Esophageal Varices 

The portal vein carries approximately 1500 mL/min of blood from the small and large bowel, the spleen, and the stomach to the liver. Obstruction of portal venous flow, whatever the etiology, results in a rise in portal venous pressure. The response to increased venous pressure is the development of a collateral circulation diverting the obstructed blood flow to the systemic veins. These portosystemic collaterals form by the opening and dilatation of preexisting vascular channels connecting the portal venous system and the superior and inferior vena cava.^{[1, 2, 3]}

High portal pressure is the main cause of the development of portosystemic collaterals; however, other factors such as active angiogenesis may also be involved. The most important portosystemic anastomoses are the gastroesophageal collaterals. Draining into the azygos vein, these collaterals include esophageal varices, which are responsible for the main complication of portal hypertension -- massive upper gastrointestinal (GI) hemorrhage.

The most common causes of upper GI bleeding are duodenal (35%) and gastric ulcers (20%). Bleeding from esophageal varices is responsible for only 5-11% upper GI bleeding (incidence varies depending on geographic location). Other causes for upper GI bleeding are acute gastric erosions/hemorrhagic gastritis (18%), Mallory-Weiss tears (10%), gastric carcinoma (6%), and other causes (6%).

For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center, Liver, Gallbladder, and Pancreas Center, and Heartburn/GERD/Reflux Center. Also, see eMedicine's patient education articles Gastrointestinal Bleeding, Cirrhosis, and Gastritis.

Obstruction of the portal venous system at any level leads to increased portal pressure. Normal pressure in the portal vein is 5-10 mm Hg because the vascular resistance in the hepatic sinusoids is low. An elevated portal venous pressure (>10 mm Hg) distends the veins proximal to the site of the block and increases capillary pressure in organs drained by the obstructed veins.

Because the portal venous system lacks valves, resistance at any level between the right side of the heart and the splanchnic vessels results in retrograde flow of blood and transmission of elevated pressure. The anastomoses connecting the portal and systemic circulation may enlarge to allow blood to bypass the obstruction and pass directly into the systemic circulation.

Studies have demonstrated the role of endothelin-1 (ET-1) and nitric oxide (NO) in the pathogenesis of portal hypertension and esophageal varices.^{[2, 4]} ET-1 is a powerful vasoconstrictor synthesized by sinusoidal endothelial cells that has been implicated in the increased hepatic vascular resistance of cirrhosis and in the development of liver fibrosis. NO is a vasodilator substance that is synthesized by sinusoidal endothelial cells. In the cirrhotic liver, the production of NO is decreased, and endothelial nitric oxide synthase (eNOS) activity and nitrite production by sinusoidal endothelial cells are reduced.

Obstruction and increased resistance can occur at 3 levels in relation to hepatic sinusoids, as follows:

• Presinusoidal venous block (eg, portal vein thrombosis, schistosomiasis, primary biliary cirrhosis): These lesions are characterized by elevated portal venous pressure but a normal wedged hepatic venous pressure (WHVP).
• Postsinusoidal obstruction (eg, Budd-Chiari syndrome, venoocclusive disease, in which the central hepatic venules are the primary site of injury): WHVP is characteristically elevated.
• Sinusoidal obstruction (eg, cirrhosis) is characterized by increased hepatic venous pressure gradient (HVPG), with WHVP being equal to portal venous pressure.

Gastroesophageal varices have 2 main inflows, the first is the left gastric or coronary vein. The other major route of inflow is the splenic hilus, through the short gastric veins. The gastroesophageal varices are important because of their propensity to bleed.

Studies of hepatic microcirculation have identified several mechanisms that may explain the increased intrahepatic vascular resistance. These mechanisms may be summarized as follows:

• A reduction of sinusoidal caliber due to hepatocyte enlargement
• An alteration in the elastic properties of the sinusoidal wall due to collagen deposition in the space of Disse
• Compression of hepatic venules by regeneration nodules
• Central vein lesions caused by perivenous fibrosis
• Venoocclusive changes
• Perisinusoidal block by portal inflammation, portal fibrosis, and piecemeal necrosis

The following are risk factors for variceal hemorrhage:

• Variceal size: The larger the varix, the higher the risk of rupture and bleeding. However, patients may bleed from small varices too.
• The presence of endoscopic red color signs (eg, red whale markings, cherry red spots)
• The Child classification, especially the presence of ascites, increases the risk of hemorrhage.
• Active alcohol intake in patients with chronic alcohol-related liver diseases
• Local changes in the distal esophagus (eg, gastroesophageal reflux) have been postulated to increase the risk of variceal hemorrhage. However, evidence to support this view is weak. Studies indicate that gastroesophageal reflux does not initiate or play a role in esophageal hemorrhage.

A well-documented association exists between variceal hemorrhage and bacterial infections, and this may represent a causal relationship. Infection could trigger variceal bleeding by a number of mechanisms, including the following:

• The release of endotoxin into the systemic circulation
• Worsening of hemostasis
• Vasoconstriction induced by contraction of stellate cells

Frequency

United States

In Western countries, alcoholic and viral cirrhosis are the leading causes of portal hypertension and esophageal varices.

• Thirty percent of patients with compensated cirrhosis and 60-70% of patients with decompensated cirrhosis have gastroesophageal varices at presentation.
• The de novo rate of development of esophageal varices in patients with chronic liver diseases is approximately 8% per year for the first 2 years and 30% by the sixth year.
• The risk of bleeding from esophageal varices is 30% in the first year after identification.
• Bleeding from esophageal varices accounts for approximately 10% of episodes of upper GI bleeding.

International

Hepatitis B is endemic in the Far East and Southeast Asia, particularly, as well as South America, North Africa, Egypt, and other countries in the Middle East. Schistosomiasis is an important cause of portal hypertension in Egypt, Sudan, and other African countries. Hepatitis C is becoming a major cause of liver cirrhosis worldwide.

Mortality/Morbidity

Patients who have bled once from esophageal varices have a 70% chance of rebleeding, and approximately one third of further bleeding episodes are fatal. The risk of death is maximal during the first few days after the bleeding episode and decreases slowly over the first 6 weeks. Mortality rates in the setting of surgical intervention for acute variceal bleeding are high.

Associated abnormalities in the renal, pulmonary, cardiovascular, and immune systems in patients with esophageal varices contribute to 20-65% of mortality.

Sex

• In females with esophageal varices, alcoholic liver disease, viral hepatitis, venoocclusive disease, and primary biliary cirrhosis are usually responsible.
• In males with esophageal varices, alcoholic liver disease and viral hepatitis are usually responsible.

Age

• Portal vein thrombosis and secondary biliary cirrhosis are the most common causes of esophageal varices in children.
• Cirrhosis is the most common cause of esophageal varices in adults.