Bio and Patho of Acid Peptic Disorders_2006_1

7/31/2019 Bio and Patho of Acid Peptic Disorders_2006_1

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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.jpg


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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
http://www.photostogo.com/store/Chubby.asp?ImageNumber=873984


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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

Bio and Patho of Acid Peptic Disorders_2006_1

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