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Pathogenese der akuten Pankreatitis

Pathogenesis of acute pancreatitis

Zusammenfassung

Die akute Pankreatitis ist charakterisiert als der Selbstverdau des Pankreas durch seine eigenen Verdauungsenzyme. Der pathophysiologische Beginn der Erkrankung liegt in der pankreatischen Azinuszelle. Hier werden die normalerweise als inaktive Vorstufen sekretierten Proteasen verfrüht aktiviert und verdauen infolgedessen die Zellen von innen heraus. Die Aktivierung von Trypsinogen zu Trypsin stellt hierbei ein Schlüsselereignis dar, da aktives Trypsin weitere Verdauungsenzyme aktivieren und somit die gesamte Aktivierung der Proteasekaskade in Gang setzen kann. Diese verfrühte Proteaseaktivierung resultiert im Zelltod der Azinuszellen wie auch in der Induktion einer stark proinflammatorisch geprägten Immunantwort. Zellen des angeborenen Immunsystems migrieren in das geschädigte Organ und potenzieren den lokalen Schaden noch einmal über die Freisetzung inflammatorischer Zytokine wie Tumor-Nekrose-Faktor α oder auch reaktiver Sauerstoffspezies. Begleitend zur lokalen Immunreaktion kommt es auch zu einer systemischen Aktivierung des Immunsystems, die sich bis hin zu einem „systemic inflammatory response syndrome“ (SIRS) entwickeln kann. Im Zuge des SIRS kann es zu schwerwiegenden Komplikationen wie dem Versagen von Organen kommen. Folge dieses ausgeprägten SIRS im späteren Krankheitsverlauf ist eine starke immunologische Gegenregulation, das sogenannte „compensatory anti-inflammatory reaction syndrome“ (CARS). Im Zuge dieser Immunsuppression können kommensale Bakterien aus dem Darm die Pankreasnekrose besiedeln. Die SIRS/CARS-Balance ist ausschlaggebend für den Verlauf und die Prognose des Patienten.

Abstract

Acute pancreatitis is characterized by the autodigestion of the pancreas by its own digestive enzymes. The pathophysiological onset of the disease occurs in the acinar cells. The normally inactive precursors of secreted proteases are prematurely activated and as a result digest the cells from within. The activation of trypsinogen to trypsin represents the key event as active trypsin activates further digestive enzymes and can therefore initiate the activation of the complete protease cascade. This premature activation of proteases results in the cell death of acinar cells and in the induction of a strong proinflammatory immune response. Cells of the innate immune system migrate into the damaged organ and potentiate the local damage again via the release of inflammatory cytokines, such as tumor necrosis factor alpha and reactive oxygen species. Concomitant to the local immune reaction, a systemic activation of the immune system also occurs, which can develop into a systemic inflammatory response syndrome (SIRS). In the course of the SIRS severe complications such as organ failure can occur. The consequence of this pronounced SIRS in the later course of the disease is a strong immunological counter-regulation, the so-called compensatory anti-inflammatory reaction syndrome (CARS). In the course of this immunosuppression commensal bacteria from the intestines can colonize the pancreatic necrosis. The outcome of the SIRS/CARS balance is decisive for the course and the prognosis of the patient.

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Correspondence to Hana Algül MPH.

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M. Sendler und H. Algül geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Markus M. Lerch, München

Joachim Mössner, Leipzig

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Sendler, M., Algül, H. Pathogenese der akuten Pankreatitis. Internist 62, 1034–1043 (2021). https://doi.org/10.1007/s00108-021-01158-y

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Schlüsselwörter

  • Kalziumsignal
  • Trypsin
  • „Systemic inflammatory response syndrome“
  • Multiorganversagen
  • Lokale und systemische Immunreaktion

Keywords

  • Calcium signaling
  • Trypsin
  • Systemic inflammatory response syndrome
  • Multi-organ failure
  • Local and systemic immune response