"Endothelium in Sepsis and Multiple Organ Dysfunction Syndrome Sepsis"

     Sepsis, defined as the systemic inflammatory response to infection, is both common and deadly. The common themes in sepsis pathophsyiology are the following: 1) it is the host response rather than the nature of the pathogen that dictates patient outcome, 2) sepsis involves the activation of the coagulation and inflammatory pathways, both of which contribute to the high degree of morbidity and mortality associated with this condition, 3) the monocyte initiates the host response to infection, 4) the endothelium plays an important role in perpetuating the host response, 5) the monocyte and endothelial cell function in concert to defend host against pathogen, but in the process may inflict collateral damage that results in organ dysfunction that is not diffuse but rather remarkably focal in its distribution. The sepsis field is plagued by a long history of failed clinical trials. An understanding of the innate immune response, particularly the importance of the link between inflammation and coagulation provides helpful insight into emerging new therapies. In this lecture, we will emphasize the potential value of the endothelium as a therapeutic target in severe sepsis.