Asthma Pathophysiology N
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Asthma Pathophysiology N Asthma Pathophysiology N Presentation Transcript

  • ?!*$# “ 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
  • Asthma Pathophysiology Dr. Venkatesh M. Shashidhar. Senior Lecturer in Pathology Fiji School of Medicine
  • 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% 
  • 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.
  • 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
  • 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
  • Asthma Pathogenetic Types:
    • Extrinsic (Allergic/Immune)
      • Atopic - IgE
      • Occupational - IgG
      • A. Bronchopulomonary Aspergillosis - IgE
    • Intrinsic (Non immune)
      • Aspirin induced
      • Infections induced
  • Pathogenesis - Atopic Asthma:
  • Mast cells in Asthma Pathogenesis:
  • Eosinophils in Asthma Pathogenesis:
  • Lung Morphology in Asthma
    • Bronchial inflammation
    • Edema, Mucousplugging
    • Bronchospasm
    • Obstruction
    • Over inflation/Atelectasis
    • COPD
  • Lung Hyperinflation in Asthma
  • Thick bronchi with Mucous plugs
  • Mucous plug in asthma:
  • 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.
  • Asthma Microscopic Pathology Obstructed Inflammed Bronchi
  • Asthma - Bronchial morphology
    • inflammation
    • Eosinophils
    • Gland hyperplasia
    • Mucous plug in lumen
    • Hypertrophy of muscle layer
  • Asthma - Bronchial morphology
    • Inflammation
    • Mucous Plug
    • Eosinophils
  • Asthma – TH2 lymphocytes immunostaining)
  • Eosinophils in Asthma:
  • Curschmann's spirals:
  • 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
  • 5-LO inhibitors Antileukotrienes Arachidonic Acid Leukotrienes LTC4, D4, E4 Cyclooxygenase 5-Lipoxygenase Prostaglandins Prostacyclins Cell Damage Cell Membrane Phospholipids Steroids NSAID
  • 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
  • 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.
  • 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 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
  • Mast cell Degranulation Barnes PJ Normal 5 Seconds 60 Seconds
  • Mast cell Degranulation Barnes PJ
  • Type I Hypersensitivity: Barnes PJ
  • Therapy - Pathology: Barnes PJ