Peptic Ulcers • Disruption of mucosal integrity of any portion of GI tract exposed to aggressive action of acidic peptic juices leading to local defect or excavation due to active inflammation
• Mostly solitary • 98% are either in first portion of duodenum or in stomach • Other sites– Margins of gastroenterostomy (stomal ulcer) – Duodenum, stomach or jejunum of patients with zollinger-ellison syndrome – Within or adjacent to meckel’s diverticulum that contains ectopic gastric mucosa
Pathogenesis Two conditions for development of peptic ulcers: 1.H. pylori infection 2.mucosal exposure to gastric acid and pepsin
Mechanism of PU
Normal mucosa
Increased damage
Impared defence mechanism
H. pylori • Most important in pathogenesis of peptic ulcer • Present in 70% to 90% of duodenal ulcers and in about 70% of gastric ulcers
• H. pylori can lead to a variety of upper gastrointestinal disorders 1.Gastric inflammation (gastritis) 2.Peptic ulcer disease (10%–20%) 3.Distal gastric adenocarcinoma (1%2%) 4.Gastric mucosal-associated lymphoid tissue (MALT) lymphoma (<1%)
Mechanisms to Escape Low pH • H. pylori produces urease • Urease convert urea into ammonia and carbon dioxide • Spiral cell shape of Helicobacter supports screwlike movement, which facilitates motility within viscous mucus using polar flagella
Adhesion to Epithelial Cells • ∼20% of H. pylori present in gastric mucosa are adhered to surface of epithelial cells • Adherence - mediated by subset of H. pylori-encoded autotransporter proteins (BabA, SabA, AlpA, AlpB, HopZ, and OipA)
â&#x20AC;˘ Interactions of H. pylori with host epithelial surfaces cause cellular damage and inflammation â&#x20AC;˘ Proteases and phospholipases break down glycoprotein-lipid complexes in gastric mucus, weakens first line of mucosal defense
• Bacteria induce Th1 type response • Producing proinflammatory cytokines IL-1, IL-6, TNF, and, IL-8 induces intense inflammatory and immune response
â&#x20AC;˘ H. pylori also expresses lipopolysaccharide which attracts inflammmatory cells to mucosa â&#x20AC;˘ Bacterial platelet-activating factor promotes thrombotic occlusion of surface capillaries
Vacuolating cytotoxin (VacA): • Block proliferation of CD4+ cells • Inhibits proliferation of B-cells and CD8+cells • Able to disrupt normal function of macrophages by either inducing apoptosis or interrupting phagosomal maturation
Role of H pylori in gastric cancer
Morphology Grossly • Round, sharply punched-out craters 2 to 4 cm in diameter • Smaller in duodenum • Common sites anterior and posterior walls of first portion of duodenum and lesser curvature of stomach
• Margins perpendicular • Mild edema of adjacent mucosa • Surrounding mucosal folds may radiate like wheel spokes • Base is clean
Gastric peptic ulcer:
Microscopically â&#x20AC;¢ Four distinguished zones: 1.Layer of necrosis 2.Layer of inflammation 3.Layer of granulation tissue 4.Layer of scar
Clinical Features • Epigastric pain - burning, or boring • Worse at night and occurs usually 1 to 3 hours after meals during day • Relieved by alkalis or food • Nausea, vomiting, bloating, belching • Significant weight loss
Complication • • • •
Bleeding Perforation/Penetration Obstruction of the pyloric channel Malignant transformation