Hemodynamics in portal hypertension

Great progress in the study of blood circulation in portal hypertension has been achieved by studying animal models. Such a model was created, for example, by ligating the portal vein or bile duct in rats or by inducing cirrhosis by administering carbon tetrachloride. The development of portal hypertension is due to an increase in both vascular resistance and portal blood flow. The main hemodynamic disorder is an increase in resistance to blood flow in the portal vein. It can be mechanical due to disruption of the liver architecture and the formation of nodes in cirrhosis or in case of portal vein obstruction. In addition, it can be caused by other intrahepatic factors, such as collagenization of the Disse space, swelling of hepatocytes, and increased resistance in the portosystemic collaterals. The intrahepatic increase in resistance to blood flow in the portal vein can be dynamic. Thus, myofibroblasts can relax, and endothelial cells of the sinusoids and cells that contain contractile proteins that can cause a “spasm”.

As portal pressure decreases due to the development of collaterals that drain blood from the portal vein to the central veins, portal hypertension is maintained by an increase in blood flow in the portal vein system due to the hyperdynamic type of circulation. It is unclear whether such a violation of the hyperdynamic type of circulation is a cause or a consequence of portal hypertension, or both at the same time. The more severe the hepatocellular insufficiency, the more pronounced the hyperdynamic type of circulation. In addition, cardiac output increases and generalized vasodilation develops. Arterial pressure remains normal or decreases.

Dilation of the vessels of the internal organs is the most important factor supporting the hyperdynamic type of blood circulation. Blood flow through the azygos vein increases. Increased blood flow to the gastric mucosa causes dilation of its capillaries; gastroscopy reveals congestive changes in the mucosa. Increased blood flow in the portal vein increases transmural pressure in the varicose veins of the esophagus. This increase occurs in all veins - both in the portal and in the collaterals. But the amount of blood entering the liver decreases. The hyperdynamic type of blood circulation in the internal organs is provided by a combination of many factors; it is probably determined by the ratio of vasodilator and vasoconstrictor factors. These substances can be formed in hepatocytes, or insufficiently destroyed by them, or not reach hepatocytes at all, forming in the intestine and passing through intra- or extrahepatic venous shunts.

Endotoxins and cytokines, which are formed mainly in the intestine, play an important stimulating role. Under the influence of endotoxin, nitric oxide (NO) and endothelin-1 are synthesized in the vascular endothelium.

NO is a powerful short-lived mediator of vascular relaxation. It is formed from L-arginine by the enzyme NO synthetase, which is induced by endotoxins and cytokines. This reaction is suppressed by arginine analogues; in induced cirrhosis in rats, a significant increase in sensitivity to these substances was found, the introduction of which causes an increase in pressure in the portal vein.

Endothelin-1 is a vasoconstrictor, and its high blood levels in cirrhosis probably play an important role in maintaining normal arterial pressure. In isolated rat livers, it has been shown in vivo to cause sinusoidal "spasm" and increased portal vein pressure.

Prostacyclin is a potent vasodilator produced by the endothelium of the portal vein. It may play a leading role in altering blood circulation in portal hypertension caused by chronic liver disease.

Glucagon is secreted by the alpha cells of the pancreas and is inactivated in the liver. Hyperglucagonemia in cirrhosis is probably due to portal vein shunting. In physiological quantities, glucagon does not have vasoactive properties, but in pharmacological concentrations it can dilate blood vessels. It is probably not the leading factor in maintaining the hyperdynamic type of blood circulation in liver diseases.

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