Synthesis of urea after stimulation with amino acids: relation to liver function

Hepatic urea synthesis is the organism's main channel for the disposal of nitrogen and it may be an 'essential' liver function. In six control subjects and five patients with cirrhosis of the liver urea synthesis was studied during continuous infusion for six to 24 hours of about 3 mmol alpha-amino nitrogen/h X kg body weight. The urea synthesis rate was calculated in intervals of two hours as urinary excretion with correction for accumulation in the total body water and for hydrolysis of urea in the gut. The peripheral venous plasma alpha-amino nitrogen concentration increased from 3 to about 14 mmol/l and the urea nitrogen synthesis rate from 25 to about 215 mmol/h. In all cases the urea synthesis rate rose linearly with the alpha-amino concentration throughout the examined range. The slope of this linear relationship is an expression of the hepatic conversion of alpha-amino nitrogen to urea nitrogen ('functional hepatic nitrogen clearance'). The functional hepatic nitrogen clearance was 22.4 l/h in control subjects and 13.7 1/h (P < 0.025) in the patients with cirrhosis. It was correlated with quantitative measures of the liver function (the galactose elimination capacity, r = 0.84, and the clearance of antipyrine, 4 = 0.80). These observations, while confirming the abundant capacity of the urea synthesis system, imply that a given urea synthesis rate requires a higher alpha-amino level in patients with reduced liver function.