Reproduced by Sabinet Gateway under licence granted by the Publisher ( dated 2012)
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Respiratory
mechanisms
ir©wfi®w
failure:
ami
management
I H YOUNG, MB, PhD, FRACP
from the atmosphere to the tissue.
There is a continuous driving pressure
in what may be considered an infinite
reservoir (the atmosphere) but the reservoir that directly supplies the tissues is on the other side of the lung.
The reservoir is the store of O2 in blood
and body fluids and is much smaller,
tance to outflow. Such a resistance will by a factor of about 7, than the correstransiently reduce flow but this situa- ponding stores of CO2. The normal
tion cannot last because the tissues lung imposes a resistance to flow so
continue to fill the tank at the same that the pressure in the blood is aprate. The level in the tank increases proximately 100 mm Hg, a drop from
then until the same flow out is estab- the 150 mm Hg pressure in the inlished. If the resistance is increased spired air. It can be seen that further
still further the level will rise again resistance imposed by lung disease will
until flow in equals flow out. Two lead to a rapid fall in pressure as the
things can then happen: (1) the level small stores readjust. Again, flow to
"overflows", or (2) acts as a brake on the tissues will be maintained unless
further flow in. This level is analogous O2 pressure in the blood falls so low
to the pressure of CO2 (PCO2) in blood that the driving pressure is inadequate
and body fluids so it can be seen that to force into the tissues. This occurs at
the early signs of respiratory failure are an arterial PO2 of about 20 mm Hg and
a rise in PCO2, not a decrease in CO2 such levels are preterminal.
output which is only a transient
I have discussed these simplified
phenomenon. It can also be ap- models of gas transport because they
preciated that a level (or pressure) high emphasize important principles in unenough to "overflow" or prevent tis- derstanding respiratory failure.
sue metabolism will again be transient
1. Respiratory failure is not failure of
and incompatible with life. A PCO2 of the lung to conduct the required flow
80-90 mm Hg will begin to have a of O2 and CO2 to and from the tissues,
narcotic effect and cause central nerv- but its failure to do so with normal
ous system depression.
efficiency.
The behaviour of oxygen with pro- • 2. A raised pressure of CO2 and regression of lung disease may be under- duced pressure of O2 in the body
stood using a similar model (Figure 2). fluids, most conveniently measured in
Here, however, flow is in the opposite the arterial blood, are the hallmarks of
direction, along a pressure gradient, respiratory failure.
3. The body stores of O2 are far
smaller than those of CO2 by a factor of
7. Sudden changes in lung resistance
This article was specially written for Modern
(eg apnoea) will cause a more rapid fall
Medicine by Dr Young, a thoracic physician
at Royal Prince Alfred Hospital, Sydney,in PO2 than PCO2 as the stores are used
up.
Australia.
The major function of the lungs u» the transfer of oxygen into
and carbon dioxide out of the blood in response to the
demands of the body. Respiratory failure is a reduction in
the lungs to cany out this function efficiently. The primary
ciin will find an understanding of (he banc mechanisms of
failure an aid to management in the early stages,
The major function of the lungs is gas
exchange, that is, the transfer of oxygen into the blood and carbon dioxide
out of the blood in response to the
metabolic demands of the body. The
body's demand for O2 may vary from
0,3 litres/min at rest to over 3 litres/
min in a fit person during strenuous
exercise and carbon dioxide production may vary by a similar amount.
The normal lungs are able to accomplish this ten-fold range in gas
transfer rates efficiently but most lung
diseases reduce the efficiency of the
lungs in exchanging O2 and CO2 with
the atmosphere. Such a reduction in
efficiency is labelled respiratory failure, and an understanding of the basic
mechanisms of this failure provides a
basis for rational therapy in the early
stages.
Basic mechanisms
What happens when lung disease
makes the uptake of O2 and elimination of CO2 more difficult? The sequence of events can be understood by
examining a simple hydraulic model.
Consider a tank of water which is being
filled from one pipe and emptied from
another (Figure 1). This is analogous
with tissue COj production (through
the first pipe) filling tissue stores (the
tank) and finally being eliminated via
the lungs (the second pipe). Lung disease acts like a tap increasing the resisModern Medicine/September
1980
35
Reproduced by Sabinet Gateway under licence granted by the Publisher ( dated 2012)
©MimffefiH i r ® w f t e w ,
The most important
mechanism in respiratory
failure is inequality of
ventilation and blood
flow within the lung.
4. It is possible to increase the PO2
in blood by increasing atmospheric
(inspired) PO2, but as the atmospheric
pressure of CO2 is essentially zero,
further reduction to lower arterial
PCO2 is impossible.
Nature of lung resistance
How does lung disease impair the exchange of O2 and CO2? What is the
nature of the "resistance" depicted in
Figures 1 and 2? The most important
mechanism by far is inequality of ventilation and blood flow among the
separate gas-exchanging units in the
lung. The lung is designed to bring
blood and air into close contact so that
O2 and CO2 can exchange by simple
physical diffusion. In order to present
an adequate surface area so that gas can
diffuse at a sufficient rate, the gasexchanging surface is formed into millions of separate sacks or alveoli. The
alveoli are in turn grouped into collections or lobules which act as individual
units for gas exchange. If the lungs
were laid out as a single sheet, their
surface area would be approximately
80 square metres — a rather difficult
organ to handle! All disease processes
are patchy and affect these units to
different degrees, thus causing the
total ventilation and blood flow to be
unevenly distributed.
The other important mechanisms
are reduction of (1) total ventilation
and (2) total blood flow to the lung.
The first, hypoventilation, is more
important and may not be associated
with lung disease at all, eg head injury,
sedative overdose. Other causes of
hypoventilation are inadequate neural
drive to the respiratory muscles due to
insensitivity of the brain stem respiratory centre to abnormal acidosis,
and weakness of the respiratory muscles, eg poliomyelitis, fatigue of the
respiratory muscles. It must be stressed, however, that in the majority of
patients with chronic respiratory failure where hypoventilation is a component cause, lung disease and
ventilation-perfusion inequality are
antecedent. This will be discussed later. The fact that a low total blood flow
to the lungs (ie low cardiac output) will
contribute to respiratory failure is not
generally recognised. This may be the
major mechanism causing hypoxaemia
following myocardial infarction and in
other shock states. Shunt, blood com-
NORMAL
pletely bypassing ventilated lung.
either through a septum defect in the
heart or through areas of totally collapsed lung, has not been mentioned
separately because, in effect, this is an
extreme form of ventilation-perfusion
inequality. Whether the process of diffusion of O2 and CO2 across the alveolar-capillary membrane limits exchange of these gases in lung disease is
a complicated question beyond the
scope of this article. Suffice it to say
that it is rarely, if ever, a factor of
clinical importance. The three important mechanisms of increased lung
"resistance" to gas flow then are, (1)
ventilation-perfusion inequality within the lungs, (2) low overall ventilation
(hypoventilation) and (3) low overall
cardiac output.
In order to conceptualize these three
processes, an analogy may be drawn
with the operation of a large bank.
Assume that there are five tellers, of
equal ability, serving the customers
and that the number of customers leaving the bank per hour is taken as an
index of efficiency analogous to the
pressure of O2 in the arterial blood
leaving the lung. It can be readily appreciated that a reduction in the
number of tellers serving the customers or a reduction in the number of
customers entering the bank will both,
independently, cause a reduction in
RESPIRATORY FAILURE
•CO:PRESSURE
CO;PRESSURE
v
"CO:
COi
LUNG
CO2 PRODUCTION
LUNG
v CO:
Figure 1. Simplified model of the blood and tissue stores of carbon dioxide. For explanation, see text.
Modern Medicine /October 1980
37
Reproduced by Sabinet Gateway under licence granted by the Publisher ( dated 2012)
dlflnDftsfflU wmfmm
the number of customers leaving per
hour. These two changes are analogous to hypoventilation and a low cardiac output respectively. However, if
these two factors are constant, the
number of customers leaving per hour
will also be reduced if they are unevenly distributed amongst the tellers,
ie some tellers have long queues
whereas others are serving only occasionally. This is analogous to
ventilation-perfusion inequality and,
as every bank customer knows, is the
most usual cause of inefficient service
in banks. So it is in the lungs although,
as with all analogies, it is unwise to
take this one too far.
Effect of respiratory failure
on O2 and CO2 pressures in
arterial blood
Ventilation-perfusion inequality will
increase the level of stores of CO2 and
decrease the stores of O2 in the blood
and body fluids — hence the changes
in POi and PCO2 in the arterial blood
which are the hallmark of respiratory
failure. An arterial PCO2 of greater
than 45 mm Hg (6,0 kPa) or a PO2 of
less than 80 mm Hg (10,6 kPa) may be
taken to indicate respiratory failure. It
is true that many elderly people without clinical lung disease will have an
arterial PO2 less than 80 mm Hg but
this is due to progressive ventilationperfusion inequality with age. In fact,
the amount of O2 in the arterial blood
does not begin to fall appreciably until
the PO2 falls below 60-65 111111 Hg
(8,0-8,6 kPa) but after this, relatively
small falls in PO2 result in larger falls
in the concentration of O2 in the blood.
This is due to the well-known shape
of the oxyhaemoglobin dissociation
curve (Figure 3) which illustrates the
critical importance of an arterial PO2
of 60 mm Hg. The dissociation curves
illustrated in Figure 3 merely relate the
driving pressure (mm Hg) necessary to
dissolve a given amount of O2 and CO2
in blood (ml of gas per 100 ml of
blood). The curve for O2 is markedly
alinear because haemoglobin takes up
a large amount of relatively insoluble
O2 until a pressure of 90-100 mm Hg is
reached when it becomes fully saturated. The subsequent increase in O2
concentration with pressure is very
small and due only to physical solution
of more O2 in the blood, in which it is
less soluble than CO2.
Ventilation-perfusion
inequality
will both increase PCO2 and decrease
PO2. However, because of the different shapes of the two dissociation
curves, an increase in the overall venti-
NORMAL
These considerations are of clinical
importance. As lung disease progresses, ventilation-perfusion inequality
becomes more marked and arterial
PO2 falls as PCO2 rises. The latter acts
as a stimulus to increase overall ventilation via the central medullary
chemoreceptors, thus bringing the
arterial PCO2 back to normal. For the
reasons discussed above, the arterial
PO2 stays low and will not act as a
significant stimulus to ventilation (via
the carotid bodies) until it reaches a
value of 50-40 mm Hg. Therefore, the
RESPIRATORY FAILURE
^ATMOSPHERE
^INFINITE Oi
-RESERVOIR ;
BODY
STORES
lation of the lungs will be able to reduce the CO2 concentration significantly in at least some parts of the lung
so that the mixed arterial blood will
have a normal concentration and pressure of CO2. It is not possible, however, for these well ventilated parts of
the lung to add much more O2 to the
blood because they are operating on
the "flat" part of the O2 dissociation
curve past a PO2 of 90 mm Hg. The O2
content and pressure of mixed arterial
blood then is predominantly influenced by parts of the lung with lower
ventilation and increasing the overall
ventilation cannot compensate for the
low PO2 coming from these areas unless the ventilation-perfusion inequality is very mild.
BODY
STORES
CONSUMPTION
LUNG
Oi CONSUMPTION =
v
O:
Figure 2. Simplified model of the blood and tissue stores of oxygen. For explanation, see text.
Modern Medicine/September
1980
39
Reproduced by Sabinet Gateway under licence granted by the Publisher ( dated 2012)
©MimfeM
most common blood gas picture as respiratory failure progresses is a normal
PCO2 but reducing PO2 in the arterial
blood. It is important to realize however, that the normal PCO2 is maintained at the expense of a greater ventilatory effort and that the lungs are
inefficient at eliminating CO2 because
the fundamental abnormality of
ventilation-perfusion inequality is still
present. There is often misunderstanding on this point. It is often
said that ventilation-perfusion inequality does not cause hypercapnia, only
hypoventilation does. In reality the
former is by far the most common
primary cause of hypercapnia although
usually such patients are stimulated to
increase overall ventilation to bring
down the arterial PCO2. If they ventilated normally they would have a high
PCO2. A minority of patients with
hypercapnia are hypoventilating due
to ineffective respiratory control or
muscle activity and may not have lung
disease at all.
Hypercapnia also develops in some
patients as their lung disease and
ventilation-perfusion inequality becomes severe. Such patients may still
be ventilating at a higher than normal
rate but for a number of possible
reasons are not ventilating sufficiently
to maintain a normal arterial PCO2 in
the presence of their disease. They
have developed an insensitivity to the
increased PCO2 and appear to tolerate
levels as high as 70 mm Hg or even
higher. This syndrome is especially
seen in some patients with chronic
bronchitis but the reasons why it develops is generally unknown. Many
appear to have developed a blunted
chemoreceptor response to CO2 as evidenced by their ability consciously to
ventilate off the extra CO2 while respiratory muscle fatigue may be an
important factor in other patients,
especially those with severe acute
exacerbations.
The ventilatory drive of such patients with hypercapnia may be largely
due to their hypoxaemia. They have
lost their ventilatory sensitivity to CO2
and hypoxia becomes the most important drive. It is these patients who are
in danger when given high O2 mixModern Medicine /October 1980
POi or PCOi (mm Hg)
Figure j. The blood oxygen and carbon dioxide dissociation curves.
tures to inspire which can "turn o f f '
their ventilatory drive leading to
dangerous narcotic levels of hypercapnia.
Implications for management
I have dwelt on the mechanisms of
respiratory failure at some length because important management principles can be understood from their consideration. Many are revelant to the
early management of patients with respiratory failure in general practice.
1. Inequality of ventilation and perfusion among the myriad gas exchanging units of the lung is by far the most
important primary cause of respiratory
failure. Chronic bronchitis, emphysema, bronchiectasis, asthma,
pulmonary vascular diseases and interstitial lung disease all cause patchy
pathology which in turn leads to this
inequality. Early therapy then should
logically be directed at making ventilation and perfusion distribution more
even. Chronic obstructive lung disease
associated with smoking is undoubtedly the major cause of chronic respiratory failure in the community.
Cessation of smoking and therapy directed toward clearing blocked airways of mucus and reducing mucosal
swellings are the appropriate practical
measures. This means aerosol sympathomimetic bronchodilators, which
also enhance ciliary action and mucus
clearance, antibiotics for acute infections, and physiotherapy, although the
efficacy of the latter is controversial.
These measures help to make the distribution of ventilation more even.
There is nothing that can be done for
the pulmonary vessel destruction of
emphysema except strongly to recommend the cessation of smoking.
2. Hypercapnic respiratory failure
develops in some patients only after
many years of chronic lung disease.
The reasons why some patients develop this syndrome and others do not
Continued on page 42
41