Gastrointestinal Ulcers in Small Animals - The Merck Veterinary Manual

Gastrointestinal Ulcers in Small Animals

The awareness of GI ulcers as a cause of GI disease has markedly increased with the advent of endoscopy in veterinary medicine, but the incidence of GI ulcers in small animals remains to be established.

Etiology and Pathophysiology:

GI ulcers result from a breakdown of the normal gastric mucosal barrier and are aggravated by an increase in hydrochloric acid or pepsin production. The gastric mucosal barrier consists of a thick mucous layer and the mucosal cells that make up the epithelial membrane. Mucus has only a weak neutralizing and buffering capacity. The epithelial cells constitute the most important anatomic barrier to acid. A healthy gastric mucosal barrier is supported by adequate mucosal blood flow, a thick mucous layer, bicarbonate secretion, epithelial cell turnover, and an electrical potential difference. Prostaglandins maintain integrity of gastric mucosa by inhibiting gastric acid secretion, enhancing gastric bicarbonate production, preserving mucosal blood flow, stimulating epithelial cell turnover, and promoting the secretion of gastric mucus with an increased protein content. Injury to the mucosal barrier results in “back diffusion” of luminal acid into the mucosa, which initiates a series of events that result in cellular damage. The small amount of acid that normally diffuses into the mucosa is rapidly cleared by mucosal blood flow. Mucosal blood flow also serves to deliver oxygen and nutrients to the epithelium. Damage to the mucosal barrier increases mucosal permeability and the amount of acid diffusing back into the mucosa. Mast cells in the submucosa and lamina propria degranulate on contact with acid, releasing histamine. Histamine stimulates parietal cell secretion of hydrochloric acid and promotes cellular injury. The back diffusion of hydrochloric acid is the principal factor eliciting mucosal erosion and ulceration. Conditions predisposing to increased acid production or mucosal damage facilitate ulcer production. Acid also damages local blood vessels and nerves.

Potential causes of GI ulceration include the following: 1) drugs—NSAID (including aspirin, phenylbutazone, ibuprofen, indomethacin, carprofen, flunixin meglumine, naproxen, and piroxicam) and corticosteroids; 2) neoplasia—lymphosarcoma, adenocarcinoma, gastrinoma (Zollinger-Ellison syndrome), and mastocytosis; 3) systemic disease—renal or hepatic disease, hypovolemic shock, hypoadrenocorticism, sepsis, spinal injury, and pancreatitis; 4) other causes— Helicobacter spp , pyloric outlet obstruction, inflammatory bowel disease, chronic gastritis.

Aspirin, an NSAID, directly injures gastric epithelial cells and impairs prostaglandin E production. Standard formulations of buffered aspirin do not provide sufficient buffering to neutralize gastric acid or prevent mucosal injury. In people, enteric-coated aspirin causes less gastric irritation but absorption is less consistent. Corticosteroids potentiate the effects of mucosal damage by decreasing cell turnover and mucus production and by stimulating gastrin and hence acid production.

Gastrinoma and mastocytosis cause ulcer formation by increasing acid production.

Renal failure results in the retention of uremic toxins and gastrin that damage the gastric mucosa and blood vessels of the gastric wall and result in increased acid production.

The exact mechanism(s) by which liver failure favors ulcer production is unknown but may include reduced mucosal blood flow, increased serum levels of gastrin and histamine, and contribution to a loss of the normal mucosal barrier.

Hypotension, hypovolemic shock, and sepsis impair normal gastric microcirculation leading to ischemia and cell death. Spinal cord lesions may affect autonomic nervous control of blood vessels to the gut causing vasodilation, vascular stasis, and ischemia. Dogs with spinal cord lesions undergoing surgery and receiving corticosteroids are prone to hemorrhagic gastroenteritis ( Hemorrhagic Gastroenteritis) and perforating gastric ulcers. Stress may precipitate sympathetic-mediated vasoconstriction and increase the production of endogenous corticosteroids, vasoactive catecholamines, and serotonin, which contribute to mucosal injury. Reflux of bile acids and pancreatic enzymes damage mucosal cells by directly damaging the mucosal barrier. Reflux may be due to a number of factors, including disorders of pyloric function.

Clinical Findings:

Animals with gastric ulceration may be asymptomatic or have a history that includes vomiting, sometimes with frank or digested blood, and abdominal discomfort that may appear less severe after a meal. Melena and pale mucous membranes supportive of anemia may be apparent. Clinical signs may be indicative of the causative factor of the ulcer, eg, clinical signs related to renal failure.

Diagnosis:

The diagnostic approach to animals with a history of vomiting, abdominal discomfort, anorexia, or weight loss of unknown etiology should begin with a CBC, biochemical profile, trypsin-like immunoreactivity analysis, urinalysis, and fecal parasite evaluation. When indicated, abdominal ultrasonography should be performed or radiographs taken. In cases in which the etiology remains obscure or in those with apparent GI pathology, gastroduodenoscopy and biopsy should be completed.

Treatment and Control:

The primary goal of ulcer management is to determine and eliminate or control the cause of the ulceration and provide supportive care. 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. H₂-blocking agents reversibly bind H₂-receptors and impede endogenous histamine occupation of the receptor. H₂-blocking agents include cimetidine, ranitidine, and famotidine. Cimetidine (10 mg/kg, PO, IM, or IV, tid) inhibits gastric acid secretion for 3-4 hr and requires dosing 3-4 times daily. Although no drug is more efficacious than another in promoting ulcer healing, ranitidine (dogs: 2 mg/kg, PO or IV, tid; cats: 2.5 mg/kg, IV, bid, or 3.5 mg/kg, PO, bid) is 4-10 times more potent than cimetidine, and famotidine (0.5-1 mg/kg, PO or IV, sid-bid) is 20-40 times more potent. Nizatidine (dogs and cats: 2.5-5 mg/kg/day, PO) is an H₂-blocking agent similar to cimetidine but up to 10 times more potent. It is primarily used as a prokinetic agent.

Omeprazole (0.7 mg/kg, PO, sid) inhibits the hydrogen-potassium ATPase responsible for hydrogen ion production in the parietal cell. It is 2-10 times more potent than cimetidine in decreasing intragastric acidity. In a study in dogs, sid administration of omeprazole was as effective as cimetidine given tid in lessening aspirin-induced gastritis.

Cytoprotective agents include antacids and sucralfate. Antacids are as effective as other antiulcerative agents but require more frequent dosing (eg, aluminum hydroxide in dogs is given at ½ -1 tablet, qid, and in cats at ¼ tablet, qid). One antacid tablet containing aluminum hydroxide given qid is as effective as higher doses of liquid antacids and cimetidine in promoting ulcer healing. Sucralfate (dogs: 0.5-1 g, PO, bid-tid; cats: 0.25 g, PO, bid-tid) forms a complex with proteinaceous exudates that adheres to the ulcer, providing a protective barrier to the penetration of acid. It also stimulates prostaglandin production, increases mucus production and mucosal turnover, inactivates pepsin, and absorbs bile acids. Sucralfate is as effective as H₂-receptor antagonists in promoting healing of ulcers in people.

Misoprostol (dogs: 2-5 µg/kg, PO, tid) is a synthetic prostaglandin E₁ analog. It decreases gastric acid secretion; increases bicarbonate and mucus secretion, epithelial cell turnover, and mucosal blood flow; and has a cytoprotective effect. It is reportedly effective in the prevention of NSAID-induced GI ulceration, whereas cimetidine and sucralfate have a therapeutic effect only if NSAID are discontinued. In spite of its efficacy, misoprostol has not been reported to decrease the frequency of GI pain associated with NSAID use. It is as effective as other antiulcerative drugs in treating GI ulcers in cases other than those associated with NSAID use, but in these cases, it offers no clear advantage over these other drugs. Misoprostol mitigates NSAID-induced gastroduodenal injury. Although partial protection is provided, gastritis may still develop and contribute to vomiting. The drug does not prevent GI hemorrhage in dogs treated with methylprednisolone and is not effective in the healing or prevention of gastric mucosal lesions in dogs with acute degenerative disk disease treated with corticosteroids. Neither does omeprazole, cimetidine, or sucralfate. Dietary management should include the use of bland diets (eg, cottage cheese and rice or chicken and rice).

Ideally, ulcer healing should be monitored with gastroduodenoscopy. Failure of ulcers to respond to appropriate medical management necessitates biopsy of the stomach and small bowel. Several biopsies should be taken because obvious lesions may not be apparent or may be located sporadically throughout the gut.

The prognosis for animals with peptic ulcers and benign gastric neoplasia is good. Prognosis is poor for those with ulcers associated with renal or hepatic failure and for animals with gastric carcinoma and gastrinoma.