Pathophysiology of Asthma

Pathophysiology of Asthma

1. ASTHMA
BY
IBEKWE CHIGOZIE BLESSING
GROUP 310

2. Definition
•Reactive airway disease
•Chronic inflammatory lung disease
Inflammation causes varying degrees of Inflammation causes varying degrees of
obstruction in the airwaysobstruction in the airways
•Asthma is reversible in early stages

4. Signs and Symptoms
•Wheezing
•Coughing
•Shortness of breathe
•Chest tightness or pain

5. Risk factors
Endogenous factors
•Genetic predisposition
•Atopy
•Airway
hyperresponsiveness
•Gender
•Ethnicity
•Obesity
•Viral infections
Exogenous factors
•Indoor allergens
•Outdoor allergens
•Occupational sensitizers
•Passive smoking
•Respiratory infections

6. Triggers
•Allergens-Dermatophagoides species(dust mite), environmental
exposure, grass pollen, ragweed, tree pollen, fungal spores, pets
furs, cockroaches etc
• Virus infection-upper respiratory tract virus such as rhinovirus,
respiratory syncytial virus, coronavirus etc
•Pharmacological agents-beta blockers, ACE inhibitors, aspirin
•Exercise(may exacerbate )
• Physical factors-cold air, hyperventilation
•Food
•Air pollutants-sulfur dioxide, irritant gases
•Irritants-household sprays paint fumes
• Occupational factors
• Hormonal factors-fall in progesterone thyrotoxicosis
Gastrointestinal reflex

7. Types of asthma
•Atopic asthma-classical type I IgE mediated
hypersensitivity, allergen sensitization, seen from
childhood, +ve history of asthma in family, skin test
+ve
•Non-atopic asthma-no allergen sensitization, no such
history, skin test –ve, virus infection?
• Drug induced asthma-sensitive to certain drugs like
aspirin, NSAIDS etc
• Occupational asthma-stimulants such as fumes,
organic and chemical dusts(wood, cotton),
gas(toluene), penicillin products etc
• Exercise induced asthma-begins after exercise and
stops after 30 minutes, worsen in cold and dry climate

8. Pathogenesis
•Early phase
•Late phase

9. Early-Phase ResponseEarly-Phase Response
–PPeaks 30-60 minutes post exposure, subsides 30-
90 minutes later
– Characterized primarily by bronchospasm
–Increased mucous secretion, edema formation,
and increased amounts of tenacious sputum
–Patient experiences wheezing, cough, chest
tightness, and dyspnea

10. Late-Phase ResponseLate-Phase Response
•Characterized primarily by inflammationCharacterized primarily by inflammation
•Histamine and other mediators set up a self-
sustaining cycle increasing airway reactivity causing
hyperresponsiveness to allergens and other stimuli
•Increased airway resistance leads to air trapping in
alveoli and hyperinflation of the lungs
•If airway inflammation is not treated or does not
resolve, may lead to irreversible lung damage

11. Early and Late Phases of Responses of Asthma
Fig. 28--1

12. Pathophysiology
•The pathophysiology of asthma is complex
and involves the following components:
•Airway inflammation
•Intermittent airflow obstruction
•Bronchial hyperresponsiveness
•Airway remodelling

13. Airway inflammation
•Chronic inflammation of the airways is
associated with increased bronchial
hyperresponsiveness, which leads to
bronchospasm and typical symptoms of
wheezing, shortness of breath, and coughing
after exposure to allergens, environmental
irritants, viruses, cold air, or exercise. In some
patients with chronic asthma, airflow
limitation may be only partially reversible

14. •Airway inflammation in asthma may represent
a loss of normal balance between two
"opposing" populations of Th lymphocytes.
Two types of Th lymphocytes have been
characterized: Th1 and Th2. Th1 cells produce
interleukin (IL)-2 and IFN-α, which are critical
in cellular defense mechanisms in response to
infection. Th2, in contrast, generates a family
of cytokines (IL-4, IL-5, IL-6, IL-9, and IL-13)
that can mediate allergic inflammation

15. Cells involved in inflammation
•Mast Cells: activated by IgE dependant
mechanism, initiate acute bronchoconstriction
action by releasing histamine,
prostaglandinD2,leukotrienes etc
•Macrophages: activated by low affinity IgE
receptor, produce various inflammatory
mediators
•Dendritic cell-macrophage like major APC in
airways, TSLP(Thymic stromal lymphopoietin) by
epithelial cell induced chemokine release for TH2
cells

16. •Eosinophils: infiltration is characteristic
feature of asthma, activated by IL-5, causes
exacerbation of asthma by producing
mediators
•Neutrophils: activated and infiltration.
•T cell: release cytokines, causes recruitment of
eosinophils, also causes maintenance of mast
cells, in asthma TH2 cell produce IL-
5(eosinophil recruitment) IL-4, IL-13(increase
IgE production and mucus secretion).CD4+ cell
also involved

17. Inflamatory mediators
•Histamine, prostaglandin D2, cysteinly
leukotrienes-cause smooth muscle contraction,
increased microvascular leakage, increased
mucus secretion, act as chemoattractant for
inflammatory cells
•Cytokines- IL-4, IL-5, IL-13-causes allergic
inflammation, IL-1beta, TNF-alpha-amplification
of inflammation, TSLP(Tymic stromal
lmphopoietin)- from epithelial cells act as
chemoattractant for TH2 cells, IL-10, IL-12-anti
inflammatory

18. •Chemokines-attract inflammatory cells,
Eotaxin(CCL11) attract eosinophil via CCR3
receptor, TARC(CCL17) and MDC (CCL 22)
from epithelial cell attract TH2 cell via CCR4.
•Oxidative stress-increase in ROS production 
NO-act as relaxant but mainly causes
vasodilatation leading to leakage.
•Transcription factor-NF-kB, activator protein-1

19. Various inflammatory mediators

20. Effects of inflammation
•Epithelium-dysfunction, damage, loss of enzyme,
loss of relaxant factors, loss of barrier function
•Fibrosis- subepithelial fibrosis, basement
membrane thickening, deposition of III and V
collagen(by factors release from eosinophil)
•Smooth muscle- increased responsiveness to
constrictor mediators, in chronic cases
hypertrophy/hyperplasia by growth factors
released by inflammatory mediators
•Vascular response-vasodilation, angiogenesis,
microvascular leakage

21. •Mucus hypersecrection- by goblet cell
hyperplasia, increase in mucus plug, leading to
blocking of airway
• Neural effect-reflex cholinergic
bronchoconstriction by increased muscarinic
action

23. Air flow obstruction
•Airflow obstruction can be caused by a variety of changes, including
acute bronchoconstriction, airway edema, chronic mucous plug
formation, and airway remodeling.
• Acute bronchoconstriction is the consequence of immunoglobulin
E-dependent mediator release upon exposure to aeroallergens and
is the primary component of the early asthmatic response. Airway
edema occurs 6-24 hours following an allergen challenge and is
referred to as the late asthmatic response. Chronic mucous plug
formation consists of an exudate of serum proteins and cell debris
that may take weeks to resolve. Airway remodeling is associated
with structural changes due to long-standing inflammation and may
profoundly affect the extent of reversibility of airway obstruction.
[9]

24. •Airway obstruction causes increased
resistance to airflow and decreased expiratory
flow rates. These changes lead to a decreased
ability to expel air and may result in
hyperinflation. The resulting overdistention
helps maintain airway patency, thereby
improving expiratory flow; however, it also
alters pulmonary mechanics and increases the
work of breathing.

25. Factors Causing Airway Obstruction in Asthma
Fig. 28--3

26. Bronchial Hyperresponsiveness
•Hyperinflation compensates for the airflow
obstruction, but this compensation is limited when the
tidal volume approaches the volume of the pulmonary
dead space; the result is alveolar hypoventilation.
Uneven changes in airflow resistance, the resulting
uneven distribution of air, and alterations in circulation
from increased intra-alveolar pressure due to
hyperinflation all lead to ventilation-perfusion
mismatch. Vasoconstriction due to alveolar hypoxia
also contributes to this mismatch. Vasoconstriction is
also considered an adaptive response to
ventilation/perfusion mismatch.

27. Airway remodelling
•Several changes can be seen
•Irreversible narrowing of lumen
•Decline in lung function
•Smooth muscle hyperplasia
• Fibrosis

29. THANK YOU