Hepatic microvascular changes associated with development of liver fibrosis and cirrhosis

Abstract

Quantitative data defining basic microvascular parameters are needed for better understanding of the relationship between liver blood flow and function under normal and pathological conditions. The present study was undertaken to quantitate the following microvascular parameters: flow velocities in sinusoids and terminal hepatic venules; the range of sizes of terminal hepatic vessels; and acinar sizes in both normal rat livers and during the development of liver cirrhosis. Fibrosis and cirrhosis were induced by either weekly administration of carbon tetrachloride (CCl4) or by choline-deficient diet. Microcirculation was observed using intravital epifluorescent video microscopy and recorded on a videotape for subsequent analysis. It was found that even early stages of liver disease, when only mild hepatic fibrosis was present, are associated with profound changes in the hepatic microvasculature. These changes include the appearance of highly fluorescent cells in the liver parenchyma (mainly in the areas where collagen is being deposited), a marked dilatation of the terminal hepatic venules, an increase in hepatic venous outflow, and appearance of sinusoids with very high flow velocities. As fibrosis progresses to cirrhosis, the proportion of these “fast sinusoids” increases from 7% in fibrotic livers to 33% in cirrhotic livers. These results demonstrate the presence of functional intrahepatic shunts in cirrhotic livers and support the hypothesis that hyperdynamic splanchnic circulation may be an important factor in the etiology of portal hypertension in liver disease.