HEPATIC ENCEPHALOPATHY: A LOOK AT GLUTAMATE SYSTEM
Keywords:
hepatic encephalopathy, acute liver failure, glutamate systemAbstract
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which is associated with liver dysfunction and has quantitatively and qualitatively distinct features relating to its severity. It defines the prognosis in acute liver injury in which up to 30 % of patients succumb from brain herniation due to brain oedema and intracranial hypertension. In cirrhosis (chronic liver dysfunction), it occurs more insidiously causing a range of neuropsychiatric disturbances which include psychomotor dysfunction, impaired memory, increased reaction time, sensory abnormalities and poor concentration. In its most severe forms, patients may develop confusion, stupor, coma and death. In minimal HE, the changes in mental function are subtle and may be observed in patients with no overt clinical evidence of encephalopathy. The neuropsychological features of minimal HE are suggestive of a disorder of executive functioning. This primarily affects selective attention and psychomotor speed, which has a huge impact on health-related quality of life and has been shown to reduce the ability to drive. Acute-on-chronic liver failure defines a group of patients that have chronic liver disease and in these patients a severe precipitating event such as sepsis, gastrointestinal bleeding (increased ammonia load) or the creation of portosystemic shunting (increased ammonia load) provides a pathophysiologic framework in which the patients with a chronic ‘phenotype’ can appear clinically indistinct from those with acute liver failure.
References
Hepatic encephalopathy — definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology / P. Ferenci, A. Lockwood, K. Mullen [et al.] // Hepatology. – 2002. – Vol. 35, N 3. – P. 716–737.
Clinical features and survivial of cirrhotic patients with subclinical cognitive alterations detected by the number connection test and computerized psychometric tests / P. Amodio, F. Del Piccolo, P. Marchetti [et al.] // Hepatology. – 1999. – Vol. 29, N 6. – P. 1662–1667.
Characteristics of minimal hepatic encephalopathy / P. Amodio, S. Montagnese, A. Gatta, M. Y. Morgan // Metab Brain Dis. – 2004. – Vol. 19, N 3/4. – P. 253–267.
Latent portasystemic encephalopathy. Nature of cerebral functional defects and their effect on fitness to drive / H. Schomerus, W. Hamster, H. Blunck [et al.] // Dig Dis Sci. – 1981. – Vol. 26, N 7. – P. 622–630.
Sen S. The pathophysiological basis of acute-on-chronic liver failure / S. Sen, R. Williams, R. Jalan // Liver. – 2002. – Vol. 22. – P. 5–13.
Butterworth R. F. Pathophysiology of hepatic encephalopathy: a new look at ammonia / R. F. Butterworth // Metab Brain Dis. – 2002. – Vol. 17, N 4. – P. 221–227.
Bender A. S. Effect of benzodiazepines and neurosteroids on ammonia-induced swelling in cultured astrocytes / A. S. Bender, M. D. Norenberg // J Neurosci Res. – 1998. – Vol. 54, N 5. – P. 673–780.
Ammonia induces MK-801-sensitive nitration and phosphorylation of protein tyrosine residues in rat astrocytes / F. Schliess, B. Görg, R. Fischer [et al.] // FASEB J. – 2002. – Vol. 16, N 7. – P. 739–780.
Suárez I. Glutamine synthetase in brain: effect of ammonia / I. Suárez, G. Bodega, B. Fernandez // Neurochem Int. – 2002. – Vol. 41, N 2/3. – P. 123–165.
Hilgier W. Decreased potassium–stimulated release of [3H]D-aspartate from hippocampal slices distinguishes encephalopathy related to acute liver failure from that induced by simple hyperammonemia / W. Hilgier, R. Haugvicova, J. Albrecht // Brain Res. – 1991. – Vol. 567, N 1. – P. 165–173.
Neuroactive amino acids and glutamate (NMDA) receptors in frontal cortex of rats with experimental acute liver failure / A. Michalak, C. Rose, J. Butterworth, R. F. Butterworth // Hepatology. – 1996. – Vol. 24, N 4. – P. 908–911.
Loss of GABAB binding sites in the cerebral cortex of rats with acute hepatic encephalopathy / S. S. Oja, P. Saransaari, U. Wysmyk, J. Albrecht // Brain Res. – 1993. – Vol. 629, N 2. – P. 355–362.
Memantine, a noncompetitive NMDA receptor antagonist improves hyperammonemiainduced encephalopathy and acute hepatic encephalopathy in rats / B. A. Vogels, M. A. Maas, J. Daalhuisen [et al.] // Hepatology. – 1997. – Vol. 25, N 4. – P. 820–827.
Acute ammonia treatment in vitro and in vivo inhibits the synthesis of a neuroprotectant kynurenic acid in rat cerebral cortical slices / T. Saran, W. Hilgier, T. Kocki [et al.] // Brain Res. – 1998. – Vol. 787, N 2. – P. 348–398.
Effect of acute exposure to ammonia on glutamate transport in glial cells isolated from the salamander retina / D. Mort, P. Marcaggi, J. Grant, D. Attwell // J. Neurophysiol. – 2001. – Vol. 86. – P. 836–844.
Rose C. Increased extracellular brain glutamate in acute liver failure: decreased uptake or increased release? / C. Rose // Metab Brain Dis. – 2002. – Vol. 17, N 4. – P. 251–311.
Role of manganese in the pathogenesis of portal systemic encephalopathy / G. P. Layrargues, C. Rose, L. Spahr [et al.] // Metab Brain Dis. – 1998. – Vol. 13, N 4. – P. 311–318.
Reversal of hepatic coma by benzodiazepine antagonist / G. Bansky, P. J. Meier, W. H. Ziegler [et al.] // Lancet. – 1985. – Vol. 1, N 8441. – P. 1324–1325.
Ferenci P. Newer approaches to therapy of hepatic encephalopathy / P. Ferenci, A. Herneth // Semin Liver Dis. – 1996. – Vol 16, N 3. – P. 329–338.
