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

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Presentation on theme: "Acid Peptic Disorders The Spotlight is On! Charmaine Rochester, PharmD, CDE, CDM, BCPS Asst Professor, University of Maryland School of Pharmacy."— Presentation transcript:

1 Acid Peptic Disorders The 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 Review the anatomy and physiology of the stomach Discuss the pathophysiology, risk factors, signs and symptoms, complications and diagnosis of ulcers 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 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) Discuss the pathophysiology, risk factors, signs and symptoms, and complications of gastroesophageal disease (GERD)

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

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

5 Normal Stomach Anatomy

6 Gastric Antrum

7 Physiology: The Secretory Epithelial Cells Surface Epithelium Opening of gastric pit Parietal cell Chief Cell Parietal cell 1. Mucus cells Mucus 2. Parietal cells HCL 3. Chief Cells Pepsinogen 4. G cells Gastrin

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

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

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

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

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

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

14 Drug Induced PUD DrugAction Iron, K+, Tetracyclines Corrosive to mucosa Reserpine. TCA, Anticholinergics  sympathetic,  parasympathetic tone –  acid output Alcohol  acid output (secretagogue) Causes gastritis, bleeding is possible, not thought to cause ulcer Caffeine  acid production (even decaffeinated); No  in ulcer formation, lowers (LES) so may cause GERD symptoms

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

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

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

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

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

20 Effects of Diet and Stress Diet and Stress Action Diet Dyspepsia, may  pain - not believed to cause ulcer or assist healing Physiologic stress ↓ mucosal blood flow, tissue hypoxia, mucosal lining degradation; e.g. ICU, sepsis, burn, trauma. Associated with multiple erosions & significant bleeding Psychological stress Similar # stressful events in ulcer vs. non-ulcer patients ↓ tolerance to discomfort Recent epidemiological data suggest possible role

21 Gastric Ulcer

22 Duodenal Peptic Ulcers

23 Stages of Ulcer Formation Sclerosis Ulcer ErosionChronic Ulcer

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

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

26 Stress Ulcer Duodenal Ulcer Gastric Ulcer Hemorrhage: Frequent, associated mortality Common in posterior wall of duodenal bulb, associated with melena Less common (associated with hematemesis, coffee grind emesis), melena Perforation:Common When in anterior wall of duodenum More common in anterior wall of stomach Obstruction: ? CommonRare Malignancy:RareRare7% Complications: PUD

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

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

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

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

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

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 Lower Esophageal Sphincter LES ClosedLES Open

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

36 Foods and Drugs Affecting LES RAISE LES Pressure LOWER LES Pressure Foods Proteins, carbohydrates Caffeine, Carminatives, Chocolates, Citrus, Garlic, Fat, Tomatoes DrugsAlpha-agonistsBeta-blockersCholinergicsCisaprideMetoclopramide Alcohol, ά - antagonists, Anticholinergics BarbituratesBeta-agonists Calcium channel blockers DiazepamDopamineMeperidineMethylxanthinesNarcoticsNicotineNitratesProgesteroneProstaglandins Tricyclic antidepressants Estrogen Adapted from Gonzales et al. DICP 1990;24:1065

37 Non Pharmacologic Interventions Helps 20% of patients Weight loss Weight loss Small size food portions Small size food portions Loose fitting clothes Loose fitting clothes Cigarette smoking cessation Cigarette smoking cessation Avoid chocolate, alcohol, peppermint, fatty meals, spicy meals, citric juices, cola, beer Avoid chocolate, alcohol, peppermint, fatty meals, spicy meals, citric juices, cola, beer Avoid meals 2 hours before lying down Avoid meals 2 hours before lying down Elevate the head of the bed with a 6-8” block 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 Infants: Failure to Thrive Esophagitis (histopathological changes) Esophagitis (histopathological changes) Gradations Gradations Grade I- erythema, edema Grade I- erythema, edema Grade II- isolated erosions Grade II- isolated erosions Grade III- confluent erosions, superficial ulceration Grade III- confluent erosions, superficial ulceration Grade IV- erosions, deep ulcers, stricture Grade IV- erosions, deep ulcers, stricture Peptic stricture Peptic stricture Worsening obstructive lung disease Worsening obstructive lung disease Barrett’s esophagus Barrett’s esophagus Malignancy Malignancy

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

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


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