Symptoms and Signs of Portal Hypertension

When portal blood flow is obstructed (either inside or outside of the liver), blood begins to pool in the vascular beds that normally empty into the portal vein. Congestion of omental tissues contributes to the pathogenesis of ascites. Sequestration of blood in the spleen causes splenic enlargement (splenomegaly) and increases splenic destruction of blood elements (hypersplenism) with secondary thrombocytopenia, neutropenia, and anemia. Eventually, a collateral circulatory system (i.e., varices) develops to decompress the portal bed by diverting portal blood flow into systemic veins. These collateral veins can become quite prominent in the esophagus, stomach, and distal intestine. Increased flow through such esophagogastric and hemorrhoidal varices can lead to vessel rupture, with devastating hemorrhage. If extensive variceal collaterals develop, significant amounts of portal blood flow are shunted away from the liver, and portal pressure may fall to within normal range. The end result, however, is that the liver is deprived of portal blood and must rely increasingly on hepatic artery blood for nurture; however, hepatic arterial blood is deficient in many of the splanchnically derived factors that are hepatotrophic. Thus, the liver’s normal capacity to regenerate is impaired and hepatic atrophy ensues, leading to a small, shrunken liver. In addition, portal–venous shunting diverts blood draining the intestines away from the liver, compromising hepatic clearance of gut-derived products. This has been implicated in the pathogenesis of hepatic encephalopathy. Increasing evidence suggests that portal-systemic shunting also permits systemic endotoxemia, which promotes the release of several proinflammatory cytokines, including tumor necrosis factor alpha (TNF) and endothelins. TNF contributes to the muscle wasting and endothelins to the renal dysfunction associated with advanced cirrhosis.

  Clinical Complications of Portal Hypertension: Gastrointestinal Bleeding

Pathogenesis

Gastrointestinal bleeding is a feared complication of portal hypertension. Although many potential sources of bleeding (e.g., peptic ulcers, portal hypertensive gastropathy, portal–venous collaterals) may coexist in cirrhotic patients, the most clinically significant hemorrhage typically occurs when dilated venous collaterals (varices) rupture. Esophageal, gastric, and hemorrhoidal collaterals have the highest propensity to bleed profusely, although varices can form in many other locations (e.g., in surgical scars, ostomies, and around the umbilicus). Esophageal and gastric varices develop through connections between the coronary and short gastric veins (tributaries of the portal vein) and the azygos vein. Hemorrhoidal varices are the result of connections between the portal system and the middle and superior hemorrhoidal veins.

The prevalence of variceal collaterals among patients with cirrhosis is unknown, but it has been estimated that perhaps as few as a third of cirrhotic patients have esophageal varices. A pressure gradient between the portal and systemic venous systems (i.e., WHVP-FHVP) of at least 12 mm Hg is necessary, but not sufficient, for esophageal varices to develop. Other factors that appear to play a role in the development of esophageal varices are the extent of other collateral routes available to drain the portal bed and the presence or absence of conditions (e.g., lower esophageal sphincter pressure) that permit blood to flow into the azygos veins. Even once esophageal varices have formed, they usually do not bleed. In fact, the risk of an index episode of variceal bleeding has been estimated to be no greater than 30% per year. The risk of variceal rupture is more directly dependent on the wall tension of the varix than on the portal pressure per se. Wall tension is determined by the diameter of the varix and its wall thickness as well as the pressure within its lumen. Hence, for any given portal pressure, large, thin-walled veins within the esophagus are at greatest risk of rupture. Endoscopy is useful in identifying which esophageal varices have the highest risk of bleeding. The identification of large varices that protrude significantly into the esophageal lumen and the presence of red or blue discolored blebs overlying a varix correlate with an extremely high short-term risk of hemorrhage. Although vessel wall thickness appears to be important in determining which collaterals rupture, erosion of esophageal varices resulting from esophagitis or nasogastric tube placement is much less a threat to variceal integrity than rupture of the vessel wall due to elevations in intravariceal (i.e., portal) pressure. Hemorrhage from esophagogastric varices is typically a dramatic event with painless hematemesis or hematochezia. Bleeding is rarely insidious or chronic. Signs of hemodynamic instability (hypotension, tachycardia) are common. The risk of dying from variceal bleeding is variable and depends on the severity of the hemorrhage and the severity of the underlying liver disease. Patients with severely decompensated liver disease have at least a 50% chance of dying after hospitalization with a hemodynamically significant variceal hemorrhage. Furthermore, once varices have bled, they are at high risk (70 to 80% probability) of bleeding again, particularly within the first few weeks to months of the index hemorrhage.

Diagnosis

As noted, upper endoscopy offers a sensitive, specific means of identifying clinically threatening esophageal varices in cirrhotic patients who have never had overt gastrointestinal bleeding. Endoscopy is also diagnostically useful in patients who present with suspected gastroesophageal variceal bleeding; however, the latter patients first must be hemodynamically resuscitated. Optimal recuscitation requires intensive monitoring of blood losses and repletion of intravascular volume in an intensive care unit. In addition, before attempting to identify the source of gastrointestinal bleeding, patients with active hematemesis should be intubated electively to protect against inadvertent aspiration. Once hemodynamic rescuscitation and airway protection have been accomplished, upper endoscopy is performed to diagnose and treat the bleeding source. Even in patients with well-documented portal hypertension, endoscopic visualization of the upper gastrointestinal tract is essential because, as noted, nonvariceal sources of gastrointestinal bleeding also are common in cirrhotic patients, and both short- and long-term management will differ markedly, depending on the source of bleeding. Active bleeding from a varix, adherent clot on a varix, or signs of redness or thinning of a varix wall (dubbed “red or blue wale signs”) in the absence of other identifiable bleeding sources will implicate varices as the source of hemorrhage.

Treatment

Prophylactic Treatments to Prevent Index Hemorrhage from Esophageal Varices

Although vessel wall thickness is an important determinant for variceal rupture, there is little evidence that treatments that decrease esophagitis decrease the risk of bleeding from esophageal varices. On the other hand, treatments that reduce portal pressure (and thus lower intravariceal pressure) are effective in reducing the incidence of bleeding from esophageal varices. Greatest benefit has been demonstrated in patients who have varices that display endoscopic features of impending rupture. In such patients, treatment with beta-blockers to reduce the resting heart rate by 25% is generally well tolerated and significantly reduces the incidence of variceal bleeding. In contrast, other strategies to lower intravariceal pressure (i.e., portal–decompressive shunt surgery or endoscopic sclerotherapy) have proven too toxic to justify widespread use in patients who have never bled.

Management of Acute Variceal Bleeding