The Metabolism of Ammonia and α-Keto-Acids in Liver Disease and Hepatic Coma1

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Abstract
Blood ammonia, peripheral and cerebral arteriovenous ammonia differences and a-keto-acid concentrations were studied in 27 patients in hepatic coma. In addition, the response of blood a-keto-acid concentration to ammonium chloride administration was determined in 5 subjects with liver disease and 4 controls. Concentrations of ammonia in both artery and vein were elevated in most cases of impending hepatic coma and coma, although normal levels were observed more frequently in venous blood. A-V differences tended to be positive but equilibrium and negative differences were observed, the latter in terminal hepatic coma. Cerebral A-V differences were also variable. Blood pyruvate and a-ketoglutarate concentrations were usually elevated in uncomplicated liver disease, impending coma and coma. Highest concentrations of arterial ammonia were observed in conjunction with presence of large amounts of gastrointestinal protein and a regimen of protein deprivation, oral broad-spectrum antibiotics usually effected a reduction in arterial ammonia concentration with either recovery of the patient or progression of the syndrome to death with a terminal rise in ammonia despite complete protein deprivation and the absence of gastrointestinal hemorrhage. Control subjects administered ammonium chloride intravenously showed no significant alteration in blood keto-acid concentrations in the succeeding 3 hours. Patients with liver disease given 3-4 g of ammonium chloride either orally or intravenously showed constant rises in both pyruvic and a-ketoglutaric acids. Uptake of ammonia by tissue is impaired in liver disease and elevations of a-keto-acid concentration may reflect a disorder of intermediary metabolism consequent to ammonia intoxication. The significance of blood ammonium concentrations in hepatic coma must take into account ammonia entering the system from the gastrointestinal tract, uptake or release of ammonia at various sites and the possibility of pre-existing defects in ammonia utilizing systems.