Organ Failure due to Systemic Injury in Acute Pancreatitis

Pathophysiology of systemic injury in acute pancreatitis
The pathophysiology of systemic injury in AP has remained enigmatic so far. The biggest 
hurdle has been the identification of mediators that are released locally in the pancreas and 
cause systemic injury. More so, as mentioned above, the systemic severity can precede local 
severity and the extent of pancreatic necrosis may not correlate with systemic injury, unless 
it is complicated by concurrent infection. It is to be noted that neither systemic involvement, 
nor its severity are related to the etiology of AP. Figure 2 summarizes the potential 
pathophysiology of systemic injury. This is based on literature in pancreatitis, as well as 
where individual agents have been studied in their ability to cause systemic injury 
irrespective of pancreatitis. The end points relevant to human disease are summarized in 
lower panel of Figure 2 and more than one positive study showing that the agent can incite 
the endpoint is taken as positive.
It is to be noted that there are numerous and parallel steps involved in acinar cell injury 
induced by a single agent like caerulein, which itself does not cause systemic injury. 
Therefore, the role of other important factors in amplifying the signaling to become 
Garg and Singh
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Gastroenterology. Author manuscript; available in PMC 2020 May 01.
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deleterious on a systemic level is essential. A clue to such factors that worsen pancreatitis 
lies in several reports showing hypertriglyceridemic AP to have a higher grade of severity 
than is usually reported. 
44-46
This may be related to the fatty acids that compose the 
triglyceride, and is discussed in detail under the section unsaturated fatty acids.