Acute Pancreatitis

Diagrammatic representation of the pancreas, anterior view - Rosen's Emergency Medicine

Definition & Epidemiology

Etiology

• Gallstones - 40% to 70% of all cases
• Chronic alcohol use - 25% to 35%

Pathophysiology

1. Precipitating event (gallstone obstruction, alcohol, etc.) triggers sustained cytosolic calcium increase in acinar cells
2. This causes colocalization of zymogens (trypsinogen) with lysosomal enzymes (cathepsin B) in cytoplasmic vacuoles
3. Cathepsin B activates trypsinogen to trypsin within these vacuoles
4. Trypsin permeabilizes the vacuoles, releasing cathepsin B into the cytosol
5. Cathepsin B permeabilizes mitochondrial membranes, releasing cytochrome C and triggering apoptotic cell death
6. Mice lacking trypsinogen-7 (the key isoform activated during AP) show significantly less injury - confirming trypsin's central role

• Synthesis of enzymes as inactive precursors (zymogens)
• Separation of production and activation sites
• Trypsin inhibitors (SPINK1) within the pancreas

Classification (Revised Atlanta Criteria 2012)

• Interstitial edematous pancreatitis - the majority (~90-95%); usually resolves within the first week
• Necrotizing pancreatitis - ~5-10% of cases; involves pancreatic parenchyma +/- peripancreatic tissue; necrotic tissue may remain sterile, liquefy, or become infected

• Within 4 weeks: Acute peripancreatic fluid collection (APFC), Acute necrotic collection (ANC)
• After 4 weeks: Pancreatic pseudocyst (APFC with wall), Walled-off necrosis (WON - ANC with wall)

Clinical Features

• Persistent epigastric or left upper quadrant pain, often radiating to the back, chest, or flanks
• Pain may be relieved by sitting up or leaning forward
• Nausea, vomiting, anorexia
• Severity of pain does NOT correlate with disease severity

• Vital signs: may be normal early; tachycardia, fever, tachypnea; hypotension in severe/complicated cases
• Jaundice suggests obstructive cause (gallstone or tumor)
• Abdominal distension, epigastric tenderness, guarding; bowel sounds may be absent (ileus)
• Right upper quadrant tenderness and Murphy's sign in gallstone pancreatitis
• Cullen sign - periumbilical bluish discoloration (hemoperitoneum) - rare, poor prognosis
• Grey Turner sign - reddish-brown flank discoloration (retroperitoneal bleeding) - rare, poor prognosis
• Pleural effusion (left-sided predominance) in up to 50% of patients

• ARDS, atelectasis, pleural effusion (pulmonary)
• Cardiovascular collapse, shock (fluid shifts)
• Acute kidney injury (hypoperfusion + inflammatory mediators)
• DIC (cytokine-mediated coagulation cascade activation)
• Hyperglycemia (decreased insulin), hypocalcemia (low albumin and Mg)

Diagnosis

1. Abdominal pain characteristic of AP
2. Serum lipase or amylase > 3x upper limit of normal
3. Characteristic findings on abdominal imaging

• Lipase is preferred - more sensitive AND specific than amylase; remains elevated ~1-2 weeks
• Amylase - rises within hours, normalizes in 3-5 days; falsely negative in alcohol and hypertriglyceridemia-induced AP; elevated in many non-pancreatic conditions
• ALT - positive predictive value 95% for biliary pancreatitis when elevated
• Triglycerides - if >1000 mg/dL without gallstones or alcohol history, points to hypertriglyceridemic etiology
• CBC, BMP (assess for SIRS, organ failure)
• Calcium (hypocalcemia = poor prognosis)
• Testing both enzymes simultaneously does NOT improve sensitivity or specificity

• Ultrasound - first-line; evaluates for gallstones, biliary dilation; limited by bowel gas obscuring pancreas
• CT scan with contrast - not routinely needed for diagnosis; used when diagnosis is uncertain or to assess complications; best performed 48-72 hours after onset (earlier imaging may underestimate necrosis)
• CT Severity Index (CTSI) / Modified CTSI - grades pancreatic inflammation (0-4) + necrosis (0-4); total score predicts morbidity
• MRI/MRCP - better for biliary pathology; useful to assess pancreatic duct integrity

Severity Scoring Systems

Management

1. Fluid Resuscitation (most critical early intervention)

• Patients are volume-depleted from decreased intake, vomiting, and third-spacing due to inflammatory mediators
• IAP/APA recommendation: Goal-directed resuscitation at 5-10 mL/kg/h targeting:
  • HR < 120/min
  • MAP 65-85 mmHg
  • Urine output > 0.5-1 mL/kg/h
• ACG recommendation: 250-500 mL/h
• Lactated Ringer's (LR) preferred over normal saline - large volumes of NS cause hyperchloremic metabolic acidosis, which worsens the inflammatory response and activates trypsinogen
• Colloids not routinely recommended (may help if Hct <24 or albumin <2 g/dL)
• Inadequate resuscitation in first 24h increases SIRS, organ failure, pancreatic necrosis, and ICU admissions
• Monitor with serial Hct, BUN, creatinine

2. Pain Control

• Adequate analgesia is essential; opioids are generally required for moderate-to-severe pain
• IV morphine or hydromorphone; the historical concern about morphine causing sphincter of Oddi spasm has not been clinically validated

3. Nutritional Support

• Early enteral nutrition (EN) is preferred - within 24-48 hours when tolerated
• Nasojejunal or nasogastric feeding are equivalent in most studies
• EN maintains gut mucosal barrier, reduces bacterial translocation, reduces infectious complications
• Total parenteral nutrition (TPN) only if enteral route is not tolerated or not feasible
• "NPO until symptoms improve" is outdated in mild-moderate disease; early feeding reduces hospital stay and complications

4. Antibiotics

• Not indicated prophylactically in sterile necrotizing pancreatitis (multiple RCTs have shown no benefit)
• Use only when infection is documented or strongly suspected (infected necrosis, cholangitis)
• Fine-needle aspiration (FNA) of pancreatic necrosis under CT guidance can confirm infection (gram stain + culture)

5. Management of Biliary Pancreatitis

• ERCP indicated within 24-72 hours if concurrent cholangitis or persistent biliary obstruction
• Early ERCP for uncomplicated gallstone pancreatitis does NOT improve outcomes
• Cholecystectomy should be performed during the same hospitalization (mild disease) or after recovery (severe disease) to prevent recurrence

6. Management of Infected Necrosis

• Step-up approach: antibiotics first, then minimally invasive drainage/debridement
• Percutaneous or endoscopic drainage before surgical necrosectomy (reduces mortality)
• Surgical necrosectomy reserved for failure of less invasive approaches
• Optimal timing: delay intervention >4 weeks to allow walled-off necrosis to mature

7. Hypertriglyceridemia-Induced AP

• Insulin infusion, plasmapheresis, or gemfibrozil to reduce TG levels rapidly
• Heparin activates lipoprotein lipase and may help acutely

Differential Diagnosis

Prognosis & Complications

• Persistent SIRS (>48h)
• Organ failure (especially multi-organ)
• Infected pancreatic necrosis
• Obesity (BMI >30)
• Age >55
• Ranson score ≥3

• Pseudocyst (>4 weeks - most common late local complication)
• Walled-off necrosis
• Pancreatic fistula
• Splenic or portal vein thrombosis
• Bowel necrosis
• Gastrointestinal bleeding
• Chronic pancreatitis (after recurrent episodes)
• Pancreatic exocrine/endocrine insufficiency