Splanchnic and Systemic Haemodynamic Derangement in Decompensated Cirrhosis

Abstract

Patients with cirrhosis and portal hypertension exhibit characteristic hemodynamic changes with hyperkinetic systemic circulation, abnormal distribution of blood volume and neurohumoral dysregulation. Their plasma and noncentral blood volumes are increased. Splanchnic vasodilation is of pathogenic significance to the low systemic vascular resistance and abnormal volume distribution of blood, which are important elements in the development of the concomitant cardiac dysfunction, recently termed 'cirrhotic cardiomyopathy'. Systolic and diastolic functions are impaired with direct relation to the degree of liver dysfunction. Significant pathophysiological mechanisms are reduced beta-adrenergic receptor signal transduction, defective cardiac excitation-contraction coupling and conductance abnormalities. Vasodilators such as nitric oxide and calcitonin gene-related peptide are among the candidates in vasodilation and increased arterial compliance. Reflex-induced, enhanced sympathetic nervous system activity, activation of the renin-angiotensin aldosterone system, and elevated circulation vasopressin and endothelin-1 are implicated in hemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the hemodynamic and neurohumoral abnormalities in cirrhosis are part of a general cardiovascular dysfunction, influencing the course of the disease with the reduction of organ function, with sodium and water retention as the outcome. These aspects are relevant to therapy.

Hypertension and liver disease

“…However, the evidence available indicates that a decreased systemic vascular resistance with low normal or decreased arterial blood pressure is most often the outcome, even in patients with primary arterial hypertension [23•-25•]. Research on vascular hyporeactivity has primarily focused on NO, calcitonin gene-related peptide (CGRP), tumor necrosis factor-α (TNF-α), adrenomedullin and endocannabinoids [17,18] (Table 2). Moreover, there is substantial evidence of autonomic defects in patients with cirrhosis.…”

Intraperitoneal LPS amplifies portal hypertension in rat liver fibrosis

“…1 The increase in portal pressure is triggered by persistent splanchnic vasodilation and increased intrahepatic vascular resistance. Molecular changes in the cirrhotic liver include alterations in the generation and degradation of vasodilators and vasoconstrictors, as well as in changes in cellular responses to the same.…”

Left ventricular hypertrophy in rats with biliary cirrhosis

“…10 Sympathetic nervous and renin-angiotensin aldosterone systems are enhanced, and the plasma levels of vasopressin and endothelin-1 are elevated. 11,12 Both hemodynamic overload and neuroendocrine activation occurring during portal hypertension are potentially able to induce cardiac hypertrophy and dysfunction. 13,14 However, although an echocardiographic study described increased left ventricular (LV) wall thickness in patients with advanced cirrhosis, 15 there is no direct eviAbbreviations: SVR, systemic vascular resistance; NO, nitric oxide; eNOS, endothelial nitric oxide synthase; LV, left ventricle; CBDL, common bile duct ligated rat; MAP, mean arterial pressure; CI, cardiac index; PAP, pulmonary artery pressure; PVR, pulmonary vascular resistance; CWI, cardiac weight index; RV, right ventricle; LVEDP, left ventricular end-diastolic pressure; LVdevP, left ventricular developed pressure;…”

“…10 Sympathetic nervous and renin-angiotensin aldosterone systems are enhanced, and the plasma levels of vasopressin and endothelin-1 are elevated. 11,12 Both hemodynamic overload and neuroendocrine activation occurring during portal hypertension are potentially able to induce cardiac hypertrophy and dysfunction. 13,14 However, although an echocardiographic study described increased left ventricular (LV) wall thickness in patients with advanced cirrhosis, 15 there is no direct evi-dence of the induction of myocardial hypertrophy by portal hypertension.…”