Ammonia: The Old and the New

Abstract

Experimental evidence relating increased blood ammonia to cerebral dysfunction dates back to 1877 when Eck first created a portocaval shunt. In the 1930’s Van Caulert and Kirk described mental disturbances in cirrhotics receiving ammonium salts.¹ However, it wasn’t until 1952 that Gabuzda, Phillips, Schwartz, and Davidson^2,3 recognized that symptoms and EEG changes indistinguishable from hepatic encephalopathy could be produced in cirrhotics given ammonium-containing cation-exchange resins, ammonium salts, urea, or protein orally. Two years later a patient with a normal liver who had a portocaval shunt following a Whipple procedure for carcinoma of the pancreas was reported by McDermoff and Adams⁴ to have recurrent episodes of irrationality, confusion, disorientation, incontinence, drowsiness, apathy, stupor, and sometimes coma Blood ammonia and EEG abnormalities were correlated with the manifestations, which were reproducible by feeding the patient meat, urea, ammonium-containing cation-exchange resin, or ammonium chloride. Such observations in cirrhotics and in patients with portacaval shunts have been confirmed many times since these early reports, so a relationship between ammonia and the clinical syndrome of hepatic coma is well established.