Elevated plasma ammonia level in hepatic cirrhosis: role of glucagon.
Elevated plasma ammonia level in hepatic cirrhosis has been attributed to a lack of conversion of enteric ammonia into urea or to its entry into systemic circulation via portasystemic shunting, or to both. It is exaggerated by excessive protein intake. Because hyperglucagonemia is well documented in cirrhosis and a protein meal is an effective glucagon secretagogue, plasma glucose, insulin, glucagon, and ammonia levels were determined in 50 cirrhotic patients after an overnight fast. Effects of a protein meal were also assessed in 20 of these patients. Plasma glucose was normal and remained unaltered after a protein meal. Insulin, glucagon, and ammonia levels were elevated, but only in patients with advanced liver dysfunction. Ammonia levels correlated significantly with glucagon (r = 0.61, p less than 0.001), but not with insulin or glucose levels. Insulin and glucagon levels rose after a protein meal in all patients and controls; whereas a significant rise in the ammonia level occurred only in decompensated cirrhotics. Elevation of the ammonia level was significantly correlated with fasting glucagon (r = 0.54, p less than 0.05), as well as with glucagon response (r = 0.65, p less than 0.01), but not with basal insulin or insulin response. Furthermore, the rise in ammonia level occurred too early to be accounted for by enteric generation. Finally, direct effects of glucagon administration on plasma glucose and serum ammonia were examined in 15 cirrhotic patients. Glucose response was significantly blunted in cirrhotic patients as compared with normal subjects, whereas serum ammonia rose promptly but only in cirrhotics, with maximum rise being noted in cirrhotic patients with advanced liver dysfunction. This study, therefore, suggests that hyperglucagonemia may contribute significantly to hyperammonemia in hepatic cirrhosis.
D000328:Adult; D000641:Ammonia / Q000097:blood*; D004044:Dietary Proteins / Q000008:administration & dosage; D005215:Fasting; D005934:Glucagon / Q000097:blood / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged
D004044:Dietary Proteins; D007328:Insulin; D000641:Ammonia; D005934:Glucagon