The immediate organ damage seen after multiple trauma and in shock is a typical example of nonbacterial inflammation triggered by activation of various mediators of both the humoral and cellular systems. Anaphylatoxins and the low-flow syndrome during the shock phase account for increased PMN* margination, which in turn causes pulmonary leukostasis and may provoke massive mediator release by PMN (oxygen radicals, proteinases, eicosanoids, PAF etc). This probably leads to severe endothelial cell damage, especially in the lung. Adherence of PMN to the endothelium appears to create the micro-environment where high concentrations of proteolytic enzymes and reactive oxygen radicals exert a deleterious effect on the cell membrane. Endothelial cell membrane injury leads to increased vascular permeability and cell edema. The development of the 'organ in shock' may require a few hours and initially cause minor or no functional impairment at all. Only when shock is severe is there early organ failure, which in this stage may still be an expression of non-bacterial inflammation. Numerous studies have reported the existence of shock-induced cardiodepressant substances in association with various forms of circulatory shock. We have determined a net negative inotropic effect of the low-molecular-weight plasma fraction in severe hypovolemic-traumatic shock and have isolated a cardiodepressant factor (CDF), which by blockade of the calcium inward current has a negative inotropic and chronotropic effect. The intestine as a shock organ appears to range first among the organs involved. The translocation of bacteria from the intestinal tract, the 'intestine in shock' represents the trigger reaction that eventually leads from the 'organ in shock', early organ failure to late (septic) organ failure. Here the most prominent factor is endotoxin (LPS) as a basic mediator of gram-negative bacteria, which also triggers the activation of humoral and cellular systems. The posttraumatic hyperdynamic phase commonly starts on days 3-5 and is mainly caused by bacteremia and/or endotoxemia. Macrophages have a major impact on the late phase of organ failure. At present, the most prominent cellular mediator of the lethal effect of endotoxin is thought to be cachectin, which is identical with the tumor necrotising factor (TNF). TNF is secreted by monocytes/macrophages (MO/MA) in response to LPS. Via macrophage derived cytokines and by LPS there is activation of endothelial cells, with increased adhesiveness for PMN. Both due to this increased adhesiveness and the presence of LPS and cytokines, PMN undergo massive activation, which causes mediator release and tissue damage. Endotoxin also plays a prominent causative role in the development of disseminated intravascular coagulation (DIC) via the expression of PCA from MO/MA in connection with activated endothelial cells (PCA)- tissue factor. This, in turn, may create microthrombosis - the morphologic substrate for organ failure. In conclusion, we can say that cell damage leading to cell death of the various organs is the precondition of both early and late organ failure, which is known as MOF.
