Intestinal barrier dysfunction in obstructive jaundice: current concepts in pathophysiology and potential therapies

Abstract

Patients with obstructive jaundice, especially when exposed
to the additional stress of an invasive diagnostic or therapeutic
procedure, are prone to septic complications and renal
dysfunction contributing to high morbidity and mortality
rates. The key-event in the pathophysiology of obstructive
jaundice-associated complications is endotoxemia of gut origin
because of intestinal barrier failure. Experimental and
clinical studies have shown that obstructive jaundice results
in increased intestinal permeability. The mechanisms implicated
in this phenomenon remain unresolved, but over the
last few years mainly experimental studies have shed light
on our knowledge in the field. Factors such as altered intestinal
tight junctions expression, oxidative stress and apoptosis
may play a key role in gut permeability alterations in
cases of biliary obstruction. This review summarises the
current knowledge on the pathophysiological mechanisms
and the potential therapeutic strategies. Clinicians facing
this very common clinical problem should not neglect protecting
the intestinal barrier function, which may improve
their patients' outcome.
Key words: obstructive jaundice, intestinal barrier, intestinal
permeability, endotoxemia, bacterial translocation, tight junctions,
occludin, claudin-4, apoptosis, oxidative stress