The pathophysiology of portal hypertension.

Portal hypertension is defined by an elevation in blood pressure in the portal system. Different causes are known and include a pre-, intra-, or posthepatic block. Portal hypertension is also classified according to the sinusoidal system. Portal pressure becomes elevated by either an increase in blood flow (Q), an increase in resistance (R), or both. Regulation of the vascular tone in the splanchnic system includes intrinsic and extrinsic aspects. A variety of metabolic end-products (e.g. adenosine), endothelium-derived substances (e.g. nitric oxide), and certain neurotransmitters (e.g. acetylcholine) are known to relax the tone and thus produce vasodilation. Important vasoconstrictor influences on splanchnic arterioles include circulating agents (e.g. angiotensin), endothelium-derived substances (e.g. endothelin), and again neurotransmitters (norepinephrine). Besides vascular tone, structural changes (thrombosis, fibrosis, shear stress, and cell regeneration) add to overall hepatic resistance. Further consequences of portal hypertension include an increase in blood flow which leads to a hyperdynamic state with fluid retention, leading to secondary involvement of other organs, such as cirrhotic cardiomyopathy, hepatopulmonary syndrome and hepatorenal syndrome. Finally, portal hypertension will end up in the formation of collateral vessels. Varices can involve the whole gastrointestinal tract and are a frequent source of bleeding.