548
U N I T 6
Respiratory Function
Tuberculosis
Pulmonary tuberculosis remains one of the deadliest dis-
eases in the world. It is estimated that, if better methods
to control infection are not developed, by the year 2020
nearly 1 billion people worldwide will be newly infected
with tuberculosis, over 150 million will become clinically
ill, and 36 million will die of the disease.
30
With the intro-
duction of antibiotics in the 1950s, the United States and
other Western countries enjoyed a long period of decline
in the number of infections. However, since the mid-1980s
the rate of infection has increased, particularly among
HIV-infected people. In the United States, the biggest
increase in new cases was from 1985 to 1993, after which
the number of reported cases has again declined.
29
In part,
this decline reflects the impact of resources committed to
assist state and local control efforts, wider screening and
prevention programs, and increased support for preven-
tion programs among HIV-infected persons.
Tuberculosis is more common among foreign-born
persons from countries with a high incidence of tuber-
culosis and among residents of high-risk congregate
settings such as correctional facilities, drug treatment
facilities, and homeless shelters. Outbreaks of a drug-
resistant form of tuberculosis have emerged, complicat-
ing the selection of drugs and affecting the duration of
treatment.
Etiology
Tuberculosis is an airborne infection caused by the
M. tuberculosis
mycobacterium. The mycobacteria are
slender, rod-shaped, aerobic bacilli that do not form
spores
2,31–33
(Fig. 22-5). They are similar to other bac-
teria except for a waxy cell wall that is responsible for
many of the bacteria’s characteristics including its slow
growth, antigenicity, and resistance to detergents, dis-
infectants, and antibiotics. It also renders the bacteria
resistant to common laboratory stains. Once stained,
the dye cannot be discolored with acid solution, hence
the name acid-fast bacilli. Although
M. tuberculosis
can
infect practically any organ of the body, the lungs are
most frequently involved.
Tuberculosis is an airborne infection spread by min-
ute, invisible particles, called
droplet nuclei,
that are
harbored in the respiratory secretions of persons with
active tuberculosis.
32,33
Coughing, sneezing, and talking
all create respiratory droplets; these droplets evaporate,
leaving the organisms (droplet nuclei), which remain
suspended in the air and are circulated by air cur-
rents. Thus, living in crowded and confined conditions
increases the risk for spread of the disease.
Pathogenesis
The pathogenesis of tuberculosis in a previously unex-
posed, immunocompetent person is centered on the
development of a cell-mediated immune response that
confers resistance to the organism and development of
tissue hypersensitivity to the tubercular antigens.
2,32,33
The destructive features of the disease result from a
cell-mediated hypersensitivity response (see Chapter 16)
rather than the destructive capabilities of the tubercle
bacillus.
Macrophages are the primary cell infected with
M. tuberculosis.
Inhaled droplet nuclei pass down the
bronchial tree without settling on the epithelium and are
deposited in the alveoli. Soon after entering the lung, the
bacilli are phagocytosed by alveolar macrophages, but
resist destruction. Although the macrophages that first
ingest
M. tuberculosis
cannot kill the organisms, they
initiate a cell-mediated immune response that eventually
contains the infection. As the tubercle bacilli multiply,
the infected macrophages degrade them and present
their antigens to helper (CD4
+
) T lymphocytes. The sen-
sitized helper T cells, in turn, stimulate the macrophages
to increase their concentration of lytic enzymes. This
boosts their ability to kill the bacilli; however, when
released, these lytic enzymes also damage lung tissue.
The development of a population of activated cytotoxic
(CD8
+
) T cells and macrophages capable of ingesting
and destroying the bacilli constitutes the cell-mediated
immune response, a process that takes about 3 to 6 weeks
to become effective.
In immunocompetent persons, the cell-mediated
immune response results in the development of a gray-
white, circumscribed granulomatous lesion, called a
Ghon focus,
that contains the tubercle bacilli, modified
macrophages, and other immune cells.
2,13
It is usually
located in the subpleural area of the upper segments of
the lower lobes or in the lower segments of the upper
lobe. When the number of organisms is high, the hyper-
sensitivity reaction causes the central portion of the
Ghon focus to undergo necrosis, producing a soft, whit-
ish core of dead cells referred to as a caseous (cheeselike)
necrosis. During this same period, tubercle bacilli, free
or inside macrophages, drain along the lymph channels
to the tracheobronchial lymph nodes of the affected lung
and there evoke the formation of caseous granulomas.
The combination of the primary lung lesion and lymph
FIGURE 22-5.
Scanning electron micrograph (SEM) depicting
some of the ultrastructural details seen in the cell wall
configuration of a number of gram-positive Mycobacterium
tuberculosis bacteria. (From the Centers for Disease Control
and Prevention Public Health Image Library. No. 9997. Courtesy
of Ray Butler.)
