Acute Pancreatitis is the Third Leading Gastrointestinal Etiology of Hospitalization in the United States (Gastroenterology, 2019) [MEDLINE]
Gallstones (Cholelithiasis) and Chronic Alcohol Use Disorder Account for Approximately 66% of Acute Pancreatitis Cases (see Cholelithiasis and Ethanol)
Incidence
Annual Incidence of Acute Pancreatitis Ranges from 4.9-35.0 Annual Cases Per 100,000 People (Lancet, 2020) [MEDLINE]
Etiology
General Comments
Recommendations (American College of Gastroenterology Guidelines: Management of Acute Pancreatitis, 2024) (Am J Gastroenterol, 2024) [MEDLINE]
In Patients >40 y/o without an Established Etiology of Acute Pancreatitis a Pnacreatic Tumor Should Be Considered as a Possible Etiology of Acute Pancreatitis
Following a Second Episode of Acute Pancreatitis with No Identifiable Etiology (and the Ability to Tolerate Surgery), a Cholecystectomy Should Be Performed to Decrease the Risk Recurrent Acute Pancreatitis Episodes
Congenital
Choledochocele Type V
Epidemiology
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Pancreas Divisum
Epidemiology
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Genetic
General Comments
Patients with Genetic Risk of Pancreatitis May Present as Recurrent Acute Pancreatitis (or Childhood Pancreatitis without a Known Etiology) with Eventual Progression to Chronic Pancreatitis
The Majority of “Idiopathic” Pancreatitis Cases Appear to Have Genetic Risk, Especially in Younger Patients (Age <35 y/o)
Pathogenic Variants in the CFTR Gene Can Be Associated with Pancreatitis with/without Associated Pulmonary Manifestations of Cystic Fibrosis (CF)
Patients with Cystic Fibrosis (CF)
Cystic Fibrosis (CF) is an Autosomal Recessive Genetic Disorder Caused by Severe Variants in the CFTR Gene
Approximately 85% of Patients with Cystic Fibrosis (CF) Have 2 Severe CFTR Variants, Such as F508del/F508del (the Most Common Allele Causing Disease)
Results in Minimal/Absent Functional CFTR Protein on Epithelial Cells of the Respiratory System, Digestive System, Reproductive Organs, and Skin
Patients with These Genotypes Have Abnormal Sweat Chloride Measurements (≥60 mmol/L) and Typically Develop Pancreatic Insufficiency Early in Life
They Rarely Develop Pancreatitis
In Patients with Cystic Fibrosis (CF), the Risk of Acute Pancreatitis is Associated with Less Severe CFTR Variants, Milder Phenotype, and Pancreatic Sufficiency (Gastroenterology, 2011) [MEDLINE]
Homozygous or Compound Heterozygous Genotypes in Which at Least One of the CFTR Gene Copies is a Functionally “Mild” Variant (or Variants of Variable Clinical Significance) Result in Some Retained CFTR Function with Milder/Limited Pulmonary Features of Cystic Fibrosis (CF)
Patients without Cystic Fibrosis (CF)
There is an Increased Risk of Acute Recurrent Pancreatitis and Chronic Pancreatitis in Patients with One or Two CFTR Variants, But Who Do Not Meet Clinical Criteria for a Diagnosis of Cystic Fibrosis (CF)
Physiology
CFTR Gene Mutations(s)
Serine Protease I Gene (PRSS1) Mutation
Epidemiology
Autosomal Dominant
Physiology
Encodes for Cationic Trypsinogen
Gain of Function Mutation
Serine Protease Inhibitor Kazal Type 1 (SPINK1) Mutation
Epidemiology
Autosomal Recessive
Physiology
May Act as a Disease Modifier and Decrease the Threshold for Developing Pancreatitis from Other Genetic or Environmental Etiologies
Chymotrypsin C (CTRC) Gene Mutation
Epidemiology
Can Cause Pancreatitis with/without Associated Manifestations of Cystic Fibrosis (Nat Genet, 2008) [MEDLINE]
CTRC Mutations Confer a Moderate Risk of Chronic Pancreatitis (Usually in Conjunction with Other Heterogeneous Pancreatitis Susceptibility Variants, Such as CFTR or SPINK1) (see Chronic Pancreatitis)
Physiology
Chymotrypsin C (CTRC) is a Digestive Enzyme Which Cooperates with Active Trypsin in Solutions with Lower Calcium Concentrations to Degrade Trypsin
Chymotrypsin C (CTRC) is an Intrapancreatic Antitrypsin Protective Mechanism Which Complements SPINK1
Gallstones are the Most Common Etiology of Acute Pancreatitis in Most Areas of the World
Gallstones Account for Approximately 40-70% of All Acute Pancreatitis Cases (Gastroenterology, 2007) [MEDLINE] (Gastroenterology, 2019) [MEDLINE] (Lancet, 2020) [MEDLINE]
However, Only 3-7% of Patients with Gallstones Develop Acute Pancreatitis (Mayo Clin Proc, 1988) [MEDLINE]
Risk Factors
Male Sex
Males Have a Higher Risk of Developing Acute Pancreatitis in the Presence of Gallstones
Females Have a Higher Incidence of Gallstone Pancreatitis Due to a Higher Prevalence of Gallstones
Gallstone Size <5 mm
Gallstones <5 mm are More Likely to Pass Through the Cystic Duct and Cause Ampullary Obstruction (Hepatology, 2005) [MEDLINE]
Ampullary Obstruction Due to the Gallstone Itself (or Due to Edema Associated with Passage of the Gallstone)
Cholecystectomy and Clearing the Common Bile Duct of Stones Prevents the Recurrence of Acute Pancreatitis, Confirming the Etiologic Relationship Between Cholelithiasis and Acute Pancreatitis
Reflux of Bile into the Pancreatic Duct Due to Transient Obstruction of the Ampulla During Gallstone Passage
Acute Pancreatitis May Occur in the Setting of Serum Triglycerides >1000 mg/dL
However, Lower Levels of Hypertriglyceridemia Can Contribute to the Severity of Acute Pancreatitis (Am J Gastroenterol, 2015) [MEDLINE] (Lipids Health Dis, 2017) [MEDLINE]
Triglyceride Levels Can Increase Transiently During Acute Pancreatitis
As Such, Hypertriglyceridemia May Be a Result of Acute Pancreatitis, Rather than a Cause of Acute Pancreatitis
Acute Pancreatitis is the Most Common Complication of Endoscopic Retrograde Cholangiopancreatography (ERCP)
Asymptomatic Hyperamylasemia Occurs in 35-70% of Patients Following Endoscopic Retrograde Cholangiopancreatography (ERCP)
However, Acute Pancreatitis Occurs in 3% of Patients Following Diagnostic Endoscopic Retrograde Cholangiopancreatography (ERCP), 5% of Patients Following Therapeutic Endoscopic Retrograde Cholangiopancreatography (ERCP), and 25% of Patients Following Sphincter of Oddi Manometry Studies
Risk Factors for Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Acute Pancreatitis (Risk Factors are Additive) (Endoscopy, 2020) [MEDLINE]
Definite Risk Factors
Patient-Related
Female Sex
History of Acute Pancreatitis
History of Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis
Suspected Sphincter of Oddi Dysfunction
Procedure-Related
Difficult Cannulation of the Bile Duct
≥1 Pancreatic Guidewire Passage (with Deep Pancreatic Duct Guidewire Passage without Pancreatic Stent) placement
Instrumentation During Endoscopic Retrograde Cholangiopancreatography (ERCP) May Cause Periampullary Inflammation, Resulting in Increased Pressure within the Main Pancreatic Duct (Gastroenterol Hepatol-NY, 2018) [MEDLINE]
Therefore, Some Risk Factors for Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis are Related to Increased Inflammation in the Region of the Ampulla and Pancreatic Head
Ethanol Consumption Accounts for 25-35% of Acute Pancreatitis Cases in the United States (Arch Intern Med, 2008) [MEDLINE]
Less <10% of Patients with Chronic Alcohol Use Disorder Develop Attacks of Clinically Acute Pancreatitis (Which are Indistinguishable from Other Forms of Acute Pancreatitis)
Relationship Between Alcohol Use and Acute/Chronic Pancreatitis (see Chronic Pancreatitis)
Historically, it was Believed that Alcohol Use Caused Chronic Pancreatitis and that Patients with Alcohol Use Disorder Who Presented with a First Episode of Acute Pancreatitis Already Had Chronic Pancreatitis (J Clin Gastroenterol, 2004) [MEDLINE]
However, Long-Term Studies of Patients with Acute Alcohol-Induced Pancreatitis Have Demonstrated that Not All Patients Progress to Chronic Pancreatitis (Even with Continued Alcohol Use) (Gastroenterology, 1996) [MEDLINE]
This Suggests that Some Patients with Alcohol Use Disorder May Have Non-Progressive Acute Alcohol-Induced Pancreatitis (Scand J Gastroenterol, 1997) [MEDLINE]
Relationshop Between Tobacco Abuse and Acute Pancreatitis (see Tobacco)
There is an Established Association Between Smoking with Acute Pancreatitis, Both by Itself and Also with Alcohol Use (Pancreatology, 2019) [MEDLINE]
Tobacco Smoking Increases the Risk of Acute and Chronic Pancreatitis and Acute and Chronic Pancreatitis Combined
There is a Dose-Response Relationship Between Increasing Number of Cigarettes and Pack-Years and Pancreatitis Risk
Serum Amylase Increases within 6-12 hrs of the Onset of Acute Pancreatitis
In Uncomplicated Acute Pancreatitis, Serum Amylase Returns to Normal within 3-5 Days
Half-Life
Half-Life of Serum Amylase: 10 hrs
Due to Short Half-Life, Serum Amylase May Not Be Elevated in Patients Who Present >24 hrs After the Onset of Acute Pancreatitis
Sensitivity/Specificity for Acute Pancreatitis (Using Serum Amylase >3x Upper Limit of Normal)
Sensitivity: 67-83%
In Alcoholic Pancreatitis, Serum Amylase Elevation to >3x Upper Limit of Normal is Not Seen in 20% of Cases (Due to Inability of Pancreas to Synthesize Amylase)
Recommendations (American College of Gastroenterology Practice Guidelines, 2013) (Am J Gastroenterol, 2013) [MEDLINE]
In the Absence of Gallstones and/or Significant Alcohol Use, Serum Triglyceride Should Be Obtained and Considered the Etiology if >1000 mg/dL (Conditional Recommendation, Moderate Quality of Evidence)
Recommendations (American College of Gastroenterology Guidelines: Management of Acute Pancreatitis, 2024) (Am J Gastroenterol, 2024) [MEDLINE]
In the Absence of Gallstones and/or Significant Alcohol Use, Serum Triglyceride Should Be Obtained and Considered the Etiology of Acute Pancreatitis if the Serum Triglycerides are >1000 mg/dL
Abdominal/Pelvic Ultrasound is Less Accurate than Abdominal/Pelvic Computed Tomography (CT) for the Diagnosis of Pancreatic Necrosis
Recommendations (American College of Gastroenterology Practice Guidelines 2013) (Am J Gastroenterol, 2013) [MEDLINE]
Abdominal Ultrasound Should Be Performed in All Patients with Acute Pancreatitis (Strong Recommendation, Low Quality of Evidence)
Recommendations (American College of Gastroenterology Guidelines: Management of Acute Pancreatitis, 2024) (Am J Gastroenterol, 2024) [MEDLINE]
Abdominal Ultrasound is Recommended in Acute Pancreatitis to Evaluate for Biliary Pancreatitis (Conditional Recommendation, Very Low Quality of Evidence)
If the Initial Unltrasound is Inconclusive, a Repeat Ultrasound is Recommended
In Patients with Idiopathic Acute Pancreatitis, Additional Diagnostic Evaluation with Repeat Abdominal Ultrasound, Magentic Resonance Cholangiopancreatography (MRCP), and/or Endoscopic Ultrasound is Recommended (Conditional Recommendation, Very Low Quality of Evidence)
Since Pancreatic Necrosis Takes Time to Develop, Computed Tomography (CT) May Be Normal in the First 48 hrs
The Association Between Contrast iInjection and Worsening of Acute Pancreatitis is Not Strong
Therefore, Comuted Tomography (CT) is Not Contraindicated
Sensitivity of Computed Tomography (CT) for the Diagnosis of Acute Pancreatitis: >90%
Specificity of Computed Tomography (CT) for the Diagnosis of Acute Pancreatitis: >90%
Recommendations (American College of Gastroenterology Practice Guidelines, 2013) (Am J Gastroenterol, 2013) [MEDLINE]
Contrast-Enhanced Computed Tomography and/or Magnetic Resonance Imaging of the Pancreas Should Be Reserved for Patients in Whom the Diagnosis is Unclear or Who Fail to Improve Clinically Within the First 48–72 hrs After Hospital Admission or to Evaluate for Complications (Strong Recommendation, Low Quality of Evidence)
In a Patient >40 y/o, a Pancreatic Tumor Should Be Considered as a Possible Cause of Acute Pancreatitis (Conditional Recommendation, Low Quality of Evidence)
Recommendations (American College of Gastroenterology Guidelines: Management of Acute Pancreatitis, 2024) (Am J Gastroenterol, 2024) [MEDLINE]
Early (or at Admission) Computed Tomograpy (CT) is Not Recommended for the Purposes of Determining the Severity of Acute Pancreatitis
Computed Tomography (CT) Should Be Reserved for Patients in Whom the Diagnosis is Unclear or Who Fail to Clinically Improve within the First 48-72 hrs After Hospital Admission and Intravenous Fluid Resuscitation
Recommendations (American College of Gastroenterology Practice Guidelines, 2013) (Am J Gastroenterol, 2013) [MEDLINE]
Endoscopic Investigation in Patients with Acute Idiopathic Pancreatitis Should Be Limited, as the Risks and Benefits of Investigation in These Patients are Unclear (Conditional Recommendation, Low Quality of Evidence)
Patients with Acute Pancreatitis and Concurrent Acute Cholangitis Should Undergo Endoscopic Retrograde Cholangiopancreatography (ERCP) within 24 hrs of Admission (Strong Recommendation, Moderate Quality of Evidence)
ERCP is Not Required in Most Patients with Gallstone Pancreatitis Who Lack Laboratory or Clinical Evidence of Ongoing Biliary Obstruction (Strong Recommendation, Low Quality of Evidence)
Prevention of Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis
Pancreatic Duct Stents and/or Postprocedure Rectal Nonsteroidal Anti-Inflammatory Drug (NSAID) Suppositories Should Be Utilized to Prevent Severe Post-ERCP Pancreatitis in High-Risk Patients (Conditional Recommendation, Moderate Quality of Evidence)
Recommendations (American College of Gastroenterology Guidelines: Management of Acute Pancreatitis, 2024) (Am J Gastroenterol, 2024) [MEDLINE]
In Acute Biliary Pancreatitis without Cholangitis, Medical Therapy is Recommended Over Early (within the First 72 hrs) Endoscopic Retrograde Cholangiopancreatography (ERCP) (Conditional Recommendation, Low Quality of Evidence)
In the Absence of Cholangitis and/or Jaundice, if a Common Bile Duct Stone is Suspected, Magnetic Resonance Cholangiopancreatography (MRCP) or Endoscopic Ultrasound (EUS) Should Be utilized to Screen for the Presence of a Common Bile Duct Stone Prior to Endoscopic Retrograde Cholangiopancreatography (ERCP)
In Acute Biliary Pancreatitis with Cholangitis, Early (within 24 hrs) Endoscopic Retrograde Cholangiopancreatography (ERCP) Decreases Morbidity and Mortality
Recommendations (American College of Gastroenterology Practice Guidelines 2013) (Am J Gastroenterol, 2013) [MEDLINE]
In the Absence of Cholangitis and/or Jaundice, MRCP or Endoscopic Ultrasound (EUS), Rather than Diagnostic ERCP Should Be Used to Screen for Choledocholithiasis if Highly Suspected (Conditional Recommendation, Low Quality of Evidence)
Recommendations (American College of Gastroenterology Guidelines: Management of Acute Pancreatitis, 2024) (Am J Gastroenterol, 2024) [MEDLINE]
In Patients with Idiopathic Acute Pancreatitis, Additional Diagnostic Evaluation with Repeat Abdominal Ultrasound, Magentic Resonance Cholangiopancreatography (MRCP), and/or Endoscopic Ultrasound is Recommended (Conditional Recommendation, Very Low Quality of Evidence)
Genetic Testing
Recommendations (American College of Gastroenterology Practice Guidelines, 2013) (Am J Gastroenterol, 2013) [MEDLINE]
Genetic Testing May Be Considered in Young Patients (< 30 y/o) if No Etiology is Evident and a Family History of Pancreatic Disease is Present (Conditional Recommendation, Low Quality of Evidence)
Fine Needle Aspiration of Pancreatic Necrosis
Recommendations (American College of Gastroenterology Guidelines: Management of Acute Pancreatitis, 2024) (Am J Gastroenterol, 2024) [MEDLINE]
In Patients with Suspected Infected Pancreatic Necrosis, Fine Needle Aspiration is Not Recommended (Conditional Recommendation, Very Low Quality of Evidence)
References
General
The prevalence of pancreatitis in organophosphate poisonings. Hum Exp Toxicol. 2002;21(4):175 [MEDLINE]
Practice guidelines in acute pancreatitis. Am J Gastroenterol. 2006;101(10):2379 [MEDLINE]
AGA Institute technical review on acute pancreatitis. Gastroenterology. 2007;132:2022 [MEDLINE]
Computed tomography severity index is a predictor of outcomes for severe pancreatitis. Am J Surg. 2000;179:352 [MEDLINE]
The Atlanta Classification, Revised Atlanta Classification, and Determinant-Based Classification of Acute Pancreatitis: Which Is Best at Stratifying Outcomes? Pancreas. 2016 Apr;45(4):510-5. doi: 10.1097/MPA.0000000000000477 [MEDLINE]
Acute Pancreatitis. N Engl J Med. 2016;375(20):1972 [MEDLINE]
Epidemiology
Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2018. Gastroenterology. 2019;156(1):254 [MEDLINE]
Physiopathogenic basis of alcoholic pancreatitis: the effects of elevated cholinergic tone and increased “pancreon” ecbolic response to CCK-PZ. Mt Sinai J Med. 1983;50(5):369 [MEDLINE]
Pancreatic duct obstruction triggers acute necrotizing pancreatitis in the opossum. Gastroenterology. 1993;104(3):853 [MEDLINE]
Ethanol-induced alterations in messenger RNA levels correlate with glandular content of pancreatic enzymes. J Lab Clin Med. 1995;125(5):634 [MEDLINE]
Course of alcoholic chronic pancreatitis: a prospective clinicomorphological long-term study. Gastroenterology. 1996;111(1):224 [MEDLINE]
Does acute alcoholic pancreatitis exist without preexisting chronic pancreatitis? Scand J Gastroenterol. 1997;32(7):625 [MEDLINE]
Does acute alcoholic pancreatitis precede the chronic form or is the opposite true? A histological study. J Clin Gastroenterol. 2004;38(3):272 [MEDLINE]
Drug-induced acute pancreatitis: an evidence-based review. Clin Gastroenterol Hepatol. 2007;5(6):648. Epub 2007 Mar 28 [MEDLINE]
AGA Institute technical review on acute pancreatitis. Gastroenterology. 2007;132(5):2022 [MEDLINE]
Gallstone pancreatitis and the effect of cholecystectomy: a population-based cohort study. Mayo Clin Proc. 1988;63(5):466 [MEDLINE]
Small gallstones, preserved gallbladder motility, and fast crystallization are associated with pancreatitis. Hepatology. 2005;41(4):738 [MEDLINE]
Epidemiology of alcohol-related liver and pancreatic disease in the United States. Arch Intern Med. 2008;168(6):649 [MEDLINE]
Ischemic acute pancreatitis: clinical features of 11 patients and review of the literature. Am J Surg. 2009 Apr;197(4):450-4. doi: 10.1016/j.amjsurg.2008.04.011 [MEDLINE]
Acute ischemic pancreatitis following cardiac arrest: a case report. JOP. 2010 Sep 6;11(5):456-9 [MEDLINE]
Issues in hypertriglyceridemic pancreatitis: an update. J Clin Gastroenterol. 2014;48(3):195 [MEDLINE]
A case report on over-replacement of oral calcium supplements causing acute pancreatitis. Ann R Coll Surg Engl. 2014 Jan;96(1):94E-95E. doi: 10.1308/003588414X13824511650056 [MEDLINE]
Association of Meloxicam Use with the Risk of Acute Pancreatitis: A Case-Control Study. Clin Drug Investig. 2015 Oct;35(10):653-7. doi: 10.1007/s40261-015-0326-2 [MEDLINE]
Acute Ischemic Pancreatitis Secondary to Aortic Dissection. Ann Vasc Surg. 2018 Oct:52:85-89. doi: 10.1016/j.avsg.2018.03.007 [MEDLINE]
Tobacco smoking and the risk of pancreatitis: A systematic review and meta-analysis of prospective studies. Pancreatology. 2019;19(8):1009 [MEDLINE]
Meloxicam-Induced Pancreatitis. Cureus. 2021 Jan 28;13(1):e12976. doi: 10.7759/cureus.12976 [MEDLINE]
Physiology
Hyperlipidemia in acute pancreatitis. Relationship with etiology, onset, and severity of the disease. Int J Pancreatol. 1991;10(3-4):261 [MEDLINE]
Trypsin secretion and turnover in patients with acute pancreatitis. Am J Physiol Gastrointest Liver Physiol 2005; 289(2):G181–G187. doi:10.1152/ajpgi.00297.2004 [MEDLINE]
Effect of admission hypertriglyceridemia on the episodes of severe acute pancreatitis. World J Gastroenterol. 2008 Jul;14(28):4558-61 [MEDLINE]
The role of free fatty acids, pancreatic lipase and Ca+ signalling in injury of isolated acinar cells and pancreatitis model in lipoprotein lipase-deficient mice. Acta Physiol (Oxf). 2009 Jan;195(1):13-28 [MEDLINE]
Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity. Sci Transl Med. 2011;3(107):107ra110 [MEDLINE]
Diagnosis
Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101(6):1644 [MEDLINE]
Procalcitonin strip test in the early detection of severe acute pancreatitis. Br J Surg. 2001;88(2):222 [MEDLINE]
Dynamic nature of early organ dysfunction determines outcome in acute pancreatitis. Br J Surg. 2002;89(3):298 [MEDLINE]
Association between early systemic inflammatory response, severity of multiorgan dysfunction and death in acute pancreatitis. Br J Surg. 2006;93(6):738 [MEDLINE]
Early systemic inflammatory response syndrome is associated with severe acute pancreatitis. Clin Gastroenterol Hepatol. 2009;7(11):1247 [MEDLINE]
