Equine gastric ulcer syndrome (EGUS) describes ulceration in the terminal part of the esophagus (see Chapter 63), nonglandular and glandular portions of the stomach, and the proximal part of the duodenum. Equine gastric ulcer syndrome is complicated and has many causes. Prevalence of 25% to 51% and 60% to 90% has been reported in foals and adult horses, respectively, depending on signalment, coexisting clinical disorders, performance level, and ulcer location. The prevalence of gastric ulcers is highest in younger performance age horses (<10 years of age) and in Thoroughbreds and Standardbreds in active training and racing. Lower prevalence figures were found in heavily used Quarter Horses. However, recently, the prevalence of EGUS in pregnant and nonpregnant broodmares under similar pasture management conditions was found to be 66.6% and 75.9%, respectively. This high prevalence of ulcers in a group of pastured horses highlights the multifactorial nature of EGUS and emphasizes the susceptibility of all horses to this syndrome.
An imbalance between mucosal aggressive factors (i.e., hydrochloric acid, pepsin, bile acids, and organic acids) and mucosal protective factors (bicarbonate, mucus) is the likely cause of EGUS. Because the glandular mucosa has more protective factors than the nonglandular mucosa, the causes of ulceration in the two parts of the stomach may be different. The mucus-bicarbonate layer covers the surface of the glandular mucosa. Prostaglandin E2 enhances mucosal blood flow, promotes secretion of this layer, and increases production of mucus and bicarbonate. In addition, prostaglandins maintain the integrity of the nonglandular and glandular mucosa by stimulation of production of surface-active protective phospholipids, enhancement of mucosal repair, and prevention of cell swelling by stimulation of transepithelial sodium transport. Stress resulting from parturition in foals or the stress of training and confinement in adult horses may lead to the release of excess endogenous corticosteroids, which can inhibit prostaglandin synthesis. This decrease in prostaglandins may lead to breakdown of mucosal protective factors and can promote development of ulcers. Glandular and nonglandular mucosal ulceration requires exposure to acid but probably also involves concurrent failure or disruption of mucosal protective factors.
Ulcers in the nonglandular mucosa primarily are caused by prolonged exposure to hydrochloric acid (HCl) and organic acids such as volatile fatty acids (VFAs), similar to the pathophysiology underlying gastroesophageal reflux disease (GERD) in humans. Excessive exposure to HCl and, to a lesser extent, VFAs (acetic, butyric, propionic, and valeric acids), may be the primary cause of ulcers in the nonglandular mucosa. The nonglandular mucosa has no overlying mucus layer and responds to acid irritation by increasing the thickness of its keratin layer, which provides only minimal protection from acid. Gastric lesion formation also may be related to desquamation of the stratified squamous epithelium of the stomach, because replacement of desquamated epithelium seems to be delayed in foals with gastric ulcers. Stomach pH has been strongly implicated in gastric ulceration in adult horses, and the pH at the margo plicatus, where most ulcers occur, can be lower than in some areas of the glandular mucosa. In addition, approximately 50% of horses with moderate to severe ulceration have a significantly lower stomach pH than those with mild or no ulceration.
In foals, when similar stomach regions are compared, mucosal surface pH does not differ among those with or without lesions. However, gastric fluid pH values are lower in recumbent foals and those that nurse infrequently, suggesting that milk buffers gastric acid, whereas recumbency may lead to increased exposure of the nonglandular mucosa to acid. Delayed gastric emptying or decreased gastric motility also may be contributory in neonatal foals with concurrent disease or gastric outflow obstruction.
In addition to stomach HCl, VFAs, which are byproducts of fermentation of carbohydrates by resident stomach bacteria, act synergistically to cause EGUS in horses. When gastric pH is less than 4.0, VFAs become undissociated (lipid soluble) and penetrate into nonglandular squamous epithelial cells, resulting in cell acidification, inhibition of sodium transport, cell swelling, and ulceration. Furthermore, HCl- and VFA-induced squamous mucosal cell injury is dose and time dependent. Because performance horses consume diets high in fermentable carbohydrates, VFAs generated in those animals are of sufficient quantity to cause ulceration.
Helicobacter pylori is the primary cause of glandular gastric ulcers in humans. However, H pylori has not been cultured from the mucosa of either region of the equine stomach; moreover, gastric ulcers in horses arise chiefly in the nonglandular (squamous) region and therefore likely have a different pathogenesis than those found in H pylori infections in humans. Investigators have isolated Helicobacter-specific DNA from normal and eroded glandular and squamous epithelia of horses. In addition, a new Helicobacter species, Helicobacter equorum, was recently cultured from feces of 2 of 7 (28.6%) foals aged less than 1 month and from 40 of 59 (67.8%) foals aged 1 to 6 months. Furthermore, Helicobacter-like DNA was detected in the stomachs of 10 Thoroughbreds and in 2 of 7 horses with gastric ulcers, 3 of 5 horses with gastritis, 5 of 6 horses with both conditions, and 1 horse with normal gastric mucosa. In that same study, however, 39% of the Helicobacter-positive horses did not have gastric lesions. These results indicate that H equorum is able to colonize the lower bowel and is excreted in the feces, but there appears to be no association of Helicobacter spp with gastrointestinal disease.
After a gastric ulcer is formed in the nonglandular mucosa, resident stomach bacteria can colonize the ulcer bed and delay ulcer healing. A variety of bacteria, including Escherichia coli, are found in the horse stomach; E coli are known to rapidly colonize acetic acid–induced gastric ulcers and impair healing in rats. Because oral administration of lactulose results in growth and colonization of the ulcer bed by Lactobacillus spp, which improves healing, antimicrobial treatment or treatment with probiotics containing Lactobacillus organisms may be indicated in some horses with chronic resistant ulcers.
Exercise and concurrent illness lead to increased prevalence of gastric ulcers. Horses involved in training and racing have a 60% to 93% prevalence of gastric ulcers. Exercise likely causes gastric ulceration by delaying gastric emptying, increasing gastric acid secretion, or both. Horses running on a high-speed treadmill have increased abdominal pressure and decreased stomach volume. Compression of the stomach during intense exercise allows acid from the glandular mucosa to reflux up into the nonglandular mucosa, leading to acid injury. Furthermore, serum gastrin concentration increases in exercising horses, which might increase glandular HCl secretion that may lead to acid damage. Poor performance in racehorses has been correlated with increasing ulcer severity.
Although racehorses have the highest prevalence of ulcers, several recent studies have reported that gastric ulcer prevalence is high (56.5% to 93%) in horses in endurance competition, show jumping, dressage, or western performance disciplines and in horses that are traveling. Gastric ulcers are present both during and after competition. Thus horses in both race and performance training are at risk for developing EGUS, and equine veterinarians should take this syndrome into consideration as a potential cause of poor performance.
Other stress-related risk factors have surfaced in an Australian study. Horses trained in urban areas are 3.9 times more likely to have gastric ulcers than those trained in rural or semi-rural areas. Also, time in work, crib biting, difficulty maintaining body weight, and playing the radio in the barn were identified as risk factors. In that study, horses that were turned out into pasture and had direct contact with other horses and horses that were trained at home rather than at the racetrack had fewer gastric ulcers.
Treatment with nonsteroidal antiinflammatory drugs (NSAIDs) is associated with gastric ulcers in horses. Nonsteroidal antiinflammatory drugs inhibit cyclooxygenase, which in turn inhibits prostaglandin E2 production, thereby resulting in increased acid secretion, decreased mucosal blood flow, and disruption of the mucus–bicarbonate barrier. Administration of NSAIDs results in ulceration of both the glandular and nonglandular mucosa in both foals and horses.
The NSAIDs are most likely to cause ulcers when horses receive doses that are greater or administered more frequently than is advised on label instructions; however, use at therapeutic doses has also been known to cause ulcers in horses. Caution should be used in combining NSAIDs (known as stacking), such as phenylbutazone and flunixin meglumine, because this also can potentiate the development of ulcers.
A relatively new NSAID, firocoxib, is a selective cyclooxygenase-2 inhibitor and may be less likely to cause gastric ulcers. The drug may be a useful alternative to treat horses with lameness. Ulcers were not detected in horses administered this drug at 0.1 mg/kg given orally every 24 hours for 30 days.
Feed deprivation is associated with ulceration of the nonglandular mucosa, likely as a result of repeated exposure of the mucosa to an acidic pH. Fasted horses have a lower median 24-hour gastric juice pH than those fed hay continuously. Eating roughage provides hours of chewing and maintains the production of salivary bicarbonate, which bathes the stomach and buffers gastric acid. The type of roughage and timing of feeding also may be contributory factors to gastric ulceration. When a horse is fed a small meal containing low-starch grains, the stomach empties significantly faster than when the horse is fed a large high-starch meal. The latter meal remains in the stomach longer and likely is fermented to VFAs and lactic acid, which reduce gastric pH and promote gastric ulcer formation. Recent information suggests that feeding small amounts of high-starch grains (0.5 kg of grain per 100 kg body weight) no more frequently than 6 hours apart can reduce the risk for EGUS. To lessen the risk for gastric ulcers, good-quality grass hay should be provided throughout the day and night and, if needed, supplemented with grain at no more than 5 pounds for a 1000-pound horse every 6 hours. For more active horses, corn oil (1 cup, PO, twice daily) or beet pulp (soaked) can be added to the grain ration to increase calories.
Alfalfa hay has a protective effect on the nonglandular mucosa, compared with grass hay; horses fed alfalfa hay had significantly fewer ulcers and higher gastric juice pH in one study. It has been postulated that the high calcium and protein concentrations in alfalfa hay serve to buffer stomach contents.