James J H, Ziparo V, Jeppsson B, Fischer J E
Lancet. 1979 Oct 13;2(8146):772-5. doi: 10.1016/s0140-6736(79)92119-6.
It is proposed that hyperammonaemia in liver cirrhosis or after portacaval shunt contributes to plasma neutral aminoacid imbalance and to increased activity of the blood-brain neutral amino-acid 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 after neurotransmitter metabolism, rather than directly, by toxic effects on neuronal metabolism.
有人提出，肝硬化或门腔分流术后的高氨血症会导致血浆中性氨基酸失衡，并使血脑中性氨基酸转运系统的活性增加。血浆中性氨基酸浓度紊乱，部分但并非完全是因为氨刺激胰高血糖素分泌；随后会出现高糖异生率和高胰岛素血症。脑对中性氨基酸的摄取增加，因为氨刺激脑谷氨酰胺合成，这导致脑谷氨酰胺与血浆中性氨基酸快速交换。因此，高氨血症通过提高神经递质代谢后脑中中性氨基酸的浓度间接导致脑病，而不是直接通过对神经元代谢的毒性作用。
