CHAPTER 35Pulmonary Function 605OTHER FUNCTIONS OF THE
RESPIRATORY SYSTEM
LUNG DEFENSE MECHANISMS
The respiratory passages that lead from the exterior to the
alveoli do more than serve as gas conduits. They humidify and
cool or warm the inspired air so that even very hot or very cold
air is at or near body temperature by the time it reaches the
alveoli. Airway epithelial cells can secrete a variety of mole-
cules that aid in lung defense. Secretory immunoglobulins
(IgA), collectins (including Surfactant A and D), defensins
and other peptides and proteases, reactive oxygen species, and
reactive nitrogen species are all generated by airway epithelial
cells. These secretions can act directly as antimicrobials to help
keep the airway free of infection. Airway epithelial cells also
secrete a variety of chemokines and cytokines that recruit the
traditional immune cells and others to site of infections.
Various mechanisms operate to prevent foreign matter
from reaching the alveoli. The hairs in the nostrils strain out
many particles larger than 10 μm in diameter. Most of the
remaining particles of this size settle on mucous membranes
in the nose and pharynx; because of their momentum, they do
not follow the airstream as it curves downward into the lungs,
and they impact on or near the tonsils and adenoids, large
collections of immunologically active lymphoid tissue in the
back of the pharynx. Particles 2 to 10 μm in diameter gener-
ally fall on the walls of the bronchi as the air flow slows in the
smaller passages. There they can initiate reflex bronchial con-
striction and coughing. Alternatively, they can be moved away
from the lungs by the “mucociliary escalator.” The epithelium
of the respiratory passages from the anterior third of the nose
to the beginning of the respiratory bronchioles is ciliated. The
cilia are bathed in a periciliary fluid where they typically beat
at rates of 10–15 Hz. On top of the periciliary layer and the
beating cilia rests a mucus layer, a complex mixture of pro-
teins and polysaccharides secreted from specialized cells,
glands, or both in the conducting airway. This combination
allows for the trapping of foreign particles (in the mucus) and
their transport out of the airway (powered by ciliary beat).
The ciliary mechanism is capable of moving particles away
from the lungs at a rate of at least 16 mm/min. When ciliary
motility is defective, as can occur from smoking, other envi-
ronmental conditions, or genetic deficiency, mucus transport
is virtually absent. This can lead to chronic sinusitis, recurrent
lung infections, and bronchiectasis. Some of these symptoms
are evident in cystic fibrosis (Clinical Box 35–4).
The pulmonary alveolar macrophages (PAMs) are another
important component of the pulmonary defense system. Like
other macrophages , these cells come originally from the bone
marrow. Particles less than 2 μm in diameter can evade the
mucociliary escalator and reach the alveoli. PAMs are actively
phagocytic and ingest these small particles. They also help
process inhaled antigens for immunologic attack, and they
secrete substances that attract granulocytes to the lungs as
well as substances that stimulate granulocyte and monocyte
formation in the bone marrow. When the PAMs ingest large
amounts of the substances in cigarette smoke or other irri-
tants, they may also release lysosomal products into the extra-
cellular space to cause inflammation.METABOLIC & ENDOCRINE
FUNCTIONS OF THE LUNGSIn addition to their functions in gas exchange, the lungs have
a number of metabolic functions. They manufacture surfac-
tant for local use, as noted above. They also contain a fibrino-
lytic system that lyses clots in the pulmonary vessels. They
release a variety of substances that enter the systemic arterial
blood (Table 35–5), and they remove other substances from
the systemic venous blood that reach them via the pulmonary
artery. Prostaglandins are removed from the circulation, but
they are also synthesized in the lungs and released into the
blood when lung tissue is stretched.CLINICAL BOX 35–4
Cystic Fibrosis
Among Caucasians, cystic fibrosis is one of the most com-
mon genetic disorders: 5% of the population carry a defec-
tive gene, and the disease occurs in 1 of every 2000 births.
The gene that is abnormal in cystic fibrosis is located on
the long arm of chromosome 7 and encodes the cystic fi-
brosis transmembrane conductance regulator (CFTR), a
regulated Cl– channel located on the apical membrane of
various secretary and reabsorptive epithelia. The number of
reported mutations in the CFTR gene that cause cystic fibro-
sis is large, and the severity of the defect varies with the mu-
tation; however, this is not surprising in a gene encoding
such a complex protein. The most common mutation caus-
ing cystic fibrosis is loss of the phenylalanine residue at po-
sition 508 of the protein (ΔF508). This hinders proper fold-
ing of the molecule, leading to reduced membrane levels.
One outcome of cystic fibrosis is repeated pulmonary in-
fections, particularly with Pseudomonas aeruginosa, and
progressive, eventually fatal destruction of the lungs. In this
congenital recessive condition, the function of a Cl– chan-
nel, the CFTR channel, is depressed by loss-of-function mu-
tations in the gene that encodes it. One would expect Na+
reabsorption to be depressed as well, and indeed in sweat
glands it is. However, in the lungs, it is enhanced, so that
the Na+ and water move out of airways, leaving their other
secretions inspissated and sticky. This results in a reduced
periciliary layer that inhibits function of the mucociliary es-
calator, and alters the local environment to reduce the ef-
fectiveness of antimicrobial secretions.