Hepatic Circulation

Under normal physiologic conditions, the liver functions as a low-resistance system, thereby enabling the accommodation of large volumes of portal blood in the absence of significant changes in pressure. Liver cells, which are predominantly responsible for function of the hepatic circulation, include endothelial cells within the sinusoids, portal venules, hepatic arteries, and hepatic venules, and contractile cells, which include hepatic stellate cells and vascular smooth muscle cells. Pathologic perturbations can impair the function of the hepatic circulation through the actions of specific autocrine and paracrine factors such as nitric oxide, endothelin, VEGF, angiopoietin, TGFβ and PDGF. In liver cirrhosis, hepatic vascular compliance is lost and portal pressure increases in response to small changes in venous inflow, due to mechanical factors such as extracellular matrix deposition as well as dynamic components such as endothelial dysfunction culminating in hepatic vascular constriction. In recent years, vascular structural changes namely angiogenesis and sinusoidal remodeling, which includes endothelial cell capillarization and increased density of activated hepatic stellate cells wrapped around the endothelium, have been identified as key steps contributing to liver fibrosis and portal hypertension. Other clinically relevant insults such as ischemia–reperfusion, alcohol, and endotoxin impair hepatic vascular function in the absence of structural changes, probably through the production of injurious cytokines from Kupffer cells. Thrombocytes and blood clots are increasingly recognized as important mediators contributing to changes in the hepatic circulation and the sinusoidal microenvironment.