The Neurohumoral Control of the Airways and an Introduction to Asthma

Question 1

Where are the cell bodies of the preganglionic fibres of the airways located?

Answer 1

Brainstem

Question 2

Where are the cell bodies of the postganglionic fibres in the airways?

Answer 2

Bronchi and bronchioles?

Question 3

(parasympathetic) Stimulation of postganglionic cholinergic fibres causes?

Answer 3

Bronchial smooth muscle contraction. Muscus Secretion.

Question 4

(parasympathetic)stimulation of the postganlionic nonchlinergic fibres causes?

Answer 4

Bronchial smooth muscle relaxation.

Question 5

(parasympathetic)What mediates the causes of Stimulation of postganglionic cholinergic fibres?

Answer 5

M3 muscarinic ACh receptors on the cells of which it caused effect.

Question 6

(parasympathetic)What mediates stimulation of the postganglionic nonchlionergic fibres?

Answer 6

Nitric oxide and vasoactivated intestenal peptide.

Question 7

(sympathetic)What do post-ganglionic fibres supply?

Answer 7

Submocosal and smooth muscle of blood vessels

Question 8

(sympathetic)Stimulation causes?

Answer 8

bronchial smooth muscle relaxation. Decreased mucus secretion. Increased mucociliary clearance. vascular smooth muscle contraction.

Question 9

(sympathetic)What mediates the causes of stimulation?

Answer 9

B2-adrenoceptors on the cells of the tissue of the cell affected (they are activated by adrenaline).

Question 10

What is the first step of the depolarisation in Excitation Contraction Coupling in Smooth Muscle?

Answer 10

Depolarisation activated Ca2+ (voltage activated) channel which allows Ca2+ to travel into the cell.

Question 11

What is the second step of the depolarisation in Excitation Contraction Coupling in Smooth Muscle?

Answer 11

The Ca2+ then acts as a ligand and activates ryanodine receptor which allows Ca2+ to pass from the sarcoplasmic reticulum into the cell. (this has stored Ca2+)

Question 12

What is the third step of the depolarisation in Excitation Contraction Coupling in Smooth Muscle?

Answer 12

The Ca2+ in the cell causes contraction.

Question 13

How does Ca2+ cause contraction in smooth muscle cells? first reaction.

Answer 13

Ca2+ binds with calmodulin to form Ca2+-calmodulin.

Question 14

How does Ca2+ cause contraction in smooth muscle cells? second reaction.

Answer 14

Ca2+-calmodulin activates myosin light chain kinase.

Question 15

How does Ca2+ cause contraction in smooth muscle cells? third reaction.

Answer 15

Myosin light chain kinase then phosphorylates myosin cross bridge with breakdown of ATP.

Question 16

What types of reactions does myosin light chain kinase and myosin phosphatase do and what does that cause?

Answer 16

Respectively, phosphorylation - contraction and dephosphorylation - relaxation.

Question 17

In the presence of elevated Ca2+ the rate of phosphorylation is what compared to the rate of dephosphorylation?

Answer 17

Exceeds the rate of dephosphylation

Question 18

How does relaxation happen after contraction?

Answer 18

It uses primary and secondary transport of Ca2+ out of the cell to make the intracellular Ca2+ concentration at basal level

Question 19

What is the first and second reaction in the regulation of myosin chain kinase and phosphatase.

Answer 19

B2-adrenoceptor (GPCR) is activated by adrenaline and then activates Gs which activates AC(adenylyl cyclase).

Question 20

What is the third and fourth reaction in the regulation of myosin chain kinase and phosphatase.

Answer 20

AC with ATP forms cAMP. cAMP is then degraded by PDE to form PKA and 5’AMP.

Question 21

What is the two options of the fifth reaction in the regulation of myosin chain kinase and phosphatase.

Answer 21

PKA phosphorlates and inhibits myosin light kinase. It also phosphoylates and stimulates phosphatase. These both cause relaxation of bronchial smooth muscle.

Question 22

State the definition of Asthma

Answer 22

It is a recurrent and reversible (in short term) obstruction to the airways in response to substances (or stimuli that are not necessarily noxious and normally do not affect non-asthmatic subjects.

Question 23

What are the causes of asthma attacks?

Answer 23

Allergens, exercise, respiratory infection and environmental pollutants (smoke/dust etc)

Question 24

What are the symptoms of asthma?

Answer 24

Tight chest, wheezing, difficulty in breathing, cough.

Question 25

Chronic asthma involves what?

Answer 25

Pathological changes to the bronchioles that result from long standing inflammation.

Question 26

What are the 5 spesific effects of asthma on the broncholes?

Answer 26

1. increase mass from smooth muscle (hyperplasia and hypertrophy) 2. accumulation of interstitial fluid (oedema) 3. increase secretion of mucus. 4. epithelial damage (exposing sensory nerve endings) 5. sub-epithelial fibrosis

Question 27

What does the narrowing by inflammation and cronchoconstriction cause?

Answer 27

increasing airway resistance which causes a decrease in FEV1 and PEFR.

Question 28

What can epithelial damage do in the bronchial?

Answer 28

Expose nerve endings that contributes to increased sensitivity of the airways to bronchoconstrictors.

Question 29

What are bronchoconstrictors?

Answer 29

They are drugs that cause the bronchial to contract (histamine or methacholine etc)

Question 30

What is hypersensitivity in asthma?

Answer 30

When it takes less of a bronchoconstrictor concentration to initiate a fall in FEV1.

Question 31

What is hyper-reactivity in asthma?

Answer 31

When the fall in FEV1 increases dramatically with an increase in concentration of bronchoconstrictor.

Question 32

What is early phase asthma attack?

Answer 32

When there is a sudden drop straight after the inhalation of a brochoconstrictor.

Question 33

What is the late phase asthma attack?

Answer 33

This is after the patient has recovered from the early phase and then suddenly drops even further again.

Question 34

What happens during an early phase asthma attack?

Answer 34

Mainly brochospasm and also acute inflammation.

Question 35

What happens during a late phase asthma attack?

Answer 35

Bronchospasm and delayed inflammation

Question 36

What is FEV1?

Answer 36

The forced expiratory volume (in litres) in 1 second.

Question 37

What is the cause of a big immune response in asthma?

Answer 37

There is more strong Th2 responce. Antibody-mediated immune response involving IgE

Question 38

What happens with the Th1 response in severe asthma

Answer 38

It can cause so much Th1 response that this contributes to the big immune response as well

Question 39

What are the two stages called in the development of allergic asthma as a whole and individually?

Answer 39

Induction phase 1. Antigen presentation 2. Clonal expansion and maturation

Question 40

What happens in the first phase of the development in allergic asthma?

Answer 40

Allergen is captured and presented to T CD4+ by an antigen presenting cell. This then activates Th0.

Question 41

What happens in the second phase of the development in allergic asthma?

Answer 41

The Th0 then becomes Th1 and preferentially matures to become Th2. Th2 then activates B cells which then mature to IgE secreting plasma cells.

Question 42

What is the two ways Th2 can activate a B cell?

Answer 42

It can bind to them and produces IL-4 which also activates them.

Question 43

The Th2 cells do what to eosinophils and mast cells?

Answer 43

They activate eosinophils through IL-5 and cause mast cells in the airway tissue to express IgE receptors through IL-13.

Question 44

How does IgE receptors help in the development of allergic asthma?

Answer 44

They bind to the surface of a activated mast cell and when the antigen binds to them then they cause the release of granules containing preformed histomine and other egents (leukotriences LTC4 and LTD4) that cause airway construction. They also release substances and platelet activating factor and prostaglandins that attract cells causing inflammation.

Question 45

What is the events in the immediate phase of asthma?

Answer 45

Allergen or non-spesific stimulus causes activates mast cells and mononuclear cells. These then activate spasmogens, CysLTs and Histamine (all of which cause bronchospasms and early inflammation).

Question 46

What connects the intermediate phase to the late phase of asthma?

Answer 46

The chemotaxins and chemokines cause the first response of the late phase.

Question 47

What is the events in the late phase of asthma?

Answer 47

infiltration of cytokines releasing Th2 cells and monisytes, activation of inflammatory cells (particularly eosinophills) This activates mediators and CysLTs which cause airway inflammation, airway hyper-responsiveness. This leads to bronchospams and the other symptoms. The first stage also activates eosinophils major basic and cationic proteins which cause epithelial damage and so airway hyper-responsiveness.