1. PEPTIC ULCER DISEASE (PUD) By Dr. Abdelaty Shawky Assistant professor of pathology 1

2. * Definition of peptic ulcer disease: Ulceration of any portion of the gastrointestinal tract exposed to the aggressive action of acidic-peptic secretion. 2

3. * Sites of peptic ulcer disease: Duodenum (DU): First portion. Anterior wall is more often affected. Stomach (GU): Usually antrum. Lesser curvature (common). At the margins of a gastroenterostomy (stomal ulcer) In the duodenum, stomach or jejunum of patients with Zollinger-Ellison syndrome. Within Meckel’s diverticulum that contains ectopic gastric mucosa. 3

4. * Pathogenesis of peptic ulcer : Peptic ulcers are produced by an imbalance between the gastro-duodenal mucosal defense mechanisms and damaging forces. 4

5. 5

6. * Mucosal defense mechanisms: Surface mucous secretion. Bicarbonate secretion into mucous. Tight adherence between epithelial cells to prevent any acid leakage to the inside. Good blood supply to the mucosa Renewal of damaged epithelial cells. Elaboration of prostaglandins. 6

7. * Damaging agents: H. pylori NSAIDs. Aspirin. Cigarette smoking. Alcoholism. Gastric hyperacidity. Duodenal-gastric reflux.. 7

8. Role of H. Pylori infection in the pathogenesis of peptic ulcer: H. pylori infection is present in almost all patients with duodenal ulcers and 70% of cases with gastric ulcers. * Mechanism: 1.H. pylori secretes damaging enzymes; Urease: breaks down urea to toxic compounds e.g. ammonium chloride. Protease breaks down glycoprotein in the gastric mucus). Phospholipases. Damage the cell membranes of surface epithelial cells. 8

9. 2. Bacterial lipopolysaccharide stimulate the surface epithelial cells to release pro-inflammatory cytokines e.g. IL-1, IL-6 and TNF. These attracts inflammatory cells (Neutrophils) to the mucosa and promote the inflammatory reaction 3. H. pylori release bacterial platelet-activating factor promotes thrombotic occlusion of surface capillaries. 9

10. 4. H. pylori enhances gastric acid secretion and impairs duodenal bicarbonate production, thus reducing luminal pH in the duodenum. This altered milieu seems to favor gastric metaplasia (the presence of gastric epithelium) in the first part of the duodenum. - Such metaplastic foci provide areas for H. pylori colonization. 10

11. 11

12. 12

13. * Gross features: Site: Gastric ulcers are located at the antrum toward the lesser curvature. The duodenal ulcer is usually located at the 1 st part anteriorly. Shape: Round, oval. Size: Usually less than 2cm in diameter.  Lesions less than 0.3 cm are likely to be shallow erosions.  Giant ulcers are usually greater than 3cm in diameter. 13

14. Base of ulcer: Firm (formed of bundles of muscles and fibrous tissue). Floor: Clean (gastric juice digest any food particles at the floor. Margin (Surrounding gastric mucosa): Edematous and reddened due to gastritis. Depth of the ulcer: Superficial ulcer penetrate the mucosa reaching up to the muscularis mucosa. Deeply ulcers having their bases on the muscularis propria. 14

15. GU 15

16. Gastric ulcer 16

17. Duodenal ulcer 17

18. * Microscopic features: - Four distinct layers are present in a peptic ulcer in the same sequence starting from the luminal side: 1. Necrotic debris. 2. Non-specific acute inflammatory reaction. 3. Granulation tissue. 4. Fibrosis: replacing the muscle wall and extending into subserosa. 18

19. Microscopic picture of peptic ulcer 19

20. * Complications of PUD: 1. Hemorrhage: leads to hematemesis or melena. 2. Perforation. 3. Healing by fibrosis: causing obstruction. 4. Malignant transformation: rare (0.5% of gastric peptic ulcer). 20

21. * Clinical presentation: A chronic, recurring lesion. Age: Most often diagnosed in middle aged to older adults. Pain: - Epigastric burning or aching pain. -Pain worse at night and 1 to 3 hours after meal during the day specially in duodenal ulcer. -Classically, the pain is relieved by alkalis or food (DU) or vomiting (GU). 21

22. Nausea, vomiting, bloating, and significant weight loss (raising the possibility of some hidden malignancy) are additional manifestations. With penetrating ulcers, the pain is occasionally referred to the back, the left upper quadrant, or chest. This type of pain may be misinterpreted as being of cardiac origin. 22

23. Thanks 23