path rapid review

8/12/2019 Path Rapid Review

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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 Xchromosome 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 tonormal 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 tothrombosis 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 mostoften due to thrombosis of the left anterior descending coronary artery.

Pharmacologic treatment of disseminated malignancies such as chronic myelogenous leukemiaresults 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 crystalsin 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, andamino 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 locatedprimarily 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 areprimarily 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 nicotinamideadenine 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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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 MPOsystem for killing bacteria. Activated nicotinamide adenosine dinucleotide phosphate (NADPH)

oxidase in the cell membrane oxidizes reduced NADPH, converting molecular O2to 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, O2is converted to peroxide (H2O2) by superoxide dismutase inthe phagolysosomes of neutrophils and monocytes. MPO catalyzes a reaction that combines

H2O2with Clto 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 C3bare 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 withphagosomes. 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 enterotoxigenicEscherichia coli, which produces a toxinthat 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 notalter theserum 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 disseminatedintravascular coagulation (DIC). In APL, the neoplastic promyelocytes contain numerous splinter-

shaped 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 mostcommon 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 fromthe 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 occursduring 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 theinfant to breathe only through the mouth. The cyanosis that develops when the infant is breast-

feeding 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 theduodenum. 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 duringpregnancy, 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 vitaminB12is 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. Thearrow points to a hypersegmented neutrophil (more than five nuclear lobes), a valuable and early

marker of vitamin B12deficiency (also folate deficiency). Pancytopenia is the rule in PA, because

deficiency of vitamin B12causes 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 B12after 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 succinylCoA using an enzyme reaction that requires vitamin B12as a cofactor. Deficiency of vitamin

B12causes 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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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 weakensthe 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. Kaposissarcoma 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. henselaeis a gram-negative bacterium that causes bacillary angiomatosis, a disease that occursalmost 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 producingCushing 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 ahormone that inhibits osteoclasts causing hypocalcemia.

Elderly individuals frequently lose their isohemagglutinins (e.g., anti-A IgM, anti-B IgM). The patientis 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 ofischemic 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 increasedclearance of urea in the urine), but an in pH (estrogen and progesterone stimulate the CNSrespiratory 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 (renalfailure), 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 bladderinto 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 toglucose, 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 theAPCsuppressor gene; (2) activation of

the RASproto-oncogene; and (3) inactivation of the TP53suppressor 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 TP53suppressor

gene and RASproto-oncogene are the two most common genes associated with cancer.

Henoch-Schnlein purpura is characterized by distinctive skin rash on the lower extremities andbuttocks, 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 acuteinflammation. 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 aconnective tissue disorder with defects in collagen synthesis and/or structure. Other clinicalfeatures 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 causedby 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 acquiredheart 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 thecoronary arteries.

Cyanide (CN) is a systemic asphyxiant that inhibits cytochrome oxidase in the electron transportchain, 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, bibasilarinspiratory 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 ismost 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 calcium-

containing calculi.

A decrease in both PTH and serum calcium is characteristic of primary hypoparathyroidism, whichis most often due to previous thyroid surgery

A decrease in PTH and an increase in serum calcium is characteristic of hypercalcemia due tomalignancy (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 secondaryhyperparathyroidism. 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 pyloriis the most common cause of peptic ulcer disease, which includes gastric andduodenal 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 thebody 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. pylorinot 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 childindicates 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 thesame 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 tochronic 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 previousviral 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 (decreasedblood 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 normallyresponsible 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 11-

deoxycortisol

The episodic history of hematuria following upper respiratory infections is characteristic of IgAglomerulopathy, which is the most common type of glomerulonephritis. Urine sediment shows anRBC cast

Primary stomach cancer that has hematogenously metastasized to both ovaries (Krukenbergtumors). 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 supraclavicularnodes (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 obstructivejaundice, 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 byinsulin.

Bronchopneumonia refers to an acute infection that begins in the bronchus and extends into thesurrounding lung parenchyma producing microabscesses. Streptococcus pneumoniaeis the most

common cause of bronchopneumonia.

AAT deficiency is an autosomal dominant disease, whose alleles are inherited codominantly (eachallele 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 (breathcessation) 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 ofhypertonic fluid produces a hyponatremia

C) Isotonic gain of fluid (e.g., excessive infusion of normal (0.9%) saline. The serum sodium remainsnormaltherefore, the POsmis normal.

D) congestive heart failure, the cardiac output is decreased and the kidney reabsorbs a slightlyhypotonic 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 isincreased , causing an increase in POsmand an increase in the height of the interrupted squares

F) hypertonic gain of sodium (e.g., excessive infusion of sodium bicarbonate; infusion of a sodiumcontaining antibiotic). The serum sodium is increased, causing an increase in POsmand an increase

in the height of the interrupted squares

Microscopic polyangiitis. It is a small vessel type of vasculitis (palpable purpura) that can byprecipitated 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 morethan 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 andincreases 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 transaminasesare 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 excessACTH 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 honey-colored, crusted lesions, which are evident in this patient. Staphylococcus aureusis the most

common cause of this superficial skin lesion. Streptococcus pyogenesis 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 (Sao295%) is shunted into a chamber or

vessel with venous blood (Sao275%), 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 Sao2in the pulmonary artery (85% versus normal of 75%).

The cytochrome P-450 system in the liver converts acetaminophen into a free radical. A large doseof acetaminophen produces numerous free radicals, which damage hepatocytes causing release oftransaminases. 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 silver-white scales. Psoriasis is a chronic inflammatory dermatosis with unregulated proliferation ofsquamous 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 squamouscell 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. DNAanti-DNA 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 ABLproto-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


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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 FEV1secto 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 isno 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 E-cadherin, 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, whichstimulate 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 cellanemia, the spleen is typically dysfunctional, which causes the patient to be susceptible to sepsisand meningitis resulting from Streptococcus pneumoniae, a Gram-positive diplococcus. Sepsis due

to S. pneumoniaeis 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. Thiscommon 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 usuallyoccurs 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 withground 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 othermaterials. On day 1, a fibrin clot (hematoma) develops at the wound site and neutrophils infiltratethe 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 glycoproteininvolved 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 IIIcollagen 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 intowarm 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 isusually 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 urineurobilinogen 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 (positivereagent 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 leukocyteesterase and routine cultures isolate the organism

Distal adenocarcinoma of the esophagus secondary to Barretts esophagus, which, in turn, issecondary 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 causesof 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 ovarywith 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 17-

ketosteroids (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 forprostaglandins, 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) thatdistort 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 inthe coronary arteries or the damaged endothelium in the left ventricle. Aspirin prevents plateletaggregation 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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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 recessivedisease 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 arefoci 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 methylalcohol 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 dinucleotidephosphate (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 O2to 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. aureusis the primary cause of death in CGD. S. aureusis

catalase-positive, and catalase degrades H2O2. Therefore, any H2O2produced by the bacteria in thephagolysosome 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-relatedpeptide, 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 embryosand 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 onlysome 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 IgA-

mediated 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, multilobedcell 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 toHIV. 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 Lewybodies (damaged neurofilaments) in the cytoplasm.

Anxiety induced respiratory alkalosis can cause tetany. Adduction of the thumb into the palm, plusnumbness 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 (doublevision), 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 anddiplopia 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 thatfavors the movement of water into the cells in the brain.

Acute bacterial endocarditis involving the mitral valve. Mitral valve regurgitation produces apansystolic murmur that does not increase in intensity with deep, held inspiration. S. aureusis 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 occursimmediately 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-diastolicrumbling 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. epidermidisis the most common cause of ABE associated with prosthetic heart valves.

Carcinogens in cigarette smoke can produce cervical cancer. However, the biopsy showskoilocytotic atypia (not cancer) due to HPV.

Diffuse membranous glomerulopathy shows granular immunofluorescence with irregular depositslocated 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 andwith 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 ofAscaris lumbricoidescause 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 RBsuppressor gene on chromosome 13. Osteosarcoma is a tumor of the connective tissue that

arises from osteocytes

The BRCA1suppressor gene is involved in DNA repair. Inactivation of the gene is associated withbreast cancer in women and prostate cancer in men.


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The c-MYCand n-MYCproto-oncogenes are involved in nuclear transcription. Activation of the c-MYCproto-oncogene by a t(8;14) translocation produces Burkitts lymphoma, whereas activation of

the n-MYCproto-oncogene produces a neuroblastoma.

The RASproto-oncogene is a signal transducer that generates second messengers. RASisactivated 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 leftgastric coronary arteries. Which usually drain in the distal esophagus and portal vein.

Folate deficiency causes microcytic anemia with hypersegmented nuetrophils and causes adecreased in N5 methyltetrahydrofolate and B12 which leads to an increase in plasma homocystenieand methionine which contribute to a MI by causing endothelial damage.

Alcoholism causes poor reabsorption in the jejunum. Hence during folate metabolism and B12metabolism is impaired and cant remove N5 methyltetrahydrofolate

Homocystinuria is deficiency of cystathionine synthase which decreases the conversion ofhomocysteine to cystathionine increasing homocystiene leading to mental retardation and

thrombosis

Vitamin B12 deficiency causes microcytic anemia pancytopenia and demylelination of posterior andlateral cortico spinal tract

When the plasma glucose concentration is low, there is an increase in the body secretion ofepinephrine, 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.

Acute bronchial constriction begins when an allergen interacts with IgE antibody attached to a mastcell which stimulates mediators like histamine, leukotrienes, PGs, PAF, IL4, IL5, and TNF alpha and beta that

cause bronchial constriction, bronchial wall edema, chemotaxis, and increased mucus production.

path rapid review

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