Liver Unit and Institute of Cellular Medicine, Freeman Hospital and Newcastle University, Newcastle Upon Tyne, UK.
J Hepatol. 2011 Jun;54(6):1154-60. doi: 10.1016/j.jhep.2010.09.030. Epub 2011 Feb 3.
BACKGROUND & AIMS: Hepatic encephalopathy (HE) is now thought to be caused by cerebral oedema although the precise pathogenesis is uncertain. We hypothesised that if ammonia is a key factor, induced hyperammonaemia would lead to transient changes in brain water distribution and metabolite concentration, detectable by diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS).
Thirteen cirrhotic patients being evaluated for liver transplantation were challenged with 54 g of equal parts of threonine, serine, and glycine. Conventional magnetic resonance imaging was performed to exclude structural lesions and localise regions of interest. DTI was used to generate white matter apparent diffusion coefficient (ADC) maps and proton MRS to measure brain metabolite concentrations before and after the challenge.
The challenge caused a mean (±SD) rise in blood ammonia of 58 (±41) μmol/L, which was accompanied by a significant 9% increase in ADC (p=0.004). Increased ADC significantly correlated with blood ammonia (r=0.58, p=0.04). The change in ammonia levels also correlated with the increase in glutamine levels (r=0.78, p=0.002). Myo-inositol concentration decreased significantly by 0.7 (±0.7)mMol/L between scans and this correlated with the mean difference in ADC (r=0.59, p<0.04).
These results show that ammonia can directly drive changes in brain water distribution as a mechanism for cerebral oedema development. Since cerebral astrocytes contain glutamine synthetase, our MRS data suggest intracerebral formation of glutamine from ammonia. The rapid decrease in myo-inositol indicates that this organic osmolyte plays a protective role in HE by release from astrocytes in order to maintain cell volume.
肝性脑病（HE）现在被认为是由脑水肿引起的，尽管确切的发病机制尚不清楚。我们假设，如果氨是一个关键因素，诱导的高氨血症将导致脑水分布和代谢物浓度的短暂变化，可通过弥散张量成像（DTI）和磁共振波谱（MRS）检测到。
13 名正在接受肝移植评估的肝硬化患者接受了 54 克等份苏氨酸、丝氨酸和甘氨酸的挑战。进行常规磁共振成像以排除结构病变并定位感兴趣区域。DTI 用于生成白质表观扩散系数（ADC）图，质子 MRS 用于测量挑战前后的脑代谢物浓度。
该挑战导致平均（±SD）血氨升高 58（±41）μmol/L，同时 ADC 显著升高 9%（p=0.004）。增加的 ADC 与血氨显著相关（r=0.58，p=0.04）。氨水平的变化也与谷氨酰胺水平的增加相关（r=0.78，p=0.002）。扫描之间肌醇浓度显著降低 0.7（±0.7）mmol/L，与 ADC 的平均差异相关（r=0.59，p<0.04）。
这些结果表明，氨可以直接驱动脑水肿发展的脑水分布变化。由于脑星形胶质细胞含有谷氨酰胺合成酶，我们的 MRS 数据表明氨在脑内形成谷氨酰胺。肌醇迅速减少表明，这种有机渗透剂通过星形胶质细胞释放以维持细胞体积，在 HE 中发挥保护作用。
