Urea synthesis by perfused rat liver- Studies of CCI₄-induced cirrhosis

Previous studies in man and experimental animals suggest that urea production is decreased in cirrhosis. In the present study, NH₄Cl solutions of increasing concentrations were infused into isolated, perfused livers of normal rats and the rates of ammonia uptake and urea production were calculated for each pre-hepatic ammonia concentration. A pattern of saturation kinetics was generated and characterized through computer analysis. The V_max was 7.4 μmoles/min and K_m was 86.3 μmoles/100 ml. The livers of rats with experimental cirrhosis induced by carbon tetrachloride produced less urea than controls (controls : 0.40 ± 0.03 ; cirrhotic 0.25 ± 0.02 μmole/min/g of wet liver weight ; P < 0.005) at infusion rates of NH₄Cl, which resulted in ammonia levels approximately twice the K_m value. Simultaneously performed taurocholate transport studies also revealed significant functional differences between cirrhotic and control livers. In summary, this study delineates a model to evaluate the kinetics of urea synthesis from NH₄Cl in the isolated perfused rat liver. It was found that the livers of rats with CCl₄-induced cirrhosis exhibited impaired ammonia utilization and urea production together with abnormalities of taurocholate transport.