Skip to main content
Log in

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

  • Original Articles
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

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 ratio 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Zieve L: Hepatic encephalopathy: Summary of present knowledge with an elaboration on recent developments.In Progress in Liver Diseases, Vol VI, H Popper, F Schaffner (eds.). New York, Grune & Stratton, 1979, pp 327–341

    Google Scholar 

  2. James JH, Jeppson B, Ziparo V, Fischer JE: Hyperammonaemia, plasma amino acid imbalance, and blood-brain amino acid transport: A unified theory of portal-systemic encephalopathy. Lancet 2:772–775, 1979

    Google Scholar 

  3. Soeters PB, Fischer JE: Insulin, glucagon, amino acid imbalance, and hepatic encephalopathy. Lancet 2:880–882, 1976

    Google Scholar 

  4. Conn HO: Ammonia tolerance as an index of portal-systemic collateral circulation in cirrhotics. Gastroenterology 41:97–106, 1961

    Google Scholar 

  5. Zoli M, Marchesini G, Angiolini A, Dondi C, Bianchi FB, Pisi E: Plasma amino acids as markers of liver dysfunction in cirrhotics. Scand J Gastroenterol 16:689–692, 1981

    Google Scholar 

  6. Paquet KJ, Albrecht M, Kliems G: Sclerotherapy of the oesophageal varices—prophylactically—with acute bleeding—at intervals?In Operative Endoskopie 1979, L Demling, W Rösch (eds). Berlin, Acron Verlag, 1979, pp 33–46

    Google Scholar 

  7. Conn HO: Ammonia tolerance in liver disease. J Lab Clin Med 55:855–861, 1960

    Google Scholar 

  8. Seligson D, Hirahara K: The measurement of ammonia in whole blood, erythrocytes, and plasma. J Lab Clin Med 49:962–974, 1957

    Google Scholar 

  9. Marchesini G, Forlani G, Zoli M, Angiolini A, Scolari MP, Bianchi FB, Pisi E: Insulin and glucagon levels in liver cirrhosis: Relationship with the plasma amino acid imbalance of chronic hepatic encephalopathy. Dig Dis Sci 24:594–601, 1979

    Google Scholar 

  10. Berger M, Zimmermann-Telschow H, Berchtold P, Drost H, Muller WA, Gries FA, Zimmermann H: Blood amino acid levels in patients with insulin excess (functioning insulinoma) and insulin deficiency (diabetic ketosis). Metabolism 27:793–799, 1978

    Google Scholar 

  11. Fischer JE, Baldessarini RJ: Pathogenesis and therapy of hepatic coma.In Progress in Liver Diseases, Vol V, H Popper, F Schaffner (eds.). New York, Grune & Stratton, 1976, pp 363–397

    Google Scholar 

  12. Mashford ML, Mahon WA, Chalmers TC: Studies of the cardiovascular system in the hypotension of liver failure. N Engl J Med 267:1071–1074, 1962

    Google Scholar 

  13. Dodsworth JM, James JH, Cummings MG, Fischer JE: Depletion of brain norepinephrine in acute hepatic coma. Surgery 75:811–820, 1974

    Google Scholar 

  14. Fischer JE, Baldessarini RJ: False neurotransmitters and hepatic failure. Lancet 2:75–79, 1971

    Google Scholar 

  15. Lam KC, Tall AR, Goldstein GB, Mistilis SP: Role of a false neurotransmitter, octopamine, in the pathogenesis of hepatic and renal encephalopathy. Scand J Gastroenterol 8:465–472, 1973

    Google Scholar 

  16. Cangiano C, Calcaterra V, Cascino A, Rossi-Fanelli F, Capocaccia L: The role of the false neurotransmitters, octopamine and phenylethanolamine, in human hepatic encephalopathy. Rendic Gastroenterol 9:189–193, 1977

    Google Scholar 

  17. Knell AJ, Davidson AR, Williams R, Kantamaneni BD, Curzon G: Dopamine and serotonin metabolism in hepatic encephalopathy. Br Med J 1:549–551, 1974

    Google Scholar 

  18. Baldessarini RJ, Karobath M: Biochemical physiology of central synapses. Annu Rev Physiol 35:273–304, 1973

    Google Scholar 

  19. Bessman SP, Bessman AW: The cerebral and peripheral uptake of ammonia in liver disease with a hypothesis for the mechanism of hepatic coma. J Clin Invest 34:622–628, 1955

    Google Scholar 

  20. Berl S: Cerebral amino metabolism in hepatic coma. Exp Biol Med 4:71–84, 1971

    Google Scholar 

  21. Strombeck DR, Rogers Q, Stern JH: The effects of intravenous ammonia infusion on plasma levels of amino acids, glucagon and insulin in dogs. Gastroenterology 74:1165, 1978 (abstract)

    Google Scholar 

  22. Doeffel M, Schlienger JL, Bockel R: Lack of correlation between insulin, glucagon and plasma amino acid imbalance in alcoholic cirrhosis. Proceedings of the 15th Meeting of the European Association for the Study of the Liver (EASL), Belgrade, Sava Centar, 1980, p 30 (abstract)

  23. Marchesini G, Zoli M, Dondi C, Cecchini L, Angiolini A, Bianchi FB, Pisi E: Prevalence of subclinical hepatic encephalopathy in cirrhotics and relationship to plasma amino acid imbalance. Dig Dis Sci 25:763–768, 1980

    Google Scholar 

  24. Sherwin R, Joshi P, Hendler R, Felig P, Conn HO: Hyperglucagonemia in Laennec's cirrhosis. The role of portalsystemic shunting. N Engl J Med 290:239–242, 1974

    Google Scholar 

  25. Sherwin RS, Fischer M, Bessoff J, Snyder N, Hendler R, Conn HO, Felig P: Hyperglucagonaemia in cirrhosis: Altered secretion and sensitivity to glucagon. Gastroenterology 74:1224–1228, 1978

    Google Scholar 

  26. Rosen HM, Yoshimura N, Hodgman JM, Fischer JE: Plasma amino acid patterns in hepatic encephalopathy of differing etiology. Gastroenterology 72:483–487, 1977

    Google Scholar 

  27. Cascino A, Cangiano C, Calcaterra V, Rossi-Fanelli F, Capocaccia L: Plasma amino acid imbalance in patients with liver disease. Am J Dig Dis 23:591–598, 1978

    Google Scholar 

  28. White LP, Phear EA, Summerskill WHJ, Sherlock S: Ammonium tolerance in liver disease: Observations based on catheterization of the hepatic veins. J Clin Invest 34:158–168, 1955

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marchesini, G., Zoli, M., Dondi, C. et al. Ammonia-induced changes in pancreatic hormones and plasma amino acids in patients with liver cirrhosis. Digest Dis Sci 27, 406–412 (1982). https://doi.org/10.1007/BF01295648

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01295648

Keywords

Navigation