Part 26

Of these cases 35 died, the day of death being indicated in the following table.

TABLE II

═══════════════════════════════════════════════╤═══════════════════════ DAY OF DISEASE ON WHICH DEATH OCCURRED │ NUMBER OF CASES ───────────────────────────────────────────────┼─────────────────────── Third │ 1 Fourth │ 3 Fifth │ 4 Sixth │ 4 Seventh │ 4 Eighth │ 5 Ninth │ 3 Tenth │ 4 Eleventh │ 3 Thirteenth │ 1 Fourteenth │ 1 Twentieth │ 1 Twenty-third │ 1 ───────────────────────────────────────────────┴───────────────────────

The time as indicated in the above table has no relation to the length of time that the patients were ill of pneumonia, but refer to the period of illness from the beginning of the influenza. The duration of the pneumonia is indicated in another table.

Of the 35 fatal cases 32 came to autopsy. Facilities were available to do the work very satisfactorily, in that the hospital was well provided with a modern post-mortem room and its accessories. The notes on the autopsies were taken immediately and fully, and the materials for subsequent study were collected in different types of preserving fluid. Portions of tissue were collected from all of the organs for microscopical study, while fluids from the chest, lungs, bronchi and heart were obtained for bacteriological investigations and for some chemical analyses.

Added to the above material we also had the opportunity of reviewing and studying the lesions of 18 autopsies performed by Dr. J. W. McMeans. These cases were very similar to our own series, in that they were cases of epidemic influenza amongst soldiers who were being cared for at the St. Francis Hospital. The disease processes were quite alike in the two series, and the analyses made by Dr. McMeans are comparable in our own and serve as a means of checking our results obtained in another institution. The similarity of the lesions in the lungs and other organs serve to indicate that what is reported in this paper is an index of the nature of the lesions of epidemic influenza as it occurred in the Pittsburgh district. In a few instances the autopsies performed by Dr. McMeans revealed more advanced pulmonary lesions with abscess and gangrene than were noted in the cases autopsied at the Military Hospital. The process, however, in the two series of autopsies was identical.

General External Features

There were no external characteristics of the bodies which were autopsied by us which were constant. Some features were more commonly present than others. Of these the cyanosis of the face, head, neck and shoulders, and in a few instances of the upper extremities, attracted our attention more than any other. This cyanosis was present in over one-half of the number of cases, and it was confined almost always to the upper part of the body. The face, ears and neck were always more affected than other parts. This cyanosis bore no relation to the length of time after death when the body was viewed, as we found that when it was present during life it maintained its prominent appearance for a long time after death.

The cyanosis differed from the bright hue or flush as it is at times observed in ordinary pneumonia, the color in these instances being of a dark purple, or better a purplish blue. The lips and ears showed the most intense color. The cyanosis was not associated with any evidence of œdema. The capillaries of the tissues were filled with blood which was of a very dark character. Cyanosis could also be seen in the finger tips about the nails. This was more marked in the upper extremities than in the lower. The skin of the body rarely showed any cyanosis, these tissues being quite pale, or at times showing a slightly yellowish tinge. In one instance the cyanosis of the head and neck was accompanied by a slight purplish rash upon the upper portion of the chest. This rash was of a petechial kind, there being slight hemorrhage into the tissues. The lesion, however, was not of the blotchy purpuric type which has been observed by others during this and past epidemics (Cole). This single case is the only one where we had evidence of superficial hemorrhages into the skin.

TABLE III

│CYANOSIS│ │ NO │ │ │CYANOSIS ═════╪════════╪═══════════════════════════════════════════════╪════════ NO.│DEGREE │DISTRIBUTION │ ─────┼────────┼───────────────────────────────────────────────┼──────── 741│+ │Chest and upper extremities │ 747 743│+ + │Face, neck and ears │ 748 744│+ + + │Head and neck (upper portion of chest and │ │ │ thighs mottled and purple) │ 749 745│+ + │Head and neck and upper extremities │ 751 746│+ + │Ears, neck and shoulders │ 752 750│+ + │Face, ears and neck │ 764 756│+ + │Neck, jaw, shoulders and upper extremities │ 765 757│+ │Face, neck, shoulders, arms and chest │ 778 758│+ + + │Face, ears, neck and upper chest │ 782 761│+ │Face, ears, neck and upper chest │ 784 762│+ │Ears, neck and chest │ 786 763│+ │Head and neck │ 793 767│+ │Face, ears and neck │ 773│+ + │Neck, ears and cheeks, extending moderately to │ │ │ upper chest. Hemorrhage into conjunctiva │ 781│+ + │Eyes, lips, ears and neck │ 783│+ + │Face, lips, neck and fingers │ 787│+ + + │Ears, neck and shoulders │ 791│+ + │Ears, neck and upper chest │ 792│+ + │Ears and back of neck │ ─────┼────────┼───────────────────────────────────────────────┼──────── 19│ │+ Blotchy or slight │ │ │ 6 │ 12 or or│ │++ Moderate │ │ │ 10 │ 38.6% 61.4%│ │+++ Well marked │ │ │ 3 │ ─────┼────────┼───────────────────────────────────────────────┼──────── 770│ │Fine petechial rash over upper chest. │ ─────┴────────┴───────────────────────────────────────────────┴────────

Occasionally we met with small hemorrhages lying in the upper layers of the subcutaneous tissue. These lesions were small and could not be seen from the external surface. Nevertheless, some of them seemed to have occurred in direct contact with the deep cutis and surrounded portions of the deep skin appendages. From an examination of our cases there was no reason at the time of autopsy to lay any particular stress upon the occurrence of these hemorrhages. Subsequently, it has come to mind, and since learning of the unusual frequency of boils and deep pustules making their appearance as post-influenzal sequelæ, that these minute lesions may have a bearing upon the localization of infection in the skin tissues. We must appreciate, of course, that other factors of a constitutional nature probably render the individual more susceptible to the invasion of the staphylococcus, and that such factors are all-important in allowing this organism to gain a foothold. Whether the decreased sugar-tolerance with hyperglycemia, which has been observed in the late stages of influenza, bears a relation to the increased susceptibility, as appears to be the case in diabetes mellitus, is an interesting point for further investigation. Other constitutional states are also undoubtedly involved in the increased susceptibility to the infection which the patient suffers. Elsewhere (Dr. Holman) it is shown that the natural complement content is considerably depressed during the height of the influenza. With such factors present and with the available infecting micro-organisms, it is possible that the minute deep skin hemorrhages bear a relation to the immediate localization of the infection.

In two instances slight hemorrhages were observed into the conjunctival tissues. In each case they were unilateral and occupied the tissues contiguous to the inner canthus. In one case there was well-marked icterus with yellow coloration of the scleræ and skin. In this case the icterus was associated with degenerative changes in the liver, there being no recognizable obstruction to the bile passages. The icterus had come on quite acutely and without any special clinical manifestations. In the epidemic of 1890 jaundice was present in a considerable number of cases (Medical Record, 1890, xxxvii, 473). Cole made similar observations in the epidemic of influenza amongst the Canadian soldiers. Œdema of the skin was not met with in any of our cases. This point is worthy of comment, inasmuch as some authors have been impressed with the serious damage taking place in the kidney and the resulting incapacity of these organs. Although, as we shall point out later, the kidney tissues in these cases showed a decided toxic degeneration, there was no evidence that a glomerular damage of serious degree ever occurred. The urinary excretion, as is pointed out in a report by Dr. Zeedick, varies considerably with the intensity of the disease. It is unusual to find derangement of kidney function to a degree to reflect seriously upon the general bodily state. At least this has been our experience in the present epidemic. Even where subsequently we were able to demonstrate a considerable tubular degeneration in the cortex of the kidney the change in the kidney function was not of sufficient magnitude to lead to a water-retention to be recognized in an anasarca. I wish to distinguish clearly at this point the difference in finding an œdema in certain involved tissue structures in various parts of the body and arising through an inflammatory reaction due to the presence of peculiar focal irritation, as compared with the accumulation of fluid in many and irregular situations as it occurs through retention and faulty excretion by the kidneys. Various organs as we have found—as, for instance, the lung, heart and liver—showed a condition of œdema which was not to be reconciled with an inadequate circulation because of a cardiac or renal incompetency. These œdemas, which we will discuss later, are local and are the result of damaging influences inducted in and upon the tissues where they are found.

Muscle

In all of our cases we have been struck with the excellent physique of the individuals succumbing to this epidemic. All were youths in the best of health, of good muscular build and strong bony frame-work. Post-mortem rigidity set in fairly rapidly after death. Where this rigidity had “set” for six or more hours it required much force to change the position of the muscles. The voluntary muscles of the thorax and abdomen were always carefully observed, and in a number of instances the muscles of the thigh were also examined. It was not possible routinely to dissect the muscles of the extremities, so that we are unable to give an accurate account of the occurrence of degenerations in these structures. We have, however, observed the reactions taking place in the pectorals, psoas and muscles of the abdominal parietes. Changes were observed with greatest frequency in the recti of the abdomen. Degeneration occurred in these muscles in 14 instances, while the same tissues suffered rupture, in part or completely with hemorrhage, in six instances. It was not uncommon to find marked degeneration in the lower segment of the rectus muscle on one side, while degeneration and hemorrhage had occurred in its fellow on the opposite side. In four cases rupture of the entire belly of the muscle had taken place, so that a considerable space had occurred between the broken ends and a large clot of blood filled the intervening space. This degeneration, which was seen only in the voluntary muscles, was quite interesting and in its milder degrees was rather difficult to detect. All gradations of loss of muscle color were seen. In some instances the muscle simply seemed to have lost its meaty lustre, while again in the more severe instances the muscle color had changed from the bright red to an insipid yellow or clay color. The most marked degeneration occurred in the midportions, while the ends of the muscle masses at the points of attachment were less involved. Complete rupture of the rectus always occurred in the lowermost segment, a short distance above the insertion into the pubic bone. At times the distribution of the degeneration within the muscle was quite patchy, and irregular islands of yellow about 2 cm. in diameter were splashed through the muscle masses, which in themselves were paler than normal. Where the muscle degeneration was advanced the tissue was soft and at times even buttery. It resembled the character of the degeneration observed in typhoid fever, although I have no recollection amongst many enteric cases of having seen the degeneration of the muscle occur so acutely. Recklinghausen claimed that these hemorrhages were most unusual in influenza. This is contrary to our findings.

Degenerations of a similar kind as those of the abdominal recti were found in both pectorals. In the chest region, however, the degeneration was less frequent and less severe. We observed it only twice, and in neither instance had the degeneration led to a rupture and hemorrhage of the muscle bundles. Kuskow observed a single case of degeneration and hemorrhage of the pectoral muscles. In the psoas muscle we observed degeneration on two occasions, in one of which the lesion was associated with a partial separation of the muscle fibers and hemorrhages into its substance. In one case clinically, but not coming to autopsy, a lesion, which from its character we presume to have been a degeneration, occurred in the sterno-mastoid, being accompanied by hemorrhage and the development of a firm clot the size of a hazel nut. In the subsequent history of this case the lesion passed through an aseptic process of organization with contracture so that the patient has recently been developing a “wryneck.” Kohts in 1890 reported the finding of muscle degeneration and abscesses in the arm. The condition arose as a late complication of influenza.

From our experience at the autopsy table in observing the relative frequency with which muscle degeneration occurs in the severe cases of epidemic influenza, we feel convinced that numerous cases which recover pass undiagnosed of this condition. Furthermore we have evidence, as illustrated in a case observed by Dr. McMeans, wherein a lesion which occurred in the gluteal muscles was followed by a localizing infection at this site that these muscle degenerations and hemorrhages may have serious consequences. There are a number of instances in which post-influenzal complications of the nature of deep-seated abscesses of the extremities, thorax, and abdomen may have their explanation for the localization in a primary muscle damage accompanied by hemorrhage and followed by an infection of variable type. Cole also comments upon the development of abscess in the deep muscles where degeneration had taken place. In illustrating some of our findings to Dr. J. Anderson he immediately recognized such a condition in the pectoral muscles of a patient in which he was unable to arrive at a conclusion of the pathological events which had taken place. It is one of the noteworthy features in this disease that the voluntary muscles of certain regions are apt to suffer severe damage, while the heart and the various unstriped muscular tissues are little if at all affected by a similar process. It would be interesting to know whether the lack of response and the delayed functional recovery on the part of the muscles of the extremities in so many patients who have suffered influenza is the result of the damaging influence of a peculiar intoxication present in this disease. One of the features in influenza is the prostration of the patient, and with it there is definite muscular weakness. We have been prone to lay the responsibility of this state entirely at the door of the nervous tissues. Here, however, we are able to offer evidence that quite aside from the lesions arising in the nervous tissue, there is definite muscle damage which, as we shall again discuss when describing the microscopic features, incapacitates even to the point of complete destruction the muscle elements in various fields of the body. Before, however, being able to state that the muscular weakness of the extremities is the result of such damage by toxins it is necessary to obtain more definite information regarding the frequency with which these degenerations occur in the limbs. In our own material we are unable to discuss the matter with adequate figures. We are, however, impressed with the changes observed in the muscles which were available to us. Naturally, too, a certain number of muscle degenerations have escaped our detection because of our unfamiliarity with the mildest grades. In fact, we have already discovered in our microscopic studies that certain cases, which in the macroscopic had escaped us, showed well-marked lesions under the microscope.

TABLE IV

MUSCLE DEGENERATION

ABDOMINAL RECTI │ PECTORAL │ PSOAS ═══════════════╤═══════════════════════╪═══════════════╪═══════════════ TOXIC │HEMORRHAGE INTO RECTUS │ TOXIC │ TOXIC DEGENERATION │ │ DEGENERATION │ DEGENERATION ───────────────┼───────────────────────┼───────────────┼─────────────── 745 on 10th day│745 both on 10th day │756 on 8th day│756 on 8th day 749 on 4th │752 both on 13th │770 on 11th │792 on 6th 752 on 13th │756 both on 8th │ │ 756 on 8th │764 both on 9th │ │ 757 on 6th │765 both on 9th │ │ 762 on 10th │778 both on 23d │ │ 763 on 11th │————————————————— │ │ 764 on 9th │ RUPTURE OF │ │ 765 on 9th │ RECTUS │ │ 767 on 10th │ │ │ 770 on 11th │745 right on 10th day │ │ 778 on 23d │756 both on 8th day │ │ 783 on 8th │778 right on 23d day │ │ 791 on 6th │ │ │ ───────────────┴───────────────────────┴───────────────┴───────────────

We have convinced ourselves that the marked hemorrhage taking place in the muscle tissue follows upon a primary degeneration of this tissue and its spontaneous rupture. The amount of hemorrhage is in proportion to the degeneration and fracture of the muscle elements. The hemorrhage does not precede the muscular change, nor does it have any antecedent relation to the actual tearing of the muscle fibers.

A much better appreciation of the muscle degeneration was obtained in the microscopic studies of these tissues. The various gradations of tissue change could be followed, which was not possible in the naked-eye examinations. Some points respecting this degeneration were quite noteworthy. Firstly, the process of degeneration in its early stages and advancing through the acute destructive periods was not accompanied by any inflammatory reaction. Evidence of inflammatory exudate was obtained only when the degeneration had proceeded to a degree permitting of rupture with hemorrhage, or in the late stages when the areas of marked muscle dissolution were undergoing repair. We have no evidence to indicate that bacteria were present during the beginning of the degenerative process. Bacteria could not be demonstrated in section. The appearance of the tissue suggested a purely toxic process which was selective in its action, picking out voluntary striped muscle tissue and attacking certain muscle groups in preference to others. It was also interesting to observe in the early stages of the degeneration that individual fibers lying amidst healthy and unchanged muscle elements would show degeneration in many of its stages. This appearance was often unique, particularly when in the early stages of the process the involved fiber would still retain its normal position and shape though markedly altered in its staining and chemical qualities.

The degeneration as observed in these cases showed many of the characters like that of waxy degeneration seen in typhoid fever. Similar appearances to these have also been described in connection with the toxic degenerations which occur in the vicinity of infections by the gas bacillus. In fact, all the stages observed in the one can be seen in the other. They differ, however, only in the degree to which final destruction takes place and in the speed with which the degeneration is accomplished. The character of the degeneration is well studied in sections stained with hematoxylin and eosin, eosin-methylene blue, and best of all in the phosphotungstic acid hematoxylin. By the latter method one is able to follow clearly the grade of degeneration as it effects the muscle striations. On the other hand, the peculiar waxy appearance of the early degenerating fibers is best seen in sections stained with eosin or fuchsin, where the striated muscle fibers are found to be changed to a more intensely staining red body of homogeneous character and devoid of all evidence of their original internal architecture. These bland waxy fibers were often of the size and shape like the normal. On the other hand, the fibers are also not uncommonly swollen, stretching the sarcolemma to almost the bursting point. Following this primary bland degeneration the fiber takes on irregular shapes, becoming constricted and collapsed at irregular intervals, so that islands of the waxy contents lie within the sarcolemma, being separated from each other by constricted areas in which the original myoplasm has undergone decomposition and sometimes complete absorption. This irregular destruction of the muscle contents often has a granular stage in which the original muscle substance has become disintegrated. The sarcolemma follows the condition within it, stretching when the fiber is swollen and shrinking, or even becoming collapsed when the inner substance is becoming liquified and absorbed. The sarcolemma does not suffer the degenerative changes of the inner fiber, nor can one observe nuclear changes in this sheath which are significant.

When first studying this process of degeneration it appeared to us that the earliest change was a loss of the transverse striations and the subsequent disappearance of the longitudinal fibrillæ. We have subsequently found that this is incorrect and that the changes observed in the markings of the fibers were not constant. At times the muscle substance would progress through stages of degeneration up to the point of disintegration and dissolution while the transverse striæ were still discernible in the altered fiber. The one constant change that we have observed in the degenerating fibers was the early loss of staining qualities as obtained by the phosphotungstic acid hematoxylin. In such preparations the earliest effect of the intoxication upon the muscle fiber was a change in reaction to this stain. Sometimes within a given fiber small irregular and poorly staining blotches could be observed, while the remaining portion of the fiber was normal in its appearance. Later these poorly staining areas became larger, occupying the entire width of the fiber and being distributed at irregular intervals in its length. Finally the characteristic staining quality was entirely lost, although in the poorly colored cell transverse striations were still discernible and a true waxy stage had not yet taken place.

At times the waxy degeneration advanced into the stage of disintegration by an irregular destruction within the fiber. When this occurred the fragments of waxy substance took on curious coiled and grotesque shapes, while a granular destruction was taking place in their periphery. Neither inflammation, œdema nor a vascular reaction could be determined in these tissues of mild or severe change. The reaction as is indicated in the table occurred quite acutely and was not accompanied by fatty products commonly seen in the slower forms of degeneration.

Gradually the debris of the degenerated fibers is absorbed and the sarcolemma shrinks and collapses upon itself. During this stage a reaction occurs in the sarcolemma with nuclear proliferation. At times the last vestiges of the muscle fiber are seen to be surrounded by a crown of nuclei and cells reminding one of the appearance of the degenerating nerve cells in the Gasserian ganglion in hydrophobia. The involved area becomes active in appearance, showing proliferation of fibroblasts and the appearance of occasional lymphocytes and plasma cells. Scar tissue continues to develop in proportion to the amount of damage done. In areas where hemorrhage had taken place the amount of scar tissue is exaggerated, owing to a process of organization which is taking place quite apart from the muscle degeneration. Thus not a few scars scattered through the voluntary striped muscles are the final outcome of this toxic degeneration occurring in epidemic influenza. Some of these lesions may account for the indefinite pains and symptoms of which the patient complains for so many months after his acute illness. I refer particularly to lesions occurring in the psoas and muscles of the back as possible explanations for the partial invaliding of some individuals.

In a certain number of cases of acute influenza the patients complain of severe abdominal pain, in the absence of any localizing symptoms or evidence of intestinal derangement. Such was the case with a number of the above cases coming to autopsy, and the sole evidence we could offer was muscle degeneration with or without massive hemorrhage. The abdominal pains complained of were more of the nature of dull aches with occasional exacerbations and shooting or lancinating “stitches.” Rarely was the patient able to define the position of the pain, not being able to state whether it was within the abdomen or in the parietes. Most frequently they claimed it was internal. We have on no occasion demonstrated an intra-abdominal lesion which could account for such pains. None of our cases was of the type of “intestinal influenza.” We are, therefore, led to the conclusion that the muscle degenerations of the various degrees, from the slight with few muscle elements involved to the severe with rupture and hemorrhage, account for a proportion of the clinical symptoms of (muscle) pains and aches as well as weakness. We cannot claim that coughing was a necessary factor in inducing rupture of the abdominal recti. In some of the cases with rupture severe coughing had not been observed during the illness.

Upper Respiratory Tract