Pathophysiology of resp disease p1

Question 1

What is asthma

Answer 1

Chronic inflammatory condition, categorised by episodes of reversible airflow limitation and bronchial hyperresponsiveness, difficulty of breathing

Question 2

Describe the two components of pathophysiology of asthma

Answer 2

Inflammatory component -> Hypersensitivity to a specific stimulus (E.g. pollen), causing response upon exposure to stimuli

Airway component -> Allergen-induced inflammation releases mediators that affect cellular function, produce limitations in tissue function, resulting in dyspnoea, excess mucus and cough for example

Question 3

What is pathophysiology

Answer 3

Physiological mechanism by which pathology is produced

Question 4

Airway smooth muscle conrtaction and mucus hypersecretion cause the lumen to

Answer 4

Reduce in size, increasing airway resistance and decreasing airflow.

Question 5

Describe the two stages of allergic asthma

Answer 5

Sensitisation - Immune system first encounters the allergen, and develops an adaptive immune response

Allergic response - Where allergen is re-encountered, the adaptive response is triggered, generating response in airways, producing symptoms.

Question 6

Why is the immune response bad

Answer 6

Produces limitations on breathing for the individual, due to reduced lumen size.

Question 7

In sensitisation, what happens when the allergen is initially inhaled

Answer 7

The allergen enters the airway, stimulating the immune system, and releasing pro-inflammatory signals. APCs encounter the allergen and engulf and process the allergen, to leave the antigen behind. APCs can present the antigen to naive helper T cells, which can mature to a T2 cell.

Question 8

What happens following the activation of a T2 cell

Answer 8

Interacts with s B cell to initiate class-switching, proliferation and production of IgE antibodies. These antibodies circulate and bind to IgE receptors on granulocytes. The granulocytes contain histamine, leukotrienes and prostaglandins.

Question 9

What is a naive helper T cell

Answer 9

Lymphocyte that acts to regulate immune response

Question 10

How do IgE antibodies bind to IgE receptors and where are the receptors located

Answer 10

Bind via heavy chain region
Receptors located on granulocytes such as mast cells

Question 11

What are mast cells

Answer 11

Immune cells involved responses to parasitic helminth infections, which contain pro-inflammatory mediators

Question 12

Which cytokines to T2 cells secrete and what do they do

Answer 12

IL-4, IL-5, and IL-13, which modulate the immune system.

IL-5 promotes survival, proliferation and trafficking of eosinophils (big role in parasite defence)

Question 13

What is degranulation

Answer 13

Granulocyte releases its contents of inflammatory mediators

Question 14

Describe the changes in the airway that occur in the asthmatic immune response

Answer 14

IgE molecules cross-linked by allergen.
Degranulation occurs, mediators bind to receptors on cells in the airway -> Changes include contraction of airway smooth muscle cells, microvascular leak, stimulation of goblet cells and activation of eosinophil granulocytes.

This causes bronchospasm and a decrease in airflow

Question 15

Why are antihistamines ineffective for treating asthma despite the involvement of allergen

Answer 15

Histamine release has a very limited role in the pathophysiology of asthma

Question 16

A later response of the presence of the allergen would be

Answer 16

T2 cell activation, inducing secondary pro-inflammatory changes hours after. Cytokine release.

Net effect - Decrease in airway function and period of airway hyper-responsiveness

Question 17

Eosinophils release

Answer 17

Reactive oxygen species, leukotrienes and proteolytic enzymes

Question 18

The long term pathology of asthma leads to

Answer 18

Long-term cycles of tissue injury and repair leads to irreversible structural changes -> Smooth muscle hypertrophy, goblet cell hyperplasia, epithelium disruption

Question 19

What is airway remodelling

Answer 19

Progressive and irreversible decline in airway and respiratory function

Question 20

How do epithelial cells display a sentinel function

Answer 20

Capable of detecting specific molecular patterns on microbial/non-microbial allergens via pattern recognition receptors

When epithelial cells are activated, inflammation occurs and release of alarmins.

Question 21

What are alarmins

Answer 21

Epithelial-derived mediators which prime antigen presenting cells, trigger downstream inflammatory responses

Question 22

What are type-2 innate lymphoid cells

Answer 22

ILC2s release cytokines and coordinate inflammatory response, but have no lymphocyte surface markers and antigen-specific receptors. They are important in the pathophysiology of asthma

Question 23

How do bronchodilator drugs work

Answer 23

Bind to specific receptor or enzyme expressed by airway smooth muscle cell, induces intracellular change to cause relaxation.

Question 24

How do beta-2 agonists treat asthma

Answer 24

Activation of beta-2 adrenergic receptors in the membrane of ASM cells. Signalling cascade that increases production of cAMP, and activation of protein kinase A, which reduces Ca2+ mobilisation and sensitivity. Relaxation occurs

Question 25

What is the difference between SABAs and LABAs

Answer 25

SABA - e.g. salbutamol, administered as reliever therapy (e.g. asthma attack)

LABA - e.g. salmeterol, administered as an add-on/preventative treatment with corticosteroids in inhalers.

Question 26

What are long-acting muscarinic receptor antagonists

Answer 26

E.g. tiotropium -> LAMAs are used as preventer therapy in asthma. Blocks acetylcholine receptors on ASM cells. Reduces level of contraction.

LAMAs also reduce mucus secretion and inhibit coughs.

Question 27

When treating airway inflammation, the efficacy of a treatment will depend

Answer 27

On its individual mechanism of action. - e.g. monoclonal antibodies targeting IgE will only be effective if IgE plays a prominent role in the patient’s pathology

Question 28

What is a corticosteroid

Answer 28

Most effective and widely used drug for reducing allergic inflammation in asthma e.g. fluticasone, budesonide.

Administered by inhaler. Bind to glucocorticoid receptors within cytosol of immune + structural cells.

Drug-receptor complex is lipid soluble, moves to nucleus of the cell, binding to DNA and modulating transcription, translation and protein expression. Decreases pro-inflammatory mediator and increases anti-inflammatory mediator expression.