Pathophysiologische Grundsätze bei Sepsis

Zusammenfassung

Präklinische und klinische Untersuchungen der vergangenen Jahre erweiterten das pathophysiologische Verständnis der bei Patienten mit schwerer Sepsis ablaufenden Störungen deutlich . Dabei wurde deutlich, dass die den septischen Krankheitsbildern zugrunde liegende Infektion im engeren Sinne für die Schwere und ungünstige Prognose der Sepsis weniger verantwortlich ist. Vielmehr ist es die außer Kontrolle geratene Reaktion des Organismus auf diese Infektion, die sich bei nicht (mehr) lokalisierter Infektion in Form einer im Wesentlichen Zytokin-vermittelten Entzündungsreaktion dem systemischen inflammatorischen Response-Syndrom mit seinen Folgen widerspiegelt.

Die im Rahmen dieses Syndroms freigesetzten Mediatoren, z.T. in Zusammenwirkung mit Produkten aus infektiösen Mikroorganismen, führen auch zu einer systemischen Aktivierung der Hämostase. Die Aktivierung von Monozyten/Makrophagen sowie die des Endothels stehen dabei im Zentrum des pathophysiologischen Modells. Die davon ausgehende Aktivierung von plasmatischen Kaskadensystemen betreffen auch Gerinnungs-und Fibrinolysesystem, wobei die bei Sepsis beobachtete Gerinnungsaktivierung und Fibrinolysehemmung ihrerseits mit Leukozyten und Endothel interagiert und zur zunehmenden Schädigung der Mikrozirkulation beiträgt. Als deren klinisches Korrelat können Organdysfunktionszustände aufgefasst werden. Es kommt zu einem individuell unterschiedlichen Nebeneinander von überschießender Fibrinbildung, Faktoren-, Inhibitoren-und Thrombozytenverbrauch sowie Störungen des Fibrinolysesystems. Klinisch kann dies neben Organdysfunktionen zu einer disseminierten intravasalen Gerinnung, z.T. mit Blutungskomplikationen, führen.

Summary

Within the recent years preclinical and clinical investigations to a great extend increased the pathophysiological understanding what is going on in patients with severe sepsis. It became evident, that not the initiating infection by itself is the main reason for the severeness and limited prognosis in sepsis. More important is the unbalanced reaction of the patient's organism to this infection, which is reflected in a mainly cytokine driven inflammation, the so called systemic inflammatory response syndrome, with its consequences.

In the context of this syndrome released mediators, in part together with toxins from infectious microorganisms, result in a systemic activation of haemostasis. In the centre of our pathophysiologic model are the activations of the monocyte/macrophage-system and of the endothelium. This results in the activation of plasmatic cascades including the coagulation and fibrinolysis systems. The observed activation of haemostasis and inhibition of fibrinolysis in patients with sepsis by themselves interact with leukocytes and endothelium and play an important role in the progressive derangement of microcirculation. This is clinically reflected in organ dysfunctions. Within a single individual patient there is increased fibrin formation, decreases in coagulation factors, inhibitors and platelets, as well as defects of the fibrinolytic system in parallel that may clinically result in disseminated intravascular coagulation with the risk of bleeding complications in addition to organ dysfunctions.

Schlüsselwörter

Sepsis - Pathophysiologie - Zytokine - Hämostase - Gerinnungshemmung

Keywords

Sepsis - pathophysiology - cytokines - haemostasis coagulation inhibitors

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