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Gapp J, Chandra S.
Introduction
Acute pancreatitis is common and is the leading cause of hospitalization amongst gastrointestinal disorders in the United
States. The severity of the disease varies widely, from mild disease needing conservative treatment to severe and complicated
disease with high morbidity and mortality. The diagnosis of acute presentation is easy, but the major challenge is predicting
progression of disease course and outcome. This is important to determine the level of care.
Etiology
In the majority of cases, alcohol use, gallstones, and hypertriglyceridemia cause acute pancreatitis. The rate of occurrence of
each etiology of acute pancreatitis varies across geographic regions and socio-economic strata. Common etiologies of acute
pancreatitis are listed below.
Alcohol use
Gallstones
Hypertriglyceridemia
Idiopathic
Drug-induced pancreatitis
Post-procedural (ERCP or abdominal surgery)
Ampullary stenosis is formerly known as sphincter of Oddi dysfunction type I
Autoimmune pancreatitis, type I (systemic IgG4 disease-related) and type II
Viral infection (Coxsackie, Cytomegalovirus, Echovirus, Epstein-Barr virus, Hepatitis A/B/C, HIV, Mumps, Rubella,
Varicella)
Bacterial infection (Campylobacter jejuni, Legionella, Leptospirosis, Mycobacterium avium, Mycobacterium
tuberculosis, Mycoplasma)
Trauma
Smoking
Congenital anomalies (annular pancreas)
Genetic disorders (hereditary pancreatitis, cystic fibrosis, alpha 1-antitrypsin deficiency)
Hypercalcemia
Parasitic infections (Ascaris lumbricoides, Cryptosporidium, Clonorchis sinensis, Microsporidia)
Renal disease (Hemodialysis)
Toxins (Scorpion bites, organophosphate poisoning)
Vasculitis (Polyarteritis nodosa, Systemic lupus erythematosus)
Epidemiology
Overall, the frequency of acute pancreatitis has been noted to be rising in the United States and the rest of the world. Whether
this trend is related to a true increase in incidence or simply increased detection is difficult to determine. The rise in incidence
is considered, in part, due to increased hypertriglyceridemia and metabolic syndrome with multiple reports showing an
increase in acute pancreatitis secondary to hypertriglyceridemia. Despite the increased incidence, mortality has decreased in
the United States with most recent studies citing mortality of approximately 2%. The peak age of incidence of acute
pancreatitis occurs in the fifth and sixth decades; however, mortality increases with age. Incidence has been thought to differ
across geographic regions and socio-economic regions and is likely related to differences in use of alcohol and occurrence of
Pathophysiology
The pathophysiology of pancreatitis incorporates both the localized destruction in the pancreas and systemic inflammatory
response. The inciting event is the premature activation of trypsinogen to trypsin within the acinar cell as opposed to in the
duct lumen. It is postulated that this can be caused by elevated ductal pressures (such as in duct obstruction) as well as
problems with calcium homeostasis and pH. Because calcium transport is an ATP driven process, particularly for
sequestration in the smooth endoplasmic reticulum, it is suspected that many toxins responsible for pancreatitis (including
alcohol) involve ATP depletion resulting in elevated intra-acinar calcium concentrations that stimulate early activation of
trypsinogen to trypsin, which activates enzymes such as elastase and phospholipases. Early activation of these zymogens leads
to localized tissue damage and release of Damage Associated Molecular Patterns (DAMPs). The release of DAMPs causes
recruitment of neutrophils and initiation of the inflammatory cascade. This inflammatory cascade is responsible for the
systemic manifestations of acute pancreatitis and can ultimately lead to increase capillary permeability and damage of
endothelium with microvascular thrombosis that causes multiorgan dysfunction syndrome (MODS), the main cause of
morbidity and mortality in acute pancreatitis.
More recently, it has become apparent that there is also a genetic predisposition for pancreatitis in some individuals. These
patients often suffer from recurrent acute pancreatitis and a progression to chronic pancreatitis. Not surprisingly, associated
genes are involved in the activation of trypsin. The cystic fibrosis transmembrane conductance regulator (CFTR) gene
involved in bicarbonate secretion into pancreatic ductules, cationic trypsinogen gene (PRSS1) gain of function mutations,
mutations in pancreatic secretory trypsin inhibitor (SPINK1), and trypsin degrading enzyme, chymotrypsin C (CTRC), all
play a role in recurrent pancreatitis. Furthermore, they are involved in the increasingly acknowledged spectrum of disease
from acute to chronic pancreatitis.
Evaluation
The diagnosis of acute pancreatitis has been defined by the Revised Atlanta Classification and requires at least 2 of 3 criteria
be met: 1) a lipase or amylase level that is three times the upper limit of normal 2) abdominal pain that is consistent with
pancreatitis 3) abdominal imaging consistent with acute pancreatitis. Initial evaluation of suspected acute pancreatitis involves
laboratory abnormalities are suggesting biliary cholestasis, hypercalcemia or severe hyperlipidemia will help in determining
the etiology of pancreatitis. An abdominal ultrasound is recommended in all the patients to assess for choledocholithiasis and
When no cause for pancreatitis is forthcoming with the evaluation mentioned above, consultation of a gastroenterology
specialist is often required for further evaluation with magnetic resonance cholangiopancreatography (MRCP), or endoscopic
ultrasound (EUS). As MRCP is non-invasive, there is no perioperative risk. MRCP is non-invasive, doesn’t require contrast
but lacks sensitivity for detection of biliary stones less than 3 mm and chronic pancreatitis and EUS is preferred. Diagnostic
ERCP is reserved for recurrent episodes of acute pancreatitis.
Treatment / Management
The foundation of management for acute pancreatitis remains early aggressive fluid resuscitation. Lactated Ringer's solution is
the recommended fluid of with an initial bolus of 15 to 20 mL/kg and following rates of 3 mL/kg per hour (usually
approximately 250 to 500 mL per hour) for the first 24 hours if no other contraindications are present. The fluid resuscitation
is monitored with a combination of blood urea nitrogen, hematocrit, and urine output, monitoring every 4 to 6 hours in first 24
hours of resuscitation to adjust the fluid rate. Continued non-response indicates a high likelihood of ensuing MODS and is
grounds for upgrading the level of care.
Another important issue is nutrition. Common practice is to keep nothing by mouth until abdominal pain, nausea, vomiting,
appetite, and ileus improve. Early feeding in mild pancreatitis is safe and does not exacerbate symptoms. Soft, low residue,
low-fat diet is recommended for initial feeding and advanced to regular consistency as tolerated. In cases of severe
pancreatitis or where peroral intake is not tolerated, nesojejunal feeding is superior to parenteral nutrition as it helps to
minimize bacterial translocation by maintaining the intestinal barrier.
Prophylactic antibiotics are not needed. If infection is suspected, empirical antibiotics are appropriate until cultures results are
back. Indication for antibiotic is limited to presence of infected necrosis.
Further management depends upon the etiology of pancreatitis. In gallstone pancreatitis, early cholecystectomy is strongly
recommended. Early ERCP (within 24 hours of presentation) is of benefit in cases of concurrent cholangitis and obvious
biliary obstruction. In cases of mild or spontaneously resolving biliary pancreatitis, ERCP is reserved for distal biliary filling
defect on intraoperative cholangiogram during cholecystectomy. In the setting of hypertriglyceridemia, the goal of specific
treatment is to bring down and maintain triglyceride level to less than 500 mg/dL. The options to achieve this goal include
apheresis and insulin drip with or without glucose.
Local complications of pancreatitis include early (less than 4 weeks, peripancreatic fluid collection and
pancreatitic/peripancreatic necrosis) and late (more than 4 weeks, pancreatic pseudocyst and walled-off necrosis). Acute
peripancreatic fluid collection resolves spontaneously in most cases, and less than 10% result in pancreatic pseudocyst. Most
of these pseudocysts resolve with observation alone with periodic follow-up using CT or MRI. Drainage is only recommended
in symptomatic, infected or rapidly enlarging pseudocysts. The drainage modalities include endoscopic (transmural or
transpapillary) or percutaneous, the endoscopic approach being the preferred modality.
Necrotic collection management remains challenging. The sterile collection is intervened if it caused symptoms such as
persistent abdominal pain, nausea, vomiting, gastric outlet obstruction, bowel obstruction and disrupted pancreatic duct. One-
third of this necrosis become infected. Infection results in clinical deterioration, lengthen the recovery, has high mortality.
Antibiotics are initiated on earliest suspicion. The preferred antibiotic regimen includes a carbapenem alone, or combination
of a quinolone, ceftazidime, or cefepime with metronidazole. Diagnosis of infected necrosis is established in the presence of
gas bubbles in it on imaging and CT-guided percutaneous aspiration culture. Surgical necrosectomy is needed in patients
Differential Diagnosis
The differentials for acute pancreatitis include the overall differential for abdominal pain and can often be greatly narrowed
with a good history and physical as described above. Differential diagnoses include but is not limited to the following:
In many of these cases, an elevated lipase level 3 times the upper limit of normal will allow for determination of pancreatitis
as the source of abdominal pain due to its high specificity. Abdominal ultrasound will help to differentiate cholecystitis
whereas CT angiogram can be used when mesenteric ischemia is high on the differential. In high-risk patients, the cardiac
source should be concurrently ruled out as pain can present atypically as epigastric. Progressing aortic dissection should be
considered due to its particularly urgent nature, though the pain is often more severe and tearing than for those with acute
pancreatitis.
Prognosis
Overall mortality of acute pancreatitis is approximately 1% to 2%; however, severe acute pancreatitis carries a much higher
but undetermined mortality rate.
Severity assessment and prognostication is important to determine the level of care. Multiple clinical prediction scales have
been developed and validated. Most are cumbersome to calculate and need 48-hour data. The Bedside Index for Severity in
Acute Pancreatitis (BISAP) is a relatively recent addition to this list. This index has good predictive performance for both
severe acute pancreatitis and mortality and has been validated prospectively, is simple and easy to calculate from initial
presentation data. Use of the CT Severity Index (CTSI) can also aid in predicting mortality with the detection of any necrosis
on CT imaging being a predictor of high mortality.
Questions
To access free multiple choice questions on this topic, click here.
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Publication Details
Author Information
1 Creighton University
2 Creighton University
Publication History
Copyright
Copyright © 2018, StatPearls Publishing LLC.
This book is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/),
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NLM Citation
Gapp J, Chandra S. Pancreatitis, Acute. [Updated 2018 Jan 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-.