So far we have talked about breathing as if it is simply a uniform repeated action of inhalation followed by exhalation. We now begin to explore the detail of this far from uniform phenomenon.

Ventilation of a room or building can be measured as flow of air, in litres per minute through that room. Normal breathing involves about 12 breaths per minute, each of about 0.5 L. The volume of air passing into the lungs per minute in this case (minute ventilation, ) is:

The symbol for ventilation, , has a dot over the V to show it is a rate. The volume breathed out is approximately equal to the volume breathed in (tidal volume, V_T), therefore the net flow over a complete cycle is zero. This is not a very helpful way of expressing ventilation if we want to express changes in breathing, as the result of exercise or disease, for example. We therefore measure the flow in one direction only – conventionally the volume breathed out per minute () – to give us minute ventilation.

In respiratory medicine ventilation is the rate of flow of air into or out of the lungs, and results from the expanding and contracting of the lungs by the changes in intrapleural pressure described in Chapter 4 (pp. 41, 42) and illustrated in Figure 5.1.

The part of the air ventilating our lungs which is of paramount functional importance is that which forms alveolar ventilation, that is which ventilates those parts of the lung where gas exchange with the blood takes place. Insufficient (hypoventilation) or excess (hyperventilation) alveolar ventilation occurs in many lung pathologies.

We all know we can consciously alter the volume of our lungs, breathing in or breathing out more than normal: what is frequently not realized is that we cannot totally empty our lungs.

At the end of a normal quiet expiration average intrapleural pressure (P_PL) is approximately −0.5 kPa (below atmospheric pressure) and lung volume (V_L) 3 L. This volume is called the functional residual capacity (FRC). When you breathe in as hard as you can and hold your breath, P_PL decreases to −2 kPa and V_L increases to about 6 L.

Alternatively, if you breathe out as hard as possible P_PL will be −0.2 kPa and V_L 1.5 L. This residual volume (RV) cannot be expelled.

The anatomy (size) of an individual’s chest, the elasticity of his lungs and chest wall and the strength of his respiratory muscles determine these volumes. Changes in lung volume can easily be measured using a spirometer, as illustrated in Figure 5.2. This instrument, which comes in many forms, consists of a closed space from which the subject breathes. In the type illustrated a hollow bell is supported in a trough of water; as the subject breathes in, air is drawn from the bell and it sinks slightly; when he breathes out the bell rises. Movements of the bell are recorded as changes in lung volume on a moving chart.

Much information about lung properties and diagnosis of disease can be obtained by measuring changes in lung volume. When a maximum inspiration is taken the increase in lung volume (inspiratory reserve volume, IRV) to reach total lung capacity (TLC) is about 3 L. A maximal expiration from TLC will expel the IRV, V_T and the expiratory reserve volume (ERV), the total of all these volumes being the vital capacity (VC). In the vocabulary of lung volumes a capacity is the sum of two or more volumes.

Except for RV and FRC (which depends on RV), these volumes can be measured using a spirometer in the living subject. If the lungs are taken out of the body and allowed to collapse there will still be a little air left in them: the minimal air; these lungs will float (see ‘lights’ Chapter 2, p. 19). The lungs of a stillborn baby who has not taken a breath will not float because they contain no air; this test is important in forensic investigations.

The names of these volumes and their abbreviations are intimidating to students, but reference to Figure 5.2 should make all clear.

The changes in intrapleural pressure that bring about these volume changes do not vary much between individuals in health or disease in either humans or animals. The volumes themselves, however, do vary with:

Because RV cannot be breathed out, it and FRC (which is made up of RV + ERV) cannot be measured directly by a spirometer. They are measured by inhaling from RV a known volume of a non-absorbable tracer gas (e.g. helium) and measuring its dilution by the unknown volume of air in the lungs. Alternatively, the subject breathes out to RV and then breathes in and out a few times from a bag containing a known volume of pure oxygen. He then breathes out again to RV into the bag. The air in his RV was approximately 80% nitrogen, and the dilution of this by the known volume of pure oxygen in the bag enables RV to be calculated.

Lung disease changes many of the lung volumes in Figure 5.2. It is usual, for diagnostic purposes, to exaggerate these changes by stressing the respiratory system by asking the patient to breathe in as deeply as he can and out as hard as he can for the single breath of a test. The forced expiratory volume in 1 second (FEV₁) is frequently abbreviated to forced expired volume (FEV), but is still the same creature: the volume of air forced out in the first second of such a test. Similarly, forced vital capacity is the total volume of air a patient can breathe out after a maximal inspiration. It is usual to express FEV₁ as a percentage of FVC: this takes into account the fact that larger people normally have larger lungs and therefore a larger FVC. Often VC is used in place of FVC in this ratio.

Much careful work has gone into preparing tables that relate spirometric measurements to a normal subject’s height and weight. Deviations from values predicted by these tables are diagnostic of lung disease.

Diseases of the thoracic cage, such as ankylosing spondylitis, diseases of the nerves and muscles of respiration, e.g. poliomyelitis, diseases that restrict expansion of the lungs, such as fibrosis, or diseases that cause airway collapse during expiration all limit these spirometric measurements. Examples of the modifications produced by diseases of the lungs on spirometric traces are shown in Chapter 11, and can be summarized in a very general way as follows:

These considerations of the various volumes that make up breathing still give an impression of uniformity of distribution which is far from true. In Chapter 2 we described the anatomy of the bronchial tree as blind-ended sacks connected to the outside through a system of tubes. Some thought enables us to see that the composition of gas in this arrangement may be different at its entrance (the lips) from that at its ends (the alveoli) – differences in series with each other; also, the composition in different alveoli may be different – differences in parallel; or a combination of both. Differences in the composition of air in different parts of the lung depend largely on how well that part is ventilated and how much gas exchange between air and blood and blood and air takes place there. In the ideal situation just the right amount of both air and blood are supplied to a particular region, so there is no ‘waste’ of either. One particular kind of inequality between air and blood supply is known as dead space.

Essentially all exchange of gas between air and blood only takes place at the alveolar surface. The system of tubes connecting this surface to the atmosphere takes little part in this exchange and can be considered anatomical dead space. These tubes are essential to bring air to the respiratory surface, but ventilating these connecting tubes is an inescapable waste of effort as far as gas exchange is concerned. To understand anatomical dead space you must understand that the lungs fill and empty in a sequential fashion (Fig. 5.3).

At the end of inspiration the contents of the alveoli have been diluted by inspired room air, which now also fills the anatomical dead space (Fig. 5.3C). As the lungs then empty during expiration, the rule of ‘last in first out’ applies and the dead space containing unmodified room air is exhaled first. At the end of expiration the anatomical dead space is filled with alveolar air, and this partly used air is inhaled first in the next inspiration (Fig. 5.3A,B). If some regions of the lung expand before others in the process of inspiration they will receive an inappropriately large part of this dead space gas, and the regions receiving air later in inspiration will receive more fresh air (Fig. 5.3C,D). So the timing of inflation of a part of the lung during inspiration will affect the composition of the gas it receives.

This type of dead space is called ‘anatomical’ because it measures the anatomical volume of the conducting airways. The strict definition of anatomical dead space is ‘the volume of an inspired breath which has not mixed with the gas in the alveoli’. Because gas exchange effectively only takes place in the alveoli there is no CO₂ excreted into the dead space, and a scientist called Fowler pointed out that anatomical dead space can be measured as the volume of expired gas leaving the mouth and nose before CO₂ appears at the lips (Fig. 5.4).

We will see in a little while that this ‘cunning plan’ for measuring anatomical dead space is fraught with difficulty, mainly because the alveolar gas appearing at the lips does not have the constant composition shown in Figure 5.4. More often there is a considerable slope, particularly when the subject is breathing vigorously, or when alveoli empty at different rates. This makes deciding where to draw the vertical line difficult.

In healthy subjects anatomical dead space is all the dead space there is, but as we get older or suffer from lung disease things become more difficult, alveolar dead space begins to appear. By the same definition we used for anatomical dead space, alveolar dead space is contained in alveoli which have insufficient blood supply to act as effective respiratory membranes. These two types of dead space added together make up physiological dead space.

A ‘rule of thumb’ is that a healthy subject’s weight in pounds (1 lb = 0.45 kg) is numerically equal to his dead space in millilitres.

It would be wrong to think of alveolar dead space as an absolute term, i.e. to imagine areas of the lung that are supplied with air by breathing but which have absolutely no blood supply to exchange O₂ and CO₂ with this air. We will see in Chapter 7 that most of the lung is ‘on target’, getting lots of blood to regions that are well ventilated and less blood to poorly ventilated regions. This ‘ matching’ is of course very important, and it is the major defect in diseases as varied as emphysema and pulmonary fibrosis, in which areas of the lung may be expanded, but, because there is only a slow change of air within that space, are poorly ventilated.

The fact that we can measure partial pressures of gases in the expired air and the volume of air breathed in a minute has enabled those with an appetite for these things to calculate mathematically the way in which the lungs exchange gases between air and blood. These calculations are not popular with the general run of students, but were not devised deliberately to cause them pain; rather, they are an exact description of what is happening in the lungs, and in the days before medicine became the high-tech subject it is today, enabled clinicians, using simple non-invasive techniques, to calculate how much of the lungs was not taking part in gas exchange (dead space), and partial pressures of O₂ and CO₂ in the alveolar gas, and hence in the arterial blood.

The definition of physiological dead space as ‘the volume of inspired air which has not taken part in gas exchange’ enables dead space to be calculated using a more analytical approach than that of Figure 5.4.

Carl Bohr, in 1891, developed an equation to calculate physiological dead space which is derived from the fact that the volume of gas expired in a single breath (V_T) is the sum of the volume from the physiological dead space (V_D) plus the volume from the alveoli (V_A):

The total amount of any gas (O₂, CO₂, N₂ or any other) in an expired breath is the volume of that breath (V_T) times the fractional concentration (%) of the gas (F_E) in the whole breath, i.e. (V_T × F_E). This total is made up of the amount from the dead space (V_D × F_D) plus the amount from the alveoli (V_A × F_A):

If there is none of the gas (e.g. CO₂) in the dead space, F_D = 0 and the equation becomes:

or

since

or

or

This is the simplified Bohr equation for CO₂.

Using this equation, and by knowing the volume of air expired, the concentration of CO₂ in it and the concentration of CO₂ in alveolar air, we can calculate dead space.

The volume of air expired and the concentration of CO₂ in it can easily be measured using a spirometer and CO₂ analyser. A modification of the procedure shown in Figure 5.4 demonstrates the essentials of how to obtain a sample of end-tidal air. The subject breathes out as far as possible into the long thin tube; he then blocks the end of the tube with his tongue, and the gas in the tube nearest him is alveolar air. Because conditions vary so much in different alveoli the air collected this way is not a very accurate average of alveolar air, and for CO₂ arterial Pco₂ is a better index of mixed alveolar CO₂, although obtaining arterial blood from a subject is a very different proposition from asking him to blow down a tube!

Because the fractional concentration (%) of a gas in a mixture is directly related to its partial pressure (P) the Bohr equation is more commonly, and perhaps usefully, expressed as follows:

which gives us the important information that the size of tidal volume influences dead space.

Because alveolar dead space in healthy individuals is small, anatomical and physiological dead space are identical (about 150 mL in an adult). Like other lung volumes this varies with the size of the individual, and as age, sex and physical training all influence lung volumes they also influence dead space.

Lung volume changes with each breath, being about 3 L at FRC and increasing to up to about 6 L at vital capacity. Under these circumstances dead space will have doubled. Physiological dead space also varies with pattern of breathing. One might imagine that a tidal volume of less than 150 mL would not ventilate the alveoli at all, but during rapid breathing axial streaming causes the fresh air to form a ‘needle’ in the middle of the airways and this penetrates deep into the alveolar region. This is the principle by which high-frequency artificial ventilation is able to ventilate patients using a tidal volume smaller than their anatomical dead space and frequencies up to 10 Hz. This type of artificial ventilation is used when the lungs or chest have been damaged and normal breathing movement and intrapleural pressure changes would make things worse. On the other hand, breath-holding also reduces dead space by increasing the time available for diffusion in the airways and for the mixing action of the movements of the heart. Even if you breathe out immediately after inspiration, expiration is equivalent to breath-holding, with the last gas expelled being subjected to a longer ‘breath-hold’ than that expelled first.

We have made much of the effect of dead space on lung function, and this is because dead space increases in disease when regions of the lung receive too little blood supply to do the job of gas exchange adequately. Remember, this exchange only takes place in the alveoli, and only in those alveoli that are ventilated and have a blood supply. The gas exchange is of course O₂ for CO₂.

Take, for example, a subject breathing with V_T = 0.5 L and f = 12/min: the flow of O₂ in and CO₂ out of the body is carried by a minute ventilation of 6 L min⁻¹. If V_D = 0.15 L, ventilation of the alveoli is only:

This is the effective ventilation that brings about the exchange of O₂ and CO₂.

Room air contains virtually no CO₂ and the alveolar gas contains 5.5%, giving an output of:

Oxygen, on the other hand, forms 21% of the atmosphere and alveolar gas contains about 14%; uptake of oxygen is therefore:

The ratio of CO₂ output divided by O₂ uptake is called the respiratory exchange ratio (or respiratory quotient, when used to describe the exchange in tissues or cells). It is usually given the symbol R and can range from 1, when only carbohydrates are being metabolized, to 0.7 when fats are being used. The ratio depends on the amount of oxygen already in the molecule being oxidized: the more oxygen the molecule contains the less has to be ‘brought in’ to complete the oxidation. For the figures above:

The partial pressure of O₂ or CO₂ in the alveoli depends on the rate at which it is being brought in (O₂) or removed (CO₂) by ventilation:

For CO₂:

where K is a constant which takes into account the air is being warmed and moistened within the lungs, is partial pressure in the alveoli or arterial blood, is the rate of production of CO₂ by the body and is alveolar ventilation.

Once has been calculated can be calculated using what is known as the alveolar gas equation. If the respiratory exchange ratio was 1, then for each molecule of O₂ taken up one molecule of CO₂ would be released, and:

However, R is seldom 1, and is computed using the slightly intimidating alveolar gas equation:

The correction factor in the square brackets is there to take care of R not being exactly 1 and its effect on the concentration of N₂ in the alveoli.

A simplified form of this equation is:

The effect of changing alveolar ventilation on alveolar partial pressure of O₂ and CO₂ is shown graphically in Figure 5.7. It is clear that increased or decreased ventilation has opposite effects on the alveolar concentrations of these two gases. You will see later (Chapter 8, Gas transport) that this does not mean that the amount of O₂ carried into the circulation can increase or decrease in a linear fashion, as does CO₂, because in the case of O₂ the carriage is limited by the capacity of a carrier rather than the amount flowing into the lungs.

Because the bronchial tree consists of a large number of paths in parallel, differences of composition can, and do, exist in series (along any path, from lips to alveoli for example or between regions (between right and left lung for example). These differences can become so large as to interfere with the functioning of the lungs and are due to the following effects.