Part 30

It is during this early phase of the reaction that the influenza bacilli can be shown within the lung structures. The distribution of bacteria is not uniform. Clusters of these minute bacilli are found in the alveoli at irregular intervals, many of the air sacs containing much exudate being quite free from organisms. When present the bacteria appeared in tightly aggregated schools lying free amongst cells of the exudate, but also certain numbers being incorporated within the large mononuclear cells. In some regions organisms of the type of the influenza bacilli were alone seen, while elsewhere again, and particularly where the exudate was assuming purulent characters other bacteria of the nature of streptococci, staphylococci and micrococcus catarrhalis, were also found.

_Lung—Secondary Stage_

Following upon the primary reaction in the lung as above described, a secondary reaction makes its appearance at variable periods. This reaction is one in which the inflammatory exudate resembles more closely but is not identical with the responses which are observed in ordinary lobar, lobular and pneumococcus-pneumonia. Whereas in the earlier period, the reaction is largely one of a serous and hemorrhagic exudate accompanied by peculiar hyaline deposits along the inner borders of the alveoli, later there is seen a change in the quality of the exudate with the accumulation of more cellular elements and some fibrin. The naked eye appearance of the involved tissue changes considerably. The lung tissue loses in weight but becomes more solid. The lung contains less fluid and the cut surfaces are drier and the color of the reaction changes from the dark congested appearance to one showing all varieties of red and gray. This change from the flabby and soggy pneumonia to the more definite type of consolidation occurs in the regions which have been previously involved and is not to be found in the lung areas which have escaped the early reaction. The gray consolidation appears to be either a stage of the influenza-pneumonia or is a new reaction superadded to those pulmonary lesions induced by the primary infection.

It is sometimes difficult to recognize the beginning of this pneumonic stage inasmuch as the gray color does not make its appearance even with the presence of fairly large quantities of cellular exudate. The amount of hemorrhage that originally lay in the affected areas for a long time overshadows the presence of the color of the cellular exudate. This is also true of the characters that may be impressed by the presence of fibrin. Small quantities of fibrin scattered through the congested and œdematous lung are not readily recognized and the beginning of this secondary reaction is also easily overlooked if one relies upon evidence of consolidation. More or less solid exudate may occupy a flabby lung without permitting one to appreciate its presence in the gross specimen. When, however, the deposit is of sufficient quantity to change the color of the involved lobe and to alter its consistency, one has little difficulty in recognizing the changes now taking place. The earliest development of this change in the inflammatory reaction was on the fourth day. In the majority of instances the gray color and the consolidation made its appearance about the sixth day. We have, however, on several occasions observed hemorrhagic lesions as late as the seventh and eighth day, at which time it was impossible to recognize a gray hue to the exudate or the character of granular consolidation to the involved lung.

The reaction naturally suggests the stage of gray hepatization as we so well appreciate it in ordinary pneumococcus-pneumonia and from the standpoint of its color and the greater solidification of the lung tissue we might speak of it as such. Here, however, it must be clearly distinguished from the gray hepatization of ordinary pneumonia. This secondary lesion of influenza-pneumonia has but little in common other than its color and the development of a consolidation with true lobar pneumonia. It is never as clear cut as we see it in the latter and the degree of the “gray hepatization” is not uniformly distributed through the involved lobe. One portion of the lobe will show a diffuse gray hue while in other parts more decided lobular or patchy areas are picked out in the advanced reaction. There is not the uniformity of lobar involvement nor is the distribution as regular as one obtains it in broncho-pneumonia. Furthermore, the character of the consolidation differs very decidedly in showing such a variety of hues in reds and grays and the cut surface is not the picture of the dry granular consolidation of our endemic disease. The gray areas are in all states of wetness and ooze a slimy fluid on the cut surface. In the later stages this exudate is most profuse resembling a sticky pus. In its appearance we were reminded of the character seen in unresolved pneumonia as well as in the pneumonias produced by the pneumococcus mucosus, and the B. mucosus capsulatus. We would, therefore, avoid the use of the term gray hepatization and in place of it, as the evidence with the microscope confirms, use the term _purulent pneumonia_.

There are three other characters which differentiate this gray stage from those of ordinary pneumonias—(1) the irregular distribution, (2) the friability of the involved tissue and (3) the interstitial reaction. We have never observed such an irregularity in the distribution of a gray stage of pneumonia as we have seen it develop in acute influenza-pneumonia. All types of involvement of the lobes are found in different cases and even sometimes in the same case. The least frequent type has been the broncho-pneumonia in its true form. Broncho-pneumonia as we see it in children and the cases following measles is usually fairly uniformly seeded through several lobes and the size of the individual patches is about that of a split pea. The small bronchus can be recognized about the center of the involvement. In those instances one has studded through the lung tissue numerous small swollen areas which are granular, dry and gray. Differing from this the patchy distribution of the gray stage of influenza-pneumonia had no regularity either in the size of the areas nor the distribution. A lobe may show one or more patches. The patches may be distributed toward one portion of the lobe more than another. Furthermore the areas do not always encircle the small bronchi but involve the terminal portion so that an entire lobule is more commonly affected. The lobular type rather than the peribronchial type is most commonly seen and it is often remarkable how sharply the gray lobule is demarcated from the surrounding congested lung tissue. On several occasions we observed a single lobule in the gray stage while the remaining portion of the lobe was in the serous and hemorrhagic condition. However, multiple lobules are commonly seen closely associated in the advancing inflammatory process. Such lobules show peculiar geographical patches or leaflet-like configuration. Varying with the number of lobules involved the extent of the gray change in the lobes assumed more or less a lobar distribution. There was no uniform position to this pneumonic state sometimes appearing in the peripheral tissues of the lung, at other times lying centrally with less involved or less advanced inflammatory reactions surrounding it. Nevertheless, the gray stage made its appearance more rapidly in the lower lobe than the upper and it was not uncommon to find this condition appearing quite early in the upper posterior portion of the lower lobes. This latter position is the one which is recognized during life by the clinician as one of the earliest localizations of the demonstrable pneumonia. It is reported by many that the first physical signs of consolidation are to be obtained close to the lower angles of the scapulae.

There is no doubt that the character of the pneumonic process in the epidemic influenza was not the same in all localities. There have been not a few who have reported a large proportion of their pulmonary lesions as a definite broncho-pneumonia with an interstitial purulent involvement. The prominent reaction was a small circumscribed yellow focus about the bronchioles from which a bead of pus could be expressed. These pea-sized foci were scattered through several or all lobes. It is this type of reaction which appears to develop by a direct extension through the bronchial walls and to remain quite localized in the alveoli about these tubes. This reaction seems to be purulent from its very beginning and does not pass through the stages as we have described them above. There is more or less fibrin present in the exudate, but usually not in the quantity observed in lobar pneumonia. These lesions closely resemble those observed in the post-measles pneumonia, and it is claimed are the result of the same agent; the hemolytic streptococcus. In only one case did we observe a lesion of this kind. The small areas of broncho-pneumonia were confined to the left lower lobe and in the lower portion of the upper lobe. Each area was about the size of a split pea, was quite yellow and in fairly sharp contrast to the background of an acute sero-hemorrhagic pneumonia. The subsequent history of these interstitial purulent broncho-pneumonias is like that in measles, where the tendency toward an organizing pneumonia has been shown. The importance of the hemolytic streptococcus in inducing purulent interstitial lesions of the lung (and also of other organs) cannot be over-impressed. It is not so much the type of the reaction during its acute stage which attracts our attention, but the manner of the healing process. It is more than probable that the organizing pneumonias of influenza, not only of this distinct bronchial type, but also the lobular, confluent and lobar variety have had an associated streptococcus infection. The more intimate discussion of this type of pneumonia has been given by MacCallum.

Our autopsy experience has led us to believe that the definite clinical signs of pneumonia are associated with the development of this gray consolidation of the lung. The lung tissue develops characters which permit the physical signs to be recognized. The tissue is more solid and more readily transmits the bronchial sounds. This is not true of the earlier stages where the inflammatory process is contained within a lung tissue which still is partially crepitant and when the so-called consolidation is due to an inflammatory œdema and not to the more solid fibrinous and cellular exudate. With the protean distribution of the gray lesion one does not wonder at the clinical difficulties in mapping out or even finding the consolidated tissues.

As soon as the lobes show this gray character and with the progressive development of an acute interstitial purulent pneumonia, the lung tissue becomes friable. All gradations of flabbiness may still be obtained and in the early stages while the cellular exudate is accumulating to change the color of the lung, little variation from the tough character of the pulmonary tissues can be recognized. When, however, a true gray character is assumed by a portion of the lobe, the tissue becomes so soft that it is handled with difficulty without rupture. The thumb can be pressed into the gray mass and pus will well up around the invading phalanx. The consistency in the late stages reminds one of the pulpy tissues in acute splenitis. In cutting such lobes it is almost impossible to obtain slices of the tissues, their own weight often breaking such a segment. When allowed to rest on the table for a few moments, the cut surface becomes coated with a dirty yellow slime representing pus and products of disintegration arising from the lung. The stroma and alveolar tissues are themselves involved in the inflammatory process and many of them have suffered complete or partial destruction so that they offer but little resistance to pressure and serve as a poor supporting stroma to the pulmonary tissues. The reaction which has taken place within the lung producing both the gray color and the destruction of the tissues is, indeed, an active suppurative one. One would not be surprised to obtain not only a purulent lesion wherein the cellular exudate occupies the air sacs and their walls but also a further stage leading to a destruction of the tissues to the extent that abscess cavities are produced. These we have met with in several instances, some of them being small while others were several centimeters in diameter. An abscess of larger extent and having a destructive process which involved the surrounding tissues so that one would speak of it as a process of gangrene, was observed by Dr. McMeans in one of his cases. A lobar distribution of the purulent lesion takes place where multiple involved lobules have fused in their periphery or where a suppurative flooding of the tissues in this violent late reaction has taken place.

The question at once comes to mind whether this gray stage is but the late event of what we have previously spoken of as influenza-pneumonia or whether this condition is superadded to what may begin as an influenza-pneumonia but end in a pulmonary inflammation with a mixed infection. Dr. Holman was not able to demonstrate a sufficient difference in the bacteriology of the lobes in the gray stages from those in the early acute stage to be able to say that the flora changes at a certain time during the progress of the disease in the individuals. It is possible, and there is some evidence in support of this, that the earlier stages of the pneumonic process represent the reaction to the influenza bacillus and that during this period the response is fairly uniform and similar owing to the fact that this infection has but a short incubation period and a high pathogenicity. In such an event the particular micro-organism may bring about a peculiar response of its own before the other organisms with which it is associated have the opportunity of producing damage. Subsequently, however, these secondary organisms impose their peculiar reactions upon an altered lung, thus inducing an inflammatory lesion which differs from the preceding reaction and also differs from the reaction usually induced by those organisms upon relatively healthy tissues. It is difficult to account for the very irregular distribution of the gray lesions by an explanation concerning the influenza bacillus alone, or by the characters peculiar to the secondary infection. There is an entire want of character to these gray lesions which makes them differ from other types of pneumonia known to us.

It is well to lay particular stress upon this peculiarity in the distribution and extent of the lesions within the lobes; and it is also important to appreciate the difference in the appearance of these gray areas from those of true lobar or broncho-pneumonia.

Finally there is another point in which this stage of the pneumonic process differs from that of pneumococcus lobar pneumonia. In frank lobar pneumonia the reactions taking place in the involved portion of the lung are fairly uniform in all its parts. The stage of red hepatization occupies about that amount of lung which subsequently shows itself in the state of gray hepatization. In other words, all of those areas which appear gray are preceded by this peculiar red consolidation, and all of the area occupied by the red hepatization will pass through the phases of gray hepatization before entering upon the final stage of resolution.

In influenza-pneumonia, on the other hand, the events taking place in a given lobe are not uniform and various stages and grades of the inflammatory reaction may be recognized at the same time, some appearing red, some congested, some flooded with blood in hemorrhage and others showing the purulent infiltration by the appearance of gray patches upon the background of red. Not only do the various reactions within the same lobe fail to show similar grades of intensity and similar stages or time of involvement, but we find that all of the red and hemorrhagic areas are not destined to pass through the gray stages. At times it is true an entire lung will enter into the purulent phase and if this becomes extreme abscess and gangrene are almost certain to develop. But often the purulent infiltration occupies only a few or scattered lobules and resolution may take place in a lung where the greater part of the lobes is occupied by the inflammatory œdema and hemorrhage and has never become truly consolidated by cellular and fibrinous exudate. This feature that the involved lung tissues need not pass through the sequence of events which is usually observed in frank lobar pneumonia is so distinctive that it differentiates the character of the inflammatory reaction very clearly. It may be that this is an indication of the unequal distribution of the micro-organism and that the first infection presumably by the _bacillus influenzæ_ has been much more diffuse and of wider extent than the secondary invading bacteria which being distributed through the bronchial tree are more or less localized to those lobules most severely involved. It is impossible to claim for influenza-pneumonia as clear and sharp-cut stages as we obtain them in the pneumococcus lobar pneumonia.

During the period of the intense purulent reaction in certain portions of the lung, the intrinsic structures within the area also partake in the damage and response. The suppurative infiltration not only occupies the alveolar walls but also extends through the tissues of the bronchioles, the arteries and the veins. The polymorphonuclear leucocytes seem to migrate into all of the parenchyma indicating some damage by bacterial invasion. On more than one occasion have we observed partial or incomplete thrombosis of arterioles and capillaries whose walls showed an acute suppurative reaction. Some of these thromboses are of importance, being associated with the interference with a blood supply not compensated by adequate anastomosis. Necrosis and small areas of gangrene and abscess are to be found in the region of the circulatory disturbances. It is also during this period of the disease when the bronchi and their ramifications contain pus or muco-pus, that the exudate from the alveoli readily finds its way into the air passages and becoming mixed with the mucus from these tracts forms a tenacious discharge.

The presence of large amounts of exudate within the bronchi brought these structures into unusual prominence. This was particularly true in the purulent stage of the reaction when beads of sticky pus would well up from the cut bronchioles. We were tempted on a number of occasions to speak of this in terms of bronchiectasis but with the intense inflammatory reaction occupying the bronchial wall and modifying its contour on this account we avoided this diagnosis. In one instance, however, the lesion was unmistakable. This was a case of purulent pneumonia (764) dying on the ninth day of the disease. The distribution of his pulmonary lesions was distinctly lobular, apparently following the course of the bronchial distribution. The bronchi were followed longitudinally and irregular pouchings of the lumen were very apparent. The bronchi had suffered marked inflammatory reaction which had also infiltrated the muscular tissues of the tubes. Goodpasture and Burnett report finding two cases of acute bronchiectasis associated with abscess and ulceration of the bronchi. In our case the bronchiectasis was found bilateral but was more marked in the lower lobes than the upper.

The lymphatic channels within the lung tissue are found active in establishing an internal drainage to the neighboring thoracic glands. The lymph vessels were often found filled with leucocytes and variable amounts of serum. During this late stage only a few of the endothelial leucocytes were observed wandering to or from the lung with a load of pigment or cell debris. These wandering endothelial cells, however, appeared to become loosened from their normal situations and in the vicinity of lymphatic nodes or communicating channels where these cells are prone to localize with their carbon pigment, again assumed their spherical form and took on migratory properties entering into the nearby tissues and scattering themselves in the looser structures. It is an interesting point to note that these pigment carrying cells, ordinarily assuming a latent existence when their cytoplasm has been crowded with foreign particles will assume all the activities of migrating cells when the œdema of the tissues alters the physical properties not conducive to a stationary existence. These cells will then be found to enter the lung alveoli, often appearing as cells which have only recently picked up their carbon load. When, however, the conditions of the experiment, that is, the production of an inflammatory œdema in the lung, are produced in the tissues of an individual with much anthracosis, he will, during the period of his pneumonia and for some time during convalescence, bring up a greater number of these cells in his sputum than are ever obtained during the times when the lung is not involved. We are convinced that inflammatory conditions of the lung tend to reduce the total number of latent pigment bearing cells present in the involved tissues, and in this way somewhat reduce the grade of anthracosis.