Part 6

The well developed post-mortem muscular rigidity, the lividity of the dependent parts, of the face with its mucous membranes, and often of the trunk, the jaundice variable in extent, the crusts of blood on the nares and mouth, and the splanchnic dilatation are features which prepare for the gross picture presented by the thoracic organs. The increased moisture within the pleural cavities associated with the even, translucent pleural surface, whose dilated lymphatics become more and more prominent towards the hilum, the large succulent lymph glands, and the exudate in the bronchial tree, are all striking, but more characteristic of the gross picture, is the great increase in volume of the lung itself, mottled with brilliant colors. The lung, too, is very wet and on section, after the syrupy, blood-stained fluid escapes from the less definitely consolidated zones, the latter appear, not as the usual granular, firm areas of hepatization, but have more the consistency of a gel, and also its translucence. Characteristic of this disease as these changes may be, the specificity of the fundamental lesion in the respiratory tract, becomes more emphatic after study of its histology (92, 162).

Histological Picture.

No matter what the portion of the lung from which the sections are derived, the fundamental changes found are the same. The subpleural sheets are spread wide apart, now by empty spaces, now by coagulated fluid. The process extends from the surface through the interlobular septa (Fig. XX), and is accentuated where the connective tissue is more prominent around vessels and bronchi. The nature of the infiltrate in the subpleural and interstitial tissues becomes more evident in the alveoli, which likewise are filled. The material varies somewhat in appearance, probably dependent upon its proteid content. Not infrequently the alveoli contain a homogeneous, pink-staining mass, which resembles the colloid of the thyroid gland. Again, it may be simply a coarse granular precipitate (Fig. XXIII), and in still other instances, small sticks and strands form the bulk of the alveolar content (47, 92, 140, 156). This subpleural, interstitial, perivascular, peribronchial, and alveolar edema, which is a term applicable to this collection of fluid, is very prominent, and although its intensity varies in different portions of the lung; and although it may be replaced in some areas by other types of exudate, unquestionably, this is the dominating expression of the inflammatory process in the early stage of the disease.

As might be expected from the gross appearance, the alveoli vary in size. At times slightly collapsed and at other times overdistended, their lumina are still the seat of the inflammatory exudate, although the mechanical change may allow of some variation in the appearance of their walls. As a rule, however, the alveolar wall is prominent and owes its conspicuousness to the tortuous, engorged vessels within. These vessels contain red blood cells almost exclusively, and on account of the partial, occasionally complete, loss of the lining epithelium, the alveolar wall appears as a huge, dilated arteriole (101) separating the lakes of coagulated material in the spaces (Fig. XXIII). There are areas, as indicated above, where the alveolar content may be more definitely arranged in the form of beaded or homogeneous strands of different caliber; the smallest resemble delicate threads. They tend to converge toward the alveolar wall like wheat in a sheaf, and often pass through this wall by way of the so-called pores of Cohn; as soon as the body of the neighboring alveolus is reached, they again present a fan-like expansion into innumerable, fine strands (Fig. XXII). Where the exudate is more fibrinous, the alveolar wall is less likely to be distended, its vessels are not so prominent, and their content of red blood cells is definitely decreased. Still this is not the most extreme type of alveolar exudate met with at this stage. Perhaps, the most striking, although not the most frequent, exudate has a superficial resemblance to a huge, red blood clot, and it may be difficult to make out the alveolar walls separating the masses of well preserved red blood cells that fill the alveolar spaces. These areas are indistinguishable from infarcts and may be associated with thrombotic arteritis in near-by pulmonary vessels (47) (Figs. XXIV and XXV). Among the red blood cells an occasional strand of fibrin, a desquamated alveolar epithelial cell, and rarely a polymorphonuclear leucocyte may be encountered. The alveolar wall itself varies in the definition of its outline. When its vessels are greatly distended, when its alveolar epithelium is gone, and when its content consists largely of red blood cells, it is difficult to distinguish from the exudate which it encloses. However, when it is more compressed or when its epithelial lining cells are still more or less intact, it may be seen as a blue-staining strand under the low power of the microscope, for the well preserved nuclei lend it prominence.

FIG. XVI. AUTOPSY NO. 112. BACTERIA DEVELOP IN THE HYALINE NECROTIC EPITHELIUM OF THE TERMINAL BRONCHIOLES. HERE THEY FORM CIRCUMSCRIBED MASSES THAT SIMULATE NUCLEI. COMPARE FIGURES V, VIII, XV, AND XVII.

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FIG. XVIII. AUTOPSY NO. 155. ILLUSTRATES A MILD FORM OF PULMONARY INTERSTITIAL EMPHYSEMA. ]

FIG. XXII. AUTOPSY NO. 175. AN ALMOST PURE FIBRINOUS EXUDATE. THE ALVEOLAR WALLS ARE SLIGHTLY HYALINIZED AND THEIR EPITHELIUM IS ALMOST ENTIRELY LACKING. ]

There are, of course, variations in the extent of the serum, the fibrin, and the hemorrhage in the exudate of the alveoli, and while these different types may occur as pure forms, often they are associated. In still other areas and varying in prominence, one finds as characteristic an exudate, not only of serum, strands of fibrin, and red blood cells, but also a diffuse dotting of the exudate with bacteria, singly, in pairs, clumps, and chains (92, 164) (Fig. XXI). This type of reaction is uncommon in pulmonary disease. It resembles more closely a streptococcus cellulitis such as is encountered frequently in the subcutaneous tissues, for example, a woody phlegmon, or a sero-hemorrhagic exudate like the avirile response to a rapidly fatal hemolytic streptococcus serositis. A similar reaction has been reproduced experimentally in animals which have been rendered aplastic with benzol previous to pulmonary insufflation, and it is conceivable that the lack of polymorphonuclear response in the inflammatory exudate may be associated with some such general destruction or temporary suspension of leucocytic formation (160).

A more striking picture, however, even than this aplastic alveolar exudate appears in the terminal bronchioles. In many instances, these are conspicuous on account of their size, for they are dilated to form prominent, often irregular, sacs (Fig. XV). The distention of these terminal bronchioles may be so great that the surrounding alveoli are compressed. 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). This same hyalinization of the epithelium, it will be recalled, occurs in the larger bronchi (Fig. V), and there, too, bacteria frequently develop in the dead tissue (Fig. VIII). In the smallest bronchiolar ramifications, acute epithelial necrosis is not infrequently encountered, even when the surrounding lung tissue is relatively normal (Fig. XVI). That the process does not stop with the epithelium, but, as in the larger bronchi, may extend through the entire structure of the bronchioles, is manifest. Even the alveolar walls may be involved and frequently homogeneous pink or red bands, now the phantom of the former viable lung tissue, mark the presence of the old wall of the alveolus (Fig. XVII). Occasionally, some architecture remains in this pink ribbon and then the involvement seems to be primarily in the vessels of the wall. Not all the vessels are involved, and next to a hyaline thrombus in one, there may be fresh blood, usually red blood, in its neighbor. The alveolar epithelium is usually denuded and thus accentuates the intensity of the change.

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. However, in influenza, as after exposure to pulmonary irritating gases, it is the lesion of characterization (158,159). The effects of this change, of course, where it involves the alveolar wall, will vary with the extent of the process; but given an absolutely necrotic wall, as yet unstrengthened by inflammatory reaction, an expected result would be its rupture with respiratory movement. 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. 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).

Interstitial emphysema is very striking at the post-mortem table. The escaped air appears as beads along the interlobular septa, but on account of their size they are always most conspicuous between the lobes and along the vessels toward the hilum (162) (Fig. XVIII). Histologically, a small bubble of escaped air confined to the interlobular septum compresses the surrounding tissue with almost complete atelectasis of many neighboring alveoli (Fig. XIX).

Summary.

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; consequently, the histology of this disease is almost as specific as that of any biological reaction.

(2) LOCALIZATION AND NECROTIZATION OF THE PNEUMONIC PROCESS

In the preceding description, the gross and microscopic anatomical changes in the lung have been discussed minutely. The picture presented persists, even though it becomes less intense, and forms a background upon which later variations may be superimposed. There is no justification for the opinion that the changes described are necessarily the most acute, but it is presumably correct to suppose that an aplastic, inflammatory reaction will terminate fatally more quickly than a cellular reaction (160), and upon this basis the sequential description in this narrative is arranged.

In the group of fatal cases of influenza, now to be discussed, the lesions of the pulmonary parenchyma are characterized by more definite lung consolidation. Thirty-nine examples presenting an average illness of ten days are included in the following description.

Gross Picture.

The external examination of the body includes nothing not described in the previous group.

FIG. XIX. AUTOPSY NO. 123. A SMALL AIR BUBBLE IN THE INTERSTITIAL TISSUE. COMPARE FIGURE XVIII.

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FIG. XX. AUTOPSY NO. 90. THE ACUTE SEROFIBRINOUS EXUDATE INVOLVES NOT ONLY ALVEOLI, BUT ALSO SUBPLEURAL AND INTERLOBULAR BANDS OF CONNECTIVE TISSUE. COMPARE FIGURES XXI, XXII, AND XXIII.

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The fluid of the pleural cavities varies volumetrically as described in the preceding section. It is, however, usually not a clear fluid, but varies from a slightly turbid, blood-stained material to a typical purulent exudate. The cloudiness may be associated with minute flecks of suspended material, but in no instance has this fluid been of the thick inspissated type which formerly would have been designated as empyema. (This is mentioned with the knowledge that the term empyema is being applied now to less viscid, purulent, pleural exudates). The turgidity of the mediastinal tissue also persists, but it is very rare indeed to find anything more than a small amount of clear fluid in the pericardial sac. Only once was there a typical, fibrinous pericarditis with effusion, and this occurred where a most extensive pleural exudate was also present. Where such complications have been described in serous membranes, the bronchial lymph glands, particularly at the hilum of the lung, are more involved and show, not only an increase in size and a red color on cross section, but frequently also focal areas of necrosis at the periphery, which appear as yellow patches and subsequently undergo suppurative disintegration (2, 47).

The lung remains increased in volume and its surface is mottled with vivid colors. Often these are an indication of deeper parenchymatous change. The pale pink zones, through the pleural surface of which distended alveoli are discernible, are still prominent in the upper lobe, around the margins, and on the anterior surface of the lung. The darker purple, slightly elevated, often circumscribed, infarct-like areas (25, 34, 108) may occur anywhere, but are more frequent in the lower lobes. Small, maroon, slightly depressed areas of atelectasis may also involve the borders of the lung, usually the posterior borders; or they may occur between larger and more elevated areas on either lobe. Besides the purple, firm, projecting foci, paler pink or grey nodules of similar consistence may be present and show no structure when viewed through the pleura. The distribution of the different types of change is variable, and, aside from the fact that they involve the middle and lower lobes more frequently than the upper, no general statement is possible. 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). Such pleural exudates are rare, and likewise it is uncommon to find so little pleural granulation as in the previous group. The roughening, as a rule, is not uniform, but is more prominent over the lower lobes and in the interlobar spaces than elsewhere. It may occur when there is no definite increase in the fluid content of the pleural sac.

The lung, now sectioned, presents a surface in accord with the changes suggested from the description of its external appearance. As compared with the first stage the amount of syrupy, blood-stained exudate may be definitely decreased, especially in the upper lobe or in those portions of the lung where the solidification is less marked. Its character, too, may be more cloudy, and more ropy, or viscid; it bathes the surface and is scraped off in abundance with the blade of a knife from the underlying consolidated foci (108, 156). The bronchi and bronchioles, however, may be prominent, irrespective of the change in the parenchyma itself. From their lumina, thick, yellow pus wells forth and their mucous membrane is intensely congested. Where such involvement occurs in unconsolidated portions of the lung, the bronchioles are even more striking than in the hepatized areas in which the more widespread changes obscure the process. The dilatation of the bronchioles, especially in their smaller ramifications, is still conspicuous.

The consolidated areas vary greatly in size and number; often they are small and involve only single lobules, which now stand out as granular, generally elevated patches on the surrounding congested plane. Their color, as on the pleura, varies. They may be dark, almost hemorrhagic, fading through the reds, pinks, and greys. They may be firm, or, at the other extreme, honeycombed by small, often narrow, cavities, from which a material similar to that described on the surface wells forth. The latter change is more frequent if the consolidated area is large. It has occurred most often in the pseudolobar and in the lobar types of the process. The pseudolobar change is differentiated, not only by the confluence of more or less definite lobular patches and by its involvement of portions of contiguous lobes rather than a single lobe, but also by variations in the color and consistence of the different lobular foci. This is in contrast with lobar involvement where the entire lobe is affected by a uniform process usually at the same stage of development. Although the consistence may vary in different portions, usually the same color is present throughout. (Compare Figs. XIV and XXVIII.) In one instance where a solid, yellow lobe was found, its center contained an irregular, fresh blood clot (Fig. XVIII), which would be sufficient to differentiate this type of consolidation from that of respiratory disease in which the initial lesion is less destructive. Sometimes the softening in a hepatized lobule or group of lobules is much more evident, and the zone becomes divided by irregular channels filled with viscid, grey or brown material (108, 149, 162). When such a condition lies just beneath the pleural surface, it may be distinctly seen from without (Fig. XXXIII). The pleura bulges, the normal topography of the local zone is lost, and it appears as a dull, somewhat projecting, circumscribed patch, two or three or more centimeters in diameter, the surface of which has a more or less characteristic brown or brownish black opacity. As soon as this is sectioned there pours from the cavity the liquefied exudate in which the destroyed pulmonary parenchyma is mixed (Fig. XXXIV). Occasionally, strands of tissue still traverse the cavity, but, as a rule, it empties itself completely, and leaves a brownish black wall. The delicate, sweet but persistent and penetrating odor is not so marked as with typical gangrene.

Histological Picture.