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?!*$# “ Twenty years from now you will be more disappointed by the things you  didn't  do  than by those you did.” ...Catc...
Asthma Pathophysiology Dr. Venkatesh M. Shashidhar. Senior Lecturer in Pathology Fiji School of Medicine
Asthma : <ul><li>Chronic  Inflammatory  disorder of bronchi characterized by   Episodic ,  reversible   bronchospasm  resu...
Asthma Facts ? <ul><li>Asthma is “all in the mind.”  </li></ul><ul><li>You will “grow out of it.”  </li></ul><ul><li>Asthm...
Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998 0 0.5 1.0 1.5 2.0 2.5 3.0 Proportion of 1965 Rate  1965 - 1998...
Pathogenesis: INFLAMMATION Airflow Limitation SYMPTOMS Cough  Wheeze Dyspnoea TRIGGERS Allergens, Exercise,  Cold Air, SO2...
Asthma Pathogenetic Types: <ul><li>Extrinsic (Allergic/Immune) </li></ul><ul><ul><li>Atopic - IgE </li></ul></ul><ul><ul><...
Pathogenesis - Atopic Asthma:
Mast cells in Asthma Pathogenesis:
Eosinophils in Asthma Pathogenesis:
Lung Morphology in Asthma <ul><li>Bronchial inflammation </li></ul><ul><li>Edema, Mucousplugging </li></ul><ul><li>Broncho...
Lung Hyperinflation in Asthma
Thick bronchi with Mucous plugs
Mucous plug in asthma:
Asthma - Micropathology <ul><li>Patchy  necrosis  of epithelium </li></ul><ul><li>Sub-mucosal  glandular   hyperplasia </l...
Asthma Microscopic Pathology Obstructed Inflammed Bronchi
Asthma - Bronchial morphology <ul><li>inflammation  </li></ul><ul><li>Eosinophils </li></ul><ul><li>Gland hyperplasia </li...
Asthma - Bronchial morphology <ul><li>Inflammation </li></ul><ul><li>Mucous Plug </li></ul><ul><li>Eosinophils </li></ul>
Asthma – TH2 lymphocytes immunostaining)
Eosinophils in Asthma:
Curschmann's spirals:
New Pathology & Drugs in Asthma: <ul><li>Leukotriences - significant role in Asthma </li></ul><ul><li>Mast cells and Eosin...
5-LO inhibitors Antileukotrienes Arachidonic Acid Leukotrienes LTC4, D4, E4 Cyclooxygenase 5-Lipoxygenase Prostaglandins P...
History of Leukotrienes: <ul><li>Samuelsson et al. (1979) Stockholm found arachidonic acid metabolites in anaphylaxis, (SR...
The Reality   <ul><li>Asthma is not yet curable * </li></ul><ul><li>Underdiagnosis & Undermanagement </li></ul><ul><li>Th...
Thank You… Dr. Venkatesh M. Shashidhar. Senior Lecturer in Pathology Fiji School of Medicine
Asthma Pathology - Modern view Barnes PJ Leukotrienes C4, D4 & E4 Allergen Mucus hypersecretion Hyperplasia Vasodilatation...
Mast cell Degranulation Barnes PJ Normal    5 Seconds 60 Seconds
Mast cell Degranulation Barnes PJ
Type I Hypersensitivity: Barnes PJ
Therapy - Pathology: Barnes PJ
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Asthma Pathophysiology N

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Asthma Pathophysiology N

  1. 1. ?!*$# “ Twenty years from now you will be more disappointed by the things you didn't do than by those you did.” ...Catch the trade winds in your sails, explore, dream, discover & live….! ”                          - Mark Twain
  2. 2. Asthma Pathophysiology Dr. Venkatesh M. Shashidhar. Senior Lecturer in Pathology Fiji School of Medicine
  3. 3. Asthma : <ul><li>Chronic Inflammatory disorder of bronchi characterized by Episodic , reversible bronchospasm resulting from an exaggerated bronchoconstrictor response to various stimuli ( allergy ) </li></ul><ul><li>Affects 10% of children & 5%-7% adults </li></ul><ul><li>Highest in NZ, Low in Fiji ~ 1%  </li></ul>
  4. 4. Asthma Facts ? <ul><li>Asthma is “all in the mind.” </li></ul><ul><li>You will “grow out of it.” </li></ul><ul><li>Asthma can be cured, </li></ul><ul><li>Not very serious disease and nobody dies from it. </li></ul><ul><li>You are likely to develop asthma if someone in your family has it. </li></ul><ul><li>You can “catch” asthma from someone else who has it. </li></ul><ul><li>Moving to a different location can cure asthma. </li></ul><ul><li>People with asthma should not exercise. </li></ul><ul><li>Asthma does not require medical treatment. </li></ul><ul><li>Medications used to treat asthma are habit-forming. </li></ul><ul><li>Someone with asthma can provoke episodes anytime. </li></ul><ul><li>Asthma can spread to other persons through caughing. </li></ul><ul><li>Asthma is born with you. Familial/genetic. </li></ul>
  5. 5. Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998 0 0.5 1.0 1.5 2.0 2.5 3.0 Proportion of 1965 Rate 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 – 59% – 64% – 35% +163% – 7% Coronary Heart Disease Stroke Other CVD COPD All Other Causes
  6. 6. Pathogenesis: INFLAMMATION Airflow Limitation SYMPTOMS Cough Wheeze Dyspnoea TRIGGERS Allergens, Exercise, Cold Air, SO2 Particulates Airway Hyperresponsiveness Genetic* INDUCERS Allergens,Chemical sensitisers, Air pollutants, Virus infections
  7. 7. Asthma Pathogenetic Types: <ul><li>Extrinsic (Allergic/Immune) </li></ul><ul><ul><li>Atopic - IgE </li></ul></ul><ul><ul><li>Occupational - IgG </li></ul></ul><ul><ul><li>A. Bronchopulomonary Aspergillosis - IgE </li></ul></ul><ul><li>Intrinsic (Non immune) </li></ul><ul><ul><li>Aspirin induced </li></ul></ul><ul><ul><li>Infections induced </li></ul></ul>
  8. 8. Pathogenesis - Atopic Asthma:
  9. 9. Mast cells in Asthma Pathogenesis:
  10. 10. Eosinophils in Asthma Pathogenesis:
  11. 11. Lung Morphology in Asthma <ul><li>Bronchial inflammation </li></ul><ul><li>Edema, Mucousplugging </li></ul><ul><li>Bronchospasm </li></ul><ul><li>Obstruction </li></ul><ul><li>Over inflation/Atelectasis </li></ul><ul><li>COPD </li></ul>
  12. 12. Lung Hyperinflation in Asthma
  13. 13. Thick bronchi with Mucous plugs
  14. 14. Mucous plug in asthma:
  15. 15. Asthma - Micropathology <ul><li>Patchy necrosis of epithelium </li></ul><ul><li>Sub-mucosal glandular hyperplasia </li></ul><ul><li>Hypertrophy of bronchial smooth muscle </li></ul><ul><li>Eosinophils , mast cells ; lympho (TH2, CD4) </li></ul><ul><li>Mucous plugs , Curschmann spirals, </li></ul><ul><li>Charcot Layden crystals. </li></ul>
  16. 16. Asthma Microscopic Pathology Obstructed Inflammed Bronchi
  17. 17. Asthma - Bronchial morphology <ul><li>inflammation </li></ul><ul><li>Eosinophils </li></ul><ul><li>Gland hyperplasia </li></ul><ul><li>Mucous plug in lumen </li></ul><ul><li>Hypertrophy of muscle layer </li></ul>
  18. 18. Asthma - Bronchial morphology <ul><li>Inflammation </li></ul><ul><li>Mucous Plug </li></ul><ul><li>Eosinophils </li></ul>
  19. 19. Asthma – TH2 lymphocytes immunostaining)
  20. 20. Eosinophils in Asthma:
  21. 21. Curschmann's spirals:
  22. 22. New Pathology & Drugs in Asthma: <ul><li>Leukotriences - significant role in Asthma </li></ul><ul><li>Mast cells and Eosinophil - Cytokines . </li></ul><ul><li>Arachidonic acid - Lipo-oxygenase – LTD4 </li></ul><ul><li>Bronchospasm – Cys-LT1 receptor </li></ul><ul><li>Zileuton – Lipoxygenase inhibitor </li></ul><ul><li>Montelukast & zafirlukast - inhibit CysLT1 </li></ul>
  23. 23. 5-LO inhibitors Antileukotrienes Arachidonic Acid Leukotrienes LTC4, D4, E4 Cyclooxygenase 5-Lipoxygenase Prostaglandins Prostacyclins Cell Damage Cell Membrane Phospholipids Steroids NSAID
  24. 24. History of Leukotrienes: <ul><li>Samuelsson et al. (1979) Stockholm found arachidonic acid metabolites in anaphylaxis, (SRS) called them &quot;leukotrienes.“ now known to be cysteinyl leukotrienes (LT-C4, D4 and E4). </li></ul><ul><li>* Samuelsson later won the Nobel Prize </li></ul>
  25. 25. The Reality  <ul><li>Asthma is not yet curable * </li></ul><ul><li>Underdiagnosis & Undermanagement </li></ul><ul><li>Therapy is still evolving </li></ul><ul><li>Hope  </li></ul><ul><li>Better understanding of Pathology </li></ul><ul><li>New line of Promissing Drugs. </li></ul><ul><li>Proper management  normal life. </li></ul>
  26. 26. Thank You… Dr. Venkatesh M. Shashidhar. Senior Lecturer in Pathology Fiji School of Medicine
  27. 27. Asthma Pathology - Modern view Barnes PJ Leukotrienes C4, D4 & E4 Allergen Mucus hypersecretion Hyperplasia Vasodilatation New vessels Plasma leak Oedema Bronchoconstriction Hypertrophy/hyperplasia Cholinergic reflex Subepithelial fibrosis Sensory nerve activation Eosinophil Mast cell Th2 cell Neutrophil Macrophage/ dendritic cell Mucus plug Epithelial shedding Nerve activation
  28. 28. Mast cell Degranulation Barnes PJ Normal 5 Seconds 60 Seconds
  29. 29. Mast cell Degranulation Barnes PJ
  30. 30. Type I Hypersensitivity: Barnes PJ
  31. 31. Therapy - Pathology: Barnes PJ

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