Gastrointestinal Ulcers in Small Animals

The gastric mucosal barrier is a complex defense mechanism that protects the normal mucosa from the harsh chemical environment of the gastric luminal contents. The acids, pepsin, and proteolytic enzymes normally present in the gastric lumen have a pH of 2. The mucous layer provides a weak buffer, maintaining a pH of 4–6 and neutralizing the acidic luminal contents. The GI barrier is maintained by a protective layer that includes mucosal cells, tight junctions, and a thick layer of mucus. High blood flow to this area supports cellular metabolism and rapid renewal of injured cells. Prostaglandins (mainly E and I) help maintain the GI mucosal blood flow and integrity, increase secretion of mucus and bicarbonate, decrease acid secretion, and stimulate epithelial cell turnover. Tight junctions seal the cellular layers of the gastric mucosa, ensuring that the luminal contents do not leak into or around these cells. The small amount of gastric acid that diffuses into the epithelial cells is quickly cleared by the high blood flow to this area.

A defect in the GI mucosal barrier leads to a self-perpetuating cycle of mucosal damage. Injury to this barrier allows hydrochloric acid, bile acids, and proteolytic enzymes to degrade the epithelial cells, disrupt lipid membranes, and induce inflammation and apoptosis. Back diffusion of luminal contents through the tight junctions leads to inflammation and hemorrhage of the GI cells, with further acid secretion mediated by inflammatory cells and their products. Mast cell degranulation occurs, causing histamine release that perpetuates further gastric acid secretion. The inflammatory environment also causes decreases in blood flow (resulting in ischemia), ability for cellular repair, and secretion of mucus and cytoprotective prostaglandins. Mucosal ulceration can result, exposing the submucosa or deeper layers of the GI tissue to the luminal contents.

In the normal GI tract, the potential disruptive properties of the luminal contents are balanced by the defense mechanisms of the GI mucosal barrier. However, many drugs and disease have the potential to upset the balance between the harsh luminal contents and the GI protective barrier.

The incidence of GI ulceration in dogs and cats is unknown. NSAID administration, neoplasia, and hepatic disease are the most common causes in dogs. NSAIDs can cause direct topical damage to the GI mucosa, and inhibition of cyclooxygenase (COX)-1 decreases production of protective prostaglandins. The use of COX-2-specific NSAIDs is thought to decrease GI ulceration, but ulceration and perforation still occur with use of these medications. Corticosteroids potentiate the effects of mucosal damage by decreasing cell turnover and mucus production and by stimulating gastrin (and acid) production.

Hepatic disease is associated with increased gastric acid secretion and alterations in mucosal blood flow, potentially leading to ulcer formation. Primary GI neoplasia such as lymphoma, adenocarcinoma, leiomyoma, and leiomyosarcoma can result in ulceration. Additionally, paraneoplastic syndromes secondary to mast cell tumors and gastrinomas (Zollinger-Ellison syndrome) have been associated with increased gastric hydrochloric acid production and ulceration in dogs.

Other drugs and diseases associated with GI ulceration in dogs include corticosteroid use in dogs with spinal disease, renal disease, hypoadrenocorticism, stress, primary GI disease (eg, inflammatory bowel disease), extreme exercise (eg, sled dog racing), shock, and sepsis. The role of Helicobacter infection in GI ulceration is unknown, because Helicobacter organisms have been found in healthy dogs and cats.

GI ulceration is uncommonly reported in cats. Neoplasia (eg, lymphoma, adenocarcinoma) has been associated with GI ulceration in cats, but the cause is often unknown.

Specific clinical signs of GI ulceration include melena, hematemesis, and hematochezia. Abdominal pain, anorexia, and signs of underlying disease may be present. Cats with GI ulceration rarely show specific signs such as melena or hematemesis but frequently show signs of life-threatening hemorrhage. Animals with severe ulceration and/or GI perforation may present with signs of pain, weakness, pallor, and shock. Clinical signs of a causative factor may be seen. Some dogs and cats with GI ulceration do not show any clinical signs.

A CBC, serum biochemistry profile, and urinalysis can help differentiate primary GI disease from non-GI disease and can identify metabolic derangements resulting from GI disease. Additional testing, such as liver function tests or an adrenocorticotropic hormone stimulation test, may be warranted depending on the clinical findings and initial test results.

Abdominal radiographs generally do not help diagnose GI ulceration, but they can help exclude GI obstruction, intussusceptions, and peritonitis. Abdominal ultrasonography may show abnormalities in GI wall thickness or presence of a mass, but its primary utility is the identification of non-GI lesions. Endoscopy allows visualization of the esophagus, stomach, duodenum, and colon and identification of mucosal lesions and ulcers. Endoscopy also allows for fine-needle aspirates of lesions or collection of biopsy samples, although full-thickness surgical biopsies may be required to identify infiltrative disease and tumors. Ulcerated areas should be biopsied only on the periphery to avoid perforation. Gastric fluid can be tested for pH to help diagnose hypersecretory states.

Primary treatment of GI ulceration is directed at the underlying cause. Supportive care may be required to correct metabolic derangements and can include fluid therapy. Medication directed at the ulcer itself reduces gastric acidity, prevents further destruction of GI mucosa, and promotes ulcer healing. In general, antiulcerative therapy should be continued for 6–8 wk.

Gastric acid production is stimulated by histamine (most potent), gastrin, and acetylcholine. Drugs that decrease acid secretion help protect damaged GI mucosa. H₂-receptor blockers (eg, cimetidine, famotidine) help promote mucosal healing, and some agents also act as prokinetics (eg, ranitidine). Famotidine (0.5–1 mg/kg, bid, PO, SC, or IV) has been shown to be more potent in reducing gastric pH than other H₂-blockers such as cimetidine or ranitidine. Proton pump inhibitors (eg, omeprazole 0.5–1 mg/kg/day, PO, or pantoprazole 0.5–1 mg/kg/day, IV) offer more complete inhibition of gastric acid secretion and are therefore useful for more severe ulcers. Prophylactic use of H₂-blockers and proton pump inhibitors to prevent GI ulceration is controversial but may be considered in animals receiving NSAIDs or that have other risk factors.

Cytoprotective agents include antacids and sucralfate. Antacids are weak bases that help neutralize gastric acid within the stomach lumen. These drugs may also promote gastric prostaglandin production. Aluminum or magnesium-containing antacids are considered the most effective agents with the fewest adverse effects, although these drugs can lead to constipation. Because of their short half-life (2–3 hr), animals may experience a rebound gastric acidity between doses, and the drugs must be given frequently. Sucralfate (dogs: 0.5–1 g, PO, bid-tid; cats: 0.25 g, PO, bid-tid) is a polyaluminum sucrose sulfate that binds to areas of eroded or ulcerated GI mucosa. Because this drug inhibits absorption, it should not be given within 1–2 hr of food or other drugs.

The prostaglandin E₂ analogue misoprostol is used to help prevent NSAID-associated ulcer formation but does not assist in mucosal healing or decrease acid secretion.

Prophylactic use of antibiotics can be considered in cases of major GI mucosal barrier disruption or shock, or in other cases when clinicopathologic signs (eg, fever, hematochezia, leukopenia, neutrophilia) suggest that bacterial translocation is of concern. First-line antibiotic therapy includes the β-lactams, with additional gram-negative coverage if necessary.

The prognosis for GI ulceration in dogs is favorable when the underlying cause can be treated or removed, ulceration is mild, or the condition is rapidly diagnosed and treated. Ulceration associated with severe or end-stage conditions (eg, hepatic insufficiency) is difficult to control. Mortality rates associated with GI perforation range as high as 70%.

GI ulceration in cats is often related to neoplasia. Intensive care frequently is needed because of the high prevalence of marked hemorrhage. In one report, median survival of cats with gastric ulceration treated with surgery and palliative care ranged from 12–15 mo. Cats with GI ulceration secondary to a non-neoplastic disease have less severe clinical disease and a good prognosis.