Organic osmolytes in hyponatremia and ammonia toxicity.
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.
Heins
Jessica
J
Département de médicine, Centre de Recherche Hôpital Saint-Luc, Université de Montréal, 264, René Lévesque Est, Montréal, Quebec, Canada, H2X 1P1.
Zwingmann
Claudia
C
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D048429:Cell Size; D004573:Electrolytes / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D022124:Hyperammonemia / Q000378:metabolism* / Q000503:physiopathology; D007010:Hyponatremia / Q000378:metabolism* / Q000503:physiopathology; D014882:Water-Electrolyte Balance / Q000502:physiology*
D004573:Electrolytes; D005973:Glutamine