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Transcript of 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.