[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Pancreas](https://durgical.com/en/general-pathology/areas/pancreas/) › Acute pancreatitis: causes, and how trypsin starts self-digestion

# Acute pancreatitis: causes, and how trypsin starts self-digestion

- Mechanism

In acute pancreatitis digestive enzymes switch on inside the pancreas and start digesting it, causing sudden severe pain.

Updated Nov 12, 2026

## Key points

- Main causes: gallstones and alcohol; then hypertriglyceridemia, post-ERCP, drugs, hypercalcemia, trauma, infections (mumps, coxsackie), genetic variants, pancreas divisum, scorpion venom; some remain idiopathic.
- Trypsin is the master switch: it activates phospholipase, elastase and other proenzymes.
- Elastase destroys vessel walls (hemorrhage); lipase and phospholipase cause fat necrosis.
- Fat necrosis binds calcium (saponification), so serum calcium may fall.
- Serum lipase (more specific) and amylase rise; a diagnosis needs two of pain, enzymes at least three times normal, and imaging.
- In Colombia and Latin America gallstones are the leading cause.

## What it is

Acute pancreatitis is reversible inflammation of the pancreas caused by premature activation of its own enzymes. Gallstones and alcohol together cause most cases. Three initiating events lead to the same end: duct obstruction, primary acinar cell injury, and defective intracellular transport of proenzymes. Once trypsinogen is activated to trypsin, it activates other enzymes, kinins, complement and clotting, causing edema, fat necrosis, hemorrhage and a systemic inflammatory response.

## Step by step

- A trigger acts: a stone at the ampulla, alcohol, high triglycerides, trauma or a drug.
- Duct obstruction raises pressure and fluid with enzymes leaks into the interstitium.
- Inside acinar cells, proenzymes meet lysosomal hydrolases and trypsinogen is activated.
- Trypsin activates other proenzymes, kallikrein, complement and coagulation.
- Lipases and elastase cause fat necrosis, vessel damage and hemorrhage.
- Cytokines spill into the blood: SIRS, ARDS, shock, DIC in severe cases.

## Causes of acute pancreatitis grouped by mechanism

| Mechanism | Causes |
| --- | --- |
| Duct obstruction | Gallstones, ampullary or pancreatic tumours, pancreas divisum, choledochocele, parasites (Ascaris) |
| Direct acinar injury | Alcohol, drugs (e.g. azathioprine, valproate, some diuretics), viruses (mumps), ischemia, trauma, post-ERCP |
| Metabolic | Hypertriglyceridemia, hypercalcemia (hyperparathyroidism) |
| Genetic | PRSS1, SPINK1, CFTR, CTRC variants |
| Toxins | Scorpion venom, organophosphates |

## Clinical notes

- Severe epigastric pain radiating to the back, nausea and vomiting.
- Severity depends on organ failure and necrosis; mild cases resolve in days.

## Memory aid

One wrong key turns all the locks: trypsin activated too early opens every other enzyme in the pancreas.

## Test yourself

Think of the answer, then tap the question to see it.

## Which enzyme acts as the trigger of autodigestion in acute pancreatitis?

Trypsin, which once activated converts other proenzymes (phospholipase, elastase) and activates kinins and complement.

## Why can serum calcium fall in acute pancreatitis?

Free fatty acids released by lipase bind calcium in areas of fat necrosis (saponification).

## What are the two most common causes of acute pancreatitis?

Gallstones and alcohol.

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## Elsewhere in DurgiPedia

- [Exocrine pancreatic secretion](https://durgical.com/en/physiology/exocrine-pancreatic-secretion/)
- [Pancreas: acini and islets](https://durgical.com/en/histology/pancreas-acini-and-islets/)

## Connections

## Related 6

- [Acute pancreatitis: morphology and complications](https://durgical.com/en/general-pathology/acute-pancreatitis-morphology-and-complications/)
- [Genetic pancreatitis: PRSS1, SPINK1, CFTR and CTRC](https://durgical.com/en/general-pathology/genetic-pancreatitis-prss1-spink1-cftr-and-ctrc/)
- [Gallstones: cholesterol vs pigment](https://durgical.com/en/general-pathology/gallstones-cholesterol-vs-pigment/)
- [Chemical (toxic) cell injury: direct and after metabolism](https://durgical.com/en/general-pathology/chemical-cell-injury-direct-and-after-metabolism/)
- [Alcohol: how it injures the liver, brain, heart and fetus](https://durgical.com/en/general-pathology/alcohol-how-it-injures-the-liver-brain-heart-and-fetus/)
- [Patterns of necrosis: coagulative, liquefactive, caseous, fat, fibrinoid, gangrenous](https://durgical.com/en/general-pathology/patterns-of-necrosis-coagulative-liquefactive-caseous-fat-fibrinoid-gangrenous/)

## Related conditions 7

- [Acute pancreatitis](https://durgical.com/en/conditions/acute-pancreatitis/)
- [Gallstones (cholelithiasis)](https://durgical.com/en/conditions/gallstones/)
- [Choledocholithiasis](https://durgical.com/en/conditions/choledocholithiasis/)
- [Alcohol use disorder](https://durgical.com/en/conditions/alcohol-use-disorder/)
- [Atherosclerosis and dyslipidaemia](https://durgical.com/en/conditions/atherosclerosis-and-dyslipidaemia/)
- [Familial chylomicronemia syndrome (lipoprotein lipase deficiency)](https://durgical.com/en/conditions/familial-chylomicronemia-syndrome/)
- [Soil-transmitted helminthiasis (ascariasis, hookworm, trichuriasis)](https://durgical.com/en/conditions/soil-transmitted-helminthiasis/)

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Acute Pancreatitis](https://www.ncbi.nlm.nih.gov/books/NBK482468/) (StatPearls (NCBI Bookshelf), 2025).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/general-pathology/acute-pancreatitis-causes-and-how-trypsin-starts-self-digestion/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/acute-pancreatitis-causes-and-how-trypsin-starts-self-digestion/