From the Guidelines
Portal hypertension is characterized by increased pressure in the portal venous system, primarily resulting from increased resistance to portal blood flow, which leads to significant hemodynamic changes in the splanchnic vasculature, including vasodilation, increased blood flow, and formation of collateral vessels 1. The pathophysiology of portal hypertension begins with structural changes in the liver, most commonly due to cirrhosis, which obstructs portal blood flow through distorted hepatic architecture, fibrosis, and regenerative nodules. This obstruction can occur at prehepatic, intrahepatic, or posthepatic levels. As portal pressure rises, significant hemodynamic changes occur in the splanchnic vasculature, including:
- Increased intrahepatic resistance to portal flow attributed to structural mechanisms and an increased intrahepatic vascular tone (functional component) 1
- Formation of portosystemic collaterals, which can lead to the development of esophageal and gastric varices 1
- Splanchnic vasodilatation, leading to increased flow into the gut and into the portal venous system, which further aggravates portal hypertension 1
- Activation of neurohumoral and vasoconstrictive systems, sodium and water retention, increased blood volume, and increased cardiac output, resulting in a hyperdynamic circulatory state 1 These hemodynamic changes lead to the development of portosystemic collaterals, most notably esophageal and gastric varices, which can rupture and cause life-threatening bleeding. Other consequences include ascites, splenomegaly, and hepatic encephalopathy. Understanding this pathophysiology is crucial for managing complications and developing targeted therapies for portal hypertension. The splanchnic circulation responds to portal hypertension with arteriolar vasodilation, increased blood flow, and formation of collateral vessels to decompress the portal system, which is mediated by excessive production of vasodilators like nitric oxide, prostacyclin, and endocannabinoids 1. Treatment of portal hypertension should target the underlying cause, as well as the mechanical and functional components of increased intrahepatic resistance, and should aim to reduce portal pressure and prevent complications, such as variceal bleeding and ascites 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Pathophysiology of Portal Hypertension
- Portal hypertension is defined as increased pressure in the portal venous system, with the most common cause being cirrhosis 2.
- In cirrhosis, there is an increase in intrahepatic resistance leading to an increase in portal pressure 2.
- Splanchnic vasodilation further aggravates portal hypertension by increasing portal blood flow 2.
Effects on Splanchnic Vasculature
- Portal hypertension leads to the development of oesophageal and gastric varices, ascites, hepatic encephalopathy, and complications secondary to circulatory dysfunction 3.
- The management of oesophageal and gastric varices is crucial, with both emergency and prophylactic management being important 3.
- Portal hypertension is responsible for most clinical consequences of cirrhosis, representing the more frequent causes of death and liver transplantation in these patients 4.
Role of the Spleen in Portal Hypertension
- The spleen plays a regulatory role in maintaining portal flow into the liver and is the key organ in the forward flow theory of portal hypertension 5.
- Splenomegaly is associated with a poor prognosis in cirrhosis and is caused by spleen congestion and by enlargement and hyperactivation of splenic lymphoid tissue 5.
- Hypersplenism can lead to thrombocytopenia caused by increased sequestering and breakdown of platelets in the spleen 5.
Diagnosis and Management
- The presence of varices at endoscopy and/or other abdominal portosystemic collaterals confirms the diagnosis of portal hypertension 2.
- Non-invasive and imaging tests play a crucial role in the diagnosis and prognosis of portal hypertension 2, 4, 6.
- Non-selective beta-blockers decrease both the risk of variceal haemorrhage and hepatic decompensation, while terlipressin, somatostatin or octreotide, in combination with early endoscopic therapy, are recommended for the treatment of acute variceal haemorrhage 2.