Pathology of Bronchial Asthma 2011

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Pathology of BronchialPathology of BronchialAsthmaAsthma

BYBY

Dr. Amira Kamal El-Hawary



IntroductionIntroduction::

Non-Specific immunityNon-Specific immunityNeutrophils, MacrophagesNeutrophils, Macrophages

Humoral ImmunityHumoral ImmunityB lymphocytes - AntibodyB lymphocytes - Antibody

Cell mediated ImmunityCell mediated ImmunityT lymphocytes –T lymphocytes –



IntroductionIntroduction::

Primary response – slow, weak.Primary response – slow, weak.

Learning period, memory cells.Learning period, memory cells.

Secondary response – rapid,Secondary response – rapid,

strongstrong



Immune DisordersImmune Disorders:: Immunodeficiency disordersImmunodeficiency disorders

AIDS, antibody deficiencyAIDS, antibody deficiency Hypersensitivity Disorders (allergy)Hypersensitivity Disorders (allergy)

excessive or altered reaction to an antigen producingexcessive or altered reaction to an antigen producing

adverse effects on the body. it is classified into 4adverse effects on the body. it is classified into 4typestypes Type-I (IgE),Type-I (IgE),

Type II-IgG,Type II-IgG,

Type III-Immune complex,Type III-Immune complex, Type IV-Cell mediated.Type IV-Cell mediated.

Autoimmune disordersAutoimmune disorders SLE, Rheumatoid, Rheumatic fever.SLE, Rheumatoid, Rheumatic fever.



Type I hypersensitivity reactionType I hypersensitivity reaction(Atopy(Atopy((

--Pathogenesis:-Pathog

enesis:-- First exposure- First exposure to an antigento an antigen

stimulation of B-lymphocytes tostimulation of B-lymphocytes totransform to IgE secreting plasma cellstransform to IgE secreting plasma cells( helped by CD4+ T-lymphocytes)( helped by CD4+ T-lymphocytes)IgE binds to the surface of mast cellsIgE binds to the surface of mast cells

and basophilsand basophils



First exposure



Type I hypersensitivity reactionType I hypersensitivity reaction

--Second exposureSecond exposure to the same antigento the same antigenresults in cross-linking of Ig E on theresults in cross-linking of Ig E on thesurface of mast cellssurface of mast cellsDegranulation of the cells with releaseDegranulation of the cells with releaseof chemical mediatorsof chemical mediators



SECOND EXPOSUREFIRST EXPOSURE



Chronic obstructive pulmonaryChronic obstructive pulmonary

disease (COPDdisease (COPD(( COPD is a disease state characterized byCOPD is a disease state characterized by

airflow limitation that is not fullyairflow limitation that is not fullyreversible. The airflow limitation isreversible. The airflow limitation isusually both progressive and associatedusually both progressive and associatedwith an abnormal inflammatory responsewith an abnormal inflammatory responseof the lungs to particles or gases.of the lungs to particles or gases.



Obstructive Pulmonary DiseasesObstructive Pulmonary Diseases Classical COPDsClassical COPDs

EmphysemaEmphysema

Chronic BronchitisChronic Bronchitis

Bronchial AsthmaBronchial Asthma



Bronchial asthmaBronchial asthma

Increased responsiveness of theIncreased responsiveness of thebronchial tree to various stimuli thatbronchial tree to various stimuli thatresults inresults in paroxysms of Bronchospasmparoxysms of Bronchospasm

reversible bronchospasmreversible bronchospasm laterlaterchronic bronchial inflammation developchronic bronchial inflammation developand airflow is limited by bronchoconstriction,and airflow is limited by bronchoconstriction,mucus plugs, and increased inflammationmucus plugs, and increased inflammation andandobstructive lung disease developobstructive lung disease develop





Incidence of asthmaIncidence of asthma

It is a common disease affecting 5% ofIt is a common disease affecting 5% ofadults and 7-10% of childrenadults and 7-10% of children..

There has been a significant increase inThere has been a significant increase inthe incidence of asthma in thethe incidence of asthma in theWestern world in the past threeWestern world in the past threedecadesdecades



-- - Clinically , it is manifested byClinically , it is manifested byrecurrent episodes of wheezing,recurrent episodes of wheezing,breathlessness, and cough that isbreathlessness, and cough that isat least partly reversible, eitherat least partly reversible, eitherspontaneously or with treatment.spontaneously or with treatment.

- Between the attacks, patientsBetween the attacks, patientsmay be virtually asymptomaticmay be virtually asymptomatic



What are the Triggering FactorsWhat are the Triggering Factors??

Domestic dust mitesDomestic dust mites Air pollutionAir pollution Tobacco smokeTobacco smoke OccupationalOccupational

irritantsirritants CockroachCockroach

Animal with furAnimal with fur PollenPollen

Respiratory (viral)Respiratory (viral)infectionsinfections

Chemical irritantsChemical irritants Strong emotionalStrong emotional

expressionsexpressions Drugs ( aspirin,Drugs ( aspirin,

beta blockers)beta blockers)



PathogenesisPathogenesis

Common denominator underlying all forms of Common denominator underlying all forms of asthma is an exaggerated bronchoconstrictor asthma is an exaggerated bronchoconstrictor

response (airwayresponse (airway hyperresponsivenesshyperresponsiveness) to a) to a

variety of stimuli. Airway hyperresponsivenessvariety of stimuli. Airway hyperresponsivenesscan be readily demonstrated in the form of can be readily demonstrated in the form of

increased sensitivity to bronchoconstrictive agentsincreased sensitivity to bronchoconstrictive agents



PathogenesisPathogenesis•

Most current evidence suggests thatMost current evidence suggests that bronchial bronchial inflammation is the substrate for hyperresponsiveness.inflammation is the substrate for hyperresponsiveness.

• What causes the bronchial inflammation?What causes the bronchial inflammation? In extrinsicIn extrinsic(allergic) asthma, it is readily explained by type I(allergic) asthma, it is readily explained by type Ihypersensitivity reactions, but the cause is much lesshypersensitivity reactions, but the cause is much lessclear in patients with intrinsic asthmaclear in patients with intrinsic asthma



INFLAMMATIONINFLAMMATION

Airflow Limitation

SYMPTOMSCough Wheeze

Dyspnoea

TRIGGERSAllergens, Exercise,

Cold Air, SO2 Particulates

PathogenesisPathogenesis

Type I hypersensitivity

INDUCERS

Allergens, Air pollutants,

Virus infections



Pathogenetic TypesPathogenetic Types

AtopicAtopic andand non atopicnon atopic asthmaasthma

•There are two types of asthma,There are two types of asthma,atopicatopic ( with( with evidence of allergen

sensitization))non atopicnon atopic (without(without evidence ofallergen sensitization))

•This distinction is useful from thepoint of pathophysiology, but inclinical practice it is not always

possible to classify asthma.



SECOND EXPOSUREFIRST EXPOSURE



Bronchial Asthma - PathophysiologyBronchial Asthma - Pathophysiology



--Pathogenesis of extrinsic (atopic) asthmaPathogenesis of extrinsic (atopic) asthma

11--Meeting the specific allergen causes sensitizationMeeting the specific allergen causes sensitizationof CD4+ (T н2) cells resulting in release ofof CD4+ (T н2) cells resulting in release ofcytokines (IL-4,5, and 13).cytokines (IL-4,5, and 13).

2- IL-4,5 and 13 cause2- IL-4,5 and 13 cause

a. Stimulation of IgE productiona. Stimulation of IgE productionb. Growth of mast cells.b. Growth of mast cells. 3- Meeting the specific allergen for the second3- Meeting the specific allergen for the secondtime results in an immune reaction which passestime results in an immune reaction which passes

into two phasesinto two phasesi- An early phase starting 30-60 min.afteri- An early phase starting 30-60 min.afterinhalation of the antigen theninhalation of the antigen thenii- A late phase develops after 4-8 hoursii- A late phase develops after 4-8 hours..



Pathogenesis of extrinsic (atopic) asthmaPathogenesis of extrinsic (atopic) asthma

44--During theDuring the

early phaseearly phase

,,

primary mediators areprimary mediators arereleased. They includereleased. They include- Leucotriens which are- Leucotriens which aresythesized from phospholipidsythesized from phospholipid

by phospholipase enzymeby phospholipase enzyme- Histamine- Histamine- Platelet –Activating Factor- Platelet –Activating Factor

--

These mediators produce …..These mediators produce …..bronchoconstriction,bronchoconstriction,vasodilatation, increasedvasodilatation, increasedvascular permeability andvascular permeability andincreased mucin secretionincreased mucin secretion..



Pathogenesis of extrinsic (atopic) asthmaPathogenesis of extrinsic (atopic) asthma

55--During theDuring the late phaselate phase secondarysecondarymediators are released includingmediators are released including- Eosinophil and neutrophil- Eosinophil and neutrophilchemotactic factorschemotactic factors- IL-4 &5- IL-4 &5

- Platelet Activating factor- Platelet Activating factor

- These mediators- These mediatorsproduce…..produce…..eosinophileosinophil and neutrophiland neutrophilinfiltration to the site of the lesioninfiltration to the site of the lesionthese cells producethese cells produce

a- More mediators that activatea- More mediators that activatemast cells and intensify the initialmast cells and intensify the initialresponse.response.b. Epithelial cell damageb. Epithelial cell damage..



Pathogenesis - Atopic AsthmaPathogenesis - Atopic Asthma::

Airway inflammation with mucosal oedemaAirway inflammation with mucosal oedema

Mucus pluggingMucus plugging



Pathogenesis of non atopicPathogenesis of non atopicasthmaasthma

In which the triggering factors include aspirin;In which the triggering factors include aspirin; pulmonary infections, especially those caused by pulmonary infections, especially those caused byviruses; cold; psychological stress; exercise; andviruses; cold; psychological stress; exercise; andinhaled irritants such as ozone and sulfur dioxide.inhaled irritants such as ozone and sulfur dioxide.

These agents increase airway hyperreactivity in bothThese agents increase airway hyperreactivity in bothnormal and asthmatic subjects. In the latter, however,normal and asthmatic subjects. In the latter, however,the bronchial response, manifested as spasm, is muchthe bronchial response, manifested as spasm, is muchmore severe and sustainedmore severe and sustained

There is usually no personal or family history of There is usually no personal or family history of allergic manifestations, and serum IgE levels areallergic manifestations, and serum IgE levels are

normalnormal..



ExtrinsicExtrinsic

--Type-I (IgE-mediated)Type-I (IgE-mediated)hyper-sensitivity orhyper-sensitivity orallergic reactionallergic reaction

--Triggered byTriggered byenvironmental antigensenvironmental antigens

(dust, pollens, food(dust, pollens, food, ..(, ..(

--Family history ofFamily history of AtopyAtopy

--Begins in childhoodBegins in childhood..

IntrinsicIntrinsic

--Not allergicNot allergic

--Triggered byTriggered byrespiratory tractrespiratory tractinfections &drugsinfections &drugs

(aspirin(aspirin(.(.

--No family historyNo family history

Bronchial Asthma



Lung Morphology in AsthmaLung Morphology in Asthma

Mucous pluggingMucous plugging

BronchospasmBronchospasm

Over inflationOver inflation



Lung Hyperinflation in AsthmaLung Hyperinflation in Asthma



Thick bronchi with MucousThick bronchi with Mucous

plugsplugs



Asthma -Asthma - Microscopic PathologyMicroscopic Pathology

PatchyPatchy necrosisnecrosis of epitheliumof epithelium Sub-mucosalSub-mucosal glandular glandular hyperplasiahyperplasia

Hypertrophy of bronchialHypertrophy of bronchial smoothsmooth musclemuscle EosinophilsEosinophils,, mastmast cellscells;; lymphocytelymphocyte MucousMucous plugs plugs, Whorled mucous plugs, Whorled mucous plugs

((Curschmann’s spiralsCurschmann’s spirals)) Debris of eosinophils (Debris of eosinophils (Charcot-LeydenCharcot-Leyden

crystalscrystals



Microscopic PathologyMicroscopic Pathology



Asthma Microscopic PathologyAsthma Microscopic Pathology

Obstructed

Inflammed

Bronchi



Asthma - Bronchial morphologyAsthma - Bronchial morphology

inflammationinflammation

Gland hyperplasiaGland hyperplasia

Mucous plug inMucous plug inlumenlumen



Inflammation epithelial

damage



Eosinophils in AsthmaEosinophils in Asthma::



Curschmann's spiralsCurschmann's spirals::



Bronchial AsthmaBronchial Asthma



ComplicationsComplications

1. Bronchpneumonia1. Bronchpneumonia

2. Emphysema2. Emphysema

3. Rarely Death may occur in status3. Rarely Death may occur in statusasthamaticus.asthamaticus.

4. Massive Lung Collapse due to bronchial4. Massive Lung Collapse due to bronchial

obstruction by the mucus plug.obstruction by the mucus plug.



Immunological MechanismsImmunological Mechanisms

TypeType ΙΙ hypersensitivity - allergen binds to IgE onhypersensitivity - allergen binds to IgE onsurface of mast cellssurface of mast cells

Degranulation (histamine)Degranulation (histamine)

muscle spasmmuscle spasm inflammatory cell influx (eosinophils)inflammatory cell influx (eosinophils)

mucosal inflammation/oedemamucosal inflammation/oedema

Inflammatory infiltrate tends to chronicityInflammatory infiltrate tends to chronicity



• Eosinophils Eosinophils are key inflammatory cells foundare key inflammatory cells found

in asthma.in asthma.

• Airway remodeling (basement membraneAirway remodeling (basement membrane

thickening and hypertrophy of bronchialthickening and hypertrophy of bronchial

smooth muscle) adds to the element of smooth muscle) adds to the element of

obstructive disease.obstructive disease.



Pathology of Bronchial Asthma 2011

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