Abstract
Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome characterized by global CNS dysfunction reSUlting in impaired consciousness and coma. The association of the syndrome with acute or chronic liver failure implicates a plethora of metabolic abnormalities and gut-derived toxins in its pathogenesis. Thus, it is difficult to ascribe the neurological and psychiatric manifestations of HE to the presence of a single agent or changes in a particular metabolic pathway. The manifestations of HE are determined by two principle components of the underlying liver disease: hepatocellular failure and systemic shunting of portal venous contents (BASILE et al. 1991 b). Significant portal venous shunting is often found in chronic liver disease. HE occurs most frequently in this setting, where it is a milder, more persistent and episodic variant of the syndrome. In contrast, fulminant hepatic failure (FHF) has no vascular component. HE associated with FHF shows an acute onset with delirium progressing to deep coma. While delirium and seizures are generally uncommon in HE, they may occur during the rapid evolution of HE due to FHF (PAPPAS 1986). Although some of the characteristics of HE associated with acute or chronic liver failure result from fundamental differences in the mechanism of pathogenesis, many findings regarding the pathogenesis and treatment of the syndrome are held in common. Finally, it is important to recognize that while many of the animal models of liver failure used in research emphasize one or the other component of liver failure, most clinical cases tend to have a mixture of both. Although a single, perfect animal model of this syndrome does not exist, the animal models in use have nonetheless provided valuahle insights into the pathogenesis of HE and allowed for the testing of new therapeutic modalities.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Albrecht J. Rafalowska U (1987) Enhanced potassium stimulated y-aminobutyric acid release by astrocytes derived from rats with hepatogenic encephalopathy. J Neurochem 49:9–11
Albrecht J, Hilgier W, Rafalowska U (1990) Activation of arginine metabolism to glutamate in rat brain synaptosomes in thioacetamide-induced hepatic encephalopathy: an adaptive response? J Neurosci Res 25:125–130
Alger BE, NicolI RA (1983) Ammonia does not selectively block IPSPs in rat hippocampal pyramidal cells. J Neurophys 49:1381–1391
Baraldi M, Zeneroli ML, Ricci P, Caselgrandi E, Ventura E (1983) Down regulation of striatal dopamine receptors in experimental hepatic encephalopathy. Life Sci 32:1417–1425
Basile AS, Gammal S, Mullen K, Jones EA, Skolnick P (1988) Differential responsiveness of cerebellar Purkinje neurons to GABA and benzodiazepine receptor ligands in an animal model of hepatic encephalopathy. J Neurosci 8:2414–2421
Basile AS, Gammal SH, Jones EA, Skolnick P (1989) The GABAA receptor complex in an experimental model of hepatic encephalopathy: evidence for elevated levels of an endogenous benzodiazepine receptor ligand. J Neurochem 53:1057–1063
Basile AS, Ostrowski NL, Gammal SH, Jones EA, Skolnick P (1990) The GABAA receptor complex in hepatic encephalopathy: autoradiographic evidence for the presence of an endogenous benzodiazepine receptor ligand. Neuropsychopharmacology 3:61–71
Basile AS, Hughes RD, Harrison PM, Murata Y, Pannell L, Jones EA, Williams R, Skolnick P (1991a) Elevated brain concentrations of 1,4-benzodiazepines in fulminant hepatic failure. N Engl J Med 325:473–478
Basile AS, Jones EA, Skolnick P (1991b) The pathogenesis and treatment of hepatic encephalopathy: evidence for the involvement of benzodiazepine receptor ligands. Pharmacol Rev 43:27–71
Basile AS, Harrison PM, Hughes RD, Gu ZQ, Pannell L, McKinney A, Jones EA, Williams R (1994a) Relationship between plasma benzodiazepine receptor ligand concentrations and severity of hepatic encephalopathy. Hepatology 19:112–121
Basile AS, Saito K, Al-Mardini H, Record CO, Hughes RD, Williams R, Li Y, Heyes MP (1995a) The relationship between plasma and brain quinolinic acid levels and the severity of hepatic encephalopathy. Gastroenterology 108:818–823
Basile AS, Saito K, Li Y, Heyes MP (1995b) The relationship between plasma and brain quinolinic acid levels and the severity of hepatic encephalopathy in animal models of fulminant hepatic failure. J Neurochem 64:2607–2614
Bassett ML, Mullen KD, Scholz B, Fenstermacher JD, Jones EA (1990) Increased brain uptake of y-aminobutyric acid in a rabbit model of hepatic encephalopathy. Gastroenterology 98:747–757
Bengtsson F, Bugge M, Hall H, Nobin A (1989) Brain 5-HT1 and 5-HT2 binding sites following portacaval shunt in the rat. Res Exp Med 189:249–256
Bergeron M, Pomier-Layrargues G, Butterworth RF (1989a) Aromatic and branched chain amino acids in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. Metab Brain Dis 4:169–176
Bergeron M, Reader T A, Layrargues GP, Butterworth RF (1989b) Monoamines and metabolites in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. Neurochem Res 14:853–859
Bernthal RE, Hays A, Tarter RE, VanThiel D, Lecky J, Hegedus A (1987) Cerebral CT scan abnormalities in cholestatic and hepatocellular disease and their relationship to neuropsychologic test performance. Hepatology 7:107–114
Blom HJ, Ferenci P, Grimm G, Yap SH, Tangerman A (1991) The role ofmethanethiol in the pathogenesis of hepatic encephalopathy. Hepatology 13:445–454
Butterworth RF, Giguere JF (1986) Cerebral amino acids in portal systemic encephalopathy: lack of evidence for altered y-aminobutyric (GABA) function. Metab Brain Dis 1:221–228
Butterworth RF, Lavoie J, Peterson C, Cotman CW, Szerb JC (1989) Excitatory amino acids and hepatic encephalopathy. In: Butterworth RF, Pomier-Layrargues G (eds) Hepatic encephalopathy. Pathophysiology and treatment. Humana, Clifton, p 417
Butterworth RF, Lavoie J, Szerb JC (1991) Effect uf purtacaval anastomusis on electrically stimulated release of glutamate from rat hippocampal slices. J Neurochem 56:1481–1484
Casellas P, Sagales T, Calzada MD, Accarino A, Vargas V, Guarneri L (1985) Visual evoked potetials in hepatic encephalopathy. Lancet 1:394–395
Cohn R, Castell DO (1966) The effect of acute hyperammonemia on the electroencephalogram. J Lab Clin Med 68:195–205
Conn HO (1993) Hepatic encephalopathy. In: Schiff L, Schiff ER (eds) Diseases of the liver, vol 2. Lippincott, Philadelphia, p 1036
Cooper AJ, Plum F (1987) Biochemistry and physiology of brain ammonia. Physiol Rev 67:440
Crossley IR, Wardle EMM, Williams R (1983) Biochemical mechanisms of hepatic encephalopathy. Clin Sci 64:247–252
Davies MG, Rowan MJ, MacMathuna P, Keeling PWN, Weir DG, Feely J (1990) The auditory P300 event-related potential: an objective marker of the encephalopathy of chronic liver disease. Hepatology 12:688–694
DeGroot GH, Schalm SW, De Vlieger M, van der Rijt CCD (1985) Objective measurement of hepatic encephalopathy by means of spectral analysis of the electroencephalogram (EEG). Brain Res 360:298–303
deKnegt RJ, Kornhuber J, Schalm SW, Rusche K, Riederer P, Tan J (1993) Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate receptor during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. Metab Brain Dis 8:81–94
Diaz-Munoz M, Tapia R (1988) Regional brain GABA metabolism and release during hepatic coma produced in rats chronically treated with carbon tetrachloride. Neurochem Res 13:37–44
Dombro RS, Hutson DG, Norenberg MD (1993) The action of ammonia on astrocyte glycogen and glycogenolysis. Mol Chern Neuropathol 19:259–268
Ferenci P, Pappas SC, Munson PJ, Jones EA (1984a) Changes in glutamate receptors on synaptic membranes associated with hepatic encephalopathy or hyperammonemia in the rabbit. Hepatology 4:25–29
Ferenci P, Pappas SC, Munson PJ, Henson K, Jones EA (1984b) Changes in the status of neurotransmitter receptors in a rabbit model of hepatic encephalopathy. Hepatology 4:186–191
Ferenci P, Jones EA, Hanbauer I (1986) Lack of evidence for impaired dopamine receptor function in experimental hepatic encephalopathy. Neurosci Lett 65:60–64
Ferenci P, Riederer P, Jellinger K, Schafer DF, Jones EA (1988) Changes in cerebral receptors for y-aminobutyric acid in patients with hepatic encephalopathy. Liver 8:225–230
Fitzpatrick SM, Cooper AJL, Hertz L (1988) Effects of ammonia and /3-methylene-DLaspartate on the oxidation of glucose and pyruvate by neurons and astrocytes in primary culture. J Neurochem 51:1197–1203
Flannery DB, Hsia YE, Wolf B (1982) Current status of hyperammonemia syndromes. Hepatology 2:495–506
Gabuzda G, Phillips GB, Davidson CS (1952) Reversible toxic manifestations in patients with cirrhosis of the liver given cation-exchange resins. N Engl J Med 246: 124–130
Gammal S, Basile AS, Geller D, Skolnick p, Jones EA (1990) Reversal of the behavioral and electrophysiological abnormalities of an animal model of hepatic encephalopathy by benzodiazepine receptor ligands. Hepatology II :371–378
Gazzard BG, Price H, Dawson AM (1986) Detection of hepatic encephalopathy. Postgrad Med J 62:163–166
Gjedde A, Lockwood AH, Duffy TE, Plum F (1978) Cerebral blood flow and metabolism in chronically hyperammonemic rats: effect of an acute ammonia challenge. Ann Neurol 3:325–330
Gregorios JB, Mozcs LW, Norenberg LOB, Norenberg MD (1985a) Morphologic effects of ammonia on primary astrocyte cultures.1. Light microscopic studies.J Neuropathol Exp Neurol 44:391–403
Gregorios JB, Mozes LW, Norenberg MD (l985b) Morphologic effects of ammonia on primary astrocyte cultures. II. Electron microscopic studies. J Neuropathol Exp Neurol 44:404–414
Hawkins RA, Jessy J (1991) Hyperammonemia does not impair brain function in the absence of net glutamine synthesis. Biochem J 277:697–703
Hawkins RA, Jessy J, Mans AM, Dejoseph MR (1993) Effect of reducing brain glutamine synthesis on metabolic symptoms of hepatic encephalopathy. J Neurochem 60:1000–1006
Hertz L, Murthy CR, Lai JC, Fitzpatrick SM, Cooper AJ (1987) Some metabolic effects of ammonia on astrocytes and neurons in primary cultures. Neurochem Pathol 6:97–129
Hindfelt B, Plum F, Duffy TE (1977) Effect of acute ammonia intoxication on cerebral metabolism in rats with porto-caval shunts. J Clin Invest 59:386–394
Horowitz ME, Schafer DR, Molnar P, Jones EA, Blasberg EG, Patlak CS, Waggoner JS, Fenstermacher JD (1983) Increased blood-brain barrier transfer in a rabbit model of acute liver failure. Gastroenterology 84:1003–1011
Huet PM, Pomier-Layrargues G, Duguay L, DuSouich P (1981) Blood-brain transport of tryptophan and phenylalanine: effect of portacaval shunt in dogs. Am J Physiol 241:G163–G169
Iles JF, Jack JJB (1980) Ammonia: assessment of its action on postsynaptic inhibition as a cause of convulsions. Brain 103:555–578
James JH, Escourrou J, Fischer JE (1978) Blood-brain neutral amino acid transport activity is increased after portacaval anastomosis. Science 200:1395–1397
Jessy J, Dejoseph MR, Hawkins RA (1991) Hyperammonaemia depresses glucose consumption throughout the brain. Biochem J 277:693–696
Johansson U, Andersson T, Persson A, Eriksson LS (1989)Visual evoked potentiala tool in the diagnosis of hepatic encephalopathy? J Hepatol 9:227–233
Jones DB, Mullen KD, Roessle M, Maynard T, Jones EA (1987) Hepatic encephalopathy: application of visual evoked responses to test hypotheses of its pathogenesis in rats. J Hepatol 4:118–126
Jouvet M (1973) Serotonin and sleep in the cat. In: Barchas J, Usdin E (eds) Serotonin and behavior. Academic Press, New York, p 385
Lavoie J, Giguere J-F, Layrargues GP, Butterworth RF (1987) Amino acid changes in autopsied brain tissue from cirrhotic patients with hepatic encephalop-athy. J Neurochem 49:692–697
Lockwood AH, Ginsberg MD, Rhoades HM, Gutierre MT (1986) Cerebral glucose metabolism after portocaval shunting in the rat. Pattern of metabolism and implications for the pathogenesis of hepatic encephalopathy. J Clin Invest 78:123–131
Loscher W, Kretz FJ, Karavias T, Dillinger U (1991) Marked increases of plasma gamma-aminobutyric acid concentrations in cirrhotic patients with portacaval shunts are not associated with alterations of cerebral functions. Digestion 49:212–220
Maddison JE, Yau D, Stewart P, Farrell GC (1986) Cerebrospinal fluid y-aminobutyric acid levels in dogs with chronic portosystemic encephalopathy. Clin Sci 71:749–753
Maddison JE, Watson WEJ, Dodd PR, Johnston GAR (1991) Alterations in cortical [3H]kainate and a-(3H]amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid binding in a spontaneous canine model of chronic hepatic encephalopathy. J Neurochem 56:1881–1888
Mans AM, Hawkins RA (1986) Brain monoamines after portacaval anastomosis. Metab Brain Dis 1:45–52
Mans AM, Saunders SJ, Kirsch RE, Biebuyck JF (1979) Correlation of plasma and brain amino acid and putative neurotransmitter alterations during acute hepatic coma in the rat. J Neurochem 32:285–292
Michel H, Solere M, Granier P, Cauvet G, Bali JP, Pons F, Bellet-Hermann H (1980) Treatment of cirrhotic hepatic encephalopathy with L-dopa. A controlled trial. Gastroenterology 79:207–211
Miller LG, Greenblatt DJ, Barnhill JG, Shader RI (1988) Chronic benzodiazepine administration. I. Tolerance is associated with benzodiazepine receptor downregulation and decreased y-aminobutyric acidA receptor function. J Pharmacol Exp Ther 246:170–176
Minuk GY, Winder A, Burgess ED, Sargeant EJ (1985) Serum y-aminobutyric acid levels in patients with hepatic encephalopathy. Hepatogastroenterology 32:171–174
Morgan MY, Alonso M, Stanger LC (1989)Lactitol and lactulose for the treatment of subclinical hepatic encephalopathy in cirrhosis patients. J Hepatol 8:208–217
Moroni F, Lombardi G, Carla V, Lal S, Etienne P, Nair NPV (1986a) Increase in the content of quinolinic acid in cerebrospinal fluid and frontal cortex of patients with hepatic failure. J Neurochem 47:1667 -1671
Moroni F, Lombardi G, Carla V, Pellegrini D, Carassale GL, Cortesini C (1986b) Content of quinolinic acid and of other tryptophan metabolites increases in brain regions of rats used as experimental models of hepatic encephalopathy. J Neurochem 46:869–874
Mullen KD, Martin JV, Bassett ML, Mendelson WB, Jones EA (1986)Hepatic encephalopathy: a syndrome modulated by an endogenous benzodiazepine ligand? Hepatology 6:1221
Mullen KD, Szauter KM, Kaminsky-Russ K (1990) “Endogenous” benzodiazepine activity in physiological fluids of patients with hepatic encephalopathy. Lancet II:81–83
Nieto C, Arias J, Alsasua A, Garcia d Jalon PD (1980) Changes in brain oxidative metabolism in rats with portocaval shunt. Experientia 36:1403–1404
Norenberg (1977) A light and electron microscopic study of experimental portalsystemic (ammonia) encephalopathy. Lab Invest 36:618–627
Norenberg LOB, Norenberg MD (1986) Synergism of hepatic coma toxins in primary astrocyte cultures. Proc Int Cong Neuropathol l0:48
Norenberg MD, Mozes LW, Papendick RE, Norenberg LOB (1985) Effect of ammonia on glutamate, GABA and rubidium uptake by astrocytes. Ann Neurol 18:149
Norenberg MD, Baker L, Norenberg LO, Blicharska J, Bruce-Gregorios JH, Neary JT (1991) Ammonia-induced astrocyte swelling in primary culture. Neurochem Res 16:833–836
O’Brien CJ, Wise RJS, O’Grady JG, Williams R (1987) Neurological sequelae in patients recovered from fulminant hepatic failure. Gut 28:93–95
Oei LT, Kuys J, Lombarts AJP, Goor C, Endtz LJ (1979) Cerebrospinal fluid glutamine levels and EEG findings in patients with hepatic encephalopathy. Clin Neurol Neurosurg 81:59–63
Oja SS, Saransaari P, Wysmyk U, Albrecht J (1993) Loss of GABAB binding sites in the cerebral cortex of rats with acute hepatic eneephalopathy. Brain Res 629:355–357
Opolon P (1980)Large-pore hemodialysis in fulminant hepatic failure. In: Brunner G, Schmidt FW (eds) Artificial liver support. Springer, Berlin Heidelberg New York, pp 141–146
Pappas SC (1986) Fulminant hepatic failure. In: Bayless TM (ed) Current therapy in gastroenterology and liver disease, vol 2. Mosby, St Louis, p 383
Pappas SC, Ferenci P, Schafer DF, Jones EA (1984) Visual evoked potentials in a rabbit model of hepatic encephalopathy. II. Comparison of hyperammonemic encephalopathy, postictal coma, and coma induced by synergistic neurotoxins. Gastroenterology 86:546–551
Peterson C, Giguere J-F, Cotman CW, Butterworth RF (1990) Selective loss of Nmethyl-D-aspartate-sensitive I-[3H]glutamate hinding sites in rat brain following portacaval anastomosis. J Neurochem 55:386–390
Plum F, Hindfelt B (1976) The neurological complications of liver disease. In: Vinken PH, Bruyn GW (eds) Handbook of clinical neurology, vol 27. Elsevier. New York, p 349
Pomier-Layrargues G, Giguere JF, Lavoie J, Perney P, Gagnon S, D’Amour M, Wells J, Butterworth RF (1994) Flumazenil in cirrhotic patients in hepatic coma: a randomized double-hlind placebo-controlled crossover trial. Hepatology 19:322–337
Raabe W (1987) Neurophysiology of ammonia intoxication. In: Butterworth R, Pomier-Layrargues G (eds) Hepatic encephalopathy. Pathophysiology and treatment. Humana, Clifton, p 49
Raabe W, Onstad G (1985) Porta-caval shunting changes neuronal sensitivity to ammonia. J Neurol Sci 71:307–314
Record CA, Buxton B, Chase RA, Curzon G, Murray-Lyon IM, Williams R (1976) Plasma and brain amino acids in fulminant hepatic failure and their relationship to hepatic encephalopathy. Eur J Clin Invest 6:387–394
Rossie M, Mullen KD, Jones EA (1989) Cortical benzodiazepine receptor binding in a rabbit model of hepatic encephalopathy: the effect of Triton X-100 on receptor solubilization. Metab Brain Dis 4:203–212
Rothstein JD, Guidotti A, Tinuper P, Cortelli P, Avoni P, Plazzi G, Lugaresi E, Schoch P, Montagna P (1992) Endogenous benzodiazepineteceptor ligands in idiopathic recurring stupor. Lancet 340:1002–1004
Saavedra J (1989) False neurotransmitters. In: Trendelenburg U, Weiner N (eds) Catecholamines’, vol II. Springer, Berlin Herdelberg New York, p 427
Schafer DF, Jones EA (1982) Hepatic encephalopathy and the γ-aminobutyric acid neurotransmitter system. Lancet 1:18–20
Schafer DF, Thakur AK, Jones EA (1980) Acute hepatic coma and inhibitory neurotransmission: increase in y-aminobutyric acid levels in plasma and receptors in brain. Gastroenterology 79:1123
Schafer DF, Pappas SC, Brody LE, Jacobs R, Jones EA (1984) Visual evoked potentials in a rabbit model of hepatic encephalopathy.I Sequential changes and comparisons with drug-induced comas. Gastroenterology 86:540–545
Schafer DRT, Fowler JM, Munson PJ, Thakur AK, Waggoner JG, Jones EA (1983) Gamma-aminobutyric acid and benzodiazepine receptors in an animal model of fulminant hepatic failure. J Lab Clin Med 102:870–880
Scollo-Lavizzari G, Steinmann E (1985) Reversal of hepatic coma by benzodiazepine antagonist (Ro 15–1788). Lancet 1:1324
Sherlock S (1958) Pathogenesis and management of hepatic coma. Am J Med 24:805–813
Sherlock S, Dooley J (1993) Diseases of the liver and biliary system. Blackwell Scientific, London
Steindl P, Ferenci P (1990) Effect of drugs modulating central benzodiazepine receptors on hepatic encephalopathy in rats with thioacetamide-induced liver failure. Gastroenterology 98:A636
Subbalakshmi GYCV, Murthy CRK (1983) Acute metabolic effects of ammonia on the enzymes of glutamate metabolism in isolated astroglial cells. Neurochem lnt 5:593–597
Swain MS, Bergeron M, Audet R, Blei AT, Butterworth RF (1992) Monitoring of neurotransmitter amino acids by means of an indwelling cisterna magna catheter: a comparison of two rodent models of fulminant liver failure. Hepatology 16:1028–1035
Takahashi K, Kameda H, Kataoka M, Sangou K, Harata N, Akaike N (1993) Ammonia potentiates GABAA response in dissociated rat cortical neurons. Neurosci Lett 151:51–54
Tangerman A, Meuwese-Arends MT, VanTongeren JHM (1985) New methods for the release of volatile sulfur compounds from human serum: its determination by Tenax trapping and gas chromatography and its application in liver diseases. J Lab Clin Med 106:175–182
Therrien G, Butterworth RF (1991) Cerebrospinal fluid amino acids in relation to neurological status in experimental portal-systemic encephalopathy. Metab Brain Dis 6:65–74
Tossman U, Delin A, Eriksson S, Ungerstedt U (1987) Brain cortical amino acids measured by intracerebral dialysis in portacaval shunted rats. Neurochem Res 12:265–269
Uribe M, Garcia-Ramos G, Ramos M, Valverdi C, Marquez MA, Farca A, Guevara L (1983) Standard and higher doses of bromocriptine for severe chronic portalsystemic encephalopathy. Am J Gastroenterol 78:517–522
Vergara J, Plum F, Duffy TE (1974) a-Ketoglutaramate: increased concentrations in the cerebrospinal fluid of patients with hepatic coma. Science 183:81–83
Wysmyk U, Oja SS, Saransaari P, Albrecht J (1992) Enhanced GABA release in cerebral cortical slices derived from rats with thioacetamide-induced hepatic encephalopathy. Neurochem Res 17:1187–1190
Yonekura T, Kamata S, Wasa M, Okada A, Kawata S, Tarui S (1991) Simultaneous analysis of plasma phenethylamine, phenylethanolamine, tyramine and octopamine in patients with hepatic encephalopathy. Clin Chim Acta 199:91–98
Yurdaydin C, Hortnagl H, Steindl P, Zimmermann C, Ferenci P (1990) Increased serotoninergic and noradrenergic activity in hepatic encephalopathy in rats with thioacetamide-induced acute liver failure. Hepatology 21:695–700
Yurdaydin C, Gu ZQ, Nowak G, Fromm C, Holt AG. Basile AS (1993) Benzodiazepine receptor ligands are elevated in an animal model of hepatic encephalopathy: relationship between brain concentration and severity of encephalopathy. J Pharmacol Exp Ther 265:565–571
Zeneroli ML, Iuliano E, Racagni G, Baraldi M (1982) Metabolism and brain uptake of y-aminobutyric acid in galactosamine-induced hepatic encephalopathy in rats. J Neurochem 38:1219–1222
Zieve L (1985) Encephalopathy due to short- and medium-chain fatty acids. In: McCandless OW (ed) Cerebral energy metabolism and metabolic encephalopathy. Plenum, New York, p 163
Zieve L. Brunner G (1985) Encephalopathy due to mercaptans and phenols. In: McCandless OW (ed) Cerebral energy metabolism and metabolic encephalopathy. Plenum, New York, p 179
Zieve L, Olsen RL (1977) Can hepatic coma be caused by a reduction of brain noradrenaline and dopamine? Gut 18:688–691
Zieve L, Doizaki WM, Lyftogt C (1984) Brain and blood methanethiol and ammonia concentrations in experimental hepatic coma and coma due to injections of various combinations of these substances. J Lab Clin Med 104:655–664
Zimmermann C, Ferenci P, Pifl C, Yurdaydin C, Ebner J, Lassmann H, Roth E, Hortnagl H (1989) Hepatic encephalopathy in thioacetamide-induced acute liver failure in rats: characterization of an improved model and study of aminoacidergic neurotransmission. Hepatology 9:594–601
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Basile, A.S. (1996). Hepatic Encephalopathy. In: Cameron, R.G., Feuer, G., de la Iglesia, F.A. (eds) Drug-Induced Hepatotoxicity. Handbook of Experimental Pharmacology, vol 121. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61013-4_11
Download citation
DOI: https://doi.org/10.1007/978-3-642-61013-4_11
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-64657-7
Online ISBN: 978-3-642-61013-4
eBook Packages: Springer Book Archive