Respiration

Question 1

Define compliance

Answer 1

A measure of the lungs ability to stretch and expand

Question 2

How does the value of airway resistance differ in healthy subjects compared with those with COPD?

Answer 2

Normal - 0.5 - 2.0

COPD - 5.0 (small airways = 70%)

Question 3

Define airway resistance

Answer 3

The opposition of flow caused by forces of friction

Question 4

Define laminar flow

Answer 4

Particles passing any point have the same speed and direction

Question 5

Which airways have laminar flow

Answer 5

Trachea and bronchi

Question 6

Define turbulent flow

Answer 6

The average velocity passes a critical value causing vortices to develop, increasing the resistance to flow

Question 7

Which airways have turbulent flow

Answer 7

Bronchioles

Question 8

What does a Reynolds number of less than 1000 indicate

Answer 8

Laminar flow

Question 9

What does a Reynolds number of more than 1500 indicate

Answer 9

Turbulent flow

Question 10

What is Reynolds equation?

Answer 10

Re=2dvp/n (d = diameter, v = velocity, p = density of gas, n = viscosity)

Question 11

What are the factors that effect airway resistance?

Answer 11

Nervous factors, chemical factors, humoral factors and mechanical factors

Question 12

How do nervous factors effect airway resistance?

Answer 12

Contribute to bronchial tone. In the parasympathetic NS the vagus nerve releases ACh which binds to M3 receptors. In the sympathetic NS NE is a weak agonist to B2 adrenergic receptors that leads to dilation and decreased glandular secretions via cAMP.

Question 13

Which drug blocks the bronchoconstriction caused by the binding of ACh to M3 receptors?

Answer 13

Atropine

Question 14

What are the chemical factors that effect airway resistance?

Answer 14

Endogenous (histamine, adrenaline, leukatrines, PACO2) and exogenous (B2 agonists and muscarinics)

Question 15

What are the humoral factors that effect airway resistance?

Answer 15

Epinephrine - released from the medulla and more potent than NE
Leukotrienes LTC4 and LTD4 are more potent than epinephrine

Question 16

How do Ptm, Ptp, Pip and Pa change during inspiration?

Answer 16

All values of Ptm increase but these begin to decrease down the airways, Pa decreases and also decreases down the airways, Pip decreases

Question 17

How do Ptm, Ptp, Pip and Pa change during expiration?

Answer 17

Ptm decreases but these values increase down the airways. Pa increases and increases down the airways. Pip increases.

Question 18

Describe what happens to the airways in Emphysema

Answer 18

There is a loss of elastic tissue and the alveolar walls break down, the tethering between adjoining air spaces is reduced. This leads to the airways becoming flimsy therefore they are less likely to resist collapse during expiration and the compression of the airways becomes exaggerated.

Question 19

How do patients overcome Emphysema?

Answer 19

Slow exhalation and exhaling through pursed lips

Question 20

Define ventilation

Answer 20

The volume of air moved out of the lung per unit time

Question 21

What is the anatomical dead space?

Answer 21

The first portion of air that enters the respiratory zone and is referred to as stale air. It is approx. 0.15 litres

Question 22

Which area of the lungs is ventilation at its highest?

Answer 22

The base

Question 23

Describe the process of capillary recruitment

Answer 23

1. Some capillaries are open and conduct blood, however some are open and not conducting or collapsed and not conducting
2. Perfusion pressure increases. During recruitment, the previously collapsed capillaries are now open but still not conducting. The previously open but not conducting airways now conduct blood. Distension widens vessels that were already open and conducting blood.
3. Perfusion pressure further increases. Later in recruitment previously collapsed vessels conduct blood. All vessels dilate and hence resistance falls.

Question 24

What are extra-alveolar blood vessels?

Answer 24

Blood vessels that don’t surround alveolar air spaces

Question 25

When is pulmonary resistance at its lowest?

Answer 25

When lungs are at functional residual capacity

Question 26

Where is the reference point for pulmonary ventilation circulation pressures?

Answer 26

Outside the heart at the level of the left atrium

Question 27

How do Ppa and Ppv change above and below the atrium?

Answer 27

They fall by about 1cm H20 for every 1cm above the left atrium and increase by 1cm H20 for every 1cm below the left atrium

Question 28

What happens to the ventilation/perfusion ratio when the alveoli aren't ventilated?

Answer 28

It becomes 0, therefore the gas composition will become that of venous blood (40mmHg O2 and 46mmHg CO2)

Question 29

What happens to the ventilation/perfusion ratio when the alveoli aren't perfused?

Answer 29

It tends to infinity. The gas composition becomes the same as that of inspired, humidified air (149 mmHg O2 and 0 mmHg CO2)

Question 30

What are the values of the V/Q ratio at the apex, base and overall?

Answer 30

Apex - 3.3 Base - 0.6 Overall -0.84

Question 31

What is the ventilation/perfusion mismatch?

Answer 31

Alveolar dead space ventilation - local reduction in perfusion (e.g. from pulmonary embolism). V/Q becomes infinite. This is compensated by blood being redirected, bronchioles are constricted and a reduction in surfactant production. Shunt - local reduction in ventilation (e.g. from tumour or foreign body). Composition becomes same as mixed venous blood as gas can't be removed from an area.

Question 32

How do Gs, Gq and Gi coupled receptors control airway smooth muscle?

Answer 32

Gq leads to bronchoconstriction through M3, H1 and Bk receptors. Gs leads to airway relaxation througb B2 and VIP receptors. Activated Bk leads to hyperpolarisation and inactivation of Ca2+ channels. Gi inhibits adenylate cyclase and counteracts the stimulatory effect of the Gs pathway. It inhibits the Bk pathway and is stimulated through M2 receptors.

Question 33

How is the parasympathetic NS responsible for the control of bronchial smooth muscle?

Answer 33

ACh from the vagus nerve acts on muscarinic receptors that lead to constriction. Muscle contraction controlled by stimulation of M3 receptors. Negative feedback of M2 on post-ganglionic nerve.

Question 34

Describe how M3 receptors lead to muscle contraction

Answer 34

ACh binds to M3 in the membrane. This stimulates the G protein which causes the dissociation of Gq-alpha from the beta and gamma subunits. Gq-alpha activates PLC which activates IP3. PLC also activates DAG which can activate PKC or lead to calcium influx. IP3 leads to calcium release from stores and calcium binds to CaM. Activated CaM phosphorylates MLCK which leads to cross bridge formation.

Question 35

What are some ways in which muscle contraction can be stopped?

Answer 35

PKA decreases MLCK activity Activation of K+ channels decreases Ca2+ influx MLCP dephosphorylates MLC which leads to muscle relaxation

Question 36

Asthma is associated with increased activity of which branch of the nervous system?

Answer 36

The parasympathetic nervous system

Question 37

Which muscarinic receptors are affected in asthma?

Answer 37

M2

Question 38

Describe the mechanism of asthma

Answer 38

Activated eosinophils release major basic protein MBP inhibits M2 receptors Too much ACh is released and leads to airway constriction Asthma activates the Gs pathway (???)

Question 39

How is asthma treated?

Answer 39

B2 adrenergic agonists (salbutamol and salmeterol) Anti-cholinergics (tiotropium - acts via m1 and m3 receptors and blocks the effects of endogenous ACh) Glucocorticoids (beclometasone - anti-inflammatory effect)

Question 40

What is the control centre for respiration?

Answer 40

The medulla - ventral and dorsal

Question 41

What are the ventral and dorsal areas of the medullary respiratory centre responsible for?

Answer 41

Ventral - forced inspiration and expiration | Dorsal - quiet inspiration but no link to expiration

Question 42

What is the Pre-Botzinger Complex?

Answer 42

A neural network in the brainstem that is responsible for generating and modulating respiratory rhythm

Question 43

What matches the Pre-Botzinger complex output?

Answer 43

The hypoglossal nerve

Question 44

What are the different pattern outputs from the Pre-Botzinger complex?

Answer 44

Eupneic (normal/fast and low), sigh (slow and large amplitude rhythm) and gasp (faster rise, shorter bursts and lower frequency)

Question 45

How do these different patterns occur?

Answer 45

By pacemaker and non-pacemaker neurons. Pacemaker cells demonstrate the the spiking and bursting activity. Sodium leak currents give the gradual depolarisation. Persistent Na channel eventually becomes inactivated.

Question 46

Discuss the importance of the NALCN

Answer 46

It contributes to the depolarisation phase. Mutants can't maintain a normal pattern and have an increased aponeas. There is also a loss of slow depolarisation and they are kept hyperpolarised.