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EQUINE VETERINARY EDUCATION / AE / JANUARY 2017
becomes more acidic reaching a pH of 3.0 - 6.0 at the margo plicatus and a pH of 1.5–4.0 in the ventral stomach near the pyloric antrum. However, when horses were fasted for 24 h, intragastric pH showed a median 24 h pH of 1.6, whereas when horses were fed hay ad libitum, a median 24 h pH of 3.1 was recorded (Murray and Schusser 1993). Presumably, a pH gradient between the proximal and distal stomach was eliminated in the fasting state; however, further studies are needed to confirm this in the horse (Argenzio 1999). In addition, stomach pH can be affected by dietary
components such as alfalfa (lucerne) and grass hays plus grain. In one study, the pH measured in the ventral portion of the stomach in horses was significantly higher in horses fed
alfalfa hay and grain (4.32 0.41) when compared with horses fed Brome grass hay (2.45 0.44) for 5 h after feeding (Nadeau et al. 2000).
The stomach contains a diverse microbiota with a high
proportion of amylolytic bacteria that respond rapidly to ingestion of starch containing feed resulting in increased concentrations of lactate as well as acetate and other volatile fatty acids (VFAs) (Al Jassim et al. 2005a,b; Varloud et al. 2007; Al Jassim and Andrews 2009; Merritt and Julliand 2013). Prolonged exposure of the squamous mucosa to a low pH environment is therefore the most likely cause of ulceration in this region and has been likened to gastro- oesophageal reflux disease in man (Pearson and Parlkh 2011). A recent study found that horses had a lower pH in the proximal stomach during early morning (01.00–09.00 h), when stomach-fill tends to be lower especially in stabled animals, suggesting a nocturnal ‘circadian’ pattern of gastric acid secretion, which may contribute to ulcer formation in the squamous mucosa (Husted et al. 2008). In addition to HCl, other potential contributors to acid
injury in the squamous mucosa are the other acids (VFA, lactic acid and bile acids) and enzymes (pepsin) especially in a low pH environment (Berschneider et al. 1999; Nadeau et al. 2000, 2003a,b; Andrews et al. 2006, 2008). Hydrochloric acid alone, and in combination with VFA (pH <4), has been shown to inhibit squamous cell sodium transport, resulting in cell swelling and eventual ulceration. The effects of VFAs were found to be dose-dependent and the severity of acid injury was correlated with increasing carbon chain length (Nadeau et al. 2003a,b; Andrews et al. 2006). However, a previous study showed that D- and L-lactic acids, also by- products of bacterial fermentation of grain, did not significantly alter squamous mucosal barrier function or sodium transport, when compared to VFAs with similar PKa (Andrews et al. 2008). Thus, the specific role (other than lowering gastric pH) of lactic acid in squamous ulceration needs further investigation. Furthermore, bile acids, in an acid environment, were
shown to increase nonglandular mucosal cell permeability to hydrogen ions, which eventually led to ulceration in tissue exposed in an in vitro Ussings chamber system (Berschneider et al. 1999). However, in vivo, the source of the bile acids is likely to be duodenal reflux, which is typically at a higher pH >4 (Argenzio 1999). In addition, a synergistic effect between mucosal acidification and taurocholic acid on alteration in bioelectric properties in the squamous mucosa was not detected (Widenhouse et al. 2002). Therefore, the role of bile acids in squamous and glandular ulceration in horses remains unclear.
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Glandular ulcers Glandular ulcers, by contrast, are probably caused by a breakdown in the mucosal defence mechanisms, including mucus, bicarbonate and blood supply rather than from excessive exposure to HCl. This is illustrated in the feed- deprivation model, where high gastric acidity resulted in increased severity of squamous ulcers, but ulcers in the glandular mucosa were not observed (Murray 1994; Murray and Eichorn 1996). Whereas, horses treated with flunixin meglumine, a nonsteroidal anti-inflammatory drug, at a dose above therapeutic recommendations (1.1 mg/kg bwt, i.v., q. 8 h, 7 days), showed increased glandular ulcer severity in addition to an increased squamous ulcer severity (MacAllister et al. 1996). In addition, orally administered phenylbutazone (4.4 mg/kg bwt, per os, q. 24 h, 5 days and 13.2 mg/kg bwt, per os, one day) showed the ability to induce oxidative stress in glandular mucosa of horses by changing the antioxidant- oxidant balance (Aranzales et al. 2015). Although other factors are involved, the results of this and other studies suggest that one of the causes of glandular ulcers might be associated with oxidative stress and inhibition of prostaglandins together with a breakdown in the mucosal defences and therefore not primarily dietary related, although diet may increase the risk (Luthersson et al. 2009). In pigs, for example, glandular mucosa exposed to VFAs, in an acidic environment, showed decreased transepithelial resistance in vitro,whichsuggests that high concentrate diets that generate VFAs may alter glandular mucosal barrier function and contribute to causes of ulceration. Although, in that study, glandular tissues were evaluated using an in vitro Ussing chamber system and
therefore the mucus plus the bicarbonate layer and blood flow were compromised (Argenzio and Eisemann 1996). It is clear that the cause of glandular ulcers in horses remains largely unknown and is likely to be multifactorial.
Risk factors
Although acid injury has been implicated as the cause of squamous ulcers, several risk factors have been identified (Murray et al. 1996; Rabuffo et al. 2002).
Exercise intensity and feeding practices Horses involved in training and racing are at high risk of developing squamous ulcers (Vatistas et al. 1999a,b). In an endoscopic study examining Thoroughbred and Standardbred horses actively racing and training, the prevalence of squamous ulcers was 88% (152/171) (Ross et al. 1981). Furthermore, the prevalence of gastric ulcers in Swedish Standardbred racehorses in race training was 70% (56/80), and ulcers were significantly associated with horses that were in preparatory training and those that had raced in the last month when compared with horses that were fit but did not race in the last month (Jonsson and Egenvall 2006). The prevalence of gastric squamous ulceration is also high in performance horses. A recent study, for example, reported that showjumping Warmblood horses, exercising ≥6 days/ week, had an increased risk of squamous as well as glandular ulceration and that horses competing at national events were more likely to have glandular ulcers compared to horses competing in FEI events (Pedersen et al. 2015). Also, the overall prevalence of squamous ulcers was 53% in a group of Danish pleasure horses and 56% in a subgroup of the older horses (mean age 13.1 years) (Luthersson et al.
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