What are the etiology, pathophysiology, typical presentation, diagnostic work‑up, management strategies, and prognostic indicators for acute pancreatitis?

Acute Pancreatitis: Comprehensive Overview

Etiology

Gallstones and alcohol account for approximately 70-75% of acute pancreatitis cases, with gallstones being the single most common cause at roughly 50%. 1

Primary Causes

• Gallstone disease: Represents approximately 50% of all cases, making it the leading etiology 1
• Alcohol abuse: Second most common cause, accounting for 20-25% of cases 1
• Hypertriglyceridemia: Serum triglyceride levels >11.3 mmol/L indicate this as the causative etiology 1
• Hypercalcemia: Must be measured in all patients, especially when gallstones and alcohol are excluded 1

Drug-Induced Pancreatitis

• Thiopurines (azathioprine, 6-mercaptopurine): Precipitate acute pancreatitis in approximately 4% of IBD patients, typically within the first 3-4 weeks of treatment 1
• 5-ASA agents: Carry markedly lower risk compared to thiopurines 1

Diagnostic Target

• The etiology should be determined in 75-80% of cases; no more than 20-25% should remain classified as "idiopathic" 2, 1
• At least two high-quality ultrasound examinations should be performed before accepting an idiopathic diagnosis 1

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Pathophysiology

Acute pancreatitis is an inflammatory process within the pancreas triggered by premature activation of digestive enzymes, leading to autodigestion of pancreatic tissue and a systemic inflammatory response. 3

Inflammatory Cascade

• Pancreatic enzyme activation causes local tissue injury and necrosis 3
• Systemic inflammatory response can lead to multiple organ dysfunction 3
• In hypertriglyceridemia-associated pancreatitis, free fatty acids released by pancreatic lipase sequester calcium intravascularly through FFA-albumin complexes, contributing to both cellular injury and systemic hypocalcemia 1

Progression to Severe Disease

• Infection of pancreatic and peripancreatic necrosis occurs in 20-40% of severe cases 3
• Mortality varies significantly: infected necrosis with organ failure (35.2%), sterile necrosis with organ failure (19.8%), infected necrosis without organ failure (1.4%) 3

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Clinical Presentation

The classic presentation includes epigastric abdominal pain radiating to the back, nausea, vomiting, and abdominal tenderness, though elderly patients often present atypically. 1

Typical Features

• Upper abdominal pain with epigastric or diffuse tenderness 2
• Nausea and vomiting 2
• Occasionally body wall ecchymoses: Cullen's sign (umbilicus) or Grey-Turner's sign (flanks) 2

Atypical Presentation in Elderly

• Fewer abdominal symptoms despite severe disease 1
• Atypical or absent abdominal pain in approximately 12% and 5% of elderly patients, respectively 1
• Murphy's sign has limited utility with sensitivity of only ~48% 1
• Fever >38°C observed in only 6.4-10% of elderly individuals 1

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Diagnostic Work-Up

Diagnosis requires at least two of three Atlanta criteria: (1) characteristic epigastric pain, (2) serum lipase or amylase ≥3× upper limit of normal, and (3) imaging evidence of pancreatic inflammation. 1, 4

Laboratory Evaluation

Primary Diagnostic Tests

• Serum lipase: Preferred over amylase due to higher sensitivity and prolonged elevation 2, 1, 4
• Serum amylase: Four times above normal supports diagnosis, though less sensitive than lipase 2, 1

Etiologic Work-Up

• Liver function tests: Early elevation of aminotransferases or bilirubin suggests biliary etiology 1
• Fasting lipid panel: Triglycerides >11.3 mmol/L indicate hypertriglyceridemia as cause 1
• Serum calcium: Must be measured in all patients to detect hypercalcemia 1

Severity Assessment Markers

• C-reactive protein: >150 mg/L at 48 hours predicts complications 2
• Procalcitonin: Most sensitive marker for detecting pancreatic infection; ≥3.8 ng/mL within 96 hours indicates necrosis with 93% sensitivity and 79% specificity 2
• Hematocrit, BUN, creatinine: Monitor for adequate tissue perfusion 3
• White blood cell count: Common inflammatory marker 1

Imaging Strategy

Initial Imaging

• Abdominal ultrasound: First-line study to detect gallstones; should be performed on admission 1, 4
• Repeat ultrasound if initial study is negative 1
• Chest and abdominal plain radiographs: Provide baseline and exclude other pathology such as perforated viscus 2

Advanced Imaging

• Contrast-enhanced CT: Standard for evaluating severity and prognosis, though not required for initial diagnosis 1
• Timing: Should be performed between 3-10 days after onset to assess pancreatic necrosis 3
• CT severity index (Balthazar): Grades severity from 0-10 based on pancreatic changes and extent of necrosis 2
• Routine CT is unnecessary in mild cases unless clinical deterioration occurs 2, 3

Indications for CT

• Patients with persisting organ failure, signs of sepsis, or clinical deterioration 6-10 days after admission 2, 4
• When diagnosis is uncertain, contrast-enhanced CT provides definitive evidence 4

Other Modalities

• MRCP: Sensitivity 97.98%, specificity 84.4% for choledocholithiasis when ultrasound is nondiagnostic 1
• Endoscopic ultrasound (EUS): Reserved for detecting microlithiasis in recurrent idiopathic cases 1

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Severity Stratification and Prognostication

Severity classification determines management intensity and predicts mortality; persistent organ failure >48 hours is the key determinant of mortality. 3, 4

Atlanta Classification (2012)

Mild Acute Pancreatitis

• No organ failure AND no local/systemic complications 4
• Accounts for approximately 80% of cases with mortality <5% 2, 1

Moderately Severe Acute Pancreatitis

• Transient organ failure (<48 hours) OR local complications OR exacerbation of comorbidities 4

Severe Acute Pancreatitis

• Persistent organ failure (>48 hours) affecting cardiovascular, respiratory, and/or renal systems 4
• Occurs in approximately 20% of patients; accounts for 95% of deaths 2
• Mortality >50% with persistent organ failure vs. essentially 0% if organ failure resolves within 48 hours 1

Prognostic Scoring Systems

The BISAP score is one of the most accurate and applicable in clinical practice due to simplicity and capability to predict severity, death, and organ failure as well as APACHE-II. 2

Timing of Assessment

• Within 24 hours: Clinical impression of severity, obesity (BMI >30), APACHE II score >8 2
• At 48 hours: Glasgow score ≥3, CRP >150 mg/L, persisting organ failure 2

Other Scoring Systems

• Ranson criteria: Traditional but time-dependent 5
• APACHE II: Complex but accurate 2
• Glasgow-Imrie score: Validated for severity prediction 2

Overall Mortality Targets

• Overall mortality should be <10%, and <30% in those with severe disease 2

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Management Strategies

Initial Management: Mild Acute Pancreatitis (80% of cases)

Patients with mild pancreatitis should be managed on a general ward with basic monitoring, early oral feeding, and no prophylactic antibiotics. 2, 1

General Care

• Manage on general ward with basic monitoring of temperature, pulse, blood pressure, urine output 2
• Peripheral intravenous line for fluids 2
• Nasogastric tube if needed 2

Nutrition

• Initiate regular oral diet immediately (within 24 hours) and advance as tolerated 1, 3
• Early feeding improves outcomes 1

Analgesia

• Oral medications for pain control 1
• Intravenous opioids are safe if used judiciously 1, 5

Antibiotics

• Prophylactic antibiotics are NOT recommended 2, 1, 3
• Antibiotics warranted only for specific infections (chest, urine, bile, catheter-related) 2, 3

Imaging

• Routine CT scanning unnecessary unless clinical deterioration 2, 3

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Management: Moderately Severe Acute Pancreatitis

Nutrition

• Prefer enteral nutrition (oral, nasogastric, or nasojejunal) 1
• Reserve parenteral nutrition for patients who cannot tolerate enteral feeding 1

Analgesia

• Intravenous opioids judiciously; Dilaudid preferred over morphine or fentanyl in non-intubated patients 3
• Consider epidural analgesia as alternative or adjunct 3
• Patient-controlled analgesia (PCA) should be integrated 3
• Avoid NSAIDs in patients with acute kidney injury 3

Fluid Therapy

• Intravenous crystalloids to maintain adequate hydration 1

Monitoring

• Serial hematocrit, BUN, creatinine guide fluid management 1
• Continuous vital-sign surveillance 1

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Management: Severe Acute Pancreatitis (20% of cases)

Patients with severe pancreatitis require ICU or HDU admission with full resuscitation, early goal-directed fluid therapy, enteral nutrition, and multidisciplinary care. 2, 3, 4

General Management

• Admit to ICU or HDU 2, 4
• Full resuscitation with multidisciplinary approach 2
• Minimum requirements: peripheral venous access, central venous line (CVP monitoring), urinary catheter, nasogastric tube 2
• Strict asepsis for invasive monitoring equipment 2

Advanced Monitoring

• Swan-Ganz catheter if cardiocirculatory compromise or failed initial resuscitation (for pulmonary artery wedge pressure, cardiac output, systemic resistance) 2
• Regular arterial blood gas analysis 2
• Hourly pulse, blood pressure, CVP, respiratory rate, oxygen saturation, urine output, temperature 2
• Target urine output >0.5 mL/kg body weight 3

Fluid Resuscitation

• Early goal-directed fluid therapy with cautious approach in first 24 hours to avoid fluid overload 1
• Lactated Ringer's solution preferred over normal saline 6, 7
• Avoid hydroxyethyl starch (HES) fluids due to increased risk of multiple organ failure 3
• Monitor hematocrit, BUN, creatinine, lactate for adequate tissue perfusion 3, 8

Nutrition

• Strongly favor enteral feeding (oral, nasogastric, or nasojejunal) because it reduces mortality, multiorgan failure, and infectious complications compared to parenteral nutrition 1, 3
• Both nasogastric and nasojejunal routes are acceptable 3
• If ileus persists >5 days, parenteral nutrition required 3
• Early enteral nutrition prevents gut failure and infectious complications 3

Respiratory Support

• Mechanical ventilation when respiratory failure develops 1

Pharmacologic Therapy

• No disease-specific drugs are indicated; treatment focuses on organ support and optimal nutrition 1
• Treatments with no proven value: aprotinin, glucagon, somatostatin, fresh frozen plasma, peritoneal lavage 2

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Antibiotic Use in Severe Pancreatitis

Routine prophylactic antibiotics are NOT recommended; antibiotics should be administered ONLY when infected pancreatic necrosis is documented. 1, 3

Evidence and Controversy

• Evidence is conflicting and difficult to interpret; some trials show benefit, others do not 2
• No consensus currently exists 2

When to Use Antibiotics

• Only for proven infected necrosis confirmed by elevated procalcitonin and/or CT/EUS-guided FNA with Gram stain and culture 1
• All patients with persistent symptoms and >30% pancreatic necrosis or clinical suspicion of sepsis should undergo image-guided FNA for culture 7-14 days after onset 3
• For specific infections (respiratory, urinary, biliary, catheter-related) 3

Antibiotic Regimens (if indicated)

• Maximum duration: 14 days 2

First-line for immunocompetent patients without MDR organisms:

• Meropenem 1 g every 6 hours (extended infusion) OR
• Doripenem 500 mg every 8 hours OR
• Imipenem/cilastatin 500 mg every 6 hours 1

For suspected MDR pathogens:

• Imipenem/cilastatin-relebactam 1.25 g every 6 hours OR
• Meropenem/vaborbactam 2 g/2 g every 8 hours 1

Alternative (reasonable balance between efficacy and cost):

• Intravenous cefuroxime 2, 3

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Management of Gallstone Pancreatitis

All patients with gallstone pancreatitis require urgent ERCP within 72 hours if severe disease, cholangitis, jaundice, or dilated common bile duct is present, followed by same-admission cholecystectomy. 2, 1, 3

Urgent ERCP Indications

• Severe gallstone pancreatitis with cholangitis, jaundice, or dilated common bile duct 2, 1
• Timing: Within 72 hours of pain onset 2, 1, 3
• All patients undergoing early ERCP require endoscopic sphincterotomy whether or not stones are found 2
• Patients with cholangitis require sphincterotomy or duct drainage by stenting 2

Cholecystectomy Timing

Mild gallstone pancreatitis:

• Perform cholecystectomy during same hospital admission (ideally within 2 weeks, no later than 4 weeks) to prevent recurrence 2, 1, 3
• Without cholecystectomy, complications develop in 14% at 6 weeks, 19% at 12 weeks, 29% at 1 year 1

Severe gallstone pancreatitis:

• Delay cholecystectomy until inflammatory process and signs of lung injury/systemic disturbance have resolved 3

Unfit patients:

• Endoscopic sphincterotomy alone is adequate treatment 3

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Management of Infected Necrosis

Infected necrosis is the most serious local complication with 40% mortality; management requires complete debridement of all necrotic material, preferably via minimally invasive approaches. 3

Intervention Strategy

• Consider minimally invasive approaches before open surgical necrosectomy 3
• Options include percutaneous drainage and surgical debridement with thorough removal of necrotic tissue 3
• Patients require intervention to completely debride all cavities containing necrotic material 3

Timing

• Intervention typically 7-14 days after onset once infection is confirmed 3

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Key Pitfalls to Avoid

• Etiologic work-up failure: Not identifying cause in 75-80% of patients increases recurrence risk 1
• Accepting "idiopathic" diagnosis prematurely: Perform at least two high-quality gallbladder ultrasounds before labeling as idiopathic 1
• Routine prophylactic antibiotics: Reserve antibiotics for proven infected necrosis only 1, 3
• Delaying cholecystectomy in mild gallstone pancreatitis: Early surgery reduces recurrence rates 1
• Defaulting to parenteral nutrition: Use enteral nutrition when tolerated; it lowers complications and mortality 1
• Overly aggressive fluid resuscitation: Adopt cautious approach in first 24 hours to avoid fluid overload 1
• Delaying ICU transfer: Patients with persistent organ failure need urgent ICU admission 4
• Early CT scanning (<72 hours): May not show necrotic areas and won't modify clinical management 4
• Using normal saline instead of lactated Ringer's solution for fluid resuscitation 6, 7

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Multidisciplinary Approach

• Every hospital should have a single nominated clinical team to manage all acute pancreatitis patients 3
• Multidisciplinary team involving intensivists, surgeons, gastroenterologists, and radiologists is essential 3
• Each case should be managed individually by a specialist pancreatic team 3