The Respiratory System
During the mid-1980s, there was an alarming increase in
TB due to TB-infected HIV patients. ±is trend has now
been brought under control and TB rates in the U.S. are again
However, deadly strains of drug-resistant (even multidrug-
resistant) TB can develop when treatment is incomplete or in-
adequate. Resistant strains are found elsewhere in the world and
have appeared in North America.
Homeless shelters, with their densely packed populations,
are ideal breeding grounds for drug-resistant strains. ±e TB
bacterium grows slowly and drug therapy entails a 12-month
course of antibiotics. ±e transient nature of shelter populations
makes it diﬃcult to track TB patients and ensure they take their
medications for the full 12 months. ±e threat of TB epidemics
is so real that health centers in some cities are detaining such pa-
tients against their will for as long as it takes to complete a cure.
Lung cancer is the leading cause of cancer death for both men
and women in North America, killing more people every year
than breast, prostate, and colorectal cancer combined. ±is is
tragic, because lung cancer is largely preventable—nearly 90%
of cases result from smoking.
±e cure rate for lung cancer is notoriously low, with most
victims dying within one year of diagnosis. ±e ﬁve-year sur-
vival rate is about 17%. Because lung cancer is aggressive and
metastasizes rapidly and widely, most cases are not diagnosed
until they are well advanced.
Lung cancer appears to follow closely the oncogene-activating
steps outlined in
A Closer Look
in Chapter 4. Ordinarily, nasal
hairs, sticky mucus, and cilia do a ﬁne job of protecting the lungs
from chemical and biological irritants, but when a person smokes,
these defenses are overwhelmed and eventually stop functioning.
In particular, smoking paralyzes the cilia that clear mucus from
the airways, allowing irritants and pathogens to accumulate. ±e
“cocktail” of free radicals and other carcinogens in tobacco smoke
eventually translates into lung cancer.
±e three most common types of lung cancer are:
(about 40% of cases), which originates in
peripheral lung areas as solitary nodules that develop from
bronchial glands and alveolar cells.
Squamous cell carcinoma
(25–30%), which arises in the ep-
ithelium of the bronchi or their larger subdivisions and tends
to form masses that may cavitate (hollow out) and bleed.
Small cell carcinoma
(about 20%), round lymphocyte-sized
cells that originate in the main bronchi and grow aggressively
in small grapelike clusters within the mediastinum. Metasta-
sis from the mediastinum is especially rapid. Some small cell
carcinomas cause additional problems because they produce
certain hormones. For example, some secrete ACTH (leading
to Cushing’s syndrome) or ADH (resulting in the syndrome of
inappropriate ADH secretion, or SIADH; see p. 601).
Because lung cancers metastasize aggressively and early,
the key to survival is early detection. A recent study of heavy
smokers showed that using helical CT scans instead of standard
chest X rays improved tumor detection and reduced mortality
by 20%. A promising screening test for lung cancer that is still
in development is a simple breath test using a detector made of
If the cancer has not metastasized before it is discovered,
complete removal of the diseased lung has the greatest potential
for prolonging life and providing a cure. With metastatic lung
cancer, radiation therapy and chemotherapy are the only op-
tions, but these have low success rates.
Fortunately, there are several new therapies on the horizon.
±ese include (1) antibodies that target speciﬁc growth factors
or other molecules required by the tumor or that deliver toxic
agents directly to the tumor, (2) cancer vaccines to stimulate
the immune system to ﬁght the tumor, and (3) various forms
of gene therapy to replace the defective genes that make tumor
cells divide continuously. As clinical trials progress, we will
learn which of these approaches is most eﬀective.
of the Respiratory System
Trace the embryonic development of the respiratory
Describe normal changes that occur in the respiratory
system from infancy to old age.
Because embryos develop in a cephalocaudal (head-to-tail)
direction, the upper respiratory structures appear ﬁrst. By the
fourth week of development, two thickened plates of ectoderm,
ōds), are present on the anterior
aspect of the head
. ±ese quickly invaginate
that form the nasal cavities. ±e olfac-
tory pits then extend posteriorly to connect with the developing
pharynx, which forms at the same time from the endodermal
±e epithelium of the lower respiratory organs develops as an
outpocketing of the foregut endoderm, which becomes the pha-
ryngeal mucosa. ±is protrusion, called the
, is present by the ﬁ²h week of development. ±e proximal
part of the bud forms the tracheal lining, and its distal end splits
and forms the mucosae of the bronchi and all their subdivisions,
including (eventually) the lung alveoli. Mesoderm covers these
endoderm-derived linings and forms the walls of the respira-
tory passageways and the stroma of the lungs.
By 28 weeks, the respiratory system has developed suﬃ-
ciently to allow a baby born prematurely to breathe on its own.
As we noted earlier, infants born before this time o²en exhibit
infant respiratory distress syndrome resulting from inadequate
During fetal life, the lungs are ﬁlled with ﬂuid and the pla-
centa makes all respiratory exchanges. Vascular shunts cause
circulating blood to largely bypass the lungs (see Chapter 28).
At birth, the respiratory passageways ﬁll with air. As the P
in the baby’s blood rises, the respiratory centers are excited,