Regional Differences in the Capacity for Ammonia Removal by Brain Following Portocaval Anastomosis
Version of Record online: 5 OCT 2006
Journal of Neurochemistry
Volume 51, Issue 2, pages 486–490, August 1988
How to Cite
Butterworth, R. F., Girard, G. and Giguère, J.-F. (1988), Regional Differences in the Capacity for Ammonia Removal by Brain Following Portocaval Anastomosis. Journal of Neurochemistry, 51: 486–490. doi: 10.1111/j.1471-4159.1988.tb01064.x
- Issue online: 5 OCT 2006
- Version of Record online: 5 OCT 2006
- Received December 22, 1987; revised manuscript received February 17, 1988; accepted February 17, 1988.
- Portocaval anastomosis;
- Glutamine synthetase;
- Hepatic encephalopathy;
- Hepatic coma
Abstract: Portocaval anastomosis (PCA) in the rat leads, within 4 weeks, to severe liver atrophy, sustained hyperam-monemia, and increased brain ammonia. Because brain is not equipped with an effective urea cycle, removal of ammonia involves glutamine synthesis and PCA results in significantly increased brain glutamine. Glutamine synthetase activities, however, are decreased by 15% in cerebral cortex and are unchanged in brainstem of shunted rats. Administration of ammonium acetate to rats following PCA results in severe encephalopathy (loss of righting reflex and, ultimately, coma). Glutamine concentrations in brainstem of comatose rats are increased a further two-fold, whereas those of cerebral cortex are unchanged. Consequently, ammonia levels in cerebral cortex reach disproportionately high levels (of the order of 5 mM). These findings suggest a limitation in the capacity of cerebral cortex to remove additional blood-borne ammonia by glutamine formation following PCA. Such mechanisms may explain the hypersensitivity of rats with PCA and of patients with portal-systemic shunting to small increases of blood ammonia. Disproportionately high levels of brain ammonia in certain regions, such as cerebral cortex, may then result in alterations of inhibitory neurotransmission and, ultimately, loss of cellular (astrocytic) integrity.