Top Causes - Stones & Spirits
The two most common causes account for ~80% of acute pancreatitis cases in the U.S.
| Feature | Gallstones (Cholelithiasis) | Alcohol |
|---|---|---|
| Pathophysiology | Ampullary obstruction by a stone → reflux of bile and/or duodenal contents into the pancreatic duct → premature enzyme activation. | Direct toxic effect on pancreatic acinar cells + sensitization to other injuries. Chronic use leads to protein plug formation. |
| Patient Profile | Classically, female, overweight, and >40 years old ("fat, female, forty"). Presents with acute, severe epigastric pain. | History of chronic, heavy alcohol use (typically >5-7 years). Often presents as an acute-on-chronic episode. |
⭐ An Alanine Aminotransferase (ALT) level >150 U/L has a >95% positive predictive value for gallstone pancreatitis.
Other Causes - The Usual Suspects
📌 Mnemonic: I GET SMASHED
- Idiopathic: No cause found after initial workup.
- Gallstones: (Covered previously)
- Ethanol (Alcohol): (Covered previously)
- Trauma: Blunt or penetrating abdominal injury; iatrogenic (e.g., post-operative).
- Steroids: High-dose corticosteroid therapy.
- Mumps: And other viruses (Coxsackie B, HIV).
- Autoimmune: IgG4-related disease, SLE, IBD.
- Scorpion sting: Venom from species like Tityus trinitatis.
- Hyperlipidemia/Hypercalcemia:
- Triglycerides > 1000 mg/dL.
- Calcium > 12 mg/dL (e.g., from hyperparathyroidism).
- ERCP: Post-procedure inflammation (5-10% of cases).
- Drugs: Thiazides, furosemide, azathioprine, valproic acid, sulfonamides.
⭐ Exam Favorite: Drug-induced pancreatitis is often idiosyncratic and dose-independent. Always review the patient's medication list for common offenders like diuretics (thiazides, furosemide) and immunosuppressants (azathioprine).
Pathophysiology - The Cascade Crash
- Core Defect: Premature activation of trypsinogen to trypsin within acinar cells, instead of the duodenal lumen.
- Mechanism: An initial insult (e.g., obstruction, toxins) disrupts normal acinar cell secretion and protective mechanisms.
- Autodigestion: Activated trypsin triggers a cascade, activating other zymogens:
- Elastase → vascular damage & hemorrhage.
- Phospholipase A2 → membrane destruction & coagulative necrosis.

⭐ Trypsin is the key trigger. It not only digests pancreatic tissue but also activates the complement and kinin systems, amplifying inflammation and vascular permeability, leading to systemic complications.
High‑Yield Points - ⚡ Biggest Takeaways
- Gallstones and chronic alcohol abuse are overwhelmingly the most common causes of acute pancreatitis.
- Post-ERCP pancreatitis is the most frequent iatrogenic cause.
- Severe hypertriglyceridemia (TGs >1000 mg/dL) is a key metabolic trigger.
- Important drug-induced causes include diuretics, valproic acid, and azathioprine.
- Mumps virus is a classic infectious cause, especially in children.
- Autoimmune (IgG4-related) and idiopathic causes are considered after ruling out common etiologies.
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