Sepsis-induced multi-organ dysfunction syndrome—a mechanistic approach

Sepsis-associated mortality is highly related to the development of the multi-organ dysfunction syndrome (MODS). MODS represents a virulent and often incremental assault on virtually all organ systems. Interestingly, the pathogenetic mechanisms that underlie MODS in sepsis are complex and not entirely elucidated. Most implicated molecular culprits are overshooting of the host immune response to the infectious trigger, endothelial cell activation and glycocalyx destruction, alterations at the mitochondrial level, and uncontrolled apoptosis. In addition, microcirculatory dysfunction characterized by perfusion heterogeneity, thrombosis, and intravascular blood cell clogging significantly decreases tissue oxygen delivery. In the background, the gut may continuously fuel MODS by sustaining systemic inflammatory processes either by propagating transmural bacterial translocation or by shedding inflammatory molecules through the intestinal lymph system. From a holistic viewpoint, all proposed pathways leading to sepsis-induced MODS probably are closely intertwined which renders a single therapeutic approach for sepsis-induced MODS irrelevant.