Módulo 7 Med. Interna Flashcards

Question

A 50-year-old woman is admitted for urinary tract infection, complicated by profound weakness, abdominal pain, vomiting, and diarrhea. Her temperature is 40.0 C (104 F), blood pressure is 90/60 mm Hg, pulse is 110/min, and respirations are 18/min. Examination reveals signs of dehydration and skin hyperpigmentation over the elbows and knees. Urinalysis shows pyuria. Laboratory studies show hyponatremia, hyperkalemia, and hypoglycemia. Complete blood count is remarkable for eosinophilia. While waiting for the results of urine and blood cultures, intravenous corticosteroids, broad-spectrum antibiotics, and volume replacement therapy is instituted. In addition to such treatment, which of the following is the most appropriate next step? (A) Cortisol level (B) Cosyntropin stimulation test (C) IV mineralocorticoids (D) Oral corticosteroids (E) Renal ultrasonography

Answer 1

**Respuesta: A** The correct **answer is A.** This patient probably has acute adrenal insufficiency, or adrenal crisis. Measurement of serum cortisol will verify the likely diagnosis (cortisol levels would normally be increased following the stress of surgery). Adrenal insufficiency occurs in patients with latent Addison disease who have stress due to events such as surgery, infections, or severe trauma. Other common situations that may precipitate an adrenal crisis include bilateral adrenalectomy, removal of a cortical adenoma that has suppressed the normal gland, and abrupt cessation of exogenous corticosteroid therapy. Withdrawal of corticosteroid treatment should be carried out by gradually tapering the doses. Acute adrenal insufficiency is characterized by signs and symptoms similar to Addison disease, but manifesting with dramatic severity. Indeed, this is a life-threatening condition requiring emergency administration of IV hydrocortisone (100-300 mg), lest the patient develop irreversible shock. Naturally, fluid infusion should be concomitantly administered, and treatment of the underlying cause (in this case, infection) carried out. The cosyntropin stimulation test (**choice B**) is used to confirm a diagnosis. However, when the clinical picture is so severe, as in this example, hydrocortisone treatment takes precedence over diagnostic confirmation. IV mineralocorticoids (**choice C**) are not necessary when such large doses of hydrocortisone are administered, as glucocorticoids also have mineralocorticoid activity. Oral corticosteroids (**choice D**) would not be appropriate in a medical emergency such as adrenal crisis. They are used once the patient’s condition has stabilized. Further, patients in adrenal crisis most often are unable to take anything by mouth because of nausea and vomiting. Renal ultrasonography (**choice E**) is used to study the kidney and collecting system to screen for such conditions as hydronephrosis and renal masses. It would be hardly justifiable in the present case.

Answer 2

**Respuesta: A** The correct **answer is A**. This patient is exhibiting the signs of Horner syndrome, resulting from damage to the cervical sympathetic plexus that contains presynaptic fibers to the superior cervical ganglion. This results in deficient sympathetic innervation to the iris and the tarsal muscles of the eye, as well as to the sweat glands and vessels in the ipsilateral face. This deficit leads to miosis and ptosis in the ipsilateral eye, and anhidrosis and redness of the ipsilateral hemiface. The most common cause of this syndrome is pulmonary cancer of the apex, which may spread to the sympathetic plexus by contiguity. A patient presenting with Horner syndrome, especially if a smoker, should undergo radiologic investigations to exclude a lung tumor. Laboratory testing for syphilis (**choice B**) would be appropriate in the presence of other neurologic signs of syphilitic involvement of the nervous system, such as impaired proprioception and vibration sense. Argyll-Robertson pupil is a manifestation of tabes dorsalis. The pupils are small and poorly reactive to light but normally reactive to accommodation. There is no indication that any type of intracranial pathology is responsible for the ocular changes seen in this case; thus, MRI scan of the head (**choice C**) would not be a useful diagnostic method. Ophthalmologic referral (**choice D**) would certainly be appropriate for more complex symptomatology, but classic Horner syndrome is an easy diagnosis, which should, without delay, prompt a search for the underlying cause. Tonometric measurement (**choice E**) is appropriate in the presence of signs suggesting narrow-angle (acute) glaucoma, including severe unilateral eye pain, redness, a dilated and fixed pupil, and blurring of vision.

Answer 3

**Respuesta: C** The correct **answer is C**. Although cirrhosis usually comes to mind first when you think of ascites, you should remember that ascites can have a variety of causes, both hepatic and nonhepatic. Hepatic causes include cirrhosis (especially alcoholic), chronic hepatitis, severe alcoholic hepatitis without cirrhosis, and BuddChiari syndrome (hepatic vein obstruction). Nonhepatic causes include generalized fluid retention (heart disease, nephrotic syndrome, severe hypoalbuminemia, renal failure), intraabdominal disease (cancer or tuberculosis involving the peritoneum; rarely pancreatitis), and, rarely, hypothyroidism. A useful rule of thumb is that ascites isolated from or disproportionate to peripheral edema is usually due to liver or intra-abdominal disease, whereas systemic diseases such as congestive heart failure tend to produce both peripheral edema and ascites. The clinical findings illustrated in the question stem are typical of congestive heart failure. Alcoholic cirrhosis (**choice A**) is the most common form of cirrhosis, but it is not usually accompanied by severe peripheral edema. Chronic hepatitis B infection (**choice B**), even in the absence of cirrhosis, can cause ascites, but it is not usually accompanied by severe peripheral edema. Intra-abdominal cancers (**choice D**) that have spread to the peritoneum can cause an ascites that is usually not accompanied by severe peripheral edema. Hypothyroidism (**choice E**) is a rare cause of significant ascites that is usually accompanied by other stigmata of hypothyroidism, such as coarse hair and facial puffiness with periorbital edema and eyelid droop.

Answer 4

**Respuesta: B** The correct **answer is B**. The clinical picture is consistent with mesothelioma, a cancer of mesothelial origin that manifests as a diffuse plaque-like thickening of the pleura. Peritoneal mesotheliomas are much more uncommon. Most mesotheliomas coming to clinical attention nowadays result from prior occupational exposure to asbestos, which was associated with shipyard work, insulation, brake lining, building and roof work, and mining, among others. Inhalation of asbestos fibers is also a risk factor for other cancers, including bronchogenic, laryngeal, and colon carcinoma. The main differential diagnosis is with bronchogenic carcinoma, which may spread to the pleura but is usually accompanied by one or more intrapulmonary nodules. Cigarette smoking (**choice A**) does not seem to predispose to the development of mesotheliomas. However, it does increase the risk of bronchogenic carcinoma in persons exposed to asbestos. Occupational exposures to coal (**choice C**) and silica (**choice D**) are associated with coal-worker pneumoconiosis and silicosis, respectively, but not mesotheliomas. Prior radiation injury (**choice E**) to the lungs may be followed by two conditions: acute radiation pneumonitis (occurring 2-3 months after radiation) and interstitial fibrosis (manifesting 6-12 months after exposure). Radiation is not a predisposing factor for either bronchogenic carcinoma or mesothelioma.

Answer 5

**Respuesta: A** The correct **answer is A**. An increased platelet count is more formally called thrombocythemia. Thrombocythemia can occur in primary form (essential thrombocythemia), as part of other myeloproliferative disorders (e.g., polycythemia vera, chronic myelogenous leukemia, and idiopathic myelofibrosis), or secondary to other processes such as acute infection, chronic inflammatory disorders (rheumatoid arthritis, inflammatory bowel disease, tuberculosis, sarcoidosis, Wegener granulomatosis), hemorrhage, iron deficiency, or tumors (cancers and lymphomas). Essential thrombocythemia is a clonal abnormality of a hemopoietic stem cell that is seen most often in patients between 50 and 70 years of age. The platelet count may reach 1,000,000/μL or higher, but may also be in a more ambiguous range down to about 500,000/μL. Helpful clinical clues on the peripheral smear are platelet aggregates, giant platelets, and megakaryocyte fragments. Increased bone marrow fibrosis (**choice B**) and tear-drop shaped RBCs (**choice E**) are features of idiopathic myelofibrosis, which can also have elevated platelet counts. Increased RBC mass (**choice C**) is a feature of polycythemia vera, which can also show elevated platelet counts. The Philadelphia chromosome (**choice D**) is a feature of chronic myelogenous leukemia, which can also show elevated platelet counts.

Answer 6

**Respuesta: C** The correct **answer is C**. This patient manifests signs and symptoms of fulminant hepatic failure. Infectious hepatitis due to hepatitis B virus (HBV) is responsible for half the cases of fulminant hepatitis in the U.S. Fulminant hepatic failure carries a 60% mortality rate. Drugs are the most frequent nonviral causes of fulminant hepatic failure. Acetaminophen produces liver injury in a dose-dependent fashion. Acute acetaminophen overdose usually manifests with doses higher than 7 g in adults, but concomitant alcohol abuse lowers the threshold of hepatic toxicity. Patients with chronic alcohol abuse may develop acute diffuse liver necrosis (the pathologic substrate of fulminant hepatic failure) after taking as little as 4 g acetaminophen within a 24-h period. The synergistic effect between alcohol and acetaminophen is mediated by the activating action of alcohol on cytochrome P-450, which converts acetaminophen into a highly toxic intermediate. This intermediate depletes hepatic glutathione stores, resulting in increasing concentration of free radicals and consequent cellular toxicity. Acetaminophen alone (**choice A**) is also capable of producing significant hepatotoxicity, especially in children. The patient’s history suggests, however, that alcohol played a contributing role. Alcohol alone (**choice B**) is also a hepatotoxic drug and in large amounts may cause acute alcoholic hepatitis. However, fulminant hepatic failure exclusively related to alcohol toxicity is exceedingly rare. Diazepam alone (**choice D**) does not explain the clinical and laboratory signs of hepatic failure. Diazepam overdose results in prolonged sedation, which usually resolves with supportive measures. Respiratory depression is the most significant and potentially life-threatening consequence. This is particularly likely when diazepam (or similar benzodiazepine) is ingested in association with alcohol (**choice E**).

Answer 7

**Respuesta: E** The correct **answer is E**. Genetic screening for MEN type II is available to persons with a family history of this condition. Mutations of the RET proto-oncogene make these patients more likely to develop all the endocrine conditions associated with MEN type IIa, including pheochromocytoma, parathyroid hyperplasia/adenoma, and medullary carcinoma of the thyroid. Medullary carcinoma of the thyroid is an aggressive cancer arising from calcitonin producing cells (C cells) in the thyroid. Although penetrance of this autosomal dominant genetic mutation is incomplete, the risk of developing medullary carcinoma warrants prophylactic thyroidectomy. Recall that MEN IIb is similar to MEN IIa, except for the additional presence of mucosal neuromas and a Marfan-like body habitus. If persons with family history of MEN type II decline genetic testing, they may be offered the possibility of screening for early medullary carcinoma by calcitonin measurements (**choice A**) following pentagastrin stimulation. Peaks greater than 190 pg/mL in males or 80 pg/mL in females are consistent with medullary carcinoma. Periodic screening with imaging studies (**choice B**) is not a valuable option to detect early medullary carcinoma, since an early lesion may be too small to be seen on CT or MRI scans. Periodic screening for latent pheochromocytoma (**choice C**) is not cost-effective, since pheochromocytomas develop less frequently than medullary carcinomas and are usually benign. However, screening for latent pheochromocytoma (urinary catecholamine levels) should be carried out before performing any major surgical procedure to avoid a hypertensive crisis. Prophylactic parathyroidectomy (**choice D**) is not indicated. Hyperplasia or adenoma of the parathyroids may lead to hyperparathyroidism, in which case parathyroidectomy may be performed.

Answer 8

**Respuesta: A** The correct **answer is A**. This is a classic presentation of achalasia, which is an esophageal disorder characterized by impaired esophageal peristalsis and impaired relaxation of the lower esophageal sphincter. It is thought to be due to malfunction of the esophageal myenteric plexus. Achalasia can occur at any age, but most frequently presents in the 3rd or 4th decade. Achalasia can be complicated by (usually nocturnal) pulmonary aspiration of regurgitated food, life-threatening esophageal rupture, and a questionably increased incidence of esophageal cancer. Treatment of achalasia is by forceful dilation of the lower esophageal sphincter. Sublingual nitroglycerin before meals and calcium channel blockers are sometimes used to prolong the times between lower esophageal forced dilation. More aggressive therapies, such as injection of botulinum toxin in the lower esophageal sphincter or myotomy of the lower esophageal sphincter, are reserved for patients who do not respond to other therapies. Esophageal cancer (**choice B**) would produce an area of ulceration or a mass in the esophagus, which would have been picked up on the barium swallow. An esophageal web (**choice C**) is a thin mucosal web that grows across the lumen of the esophagus, typically in the upper esophagus. It would have been detected on the barium studies. A lower esophageal (Schatzki) ring (**choice D**) is a 2 to 4-mm mucosal ring near the squamocolumnar junction that is probably of congenital origin and usually causes only relatively mild difficulty with swallowing of solids. Symptomatic diffuse esophageal spasm (**choice E**) differs from achalasia in that there are strong, but poorly coordinated and ineffective, esophageal contractions, rather than aperistalsis. Over many years, it may evolve into achalasia, but the disorders are clinically considered distinct.

Answer 9

**Respuesta: D** The correct **answer is D.** The patient has both significant nasal disease and significant pulmonary disease. This should suggest the possibility of Wegener granulomatosis (WG), which is a granulomatous inflammation of the upper and/or lower respiratory tract that can also destroy the kidneys. Nasal or pulmonary biopsy confirms the clinically suspected diagnosis by showing granulomas and a perivascular inflammatory infiltrate. If renal damage has occurred, urinalysis typically shows proteinuria, hematuria, and red cell casts. The clinical presentation illustrated is a common variant. Other patients may present with systemic symptoms mimicking cancer (malaise, fever, weight loss, anorexia), migratory polyarthritis, granulomatous skin lesions, or ocular manifestations. WG formerly had a dismal prognosis, but now can be well controlled with immunosuppressive cytotoxic drugs. Abdominal CT scan (**choice A**) would probably not show anything of significance. Liver (**choice C**) or pancreatic (**choice D**) enzymes would not be expected to be altered in this condition. Bladder biopsy (**choice E**) would probably not show anything of significance; however, a renal biopsy might be very helpful.

Answer 10

**Respuesta: A** The correct **answer is A**. Astrocytoma typically presents in the 40- to 60-year age range with headaches, focal neurologic symptoms, and seizures. Headaches from tumors may waken patients from sleep and are worse in the morning, presumably from increased intracranial pressure after being supine over night. Highgrade astrocytomas tend to enhance diffusely on imaging. Brain abscesses (**choice B**) may present with headache and focal findings but typically progress more rapidly. Fever is a prominent component. Imaging shows a ring-enhancing lesion. Cerebral infarcts (**choice C**) rarely cause headaches. The clinical course would not be progressive but would begin acutely and then stabilize. Infarcts may show diffuse enhancement after several weeks. Complicated migraine (**choice D**) refers to migraine headache with a focal but transient neurologic deficit, which may include language difficulty or hemiparesis. Migraine headaches do not typically waken people from sleep. Patients with complicated migraine have an increased risk of stroke, but imaging studies during a complicated migraine are usually normal. Meningiomas (**choice E**) are more common in women and may present with headaches and focal features from mass effect. The course tends to be more chronic, however, and imaging will demonstrate an extra-axial structure compressing the underlying brain.

Answer 11

**Respuesta: B** The correct **answer is B**. This patient seems to have aggressive erosive disease and requires a disease-modifying (slow- acting antirheumatic) drug (DMARD). There are numerous choices, including methotrexate, cyclosporine, minocycline, and anticytokine (tumor necrosis factor) therapies. Anti-inflammatory doses of NSAIDs are also generally required. Short-term use of prednisone may be of use to control inflammation rapidly, but only in conjunction with disease-modifying therapy. Longer-term, low-dose (less than 10 mg) use is common in as many as one fourth of patients seen in hospital-based clinics because of inadequately controlled inflammation. Anti-inflammatory therapy alone can allow progression of erosive joint disease. NSAIDs alone (**choice A**) are inappropriate in this case because of the reasons noted above. Pain relief should occur through control of inflammation, rather than the use of narcotics (**choice C**). The efficacy of narcotics alone in inflammatory arthritic pain is limited. NSAIDs with prednisone (**choice D**) may be very effective for controlling overt symptoms but not for preventing disease progression

Answer 12

**Respuesta: D** The correct **answer is D**. This patient has hepatic encephalopathy (hepatic coma, portal-systemic encephalopathy), a neuropsychiatric syndrome caused by liver disease. It is usually associated with portal-systemic shunting of venous blood, which can cause esophageal varices and dilation of veins near the umbilicus (“caput medusa”). The diagnosis is usually made on clinical, rather than laboratory, grounds, liver function tests correlate poorly. Serum ammonia level is usually elevated, but specific values correlate poorly with clinical status. Therapy is based on removing sources of nitrogen (e.g., protein) in the gut by enema, restriction of dietary protein, and reduction of bacterial load (since some bacteria produce ammonia). Two different strategies are often used for reducing the bacterial load: oral lactulose, which acts as an osmotic cathartic to “wash the bacteria out,” and oral neomycin (a poorly absorbed aminoglycoside), which can be used to kill most of the bacteria while minimizing significant systemic side effects. (Oral neomycin is also sometimes used as part of bowel preparation prior to abdominal surgery.) Other types and routes of administration of antibiotics are not usually used in this setting. In some hospitals, oral neomycin is initially used for bacterial load reduction. Patients are then switched to longer-term lactulose, thereby limiting the potential nephrotoxicity and ototoxicity of the neomycin. Oral ampicillin (**choice A**) is a commonly used antibiotic in outpatient settings. Benzathine penicillin (**choice B**) is an intramuscular, depot form of penicillin that is used most often for syphilis and for month-long prophylaxis against recurrent rheumatic fever. Oral ceftriaxone (**choice C**) is a commonly used third-generation cephalosporin. IV penicillin G (**choice E**) is reserved for treatment of patients with sensitive organisms in a hospital setting.

Answer 13

**Respuesta: B** The correct **answer is B**. The symptoms (particularly xanthopsia/verdopsia = a yellow-green cast to the vision) are characteristic of digitalis toxicity. Bradycardia and different types of arrhythmias are also effects of excess digitalis. The medication should be immediately discontinued in these cases. Acute narrow-angle glaucoma (**choice A**) manifests with unilateral severe eye pain and redness, accompanied by blurred vision and halos around lights. Diuretic-induced hypokalemia (**choice C**) is a potential risk with thiazide and loop diuretics. Intravascular volume depletion, with resultant prerenal azotemia, hyperglycemia, hyperuricemia, and hepatic dysfunction, can also occur. Enalapril overdose (**choice D**) would manifest with hypotension, which is not present in this case. ACE inhibitors have been shown to improve survival and now represent a mainstay in the treatment of congestive heart failure. They decrease ventricular preload by causing venous dilatation and diminishing venous return.

Answer 14

**Respuesta: A** The correct **answer is A**. This is an example of Addison disease, which can occur in all ages and both sexes and is caused by the destruction of the adrenal cortexes due to processes such as autoimmune disease, tuberculosis, infarction, and cancer. Although the symptoms of Addison disease (chronic adrenocortical insufficiency) are very nonspecific and can easily resemble other endocrine disorders (notably hypothyroidism), significant hyperpigmentation can be a helpful diagnostic clue. With the exception of adrenal insufficiency due to pituitary failure, pigmentation is usually increased because of large amounts of ACTH, which has some activity in stimulating melanocytes. Other symptoms and signs of Addison disease that are not mentioned in the question stem include a decreased tolerance to cold, ECG changes (decreased voltage and prolonged PR), EEG changes (generalized slowing of alpha rhythm), and, in later stages, weight loss, dehydration, hypotension, and small heart size. Adrenal crises, characterized by severe abdominal pain and cardiovascular collapse, may complicate septicemia, trauma, and operative procedures. Conn disease (**choice B**) is primary aldosteronism. It is characterized by episodic weakness, paresthesias, transient paralysis, tetany, and diastolic hypertension. Cushing disease (**choice C**) is hypercortisolism due to a pituitary adenoma. It is characterized by rounded facies, buffalo hump, muscle wasting, thin skin, abdominal striae, hypertension, glucose intolerance, and reduced resistance to infection. Graves disease (**choice D**) is an autoimmune cause of hyperthyroidism, with heat intolerance, palpitations, tachycardia, tremor, and ophthalmopathy. Hashimoto disease (**choice E**) is an autoimmune cause of (usually) hypothyroidism, with cold intolerance, rubbery goiter, facial puffiness, and sparse, coarse hair.

Answer 15

**Respuesta: C** The correct **answer is C**. This patient most likely has Hashimoto thyroiditis, which is the most common cause of thyroiditis in the U.S., with a predominance in women. Patients notice a goiter but are initially euthyroid. Needle biopsy will reveal a lymphocytic infiltration, and serum analysis typically shows antibodies directed against thyroglobulin. Fibrosis (**choice A**) is seen in Riedel struma, also known as Riedel fibrosing thyroiditis. This disorder is associated with intense fibrosis of the thyroid, leading to induration of neck tissues. The principal importance of this disorder is that it requires differentiation from thyroid neoplasia. Granulomas (**choice B**) with multinucleate giant cells are seen in subacute granulomatous (de Quervain) thyroiditis. Neutrophils (**choice D**) would be seen in subacute granulomatous (de Quervain) thyroiditis, which usually follows an upper respiratory infection. Symptoms include malaise and pain over the thyroid gland referred to the lower jaw. Patients have a high erythrocyte sediment rate (ESR). Serum T3 and T4 are high and, TSH is undetectable. Parafollicular hyperplasia (**choice E**) is associated with medullary thyroid cancer. Primary thyroid carcinomas may be classified into two varieties, depending on whether the lesions arise from the thyroid follicular epithelium or from the parafollicular, or C, cells. The mainstay of therapy is surgical excision; external radiation and chemotherapy have a palliative role for excision for recurrent or residual disease.

Answer 16

**Respuesta: A** The correct **answer is A**. This patient clearly has an anemia that is long-standing and is not related to her menses, considering that she had a hysterectomy and the anemia persists, plus this patient is of Mediterranean descent. The most likely cause of her anemia is an abnormal hemoglobin, such as thalassemia, because her RDW is less than 15%. Therefore, the most appropriate management option for this patient would be a hemoglobin electrophoresis. Bone marrow biopsy (**choice B**) in patients with microcytic anemia is indicated only if Sideroblastic anemia were suspected; in this patient, the diagnosis of sideroblastic anemia is not considered. Prescribing oral ferrous sulfate (**choice C**) or ordering iron, ferritin, and total iron binding capacity (**choice E**) would be incorrect. If this patient had iron deficiency anemia her RDW would be above 15%. If iron deficiency anemia were suspected, then iron studies would be of diagnostic value. Ordering B12 and folate levels (**choice D**) is not indicated because this is a microcytic anemia; B12 and folate deficiency would produce a macrocytic anemia.

Answer 17

**Respuesta: A** The correct **answer is A**. The most appropriate pharmacologic treatment of hypertension in diabetic patients is an ACE inhibitor, especially if there is concomitant evidence of diabetic glomerulopathy (i.e., microalbuminuria). Studies have shown that ACE inhibitors exert a beneficial effect on diabetic nephropathy by lowering the intraglomerular capillary pressure. Thus, ACE inhibitors are also used to slow the progression of asymptomatic diabetic glomerulonephropathy, even in the absence of systemic hypertension. Most studies have suggested that monotherapy with either a beta blocker (**choice B**) or a thiazide diuretic (**choice E**) is the most appropriate initial treatment for uncomplicated hypertension, i.e., hypertension without detectable end-organ damage. Calcium channel blockers (**choice C**) are frequently used as firstline antihypertensive agents. These drugs are also beneficial in case the patient has asthma, migraine, or urinary incontinence. However, recent studies have suggested an association between use of calcium channel blockers and cardiac complications. Central alpha-agonists, e.g., clonidine (**choice D**), are seldom used as first-line agents for treatment of hypertension because of their undesirable side effects. Methyldopa is frequently used in pregnancy.

Answer 18

**Respuesta: D** The correct **answer is D**. This patient has a sickle cell pain crisis, a condition caused by microvascular occlusive events. The pain is severe and often requires admission for pain control with narcotic level analgesics and rehydration. Acetaminophen (**choice A**) and aspirin (**choice B**) can be adjunct pain medications but are not likely to provide adequate control for a sickle cell pain crisis. Broad-spectrum antibiotics (**choice C**) are inappropriate. Mild infections often can cause a sickle cell crisis. Low-grade fevers, anemia, and leukocytosis are common in a sickle cell crisis and do not indicate sepsis. Plasma exchange (**choice E**) may be used if a sickle cell crisis progresses to multiorgan failure. It is not indicated for an acute pain episode.

Answer 19

**Respuesta: E** The correct **answer is E**. What is illustrated here is a classic example of nephrotic syndrome: abundant urine loss of proteins, which constitutes the first pathophysiologic event in the chain leading to hypoproteinemia; edema due to reduced oncotic pressure; and hyperlipidemia secondary to a compensatory increase in hepatic lipoprotein synthesis. Alterations in plasma proteins often result in an elevated erythrocyte sedimentation rate (ESR). Loss of plasma globulins increases susceptibility to infection. Finally, loss of antithrombin III, protein C, and protein S (circulating anticoagulants) results in predisposition for venous thrombosis. Renal venous thrombosis is particularly dangerous in this setting. Acute pyelonephritis (**choice A**) is not a complication of nephrotic syndrome or any of the diseases associated with it. Infections in the setting of nephrotic syndrome usually involve the respiratory tract and are sustained by gram-positive organisms. Acute renal failure (**choice B**) does not constitute an immediate threat for patients with nephrotic syndrome. Depending on the underlying glomerular disease, progression to chronic renal failure occurs more or less frequently. Hemorrhages (**choice C**) do not frequently occur. Nephrotic syndrome results in abnormal hypercoagulability. Hypertension (**choice D**) is a manifestation of nephritic syndrome, along with hematuria and mild proteinuria (<3 g/day).

Answer 20

**Respuesta: E** The correct **answer is E**. We already know that this woman has Hodgkin lymphoma with disease in her cervical nodes, mediastinum, and bone marrow (stage IV). The standard initial treatment for her is chemotherapy. Surgical excision of affected nodes (**choice A**) is not indicated for Hodgkin lymphoma. The role of the surgeon in this disease is limited to diagnosis. In visceral lymphoma, on the other hand, surgical resection may be part of the overall therapeutic plan. Bone marrow transplant (**choice B**) may be used in selected patients who have failed standard therapy, but it would not be first-line treatment. Radiation therapy (**choice C**) often is used for localized disease. This woman has systemic, advanced disease that is best treated with chemotherapy. In selected cases both modalities may be combined. Staging laparotomy (**choice D**) is a vanishing tool, rarely used nowadays. When radiation therapy was the main modality and CT scans were not readily available, it was important to know if abdominal disease was present to select the best treatment. Although the abdominal CT scan in this case was nondiagnostic, we already have enough information from the chest CT and the bone marrow biopsy to choose chemotherapy. Abdominal exploration is not needed.

Answer 21

**Respuesta: D** The correct **answer is D**. This presentation and past medical history are suggestive of hemolytic anemia due to glucose-6- phosphate dehydrogenase (G6PD) deficiency. This X-linked genetic defect makes erythrocytes vulnerable to oxidative damage, which may be triggered by infections, drugs, or naturally occurring substances. About 1 million people are affected by this disorder throughout the world, with the highest prevalence in some Mediterranean regions (Sardinia, Sicily, Greece, and Turkey) and western Africa. In the U.S., G6PD deficiency affects 10 to 15% of African Americans. The clinical symptomatology is characterized by recurring episodes of acute hemolysis. A more severe Mediterranean variant results in chronic hemolysis with prominent reticulocytosis, as well as classic hemolytic crises. Dark-colored urine is due to severe hemoglobinuria. Severe hemolytic episodes may be life-threatening and require urgent blood transfusion. Anemia of chronic disease (**choice A**) complicates chronic disorders, such as rheumatoid arthritis, collagen vascular diseases, cancer, and liver disease. It is a normocytic and normochromic anemia, usually of mild-to-moderate degree. It results from iron sequestration in the bone marrow. Aplastic anemia (**choice B**) is due to bone marrow suppression. Usually, it is seen in conjunction with neutropenia and thrombocytopenia (pancytopenia). Most cases are idiopathic, but drugs are among the most common identifiable causes. Chronic lymphocytic leukemia (CLL; **choice C**) is an indolent form of leukemia that affects middle-aged and elderly individuals. It is characterized by marked lymphocytosis in the blood and bone marrow, resulting from progressive accumulation of monoclonal (but well-differentiated) B lymphocytes. Anemia and thrombocytopenia eventually manifest as a result of bone marrow replacement. Hairy cell leukemia (**choice E**) is a rare form of leukemia due to neoplastic transformation of a subset of B lymphocytes. The designation derives from the characteristic hair-like cytoplasmic projections of leukemic cells. Pancytopenia and massive splenomegaly are consistently present. Hereditary spherocytosis (**choice F**) is characterized by spherocytes (small round erythrocytes lacking central pallor) and reticulocytosis on peripheral blood smears. Such abnormal spherocytes are prone to lysis. Chronic hemolysis ensues, with secondary splenomegaly. The underlying abnormality is a defect in spectrin, a cytoskeletal protein forming the scaffolding of the erythrocytic membrane. Iron-deficiency anemia (**choice G**) is characterized by small, hypochromic erythrocytes (microcytic and hypochromic anemia) and usually results from chronic blood loss. Megaloblastic anemia (**choice H**) is so designated because of the presence of megaloblasts in the bone marrow. Megaloblasts are abnormally large red blood cell precursors. Their counterparts in peripheral blood are macrocytes, large red blood cells having a mean corpuscular volume of up to 130 fL. Macrocytic (megaloblastic) anemia is due to vitamin B12 or folate deficiency. Microangiopathic anemia (**choice I**) is a form of hemolytic anemia due to “mechanical” causes, usually resulting from the presence of widespread small thrombi in the microcirculation or prosthetic cardiac devices. Fragmentation of red blood cells is the crucial pathophysiologic event, which leads to the appearance of characteristic schistocytes in peripheral blood smears. DIC and thrombotic thrombocytopenic purpura are examples of diseases leading to this form of anemia. Myelodysplastic syndrome (**choice J**) is a heterogeneous set of disorders characterized by abnormal maturation of bone marrow stem cells. Cytopenias (affecting at least two blood cell lines) associated with hypercellular bone marrow are characteristic. Myelodysplastic syndromes affect elderly persons, who may come to medical attention because of chronic fatigue or bleeding diatheses. Some subsets of myelodysplastic syndromes have a propensity to leukemic transformation. Myelofibrosis (**choice K**) is characterized by progressive bone marrow fibrosis and resultant pancytopenia. As the spleen takes over hematopoietic functions, massive splenomegaly develops. Teardrop-like erythrocytes are the most peculiar morphologic abnormalities on peripheral blood smears. Thalassemia (**choice M**) is a group of hereditary disorders due to deficient production of one of the globin chains (either alpha or beta, or both). Microcytosis is prominent. Positive family history is usually present. Alpha-thalassemia is seen most frequently in people from southeast Asia, whereas beta-thalassemia is seen most commonly in Mediterranean people. Both forms are found in African Americans. The clinical manifestations depend on whether the individual is heterozygous or homozygous. In the most severe forms, manifestations appear after 6 months of age, with growth failure, jaundice, hepatosplenomegaly, and bone and facial deformities. In carriers of thalassemia trait, microcytosis is often the only sign.

Answer 22

**Respuesta: L** The correct **answer is L**. Sickle cell anemia results from an autosomal recessive mutation of the beta-globin chain of hemoglobin, resulting in an abnormal form of hemoglobin (HbS). Chronic hemolytic anemia, painful episodes due to vaso-occlusive crises, splenomegaly, chronic ulcers of the legs, and susceptibility to infection by the pneumococci and other bacteria are among its most common manifestations. Hematocrit lower than 30%, sickle-shaped erythrocytes, reticulocytosis, and Howell-Jolly bodies are characteristic hematologic features. Approximately 8% of African Americans are carriers of the HbS gene. The diagnosis rests on electrophoretic demonstration of HbS in peripheral blood. Anemia of chronic disease (**choice A**) complicates chronic disorders, such as rheumatoid arthritis, collagen vascular diseases, cancer, and liver disease. It is a normocytic and normochromic anemia, usually of mild-to-moderate degree. It results from iron sequestration in the bone marrow. Aplastic anemia (**choice B**) is due to bone marrow suppression. Usually, it is seen in conjunction with neutropenia and thrombocytopenia (pancytopenia). Most cases are idiopathic, but drugs are among the most common identifiable causes. Chronic lymphocytic leukemia (CLL; **choice C**) is an indolent form of leukemia that affects middle-aged and elderly individuals. It is characterized by marked lymphocytosis in the blood and bone marrow, resulting from progressive accumulation of monoclonal (but well-differentiated) B lymphocytes. Anemia and thrombocytopenia eventually manifest as a result of bone marrow replacement. Hairy cell leukemia (**choice E**) is a rare form of leukemia due to neoplastic transformation of a subset of B lymphocytes. The designation derives from the characteristic hair-like cytoplasmic projections of leukemic cells. Pancytopenia and massive splenomegaly are consistently present. Hereditary spherocytosis (**choice F**) is characterized by spherocytes (small round erythrocytes lacking central pallor) and reticulocytosis on peripheral blood smears. Such abnormal spherocytes are prone to lysis. Chronic hemolysis ensues, with secondary splenomegaly. The underlying abnormality is a defect in spectrin, a cytoskeletal protein forming the scaffolding of the erythrocytic membrane. Iron-deficiency anemia (**choice G**) is characterized by small, hypochromic erythrocytes (microcytic and hypochromic anemia) and usually results from chronic blood loss. Megaloblastic anemia (**choice H**) is so designated because of the presence of megaloblasts in the bone marrow. Megaloblasts are abnormally large red blood cell precursors. Their counterparts in peripheral blood are macrocytes, large red blood cells having a mean corpuscular volume of up to 130 fL. Macrocytic (megaloblastic) anemia is due to vitamin B12 or folate deficiency. Microangiopathic anemia (**choice I**) is a form of hemolytic anemia due to “mechanical” causes, usually resulting from the presence of widespread small thrombi in the microcirculation or prosthetic cardiac devices. Fragmentation of red blood cells is the crucial pathophysiologic event, which leads to the appearance of characteristic schistocytes in peripheral blood smears. DIC and thrombotic thrombocytopenic purpura are examples of diseases leading to this form of anemia. Myelodysplastic syndrome (**choice J**) is a heterogeneous set of disorders characterized by abnormal maturation of bone marrow stem cells. Cytopenias (affecting at least two blood cell lines) associated with hypercellular bone marrow are characteristic. Myelodysplastic syndromes affect elderly persons, who may come to medical attention because of chronic fatigue or bleeding diatheses. Some subsets of myelodysplastic syndromes have a propensity to leukemic transformation. Myelofibrosis (**choice K**) is characterized by progressive bone marrow fibrosis and resultant pancytopenia. As the spleen takes over hematopoietic functions, massive splenomegaly develops. Teardrop-like erythrocytes are the most peculiar morphologic abnormalities on peripheral blood smears. Thalassemia (**choice M**) is a group of hereditary disorders due to deficient production of one of the globin chains (either alpha or beta, or both). Microcytosis is prominent. Positive family history is usually present. Alpha-thalassemia is seen most frequently in people from southeast Asia, whereas beta-thalassemia is seen most commonly in Mediterranean people. Both forms are found in African Americans. The clinical manifestations depend on whether the individual is heterozygous or homozygous. In the most severe forms, manifestations appear after 6 months of age, with growth failure, jaundice, hepatosplenomegaly, and bone and facial deformities. In carriers of thalassemia trait, microcytosis is often the only sign.

Answer 23

**Respuesta: K** The correct **answer is K**. The type of jaundice manifested by this patient is obstructive, as evidenced by mostly conjugated hyperbilirubinemia, high serum levels of alkaline phosphatase, and clay-colored stools. Concomitant weight loss and deep epigastric pain are highly suggestive of pancreatic malignancy. The presence of a distended gallbladder associated with jaundice, known as Courvoisier sign, is also suggestive of cancer. Infiltration of the pancreas may also lead to insulin deficiency and glucose intolerance (hence, the hyperglycemia detected in this patient). Although relatively rare, this cancer represents the fifth most common cause of cancer-related deaths in the U.S., since it comes to medical attention in advanced, usually inoperable, stages. Acute cholangitis (**choice A**) is usually secondary to a gallstone in the common bile duct. In this case, pain and obstructive jaundice are associated with fever, since enteric bacteria gain access to the biliary system and cause infection (ascending cholangitis). Acute cholecystitis (**choice B**) manifests with the classic picture of biliary colic, characterized by pain in the right hypochondrium radiating to the right shoulder. It is usually related to a small gallstone that becomes impacted in the cystic duct, resulting in blockage of bile outflow and acute distention and inflammation of gallbladder. Acute pancreatitis (**choice C**) is an emergency condition manifesting with extremely severe deep abdominal pain and frequently associated with shock. Elevated amylase and lipase levels in the serum support the diagnosis. Adenoma of the liver (**choice D**) is most commonly asymptomatic and may be discovered incidentally. However, severe intraperitoneal hemorrhage due to rupture may constitute a life-threatening presentation. Use of oral contraceptives and anabolic steroids are predisposing conditions. Alcoholic hepatitis (**choice E**) is similar to any other form of acute hepatitis in its clinical manifestations and laboratory findings. Abdominal pain, nausea, mild jaundice, low-grade fever, and malaise are associated with elevated serum transaminase levels. Amebic liver abscess (**choice F**) presents with right upper quadrant pain and fever. Usually, the patient comes to medical attention after several weeks of symptoms. A recent travel history to tropical countries is often elicited. Liver tests are mildly abnormal. Ultrasonography, CT, or MRI demonstrates the location and size of the lesion. Focal nodular hyperplasia (**choice G**) is a nodular lesion consisting of hepatocytes and a stellate-shaped fibrous stroma (a sort of “focal cirrhosis”). It is usually asymptomatic. It is most commonly associated with chronic alcohol abuse. Gilbert syndrome (**choice H**) is a form of hereditary jaundice due to glucuronyl transferase deficiency. Bilirubin is thus mostly of the indirect (unconjugated) type. The condition is benign and asymptomatic (except for jaundice). Hemochromatosis (**choice I**) is an autosomal recessive hereditary disorder caused by excessive intestinal absorption of iron. Iron deposition results in cirrhosis, cardiomyopathy, pancreatic damage with diabetes, and skin hyperpigmentation (due to melanin overproduction, not iron itself). Hepatocellular carcinoma (**choice J**) is most often associated with cirrhosis in industrialized countries. Its development may be unsuspected until the cirrhotic patient manifests rapid deterioration and weight loss. Primary biliary cirrhosis (**choice L**) is characteristic of middle-aged women and is associated with high titers of circulating antimitochondrial autoantibodies. Primary sclerosing cholangitis (**choice M**) is a rare disorder affecting patients with some underlying disease, most commonly ulcerative colitis. It is due to a chronic inflammatory reaction of probable autoimmune origin, which results in sclerosis and obliteration of the extrahepatic bile ducts. Progressively severe obstructive jaundice is the presenting picture. Rotor syndrome (**choice N**) is another hereditary form of jaundice caused by deficient liver excretion of conjugated bilirubin. Since activity of glucuronyl transferase is normal, most circulating bilirubin is of the direct (conjugated) type. The condition is benign. Viral hepatitis (**choice O**) manifests with an acute syndrome characterized by right upper abdominal pain, nausea, malaise, lowgrade fever, and laboratory signs of hepatocellular necrosis. This picture is shared by all forms of viral hepatitis, but acute infection due to HCV is usually asymptomatic.

Answer 24

**Respuesta: P** The correct **answer is P**. Wilson disease should be suspected in any case of cirrhosis or chronic hepatitis manifesting in children or young adults. The presence of Kayser-Fleischer rings in the cornea is pathognomonic of this condition. Neuropsychiatric manifestations may precede or follow hepatic involvement. Wilson disease is an autosomal recessive disorder caused by mutations of a gene that codes for a copper-transporting protein in the hepatocytes (not ceruloplasmin). The diagnosis is confirmed by low serum ceruloplasmin levels, high urinary copper excretion, and high copper content in liver biopsy. Acute cholangitis (**choice A**) is usually secondary to a gallstone in the common bile duct. In this case, pain and obstructive jaundice are associated with fever, since enteric bacteria gain access to the biliary system and cause infection (ascending cholangitis). Acute cholecystitis (**choice B**) manifests with the classic picture of biliary colic, characterized by pain in the right hypochondrium radiating to the right shoulder. It is usually related to a small gallstone that becomes impacted in the cystic duct, resulting in blockage of bile outflow and acute distention and inflammation of gallbladder. Acute pancreatitis (**choice C**) is an emergency condition manifesting with extremely severe deep abdominal pain and frequently associated with shock. Elevated amylase and lipase levels in the serum support the diagnosis. Adenoma of the liver (**choice D**) is most commonly asymptomatic and may be discovered incidentally. However, severe intraperitoneal hemorrhage due to rupture may constitute a life-threatening presentation. Use of oral contraceptives and anabolic steroids are predisposing conditions. Alcoholic hepatitis (**choice E**) is similar to any other form of acute hepatitis in its clinical manifestations and laboratory findings. Abdominal pain, nausea, mild jaundice, low-grade fever, and malaise are associated with elevated serum transaminase levels. Amebic liver abscess (**choice F**) presents with right upper quadrant pain and fever. Usually, the patient comes to medical attention after several weeks of symptoms. A recent travel history to tropical countries is often elicited. Liver tests are mildly abnormal. Ultrasonography, CT, or MRI demonstrates the location and size of the lesion. Focal nodular hyperplasia (**choice G**) is a nodular lesion consisting of hepatocytes and a stellate-shaped fibrous stroma (a sort of “focal cirrhosis”). It is usually asymptomatic. It is most commonly associated with chronic alcohol abuse. Gilbert syndrome (**choice H**) is a form of hereditary jaundice due to glucuronyl transferase deficiency. Bilirubin is thus mostly of the indirect (unconjugated) type. The condition is benign and asymptomatic (except for jaundice). Hemochromatosis (**choice I**) is an autosomal recessive hereditary disorder caused by excessive intestinal absorption of iron. Iron deposition results in cirrhosis, cardiomyopathy, pancreatic damage with diabetes, and skin hyperpigmentation (due to melanin overproduction, not iron itself). Hepatocellular carcinoma (**choice J**) is most often associated with cirrhosis in industrialized countries. Its development may be unsuspected until the cirrhotic patient manifests rapid deterioration and weight loss. Primary biliary cirrhosis (**choice L**) is characteristic of middle-aged women and is associated with high titers of circulating antimitochondrial autoantibodies. Primary sclerosing cholangitis (**choice M**) is a rare disorder affecting patients with some underlying disease, most commonly ulcerative colitis. It is due to a chronic inflammatory reaction of probable autoimmune origin, which results in sclerosis and obliteration of the extrahepatic bile ducts. Progressively severe obstructive jaundice is the presenting picture. Rotor syndrome (**choice N**) is another hereditary form of jaundice caused by deficient liver excretion of conjugated bilirubin. Since activity of glucuronyl transferase is normal, most circulating bilirubin is of the direct (conjugated) type. The condition is benign. Viral hepatitis (**choice O**) manifests with an acute syndrome characterized by right upper abdominal pain, nausea, malaise, lowgrade fever, and laboratory signs of hepatocellular necrosis. This picture is shared by all forms of viral hepatitis, but acute infection due to HCV is usually asymptomatic.

Answer 25

**Respuesta: E** The correct **answer is E**. When GFR falls below 25%, phosphorus excretion becomes impaired, leading to hyperphosphatemia. Hyperphosphatemia results in hypocalcemia, triggering increased release of parathyroid hormone (PTH; choice E). High PTH levels increase phosphaturia and normalize serum calcium levels, but at the expense of bone calcium. Concomitantly, renal failure results in decreased hydroxylation of 25- hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (the metabolically active form of vitamin D3 ), leading to decreased intestinal absorption of calcium. Loss of renal function causes metabolic acidosis, and the excess hydrogen ions in the blood are buffered by calcium salts deriving from bone. Finally, aluminum, used in chronic renal failure as a phosphorus binder, may itself deposit in the bone, contributing to bone damage. All these factors, in varying degrees, result in renal osteodystrophy, which manifests with rarefaction of bone (osteomalacia) on x-ray films, bone pains, muscle weakness, and pathologic fractures. On x-ray films, the phalanges and the distal third of the clavicles appear more severely affected.

Answer 26

**Respuesta: D** The correct **answer is D**. Hypertension is an inevitable consequence, and the most common complication, of chronic renal failure. Control of hypertension is crucial in the management of renal failure as high blood pressure accelerates renal damage. While fluid and salt retention (**choice D**) plays the most important pathogenetic role, other factors may contribute. Recombinant erythropoietin, used to treat anemia, causes hypertension in about 20% of cases. Hypertension may develop abruptly at the beginning of treatment. Accumulation of uremic toxins (**choice A**) has deleterious effects on many tissues and organs. It is thought responsible for the development of uremic encephalopathy (obtunded sensorium), peripheral neuropathy, and uremic pericarditis. The occurrence of any of these complications warrants initiation of renal replacement therapy to eliminate uremic toxins. Hyperkalemia (**choice B**) usually develops when GFR falls below 10% of normal, but many endogenous and exogenous factors may hasten its appearance. Hyperkalemia interferes with neuromuscular junctions and causes muscle weakness, abdominal distention, and diarrhea. It also affects cardiac fiber excitability, resulting in arrhythmias. Chronic hyperkalemia is treated with dietary restriction and, if necessary, oral administration of an ion exchange resin such as sodium polystyrene sulfonate. Platelet dysfunction (**choice C**) is thought to be the principal mechanism of coagulopathy associated with chronic renal failure. While platelet number might be only slightly decreased, platelet adhesiveness and aggregation are impaired, which manifests with prolonged bleeding time. Patients with chronic renal failure, therefore, frequently develop purpura and petechiae. Shunting of blood through arteriovenous fistula (**choice F**) occurs in patients treated with hemodialysis in which vascular access is guaranteed by establishing a permanent arteriovenous fistula. Shunting of blood through such fistula may contribute to the development of congestive heart failure. Other factors include anemia and salt and fluid retention