Role of Toxins and Synergism in Hepatic Encephalopathy
The foremost hypothesis of pathogenesis of hepatic encephalopathy recognizes that in hepatic failure, toxins with coma-inducing potential accumulate and depress neuronal function by affecting fundamental neurophysiologic processes such as postsynaptic inhibition and excitation, and fundamental metabolic processes such as mitochondrial electron transfer and microsomal Na+, K+-ATPase activity. While accumulating, the toxins interact synergistically with each other and with various augmenting endogenous metabolic abnormalities to intensify their cellular effects. Specific toxins that both accumulate with hepatic failure and induce encephalopathy and coma in experimental animals are ammonia, methanethiol, fatty acids, and phenols (Figure 1). By interacting synergistically, they have neurological effects that are out of proportion to their individual abnormalities. Of these toxins, ammonia is the most important and has the most cumulative evidence for its role as an etiologic factor. However, the relative importance of each toxin may vary with the pathologic process.
KeywordsHepatic Encephalopathy Hepatic Failure Visual Evoke Potential Fulminant Hepatic Failure Octanoic Acid
Unable to display preview. Download preview PDF.
- Baraldi, M, Pinelli, G, Ricci, P, Zeneroli ML: Toxins in hepatic encephalopathy: the role of the synergistic effect of ammonia, mercaptans and short chain fatty acids. Arch. Toxicol., Suppl. 7:103–105, 1984a.Google Scholar
- Baraldi, M, Zeneroli, ML, Ventura, E, et al: Supersensitivity of benzodiazepine receptors in hepatic encephalopathy due to fulminant hepatic failure in the rat: reversal by a benzodiazepine antagonist. Clinical Science 67: 167–175, 1984b.Google Scholar
- Challenger, F, and Walshe, JM: Methyl mercaptan in relation to foetor hepaticus. Bioch. J. 59:372–375, 1955.Google Scholar
- Conn, HO and Lieberthal, MM: The Hepatic Coma Syndromes and Lactulose. Williams and Wilkins Co. Baltimore. 1979.Google Scholar
- Muting, D: New aspects on the pathogenesis of hepatic encephalopathy. Liver Research 39:38–41, 1968.Google Scholar
- Zieve, L: Encephalopathy due to short- and medium-chain fatty acids. In DW McCandless, Ed. Cerebral Energy Metabolism and Metabolic Encephalopathy. Plenum Press. New York. 1985. pp 163–177.Google Scholar
- Zieve, L and Brunner, G: Encephalopathy due to mercaptans and Phenols. In DW McCandless, Ed. Cerebral Energy Metabolism and Metabolic Encephalopathy. Plenum Press. New York. 1985. pp 179–201.Google Scholar
- Zieve, L. Hepatic encephalopathy. In L. Schiff and ER Schiff, Eds. Diseases of the Liver, 6th edition. JB Lippincott Co. Philadelphia. 1987a. pp 925–948.Google Scholar