It has been suggested that hepatic urea synthesis, which consumes HCO₃, plays an important role in acid-base homeostasis. This study measured urea synthesis rate (R_a urea) directly to assess its role in determining the acid-base status in patients with end-stage cirrhosis and after orthotopic liver transplantation (OLT). Cirrhotic patients were studied before surgery (n = 7) and on the second postoperative day (n = 11), using a 5-h primed-constant infusion of [¹⁵N₂]urea. Six healthy volunteers served as controls. R_a urea was 5.05 ± 0.40 (SE) and 3.11 ± 0.51 µmol · kg¹ · min¹, respectively, in controls and patients with cirrhosis (P < 0.05). Arterial base excess was 0.6 ± 0.3 meq/l in controls and 1.1 ± 1.3 meq/l in cirrhotic patients (not different). After OLT, R_a urea was 15.05 ± 1.73 µmol · kg¹ · min¹, which accompanied an arterial base excess of 7.0 ± 0.3 meq/l (P < 0.001). We conclude that impaired R_a urea in cirrhotic patients does not produce metabolic alkalosis. Concurrent postoperative metabolic alkalosis and increased R_a urea indicate that the alkalosis is not caused by impaired R_a urea. It is consistent with, but does not prove, the concept that the graft liver responds to metabolic alkalosis by augmenting R_a urea, thus increasing HCO₃ consumption and moderating the severity of metabolic alkalosis produced elsewhere.

cirrhosis; acid-base metabolism; base excess; metabolic alkalosis; ammonia