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.
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 present in 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 another
case showed a large amount of a blood-stained fluid in the peritoneal
cavity.
_Summary_
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 pneumonia is 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 from the 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.