ReviewVasoactive factors and hemodynamic mechanisms in the pathophysiology of portal hypertension in cirrhosis
Introduction
Portal hypertension is a hemodynamic syndrome mostly caused by liver cirrhosis in the Western Countries. It causes a series of alterations responsible for the onset of complications of cirrhosis, such as gastrointestinal hemorrhage, ascites, portal-systemic encephalopathy, hepato-renal syndrome, hepato-pulmonary syndrome, spontaneous bacterial peritonitis. Hemodynamic alterations of portal hypertension do not only involve portal–hepatic hemodynamics but splanchnic and systemic circulation too. Portal hypertension is defined as an increase in portal pressure above the normal range of 6–10 mm Hg or, considering the gradient between portal and hepatic veins, as assessed by hepatic vein catheterization, above 5 mm Hg. Portal hypertension is considered clinically relevant, i.e., capable of causing the development and rupture of esophageal varices, when the portal–hepatic gradient is above 10–12 mm Hg. The increase in resistance to outflow from the portal system, with the subsequent increase in portal pressure, causes the opening of portal-systemic collaterals. Portal-systemic shunts are responsible on the one hand for gastrointestinal hemorrhage (mostly due to the rupture of esophageal or gastric varices) and, on the other hand, they allow access to the systemic circulation of substances usually removed by the liver, which play a role in the pathogenesis of the hyperdynamic circulation, ascites and portal-systemic encephalopathy (Gatta et al., 1999).
Section snippets
Determinants of portal pressure
Portal pressure is the result of the relationship between the blood flow volume entering the portal system and the resistance to portal blood flow. The mathematical expression of this relationship is given by the Ohm’s formula: P = Q × R, where P represents change in pressure along the vessel, Q represents blood flow and R resistance to the flow. In normal liver, resistance is mainly located in terminal portal venules, in the sinusoids and in the roots of hepatic venules. The increase in resistance
Structural mechanical factors
The progressive deposition of collagen in the hepatic acini is the main mechanism responsible for the increase in resistance in cirrhosis. Collagen deposition in the Disse’s space narrows the sinusoidal lumen, and increases the distance between sinusoidal lumen and hepatocytes. The decrease in the total cross-sectional area of hepatic sinusoids causes an increase in resistance to portal flow. The further transformation of collagen into fibrotic tissue, together with regeneration of hepatocytes,
The forward-flow theory of portal hypertension
In normal liver, with normal resistance and compliance, an increase in flow do not modify portal pressure (Blendis, 1981). On the contrary, if the outflow portal resistance is increased, as in cirrhosis, an increase in portal flow is responsible for an increase in portal pressure (forward-flow theory of portal hypertension). In patients with portal hypertension, total splanchnic inflow is increased (Tisdale et al., 1959, Gitlin et al., 1970), as it was also shown in experimental models of
Conclusion
In recent years, the role of autocrine and paracrine endothelial factors in modulating hepatic vascular resistance and splanchnic blood flow has been highlighted in patients with portal hypertension. Vasoactive systems play a key role both in increasing sinusoidal resistance and in determining splanchnic arterial vasodilation thus contributing to the hyperdynamic circulatory syndrome. The same vasoactive system can play different role in different regional vascular beds. In particular, in
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2022, Gastroenterologia y HepatologiaCitation Excerpt :The lessening in the degradation of these factors due to liver dysfunction generates splanchnic arterial vasodilation and so reduces the effective circulating volume.6 Some of these vasodilators are transferred to the systemic circulation through portosystemic shunts, produced by the reperfusion and dilatation of pre-existing vessels,7 but also through new vessels generated by angiogenic factors, like the vascular endothelial growth factor.8,9 Systemic vasodilation leads to a lower mean arterial pressure on account of a reduction in the systemic vascular resistance that, while in the early stages of cirrhosis, gets compensated with an increase in the cardiac output in order to keep mean arterial pressure within normal ranges.10
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