Intracellular ion homeostasis

• DOI: 10.1007/s13295-010-0006-x
• Publication Date: 2010-07-12T12:25:07Z
• Authors: T. Kelly; C.R. Rose
• Keywords: 0303 health sciences; 03 medical and health sciences

Abstract Hepatic encephalopathy (HE) is a neuropsy­chiatric disorder associated with acute and chronic liver failure. Ammonium is the most likely toxin responsible for the observed neu­rological deficits, reaching 5 mM in the CNS during acute HE. Additionally, ammonium preferentially affects astrocytes. Conversion of glutamate to glutamine, occurring exclu­sively in astrocytes, is the sole pathway for ammonium detoxification, while glutamine increases in astrocytes during HE. Further­more, elevated extracellular glutamate con­centrations, commonly observed in HE pa­tients, may result from reduced glutamate uptake into astrocytes. Finally, astrocytic swelling likely contributes to brain oedema, the predominant cause of mortality following acute liver failure. Alterations in intracellu­lar ion concentrations may contribute to the observed cellular changes in HE. Ammoni­um causes intracellular acidifications, and in­creases intracellular calcium and sodium con­centrations in astrocytes. In this review, we summarise current knowledge concerning ammonium-evoked changes in ion homeo­stasis, and discuss how such changes possibly contribute to the pathology of HE.