Asthma

Question 1

Define Asthma

Answer 1

Intermittent attacks of bronchoconstriction

Question 2

State five causes of asthma

Answer 2

• allergens - exercise - respiratory infections - smoke - dust/pollutants

Question 3

What are the symptoms of asthma?

Answer 3

tight chest, wheeze, cough (non-productive), shortness of breath

Question 4

Describe the pathology of asthma (4)

Answer 4

• increased smooth muscle - accumulation of interstitial fluid - increased mucus, - epithelial damage - sub-epithelial fibrosis

Question 5

Describe the accumulation of calcium in contraction

Answer 5

1. Hormone activated GPCR result in IP3 moving in through the calcium channel and this sends calcium 2+ ions of of the store 2. Depolarisation of the membrane moves calcium 2+ in through the calcium channels

Question 6

When calcium moves in through the channels what does the calcium store do?

Answer 6

Moves calcium out through the calcium channels

Question 7

What happens to the calcium ions in contraction?

Answer 7

1. calcium binds to calodium 2. this activates myosin light chain kinase 3. myosin cross bridge is phosphorylated 4. myosin binds to actin generating force contraction

Question 8

Describe relaxation

Answer 8

1. beta 2 adrenoreceptor is activated by adrenaline 2. Gs activated 3. Converted to AC 4. AC + ATP forms cAMP 5. PDE degrades cAMP to 5’AMP and PkA

Question 9

What two things can the PkA do?

Answer 9

• Phosphorylate and stimulate myosin phosphatase to facilitate relaxation - Phosphorylate and inhibit myosin light chain kinase to inhibit contraction

Question 10

What does atopic mean?

Answer 10

caused by allergy, strong TH2, IgE antibody mediated response. Severe asthma also involves TH1.

Question 11

Describe the immunological response to an allergen in atopic individuals

Answer 11

1. antigen presents to T CD4+ cell 2. TCD4+ cells mature to TH0 and then TH2 cells

Question 12

What do TH2 cells activate in response to; IL4 IL13 IL5

Answer 12

• B Cells - Mast Cells - Eosinophils

Question 13

What do the B Cells do?

Answer 13

Mature to IgE secreting plasma cells

Question 14

What do mast cells in airway tissue do?

Answer 14

express IgE receptors, which stimulates calcium entry

Question 15

In mast cells what does the release of calcium do?

Answer 15

Simulates…

• the release of secretory granules containing histamine
• production & release of LTC4/LTD4 that cause smooth muscle contraction
• the release of substances, platelet-activating factor & prostaglandins that attract cells causing inflammation

Question 16

What are the two types of asthma treatment?

Answer 16

Relievers & Preventers

Question 17

Give four types of reliever

Answer 17

• SABA - LABA - CysLT1 receptor antagonists

Question 18

Give three types of preventer

Answer 18

• Glucocorticoids - Cromoglicate - Monoclonal IgE antibodies

Question 19

What does SABA and LABA stand for? How do they work?

Answer 19

Short and Long acting beta agonists By acting as antagonists of spasmogens, they activate the receptor leading to relaxation

Question 20

How do CysLT1 Receptor Antagonists work?

Answer 20

By stopping chemical secreted by mast cells from causing contraction of smooth muscle, mucus secretion and oedema.

Question 21

What are glucocorticoids synthetic versions of?

Answer 21

Cortisol

Question 22

Name four processes that cortisol regulates

Answer 22

decreases - inflammatory responses - immunological responses - glucose utilisation

increases - protein catabolism - bone catabolism - gastric & pepsin secretion

Question 23

As well as glucocorticoid what is the other corticosteroid?

Answer 23

Mineralocorticoid - regulate the retention of salt by the kidney

Question 24

Give three examples of corticosteroids and how they are administered

Answer 24

Budenoside & beclometason - inhaled Prednisolone - oral Hydrocortisone - IV

Question 25

How do glucocorticoids work?

Answer 25

1. They combine with GR alpha in the cytoplasm causing the dissociation of shock proteins. 2. The activated receptor translocates to the nucleus 3. Receptor monomers combine to form homodimers 4. They bind to glucocorticoid receptor elements in the promotor region of specific genes

Question 26

Give two effects on transcription relevant to asthma

Answer 26

- increase expression of anti-inflammatory proteins - decrease expression of inflammatory proteins

Question 27

What is inflammatory gene expression associated with?

Answer 27

Acetylation of histones by histone acetyltransferases (HATs)

Question 28

What do glucocorticoids recruit?

Answer 28

histone deacetylases to switch off transcription

Question 29

Name four additional actions of corticosteroids

Answer 29

- decrease TH2 formation - prevent IgE production - prevent allergen induced influx - reduced number of mast cells & IgE receptors

Question 30

State four pathological changes of chronic asthma

Answer 30

- increased mass of smooth muscle - accumulation of interstitial muscle - increased secretion of mucus - epithelial damage - sub-epithelial fibrosis

Question 31

What causes bronchial hyper-responsiveness?

Answer 31

epithelial damage exposing sensory nerve endings

Question 32

Describe the curves on this graph

Answer 32

green - severe asthma red - mild asthma blue - normal subject

Question 33

What is the result of inflammation & bronchoconstriction?

Answer 33

* Airway narrowing * increase in airway resistance * decrease in FEV & PEFR (peak flow)

Question 34

What are the two phases of asthma?

Answer 34

Immediate and Late (delayed response)

Question 35

Describe the immediate phase

Answer 35

allergen/stimuli → mast cells → histamine/spasmogens/CysLTs/chemotaxis/chemokines

Question 36

What do histamine/spasmogens/CysLTs do?

Answer 36

Cause bronchospasm and early inflammation

Question 37

What do the chemotaxis & chemokines do?

Answer 37

Leads to the late phase infiltration of cytokine releasing TH2 cells & monocytes as well as activation of inflammatory cells (eosinophils)

Question 38

What does the start of the late phase lead to?

Answer 38

release of * mediators * eosinophils * major basic & cationic proteins

Question 39

What do eosinophils, major basic & cationic proteins result in?

Answer 39

epithelial damage

Question 40

All mechanisms of the late phase lead to...

Answer 40

1. Airway inflammation 2. Hyperresponsiveness These lead to; * bronchospasm * wheezing * mucus oversecretion * cough