8 Equine Gastric Ulcer Syndrome (EGUS)

• Gastrointestinal Ulcers in Horses include Gastric and Colonic Ulcers.

Objectives

• The objectives are to recognize risk factors for gastric ulcers, categorize by type and management practices.
• The objectives are to learn about treatment of gastric ulcers with mechanism of action of drugs, and understand prevention.
• An objective is to understand the mechanism of action of NSAIDs.
• Objectives are to identify affected GI tract portions and treatment for NSAID toxicity.
• Objectives are to learn how to clinically diagnose NSAID toxicity with supportive evidence.
• The objective is to differentiate between gastric and colonic ulcers.
• An objective is to prevent NSAID toxicity.

Equine Gastric Ulcer Syndrome (EGUS)

• EGUS is a common issue in adult horses and foals.
• Location is an important factor in EGUS.
• EGUS includes Ulcers of the Squamous and Glandular Stomach.

EGUS Prevalence

• Race and performance horses have a high prevalence of EGUS.
• Adult horses on pasture have a low prevalence of EGUS.
• Broodmares and non-athletic horses are reported to have a high prevalence of EGUS.
• Foals are relatively high in EGUS prevalence.
• Foals with GI illness have a higher incidence of EGUS.

Gastric Ulcer Prevalence

• 25-50% of foals are affected by gastric ulcers.
• 60% of show or performance horses are affected by gastric ulcers.
• 93% of racing thoroughbreds are affected by gastric ulcers.
• 38-56% of racing standardbreds are affected by gastric ulcers.
• 50% of horses with ulcers do not show signs.

Normal Stomach Anatomy

• The non-glandular region, present in horses and rats, is composed of stratified squamous epithelium.
• The stomach also contains glandular mucosa.

Gastric Pits-Glandular

• Gastric pits contain parietal cells producing hydrochloric acid.
• Chief cells in gastric pits create pepsinogen.
• Mucus cells in gastric pits produce mucus and HCO3-.

Parietal Cells and HCl Production

• Parietal cells produce HCl using the H+-K+-ATPase pump on the luminal side.
• Horses secrete HCl continuously.
• Parietal cells are stimulated to produce HCL via vagal stimulation, gastrin, and histamine binding to H2 receptors.

Equine Gastric Disease Classifications

• Equine Squamous Gastric Disease (ESGD) has primary and secondary classifications.
• Primary ESGD is due to management practices.
• Secondary ESGD is due to delayed gastric emptying.
• Equine Glandular Gastric Disease (EGGD) is described by anatomic location.
• EGGD is more difficult to treat than ESGD.

Gastric Ulcers in Humans vs. Horses

• Helicobacter pylori causes gastric ulcers in humans.
• There is no strong evidence in horses that Helicobacter equorum is associated with gastric ulcers.
• Resident bacteria likely play a role in gastric health.
• There is no evidence of infected ulcers.

Nonglandular Ulcers

• Nonglandular ulcers lack a mucus layer.
• Nonglandular ulcers are exposed to bile acids, pepsin, and organic acids.
• Tight junctions are important for protection in nonglandular ulcers.

Glandular Ulcers

• Glandular ulcers are always exposed to HCl.
• Glandular ulcers result from failure of mucosal protective factors.
• A factor is decreased prostaglandins (PGE2), mucosal blood flow, and loss of mucus-HCO3.

Risk Factors for Ulcers

• Feed type is a risk factor.
• High concentrates, feed deprivation, intermittent feeding, and stall confinement are risk factors.
• Alfalfa hay or pellets are protective against ulcers.
• TB race horses typically have ulcers.
• Endurance horses not in competition show 48% prevalence, while in competition show 98% prevalence.
• Theories for ulcers: increased abdominal pressure, increased gastrin and HCl, and delayed emptying.
• Other risk factors include, stress, exercise, transport, and concurrent illness.
• NSAID use may or may not be associated with ulcers in all cases.
• NSAIDs may be more important for glandular ulcers.
• NSAIDs play a more direct role with Right Dorsal Colon Ulcers.

Signs of Gastric Ulcers

• Adults may show attitude change, poor performance, and slow/poor appetite.
• Adults may show poor condition and colic.
• Foals may present with poor hair coat, pot belly/poor growth.
• Foals may present with bruxism, pytalism, and rolling up onto their backs.
• Foals may have interrupted nursing and diarrhea.
• Silent ulcers, rupture and death are also signs of gastric ulcers in foals.
• A further indication of gastric ulcers in foals is gastric outflow obstruction with strictured ulcers of the pylorus or duodenum.

Diagnosis of Ulcers

• Diagnosis of ulcers include clinical signs and endoscopic examination, which requires a long endoscope (3 m), air insufflation, and fasting.
• Ulcers are graded on a scale of 0-4 (squamous portion).
• Location can be glandular versus non-glandular, Margo, or Pylorus.

Ulcer Grading

• Grade 1 ulcers are non-glandular, have an intact epithelium, and show hyperemia and hyperkeratosis.
• Grade 2-4 refer to nonglandular ulcers of increasing severity.
• Glandular ulcers are not graded numerically, but are described.

Other Diagnostic Options

• Fecal occult blood tests are diagnostic options for ulcers.
• Succeed- blood and albumin can be tested.
• Albumin presence indicates colonic ulcer.
• Blood presence indicates gastric ulcer.
• Sensitivity and specificity present problems.

Treatment for Ulcers

• Antacids raise pH temporarily with temporary relief of clinical signs, but are not an effective treatment.
• Sucralfate binds to ulcers "Band-aid" and stimulates prostaglandin production.
• Sucralfate is used in conjunction with acid-suppressive therapy.
• H2 Receptor Antagonists like Cimetidine or Ranitidine decrease HCl production.
• H2 Receptor Antagonists are effective and given in multiple doses per day.
• Omeprazole (GastroGard) is a proton pump inhibitor approved for EGUS in the United States.
• Omeprazole (GastroGard)is the most effective drug and must be systemically absorbed within 3-5 days.
• Omeprazole (GastroGard)is given on an empty stomach.
• The therapeutic dose of Omeprazole is 4 mg/kg q 24 hours PO (14-28 days).
• Glandular Ulcers often require longer treatment with Omeprazole.
• A prophylactic dose of Omeprazole (UlcerGard®) is 1-2 mg/kg.
• Omeprazole is expensive, $34-56/day for an adult horse.
• Illegal compounding and manufacturing effectiveness is questionable.
• Misoprostol, a synthetic PGE 2 analog, can be used orally.
• Handling of misoprostol needs consideration due to abortion concerns.
• Misoprostol can cause colic and diarrhea in horses.

Preventing Ulcers

• Diet can prevent Ulcers
• Alfalfa, little to no concentrates, and grazing/turnout
• Use omeprazole 1 mg/kg, if necessary.
• It is standard practice to treat hospitalized foals with anti-ulcer medication, even normal foals.
• This practice has recently been questioned.
• An increase in diarrhea and loss of protective gastric acidity can come from anti-ulcer medication.
• Other Causes of Ulcers: Canthardin/Blister Beetle, GI irritation, Renal disease, Hypocalcemia and Neoplasia (SCC)

NSAIDs

• NSAIDs are one of the most commonly used drugs in equine practice.
• NSAIDs are non selective COX inhibitors: Phenylbutazone (Bute®) and Flunixin Meglumine (Banamine®).
• Ketoprofen and Diclofenac (topical NSAID) are NSAIDs.
• Firocoxib is a selective COX2 inhibitor.
• Steroids inhibit Phospholipase as a mechanism.
• NSAIDs inhibit COX as a mechanism.

Prostaglandins-Physiologic

• They maintain blood flow and health of the mucosa of GIT.
• Prostaglandins are important in reproduction and involve Cox-1.
• Prostaglandins are found Platelets, kidneys, and GIT.
• Prostaglandins pathologic side includes Pain, Inflammation, Fever, and associated with Endotoxemia.
• Cox-2 is an inducible form of Prostaglandins.
• Prostaglandins pathologic is found in Macs, fibroblasts, others.
• Too simple COX1 versus COX2 and Cox-2 also expressed constitutively in other organs and Kidneys.
• COX-2 is involved with GIT healing.
• Equioxx® is Only FDA approved selective COX-2 inhibitor and has Merial- FDA approved horses of Firocoxib.
• Equioxx® Safer – GIT toxicity and Options in selective cases.
• Renal disease reported (package insert) from Equioxx® and Long half-life – loading dose at first dose.

NSAID Toxicosis

• NSAID Toxicosis includes: Renal Papillary necrosis Gastrointestinal disease, Ulcers Especially Right dorsal colitis.
• Gastrointestinal Disease: Generalized NSAID toxicity Right dorsal Colitis Ulcerative disorder localized to RDC
• NSAID-Colitis-clinical signs: Edema, Anorexia, Lethargy, Colic, Diarrhea and Endotoxemia
• Clinical signs of NSAID Toxicity: similar to other diseases in which NSAID are warranted.
• Blood work-NSAID: Hypoproteinemia/hypoalbuminemia Very common, Electrolyte losses and Low WBC-endotoxemia
• RIGHT DORSAL COLITIS requires Abdominal ultrasonography right 11-15th ICS and Thickening of the wall variable (>3mm)
• Gastroscopy: Gastric Ulcers.and May not always be present in NSAID toxicity.

Diagnosis of NSAID

• Diagnosis, History of NSAID use, Clinical signs (edema), Bloodwork (low TP/albumin) Supporting ultrasound/gastroscopy and Rule out other diseases! Risk Factor NSAIDS vary in toxicity, Phenylbutazone #1, Flunixin meglumine #2 and Ketoprofen #3 NSAID Toxicity- Risk Factors: Dose, High doses, Can occur with normal doses, Duration of use, 20 yr old QH 2 gms of Bute 8 years. Predisposing Factors and Correct body weight? Ponies, foals, miniature horses and Foals more sensitive to NSAID Predisposing Factors Combining NSAID Common practice in show horses and Toxic Effects – add up USEF – only 1 NSAID at a time.

Additional Notes

• Dehydration/Hypovolemia Will potentiate NSAID toxicity Hypovolemia- prostaglandins maintain blood flow (vasodilatory) NSAID- will eliminate protective mechanism
• Treatment of NSAID Toxicity includes Stop NSAID Phenylbutazone or Flunixin and COX-2 selective also NOT recommended COX-2 – involved with healing of the GIT, Other Rx depends on location of GIT lesions Gastric Easy to treat and Colon Much more difficult to treat
• Treatment of NSAID Toxicity- Gastric Ulcers includes Omeprazole or H2 antagonist, Plus/minus combination with sucralfate
• Rx- Right Dorsal Colitis includes Low residue diet “Rest the gut”Complete pelleted feeds, No hay/roughage and 3-6 months
• Right Dorsal Colitis: Psyllium – stimulate VFA, Safflower or corn oil (Linoleic acid) andSucralfate – bind ulcers.
• Additional Treatment (as necessary) includes Dehydration = IV crystalloid fluids and Low oncotic pressure can result in inability to maintain circulatory volume Plasma Hetastarch and $$ Endotoxemia – (lecture coming) No flunixin
• Additional treatments (low neutrophil count) Concerns of bacterial translocation GIT and Antibiotics Colic = need to provide analgesia No more NSAID Opioids, alpha-2 drugs and Be aware of problems of ileus.
• Complications: Non responsive to treatment, Chronic colic Colonic fibrosis/stricture and Surgery?

Prevention of NSAID Toxicity

• Prevention of Gastric Ulcers, of omeprazole when using NSAID and Especially in foals….
• Don’t Prevention of NSAID Toxicity use in dehydrated animals! Correct doses do not combine NSAID Use of corn oil with NSAID Check TP/Albumin Use of firocoxib in with chronic use Be careful with dose Long duration
• Conclusion: Pathogenesis of Gastric and Colonic Ulcers are likely different in most cases, Gastric Ulcers- stress, management +/- NSAID, Colonic ulcers- NSAID use and Treatment of gastric versus colonic ulcers is different, Diagnosis of NSAID difficult (history)Can look similar to diseases that NSAID indicated and (infectious colitis)
• Clinical Question: 15 yr old horse with moderate laminitis. Being treated with phenylbutazone frequently. What is a way to diagnose right dorsal colitis early? Check albumin concentration orUS – measure small intestinal wall Clinical Question: 15 year old horse with navicular disease that was being treated with phenylbutazone and flunixin for laminitis. He has right dorsal colitis. What is an appropriate treatment? Stop all NSAID, use opioids for pain if necessary