Organ Failure due to Systemic Injury in Acute Pancreatitis

Mechanisms of Organ Dysfunction due to systemic perturbations – 
Lessons from Sepsis induced Organ Failure:
Mitochondria are at the center of cellular perturbations from tissue hypo-perfusion, which 
may result from hypovolemia, hypotension, and microvascular thrombi causing cellular 
hypoxia. Since mitochondrial energy production is oxygen dependent, their ability to 
generate ATP is severely compromised in such states, and can result in cellular dysfunction. 
OF may primarily be due to such mitochondrial dysfunction rather than cell death.
185
The 
following observations support this hypothesis: (i) Cellular injury and death is minimal in 
post-mortem examination of failed organs,
186
(ii) functional recovery of the organ is swift 
once the underlying pathophysiological perturbations reverse, and (iii) mitochondrial 
structural and functional changes have been documented in such patients. These 
observations are important from the point of prognosis and identifying targets for therapy.
Treatment of Organ Failure:
Treatment for OF is largely supportive. Patients with predicted severe AP should be referred 
to a tertiary care center with intensive care unit (ICU) facility. Patients with OF must be 
managed in an ICU and often require organ support such as dialysis, mechanical ventilation, 
and vasopressors.
Fluid and electrolyte balance is critical in the beginning of the illness. Ringer’s lactate has 
been shown to be better than normal saline in reducing systemic inflammation.
187, 188 
Garg and Singh
Page 11
Gastroenterology. Author manuscript; available in PMC 2020 May 01.
A
uthor Man
uscr
ipt
A
uthor Man
uscr
ipt
A
uthor Man
uscr
ipt
A
uthor Man
uscr
ipt

---

Optimal amount of fluid administration remains a challenge.
189
Both under-and aggressive 
hydration can be detrimental. A randomized trial showed worsening of OF in patients given 
aggressive fluid therapy
190
. On the contrary, relative hypovolemia due to under correction of 
fluid deficit can lead to increased risk of necrosis. A recent trial showed benefit of 
aggressive fluid administration in mild AP.
190
But the results cannot be extrapolated to 
patients with severe AP because systemic events leading to OF develop rapidly and 
overzealous fluid therapy may exacerbate the clinical condition in those with impending 
respiratory and renal failure. One of the important points to consider is that normal 
homeostatic mechanisms are disturbed in patients with systemic injury due to abnormalities 
such as increased vascular permeability and thus the capability to deal with extra fluid being 
infused is compromised unlike in patients with mild AP.
Enteral nutrition should be instituted as soon as possible and has been shown to reduce the 
length of hospital stay and possibly the risk of infected necrosis.
191
A multidisciplinary team 
comprising of a critical care expert, gastroenterologist, intervention radiologist and surgeon 
should look after the patient.