Etiology

• Equine squamous gastric disease is a consequence of sustained exposure of the squamous mucosa to acid.

Predisposing factors

General

• ESGD can be either primary or secondary.
• Primary ESGD occurs in response to risk factors inherent in domestication and intensive management that result in prolonged exposure of the squamous mucosa to acid in horses with an otherwise normal gastrointestinal tract.
• Secondary ESGD occurs as a direct consequence of delayed gastric emptying. This causes chronic gastric distension resulting in prolonged exposure of the squamous mucosa to acid. The most common cause of delayed gastric emptying in adult horses and foals is pyloric outflow obstruction secondary to glandular gastric disease.

Specific

• The prevalence is highest in performance horses and reflects changes in management and intensity of exercise inherent in competition. It has been shown that the risk of ESGD increases with an increase in the intensity of exercise and the duration of time at work. This association is well recognized in Thoroughbred and Standardbred racehorses, but has also been shown in elite endurance horses, show jumping warmbloods and other non-racing performance horses.
• Strenuous exercise causes an increase in intra-abdominal pressure associated with contraction of the abdominal muscles. This results in gastric compression and exposure of the sensitive squamous mucosa to acidic gastric content. Strenuous exercise has also been shown to cause an increase in post-prandial gastrin secretion, resulting in an increased production of HCl.
• Several additional factors associated with management have also been shown to increase the risk of ESGD, many of which are imposed on horses at the commencement of training or during active competition. These include the trainer, high starch/low roughage diets, fasting, stall confinement, transport, intermittent access to water and administration of hypertonic solutions of electrolytes.
• Exposure to a combination of a high starch diet, stall confinement and strenuous exercise has been shown to induce lesions in as little as 7 days Nutrition: adult Nutrition: work.
• Intermittent fasting is so effective at inducing lesions that it is used as a model for ESGD in experimental studies. Intermittent fasting disrupts normal pH stratification of gastric content, thereby allowing high concentrations of HCl and refluxed bile to mix in the dorsal stomach.
• Low roughage diets also disrupt normal pH stratification by causing greater gastric fluidity and mixing of dorsal and ventral gastric contents, but in addition to this, horses chew less, and this results in decreased production of saliva, which is an important buffer of acid in the dorsal stomach.
• Ingestion of large quantities of fermentable carbohydrate (starch >1 g/kg/meal) exacerbates the situation further by causing rapid production of SCFA, which acts synergistically with HCl in the presence of a low pH to cause acid injury of the squamous epithelium. High concentrate diets also stimulate secretion of gastrin which results in further acid secretion.
• Feeding of straw has been associated with an increased risk of ESGD, presumably due to the abrasive effect of the coarse roughage, and this may be relevant to other forage with a high lignin content.
• Horses that had access to some pasture turnout were less likely to have ESGD, with horses turned out with other horses having a further decreased risk, in one study. Conversely, pasture turnout was not found to be protective against ESGD in other populations in other studies.
• Non-performance horses are also susceptible to ESGD, but the prevalence is generally lower, and when lesions occur, they tend to be less severe. This suggests that risk factors other than intense exercise and management may play a role and underscores the multifactorial nature of this disease.
• There is conflicting evidence for the role that intrinsic risk factors, such as age, gender, and breed, may play a role in the development of ESGD and where evidence exists, it is likely to be confounded by other factors such as management and exercise.
• Crib-biting Behavior: crib-biting and wind-sucking is associated with an increased risk of ESGD, as are other stereotypies.
• There is no conclusive evidence to suggest that stress and administration of inappropriate doses of non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of ESGD.
• Interestingly, ESGD has also been reported in wild equids and feral horses with no apparent exposure to recognized risk factors, and it poses an interesting (and as yet unanswered) question as to whether some degree of ESGD is “constitutive” in the equine stomach and develops as a normal response to periodic exposure of the squamous mucosa to acid. This notion is supported by the fact that many horses with ESGD will not demonstrate clinical signs and the fact that mild lesions may heal spontaneously, particularly if the inciting cause has been removed.
• In foals, the prevalence of ESGD ranges from 7% to 57% depending upon the age. Older weanling foals appear to be most susceptible, however ESGD has also been reported in foals as young as 24 h. Very few risk factors have been reported for ESGD in foals. Concomitant gastrointestinal disease has been associated with the presence of ESGD at the time of necropsy, however a cause-and-effect relationship has not been demonstrated.

Pathophysiology

• The squamous mucosa of the equine stomach is inherently vulnerable to acid injury as it has a poor blood supply and does not possess a mucus-bicarbonate layer to protect itself. The thick keratinized epithelium together with the presence of high electrical resistance, tight epithelial junctions and an osmophilic phospholipid surfactant-like layer provide some protection, however this mucosal barrier is rapidly overwhelmed in the presence of acid.
• Acid injury is primarily attributable to endogenous hydrochloric acid (HCl), which erodes the outer keratinized layers of the squamous epithelium and results in disruption of the bioelectric properties of the transporting cells, thus compromising barrier function. In addition, other gastric constituents, including short chain fatty acids (SCFA), lactic acid and bile salts, have been shown to act synergistically with HCl, thus further attenuating barrier function and ultimately resulting in cellular injury.
• The sequence of events following exposure of squamous epithelial cells to acid is the movement of H+ ions across the cell membrane, acidification of cellular contents, inhibition of sodium transport, cellular swelling and ultimately cell death. The squamous epithelium initially reacts by thickening and becoming hyperkeratotic. Sloughing of superficial layers of epithelium result in the development of erosions, and with continued acid exposure, lesions deepen to form ulcers.

Timecourse

• Variable time from onset of clinical signs to presentation due to non-specific nature of these signs.