Vaquero Javier, Butterworth Roger F
Neuroscience Research Unit, Hôpital Saint-Luc (CHUM), Université de Montréal, Montréal, H2X3J4, QC., Canada.
Neurol Res. 2007 Oct;29(7):683-90. doi: 10.1179/016164107X240099.
Continued elucidation of the mechanisms of brain edema in acute liver failure (ALF) has established ammonia and the astrocyte as major players in its pathogenesis. The metabolism of ammonia to glutamine appears to be a requisite, and is followed by an osmotic disturbance in the brain, mitochondrial dysfunction with oxidative/nitrosative stress, and alterations of brain glucose metabolism. Cerebral blood flow (CBF) is also altered in ALF and strongly influence the development of brain edema and intracranial hypertension. Additional factors such as systemic inflammation, alterations of the brain extracellular concentration of amino acids and neurotransmitters, and others have been identified and may contribute to the cerebral alterations of ALF. Such pathophysiologic insights are reflected in the various clinical trials of novel therapeutic interventions using ammonia-lowering agents, N-acetylcysteine, hypertonic saline, indomethacin, high-volume plasmapheresis, bio-artificial liver assist devices, albumin dialysis and mild hypothermia.
对急性肝衰竭（ALF）脑水肿机制的持续阐明已确定氨和星形胶质细胞是其发病机制中的主要因素。氨代谢为谷氨酰胺似乎是一个必要过程，随后会出现脑部渗透压紊乱、伴有氧化/亚硝化应激的线粒体功能障碍以及脑葡萄糖代谢改变。ALF中脑血流量（CBF）也会发生改变，并强烈影响脑水肿和颅内高压的发展。已确定其他因素，如全身炎症、脑外氨基酸和神经递质浓度的改变等，可能导致ALF的脑部改变。这些病理生理学见解反映在使用降氨药物、N-乙酰半胱氨酸、高渗盐水、吲哚美辛、大容量血浆置换术、生物人工肝辅助装置、白蛋白透析和轻度低温的新型治疗干预的各种临床试验中。
