The Equine Stomach (AAEP 2003: Milne Lecture)
Every year one of the highlights of the American Association of Equine Practitioners' convention is the Milne Lecture, named for past president and distinguished life member Frank J. Milne. Each year a different speaker is chosen and honored with an award. This year the presenter was Alfred Merritt, DVM, MS, of the University of Florida, who spoke on "The Equine Stomach: A Personal Experience (1963-2003)." Merritt's presentation highlighted advances made over the last 40 years in the understanding of how the equine stomach functions and its related diseases. His presentation had a special emphasis on equine gastric ulcer syndrome (EGUS), and slides of his presentation helped attendees visualize the concepts.
Merritt has been involved in research into gastrointestinal physiology and pathophysiology, receiving numerous awards for his work. He has been the Appleton Endowed Professor in Equine Studies at the University of Florida since 1998. Merritt has published many articles in research journals and chapters in veterinary textbooks, with a majority of them about equine gastroenterology.
Merritt described the various components of mucosal anatomy (or the mucous membranes of the stomach), which include the squamous (non-glandular), fundic glandular, cardiac glandular, and the pyloric glandular regions. He noted that the fundic glandular region is where acid is made. Using a photograph taken by endoscopic exam of the horse's stomach, Merritt pointed out how the glandular region is redder than the squamous region, and the margo plicatus is the line between the non-glandular and the glandular regions. The pylorus is the opening from the stomach into the small intestine, with the duodenum being the first part of the small intestine. The pyloric sphincter is usually open most of the time.
The horse is a grazing animal, and the normal equine stomach is rarely empty. The contents will separate into different density levels within the stomach, with each layer having a different pH value, Merritt explained. The more dense layer filters to the bottom of the stomach, and it is the most acidic.
Advances in Gastroenterology
Understanding of the equine stomach has come a long way since Merritt graduated from Cornell University in 1963. "The extent of my retained knowledge of gastric function in 1963 was that horses can't vomit," he joked. In 1963, surgery was considered a last resort for colic and prognosis was usually poor. Now successful colic surgery occurs daily across the country.
Merritt reviewed the history of research into how the equine stomach works, starting with a review of work done in 1933 in which the horse's stomach was first cannulated. Cannulation involves placing a tube through the horse's side to reach into the stomach and collect gastric contents. With this procedure, researchers discovered that gastric acid was continuously secreted, and that gastric contents amounted to approximately 10-30 liters per day. They also found that these contents consisted of acid, swallowed saliva, and sometimes regurgitated intestinal contents.
In 1940, the procedure was repeated, and researchers used color-coded feeds and water to learn that water moved around the mass of feed to leave the stomach quickly. Researchers also first touched on the concept of "receptive relaxation," where the stomach responds to the size of the meal ingested. And finally, Merritt described how one researcher discovered that some microbial fermentation of ingested plant fiber and soluble carbohydrates occurred in the stomach, unlike other monogastric (single-stomach) species (other than the pig, which has some similarities in digestion to the horse). It was previously thought that the stomach had too hostile of an environment for microbial fermentation activity, especially since these organisms do not like acidic environments. However, research has discovered that certain microbes, such as Lactobacillus acidophilus, can survive in acidic environments.
The by-product of L. acidophilus is lactic acid, of which considerable quantities can be generated in the equine stomach, said Merritt. Research has also identified the existence of microbes that convert carbohydrates to volatile fatty acids (VFAs) in the equine stomach.
The various levels of acidity in the content of the stomach were discovered in 1993 when researchers used a nasogastrically introduced weighted pH probe to measure acidity. However, it has been found that foals have a uniform pH value since the contents of their stomachs are liquid; however, after milk ingestion, this value rises for about an hour.
Merritt went into an involved discussion of the mechanisms of digestion in the equine stomach. The two main digestive enzymes are pepsin and lipase. The stomach first secretes pepsinogen, which is converted to pepsin when the pH of the stomach reaches above 4. Merritt said little known about how much pepsin contributes to digestion of ingested protein. Gastric lipase also reaches peak activity at a pH of 4; again, not much is known about its importance in the processing of ingested food in the equine stomach.
The parietal cells of the fundic mucosa secrete acid. "Like any other bodily function, control of secretion involves a complex interaction between stimulatory and inhibitory signals," he said. Merritt then discussed the major mechanisms involved in control of gastric acid secretion, demonstrating that the stomach acts as its own pH meter.
One of the chemicals that induces acid secretion in the horse is histamine. Histamine-2 (H2) receptor antagonists suppress gastric acid. One example of an H2-receptor antagonist is ranitidine, which is typically used to control acid in horses with gastric ulcers. Merritt pointed out that it takes less histamine to induce maximal acid secretion in the horse than in humans and other domestic species. "This is of particular interest to GI pharmacologists and might, in part, explain why horses require such large doses of H2-receptor antagonists, relative to other species, to effectively inhibit gastric secretion," he said.
"There now exist a number of reports concerning the anti-secretory efficacy of the proton pump inhibitor (PPI) omeprazole (another acid suppressant) on both basal and pentagastrin-induced acid secretion in the horse," he said. "As with H2-receptor antagonists, the acceptable effective dose of omeprazole for the horse is considerably higher than that required in other species, especially when given orally."
As mentioned before, the stomach acts as its own pH meter. In addition, "the glandular mucosa of the stomach has a complex mechanism of protecting itself from corrosive agents such as acid, pepsin, and certain bile salts," Merritt explained. "The essence of this mucosal barrier is a combination of mucus and bicarbonate that is produced by cells of the gastric glands." Bicarbonate helps raise the pH of the stomach (decrease its acidity).
Merritt then explained the importance of prostaglandin-E2 (PGE2) and how sources of its precursor might be used in the diets of horses given long-term non-steroidal anti-inflammatory drugs (NSAIDs). PGE2 stimulates mechanisms that help protect mucosal surfaces in the stomach. It also inhibits acid production. Linoleic acid acts as a precursor to PGE2 production. Corn oil, which is approximately 40% linoleic acid, has been found to increase PGE2 and reduce gastric acid.
For years it has been well known that continuous NSAID therapy for the treatment of chronic musculoskeletal problems can cause ulcers in the glandular mucosa. Due to the protective effects of PGE2 on mucosa, Merritt recommends corn oil supplementation for horses on continuous NSAID therapy.
Researchers have been able to study motility of the equine stomach using electrodes surgically implanted into the membranous lining of the stomach to record smooth-muscle myoelectrical activity (electrical activity in the muscle). They have discovered that there is no significant motility associated with "slow wave" activity, said Merritt. Slow wave is when the smooth muscle of the GI tract produces a persistent waving motion. The equine stomach has a low slow wave frequency of only approximately three contractions per minute, which is comparable to humans but slower than other domestic animals. These contractions are important in effecting gastric emptying.
As in all species, the equine stomach can relax and expand to accommodate a meal; however, if the stomach does not relax, the volume of food that can be taken in is limited and there is a risk of rupture if a horse eats too much.
Merritt and others have measured the changes in the gastric wall as it relaxes and contracts using an electronic barostat and a balloon-like plastic bag. The bag is inserted into the stomach, and it is attached to the barostat, a computer-controlled instrument which responds to any change in the preset pressure within the bag by either injecting or removing air. The barostat maintains a constant pressure in the bag, releasing air when the stomach contracts and injecting air into the bag when it relaxes. Because the bag follows the movements of the gastric wall, the measurable changes in the volume of the bag give direct indication of changes in the pressure and, thus, the volume of the stomach itself.
With this setup, a distinct two-phase response to a meal has been noted. The first phase occurs while the horse eats and is called receptive relaxation (the stomach expands). When the horse finishes eating, the second phase, called accommodation, occurs. This phase is more prolonged and probably is under the control of feedback from the small intestine.
Two factors affect emptying of the stomach's contents into the small intestine--increased tone of the proximal (upper) half that aids in movement of the contents, and peristaltic contractions, which are progressive wave-like motions produced by successive contractions of the muscle fibers of the lower stomach wall. Various studies have concluded that liquids move through the stomach quicker than solid materials.
Diseases of the Equine Stomach
Impaction--Impaction occurs when dry contents do not move out of the stomach properly. The most common cause is grain overload. While colic from impaction of the gastrointestinal tract is a known problem, impaction of the stomach is rare. Clinical signs include lethargy, teeth grinding, weight loss, and increased heart and/or respiratory rate. Abnormally colored mucous membranes and other signs of shock can also be seen, especially if stomach rupture has occurred. Gastric impaction is diagnosed via endoscopic exam and rectal palpation. Surgery, fluid therapy, and dietary management are therapeutic options, depending upon the possible cause.
There are two forms of gastric impaction--one in which there is a partial gastric outflow obstruction with a physical cause, and one in which there is no physical obstruction to account for the impacted mass. A horse with a gastric impaction will present with colic of varying intensity, which might be recurrent, said Merritt.
Tumors--In his discussion of tumors, Merritt included inflammatory growths as well as growths of an abnormal nature (neoplasia). Neoplastic growths can include squamous cell carcinoma, which is found in the non-glandular squamous region of the stomach. If a horse older than five experiences weight loss, lack of appetite, anemia, and intermittent drooling, he should have an endoscopic exam performed to look for squamous cell carcinoma. When masses have grown large enough or spread into the peritoneal cavity, they can sometimes be felt by rectal palpation, or neoplastic cells can be seen in peritoneal fluid. A surgical procedure called a laparoscopy, in which a tiny scope is inserted into the abdomen through a small incision to inspect the abdomen, can also give a diagnosis. Necropsy (examination after death) can also indicate the presence of the disease.
Reflux--Treatment of gastric reflux has historically included passing a tube into the stomach through the nose (nasogastric intubation) to drain gastric contents. A veterinarian will examine the amount and physical properties of the gastric contents to gain more information on the problem.
"I would suggest that collection of five liters or more of gastric contents from a horse that has not drunk water within the previous few hours constitutes an excessive amount," said Merritt. "Clearly the appearance and odor of the contents must also be factored into this assessment; for instance, fluid that is reddish-colored and fetid, even if the collected volume is less than five liters, should be considered abnormal."
When reflux is caused by a physical blockage or a functional obstruction due to a lack of motility in the small intestine, the fluid could come primarily from the pancreas. The horse normally produces a lot of pancreatic juices, which are watery and have little odor. If gastric contents match this description, then the veterinarian will know more about the source of the problem. If the fluid is reddish, cloudy, and has a fetid odor, then the cause might be due to inflammation in the duodenum or jejunum (regions of the small intestine). If the fluid is in between these descriptions, then the problem could be a small intestinal obstruction.
Treatment for a physical obstruction involves surgery to remove or bypass the blockage. Horses which continue to have a blockage after surgery can be managed with decompression of the stomach through nasogastric intubation, in conjunction with intravenous fluid therapy, NSAIDs, and medication to jump-start GI motility. If endotoxemia (toxins in the blood) accompanies the problem, then Merritt will use a lidocaine infusion to reduce inflammation and pain. Another treatment might include a low dose of erythromycin lactobionate, which has been shown to increase gastric emptying, said Merritt.
If there is only a partial blockage and surgery is not necessary, then Merritt will prescribe bethanechol. However, he said, there is much still to be learned about management of this problem.
Equine Gastric Ulcer Syndrome
Merritt defined equine gastric ulcer syndrome as mucosal erosion and ulceration within the esophagus, stomach, and/or upper duodenum. EGUS is classified based on a description of the horse, management conditions, medical status, and/or primary lesion site as determined by endoscopic exam. Lesions are described as primary squamous (non-glandular) lesions, primary glandular and/or upper duodenal mucosal lesions, and primary lesions within the cardiac gland mucosa of highly stressed neonates.
Primary Erosion and/or Ulceration of the Non-Glandular (Squamous) Mucosa--These ulcers are primarily found with an endoscopic exam in adult horses in training or in some younger horses. Lesions are typically found near the margo plicatus that borders the pyloric glandular mucosa, along the whole length of the margo plicatus, or extending up into the non-glandular squamous mucosa and along the margo plicatus.
"A large number of publications have appeared over the last 10 years indicating that up to 90% of horses in training, irrespective of breed and type of exercise, may have erosive and ulcerative lesions of the squamous mucosa of varying degrees of severity," said Merritt.
With these types of lesions, horse owners might notice the horse has a poor appetite and might not want to finish grain; a reluctance to train or decreased performance, poor body condition, poor hair coat, and/or low-grade colic, especially after a grain meal.
Lesions are believed to be caused by a change in, or excessive exposure to, some part of the acidic gastric contents, said Merritt. Treatment with acid-suppressing drugs has been found to help, even in horses still in training.
Another possible cause could include the production of volatile fatty acids, which are by-products of fermentation of feedstuffs with soluble carbohydrates. These types of feedstuffs are commonly fed to horses in training. Researchers have found that feeding alfalfa hay raises pH to less acidic levels, despite more VFA production, and alfalfa-fed animals have fewer squamous lesions than horses fed bromegrass. This unexpected result is attributed to the buffering effect of constituent calcium salts and protein found in alfalfa.
Exercise has been found to be linked to ulcers. Merritt explained that a horse at a gait faster than a walk will tense his abdominal muscles, which then pushes gastric contents up into the squamous cell-lined region of the stomach, exposing it to corrosive acid that remains in lower in the stomach at the walk or at rest. Lesions have been found to resolve when a horse is taken out of training or is treated with acid-suppressing medications.
Primary Glandular Disease--This disease has been attributed to continuous NSAID therapy. NSAIDS are considered ulcerogenic since they affect the production of PGE2 as discussed previously. Merritt commented that if the recommended dosages of NSAIDs are followed, most horses will not have a problem; however, some horses seem to be more sensitive to NSAIDs. With the availability of the longer endoscopes, lesions of the glandular mucosa that are not related to NSAID therapy are also being seen in horses. The cause(s) of these lesions is still unknown.
Diagnosis can be made with a long endoscope after a veterinarian has emptied the contents of the stomach. If untreated, glandular lesions have the potential to cause scarring, which interferes with gastric outflow, and will therefore lead to secondary squamous ulceration.
Secondary Squamous Ulceration--This type of ulceration is rarely seen in horses older than one year of age and is associated with gastroduodenal ulcer disease (GDUD), where the primary lesion is found in the duodenum. Clinical signs include watery diarrhea, refusal to nurse, mild colic, and/or teeth grinding. On rare occasions, the problem becomes so severe that the secondary gastric ulcers can perforate (cause holes in) the non-glandular lining, which can kill the foal.
An endoscopic exam must include examination of the duodenum for diagnosis. The duodenum might show swelling, along with a yellowish covering of pus and lesions. Lesions might also be found in the squamous mucosa. With anti-ulcer medication, most foals can be back to normal within a week. Those that do not recover might begin drooling, grind their teeth, have periodic bouts of colic (especially after nursing), and have notable weight loss. These signs could indicate severe inflammation of the duodenum with fibrous tissue, which blocks gastric emptying and often causes severe secondary gastric squamous, and sometimes esophageal, ulceration. At this stage, a gastrojejunostomy, a surgical procedure where the stomach is surgically connected to the jejunum, thus bypassing the duodenum, is warranted. This is a risky and expensive procedure.
This problem will occasionally be seen in adult horses if any problem develops that disrupts gastric motility, such as severe primary glandular disease or duodenal obstruction.
Stress-Related Disease--This form of ulcers is perhaps related to a disruption of circulation in the mucosa of the stomach, or possibly as a result of a disruption in PGE2 production. This problem is most often seen in foals suffering from a severe illness or trauma, and due to a variety of problems that can result, antacid drugs are often routinely given to very sick foals. These lesions are mainly found in the glandular mucosa next to the margo plicatus in the cardiac gland region. Perforation and death are possible.
Treatment for ulcers can include medicating with an aluminum/magnesium hydroxide preparation to buffer gastric acid. "Clinical experience has indicated that administration of 240 mL of an extra-strength oral antacid product twice a day has been effective in treating squamous ulcer disease in some patients," said Merritt. "A few horses will actually eat flavored products mixed in with grain. There is also a feed additive for horses, which is marketed with the claim of having effective acid-buffering properties that can eliminate the signs that we associate with squamous ulcer disease. To date, however, there are no intra-gastric pH data available showing that this feed additive meets these claims."
Another type of treatment involves histamine-2 receptor antagonists, such as cimetidine and ranitidine. Merritt said any of these types of products on the market should work as long as an effective dose is given. To cut down on cost of this treatment, horse owners can now use a generic over-the-counter product.
The third type of anti-ulcer treatment involves administration of a proton-pump blocking agent, such as omeprazole. The only FDA-approved product is an oral paste called Gastrogard. Daily dosing with Gastrogard at 4 mg/kg once a day has been shown to reduce the severity and occurrence of primary squamous lesions in horses in training. Although a variety of companies have tried compounding omeprazole, experimental studies done at the University of Florida and clinical studies done at the University of California, Davis, and the University of Pennsylvania, show that the compounded drugs are not as effective. Based on the studies done at the University of Florida, Merritt recommended that the best time to exercise a horse would be between two and eight hours after treatment, and a small grain meal might allow the drug to be more quickly taken up, thus improving efficacy. The use of omeprazole in foals still needs to be studied.
Polysulfated sugar, or sucralfate, is a compound available as an ulcer-coating agent. "So far, however, clinical trials of its efficacy in treatment of experimental EGUS have not been very convincing," said Merritt. "In addition, animal experiments indicate that sucralfate binds to lesions best within an acid medium so that, ideally, it should not be given concomitantly with, or soon after, a histamine-2 receptor antagonist."
The Future of Research
Merritt closed by discussing the challenges for research in the future. "In my opinion, there are currently two major challenges on the table concerning EGUS," he said. "The first challenge is the determination of the specific cause of gastroduodenal ulcer disease syndrome. The second major challenge regarding EGUS is the development of nutritional and other management strategies to reduce the incidence of training-related squamous ulcer disease."
About the Author
Sarah Evers Conrad has a bachelor’s of arts in journalism and equine science from Western Kentucky University. As a lifelong horse lover and equestrian, Conrad started her career at The Horse: Your Guide to Equine Health Care magazine. She has also worked for the United States Equestrian Federation as the managing editor of Equestrian magazine and director of e-communications and served as content manager/travel writer for a Caribbean travel agency. When she isn’t freelancing, Conrad spends her free time enjoying her family, reading, practicing photography, traveling, crocheting, and being around animals in her Lexington, Kentucky, home.