Asthma for b.pharm degree 1st year; pathophysiology

1. -Atreyee Ganguly
Asst. Professor
Dept of Pharmacology
CIPT & AHS
Asthma

2. Introduction
 The respiratory system is responsible for the exchange of gases- Oxygen and
Carbon dioxide between the atmosphere, blood and cells.
 During aerobic respiration, oxygen is required by the organisms to oxidize
respiratory substrates like glucose to release energy for performing various
physiological activities.
 Carbon dioxide is also released during the catabolic reactions.
 It is therefore essential that oxygen should be provided continuously to the
cells and carbon dioxide produced by the cells have to be released out.
 This process of gaseous exchange i.e. Intake of oxygen from the atmosphere
and release of carbon dioxide produced by the cells is called respiration.

3. Anatomy of Respiratory System
 The human respiratory system can be
divided into two parts: (a) Upper
respiratory Tract and (b) Lower
respiratory tract.
 The human respiratory system
consists of : nose, pharynx, larynx,
trachea, bronchi and lungs
 Air moves through the body in the
following order:
Nostrils Nasal cavity pharynx
( naso, oro and laryngopharynx)
larynx trachea thoracic
cavity (chest) Bronchi( right and
left) alveoli (site of gaseous
exchange)

4. Mechanics of Breathing
 Breathing consists of two phases: (a)Inspiration and (b) Expiration
(a) Inspiration: It is initiated by contraction of inspiratory muscles (diaphragm
and external inter coastal muscles).
Insipiratory muscles contract
Thoracic cavity volume increases
Lungs stretched: intrapulmonary volume increases
Intrapulmonary pressure drops
Air flows into the lungs down its pressure gradient until intrapulmonary pressure
equals atmospheric pressure.

5. (b) Expiration: It is initiated when the diaphragm and inter coastal muscle
relaxes.
Inspiratory muscle relaxes
Thoracic cavity volume decreases
Elastic lungs recoil: intrapulmonary volume decreases
Intrapulmonary pressure rises
Air flows out from the lungs down its pressure gradient until intrapulmonary
pressure equals atmospheric pressure.

8.  It is a chronic inflammatory disorder
of the airways that causes recurrent
episodes of wheezing, breathlessness,
chest tightness and cough
particularly at night and/or early in
the morning.
Hallmarks of the disease:
 Intermittent and reversible airway
obstruction,
 chronic bronchial inflammation with
eosinophills,
 bronchial smooth cell hypertrophy
and hyperreactivity and
 increased mucus secretion.

9. Types of Asthma
a. Atopic Asthma
 Most common type of asthma.
 Classic example of type I IgE- mediated hypersensitivity reaction.
 It is triggered by environmental antigens, such as dusts, pollens, animal
dander.
 Infections can also trigger atopic asthma.
 A skin test with the allergen results in immediate wheal and flare reaction.
 Positive family history of asthma is common.
b. Non- Atopic Asthma
 No evidence of allergen sensitization
 Skin test results usually are negative
 Positive family history of asthma is uncommon
 Respiratory infections due to viruses and inhaled air pollutants are common
triggers.

10. c. Drug-Induced Asthma
 Patients with aspirin sensitivity present with recurrent rhinitis and nasal
polyps, urticaria and bronchospasm.
d. Occupational Asthma
 It is stimulated by fumes, organic and chemical dusts and other chemicals.
 Asthma attacks usually develop after repeated exposure to the inciting
antigen(s).
Clinical Features
 An attack of asthma is characterized by severe dyspnea and wheezing
 In the usual case, attacks last from 1 to several hours and subside either
spontaneously or with therapy.
 Intervals between attacks are characteristically free from overt respiratory
difficulties, but persistent, subtle deficits can be detected by pulmonary function
tests.

11.  Occasionally a severe paroxysm occurs that does not respond to therapy and
persists for days and even weeks (status asthmaticus). The associated
hypercapnia, acidosis, and severe hypoxia may be fatal, although in most cases
the condition is more disabling than lethal.
 Standard therapies include : anti-inflammatory drugs, particularly
glucocorticoids, and bronchodilators such as beta-adrenergic drugs and
leukotriene inhibitors
 Another approach called bronchial thermoplasty, which involves controlled
delivery of thermal energy during bronchoscopy to reduce the mass of smooth
muscle and airway responsiveness, is being evaluated in patients with severe,
poorly controlled.

12. Pathogenesis
1. Asthma is usually triggered by allergens such as pollen, dust, animal dandrens
etc., when it is inhaled.
2. This allergen comes in contact with specific types of antigen presenting cells
(e.g. dendritic cells) within the respiratory tract.
3. It will phagocytise the allergens and activate certain genes such as
chromosome6MHC (Major Histocompatibility Complex) class II molecules
expressed on dendritic cells Allergen expressed and bound over MHC II
complex  the dendritic cell takes this MHC II complex along with the allergen
to a T-helper 2 (Th2) cell.
4. The Th2 will express CD4 molecules on its membrane specific to the MHC class
II complex of the dendritic cells and also a Th2 receptor that is specific for
particular allergen.
5. The Th2 cell will then react with the dendritic cell. The MHC II complex will
present the antigen bound to it to the Th2 recepter present on its membrane.
6. The allergen will bind to the Th2 receptor whereas the CD4 molecule will
interact with the MHC II complex.

13. 7. Upon this interaction the Th2 cells undergoes inappropriate type of reaction
which releases two very important chemicals namely; Interleukin-4, 5 (IL-4
& IL-5).
8. IL-4 activates plasma cells and acts on it to stimulate the production of
antibodies IgE. This IgE goes and bind to particular cells known as mast
cells.
9. The mast cells have specific proteins known as Fc epsilon 1 receptor on its
membrane which then binds to the IgE antibody.
10. Binding of the IgE antibody on the mast cells triggers the mast cell
degranulation and release histamine and leukotrienes.
11. IL-5 activates eosinophills which in turn releases leukotrienes and some
proteases which overtime damages the respiratory tissues (chronic).
12. The histamine and leukotrienes released by mast cells and eosinophills goes
and effect the bronchioles.

14. SUMMARY OF PATHOPHYSIOLOGY OFASTHMA
Allergen
Dendritic cells
Phagocyto
sis
MHC II
Allergen
takes this MHC II
complex along with
the allergen to a T-
helper 2 (Th2) cell.
Th2 cells
Th2 receptor
CD4
releases
IL-4
IL-5

15. IL-4
IL-5
IL-4 activates plasma
cells and acts on it to
stimulate the production
of antibodies IgE
Plasma cells
IgE
releases binds
IgE binds
to Fc
epsilon 1
receptor
on mast
cell
Mast cell
releas
es
Histamine
and
Leukotrie
ne
activate
s
eosinophills
releases
Leukotrienes

16. Effect of Histamine and Leukotrienes on the Bronchioles:
 BRONCHOCONSTRICTIONNARROW THE PATHWAY
 INCREASED VASCULAR PERMEABILITYMUCOUS BUILDUP
 INFLAMMED MUCOSANARROW THE PATHWAY