Sepsis and septic shock: endothelial molecular pathogenesis associated with vascular microthrombotic disease

Physiological and pathological response mechanisms in sepsis. In sepsis, host response is characterized by two mechanisms. One is physiologic defensive mechanism through immune system, and the other is pathologic destructive mechanism through endothelial system. The physiologic response and pathologic clinical syndromes are notated in the Figure. Now, we know that complement system, protecting the host through innate immune system, could trigger harmful endothelial pathogenesis. This dual role of the complement must be nature’s rule just like normal hemostasis, which protects human lives in external bodily injury, but also may harm human lives in intravascular injury through thrombogenesis. Abbreviations: APC antigen presenting cell, “DIC” disseminated intravascular coagulation, DIT disseminated intravascular microthrombosis, EA-VMTD endotheliopathy-associated vascular microthrombotic disease, MAHA microangiopathic hemolytic anemia, MODS multiorgan dysfunction syndrome, MOF multiorgan failure, NO nitric oxide, IF interferon, IL interleukin, LPS lipopolysaccharide, SIRS systemic inflammatory response syndrome, TNF tumor necrosis factor, TTP thrombotic thrombocytopenic purpur