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Mechanism of Systemic Inflammation Associated Endothelial and Epithelial Cell Dysfunction Following Acute Pancreatitis, Trauma, and Burns
Systemic inflammatory response syndrome (SIRS) is difficult to study in humans because the response to injury in humans is heterogeneous, development of SIRS is unpredictable and progression to vascular leak syndrome (VLS) is highly variable, suggesting multiple hidden variables between people. Obesity and hypertriglyceridemia (HTG) increase risk of multiorgan dysfunction syndrome (MODS), giving some clues to pathophysiology, but these factors account for a minority of variability. Endothelial cell injury and VLS [leading to intravascular hypovolemia and shock], appear to link SIRS to MODS, which is prolonged by gut leak syndrome (GLS). We show that toxic serum affects the endothelial cells by at least three specific mechanisms: free fatty acids (FFAs), cytokines, and high molecular weight proteins. We are investigating if similar mechanisms lead to epithelial cell injury. We hypothesize that one or more mechanism(s) may be the major contributor(s) to VLS in individual patients, and that parallel processes cause gut permeability (allowing bacterial products to enter the circulation) and that these mechanisms are targetable.
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