Pathophysiology of asthma

Question 1

How does inflammation cause airway dysfunction? (briefly)

Answer 1

→ Allergen inhalation 
→ Immune system response 
→ Airway inflammation 
→ Impaired airway function 
→ Wheezing, coughing, dyspnoea

Question 2

What lifestyle factors make it more likely to get asthma?

Answer 2

→ Urban dwelling
→ Pollution
→poor diet
→ obesity

Question 3

What is Ohms law?

Answer 3

→ Airflow is proportional to 1/resistance

Question 4

What does the Hagen-Poiseuille law state?

Answer 4

→ As an airways radius decreases the resistance increases and airflow decreases dramatically

Question 5

What determines the radius of the lumen?

Answer 5

→ The level of contraction of smooth muscle

Question 6

What factors decrease the radius of the lumen even further?

Answer 6

→ Hypersecretion of mucus

→ Swelling

Question 7

What is wheezing caused by?

Answer 7

→ Turbulent airflow

→ Increases resistance and decreases airflow

Question 8

What is the first stage in the allergic response?

Answer 8

→sensitization
→ person breathes in allergen
→ Gets stuck in the airways
→ APC recognizes allergen as being harmful
→ Processes antigen to a helper T cell
→T cells mature and become TH2 cells
→ TH2 cells secrete cytokines like IL5
→ IL4 interacts with B cells and stimulates them
→ B cells proliferate and produce IgE antibodies
→ Antibodies bind to mast cells

Question 9

What is the second stage in the allergic response?

Answer 9

→ Exposure
→ Allergen binds to antibodies 
→ Mast cells degranulate 
→Prostaglandins, LTs and chemokines are secreted 
→ Mediators bind to receptors 
→cause smooth muscle to contract 
→ Mediators attract TH2 and eosinophils 
→ Eosinophils migrate to airways and release reactive O2 species 
→ Second round of inflammation occurs

Question 10

What is the early phase of the asthmatic response?

Answer 10

→ Initial degranulation of mast cells

→ After the first response the mediators are cleared and effects resolve themselves

Question 11

What is the secondary phase of the asthmatic response?

Answer 11

→ Eosinophils and T cells being recruited several hours later

Question 12

What are the changes in respiratory function observed in asthma?

Answer 12

→ FEV1 decreases
→ FVC is unchanged
→ FEV/FVC decreases <70%

Question 13

What are the long term changes caused by uncontrolled asthma?

Answer 13

→ Smooth muscle is being constantly worked 
→ Hypertrophy of smooth muscle
→ More muscle takes up more space and contracts harder 
→ More goblet cells and mucus glands 
→ Infiltration of immune cells 
→ Epithelium Distruption
→ Basement Membrane thickening
→ ECM deposition and Fibrosis

Question 14

What are the most effective treatments for asthma?

Answer 14

→ Beta 2 agonists and corticosteroids