Asthma Pathophysiology N

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  • it was privelege to e one of your med student back in Fiji School of Medicine...very humble professor.....thank you sir
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  • excellent slide set--of the many I have seen or used this is one of the best
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  • beautiful slide sir i want it to my presentation
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  • A good work.keep it up. Thanku
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  • pls send these to me
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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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