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Acid Peptic DisordersThe Spotlight is On!
Charmaine Rochester, PharmD, CDE, CDM, BCPS
Asst Professor, University of Maryland
School of Pharmacy
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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, signsand 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)
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Acid Peptic Disorders
Dyspepsia
Peptic Ulcers
Duodenal Ulcers Stress Ulcers
Gastroesophageal Reflux Disease
(GERD) Gastric Cancers
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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
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Normal Stomach Anatomy
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Gastric Antrum
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Physiology: The SecretoryEpithelial 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
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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
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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
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Epidemiology of Peptic UlcerDisease (PUD)
Development of PUD
4 -10% of Americans
Gastric Ulcer peaks
55-65th year
Duodenal Ulcer
increases with age
until 60 years
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Pathophysiology of Peptic UlcerDisease (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.
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Risk Factors/Aggressors of PUD
Major FactorsHelicobacter Pylori
NSAIDs
Cigarette smokingAcid and pepsin
Other FactorsGenetics
?Foods
?Stress
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Helicobacter Pylori
Bacteria
Gramve 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
http://www.hpylori.com.au/image/pylori1b.jpg7/31/2019 Bio and Patho of Acid Peptic Disorders_2006_1
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Drug Induced PUD
Drug Action
Iron, K+, Tetracyclines Corrosive to mucosaReserpine. TCA,Anticholinergics
sympathetic, parasympathetic
tone acid output
Alcohol acid output (secretagogue)
Causes gastritis, bleeding ispossible, not thought to causeulcer
Caffeine acid production (even
decaffeinated); No in ulcerformation, lowers (LES) so may
cause GERD symptoms
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NSAIDS
Inhibits prostaglandinsynthesis (COXinhibition)
Disrupts functionalmucosal integrity
mucosal blood flow cell regeneration
Direct GI irritation
Antiplatelet effect
(causing bleeding) Ion trapping
acid (basal andmaximal stimulation)
secretion
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Risk Factors for NSAID-Induced GIInjury
History of ulcer or GI complications
Increasing age
Concomitant anticoagulation therapy
Concomitant corticosteroid use
High dose NSAID use or concomitantaspirin/NSAID use
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Conditions Associated withPUD
Fig. 40-2. Feldman: Sleisenger & Fortrans Gastrointestinal and Liver Disease, 7 th ed.
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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
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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
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Effects of Diet and StressDiet and Stress Action
Diet Dyspepsia, may pain - not believed tocause ulcer or assist healing
Physiologicstress
mucosal blood flow, tissue hypoxia,
mucosal lining degradation; e.g. ICU,
sepsis, burn, trauma. Associated withmultiple erosions & significant bleeding
Psychologicalstress
Similar # stressful events in ulcer vs.
non-ulcer patients
tolerance to discomfort
Recent epidemiological data suggest
possible role
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Gastric Ulcer
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Duodenal Peptic Ulcers
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Stages of Ulcer Formation
Sclerosis
UlcerErosion Chronic Ulcer
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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
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Complications of PUD
Hematemesis
Perforation
Diarrhea Obstruction
Nausea
VomitingWeight Loss
Weakness
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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: ? Common Rare
Malignancy:
Rare
Rare 7%
Complications: PUD
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Objective Measures
Melena
Hct, Hgb
Microcytic, hypochromic indices
Pale conjunctiva
BUN/Cr Ratio
Heme +ve stool
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Diagnosis
Gastric Ulcer/Duodenal Ulcer
Upper endoscopy (gold standard)
H. pylori
Noninvasive: Urea breath test, serology
Invasive: biopsy (histology, culture, rapidurease)
NSAID- inducedHistory
Still need to rule out H pylori infection
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Gastroesophageal Reflux Disease(GERD)
Reflux of gastric or intestinal contents
Results in heartburn, burping bitter taste
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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)
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Spectrum of Gastroesophageal
Reflux Disease (GERD)
Acid reflux
Esophagitis
Esophagealulceration
Barretts
esophagus
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Possible ExtraesophagealManifestations of GERD
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
GERD Pathophysiology
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GERD PathophysiologyLoss of LESpressure
-Inappropriaterelaxation
-Increase in intra-abdominalpressure
Aggressive
Factors
Composition
acid/pepsin
-Volume of
refluxateDefects in defense
mechanisms-Anatomical-Mucosal resistance-Esophageal clearance
-Gastric emptying
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Lower Esophageal Sphincter
LES Closed LES Open
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Risk Factors
Factors that decrease LES pressureDiet
Alcohol
SmokingDrugs
Factors that increase intra-abdominal pressure
Obesity Pregnancy
Bending over
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Foods and Drugs Affecting LESRAISE LESPressure
LOWER LES Pressure
Foods Proteins,carbohydrates
Caffeine, Carminatives,
Chocolates, Citrus, Garlic, Fat,
Tomatoes
Drugs Alpha-agonists
Beta-blockersCholinergics
Cisapride
Metoclopramide
Alcohol, -
antagonists,
Anticholinergics
Barbiturates
Beta-agonists
Calcium
channelblockers
Diazepam
Dopamine
Meperidine
MethylxanthinesNarcotics
Nicotine
Nitrates
Progesterone
Prostaglandins
Tricyclic
antidepressants
Estrogen
Adapted from Gonzales et al. DICP 1990;24:1065
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Non Pharmacologic Interventions
Helps 20% of patients
Weight loss
Small size food portions
Loose fitting clothes Cigarette smoking cessation
Avoid chocolate, alcohol, peppermint, fattymeals, spicy meals, citric juices, cola, beer
Avoid meals 2 hours before lying down
Elevate the head of the bed with a 6-8 block
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Elevation of Head of Bed
Complications of GERD
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Complications of GERD
Infants: Failure to Thrive
Esophagitis (histopathological changes)Gradations
Grade I- erythema, edema
Grade II- isolated erosionsGrade III- confluent erosions, superficial ulceration
Grade IV- erosions, deep ulcers, stricture
Peptic stricture
Worsening obstructive lung disease
Barretts esophagus
Malignancy
GERD d C Ri k
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GERD and Cancer Risk
Esophageal adenocarcinoma 8 times higher inpatients with heartburn, regurgitation, or both
at least once a week
Esophageal carcinoma 11 times higher inpatients with nighttime symptoms of GERD
Lagergren J, et al. New Engl J Med. 1999;240:825-831
GERD in Obstructive Lung Disease
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GERD in Obstructive Lung Disease
Lung EffectsAcid aspiration
irritates airways
Vagally-
mediated
bronchospasmvia transient
acid reflux
Reflux Effects Chronic airflow
trapping,diaphragmatic
flattening may reduceLES competency
Lung Dx: -ve
intrathoracicpressure/+ abdominalpressure
Bronchodilators LES