Increased susceptibility of aging gastric mucosa to injury: The mechanisms and clinical implications

Figure 2 Gastric mucosal defense. Schematic representation of gastric mucosal defense mechanisms. Reproduced with permission from Laine, Takeuchi and Tarnawski[4]. (1) “Unstirred” layer of mucus/bicarbonate/phospholipids above surface epithelial cells constitutes the first line of defense. It maintains a pH of approximation 7.0 (close to the physiological cell pH) at the surface epithelial cells, while pH in the lumen is about 1.0-3.0; (2) the surface epithelial cells secrete mucus, bicarbonate and synthesize prostaglandins and heat shock proteins; (3) mucosal cell renewal from mucosal progenitor cells is driven by growth factors (transforming growth factor α and insulin like growth factor-1α) utilizing the epidermal growth factor receptors). Expression of survivin in epithelial progenitor cells prevents apoptosis and is the key for “immortality” of these cells under normal conditions; (4) “Alkaline tide”-parietal cells secreting HCl into the gastric gland lumen concurrently secrete bicarbonate into the lumen of adjacent capillary blood vessels. Bicarbonate is transported to the surface and contributes to the first line of defense; (5) mucosal microcirculation through the capillary microvessels is essential for delivery of oxygen and nutrients. Endothelial cells of microvessels generate prostaglandins, mainly PGI₂ (prostacyclin) and nitric oxide, which exert vascular and mucosal protective actions; (6) sensory nerve stimulation by H⁺-ion or other irritants causes release of neurotransmitters such as calcitonin gene related peptide (CGRP) and substance P in nerve terminals, which induce vasodilatation and enhance mucosal blood flow; and (7) continuous generation of prostaglandin E₂ (PGE₂) and prostacyclin (PGI₂) by the gastric mucosal cells is crucial for the maintenance of mucosal integrity. Almost all of the above (1-6) mucosal defense mechanisms are stimulated or facilitated by endogenous or exogenous prostaglandins. CRF: Corticotrophin-releasing factor; TRF: Thyrotropin-releasing factor; CCK: Cholecystokinin.