Respiration (L1-4)

Question 1

What are the factors that have a role in determining airflow?

Answer 1

1. Type of airflow
2. The resistance of the pathway
3. Pressure gradients generated across the airways
4. Links between lung volume, resistance and airflow

Question 2

What is the equation governing airflow into and out of the lungs? Explain it

Answer 2

V=ΔP/R - Movement of air is proportional to the pressure gradient (difference in pressure between alveolar and atmospheric), and inversely proportional to the resistance. So the higher the pressure gradient, and the lower the resistance, the higher the air flow.

Question 3

What is meant by the term laminar flow?

Answer 3

Steady flow down a tube in a uniform direction and speed - flow rate is maximal at the centre of the tube but reduces towards the edges.

Question 4

What is meant by the term turbulent flow? what is this movement proportional to?

Answer 4

When flow rate moves beyond a critical value, causing irregular currents and vortices to develop. This type of gas movement is proportional to the square root of the pressure difference

Question 5

Why is more effort required to move gas under turbulent flow than laminar flow?

Answer 5

Under turbulent flow, the pressure gradient is squarely rooted. So a greater pressure gradient is needed to obtain the same flow seen under laminar conditions i.e. more effort is required. The differences between the 2 start off small and then increases as the flow rate increases.

Question 6

What is meant by the term transitional flow?

Answer 6

When flow alters between turbulent and laminar due to bumps and bifurcations on the inner surface of the bronchioles. This creates eddies (swirling and reverse currents)

Question 7

What is flow type determined by?

Answer 7

Reynolds number (Re=2rvρ /η) r = radius of the vessel, v= velocity, ρ = density of gas, η = the viscosity. If Re is below 1000, laminar flow is present. If Re is between 1000-1500 transitional flow is present. If Re is above 1500 turbulent flow is present.

Question 8

Why is laminar flow present at the ends of the airways by the alveoli?

Answer 8

If cross section decrease, velocity as to increase to keep the same flow. In the alveoli, the total cross section is very big, so the velocity is a lot lower. This means Re will decrease so laminar flow is present in the alveoli.

Question 9

What is the impact of resistance on flow determined by? Explain it

Answer 9

Pouiseuille’s Law - Airway resistance is proportional to gas viscosity and the length of the tube but is inversely proportional to the fourth power of the radius (R=8/π x ηι/r^4). Therefore, small changes in the airway have a big impact on the resistance and therefore airflow. HOWEVER, THIS LAW CAN ONLY BE APPLIED TO LAMINAR FLOW.

Question 10

In a normal individual, what is the total airway resistance?

Answer 10

The total airway resistance is 1.5cm H2O x Litres^-1. The pharynx-larynx contribute to about 40%. Airways larger that 2mm contribute to 40% and airways smaller that 2mm contribute to 20%.

Question 11

Why is there a peak on a graph showing resistance and size of airways at about where the trachea bifurcates?

Answer 11

There’s a peak in the graph because the resistance increases in the trachea and the bronchi stay relatively unbranched but get a bit thinner, then when resistance starts to decrease (like in a parallel circuit - 1/R +1/R +1/R)

Question 12

What factors impact airway resistance due to effecting airway diameter?

Answer 12

1. Increased mucous secretion e.g. due to illness will effectively reduce airway diameter and increase resistance
2. Oedema- Increased fluid retention in the lungs will cause swelling and narrow the airways increasing resistance
3. Allergic reactions e.g. histamine causes muscle contraction which decreases diameter.

Question 13

Explain the pressure gradients in the airways.

Answer 13

Airflow alters the pressure difference across the walls of the airway, and this change in transmural pressure (difference in pressure between 2 sides of a wall -Ptm) can cause the airway to expand or collapse. If the volume of the lungs is at functional residual capacity (the volume left after a breath), The transpulmonary pressure (Transmural pressure in the alveoli) is 5 (just an example number) whether you are at rest, or breathing in or out. In the absence of air flow, the pressure inside all airways must be 0. Therefore, in the alveoli, Transpulmonary pressure must be 5, and the intrapleural pressure is - 5 because the pressure has to be balanced (ignore gravity and assume Pip is the same all the way down the lungs. So there is no overall pressure in the alveoli and trachea/bronchi, only in the pleura. Therefore Transmural pressure is equal to the airway pressure - the intrapleural pressure

Question 14

How does resistance change when breathing?

Answer 14

During inspiration - forced expansion of some higher airways due to intrapleural pressure decreasing - decreases resistance
During expiration- forced collapse of some higher airways due to intrapleural pressure increasing- increases resistance

Question 15

Explain what happens in the lungs when there is an emphysema

Answer 15

In a patient with emphysema, the airway compression in expiration is exaggerated. This is due to the loss of elastic tissue and the breakdown of the alveolar walls. the tethering between walls of adjoining airspaces is reduced. Therefore, the airways are flimsy and during a forced expiration are less able to resist collapsing. Flow and volume are reduced. To overcome the problems caused by this, patients can slowly exhale, and breath at a higher lung volume.

Question 16

Explain what happens to the lungs during COPD

Answer 16

Chronic obstructive pulmonary disease.
Airway resistance is higher, so lungs stay at a higher volume because not as much air can be exhaled. When resistance is increased, inflation is impaired. E.g. in spirometry less than 95% of air is exhaled in 1 second (FEV1) and tidal volume is lower when inflation is impaired.

Question 17

What is the equation for total ventilation?

Answer 17

The volume of air moved out per unit time (V dot = V/t). t = breaths per min so you can ventilation per min (breaths /volume per breath) nice and straight forward :)

Question 18

What zones make up the respiratory system

Answer 18

A conducting zone (not involved in gas exchange) and a respiratory zone

Question 19

What does alveolar ventilation equal and why?

Answer 19

During every breath, not all the fresh air reaches the respiratory zone. So, alveolar ventilation = total ventilation- dead space ventilation (volume in conducting zone x bpm)

Question 20

How does alveolar ventilation impact arterial gas composition?

Answer 20

Increase in ventilation leads to a direct decrease in the alveolar partial pressure of CO2 and a direct increase in the partial pressure of O2.

Question 21

How does lung ventilation vary according to the position?

Answer 21

More ventilation takes place at the base of the lungs than the apex. These differences are linked to posture and the effect of gravity. The pressure difference is higher in the base, so more flow and exchange takes place.

Question 22

Explain the difference in ventilation at different positions in the lung

Answer 22

At the apex, the weight of the lungs increases the intrapleural pressure because of the membranes being pulled apart. This makes the intrapleural pressure at the apex more negative. Therefore, the force on the alveoli from the negative pressure means they’re being held open more. Therefore, there’s the same amount of surfactant surrounding them, but it’s being spread out more because of a higher starting volume. Therefore, their compliance is decreased. This means their ventilation is less (it’s like trying to fill a partly filled balloon, you’re not gonna get as much air in). Whereas at the base of the lungs, the intrapleural pressure is less negative, so the alveoli have a lower starting volume, meaning a more concentrated surfactant and the alveoli are more compliant. Meaning they are able to inflate more, increasing ventilation.

Apex = lower intrapleural pressure, higher staring volume, lower compliance, less ventilation
Base + higher intrapleural pressure, lower starting volume, higher compliance, more ventilation

Question 23

When is pulmonary resistance lowest?

Answer 23

When the lungs are at the FRC. The pulmonary circulation system is at a lower pressure and resistance that the systemic system

Question 24

What does perfusion mean?

Answer 24

Blood flow in the lungs

Question 25

Explain the different types of vessels in the lungs

Answer 25

Alveolar vessels: Capillaries and slightly larger vessels which are surrounded on all sides by alveoli - their resistances are linked to transmural pressure and lung volume.
Extra-alveolar vessels: Vessels not surrounded by alveoli- they are sensitive to change in intrapleural pressure.

Question 26

What happens to the pressure in the vessels during breathing?

Answer 26

Expiration causes an increase of pressure so leads to the compression of alveoli. AT the end of inspiration, you get inflation of alveoli, so they intrude onto the vessels and causes an increase in pressure. But at the same time, a more negative intrapleural pressure opens up the extra-alveolar vessels and decreases their pressure.

Question 27

What happens during capillary recruitment? Why does it occur

Answer 27

Pulmonary circulation can accommodate date increases in pulmonary pressure and and flow rate by recruitment - this reduces system resistance. E.g. during exercise when flow increases so capillaries are recruited to stop the resistance getting too high (like adding new paths to a parallel circuit). Before flow increase, some vessels are open but blood doesn’t flow down them, then when theres an increase in perfusion pressure, blood flows down the open capillaries, then at the same time other vessels that were shut open but don’t conduct (like a fail safe for if it gets any higher).

Question 28

Why during inspiration does the resistance of the extra alveolar vessel decrease but the alveolar vessels increase?

Answer 28

At residual volume, your thoracic volume is small due to no contraction of your diaphragm etc. therefore, your intrapleural pressure is higher (because there’s no pull from the ribcage so it’s at a smaller volume) therefore, the transmural pressure is lower (i.e. the vessels aren’t being pulled into the space as much) so they’re more constricted and therefore have a higher resistance
When you inspire, your thoracic volume increases. This makes the interpleural pressure decrease, which allows the lungs to inflate. As the interpleural pressure decreases, the transmural pressure between the interpleural space and the extra alveolar vessels increases, causing them to dilate and therefore decrease in resistance
During inspiration, your alveoli are filled up, so have a higher pressure – therefore the alveolar vessels are more constricted and therefore have an increased resistance.

Question 29

How does the perfusion of the lungs change at the position of the lungs?

Answer 29

• Perfusion is also greater at the base of the lungs due to gravity and posture– just like ventilation

• Outside the heart at the level of the left atrium is the reference point for pulmonary circulation pressures
• Pressure in the pulmonary arterioles (PPA) has a mean of about 15mmHg (20 Cm H2O) and it’s about half that in the pulmonary venules
• These pressures fall by about 1cm H2) for every 1cm above the left atrium and increase 1cm H2) for every 1cm below.
• So basically, pressure is higher at the base – means more perfusion

Question 30

Explain the zones of the lungs

Answer 30

Lungs have zones 2,3, and 4. Zone 1 conditions only occur when the alveolar pressure is very high e.g. positive pressure ventilation or when the pressure in the arterioles is low e.g. due to a haemorrhage.
At zone 1 the vessel pressure is so low that the alveolar pressure is higher and therefore, the vessel is very constricted. The transmural pressure is negative, so blood vessels start collapsing (therefore a low perfusion rate
At zone 2, the pressure in the arterioles is higher than in the alveoli (the arteriole pressure increases going down the lung) so the vessels next to the alveoli get less constricted going down the lung, and the venules increase in pressure too.
At zone 3, the arteiole pressure is now getting a lot higher so theyre actually dilating at the alveoli because the transmural pressure is positive
•At zone 4, the transmural pressure is so high that the vessel actually constrict when not next to the alveoli. The impact of the interplearal pressure collapses the capillary

Question 31

What are some factors that cause the dilation of Pulmonary vessels?

Answer 31

Increase in arterial oxygen (decreases pressure and decreases gas exchange?)
Decrease in arterial carbon dioxide\Increase in pH
Histamine (H2) agonists
Prostacyclin
Beta-adrenergic agonists e,.g. salbutamol
Bradykinin
ACh
NO

Question 32

What are some factors that cause the constriction of pulmonary vessels ?

Answer 32

Decrease in arterial oxygen
Increase in arterial CO2
Decrease in pH
histamine H2 agonists 
Thromboxane
Alpha adrenergic agonists
serotonin
Angiotensin 2

Question 33

What do variations in the ventilation and perfusion ratio influence?

Answer 33

Gas composition
- If these alveoli are not ventilated, then the V/Q ratio becomes 0. (no air or blood flow)
- The gas composition will become the same as that of mixed venous blood (an equilibrium between O2 and CO2) 40mmHg )2 and 46mmHg CO2
- If the alveoli are not perfused – the V/Q ratio tends towards infinity (i.e. if they’re being ventilated but not perfused) because the perfusion is on the bottom, so the number will keep getting bigger. The gas composition will become the same as that of inspired humidified air (all O2 and no CO2)
• , there is a higher V/Q at the apex, because perfusion is lower than ventilation rate (so is more like inspired air)
• Whereas at the base, there’s more perfusion than ventilation so the V/Q is lower, and is more like venous blood

Question 34

Explain what happens during an ventilation/perfusion mismatch

Answer 34

• Alveolar – dead space ventilation

• Due to a local reduction of perfusion e.g. a pulmonary embolism
• Because there’s no exchange, the gas composition in the effected alveoli becomes the same as moist inspired air – therefore the V/Q tends towards infinity
• Compensation: blood is redirected to other areas, bronchiolar constriction (decreases ventilation to right the ratio), reduction in surfactant (alveoli are less compliant- leads to reduction in ventilation)

Question 35

Explain what a shunt is and why it would be used

Answer 35

• Local reduction of ventilation e.g. tumour or foreign body in airways
• Because gas can’t be removed from the area, the composition becomes the same as mixed venous blood, so a shunt is put in to open the airways back up

Question 36

How is airway diameter controlled?

Answer 36

Parasympathetic and sympathetic control of airway smooth muscle

Question 37

Explain how Gq proteins are used in the control of airway smooth muscle

Answer 37

Receptors acting through the Gq pathway include M3 muscarinic receptors (the main ones), H1 histamine receptors and BK bradykinin receptors
This pathway causes constriction. An agonist binds to of the airways.
An agonist binds to a Gq coupled receptor which will stimulate a protein cascade. The Gq alpha subunit is cleaved off when an agonist binds - it stimulates phospholipase C which leads to the production of DAG (which is actually used to stimulate growth) and IP3 - the IP3 activates a cascade to release calcium from intracellular stored. Changes in membrane potential (from nerve stimulation) also opens voltage-gated sodium channels so calcium moves into the cell. The calcium released activates CaM. This complex activates MLCK which leads to contraction

Question 38

Explain how Gs proteins are used in the control of airway smooth muscle.

Answer 38

Receptors acting through this pathway are Beta2 adrenergic receptors and VIP receptors
This pathway causes relaxation of smooth muscle
An agonist binds to the Gs protein and the alpha subunit cleaves. It stimulates adenylate cyclase which causes the increased production of cAMP and stimulates PKA. This also inactivates the calcium channels so decreases contradictory effect. This leads to smooth muscle relaxation because cAMP inhibits MLCK’s contracting effect.

Question 39

Explain how Gi proteins are used in the control of airway smooth muscle

Answer 39

Coupled to alpha 2 adrenergic receptors which is activated by noradrenaline.
Activation of Gi receptors leads to the inhibition of adenylate cyclase. This knock-on effect counteracts the stimulatory effect of Gs activation, which causes the channel to stay contracted.
It also inhibits the BK calcium channel (not the same as the bradykinin receptor) this makes calcium channels more sensitive so the Gq pathway is more efficient
M2 Muscarinic receptors also act through this pathway

Question 40

What controls bronchiole smooth muscle?

Answer 40

The autonomic nervous system - Parasympathetic - ACh is released from the vagus nerve and acts on Muscarinic receptors to cause constriction. Sympathetic stimulation - Noradrenaline released from nerves is a weak agonist of adrenergic receptors (Gs pathway) and leads to dilation

Question 41

What are some humoral factors that control bronchial smooth muscle?

Answer 41

Adrenaline in circulating blood - this is a stronger agonist that NA so leads to more dilation
Histamine- released during inflammatory response e.g allergies and causes constriction

Question 42

Explain parasympathetic control of bronchial smooth muscle

Answer 42

Parasympathetic control depends on o the location of the receptors.
The preganglionic neurone releases NA to activate N2 nicotinic and M1 receptors. This causes the postganglionic nerve to release ACh which activates M2 and M3 receptors on the airway smooth muscle and causes contraction. There are also M2 receptors on the postganglionic neurone which act as an important feedback mechanism. Basically, the ACh activates M2 receptors on the postganglionic neurones which stops it from releasing any more ACh.
Breakdown of this pathway leads to things like asthma because the airway smooth muscle remains contracted. To stop contraction of the muscle you dephosphorylate the myosin to stop cross chains rather than just decreasing the calcium like with smooth muscle.

Question 43

Explain the sympathetic control of airway smooth muscle

Answer 43

Uses classical signalling. A beta 2 agonist binds and activates the Gs protein which causes the stimulation of adenylyl cyclase which makes cAMP. The cAMP activates PKA which decreases MLCK and causes muscle relaxation. If the BK potassium transporter is activated you move potassium out of the cell - this causes the cell to hyperpolarise which shuts voltage-gated calcium channels and therefore decreases the amount of intracellular calcium - this decreases the activity of MLCK and helps with relaxation. This relaxation is useful for flight or fight because it increases ventilation and therefore how much oxygen available for transport (so you can use your muscles more)

Question 44

What can asthma attacks be triggered by?

Answer 44

Atopic (extrinsic) factors e.g. allergens

Non-atopic (intrinsic factors) e.g. respiratory infections, cold air, stress, exercise, inhaled irritants and drugs

Question 45

How does the body respond to asthma triggers?

Answer 45

Movement of inflammatory cells into the airways, the release of inflammatory mediators e.g. histamine - causes bronchoconstriction

Question 46

How does the spirometry of an asthma patient differ from a normal patient?

Answer 46

Shows a decrease in FEV1 due to constricted airways, but an unaltered FVC (lun volume doesn’t change) Its an obstructive disorder.

Question 47

What causes airway hypersensitivity in asthma patients?

Answer 47

Asthma is associated with an increase in parasympathetic activity - e.g. an increase in constriction
This manifests as an increase in basal tone of the airway smooth muscle and an increase constrictive response to irritants
Experiments have been performed using animal models: - antigen challenge (dose of antigen given to an animal sometime after primary immunisation to see if the immune system is working) was shown that viral infection, ozone exposure and Vitamin A deficiency all produce and increase parasympathetic activity
In all of these models there is no change in th function of M1 or M3 receptors but there is a decrease in M2 receptors, so the negative feedback loop to turn off ACh doesnt work properly.
In the case of the antigen challenge, the change in M2 function is linked to eosinophils which are clustered around the nerve fibre
Activated eosinophils release MBP which is what inhibits the M2 receptors

Question 48

What are some current treatments of asthma?

Answer 48

Beta 2 adrenergic agonists - Most commonly used, can be short acting e.g. salbutamol or longer acting e.g. salmeterol (needs to be delivered with corticosteroids)
Anticholinergics - blocks endogenous ACh, e.g. triotropium bromide. Inhaled once a day - acts mainly via M1 and M3 receptors so stops constriction outright
Glucocorticoids - has anti-inflammatory actions, inhaled steroids like beclometasone

Question 49

What area of the brain generates the basic rhythm of breathing?

Answer 49

The medulla - it is involuntary but can be temporarily overridden e.g. hyperventilating or holding your breath. The dorsal respiratory group is the control of inspiration and the ventral respiratory group is involved in the control of expiration and forced inspiration. The DRG shows spontaneous activity (turns on and off) and the VRG is inactive during quiet respiration

Question 50

What nerves are used to relay information on breathing pattern

Answer 50

For inspiration, the DRG (and a bit of the VRG) send signals via the phrenic nerve (to the diaphragm) and the spinal nerves (to the external intercostals) For expiration, the VRGs send signals via the spinal cord to the spinal nerves of the internal intercostals and the abdominal muscles

Question 51

What is the pre-botzinger complex?

Answer 51

The pre-botzinger complex is in the rostral VRG and sends periodic signals to the hypoglossal nerve. This was measured by putting electrodes into both and the periodic activity (on/off signals) matches up in both

Question 52

What 3 different types of pattern output can the PBC generate?

Answer 52

1. • eupneic - standard, normal breathing
2. Sigh- not as common, an increased magnitude (but still the same pattern of signals)
3. Gasp - shorter duration, happens de to a hypoxic state to increase intake of oxygen

Question 53

What cells is the PBC made up of? what is their significance?

Answer 53

The complex is made up of 2 main classes of neurones - pacemaker and non-pacemaker
The pacemaker cells can demonstrate spiking and bursting forms of activity and can generate their own rhythm.

Question 54

What causes spiking and bursting?

Answer 54

Siking is due to background depolarisation due to a sodium leak channel (NALCN). Sodium slowly leaks in, casing a small amount of depolarization, and then this opens a voltage-gated sodium channel and causes depolarization (a spike). A persistent sodium current leads to bursting and therefore inspiration

Question 55

What is fictive eupneic activity and what is it caused by?

Answer 55

Spiking then bursting then off then repeat - Overall, activity shows 1 neurone spiking, and that is what causes the inspiration

Question 56

What happens to NACLN KO mice?

Answer 56

In a knockout for NACLN, the mice die within 25hrs because they can’t create a steady breathing rhythm and die of hypoxia. They experience apnea (no breathing for lengths of time). There is no bursting, so no steady inspiration. No CLN means the membrane is more hyperpolarised, so it is harder to depolarise the membrane and make the APs n the PBC.

Question 57

Why is potassium important in breathing rate?

Answer 57

Potassium is important because it contributes to the depolarization, a higher potassium conc leads to quicker bursts
Potassium conductance helps determine the resting potential.

Question 58

What are the 2 classes of pacemaker cells in the PBC and why are they significant? How do they contribute to the transition to bursting activity?

Answer 58

The transition to bursting activity depends on 2 different types of inward current, the persistent sodium current (INAP) and thr CAN cation current (ICAN) - the pacemaker cells can split into 2 classes depending on whether bursting activity is sensitive to cadmium.
Neurones relying on ICAN for bursting are cadmium sensitive and neurones relying on INAP for bursting are cadmium insensitive. Cation current is activated more during sigh breathing. Modulation of bursting is a very complex process. When hypoxia occurs you start sighing and then if this doesn’t help you start gasping

Question 59

How is the pons involved in respiration?

Answer 59

Two centres in the pons send stimuli to the medulla to regulate rate and depth of breathing
The pneuomtaxic centre - increases rate by shortening inspiration due to an inhibitory effect on the inspiratory centre
The apneustic centre increases the depth of breaths and reduced the rate by prolonging inspirations through a stimulatory effect on the inspiration centre.

Question 60

How are stretch receptors involved in the regulation of respiration?

Answer 60

They act as a negative feedback mechanism to stop over inflation of the lungs

Question 61

What is the Hering-Breuer reflex?

Answer 61

When stretch receptors int he lungs send signals back to the medulla (via vagus nerve) to limit inspiration and prevent over-inflation of the lungs.