Pathophysiology of increased intestinal permeability in obstructive jaundice

Abstract

Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients' outcome.

Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation?

“…Surgery for relief of obstructive jaundice has a risk of sepsis and renal dysfunction [68]. Increased intestinal permeability was confirmed in these patients both by the L/M test [69] and the polyethylene glycol test [70], which may be related to frequently observed BT [71].…”

“…Bile duct ligation in animals also resulted in the regional loss of occludin expression in the intestinal epithelium, which was improved by bile feeding [76]. Bile acids inhibit the growth of Bacteroides, Clostridia, Lactobacillus and Streptococcus , and the absence of bile acids results in a disturbed intestinal bacterial balance with overgrowth of Gram-negative bacteria [68]. …”

Artificial Nutrition and Intestinal Mucosal Barrier Functionality

“…The bile salts interact with endotoxins in the intestinal lumen resulting in the formation of less permeable molecules. Reduced production of bile salts and the consequent disruption of normal flora could explain BT in case of obstructive jaundice, cirrhosis or hepatectomy [26,27,28]. Immunonutrition may protect the gut barrier function more effectively in rats with SIRS [29], can protect IMB in rats with operative stress, increase the expression of occludin, maintain the gut epithelial tight junction, and eliminate gut BT [30].…”

On the Confounding Role of Administration Solvents (Vehicles) in Animal Experimental Studies: Z-LLY-FMK or Dimethyl Sulfoxide (DMSO) Attenuates Intestinal Apoptosis in Bile Duct-Ligated Rats?

“…The mechanisms responsible for increased intestinal apoptosis in extrahepatic cholestasis remain to be elucidated, although several factors have been proposed as potential promoters, amongst which oxidative stress seems to be cardinal [3][4][5]. The role of calpains, a family of proteases involved in the cell apoptotic machinery in diverse cell systems, has not been previously investigated in obstructive jaundice and this makes the Sheen-Chen et al study novel and interesting.…”

“…Increased intestinal apoptosis has been shown to be a significant contributory factor in gut barrier dysfunction complicating obstructive jaundice [2][3][4]. The mechanisms responsible for increased intestinal apoptosis in extrahepatic cholestasis remain to be elucidated, although several factors have been proposed as potential promoters, amongst which oxidative stress seems to be cardinal [3][4][5].…”