Gastric and Duodenal ulcers

Peptic ulcer disease is a condition in which there is a localized defect in the mucosal lining of the gastrointestinal tract that extends through the muscularis mucosae. These lesions occur in areas exposed to gastric acid and pepsin, most commonly in the stomach (gastric ulcers) and the proximal duodenum (duodenal ulcers).

Etiology and Pathogenesis

Gastric Ulcer (DeBanto J., 2021)

The development of peptic ulcers is multifactorial and based on a disruption of balance between aggressive factors (gastric acid [HCl], pepsin, bile salts, medications such as NSAIDs, and infection with Helicobacter pylori) and protective (mucosal defense) mechanisms of the gastrointestinal mucosa. Under normal physiological conditions, the mucosa is protected by a combination of mechanisms including mucus and bicarbonate secretion, adequate blood flow, prostaglandin synthesis, and rapid epithelial regeneration. When these protective mechanisms are impaired or when damaging influences from aggressive factors are increased, ulcer formation may occur. The 2 most important etiological factors in peptic ulcer disease are infection with Helicobacter pylori and usage of NSAIDs.

Helicobacter Pylori (Živný J., 2025)

Helicobacter pylori is a spiral-shaped, Gram-negative bacterium that colonizes the gastric mucosa as it can adapt to survive the acidic gastric environment.

A key feature is its ability to produce the enzyme urease, which converts urea into ammonia and carbon dioxide. The ammonia neutralizes gastric acid, allowing it to survive, but it is also toxic to epithelial cells and contributes to mucosal injury. In addition, the bacterium disrupts the protective mucus layer, making the underlying epithelium more susceptible to acid and pepsin.

The infection induces a chronic inflammatory response (chronic gastritis) characterized by infiltration of neutrophils and lymphocytes into the gastric mucosa, releasing cytokines, leading to further epithelial damage and impairment of mucosal defenses.

More specifically, when the infection is predominantly located in the antrum, it leads to decreased somatostatin production and increased gastrin secretion, resulting in increased gastric acid output. By increasing the output, excess acid is delivered to the duodenum, predisposing to the formation of duodenal ulcers. In contrast, when the infection involves the body and fundus of the stomach, there is direct mucosal damage and may reduce acid secretion, contributing to the development of gastric ulcers.

Some strains of Helicobacter pylori have also virulence factors making them more pathogenic like CagA (increase inflammation and cancer risk) and VacA (cause cell injury and apoptosis).

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Another major cause of peptic ulcer disease is the use of nonsteroidal anti-inflammatory drugs, including Ibuprofen and Aspirin. These drugs inhibit the cyclooxygenase (COX) enzymes, which are responsible for the synthesis of prostaglandins (main involved are PGE2 and PGI2 produced locally in the gastric mucosa as a key defensive mechanism). Prostaglandins stimulate the secretion of mucus (forms a physical barrier over gastric lining preventing direct contact of acid with epithelial cells and bicarbonate (neutralizes hydrogen ions near mucosal surface), maintain mucosal blood flow (cause vasodilation), and promote epithelial repair (enhance cell proliferation and healing). When prostaglandin production is inhibited by NSAIDs, these protective mechanisms are significantly weakened, resulting the mucosa to become more vulnerable to damage by gastric acid and pepsin.

The risk of ulcer formation with NSAID use is higher in elderly patients, in those taking high doses or multiple NSAIDs, and in individuals with a prior history of peptic ulcer disease.

Other causes

• Gastric Acid Hypersecretion = excessive acid secretion can overwhelm mucosal defenses because increased acid secretion leads to damage of the duodenal mucosa and promotes the development of gastric metaplasia in the duodenum. Altered mucosa can then be colonized by Helicobacter pylori, further contributing to ulcer formation. One condition associated with marked acid hypersecretion is Zollinger–Ellison syndrome (a gastrin-secreting tumor “gastrinoma” leads to excessive stimulation of parietal cells and massive acid production, resulting in multiple, recurrent, and often refractory ulcers).
• Smoking is a significant risk factor for the development and persistence of peptic ulcers. It does not directly cause ulcers but contributes to their formation and impairs healing. Smoking reduces bicarbonate secretion, decreases mucosal blood flow, and interferes with prostaglandin synthesis.
• Alcohol Consumption = Alcohol acts as a mucosal irritant and can damage the gastric epithelium by disrupting the integrity of the mucosal barrier, increases permeability, and can induce inflammation. Alcohol alone is not usually sufficient to cause peptic ulcers, but exacerbates mucosal injury and may worsen existing ulcers.
• Stress-Related Mucosal Damage = Severe physiological stress, particularly in critically ill patients, can lead to the development of acute gastric ulcers. Often referred to as stress ulcers and may occur in conditions such as severe burns (Curling ulcers) or central nervous system injuries (Cushing ulcers). The primary mechanism is reduced mucosal blood flow due to systemic hypotension or shock, leading to ischemia and breakdown of the mucosal barrier. In CNS injuries, there is increased vagal stimulation that can cause excessive acid secretion.

Differences Between Gastric and Duodenal Ulcers

Feature	Gastric Ulcer (GU)	Duodenal Ulcer (DU)
Location	Stomach (usually lesser curvature)	First part of duodenum
Main Pathophysiology	↓ Mucosal defense	↑ Acid secretion
Acid levels	Normal or low	Increased
Most common cause	NSAIDs, Helicobacter pylori	Helicobacter pylori (very strong association)
Age group	Older patients (>50 years)	Younger patients (20–40 years)
Pain relation to meals	Pain worsens with food	Pain relieved by food
Timing of pain	Shortly after eating	2–3 hours after meals, night pain
Weight change	Weight loss (fear of eating)	Weight gain (eating relieves pain)
Vomiting	More common	Less common
Bleeding tendency	Less common but still possible	More common
Perforation site	Anterior wall of stomach	Anterior duodenum
Artery involvement (bleeding)	Left gastric artery	Gastroduodenal artery
Malignancy risk	Possible (must biopsy)	Rare (almost always benign)
H. pylori involvement	Present (~70%)	Present (~90%)
Response to food/antacids	Pain may worsen	Pain improves

Clinical Features

• Epigastric pain, often described as burning, gnawing, or aching. Pain may radiate to the back, especially in posterior ulcers
• Nausea and occasional vomiting
• Bloating and fullness
• Early satiety (common in gastric ulcers)
• Nocturnal pain (common in duodenal ulcers)
• Some cases, especially in elderly patients or those taking NSAIDs, ulcers may be asymptomatic until complications occur

Diagnosis

The gold standard for diagnosis is upper gastrointestinal endoscopy, which allows:

• Direct visualization of the ulcer
• Determination of its location and size
• Biopsy (important in gastric ulcers to exclude cancer)

Detection of Helicobacter pylori

Non-invasive Tests = commonly used, especially in uncomplicated cases:

• Urea breath test: Highly sensitive and specific. The patient ingests urea labeled with carbon isotopes, and if the bacterium is present, urease breaks down urea, releasing labeled carbon dioxide that can be detected in the breath.
• Stool antigen test: Detects bacterial antigens in feces and is useful for both diagnosis and confirmation of eradication after treatment.
• Serology: Less useful in current practice. Detects antibodies against the bacterium, but the test cannot distinguish between active and past infection (risk of false positives).

Invasive Tests (During Endoscopy)

When endoscopy is performed, biopsy specimens can be used for Rapid urease test (CLO test) to detect urease activity or for Histological examination for direct visualization of bacteria and mucosal inflammation

Complications

1. Gastrointestinal Bleeding = occurs when the ulcer erodes into a blood vessel. Patients may present with:

• Hematemesis (vomiting blood)
• Melena (black, tarry stools)
• Anemia or signs of hypovolemic shock

Posterior duodenal ulcers are particularly dangerous because they can erode the gastroduodenal artery.

2. Perforation = occurs when the ulcer penetrates the full thickness of the wall, allowing gastric contents to enter the peritoneal cavity, leading to

• Sudden, severe abdominal pain
• Rigid abdomen
• Signs of peritonitis

3. Penetration = ulcer extends into adjacent organs, most commonly the pancreas. This causes:

• Persistent pain
• Pain radiating to the back
• Lack of response to standard therapy

4. Gastric Outlet Obstruction = Chronic ulcers can cause edema or fibrosis, leading to narrowing of the pyloric canal. Symptoms include persistent vomiting, early satiety, and abdominal distension.

Management

1. Eradication of Helicobacter pylori = combination therapy, usually including a proton pump inhibitor (example – Omeprazole) and antibiotics (examples - Amoxicillin, Clarithromycin, Metronidazole, Tetracycline).

2. Acid Suppression = Proton pump inhibitors (Omeprazole, Pantoprazole) or H2 receptor antagonists (Ranitidine - less common).

3. Mucosal Protection

• Sucralfate = forms a protective barrier over the ulcer
• Misoprostol = replaces prostaglandins

4. Lifestyle Modifications = avoid NSAIDs if possible, stop smoking, limit alcohol consumption, manage stress

References

• Živný J. Examinations in gastroenterology [PowerPoint slides]. Ústav patologické fyziologie, 1. LF UK; 2025.

• Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology. 10th ed. Elsevier; 2021.

• DeBanto J. Peptic ulcer disease [online image]. SoCal Digestive Wellness; 2021. https://www.socaldigestive.com/peptic-ulcer-disease

• StatPearls. Treasure Island (FL): StatPearls Publishing; 2024. https://www.ncbi.nlm.nih.gov/books/NBK534233/