Organ Failure due to Systemic Injury in Acute Pancreatitis

Definition of Organ Failure:
OF, as a generic term, can be defined as significant functional impairment of an organ 
system that is critical to sustenance of life. The severity of organ dysfunction can be 
quantified based on the parameter best defining the primary function of that particular organ 
e.g. partial pressure of arterial oxygen (PaO2) for pulmonary function or serum creatinine 
for renal function. In the case of AP, 3 organ systems are considered most important i.e. 
respiratory, renal and cardiovascular which are most commonly involved.
2
The severity of 
organ dysfunction is graded by the modified Marshall grading in AP 
2
which is preferred 
over the sequential organ failure assessment (SOFA) score used in sepsis. Any organ 
dysfunction of ≥grade 2 severity persisting for >48 hours is considered as persistent OF and 
defines SAP. Transient organ failure of <48 hours is considered a criterion for moderate AP.
How common is OF in AP?
The proportion of patients with AP who develop OF varies in different studies and primarily 
depends on the setting. Data from population-based cohort studies show a lower proportion 
of patients with OF while tertiary care hospital based studies have shown a much higher 
frequency of OF. Population based studies have shown the proportion of OF (severe AP) 
between 8% and 20%.
6-8
On the other hand, the proportion of patients with OF in large 
series of patients from tertiary care hospitals may reach up to 40%.
9, 10
Risk Factors for Organ Failure:
Why some patients develop OF and others do not is a matter of great importance. Host 
factors such as age, co-morbid conditions, obesity, triglyceride levels, etiology, extent of 
local pancreatic injury, and genetic predisposition have been reported to predict the 
development of OF in patients with AP. Older age is a risk factor for OF and worse outcome 
which could also be due to co-morbidities.
11, 12
Co-morbidities, as measured by Charlson 
comorbidity index, may become worse due to AP and contribute to poor outcome but have 
not been directly related to another organ dysfunction.
13
Obesity is an established bad 
prognostic marker of outcome in patients with AP.
14
Visceral obesity predisposes to the 
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development of OF.
15
Lipotoxicity causes multi-organ failure and exacerbates AP in obesity.
16
Peripancreatic visceral fat necrosis has been shown to worsen AP independent of 
pancreatic necrosis via unsaturated fatty acids resulting in OF.
17
Triglyceride levels at 
admission have been correlated with the severity of AP and even mild to moderate 
hypertriglyceridemia was found to be associated with the development of persistent OF.
18 
Etiology has not been found to be an independent risk factor for OF although patients with 
alcohol induced AP may have a higher risk of early onset OF.
19
Association between the 
extent of local pancreatic injury as measured by the extent of necrosis and development of 
OF has been reported but the causality is not established.
3, 20-22
The mechanisms of local 
tissue injury leading to pancreatic necrosis and systemic injury manifesting as OF are 
intimately linked.
23
The issue from the pathophysiology point of view is if the extent of 
necrosis is causally related to the development of OF or do they both signify the end result 
of a severe response to acute pancreatic injury. The association between extent of necrosis 
and OF could be bidirectional. A complex inflammatory network in which the extent of 
(peri)pancreatic necrosis influences the severity of OF and OF exacerbates the development 
of pancreatic necrosis might exist.
24,25
Given the apparent similarities in the etiology and phenotype of patients with varying grades 
of severity of AP, differences in inter-individual inflammatory responses might explain the 
variability in the severity of AP. It is conceivable that the highly variable inflammatory 
response might be related to an underlying genetic predisposition. However, the data 
regarding the role of genetic polymorphisms in determining the severity of AP are scant and 
equivocal. 
TNF-
α gene polymorphism was associated with severity but this finding has not 
been validated in other studies.
26-28
MCP-1 gene polymorphism was associated with 
increased risk of severe AP with the G allele acting as the risk factor but the data were 
inconsistent.
29, 30
One study has shown genetic polymorphisms of 
IL-6 gene to alter the 
level of IL-6 but did not find any association with the severity of AP.
26