Inflammation, coagulopathy, and the pathogenesis of multiple organ dysfunction syndrome

Objective: An improved understanding of the mechanisms through which infect ing pathogens harm the host is leading to new formulations of the concept o f sepsis, We review the roles of inflammation and coagulation in the pathog enesis of the multiple organ dysfunction syndrome, and explore the potentia l of new therapies to restore the fine biological balance between procoagul ant and anticoagulant mechanisms that are disrupted during the life-threate ning processes that lead to organ dysfunction, Data Sources:Narrative review of published primary sources in the basic and clinical literature. Data Summary:Traditional models of host-pathogen interactions ascribe the m orbidity of infection to the direct cytotoxic effects of micro-organisms on host tissues. However, abundant experimental and clinical evidence has rev ealed that it is the response of the host, rather than the trigger that eli cited it, that is the more potent determinant of outcome. The elucidation o f a complex network of host-derived inflammatory mediators raised the possi bility that targeting these individually could improve patient outcomes, an d some modest successes with this approach have been achieved. More recentl y, it is becoming evident that the inflammatory response, in turn, mediates its deleterious effects by inducing tissue hypoxia, and cellular injury, e ither through tissue necrosis or through the induction of programmed cell d eath or apoptosis, Thus, treatment strategies that target the downstream co nsequences of the activation of inflammation, for example, microvascular co agulation or acute adrenal insufficiency, represent the latest, and some of the most promising approaches to attenuation of the septic response to imp rove survival, and minimize organ dysfunction, The maladaptive sequelae of systemic inflammation, embodied in the concept of the multiple organ dysfun ction syndrome, comprise the leading obstacle to survival for patients admi tted to a contemporary intensive care unit Further insights into this intim idatingly complex process will not only provide potent new therapeutic opti ons, but promise to transform critical illness from a biological standoff, during which the clinician merely supports failing organs, to a disease tha t can be successfully treated.