ByJ. W. McMeans
ByJ. W. McMeans
ByJ. W. McMeans
The recent epidemic of influenza has afforded a series of interesting autopsies in view of the very extensive and peculiar involvement that occurred in the lungs of the cases examined. Ordinary lobar pneumonia, as we know it, was not observed, although it must be said that the lungs many times exhibited a consolidation of a lobar distribution. The usual dry granular lung of the more common pneumonia was absent, and in its stead a most unusual series of pictures was observed in the several cases. A common feature of all cases was the œdema of the lung tissue, which in the majority of instances contained such an amount of fluid that it ran freely from the cut surface in almost unlimited quantity. This fluid varied in its color and consistence depending upon the age of the process. In the very early cases the lungs were boggy, very congested, and a thin serosanguinous fluid poured forth from the cut surface. It actually appeared as though the fluid within the tissue was under considerable pressure. At times blotchy deep red hemorrhages occurred in the lung substance, and hemorrhages of a bright red color were not infrequent in the pleura. That the circulation of the lungs was much embarrassed was often prettily demonstrated by the dilatation of the fine capillaries and lymphatics beneath the pleura. These small vessels stood out prominently as a meshwork more or less outlining the areas supplied by them. Not only was the peculiar consolidation in lobar arrangement, but also in many cases was there evidence of a lobular distribution. Even in some cases where the entire lobe was consolidated the cut surface presented a peculiar lobulation with patches of lung tissue projecting above the general surface. The wet trabeculated structure of the lung in this stage did not give the impression of true red hepatization, but rather a structure resembling spleen and at times a meaty, compact, glassy picture not unlike thyroid.
As the process advanced the appearance of the lung changed from deep red to yellowish red and finally to a quite yellowish gray color, still retaining, however, the very moist characters. The fluid found in the lung changed its consistency from the thin red type to a sticky, glairy variety which could be pulled out in long strings. It was noted that the change in the character of the fluid was accompanied by similar changes in the lung structure, advancing in two cases to abscess formation of a grape-bunch type. Here there was a rather extensive necrosis and cavitation of lung substance in communication with the bronchioles. However, there was also marked softening and necrosis of lung in a number of cases where abscesses did not develop, but the lesion was so advanced that the lung substance was almost diffluent. An accompaniment of these advanced cases were irregular yellow islands which appeared beneath the pleura. At times they reached the size of a circle 2 cm. in diameter and were slightly raised above the surrounding pleural surface. When these were opened they were found to be areas of softened lung substance. This reaction was so extensive in some lungs that it resembled to a degree the appearance of a caseous pneumonia. However, the former process appeared to be brought about by the interference with the lymphatic drainage, as it was not uncommon to see engorged yellow channels beneath the pleura as well as enlarged lymph nodes at some distance from the hilus. Another feature of the advanced cases were the plugs of ropy yellow material which were contained within the bronchioles, while in the early cases the bronchi and bronchioles showed intense congestion of the mucosa with blood-stained fluid in their lumina.
Of the more unusual reactions observed in the lungs an infarct was found occupying a considerable part of the lower left lobe in one case. There was a marked softening of the lung tissue with reddish, mucky-looking lung substance arranged about small irregular cavities. This reaction extended into the lung for a distance of 4.5 cm. Bordering close on these softened areas there was a dry mottled yellowish gray and deep red lung tissue. Surrounding this area again were noted a number of small blood vessels in which there were found yellowish granular plugs. One plug in a vessel was found at a distance of 3 cm. from the baseof the lobe, and another was found at a distance of 8 cm. from the apex of the lobe. On further examination it was observed that the base of this softened area was situated on the pleural surface and that the apex was directed inward about a distance of 6 cm. from the pleura. Bathing the cut surface there was a glairy and very sticky material of a reddish yellow color. Near the apex of this softened area in the lung there was found a vessel about the size of a goose-quill in which there was a grayish yellow granular plug. This plug was adherent to the vessel. Within the small bronchioles there were plugs of a soft yellowish brown material. The striking feature in addition to the softening of the lung in a number of places was the glairy material of a sticky nature which bathed the cut surface. A white infarct was present in the spleen. The lung described above as well as another showed gangrenous change. In the second of these two abscesses had formed, and there was a communication between the lung and pleural cavity in which there was a large amount of sanguino-purulent fluid and a pyopneumothorax.
In a description of these reactions it must be added that the early and late changes were not always observed independently, but in most cases occurred together, giving the lung a peculiar mottled red and yellow glassy appearance. More frequently the congested œdematous reaction was observed singly, while the purulent alteration usually was in combination with the former type. The acute serous pneumonia was noted 13 times, 6 times in combination with the purulent reaction and 7 times alone, while the acute purulent pneumonia was found in 9 cases, 3 times alone and 6 times with an acute serous process. In all but 3 of 18 cases there was evidence of a bronchial distribution. Two of these three cases showed a massive œdematous lung with in one case an extensive hemorrhage, while the third presented an advanced purulent reaction with marked necrosis and softening. An acute bronchitis which varied in character from a hemorrhagic to a purulent one was present in all the cases. The reaction observed within the bronchi in the individual cases corresponded closely to the picture found in the lungs.
In all cases except one there was an exudate in one or both pleural cavities. A serofibrinous pleurisy was noted in 11 cases with, in 2 of this number, a fibrino-purulent reaction presentin the opposite pleural cavity, while fibrino-purulent pleurisy occurred alone in 6. In 6 cases pleurisy occurred on one side only with the incidence equally divided in each cavity. Both pleurae were involved in 9 cases. Seventeen of the 18 cases showed both lungs involved. One case was an individual who had had clinical influenza and during convalescence developed gangrenous colitis and acute ascending myelitis which terminated fatally. B. influenzæ was isolated from the bronchioles in the lung of this individual.
The reaction of the body generally was evidenced by a widespread distribution of petechial hemorrhages over serosal and mucosal surfaces. However, certain other important lesions were noted such as one acute vegetative mitral endocarditis, two acute serofibrinous pericarditis, three cases in which focal necroses were prominent in the liver and two examples of infarct of spleen. Further, there were four cases of slight dilatation of the right heart. The liver was usually swollen and œdematous and the spleen presented evidence of an acute reaction, softening and reddening of its pulp with at times slight enlargement.
As evidence of the virulent character of the infection from which these patients suffered, there was not only present in the lung a peculiar hemorrhage and purulent process, but also a more or less widespread distribution of hemorrhages in other parts of the body. The gastro-intestinal tract was most affected with the stomach showing petechial hemorrhages in 17 of 18 cases and the small intestine in 15 of the same number. In the gastric mucosa of three cases there were definite erosions, while in two instances the duodenum presented an intense œdematous and hemorrhagic appearance of its mucosa. Further hemorrhages were observed on one occasion each in the mesentery and in the mesenteric and retroperitoneal lymph nodes. In the latter the mesenteric glands were so distended with hemorrhages that a soft pulp spurted out when the glands were sectioned. Next in order of frequency, hemorrhages were noted 9 times in the pleura, 8 in the pelvis of the kidney, 6 in heart muscle and 3 each in pericardium and bladder. In one case of widespread distribution of petechial hemorrhages there was a massive loose hemorrhage into the lower recti abdominis. Further anothercase showed a large amount of a blood-stained fluid in the peritoneal cavity.
In the analysis of the cases of acute epidemic influenza two important features of the disease present themselves, (1) a marked systemic intoxication with localized manifestations in certain organs, and (2) inflammatory lesions of the respiratory tract. These manifestations present themselves both to the clinician and to the pathologist, and to each they have demonstrated their importance in the disease. The pathologist not in touch with the clinical manifestations of the toxæmia has more closely linked the occurrence of these two factors with the actual findings in the cadaver. But there are those who look upon these factors as separate and distinct, viewing the toxæmia as an individual process and as illustrating the uninvolved influenza, while the inflammatory reaction of the respiratory tract is taken to be a complication arising through the activity of secondary invading organisms. This is the view held by MacCallum, who compares influenza with the acute exanthemata wherein the respiratory lesions are but secondary to the production of a lowered resistance and an invasion by a variety of bacteria. Such confusion presupposes an undetermined virus for influenza. In confirmation to such views we have the reports upon a filterable virus. Up to the present, however, the latter has been on insecure grounds.
It would appear to us that, as has been discussed by Dr. Holman, the case against the B. influenzæ not being the important causative agent has not been proved. The demonstration by others of a potent toxin from the B. influenzæ cannot be overlooked, and although the actual disease has not been reproduced in animals, there is evidence that this toxin will induce acute degenerations in various tissues. Furthermore, the in vitro symbiotic relation demonstrated for the B. influenzæ with other organisms, as the pneumococcus, streptococcus, staphylococcus pyogenes aureus and M. catarrhalis, gives ample support to the claim for a similar symbiosis in the human tissues. The evidence for the important primary relation of the B. influenzæ to epidemic influenza is such that we cannot disregard it—at least,not before we can produce some definite positive evidence that another demonstrable virus precedes it and produces those constitutional effects which initiate the remaining sequelæ.
We must agree with Christian in the statement that all cases dying during the acute stage of epidemic influenza have inflammatory lesions in the respiratory tract and largely in the lung (pneumonia). It is difficult to conceive of a disease comparable to the acute exanthemata, which beginning as a separate and distinct process ends fatally within 48 hours with a pneumonia which is claimed to be secondary.
Epidemic influenza is an acute infectious process of the respiratory tract, usually localizing in the upper respiratory system, but often and in a fairly constant percentage of cases extending into the lower portion of the same system and causing a type of broncho-pneumonia. Accompanying the initial invasion there is a marked systemic intoxication with lesions of degeneration arising in a variety of tissues. These lesions of degeneration are to be seen both locally in the respiratory system as well as in distant parts, as in the muscles, kidney and liver. The primary damage arising in the respiratory organs, and which we believe to be the result of infection by the B. influenzæ, facilitates attacks by such other bacteria as are available and pathogenic to man. The secondary invaders are not constant in type, but we find variations according to the localities where the epidemic takes place. Just as there is a difference in the bacterial flora which constitutes the secondary invasion, so, too, there is a variation in the picture of the inflammatory process which appears in the lungs. The occurrence of the miliary streptococcal broncho-pneumonia has been met with in certain localities much more frequently than in others; lobular and confluent pneumonia has been the prevailing type in certain regions, while a lobar purulent pneumonia with abscess and gangrene was most frequent with others. There does not appear to be an individual and constant character in the mode of distribution of the pneumonia in the lungs. That the pneumonias were not the usual type otherwise seen, is fairly agreed upon by all. The most astonishing feature presenting itself to us was the frequency of death occurring in the early stages of the inflammatory process and before the gray stage had definitely developed. The gray stage of influenza pneumoniais a purulent pneumonia which often also constitutes an acute interstitial pneumonia.
The extensive hemorrhage and inflammatory œdema of the lung are striking during the early stages of the lung involvement. The mononuclear infiltration which appears early and remains for a variable time, until the purulent process is well under way, is also unique. The hyaline deposit in the lung alveoli; the capillary thrombosis and necrosis of the alveolar walls and bronchi are important; while the tendency to abscess, infarct, gangrene and incomplete resolution with fibrosis differentiates this type of pneumonia from the common lobar variety.
As an organic evidence of the acute intoxication, none stands out more prominently than the degeneration of the voluntary muscles. These resemble the waxy degeneration of other bacterial intoxications, and particularly that of typhoid fever. The finding of these acute degenerations does not assist us in arriving at a conclusion as to the nature of the poisonous body, whether a true exotoxin. The presence, however, of such widespread degenerative lesions in cases showing no naked eye change suggests, at least, that the peculiar muscle weakness associated with pain has its origin in this definite process and not in primary nerve lesions.
Very interesting it is that the different muscular structures are not equally affected by the intoxication. This is particularly noteworthy in the heart and intestine. In neither of these structures have we met with lesions comparable to those in the voluntary muscles. Wherein this immunity resides we cannot state. In our own series, as well as in the majority of others, there was an unusual absence of evidence of myocardial weakness. In most of those dying during the acute illness, the heart muscle was found firm and the cavities not dilated. This finding was in striking contrast to that found in acute lobar pneumonia where dilatation of the right ventricle and auricle, along with muscle degeneration, is almost the rule. In but one case of the present series did we find myocardial degeneration leading to dilatation of the cavities and causing death. And in this particular case the intoxication was due to a streptococcus septicæmia arising as a late sequel from the middle ear. The heart in influenza withstands remarkably well the effects of an intoxication fromthe disease and carries the extra load imposed upon it by the involved lung with little evidence of fatigue.
It is also worthy of attention to note that the kidney suffers so little in this severe disease. Bacterial localization with inflammatory concomitants does not occur, and there is no lasting damage upon its structure. As in so many conditions of bacterial poisoning, tubular degeneration, varying from a cloudy swelling to a more acute damage, is to be found in a percentage of cases, but complete restoration is rapidly obtained in convalescence. It is unusual to find such severe renal damage to incapacitate function to a degree to endanger life.
Finally we can add our evidence, gained from a study of the pathology of epidemic influenza, that the primary disease induced by the invasion of the B. influenzæ opens the way for secondary infections of a variety of kinds, whose subsequent effect may be more serious than initial lesions. The many late complications which arise in this manner we have not investigated.