The Auto-Digestion Hypothesis: Digestive Enzymes on the Prowl

Did you ever wonder why you can digest an intestine that you eat, but hopefully not your own intestine? Man, like many other animals living today and in the past, require a mechanism to degrade biomolecules as food source, a process that involves the powerful digestive enzymes synthesized in the pancreas. These enzymes degrade food in the lumen of the intestine and are retained inside the intestinal lumen by the mucosal barrier. This important barrier - made up of epithelial cells and a mucin protein layer - becomes permeable in shock and allows the digestive enzymes to escape from the lumen into the wall of the intestine. As the digestive enzymes enter into the tissue they digest the intestine itself, generate lipid and protein fragments that are cytotoxic, and escape into the systemic circulation. Once in the circulation, the combination of digestive enzymes and fragments they generate causes cell dysfunctions, such as acute insulin resistance, peripheral organ failure and death. This mechanism establishes auto-digestion and death as a price for a life-long benefit to extract biomolecules and metabolic energy from the environment. I will discuss current approaches to interfere with autodigestion and the potential to reduce multi-organ failure in shock patients.