Alcoholic Pancreatitis

23.4.07

Alcoholic pancreatitis
Epidemiology
• 40 per 100,000/year.
• Associated with alcohol abuse - binge drinking.
• Increasing incidence.
• Severe in 20-30%.
• Mortality up to 10%.
• Management variable.
• Treatment inadequate.

Aetiology
• Alcoholic.
• Biliary - gallstones.
• Idiopathic.
• Others, including hypercalcaemia and hyperlipidaemia.

Alcohol consumption
Binge drinking
• People living in north of England more likely to die earlier through alcohol abuse than anywhere else.

The problem
• Rates of acute pancreatitis increased from 4.9-9.8/100,000.
• Particularly large increase in younger people.

Alcoholic pancreatitis
Clinical signs
• Upper abdo pain.
• Epigastric/diffuse abdo tenderness.
• Serum amylase activity (4X normal).
• Cullen's sign.
• Grey-Turner's sign.

Complications
• Pancreatic necrosis.
• Infected necrosis.
• Pseudocyst.
• Haemorrhage.
• Multiorgan failure.
• Death.

Non-surgical therapy
• Resuscitation.
• Analgesia.
• Stone extraction.
• Ventilation.
• Inotropes.
• Dialysis.
• Nutrition.

Major intervention
• Open necrosectomy.
• Minimal access necrosectomy.
• Pancreatic stenting etc.

Limitations to current management
• Prophylaxis restricted to removing precipitating factors after onset.
• No significant impact on course of disease made by medical treatment.

Pathogenesis
• Autolysis precipitated by known factors.
• Activated digestive enzymes within and subsequently around acinar cells.
• Co-localisation of granules and Lysosomes.
• Vacuolisation etc.

Premature digestive enzyme activation critical
• Mutations in cationic trypsinogen render trypsin resistant to inactivation.

Ca2+ hypothesis
• Abnormal, prolonged elevation of cytosolic Ca2+ initiates pancreatitis.

Alcohol-induced injury theory
• Spasm of sphincter of Oddi.
-Duodenal-pancreatic reflux.
• Formation of protein-rich secretory plugs.
• Duct obstruction causes pancreatic damage and altered Ca2+ signalling.
• Generation of free radicals.
• Sensitisation of acinar cell to CCK on zymogen conversion in vitro.
-Ethanol may sensitise CCK-induced zymogen conversion in pancreatic acinar cells.
• Toxic metabolites.

High ethanol/unsaturated fatty acid diet induces pancreatitis in rats.

Fatty acid ethyl esters induce:
• Direct pancreatic damage in vivo.
• Prolonged abnormal increase of Ca2+ concentration.