During acute hyperammonemic encephalopathy, astrocytes detoxify circulating ammonia primarily by converting glutamate to glutamine. What is the principal consequence of this reaction within the brain?
- A Activation of the urea cycle within neurons, lowering intracellular ammonia
- B Increased GABA synthesis and neuronal hyperexcitability
- C Depletion of the excitatory neurotransmitter pool and astrocyte swelling from osmotic glutamine load ✓
- D Enhanced glutathione production protecting against oxidative injury
Correct answer: C. Depletion of the excitatory neurotransmitter pool and astrocyte swelling from osmotic glutamine load
Explanation
Astrocytic glutamine synthetase consumes glutamate and ATP to form glutamine. Two effects follow: depletion of the neuronal excitatory glutamate pool impairs synaptic transmission, and accumulated intracellular glutamine acts as an osmolyte, drawing water into astrocytes and causing the cerebral edema seen in fulminant hepatic failure and urea cycle defects. Neurons lack a functional urea cycle, and GABA metabolism is not driven by this pathway.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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