Airway resistance to air ﬂ ow is normally so small that very
small pressure differences produce large volumes of air ﬂ ow. As
we have seen (see Figure 13–13), the average atmosphere-to-
alveoli pressure difference during a normal breath when at rest
is about 1 mmHg; yet approximately 500 ml of air is moved
by this tiny difference.
Physical, neural, and chemical factors affect airway radii
and therefore resistance. One important physical factor is the
transpulmonary pressure, which exerts a distending force on
the airways, just as on the alveoli. This is a major factor keeping
the smaller airways—those without cartilage to support them—
from collapsing. Because transpulmonary pressure increases dur-
ing inspiration (see Figure 13–13), airway radius becomes larger
and airway resistance lower as the lungs expand during inspira-
tion. The opposite occurs during expiration.
A second physical factor holding the airways open is the
elastic connective tissue ﬁ
bers that link the outside of the air-
ways to the surrounding alveolar tissue. These ﬁ bers are pulled
upon as the lungs expand during inspiration, and in turn they
help pull the airways open even more than between breaths.
This is termed
Thus, both the transpulmo-
nary pressure and lateral traction act in the same direction,
reducing airway resistance during inspiration.
Such physical factors also explain why the airways become
narrower and airway resistance increases during a forced expi-
ration. The increase in intrapleural pressure compresses the
small conducting airways and decreases their radii. Therefore,
because of increased airway resistance, there is a limit to how
much one can increase the air ﬂ ow rate during a forced expira-
tion no matter how intense the effort. The harder one pushes,
the greater the compression of the airways, further limiting
expiratory air ﬂ ow.
In addition to these physical factors, a variety of neuro-
endocrine and paracrine factors can inﬂ uence airway smooth
muscle and thereby airway resistance. For example, the hor-
mone epinephrine relaxes airway smooth muscle by an effect
on beta-adrenergic receptors, whereas the leukotrienes, mem-
bers of the eicosanoid family, produced in the lungs during
inﬂ ammation contract the muscle.
Why are we concerned with all the physical and chemi-
cal factors that
uence airway resistance when airway
resistance is normally so low that it poses no impediment to
air ﬂ ow? The reason is that, under abnormal circumstances,
changes in these factors may cause serious increases in airway
resistance. Asthma and chronic obstructive pulmonary disease
provide important examples, as we see next.
is a disease characterized by intermittent episodes
in which airway smooth muscle contracts strongly, markedly
increasing airway resistance. The basic defect in asthma is
chronic inﬂ ammation of the airways, the causes of which vary
from person to person and include, among others, allergy,
viral infections, and sensitivity to environmental factors. The
underlying inﬂ ammation makes the airway smooth muscle
hyperresponsive and causes it to contract strongly in response
to such things as exercise (especially in cold, dry air), cigarette
smoke, environmental pollutants, viruses, allergens, normally
released bronchoconstrictor chemicals, and a variety of other
potential triggers. In fact, the incidence of asthma is increas-
ing, possibly due in part to environmental pollution.
The ﬁ rst aim of therapy for asthma is to reduce the
chronic inﬂ ammation and airway hyperresponsiveness with
particularly inhaled glucocorti-
coids and leukotriene inhibitors. The second aim is to over-
come acute excessive airway smooth muscle contraction with
which relax the airways. The latter
drugs work on the airways either by relaxing airway smooth
muscle or by blocking the actions of bronchoconstrictors.
For example, one class of bronchodilator drugs mimics the
normal action of epinephrine on beta-adrenergic (beta-2)
receptors. Another class of inhaled drugs block musca-
rinic cholinergic receptors, which have been implicated in
Chronic Obstructive Pulmonary Disease
chronic obstructive pulmonary disease
emphysema, chronic bronchitis, or a combination of the two.
These diseases, which cause severe difﬁ culties not only in ven-
tilation but in oxygenation of the blood, are among the major
causes of disability and death in the United States. In contrast
to asthma, increased smooth muscle contraction is
cause of the airway obstruction in these diseases.
Emphysema is discussed later in this chapter; sufﬁ ce it to
say here that the cause of obstruction in this disease is destruc-
tion and collapse of the smaller airways.
is characterized by excessive mucus
production in the bronchi and chronic inﬂ
in the small airways. The cause of obstruction is an accumula-
tion of mucus in the airways and thickening of the inﬂ
airways. The same agents that cause emphysema—smoking,
for example—also cause chronic bronchitis, which is why the
two diseases frequently coexist.
Lung Volumes and Capacities
Normally the volume of air entering the lungs during a single
inspiration, called the
tidal volume (
, is approximately
equal to the volume leaving on the subsequent expiration.
The tidal volume during normal quiet breathing is termed the
resting tidal volume and is approximately 500 ml depending
on body size. As illustrated in
, the maximal
amount of air that can be increased above this value during
deepest inspiration is termed the
inspiratory reserve volume
and is about 3000 ml—i.e., six times greater than rest-
ing tidal volume.
After expiration of a resting tidal volume, the lungs still
contain a very large volume of air. As described earlier, this is
the resting position of the lungs and chest wall when there is
no contraction of the respiratory muscles; this amount of air is
functional residual capacity (FRC)
about 2400 ml. Thus, the 500 ml of air inspired with each rest-
ing breath adds to and mixes with the much larger volume of
air already in the lungs, and then 500 ml of the total is expired.
Through maximal active contraction of the expiratory muscles,
it is possible to expire much more of the air remaining after the
resting tidal volume has been expired. This additional expired