FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2000773358> ?p ?o ?g. }

• W2000773358 endingPage "1038" @default.
• W2000773358 startingPage "1035" @default.
• W2000773358 abstract "Hepatic encephalopathy (HE) is a frequent complication of chronic liver disease. Its pathogenesis is not understood, although there is agreement on the important role of neurotoxins, especially ammonia (1.Butterworth RF Giguere JF Michaud J Lavoie J Layrargue GP Ammonia: key factor in the pathogenesis of hepatic encephalopathy.Neurochem Pathol. 1987; 6: 1-12Crossref PubMed Scopus (340) Google Scholar). In the brain of HE patients, neurons appear morphologically normal, but astrocytes exhibit signs of Alzheimer type II degeneration with nuclear enlargement, peripheral margination of chromatin and prominent nucleoli. Functional alterations in HE include selective alterations of blood-brain barrier permeability, changes in cerebral energy metabolism, an increased GABA-ergic tone and changes in several other neurotransmitter systems and their receptors (for reviews see (2.Lockwood AH Hepatic Encephalopathy. Butterworth-Heinemann, Boston1992Google Scholar, 3.Ferenci P Püspök A Steindl P Current concepts in the pathogenesis of hepatic encephalopathy.Eur J Clin Invest. 1992; 22: 573-581Crossref PubMed Scopus (44) Google Scholar, 4.Riordan SM Williams R Treatment of hepatic encephalopathy.N Engl J Med. 1997; 337: 473-479Crossref PubMed Scopus (332) Google Scholar, 5.Jalan R Seery JP Taylor-Robinson SD Pathogenesis and treatment of chronic hepatic encephalopathy.Aliment Pharmacol Ther. 1996; 10: 681-697Crossref PubMed Scopus (39) Google Scholar, 6.Basile AS Jones EA Ammonia and GABA-ergic neurotransmission: interrelated factors in the pathogenesis of hepatic encephalopathy.Hepatology. 1997; 25: 1303-1305Crossref PubMed Scopus (116) Google Scholar, 7.Butterworth RF The neurobiology of hepatic encephalopathy.Semin Liver Dis. 1996; 16: 235-244Crossref PubMed Scopus (148) Google Scholar, 8.Norenberg MD Astrocytic-ammonia interactions in hepatic encephalopathy.Semin Liv Dis. 1996; 16: 245-253Crossref PubMed Scopus (158) Google Scholar)). However, previous hypotheses about the pathogenesis of HE were unable to explain all the facets of this clinical syndrome. Clearly, pathogenetic models have to explain the functional nature and reversibility of HE symptoms, and their precipitation by heterogeneous factors, such as infections, diuretics, sedatives, trauma, bleeding or high protein intake. The finding that Alzheimer type II changes can be induced experimentally in cultured astrocytes upon exposure to ammonia prompted the idea that hepatic encephalopathy is a primary disorder of glial cells, with neuronal dysfunction being the consequence (9.Norenberg MD Neary JT Bender AS Dombro RS Hepatic encephalopathy: a disorder in glial-neuronal communication.in: Yu ACH Hertz L Norenberg MD Sykova E Waxman SG Progress in Brain Research. Elsevier Publ BV, Amsterdam1992: 261-269Google Scholar, 10.Norenberg MD Itzhak Y Bender AS Baker L Aguila-Mansilla HN Zhou BG et al.Häussinger D Jungermann K Liver and Nervous System. Kluwer Acad Publ, Lancaster, England1998: 276-293Google Scholar). Astrocytes are the only cell compartment in the brain containing glutamine synthetase (11.Martinez-Hernandez A Bell KP Norenberg MD Glutamine synthetase: glial localization in the brain.Science. 1977; 195: 1356-1358Crossref PubMed Scopus (970) Google Scholar) and are accordingly the major site of cerebral ammonia detoxification. They are important constituents of the bloodbrain barrier, and uptake of substances from the blood into the brain requires transastrocytic transport. In addition, astrocytes are highly regulated cells, which communicate directly with neurons (12.Nedergaard M Direct signalling from astrocytes to neurons in cultures of mammalian brain cells.Science. 1994; 263: 1768-1771Crossref PubMed Scopus (838) Google Scholar) and participate in neurotransmitter processing, regulation of the ionic milieu in the brain and substrate provision for neurons (for reviews see (13.Murphy S Astrocytes - Pharmacology and Function. Academic Press, San Diego1993Google Scholar, 14.Kimelberg H Ransom BR Neuroglia. Oxford University Press, New York1995Google Scholar). In acute liver failure astrocytes swell; clinically overt brain edema with increased intracranial pressure is frequent and critical for the patient's outcome. This was reviewed in a recent issue of the Journal of Hepatology (15.Blei AT Larsen FS Pathophysiology of cerebral edema in fulminant hepatic failure.J Hepatol. 1999; 31: 771-776Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar). On the other hand, hepatic encephalopathy in chronic liver disease is not accompanied by clinical signs of cerebral edema. Nonetheless, recent in vivo proton-magnetic resonance-(MR)-spectroscopic (1H-MRS) studies suggest that disturbances of astrocyte cell volume homeostasis may be an early event in chronic HE in cirrhosis (16.Häussinger D Laubenberger J vom Dahl S Ernst T Bayer S Langer M et al.Proton magnetic resonance spectroscopic studies on human brain myo-inositol in hypoosmolarity and hepatic encephalopathy.Gastroenterology. 1994; 107: 1475-1480Abstract Full Text PDF PubMed Scopus (298) Google Scholar, 17.Laubenberger J Häussinger D Bayer S Gufler H Hennig J Langer M Proton magnetic resonance spectroscopy of the brain in symptomatic and asymptomatic patients with liver cirrhosis.Gastroenterology. 1997; 112: 1610-1616Abstract Full Text PDF PubMed Scopus (184) Google Scholar). 1H-MRS can be used to study metabolic abnormalities in the human brain in vivo and allows a myo-inositol signal to be picked up, which was recently identified to reflect an osmosensitive myo-inositol pool (16.Häussinger D Laubenberger J vom Dahl S Ernst T Bayer S Langer M et al.Proton magnetic resonance spectroscopic studies on human brain myo-inositol in hypoosmolarity and hepatic encephalopathy.Gastroenterology. 1994; 107: 1475-1480Abstract Full Text PDF PubMed Scopus (298) Google Scholar) of predominant glial origin (18.Brand A Leibfritz D Metabolic markers in glial cells for differentiation of brain tissue.Abstr Commun 11th Ann Meet Soc MR Med. 1992; : 649Google Scholar, 19.Zwingmann C Brand A Richter-Landsberg C Leibfritz D Multinuclear NMR spectroscopy studies on NH4Cl-induced metabolic alterations and detoxification processes in primary astrocytes and glioma cells.Dev Neurosci. 1998; 20: 417-426Crossref PubMed Scopus (29) Google Scholar). Indeed, myo-inositol is an organic osmolyte in astrocytes (20.Paredes A McManus M Kwon HM Strange K Osmoregulation of Na+-inositol cotransporter activity and mRNA levels in brain glial cells.Am J Physiol. 1992; 263: C1282-C1288PubMed Google Scholar, 21.Isaacks RE Bender AS Kim CY Norenberg MD Effect of osmolarity and anion channel inhibitors on myo-inositol efflux in cultured astrocytes.J Neurosci Res. 1999; 57: 866-871Crossref PubMed Scopus (37) Google Scholar, 22.Cordoba J Gottstein J Blei AT Glutamine, myo-inositol and organic brain osmolytes after portacaval anastomosis in the rat: implications for ammonia-induced brain edema.Hepatology. 1996; 24: 919-923PubMed Google Scholar). Such organic osmolytes play a role in cell volume regulation, in that they accumulate inside the cells in response to cell shrinkage, but are rapidly released in response to cell swelling via osmoregulated membrane channels (for reviews, see (23.Burg MB Molecular basis of osmotic regulation.Am J Physiol. 1995; 268: F983-F996PubMed Google Scholar, 24.Lang F Busch GL Ritter M Völkl H Waldegger S Gulbins E et al.Functional significance of cell volume regulatory mechanisms.Physiol Rev. 1998; 78: 247-306Crossref PubMed Scopus (1568) Google Scholar)). In vivo 1H-MRS studies on the brain from cirrhotic patients with HE consistently show a depletion of myo-inositol which is accompanied by an increase in the glutamine/glutamate signal (16.Häussinger D Laubenberger J vom Dahl S Ernst T Bayer S Langer M et al.Proton magnetic resonance spectroscopic studies on human brain myo-inositol in hypoosmolarity and hepatic encephalopathy.Gastroenterology. 1994; 107: 1475-1480Abstract Full Text PDF PubMed Scopus (298) Google Scholar, 17.Laubenberger J Häussinger D Bayer S Gufler H Hennig J Langer M Proton magnetic resonance spectroscopy of the brain in symptomatic and asymptomatic patients with liver cirrhosis.Gastroenterology. 1997; 112: 1610-1616Abstract Full Text PDF PubMed Scopus (184) Google Scholar, 25.Kreis R Farrow NA Ross BD Diagnosis of hepatic encephalopathy by proton magnetic resonance spectroscopy.Lancet. 1990; 336: 635-636Abstract PubMed Scopus (81) Google Scholar, 26.Moats RA Lien YH Filippi D Ross BD Decrease in cerebral inositols in rats and humans.Biochem J. 1993; 295: 15-18PubMed Google Scholar, 27.Ross BD Danielsen ER Bluml S Proton magnetic resonance spectroscopy: the new gold standard for diagnosis of clinical and subclinical hepatic encephalopathy.Dig Dis. 1996; 14: 30-39Crossref PubMed Scopus (74) Google Scholar, 28.Ross BD Jacobson S Villamil F Korula J Kreis R Ernst T et al.Subclinical hepatic encephalopathy: proton MR spectroscopic abnormalities.Radiology. 1994; 193: 457-463Crossref PubMed Scopus (196) Google Scholar). Such alterations are also induced in the rat following portocaval shunting (26.Moats RA Lien YH Filippi D Ross BD Decrease in cerebral inositols in rats and humans.Biochem J. 1993; 295: 15-18PubMed Google Scholar), are aggravated following institution of a transjugular intrahepatic portosystemic stent shunt (TIPS) (16.Häussinger D Laubenberger J vom Dahl S Ernst T Bayer S Langer M et al.Proton magnetic resonance spectroscopic studies on human brain myo-inositol in hypoosmolarity and hepatic encephalopathy.Gastroenterology. 1994; 107: 1475-1480Abstract Full Text PDF PubMed Scopus (298) Google Scholar) and may largely normalize following liver transplantation (27.Ross BD Danielsen ER Bluml S Proton magnetic resonance spectroscopy: the new gold standard for diagnosis of clinical and subclinical hepatic encephalopathy.Dig Dis. 1996; 14: 30-39Crossref PubMed Scopus (74) Google Scholar). There is a good correlation between the extent of these 1H-MRS-changes and the clinical severity of HE (16.Häussinger D Laubenberger J vom Dahl S Ernst T Bayer S Langer M et al.Proton magnetic resonance spectroscopic studies on human brain myo-inositol in hypoosmolarity and hepatic encephalopathy.Gastroenterology. 1994; 107: 1475-1480Abstract Full Text PDF PubMed Scopus (298) Google Scholar, 17.Laubenberger J Häussinger D Bayer S Gufler H Hennig J Langer M Proton magnetic resonance spectroscopy of the brain in symptomatic and asymptomatic patients with liver cirrhosis.Gastroenterology. 1997; 112: 1610-1616Abstract Full Text PDF PubMed Scopus (184) Google Scholar, 27.Ross BD Danielsen ER Bluml S Proton magnetic resonance spectroscopy: the new gold standard for diagnosis of clinical and subclinical hepatic encephalopathy.Dig Dis. 1996; 14: 30-39Crossref PubMed Scopus (74) Google Scholar, 28.Ross BD Jacobson S Villamil F Korula J Kreis R Ernst T et al.Subclinical hepatic encephalopathy: proton MR spectroscopic abnormalities.Radiology. 1994; 193: 457-463Crossref PubMed Scopus (196) Google Scholar) (Fig. 1). A high sensitivity and specificity of the myo-inositol signal for the diagnosis of HE in cirrhotics has been reported (27.Ross BD Danielsen ER Bluml S Proton magnetic resonance spectroscopy: the new gold standard for diagnosis of clinical and subclinical hepatic encephalopathy.Dig Dis. 1996; 14: 30-39Crossref PubMed Scopus (74) Google Scholar, 28.Ross BD Jacobson S Villamil F Korula J Kreis R Ernst T et al.Subclinical hepatic encephalopathy: proton MR spectroscopic abnormalities.Radiology. 1994; 193: 457-463Crossref PubMed Scopus (196) Google Scholar), although these changes are observed already at preclinical stages of HE (16.Häussinger D Laubenberger J vom Dahl S Ernst T Bayer S Langer M et al.Proton magnetic resonance spectroscopic studies on human brain myo-inositol in hypoosmolarity and hepatic encephalopathy.Gastroenterology. 1994; 107: 1475-1480Abstract Full Text PDF PubMed Scopus (298) Google Scholar, 17.Laubenberger J Häussinger D Bayer S Gufler H Hennig J Langer M Proton magnetic resonance spectroscopy of the brain in symptomatic and asymptomatic patients with liver cirrhosis.Gastroenterology. 1997; 112: 1610-1616Abstract Full Text PDF PubMed Scopus (184) Google Scholar, 27.Ross BD Danielsen ER Bluml S Proton magnetic resonance spectroscopy: the new gold standard for diagnosis of clinical and subclinical hepatic encephalopathy.Dig Dis. 1996; 14: 30-39Crossref PubMed Scopus (74) Google Scholar, 28.Ross BD Jacobson S Villamil F Korula J Kreis R Ernst T et al.Subclinical hepatic encephalopathy: proton MR spectroscopic abnormalities.Radiology. 1994; 193: 457-463Crossref PubMed Scopus (196) Google Scholar). In view of the role of myo-inositol as an organic osmolyte in astrocytes, these MRS findings are highly suggestive of a disturbance of cell volume homeostasis in brain (16.Häussinger D Laubenberger J vom Dahl S Ernst T Bayer S Langer M et al.Proton magnetic resonance spectroscopic studies on human brain myo-inositol in hypoosmolarity and hepatic encephalopathy.Gastroenterology. 1994; 107: 1475-1480Abstract Full Text PDF PubMed Scopus (298) Google Scholar), in the sense of a cellular (cytotoxic, but not vasogenic (29.Kimelberg HK Current concepts of brain edema.J Neurosurg. 1995; 83: 1051-1059Crossref PubMed Scopus (383) Google Scholar)) edema, and may be explained by an osmotically active intracellular accumulation of glutamine in response to hyperammonemia and counteraction of the resulting astrocyte swelling by myo-inositol depletion. In line with this, cultured astrocytes swell under the influence of ammonia (30.Norenberg MD Baker L Norenberg LOB Blicharska J Bruce-Gregorius JH Neary JT Ammonia-induced astrocyte swelling in primary culture.Neurochem Res. 1991; 16: 833-836Crossref PubMed Scopus (166) Google Scholar) in a methionine sulfoximine-sensitive way (10.Norenberg MD Itzhak Y Bender AS Baker L Aguila-Mansilla HN Zhou BG et al.Häussinger D Jungermann K Liver and Nervous System. Kluwer Acad Publ, Lancaster, England1998: 276-293Google Scholar) and the above-mentioned 1MRS changes are also found in hyperammonemic Reye's syndrome. Also in the portocaval-shunted rat in vivo, ammonia induces brain edema and intracranial hypertension in a largely methionine sulfoximine-sensitive way (31.Blei AT Olafsson S Therrien G Butterworth RF Ammonia-induced brain edema and intracranial hypertension in rats after portocaval anastomosis.Hepatology. 1994; 19: 1437-1444Crossref PubMed Scopus (206) Google Scholar). Further, 15N-ammonia positron emission tomography studies (32.Lockwood AH Yap EWH Wong HE Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephalopathy.J Cereb Blood Flow Metabol. 1991; 11: 337-341Crossref PubMed Scopus (280) Google Scholar) on human brain from encephalopathic patients showed an increased cerebral metabolic rate for ammonia, consistent with an enhanced cerebral ammonia uptake in HE and detoxification by glutamine synthesis. However, ammonia may not be the only mechanism by which astrocyte swelling is triggered in HE, because astrocyte swelling also occurs in vitro under the influence of hyponatremia (33.Kimelberg HK O'Connor ER Kettenmann H Effects of cell swelling on glial function.in: Lang F Häussinger D Interactions in Cell Volume and Cell Function. Springer Verlag, Heidelberg, Germany1993: 158-186Google Scholar, 34.Schliess F Sinnig R Fischer R Schmalenbach C Häussinger D Calcium-dependent activation of Erk-1 and Erk-2 following hypoosmotic astrocyte-swelling.Biochem J. 1996; 320: 167-171Crossref PubMed Scopus (94) Google Scholar), some neurotransmitters (33.Kimelberg HK O'Connor ER Kettenmann H Effects of cell swelling on glial function.in: Lang F Häussinger D Interactions in Cell Volume and Cell Function. Springer Verlag, Heidelberg, Germany1993: 158-186Google Scholar, 35.Bender AS Norenberg MD Effect of benzodiazepines and neurosteroids on ammonia-induced swelling in cultured astrocytes.J Neurosci Res. 1998; 54: 673-680Crossref PubMed Scopus (87) Google Scholar), tumor necrosis factor-α (36.Bender AS Rivera IV Norenberg MD Tumor necrosis factor α induces astrocyte swelling.Trans Am Neurochem. 1992; 23: 113Google Scholar), and benzodiazepines (10.Norenberg MD Itzhak Y Bender AS Baker L Aguila-Mansilla HN Zhou BG et al.Häussinger D Jungermann K Liver and Nervous System. Kluwer Acad Publ, Lancaster, England1998: 276-293Google Scholar, 35.Bender AS Norenberg MD Effect of benzodiazepines and neurosteroids on ammonia-induced swelling in cultured astrocytes.J Neurosci Res. 1998; 54: 673-680Crossref PubMed Scopus (87) Google Scholar). It should be emphasized that myo-inositol is just one indicator of astrocyte swelling in HE. In fact, recent data suggest that besides myo-inositol other well-known organic osmolytes such as taurine (19.Zwingmann C Brand A Richter-Landsberg C Leibfritz D Multinuclear NMR spectroscopy studies on NH4Cl-induced metabolic alterations and detoxification processes in primary astrocytes and glioma cells.Dev Neurosci. 1998; 20: 417-426Crossref PubMed Scopus (29) Google Scholar, 22.Cordoba J Gottstein J Blei AT Glutamine, myo-inositol and organic brain osmolytes after portacaval anastomosis in the rat: implications for ammonia-induced brain edema.Hepatology. 1996; 24: 919-923PubMed Google Scholar) and α-glycerophosphorylcholine (22.Cordoba J Gottstein J Blei AT Glutamine, myo-inositol and organic brain osmolytes after portacaval anastomosis in the rat: implications for ammonia-induced brain edema.Hepatology. 1996; 24: 919-923PubMed Google Scholar, 37.Bluml S Zuckerman E Tau J Ross BD Proton-coupled 31P magnetic resonance spectroscopy reveals osmotic and metabolic disturbances in human hepatic encephalopathy.J Neurochem. 1998; 71: 1564-1576Crossref PubMed Scopus (56) Google Scholar) are depleted in order to counteract astrocyte swelling in HE. In all cell types studied so far, the cellular hydration state was identified as an independent signal which regulates cell function and gene expression (for reviews see (24.Lang F Busch GL Ritter M Völkl H Waldegger S Gulbins E et al.Functional significance of cell volume regulatory mechanisms.Physiol Rev. 1998; 78: 247-306Crossref PubMed Scopus (1568) Google Scholar, 38.Häussinger D The role of cellular hydration in the regulation of cell function.Biochem J. 1996; 313: 697-710Crossref PubMed Scopus (494) Google Scholar)). Multiple osmosignalling pathways have been identified which provide the link between cell hydration and cell function (39.Häussinger D Schliess F Osmotic induction of signalling cascades: role in regulation of cell function.Biochem Biophys Res Commun. 1999; 255: 551-555Crossref PubMed Scopus (73) Google Scholar). In hepatocytes, i.e. the best studied cell type in this respect, small increases of cell water content (i.e. less than 10%), stimulate glycogen and protein synthesis, amino acid transport, biliary excretion, decrease proteolysis and glycogen breakdown and exert multiple effects on cytoskeletal proteins and gene expression (38.Häussinger D The role of cellular hydration in the regulation of cell function.Biochem J. 1996; 313: 697-710Crossref PubMed Scopus (494) Google Scholar). Thus, small increases in astrocyte water content, as may occur in HE, could already have important functional consequences despite the absence of clinically overt increases of intracranial pressure. This is suggested by recent evidence. Swelling of astrocytes in culture activates extracellular regulated protein kinases (Erks) (34.Schliess F Sinnig R Fischer R Schmalenbach C Häussinger D Calcium-dependent activation of Erk-1 and Erk-2 following hypoosmotic astrocyte-swelling.Biochem J. 1996; 320: 167-171Crossref PubMed Scopus (94) Google Scholar), i.e. members of the MAP-kinase family with multiple functions, in a phosphatidylinositol-3-kinase-dependent way, elevates intracellular calcium concentration (40.Fischer R Schliess F Häussinger D Characterization of the hypoosmotically-induced Ca2+ response in primary astrocytes.Glia. 1997; 20: 51-58Crossref PubMed Scopus (54) Google Scholar), upregulates the peripheral type benzodiazepine receptor (PBR) at the level of agonist binding (41.Itzhak Y Bender AS Norenberg MD Effect of hypoosmotic stress on peripheral-type benzodiazepine receptors in cultured astrocytes.Brain Res. 1994; 644: 221-225Crossref PubMed Scopus (25) Google Scholar) and mRNA (R. Fischer & Häussinger, D., unpublished) and affects multiple ion channels and amino acid transport (33.Kimelberg HK O'Connor ER Kettenmann H Effects of cell swelling on glial function.in: Lang F Häussinger D Interactions in Cell Volume and Cell Function. Springer Verlag, Heidelberg, Germany1993: 158-186Google Scholar). Further, astrocyte swelling increases the pH in endocytotic vesicles (42.Busch GL Wiesinger H Gulbins E Wagner HJ Hamprecht B Lang F Effect of astroglial swelling on pH of acidic intracellular compartments.Biochim Biophys Acta. 1996; 1285: 212-218Crossref PubMed Scopus (29) Google Scholar) through an Erk-dependent osmosignalling pathway (R. Fischer & D. Häussinger, unpublished result). Several key findings in HE can thus at least in part be explained as a result of increased astrocyte hydration. Given the important role of a low endosomal pH for receptor/ligand sorting, the marked endosomal alkalinization in response to astrocyte swelling is expected to affect receptor densities and neurotransmitter processing. Likewise, swelling-induced changes of the activity of plasma membrane transporters may underlie the selective changes in “blood-brain barrier” permeability, which are observed in HE. The increased deposition of glycogen in astrocytes in animal models of chronic HE (10.Norenberg MD Itzhak Y Bender AS Baker L Aguila-Mansilla HN Zhou BG et al.Häussinger D Jungermann K Liver and Nervous System. Kluwer Acad Publ, Lancaster, England1998: 276-293Google Scholar) may also be explained by cell swelling, because swelling of hepatocytes increases glycogen synthesis and inhibits glycogenolysis (for review (38.Häussinger D The role of cellular hydration in the regulation of cell function.Biochem J. 1996; 313: 697-710Crossref PubMed Scopus (494) Google Scholar)). Increased expression of PBR in response to astrocyte swelling augments the synthesis of neurosteroids, which are potent modulators of neuronal GABAA receptor activity (10.Norenberg MD Itzhak Y Bender AS Baker L Aguila-Mansilla HN Zhou BG et al.Häussinger D Jungermann K Liver and Nervous System. Kluwer Acad Publ, Lancaster, England1998: 276-293Google Scholar). Thus, the interaction between astrocyte swelling, PBR expression and increased neurosteroid synthesis may explain the increased GABA-ergic tone found in HE. In view of the above, it is hypothesized that one major pathogenetic event in the development of HE in chronic liver disease is an increase in astrocyte hydration, i.e. a low-grade cerebral edema without a clinically overt increase in intracranial pressure, but sufficient to trigger multiple alterations of astrocyte function (Fig. 2). This may finally result in a disturbance of glioneuronal communication and the clinical picture of HE. Since astrocyte swelling is induced not only by ammonia, but also by hyponatremia, benzodiazepines or inflammatory cytokines, such a model would explain why rather heterogeneous conditions (e.g. bleeding, electrolyte disturbances, sedatives, infections) can precipitate HE in the cirrhotic patient. Thus, multiple factors would act synergistically on the common pathogenetic endpath, i.e. glial swelling with its functional consequences. Noncirrhotics may tolerate such precipitating factors without developing HE symptoms, because their osmolyte systems for counteraction of cell swelling are not exhausted. In cirrhosis, however, organic osmolytes are largely depleted in order to compensate for glial glutamine accumulation and there may be little room for action of these volume-regulatory mechanisms against further challenges of cell volume. Thus, the 1H-MRS findings in nonencephalopathic cirrhotics may describe an early stage of a largely compensated disturbance of astrocyte volume homeostasis with few consequences yet for astrocyte hydration and function. This situation, however, can decompensate rapidly in response to precipitating factors, and hydration-dependent alterations of glial function will become clinically apparent. This labile situation may explain the rapid kinetics of HE episodes and why severe brain edema with fatal outcome can occasionally develop in endstage cirrhotics (43.Donovan JP Schafer DF Shaw BW Sorell MF Cerebral oedema and increased intracranial pressure in chronic liver disease.Lancet. 1998; 351: 719-721Abstract Full Text Full Text PDF PubMed Scopus (145) Google Scholar). Thus similarities exist with respect to the pathogenesis of HE in chronic liver disease and acute liver failure, but differences in the kinetics, extent and counterregulation of glial swelling may be responsible for differences in the clinical picture of acute versus chronic HE, respectively. At present, no new therapeutic options can be deduced from this hypothesis, but all established therapeutic measures for HE are directed against factors which also augment astrocyte swelling. One may also speculate that the respiratory alkalosis which is frequently found in cirrhotic patients, may represent a beneficial adaptation, because hypocapnia is known to decrease astrocyte hydration. It is hoped that these considerations may stimulate future research in the field of HE." @default.
• W2000773358 created "2016-06-24" @default.
• W2000773358 creator A5008452332 @default.
• W2000773358 creator A5033356488 @default.
• W2000773358 creator A5035270139 @default.
• W2000773358 creator A5081249304 @default.
• W2000773358 creator A5091782144 @default.
• W2000773358 date "2000-06-01" @default.
• W2000773358 modified "2023-10-14" @default.
• W2000773358 title "Hepatic encephalopathy in chronic liver disease: a clinical manifestation of astrocyte swelling and low-grade cerebral edema?" @default.
• W2000773358 cites W139123032 @default.
• W2000773358 cites W1968445631 @default.
• W2000773358 cites W1971848028 @default.
• W2000773358 cites W1982531948 @default.
• W2000773358 cites W1987080089 @default.
• W2000773358 cites W1996871338 @default.
• W2000773358 cites W2000268422 @default.
• W2000773358 cites W2002322884 @default.
• W2000773358 cites W2007910534 @default.
• W2000773358 cites W2014377060 @default.
• W2000773358 cites W2015214539 @default.
• W2000773358 cites W2016763168 @default.
• W2000773358 cites W2018406010 @default.
• W2000773358 cites W2018459798 @default.
• W2000773358 cites W2018736934 @default.
• W2000773358 cites W2019008972 @default.
• W2000773358 cites W2030219424 @default.
• W2000773358 cites W2047699315 @default.
• W2000773358 cites W2049913227 @default.
• W2000773358 cites W2052918018 @default.
• W2000773358 cites W2065843356 @default.
• W2000773358 cites W2080650372 @default.
• W2000773358 cites W2090002159 @default.
• W2000773358 cites W2091057443 @default.
• W2000773358 cites W2091490498 @default.
• W2000773358 cites W2095436231 @default.
• W2000773358 cites W2105269204 @default.
• W2000773358 cites W2113607189 @default.
• W2000773358 cites W2224021986 @default.
• W2000773358 cites W2288306858 @default.
• W2000773358 cites W2334982407 @default.
• W2000773358 cites W2342744565 @default.
• W2000773358 cites W2344218612 @default.
• W2000773358 cites W24535451 @default.
• W2000773358 doi "https://doi.org/10.1016/s0168-8278(00)80110-5" @default.
• W2000773358 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10898326" @default.
• W2000773358 hasPublicationYear "2000" @default.
• W2000773358 type Work @default.
• W2000773358 sameAs 2000773358 @default.
• W2000773358 citedByCount "421" @default.
• W2000773358 countsByYear W20007733582012 @default.
• W2000773358 countsByYear W20007733582013 @default.
• W2000773358 countsByYear W20007733582014 @default.
• W2000773358 countsByYear W20007733582015 @default.
• W2000773358 countsByYear W20007733582016 @default.
• W2000773358 countsByYear W20007733582017 @default.
• W2000773358 countsByYear W20007733582018 @default.
• W2000773358 countsByYear W20007733582019 @default.
• W2000773358 countsByYear W20007733582020 @default.
• W2000773358 countsByYear W20007733582021 @default.
• W2000773358 countsByYear W20007733582022 @default.
• W2000773358 countsByYear W20007733582023 @default.
• W2000773358 crossrefType "journal-article" @default.
• W2000773358 hasAuthorship W2000773358A5008452332 @default.
• W2000773358 hasAuthorship W2000773358A5033356488 @default.
• W2000773358 hasAuthorship W2000773358A5035270139 @default.
• W2000773358 hasAuthorship W2000773358A5081249304 @default.
• W2000773358 hasAuthorship W2000773358A5091782144 @default.
• W2000773358 hasBestOaLocation W20007733581 @default.
• W2000773358 hasConcept C126322002 @default.
• W2000773358 hasConcept C142724271 @default.
• W2000773358 hasConcept C2777214474 @default.
• W2000773358 hasConcept C2777542381 @default.
• W2000773358 hasConcept C2778621155 @default.
• W2000773358 hasConcept C2779102576 @default.
• W2000773358 hasConcept C2779134260 @default.
• W2000773358 hasConcept C2779493303 @default.
• W2000773358 hasConcept C2780325230 @default.
• W2000773358 hasConcept C2780886150 @default.
• W2000773358 hasConcept C3019162651 @default.
• W2000773358 hasConcept C529278444 @default.
• W2000773358 hasConcept C71924100 @default.
• W2000773358 hasConcept C90924648 @default.
• W2000773358 hasConceptScore W2000773358C126322002 @default.
• W2000773358 hasConceptScore W2000773358C142724271 @default.
• W2000773358 hasConceptScore W2000773358C2777214474 @default.
• W2000773358 hasConceptScore W2000773358C2777542381 @default.
• W2000773358 hasConceptScore W2000773358C2778621155 @default.
• W2000773358 hasConceptScore W2000773358C2779102576 @default.
• W2000773358 hasConceptScore W2000773358C2779134260 @default.
• W2000773358 hasConceptScore W2000773358C2779493303 @default.
• W2000773358 hasConceptScore W2000773358C2780325230 @default.
• W2000773358 hasConceptScore W2000773358C2780886150 @default.
• W2000773358 hasConceptScore W2000773358C3019162651 @default.
• W2000773358 hasConceptScore W2000773358C529278444 @default.
• W2000773358 hasConceptScore W2000773358C71924100 @default.
• W2000773358 hasConceptScore W2000773358C90924648 @default.
• W2000773358 hasIssue "6" @default.

• next