1. A 29-year-old woman has recently developed migraine headaches. For various reasons you cannot prescribe a triptan for abortive therapy, so you prescribe ergotamine. Which of the following is the main mechanism of action of this drug in terms of the migraine?

A. Activates serotonin receptors

B. Inhibits thromboxane synthesis/improves cerebral blood flow

C. Propranolol-like blockade of -adrenergic receptors

D. Reduces cerebral metabolic rate (reduced oxygen demand)

E. Strong antimuscarinic activity

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The answer is A.

EXPLANATION: Ergotamine has several pharmacologic properties. The one that seems to be responsible for its efficacy in migraines is activation (as a typical agonist) of serotonin receptors (5-HT_D1) in the cerebral vasculature, thus causing a triptan-like effect (but the drug should not be used with a triptan). The drug works best in prodromal phases (classical signs and symptoms the migraineur should learn to recognize before a full-blown migraine attack develops). It's less effective once the full onslaught of migraine has developed. It lacks intrinsic sedative or analgesic activity.

In addition to the effects just mentioned, toxic doses of ergotamine cause peripheral vasoconstriction intense enough to cause hypertension and tissue ischemia (including gangrene of such structures as the fingers and toes). The syndrome of poisoning is called ergotism.

The ergot alkaloids, as a group, also cause intense, prolonged uterine-contracting effects. This contraindicates their use during pregnancy, but explains the use of the related drugs ergonovine and methylergonovine postpartum to control uterine bleeding (bleeding is reduced by the strong uterine contractions).

2. A mammogram of a woman, age 48, reveals macrocalcification within the right breast, indicating the need for biopsy. The surgeon visually and manually examines the breast with negative results. The surgeon closely examines the nipple for indications of ductal carcinoma. At surgery for the biopsy, a locator needle is inserted into the region of macrocalcification and the position confirmed by mammography. The surgeon incises the skin and dissects a block of tissue. The pathology report indicates ductal carcinoma with microinvasion necessitating surgery. Both patient and surgeon agree that a modified radical mastectomy offers the best prognosis in her case. At surgery for mastectomy, the surgeon carries the dissection along the major pathway of lymphatic drainage from the mammary gland. The major lymphatic channels parallel which of the following?

A. Subcutaneous venous networks to the contralateral breast and abdominal wall

B. Tributaries of the axillary vessels to the axillary nodes

C. Tributaries of the intercostal vessels to the parasternal nodes

D. Tributaries of the internal thoracic (mammary) vessels to the parasternal nodes

E. Tributaries of the thoracoacromial vessels to the apical (subscapular) nodes

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The answer is B.

EXPLANATION: The lymphatic drainage of the mammary gland, which follows the path of its blood supply, generally parallels the tributaries of the axillary, internal thoracic (mammary), thoracoacromial, and intercostal vessels. Because about 75% of the breast lies lateral to the nipple, the more significant lateral and inferior portions of the breast drain toward the axillary nodes. The smaller medial portion drains to the parasternal lymphatic chain paralleling the internal thoracic vessels (answers c and d), whereas the very small superior portion drains toward the nodes associated with the thoracoacromial trunk and the supra-clavicular nodes. Lymph rarely crosses the midline (answer a). Lymph generally reaches subscapular (apical axillary) nodes after passing through axillary nodes (answer e).

3. During a visit to her gynecologist, a patient reports she received vitamin A treatment for her acne unknowingly during the first 2 months of an undetected pregnancy. Which of the following organ systems in the developing fetus is most likely to be affected?

A. The digestive system

B. The endocrine organs

C. The respiratory system

D. The urinary and reproductive systems

E. The skeletal and central nervous systems

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The answer is E.

EXPLANATION: Vitamin A is a member of the retinoic acid family. Retinoic acid directs the polarity of development in the central nervous system, the axial skeleton (vertebral column), and probably the appendicular skeleton. Retinoic acid induces transcription of various combinations of homeobox genes, depending on tissue type and location (distance and direction from the source of retinoic acid). Exogenous sources of retinoic acid may induce the wrong sequence or combination of homeobox genes, leading to structural abnormalities in nervous and skeletal systems. The other organ systems listed are not as susceptible to vitamin A (answers a, b, c, and d).

4. A patient with heart failure has been managed with digoxin and furosemide and is doing well by all measures, for 3 years. He develops acute rheumatoid arthritis and is placed on rather large doses of a very efficacious nonsteroidal anti-inflammatory drug—one that inhibits both cyclooxygenase pathways (COX-1 and -2). Which of the following is the most likely outcome of adding the NSAID?

A. Hyperchloremic acidosis indicative of acute diuretic toxicity

B. Dramatic increase of furosemide's potassium-sparing effects

C. Edema, weight gain, and other signs/symptoms indicative of reduced diuresis

D. Increased digoxin excretion

E. Reduced digoxin effects because the NSAID competes with digoxin for myocyte receptor-binding sites

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The answer is C.

EXPLANATION: An important element in the renal responses to furosemide is maintenance of adequate renal blood flow. That is, to a degree, prostaglandin-mediated. The NSAIDs, such as the hypothetical one described here, inhibit prostaglandin synthesis. That, in turn, antagonizes the desired effects of the loop diuretic, leading to less fluid and salt elimination: edema, weight gain, and other markers of heart failure are likely to develop as a result. Hyperchloremic alkalosis (a) is incorrect, in part, because chronic or acute excessive effects of loop diuretics are characterized by hypochloremic metabolic alkalosis. Regardless, NSAIDs are not likely to potentiate the effects of these diuretics. "Dramatic increases of furosemide's K-sparing effects (b)" is incorrect. Recall that loop diuretics are K-wasting. Digoxin is eliminated by renal excretion. If we accept the notion that loop diuretics may increase excretion of digoxin, then we should accept the likely possibility that NSAID-induced reductions of diuretic action should reduce the glycoside's renal loss, not increase it (d). The NSAIDs do not bind to and inhibit the myocyte Na⁺,K⁺-ATPase, which is digoxin's cellular receptor (e). Do remember that furosemides (and thiazides) are apt to increase the risk or severity of digoxin toxicity. The mechanism mainly involves diuretic-induced hypokalemia, not changes in circulating fluid volume or urine volume per se.

5. A divorced working mother takes her 4-year-old child to a day-care center. She has noticed that the child's frequent stools are nonbloody with mucus and are foul smelling. The child has no fever, but does complain of "tummy hurting." The increase of fat in the stool directs the pediatrician's concern toward a diagnosis of malabsorption syndrome associated with which of the following?

A. Amebiasis

B. Ascariasis

C. Balantidiasis

D. Enterobiasis

E. Giardiasis

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The answer is E.

EXPLANATION: G. lamblia is the only common protozoan found in the duodenum and jejunum. Trophozoites are commonly found in the duodenum and do not penetrate the tissues. Four nuclei cysts (infective stage) can remain viable for up to 4 months. Excystation is via digestive enzymes. The mechanical irritation to tissues leads to diarrhea, with increased fat and mucus in the foul-smelling stool. Malabsorption syndrome (vitamin A and fats) leads to weight loss, anorexia, electrolyte imbalance, and abdominal cramps. Children and immunocompromised individuals are most significantly affected. Giardiasis should be considered in the differential diagnosis of any "traveler's diarrhea."

6. A 30-year-old man is brought to the ED by emergency medical service (EMS) in respiratory distress. His initial vitals include a HR of 109 beats per minute, a BP of 180/90 mm Hg, and an RR of 20 breaths per minute with an oxygen saturation of 92% on room air. A chest x-ray shows a bilateral diffuse infiltrative process. A subsequent toxicologic screen is positive. Which of the following agents is most likely responsible for this patient's presentation?

A. Cannabis

B. Opioid

C. Crack cocaine

D. Methamphetamine

E. Ethanol

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The answer is C.

EXPLANATION: The crystallized free base of cocaine is known as "crack cocaine." This form, smoked through a pipe, produces a highly lipid-soluble vapor that allows for rapid transport from the lungs to the brain for a quicker high compared to cocaine that is snorted or injected. As a result of this mechanism, the substance can be concentrated in high amounts in the lung parenchyma causing an infiltrative inflammatory process and pneumonitis referred to as "crack lung." This can subsequently result in respiratory failure.

Cannabis (a) used in conjunction with inhaled ₂-agonists may result in bleb formation and subsequent pneumothorax, but not pneumonitis. Opioids (b), methamphetamine (d), and alcohol (e) may have pulmonary effects through secondary mechanisms, but are not primarily responsible for this type of presentation

7. A 65-year-old man presents to you complaining of abdominal pain. His pain is associated with anorexia, bloating, nausea, and vomiting. He is afebrile and denies fever. On examination, his abdomen appears distended, and he has absent bowel sounds. Abdominal percussion produces tympani. What would his abdominal x-ray most likely show?

A. Fecalith in the right lower quadrant

B. Free intraperitoneal air

C. Stool throughout the colon

D. Proximally dilated loops of bowel

E. Stones in the right upper quadrant

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The answer is D.

EXPLANATION: The patient is presenting with symptoms consistent with obstruction. In this case, abdominal radiographs are crucial in the decision-making process, and to rule in/rule out a surgical abdomen. A fecalith is a hard, stony mass of feces that can obstruct the appendix or a diverticuli. Without a fever or other evidence of appendicitis, that would be a less likely finding. In a perforation, x-ray would show free intraperitoneal air, but this patient's presentation is more consistent with obstruction. Stool may be seen on an abdominal film, but constipation would not likely present with the symptoms listed above. Gallstones are less likely to be seen on plain film.

8. A 32-year-old woman who has recently started taking -methyldopa develops dark, tea-colored urine. Physical examination reveals mild scleral icterus, a low-grade fever, and mild hepatosplenomegaly. Examination of her peripheral blood reveals many microspherocytes, while laboratory examination finds a positive Coombs' test. Which of the following is the basic pathomechanism that caused this individual's signs and symptoms?

A. Autoimmune destruction of red blood cells in the spleen

B. Drug-induced destruction of red blood cell precursors in the bone marrow

C. Hyperimmune destruction of neutrophils in the liver

D. Immune complex deposition in the capillaries of the kidneys

E. Isoimmune destruction of red blood cells in the peripheral blood

The answer is A.

EXPLANATION: The presence of microspherocytes in an individual with a positive Coombs' test is diagnostic for autoimmune hemolytic anemia (AIHA). This type of hemolytic anemia is characterized by the presence of antibodies that destroy red cells. The AIHAs are divided into two main types: those secondary to "warm" antibodies and those secondary to "cold" antibodies. The antibodies seen in warm-antibody autoimmune hemolytic anemias react at 37°C in vitro, are composed of IgG, and do not fix complement. Instead, immunoglobulin-coated red blood cells are removed by splenic macrophages that recognize the Fc portion of the immunoglobulin. These warm IgG antibodies are found in patients with malignant tumors, especially leukemia-lymphoma; they are associated with the use of such drugs as -methyldopa; and they are also found in the autoimmune diseases, especially lupus erythematosus.

9. You receive a telephone call from the mother of a 19-year-old patient. During the day, she complained of a headache, body aches, and a low-grade fever. She went to bed 30 minutes ago, and her mother is now finding it difficult to arouse her. Which of the following tests would be most likely to reveal the diagnosis?

A. Urinalysis

B. CBC

C. Toxicology screen

D. Pregnancy test

E. Lumbar puncture

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The answer is E.

EXPLANATION: While a urinalysis, CBC, toxicology screen, and pregnancy test may all reveal the cause of delirium, the patient's history is consistent with viral or bacterial meningitis. A lumbar puncture is the most likely test to reveal the diagnosis in this case.

10. A 74-year-old man is diagnosed with an acute stroke. A right middle cerebral artery occlusion is demonstrated by magnetic resonance angiogram shown below. Which of the following is the most likely cause of this patient's present condition?

A. Atherosclerosis

B. Fibromuscular dysplasia

C. Mitral valve prolapse

D. Arterial dissection

E. Meningovascular inflammation

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The answer is A.

EXPLANATION: Atherosclerosis may produce cerebral infarction by a variety of mechanisms, including emboli to the brain and local occlusion of atheromatous vessels. Platelet emboli may form on ulcerated atheromatous plaques in major vessel walls and ascend to the brain. The atherosclerotic plaque involves subintimal proliferation of smooth muscle, fatty deposits in the intima, inflammatory cells, and excessive elaboration of the connective tissue matrix in the vessel wall. Thrombi may form on the surface of the plaque and occlude the vessel, even if the plaque is not large enough to produce substantial narrowing of the vessel. Fibromuscular dysplasia is a relatively uncommon cause of cranial vessel occlusion that develops with segmental overgrowth of fibrous and muscular tissue in the media. Meningovascular inflammation is a rare process that occurs in some infectious or inflammatory disorders, such as syphilis, tuberculous meningitis, or sarcoid.

11. A 16-year-old woman develops wheezing and shortness of breath minutes after receiving ceftriaxone for gonorrhea. Her blood pressure is 110/65, her pulse rate is 92, and her respiratory rate is 32. She is anxious, but she is well-perfused peripherally. Which of the following is the treatment of choice for this patient?

A. Subcutaneous epinephrine for bronchospasm

B. Intravenous fluids

C. Prophylactic atropine

D. Diazepam to prevent seizures

E. Antihistamines

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The answer is A.

EXPLANATION: Subcutaneous epinephrine is recommended for bronchospasm and anaphylaxis. (For severe bronchospasm or shock, intravenous epinephrine might be used if the patient does not have contraindications.) Intravenous fluids would be recommended only when hypotension is present. Atropine is given only in the setting of bradycardia. Diazepam is used when seizures occur acutely as part of the hypersensitivity reaction but not as a prophylactic measure. Antihistamines, useful in urticaria, are not helpful for the anaphylactic reaction.

12. A 21-year-old woman asks you to evaluate a small painless lump in the midline of her neck that moves with swallowing. You make the clinical diagnosis of thyroglossal duct cyst. Which of the following statements regarding symptomatic thyroglossal duct cysts is true?

A. More than 90% manifest themselves before the age of 12 years.

B. Treatment includes resection of the hyoid bone.

C. They usually present as a painful swelling in the lateral neck.

D. Approximately 10% to 15% contain malignant elements.

E. They can contain ectopic thyroid tissue.

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The answer is B.

EXPLANATION: Thyroglossal duct cysts result from retention of an epithelial tract between the thyroid and its embryologic origin in the foramen cecum at the base of the tongue. This tract usually penetrates the hyoid bone. There is no sex predilection, and although these cysts are more frequently detected in children, they may not become symptomatic until adulthood. The most common presentation is a painless swelling in the midline of the neck that moves with protrusion of the tongue or swallowing. They should not be confused with midline ectopic thyroid tissue. The cysts are prone to infection and progressive enlargement. Although rare (<1%), epidermoid or papillary carcinomas do occur within thyroglossal duct cysts. Surgical resection is the standard therapy. The Sistrunk procedure, which involves local resection of the cyst and the central portion of the hyoid bone, is the operation of choice. Simple excision of the cyst results in an unacceptably high recurrence rate.

13. A child is born to a 19-year-old woman who has had two to eight drinks per day throughout her pregnancy. What is the major pathologic effect of alcohol on the central nervous system of the developing fetus?

A. Cerebral ischemia

B. Periventricular hemorrhage

C. Macrocephaly

D. Impaired neuronal migration

E. Holoprosencephaly

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The answer is D.

EXPLANATION: Alcohol abuse in pregnant women is associated with three major kinds of abnormalities in the developing fetus: intrauterine and postpartum growth retardation, dysmorphic facies in the newborn, and effects on the development of the CNS. The broad range of neurologic and systemic abnormalities observed in children born to alcohol-abusing women is referred to as the fetal alcohol syndrome. Alcohol is teratogenic at high doses and may interfere measurably in fetal development with exposure at any dose. Although the mechanism of alcohol's effect on the developing brain is not entirely clear, it appears that alcohol acts primarily to impair neuronal migration. This may result in formation of heterotopias (collections of cortical neurons in abnormal locations), cortical disorganization, and malformations of the cerebellum and brainstem. Mental retardation, learning disabilities, hyperactivity, and microcephaly, not macrocephaly, are the common clinical neurologic consequences of fetal alcohol syndrome. Ischemia and hemorrhagic complications are not part of the syndrome. Holoprosencephaly refers to a failure of the two sides of the frontal cerebrum to separate properly, leading to a fusion of the frontal poles and hippocampi with no interhemispheric fissure

14. We have a 50-year-old man with asymptomatic hyperuricemia, and we are about to start therapy for newly diagnosed essential hypertension (BP 136/90 mm Hg, based on repeated measurements with the patient supine and at rest). Which of the following antihypertensive drugs is most likely to increase his serum uric acid levels further, and possibly precipitate a gout attack?

A. Captopril

B. Hydrochlorothiazide

C. Labetalol

D. Losartan

E. Verapamil

The answer is B.

EXPLANATION: Thiazide diuretics tend to raise serum uric acid levels. This may be of little concern for patients with no history of hyperuricemia or gout, but for those with such a history it can be a problem that is not associated with any of the other answer choices given. Thiazides can be administered to hyperuricemic/gouty patients, but that usually requires another drug (allopurinol; xanthine oxidase inhibitor) to counteract diuretic-induced rises of urate levels. If we can avoid the problems by avoiding the thiazide, and the possible need for adding a second drug to counteract the hyperuricemia, why not do just that?

15. A teenage boy falls from his bicycle and is run over by a truck. On arrival in the emergency room (ER), he is awake and alert and appears frightened but in no distress. The chest radiograph suggests an air-fluid level in the left lower lung field and the nasogastric tube seems to coil upward into the left chest. Which of the following is the next best step in his management?

A. Placement of a left chest tube

B. Thoracotomy

C. Laparotomy

D. Esophagogastroscopy

E. Diagnostic peritoneal lavage

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The answer is C.

EXPLANATION: The patient has an acute diaphragmatic rupture, which occurs in about 4% of patients who sustain either blunt abdominal or chest trauma, and should be treated with immediate laparotomy, which allows both for examination of the intra-abdominal solid and hollow viscera for associated injuries and for adequate exposure of the diaphragm to allow secure repair. Because of the risk of vascular compromise of the contents of the hernia, exacerbated by the negative thoracic pressure, acute diaphragmatic rupture should be repaired immediately. Diagnosis may be difficult. The finding of an air-fluid level in the left lower chest, with a nasogastric tube entering it after blunt trauma to the abdomen, is diagnostic of diaphragmatic rupture with gastric herniation into the chest. Esophagogastroscopy is of limited value. CT scanning and MRI may be useful adjuncts, but neither can definitively rule out diaphragmatic rupture. Diagnostic peritoneal lavage is neither sensitive nor specific for diaphragmatic injuries, particularly in the absence of significant hemorrhage. Diaphragmatic repair can be accomplished via the left chest, but laparotomy is the procedure of choice for acute traumatic rupture for the stated reasons.

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