Liver-Brain Relationships in Hepatic Coma

In the century which has elapsed since the classical clinical description of Frerichs1of the neurological and mental changes in advanced liver failure, and especially since the studies in Pavlov's laboratory on meat intoxication in dogs with an Eck fistula,2and the observation of a rise in blood ammonia in man by Kirk3and several others, ammonia and related amino acids and metabolites have held the center of the field in investigations attempting to elucidate the pathogenesis of hepatic coma. Subsequently Bessman et al4showed an increased uptake of ammonia by the brain, and Fazekas et al5demonstrated a reduced cerebral oxygen consumption in hepatic coma. Critical and detailed reviews on this subject have come recently from Sherlock,6Chalmers,7Walshe,8Dastur,9and Seshadri.10 The main purpose of the present investigation was to reassess the role of ammonia and amino acids and of certain keto acids