Etiology and pathophysiology of portal hypertension

Abstract

Portal hypertension may result from increased resistance of the hepatic vascular bed ("backflow") and from a hyperdynamic splanchnic circulation ("forward flow" theory). Most likely, both mechanisms contribute to the formation of portal hypertension in man. The classical macroscopic terminology describes prehepatic, intrahepatic and posthepatic forms of portal hypertension. Increased splanchnic blood flow represents the predominant cause of some pre- and intrahepatic types of portal hypertension. Intrahepatic portal hypertension has been subclassified as presinusoidal, sinusoidal or postsinusoidal. However, one to one allotments of diseases to this classification may not be made. The relative contribution of each of these causes to the increased portal pressure of liver cirrhosis varies with the etiology of the disease. A new ultrastructural classification of the processes leading to portal hypertension differentiates primarily hepatocellular (e.g., increased hepatocellular size) from interstitional causes (e.g., sinusoidal capillarization). The role of the fenestrated sinusoidal endothelial cells in the regulation of intrahepatic resistance and, thus, for the generation of portal hypertension is poorly defined up to date. A thorough evaluation of the effects of prostanglandins, leukotrienes, catecholamines, serotonin and others on sinusoidal endothelial cells and hepatic microcirculation may provide the basis for new therapeutic avenues.