Pathophysiology of Bronchial Asthma.....

Pathophysiology of Bronchial Asthma

1. Respiratory Pathophysiology
Bronchial Asthma
Dr. Vishal Balakrushna Jadhav
Assistant Professor (Pharmacology)
School of Pharmaceutical Sciences (SOPS), SUN
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2. Content
Definition
Prevalence
Etiopathogenesisandtypesofbronchialasthma
a)Extrinsic/allergic/atopic/reaginmediatedbronchialasthma
b)Intrinsic/idiosyncratic/non-atopic/perennialbronchialasthma
c)Mixedtypebronchialasthma.
Pathologicalchanges
Clinicalfeatures
Illustration-Bronchialasthmaandmicroscopicchanges
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3. Definition
Thediseaseofairwayscharacterizedbyanincreasedresponsivenessofthe
tracheobronchialtracttowardsavarietyofthestimuliwhichleadstonarrowing
oftheairwaysalongwithincreasedmucussecretion,mucuspluggingand
mucosaledema.
Itisanepisodicdiseasecharacterizedby-
a)Paroxysms(asuddenattackorworseningorrecurrenceofsymptomsorofa
diseaseorspasmorseizures)ofdyspnoea(difficultorlabouredbreathing),
b)Cough,and
c)Wheezing(acontinuoushighpitchedwhistlingsoundheardinthepatientswith
generalizedairwaysobstruction).
Severeandunremittingformtermedasstatusasthmaticuswhichisoftenfatal,
maycausedeath.
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4. Prevalence-
Itiscommonandprevalentworldwideoccursatallthestagesofage,butnearly
50%casesdevelopsitbeforetheageof10years.Inadults,boththesexes(M/F)
areaffectedequally,butinchildren,theratioofM:Fis2:1.
Etiopathogenesisandtypesofbronchialasthma-
Basedonthestimulithatinitiatingthedevelopmentofasthma-
a)Extrinsic/allergic/atopic/reaginmediatedbronchialasthma,
b)Intrinsic/idiosyncratic/non-atopic/perennialbronchialasthma,and
c)Mixedtypebronchialasthma.
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5. a)Extrinsic/allergic/atopic/reaginmediatedbronchialasthma-
Alsocalledasepisodicbronchialasthmaasitisoccursaftertheexposureto
specificantigensorallergens,andthepatientsofthisasthmaarelessprone
towardsthedevelopmentofstatusasthmaticus.
Themostcommonformofbronchialasthma,beginsinchildhoodorinadult
(earlystages).
Patientsmayhavepersonaland/orfamilyhistoryofprecedingallergicdiseases
suchasrhinitis,urticaria,orinfantileeczema.
Characterizedbythedevelopmentofhypersensitivityreactionstoextrinsic
antigenicsubstancesorallergenswhichareinhaled,e.g.dustparticles,pollens,
animaldenders,mouldsetc.
Occupationalasthmastimulatedbyfumes,gases,organicandchemicaldustsisa
variantofextrinsictypeofbronchialasthma.
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6. CharacterizedbyanincreasedlevelofimmunoglobulinE(IgE,areaginic
antibodywhichactsasaninitiatorofimmediatehypersensitivityreactions)inthe
serumandpositiveskintest.
IgEmediatedtypeIhypersensitivityreactionwhichischaracterizedby-
1.Acuteimmediateresponse-
InitiatedbyIgEsensitizedmastcellsonthebronchialmucosalsurface.
Mastcelldegranulationleadstothereleaseofmediatorslikehistamine,
leukotriens(LTs),prostaglandins(PGs),plateletactivatingfactor(PAF)and
chemotacticfactorforeosinophils&neutrophils.
Thesereleasedinflammatorymediatorsleadstobronchoconstriction,edema,
mucushypersecretion,accumulationofeosinophilsandneutrophils.
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7. II)LatePhasereactions-
Generallyfollowsacuteresponseandisresponsibleforprolongedmanifestation
ofasthma.
CausesanexcessivemobilizationofWBCsincludesbasophilsbesides
eosinophilsandneutrophils.
Furtherreleasesthemediatorsandacceleratedtheeffectsasmentionedinacute
immediateresponse.
Characterizedbyaninflammationcausedbyneutrophilsandbymajorbasic
proteins(MBP)ofeosinophils.
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8. b)Intrinsic/idiosyncratic/non-atopic/perennialbronchialasthma-
Developslaterinadultlifewithnegativepersonalorfamilialhistoryofallergy,
negativeskintestornormallevelofIgEinserum.
Mostofthepatientsexhibitstypicalsymptoms,becomecomplexafterviral
infectiontoupperrespiratorytract.Patientsalsoshowspresenceofassociated
nasalpolypsandchronicbronchitiscondition.
Allergensarenotrecognizedasthecauseofasthma,but10%patientsbecome
hypersensitivetodrugs(smalldosesofaspirin,hencetermedasaspirinsensitive
bronchialasthma).
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9. c)Mixedtypebronchialasthma-
Inthistype,patientsexhibitstheclinicalfeaturesofbothextrinsicandintrinsic
typeofbronchialasthma.
Thepatientswhodevelopsasthmainearlylifehavestrongallergiccomponents
(extrinsictype)whilethosepatientswhodevelopsasthmalateinlifebecome
non-allergic(intrinsictype).
Mayprecipitatedbycold,exerciseandemotionalstress.
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10. Pathologicalchanges-
Pathologicalchangesinbothextrinsicandintrinsictypeofbronchialasthmaare
similar.
Pathologicalexaminationofautopsedlungofthepatientwhodyingduetostatus
asthmaticusshowsthefollowinggrossandmicroscopicchangeswhichare
expectedtobesimilarinnon-fatalcases-
a)Grossexamination-
Overdistensionoflungsduetoover-inflation(expansion,thedistensionofa
partbyair,gasorliquid).
Thecutsurfaceshowscharacteristicocclusionofthebronchi/bronchiolesby
variousmucusplugs.
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11. b)Microscopicexamination-
Mucusplugscontainsnormalordegeneratedrespiratoryepitheliumforming
twistedstripscalledasCurshmann’sspirals.
Sputumcontainsnumerouseosinophilsanddiamondshapecrystalsfroman
eosinophilscalledCharcoat-Leydencrystals(acolorless,hexagonal,needle
likecrystalsfoundinsputuminasthmaorinfaecesinamoebiasis,named
afterCharcoatandLeyden,Germanphysicians).
Bronchialwallshowsthickenedbronchialepithelium,submucosaledema
andinflammatoryexudateconsistinglymphocytesandplasmacellswith
prominenteosinophils.Italsoshowshypertrophyofsubmucosalglandsand
bronchialsmoothmuscles.
Changesofbronchitisandemphysemamayseeninintrinsicasthma.
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12. Clinicalfeatures-
Anasthmaticpatientssufferfromanepisodesofacuteexacerbations(increasein
severity).Characteristicclinicalfeaturesofbronchialasthmaareasfollow-
Paroxysmsofdyspnoea,coughandwheezing,
Mostattacksofbronchialasthmatypicallylastsforafewminutestohours.
Continuousattacksresultsinsevereconditionknownasstatusasthmaticus,
Clinicaldiagnosisshowsthepresenceofcirculatoryeosinophilsandsputum
examinationshowsthepresenceofCurshmann’sspiralsandCharcoat-
Leydencrystals,
Morechronicdiseasestateleadstothedevelopmentofcor-pulmonale
(pulmonaryheartdiseaseleadstorightventricularhypertrophy).
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13. Table indicating distinguishing feature of types of asthma
Sr. No. Feature Extrinsic asthmaIntrinsicasthma
1 Ageofonset ChildhoodorearlyadultstageAdult
2 PersonnelorfamilyhistoryCommonlypresent Absent
3
Precedingallergyillness
(Atopy)
Present(e.g.rhinitis,urticaria,
eczema)
Absent
4 Allergens
Present(e.g.dustparticles,
pollens,animaldenderetc.)
Absent/None
5 Drughypersensitivity None Present(usuallytoaspirin)
6 SerumIgElevel Elevated Normal
7
Associatednasalpolyps,
chronicbronchitis
Absent Present
8 Emphysema Unusual Common

14. Table -Factors involved in the causation of bronchial asthma and drug management
Trigger factorsMediators releasedLung response and drug management
Allergens
Irritants
Exercise
Infections
Drugs (β-blockers)
Psychological stimuli
Histamine
SRS-A
ECF-A
Bradykinin
Serotonin
PGF
2α
Smooth muscle contractions
Drugs-Anticholinergics,Sympathomimetics,
Methylxanthines
Mucosal congestion
Drugs-Corticosteroids & Cromolynsodium
Exudation
Drugs-Corticosteroids & Cromolynsodium

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