Content area
Full Text
Metab Brain Dis (2010) 25:8189 DOI 10.1007/s11011-010-9170-5
ORIGINAL PAPER
Organic osmolytes in hyponatremia and ammonia toxicity
Jessica Heins & Claudia Zwingmann
Received: 12 September 2009 /Accepted: 28 January 2010 /Published online: 2 March 2010 # Springer Science+Business Media, LLC 2010
Abstract Hyperammonemia (HA) is a major and commonly observed feature of hepatic encephalopathy. Furthermore, hyponatremia is an important pathogenetic factor in patients with hepatic encephalopathy. Both conditions have some features in common, such as the release of organic osmolytes, which might be an adaptive mechanism against cell swelling. However, the consequence of a possible relationship between osmoregulatory response in hyperammonemia and hyponatremia is not completely understood. This review gives a short introduction into the pathogenesis of hepatic encephalopathy and hyponatremia. For a comparison of both pathological events, some basics on cellular osmo- and volume regulation are explained, in particular as the mechanisms involved in the adaption of the cell to volume changes can be different under both pathological conditions. The role of brain glutamine and organic osmolytes in hyponatremia and hyperammonemia and their combination are discussed based on findings in experimental animal models, and finally on data obtained from primary astrocytes in culture. The observations that the decrease of brain organic osmolytes in astrocytes not adequately compensate for an increased intracellular osmolarity caused by glutamine are consistent with results obtained after chronic hyponatremia in rats, in which the release of osmolytes does not protect from ammonia-induced brain edema. Furthermore, a decrease in intracellular osmolarity is attributed both to the release and a reduced de novo synthesis of amino acids.
Keywords Hepatic encephalopathy. Hyperammonemia . Hyponatremia . Astrocytes . Osmoregulation .
Energy metabolism
Introduction
Hepatic encephalopathy and hyperammonemia
Hepatic encephalopathy (HE) is characterized by cerebral disorders and impairment of brain metabolism and neuronal function (Adams and Foley 1953; Albrecht and Jones 1999; Bessman and Bessman 1955; Butterworth 2000). It is a severe central nervous system (CNS) complication of both acute and chronic liver failure (ALF and CLF). While rapid deterioration in consciousness and death occur in the acute form of HE, the chronic form of HE progresses slowly. Acute HE results often from viral hepatitis or drug toxicity, and the main pathologic change in acute HE is brain edema. Death most frequently results from brainstem herniation...