3. Gaseous Transport, Exchange and Ventilation

Question 1

What is the average resting breathing rate of healthy adult subjects?

Answer 1

12-15 breaths/min, each of ~0.5L

Question 2

What is minute ventilation?

Answer 2

The volume of air entering the lungs each minute

This is given the notation V1, with a dot over the V to show that it is a rate and 1 being subscript

Minute ventilation will be 6.0L/min if breathing at 12breaths/min (12 * 0.5), or 7.5L/min if breathing at 15breaths/min

Minute ventilation is also sometimes called ‘total ventilation’ or ‘pulmonary ventilation’

Question 3

What is tidal volume?

Answer 3

The volume of air breathed in roughly equals the volume breathed out, so that the net flow over a complete cycle is zero

This volume of air is called the tidal volume (VT), with ‘T’ being subscript in this notation

Question 4

What does one do to express changes in breathing, for example as a result of exercise of disease?

Answer 4

Measure the flow in one direction only, conventionally the volume breathed out per minute (E), to calculate minute ventilation

Question 5

Outline spirometry

Answer 5

A spirometer is an instrument used to measure changes in lung volumes and consists of a closed space from which the subject breathes

It can come in many forms; one type consists of a hollow bell supported in a trough of water; as the subject breathes in, air is drawn from the bell and it sinks slightly; when the subject breathes out the bell rises

Spirometry can be used to measure most lung volumes

Question 6

What is the minute volume?

Answer 6

The minute volume equals total ventilation and will be 7,500 ml/min (500 x 15) breathing at 15 breaths/min

Question 7

What proportion of inhaled air remains in the anatomical dead space and what volume enters the respiratory zone if breathing rate is 15 breaths/min and 500ml of air is inhaled with each breath?

Answer 7

Of 500ml inhaled with each breath, 150ml (30%) stays in the anatomical dead space, which represents the volume of the conducting airways

The volume of gas entering the respiratory zone is thus (500-150) x 15, i.e. 5,250 ml/min and is termed alveolar ventilation (VA, with ‘A’ as subscript)

Question 8

Define and explain ‘alveolar ventilation’

Answer 8

Alveolar ventilation is defined as the amount of fresh inspired air available for gas exchange per breath

Insufficient alveolar ventilation, called hypoventilation, or excess, called hyperventilation, can occur in lung disease

We can also consciously alter the volume of our lungs, but we can’t totally empty our lungs

Alveolar ventilation is extremely important because it determines O2 and CO2 levels in alveolar gas; other factors affecting these levels are the rate of O2 consumption (VO2) and the rate of CO2 production (VCO2)

Question 9

Why is it important/useful to assess spirometry?

Answer 9

Diagnosis of respiratory disease, monitoring disease progression, deterioration, drug efficacy

It is also an efficient drug delivery system

Question 10

Define Tidal volume (VT, with ‘T’ as subscript)

Answer 10

The volume of air inspired during quiet respiration

Question 11

Define ‘Inspiratory reserve volume (IRV)’

Answer 11

The volume of air inspired from tidal volume to maximal inspiration

Question 12

Define ‘Expiratory reserve volume (ERV)’

Answer 12

The volume of air expelled with forced expiration

Question 13

Define ‘Functional residual capacity (FRC)’

Answer 13

The lung volume at the end of normal quiet expiration

Question 14

Define ‘Residual volume (RV)’

Answer 14

The volume that cannot be expelled after maximal expiration; this represents the volume of the airways

Question 15

Define ‘Total lung capacity (TLC)’

Answer 15

The total possible volume which can be contained within the lungs (from maximal inspiration to residual volume)

Maximal expiration from TLC expels inspiratory reserve volume (IRV), tidal volume (VT) and expiratory reserve volume (ERV)

Question 16

Define ‘Vital capacity (VC)’

Answer 16

The total volume that can be taken into the lungs after maximal expiration to maximal inspiration

The sum of two or more volumes is termed a capacity

Thus:

o IRV + VT + ERV = Vital Capacity (VC)

o TLC - RV = Vital Capacity (VC)

Question 17

How and why is an alternative method to spirometry used to calculate residual volume (RV)?

Answer 17

Since RV can’t be breathed out, RV and ERV can’t be measured with a spirometer, and therefore neither can FRC, which is the sum of RV and ERV

They are measured when the subject inhales from RV a known volume of non-absorbable tracer gas (such as helium); its’ dilution by the unknown volume in the lungs is then measured and RV can thus be calculated

Question 18

Outline the clinical relevance of VT, IRV, FRC, RV and VC

Answer 18

Tidal volume - an adequate supply is necessary to maintain oxygenation and carbon dioxide clearance

Inspiratory reserve volume - required during coughing and exercise

Functional residual capacity - product of the balance of the opposing chest wall and alveolar recoil, where the lung is at its most compliant; it is essential in maintaining open distal airways during expiration

Residual volume - may increase due to air trapping in disease, which then may alter lung mechanics

Vital capacity - critical value of 1L is used to assess whether the patient is able to maintain spontaneous ventilation or requires assistance

Question 19

How is Forced expiratory volume (FEV) calculated?

Answer 19

The patient is asked to breathe in as deeply as they can and out as fast as they can for a single breath

This gives the forced expiratory volume in 1 second (FEV1)

Question 20

What is Forced vital capacity (FVC) and what is the clinical relevance of this?

Answer 20

Forced vital capacity is the total volume of air that a patient can breathe out after a maximal inspiration

Published tables relate spirometric measurements to a normal subject’s gender and height; deviations from these ‘normal’ values suggest disease

Question 21

Outline how airway obstruction due to obstructive lung disease causes an increase in resistance, and this causes over-distention of the lungs

Answer 21

In an obstructive lung disease, airway obstruction causes an increase in resistance

During normal breathing, the pressure volume relationship is no different from a normal lung

However, when breathing rapidly, greater pressure is needed to overcome the resistance to flow, and the volume of each breath gets smaller; the increase in the effort to breathe can cause an over-distention of the lungs

Question 22

What is over-distention of the lungs due to obstructive pulmonary disease characterised by?

Answer 22

This is characterised by a disproportionate reduction in FEV1 compared to FVC, reflecting airflow limitation, and an increase in both RV and TLC reflecting hyperinflation

Question 23

State some common examples of obstructive lung diseases

Answer 23

Common obstructive diseases include asthma, COPD, bronchitis and emphysema

Question 24

Outline how restrictive lung diseases result in a normal or increased FEV1/FVC ratio, reflecting preserved airflow, and discuss other relevant indicators of this type of lung disease

Answer 24

In a restrictive lung disease, the compliance of the lung is reduced which increases the stiffness of the lung and limits expansion; in these cases, a greater pressure than normal is required to give the same increase in volume

The flow volume loop may be characterised by a normal or increased FEV1/FVC ratio, reflecting preserved airflow, and reduced RV and TLC indicating small lung volumes

Question 25

State some common causes of decreased lung compliance

Answer 25

Common causes of decreased lung compliance are pulmonary fibrosis, pneumonia and pulmonary oedema

Patients whose respiratory muscles are unable to perform normally because of a neuromuscular disease (e.g. ankylosing spondylitis) or paralysis can show a restrictive pattern

Question 26

What is Ankylosing spondylitis (AS)?

Answer 26

AS is an inflammatory condition that affects the joints in the spine, whereby vertebrae fuse as calcium is laid down where the ligaments attach to the vertebrae, forming new bone growth at the side of the vertebrae

Question 27

Outline Bibasilar atelectasis and its associated problems

Answer 27

Bibasilar atelectasis is characterised by a lack of gas exchange within alveoli, most commonly caused by reduced FRC post-surgery

Associated problems include reduced oxygenation, poor CO2 clearance, V/Q (ventilation/perfusion) mismatch, increased work of breathing, breathlessness, reduced exercise tolerance

Question 28

Explain the V/Q ratio

Answer 28

The Ventilation/Perfusion (V/Q) ratio is a ratio used to assess the efficiency and adequacy of the matching of two variables:

Ventilation - the air that reaches the alveoli

Perfusion - the blood that reaches the alveoli via the capillaries

An area with perfusion but no ventilation (V/Q ratio = 0) is termed ‘shunt’

An area with ventilation but no perfusion (V/Q ratio approaching infinity) is termed ‘dead space’

‘V/Q mismatch’ is often used as a term, as few conditions constitute ‘pure’ shunt or dead space, as these would be incompatible with life

Question 29

Explain what would happen with a decreased V/Q ratio and with an increased V/Q ratio respectively

Answer 29

A lower than normal V/Q ratio impairs pulmonary gaseous exchange is a cause of low arterial partial pressure of oxygen (paO2); excretion of CO2 is also impaired, but rise in arterial partial pressure of CO2 (paCO2) is very uncommon

A higher than normal V/Q ratio decreases paCO2 and increases paO2; due to the increased dead space ventilation, the paO2 is reduced and thus peripheral oxygenation saturation is lower than normal, leading to tachypnoea and dyspnoea; this finding is typically associated with pulmonary embolism (where blood circulation is impaired by an embolus); ventilation is wasted, as it fails to oxygenate any blood

Question 30

Define tachypnoea, bradypnoea, dyspnoea and apnoea

Answer 30

Tachypnoea - abnormally rapid breathing

Bradypnoea - abnormally slow breathing

Dyspnoea - difficult or laboured breathing

Apnoea - temporary cessation of breathing, especially during sleep

Question 31

Outline lung hyperinflation and its associated problems

Answer 31

Lung hyperinflation is characterised by air trapping and increased residual volume; this leads to a flattened diaphragm, narrow diameter appearance of the heart and mediastinum, increased AP (anterograde-posterior) diameter, increased pulmonary vasculature

Parenchymal (stromal) or suprapleural (membraneous) blebs (blisters/vesicular spaces) may also occur

Associated problems include altered respiratory mechanics, reduced tidal volume, V/Q mismatch, poor gas exchange, increased work of breathing, breathlessness, pursed lip breathing, use of accessory muscles

Question 32

Briefly outline dead space

Answer 32

Not all tidal volume air is used in gas exchange; air that isn’t is known as dead space.

There are two types of dead space; anatomical and alveolar

Question 33

Outline anatomical dead space

Answer 33

Anatomical dead space is the volume of an inspired breath which has not mixed with the gas in the alveoli but remains in the conducting zone up to the terminal bronchioles, and it measures the anatomical volume of the conducting airways

In a typical healthy adult it measures 150ml, although this may vary due to the size of the subject, tracheal intubation, tracheostomy or hypoventilation

Question 34

Outline alveolar dead space

Answer 34

Alveolar dead space is contained in alveoli which have insufficient blood supply to permit effective gas exchange

The mismatch between ventilation and perfusion is termed a V/Q mismatch. This should be zero in healthy subjects, but in disease is affected by pulmonary embolism and ventilation of non-vascular air spaces e.g. bullae (large blisters containing serous fluid)

Question 35

Outline physiological dead space

Answer 35

The combined total of anatomical and alveolar dead space

In healthy adults, this should equal the anatomical dead space = 150ml

Increased in emphysema, pulmonary embolism and pulmonary fibrosis

Decreased during rapid breathing and breath-holding

Question 36

What happen to alveolar ventilation if you double the respiratory rate and what happens to both of these factors during exercise?

Answer 36

If you double the respiratory rate (hence doubling the minute ventilation - VE) as opposed to doubling the tidal volume with the same respiratory rate, the alveolar ventilation does not increase to the same extent

In exercise both are increased to compensate for the increased oxygen demand

Question 37

Outline hypoventilation and explain how it leads to acidosis

Answer 37

Hypoventilation exists when the ratio of carbon dioxide production to alveolar ventilation increases above normal, i.e. inadequate alveolar ventilation

May be localised (infection, sputum plug), scattered (COPD, asthma) or generalised (pain, reduced respiratory drive)

Increased alveolar CO2 leads to increased arterial CO2, which leads to increased CO2 (+ H2O), therefore increased H2CO3

This results in increased HCO3 and increased H+, therefore decreased pH, which leads to acidosis

Question 38

Define acidosis

Answer 38

An excessively acidic condition of the body fluids or tissues

Question 39

Outline hyperventilation

Answer 39

Hyperventilation exists when the ratio of carbon dioxide production to alveolar ventilation decreases below normal, i.e. excess alveolar ventilation

It is caused by anxiety, metabolic disease, airway obstruction, parenchymal lung disease and altitude

It is the opposite of hypoventilation, therefore increases pH and causes respiratory alkalosis

Question 40

Define respiratory alkalosis

Answer 40

Respiratory alkalosis is a disturbance in acid and base balance due to alveolar hyperventilation

Question 41

What are O2 and CO2 levels in alveolar gas determined by?

Answer 41

Oxygen and carbon dioxide levels in alveolar gas determined by alveolar ventilation, rate of oxygen
consumption, rate of carbon dioxide production, Hb content of blood, Hb affinity, atmospheric pressure of oxygen

Question 42

What does gas exchange take place across in the lungs?

Answer 42

The alveolar membrane, purely a result of diffusion in accordance with Fick’s Law

Question 43

Outline Fick’s Law

Answer 43

Fick’s Law states that the rate of transfer of a gas through a sheet of tissue is directly proportional to:

o The area of the tissue

o The solubility of the gas in the tissue (diffusion constant)

o The difference in gaseous partial pressure between two sides

…and inversely proportional to:

o The square root of the gas’s molecular weight and the tissue thickness

Rate of diffusion = k * A * ((P2-P1) / D)

Where:

o k= diffusion constant (depends upon solubility of gas and temperature)

o A = area for gas exchange

o (P2-P1) = difference in partial pressure of gas on either side of the diffusion barrier

o D = distance/thickness of diffusion barrier

Question 44

Related to Fick’s law, explain the concentration/pressure gradient

Answer 44

Described using the term ‘partial pressure’, which refers to the amount of gas dissolved in the plasma

The steeper the difference in partial pressures between gas in alveoli and capillary blood the steeper the diffusion gradient, therefore the faster and more efficient diffusion occurs (normal pO2 is 100 in the alveoli and 40 in the pulmonary capillaries)

Carbon dioxide diffusion is much slower as the pCO2 difference is much smaller, but diffusion from the blood to the alveoli is much more rapid and efficient (suited to the necessity of removing carbon dioxide)

In the time available equal amounts of the two gases are exchanged, and have no effect on the pressure of the other (stated by Dalton’s law)

Question 45

Explain Dalton’s Law

Answer 45

Dalton’s Law (of partial pressures) states that in a mixture of non-reacting gases, the total pressure exerted is equal to the sum of the partial pressures of the individuals gases

P(Total) = ΣP(i)

Where (i) represents p(1) + p(2) + p(3) + p(n) etc.

Dalton’s Law is not strictly followed by real gases, with the deviation increasing with pressure

Question 46

Related to Fick’s law, explain gas solubility

Answer 46

CO2 is 20x more soluble than O2, but CO2 has a very small diffusion gradient and a heavier molecular weight therefore equal amounts of CO2 and O2 diffuse across the membrane in the same time period

In disease with diffusion impairment, oxygen is more strongly affected because it is less soluble

Question 47

Related to Fick’s law, explain the thickness of the alveolar membrane

Answer 47

0.5-1 μm thick, therefore gas exchange is rapid and efficient

Membrane thickening may occur due to inflammation, infection or fibrosis, leading to inadequate time for Hb saturation therefore hypoxia.

Hypercapnia not caused due to high CO2 solubility

Question 48

Define hypoxia

Answer 48

Deficiency in the amount of oxygen reaching the tissues

Question 49

Related to Fick’s law, explain the surface area of the alveolar membrane

Answer 49

If reduced, sufficient gas exchange may not be possible
despite an adequate diffusion rate

E.g. bronchial obstruction leading to alveolar collapse, leading to decreased arterial oxygen, increased arterial carbon dioxide and deranged pH

In emphysema, structural breakdown of alveolar walls leads to formation of fewer larger alveoli instead of more numerous and smaller alveoli, thus significantly reduced surface area

Question 50

Related to Fick’s law, explain ventilation-perfusion coupling

Answer 50

V/Q ratio described efficacy of the rate at which air reaches the lungs and blood reaches the lungs

In a normal lung, part of the lung is superior and part inferior to the heart, therefore impact on V/Q ratio as lower (dependent) part is better ventilated and better perfused than the apex

For efficient gas exchange there needs to be max coupling between V & Q, and the ratio can be measured with a ventilation/perfusion scan

Question 51

How much oxygen diffuses from the alveoli into the pulmonary capillary blood every minute?

Answer 51

~300ml

Question 52

What is mean alveolar pO2?

Answer 52

~13.3kPa

Question 53

What is the pO2 in an erythrocyte entering a capillary?

Answer 53

~5.3kPa

Oxygen therefore diffuses rapidly down a concentration gradient into the blood, to bind with haemoglobin

Question 54

Outline CO2 transport in the blood, with reference to pCO2 and diffusion rate

Answer 54

Alveolar pCO2 depends on CO2 production and the mean alveolar pCO2 is around 5.3 kPa

Rate of diffusion of CO2 is around 20 times greater than that of O2, so that CO2 elimination is not normally affected by a reduction in diffusion capacity

The pCO2 of blood as it enters the pulmonary capillary is around 6
kPa and the pCO2 of alveolar gas is around 5.3 kPa. The time taken to equilibrate is similar to that for oxygen

Question 55

How much CO2 is produced by tissue metabolism each minute?

Answer 55

~200-250ml

Question 56

How is CO2 carried in the blood and what are the effects of this?

Answer 56

Carbon dioxide is carried in the blood in physical solution, as bicarbonate ions, and chemically combined with amino acids in blood proteins including haemoglobin

Carbon dioxide carried in the blood thus alters blood pH, since:

CO2 + H20 –> H2CO3 –> H+ + HCO3-

A raised arterial pCO2 indicates a respiratory acidosis and a lowered arterial pCO2 indicates a respiratory alkalosis

Question 57

Define respiratory acidosis

Answer 57

Respiratory acidosis is a medical emergency in which decreased ventilation (hypoventilation) increases the concentration of carbon dioxide in the blood and decreases the blood’s pH (a condition generally called acidosis)

Question 58

Define and state Dalton’s law

Answer 58

Dalton: Pressure of a gas mixture is equal to the sum (Σ) of the partial pressures (P) of gases in that mixture

P(Gas mixture) = ΣP(Gas1) + P(Gas2) + P(Gas n)…

Question 59

Define and state Fick’s law

Answer 59

Fick: Molecules diffuse from regions of high concentration to low concentration at a rate proportional to the concentration gradient (P1-P2), the exchange surface area (A) and the diffusion capacity (D) of the gas, and inversely proportional to the thickness of the exchange surface (T)

V(Gas) = A/T * D * (P1 - P2)

Question 60

Define and state Henry’s law

Answer 60

Henry: At a constant temperature, the amount of a given gas that dissolves in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid

C(Gas) = A(Gas) * P(Gas)

Question 61

Define and state Boyle’s law

Answer 61

Boyle: At a constant temperature, the volume of a gas is inversely proportional to the pressure of that gas

P(Gas) α (1 / V(Gas))

Question 62

Define and state Charles’ law

Answer 62

At a constant pressure, the volume of a gas is proportional to the temperature of that gas

V(Gas) α T(Gas)