Portal Hypertension and Varices

Etiology

Portal hypertension can result from obstruction to portal blood flow anywhere along the course of the portal venous system (prehepatic, intrahepatic, or posthepatic). Table 394.1 outlines the various disorders associated with portal hypertension.

Portal vein thrombosis is the most common cause of extrahepatic portal hypertension. The obstruction can occur at any level of the portal vein. In neonates, portal vein thrombosis can occur from umbilical infection (omphalitis) with or without a history of catheterization of the umbilical vein, dehydration, and/or sepsis. Rare developmental anomalies producing extrahepatic portal hypertension include agenesis, atresia, stenosis, or a web of the portal vein. In older children, portal vein thrombosis can occur with intraabdominal infection (appendicitis, peritonitis, pancreatitis), inflammatory bowel disease, primary sclerosing cholangitis, or biliary infection. Portal vein thrombosis is also associated with hypercoagulable states, such as deficiencies of factor V Leiden, protein C, or protein S. The portal vein can be replaced by a fibrous remnant or contain an organized thrombus. At least half of reported cases have no defined cause. Uncommonly, presinusoidal hypertension can be caused by increased flow through the portal system as a result of a congenital or acquired arteriovenous fistula.

The intrahepatic causes of portal hypertension are numerous. The most common cause of portal hypertension in children is cirrhosis. The numerous causes of cirrhosis include recognized disorders such as biliary atresia, autoimmune hepatitis, chronic viral hepatitis, and metabolic liver disease such as α ₁ -antitrypsin deficiency, Wilson disease, glycogen storage disease type IV, hereditary fructose intolerance, and cystic fibrosis.

Portal infiltration with malignant cells or granulomas can also contribute. An idiopathic form of portal hypertension characterized by splenomegaly, hypersplenism, and portal hypertension without occlusion of portal or splenic veins and with no obvious disease in the liver has been described. In some patients, noncirrhotic portal fibrosis has been observed.

Postsinusoidal causes of portal hypertension are also observed in childhood. Budd-Chiari syndrome occurs with obstruction to hepatic veins anywhere between the efferent hepatic veins and the entry of the inferior vena cava into the right atrium. In most cases, no specific cause can be found, but thrombosis can occur from inherited and acquired hypercoagulable states (antithrombin III deficiency, protein C or S deficiency, factor V Leiden or prothrombin mutations, paroxysmal nocturnal hemoglobinemia, pregnancy, oral contraceptives) and can complicate hepatic or metastatic neoplasms, collagen vascular disease, infection, and trauma. Additional causes of the Budd-Chiari syndrome include Behçet syndrome, inflammatory bowel disease, aspergillosis, dacarbazine therapy, autoinflammatory-recurrent fever syndromes, and inferior vena cava webs.

Sinusoidal obstruction syndrome (venoocclusive disease) is the most common cause of hepatic vein obstruction in children. In this disorder, occlusion of the centrilobular venules or sublobular hepatic veins occurs. The disorder most frequently occurs in bone marrow transplant recipients after total body irradiation with or without cytotoxic drug therapy, but can also be seen in patients on azathioprine, mercaptopurine, thioguanine, and those taking herbal remedies that contain pyrrolizidine alkaloids.

Pathophysiology

The primary hemodynamic abnormality in portal hypertension is increased resistance to portal blood flow. This is the case whether the resistance to portal flow has an intrahepatic cause such as cirrhosis or is due to portal vein obstruction. Portosystemic shunting should decompress the portal system and thus significantly lower portal pressures. However, despite the development of significant collaterals deviating portal blood into systemic veins, portal hypertension is maintained by an overall increase in portal venous flow and thus maintenance of portal hypertension. A hyperdynamic circulation is achieved by tachycardia, an increase in cardiac output, decreased systemic vascular resistance, and increased splanchnic dilation. Overall, the increase in portal flow likely contributes to an increase in variceal transmural pressure. The increase in portal blood flow is related to the contribution of hepatic and collateral flow; the actual portal blood flow reaching the liver is reduced. It is also likely that hepatocellular dysfunction and portosystemic shunting lead to the generation of various humoral factors that cause vasodilation and an increase in plasma volume.

Many complications of portal hypertension can be accounted for by the development of a remarkable collateral circulation. Collateral vessels can form prominently in areas in which absorptive epithelium joins stratified epithelium, particularly in the esophagus or anorectal region. The superficial submucosal collaterals, especially those in the esophagus and stomach, and to a lesser extent, those in the duodenum, colon, or rectum, are prone to rupture and bleeding under increased pressure. In portal hypertension, the vascularity of the stomach is also abnormal and demonstrates prominent submucosal arteriovenous communications between the muscularis mucosa and dilated precapillaries and veins. The resulting lesion, a vascular ectasia, has been called congestive gastropathy and contributes to a significant risk of bleeding from the stomach.