From the Research
Elevated CSF glutamine occurs in hyperammonemia because ammonia that crosses the blood-brain barrier is detoxified by astrocytes through conversion to glutamine, as supported by the most recent study 1. When blood ammonia levels are high, excess ammonia enters the brain where astrocytes combine it with glutamate to form glutamine via the enzyme glutamine synthetase. This protective mechanism prevents direct neurotoxicity from ammonia but results in increased glutamine concentration in the cerebrospinal fluid. The elevated glutamine can contribute to cerebral edema and neurological symptoms by increasing osmotic pressure within astrocytes. This process explains why CSF glutamine levels serve as a useful marker for monitoring ammonia-related encephalopathy, even when blood ammonia levels fluctuate. Some key points to consider include:
- The pathogenesis of hepatic encephalopathy (HE) is not entirely understood, but ammonia is considered the main culprit behind primary and secondary symptoms, as discussed in 2.
- Treatment focuses on reducing ammonia production through protein restriction, lactulose administration, or specific medications for underlying disorders to prevent further glutamine accumulation and associated neurological complications, as shown in 3 and 4.
- Rifaximin has been shown to be effective in reducing blood ammonia concentration and improving hepatic spare ability and quality of life in patients with long-term HE, as demonstrated in 1.
- The relationship between rifaximin administration and the renin-angiotensin-aldosterone system may also play a role in improving refractory ascites, as suggested in 1.