USMLE USMLE-STEP-1 Online Practice Questions and Exam Preparation

USMLE USMLE-STEP-1 Online Questions & Answers

• Question 671:

  Calcium disodium edetate is most effective as an antidote for poisoning with which of the following?

  A. arsenic
  B. atropine
  C. iron
  D. lead
  E. mercury
  D. lead

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  Explanation

  Section: Pharmacology Chronic lead poisoning results in multiple toxicities including headache, hypertension, infertility, anemia, and renal insufficiency. Mental and growth retardation occur in children. Acute lead intoxication usually presents as encephalopathy or severe abdominal colic, sometimes masquerading as pancreatitis. When blood lead levels exceed 50 mcg/dL, chelation treatment is indicated. The calcium ion in calcium disodium edetate (EDTA) is readily displaced by lead, forming a lead chelate that is excreted in the urine. Arsenic poisoning (choice A) is treated with chelation therapy using dimercaprol, succimer, or penicillamine. Atropine (choice B) is a lipophilic muscarinic receptor antagonist that blocks parasympathetic function and at toxic levels produces hallucinations and psychosis. Treatment of atropine intoxication consists of symptomatic management or administration of the lipid-soluble nticholinesterase physostigmine. Toxicity from iron (choice C) may arise from ingestion of iron supplements (as with children swallowing adult preparations) or hemolytic diseases such as thalassemia. Treatment consists of the use of the iron- chelating agents deferoxamine or deferasirox. EDTA does not chelate mercury (choice E). Inorganic mercury poisoning is treated by using chelation therapy with dimercaprol, succimer, or penicillamine. Organic mercury poisoning is more difficult to treat because of the lipophilic nature of organomercury compounds.

• Question 672:

  During surgical resection of the gastrointestinal tract for treatment of long-standing irritable bowel syndrome, a surgery resident is asked to select a surgical site coinciding with the termination of the vagal innervation. Which of the following does she select?

  A. duodenojejunal junction
  B. ileocolic junction
  C. junction of the second part and third part of the duodenum
  D. left colic (splenic) flexure
  E. right colic (hepatic) flexure
  D. left colic (splenic) flexure

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  Explanation

  Section: Anatomy The left colic (splenic) flexure represents the junction of the midgut to the hindgut during embryonic development. The vagus (tenth cranial) nerve provides the parasympathetic innervation of the digestive tract up to this flexure, whereas the pelvic parasympathetic fibers from S2-S4 innervate the rest of the tract. The duodenaljejunal junction (choice A), ileocolic junction (choice B), and rightcolic (hepatic) flexure (choice E) are anatomical landmarks along the digestive tract without change in parasympathetic innervation. The junction of the second part and third part of the duodenum (choice C) represents the embryonic junction between the foregut and the midgut, but both receive vagal innervation.

• Question 673:

  A patient with AIDS has bacterial meningitis and is being treated with an antimicrobial agent cleared by both hepatic metabolism and renal excretion. The volume of distribution is 10 L and the half-life for elimination is 7 hours in this patient. If the renal contribution to the plasma clearance of the drug is 8.3 mL/ min, approximately what percentage of the drug's elimination can be attributed to hepatic metabolism?

  A. 10%
  B. 25%
  C. 50%
  D. 75%
  E. 90%
  C. 50%

• Question 674:

  An adult man suffered from stable angina pectoris for 15 years, during which time there was progressive heart failure and repeated pulmonary thromboembolism. On his death at age 63, autopsy disclosed enormous cardiomyopathy (1100 g), cardiac storage of globotriaosylceramide (11 mg lipid/g wet weight), and restricted cardiocytes. Which of the following lipid storage diseases would result in these clinical findings?

  A. Fabry disease
  B. Gaucher disease
  C. Krabbe disease
  D. Niemann-Pick disease (NPD) type I A
  E. Tay-Sachs disease
  A. Fabry disease

• Question 675:

  Opioid peptides are an important physiological mechanism of the body for relief from painful stimuli. Used as pharmacologic agents, they are highly valuable tools for pain management, although side effects are usually inevitable. Which of the following problems are most likely during opiate treatments?

  A. difficulty sleeping
  B. hypermotility of the GI tract
  C. placebo effects
  D. respiratory alkalosis
  E. tolerance (need for higher dosage to achieve the same therapeutic effect)
  E. tolerance (need for higher dosage to achieve the same therapeutic effect)

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  Explanation

  Section: Physiology Tolerance is commonly observed with many pharmacologic agents, including opioids. Difficulty sleeping (choice A), hypermotility of the GI tract (choice B), and respiratory alkalosis (choice D) are opposite to the expected effect of opiates. The placebo effect (choice C) is, at least in part, likely due to the release of endogenous opioid peptides in anticipation of pain relief, but is not a complication or side effect of therapy.

• Question 676:

  Sensations from the thoracic and abdominal organs are usually difficult to localize. They are conveyed by general visceral afferent (GVA) fibers, which synapse in which of the following nuclei?

  A. ambiguus nucleus
  B. dorsal motor nucleus of the vagus
  C. hypoglossal nucleus
  D. solitary nucleus
  E. spinal (descending) trigeminal nucleus
  D. solitary nucleus

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  Explanation

  Section: Anatomy GVA fibers from the thoracic and abdominal organs have their perikarya in the inferior vagal (nodose) ganglion and project to the solitary nucleus. The ambiguus nucleus (choice A) provides branchial efferent (motor) fibers to the stylopharyngeus, soft palate, pharyngeal, and laryngeal muscles. The dorsal motor nucleus of the vagus (choice B) sends parasympathetic preganglionic fibers to the thoracic and abdominal viscera. The hypoglossal nucleus (choice C) provides motor innervation for the muscles of the tongue. The spinal (descending) trigeminal nucleus (choice E) receives pain and temperature fibers from the face area.

• Question 677:

  Measurement of the rate of creatinine clearance is used as a key determinant of renal function. In which of the following tissues is creatinine generated?

  A. adipose
  B. kidney
  C. liver
  D. lung
  E. skeletal muscle
  E. skeletal muscle

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  Explanation

  Section: Biochemistry In cardiac and skeletal muscle, high-energy phosphate is stored through the transfer of a phosphate from ATP to creatine-generating creatine phosphate. Creatine is synthesized in liver from guanidoacetate. Guanidoacetate is derived from the amino acid arginine in the kidneys (below figure). In muscle cells, creatinine is a nonenzymatic metabolite of creatine phosphate. When measured in the serum, levels of creatinine are remarkably constant from day to day and are proportional to muscle mass. In renal dysfunction, the clearance of creatinine will be impaired and its levels will therefore rise in the serum. Although creatine is synthesized in the liver (choice C) from guanidoacetate, which is produced in the kidneys (choice B), it is not used by these two tissues, nor by the lung (choice D) or adipose tissue (choice A). Once synthesized, creatine is transported to cardiac and skeletal muscle where it is phosphorylated and stored for future energy needs.

• Question 678:

  Glucagon binding to liver cells induces an increase in intracellular cAMP concentration. The rate- limiting step in cholseterol biosynthesis is regulated as a consequence of this glucagon-mediated rise in cAMP. The effect of increased cAMP on the rate of cholesterol biosynthesis occurs because of which of the following?

  A. AMP-activated protein kinase (AMPK) is activated and directly phosphorylates human menopausal gonadotropin (HMG)-CoA reductase, leading to an increase in the activity of the latter enzyme.
  B. Cyclic AMP-dependent protein kinase (PKA) is activated and directly phosphorylates HMG-CoA reductase, reducing the activity of the latter enzyme.
  C. PKA is activated and phosphorylates AMP-regulated kinase, which then phosphorylates and activates HMGCoA reductase.
  D. Removal of phosphate from HMG-CoA reductase increases its activity. Activated PKA results in a reduced level of phosphate removal from HMG-CoA reductase so that the latter enzyme is kept less active.
  E. The increased cAMP directly inhibits HMG-CoA reductase.
  D. Removal of phosphate from HMG-CoA reductase increases its activity. Activated PKA results in a reduced level of phosphate removal from HMG-CoA reductase so that the latter enzyme is kept less active.

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  Explanation

  Section: Biochemistry Regulation of HMG-CoAreductase (the ratelimiting enzyme of cholesterol biosynthesis) activity is complex and involves a number of distinct enzyme activities (below figure).

  

  Since cholesterol biosynthesis consumes large amounts of energy, it needs to be regulated in response to energy demands, particularly in hepatocytes. The principal site for the action of the hypoglycemic response hormone, glucagon, is the liver. Glucagon binding to hepatocytes triggers the liver to stop catabolizing carbohydrate and to divert carbon atoms into the gluconeogenesis pathway. This change in hepatic metabolism, in response to glucagon, comes about through a change in the phosphorylation state of numerous enzymes. One of these enzymes is HMG-CoA reductase. HMG-CoA reductase is most active when in the nonphosphorylated state. The enzyme is phosphorylated and rendered less active through the action of AMP-regulated kinase. AMP levels rise as the energy charge in the cell declines and thus the cell is able to recognize this change, at the level of HMG-CoA reductase activity, by inducing its phosphorylation and inhibition. In order to reverse the effect of HMG-CoA phosphorylation the phosphates must be removed. This occurs through the action of HMG-CoA reductase phosphatase. HMGCoAreductase phosphatase is regulated through the action of protein phosphatase inhibitor-1 (PPI-1). In turn the activity of PPI-1 is regulated by its state of phosphorylation; it is more active when phosphorylated. When glucagon binds to hepatocytes, the result is a glucagon receptormediated activation of adenylate cyclase, which in turn produces cAMP from ATP. The effect of cAMP is to activate cAMP- dependent protein kinase which then phosphorylates a number of substrates. With respect to glucagon- mediated regulation of cholesterol metabolism, PKA phosphorylates PPI-1. Phosphorylated PPI-1 is more active at inhibiting HMG-CoA reductase phosphatase so that the removal of phosphate from HMG-CoA reductase is inhibited. This keeps HMG-CoA reductase in the phosphorylated and less active state. AMPK is not directly affected by glucagon-mediated increases in the levels of cAMP (choice A). Although glucogon action leads to an increase in PKA activity, the latter enzyme does not itself phosphorylate HMG- CoA reductase (choice B). The activity of AMP-regulated kinase is affected by its level of phosphorylation but it is not phosphorylated by PKA(choice C). Cyclic AMPitself does not have a direct effect on HMG- CoAreductase (choice E).

• Question 679:

  Which of the following occurs in the lipidosis known as Tay-Sachs disease?

  A. Ganglioside GM2 is not catabolized by lysosomal enzymes.
  B. Phosphoglycerides accumulate in the brain.
  C. Synthesis of a specific ganglioside is decreased.
  D. Synthesis of a specific ganglioside is excessive.
  E. Xanthomas, due to cholesterol deposition, are observed.
  A. Ganglioside GM2 is not catabolized by lysosomal enzymes.

• Question 680:

  A 57-year-old obese woman has Type II (noninsulindependent) diabetes mellitus of 15 years duration. Because her hyperglycemia is not well controlled with diet and oral hypoglycemic agents, she selfadministers insulin by injection. She comes to her physician's office with a fever and a draining external ear infection; Pseudomonas aeruginosa is cultured from the drainage fluid. Which of the following drugs or drug combinations is appropriate treatment for the P. aeruginosa infection in this diabetic patient?

  A. chloramphenicol
  B. nafcillin plus kanamycin
  C. sulfamethoxazole plus trimethoprim
  D. tetracycline
  E. ticarcillin plus tobramycin
  E. ticarcillin plus tobramycin

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  Explanation

  Section: Pharmacology

  P. aeruginosa is an aerobic gram-negative bacterium that is frequently the causative agent in diabetic malignant external otitis. Increased susceptibility to infection in diabetics with poor glycemic control probably arises through impairment of leukocyte function. Such serious

  P. aeruginosa infections are best treated parenterally with a broad-spectrum beta-lactam cell wall synthesis inhibitor such as ticarcillin in combination with an aminoglycoside such as tobramycin. Chloramphenicol (choice A) is a protein

  synthesis inhibitor.

  P. aeruginosa is resistant to chloramphenicol. Nafcillin plus kanamycin (choice B) is a combination of a penicillinase-resistant penicillin plus a limitedspectrum aminoglycoside. Nafcillin is useful in treating penicillinase-producing staphylococcal infections, but does not possess a broadenough antibacterial spectrum to eradicate

  P. aeruginosa. Kanamycin is ineffective against

  P. aeruginosa and is used orally or topically, not parenterally as needed here. Sulfamethoxazole plus trimethoprim

  (choice C) is a combination of a folate synthesis inhibitor and a dihydrofolate reductase inhibitor that is effective in treating urinary tract infections. P. aeruginosa is resistant to this combination. Tetracycline (choice D) is a bacteriostatic protein synthesis inhibitor. When first introduced, tetracycline was effective in treating Pseudomonas, but now all strains are resistant.