The Autodigestion Hypothesis
What is Autodigestion?
In a nutshell, the powerful digestive enzymes in the gastrointestinal tract leak into the body and
degrade cells, tissues and organs.
The idea is as follows: Digestive enzymes are discharged from the pancreas and activated in the duodenal segments of the upper ileum. The enzymes are active and degrade proteins, nucleotides, lipids and complex carbohydrates as part of daily digestion while passing along the lumen of the small intestine. The process is the foundation for daily digestion of food as the source for the nutritional support the body needs to grow and live.
Did you ever wonder:
"How is it possible that I can digest food and not digest myself."
For example, your intestine has the ablity to digest an intestine, like the skin of a sausage, and not digest itself.
This is possible by restricting digestive enzymes within the lumen of the intestine by the mucosal barrier. It is composed of epithelial cells and a mucin layer.
Breakdown of a Barrier
Disruption of this barrier allows digestive enzymes to escape into the circulation, the lymphatics, and the peritoneum. Digestive enzymes activate other families of enzymes and generate degradation products that are cytotoxic. They digest the intestinal villi, degrade cells and their receptors, the extracellular matrix, blood vessels, and tissues. An example is:
Autodigestion in Shock and Sepsis
We postulate a tissue injury mechanism that leads to cell and organ dysfunction and failure. Leakage of digestive enzymes leads to reduction of the central blood pressure and to death - even without ischemia in the systemic circulation. After injury to the small intestine, digestive enzymes leak into the circualtion and autodigestion is a major tissue destruction mechanism that causes multiorgan failure and death.
A New Opportunity for Intervention against Mortality due to Multi-organ Failure
Blockade of the powerful digestive enzymes in the lumen of the intestine in shock serves to reduce autodigestion of the intestine, destruction of the mucosal barrier, and minimizes inflammation in the circulation. Blockade of digestion in the intestine prevents peripheral organ damage, i.e. multi-organ failure in experimental forms of shock. This approach needs to be tested in patients and may save lives.
- Develop a new technology to measure digestive enzyme activity with high sensivitity and selectivity in unseparated fresh blood samples at point of care (a. Lefkowitz et al.; b. Lefkowitz et al.).
- Develop and test new procedure to reduce mortality associated with development of multi-organ-failure?
- To translate interventions against autodigestion to man.
- Determine the mechanisms that lead to breakdown of the mucosal barrier.
We may be all subject to autodigestion !
Do not despair. Instead get involved in Autodigestion research. Click for Contact
Section of a healthy small intestine with villi and a smooth muscle (bottom) layer
Crossection of an intestine not adequately perfused by blood for 30 minutes (like in shock). The digestive enzymes (blue) escape from the lumen of the intestine and enter into the wall of the intestine