Rapid Review Path HY Points

Rapid Review HY Point by Nirav Patel
ITP autoimmune destruction of platlets where IgG antibodies against GpIIb:IIIa fibrinogen receptors on platelets. Usually causes abnormally heavy mensturation, petechial rash, easy bruising, and epitaxis . BT is prolonged . commonly in children (TTP), which is caused by an acquired or genetic deficiency in von Willebrands factor (vWF)cleaving protease in endothelial cells. TTP occurs in women and is uncommon in children. The pathophysiology of TTP and HUS is similar. Widespread endothelial cell damage at the arteriole capillary junction. Platelet thrombi develop at all the injury sites, causing consumption of platelets and thrombocytopenia (epistaxis, petechiae, ecchymoses, easy bruising) as well as renal failure (increased serum BUN and serum creatinine). RBCs that collide with the platelet thrombi are damaged (fragmented RBCs or schistocytes), causing a hemolytic anemia TTP is a disorder characterized by endothelial injury with the formation of platelet thrombi that consume platelets, not coagulation factors; therefore, the PT and PTT are normal. Characterized by purpura, fatigue, pallpor, and tachycardia, and bleeding into the skin GERD causes glandular metaplasia. Goblet cells no longers are able to neutralize acid secretions due to acid reflux destruction. Barretts esophagus due to prolonged GERD leadings to glandular metaplasia of the distal esophagus may become dysplastic and develop into adenocarcinoma ( PPI reduces the risk) Dysplasia is disorderly cell growth related to either atypical hyperplasia or atypical metaplasia. It is a precursor to cancer. Dysplastic epithelial changes include an increase in mitoses, lack of normal cell orientation, and nuclear enlargement with atypical changes in chromatin. Patient anti-HLA antibodies are directed against donor leukocyte The patient has a febrile transfusion reaction. In these reactions, the recipient has anti-human leukocyte antigen (HLA) antibodies directed against foreign HLA antigens on donor leukocytes (type II hypersensitivity reaction). Destruction of the donor leukocytes releases pyrogens causing fever as well as other findings such as chills, headache, and flushing. Delayed hemolytic transfusion results in positive IgG and Coombs test. IgG attaching to foreign antigens on donor RBC this would lead to phagocytosis and RBC destruction via splenic macrophages and unconjugated hyperbilirubinemia, with a possibility of developing jaundice. alcoholic hepatitis, which produces a mixed jaundice (CB 2050%), due to decreased uptake and conjugation of unconjugated bilirubin (UCB) and destruction of bile ductules among liver cells leading to an increase in CB in the blood. Therefore, key markers for alcoholic hepatitis are AST > ALT and marked increase in GGT. Smoking is the most common cause of squamous cell cancer of the larynx, alcohol is second Acute glomerulonephritis is characterized by oliguria (decreased glomerular filtration rate), proteinuria, hematuria, and urine casts (RBC, WBC, or fatty casts), depending on the type of glomerulonephritis. Most cases are immune-mediated. Herpes simplex virus type 1 causes vesicles and pustules that usually are located on the vermilion border of the lip. The virus is located in the sensory ganglia; thus, lesions appear periodically and recede.
a- Hereditary spherocytosis, hemolytic anemia b- obstructive type of jaundice, either due to intrahepatic cholestasis (e.g., drug-induced oral contraceptives) or extrahepatic cholestasis c- alcoholic hepatitis, which produces a mixed jaundice (CB 2050%), due to decreased uptake and conjugation of unconjugated bilirubin (UCB) and destruction of bile ductules among liver cells leading to an increase in CB in the blood d- hepatitis in which there is diffuse necrosis of hepatocytes (e.g., hepatitis A). e- Gilberts disease, which is an autosomal dominant disease characterized by decreased uptake and conjugation of bilirubin particularly exacerbated by the fasting stat Acute pyelonephritis, which is an acute bacterial infection (usually caused by Escherichia coli) that involves the tubules and interstitium. Classic signs include fever, flank pain, and WBC casts accompanied by signs of a lower urinary tract infection (e.g., suprapubic discomfort, dysuria, and urinary frequency). The majority of cases occur in women who have recurrent lower urinary tract infections and vesicoureteral reflux, which refers to the passage of urine into the ureter through an incompetent ureterovesical junction. Infection then ascends into the renal pelvis and into the renal parenchyma. Neutrophils in the tubules produce a WBC cast, which is an excellent marker of acute pyelonephritis. Fever, flank pain, and WBC casts are not present in lower urinary tract infections. Over flow proteinuria - protein loss is variable (0.2 to >10g/24 hours). It is a low molecular weight proteinuria in which the amount filtered exceeds the tubular capacity to reabsorb it. The patient most likely has multiple myeloma, a malignant plasma cell disorder associated with Bence-Jones proteinuria (light chains in the urine). He has anemia and renal failure (BUN:creatinine ratio is 10). There is a disparity in the protein readings for the reagent strip and sulfosalicylic acid (SSA). This occurs in multiple myeloma with Bence-Jones proteinuria, because the reagent strip for protein detects albumin and not globulins (e.g., light chains), while the SSA reaction detects albumin and globulins. A bone marrow aspirate confirms the presence of malignant plasma cells, while a serum and urine immunoelectrophoresis determine the immunoglobulin and light chain that is involved. Clinical manifestations of Dresslers syndrome include fever, precordial friction rub, and pain that increases on inspiration but lessens when the patient leans forward. Fibrinous pericarditis also may occur in the first week of an acute transmural infarction. However, the pericarditis in this time frame is due to increased vessel permeability not related to immunologic damage of the pericardium. Coxsackievirus is the most common cause of pericarditis A ventricular aneurysm is clinically recognized within 4 to 8 weeks after a transmural infarction. It presents with a precordial bulge during systole as blood enters the aneurysm causing anterior chest wall movement. The most common complications are heart failure and embolization of clot material.
A defect in the carboxylation of coagulation factors is associated with vitamin K deficiency, which may produce bleeding diatheses (ecchymoses, gingival bleeding) but not glossitis and gum inflammation. The vitamin Kdependent coagulation factors are prothrombin, factor VII, factor IX, factor X, and protein C and S. Most vitamin K is synthesized by colonic bacteria; therefore, a poor diet is not likely to produce a deficiency Defective collagen synthesis is associated with scurvy, which is caused by a dietary deficiency of vitamin C (ascorbic acid). The photograph shows inflammation and bleeding of the gingival papillae. Other cAharacteristic findings include painful glossitis (sore tongue) and the presence of corkscrew hairs and perifollicular hemorrhage. Vitamin C is important in the hydroxylation of proline and lysine. Normally, hydroxylated lysyl residues become the binding site for the cross-links that bind chains together to increase the tensile strength of collagen. In scurvy, deficiency of vitamin C leads to diminished tensile strength of collagen, causing venules and capillaries to rupture (causing ecchymoses and pinpoint hemorrhages) and bleed into joints and subperiosteal tissue (causing pain with movement). Medulloblastoma is a common primary malignancy of the brain in children. The majority of primary brain tumors in children arise in the posterior fossa, particularly in the cerebellum. Cystic cerebellar astrocytomas are the most common primary brain tumors in children. They do not invade the fourth ventricle and in most cases, can be surgically excised. Glioblastoma multiforme is the most common primary brain cancer in adults. It is a high-grade astrocytoma that primarily occurs in the cerebral cortex & can cross corpus callosum Cimetidine, an imidazole compound that blocks histamine receptors, inhibits cytochrome enzymes in the liver microsomal mixed-function oxidase system. This system is located in the smooth endoplasmic reticulum (SER) and is responsible for drug and chemical metabolism. Inhibition of the system produces drug toxicity. Post MI reinfarction there is a presence of CK-MB post 24-72 hrs , where CK-MB peaks in 24 hours and returns to normal within 72 hours. Both serum troponin I and troponin T peak in 24 hrs and return to normal in 7-10 days Angina pectoris causes myocardial ischemia without causing myocardial cell injury. Angina pectoris does not lead to an increase in CK-MB, troponin-I, and troponin-T. Pericarditis is inflammation of the surface lining of the heart, causing precordial chest pain and a pericardial friction rub. No damage to tissue or in cardiac enzymes Right ventricular infarction produces signs of right-sided heart failure (neck vein distention, dependent pitting edema) Rupture caused by necrosis of the myocardial wall usually occurs on days 3 to 7 following an MI. Rupture of the anterior wall produces cardiac tamponade with muffled heart sounds and neck vein distention followed by rapid death. Liver cell (hepatic) adenomas are a complication of oral contraceptive use. These benign tumors arise from hepatocytes and have a tendency to rupture and cause intraperitoneal hemorrhage. Ruptured ectopic pregnancy is the most common cause of intra-abdominal hemorrhage in young women. Goodpasture syndrome is more common in men and is associated with IgG antibasement membrane antibodies that are directed against pulmonary capillary and glomerular capillary basement membranes (type II hypersensitivity reaction). Pulmonary involvement with hemoptysis
usually occurs before renal failure. Renal failure is most often due to rapidly progressive crescentic glomerulonephritis, which is associated with a nephritic presentation (hematuria, RBC casts, mild proteinuria) Treatment options include plasma exchange, immunosuppressive therapy with corticosteroids and cyclophosphamide, and renal transplantation.
good pastures syndrome Diffuse membranous glomerulopathy is the most common cause of the nephrotic syndrome in adults (pitting edema, fatty casts). It is an immunocomplex disorder with deposition of immunocomplexes in a subepithelial location, which produce granular immunofluorescence. Focal segmental glomerulosclerosis is most often associated with AIDS and with intravenous heroin addiction. It causes the nephrotic syndrome. Glomerular injury is due to cytokine damage of the visceral epithelial cells. It is not an immunocomplex disease, therefore the immunofluorescent study is negative Focal segmental glomerulosclerosis is most often associated with AIDS and with intravenous heroin addiction. It causes the nephrotic syndrome. Glomerular injury is due to cytokine damage of the visceral epithelial cells. IgA glomerulonephritis is an immunocomplex type of glomerulonephritis associated with episodic bouts of microscopic or macroscopic hematuria. The immunocomplexes produce granular immunofluorescence primarily located in the mesangium Minimal change disease (lipoid nephrosis) is the most common cause of the nephrotic syndrome in children. Cytokine damage to the basement membrane causes a loss of the negative charge, resulting in a selective loss of albumin in the urine.
Fibroadenoma of the breast.It is the most common movable mass lesion in the breast in women younger than 35 years of age. Fibroadenomas are estrogen-sensitive and often increase in size during the menstrual cycle or during pregnancy. It is a benign tumor that derives from the stroma.
Fibrocystic change is the most common breast mass in women < 50 years of age. It is considered to be a distortion of normal cyclic breast changes. Components of fibrocystic change include small and large cysts, fibrosis, proliferation of small ductules/acini in the terminal lobule (called sclerosing adenosis), and ductal hyperplasia. Pagets disease is a ductal carcinoma that has infiltrated into the squamous epithelium of the nipple causing a rash and ulceration of the surface of the nipple. It is histologically similar to Pagets disease of the vulva, except it is a ductal cancer infiltrating the nipple epithelium versus an adenocarcinoma arising within the epidermis
Bordetella pertussis is the cause of whooping cough. The lymphotoxin in this bacteria inhibits signal transduction by chemokine receptors which prevents lymphocytes from entering lymph nodes leading to lymphocytosis. In polycythemia, all cell lines except lymphocytes are increased. An increase in basophils and mast cells causes the release of histamine, which produces flushing of the face (called plethora), headaches, and pruritus after bathing. Clinical findings highly predictive of colorectal cancer in this patient include weight loss, change in consistency of stools, and blood mixed in with stools. Angiodysplasia refers to the presence of dilated vascular channels in the submucosa of the cecum, which often rupture and produce massive lower gastrointestinal bleeding. Commonly causes passage of large volumes of blood per rectum (hematochezia) that are capable of producing dizziness due to hypotension or hypovolemic shock. Acute drug-induced tubulointerstitial disease. Key clinical features of the disease are an abrupt onset of fever, oliguria, and a rash. Laboratory findings include a serum BUN:creatinine ratio < 15 (renal azotemia), WBCs and WBC casts, proteinuria, eosinophiluria, and the presence of eosinophilia in the peripheral blood. Cessation of the drug causes reversal of the renal failure. Prerenal azotemia refers to oliguria that is due to hypoperfusion of the kidneys from a decrease in cardiac output. The serum BUN:creatinine ratio > 15 and the urine sediment is normal. Renal papillary necrosis refers to sloughing off of the renal papillae. It produces gross hematuria, proteinuria, and colicky flank pain. An intravenous pyelogram shows a ring defect where one or more papillae used to reside. Other causes of renal papillary necrosis include diabetes mellitus, sickle cell trait/disease, and acute pyelonephritis. -fetoprotein is a tumor marker that is increased in 70% of cases of hepatocellular carcinoma. Paroxysmal nocturnal hemoglobinuria is an acquired memebrane defect involving common myeloid stem cells. Mutation in DAF anchor, which normally neutralizes complement attached to RBCs, neutrophils, and platelets at night. Loss of DAF causes intravascular complement destruction of RBCs, neutrophils, and platelets leading to pancytopenia and hemoglobinuria. There is an increase incidence of vessel thrombosis due to release of aggregating agents from destroyed platelets. Cold auto-immune hemolytic anemia is IgM-mediated and, in most cases, produces an intravascular hemolysis. Most cases are idiopathic. Known causes include infection (Mycoplasma, infectious mononucleosis) and cancer (chronic lymphocytic leukemia). The majority of immune hemolytic anemias have a positive direct Coombs test. Warm autoimmune hemolytic anemia is common in SLE. The RBCs are coated by IgG and C3b causing them to be phagocytosed by splenic and liver macrophages. The direct Coombs test is positive.
Asbestos body (ferruginous body), which consists of an amphibole type of asbestos fiber coated by protein and iron (ferritin), the latter synthesized by alveolar macrophages that phagocytose the asbestos body and coat the fiber with ferritin. Primary bronchogenic carcinoma is the most common cancer associated with asbestos exposure.
Decompression sickness is a gas embolism. Due to a scuba diver arising to the surface fast. Under increased pressure, nitrogen gas moves from the alveoli through the blood and dissolves in tissue and blood. Rapid ascent forces nitrogen to move out of tissue and blood as bubbles. It forms gas emboli in the blood that obstruct blood vessels, causing ischemic damage to bone (aseptic necrosis of the femoral head), spinal cord (hemiparesis), and other tissues. Gas bubbles within skeletal muscle and supporting tissues around joints cause a painful condition called the bends. Treatment involves recompression in a compression chamber to force the gas bubbles back into solution followed by slow decompression to prevent them from re-forming. Cells that are mucin postitive indicates adenocarcinoma cells. Dysplastic squamous cells have large, hyperchromatic nuclei and do not develop as isolated cells or in clusters, as in this case. Coagulation necrosis is associated with sudden cessation of arterial blood flow to the tissue. Diabetics commonly have atherosclerotic peripheral vascular disease that produces gangrene involving the lower extremities. Caseous necrosis is a variant of coagulation necrosis and appears as a soft, cheeselike material that exudes from the center of a granuloma. Caseous necrosis occurs primarily in patients with mycobacterial infection (e.g., tuberculosis) or systemic fungal infection (e.g., histoplasmosis). Enzymatic fat necrosis occurs in the pancreas, where it appears as chalky white areas in adipose tissue in and around an area of inflammation (acute pancreatitis). Fibrinoid necrosis occurs in small muscular arteries, arterioles, venules, and glomerular capillaries. Immunologic damage to these vessels causes leakage of plasma proteins into the wall of the vessels. It is commonly associated with small-vessel vasculitis in hypertension and with deposits of antigen-antibody complexes in vessel walls in immunocomplex disease. Liquefactive necrosis is associated with softening of tissue caused by the release of hydrolytic enzymes from neutrophils, often in the setting of acute bacterial infection. Hypertrophic cardiomyopathy, the most common cause of sudden cardiac death in young people. It is an AD with nearly complete penetrance. Usually a mutation in the myosin heavy chain gene on chromosome 14. There is hypertrophy of the myocardium with disproportionately greater hypertrophy of the interventricular septum (IVS) than the free left ventricular wall, as evident in the photograph. IVS hypertrophy may obstruct blood flow through the outflow tract; however, most patients do not have severe obstruction of the outflow tract. As blood exits the left ventricle, the anterior leaflet of the mitral valve is drawn against the asymmetrically hypertrophied IVS causing the obstruction. In hypertrophic cardiomyopathy the left ventricle is hypertrophied, it is noncompliant and restricts filling. A harsh systolic ejection murmur is best heard along the left sternal border and has a palpable double apical impulse. Sudden death is due to ventricular tachycardia/fibrillation, most likely related to the aberrant myofibers in the conduction system. -Blockers is therapy, because they prolong diastole allowing for more blood to enter the left ventricle. Aortic regurgitation is characterized by an early diastolic murmur directly after the second heart sound. The left ventricle would be dilated and hypertrophied Prevalence is the total number of people with disease in the population under study. The formula is TP+FN/TP+FN+TN+FP The sensitivity of a test is the likelihood of having positive test results in patients who have a selected disease. Since people with disease either have TP or FN test results, the formula for
calculating the sensitivity of a test is TP/ TP+FN. The less the FN rate, the greater the sensitivity of the test. Tests with 100% sensitivity are most often used as screening tests for disease. If the test result is negative, the likelihood (predictive value of a negative test result, PV) is a TN rather than a FN is 100%, because a test with 100% sensitivity has no FNs. Since tests with 100% sensitivity always have a PV (TN/TN+FN) of 100%, a negative test result excludes disease. There is cardiac hypertrophy when there is an increase in workload. The muscle has to contract against increased afterload (resistance the heart must overcome to pump blood out of the heart) or preload (increased volume of blood that the ventricle must eject). Increased pressure on the ventricles changes gene expression resulting in duplication of sacromeres and concentric thickening of ventricular wall. Essential HTN is the MCC of this increase in afterload and peripheral resistance in the arterioles. Aortic Regurgitation is due to Improper closing of the aortic valve leads to volume overload in the left ventricle as blood drips back into the left ventricle in diastole. This increasese preload in the left ventricle causing LV hypertrophy and dilatation. Rat poison contains warfarin, an anticoagulant that inhibits epoxide reductase, which normally converts inactive vitamin K to active vitamin K in the liver. Lack of active vitamin K leads to decrease in factor 7,9,&10. Bleeding from the mouth and gastrointestinal tract is a sign of overanticoagulation. Both the PT and aPTT are prolonged, because factor X and prothrombin are present in the final common pathway. The best treatment for this patient is infusion of fresh frozen plasma, which contains functional vitamin Kdependent factors Warfarin doesnt effect the platelet production or function therefore bleeding time and platelet count are normal. The PT evaluates the activity of coagulation factors in the extrinsic system (factor VII) to the formation of a fibrin clot in the final common pathway (factor X, factor V, prothrombin, fibrinogen). The aPTT evaluates the activity of the coagulation factors in the intrinsic system (factor XII, factor XI, factor IX, factor VIII) to the formation of a fibrin clot. A decreased platelet count (thrombocytopenia) prolongs the bleeding time, because the end of the bleeding time is marked by the formation of a temporary platelet plug consisting of platelets held together by fibrinogen. Signs of thrombocytopenia include petechiae, bleeding from superficial scratches, and easy bruising. Both PT and aPTT are normal in thrombocytopenia, because coagulation factors are normal. The most common cause of a prolonged bleeding time is aspirin or other nonsteroidal antiinflammatory drugs. The most common cause of a prolonged bleeding time and prolonged aPTT is von Willebrands disease. Warfarin does not affect the bleeding time, which evaluates platelet function. Healing fractures there is an increased osteoblastic activity which increase ALP only An increase in both ALP and GGT is present in intrahepatic and extrahepatic cholestasis. Increased pressure of bile on the bile duct epithelium causes increased synthesis of both enzymes. A normal serum ALP and increased serum GGT is present in alcoholics. Alcohol induces synthesis of enzymes located in the smooth endoplasmic reticulum of the liver. These include enzymes in the cytochrome P450 system and GGT. -glutamyltransferase Lack of insulin in DKA reduces capillary protein lipase which is required to hydrolize chlomicrons into VLDL/LDL
Absent LDL receptors cause and increase in LDL/Cholestrol causing type II familial hypercholestremia with a characteristic finding of Achilles xanthomas. Hypovolemic shock caused by blood loss (tachycardia with weak pulse; cold, clammy skin; decreased blood pressure), most likely a ruptured spleen and/or liver. In Hypyvolemia, the hemoglobin and RBC count are normal at 1st then within a few hours, plasma begins to be replaced and the RBC count and hemoglobin level drop. Cardiac output( will decrease leading to underfilling of the aortic arch, which activates the sympathetic nervous system, subsequently releasing catecholamines. Catecholamines cause venoconstriction, increased myocardial contraction, increased heart rate, and vasoconstriction of the smooth muscle cells of the peripheral resistance arterioles. In hypovolmeia a decreased renal blood flow activates the renin-angiotensin-aldosterone system, causing the release of angiotensin II, which produces peripheral arteriolar vasoconstriction. Antidiuretic hormone is also released, which produces vasoconstriction of peripheral resistance arterioles. Vasoconstriction of arterioles in the skin shunts blood to more important areas of the body, causing cold, clammy skin. Hypovolmia causes a decrease in LVEDV because there is less blood in the circulation and less venous return to the heart. Mixed venous O2 is best indicator of tissue hypoxia . It is measured in the right heart with a SwanGanz catheter and indicates the degree of extraction of O2 from the blood delivered to tissue. It is decreased in hypovolemic shock Antitopoisomerase antibodies (antiScl-70) occur in systemic sclerosis (scleroderma). Systemic sclerosis is characterized by replacement of subcutaneous tissue with collagen and a vasculitis involving interlobar arteries and arterioles in the kidneys causing hypertension and renal infarctions. Postreceptor defects are mainly responsible for insulin resistance in type 2 diabetes mellitus. Insulin receptors with tyrosine kinase activity are located on adipose cells and muscle cells. Examples of postreceptor defects are abnormalities in tyrosine kinase or problems with the translocation of the glucose transport units located in the Golgi apparatus (GLUT-4) receptors to the cell membrane for uptake of glucose. HLA-DR3 and HLA-DR4 antigens occur only in type 1 diabetes mellitus. Presence of these HLA antigens place patients at increased risk for autoimmune destruction of the islet cells, which is often triggered by a viral infection. CD8 cytotoxic T cells and antibodies directed against islet cells destroy the -islet cells (insulitis) in the pancreas only in type 1 diabetes mellitus. Barbiturate OD shows an ABG that is uncompensated respiratory acidosis with hypoxemia. Chronic bronchitis is an obstructive lung disease associated with chronic respiratory acidosis and hypoxemia. Inability to clear CO2 from the lungs because of inflammation of the segmental bronchi and terminal bronchioles decreases alveolar oxygen, causing hypoxemia and an A-a gradient > 30 mm Hg. A decrease in renal blood flow activates the RAA system, resulting in hypertension caused by renal retention of sodium by aldosterone and vasoconstriction of the peripheral resistance arterioles by angiotensin II. C. trachomatis. Two distinct forms of the organism that develop in vacuoles within metaplastic squamous cells are the elementary body (metabolically inert but infective) and the reticulate body
(metabolically active but not infective). Binary fission of the reticulate bodies in the vacuoles of the infected cell results in the production of numerous elementary bodies. Urinalysis findings suggest acute urethral syndrome, which is also due toC. trachomatis. The treatment is a 1-gm oral dose of azithromycin or doxycycline HPV produces koilocytotic atypia in squamous cells, which is characterized by a halo surrounding a pyknotic (dense) nucleus. chronic bronchitis (productive cough for 20 years) that has led to chronic obstructive pulmonary disease. Hypoxemia (decreased arterial Po2) causes a decrease in O2 saturation, which accounts for the patients cyanosis. C. neoformans is the most common systemic fungus causing chronic meningitis in patients with AIDS. Chronic bronchitis is characterized by obstruction of airflow due to inflammation and increased mucus production at the level of the segmental bronchi and terminal bronchioles. During expiration, air with high concentrations of CO2 is trapped behind obstruction by mucus plugs in the proximal terminal bronchioles. Retention of CO2 in the alveoli increases the arterial Pco2 (60 mm Hg) causing respiratory acidosis (pH 7.33). Compensation for respiratory acidosis is metabolic alkalosis (HCO334 mEq/L). A renal stone presents with a sudden onset of flank pain with radiation of pain into the ipsilateral groin. Hematuria is invariably present. Tinea corporis have annular lesions with scaly erythematous margins and central clearing. A KOH examination of material taken from the leading edge of the lesion showed yeasts and hyphae. T. rubrum is the most common cause of fungal infections involving the skin (tinea corporis), feet (tinea pedis), nails (tinea unguim), and groin (tinea cruris). The yeast and hyphae are limited to the stratum corneum; therefore, they are easily scraped off with a scalpel blade and identified under the microscope after the keratin debris is removed by KOH. CMV causes encephalitis in immunocompromised patients. Thiazide diuretics inhibit the Cl channel in the Na+-Cl cotransporter located in the early distal tubule. This causes an increase in the urinary loss of Na+ (hyponatremia) and Cl (hypochloremia). Increased delivery of Na+ to the late distal and collecting tubules results in augmented exchange of Na+ for K+ in the aldosterone-dependent Na+ channels resulting in increased urinary loss of K+ (hypokalemia with U waves on an ECG). When K+ is depleted, Na+ exchanges with H+ ions causing increased synthesis and reabsorption of HCO3 causing metabolic alkalosis. Mineralocorticoid deficiency (e.g., Addisons disease, 11-hydroxylase deficiency). There is inhibition of Na+ reabsorption and K+ secretion by the aldosterone-dependent Na+ and K+ channels located in the distal tubule and collecting ducts causing a hypertonic loss of Na+ in the urine (hyponatremia) and retention of K+ (hyperkalemia with peaked T waves). Due to dysfunction of the aldosteronedependent H+/K+ ATPase pump in the collecting tubules, there is retention of H+ ions and a subsequent lack of synthesis of HCO3, which produces metabolic acidosis. The excess H+ ions combine with Cl anions producing a normal anion gap type of metabolic acidosis In chronic renal failure there is tubular cell dysfunction resulting in retention of K+ (hyperkalemia with peaked T waves on an ECG) and an increased anion gap type of metabolic acidosis due to retention of organic acids like sulfuric and phosphaturic acid. Secretory type of diarrhea (e.g., travelers diarrhea due to enterogenicEscherichia coli, cholera). In these conditions a toxin activates adenylate cyclase in enterocytes causing the ion pumps in the
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small intestine to secrete isotonic fluid. Loss of isotonic fluid does not alter the serum Na+concentration. Diarrheal fluid is rich in K+ and HCO3, the former resulting in hypokalemia and the latter a normal anion gap type of metabolic acidosis. The serum Cl is increased, because it replaces the HCO3 anions that are lost in the diarrheal fluid to maintain electroneutrality. Mineralocorticoid excess (e.g., primary aldosteronism; 11-hydroxylase deficiency). Enhanced function of aldosterone-mediated Na+-H+ channels in the late distal and collecting ducts increases the synthesis of HCO3 leading hypernatremia, hypokalemia (initially exchanged with Na+ until depleted), and metabolic alkalosis (Na+ exchanges with H+; for every H+ lost in the urine there is a corresponding HCO3 entering the blood) Intussusception has a peak incidence between ages 1 and 5. In children, the terminal ileum invaginates into the cecum. Mounds of hyperplastic lymphoid tissue in Peyers patches serve as the nidus for the intussusception. The entrapped bowels show signs of obstruction and ischemia (colicky pain with bloody diarrhea, respectively). An oblong mass is frequently palpated in the midepigastrium (Dances sign). Congenital pyloric stenosis presents in the second or third week of life with persistent vomiting of non-bile-stained fluid and a walnut-shaped mass in the left upper quadrant. Bloody stools are not present. Duodenal atresia presents at birth with projectile vomiting of bile-stained fluid. The area of atresia begins distal to the entrance of the common bile duct into the duodenum. Air is present in the stomach and the proximal duodenum (double-bubble sign). An increased association with Down syndrome. Meckels diverticulitis presents with right lower quadrant pain and rebound tenderness (cannot be distinguished from acute appendicitis). A radionuclide scan to identify parietal cells in the diverticulum is the screening test of choice. Infiltrating ductal carcinoma presents as steallate apperacne in fat tissue of breast. Estrogen exposure without progesterone increases the risk for developing hyperplasia of the ductal epithelium, which may develop into atypical ductal hyperplasia, dysplasia, and cancer. Risk factors associated with unopposed estrogen exposure include early menarche and late menopause, nulliparity, postmenopausal obesity, and a history of endometrial carcinoma. Patients with splenic dysfunction and sickle cell anemia are very susceptible to sepsis from S. pneumoniae(encapsulated bacteria); hence, the importance of Pneumovax at an early age. A properly functioning spleen normally has macrophages in the cords of Billroth that will remove nuclear remants from RBCs w/o destroying the integrity of the cell membrane. Cryptococcosis is caused by C.neoformans. It has a polysaccharide capsule. It is contracted by exposure to pigeon excreta. It also can produce graulomatous inflammation with caseous necrosis in the lungs C. immitis produces spherules containing endospores. C. immitis pneumonia is contracted primarily in the desert regions of the southwestern United States, particularly in Arizona, New Mexico, and southern California. H. capsulatum are phagocytosed by macrophages. Histoplasmosis is common in immunocompromised patients (e.g., in those with AIDS), spelunkers living in the Ohio-Tennessee valley area of the United States, and chicken farmers. P. carinii appears on a silver stain as cysts with centrally located dots. P. carinii usually produces pneumonia in patients with HIV when the CD4 T-cell count approaches 200/mm3.
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Klinefelters syndrome (47,XXY) is associated with atrophy of the testicles (decreased testicular volume), gynecomastia, and a female hair distribution due to hyperestrinism Chronic bronchitis can lead to chronic respiratory acidosis and hypoxemia. Respiratory acidosis and hypoxemia produce vasoconstriction of the pulmonary vessels, which eventually produces pulmonary hypertension (tapering of the vessels in the radiograph) and right ventricular hypertrophy (prominence of the right border of the heart in the radiograph). The combination of pulmonary hypertension and right ventricular hypertrophy is called cor pulmonale. Commonly develop right-sided heart failure (jugular neck vein distention and dependent pitting edema). N. gonorrhoeae is the most common cause of PID. The presence of fever, abdominal pain, and adnexal tenderness with movement of the cervix (chandelier sign) suggests pelvic inflammatory disease (PID). Treatment is ceftriaxone T. vaginalis is a flagellated protozoan that produces cervicitis and vaginitis. Syringomyelia, which is a degenerative disease that produces a fluid-filled cavity in the cervical spinal cord, causing cervical cord enlargement. As the cavity expands, it destroys the crossed lateral spinothalamic tracts (loss of pain and temperature sensation) and anterior horn cells (atrophy of intrinsic muscles of the hand). ALS is a degenerative disease that causes the destruction of upper and/or lower motor neurons. Sensory abnormalities do not occur in ALS. Guillain-Barr syndrome is the most common acute peripheral neuropathy and frequently occurs after certain infections (e.g.,Mycoplasma pneumoniae pneumonia, Campylobacter jejuni dysentery). It is an autoimmune demyelination syndrome that involves peripheral and spinal nerves. It produces rapidly progressive ascending motor weakness. Multiple sclerosis is an autoimmune disease that causes destruction of myelin and myelinproducing cells (e.g., oligodendrocytes). Features include blurry vision (optic neuritis), paresthesias, spastic paraparesis, intention tremors, nystagmus, ataxia, and scanning speech. Vitamin B12 deficiency produces a macrocytic anemia and subacute combined degeneration of the spinal cord. Myelopathy involving the posterior columns causes a loss of proprioception (joint sensation) and vibratory sensation. Myelopathy involving the lateral corticospinal tract causes upper motor neuron disease with signs of spasticity. Most normal ranges are established by adding and subtracting 2 standard deviations (SD) from the mean of the test, which encompasses 95% of the normal population. Therefore, 5% of the normal population will be outside out of the normal range (outlier). The likelihood of an outlier increases as the number of tests ordered increases. The likelihood of an outlier = 100 (0.95n100), where n is the number of tests ordered. In this patient, five tests were ordered: 100 (0.955100) = 100 (0.77100) = 23% chance of an outlier in one of the five tests. Endotoxins released during sepsis associated with E. coli directly damage endothelial cells, causing the release of NO and prostaglandin I2 (prostacyclin), both of which are vasodilators. NO is a free radical gas that is produced mainly by macrophages and endothelial cells. Arteriolar vasodilation is responsible for the warm skin, which characterizes septic shock versus other types of shock (e.g., hypovolemic and cardiogenic shock), where there is vasoconstriction of arterioles and cold, clammy skin. Complement C3b is an opsonizing agent that facilitates phagocytosis by leukocytes. Leukotriene B4 activates neutrophil adhesion molecules and is a chemotactic agent for leukocytes
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Leukotrienes C4, D4, and E4 cause vasoconstriction, bronchospasm, and increased vessel permeability. Thromboxane A2 causes vasoconstriction and inhibits platelet aggregation. A maxim in surgery is that if a patient has what looks like acute appendicitis (fever, right lower quadrant pain with rebound tenderness, neutrophilic leukocytosis), consider acute Meckels diverticulitis. A Meckel diverticulum is a vitelline (omphalomesenteric) duct remnant. It is a true diverticulum, because it has all layers from mucosa to serosa. Acute cholecystitis presents with fever; right upper quadrant (not lower quadrant) constant, dull pain 15 to 30 minutes after eating; vomiting; radiation of pain to the right scapula/shoulder; and jaundice (25%) Crohns disease presents with recurrent right lower quadrant colicky pain (obstruction) with diarrhea Ischemic colitis presents with severe pain in the splenic flexure area (left upper quadrant) shortly after eating. The splenic flexure of the large bowel, which is a watershed area of two overlapping blood suppliessuperior mesenteric artery and inferior mesenteric artery. The pain in the splenic flexure after eating is classic mesenteric angina due to decreased blood flow to the splenic flexure. The pain is severe enough to cause people to lose weight, as in this patient. The bleeding is due to a localized infarction of the mucosa. Repair by fibrosis can eventually produce an ischemic stricture with large bowel obstruction. The barium enema shows thumb-printing of the colonic mucosa due to edema of the mucosa from infarction. Carbon monoxide diffusion capacity of the lung is dependent on CO reaching the alveolus, CO crossing the alveolar-capillary septum, and CO binding to hemoglobin (Hb) in RBCs in the pulmonary capillary. Carbon monoxide diffusion capacity is increased in polycythemia, because an increase in RBC mass causes more CO to bind with Hb; therefore, less CO is expired in air. In contradistinction, the DL is decreased in anemia (more CO is present in expired air), because there is a decrease in RBC mass and less binding of CO to Hb. Emphysema is associated with destruction of the distal airways and the pulmonary capillary bed, which restricts CO from diffusing through the alveolar-capillary septum, causing a decrease in the DL (more CO in expired air). Zinc is a cofactor for collagenase, which is important in remodeling of a wound. In remodeling, type III collagen is replaced by type I collagen, which increases tensile strength in the wound to 80% of the original strength. Wound healing is impaired when there is Zinc deficiency such in alcoholics Chromium is a cofactor for insulin, which helps insulin bind to receptors in the adipose and muscle, hence aiding in glucose tolerance factor. Chromium deficiency is associated with impaired glucose tolerance and peripheral neuropathy. Copper is a cofactor for lysyl oxidase, which normally places cross-bridges between the tropocollagen molecules. Selenium is a cofactor for glutathione peroxidase, which neutralizes peroxide and peroxide free radicals in cells (e.g., RBCs). Selenium deficiency is associated with muscle pain and weakness as well as a cardiomyopathy.
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Carbon monoxide (CO) commonly occurs in house fires. CO has a 230 to 270 greater binding affinity for heme groups than O2. Since the SaO2 is the average percentage of O2 bound to heme groups in hemoglobin (Hb), it is decreased in CO poisoning. In CO poisoning, a decrease in SaO2 causes tissue hypoxia (lack of O2 in tissue), which results in anaerobic glycolysis. Lactic acid is the end-product of anaerobic glycolysis and produces metabolic acidosis with a decrease in serum bicarbonate Pseudomembranous colitis caused by Clostridium difficile. History of nosocomial pneumonia suggests that the pseudomembranous colitis developed after antibiotic therapy for the pneumonia. Antibiotics destroy the normal colonic bacteria and allow C. difficile to proliferate. C. difficile produces toxins A and B, which damage the mucosa and submucosa. It is a noninvasive pathogen. A cytotoxin assay of stool is the best screening test. Infectious mononucleosis, which is caused by the Epstein-Barr virus (EBV) usually transmitted by saliva (kissing disease). Atypical lymphocytes with dark chromatin and abundant blue-gray cytoplasm these are antigenically stimulated T cells that are responding to B cells infected by the virus. Recall that EBV has CD21 receptors on B cells and causes them to produce plasma cells that generate IgM heterophile antibodies that are used to screen for the infection. The heterophil antibodies that are specific for mononucleosis are IgM antibodies against horse, sheep, or bovine RBCs. Antibodies that are also useful diagnosing mono, particularly if the heterophile antibody test is negative, are anti-viral capsid antigen antibodies and antibodies against early antigen, both of which have >90% sensitivity and specificity. Hepatosplenomegaly and painful generalized lymphadenopathy are invariably present in mononucleosis. Left-sided heart failure (dyspnea, pulmonary edema with inspiratory crackles) causing a decrease in cardiac output leading to a decrease in renal blood flow, glomerular filtration rate, and oliguria. The FENa+ Fractional excretion of sodium is a sensitive indicator of tubular function. Values < 1% indicate intact tubular function, while those > 2% indicate tubular dysfunction. In prerenal azotemia, tubular function is intact; therefore, the FENa+ < 1%. Pericarditis with effusion is the most common cardiac manifestation of SLE. Inflammation of serosal epithelium (e.g., pericardium, pleura) is a characteristic finding in SLE. Immunocomplexes directed against the pericardium cause increased vessel permeability and leakage of a fibrinous exudate onto the serosal surface, producing a friction rub heard over the precordium during filling and emptying of the heart. This prevents filling of the right side of the heart during inspiration (neck vein distention), when venous blood is normally drawn into the right side of the heart by the increasing negative intrathoracic pressure. Decreased right-sided filling causes a decrease in cardiac output, resulting in decreased pulse amplitude and blood pressure during inspiration as well; this is called pulsus paradoxus. The pain caused by inflammation of the pericardium is aggravated by leaning back and is relieved by leaning forward. Fluid must be removed from the pericardial sac by paracentesis or death will occur. Aortic dissection occurs in elderly men with hypertension or young individuals with defects in collagen (Ehlers-Danlos syndrome) or elastic tissue (Marfan syndrome). Blood enters an intimal tear and dissects proximally and/or distally through the weakened media of the aorta. Pain radiates into the back and is often associated with absent upper extremity pulses. Constrictive pericarditis is most often idiopathic or a complication of tuberculosis. Incomplete filling of the cardiac chambers is caused by thickening of the parietal pericardium.
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Restrictive cardiomyopathy is characterized by decreased ventricular compliance (decreased filling of the heart) caused by an infiltrative disease of the myocardium (e.g., amyloid). Dermatoyositis usually in women from 40-60. Muscle pain and atrophy commonly occur, with the shoulders being particularly involved. Heliotrope eyelids, or raccoon eyes, is very characteristic in this disease. Gottrons patches, which are purple-colored papules over the knuckles and proximal interphalangeal joints. There is an increase in serum creatine kinase, due to antibody destruction of muscle. Muscle biopsy shows muscle damage with a lymphocytic infiltrate. Systemic sclerosis is characterized by excessive production of collagen that primarily targets the skin (scleroderma), gastrointestinal tract, lungs, and kidneys. SIADH a decrease in POsm and an increase in serum ADH occurs . Often caused by ectopic secretion of ADH by a primary small-cell carcinoma of the lung (left hilar mass; small, hyperchromatic cells in the sputum). The most common cause of this lung carcinoma is cigarette smoking. Excess ADH causes increased reabsorption of free water and a dilutional hyponatremia (decreased POsm). Water moves by osmosis from the extracellular fluid compartment into the intracellular fluid compartment, causing cerebral edema and an increase in intracranial pressure, which is manifested by papilledema (swelling of the head of the optic nerve). The coarse inspiratory crackles are caused by increased mucus in the segmental bronchi and terminal bronchioles (chronic bronchitis). Diabetic Insipidus there is an increase in POsm and a decrease in UOsm . ADH is required to concentrate urine by reabsorbing free water from the collecting tubules of the kidneys. Therefore, absence of ADH (central diabetes insipidus) or refractoriness to ADH (nephrogenic diabetes insipidus) causes polyuria (urinary frequency) due to a loss of free water in the urine. Both types of diabetes insipidus decrease the urine osmolality and increase the POsm due to an increase in the serum sodium (hypernatremia). Schistosoma mansoni, which is found throughout Africa and Latin America including Puerto Rico. The larvae enter the superior mesenteric vein and from there into the portal vein. In the portal vein, they develop into adult worms that deposit eggs (have a sharp lateral spine) to which the host develops an inflammatory response marked by concentric fibrosis (pipestem cirrhosis) in the vessel wall. Complications of cirrhosis include portal hypertension, ascites, and esophageal varices, all of which are present in this patient. There is no association with smoking. Because it is an invasive helminthic infection, eosinophilia is present. Treatment is praziquantel. Primary sclerosing cholangitis PSC is an obliterative fibrosis of intrahepatic and extrahepatic bile ducts. It is a male dominant disease that is most often associated with inflammatory bowel disease (70%), particularly ulcerative colitis . Endoscopic retrograde cholangiopancreatography shows narrowing and dilation of bile ducts (beading). Complications include cirrhosis and cholangiocarcinoma. Drugs like alcohol and chemicals like polycyclic aromatic hydrocarbons in cigarette smoke induce this system by enhancing the rate of synthesis of NADPH-cytochrome P450 reductase and cytochrome P450 oxidase, which are the two key enzymes in the system. The increase in enzyme activity increases the metabolism of drugs, in this case, theophylline, leading to a suboptimal concentration of the drug. Idiopathic thrombocytopenic purpura in children and chronic autoimmune thrombocytopenia in adults, where an IgG antibody is directed against the GpIIb/IIIa fibrinogen receptor
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A deficiency of von Willebrand factorcleaving protease is found in thrombotic thrombocytopenic purpura, which produces a classic pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia with schistocytes, central nervous system dysfunction, and renal failure. Deficiency of von Willebrands factor prevents platelets from adhering to damaged endothelial cells. It also complexes with circulating factor VIII coagulant and prevents degradation of the factor. Therefore, a deficiency of von Willebrands factor automatically causes a corresponding decrease in VIII coagulant, which causes prolongation of the aPTT. Hemophilia A is an X-linked disorder characterized by a deficiency of factor VIII coagulant, causing a prolonged aPTT. Tubular adenoma (adenomatous polyp), which is a precursor lesion for colorectal cancer. Grossly, it is a stalked polyp that has a head with a lobulated, raspberry-like appearance. Microscopically, the fibrovascular stalk is lined by normal colonic mucosa and the branching head is surfaced by dysplastic (blue-staining) epithelial glands. Risk factors for colorectal cancer are polyp size > 2 cm and the presence of multiple polyps. The most common location for polyps is the sigmoid colon, which is also the most common site for colorectal cancer. Carcinoid turmors are neuroendocrine tumors that infiltrate the bowel wall and dont have polypoid appearance & usually localed in the tip of the appendix or terminal ileum Villous adenoma is a sessile polyp with finger-like projections (similar to villi in the small intestine) and is most commonly located in the rectosigmoid. It has a greater risk for developing colorectal cancer than a tubular adenoma. Gram-positive, lancet-shaped diplococci consistent with Streptococcus pneumonia, the most common cause of typical, community-acquired bronchial or lobar pneumonia. Typical pneumonia is characterized by high fever, productive cough, and physical signs of an alveolar exudate. Alveolar exudates are recognized on physical examination by increased tactile vocal fremitus, endinspiratory crackles, decreased percussion, and the E to A sign (patient says E but it sounds like A on auscultation). Atypical pneumonias are most often caused by Mycoplasma pneumoniae, which cannot be identified on a Grams stain. Atypical pneumonias have an insidious onset and are associated with low-grade fever, flulike symptoms, and an interstitial pneumonia. There are no signs of consolidation, and the cough is usually nonproductive Nosocomial (hospital-acquired) pneumonias with productive cough and yellow sputum are most likely caused by Staphylococcus aureus, a Gram-positive coccus. Nosocomial pneumonias associated with productive cough and green sputum are most often caused by Pseudomonas aeruginosa, a Gram-negative rod that produces the green pigment pyocyanin. P. aeruginosa is the most common cause of pneumonia in patients in intensive care units and is most commonly transmitted by respirators, since it is a water-loving organism. Klebsiella pneumonia, typical pneumonias with productive cough and thick mucoid sputum which appears as a thick Gram-negative rod surrounded by a mucoid capsule. It is a common cause of typical pneumonia in patients with alcoholism and is the most common typical pneumonia in elderly patients in nursing homes. Mitral valve prolapse (MVP) is the most common valvular lesion in the United States. A systolic click occurs when the valve prolapses into the left atrium during systole and is suddenly restrained by the chordae tendineae. The murmur following the click is caused by mitral regurgitation as blood leaks underneath the valve cusps into the left atrium. Most patients with MVP are asymptomatic. An
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increase of dermatan sulfate in the valve can cause myxomatous dengeneration. The most serious complication of MVP is rupture of the chordae leading to acute mitral regurgitation and left-sided heart failure. Aortic Regurgitation is a diastolic blowing murmur in the left side of the heart that occurs after S2 . Regurgitation murmurs are problems with closing of the valve; hence, blood dripping back into the left ventricle in early diastole is responsible for the murmur. Mitral stenosis has an opening snap followed by a mid diastolic rumbling murmur. Stenosis murmurs are problems with opening of the valve; hence, localizing the murmur of mitral stenosis in diastole. In mitral stenosis, the leaflets of the mitral valve are fibrotic and frequently calcified. It is most often caused by recurrent attacks of rheumatic fever over a period of time ranging from 210 years. Mitral Reurgitation is a pansystolic murmur located at the apex. Both the left atrium and left ventricle become volume overloaded. Drug induced hemolytic anemia can be caused by methyldopa. The drug is associated with a positive Coombs test and with hemolytic anemia. The drug alters Rh antigens on the surface of RBCs. IgG autoantibodies develop against the altered Rh antigens, attach to RBCs, and are phagocytosed by splenic macrophages (extravascular hemolysis). Patients develop fever, an unconjugated hyperbilirubinemia, spherocytes in the peripheral blood (membrane removed by macrophages), and polychromasia (blue-tinted young reticulocytes). G6PD deficiency is an X-linked recessive disease. Due to the lack of G6PD, there is a corresponding deficiency of glutathione (GSH), which is necessary to neutralize oxidants like hydrogen peroxide. Hereditary spherocytosis is an autosomal dominant disorder with a deficiency of ankyrin in the RBC membrane. Key findings include an extravascular hemolytic anemia (unconjugated hyperbilirubinemia), splenomegaly, calcium bilirubinate gallstones (black stones), an increase in the mean corpuscular hemoglobin concentration (MCHC), and the presence of spherocytes. Graves disease is a type of hyperthyroidism , which can present with exophthalmos, plus a history of palpitations (sinus tachycardia) and weight loss with no anorexia. Graves disease is an autoimmune disease with IgG thyroid-stimulating antibodies directed against the thyroid-stimulating hormone (TSH) receptor on the thyroid gland (type II hypersensitivity reaction), resulting in increased synthesis of thyroid hormone and a hypermetabolic state. Increased serum thyroxine (T4) suppresses the release of TSH from the pituitary gland. Radioactive iodine uptake increases, because the gland requires more iodine to keep pace with the synthesis of thyroid hormone. Thyrotoxicosis shows an increased serum T4 and decreased serum TSH and decreased I uptake. Which can be caused by taking excess thyroid hormone or by inflammation of the thyroid gland, causing excessive release of T4 from the damaged gland. In either case, the increase in serum T4 suppresses the release of TSH from the pituitary gland. The radioactive iodine uptake is decreased because the gland is either inactive (patient taking excess hormone) or inflamed (thyroiditis). Progressive systemic sclerosis (PSS). The serum ANA test is positive in 70% to 90% of patients with PSS. The photograph shows perioral constriction of the skin with radial furrowing (purse string appearance). Dysphagia (difficulty swallowing) for solids and liquids due to a loss of peristalsis, Raynauds, and interstitial fibrosis in the lungs (restricted movement of the chest and
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dry inspiratory crackles) are diagnostic of PSS. Anti-topoisomerase antibodies are useful in confirming the diagnosis of PSS. Anti-ribonucleoprotein antibodies are highly specific for mixed connective tissue disease. This collagen vascular disease has features of SLE, progressive systemic sclerosis, and rheumatoid arthritis. Anti DS DNA and anti smith are 100% specific for SLE Prolactinoma, the most common functioning tumor of the pituitary gland. Excess prolactin suppresses the release of gonadotropin-releasing hormone from the hypothalamus. This, in turn, causes secondary amenorrhea (absent menses) due to decreased release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the anterior pituitary gland. Prolactin also stimulates milk production in the breasts, causing galactorrhea (see photograph). Prolactinomas are treated either by surgery or by using dopamine analogues that inhibit prolactin secretion by the tumor (e.g., bromocriptine, cabergoline). Subarachnoid hemorrhage (severe occipital headache), which is most often due to a rupture of a congenital berry aneurysm. Berry aneurysms occur in 10% to 30% of patients with APKD. Hypertension is the most important risk factor for developing berry aneurysms, because cerebral vessels normally have an area of weakness at the junction of the communicating branches with the main cerebral artery (absent smooth muscle and internal elastic lamina in the media) Embolic strokes usually occur in the distribution of the middle cerebral artery ABO hemolytic disease of the newborn is the most common cause of jaundice w/in 24 hrs after birth. Individuals with blood group O normally have anti-A and anti-B antibodies of the IgM type as well as anti-A,B antibodies of the IgG type. Therefore, ABO incompatibility occurs in pregnant women who are blood group O and carrying fetuses with blood group A or blood group B. Maternal anti-A,B-IgG antibodies cross the placenta and attach to the A or B antigens of the fetal RBCs. Fetal macrophages in the spleen phagocytose and destroy the IgG-coated fetal RBCs, causing the release of unconjugated bilirubin The unconjugated bilirubin is removed by the mothers liver. In this neonate, the liver is unable to metabolize the increased unconjugated bilirubin, causing jaundice within the first 24 hours. A direct Coombs test of the RBCs is positive, because IgG antibodies coat the surface of the RBCs. The peripheral blood contains numerous spherocytes, which are produced when splenic macrophages remove part of the RBC membrane coated by the IgG antibodies rather than the entire RBC. In most cases, an exchange transfusion is unnecessary in treating ABO hemolytic disease of the newborn, because the degree of anemia is not very severe and the level of unconjugated bilirubin is not high enough to produce kernicterus. Pyruvate kinase deficiency is an autosomal recessive hemolytic anemia. In pyruvate kinase deficiency, RBCs have no adenosine triphosphate, causing dehydration of the RBCs due to damage to the RBC membrane. The RBCs have spiny protuberances from the surface. Splenic macrophages remove the damaged RBCs causing a hemolytic anemia with jaundice. PK normally converts phosphoenolpyruvate to pyruvate leading to a net gain of 2 adenosine triphosphate (ATP). In PK deficiency, lack of ATP damages the membrane causing a loss of K+ and dehydration of the RBC (echinocytes with thorny projections, arrow in the photograph). In homozygous variants, hemolytic anemia with jaundice begins at birth. There is an increase in 2,3 bisphosphoglycerate (BPG) proximal to the enzyme block, which right-shifts the O2-binding curve causing increased release of O2 to tissue. This somewhat offsets the deleterious effects of the
Rapid Review HY Point by Nirav Patel anemia. Chronic extravascular hemolysis increases the risk for developing calcium bilirubinate stones leading to cholecystitis. An RBC enzyme assay is the confirmatory test for the anemia.
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histologic section shows a thrombus (red-colored) occluding the lumen of the coronary artery. Directly underneath the thrombus is a fibrous cap (blue-colored lesion), the pathognomonic lesion of atherosclerosis. Directly beneath the blue fibrous cap is a core of necrotic material containing cholesterol (clear, needle-shaped spaces). There is a small fissure at the edge of the fibrous cap (disrupted plaque) that contains necrotic atheromatous debris. This debris was responsible for initiating the formation of a platelet thrombus in the lumen of the vessel. Aspirin is the most frequently used medication to prevent platelet aggregation. It does so by irreversibly inhibiting platelet cyclooxygenase activity. This prevents the production of prostaglandin H2 and its conversion to thromboxane A2 by the enzyme thromboxane synthase in the platelet. Thromboxane A2 is a potent vasoconstrictor and platelet aggregator. Abciximab is a monoclonal antibody that is directed against the glycoprotein (Gp) IIb/IIIa fibrinogen receptor on platelets. Fibrinogen, which is later converted into fibrin, is responsible for causing the platelet to aggregate to form a thrombus. It is most often used after angioplasty or stenting to prevent thrombus formation. Alteplase is a recombinant tissue plasminogen activator that is used to lyse a preexisting platelet thrombus. Plasminogen activators cause the release of plasmin within the thrombus which leads to cleavage of the fibrin strands holding the thrombus together Ticlopidine (or clopidogrel) inhibits ADP-induced expression of platelet GpIIb:IIIa receptors, which prevents fibrinogen binding and platelet aggregation. It is expensive and is most often used if patients are allergic to aspirin. Trichinella spiralis. It is contracted by eating raw or undercooked pork. The larvae penetrate muscle producing muscle pain and tenderness. Invasive helminths produce eosinophilia (type I hypersensitivity). Small bowel Obstruction - history of colicky pain (pain followed by a pain-free interval) is characteristic. Adhesions from previous surgery are the most common cause of bowel obstruction. The physical findings of abdominal distention, tympany to percussion, absences of rebound tenderness, and high-pitched tinkling sounds on auscultation are classic findings of bowel obstruction. Direct inguinal hernias produce a bulge in the middle of the triangle of Hesselbach, which is located above the inguinal ligament. The bulge appears when the patient is standing and disappears when the patient is lying down. Large bowel infarctions cause bloody diarrhea and localized, noncolicky abdominal pain. Atherosclerosis or embolism to the superior mesenteric artery is the most common causes of a large bowel infarction Volvulus occurs when bowel (sigmoid colon or cecum) twists around the mesenteric root, resulting in obstruction and strangulation. The affected bowel is distended and visible on a plain abdominal radiograph. Posteromedial papillary muscle in the left ventricle is supplied by the RCA. Rupture of this muscle causes acute mitral regurgitation (pansystolic murmur at the apex that does not increase in intensity with deep, held inspiration), which leads to left-sided heart failure (pulmonary edema with bibasilar
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inspiratory crackles). Serum CK-MB peaks in 24 hours and returns to normal within 72 hours; therefore, it is not expected to be increased on day 4. Both cTnI and cTnT peak in 24 hours and return to normal within 7 to 10 days, which is an expected finding. Entire anterior portion of the heart and the anterior two-thirds of the interventricular septum is supplied by the left anterior descending (LAD) coronary artery. Rupture of the anterior wall causes cardiac tamponade and rapid death. Rupture of the interventricular septum causes a systolic murmur with a left-to-right shunt, resulting in right-sided heart failure (e.g., neck vein distention, dependent pitting edema). Entire posterior portion of the left ventricle, the posterior one-third of the interventricular septum, and the right ventricle are supplied by the RCA. Rupture of the posterior wall of the heart is uncommon and causes cardiac tamponade and rapid death. Ventricular aneurysms occur 4 to 8 weeks after a myocardial infarction. They produce a precordial bulge that correlates with systole (not present in this patient). The aneurysms rarely rupture because their walls are composed of scar tissue. Congestive heart failure is the most common complication. In DKA, acetyl CoA is produced by -oxidation of fatty acids. Acetyl CoA is the substrate used to synthesize ketone bodies (acetone, acetoacetic acid, -hydroxybutyric acid) in the liver. Excess amounts of acetyl CoA are used for ketogenesis. The increase in acetic acid and -hydroxybutyric acid causes an increased anion gap metabolic acidosis.\ Acetyl CoA is used in the initial reactions in cholesterol synthesis. Acetyl CoA combines with oxaloacetate and is used to synthesize citrate. Acetyl CoA is used to inhibit pyruvate dehydrogenase and activate pyruvate carboxylase, the first reaction in gluconeogenesis, which is the most important biochemical process maintaining hyperglycemia in DKA. Glycolysis (oxidation of glucose) produces pyruvate as an end-product. Pyruvate is then converted to acetyl CoA, which is used to synthesize fatty acids or used to produce citrate in the citric acid cycle. Hyperplasia is an increase in number of cells, it commonly occurs in the glands and stroma surrounding the prostatic urethra; hence, obstructive uropathy is usually present leading to urinary stasis, infections, and the potential for sepsis. Atrophy is a decrease in tissue mass caused by cellular shrinkage or loss of cells. Dysplasia is atypical hyperplasia or atypical metaplasia. Epithelial changes include an increase in mitoses, lack of orientation of the cells, and nuclear enlargement with atypical changes in chromatin Hypertrophy refers to an increase in cell size Metaplasia is the replacement of one adult cell type by another in response to injury. Erythema infectiosum, or fifth disease, which is caused by parvovirus B19. It produces a confluent netlike erythema type of rash that begins on the cheeks (slapped face appearance) and then extends to the trunk and proximal extremities. Ascending paralysis and hypertension are due to a neurotoxin produced by the scorpion (Centruroidesspecies). Poststreptococcal glomerulonephritis, secondary to scarlet fever, which is caused by an erythrogenic strain of group A streptococcus. Multiple electron-dense deposits (immunocomplexes; type III hypersensitivity) are present directly beneath the visceral epithelial cells (subepithelial
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location). Poststreptococcal glomerulonephritis presents as a nephritic syndrome with mild to moderate proteinuria, hematuria, and RBC casts. Fatty casts are the most common casts in the nephrotic syndrome (heavy proteinuria with pitting edema). Renal tubular casts are present in acute tubular necrosis, the most common cause of acute renal failure. Waxy casts are present in chronic renal failure Thiamine deficiency results in a deficiency of adenosine triphosphate, which underlies the development of dry beriberi (peripheral neuropathies, Wernicke-Korsakoff syndrome) and wet beriberi (dilated cardiomyopathy). Wernickes encephalopathymainly hemorrhages in the periventricular gray matter and mamillary bodies, due to capillary proliferation in these areas of the brain. Red blood cells break down, causing the release of iron, which produces a rusty brown discoloration of brain tissue. The classic triad of Wernickes syndrome is confusion, ataxia, and ophthalmoplegia (which is most often due to lateral rectus muscle weakness). Korsakoffs syndrome is associated with anterograde and retrograde memory loss. Folic acid deficiency results in a macrocytic anemia with no neurologic deficits. Alcoholism is the most common cause of folic acid deficiency. Vitamin B6 (pyridoxine) deficiency causes a microcytic sideroblastic anemia with ringed sideroblasts. Seizures and peripheral neuropathies also may occur. Deficiency is most often due to interactions with medications (e.g., isoniazid), or it may be caused by alcoholism. Vitamin B12 (cyanocobalamin) deficiency causes a macrocytic anemia with neurologic abnormalities primarily involving the spinal cord (posterior columns and lateral corticospinal tracts).
A) Normal urine diution. B)- central diabetes insipidus C) Normal D) ectopic secretion of ADH by a small cell carcinoma of the lung causing the syndrome of inappropriate ADH Central diabetes insipidus due to transection of the pituitary stalk from head trauma. Due to a lack of antidiuretic hormone (ADH), the patient is always diluting her urine and never concentrating urine. Therefore, in a water deprivation test, the POsm will increase (stimulates thirst), due to excess loss of free water in the urine, and the UOsm will decrease, due to excess free water in the urine (dilution) because ADH is absent. The treatment is desmopressin acetate. Ectopic secretion of ADH by a small cell carcinoma of the lung causing the syndrome of inappropriate ADH. With constant stimulation by ADH, the kidneys are always concentrating urine (reabsorbing free water) and never diluting. Adding the free water to plasma produces a dilutional hyponatremia. decreased POsm, increased UOsm
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Enlargement of the thyroid gland is normal in pregnancy. The increase in estrogen that normally occurs during this period stimulates liver synthesis of TBG. T4 normally occupies one-third of the binding sites on TBG; therefore, estrogen will attach to one-third of the binding sites on the additional TBG molecules. This increases the bound fraction of T4, which automatically increases the total serum T4; however, it does not alter the free T4levels. Postrenal azotemia is most often due to urinary tract obstruction, which, in this case, is prostate hyperplasia. In the initial stages of urinary tract obstruction, tubular function is intact and there is a decrease in the glomerular filtration rate and back diffusion of urea into the blood causing the BUN:creatinine ratio to be >15. The FENa+ is a sensitive indicator of tubular function. Hemochromotosis is characterized by personal and family history of type 1 diabetes mellitus, cirrhosis, chronic diarrhea, and a pale gray skin color. Hemochromatosis is an autosomal recessive disease in which increased reabsorption of iron from the small intestine leads to iron overload in the liver (where it causes cirrhosis), pancreas (where it causes diabetes and malabsorption leading to diarrhea), and skin (where it causes increased pigmentation as well as increased production of melanin). The term bronze diabetes is often applied to this condition. Transferrin saturation is an excellent screening test for hemochromatosis as is serum ferritin. The biopsy stained with Prussian blue shows numerous blue-colored iron granules in the hepatocytes. The treatment is phlebotomy to reduce the serum ferritin levels and iron chelation therapy. Wilsons disease have decreased serum ceruloplasmin. Wilsons disease, an autosomal recessive disorder, is associated with chronic liver disease and a movement disorder caused by defective secretion of copper into bile and decreased incorporation of copper into ceruloplasmin in the liver. It does not produce skin discoloration or pancreatic insufficiency D-xylose absorption is an excellent screening test for small bowel disease as a cause of malabsorption. Small bowel disease (e.g., celiac disease) is characterized by the inability to reabsorb orally administered D-xylose into the blood. Acute intermittent porphyria, which is an autosomal dominant disease due to a deficiency of uroporphyrinogen synthase (aka porphobilinogen deaminase). This enzyme converts porphobilinogen (PBG) to hydroxymethylbilane in heme synthesis. Deficiency of the enzyme causes a proximal accumulation of PBG and -aminolevulinic acid, which are excreted in the urine. PBG is colorless unless it is exposed to light and is oxidized to porphobilin, which has a wine-red color. A characteristic feature of the disease is recurrent, neurologically induced abdominal pain precipitated by drugs that induce the liver cytochrome P450 system (e.g., alcohol) or dietary restriction Uroporphyrin I produces a wine-red color to urine when voided. It is increased in porphyria cutanea tarda (PCT). PCT is an acquired or hereditary disorder characterized by a deficiency of uroporphyrinogen decarboxylase, which converts uroporphyrinogen III to coproporphyrinogen III. The skin is fragile and fine hair develops over the face. The patient does not have any of these physical findings. Urobilin is the oxidation product of urobilinogen, which is normally present in trace amounts in urine. Urobilin is the pigment that is responsible for the yellow color of urine. If urobilin is increased in the urine (e.g., extravascular hemolytic anemia, hepatitis), the urine is a dark yellow color and does not turn wine-red with exposure to light. The larynx is the most common site of origin for SCC caused by smoking, a well-differentiated squamous cell carcinoma with a central area of keratin pearl formation (keratin debris).
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The most common cancer of the distal esophagus is an adenocarcinoma, not a squamous cell carcinoma. The most common precursor lesion is a Barretts esophagus due to gastroesophageal reflux disease. Infections of the urinary bladder by Schistosoma hematobium can be associated with squamous cancers of the urinary bladder arising from squamous metaplasia. Neonatal hypoglycemia (jitteriness and seizures) is caused by hyperinsulinism in the newborn related to the poor glycemic control in the mother with gestational diabetes mellitus. After delivery, the source of the fetal hyperglycemia is removed, and the increased insulin levels cause a drastic reduction in the blood glucose levels in the newborn. Growth hormone, cortisol, and epinephrine is increased in the newborns bc stress of delivery Esophageal varices are most often caused by portal hypertension secondary to cirrhosis. The most common cause of cirrhosis is alcohol abuse. The veins in esophageal varices are dilated, left gastric coronary veins, which normally drain venous blood from the distal esophagus and proximal stomach into the portal vein. Achalasia is a motor disorder of the distal esophagus characterized by failure of relaxation of the lower esophageal sphincter due to loss of ganglion cells in the myenteric plexus. This causes aperistalsis and dilation of the distal esophagus Complications associated with retching are distal esophageal tears (Mallory-Weiss syndrome) and esophageal rupture (Boerhaaves syndrome), both of which can produce hematemesis A perfusion defect occurs when blood flow to the alveoli is absent; however, there is normal ventilation of the alveoli. This produces an increase in dead space in the lungs and less exchange of O2 between the alveoli and pulmonary capillaries resulting in decreased arterial Po2 (called hypoxemia). Most often caused by Pulmonary infarctions are common in nonambulatory hospitalized patients because of blood stasis in the lower extremities, leading to deep venous thrombosis and thromboembolism to the lungs. Sacoidosis and Pulmonary edema can cause a diffusion defect which is a inhibition of diffusion of O2 into the pulmonary capillaries by fibrous tissue. A ventilation defect occurs when there is blood flow to the alveoli but ventilation is compromised (e.g., atelectasis with collapse of the airways). This produces an intrapulmonary shunt leading to hypoxemia. CF, a three-nucleotide deletion, which codes for phenylalanine, leads to transcription of a defective CF transmembrane conductance regulator (CFTR) for chloride ions. CFTR is not processed correctly in the Golgi apparatus and degrades before reaching the cell surface. This causes decreased sodium and chloride reabsorption by the sweat glands, which is the basis of the sweat test. However, in other secretions (e.g., pancreatic ducts, bronchioles), there is increased sodium and water reabsorption out of luminal secretions and decreased chloride secretion into luminal secretions, which leads to thickened, dehydrated secretions that lack sodium chloride and water. In CF patients they may exocrine ducts of the pancreas contain thick, pink, dehydrated secretions that obstruct and dilate the ducts and compress the ductal epithelium, producing tubular atrophy. Furthermore, duct obstruction by the thick secretions increases back pressure on the proximally located exocrine glands, which leads to a loss of glandular cells by apoptosis and compression atrophy. The patient's chronic diarrhea is due to malabsorption of fats and other nutrients related to a lack of pancreatic enzymes (e.g., lipase). Chronic pancreatitis eventually occurs with destruction of -islet cells resulting in type 1 diabetes mellitus.
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Acute gout, Inflammation of the metatarsophalangeal joint of the great toe is the classic presentation. It is characterized by the deposition of monosodium urate (MSU) crystals in the joint. MSU crystals have negative birefringence, which is defined by certain color changes that occur in the crystals when they are examined under compensated polarized light. MSU crystals are yellow when aligned parallel. Pseuso gout-Calcium pyrophosphate crystals are either needle- or rhomboid-shaped in synovial fluid and show positive birefringence when viewed under compensated polarized light. They are blue (not yellow) when aligned parallel to the slow ray of the compensator. Calcium pyrophosphate deposit disease most commonly involves the knee joint. Hydroxyapatite crystals are associated with degenerative osteoarthritis. Cholesterol crystals are associated with chronic inflammatory joint effusions (RA). Bells palsys is a LMN, Clinical findings in LMN disease are ipsilateral upper and lower face involvement, drooping of the corner of the mouth, difficulty speaking, inability to close the eye, and hyperacusis in some cases. Borrelia burgdorferi in Lyme disease is transmitted by a tick bite and commonly produces Bells palsy
The child on the left has kwashiorkor, and the child on the right has marasmus. Both conditions are examples of protein-energy malnutrition. Kwashiorkor is caused by decreased protein intake, which decreases the serum albumin level. The total calorie intake is normal because of increased intake of carbohydrates. A decrease in albumin decreases the plasma oncotic pressure, resulting in dependent edema (see photograph, child on left). In marasmus, serum albumin levels are normal in spite of diminished intake of calorie Somatic protein stores represent the protein in muscle. In marasmus, somatic protein stores are decreased, resulting in muscle wasting in the extremities (see photograph, child on right). Somatic proteins are used as substrate for gluconeogenesis Galactosemia, an autosomal recessive disease characterized by a deficiency of galactose 1phosphate uridyltransferase GALT. Galactose derives from the metabolism of lactose. Lactase converts lactose to glucose and galactose. Galactose is converted by galactase to galactose 1phosphate, which is converted to glucose 1-phosphate by GALT. Glucose 1-phosphate is converted to glucose 6-phosphate, which is used as a substrate for gluconeogenesis (deficiency causes fasting hypoglycemia). Deficiency GALT causes accumulation of galactose 1-phosphate, which is toxic to the brain (mental retardation) and to the liver (cirrhosis). Dairy products must be eliminated from the diet. Gluten is present in wheat products. Patients who have antibodies against gliadin (alcohol extract of gluten) develop celiac disease autoimmune destruction of intestinal villi by antigliadin, endomysial, and tissue transglutaminase antibodies due to reaction against the gliadin fraction in gluten in wheat products. , which is characterized by immunologic destruction of the villi in the small intestine, causing malabsorption of fat, carbohydrates, and proteins
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Phenylalanine is increased in phenylketonuria, an autosomal recessive disease characterized by a deficiency of phenylalanine hydroxylase, which converts phenylalanine to tyrosine. Phenylalaninecontaining foods should be eliminated (e.g., certain sweeteners) from the diet to prevent mental retardation Sucrose, is converted to glucose and fructose by sucrase. It should be avoided in hereditary fructose intolerance, an autosomal recessive disorder, that is characterized by a deficiency of aldolase B. Tyrosine-containing foods should be eliminated from the diet in patients with tyrosinosis, an autosomal recessive disease caused by a deficiency of fumarylacetoacetate hydrolase. Excess tyrosine causes chronic liver disease, which may lead to hepatocellular carcinoma Primary lung cancer can cause secondary metastatic lesions in cerebral cortex causing cerebral edema, resulting in herniation of the medial portion of the right temporal lobe (uncus) between the midbrain and tentorium cerebelli. The cerebral edema, in turn, has caused compression of the oculomotor nerve (cranial nerve [CN] III), resulting in weakness of the medial, superior, and inferior rectus; inferior oblique; and the levator palpebrae (muscle that raises the eyelid). Therefore, the patient cannot adduct, elevate, or depress the right eye and has a drooping right eyelid. Parasympathetic fibers that constrict the pupil also follow the same path as CN III, and compression of these fibers causes mydriasis. Embolic strokes are characterized by wedge-shaped areas of infarction at the periphery of the brain. They are most frequently associated with atrial fibrillation causing thromboembolic disease from the left atrium. Patients with prostate hyperplasia are more likely to present with urinary retention, because it produces urethral obstruction. Prostate cancer commonly metastasizes to the vertebral column, where it produces bone pain. Metastases are usually osteoblastic (stimulates bone formation), which increases the serum alkaline phosphatase and shows increased bone density on radiographs. Osteomyelitis involving the vertebral column is most often due to Mycobacterium tuberculosis. It produces lytic lesions of the vertebral column. Sugery may cause fibrinolysis, which causes urokinase from tissue to activate plasminogen and release plasmin. Plasmin degrades multiple coagulation factors (e.g., V, VIII, fibrinogen). This increases the PT and PTT, because factors V and VIII are in the final common pathway. The degradation products of fibrinogen interfere with platelet aggregation causing an increase in the bleeding time. N. meningitidis (gram-negative diplococcus), which is the most common cause of meningitis from 1 month to 18 years of age. The CSF findings (i.e., decreased glucose and increased protein and neutrophils) are characteristic of bacterial meningitis. Sepsis caused byN. meningitidis is commonly associated with petechial lesions (small-vessel vasculitis), which often coalesce into large ecchymotic blotches on the skin. There is increased risk that the patient could develop disseminated intravascular coagulation leading to adrenal hypofunction from hemorrhagic infarction of both adrenal glands (Waterhouse-Friderichsen syndrome). Meningitis caused by E. coliusually occurs in newborns and in individuals > 50 year age. Acral lentiginous malignant melanoma, pigmented lesion under the nail. Cigarette smoking is the most common cause of a renal cell carcinoma. These cancers invade the renal vein and metastasize to the lungs, skin, and many other sites.
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The antigen used in the RPR test system is beef cardiolipin, which reacts with the reagin antibodies of syphilis as well as anticardiolipin antibodies, which are most often present in patients with systemic lupus erythematosus. ALP is normally increased in children due to increased bone growth corresponding with an increased osteoblastic activity. HPV types 6 or 11. It is the most common sexually transmitted disease in the United States. The lesions develop in moist areas of the anogenital region. The vulva has numerous keratotic papillary processes covering the labia. The patient has condyloma acuminatum (venereal warts). Treated with topical podophyllin. Other treatment modalities include -interferon or imiquimod. Ankylosing spondylitis is a male-dominant, HLA-B27positive, inflammatory joint disease that initially targets the sacroiliac joints and then the vertebral column, resulting in fusion (ankylosis) of the vertebrae. Rheumatoid arthritis is a chronic, systemic inflammatory disease, characterized by destruction of articular cartilage by granulation tissue called a pannus. In the hands, rheumatoid arthritis targets the second and third metacarpophalangeal joints and the PIP joints. It does not affect the DIP joints unlike OA Neurofibromatosis II, an autosomal dominant disorder. It is associated with an increased risk for developing unilateral or bilateral acoustic neuromas involving the vestibulocochlear nerve (CN VIII). The photograph shows the classic Antoni A (dark bands) and Antoni B (light bands) of an acoustic neuroma. These tumors are always benign and derive from the Schwann cell. Caf-au-lait spots and pigmented nodules and pedunculated lesions (neurofibromas) are most likely present on skin. Acanthosis nigricans is a gray-brown to black colored lesion with thickened plaques and prominent skin lines. It may be a phenotypic marker for an underlying stomach adenocarcinoma or for diabetes mellitus due to severe insulin resistance. Adenoma sebaceum, or angiofibroma, is a characteristic skin lesion seen in tuberous sclerosis, an autosomal dominant disorder associated with mental retardation and astrocyte hamartomas in the brain. Renal cell carcinoma with ectopic secretion of erythropoietin (EPO). Ectopic EPO production by the tumor causes an increase in bone marrow production of RBCs. Therefore, the number of RBCs/mm3 of blood (RBC count) and the total number of RBCs produced in mL/kg body weight (RBC mass) are both increased. However, the plasma volume remains normal and does not increase in concert with the increase in RBC mass. Polycythemia due to ectopic production of EPO is not released in response to a hypoxemic stimulus. In cirrhosis, the dysfunctional liver is unable to metabolize estrogen or 17-ketosteroids (e.g., androstenedione), the latter being aromatized in the adipose into weak estrogen compounds. Hyperestrinism in men causes gynecomastia (development of breast tissue in males) and female secondary sex characteristics (palmar erythema, soft skin, female hair distribution). DKA, complete deficiency of insulin causes the release of glucagon from -islet cells (paracrine effect) in the pancreas. Glucagon is the main hormone that stimulates gluconeogenesis and maintains the hyperglycemia in DKA. In DKA there is -oxidation of fatty acids, Insulin, Anaerobic glycolysis is the oxidation of glucose to lactate for energy, and glucagon to stimulate gluconeogenesis and maintains the hyperglycemia.
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Lebers optic neuropathy is a neurodegenerative disease in which progressive loss of central vision eventually leads to blindness. Mitochondrial DNA disorders generally involve enzyme deficiencies in oxidative phosphorylation in the mitochondria. Unlike sperm, ova do not lose their mitochondria on fertilization, so affected females transmit the abnormal allele to all their children. However, affected males do not transmit it to any of their children, because mitochondria are located in the tail of the sperm, which is lost during fertilization. Familial hypercholesterolemia is an autosomal dominant disorder involving a deficiency of lowdensity lipoprotein receptors that leads to severe hypercholesterolemia. McArdles disease is a glycogen storage disease (type V), which all have an autosomal recessive inheritance pattern. In McArdles disease there is a deficiency of muscle phosphorylase, which renders muscle incapable of metabolizing glycogen to glucose. Therefore, during exercise there is no glucose for anaerobic glycolysis and no accumulation of lactic acid Polycythemia vera (PV), a myeloproliferative disorder (malignant disorder of stem cells). It is due to clonal expansion of the myeloid stem cell, most often due to mutation of the JAK2 gene on the short arm of chromosome 9. This results in increased production of RBCs, granulocytes (neutrophils, eosinophils, basophils), mast cells, and platelets. PV is an absolute polycythemia, meaning that the bone marrow is producing more RBCs than normal; hence, the total number of RBCs in the body in mL/kg (RBC mass) is increased as well as the RBC count .In PV, there is an increase in plasma volume that also accompanies the increase in RBC mass, unlike in the other types of polycythemia. Pruitus post bathing due to increased histamine is common RBC mass increased, plasma volume normal, O2 saturation decreased, EPO increased- obstructive and restrictive lung disease, cyanotic congenital heart disease, and living at high altitudes RBC mass increased, plasma volume increased, O2 saturation normal, EPO decreased Polycythemia vera RBC mass increased, plasma volume normal, O2 saturation normal, EPO increased- renal disease, hepatocellular carcinoma RBC mass normal, plasma volume decreased, O2 saturation normal, EPO normal - Any cause of volume depletion (e.g., excessive sweating, severe diarrhea) immune hemolytic anemia secondary to SLE presents with fatigue, jaundice, low hemoglobin concentration, positive Coombs test. Here the patient RBCs are coated by IgG with or without C3b and are being phagocytosed by splenic macrophages that have receptors for IgG and C3b (extravascular hemolysis). In the macrophages, the end-product of degradation of hemoglobin is unconjugated bilirubin, which enters the blood producing jaundice. A direct Coombs test detects the presence of IgG and/or C3b on the surface of the RBCs. Most immune hemolytic anemias are caused by SLE. The arrow points to one of many reticulocytes, which are young RBCs that retain threadlike RNA filaments to synthesize hemoglobin. In hemolytic anemias, erythropoietin stimulates RBC hyperplasia in the bone marrow to replace those RBCs that are being hemolyzed. This effective erythropoiesis is indicated by the presence of increased numbers of reticulocytes in the peripheral blood and is a good sign that the bone marrow is responding appropriately to an anemia. A lack of an appropriate reticulocyte response to an anemia is a sign of ineffective erythropoiesis Wilson's disease is an autosomal recessive disorder with a defect in the secretion of copper into bile and in the incorporation of copper into ceruloplasmin in the liver. Increased free copper in the liver parenchymal cells eventually leads to cirrhosis of the liver. Increased free (unbound) copper in
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the blood deposits in Descemets membrane in the limbus of the eyes (Kayser-Fleischer rings) and in the basal ganglia, particularly the putamen. Microaneurysms are due to osmotic damage of the pericytes that surround the vessel. Pericytes contain aldose reductase, which converts glucose to sorbitol. Sorbitol is osmotically active and draws water into the pericyte, leading to its destruction. This weakens the vessel wall, causing formation of a microaneurysm. Rupture of aneurysms can cause retinal detachment and neovascularization of the retina, resulting in blindness. Diabetes is the most common cause of blindness in the United States. Retinopathy and nephropathy frequently coexist in patients with poorly controlled diabetes mellitus. Nonenzymatic glycosylation occurs in DM patients. It refers to the binding of glucose to amino acids in protein within the basement membrane of vessels and in proteins such as hemoglobin. In blood vessels, it causes increased vessel permeability in arterioles, leading to hyaline arteriolosclerosis. It is the most prominent in kidneys. Parkinsons disease shows atrophy and depigmentation of the substantia nigra. Degeneration of neurons of the substantia nigra causes a loss of dopamine, the principal neurotransmitter of afferents in the nigrostriatal tract that connects the substantia nigra with the caudate and putamen. This interrupts voluntary muscle movement, resulting in muscle rigidity (cogwheel rigidity) and other extrapyramidal signs (resting tremor with pill rolling of the thumbs and index fingers). An increase in -secretases causes increased cleavage of amyloid precursor protein into fragments that are converted into -amyloid (A) protein, which when phosphorylated by activated glycogen synthase kinase (GSK)-3 initiates apoptosis neurons in the brain causing Alzheimers disease . Tau protein normally maintains microtubules in neurons. Activated GSK enhances hyperphosphorylation of tau protein causing the protein to change shape and cluster into fibers called neurofibrillary (NF) tangles. NF tangles produce neuronal dysfunction including death of the neuron. NF tangles have a prominent role in the pathogenesis of Alzheimers disease Loss of striatal neurons in the caudate nucleus occurs in Huntingtons disease. This autosomal dominant trinucleotide repeat disorder is characterized by chorea, extrapyramidal signs, and dementia. The presence of WBC casts accompanied by lower urinary tract signs of infection indicates acute pyelonephritis, which is the most common upper urinary tract infection. An upper urinary tract infection has fever, flank pain, and WBC casts. Small cell carcinoma of the lung are nueroendocrine tumors that derive from kulchitsky cells these tumors can secrete ADH leading to hyponatremia. Small cell carcinoma is associated with smoking. Primary squamous cell carcinomas of the lung ectopically secrete parathyroid hormone-related peptide, causing hypercalcemia. These tumors are centrally located and strongly associated with smoking; however, H&E-stained sections show keratin pearls and eosinophilic-staining cells rather than the basophilic staining round- to spindle-shaped cells of small cell carcinoma. In DKA, hyperglycemia is the major osmotically active solute in the vascular compartment (not sodium) and causes water to move out of the intracellular fluid (ICF) compartment into the extracellular fluid (ECF) compartment producing a dilutional hyponatremia. However, glucosuria is also present in DKA, which produces an osmotic diuresis causing loss of a hypotonic saltcontaining fluid in the urine. The loss of Na+ is responsible for the signs of volume depletion (dry mucous membranes, poor skin turgor, hypotension). Regarding the fluid compartments, the ECF
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compartment is contracted (loss of fluid by osmotic diuresis) and the ICF compartment is contracted (osmosis effect of hyperglycemia). NSAIDs inhibit platelet cyclooxygenase, which prevents the synthesis of thromboxane A2 (TXA2), a platelet aggregator and vasoconstrictor of small vessels. TXA2 is mainly responsible for producing a temporary hemostatic plug composed of platelets that stop bleeding in injured small vessels. Hence, blocking the synthesis of TXA2 causes severe bleeding from small vessels that lack temporary platelet plugs. The aPTT evaluates the intrinsic coagulation system, and the PT evaluates the extrinsic coagulation system. They are normal because they do not detect platelet abnormalities but only coagulation factor deficiencies. The bleeding time, which evaluates platelet function up to the formation of the temporary platelet plug, is prolonged because the temporary platelet plug is not formed. The platelet count is a quantitative measurement of platelets, not a means for evaluating platelet function. It is normal in patients taking NSAIDs. Rheumatoid arthritis. The photograph shows swelling of the metacarpophalangeal joints and ulnar deviation in both hands. Joint destruction is initiated by the secretion of cytokines from T cells that cause B-cell proliferation and the release of chemical mediators from macrophages and synovial cells in the joint. The B cells synthesize IgM autoantibodies that react against the Fc portion of IgG. When RF combines with IgG, it produces immunocomplexes. The immunocomplexes activate the complement system, causing the release of chemotactic factors that attract neutrophils into the joint, leading to acute synovitis and granulation tissue (pannus) formation. Pannus extends over the articular cartilage and releases cytokines that destroy cartilage leading to fibrosis and eventual ankylosis (fusion) of the joint. The HLA-B27 genotype is associated with a group of RF-negative (seronegative) spondyloarthropathies that target the sacroiliac joint and the vertebral column (e.g., ankylosing spondylitis). Vitamin Dresistant rickets is an X-linked dominant disorder that involves a defect in the reabsorption of phosphate from the gastrointestinal tract and kidneys. Decreased phosphate leads to decreased mineralization of bone and rickets (osteomalacia). X-linked dominant disorders are characterized by a dominant allele that causes both male and female carriers of the abnormal allele to express the disease. As with X-linked recessive disorders, affected males transmit the abnormal allele to all their daughters, as shown in the pedigree. Furthermore, symptomatic carrier females transmit the abnormal allele to 50% of their sons and 50% of their daughters, as is also shown. Vitamin Ddependent rickets is an autosomal recessive disorder. It is associated with a deficiency of 1-hydroxylase, resulting in a deficiency of 1.25-(OH)2D (calcitriol), which is the active form of vitamin D. Hypovitaminosis D, or rickets, is characterized by defective mineralization of bone accompanied by an increase in nonmineralized osteoid. Pathologic fractures may occur Anticentromere antibodies are most often seen in progressive systemic sclerosis and a limited variant called CREST syndrome. Antimicrosomal antibodies occur in Hashimotos thyroiditis and Graves disease. Antitopoisomerase (antiScl-70) antibodies are present in progressive systemic sclerosis. CK-MB isoenzymes, a marker for acute myocardial infarction, are usually gone by 3 days. Therefore, reappearance of CK-MB after 3 days indicates reinfarction or further extension of an existing myocardial infarction.
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Rupture of the myocardium either produces a murmur (e.g., mitral regurgitation from posteromedial papillary muscle infarction) or cardiac tamponade with muffling of the heart sounds and jugular neck vein distention and muffled heart sounds. In this question, a test is performed on people with known coronary artery disease (disease group) and on people who do not have coronary artery disease (control group). People with disease either have a true positive (TP) or a false negative (FN) test result. A TP test result is a positive test in a person with disease. A FN test result is a negative test result in a person with disease. People in a control group, who do not have disease, either have a true negative (TN) or a false positive (FP) test result. A TN test result is a negative test in a person without disease, while a FP test result is a positive test result in a person without disease. The question is asking what is the predictive value (or likelihood) that a positive test result (PV+) is a TP and not a FP. The formula for PV+ is TP/TP + FP. In this question, the PV+ is 180/180 + 60 = 75%. In other words, there is a 75% chance that the person has a TP test result and a 25% chance that it is a FP test result.
Coronary artery disease Control group Total Positive test True positive 180 False positive 60 240 Negative test False negative 20 True negative 140 160 Total 200 200 400 The prevalence of coronary artery disease is 50%. Prevalence refers to the number of people with a disease in the population under study, which includes all the people with coronary artery disease and all the people in the control group. The formula for prevalence is TP + FN/TP + FN + TN + FP. The prevalence of coronary artery disease is 180 + 20/180 + 20 + 140 + 60 = 50%. The specificity of the test is 70%. The specificity of a test refers to the likelihood of having negative test results in people without disease. Since people without disease either have TN or FP test results, the formula for calculating the specificity of a test is TN/TN + FP. The specificity of the test in this question is 140/140 + 60 = 70% The predictive value (or likelihood) that a negative test result (PV-) is a TN and not a FN is equal to 87.5%. The formula for PV- is TN/TN + FN; therefore, 140/140 + 20 = 87.5% The sensitivity of the test is 90%. The sensitivity of a test refers to the likelihood of having positive test results in people with disease. Since people with disease either have TP or FN test results, the formula for calculating the sensitivity of a test is TP/TP + FN. The sensitivity of the test is 180/180 + 20 = 90%. The patient is a pure vegan; therefore, her diet lacks vitamin B12, which is mainly obtained by eating animal products. Lack of vitamin B12 in breast milk predisposes the infant to a macrocytic anemia and the potential for neurologic dysfunction involving the posterior columns and lateral corticospinal tract. Osteogenesis imperfecta, which is characterized by a history of pathologic fractures throughout life. Some patients also have hearing loss as well. This autosomal dominant disease is associated with a defect in the synthesis of type I collagen. Blue discoloration of the sclera is due to visualization of the choroidal veins beneath the collagen-deficient sclera. Bone is a type I collagen-based matrix that is mineralized with calcium, phosphorus, and magnesium. Decreased synthesis of type I collagen results in structurally weak bone with a decrease in bone mass and density (secondary osteoporosis), resulting in pathologic fractures.
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Ehlers Danlos syndrome - connective tissue disorder with defects in collagen synthesis and/or structure. Clinical findings include hyperelastic skin, hypermobility of joints, aortic dissection, mitral valve prolapse, and rupture of the colon P. falciparummalaria, which is endemic in Nigeria. The peripheral blood shows an RBC with multiple ring forms but no other mature parasitic forms (schizonts, merozoites, gametocytes). These findings are diagnostic of P. falciparum. Parasitic hemolysis correlates with the quotidian fever pattern (recurring daily, with occasional fever spikes). Intravascular hemolysis causes hemoglobinuria (red urine), and extravascular hemolysis leads to jaundice, as splenic macrophages remove parasitized RBCs and degrade the hemoglobin into unconjugated bilirubin. Hemolytic anemias are all associated with an increase in the corrected reticulocyte count (reticulocyte count that is corrected for the degree of anemia). Delayed hemolytic transfusion reaction. She has positive direct and indirect Coombs tests, free Hb in her serum (pink staining), and a significant drop in her posttransfusion Hb concentration after leaving the hospital Cytomegalovirus is the most common pathogen transmitted by blood transfusion Lactase deficiency results in decreased hydrolyze of lactose in dairy products into glucose and galactose. Anaerobes in the colon degrade lactose into lactic acid and hydrogen gas. The gas causes distention of the bowel and explosive diarrhea. Undigested lactose is osmotically active and causes the movement of a hypotonic salt solution from the bowel mucosa into the bowel lumen. Lactase deficiency is a common genetic defect in Native Americans, Asians, and blacks. Toxins that stimulate adenylate cyclase (produced by Vibrio cholerae and some strains of enterotoxigenic Escherichia coli) cause a secretory diarrhea (loss of isotonic fluid) by stimulating ionic pumps in the small intestine. Toxins that stimulate guanylate cyclase (toxin produced by some strains of enterotoxigenic E. coli) cause a secretory diarrhea (loss of isotonic fluid) by stimulating ionic pumps in the small intestine Alkaline phosphatase is necessary to remove phosphate from pyrophosphate so that bone mineralization can occur. Phosphorus is necessary along with calcium in the mineralization process. Testicular feminization syndrome (androgen insensitivity syndrome), an X-linked recessive disorder with absence of the androgen receptors. The genotypically a male (XY), but phenotypically female, this is an example of male pseudohermaphroditism. The testes are present and either remain in the abdominal cavity or present as masses in the inguinal canal. Concentrations of testosterone and dihydrotestosterone (DHT) are normal, but the lack of androgen receptors prevents the development of male secondary sex characteristics and external genitalia. Testosterone effects normal development of the epididymis, seminal vesicles, and vas deferens from the mesonephric duct. DHT converts female-appearing external genitalia into a penis and scrotal sac and develops the prostate gland. The Sertoli cells in the seminiferous tubules produce mllerian inhibitory factor, which causes mllerian structures (fallopian tubes, uterus, cervix, upper one-third of vagina) to undergo apoptosis. In testicular feminization, due to a lack of testosterone effect, there is no epididymis, seminal vesicles, and vas deferens. Due to a lack of DHT effect, there is no prostate gland; the vagina ends as a blind pouch (lower two-thirds of the vagina develops from the urogenital sinus), and the external genitalia remains female. Breast development and female secondary sex characteristics are normal, because estrogen receptors are present. Patients are usually reared as females and both testes are removed to reduce the risk for developing a seminoma.
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Multiple myeloma complicated by renal failure. The bone marrow aspirate shows immature plasma cells with eccentric nuclei and perinuclear clearing. The cytoplasm stains blue with a Wright-Giemsa stain, indicating increased synthesis of protein. A monoclonal spike in the -globulin region can be expected on serum protein electrophoresis. The spike is caused by a single immunoglobulin (usually IgG) and its corresponding light chain (usually , which are secreted by clones derived from a single neoplastic plasma cell. multiple myeloma, which frequently causes osteolytic lesions. This is due to the release of interleukin-1 (osteoclast activating factor) from malignant plasma cells. This cytokine activates osteoclasts causing lytic lesions wherever the malignant plasma cells are located. Retinoblastoma, which is caused by inactivation of the RB (retinoblastoma) suppressor gene located on chromosome 13. In the sporadic type of cancer, both normal alleles must be inactivated by a point mutation after birth to produce a retinoblastoma (two-hit theory). In the autosomal dominant type of cancer, one allele already is inactivated in the germ cells and the other allele is normal. After birth, only a single mutation on the remaining allele is necessary to produce a retinoblastoma. Children with the autosomal dominant type of retinoblastoma have an increased incidence of osteogenic sarcoma associated with inactivation of the RB suppression gene Embryonal rhabdomyosarcoma (sarcoma botryoides) is the most common sarcoma in children and develops in the vagina of girls and the urogenital tract in boys. Methemoglobinemia is caused by Nitrites oxidizing the heme groups in RBCs to the ferric (Fe3+) state (methemoglobin), thus preventing the binding of O2 to the heme groups. This decreases O2 saturation (percentage of heme groups occupied by O2), causing cyanosis of the skin and mucous membranes. Increased concentration of deoxyhemoglobin causes the chocolate-colored blood. The arterial Po2 remains normal. Breathing O2 does not correct the cyanosis, because Fe3+ in the heme groups first must be reduced back to the ferrous (Fe2+) state before it can bind to oxygen. Intravenous methylene blue activates a methemoglobin reductase system that reduces the heme iron from Fe3+ to Fe2+. Ascorbic acid, a reducing agent, is often used along with methylene blue. Von Gierkes disease, which is an autosomal recessive glycogen storage disease characterized by a deficiency of glucose-6-phosphatase, a gluconeogenic enzyme that converts glucose 6-phosphate to glucose in the fasting state. Deficiency of glucose-6-phosphatase causes fasting hypoglycemia that does not respond to stimulators of gluconeogenesis (e.g., glucagon), because it is the last step in gluconeogenesis. There is an accumulation of glucose 6-phosphate proximal to the enzyme block. The excess glucose 6-phosphate is used to synthesize normal glycogen in sites of gluconeogenesis, including the liver and kidneys causing hepatorenomegaly. Aldolase B catalyzes a reaction that converts fructose 1-phosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate, which are substrates for gluconeogenesis. Deficiency of aldolase B is associated with hereditary fructose intolerance and causes liver disease and fasting hypoglycemia. Glucagon stimulation increases serum glucose, because there is no enzyme block in gluconeogenesis. GALT converts galactose 1-phosphate to glucose 1-phosphate, which is used as a substrate for gluconeogenesis (deficiency causes fasting hypoglycemia). Deficiency of GALT is present in galactosemia, an autosomal recessive disease that causes an accumulation of galactose 1phosphate, which is toxic to the brain (mental retardation) and liver (cirrhosis). (SIADH) caused by ectopic secretion of antidiuretic hormone (ADH) by a primary small cell carcinoma of the lung. ADH normally concentrates urine by reabsorbing H2O that is free of
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electrolytes in the collecting tubules of the kidneys back into the blood. Therefore, an excess of ADH causes increased reabsorption of H2O, which enters the extracellular fluid (ECF) and produces a dilutional hyponatremia ( serum Na+ = TBNa+/TBW). The plasma volume increases in SIADH causing an increase in the glomerular filtration rate and an increase in peritubular capillary hydrostatic pressure; hence, reabsorption of Na+ in the proximal tubule is thwarted causing the urine Na+ to be >40 mEq/L. In hyponatremic states, an osmotic gradient between the ECF and intracellular fluid (ICF) causes H2O to move into the ICF, producing cerebral edema. Since there is no increase in total body Na+ (TBNa+) in the ECF in SIADH and the primary problem is reabsorbing too much water, the most effective nonpharmacologic treatment is to restrict H2O intake and to maintain the sodium intake. DiGeorge syndrome, which is due to failure of formation of the third and fourth pharyngeal pouches. This is associated with absence of the thymus (pure T-cell immunodeficiency) and absence of the parathyroid glands, causing primary hypoparathyroidism (decreased PTH and decreased serum calcium). DiGeorge syndrome is the only syndrome associated with absence of the thymus, hypocalcemia, and cyanotic congenital heart disease. The cyanosis is most often due to a truncus arteriosus. Hypocalcemia causes tetany, which in newborns is manifested by jitteriness, repetitive blinking, and stridor.Treatment is calcium salts to correct hypocalcemia and bone marrow transplantation An increase in PTH and an increase in calcium is due to primary hyperparathyroidism, which is most often caused by a parathyroid adenoma. Gigantism occurs if the tumor is present before the epiphyses have fused, whereas acromegaly develops if the epiphyses have closed. Excess growth hormone causes hyperglycemia (growth hormone is gluconeogenic) and increased amino acid uptake in muscle and other tissues. Excess growth hormone also stimulates the liver to synthesize and release excess amounts of insulin growth factor-I. This hormone increases linear and lateral bone growth and growth of soft tissue, and also causes visceromegaly. Pituitary adenomas secreting excess growth hormone are often quite large and extend out of the sella turcica, causing headache, visual field defects, and hydrocephalus MI with Mitral valve regurg usually due to the posteromedial papillary muscle most likely ruptured, which is supplied by the RCA The LAD supplies the anterior portion of the left ventricle and anterior two-thirds of the interventricular septum. left coronary artery supplies the anterior portion of the heart left circumflex coronary artery supplies the lateral portion of the left ventricle. Cigarette smoking is the most common cause of carcinoma of the pancreas. Most pancreatic carcinomas occur in the head of the pancreas, which results in blockage of the common bile duct and obstructive jaundice. Clinical findings include weight loss, scleral icterus, a palpable gallbladder (Courvoisiers sign), and light-colored stools. Laboratory findings : greater increase in ALP and GGT than ALT and AST Carcinoma of the gallbladder is most commonly caused by cholelithiasis Actinic Keratosis or solar keratosis are premalignant lesions that progress to squamous cell carcinomas in 2% to 5% of cases. Biopsy specimens of the lesions show dysplastic squamous cells beneath a hyperkeratotic layer of cells.
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Verruca vulgaris (due to human papillomavirus) and molluscum contagiosum (due to a poxvirus) produce discrete, raised lesions on the skin. Duchennes muscular dystrophy, an X-linked recessive disorder with a deficiency of dystrophin. Dystrophin normally anchors actin to membrane glycoprotein. The boy shows generalized muscle atrophy and pseudohypertrophy of the calf muscles , and standing using the Gowers maneuver. Muscle wasting of proximal pelvic muscle and labs show an increased serum creatine kinase Mhyasthenia gravis there is IgG abs against ACh receptors that causes type II HSR causing progressive muscle weakness with normal creatine kinase Huntingtons disease is an autosomal disorder characterized by choreiform movements, dementia, and muscle rigidity. It is due to a gene defect on the short arm of chromosome 4, where errors in DNA replication lead to an abnormal repetition of trinucleotides (CAG). It shows anticipation genetics. There is atrophy of the caudate, putamen, and globus pallidus which is due to loss of neurons. Taysachs is an example of frameshift mutation caused by insertion or deletion of nucleotides into a gene that shifts the reading frame during translation of messenger RNA Tay sachs is Hexosaminidase deficient lysosomal storage disease that occurs primarily in Jews of Eastern European (Ashkenazi) descent. It is associated with accumulation of GM2 gangliosides in lysosomes and causes severe mental retardation, motor weakness, and a cherry-red macula. A missense mutation is a point mutation resulting in an altered codon that specifies a different amino acid, leading to variable phenotypic effects. Example is valine replaces glutamic in sickle cell disease A nonsense mutation is a point mutation resulting in an altered codon that is a stop codon (e.g., UAA), which causes premature termination of DNA transcription. Example in sever Beta thalassemia Niemann-Pick disease, an autosomal recessive lysosomal storage disease associated with a deficiency of sphingomyelinase and the accumulation of sphingomyelin in the lysosomes of macrophages.Giving the macrophages a foamy or soap-bubble appearance. It causes severe mental retardation, psychomotor retardation, and hepatosplenomegaly in children. Metachromatic leukodystrophy is a AR lysosmal strorage disease associated with the synthesis of abnormal myelin and the accumulation of sulfatides in lysosomes causing mental retardation and peripheral neuropathies Gauchers is deficient in glucocerebrosidase a lysosomal storage disease assoc with accumulation of glucocerebroside in the lysosomes of macrophages in the bone marrow, liver, and spleen. The macrophages have a fibrillary or wrinkled appearance causing pancytopenia and hepatosplenomegaly. Hurlers syndrome is iduronidase defeicent lysosomal storage disease associated with the accumulation of dermatan sulfate and heparan sulfate in the lysosomes. Causing severe mental retardation, a coarse facies, corneal clouding, and coronary artery disease. An increase in cytosolic Ca2+ concentration marks the beginning of irreversible damage to the cardiac muscle. Calcium within the cytosol activates phospholipase in the cell membrane, proteases in the cytosol, and endonucleases in the nucleus, which produces irreversible injury and death of the cell.
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EBV virus infects B cells causing them go undergo mitosis predisposing to a t(8;14) MYC eventually causing burkitts lymphoma. Has a starry sky appearance, with the lymphocytes representing the dark of night and the histiocytes the stars. H. pylori increases the risk for developing adenocarcinoma of the stomach HHV-8 is an oncogenic virus that causes Kaposi sarcoma in AIDS. HPV is an oncogenic virus that produces protein products that inactivate the RB suppressor gene and the TP53 suppressor gene. HPV is associated with squamous cell carcinoma of the cervix, vagina, and vulva Left middle cerebral artery infarct produces a contralateral loss of sensory and motor function in the upper extremity and face. Majority of infarctions are due to thrombosis overlying an atheromatous plaque located in the middle cerebral artery. This produces a pale infarction with subsequent liquefactive necrosis. Embolic strokes cause a hemorrhagic infarction, usually within the distribution of the middle cerebral artery. Ruptured berry (saccular) aneurysms are located at the junction of the anterior cerebral artery and anterior communicating artery. Rupture is usually into the subarachnoid space. Hypertension causes vascular changes in small vessels ranging from hyaline arteriolosclerosis to the formation of Charcot-Bouchard microaneurysms in small penetrating branches of the middle cerebral artery. Most hypertensive strokes result in intracerebral hemorrhage in the basal ganglia, particularly the putamen and external capsule Aspirin interferes with the production of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to prostaglandin Corticosteroids interfere with the production of prostaglandins by inhibiting phospholipase A2 in the cell membrane, which blocks the release of arachidonic acid, causing decreased synthesis of prostaglandins and leukotrienes. Corticosteroids decrease leukotrienes by preventing the release of arachidonic acid A staghorn calculus (struvite stone) in the renal calyces and renal pelvis. The patients urine has an ammonia smell, which is consistent with a urinary tract infection due to urease producers (e.g., Proteus species). Ammonia produces a urine with an alkaline pH. Staghorn calculi are composed of magnesium, ammonia, and phosphate (staghorn calculus). Calcium oxalate crystals and stones develop in an acid pH urine. Respiratory distress syndrome (RDS), which is caused by a deficiency of surfactant. Dilated respiratory bronchioles and alveolar ducts lined by fibrin-rich membranes (hyaline membrane). The chest x-ray shows fine, uniform granularity (ground glass appearance) throughout both lung fields. Total collapse (atelectasis) of the subjacent alveoli is also shown .Causes of RDS of the newborn include prematurity (surfactant synthesis begins at 28 weeks), poor glycemic control in a mother with diabetes mellitus (insulin inhibits surfactant synthesis), and delivery by cesarean section (lack of stimulation of surfactant synthesis by cortisol released during the stress of a vaginal delivery). Surfactant normally decreases the surface tension in small airways, which decreases the collapsing pressure of the small airways during expiration. A decrease in surfactant causes massive atelectasis in the alveoli and widespread intrapulmonary shunting of blood, because the lungs are perfused but not ventilated.
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Epidural hematoma, which is caused by rupture of the middle meningeal artery, which is firmly attached to the periosteum of the temporal bone. Fracture of the temporal bone causes the vessel to rupture. Patients usually are unconscious after the initial trauma and then have a lucid interval followed by progressive loss of consciousness and death caused by transtentorial (uncal) herniation. A pulmonary complication of scuba diving is rupture of a preexisting intrapleural bleb or a subpleural bleb, causing a hole in the pleura and a spontaneous pneumothorax, which collapses all or part of the lung. Physical findings include hyper-resonance to percussion, tracheal deviation to the side of the collapse (if the whole lung is collapsed), elevation of the diaphragm, absent breath sounds, and absent vocal tactile fremitus. Physical findings of a pleural effusion include dullness to percussion, deviation of the trachea to the contralateral side, and absent breath sounds. Clinical findings in a pulmonary infarction are pleuritic chest pain and dyspnea Tension pneumothorax is associated with a flaplike pleural tear. Inspiration causes the flap to open and allow air to enter the pleural cavity. However, the flap closes on expiration and prevents the air from leaving the cavity. Increased intrapleural pressure (greater than the atmosphere) causes compression of the lung (atelectasis) and deviation of the trachea to the contralateral side. The diaphragm is depressed. Increased intrapleural pressure causes compression of the lung (atelectasis), hyper-resonance to percussion, absent breath sounds, and deviation of the trachea to the contralateral side (right side in this patient). Treatment is to relieve pressure by inserting a needle into the second intercostal space on the mid-clavicular line. Afterwards, a chest tube is inserted. A patient with a dry, puffy facial appearance and coarse hair. These findings, plus the fatigue, brittle hair, muscle weakness, delayed deep tendon reflexes, and hypertension, characterize primary hypothyroidism, which is most often caused by Hashimotos thyroiditis. Decreased synthesis of thyroxine (T4) results in increased thyroid-stimulating hormone (TSH) Because the thyroid gland is inactive and iodine is a component of thyroid hormone, uptake of 131I is decreased. Treatment is levothyroxine. Carcinoid syndrome (facial flushing, diarrhea, tricuspid regurgitation). In carcinoid syndrome, a carcinoid tumor that secretes serotonin must metastasize to the liver. Although the appendix is the most common site for carcinoid tumors.they do not metastasize to the liver. Most tumors causing the carcinoid syndrome arise in the terminal ileum. When these tumors metastasize to the liver, tumor nodules release serotonin directly into tributaries of the hepatic vein, which allows serotonin to enter the systemic circulation. Serotonin causes vasodilation of arterioles (causes facial flushing) and increases bowel motility (causes diarrhea). Serotonin is also fibrogenic causing the tricuspid valve leaflets to fibrose producing tricuspid regurgitation (pansystolic murmur that increases with deep, held inspiration). The metabolic end-product of serotonin is 5-HIAA. Infective endocarditis involving valves on the right side of the heart usually occurs in intravenous drug abusers who have dirty needles. Giardia is the most common protozoal cause of diarrhea in the United States. It is commonly contracted by drinking contaminated water from streams and lakes. Giardiasis is a common cause of chronic diarrhea and often produces fat malabsorption in association with greasy stools. The stool antigen test is the best screen for giardiasis. The treatment is metronidazole
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Cardiac myxomas are the most common primary cardiac tumors in adults. Symptoms include nonspecific complaints such as fever and malaise. The tumor has a ball-valve effect that causes sudden blockage of blood flow through the mitral valve, resulting in episodic fainting spells. A diastolic murmur similar to that of mitral stenosis is also present. Peripheral embolization of tumor also occurs. Infarctions of the spleen cause pain in the left upper quadrant and friction rubs. Infarctions of the kidneys cause flank pain and hematuria. Calcific aortic stenosis is associated with a systolic ejection murmur. Angina with exercise occurs because of ischemia of the subendocardium in the concentrically hypertrophied left ventricle. The decreased cardiac output through the stenotic valve causes syncope with exercise. vWF is normally synthesized in endothelial cells and megakaryocytes. In endothelial cells, its function is to adhere to GpIb receptors on platelets if there is endothelial injury (platelet adhesion factor). vWF, which combines with factor VIII antigen to prevent it from becoming degraded. Retinitis due to CMV. Examination of the retina shows white areas with indistinct borders (cotton wool exudates) that represent retinal infarctions due to a CMV vasculitis. CMV retinitis is the most common cause of blindness in patients with AIDS and usually occurs when the CD4 helper T-cell count < 50 cells/mm3. Ankylosing spondylitis (AS). The photograph shows the patient in a bent position so that the patient cannot see directly ahead. A radiograph of the spine shows forward curvature of the spine (kyphosis) with ankylosis (fusion) of the vertebrae (bamboo spine). AS begins with pain in the sacroiliac joints and then involves the vertebral column. This disorder, which commonly occurs in men. There is a strong association with HLA B-27, involvement of the sacroiliac joints, and arthritis that may involve peripheral joints. The heart murmur in this patient is due to aortitis involving the ascending aorta, which is often associated with aortic regurgitation (high-pitched diastolic murmur). Acute viral hepatitis include fatigue and jaundice, which is indicated by the yellow discoloration of the patients eyes. Hepatitis A is commonly associated with travel outside the United States. Characteristic histologic changes include apoptosis of hepatocytes, swelling of hepatocytes, and the presence of lymphocytic infiltrate, which are shown in the photograph. An apoptotic (Councilmans) body is apparent along the lower border of the biopsy. Histologic features of alcoholic hepatitis include a neutrophilic infiltrate, Mallorys bodies (pinkstaining keratin intermediate filaments in hepatocytes), and fatty change in hepatocytes. Primary biliary cirrhosis (PBC), which is an autoimmune disease associated with granulomatous destruction of the bile ducts in the portal triads. Pathogenesis involves an environmental insult affecting mitochondrial proteins triggering CD8-T cell destruction of intralobular bile duct epithelium. Autoantibodies (antimitochondrial antibodies) develop against the mitochondria. Clinical findings include pruritus (cause unknown; not bile salts deposited in skin) is an early finding well before jaundice appears; painful hepatosplenomegaly; and jaundice, which is a late finding after most of the bile ducts have been destroyed. The key laboratory findings are the presence of antimitochondrial antibodies (>90%), a positive serum ANA (50%), and an increase in serum IgM. Increased alkaline phosphatase and GGT are enzymatic markers of bile duct obstruction (cholestasis). Treatment includes budesonide + ursodeoxycholic acid, cholestyramine for pruritus, and liver transplantation Increased serum -fetoprotein (AFP) occurs in hepatocellular carcinoma Central diabetes insipidus (absence of ADH), most likely caused by transection of the pituitary stalk after hitting his head in the automobile accident. ADH is synthesized in the hypothalamus and
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travels down through the pituitary stalk to the posterior pituitary, where it is secreted. ADH is required to concentrate urine by reabsorbing electrolyte-free water from the collecting tubules of the kidneys; therefore, absence of ADH causes polyuria (urinary frequency), due to a loss of free water in the urine. When the patient is deprived of water, the urine osmolality (UOsm) decreases and the POsm increases, because of increased serum sodium (hypernatremia). An increase in POsm stimulates thirst. Internal hemorrhoids are a plexus of superior hemorrhoidal veins located above the dentate line, which are covered by mucosa. The most common cause is straining at stool, often causing the hemorrhoids to protrude from the anal opening). The protrusion reduces spontaneously in most cases but sometimes cannot reduce, thus requiring surgery. Passage of bright red blood per rectum and a mucoid perianal discharge. Unless there is thrombosis of the prolapsed hemorrhoids, there usually is no pain. Colorectal cancer is associated with blood coating and mixing with stools Ischemic colitis occurs in older individuals. Ischemic colitis is associated with pain in the splenic flexure after eating (mesenteric angina) and the presence of bloody stools. Chronic renal failure, the aldosterone-mediated Na+, K+-ATPase pump in the renal tubules is dysfunctional. This leads to increased urinary loss of Na+ and retention of K+ (hyperkalemia). The ECG shows a peaked T wave, indicating hyperkalemia. Any increase or decrease in K+ concentration produces conduction disturbances in muscle that may lead to weakness. Diarrhea in adults is associated with an isotonic loss of fluid (normal serum sodium), loss of HCO3(normal anion gap metabolic acidosis), and loss of K+ (hypokalemia). On an ECG, hypokalemia is indicated by a prominent U wave Primary aldosteronism an increase in aldosterone enhances the Na+-K+ pump in the late distal and collecting tubules. This increases the exchange of Na+ for K+, causing loss of K+ in the urine (hypokalemia) and retention of Na+ (hypernatremia). Vomiting causes metabolic alkalosis due to the loss of acid and retention of Hco3-. Alkalosis causes a shift of H+ out of the cells in exchange for K+, causing hypokalemia. Wiskott-Aldrich syndrome is an X-linked recessive disorder with progressive depletion of B and T cells. The classic triad is eczema, thrombocytopenia, and recurrent sinopulmonary infections. There is an increased risk for malignant lymphoma and leukemia. Immunoglobulins show a decreased IgM, normal IgG, and increased IgA and IgE. There is defective cell mediated immunity (anergic to Candida skin test). There is an increased risk for developing malignant lymphoma. The treatment is bone marrow transplantation Ataxia telangiectasia is an autosomal recessive disorder with a mutation in DNA repair enzymes leading to increased susceptibility for chromosomal mutations. Clinical findings include cerebellar ataxia and telangiectasias of the eyes and skin. Laboratory studies reveal an increase in serum fetoprotein; decreased in IgA, IgE, low molecular weight IgM, and IgG2 or total immunoglobulins. Treatment is intravenous immunoglobulins and deferoxamine. Brutons agammaglobulinemia is an X-linked recessive disorder where a mutation in tyrosine kinase causes failure of pre-B cells to become mature B cells. This produces hypogammaglobulinemia, because there are not sufficient numbers of B cells to be antigenically stimulated to become plasma cells. Deficiency of IgG produces an opsonizing defect. The antigen recognition site of IgG attaches to the bacteria, and the Fc portion of the immunoglobulin attaches to receptors in the plasma membrane of phagocytic leukocytes (neutrophils, monocytes,
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macrophages). This facilitates the phagocytosis of bacteria by triggering engulfment of bacteria by pseudopods and eventual formation of a phagocytic vacuole. Patients have recurrent sinopulmonary infections and an increased incidence of Streptococcus pneumoniae infections. All immunoglobulins (Igs) are decreased and there is a flat -globulin peak in a serum protein electrophoresis. Treatment is intravenous immunoglobulins. Common variable immunodeficiency is the most common immunodeficiency in adults. It is characterized by recurrent sinopulmonary infections, malabsorption (celiac sprue), and an increased risk for autoimmune disease, non-Hodgkins lymphoma, and giardiasis. All immunoglobulins are decreased. Treatment is intravenous immunoglobulins. Selective IgA deficiency is the most common hereditary immunodeficiency. It is characterized by failure of IgA B cells to mature into plasma cells leading to decreased serum IgA and secretory IgA. Sinopulmonary infections and giardiasis are common findings. They may develop anaphylaxis when exposed to blood products containing IgA. SCID is an autosomal recessive disease. In some cases, there is a deficiency of adenine deaminase leading to an accumulation of adenine in B and T cells resulting in death of the cells. All immunoglobulins are decreased and there is defective cell-mediated immunity (CMI). Treatment is gene therapy and bone marrow transplantation Klinefelters syndrome include an XXY phenotype with 47 chromosomes and signs of hyperestrinism (gynecomastia, female distribution of pubic hair). Diminished testicular volume is due to testicular atrophy. The testicles show fibrosis of the seminiferous tubules and hyperplasia of the Leydig cells. Loss of the seminiferous tubules leads to absence of spermatogenesis (azoospermia) and absence of Sertoli cells, which normally contain the hormone inhibin. Inhibin has a negative feedback relationship with FSH; therefore, a decrease in inhibin causes an increase in FSH. FSH, in turn, increases the synthesis of aromatase in the hyperplastic Leydig cells leading to conversion of all the testosterone to estradiol, which produces the signs of hyperestrinism that are present in the patient. Serum testosterone levels are decreased, which leads to a decrease in libido and impotence Dermatitis Herpetiformis has painful vesicular lesions on the extensor surface of the elbow and the history of chronic diarrhea with greasy stools associated with gluten-sensitive enteropathy (celiac disease). The skin lesion is due to the deposition of IgA along the tips of the dermal papillae, resulting in an immune reaction that produces subepidermal vesicles. IgA and IgG antibodies formed against the gliadin protein fraction in gluten (component of wheat) cross-react with reticulin, which normally anchors the epidermal basement membrane to the superficial dermis. Most patients with dermatitis herpetiformis have flattening of the small bowel villi and inflammation of the lamina propria indicative of celiac disease. Antigliadin and antireticulin antibodies are commonly found in these patients. Antiendomysial antibodies directed against an enzyme that degrades gliadin peptides are also present Cysticercosis is caused by the larval form of the pork tapeworm Taenia solium. The patient most likely contracted the infection from a family member who ate improperly cooked pork containing the larvae, which developed into adults that laid eggs (family member is the definitive host). The patient must have ingested food contaminated with eggs of the adult T. solium. The larvae gain access to the systemic circulation, resulting in lesions in the muscle and brain and eosinophilia. Cysts frequently undergo calcification and also cause focal or generalized seizures.
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A venous thrombus first developed in the deep veins of the leg and then continued to propagate and eventually extend into the femoral vein, where it dislodged and embolized to the lungs. Thromboembolism is common in the postoperative setting, particularly after a total hip replacement. Sudden occlusion of the main stem pulmonary arteries produces an acute increase in pulmonary artery pressure and acute right-sided ventricular strain, leading to sudden death (acute cor pulmonale). Ulcerative colitis. The colectomy specimen shows diffuse ulceration of the mucosal surface and residual islands of inflamed, hemorrhagic mucosa (pseudopolyps). These gross findings, plus the history of recurrent bloody diarrhea, are associated with ulcerative colitis. Ulcerative colitis is a chronic ulceroinflammatory disease that targets individuals between 20 and 25 years of age. An increased incidence of colorectal cancer correlates with long duration of the disease. Presents with a history of crampy pain in the left lower quadrant and bloody diarrhea. Associated with the large bowels. Crohns is an inflammatory bowel disease characterized by chronic granulomatous ulceroconstrictive disease that mainly targets the terminal ileum. Transmural inflammation involving the terminal ileum causes narrowing of the lumen and signs of obstruction (colicky pain) in the right lower quadrant. Produces transmural inflammation that leads to obstruction. Terminal ileal involvement is characteristic. Restrictive disorders usually present with a increased FEV1:FVC ratio. Restrictive disorders are characterized by limited filling of the lungs causing all the lung volumes to be decreased (i.e., stiff lungs). Elastic recoil of the lung is increased, due to an increase of fibrous tissue in the interstitium. Due to an increase in elastic recoil in the lungs, the FEV1sec and FVC are frequently the same (e.g., 3 L) causing the ratio of the two to be normal or increased. In obstructive lung disease, the FEV1sec:FVC ratio is decreased. Emphysema is a COPD that produces permanent enlargement of all or part of the distal airways as well as destruction of the pulmonary capillary bed. In a nonsmoking individual with lower lobe emphysema, the patient most likely has panacinar emphysema due to a deficiency of 1-antitrypsin, a protein that normally neutralizes elastases produced by neutrophils Neurofibromatosis complicated by hypertension due to a pheochromocytoma. The skin lesions in neurofibromatosis include pigmented, pedunculated tumors (neurofibromas) and flat, oval-shaped, coffee-colored patches (caf-au-lait patches), which are evident in the photograph. Neurofibromatosis is an autosomal dominant neurocutaneous disorder with an increased incidence of pheochromocytoma (unilateral or bilateral) and central and peripheral nervous system tumors (e.g., meningioma, acoustic neuroma), depending on the type of neurofibromatosis. The classic triad of headache, palpitations, and excessive sweating is highly predictive of a pheochromocytoma. Catecholamine excess may cause subendocardial ischemia resulting in angina (as occurred in this patient). Hypertension is characterized as sustained, sustained with paroxysms (most common), or paroxysmal only. Plasma free metanephrine is the most sensitive test to screen and confirm a pheochromocytoma. Other tests include plasma normetanephrine and metanephrine, 24-hour urine for metanephrine (100% sensitivity), and 24-hour urine for vanillylmandelic acid. Serum electrolytes are most useful in diagnosing primary aldosteronism (not a pheochromocytoma). The benign adrenocortical adenomas arise in the zona glomerulosa of the adrenal cortex. Excess aldosterone causes hypernatremia, hypokalemia, and metabolic alkalosis.
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Serum lipase is a more specific test for acute pancreatitis than serum amylase, which may be normal in the serum after 2 to 4 days. Lipase initially increases in 3 to 6 hours; peaks in 12 to 30 hours, and returns to normal in 7 to 14 days. Severe acute pancreatitis have decreased serum calcium, increased serum glucose due to the destruction of Beta islet cells, increased WBC and trypsin. A defect in neutrophil adhesion molecules (i.e., selectins and integrins) prevents neutrophils from adhering to endothelial cells and transmigrating into tissue. Niacin is primarily synthesized by colonic bacteria and is also present in meats, fish, vegetables, and nuts. Some niacin is also synthesized from tryptophan. Patients who have corn-based diets commonly develop niacin deficiency (pellagra) because the niacin in corn is in a bound form that cannot be reabsorbed, and corn is deficient in tryptophan. The patient has diarrhea and dermatitis, two of the three major symptoms of pellagra. Dementia also may occur. Vitamin A deficiency is associated with night blindness, blindness caused by squamous metaplasia of conjunctival epithelium, respiratory infections, and dry skin (follicular hyperkeratosis). Vitamin B6 deficiency is associated with defects in heme synthesis (sideroblastic anemia), peripheral neuropathy, and convulsions. Treatment of tuberculosis with isoniazid is the most common cause of pyridoxine deficiency. Chronic pancreatitis, recurrent attacks of acute pancreatitis lead to repair by fibrosis and loss of both exocrine and endocrine function. Loss of the pancreatic enzymes results in malabsorption, which is the cause of the patients chronic diarrhea and malnutrition. Serum amylase is usually increased and serum immunoreactive trypsin is decreased, due to destruction of the pancreatic parenchyma. The D-xylose test is normal, because xylose does not require pancreatic enzymes for reabsorption. Chronic recurrent rheumatic fever and developed mitral stenosis. Recall that in rheumatic fever antibodies directed against the M proteins of certain strains of group A streptococci cross-react with antigens present in cardiac valves (most commonly the mitral valve) and other tissues. Repeated valve inflammation leads to repair by fibrosis, dystrophic calcification, and eventual stenosis of the valve. This leads to atrial dilation and hypertrophy and an increase in pulmonary venous pressure resulting in pulmonary edema and pulmonary venous hypertension. Increased pulmonary vein pressure caused right ventricular hypertrophy and right-sided heart failure. The combination of pulmonary hypertension and right ventricular hypertrophy is called cor pulmonale. Gross signs of pulmonary hypertension are atherosclerosis of the pulmonary artery and prominent vessels on cut sections of the lungs. Libman-Sacks endocarditis is the most common valvular disease in systemic lupus erythematosus. Sterile vegetations occur on the mitral valve and chordae leading to valve dysfunction characterized by mitral regurgitation Recurrent bacterial endocarditis is more likely to produce mitral regurgitation rather than mitral stenosis, because the bacteria destroy the valve leaflet and often cause rupture of the chordae tendineae. Crohns disease is an inflammatory condition that involves the terminal ileum in approximately 80% of cases; therefore, vitamin B12 deficiency may occur, because the terminal ileum is the primary site for reabsorption of the intrinsic factorvitamin B12 complex. Vitamin B12 deficiency causes a macrocytic anemia (delayed DNA maturation), pancytopenia (anemia, neutropenia, thrombocytopenia), and the formation of hypersegmented neutrophils in the peripheral blood.
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Vitamin B12 is involved in propionate metabolism (odd-chain fatty acids). Propionyl CoA is converted to methylmalonyl CoA, which is then converted to succinyl CoA, a reaction that uses vitamin B12 as a cofactor. Therefore, vitamin B12 deficiency causes an increase in both methylmalonyl CoA and propionyl CoA. Propionyl CoA replaces acetyl CoA in neuronal membranes resulting in demyelination of the posterior columns (loss of vibratory sensation and proprioception) and lateral corticospinal tract (upper motor neuron disease). Minimal change disease (lipoid nephrosis), which is the most common cause of the nephrotic syndrome in children. The nephrotic syndrome is characterized by proteinuria > 3.5 g/24 hr. Minimal change disease is due to T-cell production of cytokines that causes the loss of the negative charge of the glomerular basement membrane. This produces a selective loss of albumin, resulting in a decrease in plasma oncotic pressure with development of generalized edema with ascites. Hypoalbuminemia is a stimulus for increased cholesterol synthesis in the liver. Cholesterol is lost in the urine, resulting in the formation of fatty casts, which when polarized are shaped like Maltese crosses (see Fig. 19-2C in Rapid Review Pathology, 3rd edition). The electron micrograph shows a light gray basement membrane. The podocytes on the epithelial side of the membrane are fused, which is a characteristic finding in all cases of nephrotic syndrome, regardless of the cause. Serum-associated amyloid, an acute-phase reactant, is produced by the liver in any acute or chronic inflammatory condition. In cases of chronic inflammation (e.g., rheumatoid arthritis in this patient), serum-associated amyloid is likely to be converted to type AA amyloid, which deposits in multiple organs (e.g., kidneys, heart, liver, spleen). This type of amyloidosis is called secondary (reactive) systemic amyloidosis. The renal biopsy of a Congo red stained slide of a renal biopsy with polarization shows apple green birefringence of amyloid material deposited in the glomerulus and renal tubules.Renal amyloidosis presents with the nephrotic syndrome (i.e., fatty casts, proteinuria > 3.5 g/24 hr). Hypoalbuminemia causes a decreased oncotic pressure leading to dependent pitting edema, as in this patient. Pinch purpura, arrhythmias resistant to therapy, and carpal tunnel syndrome are common findings in systemic amyloidosis Amyloid precursor protein is a gene product produced by chromosome 21. It is converted to (amyloid (A(), which when phosphorylated is toxic to neurons in the central nervous system causing Alzheimers disease. Calcitonin is produced by C cells and converted to amyloid in medullary carcinoma of the thyroid. Light chains are amyloid precursors associated with primary amyloidosis, which is associated with multiple myeloma Coccidioides immitis. This infection occurs in desert regions of the southwestern United States, particularly in Arizona, New Mexico, and southern California. It is contracted by inhalation of arthrospores in the dust. The biopsy shows an intact spherule containing endospores. The lesions on the lower legs represent erythema nodosum, which is commonly associated with coccidioidomycosis. It is caused by inflammation of the subcutaneous fat and presents with painful, red nodules usually located on the lower extremities Allergic contact dermatitis, which is a type IV hypersensitivity reaction. Specifically, it is an example of a cell-mediated cytotoxicity reaction where CD8 T cells interact with altered class I antigens on neoplastic, virus-infected, or donor graft cells, causing cell lysis or, as in this case, a CD8 T-cell reaction against antigens in skin. Same type of HSR in acute rejection of organ transplant
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Hemolytic anemia caused by penicillin is a type II hypersensitivity reaction. IgG antibodies are directed against penicillin attached to the RBC membrane. Macrophages with Fc receptors for IgG phagocytose and destroy the sensitized RBCs. Myasthenia gravis is a type II hypersensitivity reaction. IgG antibodies are directed against acetylcholine receptors, causing muscle weakness. Urinary retention due to prostate hyperplasia has led to sepsis (most often due to Escherichia coli) and endotoxic shock, which is the most common cause of acute respiratory distress syndrome (ARDS). ARDS, there is acute damage to alveolar capillary walls and epithelial cells. Alveolar macrophages and other cells release cytokines that are chemotactic to neutrophils. Neutrophils transmigrate into the alveoli through pulmonary capillaries. Capillary damage causes leakage of a protein-rich exudate producing hyaline membranes. Neutrophils damage types I and II pneumocytes, the latter causing a decrease in surfactant leading to atelectasis with intrapulmonary shunting. Late findings include repair by type II pneumocytes and progressive interstitial fibrosis (restrictive lung disease). Clinical findings include dyspnea, tachypnea, and inspiratory crackles. Chest radiography shows interstitial and alveolar infiltrates. Arterial blood gases show hypoxemia and respiratory acidosis. Addisons disease, which is most often due to autoimmune destruction of the adrenal cortex. Destruction of the zona glomerulosa produces a deficiency of aldosterone, which is responsible for the electrolyte abnormalities. There is inhibition of Na+ reabsorption and K+ secretion by the aldosterone-dependent Na+ and K+ channels located in the distal tubule and collecting ducts causing a hypertonic loss of Na+ in the urine (hyponatremia) and retention of K+ (hyperkalemia with peaked T waves). Due to dysfunction of the aldosterone-dependent H+/K+ ATPase pump in the collecting tubules, there is retention of H+ ions and a subsequent lack of synthesis of HCO3, which produces metabolic acidosis. In chronic renal failure there is tubular cell dysfunction resulting in retention of K+(hyperkalemia with peaked T waves on an ECG) and an increased anion gap type of metabolic acidosis due to retention of organic acids like sulfuric and phosphaturic acid Secretory type of diarrhea (e.g., travelers diarrhea due to enterogenic Escherichia coli, cholera). In these conditions a toxin activates adenylate cyclase in enterocytes causing the ion pumps in the small intestine to secrete isotonic fluid. Loss of isotonic fluid does not alter the serum Na+ concentration. Diarrheal fluid is rich in K+ and HCO3, the former resulting in hypokalemia and the latter a normal anion gap type of metabolic acidosis. Thiazide and loop diuretics inhibit channels in the nephron causing decreased reabsorption of Na+. This causes a hypertonic loss of Na+ (hyponatremia) and Cl (hypochloremia). Increased delivery of Na+ to the late distal and collecting tubules results in augmented exchange of Na+ for K+ in the aldosterone-dependent Na+ channels resulting in increased urinary loss of K+(hypokalemia with U waves on an ECG). When K+ is depleted, Na+ exchanges with H+ ions causing increased synthesis and reabsorption of HCO3 causing metabolic alkalosis. In vomiting, hydrochloric acid is lost. For every H+ ion lost in the vomitus, there is a corresponding HCO3left unneutralized in the blood causing metabolic alkalosis. Alcoholic hepatitis. The photograph shows fatty change, loss of the normal liver architecture, scattered neutrophils, and eosinophilic staining material within hepatocytes consistent with Mallorys bodies (damaged keratin intermediate filaments). These findings, plus the clinical findings of fever, painful hepatomegaly, and jaundice, are compatible with alcoholic hepatitis. Alcohol is
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toxic to mitochondria and AST is located in mitochondria. Therefore, this transaminase is released in greater amounts than is alanine aminotransferase (ALT), which is located in the cytosol. Alcohol induces the cytochrome P-450 system within the smooth endoplasmic reticulum in the liver, leading to increased synthesis of GGT. An increase in this enzyme and an AST level that is higher than that of ALT is characteristic of alcoholic hepatitis Loop diuretics cause hypokalemia by blocking the Na+-K+-2 Cl cotransport system in the thick ascending limb in the renal medulla. This causes increased exchange of Na+ for K+ in the late distal tubules and collecting tubules and increased urinary loss of K+ resulting in hypokalemia. Hypokalemia causes muscle weakness by interfering with the normal repolarization of muscle. Aldosterone blocker (e.g., spironolactone) interferes with the normal exchange of Na+ for K+ in the late distal and collecting tubules, resulting in increased urinary loss of Na+ (diuretic effect) and retention of K+ (hyperkalemia). Hyperkalemia produces a peaked T wave on an ECG. Digitalis inhibits the Na+, K+-ATPase pump in cardiac muscle, which normally enhances the movement of Na+ into the muscle and the opening of calcium channels resulting in an increase in muscle contraction. Since K+ is pumped out of the cell, hyperkalemia may occur in digitalis toxicity Urachus is an embryologic canal that connects the urinary bladder of the fetus with the umbilical cord. Usually the lumen of the urachus becomes obliterated during embryonic development and becomes a solid cord. However, if the lumen remains patent, then urine (clear fluid in this patient) will leak from the umbilicus. Omphalocele is a protrusion at birth of part of the intestine through a large defect in the abdominal wall at the umbilicus. It is usually covered by a transparent membrane composed of amnion and peritoneum. Vitelline (omphalomesenteric) duct is an opening to the digestive tract that arises from the yolk sac. Usually the duct obliterates in the embryonic period; however, if its proximal part persists, it does so as a diverticulum from the small intestine called a Meckel diverticulum. Paroxysmal nocturnal hemoglobinuria is an acquired membrane defect involving common myeloid stem cells. A gene mutation causes loss of the anchor for decay accelerating factor (DAF), which normally neutralizes complement attached to RBCs, neutrophils, and platelets at night. Loss of DAF causes intravascular complement destruction of RBCs, neutrophils, and platelets leading to pancytopenia and hemoglobinuria. Glaucoma is associated with an increase in intraocular pressure due to a narrow anterior chamber (acute angle-closure glaucoma) or decreased aqueous drainage through the trabecular meshwork (open-angle glaucoma). Macular degeneration is the leading cause of permanent visual loss in the elderly. Yellow deposits are seen in the macular region (called drusen) followed by degeneration of the retina. Fat embolization occurs following traumatic fracture of long bones (e.g., femur) and pelvic bones. Microglobules of fat from the bone marrow of the fractured bones and surrounding adipose lodge in the microvasculature throughout the body where they produce ischemia and hemorrhage. Dyspnea (hypoxemia due to fat microglobules in the pulmonary capillaries) and petechial hemorrhages (due to thrombocytopenia) in the upper chest suddenly develop. Neurologic symptoms include restlessness and mental status changes with progression to coma. Diagnosis of fat embolism is usually a clinical diagnosis. Search for fat globules in urine, pulmonary alveolar lavage, and spinal fluid is sometimes helpful. Treatment is supportive with an emphasis on maintaining good arterial oxygenation
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Air embolism occurs during obstetric procedures (e.g., uterine evacuation in abortion), head and neck surgery, or as a consequence of chest trauma. Suction of air into the venous system mixes with blood in the right side of the heart, causing a frothy substance to block blood flow into the pulmonary artery. Cardiogenic shock is most commonly caused by acute myocardial infarction. Cardiac output is decreased, and left ventricular end-diastolic pressure and pulmonary capillary hydrostatic pressure are increased, causing pulmonary edema (left-sided heart failure). Septic (endotoxic) shock most often occurs in patients with indwelling urinary catheters. Sepsis due to Escherichia coli causes the release of endotoxins, which activate the complement system (releasing anaphylatoxins) and damage endothelial cells (releasing vasodilators such as prostacyclin and nitric oxide). Vasodilation of the peripheral resistance arterioles produces warm skin and increases venous return to the heart, causing high-output cardiac failure. Advanced bronchiectasis can show saccular dilation of bronchi thru the lung. The saccules are filled with pus and extend to the periphery of the lung. Chronic infection is the most common cause of this condition. During the inflammatory process, destruction of cartilage and elastic tissue results in dilation of the bronchi and collection of large quantities of pus. Common pathogens include Mycobacterium tuberculosis, Staphylococcus aureus, adenovirus, and Haemophilus influenzae. In the United States, lung infections associated with cystic fibrosis are the most common cause of bronchiectasis. Bronchiectasis is an obstructive lung disease that involves mainly the bronchi and terminal bronchioles. The immotile cilia syndrome is associated with bronchiectasis, but it is extremely rare. In this autosomal recessive syndrome, the cilia lack the dynein arm, which contains ATPase required to produce the energy for movement of the cilia. If associated with situs inversus (reversal of the internal organs) and chronic sinusitis, it is called Kartageners syndrome. Diabetic glomerulopathy, which is often associated with proteinuria in the nephrotic range (>3.5 g/24 hrs). Arteriolar and glomerular disease in poorly controlled diabetes is due to nonenzymatic glycosylation (NEG). NEG occurs when glucose attaches to amino acids in the basement membrane of arterioles/capillaries leading to the production of advanced glycosylation products that render the membrane permeable to plasma proteins. The proteins diffuse into the wall of the vessel, narrowing the lumen causing ischemic damage to the tissue. Both the afferent and efferent arterioles are hyalinized in diabetic glomerulopathy. Hypertension can also produce hyaline arteriolosclerosis by forcing plasma proteins through the basement membrane via the increased intraluminal pressure. Analgesic nephropathy is associated with chronic ingestion of aspirin and acetaminophen. Tubular and interstitial damage results from a combination of ischemia and free radical injury of the tubule cells. Ischemia is due to aspirin inhibition of renal prostaglandin synthesis, which normally produces vasodilation of the afferent arterioles. Free radical injury is due to liver conversion of acetaminophen into a drug free radical. Analgesic nephropathy may cause renal papillary necrosis. Herpes simplex 2 can cause multiple penile ulcerations. This sexually transmitted disease often recurs, because the virus remains latent in the sensory ganglia. The virus infects the nucleus of squamous cells causing them to divide. The multinucleated cells contain ground glass nuclei, which subsequently develop into eosinophilic inclusions. A Tzanck preparation is performed by unroofing one of the vesicles and scraping the base of the ulcer. Acyclovir is used to decrease the number of recurrences but does not cure the infection.
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Chlamydia trachomatis infects metaplastic squamous cells. Two distinct forms of the organism that develop in vacuoles within metaplastic squamous cells are the elementary body (metabolically inert but infective) and the reticulate body (metabolically active but not infective). Binary fission of the reticulate bodies in the vacuoles of the infected cell results in the production of numerous elementary bodies. Squamous dysplasia on the penis describes Bowens disease, which involves the shaft of the penis and/or scrotum. The lesions are white patches and are not recurrent. Squamous cells with increased mitoses and hyperchromatic nuclei describes a dysplastic cell, which is a precursor to squamous cancer. Human papillomavirus within a squamous has a cell with a pyknotic nucleus surrounded by a clear halo is the cytologic effect of the cell. The lesion is called condyloma acuminatum (venereal warts). It is an exophytic lesion in the anogenital region that has a keratotic papillary appearance. Pitting edema can partially can be caused by an increased aldosterone. Pitting edema is due to an alteration in Starlings pressure (increased in plasma hydrostatic pressure and/or decrease in oncotic pressure). Sodium retention increases plasma hydrostatic pressure and decreases oncotic pressure (dilutes serum albumin due to an excess in plasma volume). The fluid that accumulates in the interstitial tissue is protein-poor and cell-poor (i.e., transudate). The patient has signs and symptoms of both left-sided heart failure (dyspnea and bibasilar inspiratory crackles) and rightsided heart failure (distention of neck veins, hepatomegaly, and dependent pitting edema). Rightsided heart failure causes a backup of blood into the venous system, which increases the hydrostatic pressure and is the primary factor causing the pitting edema. In biventricular heart failure, decreased cardiac output decreases renal blood flow, which activates the renin-angiotensinaldosterone (RAA) system, which leads to an increase in the serum concentration of aldosterone. Edema is the accumulation of fluid in body cavities (e.g., ascites) and in the interstitial space (e.g., peripheral edema. An increase in hydrostatic pressure and/or a decrease in plasma oncotic pressure (hypoalbuminemia) cause outflow of a protein-poor (<3 g/dL) and cell poor fluid into body cavities and interstitial spaces. This defines a transudate. In cirrhosis, the portal vein encounters increased resistance to emptying blood into the liver sinusoids (intrasinusoidal hypertension) due to compression of the sinusoids by regenerative nodules and fibrosis. This causes increased hydrostatic pressure (portal hypertension) that contributes to ascites formation. The synthetic function of the liver is compromised in cirrhosis; therefore, hypoalbuminemia occurs, which decreases the plasma oncotic pressure, further contributing to ascites and peripheral edema (dependent pitting edema). Because transudates have decreased protein and cells, they obey the law of gravity and percolate through the interstitial tissue and settle in the most dependent portions of the body (e.g., feet). Movement of water between the extracellular fluid compartment (ECF) and the intracellular fluid compartment (ICF) is called osmosis.Alterations in the serum Na+ concentration in the ECF compartment is the primary cause of water movement between the compartments. In hyponatremia, water moves from the ECF into the ICF compartment, whereas in hypernatremia, water moves from the ICF into the ECF compartment. Vibrio cholerae causes secretory diarrhea. It produces a toxin that activates adenylate cyclase in enterocytes causing a secretory diarrhea with the loss of isotonic fluid. Loss of isotonic fluid doesnot alter the serum Na+ concentration. Diarrheal fluid is rich in K+ and HCO3, the former resulting in hypokalemia and the latter a normal anion gap type of metabolic acidosis. The serum
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Cl is increased, because it replaces the HCO3 anions that are lost in the diarrheal fluid to maintain electroneutrality Tear-drop shape of many of the RBCs in the peripheral blood smear is caused by membrane damage that occurs when they exit the fibrotic bone marrow. Breast cancer commonly metastasizes to bone, often to the vertebral column Multiple myeloma is the most common malignant plasma cell disorder. Evidence of multiple myeloma in the peripheral blood is the presence of rouleaux (RBCs stacked like coins). In addition, lytic lesions in bone are commonly present. Iron-deficiency anemia, which can be confirmed by the serum ferritin test. The peripheral blood smear shows RBCs with a notable increase in the central areas of pallor, which indicate decreased hemoglobin concentration. Strong evidence of iron deficiency is given by the increased RBC distribution width (RDW, increased size variation in RBCs) and the patients history of dysfunctional uterine bleeding (menorrhagia). The RDW is increased in iron deficiency, because there is a mixed population of normocytic and microcytic RBCs. The other causes of microcytic anemia (e.g., anemia of chronic disease, thalassemia) are not as likely to have this size variation in RBCs and have a normal RDW. The serum ferritin test is the best screening test for iron-related disorders, because serum ferritin levels correlate with the amount of iron stored in the bone marrow macrophages. Since mature RBCs lack mitochondria, anaerobic glycolysis is the primary source of energy adenosine-5'-triphosphate (ATP) in RBCs. Lactic acid is the end-product of anaerobic glycolysis. Lactic acid is taken up by the liver, converted into pyruvate, which is then used to synthesize glucose by gluconeogenesis in the fasting state. The glucose that is produced is used by RBCs for fuel. This is called the Cori cycle. Vitamin B12 requires intrinsic factor synthesized by parietal cells in the stomach for reabsorption into the terminal ileum. Pernicious anemia is an autoimmune disease with antibodies directed against parietal cells and intrinsic factor (type II hypersensitivity reaction), causing a decrease in intrinsic factor and malabsorption of vitamin B12. In the Schilling test, oral administration of intrinsic factor allows vitamin B12 to be reabsorbed, confirming the diagnosis of pernicious anemia. Vitamin B12removes the methyl group from methyltetrahydrofolate (circulating form of folic acid), producing methylvitamin B12 and tetrahydrofolate. The methyl group is then transferred to homocysteine, which is converted to methionine. Therefore, increased plasma homocysteine is caused by both vitamin B12and folic acid deficiency. Pancytopenia and a megaloblastic bone marrow are caused by a deficiency of vitamin B12 or folic acid, because both vitamin B12 and folic acid are required for DNA synthesis. Delayed nuclear maturation results in large nucleated hematopoietic cells (megaloblastic cells) that are destroyed in the bone marrow by macrophages or by apoptosis, causing pancytopenia (anemia, neutropenia, thrombocytopenia). Primary ovarian cancer that is seeding the omentum, which causes malignant ascites, and seeding of the rectal pouch, which causes induration of the tissue that is palpable on rectal examination. Ovarian cancers that are more likely to seed are surface-derived cancers (e.g., serous cystadenocarcinoma, mucinous cystadenocarcinoma). Nulliparity poses an increased risk for this group of cancers, because an increased number of ovulatory cycles increases risk. Oral contraceptives decrease the risk for these cancers by decreasing the number of ovulations. The tumor also has metastasized to the left lung and left pleural cavity.
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Acute rheumatic fever (ARF) several weeks after a group A streptococcal (Streptococcus pyogenes) pharyngitis. Clinical findings in ARF include sore throat, followed within several weeks by fever, joint pain, subcutaneous nodules, and skin changes (erythema marginatum, as in this case). The pansystolic murmur at the apex is caused by mitral regurgitation due to a sterile endocarditis, and the bibasilar inspiratory crackles and S3 and S4 heart sounds are caused by left-sided heart failure due to myocarditis, which decreases the force of contraction leading to a systolic dysfunction type of heart failure. Valvular regurgitation and the myocarditis produce left ventricular volume overload, which is responsible for the abnormal heart sounds. The S3 heart sound is due to blood entering a volume overloaded chamber in early diastole, while the S4 heart sound is due to blood entering a noncompliant left ventricle in late diastole. Cardiac damage is caused by antibodies directed against the streptococcal M proteins (virulence factor), which cross-react with antigens in the heart and other tissues (i.e., type II hypersensitivity reaction). Type IV hypersensitivity has also been implicated in the disease. Blood cultures are negative, because rheumatic fever causes immunologic damage (fibrinoid necrosis) to the heart and tissues. The serum antistreptolysin O titers are increased and are useful in confirming the diagnosis. Spontaneous bacterial peritonitis is characterized by diffuse abdominal pain, rebound tenderness, absent bowel sounds. The most common pathogen in SBP in cirrhosis is Escherichia coli, a Gramnegative rod, while in nephrotic syndrome, SBP is caused byStreptococcus pneumoniae. Treatment is cefotaxime. Hypertension causes vascular changes in small vessels, such as hyaline arteriolosclerosis or the formation of Charcot-Bouchard microaneurysms in small penetrating branches of the middle cerebral artery (which supplies the basal ganglia and anterior and posterior limbs of the internal capsule). Rupture of the aneurysms caused an intracerebral hematoma. The clot extends into the ventricle. Most hypertensive intracerebral bleeds occur in the basal ganglia, particularly the putamen and external capsule. Strong pulses in the upper extremities and diminished pulses in the lower extremities associated with pain in the legs with running (claudication) are indicative of postductal coarctation of the aorta Acute diverticulitis is characterized by pain in the left lower quadrant (left-sided appendicitis) rather than the epigastrium. Roseola, which is caused by human herpesvirus 6 (DNA virus). It is the most common viral exanthem in children < 2 years old. Erythematous macules develop on soft palate 48 hours before the rash. The maculopapular rash occurs abruptly after 3 to 7 days of high fever and is characterized by blanching with pressure and the presence of subtle peripheral halos around the lesions. High fever may precipitate a febrile convulsion. Molluscum contagiosum is caused by a poxvirus (DNA virus). It is characterized by bowl-shaped lesions with central depression filled with keratin. The depression contains viral particles called molluscum bodies. Self-inoculation may occur by scratching the infective viral particles out of the crater Rubella, or German measles, is an RNA togavirus that produces 3-day measles. Dusky red spots called Forchheimers spots appear on the posterior soft/hard palate and develop at the beginning of the rash. The rash is a maculopapular rash and lasts 3 days. It is a pinkish, red maculopapular eruption, begins first at the hairline and rapidly spreads cephalocaudally, lasts for 3 days, and fades in 3 days. Painful postauricular lymphadenopathy is a characteristic finding.
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Rubeola, or regular measles, initially has a prodrome of fever, cough, coryza (runny nose), and conjunctivitis. Koplik spots develop on the buccal mucosa and a maculopapular rash develops after the Koplik spots disappear. The rash typically begins on the head and then moves to the trunk and extremities. It tends to become confluent on face and trunk but discrete on the extremities C. parvum is one of the most common pathogens causing diarrhea and biliary tract disease in AIDS, particularly when the CD4 helper T-cell count < 100/mm3. The treatment is nitazoxanide. S. stercoralis is the most common helminthic infection causing diarrhea in AIDS patients. Adult worms lay eggs in the bowel mucosa that develop into rhabditiform larvae, which are excreted in the feces. It is a common parasitic infection in AIDS; however, filariform larvae would be seen in the bowel lumen. A common complication of severe aortic stenosis is an intravascular hemolytic anemia with schistocytes (fragmented RBCs; microangiopathic hemolytic anemia), which may lead to chronic iron-deficiency anemia from loss of hemoglobin in the urine. Absent haptoglobin levels is a sign for cardiovascular surgeons to replace the valve. Aortic stenosis is the most common valvular lesion associated with angina with exercise due to concentric hypertrophy of the left ventricle. The thickened muscle wall does not receive sufficient blood flow during exercise resulting in angina from subendocardial ischemia Sarcoidosis, which is a noninfectious, chronic granulomatous disease that targets the lungs and other organ systems. It is common in the black population. Chronic inflammation is associated with the release of hepcidin, an acute phase reactant synthesized and released by the liver. It is the key factor involved in the pathogenesis of ACD. Hepcidin enters bone marrow macrophages and prevents the release of iron to transferrin (binding protein of iron). Decreased delivery of iron to developing normoblasts in the bone marrow leads to a decrease in hemoglobin synthesis, which, in turn, is a stimulus for extra cell divisions and a microcytic anemia. Iron continues to enter the macrophages; however, this is not balanced by iron moving out to bind to transferrin. This results in an increase in iron stores. Ferritin, a soluble iron-binding protein, is synthesized by macrophages and small fraction leaks into the blood hence providing an indirect measurement of macrophage iron stores. In this case, it is increased. The amount of ferritin in macrophages has an inverse relationship with transferrin synthesis in the liver. Therefore, increased ferritin stores in macrophages leads to decreased transferrin synthesis in the liver and decreased transferrin, or total iron-binding capacity (TIBC) in the blood. In summary, the laboratory findings include a decreased MCV (sometimes normocytic), decreased serum iron, decreased TIBC, decreased percent saturation of transferrin, and an increase in serum ferritin Iron deficiency is the most common cause of microcytic anemia. As anticipated, serum iron is decreased, TIBC is increased (due to decrease in ferritin stores), percent saturation of transferrin is decreased, and serum ferritin is decreased. Fibrocystic change refers to a spectrum of changes that occur in the breast tissue of women during the menstrual cycle. It is the most common cause of a painful mass in women under 50 years old. Proliferative changes caused by estrogen stimulation occur in the ductal epithelium of the major ducts, terminal ducts, and lobules in the breast. Painful breast lumps increase in size as fluid accumulates in cysts Most normal ranges are established by adding and subtracting 2 standard deviations (SD) from the mean of the test. The standard deviation for the test is 4 mg/dL; therefore, 2 SD is 8 mg/dL. The mean of the test is obtained by adding up the test values for normal people and dividing the sum by
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the number of people. The mean of the test is 48 + 52 + 50 + 49 + 51 = 250 mg/dL divided by 5 = 50 mg/dL. Therefore, the lower limit of the normal range is 50 - 8 = 42 mg/dL, and the upper limit is 50 + 8 = 58 mg/dL. Reyes syndrome, which usually develops in children < 4 years of age who receive aspirin (acetylsalicylic acid) to reduce fever associated with a viral respiratory infection or chickenpox. Salicylates damage the mitochondria in the liver, which disrupts the urea cycle and -oxidation of fatty acids. Disruption of the urea cycle causes an increase in serum ammonia, which produces an encephalopathy characterized by cerebral edema, papilledema, and coma. Disruption of -oxidation of fatty acids in the liver causes microvesicular fatty change, in which small globules of fat in the cytoplasm surround a centrally located nucleus. Aminotransferases and total bilirubin are increased (ALT > AST). Apoptotic bodies (deeply eosinophilic bodies with or without a pyknotic nucleus) are present in viral hepatitis. Periodic acidSchiff-positive granules in hepatocytes are present in 1-antitrypsin (AAT) deficiency, an autosomal dominant disorder. The type of AAT deficiency associated with liver disease in children involves defective secretion of AAT by the hepatocyte. This disorder usually presents at birth with jaundice caused by cholestatic hepatitis, which progresses to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Varicocele in the left scrotal sac caused by engorgement of the internal spermatic veins above the testis forming a tangle of vessels (bag full of worms appearance; see photograph). Varicoceles almost always occur on the left side because the left spermatic vein empties into the left renal vein, which has increased resistance to blood flow. The right spermatic vein empties into the vena cava, which has less resistance to blood flow. Sudden development of a left-sided varicocele is indicative of a lesion blocking blood flow into the left renal vein, such as a renal cell carcinoma associated with invasion of the left renal vein. Cigarette smoking is the greatest risk factor for renal cell carcinoma. Hematuria is the most common presenting symptom. Epididymitis is associated with scrotal pain with radiation of the pain to the spermatic cord or flank. A hydrocele is a collection of fluid between the two layers of the tunica vaginalis producing enlargement of the scrotal sac that transilluminates. Torsion of the spermatic cord produces a sudden onset of testicular pain. The testicle draws up into the inguinal canal and there is loss of the cremasteric reflex. Diet lacking protein leading to a decrease in albumin and a corresponding decrease in total protein. Albumin is primarily responsible for maintaining plasma oncotic pressure; therefore, hypoalbuminemia leads to leakage of protein-poor fluid into the interstitial space thus causing pitting edema. Hereditary angioedema, an autosomal dominant disease characterized by a deficiency of C1 esterase inhibitor. The resultant continued activation of C1 decreases the concentration of C2 and C4 in the classic pathway and increases the concentration of their cleavage products (C2a and C4a), both of which have anaphylatoxic activity. Anaphylatoxins directly stimulate the release of histamine from mast cells, resulting in increased vascular permeability and swelling of the face and larynx. Inspiratory stridor is a symptom of upper airway obstruction. Factor B is present in the alternative complement pathway, which explains why it is normal. There is no activation of C3 in hereditary angioedema.
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Cutaneous skin testing to rule out anergy is ordered when a defect in cellular immunity is suspected (e.g., T-cell deficiency in DiGeorge syndrome). Injection of Candida into the skin does not produce an inflammatory reaction when T cells are deficient. This is erythema chronicum migrans, which is the pathognomonic skin lesion of early Lyme disease. The disease is transmitted to humans by the bite of an Ixodes tick, which carries the Gramnegative spirochete B. burgdorferi. R. rickettsii is a tick-transmitted pathogen that is the causative agent of Rocky Mountain spotted fever, which is characterized by fever, multisystem disease, and a petechial rash (not a rash with concentric circles) that begins on the palms and spreads to the trunk. The rash is due to a vasculitis. Crohns disease involving the terminal ileum, which causes colicky, right lower quadrant pain and diarrhea. Crohns disease is complicated by a macrocytic anemia caused by malabsorption of vitamin B12 in the inflamed terminal ileum, where the vitamin B12intrinsic factor complex is normally reabsorbed via a receptor for the complex. Hematologic findings in vitamin B12 deficiency include macro-ovalocytes, hypersegmented neutrophils, and pancytopenia. Macrophage destruction and apoptosis of megaloblastic hematopoietic cells in the bone marrow cause the pancytopenia. Chediak-Higashi syndrome is an autosomal recessive disease with a defect in a lysosomal transport protein that affects the synthesis and/or maintenance of storage of secretory granules in various cells (e.g., lysosomes in leukocytes, azurophilic granules in neutrophils, dense bodies in platelets). Granules in these cells tend to fuse together to become megagranules (see photograph). In addition, there is a defect in microtubule function in neutrophils and monocytes that prevents the fusion of lysosomes with phagosomes to produce phagolysosomes. This produces a bactericidal defect. In particular, there is increased susceptibility to developing S. aureus infections. Microtubular dysfunction also produces defects in chemotaxis (directed migration), which further exacerbates the susceptibility to infection. CGD is an X-linked recessive disease caused by absence of nicotinamide adenosine dinucleotide phosphate oxidase in the O2-dependent myeloperoxidase (MPO) system for killing bacteria. Lack of this enzyme causes a defect in producing a respiratory (oxidative) burst in neutrophils and monocytes. Inclusion (I) cell disease is a rare, inherited condition where there is a defect in post-translational modification of lysosomal enzymes in the Golgi. Mannose residues on newly synthesized lysosomal enzymes coming from the rough endoplasmic reticulum are not phosphorylated due to a deficiency of phosphotransferase. Without mannose-6-phosphate to direct the enzymes to lysosomes, vesicles that pinch off the Golgi empty the unmarked enzymes into the extracellular space where they are degraded in the bloodstream. Undigested substrates (e.g., carbohydrates, lipids, and proteins) accumulate as large inclusions in the cytosol of mesenchymal cells, particularly fibroblasts (not leukocytes). Symptoms include psychomotor retardation and early death. Job syndrome. It is an autosomal recessive disorder of neutrophils, characterized by abnormal chemotaxis leading to cold soft tissue abscesses due to S. aureus. Patients have red hair, a leonine face, chronic eczema, and increased IgE (hyperimmune E syndrome) Myeloperoxidase deficiency catalyzes a reaction that combines H2O2 with Cl to form hypochlorous free radicals that kill the phagocytosed bacteria. Deficiency of MPO results in a defect in microbicidal activity;
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Fragile X syndrome is X-linked recessive. The fragile site or gap at the end of the long arm of the X chromosome is where there are trinucleotide repeats (CGG). Characteristic findings include mental retardation; enlarged, nontender testicles (present at adolescence, not at birth); a long face with a prominent jaw; a high arched palate; and protruding ears. The serum concentration of troponins I and T begin to increase 3 to 12 hours after cardiac injury, peak within 24 hours, and return to normal within 7 to 10 days; hence, these would have been increased at the time of death. Levels of CK-MB begin to increase 4 to 8 hours after infarction, peak in 24 hours, and return to normal within 1.5 to 3 days. Q waves in leads I and aVL are present in an infarction involving the lateral wall of the left ventricle, which is supplied by the left circumflex coronary artery Q waves in leads I, V4V6, and aVL occur in an anterolateral wall infarction of the left ventricle due to thrombosis of the midportion of the left anterior descending coronary artery or the circumflex coronary artery. Q waves in leads V1V4are present in an anterior wall infarction of the left ventricle and are most often due to thrombosis of the left anterior descending coronary artery. Pharmacologic treatment of disseminated malignancies such as chronic myelogenous leukemia results in the release of purine nucleotides from the dead cancer cells Uric acid is the end-product of degradation of purine nucleotides. Precipitation of uric acid crystals in the collecting ducts obstructs the nephrons (urate nephropathy), causing acute renal failure. Allopurinol, a xanthine oxidase that prevents conversion of xanthine to uric acid, is given before initiation of chemotherapy to prevent acute renal failure Increased release of pyrimidines by dead cancer cells increases carbon dioxide, ammonia, and amino acids. The ammonia derived from amino acids by oxidative deamination is metabolized to urea in the urea cycle Sessile adenomas of FAP is caused by inactivation of suppressor gene. Familial polyposis is an autosomal dominant disorder characterized by inactivation of the adenomatous polyposis coli suppressor gene located on chromosome 5. In some cases, it is associated with congenital hypertrophy of retinal pigment epithelium. Peutz-Jeghers syndrome is an autosomal dominant polyposis with hamartomatous polyps located primarily in the small bowel and in the colon and stomach to a lesser extent. It is characterized by increased melanin pigmentation of the lips and buccal mucosa. An increased serum total protein is most often due to an increase in immunoglobulin (Igs). Igs are primarily increased in chronic inflammation and malignant plasma cell disorders (e.g., multiple myeloma,RA ) Preproinsulin in the -islet cells is delivered to the Golgi apparatus, proteolytic reactions generate insulin and a cleavage peptide called C-peptide. Hence, C-peptide is a marker for endogenous synthesis of insulin. Alcohol is a common cause of hypoglycemia in the fasting state. The increase in nicotinamide adenine dinucleotide (NADH) in alcohol metabolism causes pyruvate to be converted to lactic acid. This reduces the amount of pyruvate to use as a substrate for gluconeogenesis, which is the primary source of glucose in the fasting state.
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An insulin-like factor that causes hypoglycemia is most often produced by a hepatocellular carcinoma Injection of human insulin increases serum insulin and produces hypoglycemia. Hypoglycemia suppresses -islet cells, causing a decrease in endogenous synthesis of insulin and a corresponding decrease in serum C-peptide. The systolic ejection murmur indicates aortic stenosis, and the fragmented RBCs (schistocytes) in the peripheral blood indicate the presence of a microangiopathic hemolytic anemia due to intravascular destruction of the RBCs as they hit the stenotic and dystrophically calcified valve. Damaged RBC release hemoglobin directly into the blood. Haptoglobin, a protein synthesized in the liver, combines with the free hemoglobin to form complexes that are phagocytosed by macrophages in the spleen and completely degraded causing very low to absent serum haptoglobin levels. The excess hemoglobin in the plasma is then filtered into the urine producing a red color and a positive dipstick for blood. Chronic hemoglobinuria causes IDA and microcytic anemia leading to decreased serum ferritin Osmotic fragility test is used to confirm a diagnosis of hereditary spherocytosis, in which the osmotic fragility of RBCs is increased. Hereditary spherocytosis is a normocytic anemia and spherocytes in the peripheral blood Molluscum contagiosum, which is characterized by multiple, small, domed, shiny lesions with central areas of umbilication. A granular material is present in the area of umbilication and contains the cells infected by the causal poxvirus (molluscum bodies). The virus is often spread by selfinoculation. The lesions may occur in HIV infections when the CD4 helper T-cell count is 200 to 500 cells/mm3. Basal cell carcinomas are malignant tumors that develop on areas of the body that are often exposed to the sun. The lesions are dome-shaped and have telangiectasias on their walls. Central ulceration is a characteristic finding Lead, a heavy metal, denatures enzymes, deposits in the epiphyses of bone, and causes encephalopathy and peripheral neuropathy. The microcytic anemia is due to denaturation of ferrochelatase, which normally combines iron with protoporphyrin to form heme in the mitochondria. A decrease in heme causes a decrease in hemoglobin synthesis resulting in a microcytic hypochromic anemia. Lead also denatures ribonuclease, which normally degrades ribosomes. This explains the presence of coarse basophilic stippling. Lead deposits in the epiphyses of bone explain the patients growth retardation. Lead is also easily identified in an abdominal radiograph as metallic densities, which is evident in this patient. Since -aminolevulinic acid is proximal to the enzyme block in heme synthesis, it is increased and is responsible for the encephalopathy (demyelination and cerebral edema) and neuropathy in lead poisoning (abdominal colic, peripheral neuropathies). An increase in serum lead level confirms the diagnosis Alzheimers disease is the most common cause of senile dementia in patients older than 65 years of age. The arrow in the photograph shows a senile plaque containing a core of pink-staining -myloid protein surrounded by distended neurites (distal neuronal cell processes). Numerous plaques are present in the frontal, temporal, and parietal lobes in patients with Alzheimers disease. -Amyloid protein derives from amyloid precursor protein, which is normally coded for on chromosome 21. Amyloid protein when phosphorylated by activated glycogen synthase kinase-3 (GSK) acts as a signal for apoptosis of neurons, which accounts for the loss of intellectual function.
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Neurofibrillary tangles are present in patients with Alzheimers disease and in elderly individuals who do not have dementia. The tangles are best visualized with silver stains and represent proteinrich filaments arranged in helical fashion within the cytoplasm of neurons. Spongiform change in the brain is a characteristic finding in Creutzfeldt-Jakob disease, which is caused by an infectious agent (prion) that is devoid of nucleic acids. Gliosis is the repair process that occurs when the brain is injured. It consists of a proliferation of astrocytes that produce a dense network of cytoplasmic processes. Activated microglial cells commonly accompany this reactive process. Septic shock is the most common cause of DIC. In DIC, fibrin clots are produced in the microcirculation that obstruct blood flow and consume coagulation factors, causing bleeding from needle puncture sites and the gastrointestinal tract. Factors that are normally consumed in a fibrin clot are fibrinogen (factor I), prothrombin (factor II), and factors V and VIII. Since coagulating factors present in the final common pathway are consumed (fibrinogen, prothrombin, factor V), there is prolongation of the PT and aPTT. Platelets are trapped in the fibrin clots leading to thrombocytopenia, which produces petechiae and ecchymoses. The fibrinolytic system is activated (secondary fibrinolysis), and plasmin cleaves the fibrin strands holding the fibrin clots together. Fibrin strands are held together by cross-links, and cleaved fragments with cross-links are detected in the d-dimer assay, which is the most sensitive test for diagnosing DIC. (HIV-1), which is an RNA retrovirus containing reverse transcriptase. The virus infects CD4 T cells and destroys the cells. Epstein-Barr virus and cytomegalovirus infections are common in AIDS. They are potent polyclonal stimulators of B cells, which produce a polyclonal gammopathy (benign increase in -globulins). However, because patients are unable to mount an antibody response to a new antigen, they are still susceptible to bacterial infections in spite of the increase in -globulins. Multiple sclerosis. It is an autoimmune disease initiated by genetic factors (e.g., HLA-DR2) and environmental triggers, the latter including microbial pathogens (e.g., Epstein Barr virus, human herpes virus 6, Chlamydophilia pneumoniae), vitamin D, and sun exposure. Environmental triggers activate helper T-cells whose antigen-specific receptors recognize CNS myelin basic protein (other antigens as well) as an antigen. T cells release cytokines that activate macrophages, which also release cytokines (e.g., tumor necrosis factor-) that destroy the myelin sheath as well as oligodendrocytes that synthesize myelin (type IV hypersensitivity). Antibodies directed against the myelin sheath and oligodendrocytes may also be involved. The episodic course of acute relapses with optic neuritis (blurry vision), scanning speech, cerebellar ataxia, and sensory and motor dysfunction, followed by remissions, are characteristic of this disease. The demyelinating plaques in multiple sclerosis occur in the white matter of the cerebral cortex. The plaques usually have a perivenular distribution and are accompanied by a perivascular lymphoid and plasma cell infiltrate with microglial cells containing phagocytosed myelin. CSF shows an increase in CSF protein. Highresolution electrophoresis of CSF shows discrete bands of immunoglobulins in the -globulin region called oligoclonal bands.They are indicative of a demyelinating process. Exposure to benzene, a solvent, is a risk factor for acute leukemia and aplastic anemia Polycyclic hydrocarbons are the primary carcinogens in cigarette smoke. Anorexia nervosa (self-starvation). Features include loss of muscle mass and subcutaneous tissue, fine downy hair (lanugo hair), distorted body image (feel fat), and secondary amenorrhea. Excessive loss of body weight (>25% of ideal weight) leads to a decrease in secretion of gonadotropin-releasing hormone from the hypothalamus and a corresponding decrease in the
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concentration of serum gonadotropins (follicle-stimulating hormone and luteinizing hormone). Amenorrhea is caused by decreased ovarian synthesis of estradiol, which may lead to osteoporotic changes resulting in compression fractures in the vertebral column, which is most likely causing the patients back pain. All the stress hormones are increased (e.g., ACTH, cortisol, growth hormone, catecholamines). Note that there is an ACTH, cortisol, growth hormone , but a decreased GNrh A congenital leukocyte adhesion molecule defect prevents separation of the umbilical cord. Adhesion molecules activated on neutrophils include selectins and -integrins (CD11 CD18 positive). Selectins are responsible for rolling of the neutrophils in the venules, while -integrins cause neutrophils to adhere to venules (margination). Neutrophils then release collagenase, dissolve basement membranes between contracted endothelial cells in venules, and transmigrate into the interstitial tissue. Deficiency of either type of adhesion molecule causes an absence of neutrophil adhesion (margination) and an absence of neutrophils in the interstitial tissue, because neutrophils must adhere to endothelium before they can transmigrate. Other findings in leukocyte adhesion defects include an increase in the absolute neutrophil count, problems with wound healing, and severe gingivitis. The respiratory (oxidative) burst in neutrophils and monocytes is part of the O2-dependent MPO system for killing bacteria. Activated nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase in the cell membrane oxidizes reduced NADPH, converting molecular O2 to superoxide free radicals (O2-). The respiratory burst is the energy released in this reaction. In chronic granulomatous disease, an X-linked recessive disease caused by absence of NADPH oxidase, the respiratory burst is absent, resulting in a defect in microbicidal activity. In the O2-dependent MPO system, O2 is converted to peroxide (H2O2) by superoxide dismutase in the phagolysosomes of neutrophils and monocytes. MPO catalyzes a reaction that combines H2O2 with Cl to form hypochlorous free radicals that kill the phagocytosed bacteria. Deficiency of MPO results in a defect in microbicidal activity IgG and C3b are opsonizing agents that bind to the surface of bacteria. Receptors for IgG and C3b are located on the plasma membranes of phagocytic leukocytes. Binding of the opsonized bacteria to leukocytes facilitates phagocytosis of the bacteria. A deficiency of IgG or C3 produces a defect in phagocytosis; Phagolysosomes are produced by fusion of lysosomes containing hydrolytic enzymes with phagosomes. In Chdiak-Higashi syndrome, a defect in lysosomal degranulation into phagosomes is present. Leukocytes contain large azurophilic granules (lysosomes) in the cytosol and there are defects in opsonization and in the formation of phagolysosomes Travelers diarrhea is most often due to enterotoxigenic Escherichia coli, which produces a toxin that activates adenylate or guanylate cyclase in enterocytes in the small intestine causing an isotonic loss of diarrheal fluid (secretory type of diarrhea). Loss of isotonic fluid does not alter the serum Na+ concentration (serum Na+ = TBNa+/TBW); however, the decrease in TBNa+ causes signs of volume depletion (dry mucous membranes, poor skin turgor, hypotension). Regarding the fluid compartments, the extracellular fluid (ECF) compartment is contracted (loss of fluid) and the intracellular (ICF) compartment is unchanged (no osmotic effect) Acute promyelocytic leukemia is the most common leukemia associated with disseminated intravascular coagulation (DIC). In APL, the neoplastic promyelocytes contain numerous splintershaped Auer rods in the cytoplasm
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CLL is the most common leukemia in patients older than 60 years of age and is also the most common cause of generalized lymphadenopathy. The peripheral smear in CLL shows numerous lymphocytes with dense nuclear chromatin and inconspicuous nucleoli Tracheoesophageal fistula, the proximal esophagus ends blindly. The distal esophagus arises from the trachea, causing the stomach to distend with air. When the infant breast-feeds, milk refluxes into the trachea, causing coughing due to aspiration of milk into the lungs. Polyhydramnios occurs during pregnancy, because the fetus cannot swallow the amniotic fluid and reabsorb it in the duodenum. Choanal atresia is caused by a bony septum between the nose and the pharynx, which forces the infant to breathe only through the mouth. The cyanosis that develops when the infant is breastfeeding ceases when the infant breaks from the breast and begins crying. Congenital pyloric stenosis does not present at birth but at approximately 2 to 4 weeks of life. Projectile vomiting of nonbile-stained fluid occurs. Duodenal atresia (lack of a lumen) occurs just distal to the entry of the common bile duct into the duodenum. Projectile vomiting of bile-stained fluid occurs at birth. Air is present in the stomach and in the duodenum proximal to the opening of the common bile duct. Polyhydramnios occurs during pregnancy, because there is not enough duodenum to reabsorb the amniotic fluid. There is an increased association with Down syndrome. Volvulus is where the bowel twists around mesenteric root producing obstruction and strangulation. The sigmoid colon is the most common site in elderly patients and the cecum in young patients. Risk factors include chronic constipation (most common), pregnancy, and laxative abuse Pernicious anemia (PA), an autoimmune disease in which impaired intestinal absorption of vitamin B12 is caused by a lack of IF. Antibodies directed against parietal cells in the body and fundus (type II hypersensitivity reaction) cause mucosal damage (chronic atrophic gastritis), achlorhydria (loss of acid production by parietal cells), and a decrease in synthesis of IF. IF normally forms a complex with vitamin B12in the duodenum which is then reabsorbed in the terminal ileum after the complex attaches to IF receptors. The peripheral smear shows large, egg-shaped macro-ovalocytes. The arrow points to a hypersegmented neutrophil (more than five nuclear lobes), a valuable and early marker of vitamin B12 deficiency (also folate deficiency). Pancytopenia is the rule in PA, because deficiency of vitamin B12 causes decreased production of DNA leading to nuclear enlargement of hematopoietic cells in the bone marrow (megaloblasts). These cells or derivatives from these cells (e.g., mature RBCs, platelets, neutrophils) are often phagocytosed and destroyed by bone marrow macrophages or are destroyed by apoptosis before they enter the peripheral blood. Reabsorption of orally administered vitamin B12 after the addition of IF confirms the diagnosis of PA. This is called the Schilling test. Vitamin B12, unlike folic acid, is involved in propionate fatty acid metabolism (odd-chain fatty acids). Propionyl CoA is converted to methylmalonic CoA, and methylmalonic CoA is converted to succinyl CoA using an enzyme reaction that requires vitamin B12 as a cofactor. Deficiency of vitamin B12 causes an increase (not a decrease) in methylmalonic acid levels (derives from methylmalonyl CoA) in the urine. It also causes an increase in propionyl CoA (also propionic acid) in the urine. Propionyl CoA replaces acetyl CoA in neuronal membranes resulting in demyelination of the posterior columns and lateral corticospinal tract of the spinal cord (subacute combined degeneration) and peripheral nerves (peripheral neuropathy). The patient has decreased vibratory
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sensation and joint dysequilibrium (cannot stand up with her eyes closed), both of which are signs of posterior column disease History of menorrhagia, easy bruisability, bleeding from superficial scratches, and epistaxis all abating with oral contraceptives and recurring again when off of them is a classic scenario for classic von Willebrand disease. Normal squamous epithelium of the exocervix derives from squamous metaplasia of mucussecreting glandular cells moving down the endocervical canal. Infection of the squamous cells by human papillomavirus types 16 or 18 initiates conversion of the metaplastic squamous epithelium to dysplastic epithelium. If the infection persists, cervical squamous cell cancer may develop. A painless testicular mass that does not transilluminate is highly predictive of testicular cancer. Adults with a cryptorchid testis are at risk for seminoma in the undescended testis (if still present) as well as the descended testis Choriocarcinoma of the testicle typically is small and does not cause enlargement of the entire testicle. The syncytiotrophoblast component of the tumor produces human chorionic gonadotropin Hydroceles is the most common cause of scrotal enlargement. It is due to a failure of closure of the tunica vaginalis. Fluid accumulates in the serous space between the layers of the tunica virginals. The mass of fluid transilluminates. It is invariably associated with an indirect inguinal hernia. Varicocele is the tortuous dilation of the veins of the spermatic cord that is often described as a bag of worms. A variocele typically occurs on the left side, not on the right side, because the left spermatic vein empties into the left renal vein, where it encounters more resistance to blood flow. The right spermatic vein empties into the inferior vena cava, where there is less resistance to blood flow. Yolk sac tumors typically occur in infants and children and are not associated with cryptorchidism. They secrete -fetoprotein Western blot assay is the confirmatory test if the ELISA test is positive for HIV. The ELISA assay detects anti gp120 antibodies. A positive Western blot assay requires the presence of p24 and gp41 antibodies and either gp120 or gp160 antibodies. The test has close to 100% specificity. The CD4 T-cell count is used to monitor the immune status of the patient. It is useful in determining when to initiate HIV treatment and when to administer prophylaxis against opportunistic infections. It is not a confirmatory test for HIV The p24 antigen is an indicator of active viral replication. It is present before anti-gp120 antibodies are developed in the patient. It is positive at two different times in HIV infectionsprior to seroconversion and when AIDS is diagnosed Muscle cramping and abdominal pain are due to a neurotoxin produced by the black widow spider (Latrodectus mactans). A glossy black spider with a red hourglass on the ventral aspect of the abdomen. Paralysis and death may occur in very young and in very old individuals. Achalasia, a motor disorder of the smooth muscle cells of the mid and distal esophagus. There is incomplete relaxation of the lower esophageal sphincter (LES) due to autoimmune destruction of ganglion cells in the myenteric plexus causing a decrease in nitric oxide (NO) synthase producing neurons. This decreases proximal smooth muscle contraction (peristalsis). There is dilation of the esophagus proximal to the LES with absent peristalsis (detected by manometry). Clinical findings include nocturnal regurgitation of undigested food; dysphagia for solids and liquids; and chest pain and/or heartburn. The proximal esophagus is dilated and has a beaklike tapering at the distal end (arrow). Nonpharmacologic treatment includes pneumatic dilation and esophagomyotomy.
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Pharmacologic options include long-acting nitrates, calcium channel blockers, and botulinum toxin injection. There is an increased risk for esophageal cancer. Myasthenia gravis is a motor disorder (IgG antibodies inhibit acetylcholine receptors) that weakens the striated muscle of the upper esophagus, causing dysphagia for solids and liquids. Mid and distal esophageal motility is normal Kaposi sarcoma, a vascular malignancy closely associated with human herpesvirus 8. Kaposis sarcoma is the most common malignancy in patients with AIDS and is an AIDS-defining lesion. Lesions appear most often on the skin but may also occur in the intestinal tract, particularly on the hard palate. B. henselae is a gram-negative bacterium that causes bacillary angiomatosis, a disease that occurs almost exclusively in patients with AIDS. It produces highly vascular skin lesions that can mimic the lesions of Kaposis sarcoma. Systemic signs of the infection include fever, lymphadenopathy, and hepatomegaly. Small-cell carcinoma of the lung can ectopically produce adrenocorticotropic hormone producing Cushing syndrome (moon facies, truncal obesity with purple stria, thin extremities. It also produces ectopic secretion of antidiuretic hormone (ADH) resulting in the syndrome of inappropriate ADH. A medullary carcinoma of the thyroid derives from C cells that synthesize calcitonin. Calcitonin is a hormone that inhibits osteoclasts causing hypocalcemia. Elderly individuals frequently lose their isohemagglutinins (e.g., anti-A IgM, anti-B IgM). The patient is blood group A and should have anti-B IgM isohemagglutinins in the plasma. However, in vitro testing showed that reacting his plasma with test blood group B RBCs did not produce agglutination or hemolysis. Therefore, the infusion of donor group B RBCs did not produce a hemolytic transfusion reaction, because the patient has no anti-B IgM antibodies to attach to the B antigen on the donors RBCs. Hemolytic transfusion reactions are antibody-mediated type II hypersensitivity reactions Hirschsprungs disease (congenital megacolon), which is the most common cause of lower intestinal obstruction in neonates. The most common manifestation is failure to pass meconium within the first 24 hours after birth. There are no ganglion cells in both the Meissner submucosal and the Auerbach myenteric plexuses. In 75% of cases, the rectosigmoid is aganglionic. Characteristic findings include a narrow anal canal, absence of stool in the rectal vault in rectal examination, and an abdominal radiograph showing distended loops of colon. Peristalsis occurs in segments of colon that do contain ganglion cells. In 3% of cases, there is an association with Down syndrome. Enterocolitis, which is the most common complication of Hirschsprungs disease, is a type of ischemic necrosis related to an increase in intraluminal pressure and decreased intramural capillary blood flow. Presenting signs include fever and bloody diarrhea In pregnancy thre is an hemoglobin, and BUN (increase in plasma volume causes increased clearance of urea in the urine), but an in pH (estrogen and progesterone stimulate the CNS respiratory center causing respiratory alkalosis), increase in plasma volume increases the glomerular filtration rate causing an increase in the creatinine clearance. Acute drug-induced tubulointerstitial disease is characterized by a sudden onset of oliguria (renal failure), fever, and a rash shortly after taking a drug (e.g., synthetic penicillin). Other findings include eosinophilia, eosinophiluria (eosinophils in the urine), hematuria, pyuria (WBCs in the urine), and WBC casts. Withdrawal of the drug reverses these findings.
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Chronic pyelonephritis is a complication of vesicoureteral reflux (reflux of urine from the bladder into the ureter) or postrenal obstruction caused by prostate hyperplasia or a ureteral stone. An intravenous pyelogram shows blunting of the renal calyces underlying cortical scars. A ureteral stone presents with sudden onset colicky pain with radiation to the groin McArdles disease, which is an autosomal recessive glycogen storage disease characterized by a deficiency of muscle phosphorylase. This enzyme releases glucose from glycogen stored in muscle. Deficiency of muscle phosphorylase deprives the muscle of glucose for energy, and after exercise, lactic acid is not produced as an end-product of anaerobic glycolysis. Strenuous exercise may damage muscle, causing myoglobinuria (red-colored urine). There is no hypoglycemia in these patients, because glycogenolysis in the liver is still intact. Glucose obtained by glycogenolysis in muscle is used only by the muscle and does not enter the bloodstream. -1,4-Glucosidase, a lysosomal enzyme that degrades glycogen, is deficient in Pompes disease. Glycogen accumulates in cardiac muscle, resulting in death at an early age. Glucose-6-phosphatase, a gluconeogenic enzyme that normally converts glucose 6-phosphate to glucose, is deficient in von Gierkes disease. Fasting hypoglycemia occurs, and normal glycogen (with branches) accumulates in the liver and kidneys, not in muscle. Development of colorectal cancer from a tubular adenoma follows a sequence of gene mutations, which occurs in the following order: (1) inactivation of the APCsuppressor gene; (2) activation of the RAS proto-oncogene; and (3) inactivation of the TP53 suppressor gene. This sequence accounts for 80% of cases of sporadic colorectal carcinomas. This is an important concept, because cancer is rarely due to a single mutation but a certain sequence of mutations. Recall that the TP53 suppressor gene and RAS proto-oncogene are the two most common genes associated with cancer. Henoch-Schnlein purpura is characterized by distinctive skin rash on the lower extremities and buttocks, hematuria with RBC casts, gastrointestinal bleeding, and joint inflammation. It is a type III hypersensitivity reaction involving the deposition of IgAanti-IgA immunocomplexes in small vessels, glomeruli, joints, and gastrointestinal tract. A key feature of small vasculitis is palpable purpura. It is raised and painful, because it is an example of the tumor and dolor of acute inflammation. In the glomerulus, immunocomplexes deposited in the mesangium cause an acute, nephritic type of glomerulonephritis, which explains the presence of hematuria, dysmorphic RBCs (damaged by inflammation), RBC casts, and proteinuria. Gastrointestinal bleeding and polyarthritis are also common features. Previous upper respiratory infections or group A streptococcal pharyngitis frequently act as a trigger leading to antibody formation and eventual formation of immunocomplexes. Deposition of immunocomplexes in tissue activates the complement system, and chemotactic agents act as signals for neutrophils to enter the tissue producing acute inflammation. Hyperelastic skin, which is a characteristic finding in Ehlers-Danlos syndrome (EDS). EDS is a connective tissue disorder with defects in collagen synthesis and/or structure. Other clinical features that may be present include hypermobility of joints, aortic dissection, mitral valve prolapse (present in this patient), and rupture of the colon. An acquired defect in cross-bridging of collagen fibers is associated with scurvy, which is caused by deficiency of vitamin C (ascorbic acid). The weak collagen (decreased tensile strength) produces vascular instability of small vessels, leading to skin and joint hemorrhages and bleeding gums with the loss of teeth
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Kawasaki disease (mucocutaneous lymph node syndrome), which is the most common acquired heart disease in children. Characteristic findings include fever, painful cervical lymph nodes, cracked lips, oral erythema, swelling of the hands and feet, a desquamating rash involving the fingers and toes (see photograph), and vasculitis of the coronary arteries. Vasculitis often leads to coronary artery thrombosis and acute myocardial infarction. The treatment is intravenous gamma globulin. Corticosteroids are contraindicated, because they increase the risk for aneurysms in the coronary arteries. Cyanide (CN) is a systemic asphyxiant that inhibits cytochrome oxidase in the electron transport chain, hence preventing formation of adenosine triphosphate (ATP). CN poisoning may be caused by drugs (e.g., nitroprusside) or combustion of polyurethane products in house fires. It produces an initial CNS and cardiovascular stimulation, followed by CNS depression and death. Treatment is amyl nitrite (produces methemoglobin which combines with CN to form cyanmethemoglobin) followed by thiosulfate (CN is converted to thiocyanate, which is excreted). Viral-induced acute myocarditis. Clinical findings include left-sided heart failure (dyspnea, bibasilar inspiratory crackles, alveolar infiltrates); right-sided heart failure (neck vein distention, hepatomegaly, dependent pitting edema); tricuspid and mitral valve regurgitation (pansystolic murmur due to dilated valve rings) with S3 and S4 heart sounds related to volume increases in both ventricles; a decreased ejection fraction (systolic dysfunction due to decreased contractility); and myocardial damage (increased cardiac-specific troponin levels and CK-MB). Adenovirus is the most common viral cause of myocarditis. In this patient, the myocarditis has produced dilated (congestive) cardiomyopathy. Centrilobular hemorrhagic necrosis is an example of an intrahepatic obstruction of blood flow. It is most often due to a combination of left-sided heart failure (LHF) and right-sided heart failure (RHF). LHF decreases cardiac output causing hypoperfusion of the liver (produces liver cell necrosis) and RHF causes a back-up of systemic venous blood into the hepatic veins and then to the central veins and sinusoids producing an enlarged, painful liver with a mottled red appearance; and into the portal veins producing ascites and splenomegaly. ECG showing short QT intervals and a widened T wave is highly suggestive of hypercalcemia. Most common cause of hypercalcemia in ambulatory individuals is primary hyperparathyroidism due to a parathyroid adenoma. In this patient, primary hyperparathyroidism is complicated by hypertension, peptic ulcer disease, and a renal calculus composed of calcium oxalate. Hypercalcemia causes contraction of the smooth muscle cells of the peripheral resistance arterioles, which causes hypertension. Furthermore, hypercalcemia stimulates gastrin release, which causes peptic ulcer disease. Excess calcium in the urine predisposes to formation of calciumcontaining calculi. A decrease in both PTH and serum calcium is characteristic of primary hypoparathyroidism, which is most often due to previous thyroid surgery A decrease in PTH and an increase in serum calcium is characteristic of hypercalcemia due to malignancy (most common cause) or other non-parathyroid-gland-related disorders (e.g., sarcoidosis, hypervitaminosis D). Hypercalcemia suppresses the release of PTH by the parathyroid gland An increase in PTH and decrease in serum calcium is characteristic of secondary hyperparathyroidism. Hypovitaminosis D is a common pathologic cause of hypocalcemia leading to
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secondary hyperparathyroidism. Secondary hyperparathyroidism is a compensatory phenomenon that brings the serum calcium to up to or within the normal range Helicobacter pylori is the most common cause of peptic ulcer disease, which includes gastric and duodenal ulcers. Production of urease by the bacteria produces ammonia, which damages the protective mucus layer covering the pylorus and antrum of the stomach and the duodenum, sites colonized by H. pylori. Cytokines released by the bacteria cause chronic atrophic gastritis of the body and fundus with intestinal metaplasia (presence of Paneth cells and goblet cells), which is the precursor lesion for gastric adenocarcinoma at this location. Cytokines also elicit a marked lymphoid inflammatory response in the mucosa predisposing to a low-grade malignant lymphoma. Therefore, treatment of H. pylori not only prevents peptic ulcer disease, but also decreases the risk for malignant lymphoma of the stomach and gastric adenocarcinoma in the body and fundus. Down syndrome (epicanthal folds, flat nasal bridge). The presence of 46 chromosomes in the child indicates that a translocated chromosome, inherited from one of the parents, is responsible. Translocation occurs when one part of a chromosome is transferred to a nonhomologous chromosome. In balanced (robertsonian) translocation, the translocated fragment is functional. In this case, the long arm of chromosome 21 was translocated onto chromosome 14 in the mother, creating one long chromosome (14;21). The mother also has one chromosome 14 and one chromosome 21. The father has the normal 46 chromosomes. The affected child has 46 chromosomes with three functional 21 chromosomes including chromosome (14;21) and chromosome 21 from the mother and chromosome 14 and chromosome 21 from the father. Point mutation involves the substitution of a single nucleotide base. If the altered DNA codes for the same amino acid, there is no change in the phenotypic effect (silent mutation). If the altered DNA codes for a different amino acid, there is a change in the phenotypic effect (missense mutation). If the altered DNA codes for a stop codon (e.g., UAA), there is premature termination of protein synthesis (nonsense mutation). Sigmoid diverticulosis is most often caused by increased intraluminal pressure secondary to chronic constipation. The weakness occurs in the area where the vessels penetrate the bowel wall. The most common complication is diverticulitis due to impaction of stool (fecalith) in the diverticula sac, leading to ischemia and mucosal injury (same pathogenesis as acute appendicitis in adults). Patients with diverticulitis have fever, left lower quadrant pain, and rebound tenderness (left-sided acute appendicitis). A CT scan is the best diagnostic tool for diagnosing diverticulitis. Increased fiber in the diet is important in preventing sigmoid diverticulosis, because it prevents constipation. In children, appendicitis is most often a complication of lymphoid hyperplasia induced by a previous viral infection (e.g., adenovirus, measles). In adults, it usually is due to impaction of stool in the lumen (fecalith) and with ischemia and mucosal injury. Addisons disease is suggested when a case with hyperpigmentation of the buccal mucosa. This, along with the history of fatigue, weakness, and signs of hypovolemia when supine (decreased blood pressure and increased pulse rate). It is due to autoimmune destruction of the adrenal cortex. This produces deficiencies of mineralocorticoids (e.g., aldosterone), glucocorticoids (e.g., cortisol), and sex hormones (e.g., androstenedione, testosterone). Hypocortisolism causes an increase in plasma ACTH due to a negative feedback relationship. ACTH has melanocyte-stimulating properties that increase the synthesis of melanin on the skin and mucosal surfaces. Hypovolemia is related to the loss of sodium in the urine due to mineralocorticoid deficiency.
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Metyrapone is a drug that blocks 11-hydroxylase in the adrenal cortex. This enzyme is normally responsible for conversion of the glucocorticoid 11-deoxycortisol to cortisol. Therefore, a normal response to metyrapone is a decrease in cortisol with a subsequent increase in ACTH and 11deoxycortisol The episodic history of hematuria following upper respiratory infections is characteristic of IgA glomerulopathy, which is the most common type of glomerulonephritis. Urine sediment shows an RBC cast Primary stomach cancer that has hematogenously metastasized to both ovaries (Krukenberg tumors). A maxim in medicine states that palpable ovaries in a postmenopausal woman represent cancer until proven otherwise. The photograph shows classic signet ring cells (mucin pushes the nucleus to the periphery), which are primarily seen in the diffuse type of adenocarcinoma of the stomach. Stomach cancer is the most common primary cancer that metastasizes to the left supraclavicular nodes (Virchow nodes). Common signs of stomach cancer are weight loss, epigastric pain, hematemesis, and melena. Smoking is not a risk factor for gastric cancer. Most pancreatic cancers involve the head of the pancreas and are associated with obstructive jaundice, light-colored stools, and a palpable gallbladder. Pain usually radiates to the back, because the pancreas is located in the retroperitoneum. Pancreatic cancer can metastasize to the ovaries and is most commonly associated with smoking Surfactant synthesis is enhanced by glucocorticoids, thyroxine, and prolactin and decreased by insulin. Bronchopneumonia refers to an acute infection that begins in the bronchus and extends into the surrounding lung parenchyma producing microabscesses. Streptococcus pneumoniae is the most common cause of bronchopneumonia. AAT deficiency is an autosomal dominant disease, whose alleles are inherited codominantly (each allele expresses itself). The normal allele is M (95% frequency in United States), and MM is the normal genotype with AAT in the normal range. Deficient variants (decreased AAT levels) involve the Z allele and the S allele. Severe deficiency most commonly occurs in the homozygous ZZ variant. It is associated with panacinar emphysema and cirrhosis of the liver. In children, who are homozygous for ZZ, in 50% of cases, AAT is not secreted properly from hepatocytes. Pathologic accumulation of AAT in hepatocytes causes liver damage. Liver biopsies with PAS stains show red cytoplasmic granules (see photograph). It presents as neonatal hepatitis with intrahepatic cholestasis, with the hepatitis progressing into cirrhosis. In other cases, where there is no problem with secreting AAT, but levels of AAT are decreased, panacinar emphysema may develop later in life. Obstructive sleep apnea is characterized by excessive snoring with intervals of apnea (breath cessation) and may be caused by nasal polyps.
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A) Isotonic loss of fluid (e.g., secretory diarrhea in cholera and travelers diarrhea; loss of whole blood). Serum sodium remains normal (also POsm) when equal amounts of water and sodium are lost B) Hypertonic loss of fluid (e.g., diuretics, Addisons disease, 21-hydroxylase deficiency). Loss of hypertonic fluid produces a hyponatremia C) Isotonic gain of fluid (e.g., excessive infusion of normal (0.9%) saline. The serum sodium remains normaltherefore, the POsm is normal. D) congestive heart failure, the cardiac output is decreased and the kidney reabsorbs a slightly hypotonic fluid producing. An increase in total body sodium (TBNa+) is clinically manifested by weight gain, dependent pitting edema, and body effusions E) hypotonic loss of sodium (e.g., sweating, osmotic diuresis, glucosuria). The serum sodium is increased , causing an increase in POsm and an increase in the height of the interrupted squares F) hypertonic gain of sodium (e.g., excessive infusion of sodium bicarbonate; infusion of a sodium containing antibiotic). The serum sodium is increased, causing an increase in POsm and an increase in the height of the interrupted squares Microscopic polyangiitis. It is a small vessel type of vasculitis (palpable purpura) that can by precipitated by drugs (penicillin in this case), infections, and immune disorders. Whatever the triggering event is in this disease, it results in increased production of p-ANCA antibodies in more than 80% of cases. These antibodies are directed against myeloperoxidase in neutrophils, which cause degranulation and thus the release of toxins causing endothelial injury to small vessels throughout the body as well as to those in the glomeruli. Renal failure is most often due to rapidly progressive crescentic glomerulonephritis, which is associated with a nephritic presentation (hematuria, RBC casts, mild proteinuria) In cirrhosis, the urea cycle is dysfunctional; hence, ammonia is not converted into urea and increases in the blood. It is most likely responsible for the tiredness and mental status abnormalities in the patient, who is in an early stage of hepatic encephalopathy. There is a decreased cardiac output, causing the kidneys to reabsorb a slightly hypotonic fluid: serum Na+ = total body Na+/ total body water. Aldosterone is increased for two reasons: decreased metabolism of aldosterone by the liver and decreased cardiac output activating the renin-angiotensin-aldosterone system. Secondary aldosteronism increases renal exchange of Na+ for K+ leading to hypokalemia. Decreased liver synthesis of albumin automatically results in a decrease in the bound fraction of calcium and a decreased total serum calcium. Hypoglycemia is more likely to occur in cirrhosis than hyperglycemia. Due to liver dysfunction in cirrhosis, glycogen stores are depleted and there is defective gluconeogenesis, both of which lead to hypoglycemia in the fasting state.
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Centrilobular necrosis of liver (nutmeg liver), which is most often caused by left-sided heart failure (LHF) and right-sided heart failure (RHF). LHF decreases cardiac output causing hypoperfusion of the liver. This results in ischemic necrosis of hepatocytes located around the central vein. RHF causes a backup of systemic venous blood into the central veins and sinusoids, which produces congestion of central veins and sinusoids and necrosis of hepatocytes around the central vein. Clinical findings include painful hepatomegaly with or without jaundice. Increased transaminases are caused by ischemic necrosis. Left untreated, it may progress to cardiac cirrhosis with fibrosis around the central veins. Pituitary Cushings syndrome (aka Cushings disease) caused by an adenoma-secreting excess ACTH is characterized by a moon facies, truncal obesity, and purple striae. There is a mass lesion in the sella turcica. Dexamethasone, a cortisol analogue, is used as a suppression test to differentiate pituitary Cushings syndrome from adrenal Cushings syndrome (cortisol-secreting adenoma) or ectopic Cushings syndrome (e.g., ACTH-secreting small cell carcinoma of the lung). A normal response to dexamethasone is suppression of ACTH (negative feedback) and a decrease in cortisol production in the adrenal cortex. A low dose of dexamethasone is used as a screening test for hypercortisolism. It does not suppress cortisol production in pituitary, adrenal, or ectopic Cushings syndrome. However, a high dose of dexamethasone suppresses ACTH production in pituitary Cushings syndrome leading to a drop in cortisol levels. Cortisol remains increased in adrenal and ectopic Cushings syndromes. Vitamin B6 (pyridoxine) deficiency is most often associated with isoniazid therapy for tuberculosis. Clinical findings include sideroblastic anemia, convulsions, and peripheral neuropathies. These findings are not present in this patient. Impetigo. The rash usually begins on the face. Vesicles and pustules rupture to form honeycolored, crusted lesions, which are evident in this patient. Staphylococcus aureus is the most common cause of this superficial skin lesion. Streptococcus pyogenes is the second most common cause of impetigo. Impetigo is highly contagious, which explains why the childs sister developed similar lesions. Treatment is with mupirocin ointment plus dicloxacillin. (PDA). This neonate has hypoxemia (decreased arterial Po2) secondary to RDS; therefore, closure of the ductus is not stimulated. When oxygenated blood (Sao2 95%) is shunted into a chamber or vessel with venous blood (Sao2 75%), there is a step-up of Sao2 (approximately 80%) in the venous blood; this is called a left-to-right shunt. Similarly, when venous blood is shunted into a chamber or vessel with oxygenated blood, there is a step-down of the Sao2 (80%) leading to clinical cyanosis; this is called a right-to-left shunt. In PDA, there is a left-to-right shunt causing blood to flow from the aorta (where pressure is high) through the PDA to the pulmonary artery (where pressure is low), which causes a step-up of Sao2 in the pulmonary artery (85% versus normal of 75%). The cytochrome P-450 system in the liver converts acetaminophen into a free radical. A large dose of acetaminophen produces numerous free radicals, which damage hepatocytes causing release of transaminases. Hepatocytes around the central vein normally receive the least amount of O2; therefore, they are most susceptible to injury caused by hypoxia and free radicals derived from drugs. Recall that mixed blood from the hepatic artery and portal vein tributaries in the portal triad at the periphery of the hepatic lobule flows into the sinusoids, which drain into the central vein in the center of the lobule. Therefore, hepatocytes closest to the triad receive the most O2(zone 1 hepatocytes) and are less likely to be damaged than those located around the central vein (zone 3 hepatocytes). In many cases of acetaminophen overdose, necrosis can eventually involve the entire
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lobule causing fulminant hepatic failure. Acetaminophen overdose is the most common cause of drug-induced fulminant hepatic failure. Treatment with N-acetylcysteine is useful, because it increases the production of glutathione, an antioxidant that can neutralize acetaminophen free radicals. Psoriasis. The photograph shows a salmon-colored plaque covered by loosely adherent silverwhite scales. Psoriasis is a chronic inflammatory dermatosis with unregulated proliferation of squamous epithelial cells (epithelial hyperplasia). Other microscopic findings include downward extension of the rete pegs, retention of nuclei in the stratum corneum (parakeratosis), and thinning of the epidermis overlying the tips of dermal papillae. Peeling of the scales shows bleeding points due to exposure of vessels in the dermal papillae (Auspitz sign). Pitting of the nails is another common finding. Patients who have the HLA-B27 genotype may develop seronegative (rheumatoid factornegative) spondyloarthropathy, which is characterized by inflammation in the sacroiliac joints and peripheral arthritis, as noted in this patient. Dysplastic basal cells are seen in actinic (solar) keratosis, which is a precursor lesion for squamous cell carcinoma associated with excessive exposure to sunlight. The skin lesions show scaling papules and plaques that lack the salmon coloration and silver-white scales. Liquefactive degeneration is a characteristic finding of systemic lupus erythematosus. DNAantiDNA immunocomplexes deposit along the dermal-epidermal junction, causing immunologic destruction of the basal layer of the epithelium. Scaling red plaques mainly develop in sun-exposed areas (e.g., face). CML occurs in patients between 40 and 60 years of age. It is caused by translocation of the ABL proto-oncogene on chromosome 9 to chromosome 22 (Philadelphia chromosome), where it forms a fusion gene with the break cluster region. The Philadelphia chromosome is present in >95% of patients with CML; however, detection of the fusion gene has much greater specificity for confirming the diagnosis. The presence of neutrophils in all stages of development and a myeloblast count of <10% in the bone marrow indicate a chronic, not an acute leukemia. CML commonly metastasizes to the lymph nodes (lymphadenopathy), liver, and spleen (hepatosplenomegaly). Leukemia cells positive for tartrate-resistant acid phosphatase are present in hairy cell leukemia, which is a B-cell leukemia. The leukemia cells have hairlike cytoplasmic projections in the peripheral blood subdural hematoma is disruption of cortical veins that penetrate the dura and empty into the superior sagittal sinus. A venous bleed results in the formation of a blood clot in the subdural space. The photograph shows a well-formed blood clot beneath the reflected dural membrane. The pressure of the venous clot is evenly dispersed over the gyri and within the sulci, and there is no flattening of the convexities of the gyri. Rupture of the middle meningeal artery causes an epidural hematoma. Because the artery is firmly attached to the periosteum of the temporal bone, a fracture of the temporal bone causes the vessel to rupture. Blood under arterial pressure creates a space between the periosteum and the dura. Patients usually are unconscious after the initial trauma and then have a lucid interval followed by progressive loss of consciousness and death. emphysema related to smoking cigarettes. The chest radiograph shows hyperinflation in both lung fields, depression of both diaphragms, and a vertically oriented cardiac silhouette. Emphysema is a chronic obstructive pulmonary disease involving permanent enlargement of all or part of the
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respiratory unit (respiratory bronchioles, alveolar ducts, and alveoli). Elastic tissue destruction in these airways by elastases produced by neutrophils causes small airway collapse on expiration with trapping of air and distention of the distal air space. This increases the residual volume, which is the volume of air left in the lung after maximal expiration. An increase in residual volume automatically increases total lung capacity, which causes hyperinflation of the lungs, an increase in the anteroposterior diameter, depression of the diaphragms, and vertical orientation of the heart. In emphysema, lung compliance (ability to fill the lung with air) is increased and elasticity (recoil of the lung) is decreased because of destruction of elastic tissue. The FEV1sec, or the amount of air expelled from the lungs in 1 second after a maximal inspiration, is decreased (e.g., to 1 L versus the normal of 4 L) because of the trapping of air in the distended distal airways. The FVC, or total amount of air expelled after a maximal inspiration, is also decreased (e.g., to 3 L versus the normal of 5 L). Therefore, the ratio of FEV1sec to FVC is decreased (not increased) in emphysema. The patient has emphysema, with increased residual volume. As the residual volume increases, the tidal volume (volume of air that enters or leaves the lungs during normal quiet respiration) is either normal or slightly decreased (not increased). Upregulation of telomerase activity, which preserves the telomere length and ensures that there is no loss of genetic material after each cell division, is an indication of malignancy. The presence of hyperchromatic cells with atypical mitotic spindles in an endometrial biopsy specimen is also characteristic of malignancy. The cells in malignant tumors lose intercellular adhesion by decreasing the production of Ecadherin, an intercellular adhesion agent. Decreased intercellular adhesion must occur before these cells are able to invade through the basement membrane into the extracellular matrix. Malignant cells secrete vascular endothelial growth factor and basic fibroblast growth factor, which stimulate angiogenesis. Angiogenesis is necessary to provide oxygen and nutrients to the malignant cells. Bacterial meningitis (nuchal rigidity, neutrophils in CSF with phagocytosed bacteria). In sickle cell anemia, the spleen is typically dysfunctional, which causes the patient to be susceptible to sepsis and meningitis resulting from Streptococcus pneumoniae, a Gram-positive diplococcus. Sepsis due to S. pneumoniae is the most common cause of death in children with sickle cell disease Seborrheic keratosis a rough pigmented lesion that has the stuck-on, warty appearance. This common epidermal tumor shows a proliferation of pigmented basal cells on histologic examination. When such lesions develop suddenly, especially in the setting of epigastric pain and weight loss, they indicate the presence of an underlying gastric adenocarcinoma (Leser-Trlat sign). Angiodysplasia, there is dilation of mucosal and submucosal venules in cecum and right.It usually occurs in elderly individuals, because vascular ectasias in the cecum increase with age. Increased wall stress in the cecum stretches the venules producing these lesions. It presents with the loss of large volumes of blood, that can produce signs of hypovolemic shock as in this patient. Sigmoid diverticulosis is the most common cause of hematochezia. However, sigmoid diverticulitis is not, because the blood vessel next to the inflamed diverticular sac is often fibrosed and destroyed. The rule of thumb for diverticular disease causing hematochezia is: -osisyes; itis no. (HSV-2), a sexually transmitted disease. The figure shows a multinucleated squamous cell with ground glass nuclei, which will eventually develop into more discrete eosinophilic inclusions. The
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virus remains latent in sacral sensory ganglia and recurs in the same location. Acyclovir decreases the number of recurrences but does not cure the infection. Human papillomavirus causes koilocytotic atypia in squamous cells. Infected cells have pyknotic (condensed chromatin) nuclei surrounded by a clear halo. Wound healing by primary intention involves approximation of the wound edges by sutures or other materials. On day 1, a fibrin clot (hematoma) develops at the wound site and neutrophils infiltrate the wound margins. Neutrophils have no role in scar tissue formation. Macrophages begin replacing neutrophils in 2 to 3 days and have no role in scar tissue formation On day 3, granulation tissue, the precursor of scar tissue, begins to develop. Fibroblasts synthesize type III collagen, and blood vessels are formed (angiogenesis) to supply O2and nutrients. On days 4 to 6, granulation tissue formation is at its peak. Fibronectin is the key glycoprotein involved in granulation tissue formation. It is chemotactic for endothelial cells and fibroblasts and is an adhesive agent. At the end of 1 month, collagenase remodeling of the wound occurs with replacement of type III collagen by type I collagen, which increases the tensile strength of the wound. Collagenase contains zinc. A prolonged bleeding time associated with a normal platelet count, normal PT, and normal aPTT indicates a defect in platelet function (adhesion and/or aggregation). The most common cause of a prolonged bleeding time is aspirin or other NSAIDs. The patient has SLE complicated by an autoimmune hemolytic anemia. These are subdivided into warm types (IgG-mediated) and cold types (IgM-mediated). The former type is usually an extravascular hemolytic anemia, while the latter type is usually intravascular but sometimes extravascular. The direct Coombs test detects IgG and/or C3b on the surface of RBCs and must be positive in order to confirm the diagnosis of any type of immune hemolytic anemia, warm or cold. Immune hemolytic anemias that involve IgG (e.g., SLE) have macrophage removal of RBCs coated by IgG (extravascular hemolysis). The end-product of macrophage destruction of RBCs is unconjugated bilirubin, which produces jaundice (yellow eyes). Macrophage removal of portions of the RBC membrane produces spherocytes, which are characteristic findings in extravascular hemolytic anemias. Cold autoimmune hemolytic anemias involving IgM antibodies that produce hemoglobinuria and jaundice are not as likely to be present. Serum ferritin correlates with the amount of ferritin stores in bone marrow macrophages. It is usually normal in autoimmune hemolytic anemias. Ferritin levels are only decreased in iron deficiency anemia. Absence of urine urobilinogen occurs in complete obstruction of bile outflow into the intestines. Colonic bacteria normally convert bilirubin in bile into urobilinogen, which is responsible for the color of stool. A small amount of urobilinogen reabsorbed from the intestine into the blood enters the urine, where it produces the normal color of urine. In autoimmune hemolytic anemia, the urine urobilinogen is increased (not absent), because greater amounts of bilirubin from the hemolytic anemia are converted to urobilinogen in the colon and proportionately more urobilinogen is recycled into the urine. The patient has a sterile pyuria, which refers to the presence of neutrophils in the urine (positive reagent strip for leukocyte esterase), a negative reagent strip for nitrites, and no growth of organisms with a standard urine culture. Due to the close proximity of the patients urinary findings with a previous sexual encounter, the patient most likely has urethritis due to C. trachomatis.
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. In lower urinary tract infections due to E. coli, the reagent strip is positive for nitrites and leukocyte esterase and routine cultures isolate the organism Distal adenocarcinoma of the esophagus secondary to Barretts esophagus, which, in turn, is secondary to GERD. The photograph shows a raised lesion at the junction of the distal esophagus and proximal stomach. GERD is associated with reflux of gastric acid and bile into the distal esophagus due to relaxation of the lower esophageal sphincter (LES). It is the most common causes of Barretts esophagus. Squamous epithelium reacts to acid injury by replacing the epithelium with mucus-secreting cells (glandular metaplasia). Esophageal ulceration, stricture, and adenocarcinoma are complications of Barretts esophagus. Treatment of GERD is important, because it decreases the risk for developing distal adenocarcinoma of the esophagus, which is the most common primary cancer of the esophagus in the United States. Treatment includes histamine (H2) blockers, proton inhibitors, and prokinetic agents. Polycystic ovary syndrome (PCOS). The photograph shows a cross-section of an enlarged ovary with abundant central stroma and subcapsular follicles and the ultrasound shows similar findings. Serum LH is increased in PCOS. This stimulates the ovaries to produce increased amounts of 17ketosteroids (DHEA and androstenedione) and testosterone. These androgen compounds cause hirsutism (abnormal hairiness, especially in areas where hair would be found on a man). In obese patients, an increase in adipose allows greater conversion of these androgens to estrogens by aromatase (aromatization). Aromatase converts androstenedione to estrone and testosterone to estradiol. Hyperestrinism, in turn, causes endometrial hyperplasia in patients with PCOS. Increased estrogen has a negative feedback on the release of FSH and a positive feedback on LH; therefore, LH remains increased and FSH is suppressed. Decreased FSH causes degeneration of the follicles, resulting in the formation of subcapsular cysts. In PCOS, the LH:FSH ratio > 2. Cyclooxygenase converts arachidonic acid to prostaglandin H2, which is the precursor for prostaglandins, thromboxanes, and prostacyclins. Aspirin and nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase and prevent the synthesis of prostaglandins, some of which are associated with the genesis of pain (e.g., prostaglandin E2).
Uterus has multiple, well-circumscribed, gray-white nodules (leiomyomas) that distort the uterus. Leiomyomas are benign smooth-muscle tumors. Those that are submucosally located are associated with excessive menstrual bleeding (menorrhagia) and often require removal by hysterectomy, as in this patient. Menorrhagia is the most common cause of iron deficiency in women < 50 years of age. In an acute anterior myocardial infarction, aspirin is used to prevent thrombus formation either in the coronary arteries or the damaged endothelium in the left ventricle. Aspirin prevents platelet aggregation causing prolongation of the bleeding time without affecting the platelet count. Patients are frequently anticoagulated with heparin and warfarin. Heparin enhances antithrombin III activity leading to neutralization of many of the coagulation factors including thrombin and X in the final common pathway. This prolongs the PT and the PTT, although the latter test is a better test to follow heparin therapy. Warfarin inhibits further activation of the vitamin Kdependent coagulation factors (II, VII, IX, and X). Since factors II and X are in the final common pathway, the PT and PTT are both
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prolonged; however, the former test is a better test to follow warfarin therapy when it is converted into the international normalized ratio. Heparin works by enhancing the activity of anti-thrombin III; therefore, if the patient is deficient in ATIII, a standard dose of heparin is not sufficient to neutralize the clotting factors to prolong the PTT. However, using larger doses of heparin will enhance the activity of what little ATIII is present in plasma causing prolongation of the PTT. An antibody screen (indirect Coombs test) detects atypical antibodies that could potentially attack donor RBC antigens. If the antibody screen is negative, then the major crossmatch (recipient serum + donor RBCs) should be compatible Febrile transfusion reactions are due to recipient anti-human leukocyte antigen antibodies reacting against donor leukocytes (type II hypersensitivity reaction). Destruction of donor leukocytes releases pyrogens causing fever. In chronic renal failure there is tubular cell dysfunction resulting in retention of K+ (hyperkalemia with peaked T waves on an ECG) and an increased anion gap type of metabolic acidosis due to retention of organic acids like sulfuric and phosphaturic acid. Cystic teratoma of the ovary with hair and teeth (arrow). This type of tumor is derived from germ cells or midline embryonic rests, and contains tissues derived from more than one germ cell layer (e.g., bone, muscle, glands, and neural tissue) In most cases, the tumor presents with abdominal pain, as in this patient. Histamine is the primary chemical mediator of type I hypersensitivity reactions. It is stored and released by mast cells, the primary effector cell of type I hypersensitivity reactions. It contracts the venular endothelial cells and exposes the basement membrane, causing increased vessel permeability and swelling of the tissue. Causes arteriolar vasodilation, which produces redness (rubor) of the skin and increased heat (calor) and pruritus. Activated coagulation factor XII converts high-molecular-weight kininogen to bradykinin. Bradykinin causes vasodilation of arterioles, increased vessel permeability, and pain in acute inflammation N.gonorrhoeae is the mcc of septic arthritis. A characteristic pattern of disseminated gonococcemia is the presence of a purulent monoarthritis (usually the knee); tenosynovitis involving the wrist and/or ankles; and pustules on the palms, soles, or trunk. N. gonorrhoeae is always disseminated, because the membrane attack complex is important in the phagocytosis of the pathogen. Acute hemolytic anemia caused by glucose-6-phosphate dehydrogenase (G6PD) deficiency, an Xlinked recessive disorder. G6PD deficiency is most common in persons of black and Mediterranean descent (i.e., Greeks, Italians). G6PD deficiency leads to decreased synthesis of glutathione, which is necessary to neutralize H2O2, an oxidant product in RBC metabolism. Oxidant stresses that induce hemolysis include infection (most common) and drugs (e.g., primaquine, dapsone, trimethoprim). H2O2 accumulation in the RBC damages the RBC membrane (intravascular hemolysis) and denatures hemoglobin, forming discrete inclusions called Heinz bodies. Splenic macrophages often remove damaged RBC membranes, leaving cells with membrane defects, called bite cells, circulating in the peripheral blood . Dairy products should be avoided in lactase deficiency and galactosemia. Lactase, a brush border disaccharidase, catalyzes the conversion of lactose to glucose and galactose. Phenylalanine is increased in phenylketonuria, an autosomal recessive disease characterized by a deficiency of phenylalanine hydroxylase. This enzyme converts phenylalanine to tyrosine.
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Phenylalanine-containing products must be eliminated (e.g., certain sweeteners) to prevent mental retardation and tyrosine must be added to the diet. Tyrosine should be eliminated from the diet in patients with tyrosinosis, an autosomal recessive disease caused by a deficiency of fumarylacetoacetate hydrolase, to prevent chronic liver disease, causing hepatocellular carcinoma. Chronic pancreatitis can show irregular densities in the left upper quadrant of the radiograph are foci of dystrophic calcification (calcification of damaged tissue) in the parenchyma of the pancreas. Pain radiating into the back is also highly suggestive of pancreatitis and is related to the retroperitoneal location of the pancreas. In chronic pancreatitis, recurrent attacks of acute pancreatitis lead to repair by fibrosis and loss of both exocrine and endocrine function. Loss of the pancreatic enzymes results in malabsorption, which is the cause of the patients chronic diarrhea and malnutrition. Loss of islet cells leads to type 1 diabetes mellitus. Ingestion of methyl alcohol can cause optic atrophy due to Alcohol dehydrogenase converts methyl alcohol to formic acid, which causes inflammation of the optic nerve (optic neuritis) and metabolic acidosis. Optic atrophy occurs, leading to decreased visual acuity, visual field defects, and night blindness. CGD is X-linked recessive and is caused by a deficiency of nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase. This is the key enzyme in the O2-dependent MPO system, which is the most effective microbicidal system in neutrophils and monocytes. In this system, NADPH oxidase, using NADPH as a cofactor, converts molecular O2 to superoxide free radicals. This reaction releases energy called the respiratory or oxidative burst. Superoxide free radicals are normally converted to peroxide, which is then combined with chloride ions by MPO to produce hypochlorous acid to kill bacteria. A small amount is converted by iron into hydroxyl free radicals. The NBT test detects whether the respiratory burst is functioning. In CGD, the respiratory burst is absent; hence, the abnormal leukocyte NBT test. Peroxide is also absent; therefore, the cells cannot synthesize hypochlorous acid to kill bacteria. S. aureus is the primary cause of death in CGD. S. aureus is catalase-positive, and catalase degrades H2O2. Therefore, any H2O2 produced by the bacteria in the phagolysosome that could potentially be used to synthesize hypochlorous free radicals (HOCl) is neutralized and the bacteria cannot be killed. Bacteria such as Streptococcus pyogenes are catalase negative; hence, when they supply the missing peroxide in the phagolysosome, hypochlorous acid is generated and the bacteria are killed. Primary squamous cell carcinoma of the lung that ectopically secretes parathyroid hormone-related peptide, causing hypercalcemia. These tumors are centrally located (note the centrally located mass in the radiograph) and strongly associated with smoking. medullary carcinomas of the thyroid secrete calcitonin and hypocalcemia is a potential complication hepatocellular carcinomas secrete an insulin-like factor that can produce hypoglycemia. Hydatidiform mole, which is a benign neoplasm of the chorionic villus. They do not contain embryos and have a 46,XX karyotype, which is produced when an egg with no chromosomes is fertilized by two spermatozoa with a 23,X karyotype. Histologically, the villi are devoid of blood vessels and are surfaced by trophoblastic tissue (syncytiotrophoblast and cytotrophoblast). Hydatidiform moles have the capacity to transform into a choriocarcinoma, a malignancy of trophoblastic tissue. Hydatidiform moles develop in the first trimester. The ultrasound shows a snow storm appearance A benign neoplasm with a triploid karyotype describes a partial hydatidiform mole, in which only some of the villi are neoplastic and an embryo usually is present. The neoplastic chorionic villi
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contain 69 chromosomes and have an XXY karyotype, which is produced when a haploid egg with a 23,X karyotype is fertilized by two spermatozoa, one having a 23,X and the other a 23,Y karyotype. Partial hydatidiform moles do not progress into a choriocarcinoma. Cervical cancer shows a history of bleeding post sex and malodorus discharge are common. Cervical cancers are associated with HPV 16/18 STD. Cigarette smoking and OCP are risk for cervical squamous cancer. Pap smear can detect cervical squamous dysplasia precursors. If a pregnant woman is given DES pre-pregnancy is predisposed to clear cell adenocarcinoma involving the upper third of the vagina and cervix. Oral contraceptives actually decrease the risk for developing endometrial adenocarcinoma. Celiac disease will show villous atrophy and hyperplastic glands in the lamina propria. Dermatitis hereptiformis is 100% correlated with celiac disease and can present with vesicular lesions. Celiac disease is a multiorgan autoimmune disease characterized by an inappropriate T-cell and IgAmediated response against gluten in genetically predisposed persons (HLA DQ2 and HLA DQ8). Reed-Sternberg (RS) cell, the neoplastic cell found in Hodgkins lymphoma. It is a large, multilobed cell with prominent nucleoli surrounded by a halo of clear nucleoplasm. In most cases, it is a transformed germinal center B-cell that is CD15 and CD30 positive. Creutzfeldt-Jakob disease (CJD) is due to iatrogenic transmission of infectious agents called prions (proteins without nucleic acids). These disorders occur in humans (and may also be transmitted from eating infected cows (bovine spongiform encephalopathy, or mad cow disease). CJD is characterized by progressive dementia, startle myoclonus (abnormal jerking movements), and ataxia. There is no known cure, and death is inevitable. Multinucleated microglial cells are a characteristic finding in patients with AIDS dementia due to HIV. The virus causes the microglial cells to fuse. Microglial cells are the reservoir cell in the brain for HIV. In idiopathic Parkinsons disease, neurons in the substantia nigra contain pink-staining Lewy bodies (damaged neurofilaments) in the cytoplasm. Anxiety induced respiratory alkalosis can cause tetany. Adduction of the thumb into the palm, plus numbness and tingling at the tips of the fingers, are classic signs of tetany. Tetany is due to a decreased concentration of ionized calcium in the blood. This increases neuromuscular excitability by bringing the threshold potential of neuromuscular tissue closer to the resting membrane potential. Therefore, less of a stimulus is required to initiate the action potential, which results in sustained muscle contractions. Myasthenia gravis, which is characterized by drooping eyelids, history of tiredness, diplopia (double vision), and dysphagia for solids and liquids in the upper esophagus. This autoimmune disorder is characterized by the production of IgG antibodies that react against acetylcholine receptors in the neuromuscular junction of striated muscle (type II hypersensitivity reaction). The most common initial presentation is muscle weakness involving the ocular muscles, resulting in ptosis and diplopia toward the end of the day. Note drooping of the left eye in photograph. The confirmatory test is the Tensilon test. Tensilon inhibits acetylcholine esterase causing an increase in acetylcholine in the synapse, enough to bind to receptors causing a reversal of the muscle weakness Multiple sclerosis is the most common demyelinating disorder Amyotrophic lateral sclerosis is an example of an upper and/or lower motor neuron disorder. Muscle weakness begins in the hands and progresses throughout the body.
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SIADH due to excessive stimulation of ADH release by chlorpropamide, a oral hypoglycemic agent. ADH reabsorbs electrolyte-free water from the collecting tubules causing a dilutional hyponatremia (serum Na+ = TBNa+/TBW). The mental status abnormalities are due to hyponatremia, which creates an osmotic gradient that favors the movement of water into the cells in the brain. Acute bacterial endocarditis involving the mitral valve. Mitral valve regurgitation produces a pansystolic murmur that does not increase in intensity with deep, held inspiration. S. aureus is the most common pathogen in acute infective endocarditis associated with intravenous drug abuse. Aortic regurgitation is associated with a high-pitched diastolic blowing murmur that occurs immediately after S2. As with all left-sided valvular murmurs and abnormal heart sounds, it does not increase in intensity with deep, held inspiration Mitral stenosis begin with an opening snap in early of mid diastole followed by a mid-diastolic rumbling murmur. Bacterial endocarditis that is not associated with intravenous drug abuse is most often due to S. viridans, which is a pathogen that can only seed a previously damaged valve S. epidermidis is the most common cause of ABE associated with prosthetic heart valves. Carcinogens in cigarette smoke can produce cervical cancer. However, the biopsy shows koilocytotic atypia (not cancer) due to HPV. Diffuse membranous glomerulopathy shows granular immunofluorescence with irregular deposits located in the glomerular capillaries. The chronic hepatitis B infection, hypertension, dependent pitting edema, heavy proteinuria, and fatty casts with Maltese crosses is compatible with a diagnosis of nephrotic syndrome due to diffuse membranous glomerulopathy. The glomerular injury is due to immunocomplex deposition in a subepithelial location (type III hypersensitivity reaction). Focal segmental glomerulosclerosis is most often associated with AIDS in young black males and with intravenous heroin addiction. It is now considered the most common adult cause of nephrotic syndrome. Glomerular injury is due to cytokine damage of the visceral epithelial cells. It is not an immunocomplex disease; therefore, the immunofluorescent study is negative. It is a very common cause of end stage renal disease. Necator americanus (hookworm) is the most common parasite causing iron deficiency. The adult worms of Ascaris lumbricoides cause intestinal obstruction. Trichuris trichiura, or whipworm, is the most common parasite causing rectal prolapse in children Enterobius vermicularis (pinworm). The eggs are characteristically flattened on one side. The female worms lay their eggs in the anus, which causes irritation leading to anal pruritus. TREATMENT with mebendazole Serum transaminase levels are primarily elevated in diffuse liver cell necrosis (e.g., viral hepatitis) ARF is associated with an increase in serum creatinine and serum BUN and the urine sediment shows renal tubular cell casts. In prerenal azotemia there is oliguria and an increased serum BUN and creatine with a ratio > 15. Patient has osteosarcoma and a history of retinoblastoma, which together indicate inactivation of the RB suppressor gene on chromosome 13. Osteosarcoma is a tumor of the connective tissue that arises from osteocytes The BRCA1 suppressor gene is involved in DNA repair. Inactivation of the gene is associated with breast cancer in women and prostate cancer in men.
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The c-MYC and n-MYC proto-oncogenes are involved in nuclear transcription. Activation of the cMYC proto-oncogene by a t(8;14) translocation produces Burkitts lymphoma, whereas activation of the n-MYCproto-oncogene produces a neuroblastoma. The RAS proto-oncogene is a signal transducer that generates second messengers. RAS is activated by a point mutation and accounts for 30% of human cancers (e.g., cancers of the lung, colon, and pancreas; leukemias). Adrenal crisis presents as hypotension, tachycardia, hypoglycemia with history of vomiting,weightloss, abdo pain, and hyperpigmentation and should be treated with corticosteroids. MCC of portal HTN is alcohol abuse Portal HTN is caused by increased resistance of blood flow to the liver due to compression of sinusoids and central veins. It is caused by esophageal varcies, ascites, congestive splenomegaly, hemorrhoids, and caput medusa. Esophageal varacies are due to increased portal vein pressure leading to the dilatation of the left gastric coronary arteries. Which usually drain in the distal esophagus and portal vein. Folate deficiency causes microcytic anemia with hypersegmented nuetrophils and causes a decreased in N5 methyltetrahydrofolate and B12 which leads to an increase in plasma homocystenie and methionine which contribute to a MI by causing endothelial damage. Alcoholism causes poor reabsorption in the jejunum. Hence during folate metabolism and B12 metabolism is impaired and cant remove N5 methyltetrahydrofolate Homocystinuria is deficiency of cystathionine synthase which decreases the conversion of homocysteine to cystathionine increasing homocystiene leading to mental retardation and thrombosis Vitamin B12 deficiency causes microcytic anemia pancytopenia and demylelination of posterior and lateral cortico spinal tract When the plasma glucose concentration is low, there is an increase in the body secretion of epinephrine, glucagon, and, to a lesser extent cortisol and growth hormone. The increase in sympathetic activity stimulates lipolysis in the peripheral tissues and gluconeogenesis in the liver and decreases peripheral glucose consumption. The brain relies heavily on glucose as an energy source, and the level of glucose uptake by the brain is not regulated by insulin. If hypoglycemia persists despite this autonomic reaction, the activity of higher brain centers diminishes in order to reduce glucose requirements. Thus, there are two types of hypoglycemic symptoms: 1. Adrenergic symptoms such as sweating, tremor, palpitations, hunger, and nervousness occur due to epinephrine and norepinephrine release. (Recall that sweating is a cholinergic process under sympathetic control.) Adrenergic symptoms are the early signs of hypoglycemia. 2. CNS symptoms develop later and at lower glucose levels. They include behavioral changes, confusion, visual disturbances, stupor, and seizures. Prolonged CNS hypoglycemia leads to irreversible neurological deficits and death. Adult lead poising presents as colicky abdominal pain , constipation, headaches, impaired concentration, bluish pigment on gum tooth line, wrist or foot drop due to peripheral nueropathyand microcytic hyopchromic anemia with basophilic stippling.

Rapid Review Path HY Points

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Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel

Rapid Review HY Point by Nirav Patel