Liver Metabolic Zonation and Hepatic Microcirculation in Carbon Tetrachloride-Induced Experimental Cirrhosis

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Abstract
The exact cause of the hepatic failure in livercirrhosis is currently unclear, and two main theorieshave been proposed: the first is based on the alteredhepatocyte function (sick hepatocyte hypothesis); the second on the abnormal hepatic architecture(intact hepatocyte hypothesis). Moreover, themicrocirculation, a fundamental component in liverstructure, shows dramatic changes in cirrhosis thatwould heavily influence the development of thedisease. In order to determine the importance of themicrovascular alterations on liver morphofunctionalfeatures in experimentally induced cirrhosis, theirrelationships with structural, ultrastructural, andhistoenzymological hepatocyte modifications wereinvestigated. Experimental cirrhosis was induced withcontrolled intragastric CCl4 administration.Scanning electron microscopy of the vascular corrosion casttechnique, associated with light microscopy,transmission electron microscopy, and histoenzymologytechniques were employed. The results demonstrated acharacteristic micronodular cirrhosis in all the liversstudied; the microcirculation displayed the presence ofnewly formed perinodular plexus. Inside the nodule,areas with two or more hepatocyte-thick laminae were present. Moreover, a rearrangement of thehepatocyte quantitative ultrastructure without realpathological changes and a loss of normal metaboliclobular zonation were noted in the liver parenchyma.These findings support the concept that theprogressive modifications of the microcirculation duringexperimental CCl4 cirrhosis modify not onlythe normal blood flow direction, but also the normalhepatic metabolic gradient with a loss of the normal hepatocyticzonation.