Acute pancreatitis is a sudden inflammatory condition of the pancreas that can range from mild, self-limiting illness to a severe, life-threatening disease involving multiple organ systems. The pancreas, an essential organ with both endocrine and exocrine functions, becomes inflamed, and its digestive enzymes can begin to autodigest pancreatic tissue, leading to local tissue injury and systemic complications. 

Historically, descriptions of acute pancreatitis date back to ancient times, but it was not until the 19th century that it was recognized as a distinct pathological entity. Today, acute pancreatitis remains a common cause of hospitalization, with an incidence of about 13–45 cases per 100,000 population annually, depending on geographic region and underlying risk factors. 

Acute pancreatitis contributes significantly to healthcare burden, leading to substantial morbidity, prolonged hospital stays, and high healthcare costs. It often presents in middle-aged adults but can occur at any age, including in pediatric populations where etiologies and outcomes may differ. Improved understanding of risk factors and early intervention strategies have helped reduce mortality rates over recent decades. 

This article provides a detailed, evidence-based overview of acute pancreatitis—its causes, pathophysiology, clinical presentation, diagnostic workup, treatment strategies, complications, prognosis and prevention. 

Acute pancreatitis is defined as an acute inflammatory process of the pancreas, often associated with involvement of peripancreatic tissues and distant organ systems. The diagnosis requires at least two of the following three criteria: 

• Characteristic upper abdominal pain 

• Serum amylase or lipase levels elevated at least 3 times the upper limit of normal 

• Characteristic findings on imaging (typically CT, MRI or ultrasound) 

Acute pancreatitis can be classified by severity: 

• Mild acute pancreatitis — no organ failure, no local or systemic complications 

• Moderately severe acute pancreatitis — transient organ failure (resolves within 48 hours), and/or local or systemic complications without persistent organ failure 

• Severe acute pancreatitis — persistent organ failure (>48 hours), which may involve one or more organs 

The revised Atlanta classification also recognizes two morphologic subtypes: interstitial edematous pancreatitis and necrotizing pancreatitis, each with distinct imaging features and clinical implications. Early identification of the subtype helps guide management decisions, including the need for intervention in necrotizing forms. 

Acute pancreatitis results from premature activation of pancreatic enzymes within the gland, leading to autodigestion. The most common causes include: 

Gallstones (40–70%) 

• Migration of gallstones into the common bile duct can obstruct the pancreatic duct, triggering pancreatitis. 

Alcohol consumption (25–35%) 

• Chronic excessive alcohol intake (>4-5 drinks/day) increases susceptibility, often after years of use. 

Other causes 

• Hypertriglyceridemia (triglycerides >1000 mg/dL) 

• Hypercalcemia 

• Post-endoscopic retrograde cholangiopancreatography (ERCP) 

• Certain medications (e.g., azathioprine, valproic acid, thiazides, furosemide) 

• Trauma (blunt abdominal injury) 

• Genetic mutations (e.g., PRSS1, SPINK1, CFTR) 

• Infections (e.g., mumps, coxsackievirus) 

• Autoimmune pancreatitis 

• Idiopathic (in about 10–20% of cases, no cause is identified despite extensive evaluation) 

Rare causes include pancreatic tumors causing ductal obstruction, vascular abnormalities (e.g., pancreatic arteriovenous malformations), and anatomical variants such as pancreas divisum. In children, trauma and medications are more common triggers, while genetic factors may play a larger role in recurrent or idiopathic cases. 

The pathogenesis of acute pancreatitis involves several key steps: 

1. Ductal obstruction or direct injury: leads to accumulation of pancreatic enzymes 

2. Premature activation of trypsinogen to trypsin inside acinar cells: triggers a cascade of enzyme activation 

3. Autodigestion of pancreatic tissue: causes necrosis, edema, and hemorrhage 

4.  Release of inflammatory mediators (TNF-α, IL-1, IL-6): results in systemic inflammatory response syndrome (SIRS) 

The local damage can extend beyond the pancreas, leading to: 

• Peripancreatic fat necrosis 

• Formation of pseudocysts 

• Pancreatic necrosis 

In severe cases, widespread inflammation and release of cytokines cause multiorgan dysfunction, including acute respiratory distress syndrome (ARDS), renal failure, and shock. 

Microcirculatory dysfunction, ischemia, and oxidative stress further exacerbate pancreatic injury. Disruption of the gut barrier function can lead to bacterial translocation, contributing to infected necrosis and systemic sepsis in severe cases. 

Typical Symptoms 

• Sudden onset of severe epigastric pain 

• Radiates to the back (in ~50% of cases) 

• Often worsens when lying supine, relieved somewhat by sitting up or leaning forward 

• Nausea and vomiting 

• Abdominal distension and tenderness 

• Some patients may exhibit pleural effusion or basal lung atelectasis on imaging, particularly in severe cases. These thoracic complications can contribute to respiratory distress and complicate the clinical picture. 

Other Signs 

• Fever 

• Tachycardia 

• Hypotension (if significant third-spacing or hemorrhage) 

• Jaundice (if gallstones are implicated) 

In severe cases, signs of hypovolemia, shock, or organ failure may dominate. 

Rare findings: 

• Cullen’s sign (periumbilical ecchymosis) 

• Grey Turner’s sign (flank ecchymosis) 

These suggest retroperitoneal hemorrhage and are seen in severe necrotizing pancreatitis. 

Laboratory Tests 

• Serum amylase: Elevated (but nonspecific); rises within hours, normalizes within 3–5 days 

• Serum lipase: More specific; remains elevated longer 

• Liver function tests: Elevated bilirubin, ALP (if gallstones present) 

• Triglyceride levels: Check if hypertriglyceridemia suspected 

• Calcium: May be low due to fat saponification 

• CRP: Marker of inflammation; CRP >150 mg/L at 48 hours suggests severe disease 

• Hematocrit, BUN: Help assess severity and guide fluid resuscitation 

Imaging 

• Ultrasound: First-line to assess for gallstones 

• CT abdomen (contrast-enhanced): To evaluate necrosis, complications — best performed >48 hours after onset 

• MRI / MRCP: Useful if biliary obstruction suspected 

Point-of-care ultrasound (POCUS) is gaining interest for rapid bedside assessment of gallstones, ascites, and other features of pancreatitis. Additionally, procalcitonin levels may help differentiate infected from sterile pancreatic necrosis in selected patients. 

Differential Diagnosis 

Conditions that may mimic acute pancreatitis: 

• Perforated peptic ulcer 

• Acute cholecystitis 

• Mesenteric ischemia 

• Bowel obstruction 

• Myocardial infarction (especially inferior MI) 

•  Ectopic pregnancy in women of reproductive age should also be considered when evaluating lower abdominal pain with nausea, as its presentation may overlap with pancreatitis. 

Initial Supportive Care (Cornerstone of treatment) 

Aggressive IV fluid resuscitation (preferably lactated Ringer’s solution) 

• Goal: maintain adequate perfusion, urine output >0.5 mL/kg/h 

• Most beneficial in first 24 hours 

Pain management 

• IV opioids (morphine, fentanyl) 

Nutritional support 

• Early enteral feeding (nasogastric or nasojejunal tube) preferred over parenteral nutrition 

• Oral intake resumed as pain subsides and appetite returns 

Monitoring 

• Frequent vital signs, urine output, labs to assess for organ dysfunction 

Specific Interventions 

• Gallstone pancreatitis: Early ERCP if cholangitis or biliary obstruction 

• Necrotizing pancreatitis: Antibiotics only if infected necrosis is confirmed 

• Complications (e.g., pseudocyst, abscess): May require drainage or surgery 

Judicious use of antibiotics is important, as routine prophylactic antibiotics do not reduce the risk of infected necrosis and may promote resistance. In selected cases, minimally invasive approaches (e.g., endoscopic or percutaneous drainage) are preferred over open surgery for complications. 

Local complications 

• Pancreatic pseudocyst 

• Pancreatic necrosis (sterile or infected) 

• Abscess formation 

• Hemorrhage 

Systemic complications 

• Acute kidney injury 

• ARDS 

• Shock 

• Disseminated intravascular coagulation (DIC) 

• Multiorgan failure 

Venous thromboembolism (VTE) is another recognized risk, necessitating consideration of prophylactic anticoagulation in hospitalized patients with severe disease. 

The outcome varies: 

• Mild pancreatitis: >95% recover without complications 

• Severe pancreatitis: Mortality ~15–30%, especially with infected necrosis or multiorgan failure 

Prognostic scores used to stratify risk: 

• Ranson’s criteria 

• BISAP score 

• APACHE II 

• Glasgow score 

Long-term complications may include development of diabetes mellitus due to islet cell destruction and exocrine pancreatic insufficiency, requiring enzyme supplementation and dietary support. 

• Gallstone-related pancreatitis: Cholecystectomy during same hospital stay after resolution of pancreatitis (if no necrosis) 

• Alcohol-related: Counseling and rehabilitation for cessation 

• Hypertriglyceridemia: Lipid-lowering therapy, dietary changes 

• Procedure-related: Careful technique during ERCP, use of prophylactic measures (e.g., rectal NSAIDs) 

For high-risk ERCP procedures, pancreatic duct stenting alongside rectal NSAIDs may further reduce the incidence of post-ERCP pancreatitis. Lifestyle modification, including weight reduction, can help mitigate risk in individuals with gallstone disease or hypertriglyceridemia. 

Acute pancreatitis is a common but potentially life-threatening condition that requires early recognition and prompt supportive care. While the majority of cases resolve without sequelae, severe forms can lead to substantial morbidity and mortality. A structured, multidisciplinary approach—incorporating medical, nutritional, endoscopic, and sometimes surgical management—is essential for optimal patient outcomes. Ongoing research continues to refine risk stratification, treatment, and prevention strategies for this complex disease. 

Future directions in research include the exploration of biomarkers for early severity prediction and novel anti-inflammatory agents to limit pancreatic injury and systemic complications. 

1. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102-111. 

2. Tenner S, Baillie J, DeWitt J, Vege SS. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013;108(9):1400-1415. 

3. Forsmark CE, Vege SS, Wilcox CM. Acute pancreatitis. N Engl J Med. 2016;375(20):1972-1981. 

4. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013;13(4 Suppl 2):e1-e15.