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*'''Epidermal growth factors:''' found in salivary gland secretions, promote DNA synthesis and proliferation of gastric mucosal cells. Also play a role in prostaglandin synthesis and inhibit HCl secretion by the parietal glands.(EGUC)
*'''Epidermal growth factors:''' found in salivary gland secretions, promote DNA synthesis and proliferation of gastric mucosal cells. Also play a role in prostaglandin synthesis and inhibit HCl secretion by the parietal glands.(EGUC)
*'''Epithelial restitution mechanisms:''' important in the maintenance of gastric mucosal integrity (maintain tight junctions). Epithelial injury induces migration of adjacent cells to replace damaged cells within minutes without the need of new cell proliferation. Shear forces, induced by mixing of ingested material, are counteracted by epithlial restoration.(EGUC)
*'''Epithelial restitution mechanisms:''' important in the maintenance of gastric mucosal integrity (maintain tight junctions). Epithelial injury induces migration of adjacent cells to replace damaged cells within minutes without the need of new cell proliferation. Shear forces, induced by mixing of ingested material, are counteracted by epithlial restoration.(EGUC)
*'''Adequate mucosal blood supply:''' required to provide the mucosa with oxygen and nutrients to produce the mucus-bicarbonate layer and to support rapid turnover of epithelial cells. Also required to remove acid that has diffused through the mucous layer to the mucosa.(EGUC)
*'''Adequate mucosal blood supply:''' required to provide the mucosa with oxygen and nutrients to produce the mucus-bicarbonate layer and to support rapid turnover of epithelial cells. Also required to remove acid that has diffused through the mucous layer to the mucosa.(EGUC) Mucosal perfusion may be important in the stress-related ulceration of neonates(Sanchez)
*'''Prostaglandins:''' inhibit acid secretion, promote mucosal blood flow (through vasodilation), increase mucus and bicarbonate secretions and support mucosal cell repair. PGE2 is especially important in these functions.(EGUC)
*'''Prostaglandins:''' inhibit acid secretion, promote mucosal blood flow (through vasodilation), increase mucus and bicarbonate secretions and support mucosal cell repair. PGE2 is especially important in these functions.(EGUC)
=====Squamous mucosal defence mechanisms=====
=====Squamous mucosal defence mechanisms=====
The squamous mucosa has comparatively few defence mechansims:(EGUC)
*'''Intercellular tight junctions''' and '''intracellular buffering systems''' act as barriers
*'''Intercellular tight junctions''' and '''intracellular buffering systems''' act as barriers
*'''Epidermal growth factor''' has also been found to contribute to the healthy maintenance and repair of gastric squamous epithelium (Jeffrey et al. 200 in(Martineau 2009)
*'''Epidermal growth factor''' has also been found to contribute to the healthy maintenance and repair of gastric squamous epithelium (Jeffrey et al. 200 in(Martineau 2009)
*'''Leukotrienes''' provide mucosal protection
*'''Leukotrienes''' provide mucosal protection
=====Other intrinsic defence mechanisms=====
=====Other intrinsic defence mechanisms=====
'''Gastrodudodenal motility'''
*'''Gastrodudodenal motility''': critically ill neonatal foals can have a substantially different pH profile compared to clinically normal foals, possibly due to changes in gastric motility and acid secretion.(45 in Sanhcez)
====Intrinsic ulcerogneic factors====
Hydrochloric acid (HCl) and a sustained gastric pH<4.0 are the most significant factors in gastric ulceration. Volatile fatty acids (VFAs), lactic acid and bile acids act synergistically with HCl to cause changes in squamous mucosal bioelectric properties (the first sign of acidic damage). VFAs and lactic acid are by-products of bacterial fermentation of sugars in concentrate diets.
=====Hydrochloric acid=====
HCl damages the squamous mucosa by compromising the outer cell barrier. It then diffuses into the squamous cells of the ''stratum spinosum'', inhibiting cellular sodium transport and causing cell swelling, necrosis and eventual ulceration. (Argenzio and Eismann 1987; Nadeau et al. 2003a,b)
=====Volatile Fatty Acids (VFAs)=====
Whereas, VFAs (acetic, propionic, butyric and valeric acids), because of their lipid solubility, induce damage by rapidly diffusing into the squamous mucosal cells of the stratum spinosum layer and immediately inhibit sodium transport which results in cell swelling and ulceration. Squamous mucosal cells are susceptible to HCl and VFA injury in pH, dose and time dependent manner (Andrews et al. 2006).
=====Lactic acid=====
Lactic acid has a similar chemical structure to VFAs. But lactic acid (pH 1.5 and 40 mmol/l) exposed to the nonglandular mucosa increased tissue permeability, as indicated by increased transepithelial conductance (Andrews et al. 2008).
Furthermore, HCl and VFAs have been shown to cause disruption in bioelectric properties and barrier function of the NG mucosa of horses in an in vitro Ussing chamber system (Widenhouse et al. 2002; Nadeau et al. 2003a,b; Andrews et al. 2006). The proposed mechanism by which VFAs cause acid injury is as follows: at low pH (≤4.0), VFAs remain undisassociated (nonionic) and are highly lipid soluble. By penetrating the NG mucosal cells and acidifying cellular contents they disrupt cellular sodium transport, leading to cell swelling, cell death and ulceration (Argenzio and Eisemann 1996; Nadeau
et al. 2003a,b).
Lactic acid (LA), commonly found in the stomach of horses after eating, has a chemical structure and low pKa (3.8) similar to acetic acid, but LA is stronger. In previous studies, LA concentrations in the stomach were high (Wolter and Chaabouni 1979; Al Jassim 2006), compared to other regions of the digestive tract. Stomach LA is probably produced by resident acid-tolerant bacteria, such as Lactobacillus and Streptococcus spp., which have been found in abundance in the equine stomach (Al Jassim
et al. 2005; Varloud et al. 2007). Also, a recent study showed a3-fold increase in post prandial L-/D-lactate concentration (Varloud et al. 2007). Therefore, LA exposure to NG mucosa of horses in an acidic environment would be expected to cause similar acid injury to that caused by other VFAs.
Lactic acid, produced in the stomach of horses fed a high-grain diet, does not significantly alter sodium transport or permeability in equine NG mucosal tissue. Lactic acid may require a longer exposure time or may need the presence of other VFAs in HCl to cause gastric ulcers.(Andrews 2008)
==Risk Factors==
==Risk Factors==