Hepatic microcirculation as a morpho-functional basis for the metabolic zonation in normal and pathological rat liver

The hepatic microcirculation is well known as a fundamental component of the liver structure, deeply involved in the zonal organization of the acinar structure. In cirrhosis, the microvascular tree shows dramatic changes that would heavily influence the development of the disease. When the cirrhosis becomes evident the result is a progressive organ failure, also in presence of only moderately decreased hepatocyte volume. The aim of this research was to compare the role of microcirculation of the hepatic zonation in normal and cirrhotic livers. Cirrhosis was experimentally induced in 36 rats following a controlled intragastric CCl4 administration. Cirrhotic and control normal livers were processed for routine light microscopy, histoenzimology, and scanning electron microscopy vascular corrosion cast. Control livers showed normal hepatic structure and microvascularization; enzymatic activities were constantly and normally distributed. In CCl4-treated animals LM showed a characteristic micronodular cirrhosis in all livers. Vascular corrosion casts under the scanning electron microscope displayed a progressive reduction of the distance between pre- and post-sinusoidal vessels and the presence of newly formed perinodular plexus. The histoenzymatic analysis demonstrated the loss of zonation in the cirrhotic parenchyma. Moreover, the sinusoid/hepatocyte ratio was significantly reduced, because of the presence of two or more hepatocyte thick laminae during the scarring development. The altered microcirculation in cirrhosis also changed the normal acinous metabolic gradient. The histoenzymatic study revealed a zonal rearrangement of the cirrhotic liver metabolic activity, that leads to a progressive hepatic failure. These data confirm the fundamental importance of the normal relationship between the hepatocyte laminae and the sinusoids for the preservation of a normal zonation which represents the basis for a normal liver function.