Aetiology and pathophysiology of peptic ulcer disease PUD

Peptic Ulcer Disease (PUD) involves the formation of ulcers in the lining of the stomach, small intestine, or esophagus. Understanding its aetiology (causes) and pathophysiology (mechanisms) is crucial for effective treatment and management.

Aetiology of Peptic Ulcer Disease

1. Helicobacter pylori (H. pylori) Infection:

   • H. pylori is a gram-negative bacterium that colonizes the gastric epithelium. It is a major cause of PUD.
   • The bacterium produces urease, which converts urea to ammonia, neutralizing stomach acid and creating a more hospitable environment for itself.
   • This leads to chronic inflammation (chronic gastritis) and contributes to ulcer formation by damaging the mucosal lining.

2. Non-steroidal anti-inflammatory Drugs (NSAIDs):

   • NSAIDs, such as aspirin and ibuprofen, inhibit cyclooxygenase (COX) enzymes, which are crucial for the production of prostaglandins.
   • Prostaglandins protect the gastric mucosa by promoting mucus and bicarbonate secretion and maintaining mucosal blood flow.
   • Inhibition of COX leads to decreased mucosal defense, making the gastric lining more susceptible to damage from stomach acid.

3. Excessive Acid Production:

   • Conditions like Zollinger-Ellison syndrome, characterized by gastrin-secreting tumors, can lead to excessive gastric acid production.
   • This overwhelms the protective mechanisms of the gastric mucosa, resulting in ulcer formation.

4. Smoking and Alcohol:

   • Smoking impairs mucosal defenses, promotes acid secretion, and is associated with delayed healing of ulcers.
   • Alcohol increases gastric acid secretion and can directly damage the mucosal lining.

5. Stress:

   • While stress alone is not a direct cause, it can exacerbate existing ulcers or impair healing.
   • Stress may influence gastric acid secretion and mucosal protection.

6. Genetic Factors:

   • There may be a genetic predisposition to PUD, particularly in individuals with a family history of the disease.

Pathophysiology of Peptic Ulcer Disease

1. Mucosal Damage:

   • The balance between aggressive factors (e.g., gastric acid, pepsin) and defensive factors (e.g., mucus, bicarbonate, blood flow) is disrupted.
   • H. pylori infection, NSAID use, or other factors lead to increased gastric acid secretion or decreased mucosal defenses.

2. Inflammation and Ulcer Formation:

   • Inflammatory response to H. pylori or NSAIDs damages the epithelial cells of the gastric or duodenal lining.
   • Persistent inflammation leads to erosion of the mucosa and eventually ulcer formation.
   • Ulcers form when the damage extends through the mucosa to the underlying submucosa or deeper tissues.

3. Acid-Peptic Damage:

   • Gastric acid and pepsin are normally protective at physiological levels but become damaging when overproduced or when the mucosal barrier is compromised.
   • The acid damages the epithelial cells, leading to ulceration.

4. Healing and Complications:

   • Healing of ulcers involves epithelial regeneration and mucosal repair, but factors like continued H. pylori infection or NSAID use can impair healing.
   • Complications of PUD include bleeding, perforation, and gastric outlet obstruction.

Effective treatment often involves eradicating H. pylori with antibiotics, reducing gastric acid secretion with proton pump inhibitors (PPIs) or H2-receptor antagonists, and avoiding NSAIDs or other irritants. Addressing lifestyle factors such as smoking and alcohol consumption is also crucial.