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_
The pathological changes found in the nose, pharynx and larynx were of
relatively slight importance and most variable in their severity and
incidence. The majority of individuals had few clinical manifestations
of disease in these parts. Some, however, complained of dryness of the
pharynx with slight feeling of fullness. An examination of these parts
revealed some congestion, varying from a red injected mucosa to a bluish
cyanosis. In the nose the reaction was rarely as acute as is seen in
infectious coryza, but even where relatively little change was to be
seen in the tissues hemorrhage from the erectile tissue was not uncommon
during the acute stages. No particular lesion was to be found associated
with nose bleed. There was an unusual absence of excessive secretion
from nose and pharynx in the majority of cases. One was also struck with
the infrequency with which the larynx was involved. A certain number of
individuals complained of hoarseness, and in them injection of the vocal
cords with some swelling was found. In many others, however, even where
an intense infectious process was present in the lower respiratory tract
the larynx was almost without change. It was from the level below the
larynx that the acute reaction in the respiratory system was found.
In all of our cases the trachea showed definite inflammatory reaction.
Of the 32 cases there were 26 having an acute tracheitis, 5 with an
acute mucopurulent inflammation and 1 with a reaction in the subacute
stage. In the majority of the cases with acute tracheitis there was a
thin layer of exudate lying upon the mucosal surface. At times the
trachea was filled with a frothy serous fluid, the greater part of which
had its origin in the lung. Nevertheless, as we shall point out later,
we did obtain microscopical evidence indicating that during the early
acute stage of the tracheitis a considerable serous exudate escapes from
its mucosa. This serous inflammatory reaction is an important one for
all of the mucosal structures upon which the virus of influenza obtains
a footing. This we have found true for the trachea, bronchi and alveoli
of the lungs. In some cases the exudate was grey and lay in close
contact with the injected tissues. At first sight this grey exudate
suggested necrosis, but it was readily wiped from the underlying
structure. Some leucocytes and cell debris with many bacteria made up
the content of this grey exudate.
The macroscopic appearance of the trachea was that of an intensely
injected structure which had largely lost its normal lustre. The naked
eye could distinguish that anatomical change had occurred in the surface
tissue of the trachea and that there was unusual evidence of intensely
injected vessels lying in the submucosa. In only one instance was there
an appearance of a true necrotic membrane lying upon the surface of this
intensely inflamed layer. This apparent membrane was found to consist of
a wide patch of desquamated epithelial cells which was lying as a
delicate necrotic plate upon the surface. This thin layer was devoid of
a meshwork of fibrin threads as usually accompanies a true false
membrane of other sources.
The early intense inflammatory reaction of the surface membrane of the
trachea was characteristic, and in our experience was never exceeded in
intensity by other infections. A desquamation of the lining membrane was
also a common finding. Naturally this intense reaction so commonly found
in the trachea extended without interruption into the main bronchi and
their divisions. The finding of this continuous surface inflammation is
good evidence of the mode of spread of the infectious process along
these membranes, beginning in the upper portions and by direct
continuity involving more and more of the respiratory tubes toward the
lung.
The varying grades in the intensity of the inflammatory reaction upon
the inner surface of the trachea was well illustrated in the microscopic
sections. Even with the different degrees of the reaction there was a
fairly constant character to the inflammation. In this way the response
was found to differ from that commonly observed in ordinary infections
of the respiratory tract. The first striking feature is the marked
response of the vascular channels, both blood and lymphatic. The vessels
lying in the submucosa were found intensely engorged so that their walls
were stretched to the point of bursting. In fact, not a few vessels were
seen whose walls, probably under the stress of intoxication and
dilatation, had given way leading to a flooding of the neighboring
tissue with their contents. Where such vessels lay close underneath the
surface the hemorrhage escaped into the lumen of the trachea.
Accompanying this early vascular response there was found a marked
serous exudate leading to a stretching of the submucosal tissues by
distention of the interstitial spaces. This reaction resembled an acute
inflammatory œdema and occupied the area between the mucosa and the
inner border of the cartilage rings. Beyond this region no response was
found. Thus in the earliest stages, and where the mucosa was still
intact, the main reaction was of the nature of an intense serous
inflammation with congestion of the blood vessels and frequent
interstitial hemorrhages.
Shortly following the development of the serous exudate in the
submucosal tissues, the epithelial lining is found to suffer from the
reaction. The serous exudate does not remain confined to the
interstitial tissues, but is poured out through the mucosa into the
trachea. It would appear that the amount of this clear exudate may
become greater than can be dealt with by the mucosa, with the result
that an accumulation of this serous fluid takes place between this
epithelial layer and its basement membrane. We have repeatedly seen
considerable stretches of the mucosa lifted from the basement membrane
and shed in large plaques into the lumen. These mucosal cells at the
time of their desquamation retain fairly well their morphological
characters, and do not show evidence of necrosis prior to their removal.
Disintegration of these cells naturally occurs while lying in the
secretion of the trachea, and a variable cellular mass in stages of
disintegration may often be found both in smears and sections. When the
epithelial cells are lifted in wide plates, a type of bleb develops
which is easily broken and then disintegrates.
The desquamation of the lining membrane is a fairly constant occurrence
in the cases coming to autopsy. In the majority of those which we have
examined the greater portion of the trachea was completely denuded, save
for small islands lying in the recesses near the mouths of the mucous
ducts. In one case this lesion was accompanied by a process of
ulceration, due in all probability to the invasion by other
micro-organisms. The denuded tracheal surface usually shows a further
inflammatory reaction in which a cellular exudate then makes its
appearance. This reaction is mainly one in which lymphocytes and plasma
cells infiltrate the spaces previously occupied by the serous fluid. The
reaction is limited to the submucosa and does not extend into the
tissues beyond the cartilages. We have found only occasional
polymorphonuclear leucocytes lying close below the surface. During this
period, however, varying grades of degeneration may occupy the upper
layers. The basement membrane particularly seems to suffer by losing its
characteristic outline and staining qualities. This membrane becomes
swollen, softened and indefinite. At times a homogeneous precipitate
occurs along its free surface giving rise to an appearance resembling a
false membrane. This deposit is, however, distinctively different from
the diphtheritic membrane of other infections. It is interesting,
however, that where such deposits and degeneration occur in the basement
membrane more or less degeneration and necrosis also occur in the
connective tissues immediately neighboring to it. These tissues show a
peculiar granular destruction and alter their staining qualities.
Moreover, and what is more important, under these conditions the dilated
blood vessels are found to suffer from the injuries taking place in
their neighborhood. We have repeatedly found partially or completely
thrombosed capillaries, arterioles and venules in these surface layers.
These thromboses took place while the vessel was in its distended state
and thus produced a mold of the dilated vessel. This observation is of
importance in indicating the severity of the effect of the virus and
toxin upon the tissues of the trachea, and it is also of importance to
appreciate that this damaging influence is very different from that
which we encounter in pneumococcus infections, and we shall point out in
our discussion on lung a reaction very similar to that which takes place
very superficially in the trachea may also occur in the alveolar walls
of the lung.
Having referred to the intensity of the responses of the blood vascular
system, we must also indicate the part played by the lymphatics.
Simultaneously with the reactions taking place about the blood vessels
of the trachea we observed similar responses in the lymphatic channels.
At first these dilated structures contained only fluid. Later the
migration of the lymphocytes took place along these routes, and rarely
micro-organisms could be demonstrated either free or within an
occasional leucocyte. The sharp response of the lymphatics during the
serous inflammation is noteworthy, inasmuch as we have found that the
lymph glands lying about the respiratory tubes and lungs were early in
their response to the irritating virus.
Bacteria were demonstrated in the secretions lying upon the surface of
the trachea. In those specimens in which the mucous membrane was still
intact we attempted to demonstrate the clustering of the micro-organisms
about the ciliated cells as was described by Mallory in whooping cough.
Although the organisms, and particularly small Gram negative bacilli,
could be demonstrated lying about these cells no characteristic
arrangement was found. Furthermore where the mucosa was still attached
to its basement membrane we were never able to demonstrate organisms
below the surface of the epithelial layer. In several cases where the
mucosa was lifted in bleb-like structures a number of organisms were
detected below the epithelial layer and in contact with the basement
membrane of the submucosa. We have rarely demonstrated bacteria in the
interstitial spaces of the submucosa, even where large numbers of
organisms were lying upon the inner denuded surface.
The distinction which was made by the gross examination of the trachea
between the acute tracheitis with serous exudate, subacute tracheitis
and mucopurulent tracheitis was not so readily distinguished in the
microscopic sections. In the gross the character of the exudate lying
upon the surface was the main guide suggesting the nature and intensity
of the inflammatory reaction. In the microscopic sections this exudate
was largely wanting, or was not sufficiently characteristic to confirm
the gross findings. On the other hand, differences in the nature of the
injury were to be found mainly in the reaction of the submucosa. As we
have indicated above, the early inflammatory reaction of the trachea is
mainly evident in an intense congestion accompanied by an inflammatory
œdema of the submucosal tissues, hemorrhage sometimes accompanying this
response. In the later stages of the reaction a cellular deposit takes
the place of the inflammatory œdema and usually consists of lymphocytes
and plasma cells. It is only in those cases where the intensity of the
irritant continues to act over a longer period of time that a
superficial necrosis with leucocytic infiltration makes its appearance.
The epithelial layer of the trachea is desquamated early in the acute
reaction, and hence a denudation of the surface is to be found in all
stages of the acute lesion. The mucous glands have not been found to
show any particular involvement in the inflammatory process, and in the
majority of instances they were found to have escaped entirely the
damaging effect of the virus. Their response in an over-secretion of
mucus may be the outcome of a stimulation by toxins or soluble
irritants; but on the other hand, may also probably be a reflex response
to the injury of the mucosal surface, which being bared of its covering
is highly sensitive. The increased discharge of mucus from the deep
glands may well be a protective response to such injury.
_Bronchi_
The lesions in the bronchi were in every way comparable to those in the
trachea. The main bronchial tubes differ in no material way from the
structure of the trachea, and the extension of the inflammatory process
from above downwards leads to a reaction in their walls similar to what
has been above described. As we follow the subdivisions of the bronchi
we gradually lose some of the characteristics contained in the larger
tubes. The mucous glands gradually become fewer and eventually
disappear. The cartilage rings become smaller and no longer completely
encircle the bronchus, and with the further diminution in the size of
these structures disappear entirely. A relatively greater amount of
muscle tissues takes the place of the cartilage rings. This change in
the anatomy of these structures has a certain influence in modifying the
character and distribution of the inflammation.