Ganong's Review of Medical Physiology, 23rd Edition

CLINICAL BOX 35–1
Airway Diseases That Alter Airflow
Obstructive Disease: Asthma
Asthma is characterized by episodic or chronic wheezing,
cough, and a feeling of tightness in the chest as a result of
bronchoconstriction. Although the disease is not fully understood,
three airway abnormalities are present: airway obstruction
that is at least partially reversible, airway inflammation,
and airway hyperresponsiveness to a variety of stimuli. A
link to allergy has long been recognized, and plasma IgE levels
are often elevated. Proteins released from eosinophils in
the inflammatory reaction may damage the airway epithelium
and contribute to the hyperresponsiveness. Leukotrienes
are released from eosinophils and mast cells, and can
enhance bronchoconstriction. Numerous other amines, neuropeptides,
chemokines, and interleukins have effects on
bronchial smooth muscle or produce inflammation, and they
may be involved in asthma.
Because β 2 -adrenergic receptors mediate bronchodilation,
β 2 -adrenergic agonists have long been the mainstay of treatment
for mild to moderate asthma attacks. Inhaled and systemic
steroids are used even in mild to moderate cases to reduce
inflammation; they are very effective, but their side
effects can be a problem. Agents that block synthesis of leukotrienes
or their CysLT 1 receptor have also proved useful in
some cases.
Restrictive Disease: Emphysema
Emphysema is a degenerative and potentially fatal pulmonary
disease that is characterized by a loss of lung elasticity
and replacement of alveoli with large air sacs. This loss of elasticity
prevents full expansion of the lung, or airway restriction,
during breathing. The most common cause of emphysema
is heavy cigarette smoking. The smoke causes an increase
COMPLIANCE OF THE
LUNGS & CHEST WALL
The interaction between the recoil of the lungs and recoil of
the chest can be demonstrated in living subjects through a
spirometer that has a valve just beyond the mouthpiece. The
mouthpiece contains a pressure-measuring device. After the
subject inhales a given amount, the valve is shut, closing off
the airway. The respiratory muscles are then relaxed while the
pressure in the airway is recorded. The procedure is repeated
after inhaling or actively exhaling various volumes. The curve
of airway pressure obtained in this way, plotted against volume,
is the relaxation pressure curve of the total respiratory
system (Figure 35–10). The pressure is zero at a lung volume
that corresponds to the volume of gas in the lungs at the end
of quiet expiration (functional residual capacity, or FRC;
CHAPTER 35 Pulmonary Function 595
in the number of pulmonary alveolar macrophages, and these
macrophages release a chemical substance that attracts leukocytes
to the lungs. The leukocytes in turn release proteases
including elastase, which attacks the elastic tissue in the
lungs. At the same time, α 1 -antitrypsin, a plasma protein that
normally inactivates elastase and other proteases, is itself inhibited.
The α 1-antitrypsin is inactivated by oxygen radicals,
and these are released by the leukocytes. The final result is a
protease–antiprotease imbalance with increased destruction
of lung tissue. Similar protease–antiprotease imbalance can
occur through congenital deficiency α 1 -antitrypsin.
Airflow Measurements of Obstructive
& Restrictive Disease
In a healthy normal adult male, FVC is approximately 5.0 L, FEV1 is approximately 4.0 L, and thus, the calculated FEV1 /FVC is
80%. As would be expected, patients with obstructive or restrictive
diseases display reduced FVC, on the order of 3.0 L, and
this measurement alone does not differentiate between the
two. However, measurement of FEV1 can significantly vary between
the two diseases. In obstructive disorders, patients tend
to show a slow, steady slope to the FVC, resulting in a small
FEV1 , on the order of 1.3 L. However, in the restrictive disorder
patients, air flow tends to be fast at first, and then due to the
loss of elasticity, quickly levels out to approach FVC. The resultant
FEV1 is much greater, on the order of 2.8 L, even though
FVC is equivalent. A quick calculation of FEV1 /FVC for obstructive
(42%) versus restrictive (90%) patients defines the hallmark
measurements in evaluating these two diseases. Obstructive
disorders result in a marked decrease in both FVC and FEV1 /
FVC, whereas restrictive disorders result in a loss of FVC without
loss in FEV1 /FVC.
also known as relaxation volume). It is positive at greater volumes
and negative at smaller volumes. The change in lung volume
per unit change in airway pressure (ΔV/ΔP) is the
compliance (stretchability) of the lungs and chest wall. It is
normally measured in the pressure range where the relaxation
pressure curve is steepest, and the normal value is approximately
0.2 L/cm H 2O. However, compliance depends on lung
volume; an individual with only one lung has approximately
half the ΔV for a given ΔP. Compliance is also slightly greater
when measured during deflation than when measured during
inflation. Consequently, it is more informative to examine the
whole pressure–volume curve. The curve is shifted downward
and to the right (compliance is decreased) by pulmonary congestion
and interstitial pulmonary fibrosis (Figure 35–11).
Pulmonary fibrosis is a progressive restrictive airway disease
of unknown cause in which there is stiffening and scarring of