Hyperammonaemia, plasma aminoacid imbalance, and blood-brain aminoacid transport: A unified theory of portal-systemic encephalopathy

It is proposed that hyperammonaemia in liver cirrhosis or after protacaval shunt contributes to plasma neutral aminoacid imbalance and to increased activity of the blood-brain neutral aminoacid transport system. Plasma neutral aminoacid concentrations are deranged, partly, but not completely, because ammonia stimulates glucagon secretion; a high rate of gluconeogenesis and hyperinsulinaemia follow. Brain uptake of neutral aminoacids rises because ammonia stimulates brain-glutamine synthesis, which results in rapid exchange of brain glutamine for plasma neutral aminoacids. Hyperammonaemia therefore contributes to encephalopathy indirectly, by raising the brain concentration of neutral aminoacids which alter neurotransmitter metabolism, rather than directly, by toxic effects on neuronal metabolism.