Ammonia-induced changes in pancreatic hormones and plasma amino acids in patients with liver cirrhosis

Abstract

The contribution of hyperammonemia to plasma amino acid imbalance in patients with liver disease was assessed in 10 subjects with chronic hepatitis and in 17 advanced cirrhotics. Insulin, glucagon, and plasma amino acids were determined both in the basal state and 45 min after oral ammonium chloride, at doses used in the ammonia-tolerance test. In cirrhotics, ammonia increased to 3 times basal values, in association with a rise in insulin and, more marked, in glucagon. Aromatic amino acids and free tryptophan further increased, while a significant fall in branched-chain amino acids and glutamate was observed. The increase in ammonia levels strongly correlated with the increase in glucagon (r = 0.707). Two patients, with large esophageal varices, showed signs of disturbed consciousness, in association with a marked rise in ammonia and in the ration of free tryptophan to the sum of neutral amino acids. In patients with chronic hepatitis, whose ammonia levels rose slightly, minor variations in pancreatic glucoregulatory hormones and plasma amino acids were observed, as also happened in 10 healthy subjects following ammonium chloride ingestion. Our data fit with the hypothesis that the plasma amino acid imbalance of cirrhotics may be partly due to ammonia-induced changes in pancreatic hormones.

Glucose metabolism in cirrhosis: A review with some perspectives for the future

“…Thus, after intravenous infusion of ar-ginine1O3 and alanine,lO1 as well as following the ingestion of a protein meal,lo7 peripheral glucagon levels increased two-to threefold greater in cirrhotic compared to control subjects yet no difference in the plasma glucose increment between the two groups was observed. However, in these studies plasma insulin levels increased significantly more in the cirrhotic group, 101,103,105 making it difficult to separate the stimulatory effect of glucagon on hepatic glucose production from the suppressive effect of insulin. More direct evidence for hepatic resistance to gluagon is provided from the studies of Keller et al 67 and Greco et a1.1°8 These investigators infused somatostatin to suppress both endogenous glucagon and insulin secretion and infused glucagon exogenously to achieve comparable plasma levels in control and cirrhotic patients.…”

Cerebrospinal Fluid Lactate in Patients with Hepatic Encephalopathy

“…Hyperammon emia has been assumed to be an important factor for the disturbance of cerebral metab olism in hepatic encephalopathy, although the precise mechanism of neuronal cell dys function is still under discussion [1][2][3][4][5]. Bessman and Bessman [6] proposed a hypothesis that brain takes up excessive ammonia which causes depletion of cerebral alphaketoglutarate and later impairment of the Krebs cycle function.…”

Effect of ammonia on plasma and cerebrospinal fluid amino acids in dogs with and without portacaval anastomoses

“…After ammonium acetate infusion into the dogs with PCS the plasma levels of phenylalanine and tyrosine increased, as has been reported in patients with liver cirrhosis after an oral load of ammonium chloride [14]. The lowering effect of ammonia salt administration on BCAA plasma levels has been described in dogs [12,30] and in patients with cirrhosis of the liver [6,14]. Whether the decrease of BCAA plasma levels is due to an ammonia-induced increased secretion of insulin, or to an altered amino acid metabolism in the muscle induced by other factors during ammonia intoxication, is still being debated [6,10].…”

“…After ammonium acetate infusion into the dogs with PCS the plasma levels of phenylalanine and tyrosine increased, as has been reported in patients with liver cirrhosis after an oral load of ammonium chloride [14]. The lowering effect of ammonia salt administration on BCAA plasma levels has been described in dogs [12,30] and in patients with cirrhosis of the liver [6,14].…”