546 Chapter 16
directly caused by COPD, other pathological changes may
occur. These include pneumonia, pulmonary emboli (traveling
blood clots), and heart failure. Patients with COPD may develop
cor pulmonale —pulmonary hypertension with hypertrophy and
eventual failure of the right ventricle. COPD is currently the fifth
leading cause of death worldwide, and it has been estimated that
by 2020 it will become the third leading cause of death.Pulmonary Fibrosis
Under certain conditions, for reasons that are poorly under-
stood, lung damage leads to pulmonary fibrosis instead of
emphysema. In this condition, the normal structure of the lungs
is disrupted by the accumulation of fibrous connective tissue
proteins. Fibrosis can result, for example, from the inhalation of
particles less than 6 m m in size that can accumulate in the respi-
ratory zone of the lungs. Included in this category is anthraco-
sis, or black lung, which is produced by the inhalation of carbon
particles from coal dust.and destruction of alveolar walls. Included in the COPD cat-
egory is chronic obstructive bronchiolitis, with fibrosis and
obstruction of the bronchioles, and emphysema. This condi-
tion results in an accelerated age-related decline in the FEV 1.
Although asthma is also classified as a chronic inflammatory
disorder, it is distinguished from COPD in that the obstruction
in asthma is largely reversible with inhalation of a bronchodi-
lator (albuterol). Also, asthma (but not COPD) is characterized
by airway hyperresponsiveness—an abnormal bronchocon-
strictor response to a stimulus. The inflammatory cells charac-
teristic of COPD are macrophages, neutrophils, and cytotoxic
T lymphocytes, whereas in asthma they are helper T lympho-
cytes, eosinophils, and mast cells, as previously discussed.
About 90% of people with COPD are (or have been) smok-
ers. Genetic susceptibility is also a factor; not all smokers get
COPD, but a substantial proportion—10% to 20%—do. Cigarette
smoke contains over 2,000 foreign compounds and many free
radicals that promote inflammation and activate alveolar macro-
phages and neutrophils. Protein-digesting enzymes released by
these activated phagocytes, together with reactive oxygen species
(chapter 5, section 5.2), promote the lung damage that results in
emphysema. Cigarette smoking also stimulates proliferation of the
mucus-secreting goblet cells of the respiratory tract, and excessive
mucus production correlates with the severity of COPD. In addi-
tion, cigarette smoking promotes remodeling of the small airways,
in which additions of fibrous and muscle tissue to the bronchiolar
wall narrow the lumen and contribute to the obstruction of airflow.
Finally, cigarette smoke promotes remodeling in the blood ves-
sels within the lungs, resulting in pulmonary hypertension among
COPD patients. It should be noted that smoking is also the major
preventable cause of lung cancer, which is responsible for most
cancer deaths worldwide.
The vast majority of people with COPD are smokers, and
cessation of smoking once COPD has begun does not seem to
stop its progression. Inhaled corticosteroids, which are useful
in treating the inflammation of asthma, are of limited value in
the treatment of COPD. In addition to the pulmonary problems
Figure 16.17 Emphysema destroys lung tissue. These are photomicrographs of tissue ( a ) from a normal lung and ( b ) from
the lung of a person with emphysema. The destruction of lung tissue in emphysema results in fewer and larger alveoli.
(a) (b)| CHECKPOINT
5a. Describe the actions of the diaphragm and external
intercostal muscles during inspiration. How is quiet
expiration produced?
5b. Explain how forced inspiration and forced expiration
are produced.
6a. Define the terms tidal volume and vital capacity.
Explain how the total minute volume is calculated
and how this value is affected by exercise.
6b. How are the vital capacity and the forced expiratory
volume measurements affected by asthma and
pulmonary fibrosis? Give the reasons for these
effects.