METABOLISM OF N-15-AMMONIA IN PATIENTS WITH CIRRHOSIS - A 3-COMPARTMENTAL ANALYSIS

Urinary N-15-ammonia and N-15-urea were measured by gas chromatography-mass spectrometry after the intravenous administration of N-15-ammonia (0.2-mu-mol/kg/hr) to 6 volunteers and 11 patients with cirrhosis. Urinary N-15-nitrogen excretion as ammonia and urea was measured during the 210-min infusion period, and urea synthesis and ammonia conversion to amino acids were analyzed with a three-compartment model using the nonlinear least-squares method. The rate of urea synthesis in control subjects was 14.1 +/- 1.2 mg/kg/hr (mean +/- S.E.M.), and in cirrhotic patients it was 11.0 +/- 3.2 mg/kg/hr. The cirrhotic group was divided into those with compensated cirrhosis (Child class A patients) and those with decompensated cirrhosis (Child classes B and C patients), and the rates of urea synthesis for these groups were 14.5 +/- 1.5 and 8.9 +/- 1.6 mg/kg/hr, respectively. The difference between decompensated cirrhotic patients and control subjects was statistically significant (p < 0.001). The percentage of ammonia reutilization of a given dose of N-15-ammonia was 75.9% +/- 2.4% in compensated cirrhotic patients and 82.9% +/- 3.6% in decompensated cirrhotic patients (p < 0.05). Fasting venous ammonia levels correlated inversely with urea synthesis (p < 0.001) and correlated positively with ammonia reutilization (p < 0.05). These results are consistent with a decreased capacity to synthesize urea and an increased capacity to convert ammonia to amino acids in chronic liver failure.