Part 33

Too much stress cannot be placed upon the importance of the lymphatics in all forms of pneumonia. They play an important role in the drainage of the lung during inflammation. In the normal lung we hardly appreciate the lymphatic distribution except in our observations upon anthracosis. But even under these conditions when much carbon is deposited in conjunction with the lymphatic system we do not gain a true appreciation of the activity of the lymph channels and nodes during an acute process. Bacteria may be demonstrated in acute infections of the lung within the fluid and cells of the lymph channels. Less easily may we demonstrate bacteria in the lymph nodes under similar conditions, although when abscess has occurred their presence is readily recognized. The transport of bacteria is accomplished not only by a passive migration of micro-organisms in the fluid as it drains from the lung, but organisms are also found within the leucocytes as they travel with the current. Only occasionally have we demonstrated bacteria within the wandering large mononuclear cells, although we have observed them in a few instances within the cells lining the sinuses of the nodes.

Whether the inflammation of the pleura is directly related to the involvement of the pleural lymphatics we have not been able to determine. In our series of cases pleurisy has not been a prominent feature of the disease, and in many instances the grade of involvement was so slight that it was not easily recognized by the naked eye and showed only a slight reaction microscopically. That the presence of bacteria within the intricate plexus of lymphatics beneath the pleura may be responsible for the development of an inflammation of this membrane may well be the case, and in this way simulate the mode of transmission of the infection as seen in lobar pneumococcus pneumonia and in the streptococcus type of infection.

_Abdominal Viscera_

The lesions occurring in the abdominal viscera were of less importance than those within the thorax. In none of the cases of the epidemic was the intestinal type of the disease, described in previous years, encountered. The changes found in the various viscera were concomitant with evidences of intoxication as observed clinically or at autopsy in other regions of the body. We found no evidence that the bacteria of the disease localized in the tissues of the abdominal viscera, and we were led to believe that the alterations in morphology and function were the result of diffusible toxins. The action of these toxins was either upon the parenchymatous cells of the organs, as in the liver and kidney, resulting in granular degeneration, or upon the capillaries with the development of petechial or diffuse hemorrhage as was encountered in the stomach, intestines and bladder. The absence of definite localized inflammatory processes in these distant tissues, including the abdominal lymphatics, speaks against the probability of a bacteriæmia playing an important role in the disease. That transient bacteriæmias by the influenza bacillus do occur has been repeatedly demonstrated, and that the organisms associated with this bacillus may also enter the blood stream has likewise been found. But these states are accessory to the disease, and must be viewed as complications rather than the rule. Hence the occasional observations by some, of bacterial inflammatory reactions in liver and kidney must not be considered a part of epidemic influenza, for in many cases it is wanting. The majority of lesions of the abdominal viscera probably arise through the action of the unknown toxin in the blood.

In the _stomach_ and _intestines_ the lesions were of two kinds, (1) hemorrhage and (2) erosions. Petechial hemorrhages were present in the stomach 15 times, in the intestines 4 times. These small dots of blood extravasation, lying in the mucosa and submucosa, differ in no way from those observed in other acute infections and intoxications, save that the tendency for the leakage of blood into the lumen of the viscera was more pronounced. Often we could observe the presence of free and more or less altered blood in the stomach and intestines, and in 12 cases the amount was considerable, sufficient to be spoken of as melena. It is probable that the oozing of blood takes place not only from the areas visible to the eye as petechial hemorrhages, but also from the more normal-looking mucosa of stomach and bowel. The tendency to hemorrhage was not necessarily accompanied by visible alterations in the epithelial layer of the mucosa, though at times erosions were found. When hemorrhage could be observed, the extravasation of blood occupied the superficial layers of stroma, causing a separation of the tissues beneath the epithelial layer. At times the submucosa was also infiltrated, and in one instance the musculature. The lesions were isolated and sporadic, but always about small capillary loops. It appeared to us that the damage was primarily upon the vascular tissues and particularly upon the endothelial walls of the fine channels. Inflammation was not present, and the hemorrhage was more or less passive—that is, a slow oozing rather than acute hemorrhage by rhexis.

The second type of lesion of the gastro-intestinal canal was erosion. This was of the nature of a defect in the mucosa, usually multiple, small and well circumscribed. The tissue loss was superficial. In their appearance these lesions were similar to those encountered in these parts in other infections, and also as described by McMeans in experimental infections of animals. The erosions appear to arise in a process of bland necrosis, limited in the periphery by healthy tissue and not tending to enlarge. It is probable that these erosions are associated in their development with the petechial hemorrhages, being a sequel to the vascular disturbance of the mucosa and subsequent digestion of the injured tissue. Multiple lesions of the stomach were found 10 times and twice in the intestine. The largest was 1.25 cm. in diameter. They are more common on the posterior than anterior wall, and usually toward the lesser curvature. It is probable that these defects are limited in their progress and heal readily.

The changes occurring in the _liver_ were not of striking account. Cloudy swelling was observed 13 times, usually of moderate grade. The usual appearances with enlargement of the organ, bulging of the parenchyma on section and a dull gray cut surface were all that could be found. The one case with icterus was the only one in which the natural discharge of bile from the liver was interfered with through the swelling. Even in this case the obstruction to the outflow of bile in the small channels was not demonstrable in the microscopic sections, nor was there evidence of unusual bile staining of the liver-points suggesting the possible origin of the icterus in an unusual hemolysis. On no occasion did we meet with recent inflammatory reactions in the gall bladder or bile ducts, and we have no evidence that the organisms of the infection are discharged from the body by these routes. The cloudy swelling of the liver was accompanied by slight œdema of these tissues in seven cases; and in six instances focal necroses were observed. These focal necroses were similar in appearance to those seen in typhoid fever, but were much less frequent in the tissue. Only careful search revealed isolated pinhead gray dots with depressed centers. They were most commonly in the mid-zone of the lobule, and in the early stage were without inflammatory reaction. Subsequently, leucocytes infiltrated the area, but not in an amount to form pus. Bacteria were never demonstrated in the areas of focal necrosis. Four cases showed old adhesions about the gall bladder and in one a gall stone was present.

Lesions of the _pancreas_ were not encountered. In a few cases the lymph glands about the head of the pancreas were slightly enlarged.

The _spleen_ showed relatively little reaction and in only two cases was it enlarged. Fourteen times a diagnosis of acute splenitis was made on examination of the gross specimen. This diagnosis rested upon the finding of a swollen spleen with tense capsule and with a dark bulging pulp. The Malpighian bodies were usually in part or completely obliterated, though in a few instances these grayish nodules seemed even larger than normal. These spleens contained an excess of blood within the pulp. In one case several isolated areas appeared hemorrhagic as if a local rupture of the tissues had occurred. The microscopic examination of these specimens showed mainly a marked congestion of the sinusoids, a diminution in the size of the lymphoid corpuscles and some increase in the number of leucocytes within the blood spaces and reticulum. Only occasionally did we observe a proliferative reaction of the large mononuclear cells lying in the reticulum. This proliferation was not sufficiently marked nor uniformly present to be considered as characteristic. We did not find abnormal deposition of blood pigment indicating an unusual destruction of red blood cells within the spleen. It is interesting to note that 5 of the 32 cases showed obsolete miliary tubercles in the spleen.

Our analysis of the changes occurring in the _kidney_ bore out the clinical findings observed in the wards. Like in so many acute infectious diseases urinary changes were commonly present. These are in part dependent upon systemic changes in the metabolism of tissues and not entirely the result of renal lesions. In acute epidemic influenza there was no common characteristic in the urinary output. The amount excreted in 24 hours was usually diminished to a small extent, the color was darker, the specific gravity slightly increased, as well as the total solids. There was no marked change in the total quantity of output of any one of the constituents as far as they were analyzed by us. Albumin was present in the urine in variable amounts and in the more severe cases casts were also present. There was only one case in which the quantitative output was much diminished and where some fear was entertained of development of acute uremic manifestations. This individual, however, died before these made their appearance and before there was any evidence that the retention of waste products was causing definite clinical symptoms.

In 30 cases coming to autopsy more or less cloudy swelling was to be observed in the kidney. This reaction varied from a very mild swelling and granular degeneration of the tubules of the cortex to a decided parenchymatous degeneration with loss of nuclear structure and erosion of some of the cells lining the tubules. The convoluted tubules were always most markedly involved. Occasionally this tubular degeneration was accompanied by a desquamation of the lining cells of the glomerular capsules. We were, however, unable to recognize an acute inflammatory reaction in the interstitial tissue or in the glomeruli in any of the cases, except the one which had developed a streptococcus bacteriæmia as a sequel to an otitis media. The kidney lesion reminded one very much of the toxic lesion which is observed in the kidney in typhoid fever. Differing, however, from the latter there was a variable congestion of the fine vessels associated with the cyanosis which was present in a certain percentage of these cases. At times the kidneys were quite wet with blood from the venous engorgement.

The lesions in the kidney were of a toxic type and did not resemble reactions following the presence of the bacteria in the stroma of the organ. In the majority of instances in other diseases where bacteria themselves locate in tissues we are able to recognize focal lesions of acute necrosis or inflammation. In epidemic influenza where a variety of micro-organisms within the lung are able to reach distant structures in a bacteriæmia, we would, because of their type, expect to find inflammatory reactions of a definite kind. The absence of such reactions is very suggestive that the bacteria do not commonly localize in the kidney, but that their toxins alone affect it during its elimination. We have also entirely missed the finding of any vascular lesions in the renal system. Neither degeneration nor inflammatory reactions of any of the coats of the blood vessels could be distinguished.

The partial incapacity on the part of the kidneys must, therefore, be viewed as a complication resulting from the effect of a diffusible toxin reaching them by the blood stream. The damage performed in this manner may be quite extensive upon the secreting tissues of the tubules leading to an increased or decreased output of the urinary constituents. Because of the nature of the lesion, it is probable that the kidney damage incurred during the acute epidemic influenza is only temporary and not permanent. Tubular degeneration is readily repaired, and in the absence of an inflammatory reaction in the interstitial tissue or the glomeruli avoids the development of a permanent mark or derangement in the system. This is as we find it in typhoid fever.

In two cases we observed very interesting lesions in the _bladder_. These two individuals during life had been excreting markedly blood-stained urine for some days preceding death. In the one case the hemorrhage was so marked that on standing, about one-tenth of the urine was composed of sedimented red blood cells. It was assumed that the hemorrhage was of kidney origin until the autopsy revealed a simple cloudy swelling of the kidney associated with a hemorrhagic state of the submucosa of the bladder. In both cases the posterior wall of the bladder was heavily infiltrated with blood so that the mucosa was raised from the surface and the prominent folds showed a superficial erosion with small points of greenish necrosis. This bladder hemorrhage was concomitant with hemorrhagic foci elsewhere in the body, pericardium, pleura, stomach and intestine. Alone in the bladder however, the hemorrhage formed a distinct mass and allowed a considerable escape from the lesions on the surface. These areas of hemorrhage were not infected and showed no local inflammatory reaction. They also appeared to be toxic in origin and resembled the hemorrhages occurring in the muscles of the abdomen.

Changes in the _adrenal_ gland were noted in 14 instances. In all of these there was the picture of what is commonly known as cloudy swelling of the cortex and, in addition to this, in three cases small petechial hemorrhages were observed. The so-called cloudy swelling of the adrenal consists largely in a loss of the bright golden appearance of the cortical tissues accompanied by soft œdematous swelling. The tissues change color to a brown or clay color, and it is not uncommon to observe that the inner zone of pigmentation is more diffuse. There is no sharp demarcation between the layers of the cortex. With this alteration in the outer structure of the adrenal, the medulla not uncommonly appears smaller. This change is more apparent than real, and we have not been able to observe any definite lesion in the nervous portion. At times we believed that the inner tissue appeared more cellular, but it was not possible to determine any specific alteration in the cells.

The changes in the adrenal cortex are comparable to those observed in typhoid fever. The analyses of these tissues showed that the cells were almost devoid of cholesterin bodies and few doubly refractile globules could be demonstrated. This change in the adrenal is by no means specific for any acute disease, it being found in many of the severe infections. We regret that systematic analysis of the blood serum in these cases was not made to determine the cholesterin content. If the comparison bears out with typhoid fever, we would expect to find that the quantitative cholesterin of the blood is diminished. Some importance attaches itself to the study of the cholesterin metabolism, particularly in regard to the development of the peculiar fatty streaks which develop in the aorta and other arteries during these acute infections. It has been claimed that in the human these streaks bear an analogy to those produced in the experimental animals and that the arterial lesions are associated with an altered activity on the part of the adrenal cortex in handling the cholesterin compounds. In influenza there is evidence that the adrenal does not function in a normal fashion and that the storage of cholesterin-esters does not take place. From this, however, we cannot conclude that the blood content is increased, and, in fact, it is more than probable in comparing the other reactions of the disease that it follows the changes as seen in typhoid fever where the blood content of cholesterin is lowered. In this way comparison with the experimentally produced arterial lesions in animals is not clear, in as much as in the experimental work a true hypercholesterinemia was induced. Nevertheless it is possible that with the abnormal function on the part of the adrenal the cholesterin materials are made more available for absorption by other tissues and that a true hypercholesterinemia is not necessarily a constant factor, even with the abnormal accumulation of these substances in the intima. It may well be that the normal activity of the adrenal is related to the presence of toxins in the circulation and an attempt by mobilizing cholesterin to diminish the activity of these harmful substances.

OBSERVATIONS UPON THE PATHOLOGY OF EIGHTEEN CASES OF INFLUENZA

By J. 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 base of 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.