Gastric Ulcer

Gastric ulcer is a breach in the mucosal integrity of the stomach that extends through the muscularis mucosae, exposing the submucosa or deeper layers to the corrosive action of gastric acid and pepsin. In veterinary medicine, gastric ulcers are classified as acute or chronic, and can be superficial (erosion) or deep (ulcer). They may be single or multiple, and can lead to hemorrhage, perforation, and peritonitis. The condition is clinically significant due to its potential for life-threatening complications, including gastrointestinal bleeding and septic peritonitis. Gastric ulcers are commonly encountered in dogs, less frequently in cats, and can be primary or secondary to various systemic diseases or drug administration.

The etiology of gastric ulcers in dogs and cats is multifactorial. Primary causes include: (1) Non-steroidal anti-inflammatory drugs (NSAIDs) such as carprofen, meloxicam, and aspirin, which inhibit cyclooxygenase-1 (COX-1) and reduce mucosal prostaglandin synthesis, leading to decreased mucus and bicarbonate secretion, reduced mucosal blood flow, and impaired epithelial restitution. (2) Glucocorticoids, especially at high doses, which decrease mucosal protection and increase acid secretion. (3) Gastric neoplasia, including adenocarcinoma and lymphoma, which can cause ulceration. (4) Infectious agents: Helicobacter spp. (e.g., H. pylori, H. felis) have been implicated in chronic gastritis and ulceration, though their exact role in dogs and cats is debated. (5) Hepatic disease, particularly portosystemic shunts, which lead to increased gastric acid secretion and altered mucosal blood flow. (6) Renal failure, causing uremic gastritis and ulceration due to increased gastrin and ammonia. (7) Hypoadrenocorticism (Addison's disease), which may be associated with gastrointestinal bleeding. (8) Mast cell tumors, which release histamine, stimulating H2 receptors and increasing acid secretion. (9) Shock, sepsis, trauma, or burns (stress ulcers) due to splanchnic hypoperfusion and ischemia. (10) Foreign bodies or ingestion of corrosive substances. (11) Inflammatory bowel disease (IBD) can be associated with gastritis and ulceration. (12) Idiopathic or spontaneous ulcers, particularly in breeds like the Boxer and Doberman Pinscher, may have a genetic predisposition.

Gastric ulcers are more common in dogs than cats. In dogs, the prevalence is estimated at 1-2% of all gastrointestinal cases, but it is higher in certain populations, such as those receiving NSAIDs or with chronic kidney disease. There is no strong breed predilection, but some breeds like the Boxer, Doberman Pinscher, and Rottweiler may be overrepresented. Age distribution is bimodal: younger animals may develop ulcers due to foreign bodies or infectious causes, while older animals are more prone to NSAID-induced ulcers and neoplasia. Sex predilection is not clearly established. In cats, gastric ulcers are less common, but when present, they are often associated with chronic kidney disease, inflammatory bowel disease, or mast cell tumors. Geographic variation is minimal, but regions with higher prevalence of infectious agents (e.g., Helicobacter) may see more cases. Seasonal patterns are not significant, though stress-related ulcers may increase during periods of hospitalization or intense training.

The gastric mucosa is protected by a complex barrier consisting of a mucus-bicarbonate layer, tight junctions between epithelial cells, rich mucosal blood flow, and rapid epithelial restitution. Ulceration occurs when aggressive factors (acid, pepsin, bile acids, NSAIDs, ischemia) overwhelm these protective mechanisms. NSAIDs inhibit COX-1, reducing prostaglandin E2 and prostacyclin synthesis, which are critical for mucus secretion, bicarbonate production, and mucosal blood flow. This leads to focal ischemia, increased vascular permeability, and neutrophil infiltration, causing mucosal injury. Glucocorticoids similarly reduce prostaglandin synthesis and increase acid secretion. Helicobacter spp. colonize the gastric mucus layer and can cause chronic inflammation, leading to gastritis and ulceration through urease activity, production of vacuolating cytotoxin, and immune-mediated damage. In hepatic disease, portosystemic shunting allows toxins to bypass the liver, leading to increased gastrin levels and gastric acid hypersecretion. Renal failure causes uremia, which increases gastric acid secretion and ammonia production, damaging the mucosa. Mast cell tumors release histamine, which binds to H2 receptors on parietal cells, increasing acid secretion. Stress ulcers result from splanchnic vasoconstriction, leading to mucosal ischemia and reperfusion injury. The final common pathway is mucosal necrosis, erosion, and ulceration, which can extend into submucosal blood vessels, causing hemorrhage, or through the serosa, leading to perforation and peritonitis.

Intrinsic factors include: (1) Genetic predisposition in certain breeds (e.g., Boxers with histiocytic ulcerative colitis may have concurrent gastric ulcers). (2) Age: older animals are more susceptible to NSAID toxicity due to decreased renal clearance and reduced mucosal repair. (3) Concurrent diseases: chronic kidney disease, liver disease, hypoadrenocorticism, mast cell tumors, and inflammatory bowel disease increase the risk. (4) Acid hypersecretory states such as gastrinoma (Zollinger-Ellison syndrome) are rare but predispose to multiple ulcers. Extrinsic factors include: (1) Administration of ulcerogenic drugs, especially NSAIDs and corticosteroids, particularly at high doses or with prolonged use. (2) Stressful events such as surgery, trauma, or critical illness. (3) Dietary indiscretion or ingestion of foreign bodies. (4) Infection with Helicobacter spp. (5) Environmental factors such as poor husbandry or overcrowding may increase stress and susceptibility.

Clinical signs vary depending on the severity and chronicity of the ulcer. Peracute/acute ulcers may present with: (1) Hematemesis (vomiting of fresh blood or coffee-ground material). (2) Melena (dark, tarry stools due to digested blood). (3) Acute abdominal pain (praying posture, restlessness). (4) Pale mucous membranes, tachycardia, and weak pulses due to blood loss. (5) Collapse or shock in cases of perforation. Subacute/chronic ulcers may show: (1) Intermittent vomiting, often after eating. (2) Weight loss and anorexia. (3) Chronic intermittent melena or anemia. (4) Pica or bruxism. (5) Lethargy and depression. Terminal cases with perforation present with acute onset of severe abdominal pain, abdominal distension, fever, and signs of septic shock. Physical examination may reveal cranial abdominal pain, a palpable mass (if neoplastic), or evidence of peritonitis (e.g., abdominal rigidity, pain on palpation).

Differential diagnoses for gastric ulcer include: (1) Gastritis (acute or chronic) – may present with similar vomiting but typically lacks severe hemorrhage; endoscopy shows erythema and erosions but not deep ulcers. (2) Gastric neoplasia (adenocarcinoma, lymphoma) – can cause ulceration; biopsy is definitive. (3) Pancreatitis – causes vomiting and abdominal pain, but hematemesis is less common; serum lipase and imaging help differentiate. (4) Inflammatory bowel disease – chronic vomiting and diarrhea, but ulceration is not typical; biopsy confirms. (5) Esophageal disease (esophagitis, stricture) – regurgitation rather than vomiting, and hematemesis is rare; endoscopy differentiates. (6) Coagulopathies (e.g., rodenticide toxicity, immune-mediated thrombocytopenia) – cause bleeding but not necessarily ulceration; coagulation panel and platelet count are key. (7) Hepatic disease (portosystemic shunt) – may cause gastrointestinal bleeding; bile acid testing and ultrasound are useful. (8) Renal failure – uremic gastritis can cause vomiting and melena; renal parameters and urinalysis are diagnostic. (9) Hypoadrenocorticism – may present with vomiting and collapse; ACTH stimulation test is definitive. (10) Mast cell tumor – can cause gastric ulceration due to histamine release; cytology/histopathology of the tumor is needed.

The diagnostic approach to gastric ulcer should be systematic: Step 1: Obtain a thorough history, including drug administration (NSAIDs, corticosteroids), toxin exposure, and concurrent diseases. Step 2: Perform a complete physical examination, paying attention to hydration status, mucous membrane color, capillary refill time, and abdominal palpation. Step 3: Baseline laboratory tests: CBC (to assess anemia, leukocytosis), serum biochemistry (to evaluate renal, hepatic, and pancreatic function), urinalysis, and coagulation profile (to rule out coagulopathy). Step 4: Abdominal radiographs (survey) to rule out radiopaque foreign bodies or evidence of perforation (free gas). Step 5: Abdominal ultrasonography to assess gastric wall thickness, identify masses, and evaluate for peritonitis. Step 6: If the patient is stable, perform upper gastrointestinal endoscopy, which is the gold standard for diagnosing gastric ulcers. Endoscopy allows direct visualization of the ulcer, assessment of severity, and collection of biopsy samples. Step 7: If endoscopy is not available or the patient is unstable, consider contrast radiography (barium study) to identify filling defects or ulcers, though this is less sensitive. Step 8: In cases of suspected Helicobacter infection, obtain gastric mucosal biopsies for histopathology, culture, or PCR. Step 9: If a mast cell tumor is suspected, perform fine needle aspiration of any cutaneous mass and measure serum tryptase. Step 10: In cases of unexplained ulcers, consider testing for gastrinoma (serum gastrin levels) or other endocrine disorders.

Hematology: Anemia (regenerative or non-regenerative depending on chronicity) due to blood loss; microcytic hypochromic anemia may indicate chronic iron deficiency. Leukocytosis may be present due to inflammation or stress. Thrombocytopenia may be seen if there is concurrent coagulopathy. Serum biochemistry: Hypoalbuminemia due to protein loss; elevated BUN and creatinine may indicate renal disease; elevated liver enzymes (ALT, ALP) may suggest hepatic disease; hyperglobulinemia may be seen with chronic inflammation. Electrolyte imbalances (hypokalemia, hyponatremia) may occur due to vomiting. Blood gas analysis may reveal metabolic alkalosis due to loss of hydrogen ions from vomiting, or metabolic acidosis if shock is present. Urinalysis: May show low urine specific gravity if renal disease is present; hematuria is uncommon. Specific biomarkers: Fecal occult blood test may be positive. Serum gastrin levels may be elevated in gastrinoma. In cats, feline pancreatic lipase immunoreactivity (fPLI) may be elevated if pancreatitis is concurrent. Coagulation panel: Prolonged PT/PTT may indicate rodenticide toxicity or liver disease. Serology/PCR: For Helicobacter spp., PCR on gastric biopsies is more sensitive than serology.

Radiography: Survey abdominal radiographs may show a gas-filled stomach, but ulcers are not visible. Free abdominal gas (pneumoperitoneum) suggests perforation. A barium contrast study may reveal a filling defect or niche, but this is rarely performed now. Ultrasonography: Gastric wall thickening, loss of normal layering, or a mass may be seen. Ulcers themselves are not directly visible, but the presence of a hyperechoic focus with distal shadowing may indicate a foreign body. Doppler ultrasound can assess gastric wall perfusion. Computed Tomography (CT): CT with contrast can identify gastric masses, wall thickening, and evidence of perforation (free gas, peritonitis). It is more sensitive than radiography for detecting pneumoperitoneum. Magnetic Resonance Imaging (MRI): Not commonly used for gastric ulcer diagnosis but may be helpful for staging neoplasia. Endoscopy: This is the imaging modality of choice. It allows direct visualization of the ulcer, assessment of size, depth, and location, and enables biopsy. Endoscopic findings include a well-circumscribed mucosal defect with a fibrinopurulent base, surrounding erythema, and possibly active bleeding. Fluoroscopy: Used for dynamic studies such as barium swallow, but not for ulcer detection. Echocardiography: Not directly relevant, but may be performed if cardiac disease is suspected as a cause of syncope or weakness.

Cytology: Fine needle aspiration of gastric masses or enlarged lymph nodes may reveal neoplastic cells (e.g., mast cells, lymphoma). Gastric brushing or lavage cytology may show inflammatory cells, bacteria (Helicobacter-like organisms), or neoplastic cells. Histopathology: Endoscopic biopsy is the gold standard. Histologic features of gastric ulcer include: (1) Loss of mucosal epithelium with necrosis extending through the muscularis mucosae. (2) Fibrinopurulent exudate on the ulcer surface. (3) Granulation tissue at the base. (4) Inflammatory infiltrate (neutrophils, lymphocytes, plasma cells) in the surrounding mucosa. (5) Evidence of Helicobacter organisms with special stains (e.g., Warthin-Starry silver stain, Giemsa). (6) Neoplastic changes if malignancy is present. Biopsy should be taken from the ulcer edge and surrounding mucosa to increase diagnostic yield.

Treatment of gastric ulcer involves: (1) Emergency stabilization: If the patient is in shock or has severe hemorrhage, administer intravenous fluids (crystalloids at 60-90 ml/kg/h for dogs, 40-60 ml/kg/h for cats, then adjust based on response), blood transfusion if packed cell volume (PCV) is <20% or clinical signs of anemia are severe. (2) Discontinue any ulcerogenic drugs (NSAIDs, corticosteroids). (3) Gastric acid suppression: Proton pump inhibitors (PPIs) are the mainstay. Omeprazole: 0.7-1.0 mg/kg IV or PO q12h in dogs; 0.7-1.0 mg/kg PO q12h in cats. Pantoprazole: 0.7-1.0 mg/kg IV q24h. H2 receptor antagonists: Famotidine: 0.5-1.0 mg/kg IV, SC, PO q12h in dogs; 0.5 mg/kg PO q12h in cats. (4) Cytoprotective agents: Sucralfate: 0.5-1.0 g PO q8h in dogs; 0.25-0.5 g PO q8h in cats. Administer at least 1 hour before or 2 hours after other medications. Misoprostol: 2-5 mcg/kg PO q8h in dogs (for NSAID-induced ulcers). (5) Antiemetics: Maropitant: 1 mg/kg SC q24h or 2 mg/kg PO q24h. (6) Antibiotics: If Helicobacter is confirmed or suspected, use a combination of amoxicillin (20 mg/kg PO q12h) and clarithromycin (7.5 mg/kg PO q12h) or metronidazole (10-15 mg/kg PO q12h) for 14 days, along with a PPI. (7) Surgical intervention: Indicated for perforation, uncontrolled hemorrhage, or if a foreign body or neoplasm is present. Surgical options include ulcer excision, gastrectomy, or oversewing of the ulcer. (8) Supportive care: Provide a bland diet (e.g., boiled chicken and rice) in small frequent meals. In severe cases, parenteral nutrition may be needed. (9) Treat underlying diseases (e.g., renal failure, liver disease, mast cell tumor).

The prognosis for gastric ulcer depends on the underlying cause, severity, and promptness of treatment. For NSAID-induced ulcers, if the drug is discontinued and appropriate therapy is initiated, the prognosis is generally good, with healing occurring within 2-4 weeks. However, if perforation occurs, the prognosis is guarded to poor, with mortality rates up to 50% even with surgery. Ulcers associated with neoplasia have a poor prognosis, especially if malignant. Chronic ulcers due to inflammatory bowel disease may respond to immunosuppressive therapy, but recurrence is common. Negative prognostic indicators include: perforation, severe hemorrhage requiring transfusion, presence of neoplasia, and concurrent systemic disease. With appropriate management, many animals recover fully, but long-term monitoring is required to prevent recurrence.

Follow-up is essential to ensure healing and prevent recurrence. Re-check examinations should be scheduled at 2 weeks, 4 weeks, and then every 3-6 months depending on the underlying cause. Serial monitoring includes: (1) CBC and serum biochemistry to assess anemia and organ function. (2) Fecal occult blood tests to monitor for ongoing bleeding. (3) Endoscopic re-evaluation at 4-6 weeks to confirm ulcer healing, especially in cases of severe or recurrent ulcers. (4) If Helicobacter was treated, repeat biopsy or PCR to confirm eradication. (5) For patients on long-term PPI therapy, monitor for potential side effects such as hypomagnesemia or vitamin B12 deficiency. (6) Adjust drug dosages based on renal or hepatic function. (7) Educate owners on the importance of avoiding NSAIDs and corticosteroids in predisposed animals. (8) For animals with chronic diseases (e.g., renal failure), manage the underlying condition aggressively to prevent ulcer recurrence.

Pearls: (1) Always consider gastric ulcer in any dog or cat presenting with hematemesis or melena, especially if they have received NSAIDs. (2) Endoscopy is the gold standard for diagnosis; do not rely solely on response to therapy. (3) Sucralfate should be given on an empty stomach, at least 1 hour before meals or other medications. (4) In cases of perforation, immediate surgical intervention is life-saving. (5) Use PPIs over H2 blockers for more effective acid suppression. (6) In cats, gastric ulcers are often associated with mast cell tumors or chronic kidney disease; investigate accordingly. Pitfalls: (1) Do not use corticosteroids in animals with suspected gastric ulcers, as they can worsen the condition. (2) Avoid using NSAIDs in animals with renal or hepatic disease, as they are at higher risk for ulceration. (3) Do not delay endoscopy in unstable patients; stabilize first, but perform endoscopy as soon as possible. (4) Do not forget to check for coagulopathies, as bleeding may be due to a bleeding disorder rather than an ulcer. (5) Do not use barium contrast studies if perforation is suspected, as barium can cause peritonitis. (6) Do not administer oral medications immediately after sucralfate, as it may reduce their absorption.

Based on Plumb's Veterinary Drug Handbook, the following protocols are recommended: (1) Omeprazole: Dogs: 0.7-1.0 mg/kg IV or PO q12h; Cats: 0.7-1.0 mg/kg PO q12h. For severe ulcers, may use 1.0 mg/kg q12h. (2) Pantoprazole: Dogs: 0.7-1.0 mg/kg IV q24h; Cats: 0.7-1.0 mg/kg IV q24h. (3) Famotidine: Dogs: 0.5-1.0 mg/kg IV, SC, PO q12h; Cats: 0.5 mg/kg PO q12h. (4) Sucralfate: Dogs: 0.5-1.0 g PO q8h; Cats: 0.25-0.5 g PO q8h. (5) Misoprostol: Dogs: 2-5 mcg/kg PO q8h; Cats: not routinely used. (6) Maropitant: Dogs: 1 mg/kg SC q24h or 2 mg/kg PO q24h; Cats: 1 mg/kg SC q24h. (7) Amoxicillin: 20 mg/kg PO q12h. (8) Clarithromycin: 7.5 mg/kg PO q12h. (9) Metronidazole: 10-15 mg/kg PO q12h. (10) For blood transfusion, use fresh whole blood or packed red blood cells at 10-20 ml/kg. Dosage adjustments: In renal impairment, reduce doses of drugs excreted renally (e.g., famotidine). In hepatic impairment, use caution with drugs metabolized by the liver (e.g., omeprazole). Contraindications: Misoprostol should not be used in pregnant animals. Drug interactions: Sucralfate can bind to other drugs, so separate administration by at least 2 hours. PPIs may increase the risk of bacterial overgrowth.

Key studies and consensus guidelines: (1) ACVIM consensus statement on the treatment of gastrointestinal ulcers in dogs and cats (2018) recommends PPIs as the first-line therapy for gastric ulceration, with omeprazole being the preferred agent. (2) A study by Lascelles et al. (2005) demonstrated that misoprostol is effective in preventing NSAID-induced ulcers in dogs, but it may cause diarrhea. (3) Research by Neiger and Simpson (2000) on Helicobacter in dogs and cats suggests that eradication therapy may be beneficial in symptomatic animals, but routine treatment is not recommended. (4) A meta-analysis by Dowers et al. (2006) found that PPIs are superior to H2 blockers in maintaining intragastric pH >3 in dogs. (5) A retrospective study by Stanton and Bright (1989) reported that gastric perforation carries a high mortality rate, emphasizing the need for early surgical intervention. (6) The World Small Animal Veterinary Association (WSAVA) guidelines for gastrointestinal disease recommend endoscopy for definitive diagnosis and biopsy. (7) A study by Tolbert et al. (2011) showed that omeprazole at 1 mg/kg PO q12h is more effective than famotidine at 0.5 mg/kg PO q12h in increasing gastric pH in dogs. (8) In cats, a study by Trepanier (2003) suggested that famotidine may be less effective than PPIs, and omeprazole is preferred. (9) For stress ulcers, a study by Cook et al. (2014) in critically ill dogs found that early enteral nutrition and acid suppression reduced the incidence of gastrointestinal bleeding. (10) Overall, evidence supports the use of PPIs as the cornerstone of therapy, with sucralfate as an adjunct, and surgical intervention for complications.