Protection in the GI Tract
Protection
Digestive tract utilizes various mechanisms to protect the body (internal environment) from the external environment.
It specifically protects against:
- Chemical damage
- Exposure to toxins
- Microorganism entry
KEY protective features
(found throughout the entire GI tract)
1. Tight junctions
- Dense network of claudins and other proteins just below the apical surface of the GI epithelium.
- Intrinsic barrier of the digestive tract. They form a nearly impermeable barrier that prevents GI tract luminal contents from freely leaking through the mucosal layer.
Tight junctions prevent entry of microorganisms and other potentially harmful substances or toxins (such as HCl produced in the stomach) into the digestive tract wall.
2. Mucus lining
- Feature of all mucous membranes (mucosa).
- Mucus = alkaline (bicarbonate) secretion that protects against shear stress and chemical damage throughout the digestive tract.
1. Mucous cells in oral cavity
- Forms mucus lining
- Secreted as a component of saliva to primarily aid food bolus formation.
- Minor protective role in the oral cavity (protects the mouth from acidic food and pathogens)
2. Mucous neck cell in stomach.
- Mucus lining provides a chemical barrier between the stomach lumen and its epithelium
- Neutralizes acidic secretions during a meal (with its bicarbonate component), and
- Prevents autodigestion of the mucosa by proteases.
3. Goblet cells in small intestine.
- Mucus lining continues as a chemical barrier between the acidic chyme present in the intestines and the intestinal mucosa.
Unique protective features in these three GI organs.
oral cavity
Secretes saliva, which contains:
- Lysozymes, which lyse bacteria.
- IgA antibodies, which maintain mucosal immunity, and
- Defensins, which are host defense antimicrobial peptides of innate immunity.
Stomach
Parietal cells
(in the epithelium of the mucosal layer, which lines the lumen of the stomach)
- Secrete HCl, which primarily digests protein; however,
- HCl creates a harsh environment, which kills many microorganisms. The gastric mucosa is largely protected from this harsh environment by the alkaline mucus lining.
Clinical Correlate: Gastric Ulcers
- Breaks in the mucosal barrier exposes the GI wall to corrosive HCl and proteases
- Causes gastric wall erosion and inflammation
- Common cause: H. pylori (bacteria) is a common cause of gastric ulcers, which erodes the epithelial barrier.
- Ulcers can also occur in lower esophagus and in the small intestine (specifically, the duodenum).
High Cellular Turnover Rate
- GI epithelium sheds frequently as it becomes damaged from continued exposure to its lumen's harsh chemical environment and continuous shear stress gastric motility.
- Regeneration: epithelial stem cells replenish damaged or dead epithelial cells.
- The GI epithelium divides, or turns over, almost constantly to replace damaged cells with new, mature ones – unlike the heart, which almost never replaces its cardiac cells.
Stem cells
- Located at the top of gastric glands
- Replenish gastric secretory and mucous cells that protect the stomach surface.
Paneth cells
- Found in its villi crypts
- Contain secretory granules filled antimicrobial peptides, which are secreted into the GI lumen.
- Provide another layer of host defense in the small intestine.
Stem cells
- Replenish damaged, or dead, absorptive and goblet cells that are shed from villi; they reside adjacent to paneth cells in villi crypts.
Paneth cells = "protectors of stem cells"
- Secrete factors to maintain these stem cells to promote cellular renewal.
Note: Although the digestive tract relies on high rates of cellular division to replace old, damaged cells – this also corresponds to higher rates of mutations and, thus, increased incidence of cancer in GI epithelium (carcinoma).