Asthma Pathophysiology N
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““Twenty years from nowTwenty years from nowyou will be more disappointedyou will be more disappointedby the things you by the things you didn'tdidn't do do than by those you did.”than by those you did.”
...Catch the trade winds in your sails, ...Catch the trade winds in your sails, explore, dream, discover & explore, dream, discover & live….! ” live….! ” - Mark Twain
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Asthma Asthma PathophysiologyPathophysiology
Dr. Venkatesh M. Shashidhar.Senior Lecturer in PathologyFiji School of Medicine
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AsthmaAsthma::
Chronic Chronic InflammatoryInflammatory disorder of disorder of bronchi characterized bybronchi characterized by EpisodicEpisodic, , reversiblereversible bronchospasmbronchospasm resulting from resulting from an exaggerated bronchoconstrictor an exaggerated bronchoconstrictor response to various stimuli (response to various stimuli (allergyallergy) )
Affects 10% of children & 5%-7% adultsAffects 10% of children & 5%-7% adults
Highest in NZ, Highest in NZ, Low in Fiji ~ 1%Low in Fiji ~ 1%
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Asthma Facts ?Asthma Facts ? Asthma is “all in the mind.” Asthma is “all in the mind.” You will “grow out of it.” You will “grow out of it.” Asthma can be cured, Asthma can be cured, Not very serious disease and nobody dies from it. Not very serious disease and nobody dies from it. You are likely to develop asthma if someone in your You are likely to develop asthma if someone in your
family has it. family has it. You can “catch” asthma from someone else who has it. You can “catch” asthma from someone else who has it. Moving to a different location can cure asthma. Moving to a different location can cure asthma. People with asthma should not exercise. People with asthma should not exercise. Asthma does not require medical treatment. Asthma does not require medical treatment. Medications used to treat asthma are habit-forming. Medications used to treat asthma are habit-forming. Someone with asthma can provoke episodes anytime.Someone with asthma can provoke episodes anytime. Asthma can spread to other persons through caughing.Asthma can spread to other persons through caughing. Asthma is born with you. Familial/genetic.Asthma is born with you. Familial/genetic.
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Percent Change in Age-Percent Change in Age-Adjusted Death Rates, U.S., Adjusted Death Rates, U.S., 1965-19981965-1998
Percent Change in Age-Percent Change in Age-Adjusted Death Rates, U.S., Adjusted Death Rates, U.S., 1965-19981965-1998
00
0.50.5
1.01.0
1.51.5
2.02.0
2.52.5
3.03.0
Proportion of 1965 Rate Proportion of 1965 Rate
1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998
–59%–59% –64%–64% –35%–35% +163%+163% –7%–7%
CoronaryHeart
Disease
CoronaryHeart
Disease
StrokeStroke Other CVDOther CVD COPDCOPD All OtherCauses
All OtherCauses
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INFLAMMATIONINFLAMMATIONAirflow Limitation
SYMPTOMSCough Wheeze
Dyspnoea
TRIGGERS Allergens, Exercise,
Cold Air, SO2 Particulates
PathogenesiPathogenesis:s:
AirwayHyperresponsiveness
Genetic*
INDUCERSAllergens,Chemical sensitisers,Air pollutants, Virus infections
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Asthma Pathogenetic Types:Asthma Pathogenetic Types:
Extrinsic (Allergic/Immune)Extrinsic (Allergic/Immune) Atopic - IgEAtopic - IgE Occupational - IgGOccupational - IgG A. Bronchopulomonary Aspergillosis - A. Bronchopulomonary Aspergillosis -
IgEIgE Intrinsic (Non immune)Intrinsic (Non immune)
Aspirin inducedAspirin induced Infections inducedInfections induced
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Pathogenesis - Atopic Pathogenesis - Atopic Asthma:Asthma:
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Mast cells in Asthma Mast cells in Asthma Pathogenesis:Pathogenesis:
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Eosinophils in Asthma Eosinophils in Asthma Pathogenesis:Pathogenesis:
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Lung Morphology in AsthmaLung Morphology in Asthma
Bronchial Bronchial inflammationinflammation
Edema, Edema, MucouspluggingMucousplugging
BronchospasmBronchospasm ObstructionObstruction Over Over
inflation/Atelectasisinflation/Atelectasis COPDCOPD
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Lung Hyperinflation in AsthmaLung Hyperinflation in Asthma
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Thick bronchi with Mucous Thick bronchi with Mucous plugsplugs
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Mucous plug in asthma:Mucous plug in asthma:
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Asthma - MicropathologyAsthma - Micropathology
Patchy Patchy necrosisnecrosis of epithelium of epithelium Sub-mucosal Sub-mucosal glandularglandular hyperplasiahyperplasia Hypertrophy of bronchial Hypertrophy of bronchial smoothsmooth
musclemuscle EosinophilsEosinophils, , mastmast cellscells; ; lympholympho (TH2, (TH2,
CD4) CD4) Mucous Mucous plugsplugs, Curschmann spirals,, Curschmann spirals, Charcot Layden crystals.Charcot Layden crystals.
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Asthma Microscopic Asthma Microscopic PathologyPathology
ObstructedInflammedBronchi
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Asthma - Bronchial morphologyAsthma - Bronchial morphology
inflammation inflammation EosinophilsEosinophils Gland Gland
hyperplasiahyperplasia Mucous plug in Mucous plug in
lumenlumen Hypertrophy of Hypertrophy of
muscle layermuscle layer
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Asthma - Bronchial morphologyAsthma - Bronchial morphology
InflammatioInflammationn
Mucous Mucous PlugPlug
EosinophilsEosinophils
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Asthma – TH2 lymphocytesAsthma – TH2 lymphocytesimmunostaining)immunostaining)
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Eosinophils in Asthma:Eosinophils in Asthma:
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Curschmann's spirals:Curschmann's spirals:
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New Pathology & Drugs in New Pathology & Drugs in Asthma:Asthma:
Leukotriences - significant role in Leukotriences - significant role in AsthmaAsthma
Mast cells and Eosinophil - Mast cells and Eosinophil - CytokinesCytokines. . Arachidonic acid - Arachidonic acid - Lipo-oxygenaseLipo-oxygenase – –
LTD4LTD4 Bronchospasm – Bronchospasm – Cys-LT1Cys-LT1 receptor receptor ZileutonZileuton – Lipoxygenase inhibitor – Lipoxygenase inhibitor MontelukastMontelukast & & zafirlukastzafirlukast - inhibit - inhibit
CysLT1CysLT1
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Arachidonic Acid
Leukotrienes
LTC4, D4, E4
Cyclooxygenase
5-Lipoxygenase
Prostaglandins
Prostacyclins
Cell Damage
Cell Membrane Phospholipids
5-LO inhibitorsAntileukotrienes
Steroids
NSAID
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History of Leukotrienes:History of Leukotrienes:
Samuelsson et al. (1979) Stockholm Samuelsson et al. (1979) Stockholm found arachidonic acid metabolites in found arachidonic acid metabolites in anaphylaxis, (SRS) called them anaphylaxis, (SRS) called them "leukotrienes.“ now known to be "leukotrienes.“ now known to be cysteinyl leukotrienes (LT-C4, D4 and cysteinyl leukotrienes (LT-C4, D4 and E4).E4).
* Samuelsson later won the * Samuelsson later won the Nobel PrizeNobel Prize
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The Reality The Reality Asthma is not yet curable *Asthma is not yet curable * Underdiagnosis & Underdiagnosis &
UndermanagementUndermanagement Therapy is still evolvingTherapy is still evolving
Hope Hope Better understanding of Better understanding of PathologyPathology
New line of Promissing Drugs.New line of Promissing Drugs. Proper management Proper management normal life. normal life.
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Thank You…Thank You…
Dr. Venkatesh M. Shashidhar.Senior Lecturer in PathologyFiji School of Medicine
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Asthma Pathology - Modern Asthma Pathology - Modern viewview
Barnes PJ
Allergen
MucushypersecretionHyperplasia
VasodilatationNew vessels
Plasma leak Oedema
BronchoconstrictionHypertrophy/hyperplasia
Cholinergic reflex
Subepithelialfibrosis
Sensory nerve activation
Eosinophil
Mast cell
Th2 cell Neutrophil
Macrophage/dendritic cell
Mucus plugEpithelial shedding
Nerve activation
LeukotrienesC4, D4 & E4
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Mast cell DegranulationMast cell Degranulation
Barnes PJ
Normal 5 Seconds 60 Seconds
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Mast cell DegranulationMast cell Degranulation
Barnes PJ
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Type I Hypersensitivity:Type I Hypersensitivity:
Barnes PJ
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Therapy - Pathology:Therapy - Pathology:
Barnes PJ