Asthma A chronic relapsing inflammatory disorder characterized by: Hyper-reactivity of the respiratory tree to various stimuli leading to Reversible airway obstruction Obstruction produced by combination of : Constriction of bronchial musculature (bronchospasm) Mucosal inflammation (edema) Excessive secretion of mucus. Clinically Manifested by : Difficulty in breathing (Dyspnea) Wheeze (a soft whistling sound during expiration) Difficulty in expiration. Asthma is: Episodic and reversible airway disease Primarily targets the bronchi and terminal bronchioles MC chronic respiratory disease in children Two types: Extrinsic asthma (allergic, atopic) Intrinsic asthma (non-allergic asthma or idiosyncratic asthma)

1. Obstructive diseases
Part-2

2. A chronic relapsing inflammatory disorder characterized
by:
– Hyper-reactivity of the respiratory tree to various
stimuli leading to
– Reversible airway obstruction
Obstruction produced by combination of :
– Constriction of bronchial musculature (bronchospasm)
– Mucosal inflammation (edema)
– Excessive secretion of mucus.
Clinically Manifested by :
– Difficulty in breathing (Dyspnea)
– Wheeze (a soft whistling sound during expiration)
– Difficulty in expiration.
Asthma

3. Remember !!!!
Asthma is:
– Episodic and reversible airway disease
– Primarily targets the bronchi and
terminal bronchioles
– MC chronic respiratory disease in
children
Two types:
– Extrinsic asthma (allergic, atopic)
– Intrinsic asthma (non-allergic asthma or
idiosyncratic asthma)

4. Extrinsic asthma = allergic asthma
Initiated by type I hypersensitivity reaction.
Induced by exposure to an extrinsic antigen.
Typically develops in children with a family
history of allergic diseases
Associated with :
– Increased serum IgE levels
–  Blood Eosinophil Count
– Positive skin test with offending antigen.

5. Intrinsic asthma = idiosyncratic asthma
Also known as non allergic asthma
Typically develops later in life
Initiated by diverse non-immune mechanisms
Example:
– Virus induced respiratory infection
– Environmental pollutants (ozone*)
– NSAID sensitivity (Aspirin ingestion)
– Stress ,exercise , Smoke & Cold temperature
No personal or family history of allergies.
Normal serum levels of IgE

6. Pathogenesis of Atopic (Extrinsic) Asthma
Atopic asthma:
– Triggered by environmental allergens : dust,
pollen etc.
Involves type I hypersensitivity reaction.
Two phases:
1. Acute or early phase
2. Late phase

7. Asthma: The early phase
Initial sensitization to an inhaled allergen:
– Inhaled Ag  Antigen presenting cell 
– Induction of CD4 TH2 cells
– Release IL-4 and 5
– IL-4  IgE production
– IL-5  activation of eosinophils.
Inhaled ag cross-links IgE ab on mast cells
– Release of histamine and other mediators
– Functions of mediators:
Stimulate bronchoconstriction, mucus
production, increase vascular permeability
and influx of WBCs

8. Important mediators in early phase
Leukotrines C4, D4 and E4:
– Prolonged bronchoconstriction
– Increased vascular permeability
– Increase mucin secretion.
Acetylcholine:
– Smooth muscle cell constriction
Histamine: ( not very imp in asthma)
– Bronchospasm
– Increase vascular permeability

9. Late phase reaction (4-8 hrs later)
Characterized by accumulation of inflammatory
cells:
– Neutrophils, mononuclear cells and eosinophils.
– These cells amplify and maintain inflammation
in the airways.
Most important cell type is Eosinophil
– Eotaxin is chemotactic for eosinophils
– Eosinophils release
major basic protein and
cationic protein
– Damage epithelial cells and produce
airway constriction.

10. In a nut shell
In Asthma there is
narrowing of
airways due to:
– bronchospasm
– Edema
– Production of
mucus.

11. Asthma - Morphologic Pathology
Gross :
– Hyperinflation of lungs.
– Most important finding:
Occlusion of bronchi and bronchioles by
Mucus plugs.
Normal
Asthma

12. MUCUS PLUG

13. Asthma
Histologic changes in bronchi:
– Edema and eosinophil infiltrate
– Hypertrophy of submucosal glands
– Hypertrophy and hyperplasia of smooth muscle
cells.
Histologic changes in terminal bronchioles:
– Formation of spiral shaped mucus plugs
Contain shed epithelial cells called
Curschmann spirals
– Crystalline granules in eosinophils fuse to form
Charcot-Leyden crystals.

16. Curschmann's spiral
(mucous plugs
intermixed with
epithelium)
Charcot - Leyden
crystals (due to
fusion of eosinophil
granules)
Curshman Spirals
Charcot-Leyden Crystals

17. Asthmatic attack is characterized by:
– Severe dyspnea with wheezing
– Difficulty in expiration – prolonged expiration
– Patient labors to get air in, then cannot get it
out.
– Diminished breath sounds, hyper- resonance
and increased AP diameter
due to air trapping
– Attack lasts 1-several hours
– Resolves with or without treatment.
Status Asthmaticus:
– Severe attack which persists for days and
even weeks and does not respond to therapy =
Asthma - Clinical Course

18. Permanent dilatation of bronchi and bronchioles
(diff. from emphysema)
Due to
– destruction of cartilage, muscle and elastic
tissue.
Because of :
– Chronic necrotizing infections (of the bronchi
and bronchioles).
Not a primary disease.
– Occurs secondary to persisting infection or
obstruction.
Bronchiectasis

19. Normal Bronchiectasis

20. Two processes responsible in the
pathogenesis of bronchiectasis.
1. Obstruction
1. predisposes to infection and
inflammation
2. Chronic persistent infection and
inflammation
1. weakens airway walls allowing dilation
Pathogenesis

21. Obstruction
• Bronchogenic carcinoma
• foreign body
Impaired clearance
of secretions
Superimposed infection
Accumulation of secretions
Inflammation Damage to
bronchial wallMore exudate
Dilation of airways
(Bronchiectasis)

22. Causes
Cystic fibrosis:
MCC in the US
Infections:
– TB is MCC worldwide
– Necrotizing pneumonias : S. aureus, H.influenza
Bronchial obstruction:
– Bronchogenic carcinoma
Primary ciliary dyskinesia:
– Immotile cilia syndrome (Kartagener's syndrome)
Absent dynein arm in cilia
Dynein arm contains ATPase for movement of cilia

23. Bronchiectasis in cystic fibrosis
Abnormal anion secretion produces thick,
viscous mucous in large airways.
Airway obstruction and dilation occurs
Superimposed infections (staph,
pseudomonas) lead to bronchiectasis.

24. Bronchiectasis in immotile cilia syndrome
Impaired pulmonary immune defense due to
decreased airway clearance by cilia.
Predisposition to infections.
Absent cilia dynein arms are the most
common ultrastructural abnormality

25. Bronchiectasis
Gross findings:
– Dilated bronchi and bronchioles filled with pus.
Dilated airways extend to the lung periphery
Dilations are tube like or saccular.
Clinical findings:
– Cough productive of copious sputum (often
cupfuls)
– Hemoptysis that is sometimes massive
– Digital clubbing
– Hypoxemia, hypercapnia, pul HT, cor pulmonae
X ray: bronchial markings extend to lung
periphery.

26. Dilated airways with pus

27. Dilated airways

28. Spr 09 28

29. Obstructive lung diseases
Disease Anatomic
site
Pathology Etiology Signs/
symptoms
Chronic
bronchitis
Bronchus,
Terminal
bronchiloe
Mucus gland
hyperplasia,
Hyperscretion,
Obliteration
Tobacco smoke,
air pollutants
Cough, sputum
production
Bronchiectasis Bronchus,
Segmental
bronchi
Airway
dilatation
Persistent
infection
Cough, purulent
sputum, fever
Asthma Bronchus
Terminal
bronchiole
Smooth muscle
hyperplasia,
inflammation,
mucus
Immunologic/
undefined cause
Dyspnea, cough,
wheeze
Emphysema Acinus Airspace
enlargement,
wall destruction
Tobacco smoke Dyspnea