Effect of Portacaval Anastomosis on Ammonia Metabolism in Brain and Liver

Abstract

Construction of an end-to-side portacaval anastomosis (PCA) in the rat results in liver atrophy and increased blood and brain ammonia. Since brain is devoid of an effective urea cycle, removal of ammonia involves glutamine synthesis and PCA results in increased brain glutamine. Glutamine synthetase (GS) activities are decreased by 15% in cerebral cortex following PCA but are unchanged in brainstem. Administration of ammonium acetate to rats with a PCA results in severe encephalopathy progressing to coma. Glutamine content of brainstem of comatose rats is increased a further 2-fold whereas that of cerebral cortex is unchanged. Consequently, ammonia levels in cerebral cortex rise rapidly to attain levels of the order of 5 mM. These findings suggest a limitation in the capacity of cerebral cortex to remove additional blood-borne ammonia following PCA. GS activities of liver are decreased by 80% following PCA. This latter effect probably results from the selective loss of perivenous hepatocytes following PCA.