Portal hypertension

Portal hypertension is an increase in pressure in the portal vein basin caused by a disturbance in blood flow of various origins and locations - in the portal vessels, hepatic veins and inferior vena cava.

When the amount of portal blood flowing to the liver decreases due to the development of collateral circulation, the role of the hepatic artery increases. The liver decreases in volume, and its ability to regenerate decreases. This probably occurs due to insufficient supply of hepatotropic factors, including insulin and glucagon, produced by the pancreas.

Portal hypertension is most often caused by liver cirrhosis (in developed countries), schistosomiasis (in endemic areas), or vascular disorders in the liver. Sequelae include esophageal varices and portosystemic encephalopathy. Diagnosis is based on clinical findings, imaging, and endoscopy. Treatment includes endoscopic prophylaxis of gastrointestinal bleeding, drug therapy, a combination of these methods, and sometimes portocaval shunting.

The portal vein, formed by the superior mesenteric and splenic veins, delivers blood from the abdominal organs, gastrointestinal tract, spleen and pancreas to the liver. Within the reticuloendothelial blood vessels (sinusoids), blood from the terminal portal venules of the liver mixes with arterial blood. Blood from the sinusoids enters the inferior vena cava through the hepatic veins.

Normally, portal pressure is 5-10 mm Hg (7-14 cm H2O), which exceeds the pressure in the inferior vena cava by 4-5 mm Hg (portal venous gradient). Higher values are characterized as portal hypertension.

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Causes and pathophysiology of portal hypertension

Portal hypertension occurs primarily due to increased resistance to blood flow as a result of direct pathological processes in the liver, obstruction of the splenic or portal veins, or impaired venous outflow through the hepatic veins. Increased inflowing blood volume is a rare cause, although it often contributes to portal hypertension in liver cirrhosis and in hematological diseases accompanied by pronounced splenomegaly.

Classification and common causes of portal hypertension

Classification	Reasons
Subhepatic	Thrombosis of the portal or splenic vein Increased portal blood flow: arteriovenous fistula, severe splenomegaly in hematological diseases
Intrahepatic	Presinusoidal: schistosomiasis, other periportal lesions (eg, primary biliary cirrhosis, sarcoidosis, congenital hepatic fibrosis), idiopathic portal hypertension Sinusoidal: cirrhosis (of any etiology). Postsinusoidal: occlusive lesions of venules
Suprahepatic	Hepatic vein thrombosis (Budd-Chiari syndrome) Inferior vena cava obstruction Obstructed blood flow to the right side of the heart (eg, constrictive pericarditis, restrictive cardiomyopathy)

Liver cirrhosis is accompanied by tissue fibrosis and regeneration, which increases resistance in the sinusoids and terminal portal venules. At the same time, other, potentially reversible factors are important, such as the contractility of sinusoidal cells, the production of vasoactive substances (e.g., endothelial, nitric oxide), various systemic mediators of arteriolar resistance, and, possibly, hepatocyte swelling.

Over time, portal hypertension leads to the development of portosystemic venous collaterals. They contribute to some reduction in portal pressure but also to the development of complications. Dilated tortuous submucosal vessels (varices) of the distal esophagus and sometimes the fundus of the stomach may rupture, causing sudden catastrophic gastrointestinal bleeding. Bleeding is rare unless the portal pressure gradient is less than 12 mm Hg. Stasis of blood in the vessels of the gastric mucosa (gastropathy in portal hypertension) may cause acute or chronic bleeding independent of varices. Visible dilation of the collaterals of the abdominal wall is common; veins arising radially from the umbilicus (caput medusae) are less common and indicate significant blood flow in the umbilical and paraumbilical veins. Collaterals around the rectum may lead to rectal varices and bleeding.

Portosystemic collaterals shunt blood past the liver. Thus, with increased portal blood flow, less blood reaches the liver. In addition, toxic substances from the intestine enter directly into the systemic circulation, contributing to the development of portosystemic encephalopathy. Venous congestion in the viscera in portal hypertension contributes to the development of ascites as a result of the Starling phenomenon. Splenomegaly and hypersplenism usually result from increased pressure in the splenic vein. Thrombocytopenia, leukopenia, and, less commonly, hemolytic anemia may result.

Portal hypertension is often associated with hyperdynamic circulation. The mechanisms are complex and probably involve increased sympathetic tone, production of nitric oxide and other endogenous vasodilators, and increased activity of humoral factors (eg, glucagon).

Causes of portal hypertension

Pathogenesis of portal hypertension

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Symptoms of portal hypertension

Portal hypertension develops asymptomatically; symptoms and signs result from the development of complications. The most dangerous is acute bleeding from varicose veins. Patients usually complain of sudden, often massive, painless bleeding from the upper gastrointestinal tract. Bleeding in gastropathy with portal hypertension is often subacute or chronic. Ascites, splenomegaly, or portosystemic encephalopathy may be observed.

Symptoms of portal hypertension

Diagnosis of portal hypertension

In patients with chronic liver disease, portal hypertension requires the presence of dilated collaterals, splenomegaly, ascites, or portosystemic encephalopathy. Confirmation requires measurement of direct portal pressure by jugular vein catheterization, which is an invasive procedure and is not routinely performed. If cirrhosis is suspected, imaging studies are helpful. Ultrasonography or CT often shows dilated intra-abdominal collaterals, and Doppler ultrasound can assess the portal vein and blood flow velocity.

Esophageal and gastric varices and portal hypertension gastropathy are best diagnosed endoscopically, which allows for the prediction of bleeding from esophageal and gastric varices (eg, red spots on varices).

Diagnosis of portal hypertension

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Prognosis and treatment of portal hypertension

Mortality from acute variceal bleeding can exceed 50%. The prognosis depends on the liver's reserve capacity and the severity of the bleeding. For survivors, the risk of bleeding in the next 1-2 years is 50 to 75%. Endoscopic and drug therapy reduce the risk of bleeding but only slightly increase life expectancy.

Long-term therapy of gastroesophageal varicose veins, which are the source of bleeding, consists of staged endoscopic ligation or sclerotherapy to obliterate the nodes, followed by mandatory monthly endoscopic control. Ligation of varicose veins is preferable to sclerotherapy due to the lower risk.

Long-term medical therapy for bleeding esophageal and gastric varices includes beta-blockers; these drugs lower portal pressure primarily by reducing portal blood flow, although the effect is not always permanent. Propranolol (40 mg to 80 mg orally twice daily) or nadolol (40 to 160 mg once daily) titrated to reduce heart rate by about 25% are preferred. The addition of isosorbide mononitrate 10 mg to 20 mg orally twice daily may further reduce portal pressure. A more effective approach is to combine long-term endoscopic and medical therapy. Patients in whom these treatments are ineffective or not indicated require transjugular intrahepatic portal-systemic shunting (TIPS) or portacaval shunting. TIPS is a stent placed between the portal and hepatic venous circulations within the liver. At the same time, TIPS is safer than portocaval shunting in terms of mortality, especially in the setting of acute bleeding. However, over time, bleeding often recurs due to stent stenosis or obstruction. The long-term effect is unknown. A certain group of patients is indicated for liver transplantation.

In patients with varicose veins that have not been complicated by bleeding, the use of beta-blockers reduces its risk.

In gastropathy complicated by bleeding, drug therapy may be used to reduce portal pressure. Indications for bypass should be considered when drug therapy is ineffective, but its results may be less positive compared to bypass in bleeding from esophageal varices.

Because it rarely causes clinical problems, hypersplenism does not require any specific treatment and splenectomy should be avoided.

Treatment of portal hypertension

Endoscopic sclerotherapy is a method that is considered the "gold standard" of emergency treatment of bleeding from esophageal varices. In skilled hands, it allows you to stop the bleeding, but usually, to improve visibility, tamponade is first performed and somatostatin is prescribed. Thrombosis of varicose veins is achieved by introducing a sclerosing solution into them through an endoscope. Data on the effectiveness of planned sclerotherapy for esophageal varices are contradictory.