Peptic Ulcer Disease

Overview
  • Peptic Ulcer Disease (PUD) refers to ulceration of the stomach or small intestinal wall at minimum to the level of the submucosa. PUD is a disease of adult life and extremely common, especially in the western world, where as many as 10% of adults may be affected.
Pathogenesis
  • Overview
    • The gastric and duodenal mucosa possess a variety of mechanisms which serve to protect these layers from the erosive actions of stomach acid and pepsin. These include the presence of a protective supra-epithelial mucus layer in which acid neutralizing bicarbonate is secreted as well as a tight epithelial barrier which quickly self-repairs following injury. Dysfunction or overwhelming of these mechanisms is the root cause of PUD and is associated with a number of different etiologies as described below.
  • Helicobacter pylori Infection
    • H. pylori infection is more commonly found in those with duodenal ulcers and likely accounts for the fact that most peptic ulcers are of the duodenal subtype. However, the mechanisms by which H. pylori infection result in peptic ulcer disease is still being understood.
  • NSAIDs
    • Prostoglandins are key molecules in maintaining mucosal defense and repair mechanisms as well as preventing excessive stomach acid secretion. Administration of NSAIDs, especially aspirin, which inhibit prostoglandin synthesis, may result in increased stomach acid secretion as well as reduced bicarbonate and gastric mucus production.
  • Zollinger-Ellison Syndrome
    • Zollinger-Ellison Syndrome is characterized by enormous increases in stomach acid secretion which overwhelms otherwise normal mucosal defenses.
Morphology
  • The characteristic histological finding of PUD is full ulceration of the gastric or small intestinal mucosa to the level of the submucosa. Although the term ulceration typically refers to any erosion of the surface epithelium, the term "Peptic Ulcer" is reserved for deeper extents of erosion, into the submucosa. Such a special meaning of "Ulcer" in the gastric and small intestinal context is used as purely epithelial erosions are healed rapidly whereas deeper erosions into the submucosa typically take weeks or months to heal. Classically, peptic ulcers display a smooth base and perpendicular, punched out margins. They must be distinguished from gastric carcinomas of 'excavated' morphology which display an irregular base and heaped-up margins. Nearly all small intestinal ulcers occur in the first part of the duodenum and are five times more common that gastric ulcers.
Clinical Consequences
  • Peptic Ulcers classically present with a gnawing or aching epigastric pain that is relieved with intake of food or antacids; however, vomiting and weight loss can occur. Disease is usually remitting and relapsing over many years. The most feared complications are lower GI bleeding with attendant melena and coffee-ground hematemesis or bowel perforation which can be serious to fatal. Thankfully, neoplastic transformation of the alimentary mucosa due to peptic ulcers does not occur.