PEPTIC ULCER DISEASE medical management.pptx

Peptic ulcer

1. PEPTIC ULCER DISEASE ( ETIOPATHOGENESIS , INVESTIGATIONS, MEDICAL MANAGEMENT ) dr. mayank raj karn Resident 2 nd year ( general surgery) 1

2. CONTENT Introduction Epidemiology Pathogenesis Types of Ulcers Clinical features Investigations Medical management 2

3. INTRODUCTION Peptic ulcers are erosions in the GI mucosa that extend through the muscularis mucosae. The two predominant causes of PUD Helicobacter pylori NSAIDs L ess common mechanisms including ZES, other medication and infectious exposures, radiation therapy , and gastric bypass surgery. 3

4. EPIDEMIOLOGY The incidence and prevalence of PUD in developed countries have been declining in recent decades. D ue to a combination of I ncreased detection and eradication of H. pylori infection, M ore rational NSAID use , E nvironmental factors. Studies have shown decreased hospitalization and mortality related to PUD in the last two to three decades. 4

5. PATHOGENESIS Peptic ulcers are caused by Decreased defensive (protective) factors M ucosal bicarbonate secretion, M ucus production, A dequate blood flow , G rowth factors, C ell renewal, E ndogenous prostaglandins. 5

6. Increased aggressive (Damaging) factors H. pylori infection, NSAIDs, Hydrochloric acid secretion, Pepsins , E thanol ingestion, S moking , D uodenal reflux of bile, Ischemia , H ypoxia. 6

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8. HELICOBACTER PYLORI Over 50% of people worldwide are infected with Helicobacter pylori . Chronic gastritis associated with H. pylori is the most important risk factor for peptic ulcer and gastric adenocarcinoma . Up to 90% of patients with duodenal ulcers , and at least 70% of patients with gastric ulcers, have H. pylori infection . A lso associated with MALT lymphoma , dyspepsia, hyperplastic gastric polyps, and even immune thrombocytopenic purpura. 8

9. H. pylori S piral-shaped, flagellate , gram-negative bacteria. Resides in gastric-type epithelium within or beneath the mucus layer . S trains that lack either flagella or urease are nonpathogenic . Microaerophilic and can live only in gastric epithelium . Thus, can also be found in heterotopic gastric mucosa, in the proximal esophagus, in Barrett esophagus, in gastric metaplasia in the duodenum, within a Meckel diverticulum, and in heterotopic gastric mucosa in the rectum. 9

10. Pathogenesis is due to Flagella Aid its movement through the mucous layer, and it produce enzymes that help it adapt to this hostile environment . Mucolytic enzymes B oth facilitate passage through the mucus layer and protect the bacteria from mucin’s antibiotic effects . Urease Capable of splitting urea into ammonia and bicarbonate, creating an alkaline microenvironment, allowing for the bacteria’s survival in the stomach. 10

11. The bacteria attach to the gastric epithelial cells by binding to surface adhesions . Partially determined genetically, with associations shown with interleukin 1β and toll-like receptors. The exact mechanisms responsible for H. pylori – induced GI injury are still not fully understood. F our potential mechanisms to cause a derangement of normal gastric and duodenal physiology that leads to subsequent ulcer formation. 11

12. Production of toxic products that cause local tissue injury . Locally produced toxic mediators include breakdown products fro urease activity (e.g., ammonia), cytotoxins , mucinase ( which degrades mucus and glycoproteins), phospholipases. Damage both epithelial and mucus cells, and platelet-activating factor (which is known to cause mucosal injury and thrombosis I the microcirculation). 12

13. Induction of a local mucosal immune response . Cause a local inflammatory reaction in the gastric mucosa, attracting neutrophils and monocytes, W hich then produce numerous proinflammatory cytokines and reactive oxygen metabolites. Increased gastrin levels and changes in acid secretion . Basal and stimulated gastrin levels are significantly increased, presumably secondary to a reduction in somatostatin release from antral D cells because H . pylori infection . 13

14. During the acute phase of infection , acid secretion is decreased. With chronic infection, it has trophic effects on ECL and G cells, which can result in acid hypersecretion. A decrease in serum levels of somatostatin could also contribute to the gastric hyperacidity. However , if oxyntic glands are destroyed by the chronic infection, hypoacidity will result. 14

15. Gastric metaplasia occurring in the duodenum . O ccurs as a protective response to decreased duodenal pH, resulting from acid hypersecretion ; T his allows for H. pylori to colonize these areas of the duodenum, which causes duodenitis and likely predisposes to duodenal ulcer formation. The presence of H. pylori in the duodenum is more common in patients with ulcer formation compared with patients with asymptomatic infections isolated to the stomach . Peptic ulcers are also strongly associated with antral gastritis. 15

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17. NONSTEROIDAL ANTIINFLAMMATORY DRUGS NSAIDs, including aspirin, are absorbed through the stomach and small intestine and function as inhibitors of the cyclooxygenase enzymes. Cyclooxygenase enzymes form the rate-limiting step of prostaglandin synthesis in the GI tract . Prostaglandins ( including thromboxane A2) promote gastric and duodenal mucosal protection from luminal acid and pepsin via I ncreasing mucin and bicarbonate secretion, Increasing blood flow to the mucosal endothelium, P romoting epithelial cell proliferation and migration to the luminal surface. 17

18. Compared with H. pylori ulcers, which are more frequently found in the duodenum, NSAID-induced ulcers are more often found in the stomach. H . pylori ulcers are also almost always associated with chronic active gastritis. Gastritis is not frequently found with NSAID-induced ulcers. 18

19. SMOKING S mokers are about twice as likely to develop PUD as nonsmokers. Smoking increases gastric acid secretion and duodenogastric reflux. Smoking decreases both gastroduodenal prostaglandin production and pancreaticoduodenal bicarbonate production . 19

20. SEVERE SYSTEMIC DISEASE (STRESS ULCERS) A breakdown of the gastroduodenal mucosal barrier , often a result of severe physiologic stress and splanchnic hypoperfusion , combined with gastric acid. It can develop within hours in critically ill patients , typically starting in the fundus and spreading distally. Head injury : Cushing ulcer Extensive Burn : Curling ulcer 20

21. GASTRIC ULCER Gastric ulcers rarely develop before the age of 40 years. The peak incidence -- 55 to 65 years . Individuals in a lower socioeconomic class. Non-whites > whites. 21

22. In contrast to the acidification of the duodenum leading to ulcer formation. P atients with gastric ulcers caused by H . pylori can have normal or reduced gastric acid production . Ulcer formation is more likely due to an inflammatory response to the bacterial infection itself. 22

23. MODIFIED JOHNSON CLASSIFICATION Type I Most common (60%), lesser curvature near incisura. Generally not associated with excessive acid secretion and may occur with low to normal acid output . Most occur within 1.5 cm of the histologic transition zone between the fundic and antral mucosa . N ot associated with duodenal, pyloric, or prepyloric mucosal abnormalities . 23

24. Type II 15% located in the body of the stomach, incombination with a duodenal ulcer. Type III 20% Located in prepyloric regions. These two types of ulcer is associated with high gastric acid secretion. 24

25. Type IV 10% occur high on the lesser curvature, near the GE junction. N ot associated with excessive acid secretion. Type V occur at any location. A ssociated with long-term NSAIDs use. 25

26. Gastric ulcers are larger than duodenal ulcers. Most frequent complication is Perforation . Occurs along the anterior aspect of lesser curvature. Bleeding from gastric ulcer usually occur in older patient. Gastric outlet obstruction in patient with Type II and III ulcers. Fibrosis leads to hourglass deformity of stomach. 26

27. A ll gastric ulcers should be regarded as being malignant , no matter how classical the features of a benign gastric ulcer. Multiple biopsies should always be taken, perhaps as many as 10 well-targeted biopsies, before an ulcer can be tentatively accepted as being benign . 27

28. DUODENAL ULCER Duodenal ulceration is a disease with numerous causes. The only requirements are acid and pepsin secretion in combination with infection by H. pylori or ingestion of NSAIDs . Most ulcers occur in the frst part of the duodenum. A chronic ulcer penetrates the mucosa into the muscle coat, leading to fibrosis, resulting in pyloric stenosis . 28

29. When there is both a posterior and an anterior duodenal ulcer is referred to as ‘kissing ulcers ’. Anterior ulcers tends to Perforate. Posterior ulcers tends to Bleed from gastroduodenal artery . Malignancy are rare. 29

30. CLINICAL FEATURES Recurrent episodes of quiescence and relapse. Pain 90% of patient complain of epigastric pain. Duodenal ulcer : Pain 2 to 3 hours after a meal and at night. Two-thirds of patients with duodenal ulcers will complain of pain that awakens them from sleep . Gastric ulcer : Occurs with eating and is less likely to awaken the patient at night. 30

31. Associated symptoms Bloating Abdomen fullness Nausea Early satiety. 31

32. Ulcer complication Complications may be heralded by new ulcer symptoms or change in symptoms or may occur in absence of typical symptoms. Bleeding May present with nausea , Hematemesis , Malena , rarely Hematochezia ( massive bleeding). Gastric Outlet O bstruction Early satiety, bloating, indigestion, anorexia, nausea, vomiting and weight loss. 32

33. Perforation 2 to 10 % Sudden onset of severe diffuse abdomen pain. Sudden onset of abdomen pain, tachycardia, and rigidity is hallmark. Penetration and Fistulation P eptic ulcer may penetrate through the bowel wall without a free perforation or leakage of luminal contents into peritoneal cavity. 33

34. G astroduodenal fistula Gastrocolic or Duodenocolic fistula Halitosis, feculent vomiting, postprandial diarrhea, dyspepsia, and weight loss. Penetration into vascular structure – exsanguinating hemorrhage. Penetration into biliary tree Choledochoduodenal fitula Extrahepatic biliary obstruction Hemobilia . 34

35. INVESTIGATIONS Upper GI radiography Demonstration of barium within ulcer crater, which is usually round or oval and may or maynot be surrounded by edema. Useful to determine location, depth of penetration, and extent of deformation from chronic fibrosis. Double contrast technique is used. 35

36. Flexible Upper Endoscopy Most reliable method for diagnosing gastric and duodenal ulcers . In addition endoscopy provides the ability to sample tissue to evaluate for malignancy and H. pylori infection. M ay be used for therapeutic purposes in the setting of GI bleeding or obstruction. 36

37. Helicobacter pylori testing The gold standard for diagnosis of H . pylori is mucosal biopsy. Noninvasive tests offer an effective screening tool and do not require an endoscopic procedure. If endoscopy is to be performed, evaluation of biopsy samples with either a U rease assay (Sensitivity > 90 %, and specificity is 95% to 100 %) Histologic examination (Sensitivity is 95 % and specificity is 99 %) 37

38. The sensitivity of the test is lowered in patients who are taking PPIs, H2-receptor antagonists, or antibiotics. Evaluation of serum antibodies is the test of choice for initial diagnosis when endoscopy is not required but has the drawback of remaining positive after treatment and eradication of infection. For monitoring treatment efficacy, stool antigen and urea breath testing are both adequate choices. 38

39. MEDICAL MANAGEMENT Lifestyle changes, such as smoking cessation, discontinuing NSAIDs and aspirin, and avoiding coffee and alcohol , help promote ulcer healing . Three broad categories D rugs targeted against H. pylori , D rugs that reduce acid levels by decreasing secretion or chemical neutralization , D rugs that increase the mucosal protective barrier. 39

40. Drugs that reduce acid levels by decreasing secretion or chemical neutralization. Antacids. They reduce gastric acidity by reacting with hydrochloric acid, forming a salt, and raising the gastric pH . Their use has largely been replaced by the more efficacious antisecretory therapies ( either H2-receptor antagonists or PPIs) for the treatment of PUD. 40

41. H2 Receptor Antagonists The H2-receptor antagonists are structurally similar to histamine and function by inhibiting the H2 receptor on parietal cells. All undergo hepatic metabolism and are excreted by the kidney. Famotidine is the most potent, and cimetidine is the weakest. Continuous intravenous (IV) infusion of H2-receptor antagonists has been shown to produce more uniform acid inhibition than intermittent administration. 41

42. Proton pump inhibitors . The most potent antisecretory agents are PPIs. These agents irreversibly bind and inhibit the hydrogenpotassium ATPase on the parietal cell. As a result, they provide a more complete and prolonged inhibition of acid secretion than H2- receptor antagonists. 42

43. Drugs that increase the mucosal protective barrier . Sucralfate It is an aluminum salt of sulfated sucrose that dissociates under the acidic conditions in the stomach. the sucrose polymerizes and binds to the ulcer crater to produce a protective coating that can last for 6 hours . May bind and concentrate endogenous basic fibroblast growth factor, which appears to be important for mucosal healing. 43

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46. Drugs targeted against H. pylori Indications for diagnosis and treatment of Helicobacter pylori Established Active peptic ulcer disease (gastric or duodenal ulcer ). Confirmed history of peptic ulcer disease (not previously treated for H. pylori ). Gastric mucosa-associated lymphoid tissue lymphoma (low grade ). After endoscopic resection of early gastric cancer. Uninvestigated dyspepsia (depending on H pylori prevalence). 46

47. Controversial Nonulcer dyspepsia. Gastroesophageal reflux disease. Persons using NSAIDs. Unexplained iron deficiency anemia. Populations at higher risk for gastric cancer. 47

48. First-line Helicobacter pylori treatment regimen. Patients Without Penicillin Allergy, Prior Macrolide Exposure , or in Region With >15% Clarithromycin Resistance • Bismuth quadruple therapy (PPI, bismuth, tetracycline, metronidazole) • Clarithromycin triple therapy ( PPI, clarithromycin, and amoxicillin or metronidazole ) • Concomitant regimen (PPI, clarithromycin, amoxicillin, nitroimidazole ) 48

49. Patients Without Penicillin Allergy With Either Prior Macrolide Exposure or in a Region With >15% Clarithromycin Resistance • Bismuth quadruple therapy • Levofloxacin triple therapy (PPI, levofloxacin, amoxicillin) 49

50. Patients With a Penicillin Allergy But Without Prior Macrolide Exposure • Bismuth quadruple therapy • Clarithromycin triple therapy with metronidazole Patients With Both a Penicillin Allergy and Either Prior Macrolide Exposure or in a Region With > 15% Clarithromycin Resistance Bismuth quadruple therapy 50

51. Treatment Duration 14-day course of triple therapy and a 10- to 14-day course of bismuth quadruple therapy . Acid suppression can be stopped after 3 months if the ulcerogenic stimulus (e.g., H pylori, NSAIDs, or aspirin) has been removed. However , long-term maintenance PPI therapy should be considered in all patients Admitted to hospital with ulcer complications All high-risk patients on NSAIDs or aspirin (the elderly or debilitated), All patients requiring anticoagulation or antiplatelet agents or those with a history of recurrent ulcer or bleeding. 51

52. Eradication rates after an initial course of therapy have been decreasing, likely as a result of increased prevalence of antibiotic-resistant strains of H. pylori ; A pproximately 20% of patients fail initial therapy . For this reason, monitoring for infection eradication with a urea breath test, stool antigen, O r repeat endoscopy with biopsy at 4 to 6 weeks after therapy is important, M any patients will require further treatment with alternative regimens. 52

53. REFERENCES Bailey and love’s short practice of surgery 28 th edition . Sabistion textbook of surgery 21 st edition . Schwartz Principles of Surgery, 11th edition. 53

54. 54 THANK YOU..