Peptic Ulcer (peptic ulcer disease)

1. Peptic Ulcer (peptic ulcer disease) Shanghai Ren-Ji Hospital Shanghai Institute of Digestive Disease Wenzhong Liu

2. What is the peptic ulcer ?

3. Definition • Craters extending to below the muscularis mucosa of stomach (GU) or duodenum (DU). • A products of self-digestion.

4. Epidemiology • Estimated life time prevalence :10% • Male: female =3- 4:1 • Ratio of DU: GU = 3:1 • DU emerges 10-20 years earlier than GU

5. Etiology & Pathogenesis

6. Barrier of Gastric Mucosa

7. Etiology & Pathogenesis • Helicobacter pylori infection • NSAIDs & Aspirin • Acid/Pepsin • Smoking • Genetics • Psychological factors Nonsteroidal anti-inflammatory drugs, NSAIDs

8. Etiology & Pathogenesis

9. Aggressive Factors • Acid/Pepsin • H. pylori infection • NSAIDs • Smoking • Defensive Factors • Mucus-bicarbonate barrier • Barrier of apical membrane • Mucosal blood flow • Prostaglandins • Epithelial cell restitution Aggressive Factors  Defensive Factors  I II III Aggressive Factors + Defensive Factors

10. Evolving Knowledge • Dictum • No acid, no ulcer • No acid, no Hp, no ulcer • No Hp, No NSAIDs, no ulcer

11. Under Electromicroscopy

12. Clinical Evidences That H.pylori Infection Plays Major Role in Peptic Ulcer • High prevalence of Hp infection in peptic ulcer. DU: 90-100%; GU:70-90% • Eradication of Hp improves healing of ulcer. Healing refractory ulcer  Shortening treatment course: 4 - 6 weeks 1-2 weeks

13. Clinical Evidences That H.pylori Infection Plays Major Role in Peptic Ulcer • Eradication of Hp markedly reduces relapse and complication rates of ulcer.  50 - 70%/yr < 5%/yr • Prospective study shows that individuals infected with Hp has higher risk of developing peptic ulcer.  15 - 20%

14. Why anti-secretory agents can heal H.pylori associated peptic ulcer? Anti-secretory agents Acid  Mucosal Barrier

15. “Leaking Roof ” Hypothesis Mucosal Barrier

16. The strongest evidence for the pathogenic role of H. pylori in peptic ulcer disease is the marked decrease in the recurrence rate of ulcers following the eradication of infection.

17. “for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease”

20. Why only a part of patients with H.pylori infection have peptic ulcer? H.pylori Virulence Host Factor Environment Factors IL-1B polymorphism

22. NSAIDs & Peptic Ulcer

23. Gastric acid plays a central role inNSAID-associated gastroduodenal damage Bicarbonate layer Surface epithelial cells

24. NSAID Damage to the Gastric Mucosa Scanning electron micrographs of normal gastric mucosa (left) andmucosal surface (right) 16 minutes after administration of aspirin Baskin et al 1976

25. Two Common Forms of Peptic Ulcer • H.pylori – associated: 70-85% • NSAIDs – associated: 10-25% Non-Hp, Non-NSAID Ulcer: 5-30%

26. Acid /Pepsin • By definition, peptic ulcer is caused by autodigestion of acid and pepsin • Activity of pepsin is pH-depedent Pepsinogen pepsin pH< 4 Maintaining activity pH< 4 • Usual therapy toward suppression of acid

27. The influence of pH on gastricpepsin activity 1 2 3 4 Adapted from Berstad 1970

28. Smoking & Peptic Ulcer • Increasing incidence of peptic ulcer • Delaying healing of ulcer • Increasing relapse and complication • Mechanisms: Facilitating bile reflux Decreasing mucosal blood supply Inhibiting synthesis of PGs

29. Genetics & Peptic Ulcer • Familial Clustering  Genetic factors  Environment factor : H. pylori infection

30. Genetics & Peptic Ulcer • Concordance of peptic ulcer is more common in monozygotic that dizygotic twins. • Peptic ulcer occurs in a few rare inherited syndromes. Gastrinoma Mastocytosis

31. Psychological Factor in Peptic Ulcer • Controversial • Possible mechanisms through vagal mechanisms, Stimulating acid secretion Decreasing mucosal blood supply

32. Clinical Presentation • Symptoms are neither specific nor sensitive • Silent Ulcer Emergence of complications: bleeding, perforation Discovered by chance

33. Clinical Presentation • Acid dyspepsia in DU Epigastric “ hunger ” pain or discomfort； Occurred 2-4 hours after meal，or at night; Relieved by food or antacids; • Acid dyspepsia in GU More severe pain； Occurred soon after meal； Less relieved by food or antacids;

34. Physical Examination • Limited value in patients with uncomplicated ulcer. • Epigastric tenderness on deep palpitation in active stage. Sensitivity 50% Specificity 50%

35. Atypical Ulcers • Giant Ulcer DU>2cm, GU>3cm • Pyloric Channel Ulcer Pain occurring shortly after meal.  Poor relief by antacids  Vomiting • Postbulbar Ulcers • Multiple Ulcers

36. Laboratory Examination • Detection of H. pylori Infection Essential • Gastric Secretory Test For ruling out Zollinger-Ellison Syndrome • Determination of Serum Gastrin level For ruling out Zollinger-Ellison Syndrome • Fecal Occult Blood Test Nonspecific

37. Detection of H. pylori Infection Direct smear PCR 13C- Breath test

38. Warthin -Starry Stain Acridine orange stain

40. Endoscopy versus Radiography • Endoscopy has a greater accuracy of establishing diagnosis than radiography. • Endoscopy can take biopsies for histology, ruling out malignancy, and detection of Hp. • Endoscopy can carry out therapy. • Cost • Risk

43. Endoscopy Gastric ulcers

44. Endoscopy Duodenal ulcer

45. Peptic ulcers

46. Staging of peptic ulcer under endoscopy

47. Barium Radiogram

48. Differential Diagnosis • Functional dyspepsia: By Endoscopy • Zollinger Ellison Syndrome (Gastrinoma) • Gastric Malignant Ulcer: Endoscopy + Biopsy • Biliary or pancreatic diseases: Ultrosonography, MRCP, ERCP

50. Zollinger Ellison Syndrome • Clinical Characteristics  Peptic ulcer with Diarrhea Peptic ulceration in unusual location Multiple ulcers  Refractory ulcer Complications No H.pylori, no NSAIDs • Gastric Secretory Test Basic acid output > 15mEq/hour • Determination of Serum Gastrin level Fasting serum gastrin >500pg/ml