Diseases of the Stomach Frank M. Andrews, DVM, MS, DACVIM Professor of LA Medicine The University of Tennessee, CVM

Equine Gastric Ulcer Syndrome Photo courtesy of MJ Murray.

Prevalence of Equine Gastric Ulcer Syndrome (EGUS) 60% to 93% in performance horses 25% to 50% in foals Murray et al, Equine Vet J, 1996; Murray, JAVMA, 1989; Murray, AAEP, 1997.

EGUS: Public Perceptions Telephone Survey conducted in 2003, of 300 performance horse owners

Impact of EGUS on Adult Horses Results in poor body condition Can disrupt training Can impair performance Can cause colic Can have severe complications duodenal strictures Murray, AAEP, 1997; Murray, Vet Med, 1991.

Photos courtesy of MJ Murray. Impact of EGUS on Foals Gastric outflow obstruction Esophagitis Chronic ulceration Perforation (rupture) & peritonitis Photos courtesy of MJ Murray.

The Stomach of the Horse Nonglandular region (squamous epithelium) Esophagus Duodenum Margo plicatus Pylorus Glandular region (glandular epithelium)

Compartments of the Equine Stomach Squamous (nonglandular) tissue. Less resistant to acid injury. 80% of equine ulcers Glandular & mucus-secreting tissue. More resistant to acid injury. 20% of equine ulcers Pagan, World Equine Vet Rev, 1997.

Cause of EGUS: Aggressive Factors Overpowering Defensive Factors Gastric lining damage occurs when: Aggressive (acid, pepsin, bile, organic acids) factors overpower Defenses (bicarbonate, mucus) of gastric mucosa Squamous mucosa lining lacks these defenses SM MP GM Murray, Equine Vet J Suppl, 1992; Sweeney, In Practice, 1992; Pagan, World Equine Vet Rev, 1997; Murray and Schusser, Equine Vet J, 1993.

Risk Factors for EGUS: Training/Racing Intensive exercise Reduced blood flow to the stomach lining? Increased gastric acidity? Altered eating behavior? March 25 June 3

Acids forced into the proximal stomach Increased intra-abdominal presssure during intense exercise causes gastric compression, pushing acid contents into proximal stomach HCl,VFAs Bile acids Lorenzo-Figueras and Merritt, AJVR 2002;63:1481-1487

Risk Factors for EGUS: Feeding Feeding management Low prevalence of ulcers in horses at pasture Murray et al, Equine Vet J, 1996.

Risk Factors for EGUS: Feeding Decreased acid when roughage available Increased serum gastrin when fed concentrates (grains & sweet feeds) Intermittent feed deprivation = gastric ulcers Stall confinement = gastric ulcers Feeding alfalfa hay may help!

Gastric Acidity Profile: No Feed 24-Hr Gastric pH: Feed Withheld 7 6 5 4 pH 3 2 1 6 12 18 24 Time (hours) Murray and Schusser, Equine Vet J, 1993.

Gastric Acidity Profile: Grass Hay 24-Hr Gastric pH: Free Choice Hay 8 7 6 5 4 pH 3 2 1 6 12 18 24 Time (hours) Murray and Schusser, Equine Vet J, 1993.

Hydrochloric Acid-Induced Ulcers Gastric acidity is high in empty stomach Intermittent feed deprivation Lesions form in squamous mucosa No lesions form in glandular mucosa Lesions prevented by ranitidine (Zantac®) Day 0 48 hours 96 hours Murray and Schusser, Equine Vet J, 1993; Murray and Eichorn, Am J Vet Res, 1996.

Risk Factors for EGUS: Stress Physical stress Illness Painful musculoskeletal disorder Behavioral stress Stall confinement Transport Unfamiliar environment, social regrouping

Risk Factors for EGUS: Non-Steroidal Anti-Inflammatory Drugs Phenylbutazone & Flunixin Meglumine and other NSAIDs Associated with ulcers throughout the intestinal tract (Cecum & Colon) Inhibit prostaglandins, interrupting mucosal blood flow and mucus Local toxicity Murray, Vet Med, 1991.

Clinical Signs of EGUS in Adult Horses Poor appetite Poor body condition Attitude changes Decrease in performance Mild to moderate colic Murray, AAEP, 1997.

Clinical Signs of EGUS in Foals Poor appetite or intermittent nursing Colic Poor body condition Frequently lies on back Bruxism (grinding of teeth) Excessive salivation (Ptylism) Diarrhea Murray, Vet Med, 1991.

How can you tell that a Horse has EGUS? (Diagnosis) Clinical signs are suggestive of, but not specific for, EGUS Lab: Mild anemia Response to treatment can be useful Gastric endoscopy is only definitive diagnostic tool

Endoscopic Evaluation Endoscope quality & dimensions 9 ft long Small diameter Patient preparation Experience Murray, Vet Med, 1991.

Endoscopic Evaluation: Adults Squamous erosions fundus Squamous ulcer margo plicatus Squamous ulcers lesser curvature Murray (personal communication), 1999. Photos courtesy of MJ Murray.

Endoscopic Evaluation: Adults (cont’d) Glandular ulcer rugal fold Erosion, hyperplasia antrum rugal fold Pyloric ulcer Murray (personal communication), 1999. Photos courtesy of MJ Murray.

Endoscopic Evaluation: Foals Squamous erosion, desquamation 3 days old Squamous erosions 30 days old Bleeding squamous ulcers 3 months old Murray (personal communication), 1999. Photos courtesy of MJ Murray.

Endoscopic Evaluation: Foals (cont’d) Glandular corpus ulcers 14 days old 2 months old Antrum ulcers 3 months old Pyloric ulcers Murray (personal communication), 1999. Photos courtesy of MJ Murray.

Treatment of EGUS Eliminate clinical signs Promote healing Prevent complications Prevent recurrences MacAllister, Vet Med, 1995.1

There Are Two Compatible Approaches to Treatment Management modifications Medical therapy-approaches that have been used Control gastric acid Mucosal protectants Murray, AAEP, 1997; MacAllister, Vet Med, 1995.

Traditional Management Modifications Reduce level of training

Traditional Management Modifications Diet modifications Limit periods of fasting Increase roughage pasture turnout (green grass) free choice hay Alfalfa hay-dietary antacid Reduce grain/concentrates Seahorn, LSU Equine Vet Res Program Newsletter, 1998; Pagan, World Equine Vet Rev, 1997.

Dietary Management Fresh Rice Bran and Rice Bran Oil Contains surface active phospholipids and cytoprotective factors that maintain health of the stomach lining Rancidity can be a problem Produces ketoaldehydes which are ulcerogenic Steam pasteurization can help decrease potential for rancidity Storage in refrigerator

Management Modifications Limit stressful events Long-term stall confinement Trailering Overcrowding

Organic Acids (VFAs or SCFAs) High Concentrate Diets Acetic, Butyric, Propionic, and Valeric Acids Byproducts of carbohydrate fermentation in the stomach Synergistic with HCl May lead to non-glandular ulcers Increased VFA’s with increased grain

Medical Management of EGUS Neutralizing agents Antacids Antisecretory agents Histamine H2 receptor antagonists Prostaglandin analog Acid pump inhibitors Others (antibiotics, neutriceuticals) MacAllister, Vet Med, 1995.

Route of administration Commonly used Anti-Ulcer Medications, Routes, & Doses Drug Dosage (mg/kg BWT) Dosing interval Route of administration Ranitidine* 6.6 Q 6-8 h PO Ranitidine 1.5 Q 6 h i.v., i.m. Cimetidine 20-25 Omeprazole **(GastroGard) 4 Q 24 h Omeprazole 0.5 i.v. Sucralphate 20-40 Q 8 h Al/MgOH antacids 0.5 to 1.0 ml/kg Q 4-6 h **GastroGard, Merial LTD, Atlanta, GA. Only Drug Approved for horses

GASTROGARD® (Omeprazole) New oral-paste formulation of omeprazole developed specifically for horses Well-studied, effective, and safe therapy for EGUS Approved for use in horses, March 1999

Ulcer Treatments Act at Different Sites Site of Action H2 antagonists H2 (+) ACh (+) Gastrin (+) Prostaglandins (-) PARIETAL CELL GASTROGARD™ ACID PUMP H+ H+ Sucralfate MUCUS/BICARBONATE BARRIER H+ H+ H+ CI- CI- CI- H+ H+CI- STOMACH LUMEN Antacids

GastroGard® Allows Healing/Improvement of Ulcers Sham Dosed (n = 25) 69/75 (92%) 100 GASTROGARD (n = 75) 58/75 (77%) 75 Percent (%) 50 8/25 (32%) 25 1/25 (4%) Improved Healed Freedom of Information (FOI) Summary for GASTROGARD Oral Paste for Equine Ulcers; Andrews et al, Equine Vet J Suppl, 1999.

GastroGard® Advantages Profound gastric acid suppression Prolonged duration of action Once-daily dosing Well studied in horses No reported treatment-related health problems in equine trials Prevents ulcer recurrence Can maintain training program Approved for use in horses (GASTROGARD®) Andrews et al, Comp Cont Educ Pract Bet, 1996.

GastroGard®: Disadvantages No IV formulation available in US Andrews et al, Comp Cont Educ Pract Bet, 1996.

UlcerGard Prevention of ulcers Non-perscription strength of Gastrogard Sold through veterinarians

Histamine H2 Receptor Antagonists Zantac® (ranitidine), Tagamet® (cimetidine) Competitive inhibition of the interaction of histamine with parietal cell Dose-dependent inhibition of gastric acid secretion MacAllister, Vet Med, 1995.

Histamine H2 Receptor Antagonists: Advantages & Disadvantages Availability Low cost (generic) Zantac® has been shown to significantly inhibit gastric acid secretion in horses Must be administered 3X daily Murray, AAEP, 1997.

Antibiotic Treatment Amoxicillin, metronidazole, clarithromycin, bismuth compounds, etc. Primarily used in humans with Helicobacter pylori H. pylori has been associated with the stomach of horses, but not EGUS Antimicrobials may be used in horses with resistant EGUS

Recent Studies on Helicobacter spp. Helicobacter specific DNA isolated from horse stomachs 2 horses with squamous erosions 1 horse with glandular erosions ACVIM Forum-Dallas (May 2002) Scott DR, Marcus EA, Shirazi-Beechey SSP, et al. Evidence of Helicobacter infection in the horse. Proc Am Soc Microbiology 2001.

Feed Supplements (Neutriceuticals) NeighLox® (Kentucky Performance Products) Antacid and Coating Agents: Aluminum Phosphate, Calcium Carbonate Dihydroxy-Aluminium Sodium Carbonate Labeled for prevention of heartburn No studies in horses to prove or disprove Probably does not cause any harm

Feed Supplements (Neutriceuticals) G.U.T (Uckele Health & Nutrition) Gastric ulcer transnutrient for horses with ulcers Ingredients Gelatin Lactobacillus acidophilus, L. lactis Feed 15 grams (1 scoop) twice daily in horses with ulcers No studies proving efficacy

Feed Supplements (Neutriceuticals) TractGard (Foxden Equine) Equine GI rehydrator, antacid, digestaid, and electrolyte salt Ingredients (1 to 2 scoops daily) Calcium carbonate, Sodium sequiscarbonate, KCl, MgSO4, distiller’s grain, yeast, and linseed meal No studies on efficacy

Compounded & Generic Omeprazole: Beware!!

Conclusions- General EGUS is a major cause of illness 60-93% of performance horses have EGUS Impacts health, performance, economics Occurs when aggressive factors overpower gastric defenses

Conclusions- General Diagnosis requires endoscopy Presumptive diagnosis made based on clinical signs following complete diagnostic evaluation Treatment: management and medical interventions

Conclusions- Treatment Zantac®-healing 3X daily treatment Dietary supplements-not tested GastroGard® (omeprazole) Only FDA approved treatment Provides potent, long-lasting gastric acid suppression in horses (once daily administration) 92% to 99% improvement in ulcer scores in trials and a wide safety margin UlcerGard Prevention of Ulcers

Duodenal Ulcers/Stricture Part of EGUS (more commonly in foals) Similar pathogenesis Similar clinical signs Usually associated with bruxism, ptylism, and diarrhea (occurs most often in foals) Delayed gastric emptying Associated with esophageal ulcers

Duodenal Ulcers/Strictures Diagnosis Clinical signs Duodenoscopy Radiology gastric emptying with barium swallows (liquid meal=30 minutes) Necropsy

Duodenal Ulcers/Strictures Treatment Omeprazole (4 mg/kg, PO, Q24h, 28 days) Omeprazole (0.5 mg/kg, IV, Q24h) Ranitidine (6.6 mg/kg, PO, Q8h) Surgery-Gastrojejunostomy (foals only?)

Gastric Neoplasia Uncommon in older horses Squamous cell carcinoma, most common Others: lymphosarcoma, adenosarcoma Arises from squamous mucosa and metastasizes to the abdominal cavity and viscera and/or extends up the esophagus Clinical signs: Chronic weight loss Anemia Naso-gastric reflux Colic

Gastric Neoplasia Diagnosis Clinical Signs Endoscopy (definitive) Abdominal ultrasound Necropsy Treatment: None Prognosis: Grave

Gastric Impaction Infrequent cause of Colic in horses Dry feed material and decreased water intake May occur during winter when dry hay is fed and water intake is lower Diagnosed at surgery in horses with colic Endoscopic examination Treatment with dioctyl sodium succinate (DSS) 5% solution via NG tube in 4 to 6 L fluid Lavage at surgery, resolve in 24 – 48 hours