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Acid Peptic DisordersAcid Peptic DisordersThe Spotlight is On!The Spotlight is On!
Charmaine Rochester, Charmaine Rochester, PharmD, CDE, CDM, BCPSPharmD, CDE, CDM, BCPS
Asst Professor, University of Maryland Asst Professor, University of Maryland School of PharmacySchool of Pharmacy
ObjectivesObjectives
At the end of this presentation, the student should be At the end of this presentation, the student should be able to:able to:
Review the anatomy and physiology of the Review the anatomy and physiology of the stomach stomach
Discuss the pathophysiology, risk factors, signs Discuss the pathophysiology, risk factors, signs and symptoms, complications and diagnosis of and symptoms, complications and diagnosis of ulcersulcers
Given a drug associated with ulcer formation, Given a drug associated with ulcer formation, discuss the proposed mechanism of ulcerationdiscuss the proposed mechanism of ulceration
Discuss the pathophysiology, risk factors, signs Discuss the pathophysiology, risk factors, signs and symptoms, and complications of and symptoms, and complications of gastroesophageal disease (GERD) gastroesophageal disease (GERD)
Acid Peptic DisordersAcid Peptic Disorders
DyspepsiaDyspepsiaPeptic UlcersPeptic UlcersDuodenal UlcersDuodenal UlcersStress UlcersStress UlcersGastroesophageal Reflux Disease Gastroesophageal Reflux Disease
(GERD)(GERD)Gastric CancersGastric Cancers
DyspepsiaDyspepsia
A constellation of upper abdominal A constellation of upper abdominal symptomssymptoms
Accounts for up 40 - 70% of GI complaints Accounts for up 40 - 70% of GI complaints Significant societal costs Significant societal costs CausesCauses
PUD, GERD, gastric cancerPUD, GERD, gastric cancerFood, medications, but commonly idiopathic Food, medications, but commonly idiopathic
Normal Stomach AnatomyNormal Stomach Anatomy
Gastric AntrumGastric Antrum
Physiology: The Secretory Physiology: The Secretory Epithelial CellsEpithelial 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
Gastric Acid and its FunctionGastric Acid and its Function
Gastric Acid ContentsGastric Acid ContentsHCl, salts, pepsin, mucus, water, intrinsic HCl, salts, pepsin, mucus, water, intrinsic
factor, bicarbonate factor, bicarbonate
Gastric Acid FunctionGastric Acid Functionto kill micro-organisms to kill micro-organisms to activate pepsinogento activate pepsinogenbreaks down connective tissue in foodbreaks down connective tissue in food
Mucosal Defenses/ProtectionMucosal Defenses/Protection
Mucus layer on gastric surface Mucus layer on gastric surface Mucosal barrier to damageMucosal barrier to damage
Bicarbonate: Abundant in mucus layer Bicarbonate: Abundant in mucus layer Prevent acidic damage and auto digestionPrevent acidic damage and auto digestion
Prostaglandins are cytoprotective Prostaglandins are cytoprotective Increase blood flow and cell regenerationIncrease blood flow and cell regeneration
Mucosal integrityMucosal integrityMaintained by tight cell junctionsMaintained by tight cell junctions
Epidemiology of Peptic Ulcer Epidemiology of Peptic Ulcer Disease (PUD)Disease (PUD)
Development of PUDDevelopment of PUD 4 -10% of Americans4 -10% of Americans Gastric Ulcer peaks Gastric Ulcer peaks
55-6555-65thth year year Duodenal Ulcer Duodenal Ulcer
increases with age increases with age until 60 yearsuntil 60 years
Pathophysiology of Peptic Ulcer Pathophysiology of Peptic Ulcer Disease (PUD)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;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.
Risk Factors/Aggressors of PUDRisk Factors/Aggressors of PUD
Major FactorsMajor FactorsHelicobacter PyloriHelicobacter PyloriNSAIDsNSAIDsCigarette smokingCigarette smokingAcid and pepsinAcid and pepsin
Other FactorsOther FactorsGeneticsGenetics?Foods?Foods?Stress?Stress
Helicobacter PyloriHelicobacter Pylori
BacteriaBacteria Gram –ve spiral bacteriumGram –ve spiral bacterium 40% of patients >60 yrs are +ve for H.pylori40% of patients >60 yrs are +ve for H.pylori Transmitted: possibly person to personTransmitted: possibly person to person Most common cause of antral gastritisMost common cause of antral gastritis
Mechanism of gastric injuryMechanism of gastric injury CytotoxinCytotoxin Breakdown of mucosal defensesBreakdown of mucosal defenses Adherence to epithelial cellsAdherence to epithelial cells Increase gastrin releasing peptide (GRP)Increase gastrin releasing peptide (GRP) Decrease bicarbonate secretionDecrease bicarbonate secretion
Drug Induced PUDDrug Induced PUD
DrugDrug ActionAction
Iron, K+, Iron, K+, TetracyclinesTetracyclines
Corrosive to mucosaCorrosive to mucosa
Reserpine. TCA, Reserpine. TCA, AnticholinergicsAnticholinergics
sympathetic, sympathetic, parasympathetic parasympathetic tone – tone – acid output acid output
AlcoholAlcohol acid output (secretagogue)acid output (secretagogue)
Causes gastritis, bleeding is Causes gastritis, bleeding is possible, not thought to possible, not thought to causecause ulcerulcer
CaffeineCaffeine acid production (even acid production (even decaffeinated); No decaffeinated); No in ulcer in ulcer formation, lowers (LES) so may formation, lowers (LES) so may cause GERD symptomscause GERD symptoms
NSAIDSNSAIDS
Inhibits prostaglandin Inhibits prostaglandin synthesis (COX synthesis (COX inhibition) inhibition)
Disrupts functional Disrupts functional mucosal integritymucosal integrity
mucosal blood flowmucosal blood flow cell regenerationcell regeneration Direct GI irritationDirect GI irritation Antiplatelet effect Antiplatelet effect
(causing bleeding)(causing bleeding) Ion trapping Ion trapping acid (basal and acid (basal and
maximal stimulation) maximal stimulation) secretionsecretion
Risk Factors for NSAID-Induced GI Risk Factors for NSAID-Induced GI InjuryInjury
History of ulcer or GI complicationsHistory of ulcer or GI complications Increasing ageIncreasing ageConcomitant anticoagulation therapyConcomitant anticoagulation therapyConcomitant corticosteroid useConcomitant corticosteroid useHigh dose NSAID use or concomitant High dose NSAID use or concomitant
aspirin/NSAID useaspirin/NSAID use
Conditions Associated with Conditions Associated with PUDPUD
Fig. 40-2. Feldman: Sleisenger & Fortran’s Gastrointestinal and Liver Disease, 7th ed.
SmokingSmoking
Impairs ulcer healingImpairs ulcer healing Promotes ulcer recurrencePromotes ulcer recurrence Increases the likelihood of ulcer Increases the likelihood of ulcer
complicationscomplications MechanismsMechanisms
Stimulate gastric acid secretion Stimulate gastric acid secretion Stimulate bile salt refluxStimulate bile salt reflux Causes alteration in mucosal blood flowCauses alteration in mucosal blood flow Decrease mucus secretion Decrease mucus secretion Reduces prostaglandin synthesisReduces prostaglandin synthesis Decrease pancreatic bicarbonate secretionDecrease pancreatic bicarbonate secretion
Acid and PepsinAcid and Pepsin
? Mechanism of damage:? Mechanism of damage: gastrin releasing peptide (GRP) gastrin releasing peptide (GRP) defect in inhibition defect in inhibition
of acid productionof acid production mucosal bicarbonate secretionmucosal bicarbonate secretion
basal acid secretory drivebasal acid secretory drive postprandial acid secretory responsepostprandial acid secretory response sensitivity to secretagoguessensitivity to secretagogues
Effects of Diet and StressEffects of Diet and StressDiet and StressDiet and Stress ActionAction
DietDiet Dyspepsia, may Dyspepsia, may pain - not believed to pain - not believed to cause ulcer or assist healingcause ulcer or assist healing
Physiologic Physiologic stressstress
↓↓ mucosal blood flow, tissue hypoxia, mucosal blood flow, tissue hypoxia, mucosal lining degradation; e.g. ICU, mucosal lining degradation; e.g. ICU, sepsis, burn, trauma. Associated with sepsis, burn, trauma. Associated with multiple erosions & significant bleedingmultiple erosions & significant bleeding
Psychological Psychological stressstress
Similar # stressful events in ulcer vs. Similar # stressful events in ulcer vs. non-ulcer patientsnon-ulcer patients
↓↓ tolerance to discomforttolerance to discomfort
Recent epidemiological data suggest Recent epidemiological data suggest possible rolepossible role
Gastric UlcerGastric Ulcer
Duodenal Peptic UlcersDuodenal Peptic Ulcers
Stages of Ulcer FormationStages of Ulcer Formation
Sclerosis
UlcerErosion Chronic Ulcer
Signs and Symptoms of GU or DUSigns and Symptoms of GU or DU
Epigastric painEpigastric pain Not well localized Not well localized Annoying, burning, gnawing, achingAnnoying, burning, gnawing, aching
Duodenal ulcersDuodenal ulcers On an empty stomachOn an empty stomach During the nightDuring the night Between mealsBetween meals Relieved by food and antacidsRelieved by food and antacids Episodic followed with symptomatic periods then no Episodic followed with symptomatic periods then no
occurrenceoccurrence
Complications of PUDComplications of PUD
HematemesisHematemesisPerforationPerforationDiarrheaDiarrheaObstructionObstructionNauseaNauseaVomitingVomitingWeight LossWeight LossWeaknessWeakness
Stress UlcerStress Ulcer Duodenal UlcerDuodenal Ulcer Gastric UlcerGastric Ulcer
Hemorrhage:Hemorrhage:
Frequent, Frequent, associated associated mortalitymortality
Common in Common in posterior wall of posterior wall of duodenal bulb, duodenal bulb, associated with associated with melenamelena
Less common Less common (associated with (associated with hematemesis, coffee hematemesis, coffee grind emesis), melenagrind emesis), melena
Perforation:Perforation:
CommonCommon
When in anterior When in anterior wall of duodenumwall of duodenum
More common in More common in anterior wall of stomachanterior wall of stomach
Obstruction: ?Obstruction: ? CommonCommon RareRare
Malignancy:Malignancy:
RareRare
RareRare 7%7%
Complications: PUDComplications: PUD
Objective MeasuresObjective Measures
MelenaMelenaHct, HgbHct, Hgb
Microcytic, hypochromic indicesMicrocytic, hypochromic indicesPale conjunctivaPale conjunctiva
BUN/Cr RatioBUN/Cr RatioHeme +ve stoolHeme +ve stool
DiagnosisDiagnosis
Gastric Ulcer/Duodenal UlcerGastric Ulcer/Duodenal UlcerUpper endoscopy (gold standard)Upper endoscopy (gold standard)
H. pyloriH. pyloriNoninvasive: Urea breath test, serologyNoninvasive: Urea breath test, serologyInvasive: biopsy (histology, culture, rapid Invasive: biopsy (histology, culture, rapid
urease)urease)NSAID- inducedNSAID- induced
History History Still need to rule out H pylori infection Still need to rule out H pylori infection
Gastroesophageal Reflux Disease Gastroesophageal Reflux Disease (GERD)(GERD)
Reflux of gastric or intestinal contents Reflux of gastric or intestinal contents Results in heartburn, “burping” bitter tasteResults in heartburn, “burping” bitter taste
Signs and Symptoms Signs and Symptoms
Heartburn - hallmark symptomHeartburn - hallmark symptom Typical: Belching, regurgitation Typical: Belching, regurgitation Alarm symptoms: AtypicalAlarm symptoms: Atypical
Weight loss Weight loss Bleeding Bleeding Choking Choking Hoarseness, cough, wheezeHoarseness, cough, wheeze Dysphagia (difficulty swallowing)Dysphagia (difficulty swallowing) Odynophagia (painful swallowing)Odynophagia (painful swallowing) Atypical chest painAtypical chest pain Infants: spitting up, vomiting (uncommon: failure to gain Infants: spitting up, vomiting (uncommon: failure to gain
weight, Fe def anemia, recurrent pneumonia, near SIDS)weight, Fe def anemia, recurrent pneumonia, near SIDS)
Spectrum of Gastroesophageal Spectrum of Gastroesophageal Reflux Disease (GERD)Reflux Disease (GERD)
Acid refluxAcid refluxEsophagitisEsophagitisEsophageal Esophageal
ulcerationulcerationBarrett’s Barrett’s
esophagusesophagus
Possible Extraesophageal Possible Extraesophageal Manifestations of GERDManifestations of GERD
ENTENT PharyngitisPharyngitis Otitis mediaOtitis media SinusitisSinusitis Vocal cord granulomasVocal cord granulomas LaryngitisLaryngitis HoarsenessHoarseness Voice changesVoice changes Chronic coughChronic cough Dental enamel lossDental enamel loss
PulmonaryPulmonary Chronic coughChronic cough AsthmaAsthma Idiopathic pulmonary Idiopathic pulmonary
fibrosisfibrosis Chronic bronchitisChronic bronchitis PneumoniaPneumoniaOtherOther Chest painChest pain Sleep apneaSleep apnea Dental erosionsDental erosions
GERD Pathophysiology 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
Lower Esophageal SphincterLower Esophageal Sphincter
LES Closed LES Open
Risk Factors Risk Factors
Factors that decrease LES pressureFactors that decrease LES pressureDietDietAlcoholAlcoholSmokingSmokingDrugs Drugs
Factors that increase intra-abdominal Factors that increase intra-abdominal pressurepressureObesityObesityPregnancy Pregnancy Bending overBending over
Foods and Drugs Affecting LESFoods and Drugs Affecting LESRAISE LES RAISE LES PressurePressure
LOWER LES PressureLOWER LES Pressure
FoodsFoods Proteins, Proteins, carbohydratescarbohydrates
Caffeine, Carminatives, Caffeine, Carminatives, Chocolates, Citrus, Garlic, Fat, Chocolates, Citrus, Garlic, Fat, TomatoesTomatoes
DrugsDrugs Alpha-agonistsAlpha-agonists
Beta-blockersBeta-blockers
CholinergicsCholinergics
CisaprideCisapride
MetoclopramideMetoclopramide
Alcohol, Alcohol, άά--antagonists, antagonists, AnticholinergicsAnticholinergics
BarbituratesBarbiturates
Beta-agonistsBeta-agonists
Calcium Calcium channel channel blockersblockers
DiazepamDiazepam
DopamineDopamine
MeperidineMeperidine
MethylxanthinesMethylxanthines
NarcoticsNarcotics
NicotineNicotine
NitratesNitrates
ProgesteroneProgesterone
ProstaglandinsProstaglandins
Tricyclic Tricyclic antidepressantsantidepressants
EstrogenEstrogen
Adapted from Gonzales et al. DICP 1990;24:1065Adapted from Gonzales et al. DICP 1990;24:1065
Non Pharmacologic InterventionsNon Pharmacologic Interventions
Helps 20% of patientsHelps 20% of patients Weight lossWeight loss Small size food portionsSmall size food portions Loose fitting clothesLoose fitting clothes Cigarette smoking cessationCigarette smoking cessation Avoid chocolate, alcohol, peppermint, fatty Avoid chocolate, alcohol, peppermint, fatty
meals, spicy meals, citric juices, cola, beermeals, spicy meals, citric juices, cola, beer Avoid meals 2 hours before lying downAvoid meals 2 hours before lying down Elevate the head of the bed with a 6-8” blockElevate the head of the bed with a 6-8” block
Elevation of Head of BedElevation of Head of Bed
Complications of GERDComplications of GERD Infants: Failure to ThriveInfants: Failure to ThriveEsophagitis (histopathological changes) Esophagitis (histopathological changes)
Gradations Gradations Grade I- erythema, edemaGrade I- erythema, edemaGrade II- isolated erosionsGrade II- isolated erosionsGrade III- confluent erosions, superficial ulcerationGrade III- confluent erosions, superficial ulcerationGrade IV- erosions, deep ulcers, strictureGrade IV- erosions, deep ulcers, stricture
Peptic stricture Peptic stricture Worsening obstructive lung diseaseWorsening obstructive lung diseaseBarrett’s esophagus Barrett’s esophagus MalignancyMalignancy
GERD and Cancer RiskGERD and Cancer Risk
Esophageal adenocarcinoma 8 times higher in Esophageal adenocarcinoma 8 times higher in patients with heartburn, regurgitation, or both patients with heartburn, regurgitation, or both at least once a weekat least once a week
Esophageal carcinoma 11 times higher in Esophageal carcinoma 11 times higher in patients with nighttime symptoms of GERDpatients with nighttime symptoms of GERD
Lagergren J, et al. New Engl J Med. 1999;240:825-831
GERD in Obstructive Lung DiseaseGERD in Obstructive Lung Disease
Lung EffectsLung EffectsAcid aspiration Acid aspiration
irritates airwaysirritates airwaysVagally-Vagally-
mediated mediated bronchospasm bronchospasm via transient via transient acid refluxacid reflux
Reflux EffectsReflux EffectsChronic airflow Chronic airflow
trapping, diaphragmatic trapping, diaphragmatic flattening may reduce flattening may reduce LES competencyLES competency
Lung Dx: -ve Lung Dx: -ve intrathoracic pressure/+ intrathoracic pressure/+ abdominal pressureabdominal pressure
Bronchodilators Bronchodilators LES LES pressurepressure