Molecular Mechanisms Leading to Splanchnic Vasodilation in Liver Cirrhosis

Abstract

In liver cirrhosis, portal hypertension is a consequence of enhanced intrahepatic vascular resistance and portal blood flow. Significant vasodilation in the arterial splanchnic district is crucial for an increase in portal flow. In this pathological condition, increased levels of circulating endogenous vasodilators, including nitric oxide, prostacyclin, carbon monoxide, epoxyeicosatrienoic acids, glucagon, endogenous cannabinoids, and adrenomedullin, and a decreased vascular response to vasoconstrictors are the main mechanisms underlying splanchnic vasodilation. In this review, the molecular pathways leading to splanchnic vasodilation will be discussed in detail.

Long‐term administration of human albumin improves survival in patients with cirrhosis and refractory ascites

“…About 60% of patients with compensated cirrhosis develop ascites within 10 years . In cirrhosis, portal hypertension, due to increased intrahepatic resistance and splanchnic blood flow, is the main underlying physiopathological condition for the onset of ascites, since it results in an increased pressure in the splanchnic capillaries with an excess of fluid localization in the peritoneal cavity. Moreover, plasma volume expansion secondary to renal water and sodium retention fuels ascites formation .…”

Tolvaptan Response Improves Overall Survival in Patients with Refractory Ascites: A Meta-Analysis

“…Ascites represents a major complication of decompensated liver cirrhosis, associated with increased morbidity, poor quality of life, and adverse long-term outcomes [1]. The pathophysiology of ascites formation is multifactorial and is based on the presence of hypoalbuminemia, portal hypertension, and splanchnic vasodilation [2]. Dig Dis 2020;38:320-328 DOI: 10.1159/000503559 Subsequently, sympathetic nervous system and vasoconstrictor factors, especially arginine-vasopressin and renin-angiotensin-aldosterone axis are homeostatically activated, leading to sodium retention and impaired freewater excretion [3].…”

Predictors of tolvaptan short‐term response in patients with refractory ascites: A meta‐analysis

“…1 Pathogenesis of ascites is based on a multi-step process including the presence of hypoalbuminemia combined with splanchnic vasodilation that brings about the homeostatic activation of sympathetic nervous system, arginine-vasopressin, and renin-angiotensin-aldosterone axes. 3 Conventional management relies primarily on sodium restriction, albumin infusion, administration of loop diuretics, and spironolactone, although up to 10% of patients develop refractory ascites. 3 Conventional management relies primarily on sodium restriction, albumin infusion, administration of loop diuretics, and spironolactone, although up to 10% of patients develop refractory ascites.…”

“…2 Consequently, effective arterial blood volume is decreased, leading to impaired free water excretion and hyponatremia. 3 Conventional management relies primarily on sodium restriction, albumin infusion, administration of loop diuretics, and spironolactone, although up to 10% of patients develop refractory ascites. 4 Diuretic resistance arises mainly due to high sodium avidity of the proximal tubule, while high doses of diuretics may cause electrolyte disturbances and exacerbate hepatic encephalopathy.…”