Peptic Ulcer Disease

1. Peptic Ulcer Disease

4. Epidemiology Occurs in 5-10% of US population Multiple causes include infection (h. pylori), drugs (NSAID), and chemical (XS acid). Primary ulceration on the decline however drug-induced incidence is increasing due to increased use of NSAIDs.

5. Physiology Acid secretion Mucosal defense barrier

6. k Somatostatin k Physiology: Acid Secretion The parietal cell and gastric acid secretion

7. Physiology: Acid Secretion Stimulation of acid secretion

8. Physiology

9. Physiology

10. Pathophysiology Summary of pathogenic mechanisms in ulcer disease

11. Pathophysiology

12. Pathophysiology Acid & Gastrin levels vary in gastric and Duodenal Ulcer Same relationship for basal and peak levels of acid & gastrin

13. Pathophysiology Primary association with H. pylori

14. Helicobacter Pylori (H. pylori)

15. Pathophysiology: H. pylori • H. pylori promotes ulceration by: • 1. inducing local inflammation and damage to the mucosal barrier. • 2. removing feedback inhibition of acid secretion.

16. Pathophysiology: H. pylori

17. Pathophysiology: H. pylori Gastric metaplasia

18. Pathophysiology: H. pylori Helicobacter pylori's initiation of mucosal inflammation leads to loss of protective mechanisms of gastric mucosa.

19. Pathophysiology: H. pylori

20. Pathophysiology: H. pylori

21. Pathophysiology: H. pylori

22. Pathophysiology: H. pylori

23. Pathophysiology: H. pylori Acid Gastrin

24. H. pylori: 2005 Nobel Prize in Physiology & Medicine

25. Pathophysiology: NSAID induced ulcer

26. NSAID induced ulcer Physiology of endogenous prostaglandins in the stomach: 1. PGE2 and PGI2 synthesized in the gastric mucosa by COX-1 inhibit acid production by binding the EP3 receptor on parietal cells (endogenous regulation of cAMP). 2. PGE2 prevents gastric injury by stimulating the secretion of mucous and bicarbonate in superficial epithelial cells, and by increasing mucosal blood flow. NSAID-Induced Injury: 1. NSAIDs block cyclooxygenase-1 (COX-1). 2. Systemic and localized inhibition of COX-1 can: a. Decrease endogenous regulation of gastric acid release, resulting in higher basal gastric acid levels between meals. b. Decrease bicarbonate and mucous production, resulting in the loss of mucosal integrity. 3. Aspirin and many NSAIDs can directly injure or irritate the stomach lining.

27. Pathophysiology: Zollinger-Ellison ZE Syndrome Less common (~ 1%) Chemical-induced PUD

28. Pathophysiology: ZE Gastrin staining of duodenal gastrinoma

29. Pathophysiology: ZE Location of gastrinomas

30. Pathophysiology: ZE -Gastrin secretion is unregulated -Gastrin and Acid levels extremely high -20% cases are MEN I -no H. pylori present & no use of NASIDs

31. Pathophysiology: ZE Gastric folds in patient with ZE syndrome

32. Clinical Features Clinical manifestations of ulcer disease

33. Clinical Features Complications Bleeding in 10-80%

34. Clinical Features Complications Recurrent bleeding

35. Clinical Features Complications: Peptic ulcer perforation

36. Clinical Features Complications: Outflow Obstruction Acute: inflammation & muscle spasm Chronic: fibrosis & scar formation

37. Clinical Features Cigarette smoking on ulcer recurrence

38. Diagnosis

39. Diagnosis Radiographic features of gastric ulcer

40. Diagnosis Endoscopy: duodenal ulcer

41. Diagnosis Endoscopy: gastric ulcer

42. Diagnosis Urea breath test

43. Treatment: based on pathology & physiology Summary of pathogenic mechanisms in ulcer disease

44. Treatment: Antacids

45. k Somatostatin k Treatment: H-2 receptor Antagonists Plus H2 blocker

46. Treatment: Proton Pump Inhibitor (PPI) (n.b.: binding of PPIs is irreversible)

47. Treatment: Proton Pump Inhibitor (PPI) Degree of acid suppression and rate of duodenal ulcer healing

48. Triple Therapy: Bismith, metronizadole, plus amoxicillin or tetracycline

49. Treatment: Duodenal ulcer healing with Helicobacter pylori treatment + H2 blockers

50. Treatment: PPIs, but not antibiotics, have added benefit of reducing GERD .