A 44-year-old homeless man is brought to the emergency department after police officers found him agitated and confused. During transport to the hospital, he is started on intravenous fluids with dextrose. On arrival, the patient is disoriented but cooperative. Physical examination shows bruises on his forehead, forearms, and shins. Extraocular findings include bilateral horizontal nystagmus and decreased lateral eye movements. He also has an unsteady gait with widely-spaced legs and short steps. The ambulance personnel state that the patient's extraocular movements were intact when they picked him up. A review of the medical record shows that the patient has been admitted to the hospital with alcohol intoxication several times before. Which of the following reactions is likely to be the most impaired in this patient?

Question

A 44-year-old homeless man is brought to the emergency department after police officers found him agitated and confused.  During transport to the hospital, he is started on intravenous fluids with dextrose.  On arrival, the patient is disoriented but cooperative.  Physical examination shows bruises on his forehead, forearms, and shins.  Extraocular findings include bilateral horizontal nystagmus and decreased lateral eye movements.  He also has an unsteady gait with widely-spaced legs and short steps.  The ambulance personnel state that the patient's extraocular movements were intact when they picked him up.  A review of the medical record shows that the patient has been admitted to the hospital with alcohol intoxication several times before.  Which of the following reactions is likely to be the most impaired in this patient?

Quizplus · Accepted Answer

11ec160b_36f5_26ec_9249_c9c35ce85443_MD0001_00 Patients with chronic alcohol use are frequently deficient in thiamine, a necessary cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase. Administration of glucose to thiamine-deficient patients can cause rapid depletion of the small amount of thiamine remaining in the circulation. This can result in neuronal injury within highly metabolic brain regions, leading to acute Wernicke encephalopathy. The metabolism of ethanol by alcohol dehydrogenase and aldehyde dehydrogenase consumes NAD⁺ and increases the NADH to NAD⁺ ratio. This skewed ratio inhibits all pathways requiring NAD⁺; as a result, the entire citric acid cycle is inhibited. However, in the setting of Wernicke encephalopathy, thiamine-dependent enzymes are especially affected due to the lack of NAD⁺ and thiamine. (Choice A) Even though pyruvate dehydrogenase is markedly inhibited by high NADH and lack of thiamine, acetyl-CoA still accumulates intracellularly because ethanol itself is metabolized to acetyl-CoA. Thus, citrate synthase is not inhibited more than the other non-thiamine-requiring TCA cycle enzymes. (Choices C and H) α-ketoglutarate, isocitrate, and malate dehydrogenase all require NAD⁺ and will be inhibited during ethanol intoxication due to depletion of this substrate. However, of these enzymes, only α-ketoglutarate dehydrogenase also requires thiamine as a cofactor. Educational objective: Pyruvate dehydrogenase and α-ketoglutarate dehydrogenase require thiamine as a cofactor. Administration of glucose to thiamine-deficient patients (eg, those with chronic alcohol use) can result in Wernicke encephalopathy (eg, acute confusion, ophthalmoplegia, and ataxia) due to increased thiamine demand. __________ References: Thiamine pyrophosphate-requiring enzymes are altered during pyrithiamine-induced thiamine deficiency in cultured human lymphoblasts. (http://www.ncbi.nlm.nih.gov/pubmed/8683340) Dietary thiamin level influences levels of its diphosphate form and thiamin-dependent enzymic activities of rat liver. (http://www.ncbi.nlm.nih.gov/pubmed/10082768)

A 44-Year-Old Homeless Man Is Brought to the Emergency Department