WBR0978

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A 73-year-old woman presents with worsening pain in her left foot. Her past medical history is remarkable for a 20-year history of poorly type 2 controlled diabetes mellitus. Her temperature is 38.3 °C (100.9 °F), heart rate is 98/min, and blood pressure is 146/90 mmHg. On physical examination, the left foot is warm, erythematous, and tender, and an ulcer that involves the full thickness of the skin present. The right lower extremity appears normal. The patient is informed that her condition is a complication of her poorly controlled diabetes. Deficiency of which of the following enzymes in nerve cells is responsible for the organ damage associated with this patient's condition?]]
Answer A	AnswerA::Aldose reductase
Answer A Explanation	[[AnswerAExp::Aldose reductase is not deficient in Schwann cells.]]
Answer B	AnswerB::Sorbitol dehydrogenase
Answer B Explanation	[[AnswerBExp::While glucose is normally converted to sorbitol by the action of aldose reductase and then to fructose by the action of sorbitol dehydrogenase, some cells lack sorbitol dehydrogenase expression (cells of the retina, Schwann cells, and the kidneys) and are predisposed to osmotic damage when exposed to chronically high concentrations of sorbitol.]]
Answer C	AnswerC::Aldolase B
Answer C Explanation	[[AnswerCExp::Aldolase B is not involved in sorbitol metabolism. Aldolase B is involved in fructose metabolism.]]
Answer D	AnswerD::Triose kinase
Answer D Explanation	[[AnswerDExp::Triose kinase is not involved in sorbitol metabolism. Triose kinase is involved in fructose metabolism.]]
Answer E	AnswerE::NADPH oxidase
Answer E Explanation	[[AnswerEExp::NADPH oxidase is not involved in sorbitol metabolism.]]
Right Answer	RightAnswer::B
Explanation	[[Explanation::The patient presents with a foot ulcer in her left foot. The patient's signs and symptoms are consistent with an infected diabetic foot. Diabetic foot is a complication of long-standing poorly controlled diabetes mellitus. It results from chronic peripheral vasculopathy and neuropathy, and it is characterized by development of painless ulcers that often grow unnoticed over time. If left untreated, diabetic foot ulcers evolve to gangrene and require surgical amputation. The neuropathy in diabetics is the consequence of the osmotic damage caused by the sugars to Schwann cells. While glucose is normally converted to sorbitol by the action of aldose reductase and then to fructose by the action of sorbitol dehydrogenase, some cells normally lack sorbitol dehydrogenase expression (cells of the retina, Schwann cells, and the kidneys) and are predisposed to osmotic damage when exposed to chronically high concentrations of sorbitol. Accordingly, chronically elevated concentration of glucose results in sorbitol accumulation in cells that lack sorbitol dehydrogenase and ultimately causes osmotic injury and target organ damage (e.g. retinopathy, nephropathy, and neuropathy associated with long-standing diabetes mellitus). Shown below is a figure that illustrates sorbitol metabolism Educational Objective: While glucose is normally converted to sorbitol by the action of aldose reductase and then to fructose by the action of sorbitol dehydrogenase, some cells lack sorbitol dehydrogenase expression (cells of the retina, Schwann cells, and the kidneys) and are predisposed to osmotic damage when exposed to chronically high concentrations of sorbitol. References: First Aid 2014 page 107]]
Approved	Approved::No
Keyword	WBRKeyword::Sorbitol, WBRKeyword::Sorbitol dehydrogenase, WBRKeyword::Diabetic neuropathy, WBRKeyword::Diabetic vasculopathy, WBRKeyword::Vascular disease, WBRKeyword::Neuropathy, WBRKeyword::Diabetes, WBRKeyword::Metabolism, WBRKeyword::Enzyme
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::