Goljan Audios Transcribed (Margaret)

Goljan Audio Lecture Notes
Almostverbatim
Table of Contents
Cell Injury 1..pg 3
Cell Injury 2..pg 6
Inflammation 1.....pg 10
Inflammation 2.pg 15
Fluid and Hemodynamics 1...pg 28
Nutrition 1.pg 35
Nutrition 2.pg 40
Neoplasia 1..pg 45
Neoplasia 2..pg 47
Neoplasia 3..pg 53
Hematology 1..pg 57
Hematology 2..pg 59
Hematology 3..pg 63
Hematology 4..pg 67
Hematology 5..pg 72
Hematology 6..pg 78
Hematology 7..pg 84
Hematology 8..pg 91
Cardiovascular 1.pg 95
Respiratory 1...pg 123
Gastrointestinal 1pg 137
Gastrointestinal 2pg 149
Hepatobiliary-Pancreas 1..pg 153
Hepatobiliary-Pancreas 2..pg 162
Renal 1.pg 166
Renal 2.pg 172
Gyn 1.pg 180
Endocrine 1..pg 187
Endocrine 2..pg 193
Musculoskeletal...pg 200
Skinpg 205
CNS...pg 208
CNS-Special Senses..pg 211
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Cell Injury 1
Hypoxia
inadequate oxygenation of tissues; same def as shock

o O2: needed for oxidative phosphorylation pathway make ATP in inner mitochondria
membrane
O2: final electron acceptor in oxidative phosphorylation
O2 content: Hb *O2 saturation + partial pressure of arterial oxygen (PaO2)
o Hb: O2 attached to heme group O2 saturation
o Amount of O2 dissolved in plasma PaO2
Red blood cell has 4 heme groups with Fe in 2+ state
o All 4 heme groups: occupied by O2; O2 sat is 100%
o O2 sat: O2 in red cells attached to the heme groups; measured by pulse oximeter
o PaO2: O2 dissolved in plasma; O2 flows from alveoli interface dissolve in plasma
diffuses thru RBC membrane attach to heme groups on Hb
o If PaO2 is decreased: O2 sat is DECREASED (because O2 sat depends on amount
dissolved in plasma)
One cause of hypoxia: ischemia decreased ARTERIAL blood flow
o frequently caused by thrombus in muscular artery
o also include: decreased cardiac output (hypovolemia, cardiogenic shock)
Second cause of hypoxia: hypoxemia
o Hypoxemia: deals with PaO2; O2 dissolved in arterial plasma; when decreased
hypoxemia
o When CO2 is retained/increased (resp acidosis) O2 decreases! (inverse relationship)
When CO2 decreases (resp alkalosis) O2 increases
Ventilation defect
o ARDS in adults/hyaline membrane disease in children
o Loss of ventilation to alveoli but perfusion is okay interpulmonary shunt (pt with
hypoxemia; give 100% O2 for 20 minutes and PaO2 does NOT increase)
Perfusion defect: most frequently due to PE (board question!)
o Associated with prolonged flights; deep vein stasis
o Ventilation is fine but no perfusion dead space
o Give 100% O2 will INCREASE PaO2 (because other areas in the lungs that are
perfuse can make up for the difference)
Diffusion defect: something in the interface that O2 cant get through
o Due to fibrosis; seen in sarcoidosis and restrictive lung disease
o Can also due to pulmonary edema, or fluid seen in heart failure (dyspnea due to
activated J reflex/J receptor by CN 10)
Hb-related problems causing hypoxia:
o Anemia: normal gas exchangePaO2 is normal, O2 sat is normal but Hb is decreased
But inadequate amount of Hb leads to decreased O2 delivery to tissues (tissue
hypoxia, exertional dyspnea, exercise intolerance)
o CO poisoning:
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Scenario: heater in winter time in closed room; house fire (cyanide poisoning)
House fire: both CO and cyanide poisoning
Very high affinity for Hb O2 sat is decreased because heme groups are now
occupied by CO and not O2
Sign of decreased O2 sat: cyanosis; but wont see cyanosis in CO
poisoning due to cherry-red membrane
Most common symptom: headache
Treat with 100% O2
o Methehemoglobin: Fe is in 3+ state cant bind to O2
O2 sat is decreased; [Hb] normal. PaO2 normal
Typical presentation: throw up blood that is chocolate-colored
This is why RBC has Hb reductase (in the glycolytic cycle; converting Fe 3+ back
to 2+)
Climber coming out of Rocky mtn, cyanotic, and still cyanotic after 100% O2
Probably drank water in mtn that has lots of nitrite and nitrate; both are
oxidizing agents and oxidize Fe
Tx: IV methyline blue; vitamin C (a reducing agent); dapsone (also used to treat
leprosy; a sulfa drug)
Sulfa and nitro drugs: produce met-Hb; and hemolytic anemia in G6PD
deficiency
Met-Hbnemia: commonly seen in HIV pt because on TMX-SMX tx for PCP
o Hb Dissociation Curve
Right shift: release O2
Causes: 2, 3-BPG; fever; low pH (acidosis); high altitude (resp alkalosis)
In resp alkalosis: decreased CO2, increased O2
high altitude increased synthesis of 2,3-BPG
Left shift: higher affinity for O2
Causes: CO; Met-Hb, HbF, decreased 2,3-BPG; alkalosis
CO: decreased O2 sat and left shift
Problems related to oxidative pathway
o Cytochrome oxidase: last enzyme before transferring electron to O2
Cyanide and CO inhibit cytochrome oxidase (3 Cs)
3 effects of CO poisoning: decrease O2 sat (cant carry a lot of O2); left shift the
curve (cant release O2); and even after O2 released, there is no e- because
cytochrome oxidase is blocked
o Uncoupling: ability for the mitochondria to synthesize ATP is impaired
Inner mito mb is permeable to protons; only want protons to go thru ATP
synthase
Dinitrophenol (preserve wood); EtOH, salicylate uncoupling agents; protons
just go thru the membrane randomly ATP synthesis drops
Reactions that generate protons and deliver to ETC: reactions making NADH,
FADH2; thus these reactions speed up because protons are dissipated
Increased reactions: increased body temp hyperthermia
Salicylate toxicity: uncoupling agent hyperthermia
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Alcoholic on a hot day: heat stroke; hyperthermia
Review:
o Resp acidosis: Hb normal, O2 sat decrease, PaO2 decrease
o Anemia: only Hb is abnormal; O2 sat and PaO2 normal
o CO and Met-Hb: Hb normal; O2 sat decrease; PaO2 normal
o Tx CO: 100% O2
o Tx Met-Hb: IV methyline blue and vitamin C (ascorbic acid)
Decreased ATP due to tissue hypoxia
Anaerobic glycolysis: end product is lactic acid

o Due to increased in NADH
o Needs to make NAD+ for glycolytic cycle to make 2 more ATP
o The only place to make 2 ATP without going thru mitochondria: anaerobic glycolysis!
Even RBC can do so
Good news: get 2 ATP from anaerobic glycolysis; bad news: build-up lactic acid
o Lactic acidosis (anion gap metabolic acidosis)
o Increased acid in cells: denature proteins
When enzymes are denatured, cells cant auto-phagocytosis coagulative
necrosis
o Coagulative necrosis: occurs during tissue hypoxia
Gross view: infarction
all ATPases stop
o Na/K ATPase blocked
Can be blocked by digitalis; open up Ca channel increase contraction
Without ATP, Na+ goes into the cell and brings water cellular swelling
(hydropic degeneration)
Reversible upon O2 tx
Irreversible changes: Ca enters cell
o Ca ATPase: as ATP is decreased, Ca goes into cells activate lots of enzymes
Phopholipase: damage membrane
In the nucleus: nuclear pyknosis
In mitochondria: destroy mitochondria
o Acute hypercalcemia: can lead to acute pancreatitis
Enzymes released when cells die:
o CK or CK-Mb in MI
o Transaminase (AST, ALT) in hepatitis
o Amylase in pancreatitis
Free Radicals
Very commonly see in older people as their organs undergo degeneration

o Liver: brown pigment; has lipofusin (wear and tear pigment)
Without hx: brown pigment can be hemosiderin, hemosiderosis,
hemochromatosis, bilirubin
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End product of free radical damage: lipofusin

Certain things in the cells that cant be completely broken down, i.e. lipids
Free radical: has one un-paired eo Very damaging to cells
O2: can be superoxide free radical
o Associated with re-profusion injury
o Children with respiratory distress syndrome: free O2 radicals destroying retinal
retinopathy of prematurity
o Damage to lungs: bronchopulmonary dysplasia; fibrosis in lungs
H2O: can be converted into hydroxyl free radicals
o Due to ionizing radiation (i.e. radiation used in cancer tx)
o Most common cancer due to radiation: leukemia
Fe: creates free hydroxyl radicalscomplication in Fe overload
o in liver: cirrhosis
o In heart: restrictive cardiomyopathy
o In pancreas: non-functional mal-absorption and diabetes
Cell Injury 2
Free Radicals
Tylenol (acetaminophen): number 1 cause of fulminant hepatitis due to free radicals

o cytochrome P450 system in liver metabolize drugs as well as converting drugs into free
radicals
o also can damage kidneys, esp combined with ASA (cumulative effects, chronically)
renal medulla: only gets 10% of O2 supply (relatively hypoxic); free radicals
destroy medulla
also deplete PGE2 (vasodilator) made in afferent arteriole; angiotensin II (a
vasoconstrictor) is left to control renal blood flow unable to concentrate or
dilute urine; renal papilla also destroyed analgesics nephropathy
o damage in the liver centers around the central vein
tx: N-acetylcysteine neutralize free radicals
o Neutralize superoxide free radicals: superoxide dismutase
Glutathione: from pentose phosphate shunt
o Also generates NADPH used in anabolic pathways (steroids, cholesterol)
o Function: neutralize free radicals (drug induced or free radicals from peroxide)
o Glutathione is made from N-acetylcysteine; making more glutathione to neutralize free
radicals created by acetaminophen
Carbon tetrachloride: seen in dry-cleaning industry
o Forms CCl3 in the liver as free radicals fulminant liver disease
Apoptosis
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Programmed cell death; genes involved in cell death

o Aging: programmed to die
Normal functions in:
o Embryology: lumen is created via apoptosis
Y chromosome: Mullerian inhibitory factor as a signal for apoptosis with
caspases; no uterus/cervix/upper 1/3 vagina
X chromosome: Woffian duct structures are apoptosed
o Thymus: involute at adulthood due to apoptosis
No thymus: DiGeorges syndrome; tetany
o Killing cancer cells; virus-infected cells
o Atrophy: reduced cell/tissue mass
Individual cell death; without much inflammation around it
o Signal (hormone, or chemical) activate caspases tissue/cell destruction
o Ex of apoptosis: calcium body (no/pyknotic nucleus, eosinophilic/pink cytoplasm)
Necrosis
Damaged tissues that die

Types of necrosis
o Coagulation: gross manifestation is called infarction
Microscopic: resemble normal structure but no nuclei, bright red, little
inflammatory infiltrate
Due to increase in lactic acid; tissues cant be broken down; depend on PMNs
that have to come in from outside of dead tissues
Hemorrhagic vs. pale coagulative necrosis:
Depends on the consistency of the tissues
When tissue dies with blood vessels blood is released, but if tissue has
good consistency, blood cant leak out and thus looks grossly pale
o Usually seen in heart, kidney, spleen, liver (although infarct is rare
due to double blood supply)
GI tracts/bowel: tissues are loose consistency; usually would be
hemorrhagic as blood can easily trickle out of tissues
o Also seen in testicular torsion; lungs
o Common causes of bowel infarction: adhesion of bowels from
previous surgery > indirect inguinal hernia
o Testicular torsion: board question!
Lungs: hemorrhagic infarction at the periphery; wedge-shaped; went thru
pleural surface
o Effusion: exudate (polys)
o Pleuritic chest pain on expiration when pleura are inflammed
o Can also be produced from embolus
o Embolization
Most emboli arise from left side of the heart
When emboli go to spleen pale infarction
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Vegetation in acute rheumatic fever rarely embolize; but infective endocarditis
can
Mitral stenosis: heart repeated attacked by beta strep; can develop big thrombi in
the atrium
Arrhythmia mostly associated with systemic thrombosis: a-fib
o Gangrenous
Wet
Dry: no pus (usually seen in diabetic foot due to atherosclerosis and/or deep
thrombosis in popliteal artery)
Dry gangrene can also be a form of coagulative necrosis due to ischemia
Ischemia: decrease in arterial blood flow; most likely due to
atherosclerosis in popliteal artery in this pt
MI: coronary thrombosis over atherosclerotic plaque
Coagulation necrosis: usually the underlying type of necrosis seen in infarction
o Exception: brain; when infarcted (bruit over narrowed carotid artery due to platelet
thrombosis develops over atherosclerotic plaque)
o Also the place where pieces of plaque break off and produce TIA that disappears within
24 hours
o Astrocytes = fibroblasts in brain; provides structure to the brain
o When brain is infarcted: liquefactive necrosis; no more structure is left; only have
holes/cystic space left
Liquefying tissues: done by polys
Liquefactive necrosis
o Usually in infections when neutrophils are involved (abscess); acute inflammation
o Exception: liquefactive necrosis in the brain due to infarct, not infection
o Abscess: usually have gram + cocci in clusters
o Clusters: due to coagulase
Coagulase converts fibrinogen to fibrin and traps neutrophils/localize infection
abscess
o Strep: release hyaluronidase breaks down tissue GAG infection spreads i.e. cellulitis
Granulomatous necrosis:
o caseous necrosis: cheese-like consistency
Either have any mycobacterial or systemic fungal infection
Lipid in the cell walls in the organism gives the cheesy appearance
In sarcoidosis: non-caseating granuloma
o Foreign body giant cells
Enzymatic fat necrosis
o Fat necrosis related to enzymes
o pancreatitis: pain radiating to the back because pancreas is a retroperitoneal organ
usually seen in alcoholics
elevated level of lipase (more specific than amylase, which is also in parotid
glands, small bowel, fallopian tube)
o enzymes breaking down fats into fatty acids, which then combine with Ca to produce
chalky areas soapnification, can be seen on x-ray because it has Ca
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o blue in histologic section: ca; seen in dystrophic calcification of atherosclerotic plaque

Traumatic fat necrosis:
o Woman with pendulous breasts that get damaged from running
o Usually occurs in breast or other adipose tissues
o Can calcify and mimic cancer but in this case, calcification is painful
Painless calcification in cancer
fibrinoid necrosis
o noid: looks like something but its not
o Necrosis of immunologic diseases/damage
Palpable purpura (small vessel vasculitis; type 3 hypersensitivity)
Circulating immune complex activating alternative complement system
(C5a)chemotactic to neutrophils neutrophils do damage to tissues
Rheumatic fever: vegetation along mitral valve sterile, has fibrin-like material
Rheumatoid arthritis
Lupus glomerulonephritis
Liver
Portal vein, hepatic artery, bile ducts triads

o Liver has dual blood supply: hepatic vein and artery dump into sinusoids
o Other sinusoid organs: glomeruli, spleen
o Sinusoid characteristics: gaps between endothelial cells; RBCs/inflammatory cells can fit
through
Fenestrated: small pores that go thru actual cells; seen in glomerular basement
mb
o SinusoidCentral vein hepatic vein inferior vena cava right atrium
If there is right heart failure: congested liver (nutmeg liver)
o Congested hepatomegaly
o If portal vein is blocked: nothing happens to liver
The part of liver that is most easily damaged: around central vein
o Because this area gets first dip on O2 coming out of sinusoids (zone 1)
o Zone 2: where yellow fever hits (mid-zone necrosis)
o Zone 3: central vein, similar to renal medulla because there is very little O2 supply
Fatty changes around zone 3
Gets least amount of O2 and cant fight against free radical injury
Most common cause of fatty change: alcohol
o Acetyl-coA can be converted into fatty acids in the cytosol
o Increase NADH in alcoholics drives pyruvate reaction into lactic acidosis
Cant make glucose: hypoglycemia
Acetyl-coA can also make ketone bodies: beta-hydroxybutyrate in alcholics
Metabolism in alcoholics
o Lactic acidosis: driving pyruvate into lactic acid
o Increased ketone body synthesis
Fatty change: most likely due to alcoholism
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Glycolysis: lots of NADH reactions; in reaction 4 forcing it to become glycerol 3-P
Glycerol 3-P: makes triglyceride
In liver, its VLDL (endogenous triglyceride synthesis, derived from glycerol 3-P from
glycolysis)
o Restriction of carbohydrates, but not fats, would decrease VLDL synthesis
o After VLDL is made, needs to have apoproteins to export VLDL outside of cells
Decrease protein intake: decreased apolipoproteins cant export VLDL
Needs to have proteins around lipids for them to dissolve in water
Big abdomen in kids: decrease in protein (decrease in oncotic pressure
ascites); huge liver due to fatty change
Different from alcoholics fatty change: increased synthesis in VLDL due to lack of
apoproteins
When cellular debris cant be completely broken down lipofusin
Ferritin: soluble form of circulating Fe; great marker for amount of Fe in bone marrow
o Test of choice for dx any Fe-related diseases: Fe deficiency anemia; anemia of chronic
disease; Fe overload disease (hemochromotosis, hemosiderosis) all soluble form of
Fe
o Hemosiderin: insoluble form of Fe, usually stored in bone marrow mq
o Stain with Prussian blue
o
o
o
Inflammation 1
Types of Calcification
Dystrophic calcification
o Dys: abnormal; abnormal calcification
Damaged tissues get calcified
hematoma in thigh calcification
enzymatic fat necrosis with chalky white areas
atheromatous plaque; reversible with strict Ornish diet
o Most common cause of aortic stenosis; certain types of hemolytic anemia
Aortic valves are normally tri-leaflet; when damaged/calcified becomes
bicuspid
Most common cause of aortic stenosis in the US: congenital bicuspid aortic valve
o Serum Ca is normal
o Most of the time its dealing with dystrophic calcification
Metastatic calcification
o When calcium is deposited in normal, non-damaged tissues
Can occur with hypercalcemia or hyperphosphatemia
Seen in: primary hyper-PTH; malignancy-induced hypercalcemia;
o High Ca or phosphate level
High phosphate would drive Ca into normal tissues (heart, conduction system;
renal tubules and basal membrane nephrocalcinosis)
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Spherocytosis
Cant see a central area of pallor

Its a cell mb defect; due to absence of spectrin in RBC mb
o RBC cant form a bi-concave disc shape and form a sphere instead
Ubiquitin
A stress protein; level increase under stress

IF (keratin; vimetin; desmin) keeping cells connected together
When IF is damaged ubiquitin marker (by ubiquinating) and damaged tissues are destroyed
Ubiquinated products:
o Open space in liver tissue: fatty liver
Most likely due to alcohol
Pink material in liver: mallery bodies (ubiquinated kertain)
Alcoholic hepatitis
o silver stain of neurofibullary tangles: Alzheimers or Creutzfeldt (CJD)
tau protein: associated with neurofibullary tangles
o substantia nigra: Parkinsons
Lewy body inclusion; NT deficiency in Parkinsons dopamine
Three types of Cells
Labile cells:
o Division is via stem cell
o Three tissues that have stem cells: BM; basement mb of skin; base of crypts in
intestines
o Tend to be in cell cycle a lot
o Drugs that are cell cycle specific: labile cells are affected the most
When drugs block cell cycle BM suppression; diarrhea; rashes on skin;
Stable cells: in G0 phase (resting phase)
o Ex: parechymal organs (liver, spleen, kidney); smooth muscle
Hypertrophy: increase in size
Hyperplasia: increase in number
Smooth muscle cells can undergo both hypertrophy and hyperplasia
o Needs to be stimulated to move into cell cycles: hormones (estrogen in menstrual cycle
stimulating endometrial cells); growth factors
o Can divide, but needs to be stimulated
Permanent cells:
o Permanently differentiated; can no longer get into cell cycle
o Ex: striated (cardiac) cycle; neurons
o Can undergo hypertrophy but not hyperplasia
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Cell Cycle
Most variable phase: G1 phase; or proliferative phase in menstrual cycle

o Cancer cells: most have longer cell cycles due to longer G1 phase or shorter cycle due to
shorter G1 phase
Cyclin-dependent kinase (CDK)
o Kinase: always phosphorylation
Phosphorylation: usually leads to activation
Glucagon: phosphorylator; insulin: dephosphorylator
o G1 phase makes cyclin D activates CDK
Key area to control in cell cycle: from G1 to S phase
o If there is a mutation in G1 and moves into S phase duplication occurs, potential for
cancer development
o Two suppressor genes:
Rb (chromosome 13) makes Rb protein; prevents cell from going into S phase
Active CDK phosphorylates Rb protein cell can then move into S phase
Rb suppressor gene: would prevent cell go into S phase
P53 (chromosome 17): inhibit CDK prevent cells from going into S phase
Number 1 gene for human cancer
Human papilloma virus: inactivates both Rb and P53 suppressor genes
o E6: knocks off P53; E7 knocks off Rb suppressor gene
If knocking off Rb suppressor gene via point mutation
o Normally prevents cell from going into S phase
o When knocked off: cancer development
retinoblastoma
osteogenic sarcoma: knee pain in children
breast cancer
Knocking off P53:
o Kinase would always be active and always phosphorylating Rb always moving into S
phase
o P53 normally gives cell time to detect any anomalies in DNA (i.e. splicing defect)
DNA repair enzyme can then repair the cells
o If the cells are damaged too much and cant repaired apoptosis
o P53: guardian of cells
S phase: synthesis phase
o Everything is doubled: DNA, chromosome 4N
G2 phase:
o Makes tubulinmakes microtubules for mitotic spindle
o Can be blocked utopocytes? And bleomycin?
Mitosis: cell divides into 2N
o Cells go then go into G0 phase, or divide again, or become permanently differentiated
Drugs that inhibit cell cycle: must know!
o Alkaloids: mitotic spindle
o Paclitaxel: M phase
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o Colchicine: ?
o Utopocyte: G2
o Gleomycin:?
o Griseofulvin: M phase
o Methotrexate: S phase, blocking dihydrofolate reductase
Ex of drug questions:
o HIV pt that has tachypnea and dyspnea, becomes cyanosis after being put on a drug
dapsone
o This drug used to be used for acute gouty arthritis: colchicines, M phase
o Chemotherapy agent made from Yew tree: Paclitaxel; M phase
o Alkaloids made from periwinkle plants
Growth Alternation: Atrophy
Decrease in tissue mass; cells decrease in size

o Has just enough organelles to survive; less mitochondria than normal
Hydronephrosis: thinning of cortex and medulla due to compression atrophy
o Common cause: dilated pelvis stone in ureter
o Increased pressure ischemia reduced blood flow atrophy of renal tubules
Brain atrophy:
o Can be due to atherosclerosis (most common), knock-off neurons (i.e. Alzheimers,
destroy neuron in layer 3, 5 and 6 )
o Degeneration of neurons: beta-amyloid proteins are toxic to neurons
Muscle atrophy:
o Causes: ALS, denervation, guillers disease?
Endocrine-related atrophy:
o Hypopituitarism: adrenal glands (fasiculata and reticularis layers) atrophy
ACTH does not stimulate aldosterone release; hence no glomerulosa layer
o Taking thyroid hormone thyroid gland atrophy
Decreased TSH thyroid atrophy
Child with cystic fibrosis: atrophy of pancreas
o CFTR mutation on chromosome 7 problems with secretion; blocks the ducts
o Blocking lumen of glands back-pressure increases; atrophy of glands malabsorption
Atherosclerotic plaque in kidney: atrophy
o Renal vascular HTN
o Renin level in this kidney: high
o And in the opposite kidney: hypertrophy
renin level coming out of renal vein: decreased
Growth Alternation: Hypertrophy
hypertrophy of cardiac muscle, block in early G2 phase: chromosome number is 4N

o 1N: sperm
o 2N: normal diploid cell
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o 3N: trisomy disease, or cancer

Hypertrophy: increase in SIZE, not number of cells
Growth Alternation: Hyperplasia
Increase in NUMBER of cells

Normally seen in endometrial glands during proliferative phase
o Increasing number of endometrial glands with increased cell division
o Unopposed estrogen (if there is no progesterone)hyperplasia atypical hyperplasia
cancer!
Hyperplasia left UNCHECKED high risk for cancer
o Only exception: prostate hyperplasia does not predispose to prostate cancer
Gravid uterus after delivery:
o 50% hypertrophy of smooth muscles cells in the wall and 50% hyperplasia
Bone marrow:
o Normally has 3x as many WBCs as RBCs
o When there are lots of RBCs RBC hyperplasia
Seen in: COPD pt (not in thalassemia or Fe deficiency)
Hypoxemia releasing EPO, made in endothelial cells of peritubular capillary
Psoriasis:
o Unregulated proliferation/hyperplasia of squamous cellssilvery scale, red raised
plaque
o Can be blocked by methotrexate prevent basal cells from proliferating
Prostate hyperplasia:
o Hormone-related
o All hormone-stimulated glands undergo hyperplasia, not hypertrophy
Bladder:
o Wall is too thick: hypertrophy of smooth muscle cells due to increased afterload
o Hyperplasia of prostate
Growth Alternation: Metaplasia
Replacement of one adult cell type with another

Esophagus ulcerated away:
o Glandular cells (goblet cells, mucous-secreting cells) present in lower esophagus
o Should have squamous cell in this section
o Squamous glandular epithelium to deal with acid injury (needs mucous-secreting
epithelium) glandular metaplasia dysplasia adenocarcinoma of distal esophagus
o Barretts esophagus precursor for adenocarcinoma
o GERD: number 1 precursor for esophageal cancer
Lining of main stem bronchus: ciliated columnar pseudostratified
o In smoker: squamous metaplasia
Progress into squamous dysplasia squamous carcinoma
o Normally there are goblet cells main stem bronchus
Increased number: hyperplasia
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Goblet cells in terminal bronchial of a smoker metaplasia because normally there
shouldnt have any goblet cells
stomach
o Goblet cells should be present in intestines, not in stomach
o When goblet cells are in stomach: glandular metaplasia precursor for adenocarcinoma
of stomach
o Most common cause of adenocarcinoma of stomach: H. Pylori
H. pylori damages pylorus and antrum mucosa chronic atrophic gastritis
Two parasites that produce cancer:
o C. sinesis: glandular carcinoma (Chinese liver fluke)
o S. haematobium: bladder; causes transitional epithelium to undergo squamous
metaplasia squamous dysplasia squamous cancer
o
Growth Alternation: Dysplasia
atypical hyperplasia
o lacking order/orientationnuclei close to surface in epithelium
a precursor for cancer
o can be either glandular or squamous dysplasia
precursor for squamous cell carcinoma of the skin:
o actinic keratosis (aka solar keratosis): UV-light damaged skin
when scraped off, would grow back in sun-exposed area
not basal cells; but its squamous cell (basal cells more common)
Inflammation 2
Acute inflammation
characteristics:
o Rubor (redness): due to histamine, vasodilating arterioles
o Calor (warmness): due to histamine; vasodilate gives off heat
Thus warm skin in shock pt
o Tumor (swelling): due to histamine, increased vessel permeability in venules
Histamine contracts endothelial cells increase gaps in basement mb produce
exudate swelling
o Dolar (pain): due to bradykinin and PGE2
Hagemans factor 12 and 11
When intrinsic pathway is activated, also activate kininogen system end
product is bradykinin
ACE degrades bradykinin
Angioedema: one complication of ACE inhibitors due to inhibited metabolism of
bradykinin
Bradykinin vasodilate, increase vessel permeability
Another complication of ACE I: cough
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neutrophils in the small vessels begin to get sticky due to adhesion molecule synthesis, made
by endothelial cells
o neutrophils stick to the endothelial cells margination (pavementing)
o then neutrophils adhere to basement mb neutrophils have type 4 collagenase
cancer cells also have type 4 collagenase: how cancer cells get thru and
metastasize
cancer cells need to stick to endothelial cells with adhesion molecules (against
laminin and basement mb); to get thru basement mb need collagenase to
invade tissues
neutrophils then get out of small vessels (usually venules) then emigrate via directed
chemotaxis
o chemotactic agents: C5a, LTB4 (also involved in making adhesion molecules on
neutrophils)
Opsoniziation
occurs during infection; prepare bacteria before they get destroyed

o Opsonization: done by IgG and C3b
X-linked recessive in which a child lacks all Igs: hypogammaglobinemia
o Common cause of death: infection due to inability to opsonize
o Mechanism of infection: dont have IgG to opsonize bacteria and thus cant phagocytose
o X-linked recessive with decreased production of B cells: Brutons agammaglobinemia
Neutrophils/monocytes needs to have receptors for opsonized bacteria
o Chronic infection: see monocytes, which can transform into mq
Phagocytosis:
o Phagocytosing bacteria fusing with lysosome
Phagolysosome formation
o Lysosome goes down microtubules and release enzymes
o When there is no phosphorylation of mannose residue in Golgi, enzymes cant be
targeted to lysosome and there are no enzymes in lysosome I cell disease (important!)
o Chlymidia can actually get out of phagolysosome
O2-dependent myeloperoxidase system: BIG ON BOARDS
o Molecular O2 is converted by NADPH oxidase in the cell mb of monocytes and
neutrophils (but NOT mq)
o Most NADPH is synthesized in pentose phosphate shunt catalyzed G6PDH
Converts glucose-6P to 6phosphogluconate get NADPH and glutathione
o converting O2 into a free radical: superoxide, gives off energy as an unpaired electron
respiratory burst
can be measured by radiation detectors or NBT dye test
add colorless NBT enzyme: if neutrophils or monocytes are working
phagocytose, respiratory burst, creates free radical changes into BLUE color
then take some neutros out and smear on the slide: would see blue color in the
dye
o When there is no respiratory burst system: chronic granulomatous disease of childhood
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Free radical O2: converted by superoxide dismutase into peroxide
Myeloperoxidase: contained in red granules in monocytes and neutros
Combine peroxide with Cl- to form bleach kills bugs!
most potent bacteriocidal mechanism
o Mq doesnt have this system, only has lysosomes
Mq in CNS: microgial cells reservoir for CNS AIDS
Reservoir cells for AIDS outside of CNS: Dendritic cells, located in the lymph
nodes
In G5PDH deficiency: infections is the most common cause that precipitate hemolysis
o Due to lack of NADPH n functioning O2-dependent myeloperoxidase system
o When infection occurs: hemolysis occurs
o
o
Chronic Granulomatous Disease of Childhood
X-linked recessive
o All females of affected male: asymptomatic carriers; and transmit disease to 50% sons
Due to lack of NADPH oxidase; missing respiratory burst
o No superoxide/peroxide
o Yes: chloride and myeloperoxidase
o If adding peroxide into the lysosome of the affected child: would be able to carry out the
bactericidal reaction
All living organisms make peroxide
o But not all bacteria have catalase: breaks down peroxide
In this disease: can kill strep but not STAPH
o Staph: coagulase and catalase positive
When staph makes peroxide, it also makes catalase neutralize peroxide, cant
kill staph
o Strep: catalase negative
In strep infection, produces peroxide which is what affected child is missing
thus can kill strep
Myeloperoxidase Deficiency
YES: respiratory burst (intact NADPH oxidase); peroxide; superoxide free radicals; ClNO: myeloperoxidase
Normal NBT dye test, but cant kill bacteria because cant make bleach
This is a microbiocidal defect
o Also include chronic granulomatous disease of childhood: cant make bleach due to
absent respiratory burst
Autosomal recessive
Adhesion Molecule Defect
Kid whose umbilical cord doesnt fall off when it should

o When removed surgically, histologically doesnt show neutros in the tissues or see
neutros lining the vessels
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aka beta 2 integrin defect

Umbilical cord needs to have an inflammatory reaction involving neutros
When neutros cant adhere, cant get rid of umbilical cord!
Know all three defects
Review: king of chemical mediators in acute inflammationhistamine
o Action on arterioles: vasodilate
o Action on venules: increase vessel permeability
Serotonin: made from tryptophan
o A neurotransmitter; when deficient depression
Chemical Mediators
Anaphylaxin: C3a, C5a

o Role: stimulate mast cells to release histamine vasodilation and increased
permeability
o Play a role in shock via activating complement system
Prostaglandin: increase vessel permeability
NO: made in endothelial cells
o POTENT vasodilator
o Used to treat pulmonary HTN BIG ON BOARDS
o BIG role in septic shock
IL-1: associate with fever
o Pyrogen, stimulate hypothalamus to make prostaglandin stimulate thermoregulatory
center to produce fever
o ASA: inhibits prostaglandin synthesis, reduce fever
Corticosteroids: inhibit phospholipase A2
o Doesnt release arachidonic acid from phospholipid membrane doesnt make
prostaglandin or leukotriene
o Great anti-inflammatory agent
Omega-6 fatty acids: can make arachidonic acid (linoleic acid)
o Want to eat this everyday in fish oil and walnuts, because they act like ASA and block
platelet from aggregating
Zyleutin(?): blocks lipooxygenase
LTC4, D4, E4 slow-reacting substance of anaphylaxis
o POTENT bronchoconstrictor involved in bronchial asthma
o Zyleutin is great in asthma because it blocks all leukotrienes
o LTB4: adhesion molecules in chemotaxis
ASA: blocks cyclooxygenase irreversibly
PGH2: where everything seems to be derived from
PGI2: made in endothelial cells
o PGI2: vasodilator, inhibit platelet aggregation
o Prostacyclin synthase
o Antagonist: thromboxane A2, made in platelet
o Thromboxane A2: vasoconstrictor, bronchoconstrictor, platelet aggregator
Know COX2
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Thromboxane synthase blocker: dipyramidol

o Can be used in stress testing in coronary disease without using exercise-stress test
PGE2:
o vasodilator in kidney
o keeping ductus patent in fetus
o makes mucous barrier in stomach to prevent ulcer
o common cause of primary dysmenorrhea by increasing uterine contractility and abortive
effect by expressing fetal material
Corticosteroids
Anti-inflammatory agent
Blocks phospholipase A2
Decrease adhesion molecule synthesis increase neutron count on CBC
o 50% neutro already adhered to the endothelial wall; and 50% circulate (this is whats
measured)
o When adhesion molecules decrease: neutros that were adhered before now circulate
double white count
Lymphocytotoxic: kills B cells
o decrease B cells and T cells via apoptosis by signaling to caspases
Eosinophils: involved in type 1 sensitivity reaction
o Decreased by GCC
The only thing that is increased when taking GCC: neutrophils (via decreased adhesion
molecules synthesis)
o Both eosinophils and lymphocytes
Addisons disease: not enough of cortisol
o Neutrophil count: decrease
o Eosinophil count: increase
In MI pt: high white count (~18.000), mostly due to increased neutrophils
o This is due to epinephrine decrease synthesis of adhesion molecules
Electron microscopy of inflammatory cells
Neurtrophils
o Can have phagolysosome: containing debris
Previous board question: neutrophils in lungs with type 2 pneumocytes
o Black dots all over the place: alveolar mq
o Lamellar bodies: where lethicin and phosphytidalcholine are located makes surfactant
Monocytes
o Single nucleus, lots of garbage in the cytoplasm
Foam cells: in atherosclerotic plaque
o Oxidized LDL: free radical
o Neutralized by vitamin E
Lymphocyte: all nucleus with very little cytoplasm
o Odds: 60% peripheral lymphocytes are T cells and not B
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o Normal ratio of helper: suppresser T cells: 2:1

o Thus most likely its helper T cells > suppressor T cells > B cell
Plasma cells:
o Contains lots ribosomes (lots of rough ER), makes proteins
o The cell looks like finger-print; nucleus is eccentrically located; cytoplasm is sky blue
o Plasma cells are derived from B cells; located in germinal follicles
Eosinophils: granules are the same color as RBC
o Have crystals in granules Charcot-Leydin crystals
Degenerative eosinophils in the sputum of an asthmatic pt
o The only inflammatory cells that have crystals in the granules
Basophils: granules are more purple and darker
Mechanisms of killing invasive helminths:
o Type 2 hypersensitivity with major basic protein
o Schistosome eggs: coated by IgE antibodies
Eosinophils have IgE receptors release major basic protein, kills invasive
helminths
o Cell hooking to an antibody on the target cell
type 1 sensitivity: mast cells are effector cells
o release from purple granules: histamine, eosinophil chemotactic factor
o eosinophils in type 1: histaminases and arylsulfatase that neutralize leukotrienes
eosinophil: knock off some of the chemical mediators that produce type 1
reaction
but esoinophil kills helminths via type 2
CD (cluster designation) markers:
o Helper T cells : CD4
o Cytotoxic T cells: CD8
o Markers for all T cells: CD3
o Antigenic markers for histiocytes, including langerhan cells: CD1
o Marker for most common leukemia in children: CD10
o Reed-sternberg cells: CD 15/30
o Only on B cells; EBV hooks to this receptor: CD21
Atypical lymphocytes: T lymphocytes that react against infected B cells
o Burkitts lymphoma: B cell lymphoma
o CD45: on all leukocytes
Fever
Triggered by IL-1 PGE2 made by hypothalamus and acts on the thermoregulatory center
Fever is good:
o Right shift O2 saturation curve needs to have higher O2 in tissues when there is
inflammation because of O2-dependent myeloperoxidase system
Not good to relief fever in pts that have infection
o Higher temperature also bad for reproduction of both bacteria and viruses
Types of Inflammation
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Postpartum woman with pus coming out from catheterstaph aureus

Bone in a child that has sepsis: see a yellowish area in the metaphysic abscess
o Osteomyelitis: by staph aureus
o Metaphysic: because this is where all blood supplies go thus its by hematogenous
spread
o If the child has sickle cell disease: salmonella
Cellulitis: usually by strep
o Group A strep: strep pyogenes
Diphtheria with pseudomembrane: similar necrosis to clostridium dificile
o Grame + rods: make exotoxin that interferes with ADP ribosylation and EF2 toxin
damages the mucosa that bacteria do NOT invade
o Measure toxin in the stool to make the dx
Bread and butter pericarditis fibrinous-type
o Usually due to increased in vessel permeability
o Usually seen in first week of MI, coxsackie infection (always on boards!) and in lupus pt
o Most common heart lesion in lpus
Common organism producing infection in 3rd degree burn: pseudomona aeruginosa
o Color of pus: green due to pyocyain?
Wound Healing
Basal cell layer on both sides of the clot, proliferate and go under the clot
o Key of wound healing: granulation tissue formation
Granulation tissues: need to have fibronectin
o Fibronectin: adhesion and chemotactic (invite fibroblasts) agent
o Lots of blood vessels; due to fibroblast growth factor
o Lot of plasma cells, lymphocytes, highly vascular
o Granulation tissue starts on day 3 and at max on day 5
o Pyogenic granuloma: all granulation tissue
o Collagen involved: type 3
o Type 4 collagen: basement mb
o Type 1 collagen: tendons, bones, skin, ligaments high tensile strength
After weeks and months:
o Type 3 collagen is broken down by collagenase and metalloenzyme
o An enzyme that helps convert type 3 to type 1 collagenase Zn
Thus Zn deficiency poor wound healing
Needs to replace type 1 with type 1 collagen
o Maximal tensile strength in a wound by 3 months: 80%
Most common cause of poor wound healing: infection
Ehlers-Danlos syndrome: problem with collagen
o Also would have problem with wound healing
Problem with fibrilin: marfans
o Also have problem with wound healing
Scurvy: defect in hydroxylation in proline and lysine
o Hydroxylation requires ascorbic acid
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Cross bridges are involved to make 3 strands of collagen (triple helix) stick together and
form tensile strength
Lysyl oxidase catalyzes this reaction with Cu as a co-factor
o Cross bridges anchor into places where proline and lysine are hydroxylated weak
abnormal collagen in scurvy due to abnormal cross-bridging, weak tensile strength
o Cant heal wound, hemorrhage, hemoarthroses vitamin C deficiency
Keloid or hypertrophic scar
o Excess in type 3 collagen deposition
o Causes tumor-like appearance on skin
o Genetic disposition for keloid in black population
o Common cause in children: 3rd degree burn
o Squamous cell carcinoma very commonly seen in scar tissue from 3rd degree burn and
chronically draining sinus tract (i.e. chronic osteomyelitis)
Lots of turnover in scar tissues fibroblasts are involved, cell division
When there is cell division, there is a chance for mutation and cancer dev
Lots of hyperplasia of epithelium at the orifice of drinking sinus tract cancer dev
o
Chronic Inflammation
Main Igs in acute inflammation: IgM

o Most potent activator of complement system: IgM because its a pentamer and there are
10 antigen-recognition site
only 1 IgM is needed to activate complement system from C1-9
o Two IgGs are needed to activate complement and only activate up to C3
C5a: anaphylactic toxin and a chemotactic agent
After 10-14 days:
o Heavy chain defines specificity of Igs
o Now plasma cells are making IgG via isotype switching chronic inflammation
Acute inflammation: neutrophils
o Acute allergic reactions: eosinophils
Wont see mast cells because they are in the tissues
o Acute viral infection: lymphocytes
Chronic inflammation: plasma cells, lymphocytes, monocytes, mq
Acute Inflammation: see pus or exudate; not in chronic inflammation
o Increased vessel permeability and emigration of neutrophils into interstitial tissues
o Exudate: protein-rich fluid (>3g protein/dl); cell-rich
Difference in cell type and Igs, absence of exudate, and presence of granuloma: chronic
inflammation
Granuloma
o Caseous necrosis in TB
o Round-ish and pink; multi-nucleated giant cells
o Pathogenesis: type 4 hypersensitivity/delayed reaction
o Main players: cytotoxic T cells, helper T cells, CD4, mq
Cytotoxic T cells can kill virally-infected cells or neoplastic cells
NO antibodies
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Poison ivy: also type 4 hypersensitivity
TB
Alveolar mq phagocytose lympho-hematology spread via alveolar mq

Alveolar mq processes the TB antigen, then presents to helper T cells
Players: mq that process antigen, and presentation to helper T cells via MHC II
T helper cells then release gamma interferon and mq inhibitory factor involved in granuloma
development
o Mq inhibitory factors keep mq in localized area localized granuloma
Gamma interferon: activate mq to kill TB, Cryptococcus, histoplasmosis
o Mq itself cant kill those organisms
o And because these organisms have lots of lipids in cell wall caseous necrosis
o Pink-staining cells: epithelioid (looks like epithelial cells but not) activated mq by
gamma interferon
When activated mq dies form giant cells, like grave stone
Two subsets of helper T cells
o Subset 1: involved in type 4 hypersensitivity reactions
Mq have IL-12: when Mq secretes IL-12, it presents ag to subset 1, which then
becomes memory T cells
primary disease: usually recover
o granuloma becomes calcified dystrophically and can be seen on X-Ray
o organism still viable
Secondary TB: reactivation from calcified granuloma
PPD test:
o Purified protein derivative,
o Mq in the skin: langerhan, a histiocytes (CD1 positive)
Tennis-racket like granules
o Phagocytose purified protein derivative, process and present to helper T cell subset 1
that has memory of previous exposure to the protein in the wall of mycobacterium
o Helper T cells release cytokine, produce inflammatory reaction induration on the skin
People that might have decreased PPD test response
o Older people usually dont have strong type 4 hypersensitivity reaction
Thus needs to do double PPD tests sometimes less immune response
o AIDS pt: helper T cell decreases; need to have culture
Impossible to form granuloma because there are not enough helper T cells
Would see organisms all over the body but no granuloma
5mm induration: accepted as positive PPD test
Reaction to Injury
Heart: permanent reaction scar tissues, which do not contract

o More damage to the wall of left ventricle: ejection fraction (SV/EDV) decreases
Kidney: scar tissue formation
o Medulla: most susceptible to ischemia
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Most susceptible part of nephron to tissue ischemia: straight portion of proximal tubule
and medullary segment of thick ascending limb
Proximal tubule: most oxidative metabolism occurs here
brush border, most resorption occurs here
thick ascending limb: has Na/K/2Cl co-transporter, blocked by lasix
o obligated water: obligated to go out with Na, or Cl, or K (20ml for every ion)
o free water: generated by Na/K/2Cl transporter; can be reabsorbed by ADH
pumps generate free water by taking ions away
reabsorb 1 Na+: would have 20ml free water
with Na/K/2Cl: generate 80ml free water
lung: type 2 pneumocytes
o can replace type 1 pneumocytes and synthesize surfactant
o repair cell of the lungs
CNS: astrocytes; stable cell (not a neuron)
o Proliferate and produce increase in protoplasmic processes gliosis
o Astrocyte proliferation in CNS injury
Similar to fibroblast proliferation to lay down type 3 collagen in wound
PNS:
o Cut a nerve in half wallerian degeneration (BIG QUESTION!)
o Role of Schwann cells
Oligodendrocytes: in CNS; both make myelin
Tumor of Schwann cell: schwannoma or acoustic neuroma when its involved
with 8th nerve
Associated with neurofibromatosis: a genetic disease (AD)
o Axon regeneration
o
Tests ordered in Inflammation
Sed rate: pretty worthless

o Whole blood into cylinder and see how much ml an hour the blood settles
o Rouleux: increased sed rate because density is greater seen in multiple myeloma
With IgG and fibrinogen increased
What causes RBCs to stick together and clump: IgM
o IgM is big enough to cancel out the negative charge that is normally present in RBCs mb
o IgM: cold-reacting antibodies; cold agglutination
Thus can get cold Reynaud phenomenon in cold weather
IgM ab producing cold agglutination in digits, nose, ear ischemia
Once warms up, IgM falls off and the blueness goes away
o Cyroglobulin can also produce similar presentation as Reynauds
Also high association with Hep C
Multiple myeloma: increase in IgG; Walderstroms: increase in IgM
o Both would have increased sed rate
Acute inflammation (i.e. appendicitis): would see the following on peripheral blood
o Absolute neutrophilic leukocytosis on CBC true increase in number of neutrophils
o Toxic granulation
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Left shift: immature neutrophils (>10% band cells in 100 cells), or one myelocyte or just
one metamyelocyte
Toxic granulation
o O2 dependent myeloperoxidase system: myeloperoxidase is located in azurophilic
granules which are lysosomes
o Ensure that there is enough myeloperoxidase to kill bugs
o Dohle body
o
Fluid and Hemodynamics 1

Edema
Excess fluid in interstitial space

o Interstitial space: extracellular; outside of vessel
Can be pitting or non-pitting
o Pitting: transudate
Clear fluid, no pus, can be due to right heart failure and swelling of lower
extremities
o Exudate doesnt pit
Lymphatic fluid in interstitial fluid:
o Early on it can pit, but later cannot essentially non-pitting
Three things that produce edema: transudate, exudate and lymph
o Only transudate that can produce pitting edema
Transudate:
o Frank-sterling force: forces that keep fluids in and out of blood vessels
Keeping in: albumin
80% oncotic pressure related to serum [albumin]
Hypoalbuminemia: leaking of transudate (protein poor, <3g/dl, cell-poor)
into interstitial space, producing pitting edema
Pushing out: hydrostatic pressure
o Usually in health people oncotic pressure wins over hydrostatic pressure
o Decrease in oncotic pressure and increase in hydrostatic pressure: increase transudate
Albumin: made in liver
o Decreased albumin level: liver disease (cirrhosis), mal-absorption, nephrotic syndrome,
3rd degree burn on skin by losing plasma, decreased protein intake
Food coma: due to alkaline tide
o For every H+ secreted into stomach from thinking of food (vagus nerve stimulating
parietal cells and G cells) and digesting food (gastric phase) metabolic alkalosis
o When H+ in food neutralize with HCO3-: metabolic alkalosis disappears
o O2 dissociation curve: left shift; compensation for metabolic alkalosis resp acidosis
Both contribute to decreased pO2 tiredness
Pt died of MI 24 hours ago:
o Transudate in lungs: due to increased hydrostatic pressure
o Left heart failure in MI: fluid backs up into the lungs
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Decreased CO EDV in left ventricle increases pressure increases in atrium,
and pulmonary vein (normally 8mmHg)
Oncotic pressure is 25mmHg: initially is higher by 17mmHg
o As hydrostatic pressure continues to rise, approaches oncotic pressure transudate
leaks into interstitial space, activate J receptor dyspnea, would see Kerleys line on XRay
o Then fluid leaks into alveoli pulmonary edema
Bee sting in the arm and swollen face
o Exudate: anaphylactic reaction
o Type 1 hypersensitivity, increase vessel permeability histamine
o Steps of management: airway, then 1:1000 aq epinephrine subcutaneously
Cirrhosis in liver with pitting edema in legs and ascites
o Transudate: decreased oncotic pressure (cant synthesize albumin) and increased
hydrostatic pressure (increased portal HTN)
o Can also be due to increased aldosterone level with increased water and salt
reabsorption
Pitting edema in the legs:
o Increased hydrostatic pressure due to right heart failure
Post radical mastectomy with non-pitting edema
o Most common cause for developing lymph edema in the US
o W. Bancrofti can also cause this
o Other causes of lymph edema: lymphogranuloma venereum?
Subtype of Chlamydia chacomatas? Scarring of lymphatic tissues, lymph
edema of scrotum and valva
o Inflammatory carcinoma of the breast: also an ex of lymph edema
Dermal lymphatics are plugged with tumor
Lymphatic fluids leak out to interstitium
Ligaments that hold skin down usually now produces dimpling
o Can have lymphangiosarcoma when there is chronic lymph edema
ECF and ICF
ECF: two compartments vascular and interstitial

o Interstitial: 2/3; vascular 1/3
ICF: 2/3 larger than ECF
How many liters of isotonic saline that is needed to get 1 L into plasma: 3L
Osmolality of plasma (height) vs volume (width) of squares
o X axis: volume; Y axis: osmolality
Osmolality: measure of solutes in a fluid
o Mainly due to: Na, glucose and BUN
2Na + glucose/18 + BUN/3
Urea cycle located in liver (part in cytoplasm and part in mitochondria)
Urea comes from ammonia this is how body eliminates ammonia
Multiply NaX2 usually due to accompanying Clo Na is the main determinant of osmolality in normal situation
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Location of urea, Na, and glucose:

o Urea: can equilibrate between ICF and ECF
Permeable, doesnt control water movement
o But Na and glucose are restricted to ECF
o Change in concentration of Na and glucose water shifts from low to high solute
concentration (osmosis)
o Diffusion: going from high to low concentration
Hyponatremia:
o Water is going from ECF ICF via osmosis; intracellular expansion
o In brain: cerebral edema; mental status abnormalities
Hypernatremia:
o Water goes from ICF ECF
o ICF compartment is contracted
o In brain: mental status abnormalities
o But brain can produce idiogenic osmoles within 48-72 hours to rehydrate itself (not on
boards)
DKA/hyperglycemia
o Glucose is in the ECF
Glucose (also fructose and galactose) is metabolized immediately once it gets
into cytoplasm G6P in glycolysis
o Water moves from ICF ECF; contributes to dilutional hyponatremia
Tonicity
Normal plasma tonicity: controlled by Na

o Isotonic, hypertonic and hypotonic
o Normal saline: 0.9%
Total body Na / total body water
o Hypernatremia: due to loss of water, not necessarily due to increased total body Na
Serum Na: measured
Isotonic loss of fluid: losing equal amount of Na and water
o Mainly loss in ECF compartment
o Serum Na: normal
o ECF compartment would be contracted; but there is no gradient for water movement
o Ex: hemorrhage, diarrhea
Isotonic gain of fluid: equal increase of Na and water
o Ex: too much isotonic saline received
o Serum Na: normal because there is equal amount of Na and water
o ECF compartment: expanded; no gradient for water movement
Hypotonic conditions:
o Wont be affected by hyperglycemia because glucose is divided by 18
o Most common cause: hyponatremia
Loss more salt than water involving the kidney; usually due to hypertonic loss
of fluid from use of diuretics
ECF compartment: contracted because water moves into ICF
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If only gaining pure water and not salt:

o Hyponatremia
o SIADH: usually due to small cell carcinoma of the lungs (aka Oat cell carcinoma)
Total body Na: normal
In a pt with SIADH, will not excrete any water pt drinks
Always CONCENTRATING urine by taking free water away
Serum Na <120 always SIADH
o ADH: rendering distal tubule and collecting duct permeable to FREE water
Reabsorb water, dilute [Na], expand both ECF and ICF (via osmosis)
When there is no ADH: cant absorb water, DILUTE urine
o Mental status abnormalities
o Other causes of SIADH: oral sulfurylurea (esp 1st generation, used for diabetes)
produces ADH 30% of time
Hyponatremia due to gaining more water than salt:
o Pitting edema state: right heart failure, cirrhosis
o Total body Na: when its increased, always produces pitting edema
Because Na is located in the interstitial space, and as Na brings water with it
edema
Hypertonic state:
o Due to either hypernatremia or hyperglycemia
Hypernatremia:
o ICF compartment: contracts due to osmosis
True for all hypertonic conditions
o Primary aldosteronism: gain more salt than water
o When losing pure water: diabetes insipidus
o When gaining pure water: SIADH
o Can also lose more water than Na (hypotonic solution) in urine: osmotic diuresis due to
glucose or mannitol in the urine
o Baby diarrhea: hypotonic salt solution; adult diarrhea: isotonic
Body Na in baby with diarrhea: high because losing more water than salt
hypernatremia
Tx for baby diarrhea: replace hypotonic salt solution i.e. Gatorade
Glucose needs to be present in Gatorade Na needs to be reabsorbed along
with glucose or galactose in the GI tract via co-transporter
sweats: hypotonic salt solution
o would have hypernatremia when sweating excessively

Arterial Blood Volume
effective arterial blood volume = stroke volume = CO

o when CO decreases: all physiological responses would try to restore volume
o decreased CO decreased oxygenation in tissues
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baroreceptors:
o low pressure: located on the venous side
o high pressure: located on the arterial side; carotid and aortic arch; innervated by CN 9
and 10
when there is a decrease in stroke volume or CO:
o underfilling arch vessels in carotid
o rather than having a CN 9 and 10 response sympathetic response, release of
catecholamine
o constrict venous side to increase more blood returning to heart
o increase heart rate and increase force of contraction via receptor increase SV
o arterials on systemic side: constriction
tissues will not get a lot of blood
but would maintain diastolic pressure
coronary arteries are perfused during diastole!
diastolic pressure: due to amount of blood in the arterial system as the heart is
filling up during diastole
peripheral resistance in arterial: maintains diastolic pressure; controls amount of
blood in the arterial system during diastole
o Sympathetic activation of renin-angiotensin-aldosterone system
AT II: vasoconstrictor of peripheral resistant arterioles
AT II stimulates 18 hydroxylase converts corticosterone into aldosterone
Stimulate aldosterone release: increased reabsorption of salt and water
o Renal blood flow decreases:
Also a stimulus for renin-angiotensin-aldosterone release
Receptor located in the JAG in afferent arteriole
Modified smooth muscles cells that sense blood flow
ADH: also released; but doesnt contribute much to CO increase because it only
retains pure water
Thus give pt normal saline during hemorrhage
Normal saline: plasma without proteins; stay in ECF compartment because same
tonicity as plasma
Na reabsorption:
o proximal tubule: 60-80%
o the rest occurs at distal and collecting tubules via aldosterone
o Na is reabsorbed into peritubular capillaries
o Starling forces in the peritubular capillaries need to be receptive to Na reabsorption
peritubular capillary pressure:
o as renal blood flow is decreased when CO/SV decreases peritubular capillary
hydrostatic pressure decreases oncotic pressure increases
o this increase in oncotic pressure allows reabsorption of salt and fluid back into blood
stream
o any causes for CO decrease (cardiogenic shock, hypovolemic shock) would see
higher oncotic pressure than hydrostatic in peritubular capillaries
at proximal tubule:
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o isotonic fluid is reabsorbed

o aldosterone: also reabsorbing roughly isotonic solution, but less so than proximal tubule
o but as ADH is released: reabsorb free pure water
o thus kidney reabsorbs hypotonic solution when there is a decrease in CO
If SV is increased:
o Baroreceptors are stretched CN9 and 10 response
o Parasympathetic response
No increase in contractility or heart rate
o Renin-angiotensin-aldosterone system would not be activated (now there is increased
blood flow to kidneys)
o ADH release decreases
o Peritubular capillary hydrostatic pressure > oncotic pressure
Even if reabsorb the salt, cant reabsorb it back into bloodstream
o Loss of hypotonic solution
o Release of ANP due to dilatation of both right and left atrium
Eliminates salt as a natural diuretic
Only released in volume-overload disease; not during hypovolemic state
pt given 3% hypertonic saline
o Posm on Y axis and serum ADH on X axis
o Hypertonic saline: adding salts to pt increases osmolality
o When there is an increase in osmolality ADH increases
In SIADH:
o Plasma osmolality: low
o ADH level: high
o Total body Na: normal
o Serum [Na]: low
o Tx: restrict water
Diabetes insipidus:
o ADH level: no
o Serum Na: high
Total body Na: can tell from physical exam
o Dried tongue/dry mucous membrane: decreased total body Na
o Indentation in Skin: high total body Na
o Dehydration: skin turgor testing total body Na in the interstitium
o Dependent pitting edema: total body Na absolutely increases
Kidney reabsorbs hypotonic solution when there is decreased CO
total body Na: increased
total body water: greater increase
tx: restrict salt and water or use diuretics (get rid of more salt and some water)
Shock
hypovolemic shock:
o diarrhea, blood loss, sweating
o but NOT in diabetes insipidus:
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losing pure water, total body Na is normal not hypovolemic shock
needs to lose salt to be hypovolemic
mostly lose pure water from ICF compartment
but will not have signs of dehydration
Tilt test: KNOW!
o pulse and BP normal when lying down
o when pt sits up: BP decreases and pulse increases
decrease venous return to right side of heart due to opposing gravity
CO decreases
Due to catecholamine effect
o this is volume depletion hypovolemic
o tx: normal saline
running marathon without taking any water:
o losing lots of sweat (hypotonic salt solution)
o if collapsed 100/80 laying down with pulse of 120; sitting up with 70/60 and 160 pulse
o positive tilt test: give normal saline to keep BP up
o After BP is back up, there can still be signs of dehydration (i.e. dry mouth)
o now give hypotonic solution: half normal saline
do not use 5% dextrose and water: because there is no salt
o Always give pt what he lost!
o Hypovolemic: always start with normal saline
DKA:
o Osmotic diuresis: loss of hypotonic solution (little bit more water than salt)
o Hypovolemic can be fatal; not from hyperglycemia
o First step of tx: normal saline to make pt normotensive
Usually adds 6-8 L of normal saline
o Once BP is stabilized: now give hypotonic saline added with insulin
Diabetes insipidus:
o BP is stable and pt is lucid but with hypernatremia
o Tx: IV water; use 5% dextrose in water
o Pt is losing pure water; salt overloaded

Shock
Neutrogenic shock: in step 2, usually seen in spinal cord injury

Hypovolemic shock:
o Anytime when pt loses salt
Cardiogenic shock:
o Most commonly due to MI
Septic shock:
o Most commonly due to E. Coli from urinary catheter
o Gram organisms make endotoxin in cell wall (LPS)
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Gram organisms have lipid in cell wall, which is LPS, but gram+ organisms dont
Cardiogenic/hypovolemic shock:
o Skin: cold and clammy
Due to vasoconstriction of peripheral vessels due to catecholamines and AT II
Re-distribute blood to more vital organs, like brain
o BP: decreased
o Pulse: increased
Total peripheral resistance (arterioles) is related to viscosity of blood/ (radius of blood vessel)4
o Main factor controlling total peripheral resistance: (radius of blood vessel)4
o viscosity is controlled by Hb; when anemic decreased viscosity; decreased TPR
o in polycythemia vera: increased viscosity increased TPR
septic shock: released of endotoxin
o activate alternative complement systemrelease C3a and C5a anaphylactic toxins
stimulate mast cells to release histamine vasodilate arterioles
o skin: warm, like in acute inflammation
o endotoxin also damaged endothelial cells
NO and PGI2 are also released and cause more vasodilation
o TPR is decreased in septic shock
TPR of arterioles controls diastolic blood pressure
o When arterioles are constricted, can control the amount of blood that remains in the
arteriole system while the heart is filling during diastole
o When arterioles are dilated diastolic BP plummets
When arterioles are dilated:
o Lots of blood rushing into capillaries
o But tissues cant get enough O2 because blood is going thru too fast
o Blood also returns to heart faster than normal CO INCREASES in septic shock high
output difference (need to know this for step 2 too)
Swan Ganz catheter: inserted to right side of heart
o CO:
Low in cardiogenic and hypovolemic shock
Increased in septic shock
o TPR: telling you what your arterioles are doing
Increased in cardiogenic and hypovolemic shock due to vasoconstriction
Decreased in septic shock due to vasodilation
o Mixed venous O2 content (1.34*O2 Saturation + PO2) absolute best test for tissue
hypoxia
Not lactic acid because many things can increase lactic acid level
Mixed venous O2 content is what returns to the heart
In cardiogenic/hypovolemic shock: blood flows very slowly and tissues have time
to extract O2 very low mixed venous O2 content
In septic shock: high mixed venous O2 content because there is no time to
extract O2
o Pulmonary-capillary wedge pressure: measure of LV EDV and EDP
LV EDP in hypovolemic shock: low
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LV EDP in cardiogenic shock: high

LV EDP in septic shock: low
the organ suffers greatest from decreased in BP: kidneys
o esp medulla (normally 10% of CO) of the kidney
ATN: oliguria, increase in BUN and Cr in cardiogenic/hypovolemic shock
Coagulation necrosis= ATN
Would form renal tubular cast and block urine flow oliguria
Decrease in GFR
Pt with sickle cell trait, not disease, can also get kidney disease because medulla
O2 tension is low enough to induce sickling in peritubular capillaries
Can be seen in a otherwise normal young black woman except with
microscopic hematuria first step in work-up: sickle cell screening
Induce sickling infarction
o not the brain because there is circle of Willis would redistribute blood flow even when
CO is decreased
o heart also has small degree of collateral circulation
Arterial Blood Gas
Henderson-Hasselbach:
o If there is acidosis: increase in H+ ions, pH is decreased
o If there is alkalosis: decrease in H+ ions and increased pH
pH = bicarb/pCO2
o when bicarb is increased metabolic alkalosis, increase pH
o when bicarb is decreased metabolic acidosis, decrease pH
o when pCO2 is increased respiratory acidosis, decrease pH
o when pCO2 is decreased respiratory alkalosis, increase pH
Compensation
bodys attempt to try to maintain a normal pH

if there is metabolic alkalosis needs to have respiratory acidosis as compensation
if there is respiratory alkalosis due to hyperventilation compensated by metabolic acidosis
o ventilation: its a CO2 term
o hypoventilation: increase in CO2 due to decreased respiratory rate respiratory
acidosis
full compensation does not exist; normally can only bring pH close to, but no into, normal range
o except: chronic respiratory alkalosis in high altitude (i.e. Peru)
can bring pH right back into normal range
Respiratory Alkalosis and Acidosis
respiratory center is located in medulla: controls breathing rate

upper airways: if obstructed, would have problem eliminating CO2
diaphragm: most important muscle in respiration
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when diaphragm moves down increase negative intrathoracic pressure sucks air
into lungs and suck blood into heart (thus neck veins collapse during inspiration)
o on expiration: positive intrathoracic pressure helps push things out (blood out of heart
and air out of lungs)
barbiturates: depressant of respiratory center
o would get respiratory acidosis
o CNS injury to medulla: would also get respiratory acidosis
Respiratory alkalosis:
o Most common cause: anxiety
Symptoms: numb and tingly around mouth and fingers; twitchy, parenthesia,
numbness
Ionizing Ca is decreased twitchy
o Toussels sign: carpal-pedal spasm, sign of tetany
Pregnancy: also see respiratory alkalosis
o estrogen and progesterone over-stimulate respiratory center
o spider angioma: AV fistula in lungs due to high estrogen; clear more CO2 per breath
than non-pregnant woman
can also have spider angioma on skin
pt with endotoxin/septic shock: respiratory alkalosis
o over-stimulate respiratory center
o anaerobic metabolism metabolic acidosis due to lactic acids
o would get normal pH due to two blood gas disorders
salicylate intoxication: over-stimulate respiratory center respiratory alkalosis
o salicylic acid (ASA) adding acid to body metabolic acidosis normal pH
6 yo child has inspiratory stridor
o Swollen epiglottis and thumb-print sign on X-Ray: acute epiglottitis due to H. Influenza
o Vaccination has decreased incidence
o Most common causes of meningitis from 0-18 mons of age: N. Meningitimis
Above scenario in 3 months old:
o Laryngeal-tracheal bronchitis: parainfluenza
o Staple sign: obstruction is in trachea (below larynx)
o Full obstruction: pt cant talk; partially obstructed: can talk and can cough it out if its food
stuck there
Problems with diaphragm: innervated by phrenic nerve
o Breach/brachial plexus injury: diaphragm elevate on one side retain CO2
o AMLS
o guillan-barre: ascending paralysis with respiratory infection during previous week; spinal
fluid shows increased protein, slightly increase in lymphocytes, gram stain negative
a demyelinating disease
o polio: destroys UMN and LMN
o paralysis of respiratory muscles respiratory acidosis
obstructive and respiratory lung disease:
o obstructive: compliance increases, elasticity decreases problem getting air out, retain
CO2 respiratory acidosis
o
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restrictive: sarcoidosis
Arterial Blood Gas
for every 30 feet, increase 1 atm of pressure

o 760mmHg here, increase to 760*2 when down water 30 feet
o Reverse true for high altitude: atmospheric pressure is lower
Still breathing 21% O2 regardless of the altitude
o But atmospherics pressure is less
Calculate alveolar O2
o (0.21 *atmospheric pressure pCO2)/ 0.8
o Need to hyperventilate at high altitude: by lowering pCO2, would increase pO2
o When going below sea level: atmospherics pressure increases
N2 gas is dissolved in tissues
When coming up to surface too quickly: gas comes up as bubbles, which can get
into tissues or blood vessels block blood flow (the bends)
Lots of pain, quadriplegia because small vessels supplying spinal cord are very
susceptible; loss of bladder control; death
Tx: hyperbaric O2 chamber
o This is kasons disease? On boards!
Nutrition 1
Eating Disorders
Board questions! Can be under behavior science section

Includes obesity, anorexia nervosa, bulimia nervosa
o Biggest difference between anorexia and bulimia: distorted body image
o Anorexia: think they are fat when they are 60 lbs loss control over everything in their
lives except of their weight
o Loss of weight: GnRH decreases FSH, LH decreases; low estrogen level (no period);
osteoporosis as if postmenopausal (board question)
o In athletes, the body fat is so low and GnRH is decreased and would have no periods
Tx: gain enough body weight
Always think cheap tx for boards! i.e. weight loss of HTN, not drugs
DM: as adipose are lost up-regulate insulin receptors
o most common cause of death for anorexia nervosa cardiac disease; heart failure
Bulimia nervosa:
o No problem with body image: dont have to be thin, can be obese or normal weight
o Binge: eat a lot and then forced vomiting
o Know the picture: acid from vomiting wears off the enamel on the teeth brown stuff on
teeth
o Metabolic abnormality from forced vomiting: metabolic alkalosis
Compensation: respiratory acidosis; develops hypoxia
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Heart with tissue hypoxia would then have premature contraction can lead to vfib
o Metabolic alkalosis can be very dangerous for inducing cardiac arrhythmia, which
commonly occurs in bulimic pts
o Also can vomit out blood: malerywise with a tear in the distal esophagus or proximal
stomach; or Boerhaave's syndrome ruptured esophagus
Ruptured esophagus: air and secretions from esophagus enter pleural cavity
air can dissect thru subcutaneous tissues, come around into anterior
mediastinum
When putting stethoscope on the chest: hammans crunch (ruptured esophagus)
o Two things to remember for bulimia: vomiting with metabolic alkalosis and cardiac
arrhythmia; and Boerhaave's syndrome
Obesity:
o Determined by BMI: kg/m2
o Magic number 30: > 30 obese; >40 morbidly obese
o Main complication: HTN
LV hypertrophy from HTN heart failure
Cardiac disease is the most common cause of death in HTN pt
Gall bladder disease, cancer
Lots of adiposearomatize ketosteroids (i.e. androstendiol) into estrogen
Lots of estrogen estrogen-related cancers (breast cancer, endometrial
carcinoma)
But can also have colon cancer
Marasmus: total calorie deprivation; wasting away of muscles
o Good chance of survival if can get food
Kwashiorkor: total number of calories is okay but is missing proteins; anemia, cellular immunity
defective; low albumin liver, fatty liver, ascites
o Apathetic kids, need to force kid to eat frequently die
o Flaky-paint dermatitis that comes off from skin (flake sign due to Cu deficiency), pitting
edema of legs
Vitamins
Fat soluble: taken up by chylomicrons

o A,D,E,K
o More likely to be stored in fat greater chance of toxicity than water-soluble vitamins
Water soluble:
o Everything else
o Less toxicity
o All are co-factors of biochemical reactions
Vitamin A
Signs of deficiency:
o Eye: squamous metaplasia, bitot spots
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o Goose-pumps in the back of arms: follicular hyperkeratosis

Very important in child growth: bone, muscle growth
o Can have failure to thrive in vit A deficiency
iodopsin/rhodopsin: vit A deficiency leads to night blindness (nyctalopia)
vit A also prevents squamous metaplasia
o eyes are lined by low cuboidal epithelium
o when there is metaplasia: form white spots, can become very extensive grow over
eyes and softening of cornea (keratomalasia) blindness
second cause of blindness worldwide; first cause is trachoma (caused by
chlymidia)
in US: first cause of blindness is DM
o can get squamous metaplasia in main stem bronchus in a non-smoker due to vit A
deficiency
when taking too much vit A:
o big game hunter who eats bear liver (lots of vit A)
o symptoms: HA, cerebral edema, papilloedema, herniation of brain
o retinoid acid: can be used to treat acne and acute granulocytic leukemia
can produce severe liver toxicity
o affect: liver and brain
Vitamin D
most common source: sunlight

o cholesterol: main component of cell membrane, starting point for making bile salts, first
compound for synthesis of steroid hormones, can get photo-converted into vitamin D
very little vit D and K in breast milk
o needs to have supplement: or take baby outside for sun exposure
Reabsorbed in jejunum
Two hydroxylation step:
o First in liver: 25-hydroxylated
o Second in kidney: 1-hydroxylated via PTH hormone
1 hydroxylase is located on proximal tubule
Reabsorb Ca and phosphorus in jejunum
o Main job of vit D: mineralize bones
PTH:
o Reabsorption of Ca at the same place where thiazide blocks Na reabsorption, at early
part of distal tubule
There is a Ca channel: but Ca needs to wait and take turns with Na thus
needs PTH to help Ca reabsorption
When on thiazide: block Na reabsorption channel is totally open for Ca
hypercalcemia
Majority of Ca stone formers: hypercalciuria from too much Ca reabsorption in
guts
Tx: HCTZ to suck Ca out of urine
o decrease reabsorption of phosphorous at proximal tubule
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o decrease reabsorption of bicarb

o help 1 hydroxylase: help vit D get second hydroxylation
main function of vit D: mineralize bone
o osteoblasts are involved
o receptor for vit D is located on osteoblasts release alkaline phosphatase
when growing or fracture healing: vit D increased alkaline phosphatase
o PTH breaks down bone to maintain Ca level in the blood
But calcitonin receptor is located on osteoclasts: inhibit osteoclasts, can be used
to treat osteoporosis or hypercalcemia
No receptor for PTH on osteoclasts; its on osteoblasts
o When PTH is bound to receptor: release IL-1 (aka osteoclast activating factor)
IL-1: B cell stimulation, ab synthesis and fever production
Break down bone and maintain Ca level in blood
Sex hormones keep a check on IL-1 level
Male: testosterone
Women: estrogen thus get osteoporosis when lacking estrogen postmenopause
vit D deficiency:
o lack of sunlight; poor diet; liver disease
o board question: pt is on phenytoin with hypercalcemia
induces P450 system located on SER SER hyperplasia, metabolize drugs or
liver products, including 25-hydroxy vit D
alcohol, rifampin, barbiturate: all increase P450 activity decrease in vit D and
other drugs
o woman on pheyntoin and birth control pills but got pregnant:
revved up P450 increases metabolism of estrogen and progesterone not
enough of estrogen and progesterone to prevent pregnancy
o another enzyme in SER: gamma glutamyl transferase
when there is SER hyperplasia increased synthesis
gamma glutamyl transferase: test to pick up alcoholism
o liver disease: cirrhosis cant hydroxylate
o most common cause: renal disease
renal disease:
o tubular disease cant hydroxylate
o most common cause of renal disease in US: due to DM
o all pt with chronic renal failure are put on 1,25 vit D
this is RX, very dangerous
o if someone gets vit D OTC, would need to get 25 hydroxylated in liver and 1
hydroxylated in kidney before vit D becomes metabolically active
o need both liver and kidney to function to obtain active vit D
vit D deficiency:
o kids: rickets
very soft skull, easy to press in and skull would recoil
only in kids
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not enough Ca and phosphorous to mineralize osteoid excess osteoids,
bumpy rachitic rosary
osteoids are located in costo-chondroid junctions; dont see this in adults
because everything is fused
o adults: osteomalasia (soft bones)
cant mineralize bone or cartilage easy to fx (pathologic fx)
too much vit D
o hypercalcemia
o hypercalciuria stone formation
vit D dependent ricket:
o type 1: missing 1 hydroxylase
o type 2 vit D: missing receptor for vit D
Vitamin E
main function: maintain cell membrane, prevent lipid peroxidation of cell mb

o protect cell mb from being breaking down by phospholipase; prevent free radical
damage to mb
Can also neutralize oxidized LDL cardio protective
o Oxidized LDL more athero-genic than non-oxidized LDL
Oxidized LDL is phagocytosed by mq foam cells
o Vit C can also neutralize
Vit E deficiency
o Commonly see in child with cystic fibrosis
Mal-absorption in addition to respiratory problem
Mal-absorption of fat mal-absorption of A,D,E,K
o Hemolytic anemia: because cell mb is now susceptible to free radical damage
o Neurological problems
Too much vit E:
o Anything >1100 units (most capsules are about 400 units)
o Prevent vit K-dependent coagulation factors (2, 7, 9 and 10) anti-coagulation
If pt takes too much vit E when already on warfarin: can over anti-coagulate
Synergisitic action with warfarin high INR (board question!)
Vitamin K
Mostly synthesize by colonic anaerobes

o Give vit K injection to babies when they are born
o No vit K in breast milk; only have about 3 days of vit k supply from mom
o very low vit K level between day 3-5 can get hemorrhagic disease during this time
period; brain hemorrhage and die
o by day 5: babies are colonized and begin to make their own vit K
bacteria make inactive vit K: K2
o K2 needs to be converted into active form, K1, via epoxide reductase
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K1: gamma carboxylation vit K dependent factors (2, 7, 9, 10, protein C and S)
o Similar to hydroxylation of proline and lysine done by vit C crosslink doesnt work if
there is no hydroxylation
o Gamma carboxylation activates vit K dependent factors
o Vit K dependent factors: all have to be activated by K1, and need to be bound by Ca in
order to form a clot
o Gamma carboxylation of glu gla, allows Ca to bind to these factors can form a clot
Warfarin: inhibit epoxide reductase
o All vit K is in K2 form, dont have gamma carboxylation cant coagulate
Deficiency:
o Most common cause in the hospital: board-spectrum abx
o Poor diet
o Newborn
o Mal-absorption: vit K is fat-soluble
Symptoms of deficiency of vit K: hemorrhagic diathesis
o Bleeding into brain, skin because anti-coagulated
6 day old child, breast-fed and has bleeding diathesis due to inadequate vit K in breast milk
Kid that ate rat poison (warfarin)
o Tx: IM vit K
Kid lives with elderly grandparents and develop hemorrhagic diathesis: due to eating warfarin
from grandparents
Nutrition 2
Vitamin C
co-factor for making catecholamines; needs vit C to convert norepi to epi

Scenario: malnourished, not having enough vitamin from diet; bleeding gum when brushing
teeth scurvy, vit C deficiency
Vit C deficiency:
o Hydroxylation of proline and lysine: occurs at Golgi because its post-translational
modification
o Tensile strength of collagen is weak because cant form cross bridges
o Blood vessels are unstable rupture, gum bleeds due to weak type 1 collagen,
inflammation can lose teeth
o What vit deficiency is associated with severe hemophilia A:
Severe hemophilia A usually has hemathroses vit C deficiency
Unstable/weak blood vessels and rupture easily
o Parafollicular hemorrhage: hemorrhage around hair follicles
This is a PE dx of vit C deficiency
Hair follicles hemorrhage from ruptured blood vessels; forming a ring around the
follicles
Connection: like ring sideroblasts a nucleated RBC with too much Fe in the
mitochondria
In this case, its ring (hemorrhage) around follicles
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Corkscrew hair: looks like pigs tail
Tongue: smooth, painful, glossitis, kelosis around the angles?
Hemorrhagic diathesis scurvy
Too much vit C
o Mainly renal stone: increased uric acid stone formation
o Vit D: toxicity is also stone formation
Vit C as a therapeutic drug:
o Ancillary tx for methehemoglobinemia vit C is a great reducing agent
o Vit C is also a great scavenger for free radicals
o
o
Thiamine (B1)
Scenario: foot drop, pitting edema

o Dry and wet beriberi
Co-factor for many metabolic reactions
o Transkelolase reaction: involved in pentose phosphate shunt
o Know all dehydrogenase in biochem: pyruvate DH, -ketoglutarate DH, and -ketoacid
DH
pyruvate DH: pyruvate into acetyl CoA
o pyruvate can also be converted into OAA with carboxylase
combine acetyl CoA with OAA citrate, starting point of TCA cycle
o if thiamine deficient:
will not have a lot of acetyl CoA and citrate will not have lots of ATP
main problem with thiamine deficiency: ATP depletion
o generate 2 NADH when going from pyruvate to acetyl CoA
since its in mitochondria, 2 NADH 6 ATP
24 ATPs are also obtained from TCA cycle
Metabolize glucose completely: 38 ATPs
o Without thiamine lose 30 ATPs
Beriberi:
o Dry: peripheral neuropathy (aka Wernickes and Korsakoffs psychosis)
Lots of ATPs are required to make myeline: when ATP depleted cant make
myelin, get peripheral neuropathy
Foot drop due to common peroneal nerve palsy; wrist drop (radial and ulnar
nerve)
Wernickes encephalopathy: confusion, ataxia, nystagmus
Korsakoffs psychosis: cant remember although seems familiar; memory
problem
o Wet beriberi: heart failure
Congestive cardiomyopathy; bi-ventricular enlargement; the whole chest is
occupied by heart
Left heart failure right heart failure pitting edema
Pitting edema is a sign of R heart failure due to increased hydrostatic pressure
Can also get pulmonary edema from L heart failure
most common cause of thiamine deficiency in US: alcoholics
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o tx: can reverse beriberi with IV thiamine

o but if there is cardiomyopathy due to direct toxic effect of alcohol: B1 wont work
pt presents to ER, given IV 5% dextrose and normal saline, then pt develops confusion,
nystagmus, ophthalmic plegia
o there is sub-clinical thiamine deficiency
o glucose pyruvate acetyl CoA and uses up the remaining thiamine acute
Wernickes
o tx: give IV thiamine before giving any IV with any glucose
o people present to ER with (semi) comatose: give 50% glucose in case due to
hypoglycemia; naloxone for overdose; and thiamine
o this question is on all steps!!
Niacin (B3)
Rash on sun-exposed areas: pellagra niacin deficiency

o People with pellagra also have 3 Ds: dermatitis, diarrhea, and dementia
o Hyperpigmentation on sun-exposed area
All oxidation and reduction reactions require niacin
o N in NADH, NADPH is derived from nicotinamide, which is derived from niacin
o i.e. pyruvate to acetyl CoA, NAD to NADH
tryptophan: essential amino acid
o involved in niacin synthesis (although not the main source of niacin)
o also involved in synthesis of serotonin (a neurotransmitter)
Nicotinic acid: least expensive lipid lowering drug
o Side effects: flushing, thus needs to take ASA before taking nicotinic acid
o Tx for familial combined hyperlipidemia and hypercholesterolemia
Riboflavin (B2)
FAD, FMNetc all require riboflavin as a co-factor

o Niacin for NAD, NADPH reactions
Glutathione reductase also require riboflavin as a co-factor
Know these reactions!
Pyrodoxine (B6)
Deficiency: microcytic anemia

o First reaction in synthesis of heme involves syccinyl CoA and glycine catalyzed by
ALA synthase with B6 as a co-factor
o Important in synthesis of heme (porphyrin) heme proteins, and hemoglobins
Myoglobin only has 1 heme group
o There is also heme group in the cytochrome system
Transaminase:
o Most abundant substrate for making glucose in fasting state: alanine
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By transamination, alanine can be used to make glucose
Take NH2 group out of alaninepyruvate (alpha ketoacid)
Take NH2 group out of asparatate OAA (substrate for gluconeogenesis)
Reverse reactions also hold true
B6 is also involved in synthesis of neurotranmitter
o Deficiency: neurological problems, convulsions
Most common cause of deficiency: isonizid
o Thus need to give pt B6 while on it
o Otherwise pt would develop neurologic problem, pseudoblastic anemia related to heme
problem
o
Panthothenate (B5)
Involved in fatty acid synthesis

o Important in making C16 fatty acid (palmitoleic acid)
o Also involved in making coenzyme A: acetyl CoA and HMG CoA
Biotin
Co-factor involved in other pyruvate reactions: pyruvate carboxylase

o Thiamine is involved in turning pyruvate into acetyl CoA
o Biotin involve in making OAA from pyruvate
Deficiency: eating lots of raw eggs consistently
o Raw eggs have avidin that binds biotin
o Symptoms: bald, rash
If biotin deficiency: cant form OAA and citrate
o Can end up with hypoglycemia (OAA is required for gluconeogenesis)
o Pyruvate builds up forced to go into direction of lactic acid
Trace Elements
Cr: glucose tolerance factor

o Helps insulin do its job: can lower glucose level pretty fast
o Good for DM type 2
Cu: many enzymes, especially lysyl oxidase
o This enzyme is involved in forming crossbridges in collage fibrils and elastic tissues
o Deficiency: weak collagen and elastic tissues
Flake sign
Dissecting aortic aneurysm
F: required to prevent dental caries
o Too much: white-chalky teeth; white patch on teeth and cornea
o Calcification of the ligaments at insertion point to bone can rupture
Selenium: big time!
o Glutathione peroxidase requires Se for glutathione to neutralize peroxide
o Se: anti-oxidant; usually used with vit E
Se: making sure glutathione it working
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Vit E works on lipid mb, preventing oxidative damage as well as knocking off
oxidized LDL
o Deficiency: glutathione cant break down peroxide
Zn: on every exam
o Older people have abnormal taste: dysgusia
o Anosmia: lack of olfaction
Both smell and taste are deficient in Zn deficiency
o Zn: metalloenzyme
Metalloenzyme as trace elements as co-factors
Ex: ollagenase: has Zn, breaks down type 3 to type 1 collage in wound healing
o Presentation of Zn deficiency: rash on face, poor wound healing, dysgusia, anosmia
o All diabetics are Zn deficient without supplement
Top 10 causes of morbidity in the US:
o 1: smoking
o 2: deals with diets and exercise
o 3: alcohol
o This is why board loves questions on prevention!
o Nutrition questions are on Step 2 as well
Dietary Fiber
Soluble fiber: can lower cholesterol

o But not insoluble fiber
oatmeal: has insoluble fibers, suck up water in colon
o other stuff thats in colon: i.e. lipocholic acid
o 95% bile acid/salt are reabsorbed in terminal ileum
o Lipocholic acid: carcinogenic, produces colonic cancer
o As fibers (both soluble and insoluble) are present in colon, sucks up lipocholic acid into
stool so that it doesnt come in contact with mucosal mb
o Fibers also make you go poop more often: eliminating lipocholic acid
Small percentage of estrogen is recycled/recirculation
o By eliminating estrogen via fibers in diet: can decrease ovarian/breast cancer
development
Protein Restriction Diet
Seen in: chronic renal failure and cirrhosis

o Excess protein: broken down into ammonia urea, kidneys would need to excrete
more urea
o Cirrhosis: defective urea cycle and cant metabolize ammonia
Most of the ammonia in the body comes from bacterial in colon that have urease
o H. pylori, anaerobes
o Break won ammonia to urea in colon
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o
o
Ammonia is reabsorbed back to liver to be converted into urea for elimination via urea
cycle
When there is cirrhosis: increased level of ammonia hepatic encephalopathy
Metal status abnormalities, asterixis
Other causes besides ammonia: octopamine, phenaminobenzoic acid
Neoplasia 1
Definition
Benign vs. malignant

o Benign; usually dont metastasize; but malignant has the capacity to metastasize
o Exception: invasive mole benign tumor that can metastasize into lungs but will go
away
o basal cell carcinoma (most common skin cancer) invade but doesnt metastasize
leiomyoma: tumor of smooth muscle
o most common benign tumor of women: located in uterus
o fibroid is also used: looks like fibrous tissues but it isnt because its smooth muscle
o no transformation into malignancy
most common benign tumor in males
o yellow, move around lipoma
Benign tumors of glands: adenoma
o Adrenal adenoma: thinness of adrenal cortex would denote that this is functioning
Can be making cortisol suppress ACTH, atrophy of faciculata and reticularis
Induce Cushings
If tumor is making mineralocorticoids: atrophy of zona glomerulus Conns
syndrome
Tubular adenoma; most common precursor for colon cancer
o Looks like a strawberry on a stick: know this!
Carcinoma: malignancy of epithelial tissues squamous, adeno and transitional
o 3 epithelial tissues: squamous, transitional and glandular
o Squamous carcinoma: swirls, increased redness/bright red squamous pearls
Know this!
o Glands: adenocarcinoma
Would have things inside of glands
o Transitional carcinoma: comes from bladder, ureter and renal pelvis
Melanoma: malignancy of melanocytes
o First step in tx: excision
o Benign version: nevus
o Most rapidly increasing cancer in the US, not the most common cancer
o S100 Ag-positive; APUD (precursor uptake decarboxylation) tumor
Neurosecretory or neuro crest origin
Neurosecretory granules on EM
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S100: staining for neurosecretory granules/origina

o Other APUD tumors: small cell carcinoma of lung, bronchiocarcinoid (less malignant
counterpart); carcinoid on the tip of appendix; neuroblastoma in medulla in children
Neuroblastoma can metastasize to skin: multiple nodules on skin
sarcoma: malignancy of mesenchymal tissues
o osteogenic sarcoma: metaphysis split up into small periosteum Codmans triangle on
x-ray
tumor makes new bone, sun-burst appearance on x-ray
o embrynorhbdosarcoma: necrotic mass coming out of vagina of a little girl; vimetin/keratin
negative; desmin positive
striation in muscles; most common sarcoma in children
comes out of penis in little boys
o sarcoma of smooth muscle: leiomyosarcoma
o sarcoma of striated muscle: rhabdosarcoma
o sarcoma of fat: liposarcoma
movable mass at the angle of jaw: mix tumor
o its sin parotid gland: most common tumor in salivary gland; usually benign
o has two histologic different types of tissues but same cell layer from which the tumor is
derived
different from teratoma: derived from all 3 germ layers
cystic teratoma of the ovary:
o 6 yo girl with sudden onset of RLQ pain
RLQ to confuse between appendicitis and Chrons disease, follicular cyst, ectopic
pregnancy
X-ray shows calcification in the pelvic area calcification can be bone or teeth
germ cell tumor: totopotent; mid-line tumor
o tendency to stay in the midline: i.e. anterior mediastinum, pineal gland
leukemia: malignancy of stem cells in bone marrow
o always metastastize hepatosplenomegaly; generalized lymphadenopathy
o malignant lymphoma: arise from lymph nodes
can metastasize everywhere, including bone marrow
o Most common site for lymphoma not developing in the lymph node: stomach!
Extra-nodal primary lymphoma occurs in stomach
Can be produced by H. pylori
o Second most common extranodal primary lymphoma: peyers patch in terminal ileum
o Follicular B cell lymphoma:
Knocking off apoptosis gene: Bcl-2
T (14:18): inactivate bcl-2 gene inactivation of apoptosis
o auer rod: AML
Hypersegmented neutrophil: B12/folate deficiency
Trophoblastic tumors
o Can see in pregnancy but m ales can get it too
o Hydrotidiform mole: looks like a bunch of grapes
Present in 1st trimester with signs of preeclampsia: HTN, proteinuria, edema
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Do u/s: too large of uterine for gestational age and

Highest tendency for going into choriocarcinoma
o Mole: benign tumor of chorionic villus, lined by trophoblastic cells
o Syncystial trophoblast: on the outside, contact with blood and extract O2
o Cytotrophoblast: under syncystial
o Wartons jelly, chorionic villus, umbilical vein
Umbilical veins have highest O2 in the fetus
Choriocarcinoma: malignancy of lining of chorionic villus
o Syncytial and cytotrophoblasts
o Syncytial trophoblasts make beta HCG and human placental lactogen (growth hormone
of pregnancy)
H placental lactogen gives amino acid and glucose from mother to fetus
o favorite site of metastasis: lungs
o respond very well to chemotherapy: i.e. methotrexate, can achieve high remission
Neoplasia 2
More terminologies
-oma: doesnt mean its necessarily benign or malignant

o Ex: melanoma, lymphoma
-oma can also be non-neoplasam
o Hamartoma: overgrowth of tissues that are normally present there
Non-neoplastic lesion
o Bronchial hamartoma: benign cartilage, solitary point lesion in the lungs
o Hyperplastic poly in the GI tract: hamartoma
No increased risk for colon cancer because its not neoplasm
Muscle wall of stomach has benign pancreatic tissues:
o Benign tissues in the place that it shouldnt be: coristoma or heterotopic rest?
o Ex: Merkels diverticulum
Main complication: bleeding from gastric mucosa thats ulcerated (sometimes
pancreatic tissues causing ulceration)
But gastric mucosa is in the small bowel and shouldnt be in Merkels
diverticulum; nor do pancreatic tissues belong there heterotopic rest
Cancer
Increased mitotic rate doesnt mean its cancer

o What makes mitosis malignant: more chromosomes, or atypical mitotic spindle
o Aneuploid: more than normal 46 chromosome
Malignant: ability to metastasize
o Malignant cells have longer cell cycle than the cells they are derived from
Number of doubling time it takes before you can clinically detect a tumor: 30
o 30 times of going thru cell cycle
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o Tumor size: about 1cm in size, and 10-9 in mass

Malignant cells are immortal and lack adhesion
o Can live forever
o Cant metastasize if malignant cells are stuck together
Cancer cells have lots of enzymes
o Protease: used to break thru tissues
o Collagenase: break thru basement mb
Metastasis
3 modes: lymphatics, hematogenous, seeding

o Carcinoma: usually initiate metastasize via spreading to local lymph nodes (subcapsular
sinus of lymph node)
Breast cancer: axially node, or internal mammillary node
If can go thru lymph node efferent lymphatics throactic duct subclavian
hematogenous spread
Carcinoma can be hematogenous-spread, although start with lymph node
o Hematogenous: has already broke thru the lymph node, and can spread to many organs
o Sarcoma doesnt like to like to go into lymph nodes: usually start as hematogenous
Lungs and bones: very common site
o Angiosarcoma of the breast: do mastectomy; radial dissection of axilla doesnt work
o Examples of carcinoma that doesnt go to lymph nodes:
Follicular carcinoma of thyroid doesnt like to go to lymph node, by
hematogenous
Renal adenocarcinoma like to go thru renal vein
Determine prognosis
Hepatocellular carcinoma: always blood vessels
seeding:
o cancers in cavity tends to spread via seeding (malignant implants)
o ovarian cancer: surface-derived cancer (derived from lining around ovaries) easy to
seed to go over omentum, and pouch of Douglas
pouch of Douglas is similar to prostate in men can be felt during rectal exam by
pressing forward
pouch of Douglas: very important!
o Can also seed in pleural cavity from peripherally-located lung cancer
o Glioblastoma multiforme most common primary brain tumor in adults
Can seed thru spinal fluid and implant
So can medullary blastoma in a child
Metastasis: usually is more common than primary tumor in an organ
o Exception: renal adenocarcinoma
o Lung: most commonly mets from breast cancer
o Bone: mets from breast cancer
Breast cancer has Batsons system: venous complex that goes from base of the
skull down to the sacrum; no valves; small tributaries communicating with
vertebral bodies and vena cava; collect fluid around spinal cord and go back up
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Thus breast cancer can mets by a woman bending over!

o Most common bone mets: vertebral column > head of femur
Breast cancer can also mets to femur head
o Most common organ mets TO: lymph node
o Most common mets tumor to liver: lung, not colon
Colon is second due to portal vein drainage
o Where would testicular cancer mets to first: para-aortic lymph node
Not inguinal lymph node because its derived from abdomen and descends there
Testicles are initially located in the abdomen
o Left supraclavicular node: mets from stomach
Weight loss and epigastric distress
o Radionuclei scan: best to look for bone scan
Lytic and blastic metastasis
o Lytic: break bone down
Multiple myeloma has punched-out appearance because plasma cells have IL-1
IL-1: osteoclast activating factor
Pathologic fx; hypercalcemia
o Blastic: induce osteoblastic response
Alkaline phsphatase is increased
Odds: more likely prostate cancer in a male pt
Most common mets site for prostate cancer: lumbar column
o 80 yo ma with lower lumbar pain with point tenderness rectal exam as first step in
work-up
Then do a scan and PSA always pick a cheap test first on boards!
o Lucency: absence of bones due to lytic lesions
When seeing multiple lesions on a CT/X-ray/MRI on any gross specimen usually its mets
Most common of brain: mets
o Most common cancer killer both men and women: lung cancer
o Most common primary site for cancer in brain: primary lung
Most common cancer in liver: lung
Most common cancer in lung: mets from primary breast cancer
Most common cancer in adrenal gland: primary lung cancer, thus always do a CT scan of hilar
node
Stains
Desmin: great for muscle

o Embryno-rhabdomyosarcoma
Stain for keratin:
o Most carcinoma has kertin
EM is usually not used unless other methods fail
o APUD tumor: would see neurosecretory granules
o Histiocytic tumor (i.e. histiocytosis X) would see birbeck granules
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CD 1 positive
Muscle: would see actin and myosin filaments
Vascular malignancy
o Would see VWF, endothelial origin
o And know gap junctions
Oncogenesis
Know big picture!

o Big picture for tissue hypoxia: ischemia, hypoxemia, Hb-related problems, uncoupling of
oxidative phosphorylation
First step in malignancy:initiation from mutation
Second step in oncogenesis: promotion by making multiple copies of the mutation
Third step: progression; different kinds of cancer cells have different functions
o Malignant cells have one purpose: kill the host
o Sub-specializing: become able to invade, metastasize, or resistant to chemotherapy
Culture malignant cells
o Do it for melanoma
o Test for sensitivity for chemotherapy agents because some cancer cells are equipped
with resistance to chemotherapy
Two sets of genes that are involved in cancer: tumor suppressor genes and proto-oncogene
o Proto-oncogene: involved in growth process; cell cycle-related; involved in normal
growth cycle
o Tumor suppressor genes: monitoring, suppression
Trying to get a cell to divide
o Growth factors: EDGF
Proto-oncogene:
o Cancer-producing genes; but when not activated, serve normal functions in normal cell
growth
o Cis: makes growth factors
All growth factors need to hook into receptors
o Code for receptors: Erb-2 (breast cancer), RET (MEN syndrome)
o Sending signal to nucleus:
Located in cell mb: Ras GTP, sends phosphorylated protein message
Abl: in cytosol, close to mb
o Send message to a group of proto-oncogene in the nucleus
Stimulate nuclear transcription cell division
Myc: m-myc (neuroblastoma) and c-myc (burkitts lymphoma)
o Proto-oncogen is involved in normal cell cycle process: make growth factors, receptors
for growth factors, send messages (tyrosine kinase is usually attached to receptor for
phosphorylation of proteins)
Insulin: when bound to receptor on adipose tyrosine kinase phosphorylates
Glut 4 comes out of Golgi and goes to cell mb receptor for glucose
Tumor suppress genes:
o Two most important; Rb and P53
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Control cell cycle by keeping it in the G1 phase
Mutation
Initiation in oncogenesis
Most common: point mutation
o P53 suppressor and Ras oncogene usually due to point mutation (board question)
o All suppressor genes are point mutation
Amplification: making multiple copies
o Erb-2
Translocation:
o Irreversible
o T(9:22): abl (with tyrosine kinase activity) from chromosome 9 to 22, forming fusion
gene, tyrosine kinase activity sends a message cells keep dividing
Philadelphia chromosome
Seen in CML
o EBV translocates myc from 8 to 14: Burkitts lymphoma
CD21 receptor
When EBV hooks into CD21: stimulate B cells to become plasma cells lots of
division
Higher mitotic rate: higher chance of mutation
CMV can also do this
o T (14:18): B cell lymphoma; involved in inhibition of apoptosis gene
o T (15:17): acute progranulocytic leukemia
Can be treated with retinoic acid (vit A)
Vit A matures the blasts makes them benign
Knocking off tumor suppressor gene:
o Rb, P53
o Neurofibromatosis 1, Wilms tumor 1
o BRCA 1, 2: both involved in DNA repair
One on chromosome 14 and one on 17
BRCA 2: associated with breast cancer
BRCA 1: can be breast, ovarian cancer
Only 15% of breast cancer has genetic relationship
initiation of mutation: chemical, virus, and radiation
o most common mechanism for initiating cell to produce mutation: chemicals
smoking! Most common cause of death in the US
smoking lung, bladder, squamous of mouth and larynx, pancreas
secondary: cervical, leukemia and colon
papillary tumor in the bladder
o transitional cancer: most common cause smoking
o aniline dye
o Wegeners granulomatosis ending up with hematuria cyclophosphamide
Big carcinogen for transitional ell carcinoma
lung cancer:
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o smoking
o most cancer that is most associated with smoking: squamous and small cell
virus-related:
o non-puritic red raised lesions: Kaposis sarcoma due to herpes 8
o herpes 6 is roseola
o burkitts: due to EBV
other cancer due to EBV: nasopharyngeal carcinoma, mainly seen in Chinese
hepatocellular carcinoma due to Hep B: seen in Asians
aflatoxin from mold
hep C can also produce liver cancer
o HIV: primary CNS lymphoma
rapidly increasing incidence of primary CNS lymphoma in the US is directly due
to HIV
o EBV can also cause other malignant lymphoma
o Human papilloma virus: squamous of cervix, vagina, vulva
In homosexual: anus unprotected intercourse! (anal squamous carcinoma)
HPV 16, 18, 31
E6 knocks off P53 and E7 knocks off Rb
Radiation:
o Most common cancer associated with radiation: leukemia
Most common leukemia associated with radiation: CML, abl translocation (9:22)
o Papillary carcinoma of thyroid
Non-tender nodular mass in cervical region after radiation in the head/neck
region--< mets papillary thyroid carcinoma related to radiation
o Osteogenic sarcoma
o Radiologists are most likely to get leukemia; CJD seen more in neuropathologists
o Know basal cell carcinoma!
Derived from basal cell layer
Multifocal non-ionizing radiation, due to UV B
UV A: Woods lamp, fluorescence dermatophytes
Basal cell carcinoma > squamous cell
UV D: thymidine dimers
Precursor lesions commonly see in sun-exposed areas
o Solar keratosis, aka actinic keratosis
o Pearly, grayish white
o Dysplastic lesion, grows back after scraps off
o Progress into squamous carcinoma (about 3%)
o Arsenic can predispose this, especially seen in Bangladesh due to water supply
Arsenic: skin, angiosarcoma of liver, lung cancer
Know some current events!
retinoblastoma: chromosome 13
o sporadic: needs two separate mutation
o in familial autosomal dominant: only need 1 mutation
o white-eye reflex: most commonly due to congenital cataract
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but also seen in retinoblastoma

drug that predispose to cataract: corticosteroids (taken by Cushings syndrome
pt)
Neoplasia 3
Genetic Disease
Sun exposed area predisposed to skin cancer (basal, squamous cell melanoma)
XP: defect in DNA repair enzyme
o Autosomal recessive
o BRCA 1, 2, p53: also defect in DNA repair
o Chromosomal instability syndrome (fanconi, telangiectiasia, ataxiaetc)
Basal cell: upper lip up; lower lip down squamous cell carcinoma
Keloid: squamous cell carcinoma
o Squamous cell carcinoma in 3rd degree burn: develop in the area of sinus drainage or
ulcers that do not heal with abx
o With constant irritation, always a greater risk of cancer, and most commonly seen cancer
is squamous because its dealing with squamous epithelium (of skin), not glandular
epithelium
o Most scar cancer related to old TB scar is adenocarcinoma
o Related to burns and draining sinus tracts: squamous cell carcinoma
The only bacteria related to cancer:
o H. Pylori: adenomcarcinoma and low-grade malignant lymphoma
Cancer
Grade of cancer:
o Depends on what it looks like
o If can ID based on what cancer makes (i.e. making keratin, making glands) well
differentiated low grade
o Anaplastic, high grade, fully differentiated cant tell what it is, this is a grade term
o Ex: squamous because its making lots of keratin, and because we can ID it, its low
grade
Stage of cancer:
o TNM system, from least to most important
o T: size of tumor. Magic number: 2cm, if a mass is > 2cm, has a higher chance of
metastasis
o N: nodes.
o M: metastasis outside of nodes
o Most important prognostic tool of cancer: stage, and of which is metastasis
o Metastasis (i.e. liver, bones from prostate cancer) has a worse prognosis than lymph
node involvement!
Host defense:
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CD8 T cell: most important host defense system (numero uno!)
Class 1 antigens get altered when there is cancer, and get killed by CD 8 T cells
Signal (perforin) to proteases (caspases) to initiate apoptosis: breaking down
nucleus, mess up mitochondria. Cell death without any inflammatory infiltrate.
o Others: mq, natural killer cells, antibodies (type 2 hypersensitivity)
Cachexia: TNF-alpha; irreversible course. Once a patient with disseminated cancer going into
total catabolic stage, patient will not get any muscle mass back even if given parenteral
nutrition. This irreversible loss of muscle mass is due to TNF-alpha.
o
Anemia
Lots of causes of anemia are present in malignancy

Most common cause of anemia: chronic disease. Other mechanisms include:
o Side effect of colon cancer: right sided colon cancer Fe deficiency
o Metastasize to bone and replace bone marrow cells
o Chemo therapy drugs: interfere with cell cycle; wipe out bone marrow
o Autoimmune mechanism with certain types of cancers that also wipes out blood cells
o But most important cause of anemia is chronic disease
Most patients with disseminated cancers are hyper-coagulable
o Tendency to form clots
o Ex: painless jaundice, left supraclavicular node, light color stool, peculiar lesion in the
veins that seems to jump from one part of body to nextTrousseau's sign (superficial
migratory thrombophlebitis in a patient with carcinoma of pancreas)
o Trousseau's sign is asked very common; but usually describes as vascular problem in
the vein
Another commonly seen in disseminated cancer:
o Thrombocytosis: elevated platelet count
o Differential: Fe deficiency, scar, TB, myeloproliferative disease
o 40% of disseminated cancer has thrombocytosis
o Usually missed colon cancer: need to do a stool guiac (usually show up positive)
o Stool guiac: part of any normal physical exam
Fever:
o Most common cause: gram neg infection
o Internal catheter E.Coli; respirator pseudomona aeruginosa; indwelling catheter (i.e.
in the veins) staph aureus (but this is gram+)
Most common cause of death in cancer: infection
Paraneoplastic syndrome: VERY important
Signs or symptoms that say that one may have underlying cancer
o Useful because its like a clue for physicians to find cancer before it metastasizes
Most common: hypercalcemia
o Two mechanisms:
Metastasize to bone, producing IL-1, prostaglandin E2 activate osteoclasts
produce lytic lesions in bone hypercalcemia
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Squamous cell carcinoma of the mainstem bronchus: sits there, making
parathyroid-like peptides, and causes hypercalcemia (acts like PTH and breaks
down bone)
This is the paraneoplastic syndrome, not the top one
Acanthosis nigricans: seborrheic keratosis
o Acanthosis nigricans also associated with: MEN syndrome, insulin-receptor deficiency
related to diabetes
o When suddenly a crop develops overnight: lasser-trelat sign (multiple outcropping)
phenotypic marker for gastric adenocarcinoma
o Diagnosis: hypertrophic osteoarthropathy
Inflammation of the underlying bone stimulate increasing soft tissue developing
around the bone clubbing
Clubbing isnt always associated with malignancy i.e. bronchiectasis,
inflammatory bowel disease
If it were to be associated with malignancy: most likely primary lung cancer
Dermatomyositis: heliotrope (raccoon-eyes)
o Least common collagen vascular disease, but most commonly associated with
underlying cancer
o Elevation of serum CK: inflammation of the skin and muscle (hence increased serum
CK)
o High association with leukemia, lung cancer, lymphoma
o Patches over knuckles: goltrans patches
Vegetation on the mitral valve
o Sterile vegetation
o Associated with mucous-producing cancer (i.e. colon cancer)
o Paraneoplastic syndrome: morantic?? endocarditis
o These vegetations can embolize
o Needs Hx to rule out rheumatic fever (i.e. associated with polyarthritis)
o Lidman-sacs endocarditis: vegetation is all over the place
Hyponatremia or cushings: lung cancer
o Small cell carcinoma: ADH, ACTH
Opportumors? S100 antigen positive, neural crest origin, neural secretory
granules under electron microscopy
Hypercalcemia or secondary polycythemia: renal adenocarcinoma
o Making PTH-like peptides and EPO
Hypoglycemia or secondary polycythemia: hepatocellular carcinoma
o Making insulin-like factor and EPO
Hypercalcemia or cushings: can be autosomal dominant variety; rare tumor where the tumor
marker can be converted into amyloid: medullary carcinoma of thyroid
o Calcitonin can be converted into amyloid
Tumor markers when there is testicular cancer: AFP and hCG
o AFP (alpha fetal protein): yolk sac tumor (endodermal sinus tumor), commonly seen in
kids
AFP: albumin of fetus
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Also associated with hepatocellular carcinoma
Open neural tube defect is increased (need to be on folate while pregnant to
prevent open neural defect)
AFP is decreased in Downs syndrome
o Malignancy of bone associated with monoclonal spike: bence-jones protein
Multiple myeloma
Light chain of Ig (bence-jones proteins)
o Prostate cancer: PSH
Not specific, because it can also increase with hyperplasia, but its sensitive
Doesnt increase with rectal exam because PSH is not an enzyme
PSH is an antigen and is actually in the cell
o Breast cancer: CA 15-3
o Ovarian cancer, surface derived: CA 125
CEA and anti-CEA: when immune complex is deposited in the kidneydiffuse MGN of kidney
o CEA is associated with colon cancer
Trophoblastic cancer: marker is beta hCG
Brain Cancer
Most common primary tumor of brain in kids: cerebellar cystic astrocytoma

o All astrocytoma is benign
o Most common primary cancer in kids: medulloblastoma, derived from cerebellum
o Cerebellar astrocytoma is much more common than medulloblastoma
Other common cancer in childhood:
o Most common cancer in childhood: leukemia, acute lymphoblastic leukemia (ALL)
o Second: CNS tumor
o Others: neuroblastoma (adrenal medulla), berkitts lymphoma (B cell), Ewing sarcoma
(tumor of bone, onion-skinning type of calcification), embryonal rhabdomyelosarcoma
Adults:
o Incidence: women breast, lung, colon; men prostate, lung, colon
o Killer:?
Second most common cancer and cancer killer in men and women combine: colon cancer
Gyn cancer:
o Most common/highest incidence (besides breast): endometrial > ovarian > cervical
o Why cervical cancer least common? Pap smear screening
Because pap smear can pick up dysplasia (precursor to cancer), incidence drops
o Cancer killers: ovarian > cervical > endometrial
o Most common one (endometrial) has best prognosis
Vaccines available against cancer: Hep B
o Hep B
Viral burden of Hep B is higher than any other infection, including HIV
o Prevent: hepatitis B, hepatocellulocarcinoma, cirrhosis
o Eradicate Hep B, can then eradicate hepatocellulocarcinoma
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Hematology 1
Big Picture
MCV: less than 80

o Fe deficiency most common, anemia chronic disease, thalassemia pseudoblastic
anemia
Macrocytic anemia: greater than 100
o B12 Folate deficiency or alcoholics
Normocytic anemia: lower reticulocyte count (corrected)
o Aplastic anemia, renal disease
Normocytic anemia: increased reticulocyte count (corrected)
o Hemolytic anemia, sickle cells, autoimmune hemolytic anemia, microangiopathic
BEST to use MCV to classify the types of anemia!!!
Reticulocyte Count (RC)
Reticulocyte: young RBC, at exactly 24 hours, reticulocyte becomes a mature RBC as a

biconcave disk
RC tells you where the problem is: inside or outside of bone marrow
o If the problem is in the bone marrow: poor reticulocyte response
o If there is no problem with bone marrow: should have a good reticulocyte response
o With hemorrhage, takes at least 5 days before seeing an increase in reticulocyte count
Need to correct for RC for the degree of anemia
o The corrected RC is the amount of hematocrit/45 (normal) then multiple by RC given
o Ex: pt has 15% for hematocrit (severe anemia), RC is measured to be 9% (normal is <
3%)
If uncorrected, would look like bone marrow is doing great
Corrected: 15/45 * 9 =3% (right at the marker for good response)
>3%: good response; < 3% bad response from bone marrow
Need to know what reticulocyte looks like
o Black filaments: RNA filaments; still synthesizing hemoglobin need special stain
Polychromasia: blue-ish
o Younger RBCs: still have basophilia before becoming peripheral blood
o When seeing this, it shows that the bone marrow is really responding
o Takes 2-3 days before becoming mature
o When seeing these cells, need to make another correction
When doing reticulocyte stain, these cells would also be stained because they
have RNA filaments but dont want to include these cells in RC
Make first correction for degree of anemia, then DIVIDE BY 2
If CBC slip says polychromasia: 3%/2= 1.5% poor bone marrow response
o Ribosomes dont look like threads, they look like dots
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CBC Slip
Multiple hemoglobin by 3 = hematocrit

o Another rule of 3: transfusion of packs (not whole RBCs) for every unit of pack RBC
transfused, increase hemoglobin by 1 and hematocrit by 3%
o Ex: 5g Hb, 3 unit pack of RBCs, following day, hemoglobin 6 and hematocrit 18
shouldve been Hb 8, and Hct 24
o But if Hb is 6 and not 8 pt is bleeding (especially GI bleed!)
o Most common reason why Hb and Hct dont go up after transfusion: most likely due to GI
bleed
Unlikely due to hemolysis
MCV
Best way to classify anemia

Normal: 80-100 (on average)
o Less than 80: microcytic, most likely Fe deficiency
o If between 80-100: normocytic anemia
o > 100: macrocytic anemia, usually B12 or folate deficiency
But if a pt has both macro and microcytic anemia MCV would be normal
o Fe deficiency and folate deficiency: Fe is absorbed in duodenum, folate in jejunum, B12
in terminal ileum small bowel disease (celiac disease)
o Celiac disease: most common cause of mal-absorption involving duodenum and jejunum
(deficiency in both Fe and folate)
o Jejunum and terminal ileum: folate and B12 deficiency
o But usually not on the board exam
RDW: RBC distribution weight
o Machine looking at RBCs to see if RBCs are uniformly in size
o RDW can detect whether there is a change in size, and report in NUMBER
o Microcytic anemia, RDW increased microcytic, increased RDW showing that there are
different sizes (some may be small, some may be normal)
o When developing microcytic anemia, would have some small ones and some normal
ones that havent become microcytic yet will NOT all of a sudden become completely
microcytic and RDW picks this variation in size
Low MCV, increased RDW most likely Fe deficiency
o Cant be thalassemia, because its genetic
o Thalassemia usually has small/normal RDW
Whenever there is variation in RBC size RDW would increase
Spherocyte: anorexic RBC with little membrane (will not see central palor, all red)
Target cell: obese RBC with too much membrane; excessive membrane bulges out and Hb can
collect in there
o Marker for alcoholics (cholesterol concentration in the membrane), and
hemoglobinopathies (sickle cell, thalassemia, Hb C)
All microcytic anemias have decreased Hb synthesis
o Decreased Hb synthesis: decreased redness, can hardly see Hb in RBCs
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Hematology 2
Microcytic Anemia
Physical exam findings:

o Spoon nail: sign of Fe deficiency
But no specific; can also see in riboflavin deficiency
o Pale conjunctiva:
If pale: 6g or less Hb
o Palmar crease in Caucasian: if no redness anemia
o Lead line: discoloration along gum line
o Neurological exam is important in B2 deficiency knock off posterior column and lateral
corticospinal tract
Sensory deficit: proprioception, vibrationetc abnormality
Lateral corticospinal tract: babinski
Fe studies:
o 4 components:
Serum Fe: normal is 100 (same number as alveolar O2)
Serum ferritin: soluble circulating form of Fe storage
Represent amount of Fe stored in BM
Best screening test for Fe deficiency, Fe overload or anemia of chronic
disease
TIBC: total iron binding capacity
Fe carrying protein: transferritin; made in liver
Transferritin = TIBC
Fe stored in bone BM with transferritin made in the liver: inverse
relationship
o When Fe stored in BM is deficient signal to liver, make more
transferritin, more TIBC
o Fe stored increased increased transferritin, increased TIBC
Normal TIBC: 300
% saturation: serum Fe/ TIBC
Normal saturation: 100/300
1/3 of binding sites on binding proteins are usually occupied!
microcytic anemia:
o problem is in making Hb cant make Hb
o [Hb] determines number of cell divisions as RBC is made in BM
o Because of Hb synthesis is decreased extra division microcytic
o There are 4 subtypes: all have decreased Hb synthesis
Hb: heme + globin
o Heme: Fe + protoporphyrin
o Globin: , , ,
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Hb A: 2/2; Hb A2: 2/2; HbF: 2/2

o Fe deficiency: no Fe
Cant form heme because there is no Fe: no Fe no heme no Hb
o Anemia of chronic disease:
Microorganisms (esp bacteria) increase production with Fe
Thus body responds to inflammation by sequestering Fe away from
microorganisms
Fe is normally stored in mq in BM: lock Fe away in BM mq in infection
Lots of Fe in BM, but cant get it out decreased Hb synthesis
Serum Fe decreased
o sideroblastic anemia:
Sidero: aka Fe
Biochemical reactions in cytosol
Inner mitochondria mb: oxidative phosphorylation
Mitochondria matrix: beta oxidation of fatty acids, TCA
Cytosol and mito:
o Gluconeogenesis: start in mito cytosol
o Urea synthesis: mito cytosol mito
o Heme synthesis: mito cytosol mito
First part of heme synthesis (prop
Succinyl CoA + glycine protoporphyrin
o Glycine: simplest amino acid; inhibitory neurotransmitter
o Glycine blocked by tetanus toxin risus sardonicus, tetanic
contraction
o Every 3rd amino acid in collagen is glycine
Rate limiting reaction: synthesis of ALA
o Co-factor: pyridoxine
Ferrochelatase: combines Fe with protoporphyrin heme
Heme negatively feedbacks on activity of ALA synthase
More heme, decreased ALA synthase
sideroblastic anemia: rarest anemia
o Alcohol: most common cause in sideroblasic anemia
Most common anemia: anemia of chronic disease, then folate deficiency
Uncouples oxidative phosphorylation damage inner mito mb proton drainage
Marker cell: ringed sideroblast
Fe goes into mito but cant get out lots of Fe loading up in mito
Mito located by the nucleus of RBC in BM ringed sideroblast
Also seen in Fe overload disease
Would not get heme because mito is damaged by alcohol
o B6 (pyridoxine) deficiency: commonly seen in INH
No B6 no heme (first reaction of heme synthesis)
But Fe tries to get out of BM ringed sideroblast
o Lead poisoning:
All heavy metals, including lead, denature proteins
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Pb denatures ferrochelase
Can also affect ALA dehydrase
Fe enters mito cant bind to protoporphyrin to form heme decreased Hb
microcytic anemia
If ferrochelatase is decreased/inhibited, heme decreases
o Protoporphyrin is increased
Used to be screening test (RBC protoporphyrin level) for lead poisoning
o But if there is no Fe protoporphyrin is increased as well
o Test of choice in lead poisoning: blood lead level (screening and confirmatory test)
Thalassemia
Genetic disease, autosomal recessive

All Fe studies are normal; do not give Fe
Hb electrophoresis: separate based on size and charge
o HbA: predominant in adults (95-96%)
o HbA2: 1-2%
o HbF: 1%
-thalassemia:
o usually seen in: Asian, and black
all genetic hematologic diseases are seen in black: G6PD, sickle, and thal
o problem in making globin chain
Hb A, A2, F all decreased will not show up on electrophoresis
o There are 4 genes in globin chain synthesis
1 deletion: no anemia
2 deletion: mild anemia; microcytic because globin is decreased -thalassemia
minor
3 deletion: significant anemia; can form HbH (4 chains)
Would show up on electrophoresis
4 deletion: spontaneous abortion
High in Asian due to -thalassemia
Choriocarcinoma: high incidence in Asian due to high -thalassemia
4: Hb Bart would show up on electrophoresis; but doesnt matter because the
fetus is dead
o Do NOT give Fe
-Thalassemia
o Black, Greek and Italian
o : normal; +: normal but not a lot; 0 not making at all
o not due to gene deletion, but due to splicing defect, stop codons
most severe form -thalassemia is due to stop codon
o mild form of -thalassemia:
, , : okay
: slightly decreased
HbA would decrease; HbA2 and HbF would increase show up on
electrophoresis
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Use electrophoresis for dx
Severe type of -thalassemia can lead to coolies anemia: wont live past 30 yo
Require constant transfusion: usually die of Fe overload, hep B/C, HIV
o Tx: do nothing
and thalassemia:
o would predominantly have HbF (because only and are left)
o hereditary persistence HbF
o no anemia
o
o
Fe Deficiency Anemia
Preamture babies:
o every day when babies are not in uterus, they lose Fe common in premature babies
newborns
o check stool: positive for their blood; but also swallow moms blood
o would have HbA in the stool because babies swallow moms blood
o when having HbF in newborn stool most commonly due to bleeding Merkles
diverticulum
most common cause of Fe deficiency in newborn and young children
but unlikely in adults
Woman under 50: menorrhagia
Women under 20: anovulatory cycle
o Between 20-40yo: ovulatory cycle problems, pregnancy-related; endometrial polyp that
bleeds
Men under 50: peptic ulcer (most likely duodenal peptic unlcer)
Both men and women over 50: colon cancer
Fe studies in Fe deficiency
o Serum Fe: low
o TIBC: high
o % saturation: low
o Serum ferritin: low
Fe studies for anemia of chronic disease:
o Serum Fe: low
o TIBC: low (because high ferritin)
o % sat: low
o Serum ferritin: high
Fe studies for mild and thalassemia: normal
o Has nothing to do with Fe
Fe studies in sideroblastic anemia:
o The only way to see ringed sideroblastic is to look at BM and stain with Prussian blue
Mito that is full of Fe forms a ring around the nucleus in RBC
lead poisoning:
o basophilic stippling in RBCs: do not require special stain
o lead denatures ribonuclease
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ribonuclease normally breaks down ribosome thus ribosome persists in lead
poisoning
o coarse basophilic stippling very specific
o if its RNA: then its reticulocyte
o the only metal that can deposit in the epiphysis in children: lead failure to grow
o scenario of lead poisoning:
children: severe stomach colic, cerebral edema, confusion, severe anemia; pb on
flat plate, failure to thrive
cerebral edema: increased vessel permeability due to amino linoleic
acid build-up
flat plate shows: undigested Fe tablet, Hg, Pb
child eating paint; working in battery/automobile; moonshine; pottery painter
adults: neuropathy; foot slapping; wrist drop, lead line in teeth, colic and diarrhea
Fe studies in lead poisoning and sideroblastic anemia: all Fe overload
o Serum Fe: high
o TIBC: low
o Serum ferritin: high
o % sat: high
Hematology 3
Macrocytic Anemia
Megaloblastic anemia: B12 and folate deficiency:

o Cant make DNA because cant make deoxythiamindine monophosphate (TNP)
Cant mature nuclei; nuclei become mature, smaller and condensed when there
are more DNA
Any cells with nucleus would be huge due to decreased amount of DNA
o Cobalamin: B12, because it contains cobalt
o Circulating form of folate: methyl-tetrahydrofolate (m-THF)
B12 takes methyl group off m-THF B12 becomes methyl-cobalamin
Cant make DNA if methyl group is not off from folate
Need both folate and B12 to make DNA
o Cobalamin then passes methyl group to homocysteine methionine
Methionine: involved in 1C transfer; carry 1C and transfer to other reactions
If B12 or folate deficient: high serum homocysteine
High homocysteine: produces thrombosis, MI by damaging endothelial cells
Most common cause of high homocysteine: B12 or folate deficiency, but folate
deficiency is more common than B12
People with B12 or folate deficiency have increased chance for MI
o Dihydrofolate: the form to make DNA
Dihydrofolate reductase converts oxidized dihydrofolate back to THF
Man drugs block dihydrofolate reductase: methotrexate, TMS
DNA synthesis decreased macrocytic anemia
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Other function of B12:

o Even chain fatty acids can metabolize without problems
o But odd chain fatty acids only metabolize to propionyl CoA
Accumulation of propionyl CoA dementia
o Acetylate propinyl CoA methymalonyl CoA with B12 succinyl CoA TCA cycle
o B12 deficient: methylmalonyl and propionyl CoA build up
Methylmalonyl CoAmethylmalonic acid level increases
Specific for B12 deficiency
o B12 deficiency with neurological problems due to propionyl coA build-up cant
synthesize myelin dementia, demyelination of posterior column and lateral
corticospinal tract
Problem with UMN (spasticity, babinski); proprioception; vibration; dementia
o Can correct anemia but CANNOT correct neurological problems with high doses of
folate
o Can improve dementia with B12 injection
o Dementia: always work-up with TSH (r/o hypothyroidism) and B12 level
These are reversible causes of dementia
o Dont need to have anemia with B12 deficiency but can have neurological deficiency
Normal metabolism of B12:
o B12 is an animal product (meat, dairy); will not get B12 as a pure vegan
o B12 binds to R factor in saliva
R factor protects B12 from being digested by stomach acid
Intrinsic factor are made by parietal cells, located in fundus and body; also make
H+
Need to cleave off R factor before B12 can bind to intrinsic factor, via a
pancreatic enzyme move to terminal ileum to get absorption
Terminal ileum: where bile salt is also absorbed; and where Crohns
disease is
o pernicious anemia: autoimmune destruction against parietal cells and/or intrinsic factor
atrophic gastritis in body and fundus
no acid production
predisposition to gastric carcinoma
B12 deficiency:
o Pernicious anemia
o Pure vegan
o Chronic pancreatitis cant cleave off R factor
Commonly seen in alcoholics
o Giant worm (fish tape worm): always on board!
o Bacterial overgrowth
Due to stasis of intestine: problem with peristalsis; or diverticular pouches
Also true for bladder: no peristalsis infection
Bacterial love to eat bile salt, B12 and intrinsic factor
Can also have bile deficiency
o Terminal ileal disease: crohns disease
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Folate
o Seen in both animal and plant products: pure vegan have lots of folate
o Dihydrofolate reductase
o When eating folate, its in polyglutamate form cant be absorbed in jejunum
Intestinal conjugase converts poly into monoglutamate for absorption
Phenytoin blocks intestinal conjugase
Macrocytic anemia, hypersegmented neutrophils, neuro exam normal
Two things that prevent absorption of monoglutamate:
Birth control pills
alcohol
folate storage is only good for 3-4 months
o Circulating form of folate after absorption: methyl-THF
o Hypersegmented neutrophils:
Indicative of B12 or folate deficiency, even before having anemia
If neuro exam is normal folate deficiency
B12 deficiency: loss of vibration sense
Test of proprioception: Romberg
Positive: when pts eyes are closed, sway side to side because dont
know where the joints are due to abnormal posterior column
Cerebellar disease: swaying even when eyes are open; not Romberg
Immature cells in BM: big megaloblastic
Hematopoietic cells are made outside of sinusoids in BM
o Cords in spleen: fixed mq; RBCs and WBCs need to get back into sinusoid from
circulation
o Hematopoietic cells need to get thru cords in BM sinusoids circulation
o But big, immature cells cant squeeze into sinusoids: WBC, RBC and platelets cant get
out
Destroyed by mq pancytopenia in peripheral blood when there is B12 or folate
defic
Schillings test:
o Great for localizing B12 deficiency
o B12 deficiency give radiolabeled B12 by mouth, and collect urine for 24 hours
If no radiolabled B12 in urine absorption problem
o Then give:
Radioactive B12 and IF: if lots radioactivity in urine pernicious anemia
If still no radioactivity: r/o pernicious anemia
Give 10 days of broad spectrum abx and give radioactive B12
Lots of radioactive in urine: bacteria overgrowth
Pancreatic X factor and radioactive B12 if it works, chronic pancreatitis
o If none of the above works: Crohns disease
Normocytic Anemia
RC: best way to work-up

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RC: needs to make correction
First: for the degree of anemia Hct/45 *RC
Then check to see if there is polychromasia
No polychromasia: done
>3% BM responding appropriately; <2% BM not responding well
If polychromasia is present: take the number above/2 >3% good BM response;
<2% bad BM response
Need to have normocytic anemia first before becoming microcytic anemia
o Normocytic anemia with corrected RC <2%
o In Fe deficiency: first ferritin decreases Fe decrease, TIBC increase, % sat decrease
But at this point, no anemia yet
o Yet get normocytic microcytic anemia
Blood loss less than 1 week:
o Would produce normocytic anemia
o But no increased RC not enough time; takes at least 5-7 days to get the system rev up
Aplastic anemia: no bone marrow
o Pancytopenia in peripheral blood: normocytic anemia, leukocytopenia, thrombocytopenia
o Drugs: most common known cause of aplastic anemia
Chlorine phenicol: one cause, except no one is taking this drug anyone
The only occasion for this drug: rocky mtn spotty fever
o Other causes of apIastic anemia:
infection
aplasia of RBCs but everything else is okay arbovirus
but if all cells are destroyed hep C
radiation
malignancy
normocytic anemia with corrected RC <2% and renal failure decreased EPO
o there is recombinant EPO available
o athletes doping: taking EPO
summary of normocytic anemia:
o corrected RC <2%
o early in Fe deficiency and anemia of chronic disease
o
o
o
Hemolysis
can kill RBCs either extravascularly or intravascularly

o extravascular: via mq in spleen
hemolysis occurs if there are C3b or IgG on RBC surface
or if RBC is spherical or sickle cell: too big to squeeze into sinusoids
RBC containing a piece of nucleus (howell-jolly body)
Extravascular hemolytic anemia:
o Due to IgG or C3b: autoimmune hemolytic anemia
o Abnormal shaped RBC: spherocytes or sickle cell
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End product of phagocytosing RBC unconjugated bilirubin in mq in spleen

o Unconjugated bilirubin then moves into circulation lipid soluble bind to albumin
taken up by liver and conjugation
o Would see jaundice in extravascular hemolytic anemia
o Bilirubin is not in the urine because its lipid soluble and because its bound to albumin
Intravascular hemolytic anemia:
o RBCs die within a vessel because they bang into something
i.e RBC banging into calcification on congenital bicuspid aortic valve
o IgM on RBCs
Most potent complement activator: activate C1-9
IgG only activate up to C3
Anything that is IgM-mediated would lead to intravascular hemolytic anemia
o Would release Hb into blood stream
Haptoglobin would bind to Hb haptoglobin level decreases
Sometimes the complex of haptoglobin/Hb can be phagocytosed by mq to
retrieve Hb
o Can get jaundice; but usually dont
o Finding: hemoglobinuria, decreased haptoglobin
Intrinsic vs. extrinsic hemolytic anemia
o Intrinsic something wrong with RBC that is causing it to be hemolyzed
Ex: no spectrin mb defect; no decay accelerating factor on mb to neutralize
complement; no G6PD; abnormal Hb (i.e. HbS)
o Extrinsic: nothing is wrong with RBC, but RBC is at the wrong place at the wrong time
Ex: RBC flowing thru calcified valve; RBC becomes attached to C3b and/or IgG;
old RBC (has been circulating for 120 days)
Hematology 4
Intrinsic RBC Defect
Nothing wrong with BM corrected RC >3%

MAD: mb defect (spherocytosis, paroxysmal nocturnal hemoglobinuria), abnormal Hb (sickle
cell), deficient enzyme (G6PD)
Spherocytosis: removed extravasculary normocytic anemia, jaundice, unconjugated bilirubin
o Defect in spectrin; autosomal dominant
o Splenomegaly: spleen is where spherocytes are removed
o Gall bladder disease: due to gall stone disease
o Dx test: osmotic fragility test; increased osmotic fragility
o Tx: splenectomy
PNH: defect in decay accelerating factor
o When there is acidosis predispose complement to attach to all blood cells
o One is slightly respiratory acidosis when sleeping due to decreased ventilation rate
o Mb DAF: increased degradation of complement when sleeping
o Intravascular hemolysis in PNH
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o Severe normocytic anemia, pancytopenia, hemoglobinuria

Sickle cell:
o Sickle cell trait: no anemia, no sickle cell in the peripheral blood
May have sickle cell in renal medulla peritubular capillaries
o Amount of sickle Hb in RBC determines whether it sickles or not:
Magic number 60%: >60% sickling
o O2 tension in blood also determines sickling:
Low O2 tension: sickling
o Autosomal recessive:
Both parents need to have the abnormal gene on chromosome
Usually both parents have sickle cell trait: 2 traits
25% normal child; 50% sickle cell trait; 25% sickle cell 2 asymptomatic
carrier
Same as cystic fibrosis
Sickle cell trait :
o Black individual, normal on PE, normal CBC, with microscopic hematuria always get a
sickle cell screen as first step in work-up
o In black population: 1/8 have sickle cell trait
Sickle cell disease:
o Extravascular hemolytic anemia; occlusion of blood vessels by sickle cell
Occlusion ischemia pain (pain crisis)
Can occur in any organ in the body
In young children: occur in hands and feet dactylitis
o Anemia can be severe and requires transfusion
o Overtime, ischemia would damage organs
Spleen: first enlarges because of trapped RBCs then atrophies in 18-20 years
Spleen is non-functional after 2 years of sickle cell disease
o Non-functional spleen: howell-jolly body
Manifest in 2 yo time to get pneumovax
Strep pneumonia sepsis: most common infection and cause of death in a child
with sickle cell disease
If spleen is functional, mq would have removed pieces of nucleus
o When does a child develop sickle cell disease:
Occurs 6-9 months after birth because HbF inhibit sickling
70-80% of newborn blood is HbF
As HbF decreases and HbS increases induce sickling dactylitis
Sickling and infarction of bone marrow pain in bones
o Susceptible to osteomyelitis due to salmonella
Salmonella is destroyed by mq
But because spleen is non-functional, cant filter out salmonella
o Hydroxyurea: decrease incidence of vaso-occlusive crisis
Increase HbF synthesis
G6PD deficiency:
o X-linked recessive
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Most enzyme defects are recessive: albinism/PKU/homocysteinura
X-linked recessive enzyme deficiency: Leish-Nyhan syndrome, G6PD
Leish-Nyhan syndrome: has to do with purine metabolism; on all exams!
HGPRT is deficient, increased uric acid
G6P fates: make ribose DNA; make glycogen; make glutathione;
Make NADPH: major factor in anabolic reactions (i.e. steroid synthesis)
NADPH reduce oxidized glutathione neutralize peroxide into water
Riboflavin; glutathione peroxidase; Se are all involved
Every living cell makes peroxide as an end product
Catalase is present in all cells except RBC to neutralize peroxide
Glutathione: RBC has this
Increased peroxide:
Infection, oxidizing drug (nitro or sulfa drug), flava beans
Without G6PD peroxide would cause Hb to clump up Heinz body
Heinz body damages RBC mb intravascular hemolysis
Drugs that precipitate:
Primaquine: develop chills, hemolytic anemia, hemoglobinuria
Dapsone: used to treat leprosy
Do a G6PD screen test on pt with leprosy before using dapsone
Seen in: black, Greek, Italian same as -thal
If mq takes a bite of Heinz body bite cell
Heinz body requires special stain
Dx: never use enzyme assay during active hemolysis
After active hemolysis is over, do G6PD enzyme assay for confirmation
Do special stain to ID Heinz bodies
Will get G6PD on test
o
o
o
o
o
Autoimmune Hemolytic Anemia
Warm-reacting: IgG; cold-reacting: IgM

Most common hemolytic anemia is warm; and most common cause is SLE
o Certain HLA type in one autoimmune can predispose to other autoimmune diseases
o i.e lupus pt commonly has autoimmune hemolytic anemia, thrombocytopenia,
neutropenia, lymphopenia
o hashimotos hypothyroidism: also has pernicious anemia, vitiligo due to autoimmune
destruction of melanocytes
o board question: family with autoimmune disease, single best screening test HLA
not all autoimmune diseases are ANA+
causes of autoimmune hemolytic anemia:
o lupus: most common cause
IgG and C3b on surface of Rb removed by mq extravascularly
o Drugs: second common cause
PCN: BPO group of PCN attaches to RBC
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IgG ab can attach to BPO group RBC go into screen removed

extravascularly Type 2 hypersensitivity
Pt on PCN developing a rash type 1 hypersensitivity
Pt on PCN developing hemolytic anemia type 2 hypersensitivity
Methyl Dopa: aka aldomet
Used to lower HTN; one of the drugs that can give to pregnant women
besides hydralazine
o Both have complications: methyl dopa produces hemolytic
anemia; hydralazine produces drug-induced lupus
o Procainamide: also cause drug-induced lupus
Mess around with Rh antigen on surface of RBC: body begins to make
IgG against RBCs mq removal type 2 hypersensitivity
Quinidine: forms immune complex
Quinidine acts as a hapten, IgM attaches to drug immune complex
Type 3 hypersensitivity
IgM activates complement C1-9 intravascular hemolysis
Haptoglobin level is decrease, Hb in urine
Test for IgG and C3b on RBC
o Direct Coombs test
o Looking for IgG and C3b on surface of RBC
o Cant do direct coombs on platelets or neutrophils
Indirect Coombs test:
o Usually done in pregnant woman
o Look for ab in serum, not in RBC
Microangiopathic Hemolytic Anemia
Fragmented RBCs schistocytes; various forms of RBCs

Most common cause: aortic stenosis (systolic
o Intravascular hemolysis
o Chronic hemolysis: lose lots Hb as well as Fe attached to Hb can also get Fe
deficiency anemia at the same time
o PE of aortic stenosis: systolic ejection murmur by second ICS; radiating to carotid; S4,
increase intensity on expiration, prominent PMI; low MCV with fragmented RBCs
On exam!
Other causes:
o DIC: fibrin splits up RBCs
o Thrombotic thrombocytopenia purpura
o Hemolytic uremic syndrome
o When there are little platelet plugs scattered in all vessels schistocytes
microangiopathic hemolytic anemia
Long-distance runners:
o Commonly have this type of runner
o RBCs are hit against pavement
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Hemoglobinuria after finishing the race
Malaria
Falciparum:
o Ring form, and with superinfection (multiple ring forms)
o Can also have comma shaped
Hemolytic anemia:
o Correlates when cells rupture fever spike
o Fever pattern: can come up anytime
Benign changes in different WBCs
Neutrophils:
o In acute inflammation (i.e. appendicitis) absolute neutrophilic leukocytosis, left shift,
toxic granulation
o Leukomoid reaction: looks like leukemia, but its benign
Can involve any of the cell lines: neutrophils, esosinophils, lymphocytes
Caused by serious infections: TB, sepsis
Greater than 30K or 50K cells in peripheral blood
Over-exaggerated response to infection
Seen in kids, even in otitis media
Pertussis: huge lymphocytosis (60K) may mimic leukemia
But no anemia, no thrombocytopenia
o Lymphocytosis: occurs in viral infection, pertussis
Atypical lymphocytes:
o A lymphocyte that is presenting ag, responding to ag by dividing and getting bigger
Antigenic stimulations
o Seen in: mono, CMV, toxoplasmosis, viral hepatitis, phenytoin (blocks ileal conjugase,
producing macrocytic anemia)
o Mono: transmitted by EBV (kissing, because virus lives in the salivary gland)
EBV lives in B cells and CD 21 receptor
Monospot test: testing for presence heterophile ab
Anti-horse RBC ab; or anti-sheep RBC ab thus heterophile
Anti-horse RBC ab is absolutely specific to mono
Once having mono, always have it
High chance of recurrence; most people have 3-4x recurrence
Atypical lymphocytes in mono are T cells that react against infected B cells
o Mono: viremia, generalized painful lymphadenopathy, exudated tonsillitis
Most of the time its viral, not group A strep, that produces tonsillitis
Hepatitis but dont have jaundice; but super elevated transminase
Spleen: can rupture esp in contact sports for 6-8 weeks
o Big cells; lots of cytoplasm
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Hematology 5
Different WBCs (contd)
Monocytes:
o The king of chronic infection monocytosis in chronic infections
o RA, lupus, crohns disease, malignancy
o
Eosinophils:
o Seen in hay fever, rash in a pt taking PCN
Creatine gives one energy because it binds phosphate makes ATP
Serum test: creatinine is markedly elevated when someone whos taking creatine
Urea level is normal
Creatinine: end product of creatine metabolism
o protozoa does not produce eosinophilia: will not see in amoebiasis, malaria, giardia
o eosinophilia only seen invasive helminthes: not pin worm
pinworm does not invade mucosa no eosinophil
strongyloidsis
only in larva form that goes across the lungs invasive
adult ascariasis: NO eosinophilia
o anything with type 1 hypersensitivity: eosinophilia
Polycythemia
Always asked on all steps!

increased in RBC count, Hb, Hct
RBC mass vs. count
o Serum Na vs. total body Na
Serum Na: meq/liter of plasma; meq/kg body weight
o RBC mass: total number of RBCs in entire body in ml/kg body weight
o RBC count: number of RBCs per ml of blood
RBC number in circulating blood
o If volume depleted: RBC count is high hemo-concentrating RBCs by decreasing
plasma volume; but RBC mass is normal
Relative polycythemia:
o Decreased in plasma volume increased in RBC count, but RBC mass is normal
o Most common cause of PV
Absolute polycythemia: absolute increase in RBC mass
o Appropriate synthesis of RBC
Tissue hypoxia: lung disease, COPD, high altitude
o Inappropriate increase in RBC mass (blood gas normal)
P. Vera: myeloproliferative disease stem cell disease in BM
Stem cells make whatever they want and whenever they want; cant be
stopped
Can progress into leukemia
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Tumor or cyst with excess productive of EPO
Renal cell carcinoma
Polycythemia is either relative or absolute
o Relative: lose plasma volume (running) RBC count increase but mass normal
o Absolute: increase in RBC mass
Appropriate: anything that causes hypoxic stimulus for EPO release
Inappropriate: ectopically making EPO from tumor/cyst or PV
Polycythemia vera:
o Myeloproliferative disease: stem cells have lost all regulation
Myeloproliferative disease: PV, CML, myelofibrosis, essential thrombocythemia
Myelodysplastic disease: pre-leukemia syndrome
o 4 Hs of PV:
Hyperviscosity: increase total peripheral resistance
Total peripheral resistance = viscosity/(radius)4
Predispose to thrombosis anywhere in the body
Hypervolemia: increase in plasma volume that matches increase in RBC mass
Myeloproliferative disease takes years to develop, and plasma is probably
able to keep up with it
Histaminemia:
All cells are increased: RBC, WBC, platelet, basophils, mast cells
Classic hx: itch all over after showering; redness in face
o Histamine producing vasodilation can also get HA
Mast cells are increased and they are located in the skin; change in
temperature would lead to mast cell degranulation
Generalized itching:
o bile salt deposition in the skin due to obstructive jaundice
o mast cell degranulation
hyperuricemia:
nucleated hematopoietic cells are elevated; when cells die, purines are
released
end product of purine metabolism uric acid
chemotherapy drug: lots of cancer cells die; need to put pt on allopurinol
(block xanthine oxidase) to prevent too much uric acid in renal tubule
renal failure
o this is tumor lysis syndrome
o RBC mass, plasma volume, O2 sat, EPO
PV: increased, increased, normal, low
Low: lots of RBC suppress EPO production
COPD/tetrology of fallot/live at high altitude: high, normal, low, high
Renal adenocarcinoma: increased, normal, normal, high
Any renal cyst can also ectopically produce EPO
Wilms tumor/hydronephrosis/anything in kidney: increased EPO
Relative polycythemia: normal, decreased, normal, normal
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RBC Mass
Plasma Volume
Oxygen Saturation
Erythropoietin
Polycythemia Vera
Increased
Increased
Normal (inappropriate
polycythemia)
Decreased
COPD, Tetralogy of Fallot
Increased
Normal
Decreased (appropriate
polycythemia related to
hypoxia)
Increased
Renal Adenocarcinoma
with Polycythemia
Increased
Normal
Normal
Increased (being
ectopically
produced)
Relative Polycythemia
Normal
Decreased
Normal
Normal
High Altitude
Tx: phlebotomy to reduce viscosity; and to create Fe deficiency

Fe deficient: would take longer to make RBCs
Leukemia:
o Manifestations:
Malignancy of stem cells in BM, can mets everywherehepatosplenomegaly,
generalized lymphadenopathy
Abnormal cells in peripheral blood: blasts myeloblast, lymphoblasts,
megakaryoblasts, monoblasts
Crowd out normal hematopoietic cells: usually normocytic anemia;
thrombocytopenia
Increased WBC count with increased abnormal cells
o Acute vs. chronic:
Count number of blasts in BM: <30% blasts chronic; >30% acute
o Age bracket: a give away!
0-14 yo: ALL
15-39 yo: AML
Myeloblast with auer rod
40-59 yo: AML and CML
CML: Philadelphia chromosome
60 over: CLL
CLL is the overall most common leukemia regardless of age
Most common cause of generalized, non-tender lymphadenopathy in someone
over 60: mets to lymph nodes (not lymphoma, probably CLL)
o 49yo man, 150K wbc count, 1% myeloblast in blood and BM, hepatosplenomegaly,
lymphadenopathy, thrombocytopenia, normocytic anemia: CML
Get Philadelphia chromosome study to prove it
T(9:22) of abl gene fusion gene
Leukocyte alkaline phosphatase: see which neutrophils in the smear would take
it up
Mature neutrophils all have alkaline phosphate; but not neoplastic cells
If neutrophils are benign: would take up the stain
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Low leukocyte alkaline phosphatase score (usually 0) in CML

Teardrop RBC:
o Migration of hematopoietic cells from BM to spleen: extramedullary hematopoiesis
Splenomegaly
Huge spleen in adenogenic myeloid metaplasia
o Megakaryocytes return to BM and lays down collagen/fibrous tissues myelofibrosis
o As RBCs try to squeeze into sinusoids to move into peripheral blood thru fibrin
teardrop
o Huge spleen with teardrop RBC (marker for the ds) adenogenic myeloid metaplasia
Essential thrombocythemia: neoplastic stem cell making too many platelet
Acute Lymphoblastic Leukemia
Scenario: 4 yr old, sternal tenderness, fever, general non-tender lymphadenopathy,

hepatosplenomegaly, normocytic anemia
o 50,000 WBC count, many of which are abnormal
ALL is most common cancer in kids
Most Common Type Common ALL Antigen B Cell Leukemia
o CALLA Antigen cluster designation: CD10
Chronic Lymphocytic Leukemia (CLL)
65 yr old man, generalized non-tender lymphadenopathy, normocytic anemia,

hepatosplenomegaly, thrombocytopenia. 90K WBC, almost all cells resemble B cells with some
smudge cells, and hypogammaglobulinemia
o neoplastic B cells cant convert into plasma cells cant make gamma globulin
Most common cause of death in CLL is infection related to hypogammaglobulinemia
Hairy Cell Leukemia
62yo, hepatosplenomegaly (giant spleen); cells with projections out of the cytoplasm, special
TRAP stain ordered
TRAP = Tartrate Resistant Acid Phosphatase
Very rare leukemia
The only time board asks about this leukemia is on TRAP
Acute Myelogenous Leukemia (AML)
35yo, generalized non-tender lymphadenopathy; 50,000 WBC count with many abnormal cells.
70% blasts in marrow, anemia, thrombocytopenia
Abnormal cells show auer rods
o Auer rods: abnormal lysosomes, little red splinters in BM
Other Acute Leukemias
Leukemia that likes to infiltrate gums acute monocytic leukemia

o This is M5 subtype
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Acute Progranulocytic Leukemia: M3 subtype

o Always has DIC!
of all the leukemias, this is #1 cause of disseminated intravascular coagulation
o Translocation 15:17
o Tx: Vitamin A (retinoic acid) causes blasts to mature into benign adult cells
Lymph Nodes
Hardly ever ask about lymph nodes except for Hodgkins lymphoma
Lymphadenopathy
o Painful never malignant; not leukemia, or lymphoma
Inflammatory conditions causing lymphadenopathy and pain
Doesnt always need to be infection.
Lupus: generalized lymphadenopathy stretching capsule, inflammatory
condition pain
o Non-painfulmalignant
Either metastasis to lymph node or primary lymphoma originating from it
Types of lymphadenopathy:
o Generalized:
Generalized, painful lymphadenopathy systemic inflammatory disease
HIV, EBV, Lupus: systemic, generalized disease
o Localized:
Tonsilitis: only goes to local nodes; painful
Breast Cancer: local/regional node; non-painful
Localized non-painful: cancer
Brutons agammaglobulinemia
o absent germinal follicle no B cells
DiGeorge syndrome:
o paratrabecular zone no T cells
Histiocytosis X:
o True histiocytic CD1 positive tumor see it in the sinuses
Severe Combined ImmunoDeficiency (SCID):
o Due to adenine deaminase deficiency
o would only have histiocytes
when mq processes ag and deliver it to B cells germinal follicles
o B cells divide and end product is plasma cells coming out of germinal center making
ab
o This is reactive lymphadenopathy: a benign process
could be lupus, or draining tonsillitis
Follicular Lymphoma
looks like follicles, but all the cells look the same
uniform cell no heterogeneity
o no mantle zone
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o B cell tumor
most common Non-Hodgkins lymphoma
t(14:18): the apoptosis gene was destroyed cells now immortal
lymphoma: looks like fish-flesh
2 tissues that are resistant to invasion by cancer cells: board question!
o Cartilage
o Elastic tissue
Burkitts Lymphoma
Due to EBV
T(8:14): translocates Myc oncogene from 8 to 14
Starry sky:
o white areas: normal benign macrophages (look like stars)
o dark black cells: malignant burkitts lymphoma cells
#3 most common cancer in kids
o There is a French chemotherapy system that can cure this
In US, kids get Burkitts in the abdominal cavity
o in periaortic nodes, Peyers Patches, even testicle
In Africa: endemic form mandibular/jaw mass
T Cell Malignancy
Pt has no teeth, plaque-like lesions

o Plaque-like lesions: looks like fungal infection
o Section: inflammatory-looking cells in epidermis, no fungus
Suspected to be mycosis fungoides
o inflammatory looking cells actually neoplastic cells
helper T cells
neoplastic cells in mycosis fungoides: helper T cells
Usually involves skin and other organs, including lymph nodes
Cesari cell:
o Occurs when malignant cells got into peripheral blood
o Cesari syndrome
Malignant Histiocytic Disease
Scenario: a child with rash all over skin, generalized non-tender lymphadenopathy,
hepatosplenomegaly
o Biopsy done on rash: monomorphic infiltrate of CD1 positive cells
o This child has malignant histiocytic lesion
o CD1 = histiocyte marker
Birbeck granule: looks like a tennis racket
o Clostridium Tetani has a terminal-end spore that looks like a tennis racket
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Hodgkins Disease
Anyone with fever, night sweats, weight loss TB until proven otherwise
Scenario: localized non-tender lymphadenopathy,
o Biopsy: most of the cells look benign, but with Reed Sternberg cell
Reed-Sternberg cell: neoplastic malignant cell of Hodgkins disease
o looks like owl eyes
o CMV, giardia, ashoff nodule in rheumatic fever also have owl eyes
Prognosis: depends on number of R-S cells
o The lower the number of R-S cells, the better the prognosis
o The more R-S cells you have, the worse the prognosis
Know R-S is the malignant cell
Hematology 6
Lymph Nodes
Painful lymphadenopathy: inflammatory condition; not malignancy

Painless lymphadenopathy: malignant
o most common malignancy of lymph node: mets
o most common primary cancer of lymph nodes: malignant non-Hodgkins lymphoma
follicular B cell lymphoma: t(14:18) knocking out apoptosis gene, cells immortal
Hodgkins Disease
4 types, only need to know one, which is also the most common type
o Nodular sclerosing Hodgkins: more common in women
o Other types of Hodgkins are more common in men
Nodular sclerosing Hodgkins:
o Appearance: nodular (on low-power of lymph node), sclerosing with lots of collagen
deposition (pink deposition)
hard, non painful node
Classical presentation: woman with non-painful lymph node involvements in 2 places
o Site of involvement:
Anterior mediastinum mass: always!
somewhere above diaphragm: supraclavicular or cervical node
o mass in anterior mediastinum, non-painful lymph node in neck, woman nodular
sclerosing Hodgkins
Malignant cell: Reed-Sternberg cell
Serum Protein Electrophoresis
Albumin migrates the furthest because it has the most negative charges
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Gamma globulin doesnt migrate much it has the least charge

Polyclonal: many plasma cell clones
o gamma globulin region is where gamma globulins are
o abundance of globulins: G> A> M (first 3 letters in gamma)
in chronic infection: predominantly IgG; in acute infection: predominantly IgM
o ex of chronic infection: RA, crohns disease, ulcerative colitis polyclonal gammopathy
o many benign plasma cells are making IgGs diffuse elevation of the gamma globulin
peak
o gammopathy: benign and chronic inflammation
Monoclonal: one clone of plasma cells making immunoglobulin
o The other clones of plasma cells are suppressed almost always indicate malignancy of
plasma cells
o All other plasma cells are suppressed by immunologic mechanisms
o Most of the time its IgG malignancy
Making lots of IgG and light chains
When light chains get into the urine Bences Jones protein
On electrophoresis: first peak is albumin, then followed by alpha 1, alpha 2, beta, gamma
Hx: 25 yo non-smoker, emphysema of lower lobe, no peak under 1 1 anti-trypsin
deficiencies
Monoclonal: usually malignant, and usually multiple myeloma
Multiple Myeloma
Characteristics:
o Incurable: unless you get bone marrow transplant
o Seen in people over 50
o More common Women than men
Most common type: Ig Kappa
Plasma cells have IL-1: osteoclast activating factor
o Lots of lytic lesions in the bone: cookie cutter lesions nice neat cut, sharp border
o Different from Pagets disease: also have lytic areas, but very fuzzy-looking; irregular
borders
o Because IL-1 activates osteoclasts produce holes in the bones lytic lesions
o If you have a lytic lesion in your rib and cough pathological fx
Presentation: elderly woman who coughs and develops severe pain. Point tenderness over ribs.
Pathological lesion on x-ray multiple myeloma
MM key points: lytic lesions; elderly patients; bence jones protein
Plasma cell: bright blue cytoplasm, eccentrically located nucleus, clear area right next to
nucleus
o On EM: sheets and sheets of RER because the cell is making lots of proteins
o Very important to know what plasma cells look like!
Amyloid on EM:
o Non-branching linear compound
o Hole in the center
o Amyloidosis: usually in the DDx in multi-system disease
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Amyloid proteins: unique, but many different kinds of proteins can be converted into amyloid
proteins
o Free albumin; calcitonin (tumor marker of medullary carcinoma of thyroid); light chains in
MM; trisomy of chromosome 21
Chromosome 21 codes for -amyloid; in trisomy makes more -amyloid protein
-amyloid proteins are toxic to neurons
die at 40yo, autopsy shows atrophy of brain, senile plaques in frontal and
temporal lobe down syndrome pt
Down syndrome pt:
o always get Alzheimers if he lives long enough
o in childhood: die of cardiac disease, endocardial cushion defect (a combo of atrial and
ventricular septal defect)
if live past childhood: Alzheimers due to excess chromosome 21 making
excess -amyloid protein
always asked on boards
Lysosomal Storage Diseases
mq with crinkly paper-like wrinkle appearance in cytoplasm: lysosome is filled with glucose
cerebroside Gauchers disease
o autosomal recessive with a missing glucose cerebrosidase
o very wrinkled cytoplasm
bubbles in the cytoplasm, severe mental retardation, build-up product in lysosome is
sphingomyelineNiemann-Pick disease
o missing sphingomyelinase
the only glycogen storage disease that is lysosomal storage disease: Pompes disease
o missing an enzyme to break down glycogen in lysosomes
o pt usually dies of cardiac problem: excess deposition of glycogen in the heart
Hemostasis
Things in our body that prevents clots build-up in small vessels

o if the clots build up: DIC, TTP, death
o small vessels: arterioles, venules, capillaries
o small airways: terminal bronchiole, respiratory bronchiole, alveolar ducts, alveolar
Heparin: a GAG (muco-polysaccharide)
o We have it normally in our body
o Enhances the activity of anti-thrombin III (ATIII), which is made in the liver
o AT III neutralizes most of the coagulation factors
o We all have a little bit of HeparIn in vessels to prevent clotting
PGI2: prostacyclin
o made by endothelial cells
o vasodilatation of small vessels hard for thrombus to stick because blood flow is
increased
o vasodilation is antagonistic to forming thrombi (because everything moves too fast)
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also prevents platelet aggregation

Protein C and S: Vitamin K dependent factors
o inactivate/neutralize/inhibit two things: Factor 5 and Factor 8 in circulation
o ATIII cant inhibit factors 5 and 8: can only inactivate serine proteases,
Factor 5 and 8 are not serine proteases
Tissue plasminogen activator (tPA)
o Used to dissolve clots in pts with coronary thrombosis
o tPA activates plasminogen plasmin eat up everything in the vessel
Deficiency in any of the above things: clot formation/thrombogenic!
Birth control pill: thrombogenic
o increases synthesis of fibrinogen, factor 5 and 8, inhibits AT III
o act like an antagonist to Heparin blocking ATIII from doing its job
o estrogen in pill creates a thrombogenic state
Deadly Duo: birth control pill and smoking
o smoking itself is thrombogenic by damaging endothelial cells
o smoking is contraindication in birth control pills
Platelets
What stops bleeding when we cut/injure/damage a small vessel

o arteriole, capillary, venule
Bleeding time (BT): test used to evaluate PLATELET function
o even with Hemophilia A and zero factor 8 would still have normal bleeding time
o BT has nothing to do with coagulation factors; purely platelet-related
o Test done by: cut a 1mm wound on pts forearm; dap the wound every 30s with a filter
paper and measure how long it takes to stop bleeding
Normal: 7 minutes
Cutting tissue: damaged tissue immediately releases tissue thromboplastin
o tissue thromboplastin activates coagulation system
o exposes collagen in the wound activates Factor 12 starts the intrinsic system
o endothelial cells and megakaryocytes make adhesion product: a glue to stick to platelets
Von Willebrands Factor (vWF)
vWF: part of factor 8 molecule
made in endothelial cells and megakaryocytes in BM
platelets are made from megakaryocytes; thus normally carry some granules that
contain vWF
o when vessels are damaged vWF is exposed
Platelets have receptors for vWF an adhesion molecule
o platelet adhere to endothelial cells via vWF: platelets have to stick before they can carry
out their function
o when platelets stick chemicals are released (release reaction)
most important chemical: ADP potent aggregation agent; platelets start to stick
together and form a small thrombus in the vessel to block injury site
this thrombus would begin to stop bleeding but not enough
As soon as platelet has release reaction, it begins synthesizing thromboxane A2
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o platelet is the only cell in the body that has thromboxane synthase
o convert PGH2 thromboxane A
Thromboxane A2 has 3 functions: know this!
o potent vasoconstrictor: slows blood flow makes it easier for platelets to stick together
antagonist to prostacyclin
this is what causes vasoconstriction of coronary artery angina
o bronchoconstrictor: has activity in asthmatics
LTC4, D4, E4
o platelet aggregator: causes platelets to aggregate, block lumen of injured vessel end
bleeding time
o bleeding time ends once thromboxane A2 is released
Platelets release pre-formed chemicals in release reaction, and then it makes its own
Thromboxane A2like a mast cell
o Mast cells have release reaction of pre-formed elements: histamine, serotonin,
eosinophilic chemotactic factor
o Then activate release of arachidonic acid from mb; making prostaglandins and
leukotrienes further enhance the inflammation effect associated with type 1
hypersensitivity
Plug made by platelets: very temporary
o Bunch of platelets stuck together and held together by fibrinogen
o Fibrinogen is carried by every platelet
o Enough to prevent bleeding and stop bleeding time, but not very stable
Causes of prolonged bleeding time
o Thrombocytopenia:less than 90,000 platelets not enough to aggregate
o Von Willebrands disease: AD; most common genetic hereditary disease (1/250)
o Aspirin: most common cause
Mechanism: blocks platelet cyclooxegenase
Dipyramidole blocks thromboxane synthase)
Endothelial cells also have cyclooxegenase: but aspirin doesnt affect them
Different compounds; different reaction with ASA or NSAIDS
predominantly only affect platelet cyclooxygenase
Aspirin: irreversible
take daily baby aspirin no one platelet works in the body
other NSAIDs: reversible with 48 hours
Aspirin blocks platelet COX and prevents platelet aggregation
no thromboxane A2 platelets cant aggregate
Coagulation
Cutting tissue: release tissue thromboplastin, activate extrinsic system, activate Hagermans
factor (12) and activate intrinsic system due to exposed collagen
End product of intrinsic system: thrombin
o Thrombin converts fibrinogen to Fibrin
o A pile of platelets stuck together with overlaying fibrinogen; the thrombin generated by
extrinsic and intrinsic system making a stable platelet plug
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o Now the platelet plug cant be dislodged

Plasminogen: removes platelet plug from vessels
o Plasmin formed drill a hole in the plug recanalize the vessel
Bleeding Time: lasts until the formation of the temporary hemostatic plug
o This is when platelets are stuck together and draped with fibrinogen
o Stops bleeding time but very unstable and falls away easily
Shen coagulation system makes thrombin: converting fibrinogen to fibrin
o Now a very strong hemostatic plug
Platelet Abnormality
prolonged bleeding time

small vessels continue to bleed from superficial scratches/cuts cant form temporary
hemostatic plug
screw up the integrity of small vessels
symptoms:
o petechiae: pin-point area of hemorrhage; only seen in platelet abnormalities
o ecchymoses/purpura: more gray area
o epistaxis: nosebleeds most common manifestation of platelet problem
NONE of the above problems occur in coagulation factor deficiency
Coagulation Factor Deficiency
Ex: hemophilia A with deficiency in factor 8

Normal bleeding time
Problem: late re-bleeding, not bleeding from superficial scratches
o massive bleeding after an operation
o wounds are only held together by sutures and temporary hemostatic plugs
o coagulation factor deficiency cant convert fibrinogen to fibrin to stabilize the
hemostatic plug, cant hold the vessel open for too long and plug falls away
best question to ask for coagulation factor deficiency: bleeding from dental procedures
o greatest stress on hemostatic system
o no bleeding problem after wisdom tooth extraction: no prob with coagulation
if one has Hemophilia A, the bleeding is stopped temporarily by temporary hemostatic plug of
fibrinogen
o but then you go home and rinse your mouth with salt/peroxide hemostatic plugs
dissolve, bleeding, blood goes down throat and choke/suffocate to death on your own
blood
other coagulation problems:
o menorrhagia
o hemarthroses: depends on how severe coagulation factor deficiency is
bleeding into closed places
o GI bleedings
Tests to do for Platelet Problem

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Platelet count
o if you took Aspirin or NSAID: would have normal # platelets but they dont work
Bleeding Time: test for platelet function
Ristocetin Cofactor Assay: for vWF
o if missing vWF, Ristocetin cant cause platelets to aggregate
o most sensitive test to dx vWF disease
scenario: patient with osteoarthritis, sx for prostate removal, bleeding afterwards. Platelet
count/PTT/Protime normal.
o osteoarthritis: painful, most likely be taking NSAIDs
o normal protime/PTT: because coagulation is normal
o problem: platelets dont work
o tx: platelet pack transfusion (5 units)
Hematology 7
Extrinsic and Intrinsic System of Coagulation
Extrinsic system has factor 7

Intrinsic system has: factor 8, 9, 11, 12
Both systems share same final common pathway
o another system that also has a final common pathway: complement C3
o complement: classic, alternative, MAC pathway
o final common pathway in coagulation: factor 10
Facotor 10. 5, 2 (prothrombin), 1 (fibrinogen) clot
ProThrombin Time (PT)
Evaluates extrinsic system up to the formation of a clot

Factors: 7, 10, 5, 2, and 1
End stage of test clot in test tube
INR: standardized way of doing PT
o no matter what type of instrumentation or reagent usedsame value for PT
o PT would be the same regardless where in the world
PTT
Partial thromboplastin time

Tests intrinsic system up to formation of clot
Factor: 12, 11, 9, 10, 5, 2, and 1
Ex: normal PTT, prolonged protime factor 7 deficiency
o Prolonged protime 7, 10, 5, 2, or 1
o PTT is normal 12, 11, 9, 8, 10, 5, 2, 1 are normal
o Thus factor 7 is the only one that is responsible
Ex: normal PT, PTT prolonged factor 8 (most likely)
o Prolonged PTT 12, 11, 9, 8, 10, 5, 2, or 1 problem
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o Normal Protime7, 10, 5,2 and 1 are normal

o Hemophilia A, next to vWF disease, is most common factor deficiency
Warfarin: blocks epoxide reductase prevents gamma carboxylation of factor 2, 7, 9 and 10
o Usually follow warfarin by getting a PT: the only factor that is not evaluated with Pt
factor 9, because its part of intrinsic system
o PTT on warfarin: prolonged because factor 10 and 2 are in final common pathway and
both affected by warfarin
o But PT is better than PTT for monitoring because 3 out of 4 factors affected by warfarin
is included in PT
Heparin: follow with PTT
o All factors that AT III knocks out: 12, 11, 7, 10, prothrombin and thrombin
o If a patient is on Heparin, both PTT and PT are prolonged but PTT is better for eval
Both ProTime and PTT are prolonged in either warfarin or heparin
Fibrinolytic System
Plasmin: breaks down fibrin/ fibrinogen, and coagulation factors fibrinolytic

o Lots of pieces left over when clot is broken down X, Y, D, and E (fibrin degradation
products)
o Best test to screen for DIC: fibrin degradation products
Best: D-dimer
D-dimer:
o When fibrin clot is formed: there is factor 13 fibrin stabilizing factor
Stabilizing by linking strands; similar to linking collagen strands to increase
tensile strength
o D-Dimer detects only those fibrin fragments which have a link absolute prove that
there is a fibrin clot
DIC: increased D-dimer
platelet thrombus (platelets stuck together with strands of fibrin) broken down in
coronary artery: increased D-dimer
D-dimer is used as a test to see if the artery is recanalized by breaking
down the clot
Pulmonary embolus
o Excellent test to see if there is reperfusion after giving tPA
Vessel Abnormalities
Senile purpura: seen on the back of the hand of an old person

o vessels become unstable as one ages; amount of subcutaneous tissue thins
o with hitting vessels rupture, producing extensive areas of ecchymoses
o this is an age-dependent finding
o should also be present in areas that usually hit things: shins, back of hands
but if there is ecchymoses on buttocks and back abuse
o everyone would develop this!
Chronic Fe deficiency anemia due to persistent GI bleed
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o PE: small red dots on fingers: telangectasias

o Hereditary telangiectasia: aka Osler Webber Rendu
o Boards love this question!
o Most common genetic vascular disease: Fe deficiency due to chronic bleeding
Scurvy: also a vascular disease
Platelet Disorder
cant form temporary hemostatic plug

symptoms: epistaxis, petechiae/ecchymoses, bleeding from superficial scratches/cuts
12 yo kid, upper respiratory infection 1 week ago, presents with epistaxis. PE shows nonblanching lesions. Platelet count: 20,000
o petechiae dont blanch because its bleeding in the tissue board question!
o spider angioma would blanch: its AV fistula
o Diagnosis: idiopathic thrombocytopenia purpura
ITP: IgG antibody against the platelet
o Type II hypersensitivity
o macrophages in spleen remove platelets because platelets are coated with IgG
o similar to autoimmune hemolytic anemia
o tx: corticosteroids if very symptomatic; if not symptomatic: leave him alone
a woman, positive ANA, epistaxis, petechiae, splenomegaly, generalized tender
lymphadenopathy LUPUS
o Autoimmune thrombocytopenia
o IgG deposition on the platelet
o Type II Hypersensitivity
o Macrophage removal in the spleen
Thrombotic Thrombocytopenia Purpura (TTP) and Hemolytic Uremic Syndrome (HUS)
Not DIC not consuming coagulation factors

o Normal PT and PTT
Bleeding Time: small vessel injury, temporary hemostatic plug; coagulation system coverting
fibrinogen conversion to fibrin strong hemostatic plug
In TTP and HUS: something in the plasma damages small blood vessels throughout the body
platelets stick, aggregate, form firm platelet plugs in all small vessels in the entire body
o Platelets are consumed thrombocytopenia, bleeding!
o In peripheral blood: schistocytes
RBCs are smashed against the thrombi
Microangiopathic hemolytic anemia
o Symptoms: thrombocytopenia, fever, renal failure (glomerular capillaries have platelet
plugs); schistocytes, and hemolytic anemia
HUS: two causes
o 0157:87 E Coli toxin-producing E.Coli present in beef
Undercooked hamburger; toxin damages the vessel and produces the disease
Hemolytic: schistocytes; uremic due to renal failure
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One of the most common causes of acute renal failure in children: acute
hemolytic uremic syndrome
o Shigella toxin:
Vessel injury hemolytic uremic syndrome
In TTP hemolytic uremic syndreom:
o low platelet count
o Prolonged bleeding time
o Normal PT and PTT coagulation factors are not consumed, only platelets
Coagulation Factor Deficiency
Different from platelet deficiency: no epistaxis, no petechiae, no ecchymoses; no bleeding from

superficial scratches
Delayed bleeding:
o go thru surgery without problem, but when you start moving around bleed to death
most common cause of bleeding out of wound after an operation: bleeder
present
o blood constantly oozing out of molar extraction: temporary platelet plug but doesnt have
strong fibrin bonds to hold the vessels together
o hemorrhage into fascial compartment into the thigh; repeated hemarthroses due to
hemophilia A
o do not see hemarthroses or bleeding into spaces in platelet deficiency; only in
coagulation
Hemophilia A vs. Von Willebrands Disease
Know the difference between these two diseases!

Von Willebrands disease:
o Platelet adhesion defect due to missing vWF
signs and symptoms of a platelet problem
o factor 8 deficiency: very mild, never severe
o both platelet and coagulation defect menorrhagia, GI bleeding
o combo of epistaxis/easy bruising; menorrhagia
3 parts to the factor 8 molecule: all can be measured
o vWF: use ristocetin cofactor assay
o Factor 8 coagulant
o Factor 8 antigen:
Ag that carries vWF and factor 8 in the blood
Hemophilia A:
o Know its X-linked recessive males
Classic vWF disease: autosomal dominant; only 1 parent has to have the
abnormality and 50% children would have the abnormality
o Only one deficiency: decreased factor 8
But in classic vWF disease: factor 8 antigen decrease, factor 8 mildly decrease,
and so is vWF
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DDAVP:
o Aka desmopressin; related to ADH
o Increases synthesis of all 3 of part of factorf
o Help treat mild hemophilia A
o Tx of choice for von Willebrands Disease
Women with menorrahgia, normal DNC, no anovulatory bleeding vW disease
o Put on birth control pills bleeding goes away
But when off birth control pills: bleed to death
o Normal PTT and normal bleeding time
Sensitivity of normal BT and PTT in vW disease: 50%
o Should have done ristocetin cofactor assay abnormal!
Estrogen increases synthesis of all factor 8 components
o Tx of choice for women: birth control pills, not desmopressin
To Increase Synthesis of all Factor 8 molecules
o Desmopressin
o Birth control pills
Anti-phospholipid Syndrome
One of the causes of spontaneous abortion

Lupus anticoagulant: bad name!
o Vessel thrombogenic; produces vessel thrombosis
o Also seen in HIV
Anti-cardiolipin antibodies
o Vessel thrombogenic
o Produces biological false positive syphilis serology (VNRL)
Followed by FTAABS: should be negative in false positive VNRL
False positive due to the test antigen is cardiolipid; which reacts with syphilis ab
and anti-cardiolipin ab
In a woman that has biological false positive for VNRL:
o Order FTAABS
o Shes likely to develop lupus because anti-cardiolipid ab is a very common feature of
lupus
o Biological false positive of VNRL: dx criteria for lupus
Disseminated Intravascular Coagulation (DIC)
Easy to diagnose clinically, hard to diagnose in the lab

Forming clots within small vessels throughout the body
consumes fibrinogen, factor 5, 8, prothrombin, platelets
Draw blood into a clot tube, form a clot, spin it down
o Serum remains on top: missing all the things that make a clot fibrinogen, factor 5, 8,
Prothrombin, platelets
o This is what happened in DIC: only serum is left
Two diseases at once:
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o Thrombi in vessels
o Anti-coagulated because all that is circulating is serum, not plasma
o Hemero-hemorrhagic thrombosis syndrome
Causes of DIC
o Septic Shock: most commonly caused by E. Coli
Classic presentation: pt that is in shock, with rattlesnake bite, bleeds from any
orifices in body/cuts/scratch/venipuncture sites
o Snake bite: not neurotoxin by cobra, but rattlesnake
o ARDS: acute respiratory distress syndrome
Dx:
o Protime and PTT prolonged
o Platelet count: decreased
o D dimer: increased test of choice! 99% sensitivity
Plasmin: would be present to dissolve the clots)
Amniotic fluid embolism:
o complication of pregnancy, ruptured placenta
o amniotic fluid gets into circulation of mother but amniotic fluid contains thromboplastin
o true cause of death: DIC; thromboplastic activates DIC
Hereditary Thrombosis
presentation: young person with Deep Venous Thrombosis in leg

o usually dont get DVT at young age
o family history or family propensity for DVT
most common cause: factor V Leiden
o Abnormal factor V that proteins C and S cant break down
o Increased Factor V thrombosis
AntiThrombin III Deficiency
Most common cause: woman on birth control pills

o Most commonly its acquired
Can also be genetic
o Pt with DVT put on warfarin and heparin; followed by PTT that is normal
o Increase dose of heparin, PTT still normal AT III deficiency
Heparin enhances activity of AT III: if heparin doesnt cause PTT to prolong AT III deficiency
Aspirin
ITP
TTP/HUS
Platelet
Count
Normal
Low
Low
PT
Normal
Normal
PTT
Normal
Normal
Hemophilia A
VWD
Warfarin/
Heparin
Normal
Normal
Normal
Normal
Normal
Normal
Prolonged
Normal
Prolonged
Prolonged
Prolonged
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Prolonged
Bleeding
Time
Prolonged
Prolonged
Normal
Prolonged
Normal
ITP: most common cause of thrombocytopenia in kids

Main difference between Hemophilia A and Von Willebrands Disease: bleeding time
o Bleeding time is prolonged in VWD: missing Von Willebrands factor platelet adhesion
Warfarin: Protime, specifically INR
Heparin: PTT
Blood Bank
Group O: most common

o Antibodies in plasma: anti-A IgM, anti-B IgM, anti-AB IgG
Group A: 2nd most common
o Anti-B IgM
Group B: 3rd most common
o Anti-A IgM
Group AB: rarest of all
o no antibodies to RBCs
Newborn: no antibodies to RBC yet, even if they are Blood Group O
o dont begin synthesizing IgM until they are born, and RBC antibodies are IgM
o after 2-3 months, IgG synthesis begins so newborns dont have Isohemoagglutinins
Elderly: hardly any antibodies to RBC surface antigens
o If an old person is type A, and receives Type B blood by mistake and didnt develop
transfusion reaction level of ab is too low
Gastric cancer: associated with A
Duodenal ulcer: associated with O
Universal donor: O no A or B surface antigen on RBCs
o but can only receive transfusions from group O
Universal recipient: AB no antibodies to attack the other cells
5 Rh Antigens: D, C, c, E, e
Rh+: positive antigen D
Rh-: D antigen negative
Rh
Duffy Antigen
missing in the Black populationless likely to get Plasmodium Vivax malaria

the malaria needs to have this antigen in order to get into the RBC
o without this antigen P. vivax cant get into RBCs
Thalassemias and sickle cell: protect against P. Falciparum
o RBC has a shorter lifespan malaria parasite cant live out its life cycle in the RBC
Major Crossmatch
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Serum of recipient mixed with donors RBCs in a test tube to see if theyre compatible
o Looking for anything in recipients serum that will attack the antigens in donor RBCs
Antibody screen: indirect Coombs
o part of the workup for cross-matching
o if negative: then 99.99% compatible
o detecting for ab in pts serum attacking donor RBC
o need to do a separate cross-match for each unit of blood.
o But doesnt prevent a hemolytic transfusion reaction, or prevent from developing
antibodies in the future
Every unit of blood received increase the risk of developing antibodies
o It is more difficult to find compatible blood with each transfusion
increases cost/time
o DONT transfuse unless absolutely necessarily
Hematology 8
Hypersensitivity Reactions
Not everything in lupus is type 3

Everything in streptococcal disease is not type 3
o Post-streptococcal produces rheumatic fever: type 2, not immune complex
o Post-streptococcal glomerulonephritis: type 3
HUS or TTP: type 2
Penicillin rash: type I hypersensitivity
Penicillin hemolytic Anemia: type 2 hypersensitivitypenicillin group attaches to red cell
membrane
Most common antibody in US CMV antibody
o Everyone has been exposed to CMV at one time!
Diseases Associated with Transfusion
Today it is SAFEST from getting HIV from a blood transfusion of all infections
o 1/625,000 chance of getting HIV
o Due to lots of screening:
ELISA: check for anti-gp120 antibody; gp120 antigen attached to CD4 cells
Western blot: looking for other 3 or 4 ab that need to be present more specific
Most common infection transmitted by blood transfusion: CMV
o Because everyone has CMV in the blood
o When transfusing blood to a newborn, want to prevent:
Graft vs. host disease: donor lymphocytes attacking baby
CMV transmission: because babies dont have immune defense
Irradiate any blood that a newborn gets to kill the Lymphocytes if the
lymphocytes are killed, you cant get the Graft vs Host Disease (diarrahea,
jaundice, rash), and also the CMV lives in the Lymphocytes
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Irradiate blood before giving to newborn to kill lymphocytes:
cant get the Graft vs host disease: diarrhea, jaundice, rash
CMV also lives in the lymphocytes
Most common cause of post-transfusion hepatitis hepatitis C
Accidental needle stick from a pt: hep B
Accidental needle stick from HIV positive patient: 1/300 of getting HIV
o What do you do about it? Go on triple therapy as if you were HIV+
o two reverse transcriptase inhibitors (one of which AZT) and a protease inhibitor for 6
months; periodic check up with PCR and ELISA
o Accidental needle stick most common mechanism for getting HIV in medical personnel
Dont transfuse anything into a person unless they are symptomatic from whatever they are
deficient in
o if you have 10g Hb and no symptoms do not transfuse
o If Hb is 10g with COPD, and angina related to low Hb transfuse
o Low platelet count (50K): if not having epistaxis and no symptoms dont transfuse
o Every blood product is dangerous: can get infection from it
Fresh frozen plasma: never use it like isotonic saline for raising pts BP/sustain plasma volume
o FFP is used for multiple coagulation factor deficiencies
o DIC: to replenish consumed coagulation factor
o warfarin over-anti-coagulation and bleeding to death: not IM vit K because it takes 6-8
hours; immediately reverse with FFP
o overdose on heparin and bleeding to death: protamine sulfate
o cirrhosis of liver and bleeding because most coagulation factors are made in liver
o
Transfusion Reactions
Allergic reaction: most common

o Symptoms: itching, hives, anaphylaxis
o Anaphylaxis: type 1 hypersensitivity reaction
o In plasma of donor blood, there is something the recipient is allergic to (i.e. PCN)
o Treat with anti-histamine/benadryl
Febrile reaction: 2nd most common
o due to HLA antibody; anti-IgG; type II hypersensitivity reaction
o Patient has HLA antibodies against leukocytes from donor unit
o When unit of blood is transfused with leukocytes, anti-HLA ab of recipient attacks HLAtype leukocytes destroy white cell, releases pyrogenic substances fever
o If one has never been transfused should NOT have HLA ab
One only has HLA antibodies in blood if has been exposed to other humans
blood
o Women is most at risk for having febrile transfusion reaction: due to pregnancy
In women that has given birth fetal-maternal bleed
Some of babys leukocytes go into moms blood stream mom develops HLA ab
More pregnancies, more HLA ab developed
Also true for spontaneous abortion: can still get HLA ab from the fetus
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Women with higher number of pregnancies and spontaneous abortion highest risk for
a febrile transfusion reaction
Hemolytic transfusion reaction: very rare
o Transfuse Type A into a Type B or Type O person
o Receiving wrong blood: develop IgM ab most potent complement activator
As soon as the wrong RBC enters bloodstream IgM attach to it activate
complement (C1-C9), intravascular hemolysis, anaphylaxis toxin released pt
goes into shock immediately
This is due to clerical error
Delayed hemolytic transfusion reaction
o Patient has an antibody against an antigen on RBCs in donor unit
Can occur even with compatible major cross-match and negative antibody
screen (indirect coombs)
There are some antibodies arent present in the serum but one has been
exposed to with memory B cells
If one received blood 30 years ago probably no ab titer 30 years later (way
below sensitivity of ab screen); but would still have memory B cells
But if receiving transfusion with the ab: will not immediately produce the antibody
B cells start dividing in germinal center in follicle plasma cells make
ab
o Can make antibodies in a few hours, or in a week delayed reaction
Scenario: postpartum woman, with difficulty in delivery; ruptured placenta, transfused 4 units of
blood, fine when left hospital with Hb 10. 1 week later jaundiced, fatigue/weakness;
unconjugated hyperbilirubinemia and Hb 8
o Most likely cause: delayed hemolytic transfusion reaction
Halophane: takes over 1 week to develop
Hepatitis: takes 6-8 weeks
o Test to use: direct Coombs test would seeing ab coating pts RBCs
o Transfused; 1 week later with jaundice with dropping Hb delayed hemolytic transfusion
reaction
Type II hypersensitivity reaction
o
ABO Incompatibility
Blood group O women:

o Have a babymom would have problem with ABO compatibility
o Already have ab that can cross placenta
Type O people naturally have anti-AB, anti-A, anti-B IgG antibodies in
bloodstream
Ab can cross placenta and attack RBCs
ABO incompatibility can happen with the very first pregnancy
Scenario: mom is group O- and baby is group Ao no Rh incompatibility, but ABO incompatibility
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Mom has anti-AB IgG antibodies, A part of antibody attaches to babys A cells, babys
macrophages in spleen kill the RBC Type II hypersensitivity
o Mild anemia, unconjugated bilirubin derived from mq, handled by moms liver no
problem with jaundice or kernicterus in baby in utero
Mild anemia: antigen is not very strong; doesnt cause very brisk anemia
Direct coombs test on babys red cells: positive some RBCs are covered by
IgG ab
o Baby is born: mild anemia, develop jaundice in first 24 hours
o Most common cause of jaundice in a newborn baby within 24 hours ABO
Incompatibility
Not physiological jaundice start on day 3
Baby develops jaundice on day 3 because liver cant conjugate bilirubin as
efficient as adults bilirubin builds up
Benign; put babies under UVB light
o How does UVB light work? Converts bilirubin in the skin into dypyrole water-soluble,
gets urinated out
In all moms type A with type B babies: problem
o Problem starting with first pregnancy
o Unlike Rh sensitization where there is no problem with sensitization with first pregnancy
o Mom type O: problem if baby is type A or B, but not if baby is type O
o
Rh Incompatibility
Mom Rh-, baby is Rh+

o 1st pregnancy: deliver baby, there is a fetal-maternal bleed, babys Rh antigen gets into
moms blood moms develops an Anti-D antibody against Rh antigen
o Now mom becomes sensitized: now has ab against Rh D ag
o 2nd pregnancy: Rh positive babymom has an IgG antibody, crosses placenta, attaches
to babys RBCs
Of all ag, the D ag mounts the worse hemolytic anemia
Baby would be more severely anemic than in ABO incompatibility
o Babys mq phagocytose, lots of bilirubin, moms liver handles it
o When baby is born: higher bilirubin level, worse anemia 99% chance requiring
transfusion
Transfusion: take out bilirubin, sensitized RBCs, and correct anemia
st
1 pregnancy: baby is okay, mom gets sensitized
Future pregnancies: babies are involved
Prevention: mom gets an antibody screen
o If moms negative give mom Rh globulin (anti-D) around 28 weeks as prophylaxis
o Anti-D: derived from other women that have been sensitized; heat treated; cant cross
placenta remain within mom
o 28 weeks: can get fetal-maternal bleed before delivery; or there might be trauma (fall,
accidents) and babys blood can get into mom circulation
With anti-D ab from globulin: destroy D+ cells so mom doesnt get sensitized
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before moms cells even see the Rh positive baby cells so mom doesnt
develop the antibody in the first place
o At birth: if baby is Rh+ do Kleihauer-Betke test
Take some moms blood, do special stain ID fetal RBCs in moms circulation
Can accurately quantify the amount of babys bleed into mom
O negative mom, A positive baby: 2 problems
o ABO ncompatibility
o Rh incompatibility
o But no problem with sensitization: deliver baby, some babys A cell gets into moms
blood but only lasts milliseconds in moms circulation because babys A cells are
destroyed by IgM ab
Babys cells are gone before mom can develop antibodies
o ABO incompatibility protects against Rh sensitization (esp if also Rh incompatible)
Erythroblastosis Fetalis
Children with this die of heart failure due to severe anemia, secondary to severe anemia
o Severe anemia: decrease viscosity of blood
o low viscosity high output of the heart, left heart failure first, right heart failure second,
pitting edema, hepatomegaly due to extramedullary hematopoiesis in the liver
because the kid is trying so hard to make more RBCs
Cross section of brainstem in a child; color is orange-yellowishkernicterus
o From a baby who had Rh incompatibly
o unconjugated hyperbilirubinemia due to hemolytic anemia
o lipid-soluble unconjugated bilirubin gets into lipid-rich brain, basal ganglion area and
midbrain toxic, severe debilitating disease or death from kernicterus
Cardiovascular 1
Jugular Veinous Pulse
usually located on the right side

o best way to find out which wave it is: to find out when systole occurs
C wave: correspond to 1st heart sound beginning of systole
Three positive waves (A, C, V) and two negative waves (X and Y)
A wave: due to right atrial contraction in late diastole
o To get last bit of blood out of atrium to fill up left ventricle
o This last contraction, lots of blood goes into RV some blood backs up into venous
pulse creates positive A wave
C wave: tricuspid valve closes during systole
o Contraction: blood would go into pulmonary artery; some blood would hit tricuspid valve
which would bulge into the RA creates positive C wave
X wave: systole occurs, contracting, tricuspid valve closes, bulging, blood goes up pulmonary
artery, creating negative pressure, sucks the valve down
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Negative pressure creating by blood wheezing into pulmonary artery and tricuspid valve
gets sucked down negative X wave
V wave: beginning of filling up RA during systole
o Tricuspid valve is still closed, systole still occurring, blood going out of pulmonary artery
but RA needs to fill up
o Corresponding to actual beginning of diastole, S2 sound
Y wave: filled-up RA, diastole begins, tricuspid valve opens, blood goes out into ventricle
KNOW THIS COLD!
With mitral stenosis: A wave disappears
o A wave is atrial contraction; disappears in irregularly irregular pulse (a-fib)
o S4 heart sound would also be present
Tricuspid stenosis: atrium needs to contract against a valve that doesnt want to open giant A
wave
Tricuspid regurgitation: a lot of blood going back into RA and some into pulmonary artery during
systole giant CV wave
o
Lipoprotein Disorders
When there is turbidity of plasma (in blood thats drawn out) due to TG
o Only TG, not cholesterol, produces turbidity
o Two ways to carry TG:
Chylomicron: from TG ingested, saturated fats (long-chain fatty acids)
Broken down via lipase in guts, reassemble in small intestines and stick
on chylomicrons
Chylomicron: exogenous, diet-derived TG
If want to get an accurate TG level: need to fast for 12 hours; TG in diets
would still in chylomicron
Cholesterol level (and HDL) wont get affected by non-fasting: there is
only <3% of cholesterol in chylomicron dont need to fast to get correct
cholesterol and HDL level
VLDL: TG made in liver; made from G3P that comes from glucose
Increased in alcoholics: due to increased level of NADH, pushing DHAP
to G3P
VLDL is more dense than chylomicron due to proteins
Chylomicron (white-ish): floats, supernant
VLDL: pink-ish turbidity; infranant
o A simple tube placed in refrigerator at 4 degrees over night can tell what lipid fraction is
responsible for elevated TG
In one pt: excess chylomicrons (probably didnt fast) and increased VLDL
o Another tube: high chylomicron, normal VLDL
Pt was probably not fasting
very unlikely to be type 1 hyperlipoproteinemia
o if there no supernant but turbid infranant increased VLDL
type 4 hyperlipoproteinemia: most common; increase in VLDL, no chylomicrons
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when fasting:
o decreases TG derived from diets
do NOT need fasting to get accurate cholesterol and HDL
Xanthelasma: yellow eyelid
o Cholesterol underneath eyelid, causing it to be yellow
Achilles tenden xanthoma
o Pt has family hx of dying of coronary heart disease by age 20
o Familial hypercholesterolemia: autosomal dominant, absent LDL receptor
All LDL cant go into cell builds up, very high by age 18 death
At birth, put on HMG-CoA reductase inhibitor
Tried gene therapy, but not successful
Gene therapy successful in SCID: adenine deaminase that is missing in
SCID inserted into adenovirus (DNA virus) infect the affected kid,
cured
SCID: bubble kid because cant be in contact with air contamination
o Achilles tendon xanthoma: pathognomonic for FH
o This is type 2 hyperlipoproteinemia
Vascular Disorders
Atherosclerosis
o Developed as reaction to injury
o Something is injuring the endothelial cells lining muscular and elastic arteries the only
two arteries that have atherosclerosis
o Injuring: CO and ammonia in cigarette smoke; LDL (esp oxidized LDL); virus infection,
homocystein
Chlamydia pneumonia: second most common cause of atypical pneumonia
Can cause vascular injury, predisposing to atherosclerosis
Pt with MI: most of them have ab against Chlamydia pneumonia
o When endothelial cells are damaged:
Platelets stick to it and released PDGF
PDGF stimulates hyperplasia of smooth muscle
Smooth muscles migrate from media to right underneath endothelial cells
(intima)
o Monocytes have access to vessels because they have been injured
Monocytes also release growth factor
o Increase LDL: get phagocytosed by mq fatty streaks
Yellowish discoloration because mq and smooth muscles containing LDL
o Over time, fibroblast develops fibrofatty plaque
Pathognomonic lesion for atherosclerosis
o Then can be complicated by dystrophic calcification, fissuring, thrombosis complicated
atherosclerosis
o Cells involved in atherosclerosis: platelets, monocytes/mq, cytotoxic T cells and
cytokines
NOT involved: neutrophils
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Primary factor of coronary artery disease (due to atherosclerosis thrombus),
atherosclerotic stroke related to atherosclerotic plaque, abd aortic aneurysm
(atherosclerosis weakening vessel wall), non-traumatic amputation of lower extremities
(peripheral vascular disease), mesentery angina, small bowel infarction, renal vascular
HTN
Small vessels (i.e. arterioles) can also get hardened:
o Hyaline arteriole sclerosis: look like onion cut in cross-section
Whenever there are lots of pink-staining material hyaline
Hyaline arteriolosclerosis:
o Small vessel disease, esp in diabetes and HTN
Diabetes:
o Two mechanisms of damage: non-enzymatic glycosylation of small vessels (including
capillaries in kidneys) and osmotic damage
o Glycosylation: glucose attached to amino acid in protein
In HbA: glucose attached to aa in HbA HbA1C correlates with 6-8 weeks of
blood glucose level
Best way of seeing long-term glucose management; should be <6% in
diabetes
All damages in diabetes are related to high blood glucose
o Osmotic damage: tissues that have aldose reductase (lens, pericytes in retina, Schwann
cell) convert glucose into sorbital, which is osmotically active
suck water into cells cells die cataract, retinal vessel aneurysm, peripheral
neuropathy
o non-enzymatic glycosylation effect on basement mb of small vessels rendering it
permeable to proteins:
proteins in plasma leak thru basement mb into vessel wall protein deposition in
the vessel hyaline change, narrowing lumen
in glomerular basement mb: microalbuminuria (first change seen in diabetic
nephropathy)
HTN: mechanism different use brute force!
o Increased in diastolic pressure drives protein right thru basement mb
o In kidneys of HTN pt: shrunken, cobble-stone appearance on surface
Hyaline arteriolosclerosis of arterioles in the cortex ischemia wasting away,
fibrosis and atrophy of tissues
o Lacunars stroke (small area of infarction in the internal capsule area) hyaline
arteriolosclerosis related to HTN
o Much HTN and diabetes pathologies are related to hyaline arteriolosclerosis: MUST
KNOW!
Hyperplastic arteriolosclerosis:
o Seen in malignant HTN
o More common in blacks than white (because HTN is more common in blacks)
o BP >240/160, papilloedema
o See this vessel change in kidneys
o Onion-skinning appearance
o
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Aneurysm
Aneurysm:
o Area of outpouching of vessel due to weakening of vessel walls: weakening,
outpouching
Bronchiectasis: usually due to CF with infection, destruction of elastic tissues
outpouching, dilatation of bronchi
GI aneurysm: diverticular disease weakening and outpouching of mucosa
o Law of LaPlace: wall stress increases as radius increases
Once start dilating something does not stop!
Thus all aneurysm will rupture
o Most common place for aneurysm
Blood supply to the aorta below renal artery
abd aorta can only get O2 and nutrients from blood that is in its lumen
organs farthest away from abd aorta are at higher risk for injury, atherosclerosis,
weakening of wall, aneurysm
o rupture triad of abd aneurysm: sudden onset of left flank pain, hypotension, pulsatile
mass on PE
aorta is retroperitoneal: left flank pain
hypotension: can put 25% blood supply in retroperitoneum
o Biggest complication of any aneurysm: rupture
Aneurysm at the arch of aorta: most common cause is tertiary syphilis
o Pathology in syphilis: vasculitis of arterioles
o Painless chancre: little arterioles surrounded by plasma cells; the lumen is completely
shut ischemic necrosis
o Nerves are located right next to tissues also get knocked out painless
o Treponeme infects small vessels (arterioles)
o Infecting vaso vasorum of the aortic arch due to highest blood supply endarteritis
obliterans
Obliterating lumen ischemia, weakening during systole aneurysm
o Stretch the aortic valve ring: aortic regurgitation
Murmurs can occur either due to the stretch of the ring or valvular damage
In this case: murmur due to stretching the ring
The aorta should be closed during diastole; but as the valve remains open, there
will be more blood in LV would normally increase force of contraction due to
Frank-Sterling force
Normal ejection fraction: 0.66
But Frank-Sterling compensation: not very efficient, a pathological
process
Increased stroke volume related to more blood in LV: can see uvular
pulsating, nail lifting up, pulsating of vessels underneath nails, pulsating
femoral artery
o Left recurrent laryngeal nerve stretch, get hoarseness of voice
Dissecting aneurysm:
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Key factor for causing a tear in aorta: HTN imposes stress on vessel wall
Weakening of elastic arteries due to elastic tissue fragmentation
There is also cystic medial necrosis: GAGs stick together and make mucin-like cystic
pockets
Wall of aorta rubs on itself
o Whenever there is an area of weakness in the elastic artery blood dissect the artery
Proximal dissection:
o Most common
o Blood goes into pericardial sac pt dies of cardiac tamponade
o Because most of the tear is in the arch of aorta would have absence pulse
Dissect and close off the lumen to subclavian artery on the left
o Ripping/tearing chest pain right towards the back
o Chest x-ray: diameter of proximal aorta (aorta knob) would be expanded (85%
sensitivity) screening test of choice
Confirmatory test: trans-esophageal u/s or angiography
Diseases predispose to dissection:
o Marfans: AD chromosome 15 defect in fibrillin
Fibrillin: component elastic tissues
Defect in elastic tissues dislocated lenses, dissecting aortic aneurysm
Eunuchoid proportion: height from pelvic brim to the feet than that to the head;
arm span greater than height
Arachnodactyly: spider hands
Most common cause of death: mitral valve prolapse conduction defect, sudden
death
Can also have tricuspid valve prolapse
o Ehlers-Danlos: defect in collagen
o Pregnancy:
Most common catastrophic disease in aorta during pregnancy
2x plasma volume than non-pregnant woman (2:1 ratio of increasing plasma
volume to RBC mass) decrease [Hb]
In pregnant women: Hb< 11.5 and non-pregnant Hb <12.5 for anemia dx
Excess volume for 9 months can cause vessel wall weakening and aneurysm
Superior vena cava syndrome:
o Presentation: smoker, developing primary lung cancer; HA, blurry vision, retinal vein
engorgement; congested
o Primary lung cancer knocking off superior cava backup of venous blood into the
jugular system and dural sinuses
o Very bad disease! Lethal.
o Tx: radiation to shrink down the amount of tumor to improve blood flow
o Superior vena cava: nothing to do with horners syndrome
Pancoast tumor is associated with horners syndrome
o
o
o
Vascular Tumors
Sturge-weber syndrome:
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Vascular malformation in the face
Its in the trigeminal nerve distribution
o On the same side of face: AV malformation in the brain
AV malformation: predispose to bleeding
Also slightly mentally retarded
Spider telangiectasia:
o telangiectasia in the GI tract
If pressed down: blanchable
o Spider angioma: blanchable telangiectasia
always normal in pregnant women due to hyperestrinism
o but spider angioma in men: most likely due to cirrhosis
most likely cause of cirrhosis: alcoholism
cirrohosis: cant metabolize estrogen gynecomastia, warm skin, palmer
erythema, spider angioma
also cant metabolize 17-keto-steroids aromatize into estrogen in
adipose tissue
o Looks different than petechiae; also blanchable
Blanchable: AV fistula going from arteriole directly into venules and bypass
capillaries
o
Capillary Hemangioma
Presentation: a child with a red lesion on face leave it alone

o Itll be completely gone by 8yo
Kaposis Sarcoma
Organism: herpes virus 8
Bacillary Angiomatosis
The lesion is only seen in AIDS pt, looks like kaposis, but is due to bacteria
Organism: bartonella henselae
o Also the cause of cat scratch disease
Require silver stain
Treat with sulfa drugs
Very likely to be on boards!
Angiosarcoma of Liver
Asked very consistently on board

Causes: VAT
o V: vinyl chloride
Plastic, rubber
o A: arsenic
Part of pesticide, can contaminate water supply
o T: thorium dioxide
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Less common
Vasculitis
The stem of the question gives the answer away!

Seen in: small vessels (arterioles, venules, capillaries), muscular and elastic arteries
o Different symptoms in different locations
Small vessel vasculitis: 99% due to type 3 hypersensitivity
o Immune complex deposition in small vessel activate complement system C5a attract
neutrophils fibrinoid necrosis
Would have palpable purpura!
Purpura in platelet problem is not palpable
o Leukocyclastic vasculitis: all immune complex disease; fibrinoid necrosis;
Muscular artery:
o Polyarteritis nodosa, wegeners granulomatosis
o Thrombosis of vessels infarction; will not have palpable purpura
Kawasakis disease in children coronary artery vasculitis
o Kawasakis disease: most common cause of mild MI of in children
Mucocutaneous inflammation, desquamation of skin, lymphadenopathy
Thrombosis infarction coronary artery vasculitis
Elastic artery vasculitis:
o Occurring in arch vessels, pulseless
o Takayasu arteritis
o Vasculitis blocks off the lumen of arch vessels stroke (can knock out internal carotid)
o Common seen in young Asian women
Presentation: HA, generalized aches/pains; loss of vision in one eye, hurts when it chew
temporal arteritis
o Granulomatous vasculitis of temporal artery
o Can also involve other portions of the artery:
Ophthalmic artery blindness
o Sed rate: the only test to screen for temporal arteritis! (on boards)
Sed rate should be elevated because this is an inflammation
If not increased probably a TIA
o It takes time to take a biopsy and pt can go blind needs to put pt on corticosteroids
right away based on hx alone
o Step 2: polymyalgia rheumatic not polymyositis; no elevation in serum CK; only
aches/pain in joints/muscles
Polymyositis: elevation in serum CK due to muscle inflammation
Thromboangiitis Obliterans
Buergers disease; smokers disease; usually in young male

Digital vessel thrombosis
o Autoinfarction of fingers and toes
Henoch-Schonlein Purpura
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14 yo boy, upper respiratory infection a week ago, polyarthritis, joint pain, hematuria with RBC
cast, palpable purpura on the buttocks and lower extremities
Most common vasculitis in children
Immune complex (as are all small vessel vasculitis)
o Anti-IgA immune complex
RBC cast due to glomerulonephritis
o Aka IgA glomerulonephritis, but can be confused with Buergers disease
Wegners Granolomatous
Pt with saddle nose deformity; problem with sinus infection, problem upper respiratory/lung with
masses and nodules; also problem with kidneys
Granulomatous inflammation and vasculitis
Involves upper airways, lungs, kidneys,
Highly-specific ab associated with it: C-ANCA
o Anti-neutrophil cytoplasmic ab
Tx: cyclophosphamide (big C!)
o Side effects: hemorrhagic cystitis and bladder cancer
o To prevent hemorrahagic cystitis: mesna
Polyarteritis Nodosa
Male-dominant
Involves muscular artery infarction
P-ANCA
Know: highly associated with HepB surface antigen
Scenario: IV drug user with chronic hep B, with nodular inflammed mass on lower extremity,
hematuria (kidney infarct) polyarteritis nodosa
Rocky Mountain Spotted Fever
Organism: rickettsia
o Infect endothelial cells
o Spots: petechiae
Unlike other rickettsia diseases with rash: rash in spotted fever starts on extremities and go to
the trunk later
o Other ones start from trunk and then go to extremities
Vector: tick
o Tick-born disease: Lyme disease (Borrelia burgdorfi)
Borrelia recurrentis relapsing fever, antigenic shift, a lacto-spirochete
Syphilis (treponemes) is also a spirochete
Fungus, wide angle, non-spetae, pt with diabetic ketoacidosis, cerebral abscess related to
fungus mucomycosis
o Mucomycosis: diabetic ketoacidosis
Diabetic pt frequently has muco in frontal sinus; in ketoacidosis, muco start
proliferating go thru cribriform plate, infarct and infect the brain
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Raynauds Phenomenon
o Many causes: hundreds of diseases
o Cold-reacting ab and cold-reacting globulin:
Going outside in cold weather cyanosis in nose and ears, disappears when
warm again
IgM cold agglutinin disease or cryogloblinemia in old men with hep C
o Scleroderma and CREST syndrome: digital vasculitis and fibrosis
CREST: slightly different from scleroderma
First manifestation in both syndromes is Raynauds: vasculitis of digits; fibrosis;
auto-amputate the finger
C: calcinosis (dystrophic calcification); centromere ab (specific for CREST)
R: Raynauds
E: esophageal dismotility
S: sclerodactylyl (long narrowed fingers)
T: telangiectasia
similar to pin-point areas of hemorrhage seen in oster weber rendu
disease (Hereditary Hemorrhagic Telangiectasia)
o Vasoconstriction: common in people with migraine HA and taking meds
Migraine is due to vasodilatation; and meds taken would cause constriction
Can get Raynaud when taking ergot derivatives
o Raynauds: frequently on boards!
Hypertension
Most common cause of death: MI> stroke > renal failure

Essential HTN:
o Black: highest incidence
Multi-factorial/polygenic inheritance
Family hx of coronary disease, gout, DM type 2, affected disorders, congenial
pyloric stenosis all multi-factorial
Multi-factorial: one has a tendency for, but not necessarily would get the
diseases; but one can try to reduce the risk
In blacks: can control weight, reduce salt intake, exercise reduce risk
Ex: gout dont eat red meat, no alcohol (keep purine metabolism down)
Ex: DM weight control
Lose adipose tissues up-regulate insulin receptor synthesis
o Mechanism: retaining too much salt
Salt is retained in ECF plasma volume increases stroke volume increase
systolic HTN
Excess salt: salt likes to go into smooth muscle cells in peripheral resistance
arterioles
As salt goes in Ca enters smooth muscle contracts increasing
peripheral resistance, and decreasing the arteriole radisu
Retaining more blood in the arteriole system increase in diastolic pressure
o Tx of choice: HCTZ (in essential HTN and in blacks)
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eliminate salt and water decrease BP
but if there is hyperlipidemia: cant use HCTZ/thiazide/beta-blocker
need to use ACE I
thiazide/beta blocker can increase lipidemia
o low-renin: due to increased plasma volume
increased blood flow to renal artery decreased renin release
o complications:
MI, coronary artery disease: first cause of death stroke in HTN
Stroke: 2nd cause of death
Globus pallidus: almost all HTN bleeds occur here
Lenticulous striate vessels (small branches from MCA), under increased
pressure, form aneurysmCharcot-Bouchard aneurysms
Not an infarct; a hematoma (blood clot)
Kidneys: pebble surface, shrunken, destruction of glomeruli, atrophy of tubules
renal failure (3rd most common cause of death)
Pebble surface due to hyaline arteriolosclerosis (small vessel disease)
Most common overall abnormalities in HTN: LV hypertrophy
o Increased after-load: having to contract against increased resistance
o Long-standing hypertrophy: heart failure
Cardiovascular 2
Heart Hypertrophy
Concentric hypertrophy
o Increased work to contract the heart when there is increased in afterload (stenotic aortic
valve, increased TPR from HTN)
o AFTERLOAD problem
Dilated and hypertrophy
o Valvular problem with excess volume of blood in the ventricle increased preload
o Starling mechanism: increased preload stretch muscle increase force of contraction
o Volume overload/PRELOAD problem
Heart sound:
o S1: mitral and tricuspid valve closing during systole
Beginning of systole
mitral closes before tricuspid because of high pressure
o S2: aortic and pulmonic valve closing
Beginning of diastole
Inspiration: as diaphragm goes down, increased intrathroacic pressure blood is
being sucked into right side of the heart pulmonic valve closes after aortic
valve (separation of P2 from A2)
Expiration: P2 same as A2
o S3: normal in someone under 35yo; over 35yo usually pathologic
Early diastole
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Due to blood going into a chamber that is volume-overloaded
When diastole is occurring, blood from RA is going into RV that is already full
turbulent sound as blood goes in
Only hear S3 when there is volume overload in the chamber!
Can be overloaded LV from L heart failure or RV overloaded in R heart failure
S4: late diastole
When atrium is contracting/kick to get last bit of blood into ventricle
Hear S4 if there is problem with compliance
Compliance: ability to fill up; filling term
Ventricle doesnt want to fill up in late diastole
o Can be due to so hypertrophy or already filled up
Needs to put blood into already-full chamber
When compliant is low resistant to incoming blood makes a vibration
sound S4
HTN: would hear S4
Dilated heart: would have S3 and S4
When there are S1, S2, S3, S4 galloping pattern
All right sided heart murmurs and abnormal heart sounds (i.e. S3 and S4)
increase intensity on INSPIRATION
This is how to tell which side the murmurs are from
Essential HTN: left
Mitral regurgitation: right
Mitral stenosis: middle
o
o
o
o
o
o
Murmur
Stenosis: problem opening the valve

o Only occurs when valves open
Regurgitation/insufficiency: problem closing the valve
o Only occurs when valves close
Places to hear the valves or noises:
o Aortic: right 2nd ICS
o Pulmonic: left 2nd ICS
o Tricuspid: left sternal border
o Mitral: apex
Stenosis in Systole
o Opening in systole: aortic and pulmonic valve
Aortic and pulmonic murmur occur in systole, and push blood into a
o Ejection murmur: configuration would be diamond-shaped
Crescendo-decrescendo
o Aortic stenosis: heard best at right 2nd ICS during systole
Radiate into carotids
Murmur intensity increases on expiration
Would probably hear S4
o Pulmonic stenosis: heard best on left 2nd ICS
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Murmur intensity increases on inpiration

Stenosis on diastole:
o Mitral valve:
Stenosis:
LA dilates and hypetrophy predispose to stasis, thrombosis, a-fib
LA needs to get all the blood that is built up into LV
Would hear an opening snap, then mid-diastolic rumble as all the blood
gushes in
underfill the ventricle no hypertrophy of LV
murmur best heard on apex, with increasing intensity on expiration
o Tricuspid valve
Regurgitation on systole: problem with closing
o Mitral
Decreased cardiac output more blood in the LV than normal
LV gets volume overloaded
Murmur: heard thru out the entire duration of systole (pansystolic or almost
pansystolic)
Straight-line effect
Murmur can obliterate S1 and S2 sometimes
S3 and S4, increasing intensity on expiration
o Tricuspid
Pansystolic, left sternal border, increase intensity on inspiration
o Scenario: IVDU with fever, pansystolic murmur along the left sternal border, S3 and S4,
accentuation of neck vein endocarditis of the tricuspid valve
Murmur increases on inspiration on right side
If the murmur increases in intensity on expiration would have been mitral valve
Regurgitation on diastole: aortic and pulmonic valves close
o Aortic valve
Seen in syphilic aneurysm due to stretching of the ring
Blood goes out during systole and valve should be closed
i.e 80ml of blood goes out but 30ml comes back in during beginning of
diastole volume overloaded chamber
starling force: EDV increases (200ml vs 120ml)
murmur heard right after S2 valve is not closing and blood is dripping back
high-pitched diastolic blowing murmur, heard on right 2nd ICS, increases
intensity on expiration
S3 and S4: volume overloaded chamber
Bounding pulses
Anterior leaf of mitral valve: one side of outflow tract of aorta
Creates Austin-Flint murmur
When there is aortic regurge and Austin-flint murmur needs to remove the
valve because there is significant backward dripping of bloodvalve needs to
be sx replaced
o Pulmonic valve
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Heart Failure
left: forward failure; LV fails, problem with getting blood out

o Causes:
Increased afterload
Volume overload/excess volume
Too many infarcts; LV muscles turn into fibrous tissues reduced contractility
o EDV increases
o Increased pressure goes back into atrium pulmonary vessels increased hydrostatic
pressure pulmonary edema
o Symptoms: dyspnea (main)
Left heart failure is a dx of symptoms
Chronic left heart failure:
o Hemorrhage: alveolar mq phagocytose RBCs
Rusty colored sputum
o Heart failure cells: alveolar mq phagocytosed RBCs and broke them down to
hemosiderin
Right heart failure: backward failure
o Problem with right heart getting blood into pulmonary vessels
o Hydrostatic pressure increases in the venous system neck vein distension
o Signs:
Hepatomegaly: painful
Nutmeg liver: increased pressure in vena cava transmits into hepatic vein, back
into liver and to central vein
Red dots on liver that look like nutmegs
Most common cause of congestive nutmeg liver: right heart failure
Pitting edema, possible ascites
o Right heart failure is a dx of signs
Paroxysmal nocturnal dyspnea:
o When laying down sleeping: blood would go from venous side into effective circulation
due to elimination of gravity
Excess blood now goes into right and left heart
o If there is left heart failure: fluid goes back into the lungs
o Sign of left heart failure
Pillow orthopnea: quantitate degree of left heart failure
o Propping up with pillows: decreases venous return
Systolic dysfunction vs. diastolic dysfunction:
o Depends on ejection fraction
Treatment:
o Best non-pharmacological: decrease water and salt intake
o Decrease preload and afterload: ACE inhibitor
Increase longevity
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Decreases predload due to decrease aldosterone (decrease salt and water
reabsorption) and by blocking AT II (decrease vasoconstriction on peripheral
blood vessels)
Synergistic between ACE I and spirololactone
Because with ACEI alone, aldosterone eventually increases
High output failure:
o endotoxic shock
Peripheral resistance arterioles dilated
C3a, C5a, NO increased venous return to heart
o Poiseuille's law: viscosity of blood/ (radius)4
If vasodilate peripheral resistance arterioles more blood comes into right
heart more blood into left heart
o Thiamine deficiency:
Problem with thiamine deficiency: ATP depletion
Smooth muscles in the peripheral resistant arterioles need ATP for contraction
No ATP vasodilataion high output failure
o Graves disease:
Hyperthyroidism: TH increases synthesis of beta receptor in the heart increase
force of contraction more blood, higher systolic pressure high output failure
o AV fistula, AV malformation, or blood goes straight from arteriole to venule and bypass
capillaries
Blood returns to the heart faster than normal
Bruit over mass, pulsatile, and if pressing on the proximal portion and heart rate
would slow Branhams sign
Congenital Heart Disease
Know fetal circulation!

o Pulmonary vessels: very thick, difficult to get heart from pulmonary artery into LV thus
need a patent ductus
o All O2 comes from chorionic villus into a lake of blood, derived from moms spiral
arterioles
Chorionic villi extract O2 from the blood
Not very efficient in extracting O2 need HbF because it has high affinity for O2
HbF doesnt release O2 easily:
But with tissue hypoxia, EPO is released high Hb
Newborns have polycythemia (making more RBCs)
This is how fetus gets enough O2
o O2 goes thru syncytiotrophoblast in chorionic villus cytotrophoblasts myxomatous
stroma of chorionic villus blood vessel form umbilical vein
Umbilical vein: highest O2 content
o Then to liver:
One can go straight into hepatic sinusoids hepatic vein vena cava
Ductus venosus straight to inferior vena cava
o Then into right side of heart:
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Foramen ovale is open in all fetuses

Blood: RA f. ovale LA LV aorta
o Superior vena cava
Blood comes into tricuspid valve RV
Go up to pulmonary artery, but pulmonary vessels are too thick with high
pressure
Ductus arteriosus: blood then goes back into aorta
Patent due to PGE2 made by placenta
o First breath in newborns:
Pulmonary vessels open in seconds
Blood goes thru pulmonary arteries, gas exchange occurs in lungs
Patent ductus eventually closes ligamentum arteriosus
o Blood goes out of aorta two umbilical arteries
Least amount of O2
1 umbilical vein: highest amount of O2
Left to right shunt:
o O2 blood going into unoxygenated blood: mixing, step UP (increased O2 sat)
o O2 on right side of body: 75%
o O2 on left side of body: 95%
Right to left shunt:
o Unoxygenated blood into oxygenated blood: step DOWN (decreased O2 sat)
VSD: ventricular septal defect
o Membranous part of the septum
Very close relationship with aortic valve
o LV is stronger than RV
Direction of shunt: left to right
o Step-UP of O2 sat in the RV and pulmonary artery
o But right heart can be volume overloaded pulmonary HTN overtime
o Pulmonary HTN RV hypertrophy
Now the shunt can be reversed right to left shunt
o Most VSDs close spontaneously, some need to be patched
Eisenmenger syndrome:
o Uncorrected left to right shunt can be reversed now right to left cyanosis
ASD: atrial septal defect
o Normal for fetus to have patent foramen ovale; but not after they are born
o Direction of flow after birth: left to right
o Right atrium/ventricle/pulmonary artery: step UP
Difference from VSD: right atrium step UP
o Right side of the heart: overloading Eisenmenger syndrome
o Paradoxical embolization: DVT in leg embolize up, embolus can go straight into LA via
patent foramen
Venous thrombi now in arterial blood
Only seen in pt with ASD
o Most common teratogen producing ASD: fetal alcohol syndrome
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2/1000 kids have fetal alcohol syndrome

From alcohol: most common congenital heart defect is ASD
Patent ductus arteriosus:
o Connection between aorta and pulmonary artery
Aortic artery has higher pressure
Oxygenated blood from aorta goes into pulmonary artery before it even goes into
the lungs pulmonary artery step UP (now its 80% in O2 sat)
o Blood swishing back and force between systole and diastole machinery murmur
Best heart between shoulder blades
o Can volume overload right side of the heart and pulmonary HTN
Now shunt goes from unoxygenated blood aorta
Ductus is empty distal to subclavian artery: pink on top, blue on bottom
Dumping unoxygenated blood below subclavian artery differential cyanosis
o Teratogen: congenital rubella
o Tx: indomethacin non-steroidal inhibiting PGE2
Tetralogy of Fallot: most common cyanotic disease
o Overriding of aorta: straddle over the septum
o Septal defect: membranous portion
o Pulmonic stenosis below the valve
Determines the degree of cyanosis
Not all babies with tetralogy of fallot have cyanosis
If pulmonic stenosis is very severe: RV contracts most blood doesnt go into
pulmonary artery but goes from right to left step DOWN cyanotic
o RV hypertrophy
o In this pt, cardioprotective to have patent ductus arteriosus and ASD
Ductus arteriosus
Unoxygenated blood from aorta into pulmonary artery get
oxygenatedpulmonary vein more blood out
ASD: blood goes from left to right
RA: step UP
Abnormality with right to left shunting:
o Infective endocarditis
Shunt from right side to systemic circulation
Vegetation going into brain multiple cerebral abscess
All congenital heart diseases have risk of infective endocartidis
o Polycythemia
Transposition of the great vessels:
o Kartagener syndrome: normal heart, except heart is on the right side of the body
Not a transposition
o RA and LA are not transposed; problems are in the ventricles (ventricles are transposed)
o RV: being emptied by the aorta; LV: emptied by the pulmonary artery
Incompatible with life unless there is shunt
o 3 shunts: foramen ovale, patent ductus, and ventricle septal defect
Atrial side: 95% O2 sat in LA blood goes into RA RA step UP
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RV: step UP some oxygenated blood goes into aorta and some goes into LV
Need an ASD to get oxygenated blood into RV get some oxygenated blood
into systemic circulation
Would not be 95% saturated cyanosis in pt
Right to left shunt: blood is being emptied by the pulmonary artery going back
into lungs to get further oxygenated
Needs to have all three shunts working or otherwise all the blood in aorta would
be deoxygenated
o Boards: complete transposition of the vessels does not mean kartageners syndrome
Coarctation of the aorta
o Pre-ductal: before ductus arteriosus
Occurs in turner syndrome
Need to be corrected or otherwise develop heart failure
o Post-ductal
Not present at birth; can occur anytime in adulthood
Surgically correctable cause of HTN
o Stenosis of aorta:
Proximal: problem getting blood thru systolic murmur btwn shoulder blades
Pressure builds up: proximal aorta dilation increased pressure into branch
vessels (i.e. subclavian, internal carotid)
BP is higher for upper than for lower extremities
Increased blood flow into the brain: subarachnoid bleed
at the junction where communicating branches and the main cerebral
vessels no internal elastic lamina and no smooth muscle
potential for developing berry aneurysm
HTN would exacerbate this
Any cause of HTN would lead to berry aneurysm right at the junction
Stretch aortic ring aortic regurgitation murmur
Pressure on the wall of proximal aorta: potential for dissecting aneyrusm
o Distal to stenosis of aorta
Decreased blood flow
Claudication: angina of peripheral vessels
Walk calf or butt pain; stop walking and goes away
Ischemia; muscle development in the lower extremity is not going to be
good muscle mass decreased
BP different between upper and lower extremity
Reduced blood flow to kidney: activate RAAS HTN
o HTN in coarctation is due to RAAS system
o Development of collateral circulation:
Superficial epigastric artery and internal mammary artery
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Superficial epigastric artery: when sticking finger in the canal and if there is
indirect inguinal area would feel the pulse of this artery medial to the hernia
Intercostal arteries: can produce notching
Cardiovascular 3
Coronary Artery Disease
Risk factors:
o Age: most important risk factor
Men: 45; women: 55yo
Women: later age because of estrogen; reach menopause at 55yo
As estrogen level decreases HDL level decreases
o HDL, not LDL
HDL: reverse cholesterol transport; taking LDL out of fatty streaks internalize
bring back to liver liver metabolize
HDL <35
If HDL > 60: can subtract 1 risk factor
o FHx of premature coronary heart disease, stroke
o Current cigarette smoking
o HTN
o Diabetes
o LDL: dx of hypercholesterolemia is based on LDL and not on cholesterol
o Cholesterols is NOT a risk factor
Ischemic heart disease:
o 4 types: angina, MI, sudden cardiac death syndrome, chronic ischemic heart disease
Sudden cardiac death syndrome:
o Death within 1 hour
o On autopsy: will NOT see coronary thrombus
Would see severe coronary artery atherosclerosis
o Ischemia start getting a few premature ventricular contractions when hits the
susceptible area v-fib death
Die of ventricular arrhythmia, like in MI
o Because its sudden death: no change in the heart no palor, no coagulation necrosis
o Smoking is a big risk
Chronic ischemic heart disease:
o Coronary artery disease, some small infarcts (sub-endocardial infarction)
o But muscles get replaced by fibrous tissues eventually LV turns into fibrous tissues
ejection fraction decreases (0.20 instead of 0.66) die of heart failure
o Fibrous tissues have no contractility
o Second most common indication for heart transplant
Angina: most common ischemic heart disease
o 3 types: exertional, prinzmetals, unstable or resting
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Exertional: chest pain when exertion; goes away after 5-10 minutes of rest
Treadmill exam: ST depression candidate for coronary angiogram
ST depression: sub-endocardial ischemia
Coronary penetrate outside of the heart and goes in
If there is coronary artery atherosclerosis and decreased blood flow:
subendocardium gets screwed pain, and ST depression
o Prinzmetals: usually seen in women and seen in the morning
Most MI also occur in the morning
Due to vasospasm, not atherosclerosis, in the coronary artery
Thromboxane A2: responsible for vasoconstriction
Vasospasm of coronary artery: transmural ischemia
ST elevation, the entire myocardial tissues are affected
o Unstable/resting angina: angina occurs at rest
Usually start with exertional angina, and start getting chest pain while resting
Angiogram, angioplasty, CABG
Do not put pt on treadmill
In CABG: use saphenous vein
Over 10 years, the vein would arterialize start to look like an artery
given high arterial pressure
High tendency to fibrous off after 10 years
Internal mammary artery:
No problems with fibrosing, also located anatomically close to the heart
Cant do 4 vessel bypass with 1 internal mammary artery
Myocardial Infarction
o Thrombus composed of: group of platelet with fibrin
Plasmin: breaking fibrin bonds the whole mass breaks apart
But for venous clot: harder because there are more fibrin
o Reperfusion injury: oxygenated blood goes into injured tissues superoxide free
radicals calcium
Injured myocardial cells die but after these cells die, the process stops
o Complications:
LAD: most commonly thrombosed, supply the entire anterior part of the heart and
anterior 2/3 of interventricular septum
Most conduction bundle fibers are located in the anterior 2/3 complete
heart block, requiring pacemaker
Right coronary artery: supplies the entire posterior hear, posterior 1/3 of
interventricular septum, and the entire right ventricle
Mitral valve (2 valves) with papillary muscles
Postero-medial papillary muscles: supplied by posterior right coronary
artery
SA node, AV node:
o SA node has an equal distribution between right and left
o AV node: 95% supplied by branches of right coronary artery
o
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It pt with mitral regurgitation-type murmur, related to posteromedial

papillary muscle dysfunction right coronary artery thrombosis and
posteromedial papillary muscle rupture
Mitral regurgitation occurring during MI: due to thrombosis in right
coronary artery
Knocking off AV node: sinus bradycardia
Atypical chest pain:
o LAD: substernal chest pain, radiating to jaw or left arm
o Right coronary artery: can get epigastric pain atypical chest
pain, and simulate GERD
Gross and Microscopic Findings of MI
Between 4-6 hours

o Coagulation necrosis
At 24 hours
o First see gross manifestation that the heart looks pale pale infarct
Between 3rd and 7th day:
o The heart is the softest highest chance to rupture
Left atria descending artery thrombosis
o Pale infarct involving entire anterior 2/3 part of the heart
Rupture:
o Pericardium filled with blood (hemopericardium)
o Most are anterior involve left anterior descending thromboses
Pt day 3-4 complain of chest pain, muffled heart sounds, distended neck veins
Another rupture:
o Posteriomedial papillary muscle rupture only one that ruptures is the posterior medial
one
o Chordea tendinae ruptured from it because it was infarcted right coronary artery
thrombosis mitral regurgitation murmur
Day 3 pt. goes into heart failure; pansystolic murmur at apex increasing on
expiration; S3, S4 heart sounds none of these were there the day before
Posteriopapillary muscle either dysfunctional because of infarct or its ruptured
Will hear a murmur and suddenly and these all arise between day 3-7
Heart failure: massive volume overload that goes right back into the lungs
Rupture in the interventricular septum:
o Left to right shunt; step UP in the RV and pulmonary artery
o Most interventricular septum rupture is due to LAD thrombosis
Mural thrombus:
o Mural: wall; in this case thrombus on the way
o Almost always LAD thrombosis
o In anterior MI, always give ASA: to prevent thrombosis in the coronary vessel
Also put on warfarin or heparin: to prevent mural thrombosis from developing
ASA and warfarin/heparin: because mural thrombus makes a clot that is
combination of platelets and venous-like
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In transmural infarction: injury to the endothelial wall of the heart platelet stick to it
Ventricle doesnt contract wall due to infarction stasis venous-like clot (factor
5, 8, RBCs)
Mixed clot
ASA: prevent coronary thrombosis by decreasing platelet aggregation and also
prevent mural thrombosis from developing
Warfarin/heparin: prevent the venous-like portion of the clot from developing
Mural thrombosis: can embolize, very dangerous
More Complications of MI
Fibrinous pericarditis:
o Can occur 2x in a MI pt:
First week: friction rub, chest pain, relieved by leaning forward, worse when
leaning back transmural infarction, increasing vessel permeability
Autoimmune: 6 weeks later; on boards!
Autoimmune pericarditis:
o Previous hx of transmural infarction, 6 weeks later present with fever, muscle aches and
pain, and 3 component friction rub dresslers syndrome
o Damage pericardial surface after infarct, develop ab against pericardial tissues; takes 6
weeks to get a high titer, and start attacking pericardium and develop systemic
symptoms
o Tx: non-steroidal
Ventricular aneurysm:
o A later complication of MI
o Presentation: 3 week after MI, noticed that chest bulges
Systolic bulge of precordial ventricular aneurysm
o Blood collecting in the aneurysm and bulging out
o The most common complication of ventricular aneurysm: heart failure!!
This aneurysm doesnt rupture because its covered by scar tissues
But this ventricle cant contract
Scarring/fibrosis:
o After 3 weeks to 10 yearslots of scar tissues
o Scar tissues: loss of contractility
Thus need to check ejection fraction for prognosis before leaving hospital
o Good ejection fraction: didnt really damage the myocardium much; still have good
stroke volume
o Low ejection fraction: big infarct with lots of muscle destruction
o Ejection fraction: best prognosis factor on how one does after infarct
If its closer to normal (0.66) would be fine; 0.40 is bad
Dx MI:
o Good standard: CK-MB
EKG: 80% sensitivity for showing new Q wave, ST elevation and T wave change
But EKG has good specificity
Can also use CK-MB with troponin I
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CK-MB: isoenzyme of creatinine kinase
MB: only in cardiac muscle would be released and increase in level
when there is infarct
Usually comes up in hours, peak in 24 hours, and gone in 3 weeks
If there is CK-MB re-appearing after 3 days re-infarction!
Troponin I:
Appears a few hours earlier (4 hours after MI); peaks at 24 hours
Lasts 7 days
But does not indicate re-infarction
LDH:
Normally LDH2 is higher than LDH1
LDH1 is in cardiac muscle release LDH1 during infarct and LDH1 level
becomes higher than LDH2
LDH1/2 flip: occurs after 18 hours, peaks at 2-3 days, and lasts for a week
Most frequently used when: pt comes in 2-3 days after chest pain; CK-MB might
have already gone, and check for LDH 1/2 flip
But can also use troponin I
Mitral Valve Prolapse
More common in women

too much valve looks like a parachute
Blood underneath the valve pushes and prolapse mitral valve into the atrium
o When stops, makes a noise: click
Prolapsed extending into the atrium
o When cant go in the atrium anymore click
o Then followed by mitral regurgitation murmur
o Click murmur
Opening snap occurs in mitral and tricuspid stenosis
o Pathology: myxomatous degeneration
myxomatous degeneration
o GAG that makes up the valve: dermitan sulfate
o Excess dermitan sulfate in the mitral valve the valve becomes too redundant, looks
like a parachute
PE of mitral valve prolapsed:
o Increase volume of blood in LV clicking murmur comes closer to S2
It takes longer to get the blood out
Ex: when lying down increasing preload click murmur heard closer to S2
o If decreasing preload in LV clicking murmur comes closer to S1
o Clicking murmur in anxiety: less time to fill the ventricle closer to S1
Most of the time its asymptomatic
o The only common symptom: palpitation
2 genetic diseases that always have mitral valve prolapsed: marfans and Ehlers-Danlos
Scenario: a marfan syndrome pt sudden dies
o Not dissection aneurysm: would not have sudden death
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Dissection: pain radiating to the back, eventual cardiac tamponade

Due to serious mitral valve prolapsed with conduction defect
Cardiovascular 4
Aortic Stenosis
Most common valvular defect associated with syncope and angina with exercise
Also most common cause of microangiopathic hemolytic anemia
Ejection-type murmur; heard on right 2nd ICS, radiating to neck, increase intensity on expiration
Intensity of murmur with different positions:
o Increase intensity:
increase preload on LV more blood to get out increase intensity
this distinguishes from hypertrophic cardiomyopathy
exertional angina:
o pulses in aortic stenosis: diminished
o SV decreased
o Coronary artery: is filled during diastole, less filling in aortic stenosis, cant provide as
much O2 and nutrients to myocardium
Syncope:
o Decreased CO faint when exercising
Mitral Stenosis
LA is dilated
Murmur occurs in diastole
o Stenosis: problem in opening; mitral valve opens during diastole
o Snap and rumble; not click
o Heard best at apex, increase intensity on expiration
Most common causes: repeated attacks of rheumatic fever
Acute rheumatic fever:
o Group A beta-streptococcal infection: strep pyogenes
o Usually occurs post-pharyngitis (i.e. tonsillitis)
Post-strep glomerulonephritis: post-pharyngitis or post-skin infection
o Blood culture: negative
Not infective endocarditis
o M-protein: pathogenic factor in strep
Some M-protein fractions have antigens that are similar to those in heart, joint
Body makes ab against M-proteins but the same ab can against our own
tissues attack heart, joint, basal gangalion mimicry
o Most common valve involved: mitral valve
o Vegetations: sterile, lining along closure line
o Embolization: usually not a big feature
o Need to know the criteria of dz rheumatic fever
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Scenario: young person with exudative tonsillitis a few weeks ago, present with swelling, joint
pain, dyspnea. Bibasilar rales in lungs, pansystolic murmur at apex, increases intensity on
expiration, S3 and S4 present acute rheumatic fever
o Most common symptom in acute rheumatic fever: polyarthritis
In children: very limited differentials for polyarthritis
o Juvenile rheumatoid arthritis
o Henoch-schonlein purpura
o Rubella
o Acute rheumatic fever the only differential that produces heart problem and mitral
insufficiency
the most common valvular lesion in acute rheumatic fever:
o NOT mitral stenosis it takes 10 years to develop
o In acute rheumatic fever mitral regurgitation
All parts of the hear is inflammed
Pericardium pericarditis
Myocardium myocarditis
Endocardiumvalve with vegetation
Other findings in acute rheumatic fever:
o Joint pain
o Cardiac problem
o Subcutaneous nodules
o Erythema marginatum
Rheumatoid nodules and acute rheumatic nodules are the same both are
immunological diseases
o Late manifestation: chorea-form movement
ASO titer: group A strep infection
o Elevated in acute rheumatic fever
Aschoff nodule: reactive histiocytes in myocardium
Fish-mouth appearance of mitral valve
Most posteriorly located chamber of heart: LA
o Best to see mitral valve thru trans-esophageal u/s
o LA is largely dilated in mitral stenosis
Can press down on esophagus dysphagia with solids but not liquids
o Can also stretch left recurrent laryngeal nerve hoarseness (Ortners syndrome)
o Can also develop atrial fibrillation
Thrombus in LA:
o Lots of stasis of blood blood cant get thru mitral valve
o Pt needs to be anti-coagulation
o Thrombus can break off and embolize in atrial fib
Tricuspid Regurgitation
IV drug abuse with infective endocarditis

Carcinoid heart syndrome: needs to have mets to liver
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Serotonin in tumor nodules hepatic vein tributariesserotonin in venous blood invade right
side of the heart
o Serotonin produces a fibrous response of the valve
o Tricuspid insufficiency and pulmonic stenosis (TIPS)
Infective Endocarditis
Mitral valve with vegetation:

o Vegetation: not along the entire margin of the valve; scattered
o Big and bulky
o Destroy the valve infective
Most common organism: strep viridians
o Staph aureus: 2nd most common cause
o When brushing teeth transient bacteremia due to strep viridian (most common
bacteria in the mouth)
o If there is underlying cardiac disease: increased risk of endocarditis, esp on damaged
valves produce vegetation
Staph aureus:
o Can infect a normal and a damaged valves
o 1st cause in IV drug abuse
Valves involved in infective endocarditis: 1st mitral; 2nd aortic
IVDU: injecting into veins 1st tricuspid, 2nd aortic valve
o Tricuspid regurgitation: pansystolic, increase intensity inspiration
o Aortic regurgitation: high-pitched diastolic blowing murmur after S2
Colon cancer or ulcerative colitis:
o Ulceration of the colonic mucosa strep bovis causing a unique type of infective
endocarditis
Membranous portion of septum with aortic valve
o When there is vegetation in aortic valve VSD not picked up
Cause aortic valve to get infected aortic regurgitation
o Congenital heart disease or any damage to valve: increased risk of infective endocarditis
For infective endocarditis: either mitral valve or aortic valve with associated VSD
Presentation: splinter hemorrhage; janeway lesion; kopliks spot in eyes
o Kopliks spot in measles: red with a white center
o Type 3 hypersensitivity
o All the lesions are immune complex vasculitis
Libman-Sacks endocarditis:
o Positive serum ANA lupus
Not the most common heart lesion in lupus; pericarditis is
o Vegetation all over the valve with lupus hx
o Not a lot of valvular dysfunction
o Fibrinoid necrosis as in rheumatic fever
Marantic endocarditis:
o Mucous-secreting colon cancer: paraneoplastic syndrome
o Vegetations look similar to that in rheumatic fever
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Myocarditis and Pericarditis
Coxsackie: extreme common causes of many diseases

o Ex: myocarditis, pericarditis, viral meningitis, hand-foot disease, herpe angina,
Presentation: pt with heart failure, lymphocytic infiltrate on endomyocardial biopsy due to
coxsackie myocarditis
o Need biopsy of sub-endocardial tissue to dx myocarditis
o Lymphocytic infiltrate: seen in viral infection
Cardiomyopathy
Dilated/congested cardiomyopathy:
o Scenario: woman 6 weeks postpartum, dyspnea, generalized cardiomegaly on chest xray; both right and left heart failure
o Disease of the cardiac muscle
o Causes:
Postpartum: 6 weeks
Coxsackie remaining from myocarditis
Cardiotoxic drugs: tricycliates
Drug-induced congestive cardiomyopathy
Thiamine deficiency in alcoholics
o Most common reason for cardiac transplant in adults
Hypertrophic cardiomyopathy:
o Most common cause of sudden death in young athletes
o Asymmetric hypetrophy due to thick interventricular septum
o Blood flow:
Anterior leaflet of the mitral valve is pulled towards aorta
If there is aortic regurgitation and blood drips back hit mitral valve produce
subsequent murmur
o Narrow opening to aorta: very thick interventricular septum
o Obstruction: not at the level of aortic valve, its BELOW it
When things flow thru a narrow opening creates negative pressure behind it
When blood under increased force of contraction flows thru the narrow opening
negative pressure behind it sucks the anterior leaflet of mitral valve towards the
opening blocking blood flow
o To reduce murmur intensity and increase CO:
Put more blood in LV: increase preload pull the valve away from the septum
Laying down: increase venous return, increase preload, decrease murmur
intensity
Can also use beta or calcium channel blocker: decrease force of
contraction, slow heart rate, increase preload
Do not give digitalis: increase force of contraction
Do not use any positive inotropic agents
o Conduction bundle is messed up: conduction defect/abnormal conduction
Increased risk of developing v-tach: responsible for sudden death
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Restrictive cardiomyopathy:
o Endocardial fibrosis
o Restrictive: preventing the ventricles from filling up
o Most common disease producing restrictive cardiomyopathy in children: endocardial
fibroelastosis
Most common reason for heart transplant in children
o Pompes (glycogen), Fe overload, or amyloid: can also produce restrictive
cardiomyopathy
Cardiac Tumors
Cardiac myxoma
o Most are in LA (85%), the rest in right atrium (15%)
Can be seen on transesophageal u/s
o Most common primary benign tumors of the heart in adults
o Attach to a stalk, but can move
Can block the orifice of mitral valve block blood flow into LV syncope
o Can embolize: little pieces break off
o Leaking content produce fever, neurologic deficits
rhabdomyoma
o Tumor in the heart in a child
o Benign tumor of the cardiac muscle
o Associated with an autosomal dominant disease: tuberous sclerosis
Pericardial Effusion
Presentation:
o Muffled heart sounds (cant hear as well)
o neck vein distends on inspiration
Normally, when breathing in, intrathoracic pressure increases and neck vein
should collapse
Kussmauls sign
o magnitude of pulse decreases (10mmHg drop in BP on inspiration) pulsus paradoxus
Beck Triad
Effusion in the pericardial sac the heart cant fill up because there is fluid around it muffled
heart sound
When breathing in: blood cant be sucked into the heart neck expands
o There is no blood going into the right, then the left side of the heart
o Drop in pulse pulsus paradoxus
Pulsus paradoxus and kussmauls sign usually occur together
First step in work-up: echo to prove fluid in the perdicarium
Tx: pericardiocentesis
Most common cause:
o Pericarditis: commonly caused by coxsackie
o If in a woman with positive ANA due to lupus
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Any young woman with unexplained pericardial effusion or multiple pleura effusion has lupus
until prove otherwise
o Serositis: inflammation of serous membrane a feature of lupuss
Constrictive Pericarditis
Cause:
o 3rd world country: TB
o US: previous cardiac sx
Thick pericardium, but no fluid
When breathing in: blood would go into the right side of the heart but heart cant expand as
well pericardial knock
To distinguish from pericardial effusion (muffled heart sound with effusion, with no knock):
o Constrictive: some filling of the heart with pericardial knock
Dystrophic calcification on pericardium
Respiratory 1
A-a Gradient
Alveolar O2 and arterial PO2 are never the same

o The difference between these two A-a gradient
Ventilation and perfusion are not evenly matched in the lungs
o Ventilation: better at apex when standing up; perfusion: better at the lower lobe
Thus almost all pulmonary infarctions are at lower lobe perfusion is better
Activation of TB is in the apex strict aerobe, needs as much O2 as possible
Normally, alveolar O2 is 100 and arterial PO2 is 95
o Normally, A-a gradient is about 5mmHg
o Gradient expands slightly as one ages
Upper limit of A-a gradient: 30mmHg
o If >30mmHg something is wrong
o This has very high specificity/positive predictive value
the gradient between alveolar and arterial O2 is greater in primary lung disease:
o ventilation defect: produce hypoxemia
o perfusion defect
o pulmonary embolism
o diffusion defect
o depression of respiratory center by barbiturates: would NOT increase A-a gradient
A-a gradient indicates whether hypoxemia is related to something wrong in the lungs (perfusion,
ventilation, diffusion defect) vs. something outside of lungs that is causing hypoxemia
o Respiratory acidosis
PO2 decreases
Can have respiratory acidosis in pulmonary problems (i.e. obstructive disease) or
respiratory center is depressed:
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Obstruct upper airways (epiglottitis), endotracheal bronchitis, respiratory

muscle paralysis (Amyotrophic lateral sclerosis, Guillain-Barre)
In this case, normal A-a gradient
o Prolonged A-a gradient with hypoxemia: something wrong with the lungs
o Normal A-a gradient with hypoxemia: something outside of lungs
Respiratory muscle paralysis, respiratory center depression, upper airway
obstruction
o A-a gradient with blood gas and anion gap should always be calculated!
Calculate A-a gradient:
o 21% O2 * (760-47) = 150mmHg
o PCO2 is 40mmHg
o 150-40/0.8 = 100mmHg alveolar O2
Upper Airway Disease
Nasal polyp:
o Most common: allergic polyp
Develop in adults who have chronic allergies (rhinitis)
Board question: 4yo child with nasal polyp and respiratory infection; first step of
management sweat test!
any young child has nasal polyp has cystic fibrosis
o triad asthma:
taking ASA or other NSAIDs get asthma and have nasal polyp
boards dont tell you pt takes ASA nor telling you pt has nasal polyp
scenario: (always) 35yo woman with chronic HA, develops occasional bouts of
asthma mechanism developing asthma is due to taking ASA
ASA and NSAIDs block cyclooxygenase: arachinoid acid cant produce
prostaglandin but leaving lipoxygenase pathway open
LT C-D-E4: bronchoconstrictors
Chemical-mediated, non-type 1 hypersensitivity asthma
pain in general is more common in women than men (i.e. fibromyalgia)
also on boards: assume any well-built male athletes are taking anabolic steroids
Laryngeal carcinoma
o False vocal cord: lined by squamous epithelium; true vocal cord: lined by ciliated
pseudostratified columnar epithelium
o Most common cause: smoking
2nd common cause: alcohol
Synergistism of alcohol and smoking: much higher chance!
o Any squamous cancer in mouth, larynx and esophagus:
1st cause: smoking; 2nd: alcohol both together double the risk
o Most common symptom: hoarseness
Epiglottis:
o Organism: H. influenza
o Symptoms: inspiratory stridor
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o
o
3 month old kid has inflammation in trachea with inspiratory stridor croup, due to
parainfluenza
Both parainfluenza and H. influenza produce upper airway obstruction
Hyaline Membrane Disease (Respiratory Distress Syndrome)
Collapsed alveoli
o Massive atelectasis: collapsed airways due to low surfactant
Surfactant: lethicin, phosphytidylcholine, phosphytidylglycerol
Deficiency in surfactant atelectasis
o Collapsing pressure in the airways = surface tension/ radius of airway
o On expiration: radius of airway decreases increase collapse pressure
Massive atelectasis on expiration
o But normally dont have atelectasis on expiration because surfactant decreases surface
tension keeping airways open on expiration
3 causes of respiratory distress syndrome:
o Prematurity:
Surfactant synthesis peaks between 32-35 weeks
If need to deliver the baby before 32nd week: give mom glucocorticoids (gcc)
gcc stimulates surfactant synthesis
Thyroxine and prolactin also increases surfactant synthesis
o Maternal diabetes:
Gestational diabetes: woman not diabetic before pregnancy but develops
glucose intolerance after becoming pregnant
Hyperglycemia in mom hyperglycemia in babies insulin release
Insulin DECREASES surfactant
Big macrosome: insulin increases storage of triglyceride in adipose
Most adipose tissues are located centrally
Insulin increases synthesis of triglyceride and deposition of fat
Insulin increases uptake of amino acid in muscles and muscle growth
Increase in adipose, muscle massmacrosome
Babies are often hyperglycemic when born:
Moms hyperglycemia baby releases insulin
Lots of insulin when cutting the cord but there is no more glucose
hypoglycemia in baby
o C-section:
Stress is missing! Its beneficial to vaginally deliver the baby
ACTH and cortisol are not increased not making surfactant during delivery
Superoxide free radical damage: retinopathy of prematurity blindness and bronchopulmonary
dysplasia
Babies that have respiratory distress syndrome commonly have patent ductus arteriosus due
to hypoxemia
o When taking a breath: normally starting the process going to close the ductus
o But ductus arteriosus remains open in hypoxemia machinery murmur
Hyaline membrane: degeneration of type 2 pneumocytes and leakage of fibrinogen
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Pathogenesis of hypoxemia
o Massive ventilation defect: everything is collapsing
o Shunt problem: massive intrapulmonary shunting
Tx: PEEP therapy
o Positive end-expiratory pressure: airways are collapsed; need to get O2
o Put pt on respirator and set it for positive end expiratory pressure to keep airways open
on expiration
o Also add some surfactant
Type 2 pneumocytes:
o Lamellar bodies: looks like onion cut in cross-section
Contain surfactant
o Type 2 pneumocytes: repair cells
o Boards often show EM pictures of the lungs
ARDS:
o Neutrophil-related injury
Surfactant and insulin level are normal
o Most common cause: septic shock
Most common cause of septic shock: E.coli, sepsis from an indwelling catheter
Most common cause of DIC: septic shock
Septic shock presentation in ICU: within 24 hours with dyspnea ARDS; 48
hours with bleeding out every orifice DIC
o Neutrophils get into the lungs in septic shock and destroy all cells in the lungs
Type 1 and 2 pneumocytes are destroyed
Surfactant level decreases massive atelectasis
o Hyaline membrane: neutrophils need to go thru the capillaries to get into the lungs
destroy capillaries leaky capillaries
Proteins and fibrinogen leak out and produce hyaline mb
o Major Pathophysiology: intrapulmonary shunting
o Very bad prognosis
Pneumothorax:
o Spontaneous
Most common cause: ruptured sub-pleural bleb (air pocket)
Rupture hole in pleura this part of the lungs collapse
Negative intrathroacic pressure keeps the lungs inflated
When there is a hole: the pressure is not negative and is the same as
atmospheric pressure
Diaphragm would move up to take up the space and so would trachea
o Tracheal deviation to the side of collapse
Usually seen in tall males, in apex of the lung
Can also see in scuba divers when they come up too fast
o Tension:
Most commonly due to knife or gunshot wound penetrating into the lungs
Tear of pleura: a flap
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When breathing in: the air goes into pleural cavity and on expiration, the
flap closes and the air stays in the pleural cavity
Increasing pressure in the pleural cavity pushing the lungs and mediastinum to
the other side compressing the lungs producing compression atelectasis
Positive pleural pressure pushing RA, RV, vena cava would also have
problem with blood returning to the heart
Positive intrathoracic pressure: diaphragm would be pushed down
Pneumonia
Typical:
o Wake up in the morning feeling good, then high fever, productive cough
o Strep pneumonia
Gram + diplococcus
o Productive cough: exudative pus, signs of consolidation in lungs
Areas of consolidation: microabscesses
Pus in alveoli causing consolidation
o PE of lung consolidation:
decreased percussion sound
increased tactile fremitus (increased vibration on chest when speaking)
Egophony: E to A sign: pt says E but you hear A
Whisperpectoriloquy: pt whispers 1-2-3 and very loud on auscultation
o If there is pleural effusion overlying the lung: only have decreased percussion
o Tx: PCN G
Atypical:
o Insidious and slow onset; gradually feeling worse over days
o Mycoplasma pneumonia
Followed by chlamydia pneumoniae
o Do not have productive cough; not as high fever
o Interstitial pneumonia: inflammation of interstitium; no inflammation in the alveoli
o No signs of consolidation
Nosocomial:
o Get it while in the hospital
o E. coli, staph aureus, pseudomona aeruginosa
Community-acquired:
o Bronchopneumonia: most commonly due to strep pneumonia
o Lobar pneumonia: strep pnemoniae
Respiratory Microbial Pathogens
Rhinovirus: most common cause of common cold

o Acid labile: get destroyed by acid; would never get gastroenteritis from this virus
o No vaccine: over 100+ serotypes
Parainfluenza:
Respiratory syncytial virus: most common cause of bronchiolitis
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o When small airways are inflammed wheezing

o Bronchiolitis can also be caused by pneumonia
Influenza:
o Antigenic drift and shift
o hemogglutinin: help virus attach to nasal mucosa; neuraminidase penetrate mucosa
o drift: minor mutation in either hemogglutinin or neuraminidase; no need for new vaccine
o shift: major mutation in either the two, but need new vaccine
o vaccine: against only A type
chlamydia trochomatis:
o 1 week after birth, wheezing, increased AP diameter, no fever; eyes crusty bilaterally
o Staccato cough c. trochomatis pneumoniae
o Transmission: delivery thru infected cervix
o Most common cause of conjunctivitis in 2nd week: c. trochomatis
o Most common cause overall of conjunctivitis: inflammation from erythmycin eye drops
After 48 hours: GC
After 2 weeks: c. trohomatis
o Guaranteed board question
Pseudomona
o Water-loving bacteria: see pt in ICU and CCU!
o Productive cough with green color
Klebsiella pneumonia:
o Common in alcoholics
o Distinguish from strep: pt that is alcoholics, high spiking fever, productive cough of
mucoid-appearing sputum
Capsule in klebsiella is very big mucoid
o Cavitate in upper lobe: frequently confused with TB
Legionella pneumophila:
o Atypical pneumonia
o Non-productive cough, very sick, can be lethal
o Another water-loving bacteria: see in water cooler; and the mist spread in grocery store
o Scenario: classic atypical pneumonia, hyponatremia
Legionella: interstitial nephritis low renin, low aldosterone hyponatremia
Can also lead to liver disease
o Tx: erythromycin
Systemic Fungi
Candida:
o Normally from indwelling catheters
o Candida sepsis
Geographic distribution:
o Mid-west, Ohio, Tennessee: histoplasmosis
o Pigeons: Cryptococcus neoforman
o Southeast: blastomycosis
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o Southwest (New Mexico, Southern CA, AZ): coccidioides

Histoplasmosis: starling birds, bats
o Scenario: cave-exploring (spelunker) pt in Midwest, with non-productive cough
o The only systemic fungus that has yeast being phagocytosed by mq
Blastomycosis:
o Skin infection, lung infection
Coccidioides mycosis:
o Spherule: contain endospores
o Presentation:
In LA earthquake, many develop non-productive cough
Endospores are present in dust: dust comes up in earthquake, breathe in
artifact explorer in Sonoran desert (in AZ), developing non-productive cough
cave explorer with non-productive cough: not histoplasmosis even though its a
cave explorer
Cryptococcus neoforman:
o Mickey-mouse appearance: yeast form is narrow-based
o Presentation:
NY executive develop non-productive cough with pigeon resting on AC
A painter painting the Brooklyn bridge, developing respiratory infection either
histo or crypto (starling birds and pigeons rest on bridges)
Tx for both: actinomycin
Respiratory 2
Rheumatic Fever
Looks exactly like marantic vegetation: occurring along the lines of closure of the valves
Absolutely need hx to determine that its rheumatic fever and not marantic vegetations from
colon CA
Fibrinoid Necrosis
necrosis of immunological diseases
Histoplasmosis
alveolar mq phagocytosing yeasts
the only systemic fungus that has yeast form being phagocytosed by mq
o very unique to histoplasmosis
spelunkering:
o cave-exploration: lots of bats in caves
o starlings (black birds)
o pigeons: Cryptococcus
Blastomyces
broad-based buds
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Cryptococcus: pointy-end, constricted at the end
Aspergillous
3 must-know diseases:
o It loves to inhabit abandoned TB cavities fungus ball, aka aspergilloma
Very common cause of massive hemoptysis
o Vessel invader: produce thrombosis and stroke
Produce hemorrhagic infarction of the lungs
o Allergies to the moles: extrinsic asthma, type 1 hypersensitivity
Appearance: corona, septae, narrow angle
o Mucormycosis: non-septae, wide angle
Pneumocystis
Used to classified under protozoa, now considered to be fungus due to cell wall properties
Mainly seen in HIV
Most common AIDS define lesion
o Occur when T cell count <200
o Used to be the most common cause of death in AIDS, not anymore
o This is because now when T cell count < 200, pt is put on TMP/SMX
By preventing penumocystis, also prevent toxoplasmosis
o Toxo: common cause of space-occupying lesion in the brain of a pt with AIDS!
Silver stain:
o Also used for: Bartonella henselae, bacillary angiomatosis, legionella
o Pneumocystic carinii cysts: looks like ping-pong balls
In alveoli, looks like foamy, bubbly alveolar infiltrate dyspnea, tachypnea
On CXR: white-out appearance
Can see p. carinii in any organs
o Can see it in LN in HIV+ people
Tuberculosis
Most commonly seen in upper lobe of lungs
o Cavitary lesion due to reactivation
Primary TB:
o Located in the lower part of upper lobe or upper part of lower lobe in the middle
section, right near pleura
o Ghon focus and complex
o Most people recover
when there is immune suppression reactivation
o goes into apex cavitary lesion
o no Ghon focus or complex (only see this in primary TB)
other things can cavitate upper lobe:
o histoplasmosis: systemic fungus
o squamous cell carcinoma of the lungs
o klebsiella pneumoniae: with big mucous wall
need to do tests to confirm TB when seeing cavitation: acid-fast stain
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acid-fast: stains for mycolic acids
Foreign Body
standing or sitting up: go right into posterobasal segment of right lower lobe
o most posterior segment of the right lower lobe
when lying down: superior segment of the right lower lobe
o most common way to aspirate: occurs when laying down
when lying down on the right side: 2 routes
o right middle lobe
o posterior segment of right UPPER lobe
when lying down on the left: go to lingula
Abscesses in the Lungs
most common cause of abscess in the lungs: aspiration of oropharyngeal material
o commonly seen in street people: poor dentition, can be drunk aspirate
o oropharygeal material contains both aerobes and anaerobes very stenchy
contain fusobacterium, anaerobes, bacteroides
pneumonia: can also cause abscess, but not as common as aspiration
o staph aureus, klebsiella
o CXR: fluid cavities in the lungs
Pulmonary Embolus
2 types of embolus
o Small ones produce wedge-shaped hemorrhagic infarction
o Large ones
Most PE originates from:
o Deep veins of lower extremities: most common SITE of THROMBOSIS BEGINS
But not most common site for embolization
o Femoral vein: most common location for embolization to the lungs
Venous clots propagate towards the heart when gets to femoral vein, which is
a larger vessel easier to chip off
At femoral veins: site of embolization
Small embolus produces hemorrhagic infarct only if there is underlying lung disease (i.e.
smokers)
o 85% of times that embolus will not induce infarct
Saddle embolus: huge embolus!
o Blocks off the orifices of pulmonary arteries
If blocking off 3 out of 5 orifices of pulmonary vessels dead in milliseconds!
o No infarction because there isnt enough time to infarct
o Produces acute right heart strain immediate death
Screening test of choice:
o Ventilation-perfusion scan
With PE: ventilation is okay, but no perfusion
o Confirmatory test: pulmonary angiogram
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Restrictive Lung Diseases
Restrictive: something restricting it from filling
o In restrictive cardiomyopathy: restriction of filling of the heart
o Restrictive disease of the lungs: restricting from filling out with air
Compliance: inspiration, filling up the lungs with air
Elasticity: expiration, recoil of the lungs
In restrictive lung disease: picture a hot water rubber bottle
o Compliance is DECREASED hard to fill up with air
o Restriction is due to interstitial fibrosis
But once the lungs are filled with air air is quickly expired
o Increased elasticity
Sarcoidosis:
o Restrictive disease: difficult to get air in, but air comes out faster
All volumes and capacities are decreased:
o Total lung capacity, residual volume, tidal volume all decreased
FEV1/ FVC: increased
o FEV1: amount of air expired in 1 second
Normally around 4L, but in restrictive disease, down to 3L
o FVC: total amount that is expired after a deep inspiration
Also around 3L due to increased elasticity
o FEV1/FVC is 1!
Normal: 4/5 0.8
Examples of restrictive lung diseases:
o Pneumoconioses: air or dust-borne diseases
Big cities: LA, NY
Need to know: coal workers, silicosis and asbestosis
o Coal worker: PA, west VA
Increased incidence of TB but not CA
o Silicosis: sand blaster, foundry workers
Big nodule in the lungs: very hard (quartz)
Very fibrosis, increased incidence of TB but not CA
o Caplan syndrome: rheumatoid arthritis and one of pneumoconiosis (coal, asbestosis, or
silicosis)
RA nodules (same ones as those seen on the extensor surface of the hands) are
seen in the lungs, also with fibrosis
o Asbestosis:
abestosis fiber: dumb-bell shaped
the fibers are coated by Fe aka ferruginous body
most common overall pulmonary lesion associate with asbestosis exposure
fibrous plaque of pleura
not CA, but this is benign
NOT precursor for mesothelioma
Most common CA: primary lung CA; 2nd common mesothelioma
o Mesothelioma:
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Malignancy of serosal lining of the lungs

Lung looks like its covered with icing
High malignant tumor
o Smoker AND asbestosis exposure: synergistic for getting primary lung CA
No relationship with smoking and increase in mesothelioma
o Board question: a non-smoking roofer for 25 years, what would he most likely get?
Primary lung cancer
Used to have asbestosis for rooting material
If this roofer has been a smoker: still primary lung CA
Mesothelioma takes 25-30 years to develop; lung CA takes about 10 years
more common to have lung CA first
Whether a smoker or not: more than likely to get primary lung CA and not
mesothelioma with asbestosis exposure
o Occupation exposure to asbestosis: roofer and naval shipyard
All pipes in the ships are insulated with asbestosis
Sarcoidosis:
o 2nd most common cause of restrictive lung disease
o Potato nodes very enlarged hilum LNs
o Interstitial fibrosis
o Non-caseating granulomatous disease: but no relation to infection
Non-caseating: because its not systemic fungus or TB
o Primary target organ of sarcoidosis: Lungs
2nd target: face
Uveitis: produces blurry vision
Salivary/lacraminal glands can also enlarge
Nodular skin lesion: would see non-caseating granuloma on biopsy
o More common in African Americans
o Presentation: 35yo African America with dyspnea, with enlarged hilum nodes, uveitis
o Sarcoidosis is dx by exclusion: need to r/o TB, fungus
o Tx: steroids
o ACE: highly elevated (granuloma has lots of ACE)
o Hypercalcemia
Mq in granuloma (epithelioid cells) makes 1--hydroxylase
This leads to hypervit D excess amount of vit D increase absorption of Ca
and phosphate
o Most common cause of non-infectious granulomatous hepatitis
o TB: most common cause of infectious granulomatous hepatitis; 2nd pneumoconiosis
Hypersensitivity pneumonitis:
o Farmers lungs, silo fillers disease, byssinosis
Both farmers and silo fillers diseases are seen in farmers
o Remember silo fillers disease:
Gas in silo: NO2
Farmer went into a room in the barn, suddenly developed wheezing and
dyspnea because inhaled NO2 due to fermentation
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Farmers disease: thermophilic actinomycetes
Bacteria present in moldy hays
Dyspnea, hypersensitivity pneumonitis restrictive lung diseases
o Byssinosis:
Seen in worker in the textile factories
dyspnea
goodpastures syndrome:
o begins in the lungs: restrictive disease, hemoptysis, then ends in renal disease
o
Obstructive Lung Disease

no problem getting air in, but problem with getting air out
o elastic tissue is destroyed collapse on expiration, cant get air out
cant get all air out: residual volume is increased, and so is total lung capacity
o depressed diaphragm, increased AP diameter
Continuing to trap air: tidal volume/vital capacity decreases as residual volume continues to
increase
FEV1/FVC ratio:
o Very low FEV1, usually around 1L (normal is 4L)
o FVC: max is about 3L (normal is 5L)
o FEV1/FVC very LOW
o FEV1: a good way to measure lung function
4 types of obstructive lung diseases:
o Chronic bronchitis
o Emphysema
associated with smoking
o Bronchiectasis
o asthma
chronic bronchitis:
o pure clinical dx: pt has productive cough for 3 months in one year for 2 consecutive yrs
o disease is in the terminal bronchiole
turbulent air up to terminal bronchiole; after terminal bronchiole parallel
branching, airflow becomes laminar
most small airway diseases are present in terminal bronchiole produce
wheezing
terminal bronchiole also affected in: asthma, bronchiolitis
o mucous gland/goblet cell hyperplasia proximal to terminal bronchiole productive cough
mucous plug obstructs airflow huge VQ mismatch because CO2 cant get out
o BLUE bloater cyanotic, cant get rid of CO2
Emphysema:
o Present in the respiratory unit: where actual gas exchange occurs
Cant exchange gas in the terminal bronchiole
Terminal bronchiole: primary place for small airway disease and the origin for
expiratory wheezing
Respiratory unit: respiratory bronchiole, alveolar duct and alveoli
o On CXR: very low diaphragm, enlarged AP diameter obstructive pattern, trapping air
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Same CXR pattern can be seen in young child (3 mons) with bronchiolitis,
infected by respiratory syncytial virus
Or seen in newborn (1-2 wk old) with pneumonia from chlamydia trichomata
o 2 must-know types:
Centrilobular: upper lobe emphysema
Most often associated with smoking
Mostly respiratory bronchiole is destroyed by neutrophils
o Smoking is chemotaxic for neutrophils
o All smokers have increased neutrophils in the lungs
Neutrophils damage the elastic tissue support of bronchiole
o Air comes in, but cant get out forms air blebs, expansion
-1-anti-trypsin: destroy elastase produced by neutrophils; but -1-antitrypsin is denatured
Panacinar:
Entire respiratory unit is destroyed in the LOWER lobe
Associated with -1-anti-trypsin deficiency autosomal recessive
o Liver does not make -1-anti-trypsin
Breath in, air gets in, air cant get out because the entire respiratory unit
catches it
Smokers can also develop panacinar emphysema due to acquired -1anti-trypsin deficiency both upper and lower lobe emphysema
o inflammation can destroy respiratory unit as well as vasculature in the unit
even loss of ventilation and perfusion will NOT retain CO2
o PINK puffers; many pts actually have respiratory alkalosis
Bronchiectasis:
o On CXR: bronchi extends all the way to pleura; going beyond hilum
o Mechanism: infection, destruction of elastic tissue support, dilation of airways
o Bronchi filled with pus
o Presentation: pt with cup-ful productive cough
o In US, cystic fibrosis is most common cause of bronchiectasis
In 3rd world country: due to TB
Respiratory 3
Cystic Fibrosis
Most common cause of bronchiectasis in US

o In 3rd world country: its TB
Many other causes of bronchiectasis:
o Immotile cilia syndrome: aka Kartagener syndrome
9+2 configuration of microtubule in cilia
Absence dynein arm: 9 microtubules on the outside of the cilia dont have arms
to connect them together cilia cant move
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Those places that have cilia: sinuses, pseudostratified columnar epithelium,
Sinusitis, bronchiectasis, infertility in both men and women, organs
located on the opposite side (dextracardia)
Tail of the sperm is modified cilia; but the head can move
Fallopian tubes need cilia to carry the fertilized egg
Dextra cardia: normal heart on the other side; not complete shift
Can also have organ shift
Bronchial asthma:
o Extrinsic: type 1 hypersensitivity
o Intrinsic: involves chemicals; commonly seen at work place
Wheezing when come in contact with chemicals
Triad asthma: related to taking NSAIDs
Exertional asthma athletes develop wheezing when running
tx with chromolyn Na+
Cold-air induced
o Wheezing: due to inflammation in the terminal bronchiole
In smoking: irritation causing hyperplasia of goblet cells
In asthma: its due to LTC-D4-pE4, prostaglandin inflammation narrowing of
airways
Cancer
Centrally-located cancer of the lung: high association with smoking

o Include: small cell, squamous cell carcinoma of the lung\
Squamous more common than small cell
o Centrally-located: mainstem bronchus
Adenocarcinoma:
o More common primary cancer; higher than squamous cancer 2-3 years ago
o Tends to be more peripherally-located
Its at periphery because it filters cigarette
Takes out large carcinogen but small carcinogens remain and get trapped in the
periphery
Filtered cigarette is responsible for increase in periphery carcinoma
o Subtypes of adenocarcinoma:
One subtype has association to cancer
Bronchiolo-alveolar carcinoma, large cell carcinoma, scar cancer no relation to
smoking
What does squamous cancer look like with pap smear?
o Papanicolaou stains keratin bright red
Can use on all cytological specimen from all organs
o Presentation: smoking pt, centrally-located mass, sputum sample stained with Pap
shows bright red squamous cell carcinoma
If the sample is from cervix squamous cell carcinoma of cervix
Small cell carcinoma:
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o Small cells look very similar to lymphocytes

o Most malignant cancer
o Only do radiation and chemotherapy; NO surgery
o APUD tumors with neurosecretory granules; S100 Ag, can make ADH and ACTH
A slightly less malignant type of APUD tumor that is also in the lung: bronchial carcinoid
o Low-grade malignancy of the same kind of cell that produces small cell carcinoma
o Can invade, can mets, can produce carcinoid syndrome
o Can increase serotonin (even without mets)
The most common cancer of the lung: metastasis
o Pleural surface of the lung shows mets nodules; can see some cancer, lots around
bronchi, some are probably around lymphatics most likely due to breast cancer
Most common primary cancer of the lung:
o Adenocarcinoma > squamous > small cell
o Worst prognosis in ALL cancer: small cell
Horners syndrome:
o Associated with Pancoast tumors
Tumors usually located in the upper lobe, posteriorly posterior mediastium
o Most commonly caused by squamous cancer in this area
o Tumor is locally invading into the lower trunk of the brachial plexus can get some
lower trunk brachial plexus findings
o Can also knock off superior cervical ganglion, located in the posterior mediastinum
horners syndrome
Knocking off sympathetic activities
eyelids drop (ptosis), anhydrosis (no sweating); myosis (pupils constrict vs.
mydriasis normally; D for dilate)
Mediastinum
myasthenia gravis:
o thymoma: B cell hyperplasia of thymus
pleural fluid:
o transudate: less than 3g of proteins, very little cell
most common cause: heart failure
o exudate: protein > 3g, with lots of cells
causes: pneumonia, pulmonary infarction
Gastrointestinal 1
Mouth
Herpes simplex:
o Primary herpes: systemic infection fever, viremia, generalized lymphadenopathy
o But then symptoms disappear and virus remain dormant in the sensory ganglion forever
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Virus can come out during stress, menses form vesicles at the same spot, but no
more systemic symptoms
Primary herpes: systemic; recurrent herpes: not systemic
o Herpes zoster: also remain latent in the sensory ganglion; involve dermatome when its
reactivated
o Tzanck stain: shows inclusions multiple nucleated cells with inter-nucleus inclusion
Boards question: esophageal biopsy showing ulcerated lesions, multi-nucleated
cells with inter-nuclear inclusions, pt is HIV+ herpes esophagitis
o Herpes: pre-AIDS type of infection
Also true for thrush or shingles
Hairy leukoplakia:
o Usually on the lateral border of the tongue
o This is an infection due to EBV; has no dysplasia; not pre-neoplastic lesion
o Can be tx with acyclovir
o Start seeing this a few months before T cell count drops to 200; but not AIDS-defining
Thrush:
o Always in immunocompromised adults cellular immunity deficiency
o Newborns commonly get this if mom has candida in the vagina
o Not AIDS-defining lesion
Exudative tonsillitis:
o Group A hemolytic strep (30%); virus (70%) know this!
Dont give PCN by thinking that its caused by group A hemolytic strep
Virus: adenovirus, EBV
o If it were group A strep: 3 weeks later, pt developed bibasilar rales, polyarthritis,
pansystolic murmur apex radiating to axilla rheumatic fever
Blood culture: find nothing, because its not infective endocarditis
Leukoplakia:
o White lesion, plaque-like, cant be scraped off
o First step in management: biopsy
Regardless of where this occurs
Biopsy to r/o dysplasia and/or invasive cancer
Most common cause of squamous dysplasia and cancer: smoking
o 2nd: alcohol
Invasive squamous cancer vs. dysplasia:
o Look at the midline: invasive cancer is curved; not straight
o Invasive cancer also has different colored lesions
Lower lip: squamous carcinoma
Upper lip: basal cell carcinoma
Verrucous carcinoma: from chewing tobacco
o Also has a human papilloma virus relationship
Addisons disease:
o Diffuse pigmentation
o Low cortisol level increased ACTH stimulate melanocyte
o First place to see increased pigmentation: buccal mucosa
o
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Peutz-Jeghers syndrome
o Splotchy areas of hyperpigmentation
o Polyps are in small intestines
The exception to the rule to polyps in small intestines/colon most polys in the
entire GI tract are located in the sigmoid colon
o Hemartoma: not neoplastic cant transform into cancer
o No chance to evolve into cancer
Mixed tumor: aka pleomorphic adenoma
o Not a teratoma; mixed tumor two different types of tissues; same cell layer
o Most common salivary gland tumor
o Most common location: carotid
Mumps:
o Paramyxovirus
o Salivary amylase is increased
o Orchitis:
Incidence: low
Unilateral most of the time; usually does not lead to infertility
Usually in older men (teenagers and adult men)
o Oophoritis: in women
More commonly unilateral infertility usually not a problem
Esophagus Disorders
Dysphagia: difficulty swallowing

o If pt has difficulty swallowing only SOLID food obstructive lesion
Something is obstructing and preventing food from going downPlummerVinson syndrome
Fe deficiency anemia with kelosis, glossitis and esophageal web
o Esophageal cancer: dysphagia with SOLID foods
o If pt has problem with both solid and liquid foods peristalsis problem
If in the upper 1/3 of esophagus (striated muscle) myasthenia gravis
Middle 1/3 esophagus: mixed
Lowe 1/3 esophagus: smooth muscle scleroderma (progressive systemic
sclerosis), CREST syndrome, and achalasia
o To differentiate the causes of peristalsis:
Achalasia: pt goes to bed at night, and vomit out food he ate classic hx!
CREST and schleroderma would have Raynauds
Odonophagia: painful swallowing, always abnormal
o Most common cause in HIV pt: candida esophagitis
AIDS-defining
Candida is the most common fungal infection in HIV
When candida produces thrush pre-AIDS, but when it gets into esophagus
AIDS-defining
Tracheoesophageal (TE) fistula:
o Always asked!!
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Blindly-ending proximal esophagus: most common type
Distal esophagus arises from trachea mom has polyhydramnios
o Amniotic fluid is baby urine; baby has to pee
Needs to recycle otherwise mom would have a very big belly baby re-swallow
amniotic fluid and reabsorbed in the small intestine
If there is an obstruction in esophagus or proximal portion duodenum mom
would have polyhydramnios
o Associated with polyhydramnios: TE fistula, duodenal atresia in Downs syndrome
Block the ability to absorb amniotic fluid
o When these babies drink for the first time food gets into trachea cough
o VATER syndrome: step II
Zenkers diverticulum:
o Area of weakness that causes diverticulum: cricopharyngeus muscle
A little slit between fibers; mucosa and submucosa go out pouch formation
Collect in this pouch: halitosis (entrapped food)
o Tendency to regurge: undigested food coming out of nose
o This is a false, not complete diverticulum; only parts of mucosa and submucosa are
weakened
Achalasia:
o Peristalsis problem
o Problem with relaxation of the lower esophageal sphincter (LES) spasm all the time
o On biopsy: the ganglion cells are missing
Vasointestinal peptide (VIP) are in the ganglion cells
o Function of VIP: relax LES
When ganglion cells are destroyed destroy movement of lowe esophagus, also
reduce VIP level so there is constant constriction of LES
o Birds peak-appearance of esophagus: proximal portion of esophagus is dilated, but
narrows down
o In south America, where Leishmania can invade ganglion cells in the LES and rectum
producing acquired achalasia Chargas disease
Vector: kissing bug
Swelling around the eyes: Romanas sign
Produces myocarditis, congested cardiomyopathy and chronic heart failure
One of the more common causes of heart failure in S. America
Barretts esophagus:
o Ulcerated mucosa in the distal esophagus
o Glandular metaplasia on biopsy: showing goblet and mucous cells that shouldnt be
there
Esophagus cant protect itself from acid injury
o Risk: adenocarcinoma of distal esophagus
o Lesion in the mid-esophagus: squamous cell carcinoma
o Precursor lesion to adenocarcinoma in esophagus: Barretts
Esophageal varices:
o Pt: cirrhotic, alcoholic, portal hypertension left gastric vein varices
o
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o
o
o
One of the branches of portal vein right before it goes into the liver: left gastric vein
Drains distal esophagus and proximal stomach
Azygous vein drains into left gastric vein, then into portal vein
In cirrhosis, portal vein cant empty the blood as efficiently hydrostatic pressure
increases reverse blood flow into left gastric vein, splenic vein
Varices produced then rupture
Esophageal Cancer
Squamous cancer: not distal esophagus

o Most common cause: smoking > alcohol
o Solid but not liquid dysphagia
o Scenario: 50 yo alcoholic man, problem with swallowing food but not liquids; weight
loss esophageal cancer, most likely squamous cell carcinoma in mid-esophagus
Trachea has cartilage rings; esophagus; elastic artery
o Esophagus: between trachea and elastic artery
o Esophagus surrounded by white stuff everywhere:; esophageal cancer
Stomach Disorders
Hematemesis: vomiting blood

o Hemoptysis: coughing out blood
o Hematochesia: blood pouring out of anus
Different from blood coating stool internal hemorrhoids
Actual dripping of blood
Most common cause diverticulosis
Not diverticulitis: vessels are right next to diverticulated sacs; -itis: scarred
off; but in -losis: vessels are intact
When vessels are eroded bleeding
Mallory Weiss: tear right at the esophageal-gastric junction
o If in young women: most likely due to bulimia
o But usually the classic cause is alcoholic with retching
Retching: still trying to vomit, but nothing comes out
Tremendous pressure: can tear hematemasis, punctureBoerhaaves
syndrome
o Boerhaaves syndrome:
Air starts getting into pleural cavity, dissecting Hamanns crunch in anterior
mediastinum
Occurs in bulimia or retching alcoholics
Congenital pyloric stenosis:
o Scenario: male boy, at 3 weeks of age, starting vomiting non-bile-stained fluid. A nodule
at RUD area, can see hyperperistalsis
o If it was biliary atresia in Downs syndrome: vomiting bile-stained fluid at birth
Double bubble sign
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The atresia (lack of development of lumen) is distal to where bile duct

comes in; bile can still empty into the proximal portion of duodenum
bile-stained fluid
since there is no movement, air would be trapped in stomach and
proximal duodenum double bubble
Mom would also have polyhydramnios
o Multi-factorial inheritance; can be increased in future offspring
o Thickened muscle
o Tx: put a slit in belly button, split the muscle pyloriplasty
NSAID ulcers:
o NSAIDS block PGE2, which is responsible for mucous barrier of stomach, mucous
secretion, vessel dilation, and secretion of bicarbonate into mucous barrier
o When taking NSAIDS: all functions of PGE2 are destroyed ulceration occurs
o Can get significant blood loss
o Ulcers usually are not very deep; slightly thru mucosa and maybe a little bit of lamina
propria, but can cause bleeding overtime
Helicobacter Pylori:
o Silver stain used
Also used in legionnaire; pneumocystis; bartenella henselae
o Comma-shaped organism
Helicobacter: comma-shaped
But H. pylori has different cell wall composition than the other helicobacter
o Makes lots of urease convert urea to ammonia and burn thru mucous layer
Ammonia is very toxic
Urease test on GI biopsy: if positive H. pylori is present
o Also makes lots of cytokines
o Can use serology test: ab against H. pylori for first time
But since ab doesnt disappear, cant use serology to dx recurrent diease
Great for the first time; after that its useless only shows previous infection
o Parietal cells are located in fundus and body; destroyed by autoimmune ab (along with
IF) atrophic gastritis in fundus and body
o H. pylori affects pylorus and antrum
Destroys mucosa and produces gastritis of the pylorus and antrum where
cancers are
o Most stomach cancers occur along the lesser curvature of pylorus and antrum
Exact same place where gastric ulcer is located
o H. pylori lives in the mucous barrier most common cause of stomach
o H. pylori can also cause malignant lymphoma of the stomach (not 1st cause)
Gastric ulcer:
o Biopsy because trying to r/o cancer
o In ulcers: 3% chance of being malignant ulcer
Duodenal ulcer:
o Never biopsy its never malignant
o More common association of H. Pylori and peptic ulcer disease
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Not gastric ulcer

Melena: black stool; mostly due to upper GI bleeds
o Bleeding from ligament of treitz up: where duodenum hits jejunum
o Black: acid acts on Hb from bleeding convert Hb to hematin (a black pigment)!
o Black tarry stool: 95% its an upper GI bleed more likely duodenal over gastric ulcer
Vomiting coffee-ground material: blood clot that has been acted by acid and
turned into hematin coffee-ground like
Scenario: pt under great work stress; episodes of sever epigastric pain, referred into left
shoulder
o First step in management: flat-plate of abd
Would see air in the diaphragm
o This pt has perforated ulcer
o Odds: duodenal ulcer
o Shoulder pain: air got out, settle onto diaphragm, irritate C4 (phrenic nerve) same
dermatome as left shoulder
Gastric adenocarcinoma:
o Scenario: 52 yo woman with weight loss and epigastric distress; upper GI series showed
that stomach was found to not move/no peristalsis; pt then died. Biopsy showed ovaries.
o Stomach not moving: linitis plastica
o Adenocarcinoma of the stomach: cells that are invading the wall of the entire
stomachsignet-ring cells
Mucicarmine stain mucin is pink
Signet-ring cells: nucleus is pushed to the periphery; and the mucous makes
cells look empty
Similar to fatty changes in liver; but these are malignant neoplastic glandular
cells
Very characteristic of linitis plastica
o Krukenberg tumors:
Gastric cancer involving the stomach is NOT seeding at ovary hematogenous
spread to ovary
If seeding is true: cancer cells would be on the outside and invade in; but the
ovaries in this case is entirely affected and not just on the outside
o On exam: can show biopsy of stomach and ovary with signet ring cells
There is no signet-ring adenocarcinoma of the ovary; primary ovary cancer
doesnt look like this
This comes from stomach cancer that mets to ovaries
Favorite question on boards!
o Most of cancers in the stomach: ulcerated-typed lesions occurring in the lesser curvature
along antrum and pylorus
o Gastric adenocarcinoma: diffusely infiltrate into the wall of stomach leather bottle
stomach
Infiltration of cancer cells and fibrous response stomach is very very hard
o Gastric cancer in US: declining; probably related to tx of H. Pylori infection
But its primary cancer in Japan: relates to smoked (charcoal) products (bbq)
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Nasopharyngeal carcinoma: China

T cell malignant lymphoma and stomach cancer: Japan
Burkitts lymphoma: Africa
Non-tender mass in left supraclavicular area with epigastric distress, weakness
mets gastric adenocarcinoma
Cervical cancer can also mets to left supraclavicular node
Left supraclavicular node drains abd organs; but right node doesnt lung
cancer goes to right node
Malabsorption
Malabsorption of fats, carbs, proteins

Inability to absorb fats stool contains fats (steatorrhea)
o Screening test for malabsorption: steatorrhea
Fat digestion:
o Lipases: break fats down into 2 monoglycerides and fatty acids
Requires functioning pancreas
o Villi in small intestine
Increase absorptive surface
Without villidecrease absorptive area cant absorb fatty acids,
monoglycerides
o Emulsify fats: micelle
Bile salts are used to emulsify breaking up big fat molecules into small droplets
that are 1micron in size and are called micelles
Dish wash: emulsify agents used to get fats off the plates
Bile salts: made from cholesterol in liver
o Cholesterol cant be degraded: either in solubilize in bile (risk of cholesterol stone) or is
converted into bile salts/acids
o bile salt deficiency:
liver disease
anything that is obstructing bile flow
bacteria overgrowth: bacteria love salt
terminal ileum disease: in Crohns disease, cant recycle bile salts
cholestyramin: bile acid binding resin used to treat hyperlipidemia
cholestyramin: if not recycling bile salts need to make more bileupregulation of LDL receptor in liver
up-regulated LDL receptor take more cholesterol out of blood lower
cholesterol
side effects: it also affects other drugs (I.e. digitalis) can lose other
drugs in stool along with other salts
positive stool for fats: need to figure out the cause:
o pancreatic deficiency (alcoholic), bile salt deficiency, or something wrong with small
bowel
overall, small bowel wins
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Small Bowel Disorders that lead to Malabsorption
Celiac disease and dermatitis herpatiformis

o dermatitis herpatiformis with celiac disease: 100% association
o celiac disease: autoimmune ds against gluten in wheat
Most common cause of malabsorption in US
Taking wheat product gluten gets reabsorbed in the villi ab against gluten
(specificially against gliadin) destruction of villi villi become flat
Similar to ab against parietal cell and IF
Flat villi cant absorb fats, proteins, carbs
o The glands underneath the surface are intact
o Herpatiformis: not herpes; autoimmune against skin
Vesicular lesion; looks like herpes in the skin
In this case, diarrhea is due to ab against gluten/gliadin
Whipples disease:
o Infection of small intestines
o Due to an organism that is only visible under EM, cant do gram stain
Defective rods tropheryma whippelii
Cant be cultured either
o Histology: flat, blunt villi; foamy mq in lamina propia
Foamy mq: bubbly
o But in HIV+ person with 100 helper T cell count and foamy mq:
under acid fast stain mycobacterium avium
more common than MTB
produce whipple-like malabsorption in HIV+ pt
o systemic manifestation: because its an infection
fever, polyarthritis, generalized painful lymphadenopathy, peculiar color to the
skin (esp in males)
o tx: abx
other causes of malabsorption:
o pancreatitis commonly seen in alcoholics
two reasons why alcoholics have malabsorption:
chronic pancreatitis lipase deficiency
cirrhosis bile salt deficiency
Diarrhea
best way to think about diarrhea subdivide into 3 types

o invasive: due to bacteria
o secretory: bacterial produces toxin that stimulates cAMP small bowel secret excess
amount of isotonic fluid (NaCl)
o osmotic: lactase deficiency, laxatives, inborn errors of metabolism
secretory and osmotic diarrhea:
o both high volume and go frequently
Invasive diarrhea:
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o Low volume
Fecal smear for leukocytes: absolute best initial test for diarrhea
o If there are no neutrophils dont worry about it
Not invasive: no need to culture
Either secretory or osmotic would eventually go away
o If there are inflammatory cells:
Obligated to culture
Can be campylobacter, shigella
Osmotic: osmotically-active substances in the lumen of small bowel
o Sucking out water of bowel high volume, hypotonic loss of fluid
o Lactase deficient
Lactase: brush-border enzyme, a disaccharidase enzyme
In lactose intolerant pt: might not see lactase deficiency but would see brushborder or disaccharidase enzyme deficiency
o Lactose intolerance:
Cant break down lactose into glucose and galactose go into colon
Anaerobic bacteria start consuming lactose release gas, H+
hydrogen gas causes bloating/distension and explosive diarrhea
secretory diarrhea:
o cholera: due to vibrio cholera
not invasive diarrhea
o travelers diarrhea: due to enterotoxigenic E. Coli
know all the toxins of E. Coli
enterohemorrahgic: 0157:87
not an invasive diarrhea
o in above two diarrhea: bowel biopsy completely normalno inflammation
toxin activating a pump (cAMP)
not like clostridium dificile that produces pseudomembrane
o When give full replace to pt with cholera: fluid needs to have glucose!!
Glucose is used to co-transport Na+
Invasive diarrhea:
o The most common invasive bacteria infection in the US: campylobacter jejuni
Followed by shigella
o Low-volume diarrhea, may have some blood
o Gram stain shows a comma-shaped organism c. jejuni
o Shigella and campylobacter can produce pseudomembrane
o Giardia: Owls eyes that moves
This pt can be anywhere in the US, esp up in the mtn
Most common cause of chronic diarrhea due to parasites
Tx: metronidazole
o Cryptosporidium cari
Most common organism associated with AIDS diarrhea
Partially acid-fast organism!
Lethal in immunocompromised people
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When contaminating water supply: normal people recover, but AIDS pt dies
When T helper cell count around 50-75: MAC, cryptosporidium, toxoplasmosis,
CMV all start infecting the host
P. jiroveci: when T helper cell is around 200
Pseudomembranous colitis:
o Scenario: old woman in hospital with pneumonia, and developed diarrhea
o Pneumonia: most likely taking ABx
PCN > clindamycin
o ABx wiping out the good bacteria and leaving behind clostridium difficile
Everyone has c. dififcile in the stool
But kept in check by E. Coli, bacteriodes fragilis
o C. difficile makes toxin damage superficial layer of colon
Bacteria dont invade, but toxin does
Similar to corynebacterium diphtheria: produce toxin and pseudomembrane
ADP ribosylation EF-2 inhibited
First step in tx: toxin-assay in stool
not gram stain because everyone has gram + rod in stool
not blood culture because its not in blood
tx: metronidazole
but metronidazole itself can cause pseudomb colitis
tried to use vancomycin, but resistance developed
Small Bowel Obstruction
cancer: on all steps

step-ladder effect: air-fluid/air-fluid step-ladder
signs:
o when there is hallow viscous peristalsis colicky pain
unlike crampy pain that there is no pain-free interval
colicky pain: pain, and absolute pain free interval alternating! (in question stem)
sometimes can be 15 mins, even an hour apart
has to have peristalsis (against obstruction)
TOTAL obstruction of small bowel
Bile duct doesnt peristalsis crampy pain
Peristalsis move into ileus, but due to obstruction stagnation of food proximal
to the obstruct air fluid level
distal to the area of obstruction: no air
o
Obstruction: 2 things can happen
o Constipation: problem with passing stool
o obstipation: cant pass gas with constipation complete obstruction
Downs syndrome with only 46 chromosome
o Not all Downs has trisomy 21: due to non-disjunction in meiosis I
o Robertsonian translocation: 46 chromosomes
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But one of the chromosome (21) has one other chromosome attached to it
The total number is 46
o Usually mother has abnormality: 45 chromosome, and her chromosome 21 is one
chromosome but with two attached together
o Baby gets one chromosome 21 from dad, and chromosome 21 that are attached
together from mom 46 chromosomes, but 3 functioning loss
o Non-disjunction: abnormal number of chromosome
o Downs kids have two GI problems: duodenal atresia and Hirschsprung
Causes of small bowel obstruction:
o Adhesion from previous sx: most common
o Indirect inguinal hernia: 2nd common
Scenario: male lifer, colicky pain in RLQ area, never had sx
o Hirschsprung:
Missing ganglion cells
Stool cant get by because there is no peristalsis even though the lumen is open
Dilatation of proximal colon: has ganglion cells and are peristalsis
No ganglion cells no peristalsis!
If there is a child that didnt pass meconium for 24 hours:
On DRE: if no stool came out on finger Hirschsprung
o No stool in the rectum ampulla
But if stool came out on finger tight sphincter
o Intussusceptions: common in children
Terminal ileum goes into the cecum
Colicky pain because its obstruction
Compromising blood flow bleeding
Scenario: bloody stool and colicky pain in 2 yo child
Oblong mass in RUQ; currant-jelly stool
Most time it spontaneously comes out in children
Tx: use barium edema, put some pressure, and ileum comes out
Very commonly asked on all steps!
o Volvulus:
Twisting of colon around mesentery
Complete obstruction
Infarction: compromising blood supply
o Gallstone ileus: usually seen in older women
Stone fell off and settled at ileocecal vale obstruction
Signs of colicky pain and obstruction
Flat plate of abd: air in the biliary tree
Fistula (communication) between gall bladder and small bowel air can get into
gall bladder and biliary tree
Air in biliary tree and colicky pain gallstone ileus
o Meconium ileus: cystic fibrosis
Vascular Lesions
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Hemorrhagic infarction:
o Small bowel more commonly infarct than large bowel
Most of the small bowel is supplied by superior mesenteric artery
o Cause: indirect inguinal hernia a piece of small bowel is trapped
Ischemic colitis:
o Not getting enough blood
o Infarction involving the splenic flexure of the large bowel
o Scenario: severe pain after meal; blood in stool
o Pain is localized (vs. generalized pain in small bowel infarction)
Infarction of small bowel sudden onset of severe, generalized pain and bloody diarrhea
o The whole abd hurts!
The main difference btwn small bowel infarction and bloody diarrhea related to ischemic ulcer in
the splenic flexure (ischemic colitis)
o Both can have bloody diarrhea
o Small bowel infarction: diffuse abd pain, not one specific area
GI 2
Vascular Lesions
Angiodysplasia:
o Cecum with cystic spaces
o 2nd most common cause of hematochezia
Diverticulosis: number 1 cause
o In cecum: diameter is bigger here than other parts of the colon
o Because diameter is bigger wall stress is bigger
Put stress on vessels on wall of cecum pulling apart slightly telangiectasia
If blood vessels rupture can have significant bleeding
o Commonly seen in older people
o Theres relationship between angiodysplasia and aortic stenosis, and with vW disease
Meckel Diverticulum
o 2 inches long, 2 feet from ileocecal valve, 2% population
o Most common complication: bleeding
o Because its diverticulum can get inflammed diverticulitis
o Scenario: pt has hematemesis and melena, pain in the RLQ Meckel diverticulum
Crohns disease: no hematemesis
Melena from bleeding
o Embryo question: newborn that had a sinus and umbilicus is draining poop
persistence vitelline duct
Communication between small bowel and umbilicus
Feces coming out of umbilicus
If urine comes out of umbilicus persistence of urachus
most common location for cancer/polyp/diverticuli in the GI tract: sigmoid colon
Diverticulosis:
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area of weakness: blood vessels penetrate the bowel submucosa herniate right next
to this vessel
when feces get stuck in the diverticular sac (fecalith) erode the area and
vessel bleeding
diverticulosis: most common cause of hemachezia massive lower GI bleed!
Not familial polyposis:
Polyps go into the lumen, not out as in diverticulosis
Complications:
Most common: diverticulitis
Left-sided appendicitis: same presentation as acute appendicitis, in older
person
o LLQ, rebound tenderness, fever, neutrophilia cytosis
Also most common cause of fistula (communication) in the GI tract
Fistula: communication between 2 hallow organs
Colovesical fistula: most common fistula
o Between colon and bladder
o Pneumaturia (air in urine)
Rupture peritonitis
Inflammatory Bowel Disease
Crohns:
o Involves terminal ileum 80% of the time; can also involve colon; sometimes just the
colon
o Likes the anus
o Crohns: produces fistula/fissure of anus
o Transmural, jumps around, non-caseating granuloma
o Dx:
Ilecal valve/ascending colon/terminal ileum: transmural inflammation with narrow
lumen
Colicky, RLQ pain, diarrhea in young person
If in 3rd world country: due to TB (mycobacterium bovis)
o Due to lack of pasteurization
In US, TB in intestines Mycobacterium tuberculosis from swallowing it
from the lungs
o On barium study: string-like string sign
Transmural; segmental
Hugely dilated proximal small bowel cant push stool thru
Fissuring: cobble-stone appearance
Lots of linear ulceration: serpentiginous with fissures in between
o Non-caseating granuloma:
Multinucleated giant cells
Ulcerative colitis: likes rectum
o Bloody diarrhea
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o
o
o
o
o
Continuous, doesnt jump around, involves mucosa and submucosa

Always begins in the rectum
Can stay there or can move up and involve the whole colon pancolitis with high
incidence of cancer
More involvement of colon greater duration higher risk of cancer
Never involve terminal ileum
Pseudopolyps:
Ulcerated mucosa and submucosa
Residual mucosa that is inflammed
Inflammed, bloody mucosa; totally ulcerated off in between; basically looking at
submucosa of the colon
Highest association with cancer
B27+ ankylosing spondylitis
Most common cause of sclerosing peri-cholangitis
Fibrosis around the common bile duct obstructive jaundice high incidence of
cholangiocarcinoma
Polyps
Most common type in the GI tract: hyperplastic polyp

o Hamartomas; no polyposis syndrome; no neoplasm
Commonly located in sigmoid colon
Tubular adenoma:
o strawberry on a stick, stalk strawberry
o Precursor lesion for colon cancer
o
Size of adenoma determines the degree of malignancy:
> 2cm very dangerous
Juvenile polyp:
o All juvenile polyps are in the rectum
o Hamartoma, not precancerous
Internal hemorrhoids:
o Adult that has a reddish mass coming out of the butt prolapsed internal hemorrhoids
o Internal hemorrhoids: bleed; external hemorrhoids: thrombose/painful
o Blood-coating stool: from internal hemorrhoids
o Internal hemorrhoids: not painful, but prolapsed
Prolapsed out of the butt
Villius adenoma:
o Sessile polyp
o Looks like villus in the intestines: finger-like
o Greatest malignant potential of all polyps
o Usually in rectal sigmoid
o Because villus-like, lots of time have lots of mucous coating the stool
50% chance of being malignant
Secret lots of mucous coat stool
Polyposis:
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o Needs to have more than 100 polyps to be familial polyposis

Familial polyposis:
o Autosomal dominant
Characteristics: late manifestations, penetrance, variable expressivity
Pt with familial polyposis do not have polyps at birth; polyps develop between 1020yo
Same for polycystic kidneys disease: kidneys develop cysts between 10-20 yo
Huntington disease chorea: develop at 35-40yo
o APC suppressor gene; Ras oncogene, P53 are all involved
o Always get cancer: usually between 35-40yo
Prophylaxis: remove bowel
o Turcots syndrome: familial polyposis + brain tumor
Autosomal recessive
Carcinoid Tumors
APUD tumor: melanoma

All carcinoid tumors are malignant; but have low-grade potential
o Size-dependent on whether carcinoid tumor can mets
o >2cm in size can mets
Most common location: tip of appendix
o Bright yellow
o Rarely associated with carcinoid syndrome because its rarely >2cm at the tip of
appendix
Most common location that causes carcinoid syndrome: terminal ileum
o Always >2cm
All carcinoid tumors make serotonin
o Appendix and terminal ileum are drained by portal vein: serotonin enters portal vein
hepatocytes metabolized to 5-hydroxyindoleacetic acid pee out
o No signs of flushing or diarrhea because its not in contact with systemic circulation
If mets to liver:
o Mets nodule making serotonin dump into hepatic vein access to systemic circulation
o Inferior vena cava right sided heart lesions
Tricuspid insufficiency, pulmonic stenosis
Serotonin: vasodilate in carcinoid tumors
o Produces flushing and diarrhea
o Flushing: most common symptom; diarrhea: 2nd most common
Screening test of choice: blood level of 5-hydroxyindoleacetic acid
Tryptophan would be decreased fromniacin would be decreased
o Can have pellagra: dermatitis, diarrhea, dementia
Neurosecretory granules on EM: black dots
Colon Cancer
Left side obstruct, right side bleed

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Left colon: smaller diameter than right side
When cancer develops in the left colon not enough room, goes around annular,
napkin ring, produces obstruction
o Right colon: bigger diameter, greater chance of going out and forming polyp bleed
Right sided lesions: Fe deficiency; left sided lesions: alternation in bowel habits
(constipation/diarrhea)
Tumor marker: CEA (carcinoembryonic antigen)
o Not used to dx; used to follow for recurrence
Most common cause relates to diet:
o Lack of fiber in stool
o More fiber in stool less chance of colon because eliminating lipocholic acid
Age: over 50 is a risk factor
Smoking: association with colon cancer
Familial polyposis/gardeners syndrome/turcots also associated with colon cancer
o Not Peutz-Jeghers/juvenile/hyperplastic polyps
o
o
Acute Appendicitis
Covered by pus
Most common cause in adults: fecalith
o Impacted stool press on the side of appendix ischemia mucosa break down and
E. Coli gets in appendicitis
o Same mechanism for diverticulitis:
Diverticular sacs with fecalith ischemia on the wall inflammation E. Coli
o Acute cholecystitis: stone in the cystic duct pushed off on the side ischemia acute
cholecystitis E. Coli
o Something obstructing the lumen ischemia inflammation, E. Coli
Most common cause in children: measles and/or adenovirus infection
o Lymphoid tissues in the appendix
o Adenovirus/measles hyperplasia of lymphoid tissues in the appendix obstruct the
lumen mucosal injury acute appendicitis
o Usually follow viral infection
Hepatobilliary-Pancreas 1
Bilirubin Metabolism
Most bilirubin in the body is unconjugated from RBCs when they get old/phagocytosed
o Unconjugated bilirubin is the end product: went out into blood stream, bound to albumin,
went to liver and taken up
99% of bilirubin (about 1mg/dL) comes from breakdown of old RBCs all unconjugated
o No bilirubin in the urine
Bilirubin taken up by liver, gets conjugated
o Cytochrome P450 system in the liver: conjugation makes it more soluble
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o Conjugated bilirubin (direct bilirubin) water soluble

o Drugs in liver: once gets conjugated, is water soluble can pee out
Once bilirubin is taken up by liver, its not close to any vessels can never get into vascular
channel once it gets taken up to liver
o If direct conjugated bilirubin is in the urine: something happened in the liver or bile duct
to cause bilirubin to get there
Because bilirubin shouldnt have any access to the bloodstream
o Taken up in liver, conjugated, pumped into bile duct, go into triad, some stored in the gall
bladder, then go into small intestine via common bile duct
Bile contains conjugated bilirubin
o Also contain: bile salts, cholesterol, estrogens
Bacteria in the intestine would break down the conjugated bilirubin bilirubin becomes
unconjugated again
Urobilinogen:
o Further break down unconjugated bilirubin into urobilinogen
o All porphyrins are colorless; but develops color after oxidized
o Urobilinogen is oxidized to urobilin brown color
A small portion of urobilinogen is reabsorbed from the colon:
o Most of it goes to the liver
o Some go to the kidney in urine
In urine, its oxidized into urobilin cause for color of urine!
o Same pigment seen in stool is the same in urine
If there is obstruction in the bile flow (in liver, or common bile duct):
o Stool color would be light: no bilirubin to make urobilinogen
o No urobilinogen in the urine either
Jaundice:
o Total bilirubin and find out how much % of total bilirubin is conjugated
Ex: total bilirubin is 10, conjugated bilirubin is 5 % conjugation is 50%
o
3 types of jaundice:
<20% conjugation: most are not conjugated
Primarily unconjugated hyperbilirubinemia
Increase unconjugated bilirubin: hemolytic anemia, spherocytosis, sickle
cell anemia, ABO/Rh hemolytic disease in the newborn, physiologic
jaundice in the newborn
Either due to problem with conjugation enzyme or breaking down RBCs
Conjugation enzymes either immature (seen in newborns) or missing
(Crigler-Najjar syndrome)
20-50% conjugated: some are but some are not conjugated
Hepatitis/alcoholic: inflammation of entire liver
Liver is sick: doesnt want to take up unconjugated bilirubin
o Unconjugated bilirubin increases in blood
Inflammation of liver also disrupts architecture break open a few small
bile ducts that have a lot of unconjugated bilirubin
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Necrosis of liver and bile duct water-soluble (conjugated) bilirubin would

get into the blood as well
>50% conjugation: most are conjugated bilirubin
Obstruction of bile
Intrahepatic obstruction
o Intrahepatic cholestasis: blocking bile flow in the liver (little bile
ducts, triad)
Extrahepatic cholestasis: outside of liver
o The only thing outside of liver: common bile duct
o Most likely due to stone in the gall bladder
o Or carcinoma in the head of the pancreas complete bile duct
obstruction
As bile flow is blocked backs into liver cell now has access to the
sinusoid goes into blood stream
Really dark yellow urine and light color stool!
o Dark yellow urine because conjugated bilirubin is water-soluble
Gilberts (Gil-bear) disease: 2nd most common cause of jaundice
o People with this disease dont know they have it unless they fast for 24 hours (seems to
be related to not-eating)
o Problem in taking up bilirubin and conjugating bilirubin in liver
o All enzyme studies are normal
o Predominantly unconjugated hyperbilirubinemia
o To test for Gilberts disease: fasting test
Get a baseline total bilirubin
After 24 hours of fasting already jaundiced
If doubling baseline bilirubin in 24 hours Gilberts syndrome
Most common cause of jaundice in the US: Hep A
o 2nd most common: Gilberts
Dubin-Johnson syndrome:
o Genetic disease: inability to eliminate conjugated bilirubin in the bile duct
o Predominantly conjugated type of hyperbilirubinemia
o Black pigment builds up in liver black liver
Liver Function Tests
Transaminase:
o Index of liver cell necrosis: i.e hepatitis
o ALT: more specific only found in liver
o AST: present in RBC, muscle, and liver
o In viral hepatitis with massive liver cell necrosis its ALT that is predominantly elevated
Elevated in any diffuse liver cell necrosis
ALT > AST
o But in alcoholic hepatitis:
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AST is present in mito of hepatocytes; ALT is in cytosol
Alcohol is a mito toxin via uncoupling
In alcoholic hepatitis: AST is higher than ALT
When seeing AST > ALT: could be fatty change, cirrhosis, alcoholic hepatitis
Doesnt even have to be 2:1 ratio
Bile duct obstruction: alkaline phosphatase and gamma glutamyl transferase (GGT) elevate
o Transaminase can also slightly elevate
o GGT: located in SER
When SER is revved up (hyperplasia) due to drugs (alcohol, barbiturates,
rifampin, phenotyoin) increase metabolism of the drug, also causing increase
synthesis of GGT
o Alcoholic liver disease: AST > ALT; elevation of GGT
o Alkaline phosphatase is present in other organs besides liver:
Bone: osteoblastic activity
Also in placenta
But GGT is only in the liver
If alkaline phosphatase is elevated but GGT is normal not from liver!
But if both alkaline phosphatase and GGT are elevated bile duct obstruction
Albumin protime:
o Marker of severity of liver disease
o Albumin is made in the liver: if there is liver disease (i.e. cirrhosis) albumin decreases
Prothrombin time:
o Majority coagulation factors are made in the liver
vWF is not made in liver
o in severe liver damage: prothrombin time is prolonged
o slightly better test than albumin test
anti-mitochondria ab: autoimmune ab
o important in primary biliary cirrhosis
tumor marker: AFP marker for hepatocellular carcinoma
can also use alpha anti-trypsin since its also made in the liver
o increased in hepatocellular carcinoma
Hepatitis
facts:
o most common hepatitis: hep A
A > B > C> D> E
o Two hepatitis that are not necessarily transmitted parenterally:
A, E
o Hep A never produces chronic liver disease
Hep E: if get it during pregnancy can develop chronic liver disease
o Hep D requires another infection before becoming infectious
o Day care center: Hep A
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Epidemic Hep A in daycare center: any child going to daycare center should get
Hep A vaccination
o Jails: Hep A
o IVDU: Hep B
o Post-transfusion hepatitis: hep B
o Accidental needle stick: hep B
Serology:
o Hep A: anti-HAV-IgM have hep A
Anti-HAV-IgG: had hep A before, recovered, PROTECTIVE
o Hep B:
Anti-HBV-IgG: have the disease right now; not protective
Anti-HBs: protective ab
o Hep C:
Anti-HCV-IgG: not protective have the disease right now
No known protective ab
o Hep D:
Anti-HDV-IgG: not protective
o Hep E
Have protective ab
Hep B serology:
o First marker: surface antigen
Usually comes up 1 month after infection: at this time all enzymes studies are
normal and pt is asymptomatic
o Next: E antigen and Hep B DNA: both are infective
o 3rd: core ab IgM
First immunoglobulin in acute inflammation is IgM
o Most people with hep B recover (90%); but those HIV+ never recover, chronic liver
disease because dont have immune system to fight off
o If recover:
E antigen and hep B DNA disappear
Then surface antigen disappears (first one to come but last one to leave)
Impossible to be E antigen+ but surface antigeno Serology gap: there is always a 6-8 week before surface ab appears in any infection
In this window: E/DNA and surface ag is gone; surface ab is not there yet
If pt had hep B and is recovering: core ab IgM present!
Not infective during this period because dont have E antigen and hep B DNA
This window period occurs around 4-5 months after infection
o If one has Hep B: should have core ab IgG and surface ab
o Vaccination: surface ab; nothing else
Core ab IgG: not protective
o Chronic hepatitis: how long you have surface antigen
More than 6 months chronic hep B
o Infective chronic carrier: E antigen and hep B DNA positive
Hep B is transmitted by IV and sex
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o
o
o
o
o
o
If negative for E antigen and hep B DNA negative but surface antigen positive healthy
carrier
Still have chronic hep B, but chances of recovery are excellent
Surface ag would eventually disappear and surface ab would come up
Would also have core ab IgG at this time
In an infective carrier can recover too from -interferon therapy
Never give corticosteroids to pt with chronic hep B
Acute hep B:
Surface ag, E ag, hep B DNA and core ab IgM
Window period: core ab IgM
Had hep B before and recovered: core ab IgG and surface ab
Just immunized with vaccination: surface ab
If at the end of 6 months have surface ag, core ab IgM only healthy carrier
If after 6 months: surface/E ag, hep DNA, and core ab IgM infective carrier
Other Infection Diseases
Amebiasis: always asked

o Caused by emtamoeba histolytica: resistant to acid
Excess growth in cecum because its an alkaline environment
o Can drill into mucosa and produce flask-shaped ulcers
Can have bloody diarrhea
o Cecum is drained by portal vein possible that e. histolytic can be drained into the liver
and produces abscess on right lobe of liver
Dissolving liver anchovy paste (brownish liquid)
o Can also drill thru right diaphragm lungs, produce effusion systemic circulation
o Tx: metronidazole
Also used to tx: giardiasis, clostridium difficile infection, bacterial vaginosis,
trichinosis
o The only protozoa that can phagocytose RBCs can see RBCs in trophozoites
Hydatid disease:
o Definitive host: sexually active worms that have ability to lay eggs
o Intermediate host: only have larvae form
o Adults egg larvae: cant jump stages
Larvae: end stage
Sheepherders disease:
o Echinococcus multilaris
o sheep have larvae form (intermediate host)
o after sheep dog eats sheep larvae develop into adults in dogs dogs become
definitive host
o human patting dogs and pick up some eggs eat the eggs form into larvae
sheepherder: intermediate host
o dont want to rupture cysts fluid in the abd cavity anaphylactic shock
tenia solium: pig tapeworm
o undercooked pig meat: contains larvae
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o
pigs: intermediate host

human ingests meat: larvae develop into worms
human: definitive host
if one of your family is the definitive host and didnt wash hands when making dinner
you eat the dinner with eggs the eggs develop into larvae in you
larvae: cysticerci
stops at larvae stage
larvae penetrate the bowel migrate to anywhere, esp brain and eyes
larvae in brain: gets calcified host has seizure activity for the rest of his life
adults can be definite host by ingesting pig; can also be intermediate host by ingesting
eggs in mouth
eggs then develop into larvae cysticercosis in intermediate host
Obstruction of Blood Flow in Liver
nutmeg liver
o random fact: most common complication of corticosteroid therapycataract
most common cause of nutmeg liver: R heart failure
o thrombus in portal vein: no nutmeg liver because its before the portal vein empties into
liver; can have ascites, varices, and portal HTN but liver is not big and congested
o thrombus in hepatic vein:
most common cause: polycythemia vera > birth control pills
hepatic vein empties liver: liver gets huge; hemorrhage
absolute sx emergency: death 100% without sx
o Know blood flow from portal vein liver hepatic vein
Pre-hepatic: portal vein; post-hepatic: hepatic vein
Alcoholic Liver Disease
Most common manifestation of alcoholism: fatty change

o Because of alcohol metabolism: lots of NADH/acetate/acetyl-CoA
o NADH converts pyruvate into lactate metabolic acidosis, fasting hypoglycemia
o Acetyl-CoA can make fatty acids add to G3P to make TG, fatty change
o Can also convert acetyl-CoA to ketone bodies; acetoacetic acid converting to betahydroxybutyrate (a NADH reaction)
Another reason to increase anion gap metabolic acidosis
o Fatty change: completely reversible if stops drinking
Alcoholic hepatitis:
o Hepatic encephalopathy, ascite, systemic disease
o Different from fatty changes: neutrophilic leukocytosis, fever, AST higher than ALT,
increased GGT
o If doesnt stop drinking death
o Mallory bodies: ubiquinated keratin microfilaments
Toxic compound in alcohol that damages the liver: acetaldehyde
o Acetaldehyde (not by itself) bound to protein: damage the liver
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Eto cell: normally stores retinoic acid in liver

o in alcoholic, acetaldehyde/protein complex stimulates eto cell to make fibrous
tissues/collagen responsible for cirrhosis
fibrous tissues: big part of alcoholic liver disease
o trichrome stain: shows collagen tissues in liver
Obstructive Liver Disease
obstruction to bile flow: cholestasis

cholesterol stone in the common bile duct: liver is deep green
o block bile, which contains conjugated bilirubin that backs up into liver
o conjugated bilirubin refluxes into sinusoids lots of bilirubin in the urine because its
water soluble
o stool: light color
o no urobilinogen in urine; urine is very yellow due to water-soluble bilirubin
elevated alkaline phosphatase and GGT
hypercholesterolemia due to reflux bile salt
bile salt can also be deposited in the skin itching (big time!)
two other causes of cholestasis:
o bile duct radical, completely surrounded by fibrous tissues; pt also has bloody diarrhea,
RLQ crampy pain, jaundice
inflammatory bowel disease: ulcerative colitis
common bile is surrounded and obstructed by fibrous tissue producing
jaundice
this is primary sclerosing cholangitis; most common cause is ulcerative colitis
cancer involves bile duct: cholangiocarcinoma
o most common cause in the US: ulcerative colitis; in 3rd world country: clonorchis sinesis
(Chinese liver fluke)
primary biliary cirrhosis:
o scenario: 50 yo woman complaining of generalized itching; liver slightly enlarged;
bilirubin normal, but alkaline phosphatase and GGT hugely increased, transaminase
slightly elevated
o Autoimmune granulomatous destruction of the bile duct in the portal triad
o But pt doesnt have jaundice
Triad is not completely knocked out; the remaining of the triad can handle
bilirubin load and thus no jaundice
But continuous destruction can eventually lead to inability to handle bilirubin
jaundice (LATE finding!)
o Antibody ordered: anti-mitochondria ab
Anti-microsomal ab is ordered in Hashimotos
Drug Effects
Birth control pills and anabolic steroids have the same effects in liver!
Both produce intrahepatic cholestasis
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Weight lifter: taking steroids and develops jaundice
Viral serology negative; transaminase slightly elevated, sky high alka
phosphatase and GGT
o Birth control pills:
One of the most common causes of jaundice during pregnancy: intrahepatic
cholestasis due to estrogen; jaundice disappears after delivery
If one develops jaundice while on the pill but not when off the pill: its guaranteed
to develop jaundice when pregnant
If a woman was taking birth control pills, went off, became pregnant and had
peritoneal hemorrhage think ruptured ectopic pregnancy, ruptured hepatic
adenoma and ruptured splenic artery aneurysm
Both produce benign liver tumor: hepatic adenoma
o Benign, but likes to rupture intraperitoneal hemorrhage can cause death
o Board question: weight lifter (means taking anabolic steroids) suddenly becomes
hypotensive and collapses. Belly is stomached; blood in peritoneal tap. Everything else
is normal most likely due to rupture of hepatic adenoma due to steroid use
o
Hemochromatosis
Scenario: adult whos diffusely hyperpigmented; diabetic type 1

o Bronze diabetes: bronze-look
o Due to Fe overload
Hemosiderosis: acquired Fe overload
o Cause: alcohol (lots of Fe in alcohol)
o Older people dont need Fe supplement hemosiderosis
o Contraindicated to take Fe supplement in older people
Hemochromatosis:
o Genetic disease, autosomal recessive
One of the most common autosomal recessive diseases
o Instead of reabsorbing 100% Fe from food (normally: 10-15%)
o Target organ: liver
When Fe goes into cells produces hydroxyl free radicals
o Damaging liver cells fibrosis and cirrhosis
All Fe overload disease has cirrhosis
o One of the highest incidence for hepatocellular carcinoma
Fe can also go into pancreas:
o When stained with Prussian blue: the entire pancreas is full of Fe
o exocrine problem malabsorption
o endocrine problem (by destructing the islet cells)type 1 DM (very brittle)
Fe can deposit in the skin bronze look
o Combo of Fe deposition and Fe stimulating melanocytes to produce more melanin
Other organs:
o joint osteoarthritis
o pituitary gland hypopituitarism
o heart restrictive cardiomyopathy
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screening test: serum ferritin

o serum Fe: high
o TIBC: decreased
o % sat: increased
Tx: phlebotomy purposely make pt Fe deficient
o Usually dont use chelation therapy
Wilsons Disease
Findings:
o eyes: Kayser-Fleischer ring
o lenticular degeneration: abnormal movement disorder, dementia
o cirrhosis
autosomal recessive
o defect in getting rid of Cu and bile
Cu accumulates in liver very toxic
o Over time, go from chronic hepatitis cirrhosis
Total Cu level:
o Fe Cu
o Bound Cu: Cu bound to ceruloplasmin
o 95% of normal total Cu level is related to Cu bound to ceruloplasmin; not free Cu
o When Cu is bound to ceruoplasmin: not active
In Wilsons disease: cant synthesize ceruloplasmin due to cirrhosis
o Free Cu increases
o Total Cu level decreases because ceruloplasmin is DECREASED
Tx: penicillamine Cu binder
Scenario: a guy with abnormal movements, with family hx of liver disease and eye abnormalities
o Lenticular nucleus is affected
Hepatobiliary-Pancreas 2
Cirrhosis
Always diffuse, never local

Regenerative nodules
o Liver tissue is stable: usually in the G0 phase
Needs to be stimulated to move into G1 phase to divide
o Liver tissue has regenerative property
But only hepatocytes are regenerated a pile of hepatocytes, with no sinusoids
in between, no triads, no central vein
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In cirrhosis: injury regenerate; but cant regenerate basement mb, central vein, portal
triad, sinusoids totally worthless
o Wall-to-wall hepatocytes; surrounded by fibrous tissues
Start micronodular and becomes macronodular
o Micronodular: <3mm; macronodular: >3mm
o Regardless of the size still have the same problem
Lots of hepatocytes but are not working:
o No sinusoids and no triad portal vein cant empty into it portal HTN
Complications:
o Pitting edema, ascites:
o Esophageal varices
o Cant metabolize estrogen hyperestrinism
Gynecomastia:
Cant tell from looking; need to palpate, esp in men
Males have boobs 3x in life: newborn (estrogen effect of mom), puberty,
old age when testosterone drops and estrogen becomes dominant
o Newborn girls have periods: estrogen stimulation from mom in
utero; drop off of estrogen at birth menstruation
13 yo boy has unilateral mass: leave it alone
Gynecomastia: most of the time unilateral
No women have exact same size of breasts: breast tissues respond
differently to estrogen, progesterone
Palmar erythema: related to estrogen
Spider angioma
Impotence in men
o Vitamin D deficiency:
Fibromatosis: increased fibrous tissues around tendon sheathpulls finger in
Dupuytrens contracture
Very commonly associated, but now always, with alcoholics
Complication of ascites:
o Spontaneous peritonitis in adults: E. Coli
In child with nephrotic syndrome and develops ascites, spontaneous peritonitis
strep pneumonia
Spontaneously occurs
o
Hepatocellular Carcinoma (HCC)
Background: nodularity
Almost always develop in the background of cirrhosis
o Very rare to develop without an underlying cirrhosis
Alcohol is most common cause of cirrhosis, but one of the least likely causes of HCC
o More common causes of HCC:
Pigment cirrhosis from hemochromatosis
Post-necrotic cirrhosis in hep B and C
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Ectopic hormones productions:

o EPO
o Insulin-like factors: hypoglycemia, secondary polycythemia
Tumor marker: Alpha Fetal Protein
Scenario: pt with underlying cirrhosis and ascites. The ascites suddenly enlarges and pt starts
losing weight
o If doing a peritoneal tap: bloody in ascite fluid
o Do AFP test!
If there are multiple things in the tissue: mets
o Most likely: lungs
If pt is non-smoker: colon cancer, mets to lungs
Bowel obstruction but pt doesnt have sx: r/o adhesion; next best choice is
indirect inguinal hernia
Gall Bladder Disease
Know pathogenesis of stone

o Too much cholesterol in bile, too little bile salt
Super saturated bile with cholesterol cholesterol stone
Bile salt deficiency: predispose to stone
o cirrhosis
o obstruction
o cholestyramine
o crohns disease
stones are not yellow not cholesterol stone
o scenario: 25 yo female, RUQ pain, fever, neutrophilic leukocytosis, point tenderness on
RUQ, U/S reveals stone. CBC shows mild normocytic anemia, corrected reticulocyte
count 8%. Family hx of splenectomy
this woman has hereditary spherocytosis
breaking down RBC conjugate bilirubin
supersaturate bile with bilirubin calcium bulirubinate stone black
boards love this question!
Screening test of choice for stones: ultrasound
o Screening test for anything in the pancreas: CT
Bowels overly pancreas and ultrasound is not accurate
First step in management for pancreas: CT!
o Gall bladder: u/s
o Can also show if there is a stone in the common bile duct
Cystic fibrosis:
o mucous in the ducts in the pancreas; growth alternation atrophy
o blocking the lumen of exocrine duct pressure goes back to the glands pressure
atrophies the glands mal-absorption
o cystic fibrosis kids can also develop diabetes (type 1)
fibrosis of islet cells
o chromosome 7, 3 nucleotides coding for phenylalanine deletion
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o
o
o
o
o
deficiency of phe in cystic fibrosis transmembrane regulatory (CFTR) proteins

most proteins have post-translational modification in the Golgi after being made in RER
problem: when CFTR proteins get into the Golgi, modification is messed up degrades
in the cell no CFTR proteins
in the sweat glands: reabsorb Na and Cl out of sweat glands morally
deficient: losing salt sweat test
can become salt depleted when becoming overheated
3yo kid, failure to thrive, diarrhea, tastes salty when mom kiss baby
Thick secretion in lungs, pancreas and bile duct:
Lungs: need to have salt in the secretion in the lumen of the respiratory tract to
keep it viscous
Missing CFTR Na is reabsorbed out of the secretion, and Cl cant be
pumped into the lumen;
Pancreas: Na is sucked out and Cl cant be pumped in
Most common cause of death: infection due to p. aeruginosa
Fertility: % chance for male with CFTR with a child 0-5%
Most CFTR males are infertile
Females can be pregnant, but only 30%
Cervical mucus is also very thick sperms cant penetrate
Pancreas
Acute pancreatitis:
o Most common cause: alcohol
2nd most common causes: stone that gets caught in the small accessaroy ducts
o Amylase is elevated
o epigastric pain radiating to the back: pancreas is a retroperitoneal organ
o pancreatic pseudocyst:
presentation: feel a mass in the abd in a pt with hx of pancreatitis
do CT
o a lot of fluid developing around inflammed pancreas accumulates around and forms a
false capsule
o potential for rupture
o not good to have amylase in the peritoneal cavity
o peristalsis of duodenum right next to pancreatitis: stops peristalsis just in duodenum!
Air in the area that doesnt peristalsis sentinel sign
Localized ileus (ileus lack of peristalsis)
No peristalsis (due to inflammation) lots of air accumulation distention
o A segment of bowel that is distended in the RLQ could be appendicitis, producing
sentinel sign
chronic pancreatitis:
o RUQ: lots of dystrophic calcification (chronic because so much calcification)
o Most likely in alcoholics
o Steatorrhea: cause of mal-absorption
o No bile salt deficiency
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o Hemorrhagic diathesis: from vit K deficiency related to mal-absorption

Carcinoma of the head of pancreas
o Most common location
o Most likely: smoker; 2nd most common cause: chronic pancreatitis
o Painless jaundice, light color stool and palpable gall bladder (Courvoisiers sign)
Jaundice due to conjugatd bilirubin
o C sign: permanently indenting the duodenum by tumor on X-ray
Renal 1
Cast
Mold of whatever that is going on in the nephron/tubules

o Tamm-horse protein whatever that is present in the tubule at the time
o Make a mold that is passed the urine and can see under microscope
No need to do renal biopsy!
o Glomerulonephritis: inflammation of glomerulus would damage capillaries
Hematuria
RBCs in the nephron are trapped in the cast: RBC cast
o Renal tubular necrosis: tubules are sloughing off via coagulation necrosis
Renal tubular cast
o Acute pyelonephritis: neutrophils infiltrating the interstitium of the tubules cast of
neutrophils that indicate presence of infection in kidney
White blood cell cast
o Spilling lipid into urine in nephrotic syndrome:
Fatty cast, can also polarize in urine
The very first marker for renal failure: inability for kidney to concentrate urine
Taking urine from pt after sleeping over night and do a specific gravity test:
o Specific gravity: can tell how dilate/concentrated the urine is
>1.023: pt is concentrating the urine kidneys are absolutely normal
Specific gravity: 1.012 hypotonic, pt cant concentrate urine renal failure
o Urine should be concentrated if the pt is sleeping over night
Most benign cast: hyaline cast
o A cast of protein
o Most of the time it doesnt mean anything
o Can see after working out
o But other types of casts have pathological meanings
Crystals
Uric acid:
o Looks like a star
o pH of urine has to be acidic to form uric acid stone
o in a gout pt, want to stop formation of crystals ALKALINIZE urine
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use carbonic anhydrase inhibitor

blocking bicarbonate reabsorption alkalinize urine
Ca oxalate crystal:
o Looks like X in the box in tic-tac-toe
o Presentation: pt that is a street person, comes in a stupor state with increased metabolic
acidosis anion gap drank ethylene glycol
o Most common stone that is passed
Congenital Disorders and Cystic Disease of Kidney
Horseshoe kidney:
o Limiting the movement of this kidney: inferior mesenteric artery
o The artery goes over, and traps horseshoe kidney behind it
o Increased incidence with Turners syndrome
Cystic diseases:
o Infantile polycystic kidney disease:
Autosomal recessive: present at birth
Both kidneys in the baby are cystic: cant urinate oligohydramnios
Amniotic sac with amniotic fluid around it; would have mal-formation of the face
due to pressure Potters Facies
Potters facies: sign of oligohydramnio in a child with infantile polycystic kidney
disease
The lungs are also hypoplastic: kid cant breathe
The cysts can also be present in liver and pancreas
Incompatible with life
o Adult polycystic kidney disease:
Autosomal dominant: not present at birth; late onset
Incomplete penetrance: have the genetic abnormality, but phenotypically normal
Bad news: can still transmit the ds to children
Marfans: abnormality on chromosome 15 and normal phenotypically
normal
Familial polyposis: 100% penetrance
Have cysts develop by 10-12yo
Always have HTN: predispose 2 kinds of bleeds in the brain
Charcot-Bouchard aneurysms: rupture
blood in subarachnoid space and covers the brain rupture of berry
aneurysm
blood in subarachnoid space: worst HA ever
another presentation: hx of HTN, abnormality on u/s in renal pelvis area, click
murmur. The kidney ds in this pt polycystic kidney disease
click murmur: mitral valve prolapsed
high association between mitral valve and polycystic disease
also high incidence of diverticulosis and polycystic disease
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pt with HTN, abnormality on u/s on renal area, lost 600ml of blood

suddenly from butt hematochezia
most common cause of hematochezia: diverticulosis
Glomerulonephritis
ending in -itis: type 3 hypersensitivity reaction

terminology:
o diffuse: every single glomerulus has something wrong with it on biopsy
o focal: not every glomeruli are involved
o segmental: only parts of one glomerulus; not all of it
o proliferative: lots of cells
i.e >100 nuclei in one glomerulus
o if only seeing mb but not too many cells: membranous
o if there is increased in both mb and cells: membrano-proliferative
anatomy:
o glomerular capillaries: endothelial cells present
o basement mb: underneath endothelial cells
o visceral epithelial cells: outside of basement mb; have feet podocytes
o space between feet: slip pores
o blood endothelial cells basement mb visceral epithelial cells (parietal epithelial
cells lining Bowmans capsule)
o visceral epithelial cells (podocytes) make basement mb
o keeping albumin out of urine: strong negative charge of glomerular basement mb
strong negative charge of basement mb due to: heparan sulfate strongly
negative
o if immunologically damage the visceral epithelial cells would also damage basement
mb spill lots of proteins in urine can dev nephrotic syndrome (>3.5g protein/24 hrs)
to evaluate glomerulonephritis:
o H&E stain
o Silver stain
o Immunofluorescent stain (IF): can be linear or granular (lumpy bumpy)
Immune complexes are detected
In IF: add ab with fluorescent tag; if want to know if there is IgA in glomerulus,
add anti-IgA ab with fluorescent tag
Get an idea of what is in the glomerulus and what the pattern is (linear vs.
granular)
But doesnt tell us where the immune complexes are located
o EM: show where the immune complexes are located
Best to tell if podocytes are fused
Goodpastures:
o IgG anti-basement mb ab
o In the blood get into glomerular capillaries directly against basement mb
Would see ab lining up along the basement mb
o IF: shows outline the entire basement mb and its linear
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o Most common cause of linear pattern on IF

Immune complex:
o Antigen/antibody circulating in bloodstream
Ex: Lupus; antigen DNA; ab anti-DNA
Flow around the bloodstream and deposit in different places (in
glomerular capillary)
o Immune complex: larger than individual ag or ab
Bigger, different charges, and different solubility
Would not deposit in a neat fashion in the glomerulus
Depending on size or charge, or where the complex is located
o Sub-endothelial deposit: the complex too big to get thru the basement mb to be on the
podocyte side
Immune complex in lupus: cant get thru basement mb, stay on the endothelial
side
o Post-strep glomerulonephritis:
Immune complex: bacteria ag/ab very small
Can go thru basement mb and deposit on the EPITHELIAL sides
Sub-epithelial deposit
o Can tell where the immune complexes on EM because immune complexes are electondense increase density wherever they are
o Immune complexes wouldnt have linear pattern like seen in anti-basement mb ab
Ex: Lupus, post-streptococcal, IgA glomerulonephritis
o the only glomerulonephritis that can be truly dx based on IF IgA glomerulonephritis
o whenever seeing a granular, lumpy bumpy pattern immune complex disease, type 3
hypersensitivity!
o Anti-basement mb ab: type 2 hypersensitivity
2 types of glomerulonephritis: nephritic or nephrotic
o Cant have both at the same time; but one can develop into another one
o Nephritic:
Hematuria: RBC cast unique to nephritic glomerulonephritis
Mild to moderate proteinuria: but <3.5g/24 hours due to inflammatory process
If >3.5g/24 hr nephrotic syndrome
No pitting edema, no ascites because only mild proteinuria
Oliguria: glomerulus inflammed, capillaries swollen GFR decreases
HTN decreasing Na reabsorption and/or not filtering as much Na+
o Nephrotic syndrome:
Fatty cast
Proteinuria: >3.5g /24 hours
Pitting edema
o If starting on nephritic and suddenly develops pitting edema move into nephrotic,
would also have fatty cast
Nephritic Syndrome
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Pt had Scarlett fever 2 weeks ago. Present with hematuria, RBC cast, mild proteinuria, HTN.
Periorbital puffiness post-strep glomerulonephritis
o Always see periorbital puffiness when retaining Na+
o Immune complex: bacterial ag/ab
Located on the epithelial sides sub-epithelial deposit
o Tx: corticosteroids
35yo woman, positive serum ANA with rim pattern lupus
o Positive serum ANA with rim pattern: anti-dsDNA
o Lupus always involves the kidney: type 4 is most common
Diffuse proliferative glomerulonephritis
o EM: podocytes are located on epithelial side
Immune complex (DNA, anti-DNA) on basement mb
Right underneath endothelial cells sub-endothelial deposits
Fused podocytes are seen in nephrotic syndrome
Crescentic glomerulonephritis
o Glomerulus surrounded by proliferative parietal cells crest-like
o Worst glomerulonephritis: can get renal failure in 3 months and die unless on dialysis
o Good Pastures syndrome:
Classically produces cresentic glomerulonephritis
Nephrotic Syndromes
Fat cast: maltese crosses

o Cholesterol in urine: pathognomonic for nephrotic syndrome
Definition of nephrotic syndrome:
o >3.5g protein/24 hours
o Fatty cast
o Pitting edema, ascites
8 yo boy, upper respiratory infection 1 week ago; diffuse pitting edema all over the body
(anarsarca), ascite; normotensive. Renal biopsy normal. IF normal. EM shows fused podocytes
o Minimal change disease (lipoid nephrosis)
o Low albumin: liver then makes more cholesterol
All pt with nephrotic syndrome have hypercholesterolemia
Since there is glomerular disease, some cholesterol gets into the urine fatty
cast
o Loss of negative charge in the glomerular basement mb
Albumin can now get thru basement mb
selective proteinuria: the only protein in the urine is albumin
o Tx: corticosteroids for a month, can recur after a few months, but completely goes away
after a year
o Most common nephrotic disease in children
Always see fused podocytes in nephrotic syndrome
AIDS pt with pitting edema; >3.5g protein/24 hours, HTN, fatty cast in urine focal segment
glomerulosclerosis
o Most common cause of nephrotic syndrome/glomerulus lesion in AIDS pt and IVDU
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Next worse glomerular disease

o Only parts of the glomerulus are abnormal; other parts are normal
o IF and EM do not show deposits
Diffuse membranous glomerulonephritis: pitting edema, fatty cast, proteinuria. Biopsy shows
prominent basement mb
o Most common cause of nephrotic syndrome in adults
o Sub-epithelial deposit
o Silver stain: epi-membranous spikes due to immune complex
o Causes: drugs, infections, cancer, idiopathic
Non-steroidal can produce nephrotic syndrome
Hep B
Captopril: used to tx heart failure and diabetic nephropathy also produce
nephrotic syndrome
Syphilis
P. malaria
CEA/anti-CEA ab; colon cancer
o Develop into renal failure; death unless have renal transplant
Type 1 and type 2 membranoproliferative glomerulonephritis (MPGN)
o Ending in itis: its immune complex disease
o Type 1: related to Hep C
Membranous: Hep B; membranoproliferative: Hep C
Also associated with cyroglobulinemia, vasculitispolyarteritis nodosa
Sub-endothelial deposit, producing nephrotic syndrome
o Type 2: less common
Auto antibody against C3 C3 nephritic factor
Causing C3 convertase to become overactive constantly breaking complement
down
Lowest complement level!
The entire basement mb is full of immune complexes dense deposit disease
EM: shows tram track
mesangial cells (structural components) extending processes between
basement mb and endothelial cells
diabetic glomerulosclerosis:
o hyaline arteriolosclerosis: small vessel disease in HTN and diabetes
the very first vessel that is hyalinized efferent arteriole
o lumen is narrowed in the efferent arteriole as its hyalinized GFR increased
Cr clearance: increased
This produces hyperfiltration damage
o Non-enzymatic glycosylation
Glycosylating glomerular basement mb with excess blood glucose
Basement mb then becomes permeable to protein
o Hyperfiltration and non-enzymatic glycosylation:
Microalbuminuria: cant be detected by normal dipstick
If a diabetic pt has microalbuminuria: give ACE inhibitor to stop progression
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o
o
ACE inhibitor: efferent arteriole caliber is controlled by ATII

Afferent arteriole caliber is controlled by PGE2
ATII: vasoconstrictor
With ACE inhibitor AT II decreases decrease GFR
Can slow progression of renal disease/diabetic glomerular sclerosis
Can also treat for HTN commonly seen in diabetes
Pt still needs to have tight glucose control to prevent non-enzymatic glycosylation to
prevent chronic renal disease
Type 4 collagen in the mesangium:
pink balls/nodules
Kimmelstiel-Wilson disease
Nodular glomerular sclerosis
Amyloid
One of the common places to deposit: kidney

When stained by Congo red and polarize it apple green birefringence
o The same color as a green apple!
Associated with nephrotic syndrome
IgA Glomerulonephritis
Doesnt fit with nephritic or nephrotic syndrome

Probably a variant as Henoch-Schonlein purpura
Immune complex disease: IgA/IgA ab
Presentation: palpable purpura in butt and legs; polyarthritis, some GI bleed, hematuria, RBC
cast
o Looks more nephritic
IF: all immune complexes in mesangium
In children: episodic gross hematuria; goes away and might come by a few years later
In adults: episodic microscopic hematuria and then goes away; may come back after a month
later, or after infection
o recurrent
some hematuria, RBC cast, no HTN, slightly proteinuria
type 3 disease
most common of all glomerulonephritis; not completely benign
Renal 2
BUN/Cr Ratio
can separate out pre-renal azotemia vs. renal failure

BUN: blood urea nitrogen
o Urea can be filtered and reabsorbed in the proximal tubule not a perfect clearance
substance
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Cr: end product of creatin metabolism

o Only filtered in the kidney; either reabsorbed or secreted not a good clearance
substance, but commonly used
o Can be secreted in the gut, and can be excreted
Inulin: much better for clearance
Normal BUN level: about 10; normal Cr level: 1mg/dL
o Normal ratio: 10:1
Pre-renal azotemia:
o Azotemia: increase in BUN
o Before renal: due to decreased cardiac output
Causes: congestive heart failure, MI, cardiomyopathy, hypovolemia
GFR is decreased due to decreased renal blood flow
o Decreased GFR: gives proximal tubule more time to reabsorb increased proximal
reabsorption of urea
o Cr: not reabsorbed, cant be cleared as fast when GFR drops
Increase in Scr but increase is not as much as that of urea
o >15: 1 BUN to Cr ratio pre-renal azotemia
o Scenario: pt with heart failure, BUN 80, Cr 2 ratio is 40:1 pre-renal azotemia, pt
does not have ATN
Acute renal failure: renal tubular cast, oliguria
o Would affect urea and Cr equally because something is wrong with the kidney
o Both urea and Cr increase proportionally
The ratio remains the same: 10:1
o Scenario: BUN 80, Cr 8 10:1
Acute Renal Failure
Most common cause: ischemic acute tubular necrosis

o Worry about most when pt cardiac output decreases and develops oliguria
o Decrease GFR due to decreased cardiac output oliguria
Increased BUN and Cr
o But if >15:1 pre-renal, but can develop into ischemic ATN
Most common cause of ischemic ATN: not treating pre-renal azotemia
Ischemic ATN:
o BUN: Cr ratio still around 10:1
Coagulation necrosis, slough off, block lumen, contribute to oliguria
o In urine, would see renal tubular cast
o Renal tubular cast, oliguria, with BUN: Cr of 10:1 ATN
Ischemic cause of tubular necrosis:
o Killing the tubular cells and basement mb
Loss of structural integrity of tubular cells
o If basement mb is not there: if pt recovers from ATN, cant regenerate tubular cells
o More necrosis, more basement mb is destroyed worst prognosis, because can never
be able to regenerate and cant regain normal fxn
Two portions of nephron that are most susceptible to ischemic injury:
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o Straight portion of proximal tubule

o Thick ascending limb, medullary segment: where Na/K/2Cl transporter is
o These two portions are the ones undergoing coagulation necrosis and sloughing off
Drugs that are nephrotoxic:
o Gentamycin/aminoglycosides
1st cause: aminoglycosides
2nd cause: IV pyelogram dye
o First hit the proximal tubule when drugs are filtered
o Nephrotoxic tubular necrosis related to drugs only involves proximal tubule
o Basement mb remains intact better prognosis
Only affecting proximal tubules
Older people have decreased GFR and decreased Cr clearance
o If given a drug in the same amount as given in a young person older pt would get
nephrotoxicity unless the dose is lowered
o All old people, esp if getting nephrotoxic drugs, need to make sure pt get appropriate
dose and dosing interval
Urinary Tract Infections
Women: more commonly get both pyelonephritis and lower urinary infection due to shorter
urethra
Acute pyelonephritis: systemic infection
o Inflection of kidney proper
o Normally, urine goes into bladder, there is a vesicoureteral junction so there is no reflux
of urine from bladder to ureter
o When there is bladder infection and the junction is incompetent (vesicoureteral reflux)
urine reflux up to ureter ascending infection that can all the way up to kidney
Mechanism of all urinary tract infections (urethritis, cystitis, pyelonephritis, ureteritis)
ascending infection
o Ascending from the beginning of ureter
o Every woman has the same E.Coli content in stool, vagina, introitus of urethra
o With trauma or certain serotype of E. Coli, it can ascend up from urethra into
bladder incompetent vesicoureteral junction ureter kidney
o White spots: abscesses
Acute cystitis:
o Painful urination, increase frequency, suprapubic pain
o No: fever, flank pain, WBC cast with neutrophils
This is because infection develops in the renal tubule
fever, flank pain, WBC cast with neutrophils acute pyelonephritis
Ascending infection: incompetent vesicoureteral junction
o Usually shows up right at birth for girls
o Would be a problem for the rest of their lives
o Can do sx to make the junction more competent; but doesnt always work
If there is constant or recurrent attacks of pyelonephritis becomes chronic
o Chronic pyelonephritis: related to HTN and eventual kidney failure
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Signs: scarred kidney, renal calyces change from normal concave shape to blunting,
The blunting occurs right underneath where scar is
Can see blunting under IV pyelogram
o Scenario: blunting of calyces under IV pyelogram chronic pyelonephritis
Drugs producing nephritis involving interstitial tubules
o Can be acute or chronic
o Signs: fever, rash
if a pt is put on PCN and develops fever and rash, oliguria, eosinophiliuria
eosinophiliuria: pathognomonic
o this is acute drug-induced interstitial nephritis
o common cause of chronic renal failure
o drugs: PCN, lasix, methicillin (prototype)
o tx: stop the drug, and never give the same drug again a combo of type 1 and type 4
hypersensitivity
analgesic nephropathy:
o renal medulla: has discoloration, pale infarction
renal papilla disappeared
o ring sign: empty under IV pyelogram
o combo of acetaminophen and ASA over chronic use
o acetaminophen produces free radicals and does damage to medulla tubule cells with
low-circulating volume
ASA: block PGE2, which normally dilates
o Now ATII controls the vasotone of renal tubules constrict efferent arterioles
o Peritubular capillaries are also derived from efferent arterioles
o With vasoconstriction of efferent tubules affect peritubular capillaries around medulla
and collecting tubules ischemia renal papillary necrosis, gets sloughed off
o Causes: ASA and acetaminophen; diabetic nephropathy (due to ischemia), acute
pyelonephritis (due to abcess formation), sickle cell/sickle cell trait
o
Chronic Renal Failure
BUN: Cr ratio = 10:1 for more than 3 months

If both kidneys fail:
o Cant excrete: metabolites build up i.e. salt
o Cant make EPO normocytic anemia, corrected reticulocyte count < 2%
o Cant eliminate organic acid metabolic acidosis, increased gap
o Osteoporosis: because bone buffering excess H+
o 1-alpha-hydroxylase deficiency due to damage to proximal tubule vit D deficiency
hypoCa, hypoP osteomalacia
o Increased PTH: increased resorption of bones
Secondary hyperparathyroidism
o BUN and Cr both increase; i.e. 80: 8
o No normal renal function
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Essential HTN for 10 years and not well controlled:

o Kidney looks like cobble-stone, shrunken: nephrosclerosis
This is due to hyaline arteriolosclerosis reduced blood flow, tubular atrophy,
glomeruli sloughing off eventual renal failure
Malignant HTN:
o It pt wakes up with HA with blurred vision; bp 240/140; retina has papilloedema with
flame hemorrhage, BUN 80, Cr 8, hard and soft exudate
Grade 4 hypertensive retinopathy
o Flea-bitten kidney: petechiae that are visible on kidney surface
Vessel changes (hyperplastic arteriolsclerosis)
Blood vessels rupture petechiae on cortex
o Tx: IV nitroprusside
o CNS edema, retina edema need to lower BP or pt would have a stroke and die
Renal Disorders
Renal infarct:
o Pale and depressed kidney in a pt with irregularly irregular pulse
Pale infarct
Not hemorrhagic because its a solid organ
o Irregularly irregular atrial fib most dangerous for embolus
o Multiple emboli multiple pale infarct
Compression atrophy:
o Atrophy cortex and medulla, dilatation of renal pelvis hydronephrosis
o Increased pressure pressing on the medulla and cortex ischemia atrophy
Very thin cortex and medulla
Very similar to CF where ducts are filled with mucous fluid pressure on the
glands atrophy
o Cause: most common stone
o Staghorn calculus: urine pH alkaline, urine smells like ammonia
Urease-producing organism: proteus
Urease breaks urea into ammonia
Staghorn: ammonium, Mg, phosphate struvite stone
Develops in pt with urease-producing infections
These stones cant be passed
Tx: extract/sx removal
Mass in Kidney:
o in adults: renal adenocarcinoma
o in children: Wilms tumor
o when seeing a mass in kidney: its cancer
o derived from proximal tubule
o most common cause: smoking
o makes lots of ectopic hormones (PTH-like peptides hypercalcemia, EPO)
o tend to invade renal VEIN
Wilms Tumor:
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o
o
o
o
o
o
o
Presentation: flank mass, HTN in a young child

HTN is due to tumor making renin
4th common cancer in kids
Usually unilateral and produces flank mass
This tumor duplicates embryogenesis of kidney everything is primitive
See rhabdomyoblasts with striation
Likes to mets to lungs
Autosomal dominant: involve chromosomal 11
PE: aniridia (absent iris), hemi-hypertrophy of extremities
Urine Abnormalities
Associated with lower urinary tract infection

o Neutrophils, RBCs, bacteria (most likely E. Coli)
All three can be picked up by dipstick
o Hematuria: very frequent
In some cases, can be hemorrhagic hemorrhagic cystitis
Can be due to e. coli or adenovirus
o Leukocyte esterase on dipstick:
Measuring the enzyme in the leukocytes
If positive indicate presence of neutrophis
o Most urinary pathogens are nitrate reducers: reduce nitrate nitrite
E.coli: nitrate reducer dipstick positive for nitrite
Dysuria, increased frequency, suprapubic pain, urine sed shows RBC, wbc, bacterial; dipstick
positive for hematuria, leukocyte esterase, nitrite positive UTI
o If pt has fever, flank pain, WBC cast upper UTI
o If none of the above lower UTI
Increased frequency, neutrophils and few RBCs in urine, but no bacteria in sexually active pt
o Culture negative for bacteria despite dysuria
o Positive for leukocyte esterase, negative nitrite
o Chlamydia!
o Normal urine culture doesnt pick up chlamydia
Most common STI
o Sterile pyuria: because there are no bacteria but neutrophils are present
Another cause of sterile pyuria: miliary TB
Transitional cell carcinoma:
o Papillary lesion in the bladder
o Most common cause: smoking, analine dye, cyclophosphamide
Another side effect of cyclophosphamide: hemorrhagic cystitis (prevent with
MESNA)
o Most common bladder cancer
Penis
Embryology:
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o Hypospadias: failure closure of urethral fold

o Epispadias: defect of genital tubercle
Peyronies disease:
o Painful contracture of penis
priapism:
o permanent and painful erection
o often seen in sickle disease, because RBCs are trapped in the vascular channel
most common cancer: squamous
o most common reason: lack of circumcision
o this is because uncircumcised person with bad hygiene poor hygiene of uncircumcised
male
Testicles
cryptorchidism: complete or incomplete descent of testis into scrotal sac

o two phase of testicle descent:
trans-abdomen: due to mullerian inhibitory factor
inguinoscrotal: require androgen
o need to have testicles descent by 2yo or increase risk of seminoma (germ cell tumor)
but even if get testicles down before 2yo still at risk
whether the testicles are in or out, and even for the normal one, still are at risk for
seminoma
o turners syndrome: infertile (menopause before menarche)
no follicles after 2yo streak gonad
streak gonad also predispose to germ cell tumor dysgerminoma
usually remove both ovaries sx to prevent cancer
epididymitis:
o younger than 35: nisseria, chlamydia
o older than 35: E. coli, pseudomona
people older than 35 dont get STI
varicocele: big on boards!
o Located on left side: spermatic vein on left is connected to left renal vein but right
spermatic vein is connected to inferior vena cava
Abnormality and pressure greater on left
Varicocele on left increase heat most common cause of male infertility
o If blocking left renal vein develop varicocele
Testicular torsion:
o Spermatic cord twisting
o Very painful
o With torsion, spermatic cord shorten testicular moves up slightly
o Loss of cremaster reflex
Normally: scratch inner thigh and scrotum contracts
Hydrocele
o Due to persistence of the tunica vaginalis
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When you have a big scrotum dont know if its big because theres fluid in it or
because theres a testicle in it transilluminate to distinguish
If it does transilluminate then its a hydrocele
If it doesnt Cancer! (painless enlargement of testicle dont even do a
biopsy and just remove the testicle and then look at it)
Testicular Tumors
Seminoma
o Most common and has the best prognosis
o Big cells and lymphocytic infiltrate
o Looks exactly like the woman counterpart in ovary dysgerminoma
o Melts with radiation
o Usually no tumor markers, may have slight beta HCG
o Mets to para-aortic lymph node: it comes from abd and will go there
Most common testicular tumor in kid: yolk sac tumor
o Tumor marker: AFP
absolute worst testicular cancer: choriocarcinoma
o 25yo man with unilateral dyspnea and gynecomastia. Chest x-ray shows multiple
nodules and masses in lungs
o Primary choriocarcinoma
o Beta-HcG acts like LH, stimulates progesterone in male stimulate ductal and breast
tissue
60yo male with testicular cancer malignant lymphoma
o Not primary, but mets
o Testes are big for mets for leukemia or lymphoma
o Most common in old male: met malignant lymphoma
Prostate
Hyperplasia:
o Occurs in peri-urethral portion of prostate gland
o Signs: dribbling, urinary retention
Cancer: periphery of prostate gland, within the realm of finger
o Hard when pressed down on it
o Dihydrotestoerone-dependent
o 5-alpha reductase inhibitor: decrease dihydrotestoerone, increase hair on head
o Most common cancer in men
o Mets to bone osteoblastic mets
75 yo man with urinary retention, bladder is up to umbilicus, dribbling most likely cause is
prostate hyperplasia
o Not prostate cancer! It would have to invade all the way thru prostate gland, around
urethra and around bladder neck
o Prostate hyperplasia is already around urethra
Hormone that is responsible for prostate: dihydrotestosterone
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o
o
Fuse labia together scrotum

Extend clitoris penis
Gyn
Hirsutism and Virilization
Virilization: hirsutism and male secondary sex characteristics

o Secondary sex characteristics: deep voice, acne, increased muscle mass
o Clitormegaly: clitoris entends
Testosterone converts clitoris into penis in utero
This is pathognomonic in virilization
Free testosterone, dihydrotestosterone: predominantly synthesized in ovary in women
o Small amount is synthesized in adrenal gland
DHEA sulfate: 95% made in adrenal
o Its an androgen
Only two tests are needed in someone with hirsutisim:
o Testosterone level, including free testosterone from fractionation
Total can be normal, but free testosterone can be elevated
If only testosterone is elevated coming from ovaries
Most commonly its the ovarian origin
One common cause: polycystic ovarian syndrome
o DHEA sulfate:
If DHEA sulfate is elevated adrenal origin
Hydroxylase deficiency, adrenal genital syndrome, cushings
Polycystic ovarian syndrome:
o Causes of hirsutism: PCOS, stromal hyperplasia of ovaries, tumors of ovaries, idiopathic
Stroma of ovaries can make testosterone
o Hypothalamic-pituitary abnormality: FSH is suppressed, LH is increased
LH: responsible for hormone development around theca interna
Theca internal: during proliferative phase of the cycle, 17-ketosteroids are
predominantly synthesized (DHEA sulfate and androstenedione)
Androstenedione is then converted into testosterone
Testosterone crosses mb of developing follicles into granulosa cells where there
is aromatase
Aromatase converts testosterone into estradiol
LH responsible for synthesis for 17-ketosteroids and testosterone in ovaries
o In PCOS: increased level of 17-ketosteroids, testosterone hirsutism
o A good % of women with PCOS: obesity
Excess adipose: excess aromatase
Androstenedione is converted by aromatase into esterone (weak estrogen)
Testosterone is aromatized into estradiol (strong estrogen)
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o
o
o
o
Woman with signs of excess androgen (hirsutism, acne), usually no signs of virilization,
endometrial metaplasia due to excess estrogen and increased risk for endometrial
cancer
Increased androgen and increased estrogen
Increased estrogen: continued negative feedback on FSH and positive feedback
on LH
The cycle repeats itself
Break the cycle with birth control pills: progestin blocks LH
Cysts in ovaries:
Cysts develop due to FSH suppression follicle degeneration
Increased aromatase activity
Since FSH is suppressed: leave behind cystic space where follicles used to be
Related to chronic FSH suppression
Can feel cysts either on pelvic exam or seen on u/s
Very commonly asked on boards
Menstrual Dysfunction
Dysmenorrhea:
o Painful menses
o Primary: too much PGF
PGF increase contraction uterine muscles
o Secondary: endometriosis
dysfunctional uterine bleeding:
o Not bleeding abnormality related to anatomical cause; not bleeding from cancer or
endometrial polyp
o It is hormone imbalance causing bleeding abnormality
o 3 causes:
Anovulatory cycle: most common cause of abnormal bleeding in young adult up
to 20yo
Can ovulate, but problems with bleeding: inadequate luteal phase
irregular shedding of endometrial
o anovulatory phase:
persistent estrogen stimulation on mucosa, but not enough progesterone
stimulation
slight hyperplasia, build up mucosa, stroma cant hold all the mucosa and slough
off excess bleeding
amenorrhea:
o primary: problem with hypothalamus (GnRH) or pituitary (FSH, LH)
o Secondary: problem with ovaries (not making enough estrogen)
o Is it an organ/anatomical problem: less common than 2ndary amenorrhea
no vagina (Rokitansky-Kuster-Hauser syndrome)
imperforated hymen
cervical stenosis
DES exposure
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Asherman syndrome: repeated D and C
Scrape down to mucosa muscle, scar off everything: infertile and cant
menstruate again
o Can distinguish the cause by FSH and LH level:
Primary hypothalamus-pituitary problem: FSH and LH low
Primary ovary problem: high FSH and LH
Organ problem: normal FSH and LH
o First step in workup: a pregnancy test in anyone with amenorrhea
Turners syndrome:
o Very common cause of amenorrhea
o XO: no barr body
o Defect in lymphatics:
Can make dx at birth swelling of hands and feet at birth in a baby girl:
lymphadema
Webbed neck: dilated lymphatics in the neck area; fill up lymphatic fluid and
stretch the skin webbing of the skin
o Underdeveloped knuckle: knuckle-knuckle-dimple-knuckle on fist
knuckle-knuckle-dimple-dimple: pseudohyperparathyroid disease
o preductal coarctation
o NO mental retardation
o Some cases are mosaics: XO XX can be infertile
There are cases of XO XY
o Menopause before menarche by 2yo; all follicles are gone streak gonad
Susceptible to dysgerminoma
o
Uterine Disorders
Adenomyosis:
o Glands and stroma within myometrium
o Very common cause of dysmenorrhea, menorrhagia, hysterectomy
Uterus is very enlarged
o Does not predispose to cancer
Endometriosis: functioning glands and stroma outside of confines of uterus
o Most common location: ovary
o Produce bleeding in ovary: chocolate cysts
o Endometrioma: endometriosis of ovaries
o Can also be located in the pouch of douglas
painful defecation during period but not otherwise
endometrial implant collected in the pouch
Collecting seeding in ovarian cancer, collect pus in PID, unclotted blood
o reverse menses: endometrial tissues when being sloughed off, might reverse back up
the fallopian tube and implant cells at different places
umbilicus, inguinal hernia sac
o surface epithelium in the peritoneum metaplasia coelomic metaplasia
metaplastically making endometrial tissues
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o can also have lymphatic hematogenous spread

Endometrial hyperplasia:
o Unopposed estrogen; no progesterone effect
o High risk for endometrial cancer
o Unopposed estrogen:
PCOS
Early menarche: earlier estrogen exposure, worse
Late menopause
Obesity: more aromatase, estrogen factory (breast cancer, ovarian cancer,
endometrial cancer)
Type 2 DM: not a risk factor itself, but because of obesity associated with DM II
o Age brackets:
45yo: cervical
55yo/postmenopausal: endometrial
Any women 1 year after menopause with bleeding: endometrial cancer
until proven otherwise
First step in management: endometrial biopsy
65yo: ovarian
Leiomyoma
o Most common benign tumor in women
o NOT a precursor for leiomyosarcoma
Leiomyosarcoma:
o Most common sarcoma in the uterus
o All sarcomas are big bulky tumors
Ectopic pregnancy:
o Scenario: young lady with sudden onset of severe lower abd pain
o Need to do pregnancy test (-HCG) to rule out pregnancy
Ovarian Disorders
Tumors in the ovaries:

o Surface-derived: derived from the lining of ovaries
o Germ cell type: dysgerminoma, yolk sac tumor, teratoma
o Sex-cord stromal tumors: uncommon
Granulosa cell tumors: make estrogen
Hyperestrogenism bleeding, endometrial cancer
Sertoli-leydig cell tumor: making androgen
Associated with virilization and hirsutism
Follicular cyst:
o Most common cause of mass in ovary
o Not neoplasm; follicle that has ruptured, reached a certain size, palpable
o Common cause of sudden onset of pain in young women
Can rupture, spill fluid and produce peritonitis even if the fluid is sterile
o When pain occurs on the right side:
Differential dx: appendicitis, ectopic pregnancy, inflammatory diseases
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Can use u/s or -HCG to distinguish between the causes

Ovarian mass:
o <35 yo: benign
o >35yo: greater chance to be malignant
Ovarian Tumors
Surface-derived ovarian tumors: most common sub-type

o Most common of surface-derived: serous tumors
Most common benign and malignant ovarian tumor
Most commonly bilateral
o Serous cystadenoma: benign
o Serous cystadenocarcinoma: malignant
Contain psammoma bodies (blueish, apoptosis of tumor cells and replace by
dystrophic calcification)
Papillary carcinoma of thyroid, meningioma also have psammoma bodies
o Scenario: 65 yo woman, bilateral enlargement of ovaries serious cystadenocarcinoma
o Any women over 55yo and can palpate ovaries on either side is cancer until proven
otherwise
After 55 menopause: ovaries should atrophy
Cystic teratoma:
o Most common germ cell tumors
o Mostly benign
o On histology: can see cartilage, skin, sebaceous gland
o Can differentiate into any tissues germ cell tumors
Fibroma: benign
o MEIG syndrome: ovarian fibroma, ascite and right sided pleural effusion
o Taking ovary out, the tumor disappears
Granulosa cell tumor of ovary:
o Low-grade malignant tumor
o Granulosa cells normally aromatize androgen into estrogen tumor is estrogen
producing
o Signet-ring cell: mets from some other sites
Mets from stomach
o There is no primary cancer of ovaries that produce signet-ring cells
Placental Anatomy
Chorionic villus:
o Outside layer: syncytiotrophoblast
Making -HCG and human placental lactogen (growth hormone of pregnancy)
o Clear cells below syncytiotrophoblasts: cytotrophoblast
Myxomatous stroma of chorionic villus:
o Vessels coalesce into umbilical vein with highest O2 content
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Sticking into a pool of blood: O2 diffuse thru mb get into plasma increase partial
pressure O2 delivered to fetus
Neoplasm of chorionic villus: can be benign or malignant
o Hydatidiform moles:
complete moles 46XX and both X chromosomes come from dad (androgenesis)
Partial mole: triploid 69 chromosome, can have a fetus present in it
Complete moles have higher chance of developing into choriocarcinoma
o 50% of choriocarcinoma is from pre-exisiting hydatidiform mole
o 25% from spontaneous abortion, and another 25% from pregnancy
Hydatidiform moles:
o Benign tumor of chorionic villus
Choriocarcinoma: malignancy of trophoblastic tissues
o No chorionic villi; only trophoblastic tissues
o Loves to mets to lungs
o Respond very well to chemo, even with mets
o
Breast Lesions
Nipple showing: lactiferous duct, major duct, terminal lobule where milk is made, and
surrounding stroma
o Need to know where common breast lesions are located
o Nipple: Pagets disease of the breast
o Lactiferous duct: intraductal papilloma
Most common cause of bloody discharge from nipple in women under 50
o Major duct: most breast cancers develop from here
Invasive ductal cancer, medullary carcinoma, mucinous carcinoma
o Terminal lobules: lobular carcinoma
Most common tumor; bilateral
Lobular carcinoma is to the breast as serous tumor to ovaries in terms of
bilaterality
Mammogram doesnt pick up lobular cancer
Most common cause of a mass in the breast in women under 50yo: fibrocystic change
Most common cause of a mass in the breast in women over 50yo: cancer
o Infiltrating ductal carcinoma
o Not picking up cancer early enough by mammogram (5mm), but picks up in intraductal
phase technique is insensitive; only pick up when invaded
Fibroadenoma:
o Scenario: woman 35yo, movable mass in breast, gets bigger with menses cycle
progresses
o Most common in women younger than 35yo
o Fibrocystic change:
Lumpy bumpy in breast, can be painful
o Hormone-sensitive: estrogen
o Neoplastic component: stroma
As it grows, it compresses the ducts down swift-like spaces
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Ductal hyperplasia:
o Estrogen-sensitive epithelial cells lining the ducts
o Similar to glands in the endometrium are also estrogen-sensitive
o Predispose to cancer
Sclerosing adenosis:
o Located in terminal lobules
o Benign, part of fibrocystic change
Breast cancer:
o Presentation: nipple is sucked in
o Tumor is hard: when breast cancer invades stroma elicit a fibroblastic/elastic tissue
response make it hard and palpable
o Scenario: painless, palpable mass in the breast of a women over 50yo cancer
If painful and under 50: rarely cancer
Painful: inflammatory lesions, fat necrosis, fibrocystic change
Magical word: painless cancer
o Outer quadrant: most common location because most breast tissues are located there
Second most common site: around areola
o Stellate-appearing, white-ish mass: absolutely classic for invasive cancer
o On mammogram: density, spicules coming out, fine calcification
Highly predictive of cancer
o First step in management of palpable mass in breast: fine-needle aspiration!
Can make a dx, can tell whether its solid or cystic
Cold nodule in thyroid: first step also fine-needle aspiration
u/s only shows whether solid or cystic; doesnt tell you what it is
intraductal cancer:
o net-like arrangement
o comedo-carcinoma: junk comes out when pressing on it, similar to caseous necrosis
o ERB-2 oncogene
o Invasive cancer: tumor cell invading stroma
o Indian filing: sign for invasive lobular cancer, as well as infiltrating ductal cancer
Pagets disease of the breast:
o Erythematous reaction around the nipple
o Scenario: older woman with rash on nipple
Need to feel the breast and do mammogram
o Cancer of the duct underneath, spread up to skin, produce rash-like finding
o Biopsy: looks exactly like breast cancer, except its in the nipple
o Boards love this!
Inflammatory carcinoma:
o Worst cancer
o Very red
o Dimple skin:
Lymphatics are plugged with cancer
Lymphatic fluid leaks out; increased fluid in interstitium as fluid expands
dimple
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o Lymphatic tumor
Lobular carcinoma:
o Most common cancer of the terminal lobules
o Famous for: bilaterality
Lipidema in post-radical mastectomy
o Modified mastectomy: entire breast, including nipples; leave behind pec major, axillary
resection, taking pec minor
Most common complication: winged scapulacut long thoracic nerve
Lumpectomy: removes underlying tumor with good border, normal tissues around it, a few
nodes in the lower axillary chain for staging
o Usually cancer goes to lower axillary first
o Then do radiation
o Good for breast conservation
o Same prognosis as modified radical mastectomy
o But if breast tissues are too big need to do modified radical mastectomy
ERA/PRA: estrogen/progesterone receptor assay:
o Relationship between presence of estrogen and receptor synthesis
During reproductive period of life with lots of estrogen receptor is downregulated
o Young woman in reproductive age: ERA/PRA negative in breast cancer
o In post-menopausal women: estrogen level is lowered, up-regulation of estrogen
receptor ERA/PRA positive
o ERA/PRA responds to estrogen, which is feeding the tumor
Tomoxifine: weak estrogen
o Hooks into receptor on breast tumor so that normal estrogen cant get into it blocking
the receptor from normal estrogen
o Complications: menopausal-like symptoms; endometrial cancer because its an estrogen
o Does prevent osteoporosi
Endocrinology 1
Nomenclature
Primary problem: problem with the gland/organ

o i.e Hashimotos thyroid gland
Secondary problem: problem with hypopituitarism
o Dont have TSH to stimulate the gland
Tertiary problem: problem with hypothalamus
o Hypothalamic disease (i.e. sarcoidosis), no TRH
Ex: parathyroid gland
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Adenoma on parathyroid gland, making PTH and hypercalcemia primary
hyperparathyroidism
o Hypocalcemia, vit D deficiency, parathyroid hyperplasia to increase Ca level
secondary hyperparathyroidism
o After chronic making PTH, hypercalcemia tertiary hypercalcemia
Overactivity vs. underactivity of the gland
o Stimulation test: for underactivity of gland
To see if we can get the gland going again
o Suppression test: for overactive gland
To see if can suppress the gland
Most the time, cant suppress causes that lead to overactive gland, except
tumors in the pituitary gland
Prolactinoma: prevent tumor from making prolactin
o Tx for prolactinoma: bromocriptine (DA analogue)
o Normally women dont have prolactinorrhea because there are
enough dopamine
o Bromocriptine is also used to tx Parkinsons
Pituitary cushings: benign tumor in the pituitary gland making too much
ACTH
o Can be suppressed with dexamethasone
These are the only overactive tumors that can be suppressed
o Scenario: pt has hyporcortisolism, do ACTH stimulation test; collecting urine for 17hydroxycorticoids (metabolic product for cortisol)
Nothing happened hypocortisol is due to addisons
Regardless of ACTH stimulation nothing happens
If 17-hydroxycorticoids level increases: hyporcortisolism due to hypopituitarism
o Or do ACTH test on above scenario:
Addisons: ACTH high
Hypopituitarism: ACTH low
o
Hypopituitarism
Pituitary gland is located in sella turcica in sphenoid bone (trans-sphenoidal sx)

Most common cause in adults: non-functioning pituitary adenoma
o Tumor is usually non-functioning
o Overtime, destroy all the normal pituitary tissues hypopituitarism
Post-partum necrosis: 2nd most common cause of hypopituitarism
o Pregnant woman with ruptured placenta, hypovolemic shock; after recovery, start
breastfeeding baby but breast milk suddenly stops
o Infarcted pituitary: coagulation necrosis
but in the brain, its liquefactive necrosis
o ischemic, coagulation necrosis postpartum
during pregnancy, pituitary gland size increases due to prolactin
but estrogen and progesterone inhibit prolactin from being released no
galactorrhea
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after delivery, the inhibitory effects are removed start secreting milk
craniopharyngioma:
o rathkes pouch origin: part of embryological development of pituitary gland; if parts
remain, can be neoplastically transformed into craniopharyngioma
o benign tumor, but located in a bad place
o commonly located supra-sella
can go down to destroy pituitary
can also go forward and destroy optic chiasm bilateral temporal anopsia
o scenario: child with HA and visual defect craniopharyngioma
o commonly seen in children
tumor that is expanding in the sella turcica, decrease in hormone secretions occurs in
succession:
o FSH and LH (gonadotropins) are first to be destroyed:
Secondary amenorrhea in women
Impotence in male (similar to amenorrhea): inability to sustain erection during
attempted intercourse
o Growth hormone: increase amino acid uptake and gluconeogenesis
Produces the bone/soft growth: IGF-1 (aka somatomedin)
Growth hormone stimulates liver to release IGF-1 for bone/soft tissue growth
In adults: bones wouldnt get smaller
But would lose some muscle mass and fasting hypoglycemia
GH is gluconeogenic if not present, hypoglycemia
In children: pituitary dwarfism
Hypoplasia: incompletely developed
The child looks normal, except everything is smaller
Best stimulation test to see if there is GH or IGF-1 deficiency: sleep!
Collect blood at 5am to see if GH or IGF-1 is increased
Arginine and histidine are essential amino acids
Basic amino acids, stimulate GH necessary for growth
Arginine stimulation test: 2nd best
o low TSH low T4 (hypothyroidism)
cold intolerance, brittle hair, decreased reflex
o ACTH:
Hypocortisolism
Fatigued, fasting glycoglycemia because ACTH is gluconeogenic
o Prolactin:
In non-pregnant women: cant tell if there is deficiency in prolactin
Diabetes Insipidus
Central: lacking ADH

o Symptoms: polyuria, tremendous thirst
o Causes:
Trauma: sever stalk
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ADH: 1st to be gone
Made in the supraoptic paraventricular nucleus of the hypothalamus
The nerve that ADH is made go thru stalk stored in posterior pituitary
Sever the stalk: ADH deficient
Nephrogenic:
o Have ADH, but doesnt work on collecting tubule to make it permeable to water
Differentials for polyuria:
o Diabetes mellitus: glucose is osmotic diuresis
o Polydipsia: drink too much water, usually psychological problem
o hypercalcemia
to differentiate between central and nephrogenic DI:
o serum Na = TB Na/TB water
o no ADH or if ADH doesnt work losing free water, not salt
constantly diluting and cant concentrate urine
o exact opposite SIADH: too much ADH, cant dilute
o losing water serum Na goes up increase plasma osmolality
o test: restrict water
normal people: 750osm urine concentrated urine
reabsorb water to bring down plasma osmolality
pt: elevated plasma osmolality (hypernatremia), but urine osm is 110
o then give ADH
if urine osmolality increase more than 50% from baseline: central
if urine osmolality doesnt increase more than 50%: nephrogenic
o
Pituitary Hyperfunction Disorders
acromegaly:
o cheapest way to screen: look at an older picture
o gigantism: acromegaly in kids
because growth plates havent sealed: excess GH and IGF giants
die of cardiomyopathy
o in adults: acromegaly
wont get taller because bones are sealed bones grow wider
frontal bones enlarge stick out
hands enlarge
every organ in the body enlarges cardiomyopathy death
prolactorrhea:
o not seen in men because there are not enough of terminal lobules
o in women, many causes:
many drugs can stimulate prolactin synthesis
birth control pills, Ca channel blockers, hydralazine, psychotropic drugs
primary hyperthyroidism:
need to get a TSH
hashimotos: TSH, TRH are both increased; TRH is used as a stimulation
test for prolactin
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High prolactin prolactinoma
Prolactin level over 200: always prolactinoma
o Frequently women with normal work-up results still have prolactorrhea: bra rubbing on
the nipple due to tactile stimulation of nipple
Wet nurse: doesnt need to be someone who is lactating; can be an older woman
Chronic suckling on nipples produce milk
o Prolatinoma: can lead to secondary amenorrhea
Prolactin inhibits release of GnRH
3 months after pregnancy: high prolactin level cheap birth control pill
o Always asked!
Thyroid:
o Need to know T3, T4, and I131 uptake
TSH itself suffices: if TSH is normal thyroid is normal
o Decreased TSH: hypopituitarism or hypothyroidism
o Increased TSH: primary hyperthyroidism
o Thyroid-binding globulin (TBG): binding protein for thyroid
Binding protein for cortisol: transcortin
Binding protein for Ca: albumin
Binding protein for Fe: transferring
Binding protein for Cu: ceruloplasmin
Usually 1/3 binding sites are usually bound
o On birth control pill/pregnancy: increase in estrogen
TBG (and transcortin) synthesis increases decrease free hormone
transiently free T4 level is the same, TSH level normal, total T4 is increased
Increase in total T4 with normal TSH: on estrogen
Not because increase in free T4 but increase in TBG
Same true for cortisol:
transcortin increased during pregnancy or taking birth control pills
more cortisol bound, but free cortisol is still normal
o anabolic steroids:
break down proteins body doesnt use to put them in the muscle
steroids TBG is decreased (aa making TBG is now used to make muscles)
free T4 is still the same, but total T4 is decreased
since free T4 is normal, TSH is normal
Low total T4, normal TSH taking steroids
High total T4 and low TSH hyperthyroidism
Low total T4 and increased TSH primary hypothyroidism
o I131 uptake: radioactive uptake test
Thyroid hormone: tyrosine with I Tyrosine DA melanin; tyrosineDA dopa Norepi epi
Hyperthyroidism due to overactive thyroid gland: Graves disease
Would also need more I If giving I-: would see increased uptake in hyperthyroidism
Taking thyroid to lose weight:
o
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Suppress TSH
Gland atrophy
If giving I- , will not see increased uptake
I uptake is the best test to distinguish:
Increased uptake: gland is making thyroid hormone
Decreased uptake: taking thyroid hormone
Midline cyst:
o Thyroglossal duct cyst
o Thyroid gland originally located at the base of the tongue and migrated down the midline
to the anatomical location
Brachial cleft cyst: cysts in the anterio-lateral portion of the neck
o Brachial cleft derivatives: know it!
Thyroiditis: inflammation of thyroid
o Hashimotos
o Sub-acute thyroiditis
Graves Disease:
o IgG receptor against TSH receptor
Constant TSH production; type 2 hypersensitivity reaction ab against receptor
Another type 2 reaction: MG destroying receptor
o Excess GAG deposited in the orbital fat pushing eyes out (exophthalmos)
o Pathognomonic for Graves disease
o Apathetic Graves: Graves disease in elderly
o All people with Graves disease with heart problem and a-fib
In any pt with a-fib: must get TSH to r/o Graves disease
o Symptoms of hyperthyroidism:
Heat intolerance
Sinus tachycardia, sometimes a-fib
Brisk reflexes
Diarrhea
Systolic HTN
HyperCa increase bone turnover
o All the symptoms of hyperthyroidism are adrenergic
Phe tyr DA DOPA NE epi
T4 increases the synthesis of receptor
o Initial tx for Graves: beta blocker
o Then give propylthouracil, can stop all symptoms except sweating
o T4 high, TSH low, I- high
Hypothyroidism:
o Puffiness around peri-orbital area periorbital edema
Puffy because GAG deposition
o Increased GAG deposition in vocal cord hoarse throat
When deposited in tibial area pre-tibial myxedema
o First finding of increased GAG content: mitral valve prolapsed
Increased dermatan sulfate excess and redundancy of the valve
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In graves and hashimotos disease:
Both autoimmune disease: one is inhibitory and the other is stimulatory IgG
Both have GAG deposition and pre-tibial myxedema
o Signs: weakness proximal muscle myopathy
Serum CK elevated
This is most common symptom
o Other symptoms: brittle hair, coarse skin, periorbital puffiness, delayed reflex,
constiplation, DIASTOLIC HTN
Hashimotos disease:
o IgG ab against TSH receptor instead of activating, it inhibits the gland
o Decreased GAG: problem in metabolizing GAG
Lysosomal storage disease
Lysosomal enzyme breaking down dermatan sulfate
o No follicles on the gland: due to autoimmune destruction via cytotoxic T cells
But can make some antibodies germinal follicles
Thyroid looks kind of like a germinal center
o T4 low, TSH high, I- low
Brain is not completely developed at birth; takes another year and half
o Requires thyroid hormone
o Important to r/o creatinism (hypothyroidism in newborns) otherwise severely mentally
retarded
o
Endocrine 2
Goiters
Big thyroid
o Graves disease: diffuse enlargement
Most common cause of goiter: I- deficiency
o (Borderline) hypothyroidism
o T4 decreases, TSH increases gland makes more and enlarges
o In the US, salt is iodinated
Tx: thyroxine gland starts to get smaller
Sometimes nodules are present:
o Some nodules can hemorrhage: very common
o Can do fine needle aspiration for the nodule
Benign and Malignant Tumors
Cold nodules: do not uptake Io 15-20% cold nodules in women are malignant
Most cold nodules in women are benign; most are cysts
A small percentage is follicular adenoma: benign
o In men: any cold nodules are cancer until proven otherwise
o In children: any cold nodules are cancer until proven otherwise
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Any exposure to radiation in the head/neck area in any person, cold nodules cancer
(papillary carcinoma of thyroid)
Hot nodules: black dot in the location
o because the nodules are autonomously making thyroid hormone
o TSH is decreased suppress some normal part of the gland gland atrophy would
not take up IPapillary carcinoma of thyroid:
o Cant tell if its malignant, can be follicular adenoma, multi-nodular goiter
Need to biopsy or do FNA
o Cold nodules
o Blue-ish thing that scatter over the body: psammoma bodies
o Mets to: cervical lymph nodes
o Very good prognosis
o Most common thyroid cancer; the only cancer associated with radiation
Follicular cancer:
o 2nd most common type
o Invade vessels
o Do not mets to lymph nodes; hematogenous lungs, bones
Medullary carcinoma:
o Some cases have autosomal dominant relationship (MEN syndrome), some sporadic
o MEN: multiple endocrine neoplasia
MEN1: pituitary tumor, parathyroid adenoma, pancreatic tumor, peptic ulcer
MEN 2A: medullary carcinoma, pituitary pheochromocytoma
MEN 2B: medullary carcinoma, pituitary pheochromocytoma, mucosal neuroma
Screen test: RET protooncogen
Code for receptor, very unique to MEN syndrome
o Pink-staining, stain with congo red, polarize and shows up as apple green amyloid
Amyloid comes from tumor marker: calcitonin
o Scenario: where would cancer located in the body where the tumor marker is converted
into amyloid thyroid
o Medullary: worst thyroid cancer; papillary carcinoma best
o
Parathyroid Gland Disorders
Ca is bound and free; free ionized Ca is metabolically active

o Bound: metabolically inactive
o Ca interacts with PTH:
Low Ca high PTH and vice versa
o 1/3 binding site on albumin is occupied by Ca
40% of total Ca is bound to albumin
o Most common overall cause of hypoCa: hypoalbuminea
Low albumin: less albumin bound to Ca total Ca decreases
Free Ca level is not affected
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When there is alkalosis (metabolic or respiratory)
Decreased H+ ions: pH increases
Acidic amino acids: glutamate, aspirate
Acidic because they have COOH groups (basic amino acids have NH)
Albumin: great binder for Ca because it has the most negative charges of all
proteins in the body
In alkalotic state, -COOH -COO Even more negative charge can bind to more Ca take free Ca
Total Ca is not affected
Free, ionized Ca is decreased tetany
Mechanism of tetany:
Threshold of AP is lowered by decrease in free, ionized Ca partially
depolarized
Easier to activate AP tetany
In hypercalcemia: threshold is raised
Serum parathyroid hormone on y-axis vs. total Ca on x-axis
o The height of square represents serum parathyroid hormone and width serum Ca level
Serum Ca low, PTH low primary hypoparathyroidism
o Most common cause: previous thyroid sx
Gland that is left behind: reactive damage, infarct
o Scenario: pt with previous thyroid sx and now with tetany
DiGeorges syndrome:
o Newborn, irritable, cyanosis, and no anterior mediastinum shadow on x-ray
o Hypoparathyroidism, absent thymus
Secondary hyperparathyroidism: low Ca, high PTH
o Most common cause: renal failure
o Hypovitaminosis D: decrease Ca increase PTH
Primary hyperparathyroidism: high Ca, high PTH
o The gland is not obeying negative feedback
o Most common cause of hyperCa in a community
o If in the hospital: high Ca is most likely malignancy-induced
o Primary hyperparathyroidism pt: usually asymptomatic
The most common symptom: stone
o PTH: high, Ca: high, PO43-: low
PTH increases Ca and decreases PO43-reabsorption
o Almost always >50yo, more common in women
high Ca, low PTH: normal
o all of the causes of hypercalcemia except primary hyperparathyroidism
o most commonly due to malignancy
o PTH-rp can also cause hypercalcemia
Increase Ca reabsorption
High PO43o
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malignancy: squamous cancer of the lung, renal adenocarcinoma, or mets to bone,

breaking bone down, sarcoidosis producing hypercalcemia, multiple myeloma with
hypercalcemia all low PTH
PTH is the best way to determine cause of hypercalcemia:
If PTH is high: primary hyperparathyroidism
If PTH low: other causes, most likely malignancy
Cushings
Purple striae, thin extremities, central obesity

Most common cause:
o long-term steroid therapy (renal transplant pt, lupus)
o pituitary cushing: 2/3 of cases
o adrenal cushing: lowest ACTH
making lots of cortisol suppress ACTH
o ectopic cushing: highest ACTH level
2 grades screening test after r/o steroid use:
o 24 hour urine free cortisol
Cortisol that is in the urine, not attached to any proteins
Needs to have lots of cortisol for free cortisol to be in urine
Absolute single best test to distinguish Cushings from cushinoid obesity
99% sensitivity and specificity
o Suppression test: dexamethasone
Dexamethasone: cortisol analogue
Give dexamethasone: suppress ACTH cortisol level should be low
Low dose given to Cushings:
Lack of suppression; but doesnt tell you the type of Cushings
High dose: able to suppress ACTH released by pituitary tumor and cortisol goes
down
But doesnt work for adrenal or ectopic cushings (usually due to small cell
carcinoma)
o Scenario: Cushings syndrome
Look at high dose suppression test first: if ACTH is suppressed pituitary
Cushings
Hypercortisolism:
o Cortisol is gluconeogenic, and needs substrate
o Main substrate for gluconeogenesis: aa from muscles
Break down muscles thin extremities
o Alanine transaminated into pyruvate
o Glucose: high increase insulin release
Insulin increases fat storage
o Face and trunk have the highest adipose tissues
o Insulin deposition of triglyceride
o On face: moon facie; on neck: buffalo hump; on body: central obesity
Stretch marks:
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o
o
o
Due to normal obesity

Purple: cortisol decreases collagen synthesis
Structurally-weaker collagen
Purpura within stretch mark, vessel instability
Hyperaldosteronsim
Primary aldosteronsim: Conns syndrome

o Trousseaus sign: tetany
o HTN, hypernatremia, hypokalemia, metabolic alkalosis
Tetany:
o Alkalosis increase negative charge on albumindecrease free Ca level
Adrenal Medulla Tumors
Most common in adults: if HTN pheochromocytoma, benign

If in children: HTN neuroblastoma, malignant
Both are in adrenal medulla, and both are neural crest origin
Both produce HTN
Pheochromocytoma:
o Scenario: pt with very unstable HTN, very anxious, sweat a lot
Then do 24 hour urine for VMA and metanephrine (metabolic products of NE and
epi)
o Association with: MEN 2A, 2B; neurofibromatosis
o Neurofibromatosis pt with HTN do VMA or metanephrine in 24 hour urine
Waterhouse-Friderichsen syndrome
o Scenario: high fever, nuchal rigidity, spinal tap shows neutrophils; petechial lesion,
hypovolemic shock and death; autopsy shows hemorrhage of both adrenal glands
o Organism: N. menigitimus
Most common cause of meningitis from 1 month to 18yo
The only meningitis with petechial lesions!
o Very common on boards!
Addisons Disease
A common cause of hypocortisolism

Cause of addisons: autoimmune destruction of the gland
o It used to be miliary TB spread
Entire adrenal cortex is destroyed:
o Mineralocorticoid: no aldosterone
Lose salt hyponatremia
Hyperkalemia Peaked T waves
Metabolic acidosis
o Glucocorticoids: low cortisol high ACTH
Increase melanocyte in the skin Hyperpigmentation (esp in mouth)
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Adrenal Genital Syndrome
Ambiguous genitalia
First step in work-up: chromosome analysisneed to find out the genetic sex
o If XX with ambiguous genitalia, phenotypically ambiguous female pseudohermaphrodite
21-hydroxylase deficiency
17-hydroxylase: responsible for 17-ketosteroids
o DHEA, androstenedione (weak androgen)
androstenedione can be converted into testosterone, then into DHT
testosterone is not 17-ketosteroid
17-hydroxycorticoids:
o 11-deoxycortisol and cortisol
When there is an enzyme deficiency:
o proximal to the block increase
o distal to the block decrease
21-hydroxylase deficiency:
o Distal decrease: mineralocorticoids, 17-hydroxycorticoids
o Proximal increase: 17-ketosteroid
o Female baby with excess androgen: ambiguous genitalia, losing salt
Similar to Addisons
ACTH is high, cortisol level decreasedhyperpigmented
o Decreased: cortisol, aldosterone, corticosterone
o Increased: 11-deoxycorticosterone, 11-deoxcortiol
o 17-hydroxycorticoid is increased
o 17-ketosteroids increased: excess androgen
Big genitalia, precocious puberty
o Salt retainer: HTN
o Increased: mineralocorticoids
o Decreased: 17-hydroxycorticoids, 17-ketosteroids
o Salt retainer HTN
o Little boy with low 17-ketosteroids: no testosterone, looks like a female
o Little girl with low 17-ketosteroids: underdeveloped
Islet Cell Tumors
Insulinoma:
o Making too much gastrin peptic ulcer
o When breaking pro-insulin down into insulin, release C peptide
o If injecting human insulin into oneself produce low glucose level, high insulin level, C
peptide would be suppressed
Often seen in healthcare professionals who have access to insulin
o Insulinoma: hypoglycemia, high insulin level, C peptide is high
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Diabetes:
o Type 1:
Absolute insulin dependency
Ab against islet cells (insulitis, inflammation of islet cells)
Ketoacidosis
HLA relationship
Certain HLA type propensity for developing something
Certain environmental factor as a trigger plus certain HLA typehigher
chance of developing certain disorders
Environmental factors: infection (coxsackie, mumps, EBVetc)
Viral infection is very common in type 1 DM; can develop DM type 1
following a viral infection
Require insulin usage
o Type 2:
Family hx of diabetes
Obesity
Amyloid in the islet cell (chronic process)
Require Insulin usage, after developing resistant to sulfonylurea
o Pathogenesis:
Osmotic damage
Tissues need to have aldose reductase
Lens: converts glucose sorbitol, which is osmotically active sucks
water in
Pericytes in the retinal vessels: becomes weak microaneurysm,
rupture, blindness
Schwann cells: osmotic damage peripheral neuropathy
Non-enzymatic glycosylation:
Glucose attached to aa and proteins and render the protein (usually
basement mb) permeable to proteins
Hyaline arteriosclerosis, diabetic nephropathy
o HbA1C: example of glycosylation index of long term glycemic control
o Diabetic nephropathy: significant hyaline arteriosclerosis
Kimmelstiel-Wilson: type 4 collagen
o Dry ganglion: increased incidence of atherosclerosis
o Microaneurysm
o Proliferative retinopathy: rupture and separation of retina blind
o Scenario: 50yo pt has blurry vision, optometrist gives a new set of glasses; blurry vision
returns 2 weeks again, constant change in refraction diabetes
converting glucose to sorbital, water is drawn in, changing refraction of lens
o fasting glucose: >126mg/dl on 2 separate occasions diabetes
comparing to older criteria of 140 126 has higher sensitivity because its closer
to normal, and 140 has higher specificity
o gestational diabetes: a woman who doesnt have diabetes before pregnancy
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risk factors for babies in mom with poor glycemic control: respiratory distress
syndrome, premature delivery
women with gestational diabetes also have higher chance of developing diabetes
later in life
Musculoskeletal
Arthritis
crystals in the synovial fluid: gout vs. pseudo-gout

2 types of crystals in pseudo-gout:
o Rhomboid: very specific; pathognomonic for pseudo-gout
o Needle-shaped: also seen in monosodium urate
Get a sample of synovial fluid, and makes background red
Look at the crystals in the same direction as the analyzer of the microscope
Yellow and parallel to analyzer: negative birefringence, monosodium urate (gout)
Blue and parallel to analyzer: positive birefringence, pseudo-gout
Osteoarthrisi:
o Non-inflammatory
o Most common arthritis
o Degenerative; wear-and-tear of articular cartilage
Joint space is narrowed
o Reaction to injury at the margin of the joint to the wearing down of collagen
New bone formation spur, bone osteophyte
Heberdens node, buchards node: osteophytes
o Joints in hands:
Knuckles: metacarpal phalangeal
Proximal and distal interphalageal
Osteroarthritis: DIP and PIP
Rheumatoid arthritis:
o Inflammatory
Rh factor: IgM ab against IgG
When IgM ab is in the synovial fluid form complex with IgG activate
complement damage joint
Synovial tissues get inflammed hyperplastic, grow over articular cartilage
(pannus) destroy articular cartilage
Reaction to injury/destruction: fibrosis
Joints can be ankylosed if not treated fixed, not movable
o Involves PIP and MCP
o Ulnar deviation
o Symmetrical: in both extremities
o Rheumatoid nodule: can also see in rheumatic fever
o Rheumatoid nodule in lung with pneumoconiosis
o Tx: methotrexate; early tx less chronic damage
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Scenario: pt with TA, develops macrocytic anemia with hypersegmented neutrophils and
nl neurological exam on methotrexate
Sjogrens syndrome:
o Older pt has trouble eating and swallowing crackers; dry tongue and eyes sjogrens
syndrome
o RA then developed autoimmune destruction of lacrimal gland
Keratoconjuncitivis sicca: dry eyes
sand in eyes
o Destruction of salivary gland dry mouth
o RA, dry eyes, dry mouth sjogrens syndrome
Gout: aka podagra
o Usually first joint involved in acute gouty arthritis: big toe
Precipitate monosodium urate crystals in synovial fluid neutrophils
phagocytose and release cytokines
Elevated monosodium urate level: doesnt necessarily mean gout
o Gout: inflammatory joint, and monosodium urate crystal in synovial fluid
There is also gout where uric acid crystal level is normal
Do not define gout based on uric acid crystal level
o Tx: initially with anti-inflammatory
Colchicines: too toxin
o Then decide what caused the gout: overproduction or under-excretion of uric acid
Over 90% cases due to under-secretion
Over-production: allopurinol
Blocks xanthine oxidase
Under-secretion: probenecid, Sulfinpyrazone
o Tophus: chronic gout presentation
Stick with lacet: crystaline material with multinucleated cells reacting to foreign
body
Monosodium urate deposition in soft tissues
Can be seen in hands, ear; disfiguring deposition
Very destructive when right next to joint disabling arthritis
The only tx once tophus is developed: allopurinol
o Little genetics and lots of environmental factors
Do not eat: red meat, red wine, alcohol
Alcohol: metabolic acidosis (lactic acidosis and beta-hydroxybutyrate
ketoacidosis)
All acids in bodies compete to be excreted in proximal tubule
More lactic acid and beta-hydroxybutyric acid than uric acid
o
Seronegative Spondyloarthropathies
Male dominance
Ankylosing spondylosis:
o Inflammatory process
o Tremendous lower back pain in sacroiliac when waking up in the morning
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The inflammation then eventually involves vertebral column fusion of v. column
Bamboo spine
o HLA B27 positive
o Aortitis: inflammation of aorta and aortic regurgitation
o Uveitis: blurry vision, blindness
Alkaptouria:
o Genetic disease: autosomal recessive
Absent homogentisate oxidase build up of homogenitisic acid
o Degenerative arthritis in the v. column and other places
o Autopsy shows black cartilage between vertebral bodies
o Urine exposed to sunlight: turns black
o homogenitisic acid depots in cartilage destroy cartilage, black pigment
Reiters syndrome:
o non-specific urethritis chlamydia
dysuria, UA shows neutrophils but no bacteria, positive leukocyte esterase,
negative nitrite sterile pyuria
o a few weeks later after tx of Chlamydia:
sterile conjunctivitis
arthritis and Achilles tendon periostitis
Achilles tendonitis, right at where Achilles tendon inserts into calcaneous
This is pathognomonic for Reiters syndrome
o HLA B27 positive, with chlamydia as a trigger to develop into ankylosing spondylosis
Ulcerative colitis can also be an environmental trigger for HLA B27+ individuals
o Other triggers: psoriasis, shigellaetc
o
Septic Arthritis
Hot joint at knee, pustule on palm, aspiration of pustule shows gram- diplococci disseminated
gonoccemia
o S: synovitis (inflammation of joints, specifically knee)
o T: tinosynovitis (joints in the hands, feet)
o D: dermatitis (pustules in hands, feet; aspirate shows GC)
o If have GC, factors that predispose one to disseminated GC: missing complement C5 to
C9 (final common pathway)
Need these complement components to phagocytose GC
o Most common cause of septic arthritis: GC
Lyme disease
o Borrelia burgdorferi; in ticks (Long Island, Conneticut)
o Erythema chonicum migrans pathognomonic for lyme disease
o Tx: tetracycline in early stage
o If not treated and develop into chronic progress:
Disabling joint disease
Myocarditis
Any pt with bilateral bells palsy: lyme disease until proven otherwise
Most common CN involved in chronic lyme disease: CN 7
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Usually idiopathic bells palsy is due to herpes simplex, but unilateral

Hemolytic anemia, peripheral blood smear shows babesia microti
Ixodes tick has reservoir for b. burgdorferi; white tailed deer also has b. microti
B. microti: intraerythrocytic parasite hemolytic anemia
Very similar to ring form of plasmodium falciparum
Very common to have both b. microti and b. burgdorferi together
Tx: chronic ceftriaxone
Bone Disorders
Osteogenesis imperfecta:
o Blue-ish discoloration of sclera
Collagen in sclera
Since type 1 collage is defective/thin would see the underlying choroidal vein
that gives blue color
o Defect in making type 1 collagen
Osteopetrosis:
o Defect in osteoclast cant break bone down no BM
o marble bone disease
o Severe anemia
Osteoporosis:
o Cartilage between vertebral column thins
o Dowager hump
o Mechanism in elderly women: breaking more bone down than putting in
Not enough estrogen to inhibit IL-1 (osteoclast-activating factor)
o Overall reduction in bone mass in both mineral and organic components
o Dx: dual-photo absorptiometry measure bone density
o Most common fracture: compression fx
Collapsing vertebral column, becomes shorter
Weight of head lean forward, back goes out due to weakness of bone
nd
o 2 common fx: colles fx of distal radius
o Prevention:
Weight-bearing exercise; no swimming (no stress on bones!)
Walking, weight-training
Ca (1500mg) and vit D (400-800 units/day) supplement
Also need vitamin pill that contains Fe in a young female in repro age
o Astronauts: serious osteoporosis due to lack of gravity in space
Osteomalacia:
o Decreased mineralization; organic part is fine
Cartilage, osteoids are fine; just cant mineralize
Bone Tumor
Osteochodroma
o Overall most common benign bone tumor
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overgrowth/neoplasm of cartilage, kept by bone on surface
exostosis
o predispose to chondrosarcoma
chondrosarcoma: most common malignant tumor
osteogenic sarcoma:
o always around the knee: distal femur and proximal tibia
o teens/early 20s
o develops in metaphysic of bones
o invading up into muscle, going thru periosteum
codmans triangle tumor lifting periosteum
o sunburst appearance: speculated pattern from calcified malignant osteoid
o related to Rb suppressor gene, chromosome 13
o
Muscle Disorders
Duchennes muscular dystrophy

o X-linked recessive
o pseudo-hypertrophy
Gowers maneuver: climbing up on his legs to stand up
o elevated serum CK
o absence of dystrophin
o a variant of this disease: Beckers dystrophy
still x-linked recessive
make abnormal dystrophin, defected
o similar to 1-antitrypsin deficiency:
most common cause of hepatocellular carcinoma in children
in adults: pan-acinar emphysema
when not making 1-antitrypsin at all: pan-emphysema in young adults
one other subtype: can make 1-antitrypsin, but cant get out of hepatocytes
damage hepatocytes predispose to HCC
PAS stain of hepatocytes: lots of 1-antitrypsin
Myotonic dystrophy:
o Most common adult muscular dystrophy6
o Triplet-repeat disease:
Repetition of trinucleotides
Huntingtons chorea
Myotonic dystrophy
Fredericks ataxia
Fragile X: mental retardation and macro-orchidism (big testicles seen in teens)
o Anticipation of triplet-repeat disease: future generation of kin the disease gets worse
Each generation: more triplet-repeats added on coding more defective proteins
o Scenario: a couple with a type of disease, if they were to have children, children would
die before 1 year. Their child died after a month triplet-repeat disorder
o Myotonic dystrophy:
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Frontal bulging
Muscle weakness in face mouth drooping
Usually first sign
Scenario: couldnt release hand grip myotonic, failure to relax muscle
Diabetes
Cardiac abnormalities
Myasthenia gravis:
o Autoab (IgG) against Ach receptor
Type 2 hypersensitivity; like in Graves disease
o Ach cant attach to receptor muscle weakness
First muscle affected: eyelid ptosis
Eye muscles also affected: diplopia
Dysphagia: cant swallow solid/liquid
Progressive muscle weakness
o Mostly striated muscles are affected; not so much on smooth muscle
o Feels great in the morning, but progressively feels worse thru the day
o Test: tensilon
o When all receptors are inhibited, Achesterase inhibitor wouldnt work
o Tx: acetylcholine esterase inhibitor
Later on: thymectomy
Thymus:
o Anterior mediastinum
o Thymoma: malignancy of thymus occurring in 15-20% cases
Not seen in MG
Thymus: usually only have T cells
o In MG: germinal follicles in thymus making ab
Ab made in the germinal follicles in thymus
o By doing thymectomy can have complete cure in 1/3 pts
o MG: B cell hyperplasia
Skin
Lupus
Collagen vascular disease

Butterfly rash on face
Most likely to have positive ANA among all autoimmune diseases (99% sensitivity)
To confirm dx of lupus after having positive ANA, order:
o anti-smith ab: 100% specificity for lupus
Positive anti-smith no false positives true lupus
o Anti-dsDNA: if positive, lupus AND kidney disease
98% specificity
Symptoms:
o Morning stiffness: like RA
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o Photophobia
o Malar rash
o pericarditis
LE cell: never order it
o anti-DNA ab react against DNA, neutrophils phagocytose these cells
o altered DNA in neutrophils
o but not specific to lupus
progressive systemic sclerosis or CREST syndrome
o Presentation: tight face, dysphagia of liquid and solid, telangiectasia, dystrophic
calcification on hands, Reynauds phenomenon, sclerodactyly
o If kidney is involved: progressive systemic sclerosis
CREST doesnt involve kidney
Dermatomyositis
o Elevated serum CK, raccoon eyes
o Silver rash over proximal and phalangeal joints Gottrons patches
o Highest association with underlying cancer
Sjogrens syndrome:
o Ab destroy salivary gland and lacrimal gland dry eyes and mouth
o Biopsy of lower lip: confirmation test
Looking for lymphocytic destruction around the salivary gland
o Anti-SSA (anti-Ro) and anti-SSB (anti-La)
Anti-Ro: can be seen in Lupus
Can cros placenta and attack babys conduction system baby with
complete heart block
Skin Disorders
Basal cell carcinoma

Squamous cell carcinoma: lower lip
Actinic keratosis: rub off the lesion but comes back
Psoriasis: silvery plaque, red, raised lesion
o Involve the scalp, hands, pressure point (i.e elbow)
o Black pt with psoriasis: would see silvery plaque
Atopic dermatitis:
o Allergic diaphysis
o Ezema
o Type 1 hypersensitivity
Contact dermatitis:
o Reaction to metal (i.e. Ni)
o Type 4 hypersensitivity reaction
Pathophyiology: similar to positive PPD
Seborrheic dermatitis
o Disseminated seborrheic dermatitis due Malazzesia furfur: pre-AIDS defining lesion
Bald spot on head, when using black light (UVA) and fluoresces microsporum canis
o Used to be the most common cause of tinea capitis
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Now it is trichophyton tonsurans

o Fungus involes the inner portion of the shaft no flurescent metabolite woods light
negative
o Most common cause of tinea capitis (superficial dermatophyte): trichophyton tonsurans
superficial dermatophytes infections:
o Ring worm
o Red outer edge and clear center scrape outside, and do KOH prep
Would see hyphae and yeast form
o All other superficial dermatophytes infections except tinea capitis: trichophyton rubrum
Red color
Molluscum contagiosum:
o Very common infection in children
o Sandy-like material in the center of the crater
o Self-inoculate; spread all over
o Due to pox virus: DNA virus
o Basal cell carcinoma: volcano crater-like
Same appearance on the skin of a kid with sandy material in the center:
molluscum contagious
Pityriasis rosea
o Rash on butt, non-puritic, red on the outside and pale in the center, oblong-looking (not
circular) and KOH negative. Tx with topical steroids, but pt returns with rash in lines of
cleavage and Christmas tree-like distribution on trunk
o Harold patch
o Not a fungus
o COMMON board question!
Dysplastic nevus:
o Precursor lesion for malignant melanoma
o If >100 such nevi dysplastic nevus syndrome
o Very common; need to see dermatologist 1x/year to look at the entire body
o Irregular, color differentiation
Malignant melanoma:
o Superficial spreading malignant melanoma
Excision!
Most common type
o Lentigo melanoma
Commonly seen on older people, always on the face (sun-exposed area)
Fawn-colored, irregular border
Least likely to mets
o Acral lentiginous melanoma
Black population doesnt get melanoma because the pigment in the skin prevents
from UV damage, except on type of melanoma
Scenario: black pt, dyspnea, x-ray shows multiple mets nodules all over
the body; biopsy shows malignant melanoma
The parts of the body that have primary lesions: under nails, palms, soles
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o
o
Most aggressive melanoma

Not due to radiation
Looks very similar to pagets disease of the skin
Nodular malignant melanoma
Also aggressive
Determinant of prognosis: depth of invasion
<0.76mm no chance of mets
>0.76mm increased chance for mets
Spiders
Black widow:
o Neurotoxin: spasm of muscles in upper thigh and abdalmost like tetanus
o Painful muscle contraction, esp in abd
o Scenario: a person went down to cellular, lifted boxes, felt a sharp prick on the finger;
over a few hours, start having contraction of abd
Brown recluse spider: aka violin spider
o Painless
o Necro-toxin: producing ulcer in the skin
o Most potent of all venom in the world
Structural responsible for piloerection: arrector muscle
Receptor of androgen in the skin: sebaceous glands
o Testosterone and dihydrotestosterone bind to the receptor
o Men more likely to get acne: more testosterone more stimulation of sebaceous glad to
release lipid-rich material gets into hair follicle
o Propionibacterium acnes on the skin:
Anaerobe
Lipase: breaks down fats from sebaceous gland fatty acid that irritates follicle
acne
Prevent hirsutism: spironolactone
o Also used to block aldosterone
o Blocks androgen receptor
o Can also lead to gynecomastia in males
CNS
Spinal Fluids
Derived from choroid plexus located in the ventricles

o Lateral, 3rd and 4th ventricles
Ultrafiltrate of plasma
o Spinal fluid less of: proteins, very little cells, 60% glucose of plasma,
Even if just one neutrophils in spinal fluid abnormal,
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If glucose is < 60% of plasma: low glucose, something in spinal fluid utilizing it for
energy bacteria, fungus, cancer cells
o Spinal fluid has more of: Cl
o Injury to the head area (i.e. baseball hitting eyes orbital blowout fracture), break
cribriform plate, dripping of fluid from nose or ear
Fracture of basilar plate: battle sign
Can have spinal fluid dripping out
Aqueduct of sylvius:
o Most common cause of hydrocephalus in children
o When blocked buildup of spinal fluid in the 3rd and lateral ventricle hydrocephalus
Fluid needs to get out of 4th ventricle to subarachnoid space foramen magendie
Dura: strong, tightly adhered to periosteum
o Epidural hematoma: blood clot between the bone and the dura; the only pressure to slip
the dura away from bone is arterial pressure
o Split periosteum from the dura
Subarachnoid space:
o Main purpose: protect brain and spinal cord from injury; cushion
o Eliminated from arachnoid granulation
o Tumor derived from arachnoid granulation: meningioma
Granulation dural sinuses jugular vein right side of the heart
o No lymphatics in the brain
o When doing valsalva: neck vein distends the pressure transmits back to dural sinuses,
arachnoid granulation, spinal fluid right down to the needle in the subarachnoid space
in L4, and pressure increases
To see if the entire subarachnoid space is patent
If the pressure doesnt increase: there is something blocking spinal fluid
Do not hold breath when weight-lifting or exercise: pressure in spinal fluid can be
very high, can lead to disc herniation
Tentorum cerebelli:
o 70% of brain tumors in adults are supratentorial: involves cerebral cortex
o 70% of primary brain tumors in kids: intratentorial
Most are: cerebellar cystic astrocytoma, medulloblastoma
Hydrocephalus:
o Communicating of spinal fluid in the ventricle with arachnoid space
Pressure still builds up despite communicating
Benign tumor of choroid plexus
Greater ultrafiltrate of plasma, making more spinal fluid, but pressure is
built up because making more than normal
Subarachnoid bleeder, meningitis and scar off granulation cant drain out
o Non-communicating
spinal fluid in the ventricles is prevented from getting into arachnoid space
Most common cause: aqueduct stenosis
Suture has not fused in kids hydrocephalus
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In adults: sutures fused; dilatation of ventricles over year, pressure

turns back to normal
But with increased pressure over a period of time ventricles dilated
dementia, ataxia, urinary incontinences (normal pressure hydrocephalus)
Ependymoma in the 4th ventricle
Meningitis at the base of the brain (TB) lots of scar tissues block foramen
Magendie
Developmental Disorders
Arnold-Chiari malformation
o Medulla and part of cerebellum in the cervical area
o Platybasia: flattening of base of skull
o hydrocephalus
Dandy-Walker syndrome:
o Cerebellum and 4th ventricle dont develop
Herniation
Cerebral edema, no place to go herniation of brian

Tonsillar herniation thru f. magnum:
o Part of cerebellum is squeezed into f. magnum instant death
Uncal herniation:
o Medial portion of temporal lobe (uncus) herniates thru tentorium cerebelli pressure
against midbrain
o Cause hemorrhage in the midbrain Durets hemorrhage
o Compress oculomotor nerve ophthamoplegia
Oculomotor nerves innervate eye muscles except lateral rectus and superior
oblique
Oculomotor nerve palsy: pupil down and out
Trochlears nerve palsy: pupil down and in
o Parasympathetic nerves compressed
Constrict pupils normally, when compressed mydrasis (dilated)
First sign of uncal herniation on the side of mydriasis
o Posterior cerebral artery compressed occipital lobe infarction
Know where all CNs are on the brainstem
Papilledema:
o Due to any causes of increased intracranial pressure
o Loss of sharp margin around the disc
o Vitamin A toxicity
o lead poisoning increased vessel permeability due to -amino-levulinic acid
CNS/Special Senses
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Tuberous Sclerosis
Autosomal dominant
Hamartoma: non-neoplastic proliferation
o In ventricle: bumps tubercle
o Proliferation of astrocytes hamartoma that can bulge into ventricles (candle stick
dripping)
In kidney: angiomyolipoma
Mental retardation
Cardiac tumor: rhabdomyoma
Shagreen patches: hypopigmented areas
o Needs to be seen under woods light
o Not infection due to fungi
Neural Tube Defects
Anacephaly:
o Absent brain
o Vertebral arch defect
Spina bifida occulta:
o Vertebral arches dont quite touch each other
o No meninges coming out, not too much to worry about
Meningocele:
o Spinal bifida with cystic mass containing meninges
Meningomyelocele:
o Spinal bifida with cystic mass containing meninges and spinal cord
AFP in mother: high
o When decreased: Downs syndrome
Mother needs to be on folate before pregnancy to prevent open neural defect
o Neural tube development is finished by 26-29 days
o Most women dont know they are pregnant yet too late to take folate
Syringomyelia:
o Big cystic cavity in the cervical cord: knocking out spinalthalamic tranct (pain and temp),
corticospinal tract, anterior horn cells (motor)
Combination of motor and sensory
o Can also problem with lower extremity and bladder problem
ALS: no bladder problem
o Scenario: person working in the factory, doesnt feel hand being burnt. Exam shows loss
of musculature of hand intrinsic muscles, absence of pain and temperature, cape-like
distribution across the shoulder
Not ALS: its upper and lower motor neuron problem; purely motor
In this case: lower-motor neuron type of manifestation with lack of pain
Phakomatoses
Tuberous sclerosis
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Neurofibromatosis: autosomal dominant

o Very common
o Caf-au-lait macules
Not specific
Can also be seen in albrights symdrome:
precocious puberty, caf-au-lait, bone zits (polyarthritic fibrodysplasia)
coffee colored, non-raised lesions
o Brown pigmentation axillary freckling
o Plexiform neurofibroma: autosomal dominant
Late manifestation
Variable expressivity: expressing the disease but there are different severities
that can be seen in the family, from mild to very severe
o High association between neurofibromatosis and pheochromatosis:
Test: 24 hour VMA or metanephrine
Sturge-webber
Brain Tumors
acoustic neuroma:
o central neural hearing loss
o involves CN8
o benign tumor of Schwann cells
meningioma
optic nerve glioma
o most common overall
o benign tumor
Infections
bacterial meningitis:
o inflammation of meninges
o nuchal rigidity: neck hurts when moving head or raising leg up stretch meninges
o pus at the base of the brain:
can block f. magendie obstructing/non-communicating hydrocephalus
o tx: abx and steroids
steroids: to prevent scar tissue formation and decrease complications related to
scar tissues (i.e. hydrocephalus)
o TB meningitis: treat with abx and steroids
TB in brain: produces scar tissues; infarction produces vasculitis
o Most common meningitis in 1st month of life: group B strep (strep agalactiae)
Also most common cause of sepsis in newborn
Many women are carrier for organism in the vagina: if there is premature rupture
mb chorioamnionitis bloodstream of fetus
2nd cause: E. coli, 3rd: listeria monocytogenes
Pregnant women shouldnt eat soft cheese (ricotta) lots of listeria
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o
o
o
Gram+ with tumbling motility

Other tumbling motility: trochomonis vaginalis
From 1 month to 18yo: neisseria meningitimus
Beyond 18yo: strep pneumoniae
Scenario: 52 yo man with nuchal rigidity, spinal tap shows increased protein, increased
neutrophils, decreased glucose
Gram stain shows: gram+ diplococcus (strep pneumoniae)
o
Encephalitis: think sleeping sickness
o Always sleepy, drowsy
o Mental state abnormality
o No nuchal rigidity
Cerebral abscess
o Rabies: most common cause in US: skunks
o Nigri bodies: purkinje cells
Viral CNS Infections
Periventricular calcification
o Due to CMV, encephalitis
o Dystrophic calcification
o CMV: most common congenital infection in kids
Urine: most productive to culture to dx congenital CMV
Fungal and Parasitic Infections of CNS
Cryptococcus:
o India ink: big nucleus like klebsiella pneumonia
o Pigeons
o Immunocompromised pt: mostly AIDS
o Cryptococcus: most common cause of meningitis in AIDS pt
Mucor mycosis:
o Involves frontal lobe in diabetic pt with ketoacidosis
toxoplasmosis
o AIDS pt with T cell count of 50; CT shows multiple space-occupying lesions in the brain
Cysticercosis:
o Pig herder, long-term focal epileptic seizure requiring dilatin. Autopsy shows multiple
cysts and calcified lesions
Creutzfeldt-Jakob disease:
o Transmissible agent: prions
o Susceptible person: neuropathologists, neurosurgeons, eating beef, lettuce from AZ
(using cow manure for fertilization)
Traumatic Lesions
Epidural hematoma:
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Blood collected above the dura
Blow to temporal-parietal lobe:
Blood vessel that goes thru the bone: middle meningeal
Requires bone fracture!
Under arterial pressure separate dura from periosteum
o Takes about 6 hours
o 50ml of blood collected uncal herniation death
Subdural hematoma:
o Rupture bridging vein between dura and arachnoid membrane
o If there is cerebral atrophy (alcoholics, older people): space between dura and arachnoid
mb is greater bridging veins are more stretched out
o Bleeding blood clot that covers the convexity of the brain
o Fluctuating level of consciousness
o Left untreated: dementia
o Always doing CT if there is head trauma, or stroke
CT picks up blood
Cant put pt on heparin if there is blood in the brain hemorrhagic stroke
Stroke:
o Atherosclerotic stroke: break down of grey and white matter
No hemorrhage; pale infarct of brain
At the bifurcation: big of atherosclerotic plaque occluding the lumen platelet
thrombus develops on top
Infarct in brain no reperfusion because of thrombus tissues break down
pale infarct
Candidate for heparin therapy
Consequence of stroke: big cystic space where infarction was
Liquefactive necrosis
o Hemorrhagic stroke:
If thrombus breaks down and there is reperfusion
Blood is at the edge of the brain; wedge-shaped
Embolic infarct
Embolus from the left side of the heart embolize to middle cerebral
artery (or superior mesenteric artery in the other direction)
Break down of embolus by fibrinolytic system reperfusion
Hemorrhagic infarct
This is embolic stroke
o In HTN, pressure causing lenticulostriate vessels (derived from MCA) form aneurysm
charcot-bouchard aneurysm
Aneurysm ruptures big clot, big hematoma, not an infarct
Intracerebral hemorrhage:
o In HTN, pressure causing lenticulostriate vessels (derived from MCA) form aneurysm
charcot-bouchard aneurysm
Aneurysm ruptures big clot, big hematoma, not an infarct
Pushing brain aside
o
o
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o Can suck out the blood to alleviate symptoms

Subarachnoid hemorrhage:
o Rupture of congenital berry aneurysm
o At the junction of ACA and anterior communication branch AV malformation
Sturge-Weber: skin lesion on the same side as AV malformation
Lacunar infarct
o Occurring in a very small area in the internal capsule
o Depending on the location, can have pure motor, pure sensory stroke
Not combination of both motor and sensory
o Most commonly due to HTN
Multiple Sclerosis
Most common demyelinating disease in the US

o Grey matter doesnt have myelin; when myelin is destroyed grey matter
autoimmune
two ways to demyelinate:
o knock out myelin-producing cells: oligodendrocytes in CNS, Schwann cells in PNS
viruses, measles, papilloma, subacute sclerosing panencephalitis, progressive
multifocal leukoencephalopathy
infect oligodendrocyte demylination
o autoantibody against myelin and destroy myelin sheath: MS
o symptoms:
nystagmus: internuclear ophthalmoplegia
pathognomonic for MS demyelination of bilateral medial longitudinal
fasiculus
ataxia
optic neuritis: blurry vision
MS is the most common cause of optic neuritis
o Spinal tap: increased protein, glucose normal, lymphocytes increased associated with
autoimmune diseases (cytotoxic T cells)
Alzheimers
Atrophy of the brain ventricle a lot bigger

o This is called hydrocephalus exvacuole
Silver stain: senile plaque
o Center: congo red stain amyloid (-amyloid protein)
o Surrounding: neurites
-amyloid protein is toxic to neurons
o more -amyloid protein, more toxic, more dementia
o synthesized by chromosome 21: Downs pt have Alzheimer by age 35-40
o pathognomoic for Alzheimers
neurofibrillary tangles
o but present in any type of dementia, and Huntingtons chorea
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higher intellectual problem problem with memory

a clinical dx
the only way to confirm Alzheimers: autopsy with senile plaque
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Goljan Audio Lecture Notes

inadequate oxygenation of tissues; same def as shock

Alcoholic on a hot day: heat stroke; hyperthermia

Decreased ATP due to tissue hypoxia

Anaerobic glycolysis: end product is lactic acid

Very commonly see in older people as their organs undergo degeneration

End product of free radical damage: lipofusin

Tylenol (acetaminophen): number 1 cause of fulminant hepatitis due to free radicals

Programmed cell death; genes involved in cell death

Damaged tissues that die

o blue in histologic section: ca; seen in dystrophic calcification of atherosclerotic plaque

Portal vein, hepatic artery, bile ducts triads

Cant see a central area of pallor

A stress protein; level increase under stress

Three types of Cells

Most variable phase: G1 phase; or proliferative phase in menstrual cycle

Growth Alternation: Atrophy

Decrease in tissue mass; cells decrease in size

Growth Alternation: Hypertrophy

hypertrophy of cardiac muscle, block in early G2 phase: chromosome number is 4N

o 3N: trisomy disease, or cancer

Growth Alternation: Hyperplasia

Increase in NUMBER of cells

Growth Alternation: Metaplasia

Replacement of one adult cell type with another

Growth Alternation: Dysplasia

occurs during infection; prepare bacteria before they get destroyed

Chronic Granulomatous Disease of Childhood

Adhesion Molecule Defect

Kid whose umbilical cord doesnt fall off when it should

aka beta 2 integrin defect

Anaphylaxin: C3a, C5a

Thromboxane synthase blocker: dipyramidol

Electron microscopy of inflammatory cells

o Normal ratio of helper: suppresser T cells: 2:1

Postpartum woman with pus coming out from catheterstaph aureus

Main Igs in acute inflammation: IgM

Poison ivy: also type 4 hypersensitivity

Alveolar mq phagocytose lympho-hematology spread via alveolar mq

Heart: permanent reaction scar tissues, which do not contract

Tests ordered in Inflammation

Sed rate: pretty worthless

Fluid and Hemodynamics 1

Excess fluid in interstitial space

ECF and ICF

ECF: two compartments vascular and interstitial

Location of urea, Na, and glucose:

Normal plasma tonicity: controlled by Na

If only gaining pure water and not salt:

Fluid and Hemodynamics 2

effective arterial blood volume = stroke volume = CO

o isotonic fluid is reabsorbed

Fluid and Hemodynamics 3

Neutrogenic shock: in step 2, usually seen in spinal cord injury

LV EDP in cardiogenic shock: high

Arterial Blood Gas

bodys attempt to try to maintain a normal pH

Respiratory Alkalosis and Acidosis

respiratory center is located in medulla: controls breathing rate

Arterial Blood Gas

for every 30 feet, increase 1 atm of pressure

Board questions! Can be under behavior science section

Fat soluble: taken up by chylomicrons

o Goose-pumps in the back of arms: follicular hyperkeratosis