A 55-year-old woman with known chronic hepatitis C cirrhosis (Child-Pugh B) presents with confusion, asterixis, and inability to perform serial subtractions. She recently had an episode of GI bleeding. Serum ammonia is 112 μmol/L. Which of the following mechanisms best explains the pathogenesis of hepatic encephalopathy?
- A Deposition of unconjugated bilirubin in the basal ganglia
- B Decreased hepatic synthesis of coagulation factors causing cerebral microhemorrhages
- C Ammonia-mediated astrocyte swelling and glutamine accumulation causing cerebral edema and neuronal dysfunction ✓
- D Bile acid accumulation causing axonal demyelination
Correct answer: C. Ammonia-mediated astrocyte swelling and glutamine accumulation causing cerebral edema and neuronal dysfunction
Explanation
In hepatic encephalopathy, impaired hepatic clearance of gut-derived ammonia leads to its accumulation in astrocytes, where it is metabolized to glutamine via glutamine synthetase. Glutamine accumulation causes osmotic astrocyte swelling and mitochondrial dysfunction, contributing to cerebral edema and altered neurotransmission. GI bleeding increases the ammonia load from protein catabolism in the gut. Treatment includes lactulose (reduces colonic ammonia production), rifaximin, and addressing precipitants.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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