Frank P. McNamara

“ The blood vessels of the lymph gland, greatly congested, contain almost exclusively red blood cells. As a rule, the lymph follicles and the lymph cords take little part in the process. If there is any change in these structures, it is a rarefication. Occasionally, hemorrhage is encountered in a follicle or even in a cord, and this hemorrhage may involve not only the cells of the cord, but its supporting reticular structure, and may form the nucleus of a subsequent necrotizing or suppurative focus. ”

“ Microscopic examination of sections from the lung showed an extensive bronchopneumonia. The alveoli of an occasional group of lobules were filled with serum or red blood cells, while still other areas showed foci of necrotizing pneumonia, actual miliary abscesses in which there were large clumps of bacteria (Fig. XLI) . Throughout the sections, however, the striking change was an organization of the exudate, which varied from a few fibroblasts to a well defined connective tissue almost obliterating the normal architecture (Figs. XLI and XLIV) . ”

“ Furthermore, it must be emphasized that even the mildest and the most extreme of these stages are not infrequently encountered in the same lung. The earliest lesion is manifested by an increased homogeneity of the protoplasm of the epithelial lining of the bronchus. The cell protoplasm loses its normal granulation and the nucleus, somewhat darker than usual, becomes conspicuous on a red base (Fig. V) . In the lumen of such a tube a serous exudate, perhaps mixed with mucus, is encountered, and there is some spreading apart of the surrounding muscular tissue with engorgement of the vessels. ”

“ There is no reason to believe that malignancy might not result from the continuous stimulation of the epithelium to proliferate, in the chronic inflammatory process of the lung in influenza, just as chronic infection in the lung of a mouse results in a much higher percentage of spontaneous neoplasms of the respiratory tract in this species (132) than in those animals where chronic pulmonary inflammatory processes are uncommon. ”

“ They are dependent upon the fact that the pneumonic process has a very striking tendency to undergo organization, a process which involves not only the exudate in the alveoli, but also that within the bronchioles. The organizing process may be present in both these portions of the lung or may be confined to the bronchiole alone, and lead to a progressive interference with the ingress and egress of alveolar air, so that atelectasis and emphysema become permanent, and in turn lead to narrowing of the vascular bed, ultimately producing right-sided cardiac decompensation. ”

“ At this stage, the lung has a translucency on gross examination, which is not the case when the cellular content of the alveoli is increased. This picture is not the one spoken of most commonly as red hepatization; for, although it appears as a relatively red lung in the gross, difficulty is encountered in its histological correlation, for the exudate is composed, not of red cells, but largely of serum and fibrin. The red color may persist even when numerous polymorphonuclear leucocytes and desquamated alveolar wall cells are within the alveoli, the walls of which are markedly engorged. ”

“ Repeated cultures from the mouth before the exposure of the animal to gas have been followed by the recovery of the same organisms, including the pneumococci, the streptococci, the staphylococci, and a gram-negative, hemoglobinophilic, small bacillus from the pneumonic lung. They find their way into the lung after the destruction or incapacitation of the protective mechanism (70) of the upper respiratory tract,—into a lung which has been so damaged by the irritative gas that bacteria innocuous in the normal pharynx now find a favorable medium for their development. ”

“ After removal, the lung retains its shape, but is more flaccid than the consolidated lung of lobar pneumonia. It cuts with very little resistance and immediately a large amount of a syrupy, pink fluid escapes and obscures the entire area. With the fluid scraped away, the variations in the consistency of the lung become visible. The pale areas around the borders and chiefly at the apex in which the air sacs are discernible with the naked eye, sink slightly below the remainder of the surface, and the pleural edge inverts. ”

“ If this comparison be applied to the pulmonary changes in influenza and after the inhalation of poisonous gases, it will be seen that in both processes the initial damage is extensive, as has been indicated in the discussion of necrotization. Where the lesion is superficial, tracheal, bronchial, and alveolar epithelia rapidly regenerate and restore the injured surface. Where, however, the lesions are more extensive, alveolar and bronchiolar exudates are transformed into granulation tissue, even though the epithelium may manifest unusual activity in its attempt to repair a denuded area. ”

“ In the tissues the blood is always fairly well preserved. It may be scattered diffusely through the cellular exudate (Fig. XXIV) or so abundantly that the area resembles an infarct (Fig. XXV) . These hemorrhagic foci, which vary considerably in size, are found not only in the cases that terminate fatally within a few days, but may occur at any time during the acute manifestation of the disease. They are an exaggerated form of red hepatization and it is difficult to see how such red foci could ever change to areas of grey pneumonia. ”

“ Often these leucocytes are multilobed and frequently their protoplasm is granulated with phagocytized bacteria. The bacteria are also encountered free in the alveolus along with other elements; namely, red blood cells, strands of fibrin, or precipitated albumin (Fig. XXI) . The bacteria, however, are not particularly conspicuous, for generally they are either single, in pairs, or in chains; and it is only when they become clumped to form large masses, often larger than any normal tissue cell, that they attract attention. ”

“ In a few instances, one lobe, almost always the lower, may be more voluminous than the others, and although its pleura often suggests lobular involvement, the masses tend to be confluent and suggest a pseudolobar change. Sometimes, though rarely, this approaches a true lobar type of consolidation. (Compare Figs. XIII and XXVII.) Occasionally, the changes in the lung, except its increase in size, are obscured by pleural exudate which may form a thick, buttery, rather sticky mass on the surface (12, 19, 157) (Fig. XXXVII) . ”

“ The acute death which involves the tracheal, bronchial, and bronchiolar epithelium and which may extend beyond the epithelium into the walls of these structures and kill en masse the walls of the alveoli, is a lesion which does not occur in other types of acute pulmonary infection. ”

“ The changes are less marked, perhaps, in the trachea than in its finer ramifications. The mucosa is constantly more or less destroyed and large areas, usually focal, are entirely devoid of their epithelial covering. This is replaced by a sparse exudate, composed largely of red blood cells, mucus, a small amount of fibrin, and nuclear fragments (Fig. II) . It may dip into the submucosa for a short distance, but usually these indentures are associated with the ducts of the mucous glands into which the inflammatory reaction extends. ”

“ So little attention has been paid to earlier stages of the usual types of pneumonia, for example lobar, that it is impossible to say whether or not diffuse involvement of the pulmonary parenchyma initiates the process which later becomes localized in one or more lobes. The initial edema of influenzal pneumonia is the expression of a widespread irritation. If the injury has not extended deeply, the edema may disappear within a relatively short time, and exfoliated lining cells fill the alveoli; those remaining in their normal position are frequently in process of division (Fig. XLVII) . ”

“ The more firm areas stand out, too, on account of their difference in color. The scheme is not unlike that seen on the pleural surface, and while dark, almost black, infarct-like areas occur on the cut surface, the solid areas are more likely to be translucent, dull, light red, brown or even grey. They have a surface similar to a very fresh, tuberculous, gelatinous pneumonia, but the color differs from the cloudy grey of the latter on account of the admixture of blood in the exudate and the great congestion of the vessels (Fig. XIV) . ”

“ The diffuse involvement of all the lung tissue, chiefly with a serous exudate in the subpleural, interstitial, perivascular, and peribronchial tissues, as well as in the alveoli, is associated with other elements which occur in aplastic reactions; red blood cells, fibrin, and bacteria. Added to the aplastic exudate is an acute necrosis of bronchial and alveolar epithelium involving at times the walls of these structures ”

“ The inflammatory reaction which develops into pneumonia, perhaps necrotizing, perhaps later organizing, can only be explained by the combined action of the corrosive gas and the organisms saprophytic in the normal mouth, but now pathogenic in varying degrees in the lung whose vital reactions have either been inhibited or impaired by the gas. ”

“ What makes them even more conspicuous is their lining, once epithelium, but now a swollen, thick, homogeneously staining material, with complete loss of architecture; the material forms (with hematoxylin and eosin) a red band limiting the lung tissue and sharply demarcating it from the exudate within the bronchioles (48, 92) . However, this ribbon of red, often thickened by fibrin deposition, is not always pure, for bacteria thrive in the dead tissue. They occur singly, paired, in chains, and also as circumscribed, dense masses which in size and position, simulate nuclei (162) (Fig. XVI) . ”

“ In the early cases especially, or in cases which terminate fatally at an early period, both lungs are often involved, and, on histological examination, only a small portion of the pulmonary parenchyma is found unaffected. The exudate, largely acellular, presents serum as its most conspicuous feature. The picture is one of a patchy pneumonia with intermediary areas of what might be called edema, although fibrin is often demonstrable in the coagulated, albuminous material. ”

“ In the other group, where there is not only a free ingress to the pulmonary parenchyma by the bacteria of the mouth, but where there is, in all probability, also a simultaneous or preliminary pulmonary damage furnishing a proper medium for relatively innocuous organisms, the lesion of response will surely depend upon other factors as much as upon the infecting organism. ”

“ The point of rupture is important, but where so many alveoli are involved, disturbance of continuity will occur, occasionally in such position that the result will be the escape of air into the interstitial tissues. [7] There is ample evidence that this happens. Indeed, among the clinical manifestations of the disease, interstitial emphysema of the lung spreading through the fascial planes to the subcutaneous tissues of neck and thorax is well known; the phenomenon is more frequent and extensive in influenza than in any other disease (8, 17, 52, 143) . ”

“ Beginning with that portion of the lung the least involved, the lesion may be limited to congestion of the alveolar wall with a serofibrinous exudate in the lumen, but this stage passes rather rapidly into another where cellular exudate, chiefly of polymorphonuclear leucocytes, predominates. Moreover, the leucocytes form not only the bulk of the alveolar content, but also distend the vessels and accumulate in the interstitial tissue around blood vessels and lymphatics. Passing toward the center of the gangrenous cavity, the lung rapidly changes in appearance. ”

“ The alveolar and bronchiolar exudates were everywhere being invaded by a young granulation tissue, rich in fibroblasts and capillaries. Mononuclear cells abounded in the new tissue. Even more striking than the mesodermal new growth was the epithelial proliferation which could be seen in many areas. It not only attempted to cover the denuded bronchial surfaces, but stretched over masses of exudate and granulation in the lumina and extended in tongue-like projections for a considerable distance into the surrounding lung tissue (Fig. XLVIII) . ”

“ Fibrin not only covers the alveolar wall, but crosses this structure and often forms intracapillary plugs. In fact, besides the red blood cells, the serum and the fibrin, one often sees, not only an excess of polymorphonuclear leucocytes in the vessels of the lung, but these appear in process of migration within a few hours after the animal has been exposed.
Animals surviving this stage often succumb later with a typical pneumonic process. Although frequently pseudolobar, the process may be lobar in extent, and as time goes on more definite lobular involvement is frequently encountered. ”