Solution:

1>The correct answer is A. A number of physiologic changes occur in a person living at high altitude. The diminished barometric pressure at high altitude causes alveolar hypoxia and arterial hypoxia. Pulmonary vasoconstriction occurs in response to alveolar hypoxia; therefore, the diameter of the pulmonary vessels would be greater in the brother living at sea level. All the other choices describe physiologic processes that would be enhanced by living at high altitude. Increased erythropoietin production (choice B), caused by arterial hypoxia, leads to increases in hematocrit in people living at high altitude. Mitochondrial density increases (choice C) in people chronically exposed to the hypoxemia caused by living at high altitude. At high altitudes, the ventilation rate increases, causing a respiratory alkalosis. The kidney then compensates by increasing the excretion of HCO3- (choice D). Increasing the rate of respiration (choice E) is a very useful adaptation to the hypoxic conditions of high altitude. The primary stimulus is the hypoxic stimulation of peripheral chemoreceptors.

2>The correct answer is C. The loading of O2 is facilitated when the oxygen dissociation curve shifts to the left, and the unloading of O2 is facilitated when the oxygen dissociation curve shifts to the right. A good way to remember the conditions that promote dissociation of O2 is to think of exercising muscle, which has decreased pH (choice C) because of the accumulation of lactic acid, increased PCO2 (compare with choice B) because of the increased rate of aerobic metabolism, increased temperature (compare with choice D), and increased 2,3-DPG (2,3-diphosphoglycerate; compare with choice E) because of increased glycolysis.

3>The correct answer is A. This patient has Huntington's disease, which has autosomal dominant inheritance. It is characterized by severe degeneration of the caudate nucleus along with degenerative changes in the putamen and cortex. In addition to chorea, these patients frequently suffer from athetoid (writhing) movements, progressive dementia, and behavioral disorders.

4>The correct answer is E. The most common bacteria implicated in community-acquired pneumonia is the pneumococcus, Streptococcus pneumoniae. Other organisms frequently implicated in patients less than age 60 without comorbidity include Mycoplasma pneumoniae, respiratory viruses, Chlamydia pneumoniae, and Haemophilus influenzae. When community-acquired pneumonia occurs in elderly patients or patients with comorbidity, aerobic gram-negative bacilli and Staphylococcus aureus are added to the list. The organisms listed in choices A, B, and C are important causes of community-acquired pneumonia, but are not the most frequent causes.

5>The correct answer is E. By the third week of development, hematopoiesis begins in the blood islands of the yolk sac. Beginning at 1 month of age and continuing until 7 months of age, blood elements are also formed in the liver. Hematopoiesis occurs in the spleen and lymphatic organs between 2 and 4 months, and in the bone marrow after 4 months.

6>The correct answer is E. Familial hypercholesterolemia, which is due to defective function of the LDL receptor, is an area of intense research. The molecular basis of LDL receptor abnormalities is becoming better understood, and more than 200 mutations in the gene for the LDL receptor have been identified

8>The correct answer is D. The patient has a megaloblastic anemia, which can be due to deficiency of folate or B12. Pregnancy increases the need for folate and other nutrients used by both baby and mother, and may "unmask" a borderline dietary deficiency. For this reason, most obstetricians recommend vitamin supplements for pregnant women. Ascorbic acid (choice A) is vitamin C, and its deficiency predisposes for capillary fragility and oral lesions. Calcium deficiency (choice B) predisposes for osteoporosis/osteopenia. Copper deficiency (choice C) is rare; when it occurs, it may cause a hypochromic anemia, neutropenia, osteoporosis, or hypotonia. Iron deficiency (choice E) causes a microcytic, hypochromic anemia, with reduced mental and physical Performance

9>The correct answer is A. Cyclophosphamide is metabolized to acrolein, which is excreted in the urine. If the patient's urine is concentrated, the toxic metabolite may cause severe bladder damage. Early symptoms of bladder toxicity include dysuria and frequency. This can be distinguished from a urinary tract infection, since there is no bacteriuria with cyclophosphamide-induced bladder toxicity. However, microscopic hematuria is often present on urinalysis. In severe hemorrhagic cystitis, large segments of the bladder mucosa may be shed which can lead to prolonged, gross hematuria. The incidence of cyclophosphamide-induced hemorrhagic cystitis can be decreased by ensuring that the patient maintains a high fluid intake. Cyclophosphamide is an alkylating agent used in the treatment of breast carcinoma, malignant lymphoma, multiple myeloma, and adenocarcinoma of the ovary, as well as various other forms of cancer. The major toxic reactions commonly seen with this agent include mucositis, nausea, hepatotoxicity, sterile hemorrhagic and non-hemorrhagic cystitis, leukopenia, neutropenia, and interstitial pulmonary fibrosis.

11>The correct answer is A. Coarctation of the aorta occurs in two patterns. In the infantile type, the stenosis is proximal to the insertion of the ductus arteriosus (preductal); this pattern is associated with Turner's syndrome. In the adult form, the stenosis is distal to the ductus arteriosus (postductal) and is associated with notching of the ribs (secondary to continued pressure from the aorta on them), hypertension in the upper extremities, and weak pulses in the lower extremities.

12> Explanation: The correct answer is E. Follicles in different stages of maturation have different appearances. The most primitive follicles, primordial follicles (choice D), are inactive reserve follicles that contain primary oocytes (arrested in prophase of first meiotic division) surrounded by a single layer of flattened follicular cells. Primary follicles (choice C), the next stage, are slightly larger and contain a central oocyte surrounded by one or several cuboidal follicular cells. When several small spaces in the follicular mass fuse to form the antrum (follicular cavity), the follicle is termed a secondary follicle (choice E). The secondary follicles continue to enlarge, and develop a more complex structure that includes cumulus oophorus, corona radiata, theca interna, theca externa, and zona pellucida. The Graafian follicle (choice B) is the mature form of the follicle, which extends through the

entire cortex and bulges out at the ovarian surface. After it ruptures and releases the ovum, the corpus luteum (choice A)develops as the cells of the follicle and the theca interna cells enlarge, become epithelioid, and secrete estrogen. The granulosa lutein cells contain yellow pigment and secrete progesterone. If pregnancy does not occur, the corpus luteum eventually degenerates; if pregnancy occurs, it is maintained throughout the pregnancy. 13. The correct answer is B. The findings suggest disseminated intravascular coagulation (DIC), which is a feared complication of many other disorders, such as obstetrical catastrophes, metastatic cancer, massive trauma, and bacterial sepsis. The basic defect in DIC is a coagulopathy characterized by bleeding from mucosal surfaces, thrombocytopenia, prolonged PT and PTT, decreased fibrinogen level, and elevated fibrin split products. Helmet cells and schistocytes (fragmented red blood cells) are seen on peripheral blood smear. Autoimmune hemolysis (choice A) and hereditary spherocytosis (choice C) would be characterized by spherocytes in the peripheral smear. Macro-ovalocytes and hypersegmented neutrophils can be seen in megaloblastic anemia (choice D). Sickle cells are seen in sickle cell anemia (choice E). 15. The correct answer is D. The disease is Down syndrome (trisomy 21). In addition to mental retardation and the characteristic physical findings described in the question stem, duodenal atresia is fairly common, as evidenced by the "double bubble" sign on x-ray. These children are also likely to have various cardiac anomalies; endocardial cushion defect is the most common. Atrial septal defect (choice A) is one of the most common genetic defects in the general population, but is less common than endocardial cushion defect in patients with Down syndrome. Berry aneurysms (choice B), also known as saccular aneurysms, are typically located in the circle of Willis on the ventral surface of the brain. They occur more frequently in patients with adult polycystic disease. Rupture can produce subarachnoid hemorrhage. Coarctation of the aorta (choice C) occurs more commonly in females with a 45, XO genotype (Turner syndrome). Tetralogy of Fallot (choice E) is the most common cause of early cyanosis, consisting of a ventricular septal defect, right ventricular outflow tract obstruction, an overriding aorta, and right ventricular hypertrophy. 16.The correct answer is A. The obturator nerve innervates the muscles of the medial compartment of the thigh. These include the adductor longus, adductor brevis, adductor magnus, and gracilis muscles. The adductor magnus is also innervated by the tibial nerve. The biceps femoris (choice B) is in the posterior compartment of the thigh. The long head of the biceps femoris is innervated by the tibial portion of the sciatic nerve, and the short head of the biceps femoris is innervated by the common peroneal portion of the sciatic nerve 17>The

correct answer is E. Beta-adrenergic blockade may blunt or prevent the premonitory signs and symptoms (e.g., tachycardia, blood pressure changes) of acute episodes of hypoglycemia. Non-selective beta-blockers, such as propranolol, may even potentiate insulin-induced hypoglycemia. Even though this effect is less likely with cardioselective agents, the use of either cardioselective or non-selective beta-blockers in diabetics is not recommended due to their "masking" effect of the normal warning signs and symptoms of hypoglycemia. None of the drugs listed in the othe r choices will blunt the premonitory signs and symptoms of hypoglycemia. Captopril (choice A) is an angiotensin-converting enzyme (ACE) inhibito r that can be safely used for the treatment of hypertension in diabetic patients. Diltiazem (choice B) is a calcium channel blocker that is also considered to be safe and effective for the treatment of hypertension in diabetic patients.

Both methyldopa (choice C), a centrally acting alpha-adrenergic agonist , and prazosin (choice D), an alpha1-adrenergic antagonist, can be safely used to treat hypertension in diabetic patients. However, due to the side effect profile of these medications, they are generally used only in diabetic patients who are unresponsive to ACE inhibitors and calcium channel blockers. 18>The correct answer is A. Fibrinogen is cleaved by thrombin twice as it is activated to form fibrin. The initial cleavage causes it to polymerize and the second causes it to branch. Thrombin also activates Factor XIII to XIIIa, which crosslinks the fibrin strands and strengthens the clot. HMWK (choice B) is a cofactor in the intrinsic pathway that converts Factor XI to XIa. Plasminogen (choice C) is a central proenzyme in clot lysis. When plasminogen is converted to plasmin, it digests fibrin threads, as well as a number of protein factors including Factors V, VIII, XII, and prothrombin. Thrombin (choice D) is an enzyme derived from prothrombin. It converts fibrinogen to fibrin, and activates factor XIII. vWF (choice E) is a tissue-bound protein which is exposed with vascular trauma and helps in the process of platelet adhesion. 19>The correct answer is B. The diagnosis of chronic bronchitis requires the presence of chronic productive cough over at least 3 months of the year for 2 successive years. The symptoms in this patient (green productive sputum, fever) suggest that he has an acute infection superimposed on chronic bronchitis (history of cigarette smoking, history of excessive mucus production over many years). Histologically, the mucus-producing glands in the bronchi would show hyperplasia and hypertrophy and extend to a greater depth in the bronchial wall, resulting in a higher Reid index (ratio of thickness of mucus gland to thickness of bronchial wall).

20>The correct answer is A. Most of the venous drainage of the skin of the lower extremity is to the long saphenous vein, the accompanying lymphatics of which drain into the superficial group of the inguinal lymph nodes. However, the skin drained by the short saphenous vein, including that of the lateral aspect of the dorsum of the foot, is an exception to this rule. Lymphatic fluid from this area drains into lymphatics accompanying the short saphenous vein, then drains into lymph nodes behind the knee in the popliteal fossa. The lateral side of the thigh (choice B), the medial side of the leg below the knee (choice C), the medial side of the sole of the foot (choice D), and the medial side of the thigh (choice E) all drain to the superficial inguinal nodes. 21>The correct answer is C. The corpus luteum secretes estrogens, progesterone, and relaxin. hCG, secreted by the syncytiotrophoblast lining the placental villi, maintains the corpus luteum during the first trimester of pregnancy. Antidiuretic hormone (vasopressin; choice A) does not play a significant role during pregnancy. FSH (choice B) acts on granulosa cells to promote the conversion of androstenedione to

estradiol. LH (choice D) acts on theca cells to promote androstenedione secretion. Progesterone (choice E) is important for maintaining the pregnancy, however, it does not act to maintain the corpus luteum. 22>The correct answer is E. A femoral hernia exits the abdominal cavity through the femoral ring to enter the femoral canal. The femoral ring is bounded medially by the lacunar ligament. Compression of the herniated intestine against the sharp edge of the lacunar ligament may cause strangulation of the intestine. The other borders of the inguinal ring are the inguinal ligament anteriorly, the pubis posteriorly, and the femoral vein laterally. The femoral artery (choice A) is within the femoral sheath along with the femoral hernia, but is lateral to the femoral vein, which separates the artery from the hernia. The femoral nerve (choice B) is not inside of the femoral sheath, but is lateral to the sheath. The femoral vein (choice C) is lateral to the femoral canal within the femoral sheath. The inferior epigastric artery (choice D) is not related to a femoral hernia. This artery is on the anterior abdominal wall and passes immediately medial to the deep inguinal ring. Indirect inguinal hernias pass lateral to this artery and direct inguinal hernias pass medial to this artery

23>The correct answer is D. While not of major medical concern, urine color changes as a result of medications can be very distressing to patients. These changes are consequently worth learning so that you can warn patients when you prescribe the medicine. Rifampin is a safe drug that is used both for prophylaxis and for active tuberculosis therapy. In addition to discoloring urine, rifampin and its metabolites can discolor feces, saliva, sweat, and tears (and apparently can stain soft contact lenses). Ethambutol (choice A) is an antituberculosis agent that is added if isoniazid-resistance is suspected and does not alter urine color. Isoniazid (choice B) remains the principle antituberculosis agent and does not alter urine color. Pyridoxine (choice C) is used principally in prophylaxis against tuberculosis and does not alter urine color. Streptomycin (choice E), which must be given intramuscularly, is sometimes used as an adjunctive agent very early in antituberculosis therapy and has sometimes been lifesaving in critically ill patients. It does not cause a urine color change. 24>The correct answer is C. Laryngeal cartilages (e.g., the thyroid, cricoid, arytenoid cartilages) are derived from neural crest. The endothelial cells (choice A) in the simple squamous epithelium that lines the pulmonary capillaries are derived from visceral mesoderm. The epithelial lining of primary bronchi (choice B) is derived from endoderm. Tracheal glands (choice D) and epithelium both derive from endoderm. Type I pneumocytes (choice E) are derived from endoderm. 25>The correct answer is B. The principle host defense in mycobacterial infections (such as this patient's tuberculosis) is cell-mediated immunity, which causes formation of granulomas.

Unfortunately, in tuberculosis and in many other infectious diseases characterized by granuloma formation, the organisms may persist intracellularly for years in the granulomas, only to be a source of activation of the infection up to decades later. While antibody-mediated phagocytosis (choice A) is a major host defense against many bacteria, it is not the principle defense against Mycobacteria. IgA-mediated hypersensitivity (choice C) is not involved in the body's defense against Mycobacteria. IgE-mediated hypersensitivity (choice D) is not involved in the body's defense against Mycobacteria. It is important in allergic reactions. Neutrophil ingestion of bacteria (choice E) is a major host defense against bacteria, but is not the principle defense against Mycobacteria.

26>The correct answer is E. This is the classic presentation of a psoas abscess. This clinical entity was formerly a fairly common complication of vertebral tuberculosis, but is now rare in clinical practice in this country. The psoas muscle is covered by a fibrous sheath known as the psoas fascia. This sheath is open superiorly, permitting an infection involving the soft tissues around the spine to enter the sheath, then track down to the groin. The adductor longus (choice A) is a muscle of the anterior thigh, and is not related to the lumbar portion of the back. The gluteus maximus (choice B) gluteus minimus (choice C) and piriformis (choice D) are muscles of the buttock with no relationship to the groin. 27>The correct answer is B. Streptococcus bovis is a Group D streptococcus. There is a significant association between S. bovis bacteremia and endocarditis with carcinoma of the colon and other colonic diseases. Every patient with S. bovis bacteremia should undergo gastrointestinal and cardiac evaluation. Up to 50% of patients with S. bovis bacteremia are reported to have underlying colonic malignancies. In another study, 25-50% of cases of S. bovis bacteremia were associated with endocarditis, especially in patients with preexisting valvular lesions. Streptococcus agalactiae (choice A) is an important cause of maternal and neonatal bacteremia and neonatal meningitis. It is part of the normal flora of the gastrointestinal tract and the female genital tract. Streptococcus pneumoniae (choice C) is a leading cause of community-acquired pneumonia, meningitis in adults, otitis media (especially in children), and sinusitis. Spontaneous peritonitis due to S. pneumoniae is reported in children with ascites from nephrotic syndrome. Asplenia predisposes patients to severe infections with S. pneumoniae and other encapsulated organisms. S. pneumoniae infections are also more frequent and unusually severe in patients with sickle cell anemia, multiple myeloma, alcoholism, and hypogammaglobulinemia. S. pneumoniae is now the leading cause of invasive bacterial respiratory disease in patients with AIDS. Streptococcus pyogenes (choice D) is the most common cause of bacterial pharyngitis. Complications include paratonsillar abscesses, otitis media, and sinusitis. Long-term sequelae include rheumatic fever and poststreptococcal glomerulonephritis. S. pyogenes is also responsible for many skin and soft tissue infections. The organism also produces many toxins that produce a variety of diseases.

Streptococcus viridans (choice E), or the viridans Streptococci, are the most common cause of subacute bacterial endocarditis, which should be suspected in cases of viridans streptococcal bacteremia. One species of viridans Streptococci, Streptococcus milleri, is frequently associated with pyogenic abscesses, especially of the liver.

28. The answer is b. Cells of the inner cell mass (embryoblast) of the blastocyst differentiate into the epiblast and hypoblast. Cells of the epiblast migrate toward the primitive streak during the second week and become internalized, forming the mesodermal and endodermal germ layers. Remaining cells of the epiblast become the ectodermal germ layer. Cells of the hypoblast (answer d) will contribute to the yolk sac. Cells of the outer cell mass of the blastocyst will differentiate into the cytotrophoblast and syncytiotrophoblast (answers a and c), which will contribute to formation of the placenta. The yolk sac (answer e) is incorporated into the embryo as the primitive gut during embryonic folding.

29. The answer is b. Blood from the placenta in the umbilical cord is about 80% oxygenated. Mixture with unoxygenated blood from the vitelline veins and the Inferior vena cava reduces the oxygen content somewhat. However, this stream with relatively high oxygen content is directed by the valve of the inferior vena cava directly through the foramen ovale into the left atrium. This prevents admixture with oxygen-depleted blood entering the right atrium from the superior vena cava. Thus, the oxygen-saturated blood entering the left ventricle and pumped into the aortic arch, subclavian arteries, and common carotid arteries has the highest oxygen content. 30> The answer is b. A mutation resulting in loss of integrin function would prevent leukocytes from extravasting from the blood to the lymph nodes (see figure below) and sites of inflammation resulting in increased lymphocytes in the blood (leukocytosis), not leucopenia 31> The answer is c. Vasa vasorum (VV) are vessels within a vessel and are found primarily in the adventitia of large arteries and veins. They provide nutrition and oxygenated blood to the thick media and adventitia of these vessels, which are unable to obtain nutrition by diffusion from the lumen. Coronary arteries fulfill a similar function for the myocardium.

32. The answer is a. The iliac crest is the best location for bone marrow sampling. The sternum is not as safe a place for bone marrow aspiration and biopsy because of possible damage to thoracic structures (answer b). The patient in the vignette suffers from chronic lymphocytic leukemia CLL more common in adults over 60 years old. Hematopoiesis occurs in the flat bones (answer c) and other bones in the adult human. Although most bones in the body are involved in hematopoiesis during growth, the marrow of the sternum, ribs, vertebrae, iliac crest, skull, and proximal femora are the primary sites of blood cell development by the time that skeletal maturity is achieved. It also occurs in the long bones (answers d, and e) during development, but many of those areas become dominated by yellow marrow that contains many fat cells (adipose tissue). The inactive yellow marrow can be reactivated

on exposure to the proper stimulus (e.g., severe blood loss). 33. The answer is c. The alveolar macrophage (containing hemosiderin) has been called the congestive heart failure cell. The presence of large numbers of these cells, containing hemosiderin granules, is an indicator of edematous lung changes. During congestive heart failure, edema results in leakage of erythrocytes into the alveoli. Transferrin and hemoglobin are also present in the edematous fluid released from the capillaries. These two products are phagocytosed by alveolar macrophages, which convert those products to hemosiderin

34. The answer is a. The cause of cell injury and death may sometimes be inferred from the type of necrosis present. Coagulative necrosis, characterized by loss of the cell nucleus, acidophilic change of the cytoplasm, and preservation of the outline of the cell, is seen in sudden, severe ischemia of many organs. It is not present, however, in acute ischemic necrosis of the brain. Myocardial infarction resulting from the sudden occlusion of the coronary artery is a classic example of coagulative necrosis. In contrast, with liquefactive necrosis the dead cells are completely dissolved by hydrolytic enzymes. This type of necrosis can be seen in ischemic necrosis of the brain, but classically it is associated with acute bacterial infections. Fat necrosis, seen with acute pancreatic necrosis, is fat cell death caused by lipases. Fibrinoid necrosis is an abnormality seen sometimes in injured blood vessels where plasma proteins abnormally accumulate within the vessel walls. Caseous necrosis is a combination of coagulative and liquefactive necrosis, but the necrotic cells are not totally dissolved and remain as amorphic, coarsely granular, eosinophilic debris. This type of necrosis grossly has the appearance of clumped cheese. It is classically seen in tuberculous infections. Gangrenous necrosis of extremities is also a combination of coagulative and liquefactive necrosis. In dry gangrene the coagulative pattern is predominate, while in wet gangrene the liquefactive pattern is predominate.

3 5. The answer is e. Products of arachidonic acid (AA) metabolism are involved extensively in inflammation. In this pathway, arachidonic acid is broken down into leukotrienes (vasoconstrictors) and prostaglandins (vasodilators). Arachidonic acid is a polyunsaturated fatty acid that is normally found esterified in plasma membrane phospholipids. It is released by the activation of phospholipases, such as phospholipase A . Cyclooxygenase transforms AA into the prostaglandin endoperoxide PGG
2 2

, which is then converted into PGH and subsequently into three products: thromboxane A
2

(TxA
2 2

), prostacyclin (PGI ), and the

more stable prostaglandins PGE

2

, PGF2 , and PGD . Thromboxane, found in platelets, is a potent platelet aggregator and blood vessel constrictor.

37 The answer is d Most cases of lobar pneumonia Are caused by S. pneumoniae (reclassification of the pneumococcus). Streptococcal or pneumococcal pneumonia involves one or more lobes and is often seen in alcoholics or debilitated persons. Type 3 pneumococcus ( S. pneumoniae) causes a virulent lobar pneumonia characterized by mucoid sputum, which is also seen in K. pneumoniae. K. pneumoniae (Friedlnders bacillus) usually produces a bronchopneumonia, rather than lobar pneumonia, but this is clinically indistinguishable from pneumococcal lobar pneumonia. Legionella species cause a fibrinopurulent lobular pneumonia that tends to be confluent, almost appearing lobar.

38. The answer is d. Tuberculosis (TB) is caused by infection with M. tuberculosis. Mycobacteriaceae are slow-growing aerobic rods with cell walls rich in glycolipids, true waxes, and long-chain fatty acids called mycolic acids. The lipid-rich mycolic acidcontaining cell wall is responsible for the unique staining properties of the mycobacteria, namely their impermeability to most basic dyes and their resistance to acid decolorization (acid-fast staining). Infection with M. tuberculosis occurs either as a primary infection or a secondary reactivation or reinfection 39. The answer is b. A disorder in newborns that is histologically identical to ARDS is called neonatal respiratory distress syndrome [hyaline membrane disease (HMD)]. HMD, which accounts for 20% of all deaths in the first 28 days of life, is basically a disease of premature infants; most affected infants weigh 1000 to 1500 g. Contributing factors in the development of HMD include diabetes in the mother (maternal diabetes with increased glucose causes increased fetal secretion of insulin, which inhibits the effects of steroids such as lung maturation and production of surfactant) and cesarean section. Infants who develop HMD appear normal at birth, but within minutes to hours their respirations become labored. Grossly the lungs are a mottled, red-purple color, while microscopically

there are hyaline membranes in air spaces, similar to those of ARDS. Two defects have been identified in infants with HMD. One is a deficiency of pulmonary surfactant. Surfactant, a lipid consisting of dipalmitoyl phosphatidylcholine, reduces the surface tension in air-fluid interfaces by getting between the molecules in the liquid and reducing their attraction to each other. This reduces the tendency for the alveoli to collapse after birth on expiration. Synthesis of surfactant increases throughout fetal development, but becomes maximal at 34 to 36 weeks. With a deficiency of surfactant, the lungs tend to collapse on expiration (atelectasis) and become stiff. The other defect is increased pulmonary epithelial permeability. 40. The answer is b. Lipids are transported in the blood complexed to proteins called apolipoproteins. Abnormalities of this lipid transport or metabolism result in hyperlipoproteinemias, which are responsible for most syndromes of premature atherosclerosis. The primary hyperlipidemias are divided into five distinct electrophoretic patterns. Type I hyperlipoproteinemia, caused by a mutation in the lipoprotein lipase gene, results in increased chylomicrons and triglycerides. Type II hyperlipoproteinemia, perhaps the most frequent

Mendelian disorder, is caused by a mutation in the low-density lipoprotein (LDL) receptor gene. This results in increased LDL and cholesterol 41. The answer is e. Antineutrophil cytoplasmic antibodies (ANCAs) may be found in patients with certain inflammatory vascular diseases or glomerular diseases, and their presence is of clinical importance for diagnosing these diseases. Immunofluorescence reveals ANCAs to have two dif- ferent patterns. One is directed toward myeloperoxidase of neutrophils and is found in a perinuclear location (P-ANCAs). This pattern is seen in patients with microscopic polyarteritis nodosa (PAN) or idiopathic crescentic glomerulonephritis without systemic disease. Microscopic polyarteritis commonly involves glomerular and pulmonary capillaries and may produce hematuria, hemoptysis, and renal failure. Histologic sections reveal segmental fibrinoid necrosis. The other ANCA pattern reveals the antibodies to be directed against neutral leukocyte protease (proteinase 3) and results in a cytoplasmic staining pattern (C-ANCAs). This pattern is seen in patients with Wegeners granulomatosis or Churg-Strauss syndrome.

42. The answer is e There are many causes of congestive heart failure, but basically the heart will fail if it is forced to work in an abnormal state for a prolonged period of time. These abnormal states can cause systolic dysfunction or diastolic dysfunction. Systolic dysfunction may result from increased preload, increased afterload, or decreased contractility. Causes of increased preload (volume overload) include regurgitation (mitral regurgitation and aortic regurgitation), anemia, hyperthyroidism, and beriberi. 43. The answer is d. The normal mitral valve (MV) is a bicuspid valve with the anterior cusp approximately twice the area of the posterior cusp. The MV area is normally 5 to 6 cm
2

. Clinically significant mitral stenosis (MS) usually results when the valve area decreases to less than 1 cm
2

. MS most commonly develops as a consequence of rheumatic heart disease. It may also develop due to congenital abnormalities or calcium deposition. In patients with mitral stenosis there is decreased flow across the MV due to the stenosis of the valve. In order to move the blood into the left ventricle (LV), the left atrial (LA) pressure during diastole is greater than normal and greater than the LV pressure. Instead of producing changes in the LV, mitral stenosis causes the left atrium to hypertrophy and

dilate. These changes predispose patients with MS to arrhythmias (which are felt as palpitations) and to the development of LA thrombi (which may lead to systemic emboli). The hypertrophied left atrium may also compress the esophagus (resulting in dysphagia, or problems swallowing food) or irritate the recurrent laryngeal nerve (producing hoarseness). The increased LA pressure also causes a middiastolic murmur and can be reflected back into the lungs and to the right ventricle. In the lungs this produces venous congestion and hemorrhage, which cause dyspnea, fatigue, and hemoptysis..

THE END .