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Pancreatitis — Complete Overview

Definition

• Acute pancreatitis — a discrete episode of cellular injury with potential for full recovery
• Chronic pancreatitis — irreversible parenchymal destruction and fibrosis
• Recurrent acute episodes can transition into chronic pancreatitis; the two are on a continuum

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Epidemiology

• Incidence: ~40 cases per 100,000 in the United States; ~300,000 hospital admissions/year
• One of the most common GI discharge diagnoses in US hospitals
• Cost: $4–6 billion annually
• Incidence is rising — driven by the obesity epidemic, increasing gallstone prevalence, and more frequent diagnostic testing
• Overall mortality: ~5% (higher in necrotizing disease)
• Alcoholic pancreatitis peaks in ages 20–50; more common in men

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Causes & Risk Factors

• Only ~5% of patients with gallstones develop pancreatitis; those with smaller stones (≤5 mm) are at highest risk
• Most patients with a first episode of alcoholic pancreatitis already have underlying chronic pancreatitis

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Pathophysiology

1. Trigger (stone obstruction, alcohol, toxin, etc.) disrupts normal secretion of zymogens
2. Trypsinogen → Trypsin (via elevated intracellular calcium) — the critical initiating step
3. Trypsin then activates other proteases (elastase, phospholipase A2, lipase, kallikrein)
4. Autodigestion of pancreatic parenchyma → fat necrosis, cell death, hemorrhage
5. Release of pro-inflammatory cytokines (IL-1, IL-6, TNF-α) and activated enzymes into systemic circulation → SIRS → organ failure (hypotension, AKI, ARDS)
6. Fluid extravasation into retroperitoneal spaces ("third space" losses)

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Classification (Revised Atlanta, 2012)

By Type

By Severity

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Clinical Presentation

• Abdominal pain — hallmark; typically epigastric or periumbilical, radiating to the back; constant, severe, often "boring" in quality; worse supine, better leaning forward
• Nausea and vomiting — nearly universal
• Fever — low-grade initially; high fever suggests infection/sepsis
• Tachycardia, hypotension — from third-space losses and SIRS
• Abdominal tenderness — diffuse or localized to epigastrium; guarding/rigidity in severe cases
• Distension/ileus — from peritoneal irritation

• Cullen's sign — periumbilical ecchymosis (retroperitoneal hemorrhage tracking anteriorly)
• Grey Turner's sign — flank ecchymosis (same mechanism)
• Jaundice — if common bile duct compression or concomitant choledocholithiasis

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Diagnosis

Diagnostic Criteria (any 2 of 3 required):

1. Characteristic abdominal pain
2. Serum amylase or lipase ≥ 3× upper limit of normal
3. Characteristic findings on imaging (CT/MRI/US)

Laboratory Tests

Imaging

• Identifies gallstones, biliary dilation
• Limited pancreatic visualization due to bowel gas

• Indicated when diagnosis is uncertain, or if no improvement in 48–72 hours
• Identifies necrosis (areas of non-enhancement), fluid collections, vascular complications
• CT Severity Index (Balthazar score) grades A–E based on inflammation and necrosis

• Choledocholithiasis without ERCP radiation risk
• Identifying duct disruption
• Allergy to iodinated contrast

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Severity Scoring

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Complications

Local Complications

Systemic Complications

• ARDS / respiratory failure (pleural effusion, atelectasis, ARDS)
• Acute kidney injury
• Shock (distributive, hypovolemic)
• DIC
• Hypocalcemia (fat saponification)
• Hyperglycemia
• Ileus
• Splenic/portal/mesenteric vein thrombosis
• Pseudoaneurysm (splenic artery most common) → can rupture

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Management

Acute Pancreatitis — General Principles

• Most critical early intervention
• Lactated Ringer's (LR) preferred over normal saline — lower risk of acidosis and possibly reduced SIRS
• Goal-directed: 250–500 mL/hr initially; reassess at 6 and 24 hours
• Aggressive hydration (>4 L in first 24 h) may be harmful in elderly/cardiac patients
• Markers of adequate resuscitation: urine output >0.5 mL/kg/hr, decreasing BUN, HR normalization

• IV opioid analgesia (e.g., hydromorphone or fentanyl) — morphine historically avoided but current evidence shows no increased sphincter-of-Oddi pressure clinically
• NSAIDs and epidural analgesia used in some centers

• Oral feeding should be started as early as tolerated (as soon as pain improving and patient hungry)
• Enteral nutrition (via nasojejunal or even nasogastric tube) preferred over parenteral in severe pancreatitis
• Total parenteral nutrition (TPN) only if enteral route is not feasible
• "NPO" protocols are now discouraged in mild pancreatitis

• Prophylactic antibiotics do NOT prevent infected necrosis and are not recommended
• Antibiotics only if confirmed/strongly suspected infected necrosis (imipenem or meropenem ± antifungal)

• Gallstone pancreatitis: Urgent ERCP (within 24 h) ONLY if concurrent acute cholangitis; cholecystectomy should be performed during the same admission (mild) or after resolution (severe) to prevent recurrence
• Hypertriglyceridemia: Insulin infusion (activates lipoprotein lipase), plasmapheresis in extreme cases
• Alcohol: Cessation counseling; treat withdrawal
• Drug-induced: Discontinue offending drug

• Infected necrosis: Step-up approach — percutaneous drainage first, then endoscopic (transluminal) or minimally invasive surgical necrosectomy if failing
• Pancreatic pseudocyst: Expectant management if asymptomatic; endoscopic drainage (cyst-gastrostomy) if symptomatic or enlarging
• Walled-off necrosis: Endoscopic transmural drainage ± necrosectomy (lumen-apposing metal stent)
• Open surgical necrosectomy is a last resort due to high morbidity

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Chronic Pancreatitis

Definition & Pathology

Causes

• Chronic alcohol use — most common in adults
• Genetic — PRSS1, SPINK1, CFTR mutations (especially in young patients)
• Autoimmune (IgG4-related — Type 1; duct-centric — Type 2)
• Tropical pancreatitis — malnourishment, cassava toxin (Southeast Asia, Africa)
• Obstructive — pancreatic duct stricture, tumor
• Idiopathic — significant proportion

Clinical Features

• Chronic abdominal pain — epigastric, radiating to back; often persistent; can be paroxysmal
• Exocrine insufficiency (late):
  • Steatorrhea (>90% exocrine function must be lost before malabsorption occurs)
  • Weight loss, malnutrition
  • Fat-soluble vitamin deficiencies (A, D, E, K)
• Endocrine insufficiency (late):
  • Diabetes mellitus (Type 3c or "pancreatogenic diabetes")
  • Brittle insulin-dependent diabetes (also loss of glucagon → hypoglycemia risk)
• Obstructive jaundice — fibrotic compression of common bile duct
• Pancreatic cancer risk — significantly increased (cumulative lifetime risk ~4%)

Diagnosis of Chronic Pancreatitis

• CT scan: Pancreatic calcifications (pathognomonic), ductal dilation, atrophy
• MRCP/EUS: Ductal changes (chain-of-lakes), parenchymal changes
• Fecal elastase-1 (<200 µg/g stool) — most widely used test for exocrine insufficiency
• 72-hour fecal fat — quantifies fat malabsorption
• Secretin-stimulated MRI/MRCP — functional assessment
• Serum IgG4 — elevated in autoimmune pancreatitis Type 1

Management of Chronic Pancreatitis

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Pathology (Gross & Microscopic)

Acute Pancreatitis

• Mild/interstitial: Edema, focal fat necrosis, mild inflammatory infiltrate
• Severe/necrotizing: Widespread hemorrhagic necrosis; chalky white fat necrosis (calcium soap deposits); destruction of acini, ducts, and islets; pseudocyst formation possible

Chronic Pancreatitis

• Irreversible fibrosis, loss of acinar tissue
• Dilated ducts filled with inspissated protein plugs and calculi
• Relatively preserved islets of Langerhans (initially), then progressive islet loss
• Eventual atrophy of the entire gland

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Prevention of Recurrence

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Key Points Summary

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