Sepsis und Multiorganversagen – Pathophysiologie der Sepsis

Zusammenfassung

Unser Verständnis der Ursachen und pathophysiologischen Grundlagen der Sepsis war im Laufe der Zeit einem stetigen Wandel unterworfen. Nach heutigem Verständnis handelt es sich bei der Sepsis um eine Immunpathologie, die zwar durch eine Infektion ausgelöst wird, deren klinisches Bild jedoch maßgeblich von der Reaktion des Wirtsorganismus bestimmt wird. Die Sepsis ist daher weder als rein pro-, noch als anti-inflammatorisches Syndrom zu verstehen. Vielmehr kommt es im Verlauf zu einer Überlagerung verschiedener Mechanismen des Immunsystems. Während in einer frühen Phase der Sepsis die überschießende (proinflammatorische) Immunreaktion dominiert, kommt es schnell zu einer antiinflammatorischen Kompensation dieser Reaktion, welche oftmals in einer Immundysfunktion mit konsekutiver Anfälligkeit für Sekundärinfektionen resultiert. Die vorliegende Übersichtsarbeit soll einen Überblick über die breite Palette an molekularen Mechanismen geben, die dem klinischen Bild der Sepsis zugrunde liegen.

Abstract

Our understanding of the causes and pathophysiological basis of sepsis has been subject to constant change over the last decades. In today's understanding, sepsis is primarily a pathology of the immune system, triggered by an underlying infection but perpetuated by the host's response itself. Thereby, sepsis should not be categorized to be either a sole pro- or anti-inflammatory syndrome, but rather as a variable continuum of overlaying immune mechanisms. While a overshooting immune reaction predominates in early sepsis, this reaction is rapidly compensated, often leading to a immune dysfunction, rendering the host susceptible for secondary infections. This review aims to provide the reader with an overview of the broad molecular mechanisms contributing to the clinical picture of sepsis.

Kernaussagen

• Sepsis ist eine Immunpathologie, ausgelöst durch eine Infektion und getragen durch die Immunreaktion des Organismus.

• Der Verlauf der Erkrankung ist sowohl abhängig von der individuellen Prädisposition des Patienten als auch von der Infektion.

• Im Schwerpunkt der Pathogenese stehen die Zellen des angeborenen Immunsystems.

• Pro- und anti-inflammatorische Mechanismen koexistieren in der Sepsis.

• Aufgrund der engen Interaktion von Gerinnungs- und Immunsystem sowie des Endothels kommt es zur Beeinträchtigung der Hämodynamik und daraus resultierend zum Funktionsverlust zahlreicher Organe.

• In der späten Phase der Sepsis dominiert oftmals eine Immunparalyse, welche die Entstehung von Sekundärinfektionen begünstigt.

• Biomarker-gestützte, individualisierte Therapieverfahren können zu einer Rekonstituierung der Immunhomöostase führen.

• Sepsis ist eine interdisziplinäre Herausforderung von Ärzten und Wissenschaftlern.

Schlüsselworte:

SIRS - CARS - späte Sepsis - Zytokine - angeborene Immunität

Key words:

SIRS - CARS - late sepsis - cytokines - innate immunity

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