Pathophysiology of Portal Hypertension

Abstract

Portal hypertension is a major complication of liver disease, which results from a variety of pathological conditions that increase the resistance to the portal blood flow into the liver. The primary cause of portal hypertension in cirrhosis is an increase in intrahepatic vascular resistance due to massive structural changes associated with fibrosis and increased vascular tone in the hepatic microcirculation. As portal hypertension develops, the formation of collateral vessels and arterial vasodilation progress, which results in increased blood flow to the portal circulation. Eventually the hyperdynamic circulatory syndrome develops, leading to esophageal varices or ascites. This review article will summarize the factors that increase 1) intrahepatic vascular resistance and 2) the blood flow in the splanchnic and systemic circulations in liver cirrhosis. Finally, the future directions of basic/clinical research in portal hypertension will be discussed.

Hemodynamic effects of renin-angiotensin-aldosterone inhibitor and β-blocker combination therapy vs. β-blocker monotherapy for portal hypertension in cirrhosis: A meta-analysis

“…There are three main aspects in the pathophysiology of portal hypertension (74). The first is structural changes caused by fibrosis, vascular occlusion and regenerative nodule formation or remodeling.…”

Synectin promotes fibrogenesis by regulating PDGFR isoforms through distinct mechanisms

“…In response to various stimuli, HSC assume a myofibroblast phenotype characterized by increased migration, proliferation, and release of extracellular matrix proteins. HSC migration is conspicuous in fibrogenesis and also because their motility wraps adjacent endothelial cells and constrict sinusoids, thereby elevating intravascular pressure and leading to morbid portal hypertension (4). Thus, it follows that extending our understanding of how alterations in the biology of HSC occur during the fibrogenic processes may pave the way toward the development of effective treatments for many liver diseases.…”

Cirrhotic Portal Hypertension: New Insights in an Old Syndrome

“…In a cirrhotic liver, the production of TxA2 is increased by the Liver Sinusoidal Endothelial Cells (LSEC) and contributes to the increase of intrahepatic resistance (RVIH) (IWAKIRI, 2014).…”

“…The transdifferentiation of the HSC in myofibroblast occurs, and these cells show an increase of gene expression of the transformation growth factor beta (TGF beta) and platelet derived growth factor (PDGF) (IWAKIRI, 2012). The Stellate cell, while active, presents less response to vasodilators such as nitric oxide and suffers the action of endothelin 1, which is found increased in hepatic cirrhosis, leading to vasoconstriction (IWAKIRI, 2014). Picture 1.…”