Hepatic encephalopathy (HE) pathogenesis is primarily attributed to which metabolite acting on astrocytes and neurons?

• A Elevated bile acids causing mitochondrial permeability transition
• B Elevated aromatic amino acids (phenylalanine, tyrosine) replacing true neurotransmitters
• C Manganese deposition in the globus pallidus causing parkinsonism
• D Ammonia converting to glutamine in astrocytes, causing astrocyte swelling and neuroinflammation ✓

Explanation

Ammonia is the central mediator of hepatic encephalopathy. Astrocytes convert ammonia to glutamine via glutamine synthetase; glutamine accumulation causes astrocyte swelling (cytotoxic oedema), which together with neuroinflammation (from systemic inflammation, bacterial translocation, and oxidative stress) impairs neurotransmission. This forms the basis for lactulose (reduces ammonia production/absorption) and rifaximin (reduces ammonia-producing gut bacteria) treatment. Manganese accumulates in cirrhosis (T1 hyperintensity in globus pallidus on MRI) and contributes to acquired hepatocerebral degeneration but is not the primary HE mediator.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.