Canine Gastrointestinal Ulceration Study Guide

Overview and Clinical Importance

Gastrointestinal ulceration represents a significant clinical entity in canine medicine and is an important topic for the NAVLE examination. Gastric and duodenal ulcers result from disruption of the protective mucosal barrier, allowing hydrochloric acid, bile acids, and proteolytic enzymes to damage the underlying tissues. Understanding the pathophysiology, etiology, clinical presentation, diagnosis, and treatment of GI ulceration is essential for successful clinical practice and board examination performance.

The stomach and duodenum are the primary sites of ulceration in dogs. NSAID administration, neoplasia, and hepatic disease are the most commonly reported causes of gastroduodenal ulceration in dogs. Ulcers can range from superficial erosions to full-thickness perforations, which carry significant morbidity and mortality.

Pathophysiology

The Gastric Mucosal Barrier

The gastric mucosal barrier is a complex defense mechanism that protects the stomach lining from the harsh chemical environment of gastric luminal contents. This barrier consists of three primary components:

• Surface epithelial cells: Bound by tight junctions that repel fluids and prevent back-diffusion of hydrogen ions
• Mucus layer: Secreted by surface epithelial cells and foveolar cells, forming a protective gel-like coating over the gastric mucosa
• Bicarbonate layer: Secreted by surface epithelial cells, creating a pH gradient that neutralizes acids at the epithelial surface

Mechanisms of Ulcer Formation

Ulceration occurs when there is either increased gastric acid secretion that overwhelms protective mechanisms, or a breakdown of mucosal defenses. The pathophysiological cascade involves:

Injury to the mucosal barrier allows hydrochloric acid, bile acids, and proteolytic enzymes to degrade epithelial cells, disrupt lipid membranes, and induce inflammation and apoptosis. Back diffusion of luminal contents through disrupted tight junctions leads to inflammation and hemorrhage with further acid secretion mediated by inflammatory cells. Mast cell degranulation causes histamine release, perpetuating gastric acid secretion. The inflammatory environment decreases blood flow, resulting in ischemia, impaired cellular repair, and decreased secretion of mucus and cytoprotective prostaglandins.

Regulation of Gastric Acid Secretion

Gastric acid secretion is controlled by central and peripheral neurological and hormonal stimuli. The three primary mediators of gastric acid secretion from parietal cells are:

Etiology of Gastrointestinal Ulceration

Drug-Induced Ulceration

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDs are the most common cause of GI ulceration in dogs. They cause ulceration through two mechanisms:

• Direct topical damage: NSAIDs cause direct irritation to the GI mucosa
• COX-1 inhibition: Cyclooxygenase-1 produces protective prostaglandins (PGE2) that maintain mucosal blood flow, stimulate mucus and bicarbonate secretion, and promote epithelial cell turnover

COX-2 selective NSAIDs (e.g., carprofen, meloxicam, deracoxib) were developed to reduce GI side effects but can still cause ulceration and perforation, even at recommended doses. Studies have shown that 83% of dogs on chronic NSAID therapy have endoscopically visible GI erosions.

NSAID Risk Factors for Ulceration

Corticosteroids

Corticosteroids alone are a controversial cause of GI ulceration. However, healthy dogs receiving corticosteroids at 2 mg/kg/day are 7-11 times more likely to have higher endoscopic lesion scores compared to control groups. The mechanism is thought to involve inhibition of phospholipase A, which reduces cytoprotective prostaglandins.

Neoplasia-Associated Ulceration

Mast Cell Tumors

Mast cell tumors (MCTs) are the most common skin tumor in dogs and are an important cause of GI ulceration. Neoplastic mast cells release histamine, which stimulates H2 receptors on parietal cells, causing gastric acid hypersecretion. Studies show that dogs with MCTs have significantly higher plasma histamine concentrations and GI ulceration occurs in 35-83% of affected dogs at necropsy.

Clinical signs: Vomiting, hematemesis, melena, anorexia, abdominal pain, and in severe cases, intestinal perforation with septic peritonitis.

Treatment: H1 blockers (diphenhydramine 2-4 mg/kg PO BID), H2 blockers (famotidine 0.5-1 mg/kg PO BID), or proton pump inhibitors (omeprazole 0.5-1 mg/kg PO SID-BID) should be administered to all dogs with MCTs.

Gastrinoma (Zollinger-Ellison Syndrome)

Gastrinomas are rare functional neuroendocrine tumors that autonomously secrete gastrin, leading to gastric acid hypersecretion and severe GI ulceration. The classic triad is:

• Non-beta cell pancreatic neuroendocrine tumor
• Hypergastrinemia
• Severe gastroduodenal ulceration

Key diagnostic feature: Fasting serum gastrin concentration is markedly elevated (normal: 15-79 ng/L; gastrinoma: may exceed 1,000 ng/L). Multifocal duodenal ulcers or recurrent gastric ulcers without identifiable cause should prompt evaluation for gastrinoma.

Prognosis: Approximately 72-85% of gastrinomas have already metastasized at diagnosis, primarily to regional lymph nodes and liver.

Primary Gastrointestinal Neoplasia

Primary GI tumors including lymphoma, adenocarcinoma, leiomyoma, and leiomyosarcoma can cause ulceration through direct disruption of the mucosal barrier. Adenocarcinoma is the most common gastric neoplasm in dogs and is often located in the antrum or lesser curvature. Leiomyoma and leiomyosarcoma are particularly prone to causing dramatic GI bleeding.

Metabolic and Systemic Causes

Clinical Signs and Presentation

Most dogs with GI ulceration have nonspecific clinical signs, which can delay diagnosis. It is important to recognize that many dogs with endoscopically confirmed ulcers may be completely asymptomatic.

Common Clinical Signs

Signs of Ulcer Perforation

Perforating ulcers allow gastric contents to leak into the peritoneal cavity, causing septic peritonitis, a life-threatening emergency. Clinical signs include:

• Acute severe abdominal pain with rigid abdomen
• Signs of shock: tachycardia, weak pulses, cool extremities, prolonged CRT
• Fever or hypothermia
• Weakness, collapse, altered mentation
• Vomiting and depression

Exam Focus: The classic "coffee grounds" hematemesis indicates digested blood from upper GI bleeding. True melena is pitch-black and tarry - don't confuse with dark stools from Pepto-Bismol (bismuth) or high-iron diets. Important: GI ulceration does not exclude normal-appearing stool - most dogs with bleeding ulcers do NOT have visible fecal changes.

Diagnostic Approach

Initial Evaluation

A thorough history is critical. Key questions include: recent or current NSAID or corticosteroid use, previous GI disease, known masses or tumors, exposure to toxins, and duration of clinical signs.

Laboratory Abnormalities

Diagnostic Imaging

Abdominal Radiography

Radiographs generally do not diagnose non-perforating ulcers but are useful to rule out obstruction, intussusception, and to detect signs of perforation. Free abdominal gas (pneumoperitoneum) on radiographs is highly suggestive of GI perforation and is a surgical emergency.

Abdominal Ultrasonography

Ultrasound can reveal mural lesions, masses, and peritoneal effusion. Limitations: Overall sensitivity for detecting non-perforated ulcers is low. Gas in the stomach can interfere with visualization. Ultrasound is more useful for detecting masses, peritoneal fluid, and assessing other abdominal organs.

Upper GI Endoscopy (Gold Standard)

Endoscopy is the gold standard for diagnosing GI ulceration. It allows direct visualization of the esophagus, stomach, and proximal duodenum, identification of ulcers and erosions, assessment of bleeding sources, and tissue biopsy for histopathology.

Endoscopic findings: Erosions appear as shallow mucosal disruptions (red to brown/black). Ulcers are deeper, extending into submucosa with a crater-like appearance, often with a central dark (dried blood) or yellow/white (necrosis) area surrounded by elevated, thickened borders. Ulcers are commonly found in the antrum and pylorus.

Abdominocentesis for Suspected Perforation

If perforation is suspected, abdominocentesis with cytology and fluid analysis is diagnostic. Findings consistent with septic peritonitis include:

• Glucose concentration in abdominal fluid significantly lower than blood glucose (difference greater than 20 mg/dL)
• Marked neutrophilic inflammation with degenerate neutrophils
• Intracellular bacteria
• Elevated lactate in peritoneal fluid

Treatment

Treatment of GI ulceration involves three key components: (1) removal of the underlying cause, (2) acid suppression and mucosal protection, and (3) supportive care.

Remove or Address Underlying Cause

• Discontinue NSAIDs and corticosteroids
• Treat mast cell tumors with H1/H2 blockers and consider surgical excision or chemotherapy
• Manage hepatic or renal disease
• Address hypoadrenocorticism with appropriate hormone replacement
• Stabilize critically ill patients and optimize perfusion

Pharmacological Treatment

Supportive Care

• Fluid therapy: Correct dehydration and maintain adequate perfusion; isotonic crystalloids are first-line
• Blood transfusion: pRBCs for significant anemia (PCV less than 20-25%); whole blood if concurrent coagulopathy
• Antiemetics: Maropitant (1 mg/kg SQ/IV q24h) or ondansetron (0.5 mg/kg IV q8-12h) for persistent vomiting
• Nutritional support: Highly digestible, low-fat diet when eating resumes; small frequent meals
• NPO: Nothing per os if perforation suspected or patient is vomiting actively

Surgical Treatment

Indications for surgery include perforated ulcer with peritonitis, uncontrolled hemorrhage despite medical management, failure to respond to 5-7 days of appropriate therapy, and neoplasia requiring resection.

Surgical approach: Primary repair of perforated ulcers can be successful. In one study, 73% of dogs with NSAID-associated full-thickness ulcers survived to discharge following primary surgical repair. Gastrectomy or enterectomy may be required for extensive or neoplastic lesions.

Prognosis

Prognosis varies significantly based on the underlying cause and severity:

• Non-perforating ulcers: Generally good prognosis; most respond to treatment within 5-7 days
• Drug-induced ulcers: Good prognosis if offending drug is discontinued and appropriate treatment initiated
• Perforating ulcers: Approximately 60% mortality rate with perforation and peritonitis
• Neoplasia-associated: Poor prognosis, depending on tumor type; gastrinomas have 72-85% metastasis at diagnosis
• Chronic metabolic disease: Guarded; prognosis depends on management of underlying condition (renal failure, hepatic disease)