Gastric Ulcer Syndrome

CHAPTER 82 Gastric Ulcer Syndrome



Jenifer A. Nadeau, Frank M. Andrews


Equine gastric ulcer syndrome (EGUS) is a complicated, multifactorial problem that has a prevalence ranging from 25% to 51% in foals and from 60% to 90% in adult horses, depending on signalment, coexisting clinical disorders, performance level, and location of the ulcer within the stomach. Studies have revealed that severity of gastric ulceration is significantly higher in horses 3 years of age or older.



PATHOGENESIS


EGUS develops when there is imbalance between mucosal aggressive factors (such as hydrochloric acid, pepsin, bile acids, and organic acids) and mucosal protective factors (including bicarbonate and mucus secretion). Because there are more protective factors in the glandular mucosa than in nonglandular mucosa, the causes for ulceration may be different in each of these regions. Prostaglandin E2 promotes secretion of the mucus-bicarbonate layer that covers the surface of the glandular mucosa and enhances mucosal blood flow. Prostaglandins also may help maintain the integrity of nonglandular and glandular mucosa by stimulating production of surface-active protective phospholipids, enhancing mucosal repair, and preventing cell swelling by stimulating sodium transport. Consequently, inhibiting prostaglandin synthesis decreases mucosal blood flow and secretion of mucus and bicarbonate and also increases gastric acid secretion by the glandular mucosa. The stress of parturition in foals or stress of training and confinement in adult horses may lead to excessive release of 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 mucosal ulceration requires exposure to acid, but it is probably also associated with concurrent loss of mucosal protective factors. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be involved in the latter mechanism because they inhibit the activity of cyclo-oxygenase, which reduces prostaglandin E2 production and leads to increased acid secretion, decreased mucosal blood flow, and disruption of the mucus-bicarbonate barrier. Administration of NSAIDs to foals results in ulceration of glandular and squamous mucosa. Gastric mucosal damage was found at necropsy in six of eight mature horses given 10 mg/kg phenylbutazone in one study. Although one study in racehorses in southern California revealed no correlation between NSAID administration and gastric ulceration, the ulcers in those racehorses primarily involved the nonglandular mucosa. This observation suggests that ulcer formation in the nonglandular region may involve different mechanisms than development of ulcers that arise in the glandular region. Administration of furosemide has been associated with a reduced prevalence of ulceration in the glandular portion of the stomach, possibly as a result of positive effects on gastric blood flow. There is evidence that furosemide acts to increase production of PGE2, thereby causing vasodilation. Therefore, gastric blood flow may play a central role in glandular gastric ulceration.


Ulcers in the nonglandular mucosa are caused primarily by prolonged exposure to hydrochloric acid, pepsin, bile acids, and organic acids such as volatile fatty acids (VFAs), an etiopathogenesis similar to that of gastroesophageal reflux disease in humans. Excessive exposure to hydrochloric acid and, to a lesser extent, VFAs (acetic, butyric, propionic, and valeric acids) may be the primary cause of nonglandular mucosal ulceration. The nonglandular mucosa has no mucus layer and responds to acid irritation by increasing the thickness of the keratin layer, but that provides only minimal protection from acid and pepsin. Gastric lesion formation may also be related to desquamation of the stratified squamous epithelium of the stomach, a normal part of the maturation process, because replacement of desquamated epithelium seems to be delayed in foals. These lesions are not histologically ulcers; rather, they are sites where the top layer of keratinocytes has eroded. However, when viewed endoscopically, they can appear to be ulcers. Because foals are slow to replace the squamous layer, as long as an erosion in the mucosa persists, the foal is prone to acid injury and development of a true gastric ulcer at the site.


Stomach pH also has been strongly implicated in gastric ulceration in adult horses. In one study, the squamous epithelium had a lower pH than the glandular mucosa, and pH values were lowest near the margo plicatus, where most ulcers naturally occur. Fifty percent of horses with moderate to severe ulceration in that study had a significantly lower stomach pH than horses with mild or no ulceration. Similar studies in foals revealed no difference in mucosal surface pH in the same region of the stomach of foals with or without lesions. However, lower gastric fluid pH values were found in recumbent foals and in those that nursed infrequently. This suggests that intraluminal milk buffers gastric acid, whereas recumbency may lead to increased exposure of the nonglandular mucosa to acid. Delayed gastric emptying or decreased gastric motility may also contribute to ulcer development in neonatal foals with concurrent disease or gastric outflow obstruction.


The stomach of the horse secretes gastric acid continuously. Gastric acidity is least when the horse is consuming feed or when a foal is suckling because the ingesta absorbs gastric secretions and prevents contact of acid with the mucosal surface. Luminal contents also stimulate secretion of salivary bicarbonate that serves to neutralize gastric acid. During times without feed consumption, gastric pH can decrease rapidly, with the pH falling below 2.0 and remaining low until the horse resumes eating. The same scenario can occur within 30 to 45 minutes after nursing in foals. Intermittent feeding of horses can cause ulcers and increase their severity. Indeed, an alternating feed-deprivation model can be used to induce gastric ulcers. Stomach pH decreases 6 hours after feeding; thus, horses should be fed hay continuously or every 5 to 6 hours to buffer stomach pH.


Organic acids may act synergistically with hydrochloric acid to cause EGUS in horses. For example, VFAs or short-chain fatty acids produced as a byproduct of carbohydrate fermentation induce injury to the nonglandular mucosa of the equine stomach in the presence of low pH. This is because VFAs become undissociated at low pH and are able to penetrate nonglandular epithelial cells, resulting in acidification, cell swelling, inflammation, and ulceration. In the equine stomach, VFAs are present in quantities sufficient to cause cellular acid injury. Because performance horses consume diets high in fermentable carbohydrates, VFAs generated by resident bacteria may cause acid injury and ulceration in the nonglandular mucosa. Serum gastrin concentrations are high in horses fed high-concentrate diets. Bile salts from duodenal reflux and pepsin have been implicated in causing gastric ulcer disease in other species and may also promote ulcer development in horses. Bile acids increase the permeability of the nonglandular mucosa to hydrogen ions and act synergistically with acid to cause mucosal ulceration. Horses fed mixed feed (128 g of crude protein and 175 g of crude fiber/kg dry matter) for at least 14 days had more gastric ulcers in the nonglandular mucosa compared with horses fed a hay diet.


Feed deprivation is a cause of nonglandular mucosal ulceration because it enables persistent exposure of the nonglandular mucosa to high-acid conditions. For instance, horses fed hay continuously had a higher median 24-hour gastric juice pH value (3.1) than fasted horses (1.6). In addition, type of roughage and timing of feeding may be contributory factors to gastric ulceration. In one study, horses fed alfalfa hay had significantly higher gastric juice pH and lower gastric ulcer scores compared with horses fed brome grass hay. In that study, it was postulated that alfalfa hay has a protective effect on the mucosa as a result of high calcium or protein concentrations. Results from a subsequent study lent credence to this postulation in that the degree and incidence of ulceration were influenced by diet, with horses fed coastal Bermuda grass having a significantly higher ulcer score (increased by 1.5) compared with horses fed alfalfa hay. In general, high-roughage diets stimulate bicarbonate-rich saliva production, which may buffer gastric acid. In addition, corn oil fed at 45 mL per day significantly decreased acid production and increased the prostaglandin concentration in gastric juice.


Helicobacter pylori is considered the primary cause of peptic ulcers in humans, but this organism has not been found in the horse. However, in a recent study, Helicobacter-specific DNA was detected in the glandular and squamous epithelia of seven horse stomachs, including two horses with squamous erosions and one horse with glandular epithelial erosions. This suggests that Helicobacter spp. may be involved in the etiology of equine gastric ulcer syndrome. Many other types of bacteria have been associated with lesions in the horse, but none appear to be pathogenic.

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May 28, 2016 | Posted by in EQUINE MEDICINE | Comments Off on Gastric Ulcer Syndrome

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