treated with multiple drugs, develops breast hypertrophy, central
adiposity, hyperlipidemia, insulin resistance and nephrolithiasis. If these changes are related to his drug treatment, this drug
belongs to which group of antiretroviral drugs?
1. Nucleoside reverse transcriptase inhibitors
2. Non-nucleoside reverse transcriptase inhibitors
3. Fusion inhibitors
4. Protease inhibitors
5. Integrase inhibitors
Ans. 4. Protease inhibitors

USMLE Case Scenario

A 39-year-old HIV positive male from Chicago patient comes to the OPD with complaint of anorexia, nausea and vomiting and
abdominal pain. His abdomen is tender in the epigastric area. Laboratory results reveal a raised serum amylase activity and
a preliminary diagnosis is made of acute pancreatitis. Which of the following antiretroviral drugs has the patient most likely
been taking?
1. Saquinavir
2. Zidovudine

Pharmacology

547

3. Didanosine
4. Efavirenz
5. Enfuvirtide
Ans. 3. Didanosine

USMLE Case Scenario

A 44-year-old HIV positive patient is receiving HAART regimen (Highly active antiretroviral therapy). Four weeks after initiating
therapy, he comes to the emergency department complaining of severe pain in the flank, nausea and frequent urination. A
USG Diagnosis of Nephrolithiasis is made. Which one of the following drugs is most likely the cause of his symptoms?
1. Zidovudine
2. Indinavir
3. Efavirenz
4. Nevirapine
5. Nelfinavir
Ans. 2. Indinavir

USMLE Case Scenario

A 66-year-old woman after having received an infected blood transfusion is diagnosed with chronic hepatitis B infection and
therapy is initiated. Just after a few hours she comes to the emergency department complaining of fever, chills and muscle
aches. Which one of the following drugs most likely caused these symptoms?
1. Infliximab
2. Adefovir
3. Acyclovir
4. Interferon alfa
5. Ribavirin
Ans. 4. Interferon alfa

USMLE Case Scenario

A 55-year-old patient with disseminated tuberculosis is prescribed drugs. Which of the following might be seen in patient of
TB, who has regularly been injecting intramuscular injection of streptomycin:
1. Blindness
2. Increased AST levels
3. Impotence
4. Deafness
5. Sweating in excess
Ans. 4. Deafness

USMLE Case Scenario

A 38-year-old Indian origin male with known TB infection and taking medication since 1 month comes to the Eye OPD with
complaint of visual disturbances including decreased visibility and slight color blindness. If these symptoms are due to his
drug treatment, which one of the following drugs is most likely the cause of his symptoms?
1. Streptomycin
2. Ciprofloxacin
3. Ethambutol
4. Rifampicin
5. Isoniazid
Ans. 3. Ethambutol

548

USMLE Step 1 Platinum Notes

USMLE Case Scenario

A 62-year-male from Texas who was on antipsychotic treatment was brought to the hospital with history of having taken
overdose, He was complaining of dry mouth, blurring of vision and mydriasis. He has not passed urine for 14 hours now. The
bladder is palpable, the medication could be:
1. Lithium
2. Selengilline
3. Amitryptiline
4. Denamphetamine
Ans. 3. Amitryptiline

USMLE Case Scenario

A 55-year-old is given intravenous Diazepam by an inexperienced anesthesiologist to supplement the local anesthetics that
are injected into her foot. Halfway through the surgery, she suddenly becomes agitated, combative, and exhibits involuntary
movements. The anesthesiologist determines that she is having a reaction to the drug which has been given in excess. Most
effective drug to be adminstered will be:
1. Glucagon
2. Naloxone
3. Nitrite
4. Protamine
5. Flumazenil
6. Buprenorphine
7. Morphine
Ans. 5. Flumazenil

USMLE Case Scenario

Digitalis toxicity aggrevated by:
1. Hypocalcemia
2. Hypercalcemia
3. Hypokalemia
4. Hyperkalemia
Ans. 3. Hypokalemia

BIOSTATISTICS

Biostatistics

NORMAL CURVE

Normal curve
Normal curve is smooth, bell shaped symmetrical curve with
Total area under curve = 1
Mean of curve = 0
Standard deviation = 1
Mean, Median and Mode coincide
Normal standard deviation has variance = 1
Standard deviation is a measure of deviation from mean
A graph representing the density function of the Normal probability distribution is also known as a Normal Curve or a Bell Curve
To draw such a curve, one needs to specify two parameters, the mean and the standard deviation
The graph above has a mean of zero and a standard deviation of 1
1SD = 68% of values
2SD = 95% of values
3SD = 99.7% of values
Z score determines how many standard deviations an observation is above or below the mean
Z score is done for normal distribution
Standard error = SD/root of sample size

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Standard deviations

Correlation

Deviations

Tests Used in Biostatistics

The student t-test is used to compare two means derived from two samples.
Analysis of variance is used when the means of a continuous variable are being compared in three or more groups or when the
independent variable responsible for a difference in means is being sought.
The chi-square test is commonly used to compare noncontinuous data in two groups
Both samples should be mutually exclusive.
The Fisher Exact Test and the Pittman Welch Permutation Test considers all possible permutations of the data and compares
them with the values actually observed.
Multiple Linear Regression is used to consider the impact of more than one independent variable on the dependent variable.

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The Paired t-test is typically used when an observation is made twice on a sample.
The Pearson Correlation Formula can be used for ranked data that have no intrinsic numeric value, where the ranking system
represents equal intervals between measurement units.
Simple Linear Regression is a process by which the data collected are fitted to the best straight line.
The Spearman Rank Order Formula produces a correlation coefficientA numeric way of describing the direction and strength
of the linear relationship between two variables. This particular formula is used for data that are continuous and based on ranking.
To compare the results obtained by a new test and a gold standard test, Bland and Altman test is used
Sensitivity and specificity are used for assessing criterion validity
Correlation indicates degree of association between two variables
Correlation coefficient of 1 means two variables expresses linear relationship
Causation implies correlation
True positive (TP) = A positive test result in the presence of the disease
True negative (TN) = A negative test result in the absence of the disease
False positive (FP) = A positive test result in the absence of the disease
False negative (FN) = A negative test result in the presence of the disease
Sensitivity = The ability of the test to identify the disease in those who have it
Equals TP/(TP + FN)
Specificity = The ability of the test to exclude the disease in the absence of the disease
Equals TN/(TN + FP)
Sensitivity and specificity determine validity of screening test
Screening is useful when incidence of disease in community is high.
The reliability of a measurement refers to the ability of other researchers to reproduce the results.
The accuracy of a measurement refers to the trueness of the measurement, i.e. how close the measured value is to the true
value
LJ chart measures accuracy.
The power of a study is best conceptualized as the probability of rejecting a null hypothesis that is in fact false. This is equal to 1
minus the probability of a type II error
The validity of a measurement is an index of how well the test measures what it purport to measure
Tests in parallel: sensitivity, specificity, PPV, NPV
Tests in series: sensitivity, specificity, PPV, NPV

True positivity is sensitivity

True negativity is specificity
False positive = 1-specificity
False negative = 1-sensitivity
Likelihood ratio for a negative test = 1-sensitivity/specificity
Likelihood ratio for a positive test = sensitivity/1-specificity

True positive is directly related to sensitivity

True negative is directly related to specificity
False positive is inversely related to specificity
False negative is inversely related to sensitivity
Prevalence = Incidence x duration. (prevalence duration)
Diagnostic power of a test to correctly exclude a disease is negative predictive value
Diagnostic power of a test to correctly diagnose a disease is positive predictive value
Bayes theorem gives relationship between PPV, sensitivity, specificity, prevalence of a screening test.

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EVALUATION OF SCREENING TESTS

Criteria

Numerator

Denominator

Sensitivity

True positive (a)

True positive + false negatives (a + c)

Specificity

True negatives (d)

True negatives + false positives (b + d)

PPV

True positives (a)

True positive + false positives (a + b)

NPV

True negatives (d)

True negatives + false negatives (b + d)

% False positives

False positives (b)

True negatives + false positives (b + d)

% False negatives

False negatives

True positives + false negatives (a + c)

Sensitivity is defined as the ability of a test to detect diseasemathematically, the number of true positives divided by the
number of people with the disease. Tests with high sensitivity are used for disease screening. False positives occur, but the test
does not miss many people with the disease (low false-negative rate).
Specificity is defined as the ability of a test to detect health (or nondisease)mathematically, the number of true negatives
divided by the number of people without the disease. Tests with high specificity are used for disease confirmation. False negatives
occur, but the test does not call anyone sick who is actually healthy (low false-positive rate). The ideal confirmatory test must have
high sensitivity and high specificity; otherwise, people with the disease maybe called healthy.
Positive predictive value (PPV): When a test is positive for disease, the PPV measures how likely it is that the patient has the
disease (probability of having a condition, given a positive test). PPV is calculated mathematically by dividing the number of
true positives by the total number of people with a positive test. PPV depends on the prevalence of a disease (the higher the
prevalence, the higher the PPV) and the sensitivity and specificity of the test, (e.g. an overly sensitive test that gives more false
positives has a lower PPV).
Negative predictive value (NPV): When a test comes back negative for disease, the NPV measures how likely it is that the patient
is healthy and does not have the disease (probability of not having a condition.
Experimental studies are the gold standard. They compare two equal groups in which one variable is manipulated and its effect
is measured. Experimental studies use double-blinding (or at least single-blinding) and well-matched controls to ensure accurate
data. It is not always possible to do experimental studies because of ethical concerns.
Prospective studies (also known as observational, longitudinal, cohort, incidence, or follow-up studies): Involve choosing
a sample and dividing it into two groups based on the presence or absence of a risk factor and following the groups overtime to
see what diseases they develop. For example, you can follow people with and without asymptomatic hypercholesterolemia to see
if people with hypercholesterolemia have a higher incidence of myocardial infarction later in life. You can calculate relative risk and
incidence from this type of study. Prospective studies are time-consuming and expensive but practical for common diseases.
Retrospective (case-control) studies: Choose population samples after the fact, based on the presence (cases) or absence
(controls) of disease. Information can be collected about risk factors. For example, you can compare people with lung cancer
and people without lung cancer to see if people with lung cancer smoked more before they developed lung cancer. With a
retrospective study you can calculate an odds ratio, but you cannot calculate a true relative risk or measure incidence. Compared
with prospective studies, retrospective studies are less expensive, less time-consuming and more practical for rare diseases.
A case series study simply describes the clinical presentation of people with a certain disease. This type of study is good for
extremely rare diseases (as are retrospective studies) and may suggest a need for a retrospective or prospective study.
Prevalence (cross-sectional) surveys look at the prevalence of a disease and the prevalence of risk-factors. When used to compare
two different cultures or populations, a prevalence survey may suggest a possible cause of a disease. The hypothesis then can be
tested with a prospective study.
Incidence is the number of new cases of a disease in a unit of time (generally 1 year, but anytime frame can be used). The incidence
of a disease is equal to the absolute (or total) risk of developing a condition (as distinguished from relative or attributable risk).
Prevalence is the total number of cases of a disease (new or old) at a certain point in time.

Positive skew: Mean > Median > Mode

Negative Skew: Mean < Median < Mode
Type I error: Null hypothesis true but rejected
Type II error: Null hypothesis wrong but accepted

Biostatistics
Cross-sectional studies:
Cohort studies:
Case control study:

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Chi-square test
Relative risk, Attributable risk, Incidence rate
Odds ratio

Odds Ratio >1 = Risk

Odds Ratio < 1 = Protective
Odds Ratio = 0 = No effect
Odds = probability/1-probability

Chi-square test: Compare proportions

Two sample Z test: Compare populations
Two sample t Test: Compare samples
Anova: Three or more variables
Meta Analysis: Pooling of data from several studies. Gives most accurate results

Usefulness of screening test: Sensitivity

Statistical index of diagnostic accuracy: Sensitivity
Power of a test= 1-
Relative risk: Incidence among exposed/incidence among nonexposed
Attributable risk: Incidence among exposed minus incidence among nonexposed/incidence among exposed multiplied by 100.
For example a study showing 80% of lung cancers are due to smoking is an attributable risk
Population attributable risk: Incidence of disease (or death). In total population minus incidence of disease (or death) among
those who were not exposed to suspected casual factor.

P-value
The likelihood that an observed difference or an even more extreme difference is due to chance alone is called the p-value. In our
study, if certain differences between mean values in treatment say BP in treatment and control groups was observed, p < 0.05
would mean: given that the null hypothesis is true, there is a < 5% likelihood that this difference or a larger difference is due
to random sampling
Thus, if the p-value is small, it is unlikely that an observed difference is due to random sampling, the null hypothesis is
rejected, and it is inferred that real population differences or a real association exists between treatment and response
A small p-value (the conventional level for small has been traditionally accepted as 0.05) safeguards against chance leading
us to reject a null hypothesis which is true
A very low p-value strongly suggests that the observed data are inconsistent with the null hypothesis
The error of rejecting a true null hypothesis is called type I error. This occurs when chance leads to inferring differences or
associations that do not exist
In contrast, type II error occurs when a large p-value leads to the incorrect conclusion that a difference does not exist (incorrectly
not rejecting a null hypothesis).
Chi-square test is the most important test measuring association between two variables
It measures the probability of association between two variables.
The chi-square test assumes that no association exists between two events
Chi-square test is a nonparametric test
Tests significance of assosciation between two or more qualitative variables.
Correlation
Describes the strength of linear relationship between two variables
It is denoted by Correlation coefficient or Pearsons Coefficent
Its Value ranges from 1 to + 1

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Correlation
Types of correlation

Correlation coefficient

Examples

Perfectly positive

r=+1

Height and age

Perfectly negative

r=1

Pressure and volume of gas

Moderately positive

0<r<+1

Temperature and pulse rate

Moderately negative

1< r<0

Age and vital capacity

No corelation

r=0

Husbands skin color and fertility

Spurious coorelation

Skin color and IQ

Z-score is done for normal type of distribution

Z-score is calculated using a standard normal distribution curve. The distance of a value (x) from the mean (x) of the curve in units of
standard deviation is called relative deviate or standard normal variate and is usually denoted by Z.
Binomial Distribution The probability that a specific combination of mutually exclusive independent events will occur can be
determined by the use of the binomial distribution. A binomial distribution is one in which there are only two possibilities, such as Yes/
No, male/female, healthy/sickly. A typical medical use of the binomial distribution is in genetic counseling.
Comparison of Proportions Proportions are compared when the data is measured on a nominal or ordinal scale
The test, which is commonly used, is the chi-square test. It is a nonparametric test
The test is done by constructing 2 2 contingency table and calculating the expected frequency of the variable from the observed
frequency. The test can be applied in two or more independent groups and a paired group.

Cronbachs (alpha)
Cronbachs (alpha) is a measure of internal consistency reliability
Internal consistency reliability is used when one wants to know whether the items on a test are consistency with one another in
that they represent one, and only one, dimension, construct, or area of interest.

Correlation Coefficient
A correlation simply expresses the strength and direction of the relationship between two variables in terms of a correlation
coefficient
It does not tell about causation
It does not tell about the risk of diseases.

Probability

It is the chance that a particular event will occur. Probability range is zero to hundred
Percent (01) Probability can never be zero
Probability cannot exceed one
Probabilities are added for mutually exclusive events
Probabilities are multiplied for independent events

Quantitative Continuous Data is represented by

Histogram
Bar Diagram
Frequency polygon
Pie chart

Biostatistics

Division of Distribution
Divides distribution into

No. of intercepts

Tertile

3 equal parts

Quartile

4 equal parts

Pentile

5 equal parts

Hextile

6 equal parts

Heptile

7 equal parts

Octile

8 equal parts

Ductile

10 equal parts

Centile (percentile)

100 equal parts

99

Variables

Quantitative: can be measured directly. Height, weight

Qualitative: cannot be measured directly. Weather, gender
Discrete variable: has few possible values, no in-between values. Blood group, gender
Continuous variable: large number of possible values and several in-between values. Weight, height
Dichotomous variable: only two possibilities exist, e.g. Blood group A + or
Polyotomous variable: more than 2 possibilities exist. Weight, height

So
Height is a quantitative, polyotomous variable
Gender is a qualitative, discrete, dichotomous variable

Variable
It is a charactertistic or attribute that varies from person to person
Quantitative:
Variable that can be measured directly
Height
Weight
Hemoglobin
Blood urea
Qualitative:
Variable that cannot be measured directly
Weather
Obesity
Gender
Discrete variable:
It is a variable that has few possible values and no in-between values
Examples:
Parity
Gender
Obesity

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Continuous variable
It is a variable that has large number of possible values and few in-between values
Examples:
Weight
Height
Blood sugar level
Dichotomous variable
It is a variable that has only two possible values
Examples:
Blood group A present or absent
Gender: male/female
Polyotomous variable
It is a variable that has more than two possible values
Examples:
Weight
Height
Serum cholesterol

Scales of Measurement
Categorical scales
Nominal scale

Ordinal scale

Dimensional scales
Metric scales

Definition

Based on NOM (names):

No specific order

Based on ORD (order):

Grading into categories

Based on ME (measurement): in terms of

quantities

Variables

Qualitative

Qualitative

Quantitative

Examples

Race

TNM staging(cancers)

Blood glucose

Religion

Severity of a disease

Hemoglobin level

Country of birth

Social classes

Serum cholesterol

Clinical features

Weight

Sites of lymphadenopathy

Height

Sex of child

Mid arm circumference

Type of anemia

Blood pressure

ABO blood group

Pulse rate

Site of malignancy

Temperature(C, F,K)scale
Ratio scale: Geometric mean
Harmonic mean, coefficient of variation

Case control study

Cohort Study

Proceeds from effect to cause (retrospective)

Usually Proceeds from cause to effect

Starts with disease

Easy to carry

Starts with people exposed to risk

Involves fewer subjects

Involves larger number of subjects

Gives quick results

Gives delayed results

Suitable for rare diseases

Suitable for common diseases

Contd...

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559

Contd...

Case control study

Cohort Study

Yields odds ratio

Yields casual association
Risk factor can be identified

Yields
Incidence
Attributable risk
Relative risk

Inexpensive

Expensive

Attrition can be a problem

Attrition not a problem

Minimal ethical problems
No risk to subjects
Rapid
Inexpensive

Nested Case Control Studies

It is a type of case control study that draws its cases and controls from population that has been followed for a pretty long
period of time
Potential recall bias and temporal ambuiguity are reduced
Likelihood of selection bias is also reduced
It is considered to be a strong observational study
It is cost effective as well

Cross-sectional Study

Based on single examination of a cross-section of population at one point of time

Provides information about prevalence of disease
Gives snapshot of a population
More useful for chronic diseases
Does not establish time sequence

Different Types of Bias

Proficiency Bias occurs when the intervention under consideration is delivered with unusual skill (or incompetence) so that it cannot
be reproduced in typical settings.
Ascertainment Bias occurs when patients with the suspected outcome are most extensively probed about their symptoms and
histories than are patients without the suspected outcome.
Detection Bias occurs when more information is solicited from the treatment group than from the placebo group.
Recall Bias occurs in retrospective studies. Patients may not remember the severity of their symptoms or how much intervention
occurred over the specified course of time.
Referral Bias occurs when the sample of patients used in a study is not typical of the general population. For example, if an academic
medical center sees the most acutely ill patients admitted for bypass mortality rates will appear extraordinarily high.
Susceptibility Bias occurs when patients receive one intervention or another on the basis of the severity of their disease. For example,
since sicker patients would be less likely to survive a coronary bypass operation, they might be designated to receive medical
therapy instead. This, however, might result in poorer outcomes for the medical therapy group. Susceptibility bias can be avoided by
randomizing subjects to different study groups
Attention bias (Hawthorne effect) occurs when subjects under study may alter their behavior when they know they are being observed.
Berkensionian bias admission rates to hospital differ.