Resp 2

Question 1

What is airway smooth muscle function dependant on

Answer 1

G protein coupled pathways.

Gq Gs Gi

Question 2

Gq

Answer 2

Airway constriction.

The G alpha q subunit stimulates phospholipase C. This makes DAglycerol and IP3.
The IP3 activates the cascade which cause Ca release in cells.
This changes the membrane potential and open more Ca channels causing Ca influx.
This activates CaM which activates myosinLCK by phosphorylation and causes contraction.

Question 3

What receptors cause Gq

Answer 3

M3 muscarinic.

H1 histamine

BK bradykinin.

Question 4

Gs

Answer 4

Airway relaxation

The alpha S subunit stimulates adenine Cyclase and makes cAMP and stimulates PKA.
PKA phosphorylates MLCK and relaxes the smooth muscle.

The alpha S subunit also activates BK K channel which causes hyperpolarisation and inactivates the Ca channels to stop contraction.

Question 5

Gs receptors

Answer 5

B2 adrenergic

VIP receptors

Question 6

Gi pathway

Answer 6

Activation of Gi receptors leads to inhibition of adenylate cyclase.

This stops the Gs pathway and muscles relaxing.

Gi also inhibits the BK K channel to cause depolarisation. This allows Ca channel opening.

Uses M2 muscarinic.

Question 7

Control of bronchial smooth muscle by NS.

Answer 7

Parasymp-
Arch released from vagus and acts on muscarinic receptors causing constriction.

Symp-
Release noradrenaline and it’s a weak agonist that causes dilation.

Question 8

Humoral affects on the bronchial smooth muscle.

Answer 8

Adrenaline in the blood is a stronger agonist for dilation.

Histamine released from inflammatory response leads to constriction.

Question 9

Parasympathetic control of muscle constriction

Answer 9

On the presynapse of the post ganglionic nerve there are M2 receptors.
On the smooth muscle there is M2 and M3 receptors.

Activation of M3 receptors causes contraction.
Ach travels across the cleft and some binds to M3 on the muscle. And some binds to M2 back on the pre synapse.

M2 causes ach release prevention and stop over stimulation.

Question 10

Activation of M3 receptors on smooth muscle causes

Answer 10

Gq pathway.
Ends with MLCK being phosphorylated and activated.

MLCK phosphorylates mysoinLC which causes cross bridge formation and contraction.

At the same time PKC inhibits MLC phosphatase and prevents relaxation.

Question 11

How to stop muscle contraction

Answer 11

Dephosphorylate myosinLC

Question 12

Sympathetic control of muscle constriction

Answer 12

When PKA has been stimulated it will phosphorylate MLCK and decrease it’s activity.

The BK K channel activation will also stop MLCK action.

Question 13

If the myosin LC is phosphorylated…

What does myosin LC phosphatase do ?

Answer 13

Cross bridges can form.

Dephosphorylated myosin LC causing muscle relaxation.

Question 14

Asthma and causes

Answer 14

Hyper active airways.

Atopic causes- allergies and inhaled allergens.

Non atopic- respiratory infections, cold air, stress,exercise.

Inflammatory cells move into airways and release mediators which cause bronchi constriction.

Their vital capacity is normal.

FEV1 drops below 80% of vital capacity as they have increased resistance so it’s harder to exhale.

Question 15

What should FEV1 be

Answer 15

Should be able to blow 80% or more of the vital capacity out.

Question 16

Parasympathetic NS causing asthma.

What happens when you inhale irritant.

Answer 16

The para NS is the one that causes constriction.

When you inhale irritants it causes increased para NS activity.

Decreased M2 function. Which usually stops over stimulation. So low M2 means the muscles are getting too much stimulation and it will contract too much.

Question 17

Three Experiments done to show airway hypersensitivity

Answer 17

Antigen challenge was given and caused eosenophils to cluster around neurons and release MBP (major basic protein) which inhibits M2 receptors.

Viruses cause interferons to down regulate M2 gene expression meaning less receptors are being made.

Neuraminidase cleaves M2 receptors and changes the binding affinity for ach. So less binds and less helps to stop overstimulation

Question 18

Diabetes and asthma.

Answer 18

Diabetics have a reduced number of asthma cases.

Suggesting the insulin pathway has something to do with asthma.

Question 19

Asthma treatments. 4

Answer 19

Salbutamol is a B2 adrenergic agonist which stimulates the Gs pathway for relaxation of muscle. It is short acting.

Salmeterol is longer acting and is delivered with corticosteroids.

Anticholinergics block ach and stop it activating M3 which causes constriction.
Tiotropium bromide inhales once daily and stops M3.

Glucocorticoids are anti inflammatory. Reduce binding of eosinophils. Turns off inflammatory genes to stop constriction.
They are inhaled, beclometasone

Question 20

What is breathing

Lesion between medulla and pons

Lesion between medulla and spinal cord

Answer 20

Automatic rhythmical process that is regulated by centres in the medulla. It is usually involuntary but can be voluntary for breath holding etc but this can be overridden.

Maintain basic breathing rhythm.
Pontomedullary transection

Breathing pattern is lost.
Spinonedullary transection.

Question 21

Which group of neurons is linked to inspiration and which is linked to expiration.

Answer 21

Dorsal respiratory group is linked to inspiration

Ventral respiratory group is linked to forced expiration and inspiration

Question 22

What does activity in the hypoglossal nerve match

Answer 22

The pre botzinger complex output.

Every few seconds the pre BOTC shows a burst of activity and this is also shown in the hypoglossal nerve.

Question 23

The pre BOTC can generate three types of pattern output:

Answer 23

Eupneic- normal breathing.

Sigh- increased magnitude and larger breath.

Gasp- short bursts and hypoxic.

Question 24

Two main classes of neurons in the pre BOTC

Spiking and bursting

Answer 24

Pacemaker cells and non pacemaker cells

Pacemaker cells generate their own rhythmic action potentials (spiking or bursting)
The spiking phase is where there are constant spikes of action and is linked with a slow background depolarisation. The Na leak current causes the gradual depolarisation.

The membrane potential then remains depolarised and this is the bursting phase. The persistent Na current is activated and it causes inspiration. Then it will inactivate and happen again.

The spiking phase leads to the bursting phase. Slow depolarisation leading to constant high depolarisation and then inhalation.

Question 25

Na leak channel for depolarisation in mice

Answer 25

Mice with this channel KO die within 24 hours because they can’t maintain a normal breathing pattern.

Show periods of apnea (stopping breathing for short periods of time)

Membrane potential stays hyperpolarised.

Question 26

Role of K in breathing

Answer 26

Background membrane potential is governed by K and it determines the starting membrane potential.

Increasing K in the neurons causes depolarisation. This makes the bursting phase more possible.

Question 27

The transition to bursting activity depends on two currents.

Classes of pacemaker cells

Answer 27

Persistent Na current INAP
CAN Cation current ICAN.

The ICAN current is activated by Ca influx and during the sigh breathing pattern.

Neurons relying on ICAN for bursting are cadmium sensitive.

Neurons relying on INAP for bursting cadmium insensitive.

Question 28

How breathing changes during hypoxia

What is lost

Answer 28

Sighs happen to get more air and oxygen into the body.
Gasps happen as it worsens.

Inhibit the inhibitory post synaptic potentials to cause depolarisation and help the bursting phase.

Spiking neurons are lost first during hypoxia then cadmium sensitive neurons are lost.

Some cadmium insensitive neurons remain active and these are responsible for gasps.

Question 29

What are the medullary centres used for breathing.

Answer 29

Dorsal group of neurons-
Controls inspiration by sending signals to the inspiratory muscles.
Spontaneously active and shows a period of activity then shuts off for quiet expiration.

Ventral group of neurons-
Controls inspiration and expiration and it is inactivate during quiet respiration.

LOOK AT PHOTOS

Question 30

How does the pons help breathing

Answer 30

Two centre in the pons send stimuli to the medulla to regulate rate and depth of breathing.

Pneumotaxic- increases the rate by shortening inspirations and has an inhibitory effect on the inspiratory centre.

Apneustic centre- increases the depth and reduces the rate by prolonging inspirations and it stimulates the inspiratory centre.

Question 31

Stretch receptors and breathing

Answer 31

The hering Breuer reflex-
Stretch receptors in the lungs send signals back to the medulla to limit inspiration and prevent over inflation if the lungs.

The inspiratory centre sends an impulse down the phrenic nerve and the diaphragm contracts.
The stretch receptors in the lung are activated and send a signal via the vagus nerve to the inspiratory centre. And when the signal becomes too large inspiration will stop.

Question 32

Chemoreceptors

Answer 32

The central ones monitor conditions in the CBSF by sensing CO2 and pH. A rise in CO2 stimulates a rise in ventilation.

The peripheral ones in the carotid body and aortic arch respond to high CO2 and low O2 and pH. Stimulation leads to an increased ventilation.