Pathophysiology of Asthma

Question 1

what is asthma?

Answer 1

• a chronic, inflammatory and obstructive disease of the airways which is diagnosed and characterised by a certain pattern of symptoms
• the inflammation of the airways causes pathological effects which impair the function of the airways, leading to the generation of symptoms of asthma (wheezing, breathlessness)
• If the person can’t breathe sufficiently you therefore get decreased ventilation of the alveoli, build-up of co2 and hypoxaemia (people can die of asthma)

Question 2

name a subtype of asthma and what components it has:

Answer 2

allergic asthma

• due to allergens/pollen/dust mites/molecules that can cause an allergic inflammatory response and disease
• eosinophilic component
• TH2 component

Question 3

what factors are involved in asthma?

Answer 3

genetic
-number of genes have been found that more a person more susceptible to asthma or give them protection against asthma

environmental

• this includes immunological development and lifestyle
• immunological development refers to the way in which you experience different infections at different times throughout your life

Question 4

to reach gas exchange structures, what must air pass through?

Answer 4

the respiratory tree

Question 5

airflow through airways is proportional to what?

Answer 5

the level of airway resistance

Question 6

how does airway radius affect resistance and airflow

Answer 6

as the airway radius decreases, resistance increases and airflow decreases

Question 7

the size of the airway lumen is proportional to what?

Answer 7

Airflow

Question 8

what determines the size of the airway lumen?

Answer 8

The level of contraction of the smooth muscle layer that surrounds the wall of the airway

Question 9

how does airway inflammation affect resistance and airflow?

Answer 9

• increases airway resistance

- decreases airflow

Question 10

4 things are indicative of an asthmatic airway:

Answer 10

contraction of smooth muscle
-causes a decrease in lumen size due to constriction, leading to symptoms.

hypersecretion of mucus
-the more mucus within the airway, the less space there is for air to flow through

inflammation
-swelling which will increase the wall of the airway at the expense of the lumen

coughing
-due to irritation of sensory neurons within the airway structure

Question 11

what type of flow increases airway resistance?

Answer 11

turbulent, and this flow generates an audible “wheezing” sound

Question 12

what do allergic responses require?

Answer 12

prior exposure and sensitisation

Question 13

what is sensitisation?

Answer 13

• it’s when the person first encounters the allergen
• they don’t actually have an allergic response because the immune system response is being developed/primed through the generation of antibodies
• so the next time the allergen enters the body, an allergic response occurs because the immune system is already primed so the allergen is recognised by these antibodies
• downstream responses are triggered, leading to a big allergic response and the symptoms of an asthma attack

Question 14

what does sensitisation involve?

Answer 14

• the presentation of antigens to T cells

- B cell-Ab production

Question 15

so, what happens when an allergen in inhaled and enters the airway tissue for the first time?

Answer 15

• the APC engulfs and processes the antigen
• APC presents antigen to t-helper cells, which mature into TH2 cells
• Mature th2 cells secrete:
• -> IL5 which will bind to receptors on eosinophils, activating them and causing them to proliferate
• -> IL4, which interacts with B cells and starts to initiate antibody production
• B-cells produce IgE, which bind to mast cells (tail region of antibody binds to the receptor).

Question 16

what is the asthmatic response triggered by?

Answer 16

allergen-induced degranulation and airway inflammation

Question 17

what happens the second time the allergen enters the body?

Answer 17

-this time when the antigen fragments are formed they bind to receptors on mast cells (IgE), causing degranulation and release of inflammatory mediators (chemokines, prostaglandins etc.) into the surrounding airway tissue

Question 18

explain what the mediators that are released into the airway tissue do the second time the allergen is in the body:

Answer 18

The different mediators bind to receptors on smooth muscle causing effects:

1. muscle contraction leading to shortness of breath because airway is constricted
2. activation of goblet cells leading to hypersecretion of mucus
3. activation of sensory neurons to generate coughing)

Question 19

so, what do these inflammatory mediators generate?

Answer 19

they generate the acute pathological features

Question 20

as well as causing pathological features, what else do these inflammatory mediators do?

Answer 20

• they act as an alert signal, attracting other cells (TH2 cells, eosinophils) to the airways
• over a few hours, the eosinophils will migrate to the airways and release further mediators and ROS (reactive oxygen species)
• so, several hours later you usually get a second round of inflammation/airway obstruction and a second round of pathology/symptoms

Question 21

why would you get a second round of inflammation several hours after the allergen has entered the body second time around?

Answer 21

because the eosinophils migrate to the airways and release further mediators and ROS (reactive oxygen species), causing a second round of inflammation/airway obstruction and a second round of pathology/symptoms

Question 22

what phases can the asthmatic response to an allergen can have?

Answer 22

early and late phases

Question 23

explain what the early response is

Answer 23

the initial drop in airway function, due to degranulation and bronchospasm

Question 24

what is the late response?

Answer 24

second wave of airway obstruction and therefore a second wave of symptoms

Question 25

What changes would we expect on respiratory function with on obstructive airway?

Answer 25

The VC is not affected, just the speed at which it happens

FEV1 decreases

Question 26

what can chronic, uncontrolled asthma lead to?

Answer 26

negative long-term changes in airway structure

Question 27

define the term “remodelling”?

Answer 27

irreversible long-term changes to structure and function of airways

Question 28

over time what happens in terms of tissue damage?

Answer 28

greater and greater injury and long-term issues to tissue structure and function.

Question 29

what is the consequence of permanent airway obstruction?

Answer 29

permanent long-term problems on the persons respiratory function

Question 30

what happens to smooth muscle long term, and what are the consequences of this?

Answer 30

• smooth muscle starts to build up because it’s constantly being worked - hypertrophy
• this takes up space and makes it more likely to contract, and contract harder

Question 31

what is the most effective pharmacological treatment for asthma?

Answer 31

beta-2 agonists (work on the symptoms)

Question 32

does every patient who has asthma experience the same immune response?

Answer 32

no

the characteristics of the immune system response differs substantially between asthma patients- so the whole mast cells, igE etc.. doesn’t even happen in some patients.

Question 33

what is acute breathlessness caused by?

Answer 33

airway dysfunction, resulting from inflammation triggered by allergen exposure