NBME 26 GRADED A - Comprehensive Basic Science Self-Assessment 1 F...

NBME 26 GRADED A+

Exam Section 1: Item 2 of 50

National, Board of Medical Examiners Comprehensive Basic Science Self-Assessment

• Free purine and pyrimidine bases are reutilized in normal

metabolism. In children with Lesch-Nyhan syndrome who have intellectual disability, poor muscle coordination, and self-mutilation tendencies, there is a defect in the salvage of which of the following pairs of bases?

• Adenine and thymine
• Guanine and hypoxanthine
• Guanine and uric acid
• Uracil and cytosine
• Xanthine and hypoxanthine Correct Answer B.

Lesch-Nyhan syndrome presents with intellectual disability, aggressive behavior, self-mutilation, gout, and dystonia. The disorder is due to inactivating mutations of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), a key enzyme in the purine salvage pathway, and is inherited in an X-linked recessive fashion.HGPRT catalyzes the conversion of guanine to guanosine monophosphate and hypoxanthine to inosine monophosphate.Patients with deficient activity of HGPRT are unable to salvage guanine and 1 / 4

hypoxanthine and develop resultant increased levels of xanthine and uric acid. Hyperuricemia in Lesch-Nyhan syndrome is treated with xanthine oxidase inhibitors, such as allopurinol or febuxostat, in order to reduce the synthesis of uric acid.

InCorrect Answers: A, C, D and E.

Adenine and thymine (Choice A) are purine and pyrimidine bases, respectively. Purine and pyrimidine salvage are handled through two distinct pathways that are not commonly involved in a single disease process.Guanine and uric acid (Choice C) accumulation may occur as part of Lesch-Nyhan syndrome, however, the accumulation of uric acid is also secondary to accumulation of hypoxanthine. Choice B more accurately describes defective salvage of guanine and hypoxanthine as the fundamental effect of HGPRT dysfunction.The accumulation of uric acid is secondary.Uracil and cytosine (Choice D) are pyrimidine nucleotides.Pyrimidine salvage is not affected by mutations of HGPRT.Defects of xanthine and hypoxanthine (Choice E) metabolism may result from defects in HGPRT. However, HGPRT dysfunction results in impaired hypoxanthine salvage with resultant excessive production of xanthine, rather than impaired xanthine salvage.

Educational Objective: Lesch-Nyhan syndrome presents with

intellectual disability, aggressive behavior, self-mutilation, gout, and dyst

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Exam Section 1: Item 3 of 50 2 / 4

National Board of Medical Examiners Comprehensive Basic Science Self-Assessment

• A 42-year-old man is struck by a motor vehicle. His only injury

is a closed fracture of the proximal tibia. Initial neurovascular examination shows no deficits. Twenty-four hours later, he has increased leg pain and paresthesias in the dorsal space between his first and second toes. The patient begins to pass dark red urine and becomes oliguric. Urinalysis is positive for blood but no erythrocytes are seen on microscopic examination. Which of the following acute disorders is the most likely cause of the renal failure?

• Glomerulonephritis
• Hemolytic-uremic syndrome
• Interstitial nephritis
• Nephrotic syndrome
• Tubular necrosis Correct Answer E.

Tibial fractures present a high risk for compartment syndrome.The fracture results in blood vessel injury and muscle injury, inflammation, and edema. Because the fascia containing the anterior compartment of the leg does not stretch, bleeding and swelling can cause increased pressure in the compartment. This increased pressure in turn inhibits venous drainage, further increasing pressure in the compartment. Eventually the nerve supply and associated arteries are compromised, leading to the classic signs and 3 / 4

symptoms of compartment syndrome. Signs and symptoms of compartment syndrome include pain out of proportion to examination findings, pain with passive movement of the muscles, paresthesia, pallor, pulselessness, and paralysis. Compromised blood supply deprives muscle and tissue of oxygen and glucose, leading to tissue ischemia and necrosis. Muscle necrosis leads to rhabdomyolysis, myoglobinuria, and acute renal failure.Evaluation of rhabdomyolysis reveals red or brown urine and urinalysis is typically positive for blood due to the presence of myoglobinuria without microscopic evidence of red blood cells. A complication of rhabdomyolysis is acute kidney injury from acute tubular necrosis secondary to the release of nephrotoxic myoglobin and nonprotein heme pigments.Acute tubular necrosis typically occurs following an ischemic or nephrotoxic insult to the kidneys, which results in loss of the tubular epithelium. Granular, muddy brown casts are common on urinalysis. Compartment syndrome is treated by immediate fasciotomy to decrease compartment pressure and support tissue perfusion.

InCorrect Answers: A, B, C, and D.

Glomerulonephritis (Choice A) refers to a variety of glomerular diseases, including nephritic and nephrotic syndromes. Nephritic syndromes typically present with acute renal failure associated with h

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