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Brain Metabolism in Hepatic Encephalopathy and Hyperammonemia

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Cirrhosis, Hyperammonemia, and Hepatic Encephalopathy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 341))

Abstract

In the United States of America liver failure is the sixth leading cause of death in persons aged 25–65 years. Liver failure may occur within days as a result of fulminant hepatic necrosis or over many years in chronic conditions such as alcoholic fatty liver or cirrhosis. When the liver fails, or when blood is shunted around a cirrhotic liver directly from the intestines into the systemic circulation, brain function deteriorates: a disorder known as hepatic encephalopathy [1,18, 36,47, 53]. This syndrome is manifest by signs that range from a rapidly developing sequence of delirium, convulsions and coma in fulminant hepatic necrosis to a more gradually developing intellectual impairment that may lead to stupor and coma in patients with chronic liver disease. The latter form is more prevalent and may affect several millions of people to some degree [34, 441].

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References

  1. Adams, R. D., and Foley, J. M., 1953, The neurological disorder associated with liver disease, Res. Publ. Assoc. Nerve. Ment. Dis. 32:198–237.

    CAS  Google Scholar 

  2. Bachmann, C., and Colombo, J. P., 1984, Increase of tryptophan and 5-hydroxyindole acetic acid in the brain of ornithine carbamoyltransferase deficient sparse-fur mice, Pediatr. Res. 18:372–375.

    Article  PubMed  CAS  Google Scholar 

  3. Benjamin, A. M., 1881, Control of glutaminase activity in rat brain cortex in vitro, influence of glutamate, phosphate, ammonium, calcium and hydrogen ions, Brain Res. 208:363–377.

    Article  Google Scholar 

  4. Bradford, H. F., and Ward, H. K., 1975, Glutamine as a metabolic substrate for isolated nerve-endings: inhibition by ammonium ions, Biochem. Soc. Trans. 3:1223–1226.

    CAS  Google Scholar 

  5. Bradford, H. F., Ward, H. K., and Thomas, A. J., 1978, Glutamine-A major substrate for nerve endings, J. Neurochem. 30:1453–1459.

    Article  PubMed  CAS  Google Scholar 

  6. Butterwork, R. F., Giguere, J. F., Michaud, J., Lavoie, J., and Pomier-Layrargues, G., 1987, Ammonia: Key factor in the pathogenesis of hepatic encephalopathy, Neurochem. Pathol. 6:1–12.

    Article  Google Scholar 

  7. Butterworth, R. F., Lavoie, J., Giguere, J. F., Layrargues, G. P., and Bergeron, M., 1987, Cerebral GABA-ergic and glutamatergic function in hepatic encephalopathy, Neurochem. Pathol. 6:131–144.

    Article  PubMed  CAS  Google Scholar 

  8. Cavanagh, J. B., and Kyu, M. H., 1971, Type II Alzheimer change experimentally produced in astrocytes in the rat, J.Neurol. Sci. 12:63–75.

    Article  PubMed  CAS  Google Scholar 

  9. Cooper, A. J., and Plum, F., 1987, Biochemistry and physiology of brain ammonia, Physiol. Rev. 67:440–519.

    PubMed  CAS  Google Scholar 

  10. DeJoseph, M. R., and Hawkins R. A., 1991, Glucose consumption decreases throughout the brain only hours after portacaval shunting, Am. J. Physiol. 260:E613–E619.

    PubMed  CAS  Google Scholar 

  11. Elsass, P., Lund, Y., and Ranek, L., 1978, Encephalopathy in patients with cirrhosis of the liver. A neuro-psychological study, Scand. J. Gastroenterol. 13:241–247.

    Article  PubMed  CAS  Google Scholar 

  12. Gilbestadt, S. J., Gilberstadt, H., Zieve, L., Buegel, B., Collier Jr, R. O., and McClain, C. J., 1980, Psychomotor performance defects in cirrhotic patients without overt encephalopathy, Arch. Intern. Med. 140:519–521.

    Article  Google Scholar 

  13. Hamberger, A., Hedquist, B., and Nystrom, B., 1979, Ammonium ion inhibition of evoked release of endogenous glutamate from hippocampal slices, J. Neurochem. 33:1295–1302.

    Article  PubMed  CAS  Google Scholar 

  14. Hawkins, R. A., and Jessy, J., 1991, Hyperammonemia does not impair brain function in the absence of glutamine hesis, Biochem. J. 277:697–703.

    PubMed  CAS  Google Scholar 

  15. Hawkins, R. A., Jessy, J., Mans A. M., and De Joseph, M. R., 1992, Effect of reducing brain glutamine synthesis on metabolic signs of hepatic encephalopathy, J Neurochem. In press.

    Google Scholar 

  16. Hawkins, R. A., and Mans, A. M., 1989, Brain energy metabolism in hepatic encephalopathy. In: Hepatic Encephalopathy, edited by Butterworth, R. F., and Pomier-Layrargues, G., 1989, Clifton, NJ: Humana Press Inc., p. 159–176.

    Chapter  Google Scholar 

  17. Hourani, B. T., Hamlin, E. M., and Reynolds, T. B., 1971, Cerebrospinal fluid glutamine as a measure of hepatic encephalopathy, Arch. Intern. Med. 127:1033–1036.

    Article  PubMed  CAS  Google Scholar 

  18. Hoyumpa Jr., A. M., Desmond, P. V., Avant, G. R., Roberts, R. K.,and Schenker, S., 1979, Hepatic encephalopathy, Gastroenterology, 76:184–195.

    PubMed  Google Scholar 

  19. James, J. H., Escourrou, J., and Fischer, J. E., 1978, Blood-brain neutral amino acid transport activity is increased after portacaval anastomosis, Science 200:1395–1397.

    Article  PubMed  CAS  Google Scholar 

  20. James, J. H., Hodgman, J. M., Funovics, J. M., and Fischer, J. E., 1976, Alterations in brain octopamine and brain tyrosine following portacaval anastomosis in rats. J. Neurochem. 27: 223–227.

    Article  PubMed  CAS  Google Scholar 

  21. Jeppsson, B., James, J. H., Edwards, L. L., and Fischer, J. E., 1985, Relationship of brain glutamine and brain neutral amino acid concentrations after portacaval anastomosis in rats, Eur. J. Clin. Invest. 15:179–187.

    Article  PubMed  CAS  Google Scholar 

  22. Jessy, J., DeJoseph, M. R., and Hawkins, R. A., 1991, Hyperammonemia depresses glucose consumption throughout brain. Biochem. J. 277:693–696.

    PubMed  CAS  Google Scholar 

  23. Jessy, J., Mans, A. M., DeJoseph, M. R., and Hawkins, R. A., 1990, Hyperammonemia causes man of the changes found after portacaval shunting, Biochem. J. 272:311–317.

    PubMed  CAS  Google Scholar 

  24. Jonung, T., Rigotti, P., Jeppsson, B., James, J. H., Peters J. C., and Fischer, J. E., 1984, Methionine sulfoximine prevents the accumulation of large neutral amino acids in brain of hyperammonemic rats, J. Surg. Res. 36:349–353.

    Article  PubMed  CAS  Google Scholar 

  25. Krebs, H. A., 1936, Metabolism of amino acids, IV, The synthesis of glutamine animal tissue, Biochem. J. 29:1951–1969.

    Google Scholar 

  26. Lockwood, A. H., 1987, Metabolic encephalopathies: opportunities and challenges. J. Cereb. Blood Flow Metab. 7:523–526.

    Article  PubMed  CAS  Google Scholar 

  27. Mans, A. M., Biebuyck, J. F., Davis, D.W., and Hawkins, R. A., 1984, Portacaval anastomosis: brain and plasma metabolite abormalities and the effect of nutritional therapy, J. Neurochem. 43:697–705.

    Article  PubMed  CAS  Google Scholar 

  28. Mans, A. M., Biebuyck, J. F., and Hawkins, R. A., 1983, Ammonia selectively stimulates neutral amino acid transport across blood-brain barrier, Am. J. Physiol. 245:C74–C77.

    PubMed  CAS  Google Scholar 

  29. Mans, A. M., Biebuyck, J. F., Saunders, S. J., Kirsch, R. E., and Hawkins, R. A., 1979, Tryp tophan transport across the blood-brain barrier during acute hepatic failure, J. Neurochem. 33:409–418.

    Article  PubMed  CAS  Google Scholar 

  30. Mans, A. M., Biebuyck, J. F., Shelly, K., and Hawkins, R. A., 1982, Regional blood-brain barrier permeability to amino acids after portacaval anastomosis, J. Neurochem. 38:705–717.

    Article  PubMed  CAS  Google Scholar 

  31. Mans, A. M., DeJoseph, M. R., Davis, D. W., Viña, J. R., and Hawkins, R. A., 1990, Early establishment of cerebral dysfunction after portacaval shunting, Am. J. Physiol. 258:E104–E110.

    Google Scholar 

  32. Mans, A. M., and Hawkins, R. A., 1986, Brain monoamines after portacaval anastomosis, Metab. Brain Dis. 1:45–52.

    Article  PubMed  CAS  Google Scholar 

  33. Matheson, D. F., and Van den Berg, C. J., 1975, Ammonia and brain glutamine: inhibition of glutamine degradation by ammonia, Biochem. Soc. Trans. 3:525–528.

    PubMed  CAS  Google Scholar 

  34. Mendenhall, D. L., 1981, Alcoholic Hepatitis. Clin. Gastroenterol. 10:417–441.

    PubMed  CAS  Google Scholar 

  35. Norenberg, M. D., 1979, The distribution of glutamine synthetase in the rat central nervous system, J. Histochem. Cytochem. 27:756–762.

    Article  PubMed  CAS  Google Scholar 

  36. Plum, F., and Hindfelt, B., 1976, The neurological complications of liver disease. In: Metabolic and Deficiency Diseases of the Nervous System. Part I, edited by Vinken, P. J., Bruyn G. W., and Klawans, H. L., 1976, New York: American Elsevier Publishing Co. Inc. p. 349–377.

    Google Scholar 

  37. Raabe, W., 1982, Ammonia and postsynaptic inhibition in cat motor cortex. In: Physiology and Pharmacology of Epileptogenic Phenomena, edited by Klee, M. R., Lux, H. D., and Speckmann, E. J., New York: Raven Press, p. 73–80.

    Google Scholar 

  38. Raabe, W., 1989, Ammonium decreases excitatory synaptic transmission in cat spinal cord in vivo, J. Neurophysiol. 62:1461–1473.

    PubMed  CAS  Google Scholar 

  39. Raabe, W., 1989, Neurophysiology of ammonia intoxication. In: Hepatic Encephalopathy: Pathophysiology and Treatment, edited by Butterworth, R., and Pomier-Layrargues, G., Clifton, NJ: Humana Press, Inc., p.49–77.

    Google Scholar 

  40. Raabe, W., 1991, Effects of NH4 + on the function of the CNS, Adv. Exp. Med. Biol. 272:89–98.

    Google Scholar 

  41. Rigotti, P., Jonung, T., Peters, J. C., James, J. H., and Fischer, J. E., 1985, Methionine sulfoximine prevents the accumulation of large neutral amino acids in brain of portacaval-shunted rats, J. Neurochem. 44:929–933.

    Article  PubMed  CAS  Google Scholar 

  42. Rikkers, L., Jenko, P., Rudman, D., and Freides, D., 1978, Subclinical hepatic encephalopathy: detetion, prevalence, and relationship to nitrogen metabolism. Gastroenterology. 75:462–469.

    PubMed  CAS  Google Scholar 

  43. Sarna, G. S., Bradbury, M. W., Cremer, J. E., Lai, J. C., and Teal, H. M., 1979, Brain metabolism and specific transport at the blood-brain barrier after portacaval anastomosis in the rat, Brain Res. 160:69–83.

    Article  PubMed  CAS  Google Scholar 

  44. Scheig, R., 1991, That demon rum. Am. J. Gastroenerol. 86:150–152.

    CAS  Google Scholar 

  45. Schenker, S., and Brady, C. E., 1990, Pathogenesis of hepatic encephalopathy. In: Hepatic Encephalopathy: Management with Lactulose and Related Carbohydrates, edited by Conn, H. O., and Bircher, J., East Lansing, MI: Medi-Ed Press, p. 15–30.

    Google Scholar 

  46. erlock, S., 1958, Pathogenesis and management of hepatic coma, Am. J. Med. 24:805–813.

    Article  Google Scholar 

  47. Sherlock, S., Summerskill, W. H. J., White, L. P., and Phear, E. A., 1954, Portalsystemic encephalopathy. Neurological complications of liver disease, Lancet 2:453–457.

    Article  Google Scholar 

  48. Soeters, P. B., van Leuwen, P. A. M., and van Berlo, C. L. H., 1989, Nitrogen metabolism in the gut. In: Hepatic Encephalopathy: Management with lactulose and related carbohydrates, edited by Conn, H. O., and Bircher, J., East Lansing, MI: Medi-Ed Press, p. 31–40.

    Google Scholar 

  49. Vergara, F., Plum, F., and Duffly, T. E., 1974, a-Ketoglutaramate: Increased concentrations in the cerebrospinal fluid of patients in hepatic coma. Science 183:81–83.

    Article  PubMed  CAS  Google Scholar 

  50. Weil-Malherbe, H., 1950, Significance of glutamic acid for the metabolism of nervous tissue, Physiol. Rev. 30:549–568.

    PubMed  CAS  Google Scholar 

  51. Windmueller, H. G., 1984, Metabolism of vascular and luminal glutamine by intestinal mucosa in vivo. In: Glutamine Metabolism in Mammalian tissues, edited by Gayssubgerm, D., and Sies, H., Berlin: Springer-Verlag, p. 61–77.

    Chapter  Google Scholar 

  52. Zamora, A. J., Cavanagh, J. B., and Kyu, M. H., 1973, Ultrastructural responses of the astrocytes to portacaval anastomosis in the rat, J. Neurol. Sci. 18:25–45.

    Article  PubMed  CAS  Google Scholar 

  53. Zieve, L., 1979, Hepatic encephalopathy: summary of present knowledge with an elaboration on recent developments. In: Progress in Liver Diseases, edited by Popper, H., and Schaffner, F., New York: Grune and Stratton, p. 327–341.

    Google Scholar 

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Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Health Sciences/The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL, 60064, USA

    Richard A. Hawkins & Anke M. Mans

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  1. Richard A. Hawkins
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  2. Anke M. Mans
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  1. Instituto de Investigaciones Citologicas, Valencia, Spain

    Santiago Grisolía  & Vicente Felipo  & 

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Hawkins, R.A., Mans, A.M. (1993). Brain Metabolism in Hepatic Encephalopathy and Hyperammonemia. In: Grisolía, S., Felipo, V. (eds) Cirrhosis, Hyperammonemia, and Hepatic Encephalopathy. Advances in Experimental Medicine and Biology, vol 341. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2484-7_2

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  • DOI: https://doi.org/10.1007/978-1-4615-2484-7_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6058-2

  • Online ISBN: 978-1-4615-2484-7

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