[Pathogenesis of severe sepsis--from macrocirculation to mitochondria]

Severe sepsis is at present serious medical and social problem. In contrast to many other diseases its incidence shows an upward tendency and so does mortality due to sepsis. From the point of view of pathogenesis the cause of this complaint is a disturbed response to infection. The basis of this disruption is either a huge local inflammation that goes hand in hand with the penetration of proinflammatory cytokines into systemic circulation or an excessive proinflammatory systemic response. In the first instance the consequence is a systemic proinflammatory response accompanied by a disruption of macrocirculation, later also of microcirculation and finally mitochondrial failure. These mechanisms are responsible for the gradual failure of distant organs. In the second instance the consequence is a deactivation of systemic and local immunocompetent cells accompanied by the risk of uncontrolled proliferation of microorganisms. Affected are organs with a disturbed antimicrobial barrier, especially the lungs du ring mechanical ventilation, the bloodstream or the urinary system during catheterization. A large group of selectively acting preparations has been clinically tested in the management of this disorder, but only very few of these preparations were efficacious. We may postulate that the great diversity of the investigated population of patients was responsible for this lack of success.