Acid Peptic Disorders The Spotlight is On!

1. Acid Peptic DisordersThe Spotlight is On! Charmaine Rochester, PharmD, CDE, CDM, BCPS Asst Professor, University of Maryland School of Pharmacy

2. Objectives At the end of this presentation, the student should be able to: • Review the anatomy and physiology of the stomach • Discuss the pathophysiology, risk factors, signs and symptoms, complications and diagnosis of ulcers • Given a drug associated with ulcer formation, discuss the proposed mechanism of ulceration • Discuss the pathophysiology, risk factors, signs and symptoms, and complications of gastroesophageal disease (GERD)

3. Acid Peptic Disorders • Dyspepsia • Peptic Ulcers • Duodenal Ulcers • Stress Ulcers • Gastroesophageal Reflux Disease (GERD) • Gastric Cancers

4. Dyspepsia • A constellation of upper abdominal symptoms • Accounts for up 40 - 70% of GI complaints • Significant societal costs • Causes • PUD, GERD, gastric cancer • Food, medications, but commonly idiopathic

5. Normal Stomach Anatomy

6. Gastric Antrum

7. Physiology: The Secretory Epithelial Cells Surface Epithelium • Mucus cells • Mucus • 2. Parietal cells • HCL • 3. Chief Cells • Pepsinogen • 4. G cells • Gastrin Opening of gastric pit Parietal cell Chief Cell Parietal cell

8. Gastric Acid and its Function • Gastric Acid Contents • HCl, salts, pepsin, mucus, water, intrinsic factor, bicarbonate • Gastric Acid Function • to kill micro-organisms • to activate pepsinogen • breaks down connective tissue in food

9. Mucosal Defenses/Protection • Mucus layer on gastric surface • Mucosal barrier to damage • Bicarbonate: Abundant in mucus layer • Prevent acidic damage and auto digestion • Prostaglandins are cytoprotective • Increase blood flow and cell regeneration • Mucosal integrity • Maintained by tight cell junctions

10. Development of PUD 4 -10% of Americans Gastric Ulcer peaks 55-65th year Duodenal Ulcer increases with age until 60 years Epidemiology of Peptic Ulcer Disease (PUD)

11. Pathophysiology of Peptic Ulcer Disease (PUD) • Luminal Aggressors • H. pylori • NSAIDs • Acid • Pepsin • Mucosal Defenses • Bicarbonate • Mucus • Prostaglandin • Growth factor • Mucosal regeneration Goldin GF, et al. Gastr Endosco Clin Nor Am. 1996;6;505-526. Saggioro A, et al. Ital J Gastroenterol. 1994;269(suppl 1):3-9. Modlin IN, et al. Acid Related Diseases. 1998;317-362.

12. Risk Factors/Aggressors of PUD • Major Factors • Helicobacter Pylori • NSAIDs • Cigarette smoking • Acid and pepsin • Other Factors • Genetics • ?Foods • ?Stress

13. Helicobacter Pylori • Bacteria • Gram –ve spiral bacterium • 40% of patients >60 yrs are +ve for H.pylori • Transmitted: possibly person to person • Most common cause of antral gastritis • Mechanism of gastric injury • Cytotoxin • Breakdown of mucosal defenses • Adherence to epithelial cells • Increase gastrin releasing peptide (GRP) • Decrease bicarbonate secretion

14. Drug Induced PUD

15. Inhibits prostaglandin synthesis (COX inhibition) Disrupts functional mucosal integrity  mucosal blood flow  cell regeneration Direct GI irritation Antiplatelet effect (causing bleeding) Ion trapping  acid (basal and maximal stimulation) secretion NSAIDS

16. Risk Factors for NSAID-Induced GI Injury • History of ulcer or GI complications • Increasing age • Concomitant anticoagulation therapy • Concomitant corticosteroid use • High dose NSAID use or concomitant aspirin/NSAID use

17. Conditions Associated with PUD Fig. 40-2. Feldman: Sleisenger & Fortran’s Gastrointestinal and Liver Disease, 7th ed.

18. Smoking • Impairs ulcer healing • Promotes ulcer recurrence • Increases the likelihood of ulcer complications • Mechanisms • Stimulate gastric acid secretion • Stimulate bile salt reflux • Causes alteration in mucosal blood flow • Decrease mucus secretion • Reduces prostaglandin synthesis • Decrease pancreatic bicarbonate secretion

19. Acid and Pepsin ? Mechanism of damage: •  gastrin releasing peptide (GRP) defect in inhibition of acid production •  mucosal bicarbonate secretion •  basal acid secretory drive •  postprandial acid secretory response •  sensitivity to secretagogues

20. Effects of Diet and Stress

21. Gastric Ulcer

22. Duodenal Peptic Ulcers

23. Erosion Chronic Ulcer Ulcer Sclerosis Stages of Ulcer Formation

24. Signs and Symptoms of GU or DU • Epigastric pain • Not well localized • Annoying, burning, gnawing, aching • Duodenal ulcers • On an empty stomach • During the night • Between meals • Relieved by food and antacids • Episodic followed with symptomatic periods then no occurrence

25. Hematemesis Perforation Diarrhea Obstruction Nausea Vomiting Weight Loss Weakness Complications of PUD

26. Complications: PUD

27. Objective Measures • Melena • Hct, Hgb • Microcytic, hypochromic indices • Pale conjunctiva •  BUN/Cr Ratio • Heme +ve stool

28. Diagnosis • Gastric Ulcer/Duodenal Ulcer • Upper endoscopy (gold standard) • H. pylori • Noninvasive: Urea breath test, serology • Invasive: biopsy (histology, culture, rapid urease) • NSAID- induced • History • Still need to rule out H pylori infection

29. Gastroesophageal Reflux Disease (GERD) • Reflux of gastric or intestinal contents • Results in heartburn, “burping” bitter taste

30. Signs and Symptoms • Heartburn - hallmark symptom • Typical: Belching, regurgitation • Alarm symptoms: Atypical • Weight loss • Bleeding • Choking • Hoarseness, cough, wheeze • Dysphagia (difficulty swallowing) • Odynophagia (painful swallowing) • Atypical chest pain • Infants: spitting up, vomiting (uncommon: failure to gain weight, Fe def anemia, recurrent pneumonia, near SIDS)

31. Spectrum of Gastroesophageal Reflux Disease (GERD) • Acid reflux • Esophagitis • Esophageal ulceration • Barrett’s esophagus

32. ENT Pharyngitis Otitis media Sinusitis Vocal cord granulomas Laryngitis Hoarseness Voice changes Chronic cough Dental enamel loss Pulmonary Chronic cough Asthma Idiopathic pulmonary fibrosis Chronic bronchitis Pneumonia Other Chest pain Sleep apnea Dental erosions Possible Extraesophageal Manifestations of GERD

33. GERD Pathophysiology Loss of LES pressure -Inappropriate relaxation -Increase in intra-abdominal pressure Aggressive Factors Composition acid/pepsin -Volume of refluxate Defects in defense mechanisms -Anatomical -Mucosal resistance -Esophageal clearance -Gastric emptying

34. Lower Esophageal Sphincter LES Closed LES Open

35. Risk Factors • Factors that decrease LES pressure • Diet • Alcohol • Smoking • Drugs • Factors that increase intra-abdominal pressure • Obesity • Pregnancy • Bending over

36. Foods and Drugs Affecting LES

37. Non Pharmacologic Interventions Helps 20% of patients • Weight loss • Small size food portions • Loose fitting clothes • Cigarette smoking cessation • Avoid chocolate, alcohol, peppermint, fatty meals, spicy meals, citric juices, cola, beer • Avoid meals 2 hours before lying down • Elevate the head of the bed with a 6-8” block

38. Elevation of Head of Bed

39. Complications of GERD • Infants: Failure to Thrive • Esophagitis (histopathological changes) • Gradations • Grade I- erythema, edema • Grade II- isolated erosions • Grade III- confluent erosions, superficial ulceration • Grade IV- erosions, deep ulcers, stricture • Peptic stricture • Worsening obstructive lung disease • Barrett’s esophagus • Malignancy

40. GERD and Cancer Risk • Esophageal adenocarcinoma 8 times higher in patients with heartburn, regurgitation, or both at least once a week • Esophageal carcinoma 11 times higher in patients with nighttime symptoms of GERD Lagergren J, et al. New Engl J Med. 1999;240:825-831

41. GERD in Obstructive Lung Disease Lung Effects • Acid aspiration irritates airways • Vagally-mediated bronchospasm via transient acid reflux Reflux Effects • Chronic airflow trapping, diaphragmatic flattening may reduce LES competency • Lung Dx: -ve intrathoracic pressure/+ abdominal pressure • Bronchodilators  LES pressure