Asthma Pathophysiology

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...Catch the trade winds in your sails, explore,
dream, discover live.!                      
   - Mark Twain
?!
Twenty years from nowyou will be more
disappointedby the things you didn't do than by
those you did.
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Asthma Pathophysiology
Dr. Venkatesh M. Shashidhar. Senior Lecturer in
Pathology Fiji School of Medicine
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Asthma

• Chronic Inflammatory disorder of bronchi
  characterized by Episodic, reversible
  bronchospasm resulting from an exaggerated
  bronchoconstrictor response to various stimuli
  (allergy)
• Affects 10 of children 5-7 adults
• Highest in NZ, Low in Fiji 1 ?

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Asthma Facts ?

• Asthma is all in the mind.
• You will grow out of it.
• Asthma can be cured,
• Not very serious disease and nobody dies from it.
  
• You are likely to develop asthma if someone in
  your family has it.
• You can catch asthma from someone else who has
  it.
• Moving to a different location can cure asthma.
• People with asthma should not exercise.
• Asthma does not require medical treatment.
• Medications used to treat asthma are
  habit-forming.
• Someone with asthma can provoke episodes anytime.
• Asthma can spread to other persons through
  caughing.
• Asthma is born with you. Familial/genetic.

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Percent Change in Age-Adjusted Death Rates, U.S.,
1965-1998
Proportion of 1965 Rate
3.0
Coronary Heart Disease
Stroke
Other CVD
COPD
All Other Causes
2.5
2.0
1.5
1.0
0.5
59
64
35
163
7
0
1965 - 1998
1965 - 1998
1965 - 1998
1965 - 1998
1965 - 1998
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Pathogenesis
INFLAMMATION
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Asthma Pathogenetic Types

• Extrinsic (Allergic/Immune)
• Atopic - IgE
• Occupational - IgG
• A. Bronchopulomonary Aspergillosis - IgE
• Intrinsic (Non immune)
• Aspirin induced
• Infections induced

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Pathogenesis - Atopic Asthma
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Mast cells in Asthma Pathogenesis
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Eosinophils in Asthma Pathogenesis
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Lung Morphology in Asthma

• Bronchial inflammation
• Edema, Mucousplugging
• Bronchospasm
• Obstruction
• Over inflation/Atelectasis
• COPD

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Lung Hyperinflation in Asthma
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Thick bronchi with Mucous plugs
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Mucous plug in asthma
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Asthma - Micropathology

• Patchy necrosis of epithelium
• Sub-mucosal glandular hyperplasia
• Hypertrophy of bronchial smooth muscle
• Eosinophils, mast cells lympho (TH2, CD4)
• Mucous plugs, Curschmann spirals,
• Charcot Layden crystals.

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Asthma Microscopic Pathology
Obstructed Inflammed Bronchi
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Asthma - Bronchial morphology

• inflammation
• Eosinophils
• Gland hyperplasia
• Mucous plug in lumen
• Hypertrophy of muscle layer

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Asthma - Bronchial morphology

• Inflammation
• Mucous Plug
• Eosinophils

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Asthma TH2 lymphocytesimmunostaining)
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Eosinophils in Asthma
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Curschmann's spirals
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New Pathology Drugs in Asthma

• Leukotriences - significant role in Asthma
• Mast cells and Eosinophil - Cytokines.
• Arachidonic acid - Lipo-oxygenase LTD4
• Bronchospasm Cys-LT1 receptor
• Zileuton Lipoxygenase inhibitor
• Montelukast zafirlukast - inhibit CysLT1

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5-LO inhibitors Antileukotrienes
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History of Leukotrienes

• Samuelsson et al. (1979) Stockholm found
  arachidonic acid metabolites in anaphylaxis,
  (SRS) called them "leukotrienes. now known to
  be cysteinyl leukotrienes (LT-C4, D4 and E4).
• Samuelsson later won the Nobel Prize

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The Reality ?

• Asthma is not yet curable
• Underdiagnosis Undermanagement
• Therapy is still evolving
• Hope ?
• Better understanding of Pathology
• New line of Promissing Drugs.
• Proper management ? normal life.

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Thank You
Dr. Venkatesh M. Shashidhar. Senior Lecturer in
Pathology Fiji School of Medicine
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Asthma Pathology - Modern view
Leukotrienes C4, D4 E4
Barnes PJ
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Mast cell Degranulation
Normal 5 Seconds 60 Seconds
Barnes PJ
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Mast cell Degranulation
Barnes PJ
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Type I Hypersensitivity
Barnes PJ
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Therapy - Pathology
Barnes PJ