THE MECHANISM OF DUST CLEARANCE FROM THE LUNG
A
THEORY
PAUL GROSS, M.D.
Industrial Hygiene Foundation, Mellon Institute, and St. Joseph's Hospital,
Pennsylvania
Pittsburgh,
Most of the dust particles that find lodgment in an alveolus are removed by
way of the ciliated epithelium of the bronchial passages. This process of removal
seems generally to be efficient but evidence of inadequacy appears when the
inhaled air is grossly overloaded with suspended, fine particulate matter. I h e
dust particles that escape removal via the bronchi may become the inciting
cause of pneumoconiosis. .
Whereas much has been written about the mechanism of production of the
pneumoconioses, the literature is silent in regard to the mechanism for transporting particulate matter from the respiratory membrane to the bronchiolar
epithelium.
Alveolar macrophages are common to both mechanisms as the carriers of the
foreign material. These cells, varying in number and distribution and containing
different amounts of pigment, are frequently present in lung sections that show
little indication of active inflammation. In the routine examination of lung sections the alveolar macrophages are usually dismissed as "dust cells," the cytologic response of the alveolar wall to the irritation evoked by inhaled dust particles. Such a concept, however, is not sufficiently comprehensive. It does not take
into consideration the phagocytosis of endogenous materials as hemosiderin and
lipids. Nor does it explain the frequently focalized distribution of alveolar macrophages or their presence in some sections containing little pigment and their
absence in other sections having considerable pigment.
Based on a general impression that the distribution of alveolar macrophages
followed a definite pattern, this study was undertaken to determine the relationship between this pattern and the excursionary activity of alveolar tissue.
M A T E R I A L S AND METHOD
The lung sections of 87 adult persons in consecutive autopsies were examined,
special attention being given to the presence or absence of alveolar macrophages,
their numbers and their relationship to bronchi, vessels, scars, atelectasis and
edema fluid. Cases in which macrophages were associated with polymorphonuclear leukocytes were excluded from the evaluation.
RESULTS
There were 15 cases in which leukocytes indicated the presence of active
inflammation and 15 cases in which only an occasional alveolar macrophage was
Received for publication June 9, 1952.
Read at the Thirty-First Annual Meeting of .the American Society of Clinical Pathologists, in Chicago, October 15, 1952.
Dr. Gross is Research Pathologist at the Industrial Hygiene Foundation of America.
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DUST C L E A R A N C E
FROM
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LUNG
found in the lung sections. In 14 other cases, the number of alveolar macrophages
was designated as "few." The remaining 43 cases (about 50 per cent of the entire
series) exhibited moderate to large numbers of alveolar macrophages without
association of other inflammatory cells. These cases are the subject of more
detailed study.
A listing of the various types of localization of alveolar macrophages and the
number as well as percentage of cases found with each type is given in Table 1.
Some of the cases showed focal accumulations of alveolar macrophages that
could not be related to any anatomic change or structure and were accordingly
listed under "no demonstrable localization." Some of the latter cases also contained regions manifesting unequivocal focalization of alveolar macrophages to
peribronchial regions, areas of atelectasis, or other categories listed. Such cases
were given multiple listings.
Atelectasis, focal or extensive, was the most common pulmonary lesion associated with the presence of alveolar macrophages. The atelectasis was usually
of a compression type owing to hydrothorax or elevation of the diaphragm from
TABLE 1
CONDITIONS U N D E R W H I C H ACCUMULATIONS OP MACROPHAGES W E R E F O U N D
CONDITION
Atelectasis
Alveolar edema
Thickened alveolar walls
Proximity to bronchi or vessels
Proximity to scars
No demonstrable localization
NUMBER OF CASES*
PERCENTAGE OF CASES*
22
13
13
11
9
11
50
30
30
25
20
25
* Some cases have multiple listings.
ascites, peritonitis, abdominal distention or paralytic ileus. There were also a
few cases in which bronchial obstruction could not be entirely dismissed as a
factor in the atelectasis.
These cases included persons in prolonged coma, who had reduction in the
vigor of respiratory activity and inhibition of the coughing reflex. The accumulation of macrophages was greater when the atelectasis was only partial than
when it was nearly complete.
The number of alveolar macrophages associated with edema fluid was distinctly smaller than was the case in partial atelectasis. Nevertheless, it was
often striking to note an appreciable number of macrophages in an edematous
alveolus while none were to be seen in adjacent, apparently dry alveoli. Whether
the edema fluid was due to shock or other causes did not appear to be a significant factor in determining the frequency or extent of accumulations of
macrophages.
Collections of alveolar macrophages in the vicinity of bronchi, vessels and
scars, or within alveoli with thickened walls, were conspicuous because of their
sharply focalized nature. Another reason for their prominence was the frequent,
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heavy pigmentation of these cells. The pigment was largely carbon except in
those cases marked by diffuse fibrous thickening of alveolar walls, as occurred
with mitral stenosis or cor pulmonale with chronic right heart failure, where the
pigment was largely hemosiderin.
There were no significant effects of age or sex in the distribution or degree of
reaction of alveolar macrophages.
DISCUSSION
Interference with the exclusionary activity of alveoli is caused by factors
that are intrinsic as well as extrinsic. Thus, alveoli situated in the proximity of
relatively firm structures, such as subpleural or other sizable scars, bronchi and
vessels, are not as free to collapse and expand as other alveoli. Since fluid is
incompressible and its rapid displacement from edematous alveoli is difficult,
it would seem that alveoli so involved are likewise unable to participate normally
in respiratory excursions. Still another intrinsic factor that inhibits respiratory
excursions of an alveolus is fibrous thickening of its walls. The outstanding extrinsic cause of inhibited respiratory excursions is compression atelectasis, although it must be conceded that in a few instances intrinsic factors may also
have caused atelectasis.
In more than 75 per cent of the cases having appreciable collections of alveolar
macrophages there was interference of some sort with the respiratory excursions
of the alveoli in which the cells were observed. In the other cases of this series,
such interference was neither ruled out nor established.
The daily expectoration of large numbers of alveolar macrophages by apparently healthy persons, particularly in urban communities, suggests that a certain
amount of proliferation and desquamation of alveolar macrophages is a part of
normal pulmonary activity. The fact that these cells are usually scanty or absent
in most normal lung sections could be interpreted to indicate that the rate of
removal or clearance of these cells by way of the bronchial passages is equal to
or greater than their rate of production. Conversely, the clearance is smaller
than the rate of production in those cases in which macrophages are found in
abundance within the alveoli—a condition that may properly be designated as
alveolar stasis.
The following conditions may establish alveolar stasis: normal macrophage
production but diminished clearance; normal clearance but increased macrophage production; and increased macrophage production with diminished
clearance.
In some of the cases in this series there was slight to marked proliferative
activity on the part of macrophages. This was indicated by excessive cellularity
of the alveolar walls. On the other hand, in most of the cases there was little
or no evidence of such proliferation. This fact suggests that in most cases the
presence of alveolar macrophages is due largely to a decrease in the rate of their
removal. The common factor associated with this alveolar stasis is some interference with the respiratory excursions of the alveoli.
As previously indicated, there is a significant hiatus in the textual descrip-
DUST CLEARANCE FROM
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tions of the normal mechanism by which dust is removed from the interior of
the lung, since these descriptions begin with the entrapment of phagocytes and
free dust particles in the bronchiolar mucus. Based on the conclusion that there
is a relationship between macrophage clearance and the respiratory excursions
of an alveolus, the following theory was evolved to explain how particulate matter
is moved from the respiratory membrane to the ciliated epithelium.
As a premise, it may be stated that there is an uninterrupted thin film of
protein-containing fluid covering the respiratory membrane from the alveolus
to the alveolar duct and extending over the ciliated epithelium of the bronchiole
to become continuous with the bronchiolar mucus. According to Drinker 1 there
is continuous seepage of fluid through the wall of alveolar capillaries which is
regulated by a homeostatic mechanism. This seepage provides the interstitial
fluid or pulmonary lymph as well as the film of fluid covering the respiratory
membrane. Normally the fluid film furnishes the water vapor with which alveolar
air is constantly saturated. When the homeostatic mechanism is disturbed the
fluid film may become transformed into alveolar edema fluid.
Because of contracture of the surface during expiration, the film covering the
respiratory membrane becomes increased in depth and is extruded so as to overlap to some extent the steadily moving (through ciliary action) mucinous fluid
covering the more rigid bronchiole. The phagocytes and extracellular dust
particles adherent to this film are thereby brought nearer to the ciliated epithelium. During inspiration the surface area again increases, tending to pull the
film of fluid centrifugally (toward the pleura). This tendency is opposed by the
viscosity of the fluid film. The latter varies in thickness during the respiratory
cycle. Just prior to inspiration the fluid film covering the respiratory membrane
has attained its greatest depth because of maximal contracture of its surface.
At this time it also exhibits a maximal gradient of viscosity. The viscosity is
greatest at the free surface owing to constant evaporation and is least at the
base because of the steady flow of fresh fluid from the alveolar wall. Thus the
luminal portion of the film, containing the adherent phagocytes and extracellular
dust particles, tends to move backward less freely than the subjacent, deeper
portion, which moves back with the expanding respiratory membrane. The net
result is a tendency of entrapped particulate matter to be moved progressively
toward the bronchiole with each respiration, a type of transport reminiscent of
the propulsion that brings flotsam to a beach. In order to complete the analogy
it is only necessary to have the waves deposit the scum and rubbish upon a
moving endless belt which carries it to the top of a high cliff where suitable
means for its disposal exist.
Any appreciable reduction in the excursions of alveolar tissue should, in conformity with this hypothesis, lead to alveolar stasis and adversely affect the dustremoval mechanism in those regions.
SUMMARY AND
CONCLUSIONS
In a series of consecutive autopsies of 87 adult persons, 43 showed appreciable numbers of alveolar macrophages which were unrelated to active in flam-
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mation. In most instances atelectasis was the underlying cause of accumulation
of macrophages. Other causes were alveolar edema, thickened alveolar walls,
proximity to bronchi, vessels, or scars and no demonstrable cause. The common
factor in all instances in which demonstrable causes were recognized was reduction in the excursions of alveolar tissue.
A theory is described which satisfactorily explains the normal mechanism for
dust and cell removal from the alveolus to the bronchiole and takes into account
the demonstrated relationship between alveolar stasis and reduced excursionary
activity of alveolar tissue.
Acknowledgment. The author gratefully acknowledges a suggestion made by Dr. Joseph
Kun, which assisted the author in the formulation of the theory. Thanks are also due to
Dr. Harry Goldblatt and Dr. Thomas J. Moran for helpful criticism.
REFERENCE
1. DEINKEB, C. K.: Pulmonary Edema and Inflammation. Cambridge: Harvard University Press, 1945, 106 pp.