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Mucin (blue) on villi of the small intestine
Frank A DeLano
Autodigestion is a pathophysiological process
Autodigestion is a pathophysiological process
that may be present in many diseases.
that may be present in many diseases.
On this webpage, you find some examples.
On this webpage, you find some examples.
In 2000, we postulated a tissue injury mechanism due to Autodigestion. It occurs when unchecked pancreatic digestive enzymes escape from the gastrointestinal tract and enter tissue outside the tract.
The basic idea is simple. Digestive enzymes are discharged from the pancreas as proenzymes (zymogens), activated by enterokinases, and in the small intestine, are highly concentrated as a requirement for normal digestion. They degrade proteins, nucleotides, lipids, and complex carbohydrates in food as part of normal nutrition. The digestive enzymes can degrade any tissue in our body.
What prevents digestion of one's own intestine?
In a nutshell, digestive enzymes are compartmentalized by a barrier inside the lumen of the intestine. The barrier consists of a single layer of epithelial cells that is covered by a mucus layer along the entire gastrointestinal tract. The mucus layer is thin (~ 5 µm = 1/60 of a human hair), but still serves as the barrier for digestive enzymes.
Low molecular weight nutrients (ions, water, amino acids, lipid fragments, sugars) can always pass across the mucosal barrier. But higher molecular weight molecules, like digestive enzymes, pass across the mucosal barrier only after injury to the mucosal barrier (for example, partially digested food items or inadequate blood flow to the intestine. When this happens, digestive enzymes are transported into the circulation, and autodigestion starts. Natural protease inhibitors (e.g., serine-1), become saturated and inadequate to block digestive proteases.
Pancreatic digestive enzymes appear active in all organs and destroy their extracellular matrix (i.e., collagen, elastin) and their cell functions. No tissue and cells are spared.
Future Outlook
Opportunities for interventions against Autodigestion are numerous.
Michael Heller, Ph.D. developed a method to measure protease activity in whole human blood samples with enhanced sensitivity (click). Measurements in whole blood of patients are possible.
Can this procedure reduce the high mortality associated with the development of multi-organ failure during shock? It needs to be tested in man. We are working to translate the procedure to man.
Opportunities for Intervention against Multi-organ Failure
Blockade of the powerful digestive enzymes in the lumen of the intestine in experimental forms of sepsis and shock serves to reduce auto-digestion of the intestine, destruction of the mucosal barrier and minimizes inflammation, tissue degradation, and cell dysfunctions. Blockade of digestion in the intestine also prevents peripheral organ damage, i.e., multi-organ failure in experimental forms of shock. The intervention needs to be tested in clinical trials.
Terminology
The term Autodigestion has been used in the past for the digestion of one's own pancreas. Autodigestion 2.0 refers to autodigestion in general to many organs.
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