Portal Hypertension and Variceal Hemorrhage

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Portal hypertension, a major hallmark of cirrhosis, is defined as a portal pressure gradient exceeding 5 mm Hg. In portal hypertension, porto-systemic collaterals decompress the portal circulation and give rise to varices. Successful management of portal hypertension and its complications requires knowledge of the underlying pathophysiology, the pertinent anatomy, and the natural history of the collateral circulation, particularly the gastroesophageal varices.

Section snippets

Hemodynamic principles and causes of portal hypertension

Portal hypertension is a pathologic increase in the portal venous pressure gradient between the portal vein and the inferior vena cava. It results from changes in portal resistance together with changes in portal inflow, as defined by Ohm's law:P(pressure)=Q(blood flow)×R(resistance)

The mechanism of the increase in portal pressure depends on the site and the cause of portal hypertension (Box 1), cirrhosis being the most common cause in the Western world [2]. The initial event in the development

Collateral circulation

Portal hypertension caused by cirrhosis persists and progresses due to (1) prominent obstructive resistance within the liver, (2) resistance within the collaterals, and (3) continued increase in portal vein inflow. This hypertension leads to the formation of collaterals that decompress the portal circulation by returning blood to the heart via the systemic venous circulation. The major sites of collaterals are:

  • Rectum, where the systemic inferior mesenteric vein connects with the portal pudendal

Diagnosis of varices

Upper gastrointestinal endoscopy is the most common method to diagnose varices. Various criteria have been used to standardize the description of esophageal varices. The Japanese Research Society for Portal Hypertension described varices in terms of red color signs, color of the varix, form (size) of the varix, and location of the varix [25]. The Northern Italian Endoscopy Club simplified this scheme by classifying varices as F1, F2, or F3 (corresponding to small, medium, or large) with or

Natural history of gastroesophageal varices

De novo varices develop in 5% to 15% of patients who have cirrhosis per annum and enlarge by 4% to 10% per annum. Most patients who have cirrhosis develop varices, but only one third of them experiences variceal bleeding. Only 40% to 50% of actively bleeding varices spontaneously stop bleeding.

Risk factors for variceal bleeding are listed in Table 1[21]. When combined, these factors reasonably accurately predict the risk of bleeding (see Table 1) [30]. Varices with a high risk of bleeding

Pharmacologic therapy

Nonselective beta-blockers (nadolol and propranolol) are the firstline treatment for primary prophylaxis. They block vasodilatory beta-adrenergic receptors, permitting unopposed alpha-adrenergic vasoconstriction in the mesenteric arterioles, thereby reducing portal venous inflow and pressure. They also decrease cardiac output, which further decreases the portal inflow. Meta-analysis of clinical trials shows that the risk of bleeding is reduced by beta-blocker therapy versus placebo from 25% to

Management of acute variceal bleed

The management of acute variceal bleeding includes hemodynamic resuscitation, general treatments, prevention of complications, and achievement of hemostasis. Intravenous access must be promptly secured (Box 2). Airway intubation is indicated in patients who are bleeding severely or who have mental status changes that preclude their ability to protect their airway. Intravascular volume loss is estimated and replaced with crystalloids and packed red cells. The systolic blood pressure should be

Vasopressin and its analogs

Vasopressin is an endogenous nonopeptide that causes splanchnic vasoconstriction by acting on V1 receptors located in arterial smooth muscle, reduces portal venous inflow, and reduces portal pressure [60]. It has severe toxicity, including bowel necrosis from vasoconstriction. Terlipressin, a semisynthetic analog of vasopressin, has a lower rate of systemic side effects. It increases survival in patients who have variceal bleeding. It is not available in the United States [61].

Somatostatin and its analogs

Somatostatin has

Endoscopic sclerotherapy

EST has largely been supplanted by EVL, except when poor visualization precludes effective band ligation of bleeding varices. Current evidence does not support emergency EST as first-line treatment of variceal bleeding [68]. The technique involves injection of a sclerosant into (intravariceal) or adjacent to (paravariceal) a varix. Complications of EST occurring during or after the procedure include chest discomfort, ulcers (and ulcer-related bleeding), strictures, and perforation. The risk of

Transjugular intrahepatic portosystemic shunts

TIPS reduces elevated portal pressure by creating a communication between the hepatic vein and an intrahepatic branch of the portal vein. It produces hemostasis in more than 90% of cases [77], [78]. Once complications from bleeding of aspiration pneumonia or multiorgan failure occur, the prognosis is dismal regardless of the achievement of hemostasis, as demonstrated by a 10% survival at 30 days in patients who have aspiration pneumonia [79]. In the absence of aspiration pneumonia, a 90%

Secondary prophylaxis

Once acute variceal bleeding is controlled, prevention of recurrent bleeding should be emphasized. After an index bleed, 70% of patients experience recurrent variceal hemorrhage within 1 year [80], and these patients have a 70% 1-year mortality. The risk of rebleeding is greatest within the first 6 weeks, with more than 50% of rebleeding occurring within 3 to 4 days. Risk factors for rebleeding include severe initial bleeding as defined by a hemoglobin level less than 8 mg/dL, gastric variceal

Gastric varices

Gastric varices most commonly are caused by portal hypertension, usually in patients who have cirrhosis. Patients who have splenic vein thrombosis or spontaneous splenorenal collaterals can develop isolated gastric varices, particularly IGV1. GOV1 disappears in approximately 58% and 70% after EST and EVL of esophageal varices, respectively [89], [90]. The obliteration of varices at the gastroesophageal junction blocks the shunting veins in the palisade zone, leading to dilatation and the

Ectopic varices

Ectopic varices are defined as portosystemic shunts, resulting from portal hypertension, that occur at any site in the gut or abdomen except in the gastroesophageal region. These sites include the duodenum, jejunum, ileum, colon, rectum, biliary tree, and ostomy sites [115], [116]. It is important to differentiate anal varices from hemorrhoids: Anal varices collapse with digital pressure, whereas hemorrhoids do not [115].

Ectopic varices account for 1% to 5% of all variceal bleeding [117].

Gastric antral vascular ectasia

Gastric antral vascular ectasia (GAVE), or watermelon stomach, describes a vascular lesion of the gastric antrum that consists of ectatic and sacculated antral mucosal vessels radiating toward from the pylorus (Fig. 5). Its cause is unknown, but it has been proposed that gastric peristalsis causes prolapse of the loose antral mucosa into the duodenum with consequent elongation and ectasia of the mucosal vessels [120], [121]. Microscopic features include dilated capillaries with focal

Portal hypertensive gastropathy

Portal hypertensive gastropathy (PHG) is characterized endoscopically by three patterns: (1) fine red speckling of gastric mucosa; (2) superficial reddening, especially on the tips of the gastric rugae; and, most commonly, (3) the presence of a mosaic pattern with red spots (snake-skin appearance) in the gastric fundus or body. Histologically, the stomach in PHG contains dilated, tortuous, irregular veins in the mucosa and submucosa, sometimes with intimal thickening, usually in the absence of

Downhill varices

Esophageal veins form a plexus on the outer surface of the esophagus. The lower part drains into the short and left gastric veins of the portal system, whereas the upper part drains into the azygous, thyroid, and internal mammary veins and then into the superior vena cava. “Downhill” esophageal varices (DEV) form in the upper third of the esophagus as collateral branches directing blood flow “downward” to bypass superior vena cava (SVC) obstruction via the azygous vein or to drain the systemic

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    This work was supported, in part, by a grant from the NIH (K24 DK 02755-08) to Dr. Sanyal.

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