Asthma Pathophysiology

1
Twenty years from nowyou will be more
disappointedby the things you didn't do than by
those you did
?!
So Catch the trade winds in your sails,
explore, dream, discover live.!
                                    - Mark Twain
2
Asthma Pathophysiology
Dr. Venkatesh M. Shashidhar. Senior Lecturer in
Pathology Fiji School of Medicine
3
Introduction

• Between 100 - 150 million worldwide 1
• Major factors contributing to asthma morbidity
  and mortality are under diagnosis and
  inappropriate treatment 2
• Prevalence increasing by 50 / decade

1. WHO Bronchial Asthma Fact Sheet 2000 2. GINA
Guidelines 1998
4
Asthma

• Definition
• Episodic, reversible bronchospasm resulting from
  an exaggerated bronchoconstrictor response to
  various stimuli (allergy)
• Affects 10 of children 5-7 adults

5
INDUCERS Allergens,Chemical sensitisers, Air
pollutants, Virus infections
INFLAMMATION
Airway Hyperresponsiveness
Airflow Limitation
SYMPTOMS Cough Wheeze Chest tightness Dyspnoea
TRIGGERS Allergens, Exercise Cold Air, SO2
Particulates
6
Asthma Pathogenetic Types

• Atopic Asthma Classic, IgE, common
• Non-Atopic Asthma
• infections, noAtopy, IgE levels normal.
• Drug-Induced Asthma
• Aspirin sensitive asthma, rhinits, polyps.
• Occupational Asthma
• toxins, wood, resins, penicillins etc.
• Allergic Bronchopulmonary aspergillosis

7
Asthma Pathogenetic Types

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

8
Asthma

• One hypothesis which explains all types is that
  Bronchial ? receptors are insensitive to
  catecholamines, do not dilate in response to ?
  agonists such as adrenaline. And are
  hyper-reactive to various allergens.

9
Asthma Pathogenesis
10
Lung Hyperinflation in Asthma
11
Lung Morphology in Asthma

• Over inflation
• Atelectasis
• Inflammation
• Mucous plugging
• Bronchospasm

12
Thick bronchi with Mucous plugs
13
Asthma - Micropathology

• Inflammation of bronchioles
• Patchy necrosis of epithelium
• Eosinophils gt mast cells lymphocytes (CD4)
• Basement membrane collagen ?
• Sub-mucosal glandular hyperplasia
• Hypertrophy hyperplasia of bronchial smooth
  muscle
• Mucous plugging of bronchi, casts spirals

14
Asthma - Bronchial morphology

• Epithelial necrosis
• Thick basement mem.
• Edema and inflammation of wall
• Plenty of Eosinophils
• Gland hyperplasia
• Mucous plugs in lumen
• Hypertrophy of muscle layer

15
Bronchial inflammation in Asthma
16
Eosinophils in Asthma
17
Asthma Microscopic Pathology
Atelectasis Obstructed Inflammed Bronchi
18
Atelectasis in Asthma
NORMAL ASTHMA
19
Mucous plug in asthma
20
Curschmann's spirals
21
Asthma Pathology - Modern view
Leukotrienes C4, D4 E4
Barnes PJ
22
5-LO inhibitors Antileukotrienes
23
History of Leukotrienes

• In Samuelsson et al. (1979) at Stockholm found
  arachidonic acid metabolites in anaphylaxis,
  which they called "leukotrienes. now known to be
  cysteinyl leukotrienes (LT-C4, D4 and E4).
• Samuelsson later won the Nobel Prize in
  Medicine and Physiology, in part for this
  discovery

24
New Drugs in Asthma

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

25
The Reality is

• Asthma is not yet curable
• Underdiagnosis
• improper management
• Therapy is still evolving
• Hope..?
• Understanding of Pathology
• New line of Drugs..

26
(No Transcript)