Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3016_Библиотеки_им_академика_М_И_Перельмана.pdf
AIRFLOW AND RESISTANCE IN THE RESPIRATORY SYSTEM
4
59THE RESPIRATORY SYSTEM
A
B
Fig. 4.22 Normal (A) and emphysematous lungs (B). (Source: Stevens,
A., Lowe, J.S., Young, B., 2002. Wheater’s Basic Histopathology.
Churchill Livingstone.)
Airflow in the respiratory system
Asthma
Mr Graham is a 25- year- old man who suffers from asthma.
Hehas hadtheconditionsincehe wasaboy.Hends that
hisasthmaisbroughtonbydomesticanimals(e.g.catsand
dogs),cold or windy weather,and ifheexercisestoohard.
However,his condition is kept under control with inhalers.
Twiceaday,he takestwoinhaleddoses of beclometasone,
and he always keeps a salbutamol inhaler with him, which
he uses when he gets wheezy. The salbutamol inhaler
nearly always relieves his asthma.
Wewillconsider:
1. Thepathophysiologyofasthma.
2. Whatprovokesanasthmaattack?
3. Thedrugtreatmentofasthma.
Case
4.1
Airflow in the respiratory system
The pathophysiology of asthma
Mr Graham attended a routine clinic appointment feeling
a little wheezy. Figure4.19A shows the forced expiratory
spirogram which Mr Graham made at that appointment.
After making the recording, Mr Graham used his salbuta-
mol inhaler,which relieved his wheeziness. He then made
a second forced expiratory spirogram, shown in Figure
4.19B. The principle behind measuring forced vital capac-
ity(FVC)andforcedexpiratoryvolumeinonesecond(FEV
1
)
is explained in Chapter 11. The spirogram in Figure 4.19A
showsareduced FEV
1
,althoughthe FVC is not particularly
abnormal. In other words, the FEV
1
/FVC ratio is reduced,
indicatinganobstructiveabnormality.Followingtheadmin-
istration of salbutamol, the airway narrowing reversed and
the obstructive pattern on the spirogram improved. This
reversibility of airway narrowing is characteristic of asthma.
Case
4.1
Airflow in the respiratory system
What provokes an asthma attack in patients
with nonallergic or extrinsic asthma?
One day, Mr Graham suffered a particularly bad attack of
asthma.He had had a coldfor a week orso,but apart from
that there did not seem to be any particular trigger for his
attack.However,hebecameincreasinglywheezyandfoundit
moreandmoredifculttobreathe.Hefounditespeciallydif-
cultto exhale. Heused his salbutamolinhaler several times
but did not get any relief from it. Mr Graham’s wife became
increasingly worried about him and decided to call an ambu-
lance. In the ambulance, Mr Graham was given oxygen to
breathe; he was taken to the hospital where he was examined
bytheemergencydoctor.ThedoctornotedthatMrGraham’s
respiratory rate was over 30 breaths per minute and that his
chest was very expanded. Upon auscultation, the air entering
into Mr Graham’s lungs was reduced and there were wheezes
throughout his chest. The doctor asked Mr Graham to per-
form a peak expiratory flow test. Mr Graham’s peak expira-
tory flow was about two- thirds of his normal value. In most
patients with asthma, a range of ‘triggers’ provoke attacks of
bronchoconstriction. Such triggers include specific allergens,
other nonspecific substances, exercise, and some drugs.
Allergens
Allergens are foreign substances that are able to provoke an
immune response in susceptible individuals. In patients with
extrinsic or allergic asthma, an attack of bronchoconstriction
may be provoked by exposure to a specific allergen or to a
range of allergens. The most common allergen responsible
Case
4.1
AIRFLOW AND RESISTANCE IN THE RESPIRATORY SYSTEM
4
60 SYSTEMS OF THE BODY
4
References and further reading
Busse, W., Kraft, M., 2005. Cysteinyl leukotrienes in allergic inflam-
mation: strategic targets for therapy. Chest 127, 1312–1326.
Healthcare Improvement Scotland, SIGN and British Thoracic
Society, 2019. British Guideline on the Management of Asthma.
Available at: sign158- updated.pdf (Accessed 31 December 2020).
Lumb, A.B., Thomas, C.R., 2020. Respiratory system resistance.
In: Lumb, A.B., Thomas, C.R. (Eds.), Nunn Applied Respiratory
Physiology. Elsevier, pp. 27–41.
Stevens, A., Lowe, J.S., Young, B., 2002. Wheater’s Basic
Histopathology. Churchill Livingstone.
Viegi, G., Pistelli, F., Sherrill, D.L., et al., 2007. Definition, epidemiol-
ogy, and natural history of COPD. Eur. Respir. J. 30, 993–1013.
World Health Organization, 2007. Asthma and chronic obstructive
pulmonary disease. In: Bousquet, J., Khaltaev, N. (Eds.), Global
Surveillance, Prevention, and Control of Chronic Respiratory
Diseases: A Comprehensive Approach. WHO Press, pp. 15–31.
Airflow in the respiratory system
Treatment of asthma
After examining him, the emergency doctor gave Mr
Graham nebulised salbutamol, the same drug as in Mr
Graham’s inhaler. However, whereas Mr Graham’s inhaler
administers a dose of 100 μg, each time it is used, the doc-
tor prescribed 5 mg of salbutamol via the nebuliser. A
nebuliser produces a fine aerosol of drug in a flow of oxy-
gen. Mr Graham inhaled the aerosol, although only a small
proportion of it would have reached his lungs. Figure4.12
shows a nebuliser of the type that might be used. In addi-
tion, the doctor administered steroids (intravenous hydro-
cortisone)toMrGraham.
Fortunately, Mr Graham’s condition began to improve
with the nebulised salbutamol. He was, nevertheless,
admitted to the hospital and received regular doses of
nebulisedsalbutamol.Thenextdayheleftthehospital.
As we have already established, there are a number of
components to asthma. The airways are hyperreactive,
resulting in constriction of the bronchial smooth mus-
cle; there is a generalised inflammation of the airway
mucosa and, in many cases, the immune system is involved.
Treatmentsforasthmaareaimedat:
1. relieving bronchoconstriction,
2. reducing airway inflammation, and
3. influencing the immune system.
Case
4.1
for provoking asthma is a protein derived from the faeces of
the house dust mite, which lives in warm locations, such as
bedding,and feedsonscales ofshedhumanskin. Formany
asthmatic patients, the presence of animals, such as cats,
dogs, and birds, can provoke bronchoconstriction. In these
cases, the allergen responsible is derived from animal skin,
fur, feathers, or excreta. Allergens derived from pollen, par-
ticularly grass pollen, can provoke asthma as well as cause
hay fever. In such cases, asthma may be confined to certain
seasons of the year. Although the allergen normally has to
be inhaled to provoke bronchoconstriction, in a small num-
ber of patients, an attack of asthma may be provoked by
eating specific foods or chemicals.
Nonspecific provokers of asthma
In addition to reacting to specific allergens, the hyperreac-
tive airways of asthmatic patients may also respond to a
wide range of substances, including strong smells, dusts,
vapours, smoke (including tobacco smoke), and airborne
chemicals.Theseagentsarethoughttoactdirectlyonthe
airway itself, and an immune response is not provoked.
Exercise
In many patients, asthma may be provoked by exercise.
Theexact mechanism by which this occurs is not clear,but
it is likely that cooling of hyperreactive airways may have
an important role to play, as exercise- induced asthma
often occurs more readily during cold weather. Drying of
the airway mucosa may also play a role, as many asthmat-
ics report that swimming is less likely to induce bronchos-
pasms than other forms of exercise.
Drugs
A variety of drugs are known to induce asthma. Aspirin and
other anti- inflammatory drugs can provoke bronchocon-
striction in a small proportion of asthmatics. This action is
probably brought about because these drugs affect the pro-
duction of prostaglandins and leukotrienes; an imbalance of
these substances in the airway may cause bronchoconstric-
tion. β-Blocking drugs are alsoprone to producingbroncho-
constriction in asthmatic patients, presumably by blocking β2
receptors on the bronchial smooth muscle; however, these
drugs may also influence cells of the immune system.
Emotions
In many patients, strong emotional responses may result in
attacksofbronchoconstriction.Thisismostprobablymedi-
ated by a central neural mechanism.
Airflow in the respiratory system –
cont’d
Case
4.1
5
PULMONARY
VENTILATION
Chapter objectives
After studying this chapter, you should be able to:
1. Define ventilation.
2. Define the common lung volumes and capacities and how they are
changed by restrictive and obstructive diseases.
3. Explain the importance of the structure of the respiratory system (as
blind- ended tracts in parallel) on ventilation.
4. Differentiate between physiological and anatomical dead space and
relate increased dead space to disease states.
5. Explain the composition of the parts of a single exhaled breath and
why these are changed by disease.
6. Understand the alveolar gas equation.
7. Describe the physiological factors influencing the distribution of
ventilation.
5
62 SYSTEMS OF THE BODY
Introduction
In respiratory medicine, the term ventilation is used to
describe the rate of flow of air into or out of the lungs.
This results from the expansion and contraction of the
lungs caused by changes in intrapleural pressure. These
are described in Chapter 4 and illustrated in Figure 5.1.
‘Normal’ breathing consists of about 12 breaths per min-
ute, each breath being around 0.5 litres (L) L.
The symbol for ventilation,
˙
V
, has a dot over the V
to indicate that it is a rate. Because the volume expired
is approximately equal to the volume inspired (tidal vol-
ume, V
T
), 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 a result of exer-
cise or disease. Flow is therefore measured in one direc-
tion only, and this is conventionally the volume expired
per minute (
˙
V
E
) to give us minute ventilation, as below:
r
espiratoryrate ∼12min
−
1
× tidalvolume (∼0.5L
)
= minuteventilation ∼6.0Lmin
− 1
Alveolar ventilation is a part of the V
T
which ven-
tilates the alveoli, where gas exchange with the blood
takes place. Alterations in alveolar ventilation occur in
many lung pathologies.
Lung volumes, capacities and spirometry
In respiratory physiology, capacity is the sum of two or
more volumes. We can consciously alter the volume of
our lungs by breathing in or out more deeply than nor-
mal, but we cannot completely empty our lungs. At
the end of a normal quiet expiration, the average intra-
pleural pressure is approximately −0.5 kPa (i.e. below
atmospheric pressure) and the lung volume is around
2.5 L. This volume represents the functional residual
capacity (FRC). When a subject inhales as much as they
can and then holds their breath, intrapleural pressure
decreases to − 2 kPa and lung volume increases to about
6 L. After exhaling as much as possible, the intrapleural
pressure will increase to − 0.2 kPa and the lung volume
will decrease to 1.0 L. This is the residual volume (RV)
that cannot be expelled.
Fig. 5.1 A single respiratory
cycle. Airflow is measured using a
pneumotachograph and integrated
to give tidal volume. Recoil pressure
has a negative sign because it is the
difference between alveolar and
intrapleural pressure, relative to
atmospheric pressure. FRC, functional
residual capacity.
Intrapleural pressure (P
pl
)
–0.5
–1.0
(kPa)
02
4
Time (s)
+0.05
–0.05
0
(kPa)
Alveolar pressure (P
A
)
–0.5
–1.0
(kPa)
Recoil pressure (P
el
)
–1.0
–0.5
0
+0.5
+1.0
(litres/s
–
1
)
Airflow (V)
+1.0
+0.5
FRC
Volume (V)
ExpirationInspiration
(litres)
.
5
63THE RESPIRATORY SYSTEM
The size of an individual’s chest, the elasticity of the
lungs and chest wall, and the strength of the respiratory
muscles determine these volumes. Changes in lung vol-
ume can 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 sup-
ported in a trough of water. As the subject inspires, air
is drawn from the bell, and it sinks slightly; upon expi-
ration, the bell rises. Movements of the bell are recorded
as changes in the lung volume on a moving chart.
Information about lung properties and the diagnosis of
diseases can be obtained by measuring changes in lung
volume.
Static lung volumes are those which are independent
of the rate of flow. Five of these can be measured using
the spirometer technique described above. These are the
V
T
, inspiratory reserve volume (IRV), expiratory reserve
volume (ERV), vital capacity (VC) and inspiratory capac-
ity which is the sum of the V
T
and IRV. To ascertain the
RV, FRC and total lung capacity (TLC), an alternative
methodology is required (see below).
When maximum inspiration is taken, the increase
in lung volume (IRV) to reach the TLC is about 3 L. A
maximal expiration from TLC will expel the IRV, V
T
,
and ERV, the total of all these volumes being the VC.
If the lungs are taken out of the body, postmortem,
and allowed to collapse, there will still be a little air
left in them. This is called minimal air (see Chapter 2,
‘Lights’).
The changes in intrapleural pressure that bring about
these volume changes do not vary much between indi-
viduals in health or disease. However, a number of fac-
tors lead to greater or smaller lung volumes. These
factors include:
• Body size. All are linearly related to height. Obesity
causes a reduction in static lung volumes, except
for V
T
.
• Age. Volumes are smaller in children, only partially
due to their smaller body size. With increasing age,
VC decreases, but both FRC and RV increase because
of degenerative changes in the tissues, leading to a
reduced recoil pressure.
• Sex. Volumes are smaller in females (e.g. the FRC of
females is 10% less than that of males of the same
height). This is due to the more muscular chest of
males.
• Posture. FRC is reduced in the supine position
compared with measurements made when a subject
is upright because the diaphragm is displaced
cephalad by the abdominal contents.
• Muscle training. This increases all lung volumes and
allows greater maximal ventilation during exercise.
• Disease. Changes in lung volumes from the normal
values are used in the diagnosis of many diseases of
the lungs and respiratory system.
Because the RV cannot be expired, the RV, FRC and TLC
(the latter two include the RV) cannot be directly measured
using a spirometer. If one of these is measured, the others
can be derived, and the capacity most usually measured
is the FRC. Three techniques can be used to measure FRC.
A gas dilution technique may be used, whereby a subject
inhales a known volume of a non- absorbable tracer gas,
such as helium, and its concentration is then measured,
allowing the volume to be calculated. Alternatively, a nitro-
gen washout technique may be used. Here, the subject
begins from the FRC and breathes from a bag containing a
known volume of 100% oxygen. Then, they breathe out into
the bag. Because the air in the FRC contained approximately
80% nitrogen, the dilution of this by the known volume of
pure oxygen in the bag enables the volume to be calculated.
The third method uses body plethysmography (see Chapter
11, ‘Helium Dilution Method and Plethysmography’),
which is the only technique that accounts for gas trapping
in the lung beyond closed airways.
Spirometric abnormalities in disease
Lung disease changes many lung volumes, as shown in
Figure 5.2. Dynamic studies can be performed to assist
diagnoses; the patient breathes in as deeply as possible
and out as hard as possible to obtain data from a single
breath. Measurements made under these circumstances
Fig. 5.2 A spirometer record of breathing. Average
adult volumes are shown. Because the lungs cannot
be completely emptied, RV and FRC cannot be
measured by direct spirometry. ERV, expiratory
reserve volume; FRC, functional residual capacity; IRV,
inspiratory reserve volume; RV, residual volume; VC,
vital capacity; V
T
, tidal volume.
6
4
2
0
Volume (litres)
FRC
ERV
RV
V
T
Out
In
VC
IRV
5
64 SYSTEMS OF THE BODY
include the forced expiratory volume in 1 second (FEV
1
)
and forced vital capacity (FVC), which is the total vol-
ume of air a patient can breathe out after maximal inspi-
ration. It is usual to express FEV
1
as a percentage of
FVC. This takes into account the fact that taller people
normally have larger lungs and therefore a greater FVC.
Much careful work has gone into preparing tables that
relate spirometric measurements to a normal subject’s
height and weight. Deviations from the values predicted
by these tables are diagnostic of lung diseases.
Diseases of the thoracic cage (such as ankylosing
spondylitis), diseases of the nerves and muscles of res-
piration (such as poliomyelitis), diseases that restrict
expansion of the lungs (such as fibrosis) and diseases
that cause airway collapse during expiration limit
these spirometric measurements. The spirometric trace
changes produced by lung diseases can be summarised
in a general way as follows (see Chapter 11):
Variable Restrictive disease Obstructive disease
FVC − −
FEV
1
− −
FEV
1
/FVC 0 −
FRC − +
RV − +
TLC − +
0, no change; +, increase; −, decrease.
FEV
1
, forced expiratory volume in 1 second; FRC, functional residual
capacity; FVC, forced vital ca pacity; RV, residual volume; TLC, total
lung capacity.
NB: Some of these changes are not observed to any degree until the
disease is very advanced.
Dead space
The distribution of ventilation within the lungs is not
uniform. In Chapter 2, the anatomy of the bronchial tree
was described as blind- ended sacs connected to the out-
side environment through a system of tubes. The com-
position of gas may be different at the entrance to the
respiratory system (the lips or nares) from that at the end
(the alveoli), and these can be considered differences in
series. The composition of gas in different alveoli may
also vary, and this variation can be considered differ-
ences in parallel. In addition, a combination of both
variations may exist. Differences in the composition of
air in different parts of the lung depend largely on how
well that part is ventilated and the extent to which gas
exchange between the air and blood takes place. In the
ideal situation, just the right amount of both air and
blood are supplied to a particular region so that there
is no ‘waste’ or under- delivery of either. One particu-
lar example of inequality between air (ventilation) and
blood supply (perfusion) is known as the dead space.
Anatomical and alveolar dead space
The exchange of gases between air and blood occurs only
at the alveolar surface. The conducting airways, connect-
ing this surface to the atmosphere, do not participate in
gas exchange and comprise the anatomical dead space. It
is called ‘anatomical’ because it is equivalent to the ana-
tomical volume of the conducting airways. Anatomical
dead space may be considered as the volume of an
inspired breath which does not mix with the gas in the
alveoli. To understand anatomical dead space, the lungs
must be understood to fill and empty in a sequential fash-
ion (Fig. 5.3). At the end of inspiration, the contents of the
alveoli have been diluted by inspired air, which now also
fills the anatomical dead space (see Fig. 5.3C). As the lungs
then empty during expiration, the rule of ‘last in first
out’ applies, and the dead space containing unmodified
air is exhaled first. At the end of expiration, the anatomi-
cal dead space is filled with alveolar air, and this is then
inhaled first in the next inspiration (see Fig. 5.3A and B).
Healthy lungs are generally composed of tissues which
inflate and deflate at similar rates. However, if some
regions of the lung have different time constants and
expand more quickly than others during the process of
inspiration (see Chapter 3), they will receive an inappro-
priately large part of this dead space gas, and the regions
receiving air later in inspiration will receive more fresh air
(see Fig. 5.3 C and D). The timing of the inflation of a part
of the lung during inspiration affects the composition of
the gas it receives.
AB CD
End-expiration
A
lveolar
space
Dead
space
Dead space
inspired
End-inspiration
Fast Slow
Fig. 5.3 Distribution of dead space gas. (a) At the end of expiration, dead space is filled with ‘used’ alveolar gas. (b) When the lungs inspire a
volume of fresh air equal to the dead space, the alveolar region is expanded but the composition of the gas it contains has not changed. There is
fresh air in the dead space and ‘used’ air in the alveoli. (c) The alveolar air will be diluted by further inspiration, but the composition of the dead
space air will remain that of the fresh air. (d) If the alveoli fill at different rates, they are said to have different time constants and receive different
amounts of dead space gas. The alveoli that expand first will therefore receive most dead space gas.
5
65THE RESPIRATORY SYSTEM
In healthy subjects, the anatomical dead space is all
dead space, but with ageing and/or lung disease, alve-
olar dead space begins to appear. Alveolar dead space
is the volume of inspired air which reaches the respira-
tory surfaces of the alveoli, which then have insufficient
blood supply to act as effective respiratory membranes.
Anatomical and alveolar dead spaces, together, consti-
tute a 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 their dead space, in millilitres, or
around 150 mL in a 70- kg adult.
The alveolar dead space is not a fixed volume. In
Chapter 7, we will see that the body is generally effec-
tive at promoting blood flow to regions of the lung that
are well ventilated and supplying relatively less blood to
poorly ventilated regions. This matching of ventilation
and perfusion is very important and is a major defect in
a wide variety of diseases.
Measuring and calculating dead space
Fowler’s method
Because gas exchange occurs effectively only in the
alveoli, there is no carbon dioxide (CO
2
) excreted by the
dead space. In 1948, a physiologist named W.S. Fowler
described how anatomical dead space could be measured
as the volume of gas expired prior to CO
2
appearing at
the lips (Fig. 5.4). However, there may be a considerable
slope, particularly when the subject is breathing vigor-
ously or when alveoli empty at different rates, making it
difficult to decide where to draw the vertical line. This can
be a particular issue if a patient has, for example, chronic
obstructive pulmonary disease and has rather varied time
constants across different functional lung units.
Bohr equation
The physiological dead space is the volume of inspired
air which has not taken part in gas exchange and
includes both the anatomical and alveolar dead space. In
1891, Carl Bohr developed an equation to calculate the
ratio of physiological dead space volume to V
T
:
V
D
V
T
=
( Pa
CO
2
− PE
CO
2
)
Pa
CO
2
Fig. 5.4 Estimating dead space volume. Carbon
dioxide concentrations rise rapidly in the expired
air when the dead space has been expired. The
volume at the midpoint of this rapid rise is taken
as dead space volume. The flat part of the curve is
called the alveolar plateau.
CO
2
meter
Anatomical
dead space
Alveolar gas
Volume expired
CO
2
(%)
6.0
0
0
where V
D
is the volume of the physiological dead space,
V
T
is the tidal volume, PE
CO2
is the partial pressure of
CO
2
in expired air and Pa
CO2
is the partial pressure of
CO
2
in the arterial blood. 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 taking
part in alveolar ventilation (V
A
):
V
T
=V
D
+ V
A
V
A
isthereforeV
T
− V
D
The other terms which appear in the derivation of
the equation are those used to describe the fractional
CO
2
concentrations in inhaled, exhaled and alveolar
gas, which are F
I
, F
E
and F
A
, respectively. The CO
2
in an
expired breath is the volume of that breath (V
T
) multi-
plied by the fractional concentration (%) of the CO
2
(F
E
)
in the whole breath, that is, F
E
× V
T
. This total is made
up of alveolar gas (F
A
[V
T
– V
D
]) and dead space gas (F
I
× V
D
).
The Bohr equation is derived as follows:
F
E
× V
T
= (F
I
× V
D
) + (F
A
[V
T
− V
D
]) ,
The F
I
is 0, so (F
I
× V
D
) is eliminated.
E
× V
T
=F
A
(
V
T
− V
D
)
whichcanberearrangedto
F
E
×V
T
=
(
F
A
V
T
)
−
(
F
A
× V
D
)
. This is rearranged to give
E
× V
T
) + (F
A
× V
D
) =F
A
× V
T
.Then,
F
A
× V
D
=
(
F
A
× V
T
)
−
(
F
E
× V
T
)
. This is simplified to
F
A
× V
D
=V
T
(
F
A
− F
E
)
andrearrangedto
V
D
/V
T
= (F
A
− F
E
) /F
A
Because, as above, the F
A
is the PA
CO2
, and F
E
is
PE
CO2
, the Bohr equation is
V
D
V
T
=
( Pa
CO
2
– PE
CO
2
)
Pa
CO
2
5
66 SYSTEMS OF THE BODY
The partial pressure of arterial CO
2
(Pa
CO2
) is almost
identical to the partial pressure of alveolar CO
2
(PA
CO2
);
therefore, the equation is written as
V
D
V
T
=
( Pa
CO
2
– PE
CO
2
)
Pa
CO
2
In health, the dead space volume is around 30% of the
V
T
, and the normal ratio is 0.3.
Factors affecting dead space
Because the alveolar dead space is small in health, the
anatomical and physiological dead spaces are very simi-
lar at around 150 mL. Like other lung volumes, this varies
with the height of the individual. Posture, age and sex also
affect the physiological dead space, with males having a
larger dead space than females. Changes in dead space are
a feature of lung diseases, including pulmonary embolus
(see Chapter 7), where ventilation is maintained in the
presence of restricted perfusion due to the embolus.
Alveolar ventilation and respiratory exchange
Gas exchange only takes place in the alveoli, and only
takes place efficiently in alveoli that are both ventilated
and perfused. Dead space increases in disease when
regions of the lung receive too little blood to carry out
adequate gas exchange, which may adversely affect lung
function. In a subject breathing with a V
T
of 0.5 L and a
respiratory rate of 12 min
−1
, the flow of O
2
into and CO
2
out of the body is carried by a minute ventilation of 6 L
min
–1
. If V
D
= 0.15 L, the effective ventilation that brings
about the exchange of O
2
and CO
2
ventilation of the
alveoli is
6 −
( 12
×
0.15) = 4. 2 L min
−1
Room air contains virtually no CO
2
, and the alveolar
gas contains 5.5%, giving an output of
4
.2 ×
(
5
.
5 − 0
)
100
= 231 mL min
−
1
Oxygen, on the other hand, forms 21% of the atmos-
phere, and alveolar gas contains about 14%; therefore,
the uptake of oxygen is:
4
.2 ×
( 21 − 14)
100
= 294 mL min
−
1
The ratio of CO
2
output divided by O
2
uptake is
called the respiratory exchange ratio (or respiratory
quotient, when used to describe the exchange in tissues
or cells). It is given the symbol R and can range from 1,
when only carbohydrates are being metabolised, to 0.7,
when only fats are being used. In a subject with a mixed
diet, it is around 0.8. The ratio depends on the amount
of oxygen already in the molecule being oxidised; the
more oxygen the molecule contains, the less has to be
‘brought in’ to complete the oxidation. For the figures
above:
R
=
231
294
=0.
79
The partial pressure of oxygen or CO
2
in the alveoli
depends on the rate at which it is supplied (oxygen) or
removed (CO
2
) by ventilation. For CO
2
this is:
P
A
CO
2
=
˙
V
CO
2
˙
V
A
×
K
where PA
CO2
is the partial pressure of alveolar CO
2
in
the alveoli, V
CO2
is the rate of CO
2
production by the
body, V
A
is alveolar ventilation and K is a constant
which takes into account the air being warmed and
moistened within the lungs. However, because PA
CO2
is in equilibrium with Pa
CO2
, they are usually assumed
to be equal, and Pa
CO2
may be obtained from arterial
blood gas sampling.
Left lung
Heart
Border of right
lung which is
partially deflated
Fig 5.5 A right-sided pneumothorax. There is no space between
the left lung and the chest wall whereas the right lung is partially
collapsed and there is air in the intrapleural space.
Summary 1
• Ventilationcanbemeasuredasthenumberof
changes in air or the rate of airflow through a region
of the lung per minute.
• Theanatomicaldeadspaceisequivalenttothevolumeof
the conducting airways and is present in all individuals.
• Alveolardeadspaceisvariable,andincreased
alveolar dead space occurs in lung pathology
• Physiologicaldeadspaceisthesumofallpartsofthe
V
T
that do not participate in gas exchange.
• Fowler’smethodmaybeusedtomeasurethe
anatomical dead space.
• TheBohrequationisusedtocalculatethe
physiological dead space.
5
67THE RESPIRATORY SYSTEM
Alveolar gas equation
The alveolar gas equation can be used to find the partial
pressure of oxygen in an alveolus (PA
O2
) when supplied
with a varying fraction of inspired oxygen:
PA
O
2
= [FI
O
2
× ( P
ATM
− P
H
2
O
)] − ( PA
CO
2
/R)
where FI
O2
is the fraction of inspired oxygen (e.g. 0.21) in
the case of room air with an oxygen content of 21%, P
ATM
is atmospheric pressure in kPa, P
H
2
O
is the standard
vapour pressure (SVP) of water at 37
◦
C in kPa and R is
the respiratory exchange ratio or quotient, as described
above. The SVP of water is subtracted because the frac-
tional concentration of oxygen only applies to the dry
gas component.
A worked example to demonstrate the situation under
normal conditions is therefore:
PA
O
2
=
= 13.3 kPa
=
( 0.21 94.7) 6.6×
−
[0.21 ( 101 6.3)] 5.3/0.8×
− −
= 19.88 6.6
−
The effect of changing alveolar ventilation on the
alveolar partial pressures of oxygen and CO
2
is shown
graphically in Figure 5.7. Increased or decreased ven-
tilation have opposite effects on the alveolar con-
centrations of these two gases. You will see later (see
Chapter 8) that this does not mean that the amount
of oxygen carried into the circulation can increase or
decrease in a linear fashion, as with CO
2
, because in
the case of oxygen, carriage is limited by the capacity
of its carrier rather than by the amount flowing into
the lungs.
Variations in the composition and distribution of
inspired air
Because the bronchial tree consists of a large number of
paths in parallel, differences in the composition of the air
exist both in series (along any path from the atmosphere
to the alveoli) or between regions (e.g. between the right
and left lungs or between functional units within the
same lung). These differences can become so significant
that they interfere with gas exchange.
Differences along the airway from atmosphere to
alveoli
It can be seen from Figure 5.4 that the concentration of
CO
2
in an expired breath does not rise as a sudden step
(GJHRI
FROODSVHG
OXQJ
$LULQLQWHUSOHXUDOVSDFH
$
%
Fig. 5.6 Small left- sided pneumothorax. (A) Diagram showing that the left lung has partially collapsed and there is air between it and the inside of
the right chest wall. (B) Chest X- ray of a patient with a left- sided pneumothorax. This chest X- ray is similar to the diagram in (A). The border of the
left lung is clearly visible, and the air- filled space between the lung margin and the chest wall appears darker than the adjacent lung on the X- ray.
15
10
5
0
0510 15 20 25
30
Alveolar ventilation (L/min)
CO
2
O
2
Alveolar partial pressure (kPa)
Fig. 5.7 The relationship between alveolar ventilation and alveolar
partial pressures of O
2
and CO
2
. The alveolar partial pressure of CO
2
(PCO
2
) varies inversely with ventilation in an asymptotic fashion. The
alveolar partial pressure of O
2
(PO
2
) rises with increasing ventilation
and reaches a plateau.
5
68 SYSTEMS OF THE BODY
to its alveolar value, as might have been expected from
the serial arrangement of anatomical dead space and
alveolar space described so far. In other words, there is
no clear- cut boundary between the two spaces. This is
due to the following factors.
• Flowmaybelaminarorturbulent(Fig. 5.8), and both
cause a gradient of concentration along the tube. In
laminar flow, there is a central spike of faster flow
because of axial streaming, and in turbulent flow, the
square front mixes with the original air as it advances
(see Chapter 4).
• Eddiesofturbulenceatthepointsofairwaybranching
and heartbeat cause gas mixing in the airways.
• Unequalpathwaylengthsfromtherespiratorysurface
to the lips or nares mean alveolar gas has varying
distances to travel to be expired.
• Differencesincomplianceandresistanceindifferent
regions mean that they have different time constants
and take different lengths of time to fill and empty.
These considerations apply to both the inspired and
expired air flowing through the conducting airways
of the lung. As inspired air approaches the alveoli, it
moves into a region of rapidly increasing cross- sectional
area and volume (see Fig. 2.6 and Fig. 5.9). The conse-
quence of this is that the forward velocity of the gas
slows down, almost to a standstill; this slowing down
of the advancing front allows concentration gradients
to build up along the smaller airways. This stratifica-
tion of inspired gas reduces the concentration of fresh air
near the respiratory surface but is not clinically relevant
in healthy lungs. However, in some lung diseases (e.g.
emphysema), the geometry of the airways is changed,
increasing the distance for diffusion; hence, the effects
of stratification increase to significant levels. Similarly,
when direct pathways to the alveolar surface are blocked
by disease, the only ventilation may be via collateral
channels (the pores of Kohn, see Chapter 2) in the walls
of adjacent, normally ventilated alveoli.
Regional differences
Clinically, more important differences in the composition
of alveolar gas exist between regions of the lungs. These
are due to:
• differencesinregionalventilationcausedbydifferent
dilutions of alveolar gas by inspired air, and
• differencesinperfusionaffectingtheexchangeofO
2
and CO
2
with the alveolar gas at different rates (see
Chapter 7).
The greatest difference in regional ventilation in
a healthy, standing subject is between the apex (top)
and the base of the lungs; ventilation in a horizontal
plane is similar in different regions. To explain this
vertical difference in regional ventilation, we must
remember:
• Ventilationistheamountofgasmovedintoandout
of a region, irrespective of the initial volume of that
region.
• Themotiveforcewhichbringsaboutventilationis
the change in the intrapleural pressure around the
AB
Flow Flow
Fig. 5.8 Laminar and turbulent flow. Laminar flow (A) moves in
organised layers parallel to the sides of the airway, with the maximum
velocity at the centre. Turbulent flow (B) is disorganised, and the
velocity profile is flat.
Cross-section
3 cm
2
Trachea
Distance into
tracheobronchial
tree
Total cross-section
9
10
5
cm
2
Fig. 5.9 Airway cross- sectional areas. The total cross- sectional area
increases as you penetrate deeper into the bronchial tree. The area of
the alveolar respiratory surface, represented by the horizontal line, is
300 000 times greater than the cross- sectional area of the trachea.
To air or
suction
To patient
Column of water
falls on e
xpiration
and rises on
inspiration
Ster
ile
w
ater
Fig. 5.10 An underwater seal. Gas from the pneumothorax passes
from the chest drain and bubbles through the water in the seal. The
water prevents gas passing from the atmosphere into the intrapleural
space and also collects blood and other liquid secretions, which might
block a mechanical valve (Gardner, 2010).