Teresa R Scott, Victoria T Kronsten, Robin D Hughes, Debbie L Shawcross, Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, King's College Hospital, London SE5 9RS, United Kingdom.
World J Gastroenterol. 2013 Dec 28;19(48):9240-55. doi: 10.3748/wjg.v19.i48.9240.
Cerebral oedema is a devastating consequence of acute liver failure (ALF) and may be associated with the development of intracranial hypertension and death. In ALF, some patients may develop cerebral oedema and increased intracranial pressure but progression to life-threatening intracranial hypertension is less frequent than previously described, complicating less than one third of cases who have proceeded to coma since the advent of improved clinical care. The rapid onset of encephalopathy may be dramatic with the development of asterixis, delirium, seizures and coma. Cytotoxic and vasogenic oedema mechanisms have been implicated with a preponderance of experimental data favouring a cytotoxic mechanism. Astrocyte swelling is the most consistent neuropathological finding in humans with ALF and ammonia plays a definitive role in the development of cytotoxic brain oedema. The mechanism(s) by which ammonia induces astrocyte swelling remains unclear but glutamine accumulation within astrocytes has led to the osmolyte hypothesis. Current evidence also supports an alternate 'Trojan horse' hypothesis, with glutamine as a carrier of ammonia into mitochondria, where its accumulation results in oxidative stress, energy failure and ultimately astrocyte swelling. Although a complete breakdown of the blood-brain barrier is not evident in human ALF, increased permeation to water and other small molecules such as ammonia has been demonstrated resulting from subtle alterations in the protein composition of paracellular tight junctions. At present, there is no fully efficacious therapy for cerebral oedema other than liver transplantation and this reflects our incomplete knowledge of the precise mechanisms underlying this process which remain largely unknown.
脑水肿是急性肝衰竭（ALF）的一种严重后果，可能与颅内高压的发展和死亡有关。在 ALF 中，一些患者可能会出现脑水肿和颅内压增高，但进展为危及生命的颅内高压并不像以前描述的那么频繁，在改善临床治疗后出现昏迷的病例中，不到三分之一的病例出现这种情况。肝性脑病的快速发作可能很明显，出现扑翼样震颤、谵妄、癫痫发作和昏迷。细胞毒性和血管源性水肿机制与大量支持细胞毒性机制的实验数据有关。星形胶质细胞肿胀是人类 ALF 中最一致的神经病理学发现，氨在细胞毒性脑水肿的发展中起着明确的作用。氨诱导星形胶质细胞肿胀的机制尚不清楚，但星形胶质细胞内谷氨酰胺的积累导致了渗透调节剂假说。目前的证据还支持另一种“特洛伊木马”假说，即谷氨酰胺作为氨进入线粒体的载体，其积累导致氧化应激、能量衰竭，最终导致星形胶质细胞肿胀。尽管在人类 ALF 中没有明显的血脑屏障破裂，但已经证明水和其他小分子（如氨）的通透性增加，这是由于细胞旁紧密连接的蛋白组成发生了微妙的改变。目前，除了肝移植之外，对于脑水肿还没有完全有效的治疗方法，这反映了我们对这一过程的确切机制的认识还不完全，这些机制在很大程度上仍不清楚。
