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Peptic Ulcer Disease.pptx
- 1. Clinical Therapeutics PEPTIC ULCER DISEASE MaripolU. Tucjang MEDICINE 3C Cagayan State University
- 2. Definition • Ulcers aredefined as a breach in the mucosa of the alimentary tract, which extends through the muscularis mucosa into the submucosa or deeper. • Erosion differs from an ulcer in being partial thickness mucosal defect. • Peptic Ulcers are Chronic most often solitary lesions that occur in any portion of GIT exposed to the aggressive action of acid-peptic juices.
- 3. Gastric Anatomy • Thestomach is “gland with cavity”, extending from its junction with lower end of the esophagus (cardia) to its junction with the duodenum (pylorus). • The stomach has 5 anatomical regions: 1.Cardia 2. Fundus 3. Body 4. Pyloric antrum 5. Pylorus
- 4. Gastric Anatomy • Gastriccardia comprises < 5% of the gastric gland area and contain mucous and endocrine cells. • The 75% of gastric glands are found within the oxyntic mucosa and contain mucous neck, parietal, chief, endocrine, enterochromaffin, and entero-chromaffin-like (ECL) cells. • Pyloric glands contain mucous and endocrine cells (including gastrin cells) and are found in the antrum.
- 5. Physiology of GastricSecretion • Hydrochloric acid and pepsinogen- mucosal injury • Basal Acid- circadian pattern • Cholinergic (Acetylcholine, Gastrin) and Histaminergic (Histamine) inputs- basal acid secretion 5
- 6. Gastroduodenal Mucosal Defense • 3-levelbarrier mucosal defense system: 1. Pre-epithelial- mucus- bicarbonate-phospho lipid layer 2. Epithelial- Surface epithelial cells 3. Subepithelial- microvascular system - prostaglandins regulates the release of mucosal bicarbonate and mucus, inhibit parietal cell secretion, maintain mucosal blood flow and epithelial cell restitution.
- 7. Pathogenesis Gastric acidity Peptic enzymes Aggressive factors • Surface mucus secretion • Bicarbonate secretion into mucus • Mucosal blood flow • Apical surface membrane transport • Epithelial regenerative capacity • Elaboration of PG Defensive Factors
- 8. Pathogenesis • H. pyloriinfection • NSAID • Tobacco • Alcohol • Gastric hyperacidity • Duodenal gatric-reflux • Impaired Defenses • Ischemia • Shock • Delayed gastric-emptying PEPTIC ULCER
- 9. Risk Factors • H.pylori infection • NSAIDS • COPD • Cigarette use • CHD • Alcohol • Obesity • Physiological stress
- 10. Helicobacter pylori Major causeof peptic ulcer disease • Gram-negative, microaerophilic and spiral bacteria • 50% of the world’s population estimated to be infected. • 80-90% in developing countries • 35-40% in the United States -50-70% of duodenal ulcers -30-60% of gastric ulcers • Transmission occurs from person to person- oral-oral or fecal- oral route
- 11. Pathophysiology H. pylori Bacterial Geneproducts Lipopolysaccharide antigens Urease Phospholipases Proteases Pro-inflmmatory cytokines TNF, IL-8 IL-1, IL-6 Immunologic (T & B cells) Thrombotic effect of PAF Enhances acid secretion Impairs duodenal HCO3- MUCOSAL EPITHELIAL DAMAGE
- 12. Pathophysiology Phospholipase A2 inhibits NSAIDS COX Membranephospholipids Arachidonic Acid PG depletion Endothelial Effects Stasis Ischemia Epithelial effects Increase in HCl secretion Decrease mucin secretion Decrease HCO3- secretion Decrease surface active phospholipids secretion Decrease epithelial cell proliferation
- 13. PUD in thePhilippines • According to the latest WHO data published in 2018. • Number of deaths: 6,283 (1.03%) • Death Rate (Deaths per 100,000 population): 9.69 • Cause of death world rank: 18 Source: Peptic Ulcer Disease in Philippines https://causesofdeathin.com/peptic-ulcer-disease-in-philippines/
- 14. Peptic Ulcer Disease •Peptic Ulcer is the disruption of the mucosal integrity of stomach and/or duodenum leading to a local defect or excavation due to active inflammation. • Ulcers- > 5 mm in size, with depth to the submucosa
- 15. Epidemiology • Duodenal Ulcers -6-15% of the Western population - The incidence of DUs declined • Gastric Ulcers -occur later in life than duodenal lesions -peak incidence reported in the 6th decade of life -more than one-half of gastric ulcers seen in males
- 16. Duodenal vs. GastricUlcers • Duodenal Ulcers - first portion of the duodenum (> 95%) - 1 cm in diameter – can reach 3-6 cm ( giant ulcer) - Ulcers are sharply demarcated - Malignant duodenal ulcers are extremely rare. • Gastric Ulcers - Gastric ulcers can represent a malignancy – biopsied - Benign- distal to the junction between the antrum and the acid secretory mucosa.
- 17. Clinical manifestations Dyspepsia-most common symptoms gnawing, burning, bloating • Abdominal fullness • Nausea and vomiting • Epigastric pain • Bleeding • hematemesis • melena • Changes in weight
- 18. Duodenal vs. GastricUlcers Gastric Ulcers Duodenal Ulcers Malignancy risk Common (should be biopsied) Extremely rare Usual Etiology H. pylori, NSAID- induced injury H. pylori, NSAID- induced injury Pathophysiology Gastric acid output normal or decreased Gastric acid appears to be increased Bicarbonate secretion is significantly decreased Clinical features -Symptoms worse with eating -epigastric pain 15-30 minutes following a meal -pain may be found to the right of the midline in 20% of patients -characterized as burning -Epigastric pain 90 mins-3 hours after a meal -relieved by food and antacids -may interrupt sleep periods of symptoms alternating with periods of remission
- 19. Gastric Ulcers- classified basedon location • Type 1 – Gastric body – low gastric acid production; • Type II – Antrum. Gastric acid from low to normal • Type III- Within 3 cm of the pylorus, accompanied by duodenal ulcers, normal or high gastric acid production; • Type IV- cardia, low gastric acid production
- 20. PUD-related complications 1. Gastrointestinalbleeding – 15% of patients -mortality rate- 2.5 -10% 2. Perforation – 6-7% -mortality rate- > 20% -penetration- ulcer bed tunnels into an adjacent organ - GU: tends to penetrate into the left hepatic lobe - DU: tends to penetrate posteriorly into the pancreas pancreatitis 3. Gastric Outlet Obstruction – 1-2% -relative obstruction- edema in the peripyloric region, often resolves with ulcer healing - fixed, mechanical obstruction- scar formation in the peripyloric area
- 21. Diagnostics for UlcerDetection DIAGNOSTICS REMARKS Barium Studies of Proximal GIT Previously used as a first test for documenting an ulcer. Sensitivity: single contrast= 80%, double contrast= 90% Decreased sensitivity in small ulcers of < .5cm. Upper endoscopy (EGD) Most sensitive and specific approach for examining the upper GIT Allows direct visualization of the mucosa Facilitates documentation of a mucosal defect and tissue biopsy to rule out malignancy (GU) or H. pylori 21
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- 23. Diagnostics for H.pylori Detection
- 24. Forrest Classification CLASSIFICATION DESCRIPTIONRISK OF REBLEEDING IF UNTREATED Acute Hemorrhage Type 1A Arterial Spurting 100% Type 1B Arterial oozing 55% Signs of Recent Hemorrhage Type IIA Non-bleeding visible vessel 43% Type IIB Adherent Clot 22% Type IIC Pigmented flat spot 10% Lesions without Active Bleeding Type III No stigmata of recent bleed Fibrin-coated clean ulcer base 5% 24 Type 1A Type1B Type IIA Type IIB Type IIC Type III
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- 26. MANAGEMENT OF PEPTIC ULCERDSE GOALS: 1. Relief of symptoms 2. Promote ulcer healing 3. Prevent ulcer recurrence and complications A. ACID NEUTRALIZING/INHIBITORY DRUGS • Antacids • H2 Receptor Antagonists • Proton pump inhibitors B. CYTOPROTECTIVE AGENTS • Sucralfate • Bismuth-containing preparations • Prostaglandin analogues
- 27. TREATMENT OF PEPTICULCER DISEASE Class Examples MOA Side Effects Antacids • Aluminum hydroxide 5-30 ml between meals and HS Neutralize gastric acidity • Constipation • Magnesium hydrxide 400 mg PO q4 ( max of 4 doses per day) • Diarrhea H2 Receptor Antagonists • Cimetidine 400 mg BID • Ranitidine 300mg HS • Famotidine 40 mg HS • Competitive inhibition at the parietal cell H2- receptor, suppresses acid secretion • Headache, fatigue, myalgias Proton pump inhibitors • Omeprazole 20 mg BID • Esomeprazole 40 mg BID • Rabeprazole 20mg BID • Pantoprazole 40mg BID • Lanzoprazole 30mg BID • Dexlansoprazole 30mg BID • Covalently bind and irreversibly inhibit H+, K+ - ATPase • Most potent acid inhibitory agent • Maximum efficacy if taken (30-60 minutes) before a meal • Headache, abdominal pain, diarrhea, flatulence, dermatitis, pruritus, dry mouth, blurred vision, angioedema, elevated liver enzymes 27 A. ACID NEUTRALIZING/INHIBITORY DRUGS
- 28. TREATMENT OF PEPTICULCER DISEASE Class Examples Description Side Effects Sucralfate Sucralfate 1 g QID • Becomes a viscous paste within the stomach and duodenum, binding primarily to sites of active ulceration • Act as a physiochemical barrier Constipation Bismuth- Containing Preparations Bismuth subsalicylate 300 mg QID (BSS, Pepto-Bismol) • Mechanism is unclear Black stools Constipation Darkening of the tongue Neurotoxicity (long-term) Prostaglandin Analogues Misoprostol 200 mcg QID • Enhancement of mucosal defense and repair Diarrhea Contraindicate in pregnancy (Misoprostol) 28 B. CYTOPROTECTIVE AGENTS
- 29. ACG H PyloriInfection Guidelines The 2017 American College of Gastroenterology (ACG) guidelines for the treatment of H pylori infection (HPI) include the following recommendations for testing for H pylori : • All patients with active or past history of peptic ulcer disease (unless previous cure of HPI has been documented), or • Those who have low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma • History of endoscopic resection of early gastric cancer • Patients with dyspepsia who are undergoing upper endoscopy (gastric biopsy specimens) • Patients on long-term, low-dose aspirin • Patients initiating long-term therapy with nonsteroidal anti-inflammatory agents (NSAIDs) • Patients with unexplained iron deficiency anemia following standard workup • Adults with idiopathic thrombocytopenic purpura
- 30. First-line therapies of H.pylori Infection • Antibiotic-resistants strains are the most common cause for treatment failure in compliant patients • Choice is based on bacterial resistance patterns, local recommendations and availability. 30
- 32. MANAGEMENT FOR NSAID-INDUCEDULCERS • Intervention for NSAID-related mucosal injury includes: -Treatment of active ulcers -Prevention of future injury A. Treatment of Active Ulcers Medications Remarks Proton Pump Inhibitors • Superior to standard-dose H2 RAs in healing NSAID-induced peptic ulcers • Only PPIs can heal gastric/duodenal ulcers, independent of whether NSAIDS are discontinued or not H2 receptor Antagonists • More effective in healing DUs than GUs • Not preferred agents in patients who require continuous NSAID therapy Misoprostol • Not as effective as PPIs in NSAID-induced ulcer healing • Only gastroprotective agent which can reduce risk of NSAID-induced ulcer complications • Full dose: misoprostol 200mcg QID
- 33. MANAGEMENT FOR NSAID-INDUCEDULCERS B. Prevention of Further Injury Approach to prevention includes: Avoidance of injurious agent or use the lowest possible dose of the agent. Use NSAIDS that are theoretically less injurious Use newer topical NSAID preparations Add concomitant medical therapy to prevent NSAID-induced injury 33 Possible Preventive Measures REMARKS Use nonselective NSAIDS associated with a lower likelihood of GI toxicity • Includes diclofenac, aceclofenac, ibuprofen • However, beneficial effect may be eliminated if higher doses are used. Use concomitant medications prevent injury • Includes a PPI or misoprostol • High-dose H2- receptor blockers (famotidine 40mg BID) have shown promise in preventing ulcers, but PPIs are better Use of selective COX-2 inhibitors like Celecoxib • Advantage of celecoxib in preventing GI complications is offset when aspirin is used simultaneously.
- 34. GUIDE TO NSAIDTHERAPY • Individuals not at risk for cardiovascular events & do not use aspirin and are without risk for GI complications can receive nonselective NSAIDs without gastric protection. • Individuals without cardiovascular risk but with high risk for NSAID-induced GI injury may cautiously use a selective COX-2 inhibitor + high-dose PPI or misoprostol, or consider non- NSAID therapy. • Individuals with CV risk factors & require intake of aspirin and have no risk factors for NSAID- induced GI injury may consider using non- NSAID agent or traditional NSAID with gastric protection, or consider non-NSAID therapy. • Individuals with CV and GI risk factors & require intake of aspirin must consider non- NSAID therapy, and if not possible, then gastric protection must be considered. 34
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- 38. SURGICAL THERAPY 1. Truncal vagotomyand Drainage ( gastrojejunostomy or pyroplasty) - has intermediate complication rate - has 10% ulcer recurrence rate 2. Highly selective vagotomy (which does not require a drainage procedure) - >10% ulcer recurrence rates - lowest overall complication rates 3. Vagotomy and antrectomy (selective) - 1% ulcer recurrence rate - highest complication rates Operations for Duodenal Ulcers:
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- 41. • Selective Vagotomy SelectiveVagotomy is the complete division of the anterior and posterior branches distal to the branching of the hepatobiliary and celiac branches.
- 42. 2 PRINCIPAL TYPESOF REANASTOMOSES: 1. Gastroduodenostomy (Bilroth I) - creation of an anastomosis between the duodenum and the gastric remnant (gastroduodenostomy). 2. Gastrojejunostomy (Bilroth II) - Constructed by sewing a loop of jejunum to the gastric remnant (gastrojejunostomy). 42
- 43. Billroth 1 &Billroth II 43
- 44. SURGICAL THERAPY Operations forGastric Ulcers: 1. Csendes’ Procedure- surgical treatment for gastric ulcers high in the cardia, consisting of subtotal gastrectomy and a large Roux en Y anastomosis 2. Kelling- Madlener procedure- operation for treatment of gastric ulcer located in the proximal cardia that involves 75% gastrectomy and gastrojejunostomy.
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