Part 28

═══════╤════════════╤════════════╤════════════╤══════════ AUTOPSY│ TYPE OF │ PLEURA. │ ABSCESS OF │ DAY OF NUMBER.│ LESION. │ │ LUNG. │ DISEASE. ───────┼────────────┼──────┬─────┼────────────┼────────── │ │ │ │ │ │ │ │ │ │ │ │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── │ │RIGHT.│LEFT.│ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 741│Lobar S. & │S.F. │S.F. │ │ 3d. │ H. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 743│Lobar S. & │F. │S.F. │ │ 5th │ H. Early │ │ │ │ │ P. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 744│Lobar S. & │S.F. │S.F. │ │ 7th │ H. │ │ │ │ │ │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 745│B.P. with │S.F. │– │ + │ 10th │ Necrosis. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 746│Lobar S. & │– │– │ │ 5th │ H. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 747│Lobar S. & │S.F. │– │ │ 6th │ H. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 748│Lobar S. & │– │– │ │ 4th │ H. and │ │ │ │ │ B.P. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 749│Lobar S. & │F. │– │ │ 4th │ H. Slight │ │ │ │ │ P. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 750│Lobar and │F. │F. │ │ 9th │ Lobular. │ │ │ │ │ Early P. │ │ │ │ │ │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 751│B.P. slight.│S.F. │– │ │ 7th │ │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 752│B.P. and │F. │S.F. │ │ 13th │ Lobar P. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 756│Lobar and │F. │S.F. │ │ 8th │ Lobular S.│ │ │ │ │ & H. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 757│Lobar S. & │F. │F. │ │ 6th │ H. and │ │ │ │ │ Purulent. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 758│Lobar │F. │F. │ │ 14th │ Purulent. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 761│Lobular S. &│– │– │ │ 7th │ H. │ │ │ │ │ │ │ │ │ │ │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 762│Lobar S. & │S.F. │S.F. │ │ 10th │ H. and │ │ │ │ │ Lobular P.│ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 763│B.P. │F.P. │– │ │ 11th │ │ │ │ │ │ │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 764│B.P. │– │– │ │ 9th │ │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 765│Lobar S. & │– │– │ │ 9th │ H. and │ │ │ │ │ Early P. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 767│Lobar S. & │– │F. │ │ 10th │ H. Lobular│ │ │ │ │ P. │ │ │ │ │ │ │ │ │ │ │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 770│Lobar S. & │S.F. │F. │ + │ 11th │ H. Lobular│ │ │ │ │ P. │ │ │ │ │ │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 773│Lobar S. & │F. │F. │ │ 20th │ H. Lobular│ │ │ │recurrence │ P. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 778│Interstitial│S.F. │S.F. │ │ 23d │ Pneumonia.│ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 781│Lobar S. & │S.F. │S.F. │ + │ 5th │ H. │ │ │ │ │ Purulent. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 782│Lobar S. & │F. │F. │ │ 8th │ H. and │ │ │ │ │ Early P. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 783│Lobar S. & │S.F. │S.F. │ │ 8th │ H. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 784│Lobar S. & │S.F. │S.F. │ │ 8th │ H. and │ │ │ │ │ Purulent. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 786│Lobar S. & │S.F. │– │ │ 4th │ H. and │ │ │ │ │ Early P. │ │ │ │ │ │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 787│Lobar S. & │S.F. │S.F. │ │ 8th │ H. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 791│Lobar S. & │F. │S.F. │ │ 6th │ H. and │ │ │ │ │ Slight P. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 792│Lobar and │S.F. │S.F. │ │ 6th │ Lobular S.│ │ │ │ │ & H. │ │ │ │ ───────┼────────────┼──────┼─────┼────────────┼────────── 793│Slight │– │F. │ Strep. │ 10th │ Lobular │ │ │Bacteriemia.│ │ Purulent. │ │ │ │ ───────┴────────────┴──────┴─────┴────────────┴──────────

S—Serous. H—Hemorrhagic. P—Purulent. B.P.—Broncho-pneumonia. S.F.—Serofibrinous. F.—Fibrinous. F.P.—Fibrinopurulent.

It was very evident that the smaller bronchi and bronchioles were much more readily involved in a severe inflammatory reaction than the larger tubes. A purulent inflammation was not uncommonly found in the bronchioles of the lung when a pneumonic state with leucocytic infiltration was present. Even where such purulent infiltration of the walls of the bronchioles was readily demonstrable the trachea and main bronchi were devoid of this intense reaction. These purulent inflammations were not uniformly distributed in the bronchioles of the lung, but only occurred in those regions where the parenchymatous tissues were in themselves involved in a purulent reaction. It was difficult to find the evidence whether the purulent bronchitis preceded or followed the presence of a purulent pneumonia. The intimacy of the lung tissues with those of the small bronchioles makes it impossible for one or other of these structures to escape when one of them is implicated in a purulent reaction. It is equally important to appreciate that to a considerable extent the lung tissue surrounding the small bronchioles becomes involved by a direct radial extension through the walls of the thin respiratory tubes. Such extension laterally is assisted by the free lymphatic communication lying about the bronchioles and stretching into the lung parenchyma. Purulent processes of the small air tubes always showed a similar reaction in the interstitial tissues of the neighboring air sacs.

Our material did not permit of following the bronchial reactions to their conclusion. In some instances we have found that where abscesses developed within the lung the contiguous bronchi and bronchioles either became eroded or suffered intense suppurative inflammatory lesions on their inner surface. The manner in which repair of the more common inflammatory processes of the bronchi is accomplished could not be demonstrated in the cases dying during the acute stage. In one case an organizing bronchitis was associated with an organizing lobular pneumonia. In this instance the connective tissues were proliferating freely from the inner wall of the bronchi, there being no evidence of a basement membrane at the point where the connective tissue was growing. The development of the connective tissue appeared to be spontaneous and was not taking place within an unresolved fibrinous exudate. In as much as the fibrosing process was largely scattered through all of the lobes, the numerical involvement of the respiratory tubes was quite great. In this instance the amount of obstruction which was imposed upon the respiratory tissues by the fibrosing pneumonia and bronchitis was sufficient to cause considerable distress and dyspnœa during the last few days of the patient’s life. The amount of dyspnœa was out of proportion to the clinical manifestations of pulmonary involvement, and from a clinical point of view it was difficult to arrive at a conclusion of the nature of the lung lesion.

Undoubtedly during the subsidence of the inflammatory process within the bronchi the gradual restitution of the tissues with little or no fibrosis is accompanied by a reproduction of the lining membrane arising from the epithelial remnants in the small mucous crypts. In a few cases lately coming to autopsy where the patients had suffered an influenza five or six weeks previously, the mucosa of the trachea and bronchi had assumed its normal appearance and was fully clothed by a normal epithelial covering.

_Lung—Early Stage_

We have just discussed the importance of the inflammation of the trachea and bronchi in the cases of influenza. It is our belief that every case of influenza has some tracheitis, and a great many have both tracheitis and bronchitis. This is true in the absence of localizing signs and symptoms, as was evident even in these cases in which the simple influenza passed into its more severe type with its pulmonary lesions. In many of these instances clinical evidences of an inflammatory reaction in the respiratory tubes were wanting, while the reactions observed at autopsy were often astounding.

Just as we feel that simple influenza and inflammation of the respiratory tubes go hand in hand, or better that these respiratory localizations are the all-important ones in every case of simple influenza, so, too, we are of the belief that the pulmonary lesions bear the same relation to all cases of severe and fatal epidemic influenza. We hold that no case comes to his death through acute epidemic influenza without having a lesion in the lung. The pulmonary condition, therefore, is of first importance and its analysis is imperative for a proper understanding of this disease. There has been divided opinion as to the part played by the pulmonary lesion in epidemic influenza, some holding that it is to be looked upon as a part of the disease and others that it must be viewed as a complicating lesion. Complications of various kinds are very common, and there are a number of conditions arising in the lung (abscess, gangrene, necrosis) which must be viewed as complications. There is, however, a type of pneumonia, and here I use the term in its broad sense, which is not in truth a complication but merely a wider extent of involvement of the respiratory tract by the same virus which is always present to cause lesions in the respiratory tubes. The reaction within the lungs is distinctive and differs from the pneumonias which are met with under other conditions and with various bacterial agencies. Nor are our findings in this matter unique for this epidemic. They have been described and discussed in the past. True it is that, like in the epidemic which has just passed us, the incidence of clinical and pathological pneumonia varied quite widely in different communities, so, too, the reports of past epidemics do not give a uniform description of a pulmonary lesion. Where, however, the analysis has been made during the four weeks’ period of the acute epidemic and where the descriptions have been recorded by painstaking observers, the similarity with our present findings is very striking. I would refer in particular to one report made in 1893 in Petrograd by Kuskow. His report deals with 40 carefully studied cases in which records both macroscopic and microscopic were accurately made.

One of the great difficulties in placing an accurate interpretation upon the pulmonary findings lies in the fact that true pneumonia as seen in epidemic influenza in man has not been reproduced in animals. Furthermore, as the majority of the fatal human cases of epidemic influenza with their associated pneumonias present a mixed infection of the lung tissues, it is difficult, if not impossible, to indicate the lesions which have resulted through the activity of one of these as against those induced by the other bacteria present. In our own carefully studied cases wherein bacteriological cultures were taken from every lung there was not a single instance in which the influenza bacillus was present in pure culture. This is more fully commented upon in the studies by Dr. Holman, but the point we wish to make here is the difficulty in arriving at a conclusion in our material as to the actual effects induced by any one type of organism. As it is fully discussed by Dr. Holman we are convinced of the importance of the influenza bacillus in this epidemic. We also appreciate that pneumonia lesions in animals have been induced by a variety of materials gained from influenza patients, but yet in view of the abnormal manner of producing such lesions these are hardly comparable to those in man. We may well expect severe œdema, inflammation and hemorrhage, if in guinea pigs, rabbits and monkeys we introduce by intra-tracheal insufflation large quantities of fluid suspensions of bacteria. And thus we find positive results obtained by the use of a filtrable virus, streptococci, influenza bacilli and other organisms. The lung is a sensitive tissue which quite readily responds to a variety of irritants. In many respects some of these lesions simulate those in influenza, but still we are far from the conclusion that the disease, influenza, with all its manifestations has been actually reproduced.

The pathology of the pulmonary lesions in acute epidemic influenza is so distinctive that except for the late purulent stage which may resemble types of reinfected and unresolved pneumonia the condition cannot be confused with the stages of frank lobar pneumonia. We appreciate that this is a very positive statement, and that opposition will be taken by those who resting their opinion upon individual factors may claim that a clear distinction from other forms of pneumonia is not available. We, however, base our opinion not upon a single feature, but upon the combined pathological complex observed in many individual cases. These features are mainly those seen in the type of the lesion, the character of the distribution, extent of involvement and the multiple stages so commonly present at one time in different portions of the lung. The type lesion that has become so well known in pneumococcus lobar pneumonia has its distinctive stages which for teaching purposes are divided into the stage of (1) congestion, (2) red hepatization, (3) gray hepatization and (4) resolution. In dealing with lobar pneumonia from the standpoint of illustrating these stages the majority of teachers annually confess their inability to present for the student’s study the stage of congestion. The student is impressed that the congestive stage of lobar pneumonia is very transient and rapidly passes into the stage of red hepatization. Patients do not die with pneumococcus pneumonia in the stage of congestion. And this is also largely true of the stage of red hepatization, which is but rarely seen at the autopsy table. This community (Pittsburgh) gives its large quota to the mortality statistics of pneumococcus pneumonia, but it is most unusual to meet with a specimen of red hepatization except for the borders of the advancing gray area. And, furthermore, red hepatization even when found in the unusual cases shows remarkably little of this character when seen under the microscope. True it is that a certain number of red blood cells will be found in the alveoli and a certain degree of congestion will occupy the alveolar walls, but its extent is far less than what we may have hoped to demonstrate to others. So that broadly speaking the intensely congested lung with or without red hepatization is unusual in our frank lobar pneumonia. This was quite the reverse in our cases of acute epidemic influenza-pneumonia. Furthermore lobar pneumonia in the great majority of instances illustrates a distribution distinctive for the name. Massive lobar, or pneumococcus pneumonia is found to occupy one or more lobes or parts of lobes. The involved lobe is fairly uniform in the stage of the inflammatory process. If it is in the early gray stage, this will be seen with equal intensity in the different areas of the lobe. Patches of pneumonia in different stages within the same lobe are not to be found, while this finding is not uncommon in the pneumonias of acute epidemic influenza. And lastly, the frequency with which an inflammatory œdema occupied the lungs in the cases of influenza was in quite striking contrast with the dry fibrinous lesion of common pneumonia. This wet state of the lung was but a stage in the inflammatory process varying in its extent in the different periods, but nevertheless inducing a character in the early pulmonary lesions which was quite foreign to our usual finding. This wet state also assisted in modifying the subsequent picture so that when the lung assumed its gray appearance it was rather of a slimy character than of the firm dry nature. In this late gray stage the slimy lung somewhat resembled the appearance of unresolved pneumonia where this condition had been brought about by a new infection upon the original cause of the pneumonia.

It is incorrect in influenza pneumonia to speak of the lesions as lobar pneumonia or broncho-pneumonia if by these terms we have in mind the pathological characters observed in the pneumococcic pneumonia with its lobar or bronchial distribution. Influenza-pneumonia appeared with both lobar and lobular characteristics. Nearly every case had both types of lesions present, but the nature of the inflammatory process is so decidedly different from that of the ordinary endemic pneumonia that a confusion in the interpretation is likely to arise and in fact has already raised a considerable polemic. Influenza-pneumonia is commonly lobar, lobular or bronchial in distribution. It is, however, not of the characters that are associated with the lesions designated under these terms. When, therefore, we here use the word “lobar” we mean lobar _in distribution_ but not lobar in type. As will be seen from our table, it was usual to have multiple lobes involved. But the lesions, not only in the different lobes varied in their character and distribution, but even within the same lobe a variety of types was present.

TABLE VII

═══════════════════════════════════════════════╤═══════════════════════ Day of Pneumonia on Which Death Occurred │ No. of Cases ───────────────────────────────────────────────┼─────────────────────── Second │ 2 Third │ 4 Fourth │ 7 Fifth │ 6 Sixth │ 7 Seventh │ 3 Eighth │ 1 Tenth │ 1 Twentieth │ 1 ───────────────────────────────────────────────┴───────────────────────

To a certain degree we were able to analyze the types of the lesions as they occurred in the different stages and progress of the pulmonary inflammation. Briefly, these were as follows: the earliest stage of congestion following rapidly upon the infection from the bronchi was followed by (1) inflammatory œdema, (2) hemorrhage, (3) cellular exudate (a. mononuclear cells, b. leucocytes, c. interstitial infiltration) and (4) resolution or organization, abscess, infarct and gangrene. The majority of our cases died during the stages of congestion, hemorrhage or early purulent infiltration. In the early stages the amount of fibrin was small or entirely absent, later, with the appearance of leucocytes, some fibrin was present.