CHAPTER III
PATHOLOGICALANATOMY
Inorder to portray the pathology of the respiratory diseases of the WorldWar it isnecessary to classify the lesions and to define the meaning of certaindescriptive terms so thatmisunderstanding may be minimized. While it is impossible in thepresent state of ourknowledge to separate the lesions according to the organisms producingthem, certain conditionsfound in the respiratory tract appear to have been associated with someorganisms morefrequently than with others. Bacteria, therefore, must be considered,and it is convenient todescribe a type of pathological change as most characteristicallyproduced, in so far as carefuland painstaking bacteriological research of the period of this war hasdivulged, by one organism.For instance, interstitial pneumonia, as described by MacCullum,1is the result of infection of thelung with a hemolytic streptococcus, although there were found numerouschanges of interstitialtype in lungs from which this organism was not isolated by methodswhich ordinarily showed itspresence, other organisms, as Streptococcus viridans or GroupIV pneumococci, apparentlyacting as the etiologic agents.
Byforce of circumstances we are unable to portray the acute respiratorylesions whichdid not prove fatal. While undoubtedly persons in the early stages ofacute respiratory diseasedied from other causes, no observations have been found on thepathology of the respiratory tractin such cases. Certain assumptions are based on the condition oftissues at death which seem toindicate the sequence of events leading up to the final condition.Furthermore, it is manifest thatthe complete sequence can be surmised only from the study of lesionsobserved at varyingperiods after the onset of clinical symptoms. Here variations injudgment are bound to occur asthe variables are numerous, including, as these do, the virulence ofthe organism, its numbers,the resistance of the host both physically and chemically, and thoseaccidents which, on the onehand, favor the patient, on the other, assure a fatal outcome of thedisease. Examples are thepenetration of a pulmonary vein by an abscess and superimposedinfections with additionalspecies of organisms. The previous experience of those who made theexaminations and of thosewho interpreted them is also responsible for variations not only byreason of the amount of thisexperience but also its character. The endeavor is therefore made todelineate a picture whichwill be clear and interpretable in the light of both present and futureknowledge.
Thespecimens which form the basis of the illustrations were selected fromthecollections of the Army Medical Museum and were obtained in thenecropsies of over 600 casesat various Army stations during and immediately following the WorldWar. The fatal respiratorylesions were considered primary by those writing the protocols in arelatively small proportion ofthe cases. The majority were considered secondary to clinicalinfluenza, measles, or other acuterespiratory infections, either not definitely diagnosed or diagnosed asacute pharyngitis,
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bronchitis, tonsillitis,or rhinitis. The indefinite diagnoses, acute pharangitis, bronchitis,tonsillitis, and rhinitis were found rarely in the material sent to theArmy Medical Museum, asmost of the specimens were collected during waves of acute respiratorydisease of epidemicproportions.
Thepathology of measles independent of its serious complications will notbe described,as the material studied offers no possibility of clearlydifferentiating it from the secondaryinfections responsible, in large part at least, for death. A fewobservers were of the opinion thatthe virus or etiologic organism causing measles produced acharacteristic picture in the lungs.2 Asimilar picture was described as probably due to the influenza bacillusand indeed a similarorganism was present in cases complicating or following measles. Since,clinically, both measles and influenza were prevalent at the same timeit is quite possible that patients withmeasles were affected also by influenza. It is impossible, in the lightof present knowledge, todetermine where the lesions due to the cause of influenza left off andthose of secondaryinvaders began, but in certain instances the sequence of events leadingto death occurred sorapidly as to make the process clinically and anatomically a diseaseentity. It is quite possible,however, that the secondary invader produced its lesions synchronouslywith those of the primary, the latter acting either to increase thevirulence of the secondary or to depress theresistance of the host.
Inthe larger waves of acute respiratory disease in the spring and fall of1918, and in thefall of 1917, an acute infection with measles or influenza-like diseasewas followed by varyingnumbers of some type of pneumonia. In a few of the measles casespneumonia occurred afterdischarge from hospital, but in most instances this disease wasmanifest during hospitalizationand while measles was present. The onset of the pneumonia was sometimessimultaneous with that of measles but more often followed the drop intemperature at the stage of full eruption.
In the casesdiagnosed clinically as influenza, there was also a lack of uniformityin thetime of onset of pneumonic symptons. The fulminant cases appeared tohave serious pulmonaryinvolvement from the start, while others, though showing theprostration and other symptoms ofthe clinical disease, did not have definite pulmonary signs for avarying time afterwards.
Caseswhich were fulminant from the start were the ones in which cultureshowed B.influenzae most often, and in which this organism was found mostfrequently alone in theculture from the lungs. Such cases occurred, according to availabledata, rarely in the fall of1917, more frequently in the spring epidemies of 1918, and most oftenduring the pandemic ofthe early fall of 1918. The same anatomical picture varying in theextent of the process in thelungs and in the stage of the lesion was found in some part of thepulmonary parenchyma inmost of the lungs of the pandemic wave and in many of those from thespring epidemic. Thematerial available is too scanty to enable one to judge of itsfrequency in the fall of 1917, but itdid occur. Lesions in which other organisms, pneumococci, streptococciand staphylococciappeared to be responsible varied in time of appearance of clinicalsymptoms, in extent of tissue involved, and in severity. Some of them(pneumococcus Type II at Camp Grant) invaded early inthe course of the pandemic infection and some fulminant
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cases appeared to beattributable to these organisms alone, though this was the exception.
Thelesions in the lung at necropsies, whether such cases were recorded asprimary orsecondary, were characterized by their extreme variety not only indifferent cases but also in thesame case. It was frequently difficult to decide which type ofpneumonic process predominatedin the lungs of a single case, and the more carefully these organs weresectioned, the moredifficult the decision. For example, a lower lobe might show a largepart uniformly consoli-dated by a fibrinous exudate of the character usually seen in lobarpneumonia, the peripheralportions lax and studded with small peribronchiolar consolidations, inthe lower lobe on theother side a pneumonic consolidation surrounding and spreading out fromthe bronchus nearestthe vertebrae, in the balance a scattering or confluent lobularconsolidation, while the upperlobes contained scattered lobular and peribronchiolar consolidationsand strie of interstitiallymphangitis about bronchi and in interlobular septa.
Theage of the lesions as judged by the gross and microscopic appearances,also variedand often to extreme degrees, so that it was evident to thepathologists that in most of the fatalcases at least there had been several periods of advance, or theinfection, originating in one partof the lungs, had spread to another and then another part, or elseother organisms than thosecausing the initial process had gained entrance and, in turn, hadproduced pulmonary inflammation. The organisms recovered were often ofdifferent species and varieties, which accountsin large part for the varied bacteriological findings at necropsy andprobably also the changeswhich occurred in the bacterial flora as determined by culture of thedischarges from therespiratory tract during life. In fact, the varied bacterial flora,with the differences in the mediarequired for their growth, made it extremely difficult to ascertain thebacterial cause or causesof the pneumonic lesions. The epidemic proportions in which thesediseases appeared made itphysically impossible for the laboratories to carry out sufficientlyextensive cultural work todetermine the organisms concerned with any degree of certainty, thoughat most camps thepredominant ones in the etiology of the secondary pneumonia undoubtedlywere recognized.
It wasdifficult in many instances to determine the boundaries of thepathological anatomicalprocesses, yet certain distinct types or distributions did occur as theonly ones in a given lobe orlung, or were so separated from others as to render differentiationpossible and to enable thepathologist to determine the organisms they contained as shown bysmear, culture, and microscopical section of the tissue. In theillustrated description which follows, the lesions areconsidered according to anatomical type and are preceded by definitionsdescriptive of thesetypes.
LOBARPNEUMONIA
Typicallobar pneumonia was present in all camps and was particularly notedduringthe fall and winter of 1917-18. Its exact incidence can not bedetermined, since the clinicaldiagnosis, lobar pneumonia, frequently was proven incorrect atnecropsy. The morbidity, asjudged by a study of the reports in the literature from the Army campsand the protocols at theArmy Medical
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Museum, was not high,and the case fatality rate was low. The condition followed measles andacute epidemic respiratory disease but was not nearly as frequent asother types, and if found,usually was associated with other varieties of pneumonia in lobes ofthe lung not affected by thelobar process. In order to separate the anatomical types of pneumoniaone from the other, arather narrow interpretation has been made of the anatomicalcharacteristics used as
FIG.1.- Postinfluenzal pneumonia. Typical lobar pneumonia in the rightupperlobe at the stage ofgray hepatization. Confluent bronchopneumonia in the right lower lobesurrounding two of thelarger bronchi. In the vertebral portion of the right lower lobe areseen numerous peribronchiolarfoci of consolidation with confluent lobular pneumonia. Acutehemorrhagic bronchitis of bothlungs, congestion of the left upper lobe, peribronchial consolidationsin the left lower lobe. Justbeneath the bifurcation of the trachea there is an abscess involvingthe lymph nodes of the mediastinum. Pneumococcus Group IV was isolatedfrom the sputum and lung. Sections oftissue show streptococci in the abscess of the interlobular septum inthe right upper lobe andGram-negative bacilli in the peribronchiolar consolidations. Accessionnumber 2711, ArmyMedical Museum. Negative number 30583
criteria of thediagnosis, lobar pneumonia. The pathologic anatomy of the condition hasbeendescribed in detail so that it may be easily differentiated from theother pneumonia types.
Lobarpneumonia is an inflammation of the lung characterized by the uniformconsolidation of a whole lobe or practically all of a lobe. (Fig.1.)Three stages are presented inthis type.
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In the first, orcongestivestage, the lung is heavy but compressible, there is little or nocrepitation, it is moist, red in color, drips blood on section and themarkings are visible. It is notfirmly consolidated but collapses slightly if at
FIG. 2.–Dilatedsmall vessel in the congestive stage of lobar pneumonia. Capillaryvessels areengorged and there is an escape of red blood corpuscles, serum, a smallamount of fibrin, andfairly numerous leucocytes into the alveoli adjudacent to the smallvessel. The lymphaticssurrounding the vessel are distended with leucocytes, which infiltratethe alveolar walls.Accession number 22728. Army Medical Museum. Negative number 41224.Hematoxylin andeosin stain; X 400
all. The vessels areengorged with blood which distends the alveolar capillaries, increasingthethicknesss of the alveolar walls. The alveolar walls are also thickenedby edema, the epitheliumis more or less desquaniated, and the
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alveoli contain serum,red blood corpuscles in varying numbers, and a few leucocytes. Strandsoffibrin form early but do not dominate the picture at this stage. (Fig.2).
Inthe second or red hepatization stage, the lung is firmly consolidated.It fills the pleuralcavity and usually shows the rib markings. It is friable and darkpurplish red in color. On sectionthe surface is dry, a dull dark-red in color. Plugs of firm exudate canbe expressed with the knifeedge. The markings are obscured but bronchi of medium and large sizeare distinct and do notproject above the surface. The degree of completeness of theconsolidation is common topractically all of the tissue involved though the process is usuallyslightly more advanced aboutthe larger bronchial and vascular trunks near the hilus. The largervessels are filled with bloodbut the smaller vessels and alveolar capillaries are compressed to agreater or lesser degree bythe exudate which now fills the alveoli, compressing the walls. Theexudate usually containsmany leucocytes and a dense fibrin mesh has formed, producing a clot ofthe entire exudatemass. Red corpuscles retain their stain and vessels still contain anexcess of blood. (Figs. 3 and4.)
Inthe third or gray hepatization stage, the lobe affected is large, doesnot collapse, is firmand usually shows rib markings. The color is lighter than in the secondstage and may beyellowish gray. It is friable to a greater extent usually than in thepreceding stage. On section thecut surface is plane, dull and dry. It is usually somewhat mottled areddish-gray to yellowish-gray. Firm plugs may be expressed by theknife edge. Because of the lighter color the bronchialwalls do not stand out distinctly. The process is uniform forpractically all of the tissue affectedexcept that it is slightly more advanced near the hilus where, in thelungs typical of this stage,some liquefaction of the exudate may have occurred. The alveoli aredistended with exudatecomposed of a dense mass of leucocytes in a meshwork of fibrin. Redblood corpuscles do notstain well and the alveolar walls are compressed to such a degree thatit is difficult to see them orto make out the capillaries. In the later stages the exudate becomesnecrotic and autolyzed assolution takes place and this is accompanied by a filling of thecapillaries with blood. (Figs. 5and 6.) This stage passes over gradually into that of resolution whichis somewhat less uniformas the resumption of the full blood and lymphatic circulation isirregular. Lesions correspondingto the description of the three stages but not involving practicallyall of a lobe are not designatedas lobar. Neither are lesions of the same type in lobules which showvarying stages in theprocess even when the greater part of a lobe was thus consolidated.
BRONCHOPNEUMONIA
Bronchopneumoniais a pneumonic consolidation spreading outward from the bronchi avarying distance into the surrounding alveoli, the oldest process beingin the vicinity of thebronchus situated in the approximate center of the lesion.Macroscopically, a lung so affected isirregularly consolidated; usually both lungs are affected. On section,the consolidations surroundthe bronchi extending irregularly out into the parenchyma. When two ormore neighboring oradjacent bronchi are affected the lesions may coalesce to form
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one large pneumonic mass, the lines of division into separate components being difficult to determine macroscopically, though microscopically variations in the
FIG. 3.- Alveolus in the early stage of red hepatization, showing capillary engorgement, nearly complete desquarnation of the epithelium, and an alveolar exudate in which fibrin is abundant. Swollen epithelial cells are seen along the alveoiar wall and free in the serum-filled space between the fibrinous mass and the alveolar wall. Accession number 2272, Army-Medical Museum. Negative number 41217. Hematoxylin and eosin stain; X 600
stage of the process in different areas can usually be made out. The character of lesion varies widely and may show the same stages as the lobar type but is more irregular, the oldest lesions being near the bronchi. Hemorrhagic areas
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are frequent and may predominate or constitute practically the entire gross picture. As a rule, there is less fibrin formation and the distribution is irregular
FIG. 4- Stage of late red hepatization stained for retictilurn and show ing the dilated capillaries in the alveolar walls. Accession number 3115, Army Medieal Museum Negative number 45556. Reticulum stain; X250
Sections of small areas frequently show a wide variation in the character of the exudate between neighboring alveoli. (Fig. 7.)
There are two types of pneumonia which answer the description above. In one the bronchi are the site of a severe inflammation usually purulent in
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character. Theepithelium is largely desquamated, the wall densely infiltrated withexudate, oftenpredominantly purulent and sometimes the wall is necrotic. The processappears to haveextended through the bronchial wall to the surrounding alveoli. In thesecond, the bronchialmucosa is little affected in the earlier stages. The peribronchial andperivascular tissues aredensely infil-
FIG. 5- Alveolis of early grayhepatization.The exudate as contracted as the result of fixation. Alveolar walls arecompressed some capillaries still being filled with red bloodcorpuscles. Some of the epitheliurn is still adherent tothe alveolar wall. Accession number 22728, Army Medical Museum.Negative number,41223. Hematoxylin andeosin stain: X 400
trated with exudate,usually purulent, but, the leucocytes are often predominatelylymphocyticand the inflammation appeats to have extended primarily as, alymphangitis along theperibronchial and perivascular lymphatics and then extended out intothe surrounding alveoli. Inthe later stages the inflammation extends through the bronchial wall tothe mucosa which is thussecondarily affected.
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LOBULAR PNEUMONIA
Groups of lobules, occasionally single isolated lobules, are affected. Approximation of groups may cause most of a lobe to be involved. Grossly there
FIG. 6.- Lung in gray hepatization, showing compression of the alveolar walls and capillaries. Accession number 3115, Army Medical Museuim. Negative number 45562. Reticulum stain; X 250
are scattered nodular areas of varying size throughout one, usually many lobes. Where these nodules reach the pleural surface as in those of the periphery of the pulmonary parenchyma, the outlines of the lobtules clan be muade out as a
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mosaic-like pattern on the pleural surface. The individual lobule is usually uniformly consolidated though the lesions microscopically appear more advanced near the bronchiole of the lobule. The nodules vary in firmness and in
FIG. 7.- Postinfluenzal pneumonia. Spreading bronchopneumonia of left upper lobe and upper portion of left lower lobe. Peribronchiolar foci in base ofleft lower lobe. Confluent lobular pneumonia of right upper and middle lobes. Peribronchiolar foci in right lower lobe. Pneumococcus,Group IV, in sputum. Streptococci and bacillus of Friedlander in cultures from the bronchi. Accession number 1433. Army Medical Museum Negative number 30649
friability. Hepatization as seen in the lobar type is occasionatlly found in affected lobules and groups of lobules, but is rarely found at the same stage in many lobules of the same group. More often the consolidation is less dense and the tissue is more resilient. This type of lesion is usually found accompanied by other types. (Fig. 8.)
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INTERSTITIAL PNEUMONIA
A reaction, the greatest intensity of which is in the supporting tissue of the lung, has been recognized for some time as a part of the process in some cases of bronchopneumonia. Such a reaction is seen in the lungs of pneumonic plague, where it constitutes a prominent part of the picture. It is never the only type of reaction but lungs have been seen in pneumonic plague, and were described in the influenza of 1918, in which reactions other than inter stitial inflammation and its accompanying alveolar edema were not evident on macroscopical examination, though microscopical sections showed at least the early stages of consolidation.
The more acute stage was seen in cases dying in the first two to four days of illness. Grossly the lung resembled that of the acute fulminant type of reaction seen in the influenza pandemic but were more hemorrhagic, that is areas of frank hemorrhage were usual. (Plate I.)
Macroscopically such a lung is heavy and boggy. Though it does not collapse, crepitation is not easily elicited. On section the lung drips blood, and bloody serum which appears dull and brownish. The bronchi stand out, filled with hemorrhagic euxdate, the walls are thickened and often surrounded by hemorrhagic zones, while areas of frank hemorrhage already clotted are frequent. Histologically the peribronchial and perivascular tissues, aside from edema and hemorrhage, are infiltrated with lymphocytes, large mononuclear and polymorphonuclear cells, and the same infiltration is present in the alveolar walls. The alveoli are filled with a serous exudate which rarely contains fibrin. Streptococci are abundant in the bronchi and peribronchial and perivascular lymphatics but are seen in minimal numbers in the alveoli. They are present in the pleural exudate which often forms even in the rapidly fatal cases, presumably through infection spreading to the pleura from the hilus region.
Cases of interstitial pneumonia which live a longer period are accompanied by more involvement of the interstitial tissues and are relativley easy to diagnose macroscopically. The lungs of such cases are less distended and show areas of partial collapse. Areas of lobular pneumonia and of pneumonic consolidation extending from the peribronchial tissues, are always present. The bronchi show markedly thickened walls. The same type of thickening is present also along the vessels which frequently, except for the character of their lining, are indistinguishable from the bronchi. Fibrous tissue, separating lobules and groups of lobules which are involved in the process, shows marked thickening, is pale and opaque, the thickening being frequently of nodular character, due to irregular distention of the lymphatics with purulent exudate. (Plate II). All stages are seen from the acute hemorrhagic process, difficult to differentiate macroscopically, to advanced abscess formation in the interstitial tissues, accompanied by lobular and spreading bronchopneumonic consolidations, and empyema. In some instances the pneumonic consolidations are in excess, in others the interstitial reaction.
PERIBRONCHIOLAR PNEUMONIA
This is apparently the typical reaction of B. influenzae and is basically an involvement of the bronchi at their terminations in the respiratory bronchioles. At these terminal sites the infection extends to the alveoli grouped at the termi-
PLATE I
DIFFUSE, HEMORRHAGIC PNEUMONIA.
Streptococcus hemolyticus infection following influenza. Beginning consolidation. Accession 2696, Army Medical Museum. Colored photograph.
PLATE II
GENERALIZED STREPTOCOCCUS LYMPHANGITIS.
Secondary to confluent lobular pneumonia following influenza.
Accession 16646, Army Medical Museum. Colored photograph.
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nation of the bronchial radicles producing minute miliary nodules, primarily hemorrhagic, later becoming necrotic and resembling tubercles either single or in groups, at times practically uniformly consolidating the lobule, the lesion appearing more advanced centrally. (See frontispiece.)
In the acute fulminant type, which is described under Camp Devens (p. 42), practically every bronchial termination is involved and the gross picture is that of hemorrhagic inflammation. Much more frequently fewer areas are involved in the early stage and other organisms determine the majority of the terminal pictures. In the peripheral portion of such lungs, however, the lesions at the ductus alveolaris are still evident usually presenting alveoli filled with leucocytes, many of which are the large mononuclear types, while proliferative changes are practically always present and may appear advanced even in cases which died within two weeks after the clinical onset. Metaplastic types of change are seen in the bronchial epithelium even in the fulminant types of a few days' duration.
Where the patients live a longer time the bronchial inflammatory reaction becomes frankly purulent. The process originally does not involve the entire lung but is progressive, involving one portion and then a succeeding one, so that in parts of the lung the hemorrhagic type of reaction is present, in others a purulent reaction in the bronchi with secondary thickening of the wall, a loss of epithelium and an extension by continuity for greater or lesser distances in the surrounding alveoli. In such cases, the smaller bronchi and surrounding infiltration microscopically resemble nodular tubercles. The pus in such cases usually contains very numerous influenza bacilli not infrequently mixed with Gram-positive cocci, of which the most frequent is the streptococcus. With a mixture of streptococcus in which the organism is found in the peribronchial tissue, it is difficult to decide which organism preceded, as either alone may result in an interstitial reaction, while bronchi are also blocked and organizing processes occur in both varieties of infection, perhaps somewhat more frequently and rapidly in cases due to influenza bacillus. However, there is a reasonable doubt as to whether the influenza bacillus itself produces a definite interstitial reaction unless the organizing processes in areas of atelectasis are so considered.
The definitions given above appear to be necessary in order to avoid confusion. These are based on the pathological anatomy rather than on the clinical aspects of the case, because it appears that there is general agreement neither between clinicians and pathologists nor among pathologists. There was wide variation in the physical signs which clinicians considered indicative of the type of pneumonia present. An abrupt onset, with pleural pain, particularly if dullness involved most of a lobar area, was generally termed lobar pneumonia. If a crisis occurred practically all would so diagnose it. Lobar is an anatomical term, however, and depends on the pathologic anatomy of the disease. A slow onset and a termination by lysis made little difference to the diagnostician, while to many pathologists the fact that a lobe was involved to a large extent, whatever the type or variation in type of the pathological process, was sufficient to cause him to designate it as lobar pneumonia. Many of the pathologists, however, stated that any type designation was not adequate, since practically all the cases showed various types, and several preferred the term pneumonitis or
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inflammation of the lung to pneumonia, with the various qualifying terms commonly used.
Every type of acute respiratory lesion noted during the World War occurred during the influenza pandemic and in sufficient numbers to enable one roughly to classify them. The rapidly fatal type which was such a prominent and spectacular feature will be described first and illustrated, as it is considered that the lesions seen were but modified in extent, intensity, or both, in practically all cases to which the clinical diagnosis influenza was applied, while other lesions, except primary lobar pneumonia, were later complicating infections. Whether the fulminant cases were the result of the action of the bacillus of Pfeiffer or of this organism as a secondary invader, or of symbiotic action is still to be determined. The evidence even now, nine years after the pandemic, does not allow a definite answer to the important question of etiology.
LESIONS ASSOCIATED WITH INFECTION BY B. INFLUENZAE
With regard to the most numerous group-those who recovered in a few days-one may surmise a reaction less violent or less extensive than those seen in the fatal cases, but of similar type. Whether influenza is always primarily a respiratory disease or whether the infective agent may enter by other portals is not known. In the pandemic of 1918 the respiratory tract appeared always to be involved, at least in its upper portion.
Discussion of the lesions in these cases, in so far as these can be described from the Army material, follows:
Nose.- Grossly the redness, swelling, and mucous flow varied. In the earliest stages a sense of dryness and discomfort was followed by more or less profuse discharge of mucus. This might terminate the symptoms or more frequently a purulent inflammation followed. Accessory sinuses.- The ethmoids usually were involved if there were any marked lesion in the nose. The frontal sinus, maxillary antrum, and sphenoid frequently presented symptoms and at necropsy purulent inflammations of the mucous membrane lining them (one or several) were found, not infrequently accompanied by hemorrhage into the mucous membrane and exudate. The bacteriology is uncertain as so few were carefully examined. B. infIuenzae was found both early and late and the same is true for both pneumococci and streptococci. Extension of the process along the Eustachian canal and to the middle ear and involvement of the mastoid antrum in a purulent inflammation was observed with varying frequency. In the mastoid antrum bone necrosis often was observed while extension to the bones from the other sinuses was not frequent. It was more often seen in cases from which streptococcus was isolated. By bone involvement, extension occurred to the membranes of the brain both primarily and subsequent to operations on these sinuses. (Fig. 9.)
Nasopharynx.- The mucous membrane here, so far as observed, was always reddened and the lymphatic structures swollen but not often to a great degree. No tissues were described.
Tonsils.- As a whole, little early change was seen except for hyperemia, especially in the crypts, which frequently showed red injected openings. The more pronounced changes seen in the cases of clinical influenza appear to have
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been due to invasion by streptococcus and were not a part of the influenzal picture. The pillars of the fauces were reddened as was the uvula. Careful observation of the mucosa of the buccal cavity sometimes showed numerous reddened spots simulating an eruption; these were the inflamed openings of the buccal mucous glands.
Larynx.- The mucosa was swollen, reddened, and frequently showed smallerorlargerhemorrhagicinfiltrations of the superficial layers. Thecolumnar
FIG. 9.- Subdural abscess following suppurative frontal Sinusitis after influenza, Streptococcus hemolyticus. Accession number 12726, Army Medical Museum. Negative number 30804
cells were missing in some areas and the submucosa was edematous while the basement membrane was swollen and hyaline in appearance. On the surface small Gram-negative bacteria were seen and usually Gram-positive cocci having the morphology of pneumococci, streptococci, or both. In cases dying in the first few days the cellular exudate was often not abundant and contained a
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large proportion of mononuclear cells. Occasionally, even early, the exudate along the surface was distinctly purulent and frequently contained numerous minute Gram-negative bacilli with a greater or lesser mixture of Gram-positive cocci.
Ulceration had not had the opportunity to form at this early stage and when present later it was probably due to organisms other than those of the primary infection. Atria of ingress, for whatever bacteria were present, were formed as a result of the denudation of the columnar cell layer.
Trachea.-The picture here was essentially the same as in the larynx. The mucous glands of the submucosa were more or less swollen and the ducts were filled with mucinous material containing mononuclear cells and occasionally frank pus. The gland cells appeared active and, as a rule, did not show marked degeneration or many bacteria in their vicinity. Rarely a few Gram-negative, small bacilli were found in the acini nearer the mucosa. Hemorrhages into the superficial mucosa were frequent and there were usually small areas filled with red blood corpuscles about smaller vessels in the submucous zone. The tissue between the ends of the cartilaginous tracheal rings was more or less infiltrated with mononuclear cells. Nodular accumulations of lymphocytes were reported occasionally as occurring in the submucosa and some of these showed the typical area of lymphocytic accumulation normally present at the bifurcation of bronchi within the lung, including a certain amount of reticular structure and reticulum cells. Ulceration was seen in patients who survived for some time but were not reported in the acute fulminant cases and were probably due in large part to secondary invasion. (Fig. 10.)
The tracheal lymph nodes were moderately swollen, moist, and red. The peripheral sinuses were dilated with fluid containing large mononuclear cells and lymphocytes while there was a general edema and an increased number of large mononjuclear cells in the tissue. In a considerable number of cases the enlargement of these nodes was extreme. Such nodes dripped blood and serum on section ahd hemorrhages were visible. The blood vessels of small caliber showed swelling and proliferation of the intimal endothelium and capillaries were often distended by hyaline "thrombi." The large mononuclear cells had often phagtcytosed leucocytes and occasionally contained red blood corpuscles, but it was unusual to find bacteria in their cytoplasm and when found the organisms were usually in phagocytosed polymorphonuclear leucocytes.
Proliferation of the reticulum cells, particularly those of the follicles, was usual and varied greatly in amount. It was most marked in cases surviving longest. (Fig. 11.)
Thorax.- On opening the chest the appearance of the thorax was rather characteristic. The lungs filled the pleural cavities and presented a large surface overlapping the heart, and decreasing the exposed area of the pericardium.
The loose tissues of the mediastinum were edematous and occasionally contained air. The pleural cavities contained a slight excess of fluid which was either clear or blood tinged.
The parietal pleura was more or less reddened and small hemorrhages into this membrane were observed. Definite pleural exudate in these fulminant cases was usually lacking. The lungs were a deep red or purplish color with
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FIG. 11.- Cellular reaction in a bronchial lympb node in pneumonia following influenza, showing the character of the cell exudate along the reticular tissue of the node. Very few polymorphonuclear leucocytes are seen, lymphocytes are moderately numerous, while large mononuclear cells preponderate; they were evidently actively proliferating as indicated by mitotic figures. Accession number 1049, Army Medical Museum. Negative number 45170. Hematoxylin and eosin stain; X 580
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occasional flecks or small extravasations of blood beneath the serosa. The lymph nodes at the hilus were large, moist, dark in color, and dripped blood on section; occasionally minute punctate hemorrhages could be seen. The lungs showed no firm consolidation but were boggy or rubbery in consistency, crepitation though present being elicited only in slight degree. The lungs were heavy and showed, even in necropsies made within a few hours after death, a greater density in the lower and posterior portions. (Fig. 12.)
Blisterlike structures often were seen on the pleural surface, more abundant anteriorly, but small ones were scattered over the entire surface in some cases. Some of these contained fluid but the majority were filled with air.
On sectioning such lungs, a great deal of fluid welled up on the cut surface. This fluid appeared to be blood and serum mixed, the blood content varying considerably so that from some parts of the lung, particularly the anterior portions, serum predominated, while from other parts the fluid appeared to be thin, dark blood. Large quantities of fluid escaped and more could be squeezed out as from a sponge, leaving a brownish-red tissue without definite consolidation. The fluid was frothy from air admixture and this was especially true of that which bubbled up in the severed bronchi, which usually contained less blood than that from the parenchyma. The tissue, as seen after wiping off the fluid with the knife, appeared firmer than normal, and with a lens the walls of the alveoli appeared thickened. In some cases hemorrhagic consolidations, appearing like small infarcts, could be made out surrounded by the hemorrhagic edema. At the time of necropsy these areas showed little evidence of inflammatory consolidation, but after the lungs had been fixed the center of these areas showed as paler nodules of peribronchiolar consolidation surrounded by zones of hemorrhage. (Fig. 13.) Emphysema was indicated by air vesicles protruding from the surface. Although there was some variation in the intensity of the reaction, the mucosa of all the bronchi was reddened and somewhat swollen, with a velvety sheen flecked with small hemorrhages.
Primary bronchi.- The process being described appeared to extend along the respiratory passages with great rapidity. In a few hours an inflammation, apparently.starting in the nose or pharynx, would involve successively the larynx, trachea, and entire bronchial tree. Thus the bronchi showed the same type of changes seen in the trachea and because of the uniform involvement present throughouit the respiratory tract, little unchanged bronchial mucosa was seen in these fulminant cases at necropsy.
The mucus membrane, particularly of the larger bronchi, was usuallv intensely red, with a velvety sheen with occasional splashes or flecks of actual hemiorrhage. These tubes were filled with a frothy somewhat viscid mucus, tinged and streaked with blood, little exudate of a purulent nature being evident, though pus quickly appeared in the mitucuis if the patient survived for a sufficient time. Microscopically the columnar cells were swollen, many individual ones being cast off while here and there small areas of cells were raised from the basement membrane in small vesicles by fluid exudate. (Figs. 14 and 15.) It was unusual in cases dying in the first two to four days to find either grossly or microscopically complete denudation of very large areas. Suitably fixed speeimens show marked vascular engorgement particularly
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of the capillaries just beneath the mucosa, while the lymphatic network in contact with the basement membrane was markedly dilated. The mucus glands appeared active and the nuclei as a whole stained well. Cellular infiltration was not marked. The majority of the infiltrating cells were of the lymphocytic type with rather numerous large mononuclear cells with pale cytoplasm, most abundant near the basement membrane.
FIG. 13.- Postinfluenzal pneumonia. Both lobes contain numerous disseminated nodules of consolidation, most of which are surrounded by zones of hemorrage. At necropsy the pale centers did not appear, being infiltrated with blood which tsasked the dense consolidation. The lesion in the left lung was a confluent lobular pneumonia superimposed on smaller foci of consolidation about the terminal bronchioles. Pneumococcus, Group IV, was isolated, but histological sections show minute Gram-negative bacilli. Acute tracheitis and bronchitis with flecks of hemorrhage into the mucosa. Accession number 2694, Army Medical Museum. Negative number 45879
In the well-fixed material minute Grain-negative bacteria were found, free along the mucosal surface, in the blisterlike areas and engulfed, sometimes in large numbers, by the large mononuelears. (Figs. 16, 17, 18, 19, 20, 91, and 22.) These organisms were not found deep in the tissues but were seen occasionally in phagocytes at 8 to 20 cells depth (50 to 200 u) beneath the surface. The higher up the bronchial tree sections were made, the more organ-
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isms of the Gram-positive coccus type were found. These were rarely seen in the smaller tubes until later in the disease. Pus formed relatively early in the smaller bronchi and by the fifth or sixth day was usually abundant there. In tnis pus the Gram-negative bacilli were often present in enormous numbers, and as the disease continued the Gram-positive cocci increased in number as determined by stains of the tissue. (Figs. 23, 24, and 25.) These Gram- negative bacilli were not found as above described by all pathologists. They were present, however, in well-fixed tissue from all cases dying relatively early and subjected to necropsy soon after death which were examined in the studies on which this description is based.
Smaller bronchi.- The changes continued of the same intense character as seen in the larger bronchi though with less regularity. Some bronchioles showed what appeared to be earlier, or at least less intense reactions, with less cellular response, less edema and desquamation and few bacilli. These structures of the smaller type were filled with exudate containing air or open spaces as seen in the sections. (Figs. 26 and 27.) There was less casting off of the mucosa and in many in which the inflammatory reaction was less intense there was a piling up of the cells from the basal layer with a loss of the columnar type of cell and an appearance of begininng metaplastic-like change toward the stratified squamous type, even in cases the duration of which was less than a week. (Figs. 28 and 29.) Consequently, these smaller bronchi were completely plugged by viscous secretion, the plug continuing down to their terminal branches and containing fibrin strands. The tissue distal to such a block was atelectatic.
The most characteristic changes in the pulmonary inflammation being described occurred in the true lung unit of Miller.2 This unit consists of the respiratory bronchiole opening into the ductuli alveolares which terminate in more or less spherical spaces beyond a dilated extremity. These spaces or atria lead from air sacs into which open the alveoli. In addition there are some alveoli along the respiratory bronchiole and ductuli which open directly into them.
The inflammatory reaction extends along the surface of the terminal bronchiole as a serous inflammation, the secretion filling the ductus alveolaris. It also extends into the alveoli leading off directly from the bronchiolar wall and to a greater or lesser extent into the atria and alveoli. In the fulminant cases many or most of these lung units are involved with a reaction varying from a serous to a hemorrhagic type accompanied by marked congestion and little cellular infiltration, giving rise to the edematous hemorrhagic picture seen macroscopically in the lung. (Pls. III and IV.) The distribution was rarely uniform but the more uniformly the lung as a whole was affected, the less varied the picture and the more rapid the death. Microscopically the ductuli alveolares were filled with viscid albuminous fluid containing air bubbles, while the atria contained more or less air, the exudate lying along the walls of the air sacs and alveoli. (Figs. 30 and 31.) The block by the exudate at the opening of the atria into the ductus alveolaris thus caused an increased pressure in the alveoli, a factor of undoubted relationship to the rupture of alveolar walls which so commonly occurred. The air sacs and alveoli opening from one ductus were rather
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evenly involved and were often sharply defined by reason of the noninvolvement of the alveoli surrounding, and supplied by, other terminal bronchioles, though in the fulminant cases few of these terminal lung units escaped, most of them being filled with exudate mixed with air.
The exudate appeared to be viscid as it adhered along the alveolar walls as a homogeneous, eosin-staining, membranelike structure, the center of many alveoli being occupied by air. (Figs. 32 and 33.) In others a thinner serous exudate completed the filling of the alveoli as though the thin exudate had been thrown out early and was followed by the denser more viscid material which continued to adhere to the walls als a pseudomembrane. Beneath it the alveolar epithelium for the most part was lost, occasional cells and groups of cells remaining. Less of the viscid exudate was seen in alveoli the epithelium of which still remained. Fibrin stains revealed that there was little fibrin in this exudate, though occasional fibers were seen and the border of the membrane appeared more dense, stained more deeply with eosin, and reacted but slightly to the fibrin stain. The blood vessels of the alveolar wall were engorged with blood and there was escape of blood along the ductus alveolaris and about and into the alveoli. Rarely there was frank hemorrhage of considerable amount as occurred more often in lesions associated with streptococci. The hemorrhagic edema and universal vascular engorgement were responsible for the gross picture at necropsy.
The alveolar walls, due to edema and vascular engorgement, were prominent. Cellular infiltration, largely of cells of the lymphocyte type and large mononuclear cells from the tissue, was present in alveolar walls, and about the walls of the terminal bronchioles, while varying numbers were in the exudate. (Fig. 34 and Pl. V.) A frankly purulent exudate was rare in the fulminant case. The epithelium of the alveolar wall was lifted off by the exudate forming between it and the underlying reticulumn and appeared in the alveoli as single cells or small groups of cells. (Fig. 35.) The epithelium apparently formed a barrier to the egress of the exudate which, as stated above, appeared to be more abundant in alveoli, the epithelium of which had been cast off.
There are certain areas in the walls of the atria and alveoli where no capillaries are seen and special stains reveal no reticulum or very few fibers. Stains which differentiate elastic and collagen fibers reveal that such walls are made up of elastic and collagenous fibers on which rest the epithelial plates, there being a minimum of loose alveolar tissue between. The anatomical location of this type of wall suggests that there is a point of physical stress which has been reinforced by elastic fibers. These areas even in the earliest cases showed a swelling of the loose tissue beneath the epithelium which appeared to have no definite structure, and where epithelium was desquamated it merged with the exudate in the alveoli. Reticulum fibers were minimal or absent. Elastic fibers in their collagenous matrix remained as the only formed elements, the rest appearing necrotic. (Fig. 36.) At such places the ruptures of acute emphysema occurred. It would appear that though fibrous and elastic tissue was here in excess, a small vascular supply, possibly only a lymphatic supply, favored the necrosis of the tissue which, being at points of stress in the structure, yielded to the increased tension from exudate blocking plus respiratory effort. Whatever maty be the explanation, the ruptures of the walls of the air-containing tissue occurred most
PLATE III
HEMORRHAGIC EDEMA,
Beginning purulent consolidation. Minute Gram-negative bacteria were seen in smaller air passages, a few streptococci were present in purulent exudate. Accession 2696, Army Medical Museum. H. & E. stain. Autochrome.
PLATE IV
HEMORRHAGIC EDEMA, ACUTE BRONCHIECTASIS.
With beginning leucocytic infiltration of interlobular septum and alveolar walls, beginning streptococcus infection, many Gram-negative bacteria were seen along the bronchioles a few streptococci were present in bronchi and interstitial tissue.
Accession 2696, Army Medical Museum. H. & E. stain. Autochrome.
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frequently at these points. Such ruptures caused emphysemnatous areas so that the atria and alveoli of one lung unit opened into adjacent ones. (P1. VI.)
Ruptures occurring near the interlobular septa caused escape of air into this tissue. The air then extended along the septa to the pleura, giving rise to air "blisters" beneath the pleura, and by extending mesially reached the peribronchial and perivascular areolar tissues. From the latter structures access to the mediastinal tissues occurred, there being no endothelial barrier. From the mediastinal tissues to the subcutaneous tissues the air extended along vascular trunks giving rise to the cutaneous emphysema. Air may also have escaped into the interstitial tissues from rupture of the bronchioles in the acute dilatations or bronchiectases which occurred in these structures, and escaped along this interstitial tissue to the hilus in the same manner as along the septa. Several observers considered this the chief method of escape of the air which in quantity gave rise to emphysema of the mediastinal and subcutaneous tissues.
The general picture just described, was not a frequent one, but occurred occasionally throughout the period of the war. It is not distinguishable grossly from the acute fulminant cases, where apparently Streptococcus hemolyticus was the etiological agent and, in many cases, the only organism found. In the lungs of cases dying within the first 10 days to 2 weeks, and often in those of longer duration, the picture described above was present in some portion of the lung, and probably represented an extension or a reinfection occurring during the clinical course of the illness. The study of many cases who succumbed later in the course of the disease revealed the subsequent stages in this process. In such cases the amount of pulmonary tissue affected by this type of reaction varied but was usually found unaccompanied by other processes in a relatively small proportion of the lung substance. An entire lobe or more than one might thus escape; more frequently the inflammation spread along all the main bronchi but did not involve all of the terminal bronchioles, so that the foci of inflammation were separated one from the other by intervening spaces of relatively normal tissue. In other words, the bronchitis was universal but the extension to the parenchyma was in scattered foci. (Fig. 37 and P1. VII.)
By studying portions of many lungs, it is possible to portray the various stages of the process. In the lungs of cases not dying during the stage of edema, the exudate gradually became more purulent; groups and single lung units became filled with pus in which polymorphonuclear leucocytes appeared in increasing numbers. While hemorrhage and engorgement predominated the foci were, macroscopically, small nodular areas, firmer than the surrounding air-containing tissue. The number of small Gram-negative bacilli increased and the inflammation extended to a limited extent into the alveoli and air sacs of hlng units adjacent to the original process. (Figs. 38, 39, and 40.) The filling up of the air sacs and alveoli with exudate gradually caused a change in the gross picture. The nodular foci became paler and less hemorrhagic and finally a reddish or yellowish-gray color resembling submiliary tubercles from which, macroscopically, they were practically indistinguishable. (Figs. 41, 42, 43, 43, 44, 45, and 46.) Fibrin appeared in relatively small quantities and lymphocytes and large mononuclear cells formed a prominent part of the cellular exudate. Some of the large mononuclears were actively phagocytic for leucocytes
PLATE V
PERIVASCULAR ADVENTITIAL PROLIFERATION AND INFILTRATION.
Hemorrhagic peribronchiolar pneumonia. Accession 1049, Army Medical Museum. Weigert hematoxylin, picro-eosin stain. Autochrome.
PLATE VI
TWO RUPTURES IN AN ATRIAL WALL.
One of which involves the neighboring alveolus, the opposite wall of which is also ruptured. Accession 1519, Army Medical Museum. Elastic stain. Autochrome.
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and occasionally contained red blood corpuscles. Occassional ones contained several nuclei either of nuclear division without cell division or formed as the result of the fusion of several cells. (Fig. 47.) The epithelium of the trachea and bronchi proliferated and appeared in multiple layers (figs. 48, 49, and 50), the cells approaching the squamous type in morphology and in arrangement, while the epithelial cells of some of the air sacs, particularly those not filled with purulent exudate, proliferated, were distinct, and appeared more numerous than normal. (Fig. 51.)
In some instances the stratified, squamous type of epithelium extended from the bronchioles into the alveoli or else the alveolar epithelium underwent this metaplastic-like change and filled the alveoli with solid masses of sells resembling foci of carcinoma. (Figs. 52 and 53.) If no secondary infection occurred to complicate the picture, the proliferative changes continued. Large mononuclear cells which previously had been seen about the adventitia of the arteries of the terminal bronchioles increased in number, and wandered through the exudate preceding the formation of reticulum which extended out from the walls of the atria, air sacs, and alveoli and formed a network in the exudate. (Figs. 54, 55, 56, 57, 58.) Collagenous fibrils were then laid down along and between the strands of reticulum which gradually disappeared except about vessels. (Fig. 59 and P1.IX; fig. 60 and P1.X.) In the early stages reticulum was laid down in irregular lines often beaded and also formed basket-like networks around individual cells which were morphologically large mononuclears, while collagenous fibrils were laid down in more or less parallel lines between fusiform cells of the fibroblast type. (Figs. 61, 62, and 63.) In addition to the reticulum formed in the exudate this material increased in the walls of the alveoli not always surrounding additional capillaries, though it is probable that, to some extent, these were formed later, the whole appearing as a sort of granulation tissue increasing the thickness of the walls of the atria, air sacs, and alveoli. (Figs. 64, 65, and 66.)
The organizing process as seen in cases living several weeks, usually dying from other infections, appeared grossly as indurated areas not definitely nodular, extending into the tissue somewhat diffusely and rather cyanotic, like recently formed scar tissue. This organizing pneumonia or organization of pneumonic exudate which occurred with extreme rapidity was characteristic of this inflammatory process. While this organization is seen most beautifully in the air sacs and alveoli, it also occurrred in the bronchi, though there it took the form of granulation tissue extending out into the lumens of the bronchioles from the capillary network beneath the basement membrane, no remnants of the latter being visible, thus indicating its complete destruction. (Figs. 67, 68, 69, and 70.)
The process described above in the terminal lung units was accompanied by similar changes in the bronchial tree. The bronchitis which early was of a catarrhal or serous type became purulent, the mucosa was desquamated from irregular areas and the infection extended into the peribronchial tissue. In the earliest stages the limiting membrane of the submucosa or basement layer became thickened and appeared hyaline and necrotic. The capillaries which terminated their loops at this membrane appeared increased in number. Ex-
PLATE VIII
PERIBRONCHIOLAR, HEMORRHAGIC CONSOLIDATION.
Leucocytic infiltration of interlobular septa surrounded by hemorrhage. Minute Gram-negative bacteria and streptococcus forms were seen in the bronchioles, streptococci in the lymphatics of the septa.
Accession 2694, Army Medical Museum. H. & E. stain. Autochrome.
PLATE VIII
ORGANIZING PNEUMONIC PROCESS.
Alveoli lined by columnar cells. Accession 22073, Army Medical Museum. H. & E. stain. Autochrome.
PLATE IX
POST INFLUENZAL ORGANIZATION.
Accession 3036. Army Medical Museum. Reticulum stain. Autochrome.
PLATE X
POST INFUENZAL ORGANIZATION .
Accesion 1390, Army Museum. Reticulum stain. Autochrome.
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FIG. 65.- Increase in the number of capillaries in alveolar wzalls in the late stage of an interstitial inflammation of these structures, Accession number 3042, Army Medical Museum. Negative number 45564. Reticulum stain; X 255
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tension to the air cells adjacent to the bronchioles, plus the thickening of the bronchiolar wall, caused these lesions to stand out prominently on the cut section of the lung as hemorrhagic to yellowish-gray opaque foci with a central opening, the lumen of the bronchiole, the color depending on the stage of the process at death. Proliferation of fibroblasts occurred at an early period of the process in the walls of bronchi and bronchioles.
The edematous bronchial wall thus was infiltrated with granulation tissue which gradually became dense connective tissue in an amount far in excess of that normally found. The infiltrating cells in such forming tissue were predominantly lymphocytes, which were sometimes very numerous.
The smaller bronchioles showed considerable distention in all stages of the process and frequently fusiform, and irregular dilatations or bronchiectases occurred and were evidenton the gross examination of the lung. Microscopically the dilated bronchioles usually showed complete desquamation of the columnar cells; the bundles of unstriped muscles were separated by more than the normal amount of intervening tissue which was edematous, the lymph spaces being widely dilated and the collagen fibers proportionately diminished. The hyaline layer of the basement membrane was interrupted and sometimes not visible in these dilated areas. The inflammatory reaction appeared more purulent, and the bronchial wall became infiltrated with leucocytes earlier than was the case of bronchioles not so affected. The alveoli adjacent to these bronchiectases were found in a more advanced stage of inflammatory reaction than those surrounding bronchioles whose walls were still relatively intact. Increased pressure was undoubtedly present in the terminal bronchioles due to the blocking of larger air passages by the viscid exudate of the disease plus respiratory effort. The focal character of these dilatations, however, is not readily explained. The presence of more advanced inflammatory reactions at these points may be either the cause or the result of the dilatation and injury of the tube.It is probable that the patchy distribution of the bronchiolar ulceration accounts for the focal character of the lesions. Proliferation of capillaries appeared to be unusually marked about bronchiectases and the fibrosis of the healing process was responsible for further distortion of the lumens of the bronchi and bronchioles. (Figs. 71, 72, 73, and 74.)
SECONDARY BRONCHOPNEUMONIA
In few cases which died of pneumonia during the influenza epidemic and in relatively few deaths during the World War were the lesions in the lungs found to be of only one type. Pneumonic consolidation spreading out about bronchi was present in some part of the lungs in a large proportion of the fatal cases of acute respiratory disease. This lesion was associated with or produced by many different organisms; in fact, practically every organism isolated from the lungs was believed to have caused this reaction. Histologically, there were two forms of the condition both of which, however, were found associated in many lungs; these are described under the definitions.
Spreading bronchopneumonia, in so far as can be determined from the material reviewed, was a secondary type of pneumonia. In every instance where adequate histories were obtained there was abundant evidence of a preceding
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disease most often definitely diagnosed either measles or influenza. The organism found in the tissues of such cases by examining microscopical slides was morphologically most frequently a pneumococcus. From the cultural standpoint pneumococcus Group IV was the most frequent organism, pneumococcus Type II atypical, streptococci of the nonhemolytic varieties, the hemolytic streptococcus and the type pneumococci, pneumococcus Type III being distinctly more frequent than Types I and II, were recorded as present in this type of lesion.
With the exception of the lesions in which streptococci were found, the sequence of events appeared to be first, a preliminary infection, most often bronchitis, as described under the fulminant cases in which the exudate in the bronchi became more purulent, pneumococci were found in addition to Gram-negative bacilli, the wall of the bronchus was infiltrated with leucocytes, the peribronchial area frequently contained fibrin in addition to serum, while strands of fibrin were often present in the purulent exudate in the lumen of the bronchi. (Plate IX; Figs. 75, 76, 77, 78, 79, 80, 81, 82 and 83.) Inflammation extended by continuity outwards into the adjacent alveoli apparently directly across the tissues and thence by the same process involved alveoli farther separated from the bronchus. In this way smaller bronchioles were involved as well as alveoli, so that the distal portions of bronchi supplying the air sacs in the vicinity of another bronchus might be involved from without, appearing from the microscopical section to have had the process extend to them along the peribronchial tissues, the lumen and the mucosa being affected last. (Fig. 84.) This caused: some confusion and resulted in the diagnosis of an interstitial type of reaction as the result of studying small microscopical sections when the actual process was an extension by continuity from purulent inflammation within another. bronchus.
Macroscopically, the lungs were more voluminous than normal, collapsing to a greater or less degree, depending upon the amount of tissue involved in the consolidation. Early in the process the periphery of the lung was sometimes free of involvement; more often it presented nodular areas which projected above the surface of the rest of the lung, the latter being somewhat collapsed, as the result of opening the chest cavity. The pleural surface of such areas usually was covered with a fibrinous exudate, which later in the process extended to the rest of the pleura and still later terminated in empyema, the organism present being that found in the tissue or, in lesions due to other organisms than the hemolytic streptococcus, that organism was usually found as well. Streptococcus also appeared alone in such cases, having reached the pleura and involved it possibly before the consolidation caused by other organisms had reached the periphery.
On section, the parts of lung affected by this process varied in their consistency. If caused by the pneumococcus they were usually firmer than normal, and sometimes distinctly dry, presenting reactions much like that of lobar pneumonia, though more frequently, as the result of there being less fibrin in the exudate, the consolidation was more elastic and less fragile. The more dense consolidation was near the bronchi and toward the hilus of the lung where several bronchi and their surrounding consolidations made one pneumonic mass.
