Organ Failure due to Systemic Injury in Acute Pancreatitis

Table 1:
Differences between primary and secondary organ failure
Characteristic
Primary Organ Failure
Secondary Organ Failure
Cause
Sterile inflammation
Sepsis
Timing
Early
Late
Therapeutic window of opportunity
Small
Large
Treatment
Supportive
Control of sepsis
Prognosis
Poor
Relatively better
Table 1 is adapted from reference 9
Gastroenterology. Author manuscript; available in PMC 2020 May 01.

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Table 2:
Summary of Results of Recent Studies highlighting Mortality in Patients with Persistent Organ Failure
Study*
Number of
patients with
AP
Number of
patients with
POF
Mortality in
patients with
POF
Mortality in patients
with early onset
POF
$
Mortality in
patients with late
onset
POF
Padhan et al 2018 (ref 9)
805
365
156 (42.7%)
104/225 (46%)
52/140 (37%)
Schepers et al 2018 (ref 10)
639
219
83 (38%)
47/112 (42%)
36/107 (33.6%)
Sternby et al 2018 (ref 13)
1655
113
59 (52.2%)
47/89 (52.8%)
12/24 (50%)
POF = persistent organ failure
*
These are recent large studies, which had categorized patients according to revised Atlanta classification and the patients were treated as per 
current standard of care.
$
Early OF defined by development of OF within the first week of onset of AP
Gastroenterology. Author manuscript; available in PMC 2020 May 01.

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ipt
A
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uscr
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Garg and Singh
Page 29
Table 3:
Markers and mediators of systemic injury in acute pancreatit
Markers and mediators of systemic injury
Released from acinar cells
Trypsin
Inflammatory cells and their products
Neutrophils
NET
Inflammasome
Cytokines
IL-6
IL-1
β
TNF-
α
IL-12
IL-18
Adipokines
Resistin
Visfatin
Lipid mediators:
Unsaturated fatty acids
Platelet activating factor
DAMPs
HMGB1
sRAGE
ds-DNA
Histones/ nucleosomes
S100 proteins
ATP
Extracellular matric (e.g. hyaluronan)
Gastroenterology. Author manuscript; available in PMC 2020 May 01.

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Document Outline

• Abstract
• Definition of Organ Failure:
• How common is OF in AP?
  • Risk Factors for Organ Failure:
  • Clinical determinants/Characteristics of Organ Failure:
• Primary (Early) Sterile and Secondary (Late) Septic Organ Failure in Acute Pancreatitis:
• Clinical correlates of OF: Can we predict Organ Failure?
• Clinical trajectory of Organ Failure - Impact on outcome:
• Pathophysiology of systemic injury in acute pancreatitis
  • Distinction between markers, mediators and end-points of systemic injury:
  • Animal models and systemic injury in AP:
• Potential mediators of systemic injury in AP:
  • Trypsin:
  • Neutrophils:
  • Neutrophil extracellular traps (NETs):
  • Damage associated Molecular patterns (DAMPs):
  • Inflammasome:
  • Adipokines and Cytokines:
  • Coagulation pathway:
• Lipid mediators:
  • Platelet activating factor (PAF):
  • Unsaturated fatty acids (UFAs):
  • Role of Intestine in systemic injury:
• Mechanisms of Organ Dysfunction due to systemic perturbations – Lessons from Sepsis induced Organ Failure:
  • Treatment of Organ Failure:
  • Specific therapy for Organ Failure:
  • Unmet needs and potential areas for future research:
• References
• Figure 1:
• Figure 2:
• Table 1:
• Table 2:
• Table 3: