Etiology and Pathophysiology

Portal hypertension develops due to a combination of increased vascular resistance coupled with a hyperdynamic circulatory state. Portal hypertension, by definition, is present when the hepatic venous pressure gradient (wedged hepatic venous pressure minus free hepatic venous pressure [HVPG]) exceeds 6 mm Hg. Resistance to outflow from the portal venous bed is the first step in the development of por tal hypertension. The observed increase in resistance can be characterized anatomically as presinusoidal (eg, portal vein thrombosis, schistosomiasis), sinusoidal (eg, cirrhosis, primary sclerosing cholangitis, alcoholic hepatitis) or post-sinusoidal (eg, Budd-Chiari, veno-occlusive disease) (Table 117-1). Of note, in those patients with presinusoidal and postsinusoidal portal hypertension, the increased resistance can be either intrahepatic or extrahepatic. Although some of the increased resistance is due to anatomic alterations, such as fibrosis and regenerative nodules, which are irreversible, there are also dynamic elements involving vascular tone. The alterations in vascular tone are mediated by an increase in the endogenous production of endothelin, a potent vasoconstrictor, and a decrease in the intrahepatic production of nitric oxide (NO), a potent vasodilator, leading to alterations in the level of vascular resistance. An additional site of increased vascular resistance is found in portosystemic collaterals. Although portosystemic collaterals form in response to portal hypertension, they also represent sites of increased resistance compared to normal intrahepatic resistance.

TABLE 117-1. Causes of Portal Hypertension

Presinusoidal

Sinusoidal or Mixed

Postsinusoidal

Infectious (other than hepatitis) Toxin-mediated

Cirrhotic

Autoimmune/Oncologic/Primary Fibrotic

Vascular

Other

Schistosomiasis Azathioprine Chronic arsenic ingestion Vinyl chloride

Early primary biliary cirrhosis

Sarcoidosis

Myeloproliferative diseases

Congenital hepatic fibrosis

Early primary sclerosing cholangitis

Splenic vein thrombosis

Portal vein thrombosis

Cavernous transformation of the portal vein

Extrinsic compression of the portal vein

Idiopathic portal hypertension

Methotrexate Alcoholic hepatitis Hypervitaminosis A Chronic hepatitis Alcoholic cirrhosis Cryptogenic cirrhosis Primary biliary cirrhosis Incomplete septal fibrosis Nodular regenerative hyperplasia Primary sclerosing cholangitis

Veno-occlusive disease Hepatic vein thrombosis Budd-Chiari

Constrictive pericarditis Tricuspid valve disease Severe congestive cardiomyopathy

In addition to increased vascular resistance, there are also significant hemodynamic alterations seen in portal hypertension which act by increasing splanchnic blood flow. In the presence of systemic and local vasodilators, such as NO and prostaglandins, peripheral vascular resistance is reduced. This leads to sodium retention and a subsequent increase in plasma volume. The net effect is increases in splanchnic blood flow and cardiac index. Thus, it is a combination of increased intrahepatic vascular resistance and systemic hemodynamic alterations that result in the observed elevations in portal pressure.

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