Pancreatitis

1. Acute Pancreatitis

Definition

• Reversible inflammation; can return to normal if cause is removed.

Causes

• 40–50 %: cholelithiasis (#1)
• 30–40 %: alcoholism
• 10–30 %: idiopathic
• Others: trauma / surgery, hypercalcemia, hyperlipoproteinemia, ampulla of Vater obstruction, viral infections (mumps, coxsackie), iatrogenic (ERCP), hereditary (PRSS1, SPINK1).

Two morphologic forms

Form	Frequency	Lethality	Features
Interstitial (edematous)	80–90 %	0.3 %	Interstitial edema + focal fat necrosis (lipase → FFA + Ca²⁺ → chalky soap deposits)
Hemorrhagic (necrotizing)	10–15 %	50–90 %	Necrosis of acini, ducts, islets + vascular damage → hemorrhage; red-black + yellow-white chalky mottling

Pathogenesis (auto-digestion)

Key triggers:

• ↑ Intraductal pressure (obstruction)
• Duodeno-pancreatic / bilio-pancreatic reflux
• Bile acid mucosal damage
• Inappropriate trypsinogen → trypsin activation (central event)

Three pathways of enzyme activation:

1. Acinar cell injury — alcohol, viruses, drugs, trauma → release & activation of pro-enzymes.
2. Ductal obstruction — gallstones, CF, tumors, Oddi-sphincter edema → ↑ pressure → lipase leaks → fat necrosis → ischemia.
3. Defective intracellular transport — ductal obstruction, alcohol, metabolic injury → pro-enzymes + hydrolases co-packaged → intracellular activation.

Activated enzymes:

• Amylase → diagnostic marker
• Lipase → fat necrosis (more specific)
• Proteases → hemorrhage

Clinical features

• Abdominal pain = hallmark.
• Severe form: “acute abdomen” — rigid, painful abdomen, absent bowel sounds.
• Lab: ↑ amylase, ↑ lipase.

Consequences

Local

1. Recovery, fat necrosis, pseudocyst — walled-off liquefied necrosis, lacks epithelial lining (hence “pseudo”).
2. Abscess, ascites, fistula, pancreatic apoplexy (destructive hemorrhage).
3. Retroperitoneal hemorrhage, digestion of surrounding organs.

Systemic

• Paralytic ileus
• Shock (electrolyte loss, hypovolemia, endotoxemia, cytokine storm)
• Acute renal failure
• ARDS, MOF
• Secondary DM

2. Chronic Pancreatitis

Definition

• Long-standing inflammation + fibrosis with destruction of exocrine pancreas (± later endocrine loss).
• Distinction from acute: irreversible impairment of pancreatic function.

Causes

• Long-term alcohol abuse (most common).
• Long-standing ductal obstruction, CF, hereditary pancreatitis.

Forms

• Chronic fibrotizing pancreatitis — most common, alcoholic; firm fibrotic pancreas with enzyme insufficiency.
• Chronic obstructive pancreatitis — periductal fibrosis + ductal dilation.
• Chronic autoimmune pancreatitis — mimics pancreatic carcinoma (IgG4-related).

Pathogenesis hypotheses

• Ductal obstruction by protein plugs.
• Toxic-metabolic — direct acinar injury by alcohol/metabolites.
• Oxidative stress — free radicals + chemokine-recruited mononuclear cells.
• Necrosis-fibrosis — repeated acute episodes → perilobular fibrosis.

Morphology

• Parenchymal fibrosis, ↓ acini number/size, ductal dilation.
• Ductal epithelium: atrophy, hyperplasia, or squamous metaplasia.
• Macro: hard pancreas, dilated ducts, calcifications.

Clinical features

• Repeated jaundice, vague indigestion.
• Persistent / recurrent abdominal + back pain.
• May be silent until pancreatic insufficiency (malabsorption, steatorrhea) + secondary DM.

💡 High-yield: Acute pancreatitis = gallstones (#1) + alcohol → inappropriate trypsin activation → auto-digestion. Interstitial (mild, fat necrosis with Ca²⁺ soap) vs hemorrhagic (rare but >50 % mortality). Pseudocyst = no epithelial lining; complications include shock, ARDS, MOF, secondary DM. Chronic = irreversible fibrosis + exocrine → endocrine loss; #1 cause = chronic alcoholism; presents with persistent back pain, steatorrhea, DM.