title: Liver metabolic zonation and hepatic microcirculation in carbon tetrachloride-induced experimental cirrhosis.
abstract: The exact cause of the hepatic failure in liver cirrhosis is currently unclear, and two main theories have been proposed: the first is based on the altered hepatocyte function (sick hepatocyte hypothesis); the second on the abnormal hepatic architecture (intact hepatocyte hypothesis). Moreover, the microcirculation, a fundamental component in liver structure, shows dramatic changes in cirrhosis that would heavily influence the development of the disease. In order to determine the importance of the microvascular alterations on liver morphofunctional features in experimentally induced cirrhosis, their relationships with structural, ultrastructural, and histoenzymological hepatocyte modifications were investigated. Experimental cirrhosis was induced with controlled intragastric CCl4 administration. Scanning electron microscopy of the vascular corrosion cast technique, associated with light microscopy, transmission electron microscopy, and histoenzymology techniques were employed. The results demonstrated a characteristic micronodular cirrhosis in all the livers studied; the microcirculation displayed the presence of newly formed perinodular plexus. Inside the nodule, areas with two or more hepatocyte-thick laminae were present. Moreover, a rearrangement of the hepatocyte quantitative ultrastructure without real pathological changes and a loss of normal metabolic lobular zonation were noted in the liver parenchyma. These findings support the concept that the progressive modifications of the microcirculation during experimental CC14 cirrhosis modify not only the normal blood flow direction, but also the normal hepatic metabolic gradient with a loss of the normal hepatocytic zonation.
authors.affiliation: Department of Experimental Medicine, State University of L'Aquila, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Gaudio
authors.forename: P
authors.initials: P
authors.lastname: Onori
authors.forename: A
authors.initials: A
authors.lastname: Franchitto
authors.forename: R
authors.initials: R
authors.lastname: Sferra
authors.forename: O
authors.initials: O
authors.lastname: Riggio
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D006651:Histocytochemistry; D008099:Liver / Q000098:blood supply / Q000201:enzymology* / Q000648:ultrastructure; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D008833:Microcirculation / Q000473:pathology; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002251:Carbon Tetrachloride