Pathophysiologie der Sepsis

Die Sepsis ist noch immer eines der bedrohlichsten Krankheitsbilder der modernen Medizin mit einer hohen Mortalitätsrate. Das zunehmende Wissen um die Komplexität und Heterogenität der septischen Immunpathologie kann Wege eröffnen, zukünftig Sepsispatienten individueller – und somit erfolgreicher – behandeln zu können. Dieser Beitrag stellt den aktuellen Kenntnisstand der Pathophysiologie der Sepsis und des septischen Schocks dar.

Abstract

Up to now, sepsis is one of the most threatening diseases and its therapy remains challenging. Sepsis is currently defined as a severely dysregulated immune response to an infection resulting in organ dysfunction. The pathophysiology is mainly driven by exogenous PAMPs (“pathogen-associated molecular patterns”) and endogenous DAMPs (“damage-associated molecular patterns“), which can activate PRRs (“pattern recognition receptors”) on different cell types (mainly immune cells), leading to the initiation of manifold downstream pathways and a perpetuation of patients’ immune response. Sepsis is neither an exclusive pro- nor an anti-inflammatory disease: both processes take place in parallel, resulting in an individual immunologic disease state depending on the severity of each component at different time points. Septic shock is a complex disorder of the macro- and microcirculation, provoking a severe lack of oxygenation further aggravating sepsis defining organ dysfunctions. An in-depth knowledge of the heterogeneity and the time-dependency of the septic immunopathology will be essential for the design of future sepsis trials and therapy planning in patients with sepsis. The big aim is to achieve a more individualized treatment strategy in patients suffering from sepsis or septic shock.

Kernaussagen

• Sepsis ist definiert als eine schwerwiegende dysregulierte Immunantwort auf dem Boden einer Infektion, aus der eine Endorganstörung resultiert.

• Im Zentrum der septischen Pathophysiologie steht zu Beginn ein sog. Zytokinsturm, der maßgeblich durch die Antwort des angeborenen Immunsystems getragen wird. Im Verlauf kann sich eine eher immunparalytische Situation einstellen.

• Exogene PAMPs und endogene DAMPs aktivieren sog. PRRs, welche mannigfaltige Downstream-Pathways aktivieren und die weitere Immunantwort bahnen.

• Die Sepsis ist weder ein reines pro- noch antiinflammatorisches Krankheitsbild. Vielmehr laufen pro- und antiinflammatorische Prozesse stets parallel zueinander ab, sodass die immunologische Gesamtsituation je nach Ausprägungsgrad der einzelnen Komponenten patientenindividuell und zeitabhängig deutlich differiert.

• Der septische Schock zeichnet sich durch eine kombinierte Störung sowohl der Makro- als auch der Mikrozirkulation aus. Die hieraus resultierenden Oxygenierungsstörungen bedingen die sepsisdefinierenden Endorganstörungen.

• Das Wissen um die Heterogenität der septischen Immunpathologie muss bei der Konzeption zukünftiger Sepsisstudien sowie der Therapieplanung des individuellen Sepsispatienten Berücksichtigung finden. Das Ziel ist es, eine zunehmende Individualisierung der Sepsistherapie zu erreichen!

Schlüsselwörter

Sepsis - septischer Schock - Inflammation - COVID-19

Publication History

Article published online:
10 October 2023

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