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Acute and Chronic Pancreatitis: A Comprehensive Review

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PART I — ACUTE PANCREATITIS

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1. Classification

1.1 By Morphology (Revised Atlanta Classification, 2012)

1.2 By Severity (Revised Atlanta Classification)

1.3 Local Complications (time-based terminology)

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2. Etiology

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3. Pathogenesis

1. Triggering event (gallstone, alcohol, etc.) disrupts acinar cell homeostasis
2. Trypsinogen activation — normally trypsinogen is activated only in the duodenum by enterokinase; pathologically activated intracellularly
   • Cathepsin B (lysosomal enzyme) co-localizes with zymogen granules → activates trypsinogen → activates other zymogens (chymotrypsinogen, proelastase, prophospholipase A2)
   • Protective mechanisms overwhelmed: SPINK1 (trypsin inhibitor), trypsin autolysis, mesotrypsin
3. Acinar cell injury → release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, PAF)
4. Local inflammation → pancreatic edema, hemorrhage, fat necrosis, vascular injury
5. Systemic inflammatory response syndrome (SIRS) → capillary leak, hypotension, remote organ failure (ARDS, AKI, shock)
6. Two-peak mortality model:
   • Early (<1 week): Driven by SIRS and multi-organ failure
   • Late (>1 week): Driven by infected pancreatic necrosis and sepsis

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4. Clinical Presentation

• Epigastric pain — cardinal symptom; acute onset, severe, constant; classically radiates to the back ("boring" quality); partially relieved by leaning forward
• Nausea and vomiting (often bilious, not relieving pain)
• Anorexia, fever (low-grade in edematous; high in infected necrosis)

• Epigastric tenderness ± guarding
• Abdominal distension (paralytic ileus)
• Reduced/absent bowel sounds
• Grey Turner's sign — flank ecchymosis (retroperitoneal hemorrhage) — late, rare
• Cullen's sign — periumbilical ecchymosis — late, rare
• Jaundice if common bile duct obstruction (choledocholithiasis or head edema)
• Signs of SIRS: tachycardia, tachypnea, fever/hypothermia

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5. Complications

Local Complications

Systemic Complications

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6. Diagnosis

6.1 Diagnostic Criteria (Any 2 of 3):

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

6.2 Laboratory Tests

6.3 Imaging

6.4 Severity Scoring Systems

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7. Treatment

7.1 General (Supportive) Management

1. Fluid resuscitation — cornerstone of early management
   • Aggressive early IV fluids: Lactated Ringer's preferred over normal saline (reduces SIRS, acidosis)
   • Goal-directed: 250–500 mL/h in first 12–24 h; reassess at 6 h intervals
   • Avoid over-resuscitation (abdominal compartment syndrome, ARDS)
2. Analgesia
   • IV opioids (morphine, hydromorphone, fentanyl); historical concern about morphine causing Sphincter of Oddi spasm not clinically relevant
   • Epidural analgesia in severe cases
3. Nutrition
   • Mild AP: resume oral feeds once pain and nausea controlled (low-fat soft diet; nothing-by-mouth period no longer routinely indicated)
   • Severe/moderately severe AP: enteral feeding (nasojejunal or nasogastric) preferred over parenteral — reduces infections, preserves gut barrier, lowers mortality
   • Total parenteral nutrition (TPN): only if enteral route not tolerated
4. No routine antibiotics — prophylactic antibiotics do NOT reduce infected necrosis or mortality; use only for proven/suspected infection (fever + CT gas in necrosis + FNA positive culture)
5. Antibiotic choice for infected necrosis: Imipenem, meropenem, or ciprofloxacin + metronidazole (pancreas-penetrating drugs)
6. Specific etiologic treatment:
   • Gallstone AP + cholangitis → urgent ERCP (within 24 h)
   • Gallstone AP without cholangitis → ERCP if CBD obstruction; cholecystectomy during same admission (mild) or after recovery (severe)
   • Hypertriglyceridemia → insulin drip, plasmapheresis (TG >1000 with severe AP)
   • Hypercalcemia → treat underlying cause
   • Autoimmune → corticosteroids

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8. Indications for Surgical Intervention in Acute Pancreatitis

Step-Up Approach for Infected Necrosis (PANTER/TENSION trials evidence):

1. Step 1: CT-guided percutaneous catheter drainage
2. Step 2: Endoscopic transmural drainage / direct endoscopic necrosectomy (if WON accessible endoscopically — preferred over surgery; PENGUIN trial)
3. Step 3: Minimally invasive surgical necrosectomy (video-assisted retroperitoneal debridement — VARD; laparoscopic transgastric necrosectomy)
4. Step 4: Open surgical necrosectomy (last resort; highest morbidity)

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PART II — CHRONIC PANCREATITIS

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1. Classification

1.1 TIGAR-O Classification (Most Widely Used)

1.2 M-ANNHEIM Classification

1.3 Cambridge Classification (Morphological/Imaging-based)

1.4 Functional Classification:

• Exocrine insufficiency stages
• Endocrine insufficiency (pancreatogenic/Type 3c diabetes)

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2. Etiology and Pathogenesis of Chronic Pancreatitis

• Alcohol — most common cause (70–80%) in Western countries; requires >5 years of heavy use; only 5–10% of heavy drinkers develop CP
• Tobacco — independent risk factor; synergistic with alcohol; dose-dependent
• Genetic: PRSS1 (autosomal dominant; gain-of-function → persistent trypsin activity), SPINK1 (loss of trypsin inhibition), CFTR (ductal secretion defects), CTRC (chymotrypsin C mutations)
• Tropical (nutritional) pancreatitis — common in India, Africa, Southeast Asia; cassava toxin hypothesis (cyanogen); characterized by massive pancreatic calcifications and early-onset diabetes
• Autoimmune — Type 1: IgG4+ plasma cell infiltration; "sausage-shaped" pancreas; responds to steroids. Type 2: neutrophilic infiltration; associated with IBD; no IgG4 elevation
• Obstructive — chronic ductal obstruction from any cause leads to upstream atrophy and fibrosis
• Idiopathic — early onset (<35 y, painful) and late onset (>50 y, painless, exocrine failure)

• Repeated acute pancreatitis episodes → chronic stellate cell activation
• Pancreatic stellate cells (PSCs) normally quiescent; activated by oxidative stress, cytokines (TGF-β, TNF-α, IL-1, IL-6, PDGF, ET-1)
• Activated PSCs → synthesize and deposit collagen (I, III) and extracellular matrix → pancreatic fibrosis
• Progressive acinar cell loss → exocrine insufficiency
• Progressive islet cell loss → endocrine insufficiency (pancreatogenic diabetes)
• Calcification: intraductal protein plugs calcify → ductal obstruction → further fibrosis

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3. Clinical Presentation

• Cardinal symptom; epigastric, radiates to back
• Type A (episodic, <10 days/episode with pain-free intervals) — early disease
• Type B (persistent, continuous pain) — late disease
• Pain paradoxically "burns out" in ~30% as gland becomes completely fibrotic ("burned-out pancreas")

• Steatorrhea — greasy, foul-smelling, floating stools (fat malabsorption)
• Malabsorption of fat-soluble vitamins (A, D, E, K)
• Weight loss, malnutrition

• Late complication; ~50% at 25 years
• Brittle, insulin-dependent diabetes
• Hypoglycemia-prone (loss of glucagon from α-cells too)
• Different from Type 1 and Type 2 DM — reduced glucagon response

• Jaundice (CBD stricture from fibrosis)
• Duodenal obstruction (rare; peri-pancreatic fibrosis)
• Pancreatic ascites or pleural effusion (pancreatic duct disruption → pancreatic fistula)
• Venous thrombosis (splenic/portal)
• Palpable mass (inflammatory mass — must exclude malignancy)

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4. Complications

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5. Diagnosis

5.1 Laboratory Tests

5.2 Imaging

5.3 Histology (gold standard but rarely needed)

• Acinar cell loss, fibrosis, chronic inflammatory infiltrate, ductal changes

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6. Treatment of Chronic Pancreatitis

6.1 Medical Management

• Lifestyle: abstinence from alcohol and tobacco (most important; slows progression)
• Analgesic ladder: NSAIDs → weak opioids → strong opioids (addiction risk)
• Pancreatic enzyme supplementation — may reduce pain by suppressing CCK-mediated stimulation (negative feedback); mixed evidence
• Antioxidants (selenium, beta-carotene, vitamins C and E, methionine) — some benefit in idiopathic CP
• Pregabalin/gabapentin — neuropathic pain component
• Tricyclic antidepressants — central sensitization
• Celiac plexus block/neurolysis — temporary relief; EUS-guided preferred; effect lasts months

• High-dose enteric-coated pancreatic enzyme replacement therapy (PERT): lipase 40,000–50,000 IU per meal, 25,000 IU per snack
• H2-blocker/PPI to prevent acid degradation
• Fat-soluble vitamin supplementation (A, D, E, K)
• Medium-chain triglycerides (do not require lipase for absorption)

• Insulin therapy; metformin may be used early
• Avoid sulfonylureas (hypoglycemia risk from absent glucagon)
• Monitor for hypoglycemia carefully

6.2 Endoscopic Treatment

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7. Indications for Surgical Intervention in Chronic Pancreatitis

1. Intractable pain unresponsive to medical and endoscopic therapy
2. Complications requiring surgery:
   • Bile duct obstruction (obstructive jaundice/cholangitis unresponsive to stenting)
   • Duodenal obstruction
   • Pancreatic pseudocyst (if not amenable to endoscopic drainage)
   • Arterial pseudoaneurysm
   • Pancreatic fistula/ascites failing conservative management
3. Suspicion of malignancy — inability to exclude pancreatic cancer
4. Portal/splenic vein thrombosis with symptomatic varices
5. Failure or complications of endoscopic therapy

• Surgery should be considered early in patients with dilated main pancreatic duct (>7 mm) and disabling pain — better outcomes than repeated endoscopy (ESCAPE trial, LEIDEN data)
• Aim: pain relief, preservation of pancreatic function (avoid unnecessary resection), treatment of complications

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8. Types of Surgery for Chronic Pancreatitis

8.1 Drainage Procedures (for "big duct" disease — MPD >7 mm)

8.2 Resection Procedures

8.3 Combined Drainage and Resection Procedures (for head-dominant disease with ductal dilation)

8.4 Total Pancreatectomy with Islet Auto-Transplantation (TPIAT)

• Total pancreatectomy followed by isolation and autotransplantation of islets into portal vein
• Aim: cure pain while preserving some insulin production
• Best results in small-duct disease (idiopathic, hereditary) before islet cell burnout
• ~30–40% insulin-independent at 1 year

8.5 Special Case: Tropical Chronic Pancreatitis

• Surgery reserved for intractable pain
• Procedures: side-to-side pancreaticojejunostomy; resection in extreme cases

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Summary Comparison Table

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• Harrison's Principles of Internal Medicine, 21st Edition, p. 9718
• Bailey and Love's Short Practice of Surgery, 28th Edition, p. 107