Pathophysiologie der Sepsis

Kernaussagen

• In den letzten Jahren steigt die Rate an nosokomialen Infektionen und Infektionen mit multiresistenten Erregern.

• Zentrale Pathomechanismen der Sepsis sind neben der systemischen Inflammation die Koagulopathie, die endotheliale Dysfunktion und die Mikrozirkulationsstörung. Diese sind eng miteinander verzahnt und sollten lediglich zu didaktischen Zwecken isoliert betrachtet werden.

• Die Immunantwort wird induziert durch die Erkennung exogener und endogener Virulenzfaktoren durch spezifische Oberflächenrezeptoren auf immunkompetenten Zellen.

• Der infektassoziierten Depression des Immunsystems ist ein mindestens ebenso hoher Stellenwert wie der in der Initialphase klinisch offenkundigen Inflammation beizumessen.

• Die septische Koagulopathie beinhaltet nicht nur eine Aktivierung prothrombotischer Kaskaden, sondern auch eine Abschwächung gerinnungshemmender Mechanismen und eine Unterdrückung des Fibrinolysesystems.

• Die endotheliale Dysfunktion führt zu einer Vasodilatation, einem Kapillarleck mit konsekutiver Ödembildung sowie zu proinflammatorischen und thrombogenen Stimuli.

• Die Mikrozirkulationsstörung ist durch eine „heterogene Perfusion“ charakterisiert. Neben normal perfundierten Bereichen gibt es Areale mit reduzierter oder erloschener Perfusion, aber auch solche mit deutlich erhöhtem arteriolärem Blutfluss.

• Die Orientierung der supportiven hämodynamischen Therapie an Parametern der Makrodynamik wird zunehmend kritisch hinterfragt. Neue Techniken ermöglichen mittlerweile die bettseitige Überwachung der Mikrozirkulation.

• Die „zytopathische Hypoxie“, also die Störung des zellulären Energiestoffwechsels trotz normalem bis supranormalem Sauerstoffpartialdruck, ist hauptverantwortlich für die sepsisassoziierte Einschränkung der Organfunktionen.

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