Emphysema is defined
as a condition of the lung characterized by abnormal permanent
enlargement of the airspaces distal to the terminal bronchiole,
accompanied by destruction of their walls without obvious fibrosis.
Emphysema is
classified in anatomic terms, but the classification should not ignore the fact that the severity of emphysema is more important
than the type.
As emphysema becomes more severe it
becomes more difficult to classify, a situation similar to that of end
stage of renal disease or cirrhosis of the liver.
Emphysema is more
common, being found in about half of all autopsies, and is easily
recognizable.
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Proximal Acinar (Centriacinar) Emphysema:
Proximal part of the
acinus (respiratory bronchioles) is selectively or predominantly involved
in centriacinar emphysema, of which there are two forms.
Centrilobular emphysema is the common form of emphysema in
nonindustrial populations. Focal emphysema is recognized in dusty
occupations, such as coal mining (coal workers emphysema or simple
pneumoconiosis).
Centrilobular Emphysema:
Centrilobular
emphysema is the form of the disease most frequently encountered and the
one usually associated with clinical symptoms. It
involves the central part of the lobule (the smallest portion of the lung
bounded by lobular septa, or the cluster of terminal
bronchioles near the end of the bronchiolar tree). More exactly, it
involves the proximal part of the acinus. It is associated with, and
probably due to, tobacco smoking. The destroyed and enlarged
respiratory bronchioles form airspaces that are separated from each other
and from lobular septa by normal alveolar ducts and sacs. As the lesion
progresses, these distal structures may also be involved. The bronchioles
proximal to the emphysematous spaces are inflamed and narrowed.
Centrilobular emphysema is most common and most severe in the upper zones
of the lung (upper lobe and superior segment of lower lobe). It occurs
much more often in men than in women and is commonly associated with
chronic bronchitis
.
Coal Pneumoconiosis:
Working with coal,
whether as a miner or in other ways, results in an accumulation of coal or
other dust in macrophages in and around respiratory bronchioles. Mild
dilatation of respiratory bronchioles results, probably from atrophy of
muscle. The lesion resembles centrilobular emphysema but differs in
that the enlarged spaces are smaller and more regular, and inflammation of
bronchioles is not apparent. Thus, the lesion is primarily distensive
rather than destructive. The anatomic lesion is usually equated with a
chest radiograph that shows small nodular densities, although the complete
correlation has not been proved. The condition, also referred to as
black lung, has been considered to cause severe disability.
Contemporary evidence, however, suggests that simple coal pneumoconiosis
causes only minor impairment of pulmonary function. When coal miners have
severe chronic airflow obstruction, it is usually due to other forms of
emphysema, notably tobacco-related centrilobular emphysema. Other forms of
dust, including iron and urban soot, may also be associated with similar
lesions.
Panacinar
Emphysema:
The acinus is
uniformly involved in panacinar emphysema. All parts of
the acinus are destroyed and in the final stage a lacy network of
supporting tissue is left behind (the “cotton candy lung” ). Panacinar
emphysema occurs in several different situations.
Familial
Emphysema:
Familial
emphysema is usually due to a defect in circulating alpha1-antiproteinase.
Originally described as alpha1-antitrypsin deficiency, it is now recognized
that protein has several antiproteinase effects, notably antielastase. The
amount and type of alpha1-antitrypsin is determined by a pair of
co-dominant alleles, referred to as Pi (proteinase inhibitor). The most
common phenotype is PiM . The most
serious abnormality is associated with the PiZ allele, which occurs in
some 5% of the population, is commoner in those of Scandinavian origin,
and is rare in Jews, blacks, and Japanese. The phenotype PiZ is
associated with very low levels of circulating antiproteinase inhibitor,
which also has an abnormal electrophoretic mobility.
People with this phenotype often develop cirrhosis of the liver in infancy
and emphysema as adults. The
majority of all patients with
clinically
diagnosed emphysema under the age of 40 have a alpha1-antitrypsin deficiency (PiZ).
Symptomatic emphysema is uncommon under the age of 50. Cigarette smoking
plays an important role in the causation of emphysema in most affected
individuals, but a small number of nonsmokers with PiZ also develop
emphysema. PiZ is associated with panacinar emphysema, which is
characteristically worse in the lower zones of the lung. Clinically, the
patients usually have the “pink puffer syndrome”, with greatly enlarged
lung volumes and normal blood gases. Other alleles
are also associated with emphysema, the most important being PiS, which
is found frequently among southern Europeans.
Panacinar
Emphysema in association with Centrilobular Emphysema:
Panacinar emphysema
is often associated with centrilobular emphysema. In such cases, the
panacinar form tends to occur in the lower zones of the lung, whereas
centrilobular emphysema is seen in the upper ones. The associations are
the same as for centrilobular emphysema alone, notably cigarette smoking,
chronic bronchitis, and chronic airflow obstruction.
Clinical Features of Emphysema:
When emphysema gets worse it is hard to classify, and experts may classify
the same lung differently, as centrilobular, panacinar, or unclassified
emphysema. The severity of emphysema is more
important than the type in producing chronic airflow obstruction.
People may have severe emphysema at autopsy without clinical
manifestations of chronic airflow obstruction. The frequency of chronic
bronchitis increases with the severity of emphysema, and almost all
patients with severe emphysema have chronic bronchitis. Although it was
once thought that chronic bronchitis leads to emphysema, it is now recognized that
chronic bronchitis and emphysema share a common etiologic agent, which is tobacco
smoke.
Patients usually
present to their physician between 55 and 60 years of age with dyspnea of
insidious onset. Weight loss is probably due less to lack of calories than
to the increased work of breathing. It may be that caloric deficiency
aggravates emphysema in man.
The “Pink Puffer” and the “Blue Bloater”
The literature in
1960s emphasized that patients with severe chronic airflow obstruction
present with two distinct appearances. One type of patient is severely
hypoxic and hypercapneic, has peripheral edema because of right
ventricular failure, and often has a rate of ventilation less than that
suggested by the concentrations of blood gases. Conversely, another
patient is thin and has normal blood gas levels because of a sustained
high ventilation rate. The former was known as the “blue bloater”, and
airflow obstruction was thought to be due to chronic bronchitis, the
latter was labeled the “pink puffer”, and chronic airflow obstruction was
attributed to emphysema. The two types of
chronic airflow obstruction are still identifiable and represent
the opposite ends of a spectrum. Most patients have features of both.
The blue-bloater syndrome is likely to occur in those with diminished
response to hypercapnea and perhaps hypoxia. Among the patients, those
with the greatest degree of right ventricular hypertrophy have more
narrowed peripheral airways. This is a logical observation since those
with the blue-bloater syndrome, have the greatest ventilation-perfusion
inequalities, a situation consistent with severe bronchiolar narrowing.
One should regard
chronic airflow obstruction as multifactorial. In the central airways, the
bronchioles, and the lung parenchyma, a variety of lesions may contribute
to chronic airflow obstruction. They occur together because of a common
etiologic agent - tobacco smoke. In patients with mild chronic airflow
obstruction, bronchiolar lesions, like inflammation, are
predominant. In patients with severe chronic airflow obstruction,
emphysema is the most important.
Etiology and Pathogenesis of Emphysema:
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Conclusive
evidence now exists that the major cause of emphysema is tobacco smoking,
especially cigarette smoking. Moderate to severe emphysema is rarely found
in nonsmokers. The dominant hypothesis concerning the pathogenesis of
emphyema is the proteolysis-antiproteolysis theory. It is now thought that there is a
balance between elastin synthesis and catabolism in the lung. If
elastolytic activity increases or antielastolytic activity decreases,
emphysema results. Increased numbers of neutrophils, which contain serine
elastase, are found in the bronchoalveolar lavage fluid of smokers.
Smoking also reduces alpha1-antiproteinase activity in the lung, owing to
the oxidation of methionine residues in alpha1-antiproteinase. In this way, unopposed and increased elastolytic activity leads to emphysema.
The most
important radiologic abnormalities include overinflation of the lung, as
evidenced by enlarged lungs, depressed diaphragm levels, an inversion of
the convexity of the diaphragm and an increased posteroanterior diameter
(“barrel chest”). Relative avascularity of the peripheral lung
is also described as a sign.
Using MRI clear pulmonary vascular information can be
obtained easily, and the relative pulmonary blood flow in the lung
parenchyma can be quantified.
Tests of expiratory flow are poorly related
to the severity of emphysema because emphysema is only one cause of
chronic airflow obstruction. Tests that
reflect the loss of elastic recoil, such as increased functional residual
capacity, and particularly total lung capacity, show a better correlation.
The best predictor has been the diffusing capacity (transfer factor) for
carbon monoxide, although no single test is entirely adequate. It is
appropriate to think of chronic airflow obstruction as a multifactorial
syndrome, the most important of which is emphysema. The severity of
emphysema can be assessed only by an integrated approach. Tests for
expiratory flow establish the severity of chronic airflow obstruction. If
a patient is young and a nonsmoker, he is unlikely to have emphysema. If
he is a middle aged smoker with chronic bronchitis, he is likely to have
emphysema. The chest radiograph provides supplementary evidence, as do the
functional tests previously mentioned. In the final analysis, clinical
common sense, a chest radiograph, and measurement of the diffusing
capacity go a long way in making the assessment.
