Abstract
LOCALIZATION of injury to specific zones in the liver lobule after the administration of many toxins is well recognized1. Carbon tetrachloride, an agent extensively examined in hepatotoxicology, characteristically produces centrilobular necrosis and lipid accumulation. Himsworth2 and, more recently, Brody3 suggested that the centriobular location of injury after acute carbon tetrachloride intoxication resulted from centrilobular ischaemia secondary to the hydrocarbon's effect (directly or indirectly) on blood passing from the periphery to the centre of the lobule. This concept has been challenged on several grounds including the observation that the earliest signs of parenchymal cell injury precede vascular changes associated with ischaemia4. Several investigations have indicated that hepatic cells within different zones of the lobule have dissimilar function5. This has been ascribed to the relation of the hepatic cell to the blood flow through the lobule which causes these cells to adopt particular functions in accordance with available substrates or metabolites in the blood. Wilson describes certain zonal functions as representing habitual patterns of activity which become characteristic of hepatocytes in a particular location6. Zonal heterogeneity of function may explain the centrilobular location of acute carbon tetrachloride injury if it is assumed that hepatocytes in this location are susceptible to its effect.
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References
Stoner, H. B., and Magee, P. N., Brit. Med. Bull., 13, 102 (1957).
Himsworth, H. P., The Liver and Its Diseases (Harvard University Press, Cambridge, Mass., 1954).
Brody, T. M., Calvert, D. N., and Schneider, A. F., J. Pharmacol. Exp. Therap., 131, 341 (1961).
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Novikoff, A. B., and Essner, E., Amer. J. Med., 29, 102 (1960).
Wilson, J. W., in Liver Function (edit. by Brauer, R. W.), 182 (Amer. Inst. of Biol. Sciences, Washington, D.C., 1958).
Sigel, B., Baldia, L. B., and Dunn, M. R., Surgical Forum, 16, 288 (1965).
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Brauer, R. W. NATO Symposium, The Biliary System, 101 (Blackwell Scientific Publications, 1965).
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SIGEL, B., BALDIA, L., DUNN, M. et al. Carbon Tetrachloride Effect on Liver Autotransplants with Totally Reversed Blood Flow. Nature 213, 1258–1259 (1967). https://doi.org/10.1038/2131258a0
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DOI: https://doi.org/10.1038/2131258a0
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