THE ROLE OF ENDOTHELIAL DYSFUNCTION IN THE PATHOGENESIS OF LIVER FAILURE IN OBSTRUCTIVE JAUNDICE OF BENIGN ORIGIN

Abstract

Objective: To study the role of endothelial dysfunction in the pathogenesis of liver failure (LF) in obstructive jaundice of benign origin (OJBO). Methods: The study was based on the analysis of the results of a clinical examination of 68 patients with varying degrees of OJBO severity. For the determination of the severity of OJBO the classification proposed by Galperin EI (2012) was used. The class A severity was noted in 28 (43.7%) patients, class B – in 20 (36.5%) patients. The class C was determined in 20 (19.8%) patients which developed sepsis, encephalopathy, mono- or multiple organ failure. To assess endothelial dysfunction and its significance in the pathogenesis of OJBO and LF, the levels of markers of endothelial dysfunction in blood were assessed in patients with OJBO at various degrees of its severity. Results: The progression of OJBO, especially in patients with class B and C, contributed to a more pronounced changes of the level of markers of endothelial dysfunction and endotoxemia, leading to the development of LF. Thus, the increase in the level of mid-molecules (MM) in patients with OJBO complicated by LF reached 0.973±0.68 units, while with cholangitis added it comprised 0.1274±0.7 units; conjugated dienes (DC) levels were 1.58±0.17 mmol/ml of serum and 1.97±0.10 mmol/ml of serum; malondialdehyde (MDA) – 3.9±0.12 nmol/ml of serum and 4.8±0.16 nmol/ml of serum; the level of nitric oxide (NO) decreased up to 19.2±1.3 μmol/l and 16.4±1.4 μmol/l and the level of thrombomodulin – up to 78.6±5.4 pg/ml and 53.4±4.3 pg/ml, respectively. There was a significant increase in the indices of circulating desquamated endotheliocytes (CDE) up to 8.4±0.1 %/100 μl and 13.9±1.2 %/100 μl; and the level of endothelin-1 reached 1.2±0.07 fmol/ml and 1.4±0.05 fmol/ml, respectively, which was caused by the activation of free radicals. In addition, there was an increase in the diameter of the portal vein (1.02±0.03 cm and 1.921±0.02 cm), as well as linear (19.8±1.3 cm/ sec and 25.1±1.4 cm/sec) and volumetric (1321±124 ml/min and 1647±140 ml/min) blood flow velocities. Conclusion: With the progression of the OJBO (class B and C), significant and pronounced changes were found in the indicators of oxidative endotoxemia, hypoxia and cytokine profile, as well as marked circulatory disorders in the liver, directly correlating with the severity of endothelial dysfunction, which is the leading mechanism for the LF development. Keywords: Obstructive jaundice, cholestasis, cholemia, cholangitis, endothelial dysfunction, liver failure.