What is the pathophysiological mechanism by which ethanol (alcohol) induces pancreatitis?

From the Guidelines

Alcohol causes pancreatitis by inducing a complex interplay of toxic metabolic byproducts, premature enzyme activation, and ductal obstruction, ultimately leading to pancreatic inflammation, fibrosis, and calcification, as supported by the most recent evidence from 2017 1. When alcohol is consumed, it is metabolized in the pancreas, producing toxic byproducts that directly injure pancreatic cells, as noted in the 2006 ESPEN guidelines on enteral nutrition: pancreas 1. These toxins cause inflammation and premature activation of digestive enzymes inside the pancreas rather than in the small intestine where they should normally activate. This leads to autodigestion, where the pancreas essentially begins to digest itself. Some key points to consider include:

• The dominant aetiology for chronic pancreatitis in western countries is excess alcohol consumption, with heavy smoking also increasing the risk of developing chronic pancreatitis 1.
• Chronic alcohol use damages pancreatic cells over time, leading to fibrosis and calcification, and the risk increases with the amount and duration of alcohol consumption.
• The morphological changes in chronic pancreatitis include oedema, acute inflammation, and necrosis, superimposed on the background of chronic changes that include fibrosis, calcification, inflammation, and loss of exocrine tissue 1.
• Exocrine impairment, or pancreatic exocrine insufficiency (PEI), may be measured indirectly by methods such as measurement of faecal fat, measurement of the enzyme faecal elastase-1, or evidence of pathological pancreatic function along with clinical signs of malabsorption 1. The most effective treatment for PEI is the administration of exogenous enzymes, or pancreatic enzyme replacement therapy (PERT), which reduces fat malabsorption and helps achieve normal nutritional status, as reported in the 2017 study 1.

From the Research

Mechanisms of Alcohol-Induced Pancreatitis

Alcohol consumption can cause pancreatitis through several mechanisms, including:

• Direct damage to pancreatic tissue 2, 3
• Increased pancreatic vulnerability to damage, requiring additional risk factors and pancreatic costressors to develop pancreatitis 2
• Blockage of small pancreatic ducts and destruction of pancreatic tissue by digestive enzymes 3
• Damage to cell membranes by by-products of alcohol metabolism within the pancreas 3
• Concentration and acidification of pancreatic juice, predisposing to protein precipitation 4
• Relative hyperstimulation of the pancreas during withdrawal period, leading to experimental acute pancreatitis 4

Risk Factors and Epidemiology

The risk of developing pancreatitis increases with:

• High alcohol intake, with around 2.5%-3% of heavy drinkers developing pancreatitis compared to 1.3% of non-drinkers 5
• Chronic heavy alcohol consumption, accounting for about 70% of pancreatitis cases 5
• Long-term high alcohol consumption, resulting in lowered cholecystokinin and cholinergic stimulus of the pancreas 4
• Genetic variability and environmental exposures, such as smoking and diet, which modify the risk of developing pancreatitis and pancreatic cancer 5

Diagnosis and Biomarkers

Diagnosis of acute pancreatitis is based on:

• Presence of abdominal pain, serum increase of pancreatic enzymes, or their presence in urine and/or alterations of the pancreas imaging 6
• Elevated levels of serum amylase, lipase, and pancreatic isoamylase in chronic alcoholics and patients with alcoholic acute pancreatitis 6