Autodigestion in Physiological Shock and Multiorgan Failure

 In All Presenters, Schmid-Schonbein, Geert W.

Presenting Author: Geert W. Schmid-Schönbein, PhD

Center for Autodigestion Research, Microcirculation Laboratory, Department of Bioengineering University of California San Diego, La Jolla, CA 92093-0412

Abstract: Reduction of blood perfusion to the intestine, be it by occlusion of blood vessels or loss of blood volume, sets in a rapid progression of cell dysfunction and failure of organ functions that within hours can lead to death.  Decades of research into the mechanisms that cause such acute multi-organ dysfunction in shock after reduction of blood flow to the intestine have remained inconclusive.  We have proposed a new hypothesis that involves digestive enzymes.  During a meal the pancreas releases a set of powerful digestive enzymes into the small intestine to degrade food as requirement for nutrition.  Digestive enzymes are usually contained inside the lumen of the small intestine by the mucosal barrier, an epithelial cell sheet with a mucus layer that is usually impermeable to molecules the size of digestive enzymes.  But systematic analysis shows that this barrier can fail when the intestine is underperfused; digestive enzymes are then transported out of the lumen of the small intestine into the systemic circulation where they degrade plasma proteins and membrane receptors.  The process causes numerous cell dysfunction and depending on the magnitude of enzyme escape may lead to multi-organ failure and death.  Inhibition of digestive enzymes inside the lumen of the small intestine in experimental models of shock leads to a dramatic reduction of organ dysfunction and mortality.  This treatment is currently being tested on patients in intensive care units.  Supported by NIH Grant GM85052

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