Mediators in the Pathogenesis of Septic Shock — State of the Art

Abstract

The past 50 years of research into shock have shown that the events leading to malnutrition of organs, cellular hypoxia, insufficiency of cellular and organ systems, and death in shock are predominantly due to early disturbances in microcirculatory functions rather than to failures in the macrocirculation. It is generally accepted that local regulation of the microcirculatory blood flow is largely dependent on the liberation and/or formation of chemical mediators, either from the parenchymal tissues in the immediate vicinity of the small blood vessels, from the vascular smooth-muscle endothelial cell complexes, or directly from various blood cells [12–14]. A variety of mediator concepts have been discussed during the past 15 years in descriptions of microcirculatory dysfunctions and causal relationships, especially in the pathogenesis of the septic shock syndrome. However, there is no general agreement among specialists on shock concerning the significance of specific, individual mediators or other active substances. This is due chiefly to different shock paradigms, the change of factors’ causal roles at various stages in the evolution of shock, and species-specific responses. This chapter presents an overview of the current state of research in this area. Furthermore, new concepts (a) to establish and (b) to assess the causal role of single mediators in the pathogenesis of septic shock are described. Application of these concepts may help to improve current therapeutic strategies and improve the outcome of this severe disease syndrome, with its unacceptably high mortality rate.

Supported by grant from the Deutsche Forschungsgemeinschaft Lo 199/14-2.