Pneumococcus I and II, which are found a_Epidemic Respiratory Disease The pneumonias and other infections of the repiratory tract accompanying influenza and measles

instances of lobar pneumonia occurring in cities, have an insignificant

part in the production of these lesions. Pneumococcus IV and atypical

Pneumococcus II, which are commonly found in the mouth, are the

predominant cause of these lesions, and with Pneumococcus III, also an

inhabitant of the mouths of normal individuals, have been the cause of

two-thirds of all instances of lobar pneumonia observed in this camp.

TABLE XXXII

WITH LOBAR PNEUMONIA

════════╤════════╤═════════════════╤═════════════════╤═════════════════

│ NO. OF │ │ │ PNEUMOCOCCUS II

│CULTURES│ PNEUMOCOCCUS I │ PNEUMOCOCCUS II │ (Atyp.)

────────┼────────┼────────┬────────┼────────┬────────┼────────┬────────

│ │ NO. │PER CENT│ NO. │PER CENT│ NO. │PER CENT

│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE

────────┼────────┼────────┼────────┼────────┼────────┼────────┼────────

Bronchus│ 30│ 1│ 3.3│ 1│ 3.3│ 4│ 13.3

Lung │ 34│ 1│ 2.9│ 2│ 5.9│ 9│ 26.5

Blood │ 54│ 2│ 3.7│ 2│ 3.7│ 12│ 22.2

────────┴────────┴────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════

│ │

│PNEUMOCOCCUS III │ PNEUMOCOCCUS IV

────────┼────────┬────────┼────────┬────────

│ NO. │PER CENT│ NO. │PER CENT

│POSITIVE│POSITIVE│POSITIVE│POSITIVE

────────┼────────┼────────┼────────┼────────

Bronchus│ 4│ 13.3│ 10│ 33.3

Lung │ 6│ 17.6│ 11│ 32.4

Blood │ 3│ 5.6│ 17│ 31.5

────────┴────────┴────────┴────────┴────────

WITH COMBINED LOBAR AND BRONCHOPNEUMONIA

│ NO. OF │ │ │ PNEUMOCOCCUS II

│CULTURES│ PNEUMOCOCCUS I │ PNEUMOCOCCUS II │ (Atyp.)

│ │ NO. │PER CENT│ NO. │PER CENT│ NO. │PER CENT

│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE

Bronchus│ 14│ 2│ 14.3│ 1│ 7.1│ 3│ 21.4

Lung │ 19│ 1│ 5.3│ │ │ 5│ 26.3

Blood │ 33│ 2│ 6.1│ 3│ 9.1│ 4│ 12.1

════════╤═════════════════╤═════════════════

│ │

│PNEUMOCOCCUS III │ PNEUMOCOCCUS IV

────────┼────────┬────────┼────────┬────────

│ NO. │PER CENT│ NO. │PER CENT

│POSITIVE│POSITIVE│POSITIVE│POSITIVE

────────┼────────┼────────┼────────┼────────

Bronchus│ │ │ 3│ 21.4

Lung │ │ │ 6│ 31.6

Blood │ │ │ 12│ 36.4

────────┴────────┴────────┴────────┴────────

There is no noteworthy difference in the occurrence of these types of

pneumococci among instances of lobar pneumonia, on the one hand, and of

combined lobar and bronchopneumonia, on the other. Different types

exhibit no noteworthy differences in their ability to penetrate into

lungs and blood.

=Hemolytic Streptococcus with Lobar Pneumonia.=—There can be no doubt

that the concurrent infection with microorganisms other than

pneumococcus modifies the progress of lobar pneumonia. With lobar

pneumonia alone hemolytic streptococci have entered the bronchi in 30

per cent of instances and have penetrated into the lungs in 20.6 per

cent; with associated lobar and bronchopneumonia the same microorganism

has entered the bronchi in 34.3 per cent of instances and invaded the

lung in 31.6 per cent. Hemolytic streptococci are the only

microorganisms other than pneumococci which, in association with lobar

pneumonia, have found their way from the lungs to the blood stream; more

than one-third of all instances of lobar pneumonia in which hemolytic

streptococci find entrance into the bronchi die with streptococcus

septicemia.

Separation of instances of lobar pneumonia into groups on the basis of

the occurrence of red or gray hepatization shows that infection with

hemolytic streptococcus is more likely to occur during the early stages

of the disease. The average duration of lobar pneumonia with red

hepatization has been 3.7 days, with red and gray hepatization, 5.1

days, and with gray hepatization, 7.5 days. Infection with hemolytic

streptococcus has occurred in association with red or gray hepatization

as shown in Table XXXIII.

TABLE XXXIII

═════════════════════════════╤═════════════╤═════════════╤═════════════

│ │ NO. WITH │PER CENT WITH

│ NO. OF │ HEMOLYTIC │ HEMOLYTIC

│ AUTOPSIES │STREPTOCOCCUS│STREPTOCOCCUS

─────────────────────────────┼─────────────┼─────────────┼─────────────

Lobar pneumonia with red │ │ │

hepatization │ 16│ 6│ 37.5

Lobar pneumonia with red and │ │ │

gray hepatization │ 28│ 6│ 21.4

Lobar pneumonia with gray │ │ │

hepatization │ 20│ 1│ 5.0

─────────────────────────────┴─────────────┴─────────────┴─────────────

Notwithstanding the longer duration of the disease and consequent

prolongation of exposure to infection, lobar pneumonia, which has

reached the stage of gray hepatization, has shown the smallest incidence

of infection with hemolytic streptococci. In the stage of gray

hepatization there is diminished susceptibility to secondary infection

with this microorganism.

Characteristic histologic changes have been found in the lungs of those

who have died with lobar pneumonia followed by invasion of lungs and

blood by hemolytic streptococci (_e. g._, Autopsies 273, 430), but with

no evidence of suppuration found at autopsy. Within the pneumonic lung

occur patches of necrosis implicating both exuded cells and alveolar

walls; in some places nuclei have disappeared; elsewhere nuclear

fragments are abundant. In these patches of necrosis Gram-positive

streptococci in short chains occur in immense number. In some instances

(_e. g._, Autopsies 273, 346, 479) interlobular septa are very edematous

and often contain a network of fibrin; lymphatics are dilated and

contain polynuclear leucocytes in abundance. Streptococci are found

within these lymphatics. The histologic changes which have been

described represent the earliest stages of abscess formation and

interstitial suppuration, lesions almost invariably caused by hemolytic

streptococci.

[Illustration:

Chart 2.—Showing the relation of (_a_) date of onset of cases in which

autopsy demonstrated lobar pneumonia, indicated by upper continuous

line with single hatch, and of (_b_) date of death of these cases,

indicated by lower continuous line with double hatch to (_c_) the

occurrence of influenza, indicated by the broken line, and to (_d_)

the total number of fatal cases of pneumonia, indicated by the

broken dotted line. Each case of fatal pneumonia is indicated by one

division of the scale as numbered on the left of the chart; cases of

influenza are indicated by the numbers on the right of the chart.

]

=Relation of Lobar Pneumonia to Influenza.=—Some writers have suggested

that lobar pneumonia, heretofore observed during the course of epidemics

of influenza, is an independent disease with no relation to influenza,

both diseases being referable perhaps to similar meteorologic or other

conditions. Chart 2, which shows by weeks from September 1 to October 31

the relation of deaths from lobar pneumonia (indicated by double hatch)

to deaths from all forms of pneumonia, disproves this suggestion. The

two curves follow parallel courses; that representing lobar pneumonia

reaches a maximum approximately one week after the outbreak of influenza

had reached its height. Lobar pneumonia, like other forms of pneumonia,

was secondary to influenza. When a chart is plotted to represent the

dates of onset of fatal cases of lobar pneumonia (indicated by single

hatch in Chart 2), it becomes evident that the greatest number of these

cases of pneumonia had their onset at the beginning of the influenza

epidemic, approximately one week before it reached its height. Fatal

lobar pneumonia developed less frequently in the latter part of the

epidemic; to obtain an explanation of this relation it is necessary to

chart separately cases of lobar pneumonia with secondary streptococcus

infection, for we have already learned that streptococcus infection was

the predominant cause of death in the early period of the influenza

epidemic. Exclusion of these instances of secondary streptococcus

infection makes no noteworthy change in the character of the chart.

Fatal lobar pneumonia, like all forms of fatal pneumonia (p. 140), was

more frequent in the first half than in the second half of the epidemic.

This difference is referable either to greater virulence of the virus of

influenza or to the greater susceptibility of those first selected by

the disease or, as more probable, to conditions such as crowding

together of patients with influenza, favoring the transmission of

microorganisms which cause pneumonia.

Bronchopneumonia

For the purpose of the present study it is convenient to group together

instances of bronchopneumonia which have been unaccompanied, on the one

hand, by lobar pneumonia (p. 155) or, on the other hand, by suppuration,

which with few exceptions is caused by hemolytic streptococci or by

staphylococci. A group of cases in which lobar and bronchopneumonia have

occurred in the same individual have already been considered. In many

instances, bronchopneumonia is accompanied by abscess formation or by

some other form of suppuration; these lesions will be discussed

elsewhere.

Bronchopneumonia unaccompanied by lobar pneumonia or by suppuration

occurred in 80 autopsies.

Pneumonic consolidation distributed with relation to the bronchi

exhibits considerable variety, and an attempt to define a type of

bronchopneumonia characteristic of influenza would be futile.

Nevertheless, the bronchopneumonia of influenza has in many instances

distinctive characters.

Lesions of bronchopneumonia which are frequently found in the autopsies

under consideration may be conveniently designated by descriptive terms,

indicative of their location in the lung tissue. These lesions, of which

two or more often occur in the same lung, are:

1. Peribronchiolar consolidation with which the inflammatory exudate is

limited to the alveoli in the immediate neighborhood of the bronchioles.

2. Hemorrhagic peribronchiolar consolidation in which gray patches of

peribronchiolar pneumonia occur upon a deep red background produced by

hemorrhage into alveoli. Pfeiffer believed that this lesion was

characteristic of influenza.

3. Lobular consolidation with which consolidation is limited to lobules

or groups of lobules.

4. Peribronchial pneumonia with which small bronchi are encircled by

pneumonic consolidation.

Each one of these lesions will be discussed separately.

Following is a list of the bacteria which have been isolated from the

consolidated lung of individuals with bronchopneumonia unaccompanied by

lobar pneumonia or by suppuration:

B. influenzæ 1

Pneumococci 5

S. hemolyticus 5

S. viridans 1

B. influenzæ, pneumococci 9

B. influenzæ, S. hemolyticus 4

B. influenzæ, staphylococci 4

Pneumococci, S. hemolyticus 1

Pneumococci, staphylococci 2

S. hemolyticus, staphylococci 1

S. hemolyticus, B. coli 1

Staphylococci, S. viridans 1

Staphylococci, B. coli 1

B. influenzæ, pneumococci, staphylococci 1

B. influenzæ, pneumococci, S. viridans 1

B. influenzæ, S. hemolyticus, staphylococci 2

B. influenzæ, pneumococci, staphylococci, S. viridans 1

No microorganisms found 6

——

The similarity of this list to that representing the bacteriology of

bronchitis is evident; there is the same multiplicity of microorganisms

and the frequent occurrence of mixed infections. B. influenzæ is much

less frequently found in the lung. The relative pathogenicity of the

large group of microorganisms enumerated above is better indicated by

the following list which shows what microorganisms have penetrated into

the blood in autopsies performed on individuals with bronchopneumonia:

Pneumococci 20

S. hemolyticus 23

S. viridans 1

Pneumococci, S. hemolyticus 2

No bacteria found 25

——

Total 71

Table XXXIV shows the percentage incidence of pneumococcus, hemolytic

streptococcus, staphylococcus and B. influenzæ in the bronchi, lungs and

blood and is inserted for comparison with the similar table (Table XXX)

showing the incidence of these bacteria in lobar pneumonia.

TABLE XXXIV

════════╤════════╤═════════════════╤═════════════════

│ NO. OF │ │ HEMOLYTIC

│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI

────────┼────────┼────────┬────────┼────────┬────────

│ │ NO. │PER CENT│ NO. │PER CENT

│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE

────────┼────────┼────────┼────────┼────────┼────────

Bronchus│ 37│ 19│ 48.6│ 13│ 35.1

Lung │ 47│ 20│ 42.6│ 14│ 29.8

Blood │ 70│ 22│ 31.4│ 24│ 34.3

────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════

│ │

│ STAPHYLOCOCCI │ B. INFLUENZÆ

────────┼────────┬────────┼────────┬────────

│ NO. │PER CENT│ NO. │PER CENT

│POSITIVE│POSITIVE│POSITIVE│POSITIVE

────────┼────────┼────────┼────────┼────────

Bronchus│ 22│ 59.5│ 28│ 75.7

Lung │ 13│ 27.7│ 23│ 48.9

Blood │ │ │ │

────────┴────────┴────────┴────────┴────────

Table XXXIV shows that pneumococci have a less important part in the

production of broncho than of lobar pneumonia; with lobar pneumonia this

microorganism was found in the lungs in 77.3 per cent of instances and

in the blood, in 65.5 per cent, whereas with bronchopneumonia it was

found in the lungs in 42.6 per cent and in the blood in 31.4 per cent.

Hemolytic streptococci (in lungs and blood) and staphylococci (in

lungs), on the contrary, were more common with bronchopneumonia, and

doubtless have a part in the production of the lesion. Streptococcus

viridans, B. coli and M. catarrhalis, which are not infrequently found

in the bronchi (p. 151), occasionally enter the lungs with

bronchopneumonia but are rarely found with lobar pneumonia. B. influenzæ

has been found in less than 80 per cent of instances in the bronchi and

in about half of the lungs, maintaining an incidence approximately the

same as that with lobar pneumonia.

Table XXXV shows the types of pneumococci found in association with

bronchopneumonia and is inserted for comparison with the similar table

(Table XXXII) showing types of pneumococci with lobar pneumonia.

With broncho as with lobar pneumonia pneumococci commonly found in the

mouth, namely, atypical II, and Types III and IV, have a more important

part in production of the lesion than the so-called fixed types, I and

II. Atypical Pneumococcus II has been less frequently encountered with

broncho than with lobar pneumonia.

TABLE XXXV

│ NO. OF │ │ │ PNEUMOCOCCUS II

│CULTURES│ PNEUMOCOCCUS I │ PNEUMOCOCCUS II │ (Atyp.)

│ │ NO. │PER CENT│ NO. │PER CENT│ NO. │PER CENT

│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE

Bronchus│ 37│ 1│ 2.7│ 3│ 8.1│ │

Lung │ 47│ 2│ 4.3│ 2│ 4.3│ 2│ 4.3

Blood │ 70│ 1│ 1.4│ 1│ 1.4│ 5│ 7.1

════════╤═════════════════╤═════════════════

│ │

│PNEUMOCOCCUS III │ PNEUMOCOCCUS IV

────────┼────────┬────────┼────────┬────────

│ NO. │PER CENT│ NO. │PER CENT

│POSITIVE│POSITIVE│POSITIVE│POSITIVE

────────┼────────┼────────┼────────┼────────

Bronchus│ │ │ 14│ 37.8

Lung │ 2│ 4.3│ 12│ 25.2

Blood │ 4│ 5.7│ 11│ 15.9

────────┴────────┴────────┴────────┴────────

=Peribronchiolar Consolidation.=—In many instances of bronchopneumonia,

usually in association with lobular or confluent consolidation, small

firm nodules of consolidation are clustered about the bronchioles (Fig.

2). These nodular foci of consolidation are usually 1.5 to 2 mm. in

diameter, being sometimes slightly smaller or slightly larger. They are

usually gray and occasionally surrounded by a red halo; sometimes they

are yellowish gray. They are clustered about the smallest bronchial

tubes to form groups which are from 0.5 to 1 cm. across. A group of

nodular foci of consolidation occupies the central part of a lobule of

lung tissue. When pneumonia has been of short duration these foci are

fairly soft and not sharply defined, and in many instances this form of

bronchopneumonia is first recognized by microscopic examination. When

the disease has lasted from ten days to two weeks, the consolidated

nodules are very firm and sharply circumscribed, closely resembling

tubercles. When they have assumed this character, microscopic

examination shows that chronic changes indicated by new formation of

interstitial tissue have occurred.

The lesion may be designated peribronchiolar consolidation. It has

occurred usually in association with other types of pneumonic lesion in

61 instances, being recognized at autopsy in 18 and by microscopic

examination in 43.

[Illustration:

Fig. 2.—Acute bronchopneumonia with nodules of peribronchiolar

consolidation and purulent bronchitis. Autopsy 429.

]

In association with this lesion there are almost invariably severe

lesions of the bronchi. Purulent bronchitis was noted in 47 of the 61

instances, in which this nodular bronchopneumonia was found at autopsy.

An index of the severity of the bronchial injury is the frequency with

which bronchiectasis has occurred; dilatation of small bronchi was

observed in 24 instances. In 10 instances the bronchi were encircled by

conspicuous zones of hemorrhage.

In association with this peribronchiolar lesion the lung is often

voluminous and fails to collapse on removal from the chest. Pressure

upon the lung squeezes from the smallest bronchi, both in the

neighborhood of the nodular consolidation and elsewhere, a droplet of

viscid, semifluid mucopurulent material. The presence of this tenacious

material throughout the small bronchi doubtless explains the failure of

the lung tissue to collapse. Interstitial emphysema has been present in

some of these lungs.

A red zone of hemorrhage has occasionally been observed about the foci

of peribronchiolar pneumonia. A further stage in the same process is

represented by hemorrhage into all of the alveoli separating these

patches of consolidation. This hemorrhagic lesion, which will be

described in more detail later, has been found repeatedly in the same

lung with peribronchiolar pneumonia, being present in 8 among the 61

autopsies cited. Lobular bronchopneumonia accompanied the

peribronchiolar lesion 27 times and lobar pneumonia accompanied it 20

times.

When an abscess caused by hemolytic streptococcus is associated with

peribronchiolar pneumonia, empyema is present, but otherwise pleurisy is

absent or limited to a scant fibrinous exudate.

[Illustration:

Fig. 3.—Acute bronchopneumonia with peribronchiolar consolidation; a

respiratory bronchiole partially lined by columnar epithelium passes

into alveolar duct and the adjacent alveoli are filled by

polynuclear leucocytes. Autopsy 333.

]

Histologic examination demonstrates very clearly the relation of this

lesion to the bronchioles (Fig. 3). These passages are filled and

distended with an inflammatory exudate consisting almost entirely of

polynuclear leucocytes. The respiratory bronchioles are beset with

alveoli often limited to one side of the tubule and these alveoli are

filled with leucocytes. The alveolar ducts, distinguishable from the

bronchioles by the absence of columnar or cubical epithelium and by

possession of smooth muscle, are similarly filled with leucocytes; the

numerous alveoli which form the walls of the alveolar ducts are

distended by an inflammatory exudate. In sections which pass through an

alveolar duct and one or more of its infundibula, the further extension

of the lesion may be determined (Fig. 4). The infundibulum in proximity

with the alveolar duct contains polynuclear leucocytes and the same

cells are seen in the alveoli which here form its wall, but the

intensity of the inflammatory reaction diminishes toward the periphery,

so that the distal part of the infundibulum, which is much distended and

in consequence more readily definable than usual, is free from

inflammatory exudate.

[Illustration:

Fig. 4.—Acute bronchopneumonia with peribronchiolar consolidation; a

respiratory bronchiole is in continuity with an alveolar duct and

two distended infundibula; alveoli about bronchiole, alveolar duct

and proximal part of infundibula contain polynuclear leucocytes, the

distal part of the infundibula showing no evidence of inflammation.

Autopsy 333.

]

Occasionally there is irregularly distributed hemorrhage and perhaps

some edema in the alveoli immediately adjacent to those which form the

peribronchiolar focus of inflammation. In such instances small bronchi,

that is, air passages, lined by columnar epithelium and devoid of

tributary alveoli, may be surrounded by a zone of hemorrhage;

immediately surrounding the bronchus, the wall of which shows intense

inflammation, alveoli, in a zone of which the radius represents several

alveoli, are filled with blood. This hemorrhagic zone is continued from

the bronchus over the focus of inflammation which surrounds the

bronchiole.

Another variation in the character of the lesion is doubtless referable

to variation in the severity of primary bronchial injury. Alveoli

immediately surrounding small bronchi are filled with dense plugs of

fibrin. The alveoli which besot the walls of the bronchioles contain

fibrin, but the alveolar duct and its tributary alveoli are filled with

polynuclear leucocytes.

The bacteria which have been cultivated from the lung in autopsies with

peribronchiolar pneumonia are as follows:

Pneumococcus 5

S. hemolyticus 8

B. influenzæ, pneumococcus 5

B influenzæ, S. hemolyticus 7

B. influenzæ, staphylococcus 1

Pneumococcus, staphylococcus 2

S. hemolyticus, staphylococcus 2

B. influenzæ, pneumococcus, S. hemolyticus 2

B. influenzæ, pneumococcus, staphylococcus 1

B. influenzæ, S. hemolyticus, staphylococcus 2

Pneumococcus, S. hemolyticus, staphylococcus 3

No organism 3

——

Total 41

The following list which shows the bacteria found in the blood is an

index to the pathogenicity of pneumococci and hemolytic streptococci:

Pneumococcus 22

S. hemolyticus 20

Pneumococcus, S. hemolyticus 1

No organism 14

——

Total 57

The percentage incidence of pneumococcus, hemolytic streptococcus,

staphylococcus and B. influenzæ in bronchus, lung and blood, given in

Table XXXVI, is inserted to indicate with what readiness each one of

these microorganisms passes from the bronchus through the lung into the

circulating blood.

TABLE XXXVI

══════════════╤═════════════╤═════════════╤══════════════╤═════════════

│PNEUMOCOCCUS │ HEMOLYTIC │STAPHYLOCOCCUS│B. INFLUENZA

│ │STREPTOCOCCUS│ │

──────────────┼─────────────┼─────────────┼──────────────┼─────────────

Bronchus │ 39.4%│ 57.7%│ 60.6%│ 84.8%

Lung │ 43.9%│ 61.0%│ 21.9%│ 43.9%

Blood │ 40.3%│ 36.8%│ 0. %│ 0. %

──────────────┴─────────────┴─────────────┴──────────────┴─────────────

B. influenzæ is present in the bronchi in a very large proportion (84.8

per cent) of those in whom this type of bronchopneumonia has been found

at autopsy; it is much less frequently recovered from the lungs.

Staphylococci, in part S. albus and in part S. aureus, are less

frequently found in the bronchi and are recovered from the lungs in a

relatively small proportion of autopsies. The percentage incidence of

pneumococci and streptococci in lungs and blood demonstrates the

pathogenicity of these microorganisms, for whereas pneumococci and

hemolytic streptococci are found in the consolidated lungs in 43.9 and

61.0 per cent of instances of the lesion respectively, they make their

way into the blood in 40.3 and 36.8 per cent of instances.

Coexisting infection with pneumococci and hemolytic streptococci has

been not uncommon e. g., Autopsy 275 in which both were in the blood; in

2 instances (Autopsies 333 and 378) in which pneumococci were obtained

from the blood, hemolytic streptococci were found in the lungs and

bronchi; in 3 instances (Autopsies 258, 273 and 445) in which hemolytic

streptococci were present in the blood, pneumococci were obtained from

the lungs.

In the group of autopsies under consideration, examination of the sputum

was made during life and after onset of pneumonia in 11 instances. The

microorganisms found in the sputum and at autopsy were as follows:

SPUTUM IN BLOOD, LUNGS OR BRONCHUS

AT AUTOPSY

Autopsy 240 Pneum. IV Pneum. IV

246 Pneum. atyp. II, B. inf.

247 Pneum. IV, B. inf. Pneum. IV

250 Pneum. atyp. II, B. inf. Pneum. atyp. II

253 Pneum. atyp. II Pneum. II

285 Pneum. atyp. II, B. Inf. S. hem., B. inf.

288 S. hem., B. inf. S. hem., B. inf.

291 Pneum. IV, B. inf. Staph., B. inf.

300 Pneum. atyp. II, B. inf. Pneum. atyp. II, B. inf.

312 Pneum. IV, S. hem., B. inf. S. hem., B. inf.

346 Pneum. IV, B. inf. S. hem., B. inf.

In 2 instances (Autopsies 285 and 346) among this small group of cases,

pneumococci but no hemolytic streptococci were found in the sputum

several days before death, whereas death occurred as the result of

secondary invasion with hemolytic streptococci and no pneumococci were

found at autopsy. It is probable that this sequence of events is not

uncommon. B. influenzæ finds its way into the bronchi and pneumococci

follow it; pneumonia limited to peribronchiolar alveoli may occur in

consequence of this invasion. Later hemolytic streptococci may follow

the same path and cause death with bacteremia.

=Hemorrhagic Peribronchiolar Consolidation.=—Peribronchiolar pneumonia

accompanied by diffuse accumulation of blood within the alveoli is one

of the most frequent complications of influenza. The lung tissue is

laxly consolidated, and on section there is a homogeneous dull deep red

background upon which are seen small gray spots (1.5 to 2 mm. in

diameter) grouped in clusters about the smallest bronchi (Fig. 5). Wide

areas of lung tissue are implicated and the lesion is more common in the

dependent parts of the lung than elsewhere. In common with other forms

of bronchopneumonia the lesion is in most instances associated with

changes in the bronchi; in 55 instances of hemorrhagic bronchiolar

pneumonia purulent bronchitis was found in 43 instances; it is

noteworthy that purulent bronchitis often is not evident in the presence

of pulmonary edema and edema is not infrequent with this pneumonic

lesion.

Microscopic examination demonstrates the presence of acute bronchitis;

the lumina of the small bronchi contain polynuclear leucocytes and red

blood corpuscles. Accumulation of blood may separate the epithelium from

the basement membrane. The mucosa immediately below the epithelium

contains polynuclear leucocytes in fair abundance and the blood vessels

of the bronchial wall are much engorged. Respiratory bronchioles are

distended with polynuclear leucocytes and red blood corpuscles. In a

zone about each bronchiole, in areas corresponding to the small gray

spots seen upon the cut surface of the lung, the alveoli are filled with

polynuclear leucocytes. In the lung tissue intervening between these

spots of leucocytic pneumonia the alveoli are distended with red blood

corpuscles.

[Illustration:

Fig. 5.—Bronchopneumonia with hemorrhagic peribronchiolar

consolidation.

]

In favorable sections it is occasionally possible to follow the

bronchiole and alveolar duct, both filled with leucocytes, into an

infundibulum. The proximal part of the infundibulum contains polynuclear

leucocytes, whereas the distal part and its tributary alveoli are filled

with serum and red blood corpuscles.

When the lesion has persisted for a short time there is evidence of

beginning migration of polynuclear leucocytes from the blood vessels

into the alveoli which are filled with blood. The alveolar walls contain

numerous polynuclear leucocytes and leucocytes which have entered the

intraalveolar blood are numerous in contact with the wall but occur in

scant number in the center of the alveolar lumen.

Alveolar epithelium in contact with the blood in the lumen is usually

swollen and often uniformly nucleated.

The inflammatory process is evidently transmitted from the bronchioles

and to a less degree from the small bronchi to the adjacent alveoli.

Polynuclear leucocytes fill the lumen of the bronchiole and the alveoli

immediately adjacent; at the periphery of the focus of pneumonia, the

alveoli may contain fibrin. In such instances small bronchi (lined by a

continuous layer of columnar epithelial cells) may be surrounded by

alveoli containing fibrin.

In sections from one part of the lung, the alveoli between the

peribronchiolar foci of pneumonia may be uniformly filled with red blood

corpuscles, whereas in sections from another part pneumonic foci may be

surrounded by a zone of intraalveolar hemorrhage or of hemorrhage and

edema outside of which some air-containing tissue occurs. There are

transitions between this halo of intraalveolar hemorrhage and edema

surrounding each bronchiolar focus and complete hemorrhagic infiltration

of all intervening alveoli.

Large mononuclear cells are occasionally fairly numerous within the

alveoli containing blood. These cells act as phagocytes ingesting red

corpuscles, so that at times they are filled with corpuscles.

Disintegration of red corpuscles occurs and brown pigment remains within

the cell. It is not uncommon to find numerous mononuclear pigment

containing cells which resemble those found with chronic passive

congestion of the lungs.

Lungs, the site of hemorrhagic peribronchiolar pneumonia, may undergo

chronic changes which will be described elsewhere.

The lesion which has been designated hemorrhagic peribronchiolar

pneumonia is that which Pfeiffer regarded as the characteristic type of

influenzal pneumonia. In the small bronchi containing pus and in lung

tissue, Pfeiffer states, influenza bacilli are predominant and present

in astonishing number in smear preparations. The demonstration of B.

influenzæ by cultures from pneumonic lung is mentioned by him but its

association with other microorganisms in such cultures is not discussed.

Microorganisms which we have isolated from the lungs of individuals with

hemorrhagic peribronchiolar pneumonia are as follows:

B. influenzæ 1

Pneumococcus 2

S. hemolyticus 10

B. influenzæ, pneumococcus 7

B. influenzæ, S. hemolyticus 3

B. influenzæ, staphylococcus 2

S. hemolyticus, B. coli 3

B. influenzæ, pneumococcus, staphylococcus 2

B. influenzæ, S. hemolyticus, staphylococcus 5

Pneumococcus, S. hemolyticus, staphylococcus 1

No organisms 2

——

Total 38

With this type of pneumonia B. influenzæ has not been isolated in pure

culture; B. influenzæ alone is recorded only once (Autopsy 435), but in

this instance the culture has been so obscured by contamination that the

occurrence of pneumococci or streptococci cannot be excluded; S.

hemolyticus has doubtless been present in this lung, for it has been

found in the heart’s blood, in the bronchus, and in the peritoneal

exudate of the same individual.

The incidence of pneumococci and hemolytic streptococci in this list

does not differ materially from that with peribronchiolar pneumonia

unaccompanied by extensive intraalveolar hemorrhage, though hemolytic

streptococci are somewhat more frequent with the hemorrhagic lesion. The

following table shows the frequency with which pneumococci and hemolytic

streptococci have penetrated into the blood:

Pneumococcus 11

S. hemolyticus 24

Pneumococcus, S. hemolyticus 1

No organism 12

——

Total 48

Table XXXVII showing the percentage incidence of pneumococci, hemolytic

streptococci, staphylococci and B. influenzæ further emphasizes the

similarity between the bacteriology of peribronchiolar pneumonia (Table

XXXVI) and the closely related hemorrhagic lesion:

TABLE XXXVII

│ │ HEMOLYTIC │ │

│PNEUMOCOCCUS │STREPTOCOCCUS│STAPHYLOCOCCUS│B. INFLUENZÆ

Bronchus │ 44.0%│ 64.0%│ 44.0%│ 72.0%

Lung │ 31.6%│ 57.9%│ 26.8%│ 52.6%

Blood of heart│ 25.0%│ 52.1%│ 0%│ 0%

Pneumococci have been found in the lungs (31.6 per cent) and blood (25

per cent), somewhat less frequently than with peribronchiolar pneumonia

(43.9 and 40.3 per cent respectively), and hemolytic streptococci have

been found in the blood more frequently (52.1 per cent) than with the

latter (36.8 per cent) but otherwise the bacteriology of the two lesions

corresponds closely. The low incidence of B. influenzæ in the bronchi

(72 per cent) with hemorrhagic peribronchiolar pneumonia is perhaps

incorrect as the result of the relatively small number of bacteriologic

examinations (namely, 25), but the incidence of the same microorganism

in the lung has been higher (52.6 per cent) than with nonhemorrhagic

peribronchiolar lesion (43.9 per cent).

In some instances infection with hemolytic streptococci has occurred

after the onset of pneumonia. The following list compares the results of

bacteriologic examination of the sputum made after the onset of

pneumonia with that of blood, lungs or bronchus after death:

SPUTUM IN BLOOD, LUNGS OR BRONCHUS

AT AUTOPSY

Autopsy 237 S. hem. S. hem.

242 Pneum. atyp. II, B. inf. Pneum. atyp. II

247 Pneum. IV, B. inf. Pneum. IV

266 S. hem. S. hem., B. inf.

346 Pneum. IV, B. inf. S. hem., B. inf.

376 (No. S. hem.) S. hem., staph., B. inf.

Instances of secondary infection with hemolytic streptococcus occur in

the list, namely, Autopsies 346 and 376.

From the foregoing studies of the bacteriology of peribronchiolar and

hemorrhagic peribronchiolar pneumonia the following conclusions may be

drawn: (_a_) B. influenzæ is found in most instances of these lesions in

the bronchi and in about half of all instances in the lungs, but does

not occur unaccompanied by other microorganisms. (_b_) In a considerable

number of autopsies pneumococcus is the only microorganism that

accompanies B. influenzæ; from the lungs it penetrates into the blood

from which it is obtained in pure culture. (_c_) In a considerable

number of instances S. hemolyticus accompanies B. influenzæ, and in some

of these instances (representing a large proportion of the relatively

small number of cases examined during life), examination of the sputum

has demonstrated that infection has been secondary to a pneumonia with

which no hemolytic streptococci have been found in the sputum.

=Lobular Consolidation.=—Consolidation of scattered lobules or groups of

lobules has occurred in nearly all instances, namely, 71 of 80 autopsies

with bronchopneumonia unaccompanied by lobar pneumonia or by

suppuration. When death follows shortly after the onset of pneumonia,

patches of consolidation have a dull deep red color; blood-tinged fluid

escapes from the cut surface which is almost homogeneous or finely

granular. The consolidated tissue seen through the pleura, which is

raised above the general level, has a bluish red color. Isolated lobules

or groups of lobules which have undergone consolidation may be scattered

throughout the lungs, but not infrequently there is confluent

consolidation of the greater part of lobes, of whole lobes or of almost

an entire lung. Such lungs are very heavy and may weigh 1,400 or 1,500

grams; bloody serous fluid exudes from the cut surface. The lesion

resembles the red hepatization of lobar pneumonia, but confluent patches

of pneumonia are usually well defined by lobule boundaries. The tissue

is soft and the granulation of lobar pneumonia is absent. In many

instances the lobular or confluent areas of consolidation are reddish

gray; in some instances consolidated tissue is in places red and

elsewhere gray, and in a smaller group of autopsies there is gray

consolidation only (Fig. 6). Red lobular consolidation is often seen in

those who have died within the first four days following the onset of

pneumonia, but is almost equally frequent after from five to ten days;

the average duration of pneumonia in these cases was 5.5 days. Combined

red and gray consolidation was more frequently found when pneumonia had

lasted more than five days, the average duration of pneumonia being 7.3

days. The greater number of instances of gray consolidation were found

after seven days of pneumonia, the average duration of the disease being

10.0 days. These figures are cited to show that lobular, like lobar,

consolidation passes gradually from a stage of red to gray hepatization,

but the change occurs more slowly and is often long delayed.

Lobular pneumonia, which occurred 71 times among 80 cases classified as

bronchopneumonia, may be regarded as an almost constant lesion of the

disease. It is found not only in association with other lesions of

bronchopneumonia, but with lobar pneumonia of influenza as well.

The bacteriology of this lesion shows no deviation from that of the

slightly larger group of bronchopneumonia (p. 163). All types of

pneumococcus have been found in association with the lesion,

Pneumococcus I in 2 instances, Pneumococcus II in 1 instance; atypical

Pneumococcus II and Pneumococcus IV have been found much more

frequently. Pneumococci have been found in more than a third of these

autopsies (42.9 per cent in the lungs, 33.3 per cent in the blood);

hemolytic streptococci in less than one-third (28.5 per cent in the

lungs, 30.2 per cent in the blood).

[Illustration:

Fig. 6.—Acute bronchopneumonia with confluent gray lobular

consolidation in lower part of upper lobe and hemorrhagic

peribronchiolar pneumonia in lower lobe; purulent bronchitis.

]

The following list shows the bacteriology of a small group of autopsies

in which the sputum was examined after onset of pneumonia:

SPUTUM BLOOD, LUNGS OR BRONCHUS AT

AUTOPSY

Autopsy 233 Pneum. atyp. II Pneum.

237 S. hem. S. hem.

242 Pneum. atyp. II, B. inf. Pneum. atyp. II

250 Pneum. atyp. II, B. inf. Pneum. atyp. II

253 Pneum. atyp. II Pneum. atyp. II, staph., B.

inf.

266 S. hem. S. hem., B. inf.

274 Pneum. IV S. hem.

291 Pneum. IV, B. inf. Staph., B. inf.

312 Pneum. IV, S. hem., B. inf. S. hem., staph., B. inf.

In one instance of streptococcus pneumonia (Autopsy 274) infection with

streptococci occurred subsequent to the examination of the sputum made

five days before death; pneumococcus was found in the washed sputum.

With lobar pneumonia there was evidence that superimposed infection

occurred more frequently during the stage of red than of gray

hepatization. With the lobular consolidation of bronchopneumonia this

relation has not been found. Among 27 instances of red lobular

consolidation, hemolytic streptococcus has occurred 6 times, namely in

22.2 per cent; among 26 instances of red and gray consolidation, 8

times, namely, in 30.7 per cent; among 13 instances of gray

consolidation, 5 times, namely, in 38.5 per cent. Infection with

hemolytic streptococci is more frequent when the lesion has persisted to

the stage of gray hepatization. This difference between lobar and

bronchopneumonia is probably dependent in part at least upon the more

severe and persistent lesions of the bronchi with bronchopneumonia.

The histology of consolidation which is definitely limited to secondary

lobules or groups of lobules varies considerably. When death occurs in

the early stage of the lesion, consolidated patches are deep red and

somewhat edematous, so that bloody serous fluid escapes from the cut

surface of the lung and red blood corpuscles are present in the alveoli

in great abundance together with polynuclear leucocytes, fibrin and

serum in varying quantity. It is not uncommon to find evidence that the

lesion has had its origin in the bronchioles and extended from them to

other parts of the lobule. Polynuclear leucocytes may be relatively

abundant within and immediately about the bronchioles and alveolar

ducts, whereas the intervening alveoli and infundibula are filled with

red blood corpuscles among which are polynuclear leucocytes and perhaps

some fibrin. It may be evident that bronchiolar pneumonia with

hemorrhage into intervening alveoli is in process of transformation into

a more diffuse leucocytic pneumonia, for polynuclear leucocytes are

making their way from the alveolar wall into the blood-filled lumen and,

as the result of the presence of blood, remain for a time close to the

lining of the alveolus.

When the consolidated lobules have assumed a gray or reddish gray color,

polynuclear leucocytes are more abundant and often almost homogeneously

pack every alveolus within the boundaries of the lobule. In some

instances there is fibrin partially obscured by the presence of

leucocytes in great number.

Although fibrin is less abundant with bronchopneumonia than with lobar

pneumonia, nevertheless in a considerable proportion of instances it is

a very conspicuous element of the inflammatory exudate within the

bronchioles, alveolar ducts and alveoli. It is unusual to find the

alveolar ducts and alveoli uniformly plugged with fibrin containing

leucocytes; there is a variegated distribution of exudate which has

little resemblance to that of lobar pneumonia. Occasionally (Autopsies

242 and 247) polynuclear leucocytes fill the bronchioles, alveolar ducts

and infundibula, whereas the surrounding tributary alveoli contain

fibrin and polynuclear leucocytes in moderate number; red blood

corpuscles may be present in sufficient number to give a homogeneously

red color to the lobular consolidation.

In association with lobular pneumonia, fibrin within the lung tissue

undergoes certain changes which outline very sharply the alveolar ducts

and the other structures usually ill defined in preparations of the

lung. A remarkable appearance is produced by the deposit of hyalin

fibrin upon the surface of the alveolar ducts and infundibula. This

lesion has been described by LeCount.

Within the alveolar tissue of the lung, spaces are seen lined by a layer

of fibrin which stains homogeneously and very brightly with eosin. They

are recognized as alveolar ducts by the presence of scattered bundles of

smooth muscle in their wall. The layer of hyaline fibrin overlying the

surface of the alveolar duct usually forms a continuous lining and

covers over the orifices of the alveoli which surround the alveolar

duct. These ducts are rendered still more conspicuous by the character

of their contents which exhibits a sharp contrast with that of the

surrounding alveoli. The alveoli duct occasionally contains a bubble of

air, but more frequently it is filled with serum in which red blood

corpuscles are sometimes numerous. There is within the lumen scant

fibrin and very few cells, among which polynuclear leucocytes are

predominant. In the surrounding alveoli on the contrary leucocytes and

fibrin are abundant. A similar change is found in the infundibula very

clearly defined by their conical form, which is especially well outlined

below the pleura or in contact with interlobular septa. The infundibulum

is outlined by hyaline fibrin which passes over the orifices of the

tributary alveoli and separates the serous contents of the infundibulum

from the cellular fibrinous contents of the alveoli about.

The lesion which has been described is often associated with acute

bronchitis and bronchiolitis, and the alveoli immediately about the

respiratory bronchioles may be filled with polynuclear leucocytes. It is

very common to find large bubbles of air sharply defined within the

purulent contents of the bronchiole. In some lobules the alveolar ducts,

infundibula and alveoli intervening between these foci of leucocytic

pneumonia are almost uniformly filled with fibrin and polynuclear

leucocytes, but in other places the formation of complete layers of

hyaline fibrin is in process. Bubbles of air are often seen within the

alveolar ducts, and about them is an irregular layer of fibrin formed by

the penetration of air into a channel previously filled with a loose

network of fibrin containing serum in its meshes. The fibrin compressed

against the walls of alveolar duct and infundibulum remains as a compact

layer separating these structures from the alveoli which project from

their walls. The bubble of air is doubtless later absorbed and replaced

by serum, so that many alveolar ducts are filled with serum almost

wholly free from cells, whereas alveoli outside the fibrinous membrane

contain a network of fibrin with leucocytes in greater or less

abundance.

In association with this fibrinous pneumonia, which has been described,

hyaline thrombosis of the capillaries is not uncommon. This hyalin

material within the capillaries gives reactions of fibrin, and in

sections stained by the Gram-Weigert method for demonstration of fibrin,

these thrombosed vessels have the appearance of capillaries irregularly

injected with a blue material.

The interstitial tissue surrounding consolidated lobules is often

edematous; the lymphatics are distended with serum and contain a

moderate number of lymphocytes and polynuclear leucocytes.

Among the lungs which have been studied histologically, pneumococcus has

been almost invariably associated with the lobular lesions which have

just been described, whether hemorrhagic, leucocytic or fibrinous; the

histologic changes accompanying infection of the lung with streptococcus

will be described later. Pneumococcus has been cultivated from the

consolidated lung and is found in section of the lung. B. influenzæ is

found in cultures made from the bronchi. Table XXXVIII includes those

instances in which the histology of the consolidated lung accords with

the description given above.

TABLE XXXVIII

══════════╤═════════════╤════════════╤═══════════╤══════════╤══════════

NO. OF │CHARACTER OF │PREDOMINANT │ CULTURE │ CULTURE │ CULTURE

AUTOPSY │ LOBULAR │ TYPE OF │ FROM │FROM LUNG │ FROM

│CONSOLIDATION│INFLAMMATORY│ HEART’S │ │ BRONCHUS

│ │ EXUDATE │ BLOOD │ │

──────────┼─────────────┼────────────┼───────────┼──────────┼──────────

242 │ Red │ Fibrinous │ Pneum. │ │

│ │ │ atyp. II │ │

244 │ Red │ Leucocytic │ │Pneum. IV │Pneum. IV,

│ │ and │ │ B. inf. │ B. inf.

│ │hemorrhagic │ │ │

247 │Red and gray │ Fibrinous │ Pneum. IV │ │

249 │Red and gray │ Fibrinous │Pneum. III │ │

252 │Red and gray │ Fibrinous │ │Pneum. II │Pneum. II,

│ │ │ │ B. inf. │ B. inf.,

│ │ │ │ │ S. vir.

257 │Red and gray │ Leucocytic │ Pneum. I │ │ B. inf.,

│ │ │ │ │ staph.

303 │ Red │ Fibrinous │ │Pneum. IV │Pneum. IV,

│ │ │ │ B. inf. │ B. inf.,

│ │ │ │ │ staph.

314 │ ? │ Fibrinous │ Pneum. IV │Pneum. IV │Pneum. IV,

│ │ │ │ │ B. inf.,

│ │ │ │ │ staph.

336 │ Red │ Fibrinous │ │ │

395 │Red and gray │ Leucocytic │ Pneum. │ Pneum. │

│ │ │ atyp. II │ atyp. II │

464 │ Red │ Leucocytic │ │ Pneum. I │Pneum. I,

│ │ and │ │ B. inf. │ B. inf.,

│ │hemorrhagic │ │ │ staph.

476 │ Red │ Leucocytic │ │ │

│ │ and │ │ │

│ │hemorrhagic │ │ │

498 │Red and gray │ Fibrinous │ │ S. aur. │

506 │ Red │ Fibrinous │ Pneum. IV │Pneum. IV │Pneum. IV,

│ │ │ │ S. aur. │ B. inf.,

│ │ │ │ │ S. aur.,

│ │ │ │ │M. catarrh

──────────┴─────────────┴────────────┴───────────┴──────────┴──────────

Pneumococcus was found in all but 2 instances, and in one of these

(Autopsy 336) the only culture was from the heart’s blood and in the

other (Autopsy 498) cultures were unsatisfactory because proper media

were not obtainable. Pneumococci of Types I, II, II atypical, III and IV

are represented in the list. B. influenzæ has been found in a

considerable number of instances in which cultures have been made from

the lung and in every instance in which cultures have been made from the

bronchi. Staphylococci are often found in the bronchi, but in most

instances they do not penetrate into the lung.

Another group of cases of lobular pneumonia are important because in

association with necrosis of lung tissue recognized by the microscope

hemolytic streptococci have been found in the lungs. In such instances

serum is abundant and polynuclear leucocytes are relatively scant though

their distribution varies considerably; in some places leucocytes are

fairly abundant though elsewhere almost absent, but this distribution

bears no obvious relation to the bronchioles. In some instances

(Autopsies 274 and 487) red blood corpuscles are numerous but in others

(Autopsies 275 and 312) they are inconspicuous. The characteristic

feature of the lesion is the occurrence of patches of necrosis within

which the nuclei both of exudate and of alveolar walls have partially or

completely disappeared. In these areas of necrosis short chains of

streptococci are found in immense number whereas in living tissue they

are present in moderate number. There has been a relatively inactive

inflammatory reaction, great proliferation of streptococci and necrosis

of invaded tissue. The bacteriology of instances of lobular pneumonia

with necrosis is shown in Table XXXIX.

TABLE XXXIX

NO. OF │CHARACTER OF │PREDOMINANT │ CULTURE │ CULTURE │ CULTURE

AUTOPSY │ LOBULAR │ TYPE OF │ FROM │FROM LUNG │ FROM

│CONSOLIDATION│INFLAMMATORY│ HEART’S │ │ BRONCHUS

│ │ EXUDATE │ BLOOD │ │

274 │ Red │ Leucocytic │ S. hem. │ S. hem. │ S. hem.,

│ │ and │ │ │ staph.

│ │hemorrhagic │ │ │

275 │Red and gray │ Leucocytic │ Pneum. IV │ S. hem., │ S. hem.,

│ │ │ S. hem. │ B. inf., │ B. inf.,

│ │ │ │ staph. │ staph.

312 │Red and gray │ Leucocytic │ S. hem. │ S. hem., │ S. hem.,

│ │ │ │ B. inf. │ B. inf.,

│ │ │ │ │ staph.

478 │ Red │ Leucocytic │ S. hem. │ S. hem. │

│ │ and │ │ │

│ │hemorrhagic │ │ │

Lobular pneumonia, in some of these instances at least, has been caused

primarily by pneumococci; necrosis has been the result of secondary

invasion by streptococci. In Autopsy 275 Pneumococcus IV has been

obtained from the blood, but in the presence of streptococci has

presumably disappeared from the lung and bronchus. In the case

represented by Autopsy 274, Pneumococcus IV has been found in the sputum

five days before death at the onset of pneumonia, but at this time no

hemolytic streptococci have been found. In the case represented by

Autopsy 312, Pneumococcus IV, B. influenzæ and a few colonies of

hemolytic streptococci have been obtained from the sputum two days after

recognition of pneumonia and five days before death.

The hemorrhagic and edematous consolidation of the early pulmonary

lesions of influenzal pneumonia is their most distinctive feature. Red

confluent lobular pneumonia is frequently found in those who have died

within the first week following the onset of influenza. The lungs are

voluminous and heavy and may weigh as much as 1,500 grams; the pleura

which overlies the consolidated area is blue or plum colored and usually

shows scant if any evidence of pleurisy. Scattered patches of

consolidation are accurately limited to lobules, but in addition there

are large areas often involving the greater part of the lobes and not

infrequently situated in the lowermost part of the lower lobes. This

confluent consolidation may be obviously limited by lobule boundaries.

The consolidated tissue is deep red and laxly consolidated; red serous

fluid escapes from the cut surface. The lesion not infrequently occurs

in association with hemorrhagic peribronchiolar pneumonia.

The histology of this confluent lesion has been studied in Autopsies

242, 244, 303, 336, 464, 474 and 506. The histology varies, because, in

some instances, leucocytes, in other instances, fibrin, is abundant, but

the presence of red blood corpuscles in large number within the alveoli

gives a red color to the consolidated tissue. In these cases

pneumococci, associated in the lungs or in the bronchi with B.

influenzæ, have been the cause of pneumonia. In two autopsies studied

histologically (Autopsies 274 and 478) there was red lobular and

confluent pneumonia and the blood and lungs contain hemolytic

streptococci demonstrated by cultures; microscopic examination showed

the presence of a widespread necrosis of the lung tissue.

In the group of autopsies in Table XL there was red confluent lobular

pneumonia. These autopsies are separated from those just cited because

there was no histologic examination of the tissue.

TABLE XL

═════════════════╤═════════════════╤═════════════════╤═════════════════

NO. OF AUTOPSY │ BACTERIOLOGY OF │ BACTERIOLOGY OF │ BACTERIOLOGY OF

│ HEART’S BLOOD │ LUNGS │ BRONCHUS

─────────────────┼─────────────────┼─────────────────┼─────────────────

289 │ Pneum. IV │ Pneum. IV │ Pneum. IV, B.

│ │ │ inf., staph.

297 │ │ Pneum. IV, B. │ Pneum. IV, B.

│ │ inf. │inf., S. hem. (a

│ │ │ few)

306 │ │ │

339 │ Pneum. IV │ │

364 │ S. hem. │ │

418 │ Pneum. atyp. II │Pneum. atyp. II, │

│ │B. inf., S. vir. │

424 │ │ Pneum. IV. │

─────────────────┴─────────────────┴─────────────────┴─────────────────

This group of autopsies confirms the view that the red confluent lobular

pneumonia is caused by pneumococci in association with B. influenzæ.

Hemolytic streptococci may invade secondarily. In Autopsy 297 a few

hemolytic streptococci were found in the bronchus but apparently had not

entered the lungs. In the absence of histologic examination it is not

possible to determine if the invasion of hemolytic streptococcus (in

Autopsy 364) has caused necrosis of the pneumonic tissue.

[Illustration:

Fig. 7.—Bronchopneumonia with purulent bronchitis and peribronchial

hemorrhage.

]

Peribronchial Hemorrhage and Pneumonia

In a considerable number of instances, namely, in 19 autopsies,

hemorrhage about the small bronchi has been recognizable upon gross

examination of the lung. A conspicuous zone of hemorrhage 2 or 3 mm. in

thickness surrounds small (with no cartilage) often dilated bronchi and

on longitudinal section may be tracted for a considerable distance along

the bronchus (Fig. 7). In many additional instances peribronchial

hemorrhage has been found by microscopic examination. In some instances

the peribronchial zone of hemorrhage is firmer than the tissue elsewhere

and it is occasionally difficult to determine whether the lesion is

hemorrhage or pneumonia. In 7 instances frank red consolidation of

peribronchial tissue was recognized at autopsy; this lesion will be

considered later under peribronchial pneumonia. Hemorrhage about

bronchi, like other evidences of severe injury to bronchi following

influenza, is more frequently found in the lowermost parts of the lungs

than elsewhere. It is invariably associated with severe bronchitis; the

bronchi have contained purulent fluid in 15 of 19 instances of

peribronchial hemorrhage and in 10 instances the lesion has been

associated with dilatation of the bronchi.

Microscopic examination furnishes further evidence of the severity of

the bronchial changes which have brought about hemorrhage into the

surrounding alveoli. The lumen of the bronchus contains blood and

leucocytes; the epithelium is sometimes raised in places from the

underlying basement membrane by blood; blood vessels of the bronchial

wall are engorged, and there is hemorrhage into the tissue of the

bronchus. More frequently the bronchial epithelium is completely lost

and the denuded surface is often covered by a layer of fibrin intimately

adherent to the inflamed mucosa. Transitions between simple hemorrhage

and pneumonia are found, polynuclear leucocytes being mingled with red

blood corpuscles. In several instances the alveoli in immediate contact

with the bronchial wall have contained fibrin, whereas those in the

surrounding zone have contained blood.

Bacteria found in the bronchi in 10 instances of peribronchial

hemorrhage have been as follows:

Staphylococci 1

B. influenzæ, pneumococci 1

B. influenzæ, S. hemolyticus 2

B. influenzæ, pneumococci, staphylococci 1

B. influenzæ, S. hemolyticus, staphylococci 4

No organism found 1

The high incidence of B. influenzæ and the frequent association of B.

influenzæ and hemolytic streptococci are noteworthy. The instance in

which no organisms were found is probably due to a defect in media and

should perhaps be excluded from the list.

The percentage incidence of pneumococci, hemolytic streptococci,

staphylococci and B. influenzæ in the bronchus, lungs and blood of the

heart is an index of the facility with which these microorganisms

penetrate internal organs when the bronchi are the site of this

hemorrhagic lesion.

TABLE XLI

════════╤════════╤═════════════════╤═════════════════

│ NO. OF │ │ HEMOLYTIC

│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI

────────┼────────┼────────┬────────┼────────┬────────

│ │ NO. │PER CENT│ NO. │PER CENT

│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE

────────┼────────┼────────┼────────┼────────┼────────

Bronchus│ 10│ 2│ 20.0│ 6│ 60.0

Lung │ 13│ 4│ 30.8│ 7│ 53.8

Blood │ 17│ 4│ 23.5│ 9│ 52.9

────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════

│ │

│ STAPHYLOCOCCI │ B. INFLUENZÆ

────────┼────────┬────────┼────────┬────────

│ NO. │PER CENT│ NO. │PER CENT

│POSITIVE│POSITIVE│POSITIVE│POSITIVE

────────┼────────┼────────┼────────┼────────

Bronchus│ 6│ 60.0│ 8│ 80.0

Lung │ 3│ 23.1│ 5│ 38.5

Blood │ │ │ │

────────┴────────┴────────┴────────┴────────

When these figures are compared with those for all forms of bronchitis

no very noteworthy differences are found; the incidence of pneumococci

here is less and that of hemolytic streptococci greater. In association

with the severe changes present in the bronchi, hemolytic streptococci

which enter the lungs almost invariably find their way into the blood.

In 6 instances there has been frank pneumonic consolidation limited to a

zone encircling small and medium-sized bronchi which have often been

obviously dilated. On cross section these patches of pneumonia are

circular, from 1 to 2 cm. in diameter and each contains a bronchus at

its center. When the bronchus is cut longitudinally it is evident that

pneumonic consolidation forms a cylindrical sheath about the tube. The

consolidation varies in color from red to grayish red. In one instance

(Autopsy 253) the consolidated tissue has formed a gray zone in contact

with the bronchus and is red in a peripheral zone; microscopic

examination shows that the alveoli about the bronchus contain fibrin,

whereas those at a greater distance contain red blood corpuscles. In

this instance, the associated pneumonia in another part of the lung has

been somewhat anomalous and has had characters both of lobar and

bronchopneumonia, for scattered in the left lung there have been patches

of firm consolidation not more than 2 cm. across. The smaller of these

patches are deep red, but the larger are coarsely granular and gray in

the center. The patchy character of the lesion has suggested

bronchopneumonia, but the coarse granulation on section and the presence

of fibrinous plugs within the small bronchi have presented a close

resemblance to lobar pneumonia. This autopsy is one of the few instances

in which Pneumococcus II has been found, Pneumococcus II being present

in blood and lungs, B. influenzæ, in lungs and bronchi. In 2 additional

instances (Autopsies 374 and 392) peribronchial pneumonia, recognizable

at autopsy, has been associated with consolidation having the characters

of lobar pneumonia. In one instance, Autopsy 374, the right lung has

contained two patches of firm, mottled red and pinkish red coarsely

granular consolidation each about 6 cm. across, one situated in the

upper lobe and the other in the lower lobe. Elsewhere in the lung, in

definite relation to dilated bronchi, occur patches of firm, red,

coarsely granular consolidation from 1 to 1.5 cm. in diameter when cut

transversely. The bronchus in the center has contained purulent fluid.

In the opposite lung similar consolidation has been limited to zones

about dilated bronchi which contain purulent fluid. Pneumococcus IV has

been obtained from the blood of the heart.

The peribronchial pneumonia which has been described occurs in

association with evidence of profound injury to the bronchial wall. In 5

of 6 instances purulent bronchitis has been found at autopsy; in half of

these instances bronchiectasis has been noted. The epithelium of the

bronchus has been found separated from the underlying tissue by serous

exudate, blood and leucocytes; epithelial cells undergo necrosis and

disappear, the denuded surface being covered by fibrin. Necrosis extends

a varying depth into the wall of the bronchus; blood vessels are

engorged, and there is in some instances hemorrhage throughout the wall

of the bronchus.

The character of the exudate in the alveoli surrounding the bronchus

differs considerably in different instances. In some instances

(Autopsies 374 and 392) red blood corpuscles are predominant in the

alveoli in contact with the bronchial wall, whereas in a peripheral zone

polynuclear leucocytes are more abundant. In other instances (Autopsies

253 and 402) alveoli next the bronchial wall contain abundant fibrin and

these are surrounded by a zone in which the alveoli are filled with

blood.

Peribronchial pneumonia is the result of the direct extension of the

inflammatory process through the wall of the bronchus; it occurs when

the epithelium of the bronchus is destroyed and the underlying tissues

are injured, but may be present in a wide encircling zone even when the

lesion has not penetrated the bronchial wall. The distribution of the

pneumonia demonstrates very clearly that the inflammatory process does

not reach the affected peribronchial alveoli by way of the bronchioles

tributary to the bronchus.

The bacteriology of these instances of peribronchial pneumonia is

noteworthy. (Table XLII.)

TABLE XLII

AUTOPSY │ BLOOD │ LUNG │ BRONCHUS

253 │Pneum. II │Pneum. II, B. │Staph., B. inf.

│ │ inf. │

374 │Pneum. IV │ │

387 │Pneum. II, S. │Pneum. II, │Pneum. II, S.

│ hem. │ staph., B. inf.│ hem., staph.,

│ │ │ B. inf.

392 │Pneum. II │ │

402 │Pneum. IV, S. │ │

│ hem. │ │

424 │? │Pneum. IV │

Pneumococcus has been found in every instance either in the lungs or

blood. Pneumococcus II, which has been uncommon with the pneumonia

following influenza at Camp Pike and has occurred only ten times in more

than 200 autopsies, has been present in one-half of these cases. The

constant association of the lesion with pneumococcus is particularly

significant when a comparison is made between the incidence of

pneumococcus with peribronchial hemorrhage, on the one hand, and

peribronchial pneumonia on the other; pneumococcus has been present in

less than a third of the instances of hemorrhage but in all instances of

pneumonia.

In addition to the instances in which gross peribronchial consolidation

has been noted at autopsy, microscopic examination has demonstrated the

presence of fibrinous pneumonia surrounding bronchi in a considerable

number of autopsies. In a zone encircling small bronchi (with no

cartilage) alveoli are filled by plugs of dense fibrin (Fig. 20)

containing in variable number polynuclear leucocytes and mononuclear

cells. The width of the zone is often equal or greater than the diameter

of the bronchus. Alveoli outside the zone of fibrinous inflammation may

contain red blood corpuscles or serum, and desquamated epithelial cells

are often abundant.

Of 21 instances of peribronchial fibrinous pneumonia 20 were associated

with purulent bronchitis. Further evidence of the relation of the lesion

to profound injury to the bronchi is its association with bronchiectasis

in 17 instances.

Peribronchial fibrinous pneumonia, like other lesions encircling the

small bronchi, bears a direct relation to the severity of microscopic

changes in the bronchus. The epithelium of the bronchus is either

partially or completely lost. Occasionally epithelium is raised by

hemorrhage or leucocytes from the underlying tissue but more frequently

it is wholly lost and the surface is covered by a layer of fibrin. In

the early stages of the lesion, polynuclear leucocytes may be numerous

throughout the bronchial wall, indicating that the inflammatory irritant

within the lumen is affecting the entire wall and extending its

influence to the surrounding pulmonary tissue. Later lymphoid and plasma

cells are more abundant than polynuclear leucocytes. Coagulative

necrosis and disintegration of the bronchial wall, proceeding from the

inner surface outward, may extend more or less deeply, and fibrinous

inflammation of adjacent alveoli is often more extensive about that

segment of the bronchus which shows the greatest change. In some

instances segments of the bronchial wall or even the entire wall has

disappeared, so that alveoli containing fibrin form part of the wall of

the cavity thus formed. When bronchiectasis has occurred, there are

often fissures from the lumen through the entire wall extending into the

surrounding lung tissue: here fibrinous pneumonia is particularly

conspicuous, occurring in a zone about the edges of the defect. This

deposition of fibrin within the alveoli adjacent to the injury doubtless

has a part in limiting the distribution of bacterial infection.

Nevertheless breaks in the continuity of the bronchial wall are not

essential to the production of the lesion and the irritant, which is

responsible for the lesion, may penetrate through the bronchial wall to

surrounding alveoli and from alveoli to other alveoli immediately

adjacent.

With this peribronchial pneumonia the smallest bronchi are distended

with pus and their walls are infiltrated with polynuclear leucocytes,

lymphoid and plasma cells. In a broad zone encircling the bronchus the

alveoli are filled with plugs of fibrin. Bronchioles are similarly

distended with polynuclear leucocytes; the alveoli which occur upon the

wall of the bronchiole are often limited to one side of the wall and are

filled with fibrin. This fibrin occasionally projects into the lumen of

the bronchiole and forms a continuous layer in contact with the wall on

the same side. The alveolar duct and infundibulum are distended with

polynuclear leucocytes. The alveoli upon the wall of the alveolar duct

and upon the proximal part of the infundibulum are filled with fibrin.

The bronchus, bronchiole, alveolar duct and part of the infundibulum are

thus surrounded by a continuous zone of alveoli containing fibrin. The

alveoli about the distal part of the infundibulum may be filled with

polynuclear leucocytes. Lung tissue between adjacent zones of fibrinous

pneumonia may contain serum and desquamated epithelial cells.

Organization of peribronchial fibrin was found in 10 of the 22 autopsies

in which peribronchial fibrinous pneumonia had been found. Fibroblasts

have invaded the fibrin and newly formed capillaries have penetrated

into it. In some instances the interalveolar septa are thickened and

infiltrated with lymphoid and plasma cells, and in 7 instances there was

chronic pneumonia with thickening and mononuclear infiltration of the

interstitial tissue about the bronchi and blood vessels, and elsewhere.

The duration of the fatal illness in 12 instances with no organization

was usually from ten days to two weeks, though in 3 instances there was

no organization although the respiratory disease had lasted from

seventeen to nineteen days (average duration with no organization, 13.5

days). The duration of illness in 10 instances with organization of

fibrin was slightly less than three weeks (average 18.9 days). These

figures do not accurately represent the duration of pneumonia which

usually develops after a period of several days following onset of

influenza.

This group of instances of peribronchial fibrinous pneumonia has offered

an opportunity to study the bacteriology of pneumonia with organization

and to determine if it presents any unusual characters. The bacteriology

of autopsies with peribronchial fibrinous pneumonia with no organization

is shown in Table XLIII:

TABLE XLIII

AUTOPSY │ BLOOD │ LUNG │ BRONCHUS

289 │Pneum. IV │Pneum. IV │Pneum. IV, B.

│ │ │ inf., staph.

372 │ │ │

376 │S. hem. │S. hem. │S. hem., B. inf.,

│ │ │ S. aur.

409 │0 │ │

410 │ │S. hem., B. inf. │

│ │ S. aur. │

412 │Pneum. II │ │Pneum. II, B.

│ │ │ inf.

420 │S. hem. │S. hem., B. inf. │

│ │ S. aur. │

423 │S. hem. │S. hem., B. inf. │

440 │0 │B. inf., S. aur. │B. inf., S. aur.

448 │0 │0 │0

482 │0 │B. inf., Pneum. │B. inf., Pneum.

│ │ IV │ IV, S. hem.

489 │0 │Pneum. IV, B. │Pneum. IV, B.

│ │ inf. │ inf.

The bacteriology of instances of peribronchial fibrinous pneumonia with

organization of the intraalveolar fibrin is shown in Table XLIV:

TABLE XLIV

AUTOPSY │ BLOOD │ LUNG │ BRONCHUS

283 │Pneum. IV │Staph., B. inf. │B. inf., Pneum.

│ │ │ IV, staph.

291 │0 │0 │B. inf., staph.

398 │0 │ │

419 │0 │Pneum. II, B. │Pneum. II, B.

│ │ inf. │ inf.

421 │S. hem. │Pneum. IV, S. │

│ │ hem. │

422 │0 │Pneum. II atyp., │

│ │ B. inf. │

425 │S. hem. │S. hem., B. inf.,│

│ │ S. alb. │

433 │0 │S. hem., B. inf.,│

│ │ S. aur. │

460 │S. hem. │S. hem., B. inf. │S. hem., B. inf.,

│ │ │ staph.

463 │0 │B. inf., staph. │B. inf., staph.,

│ │ │ Pneum. IV

B. influenzæ has been present in the bronchi in every instance save one

in which cultures have been made, and it is probable that in this

exceptional instance cultures have remained sterile because the media

employed have been defective. The incidence of B. influenzæ in the lung

has been unusually high both with and without organization (66.7 per

cent with no organization; 77.8 per cent with organization).

Streptococci and staphylococci have been found in a considerable

proportion of all instances of peribronchial fibrinous pneumonia, but

there has been no notable preponderance of these microorganisms when

organization has occurred. Organization has been present in instances in

which pneumonia is referable to pneumococcus associated with B.

influenzæ and unaccompanied by either streptococci or staphylococci

(Autopsies 419 and 422). Wadsworth[81] found no organization after

inoculation of the lungs of dogs with pneumococcus or with

staphylococcus alone, but produced organization when he inoculated

animals with both microorganisms.

Injury to bronchi produced in part at least by B. influenzæ exposes the

bronchi and lung tissue to repeated infection with a variety of

microorganisms; absorption of fibrin and regeneration of alveolar

epithelium are prevented, resolution fails to occur and organization of

fibrin follows.

Suppurative Pneumonia With Necrosis and Abscess Formation

Three varieties of suppurative pneumonia have occurred in association

with influenza.

A. Necrosis and suppuration with formation of one or several abscesses

usually below the pleura and almost invariably caused by hemolytic

streptococci.

B. Interstitial suppurative pneumonia caused by hemolytic streptococcus.

C. Multiple abscesses in clusters caused by staphylococci.

Suppurative pneumonia with necrosis and abscess formation will be

discussed in this section. Pulmonary abscesses which occurred in 43

autopsies may be included in this group; in 4 of these autopsies abscess

and interstitial suppurative pneumonia occurred in the same individual.

These abscesses were much more frequently situated in the lower than in

the upper lobes and more often in the right than in the left lung. In

most instances there was one or several abscesses situated below the

pleura of one lobe; occasionally abscesses occurred in two lobes of the

same lung or in both lungs. The distribution was as follows: Abscess in

only one lung occurred in right upper lobe in 6 autopsies; middle lobe,

3; lower lobe, 15; left upper lobe, 2; lower lobe, 16. Abscesses

occurred in both right and left lower lobes, twice. The usual situation

was at the lower and posterior part of the lower lobe at or near the

basal edge, less frequently below the posterior border or upon the basal

surface of the lobe. These abscesses in almost every instance were found

immediately below the pleural surface, so that they appeared upon the

pleura as opaque yellow spots usually surrounded by narrow zones of

hemorrhage. In one instance (Autopsy 376) the abscess cavity was

separated from the pleural cavity by remains of the pleura which was as

thin as tissue paper and in other instances perforation had occurred

(Fig. 9). In Autopsy 480 the abscess cavity which had perforated the

pleura was in free communication with a bronchus of medium size.

In most instances of suppurative pneumonia there have been associated

lesions of bronchopneumonia which have been peribronchiolar, hemorrhagic

or lobular and have exhibited no unusual characters. The abscess or

abscesses are situated within an area of pneumonic consolidation which

is not limited by lobule boundaries and has not the characters of

bronchopneumonic consolidation. In some instances this consolidation is

limited to a zone immediately about the abscess, but often it involves

the greater part of a lobe. The tissue is laxly consolidated and flabby;

on section it has a dull, conspicuously cloudy appearance and is grayish

red, pinkish gray or gray; it is homogeneous or very finely granular.

Turbid gray fluid, which sometimes resembles thin pus, oozes from the

cut surface.

Widespread necrosis of tissue is not infrequently a conspicuous feature

of this pyogenic pneumonia (Fig. 8). Upon a cloudy gray background of

consolidation are numerous opaque yellowish gray or yellow patches,

occasionally 2 or 3 cm. across, giving a mottled character to the cut

surface. Upon the pleura these necrotic patches appear as dull opaque

yellow spots. They may be surrounded by a zone of hemorrhage. The opaque

material is at first firm but may undergo softening, becoming semisolid

and finally purulent. Necrotic patches may be scattered throughout a

lobe, but fully formed abscesses are with few exceptions immediately

below the pleura (Fig. 9).

[Illustration:

Fig. 8.—Streptococcus pneumonia with massive necrosis. Autopsy 354.

]

[Illustration:

Fig. 9.—Abscess below pleura with perforation caused by hemolytic

streptococci. Healing suppurative interstitial pneumonia indicated

by yellowish gray lines marking interlobular septa at base of lower

lobe. Autopsy 474; right lung. (See left lung, Fig. 10.)

]

The duration of illness in cases of pneumonia with abscess varied from a

week or less (11 instances) to more than four weeks. The duration of the

greater number of cases (17 instances) was between one and two weeks. In

one instance onset occurred with symptoms of influenza, pneumonia was

recognized two days later, and death occurred only four days after the

onset of illness. When the duration of the illness was less than a week

the symptoms of onset were in some instances those of pneumonia.

Table XLV shows the incidence of pneumococcus, S. hemolyticus,

staphylococcus and B. influenzæ in instances of suppurative pneumonia

with abscess formation, 4 instances of abscess with interstitial

suppurative pneumonia being excluded:

TABLE XLV

════════╤════════╤═════════════════╤═════════════════

│ NO. OF │ │ HEMOLYTIC

│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI

────────┼────────┼────────┬────────┼────────┬────────

│ │ NO. │PER CENT│ NO. │PER CENT

│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE

────────┼────────┼────────┼────────┼────────┼────────

Bronchus│ 24│ 5│ 20.8│ 22│ 91.6

Lung │ 36│ 9│ 25.0│ 30│ 83.3

Blood │ 37│ 6│ 16.2│ 31│ 83.8

────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════

│ │

│ STAPHYLOCOCCI │ B. INFLUENZÆ

────────┼────────┬────────┼────────┬────────

│ NO. │PER CENT│ NO. │PER CENT

│POSITIVE│POSITIVE│POSITIVE│POSITIVE

────────┼────────┼────────┼────────┼────────

Bronchus│ 12│ 50.0│ 18│ 75.0

Lung │ 14│ 35.6│ 8│ 22.2

Blood │ │ │ │

────────┴────────┴────────┴────────┴────────

In over 80 per cent of instances of pulmonary abscess hemolytic

streptococcus has been found in blood, lungs and bronchus and, when

cultures have been made, in the inflamed pleural cavity as well.

Streptococci have been found in immense number in sections from the

necrotic lung tissue and the abscesses which have been formed. It is

evident that hemolytic streptococci have caused suppurative pneumonia

and death, being found in the blood of the heart just as frequently as

in the lungs (83 per cent). The relative unimportance of pneumococci is

indicated by their low incidence in the blood (16.2 per cent) when

compared with that of lobar pneumonia (65.5 per cent) or of

bronchopneumonia (31.4 per cent). B. influenzæ has been found in

three-fourths of these autopsies in the bronchus, but its incidence in

the lungs has been much smaller.

In 3 instances of suppurative pneumonia with abscess formation no

hemolytic streptococci were found; they are as follows:

=Autopsy 380.=—Bronchopneumonia with gray and red lobular

consolidation in right upper and lower lobes; peribronchiolar

nodules of consolidation in left lower lobe; abscess, 1.5 cm.

across, below the pleura of the posterior border of the left lower

lobe near its base; fibrinopurulent pleurisy (300 c.c.) on right

side; serous pleurisy (200 c.c.) on left. Pneumococcus III was found

in cultures from the blood of the heart from the right lung and with

B. influenzæ from the right pleural cavity. No culture was made from

the left lung which contained the abscess. In sections of the

abscess gram-positive streptococci in chains of 4 to 8 cocci were

numerous.

=Autopsy 406.=—Acute lobar pneumonia with red hepatization of

greater part of right lung; patch of consolidation in lower lobe of

left lung containing an abscess cavity 2.5 x 1.5 cm.; localized

seropurulent pleurisy (375 c.c.) on left side. Pneumococcus IV was

obtained from the blood of the heart; a culture from the lung was

contaminated. Tissue from the abscess was not saved for histologic

examination.

=Autopsy 416.=—Suppurative pneumonia with necrosis and abscess

formation in right lower lobe; fibrinous pleurisy on right side.

Pneumococcus IV was obtained from the blood, right lung and right

main bronchus. No streptococci were found in sections from the

abscess in the right lung.

The foregoing observations demonstrate that suppurative pneumonia with

abscess formation following influenza is with few exceptions caused by

S. hemolyticus.

The autopsies (Table XLVI) in which pneumococci have been found in

association with hemolytic streptococci in the blood or lungs indicate

that pneumococci have had a part in the production of fatal pneumonia.

TABLE XLVI

AUTOPSY │ CULTURE FROM │ CULTURE FROM │ CULTURE FROM

│ BLOOD │ LUNGS │ BRONCHUS

258 │S. hem. │S. hem., Pneum. │

│ │ IV B. inf. │

282 │S. hem., Pneum. │S. hem., Pneum. │S. hem., B. inf.

│ II │ II │ Pneum. II,

│ │ │ staph.

345 │ │S. hem., Pneum. │

│ │ II, staph. │

378 │Pneum. atyp. II │S. hem., Pneum. │S. hem., B. inf.,

│ │ atyp. II │ Pneum. atyp. II

381 │S. hem. │S. hem., Pneum. │

│ │ II Pneum. IV, │

│ │ staph. │

383 │Pneum. III │S. hem., Pneum. │

│ │ III B. inf. │

387 │S. hem. │Pneum. II, │S. hem., pneum.,

│ │ staph., B. inf.│ staph., B. inf.

These autopsies, notably those in which pneumococci have been found in

the blood, suggest that infection with pneumococci has preceded

suppurative pneumonia caused by hemolytic streptococci. In a small

number of instances the sputum was examined in life after onset of

pneumonia.

TABLE XLVII

═══════╤═══════════════════════════════╤═══════════════════════════════

AUTOPSY│ SPUTUM │CULTURES FROM BLOOD, LUNGS AND

│ │ BRONCHUS

───────┼───────────────────────────────┼───────────────────────────────

282 │Pneum. IV. B. inf. │S. hem., Pneum. II, staph., B.

│ │ inf.

288 │S. hem., B. inf. │S. hem., B. inf.

376 │(No S. hem., Oct. 8) │S. hem., staph., B. inf. (Oct.

│ │ 11)

───────┴───────────────────────────────┴───────────────────────────────

In 2 of these 3 cases infection with hemolytic streptococcus occurred

subsequent to the onset of pneumonia.

Several observations help to explain the occurrence of abscess in

association with the pneumonia of influenza. The fissures which will be

described in association with bronchiectasis represent traumatic

ruptures of the bronchial wall consequent upon weakening by necrosis and

over distention. They expose the injured bronchial wall and the alveolar

tissue adjacent to it to infection by the microorganisms contained

within the lumen of the inflamed bronchus. Occasionally a favorable

microscopic section demonstrates the relation of pulmonary necrosis and

consequent suppuration to injuries of the bronchial wall. Peribronchial

fibrinous pneumonia occurs about the bronchi of which the epithelial

lining has been destroyed, and when a fissure penetrates the bronchial

wall fibrinous pneumonia is almost invariably found in a zone about the

tear; it doubtless tends to limit the extension of the process.

Occasionally, wide areas of necrosis occur within consolidated tissue

near the site of the fissure (Autopsy 312 with S. hemolyticus and B.

influenzæ, p. 254). Accumulation of polynuclear leucocytes between

living and dead tissue may form a line of demarcation (Autopsy 387);

finally, fairly large, irregularly formed, abscess cavities are found.

Necrosis and beginning suppuration in contact with the lumen of the

bronchus will be described in association with bronchiectasis (Autopsies

312, Fig. 24, and 423, p. 256). In the following autopsies upon

individuals who have died with pulmonary abscesses, favorable

microscopic sections have demonstrated abscess formation in contact with

lesions which have penetrated the walls of small bronchi. They help to

explain the pathogenesis of abscess in association with influenza.

=Autopsy 376.=—H. M., white, aged twenty-four, a fireman, resident

of Oklahoma, had been in military service one month. Onset of

illness occurred October 1, ten days before his death; he was

admitted to the base hospital on the fourth day of his illness with

the diagnosis of bronchopneumonia.

=Anatomic Diagnosis.=—Acute bronchopneumonia with patches of lobular

and confluent lobular consolidation in both lungs and hemorrhagic

peribronchiolar consolidation in right upper lobe; abscess in right

upper lobe below pleura; fibrinopurulent pleurisy on right side;

purulent bronchitis; bronchiectasis at base of left lobe.

An irregular abscess, 2 x 1 cm., filled with creamy purulent fluid

is separated from the interlobular surface of the right upper lobe

by a thin membrane representing the pleura. The right pleural cavity

contains 200 c.c. of turbid yellow fluid in which is soft fibrin.

The bronchi contain purulent fluid in great abundance. The bronchi

at the base of the left lower lobe are widely dilated, so that many

small bronchi with no cartilage in their wall measure from 3 to 5

mm. in diameter.

Cultures show the presence of hemolytic streptococci in the blood of

the heart and in three plates from the lung; B. influenzæ and S.

aureus were found in the left bronchus.

The bronchi have wholly or partially lost their epithelium and there

is deep erosion of the walls. Cavities containing polynuclear

leucocytes occur within the alveolar tissue; in some instances pus

containing cavities are surrounded by alveolar tissue, but in other

places it is evident, that they have had their origin in bronchi. In

a short segment of the circumference the wall of the preexisting

bronchus is preserved and consists of squamous epithelium, vascular

connective tissue and smooth muscle. The remainder of the bronchus

has disappeared and a cavity is produced. The very irregular wall of

the cavity is formed by partially destroyed alveoli filled with

fibrin and leucocytes.

=Autopsy 387.=—C. M., white, aged twenty-one, laborer, resident of

Mississippi, had been in military service twenty-one days. Illness

began on September 22, nineteen days before death, and the patient

was admitted to the hospital on the same day with a diagnosis of

bronchitis; a diagnosis of bronchopneumonia was made on October 2,

nine days before death. The leucocytes on October 3 numbered 8000

(small mononuclear, 36 per cent; large mononuclear, 5 per cent;

polynuclear, 59 per cent).

=Anatomic Diagnosis.=—Acute bronchopneumonia with consolidation in

right upper lobe and hemorrhagic peribronchiolar consolidation in

left lower lobe; abscess below pleura in left lower lobe; purulent

pleurisy on both sides; edema of mediastinum; purulent bronchitis;

bronchiectasis.

There is advanced bronchiectasis, and bronchi with no visible

cartilage are dilated to from 4 to 8 mm. in diameter; they contain

purulent fluid which wells up from the cut surface. About dilated

bronchi there is in places dull red or grayish red consolidation

forming an encircling zone. Situated below the pleural surface

within an area of consolidation at the posterior border of the left

lower lobe there is a spot 3 cm. across where the tissue is yellow

and has in places undergone purulent softening. Several smaller

abscesses occur nearby.

Cultures from the blood of the heart and from the edematous

mediastinum contain hemolytic streptococci. From the abscess are

grown S. albus, Pneumococcus II and B. influenzæ. The purulent

contents of a small bronchus contains S. hemolyticus, B. influenzæ,

S. aureus and a few pneumococci.

Microscopic examination shows that the epithelium of dilated bronchi

has disappeared and the denuded surface is covered by fibrin and

polynuclear leucocytes; fissures extend from the lumen through the

bronchial wall into the surrounding alveolar tissue. A zone of

fibrinous pneumonia surrounds these bronchi and fissures in the

bronchial wall penetrate into this zone. One dilated bronchus 2.4

mm. in diameter with no cartilage in its wall has vascular

connective tissue covered by epithelium on one side, whereas the

remainder of the circumference is formed by exposed alveoli filled

with fibrin, the bronchial wall having disappeared. A section

through a part of the abscess which has been mentioned shows a very

irregularly formed cavity approximately 1 x 0.7 cm. Remains of

bronchial wall, consisting of very vascular tissue covered by flat

epithelium in several layers, indicate the origin of the cavity.

Between these remnants of bronchi deep pockets extend into the

pulmonary tissue which in the margin of the cavity is the site of

fibrinous pneumonia. In one place, in contact with the cavity, a

wide area of consolidated tissue has undergone necrosis and both

alveolar walls and their contents have lost their nuclei. Leucocytes

which are accumulating at the margin of the necrotic patch form a

line of demarcation between living and dead tissue.

Abscess may be the result of the profound changes which occur in the

bronchi as the result of influenza. Necrosis caused by bacteria within

the bronchi weakens and in places destroys the wall. Bacteria penetrate

into the surrounding tissue and hemolytic streptococci (or

staphylococci) may produce localized abscesses. These abscesses are

usually situated near the pleural surface of the lung, because

destructive changes causing rupture of the bronchial wall occur more

frequently in the smaller peripheral bronchi than in the larger bronchi

containing cartilage. Abscesses occur more frequently at the bases of

the lungs, because the most severe changes in the bronchi occur in the

dependent part. (See “Bronchiectasis,” p. 240.)

=Healing of Abscess.=—The following autopsy is of interest in relation

to the treatment of pulmonary abscess and associated empyema.

=Autopsy 467.=—P. C., white, aged twenty-five, a farmer from

Missouri, had been in military service three months. Illness began

September 27, thirty days before death, and the patient was admitted

the day following onset with headache, backache and cough. Pneumonia

with consolidation in the right lower lobe was recognized on the

sixth day of illness. On the ninth day 500 c.c. of fluid were

withdrawn from the right pleural cavity; there were cyanosis and

dyspnea. On the eleventh day 700 c.c. of fluid were withdrawn. On

the twelfth day thoracotomy was performed and 100 c.c. of greenish

fluid were removed. The patient’s condition improved for a time, but

on the twenty-sixth day 1,000 c.c. of straw colored fluid were

aspirated from the left pleural cavity and on the twenty-eighth day

the same amount of seropurulent fluid was withdrawn.

=Anatomic Diagnosis.=—Healing abscess of right lower lobe

communicating with the pleural cavity; acute purulent pleurisy with

closed thoracotomy wound on the right side; purulent pleurisy on the

left side; acute bronchopneumonia with lobular consolidation in the

left lung; purulent bronchitis; bronchiectasis with formation of

spherical bronchiectatic cavities; acute splenic tumor.

At the base of the right chest is a closed thoracotomy wound 2 cm.

in length; the right pleural cavity contains 200 c.c. of thick

creamy pus and the cavity is lined by a thick tough membrane. The

left pleural cavity contains 800 c.c. of white purulent fluid

thinner than that on the right side. The right lung is compressed

into the posterior and inner part of the chest. The upper lobe is

pink and air containing; the posterior and lower part of the lower

lobe is red and atelectatic, and fibrous septa are more conspicuous

than elsewhere. The pleura of the external surface near the basal

edge, in an area 2 cm. across, is depressed and yellowish gray in

color. In the center of this area is a small opening communicating

with a pocket 0.5 cm. across within the substance of the lung.

In the lower lobe beneath the interlobular surface are two spherical

bronchiectatic cavities, each about 1.5 cm. across, with smooth

lining in continuity with two branches of the same bronchus of

medium size.

Bacteriologic examination showed the presence of S. hemolyticus in

the blood of the heart. No growth was obtained from the left lung;

the left pleural cavity contained hemolytic streptococci and S.

aureus, the latter in small number. S. hemolyticus and B. influenzæ

were grown from the left main bronchus.

A microscopic section through the abscess and its communication with

the pleura shows that its cavity contains polynuclear leucocytes and

the wall is formed by granulation tissue covered by fibrin. Some

alveoli outside the abscess contain compact balls of fibrin

containing a few fibroblasts; this fibrin stains deeply with

hematoxylin as if it contained calcium. The surface of the lung is

covered by fibrin in process of organization.

In the foregoing instance a pulmonary abscess on the right side has

ruptured into the pleura and, completely separated from the adjacent

lung by a wall of newly formed tissue, is in process of healing. It

shows that these pulmonary abscesses below the pleura may heal provided

drainage is established by rupture into the pleural cavity and

subsequent evacuation of pleural exudate. It is noteworthy that in this

instance empyema extended from the right to the left pleural cavity,

both S. hemolyticus and S. aureus were found at autopsy. The thoracotomy

wound on the right side was closed at autopsy.

Interstitial Suppurative Pneumonia

A second type of suppurative pneumonia is characterized by acute

inflammation of interstitial tissue between the secondary lobules of the

lung and by acute lymphangitis; suppuration involves the interstitial

septa and the walls of the lymphatics. The lesion is designated by

Kaufmann,[82] Beitzke[83] and others acute interstitial pneumonia.

_Pneumonia dissecans_ in which solution of interstitial tissue isolates

sections of lung tissue is said to be a consequence of the lesion. Many

text books of pathology, overlooking the occurrence of this lesion,

limit the consideration of interstitial pneumonia to chronic processes

in which the interlobular and interalveolar fibrous tissue is increased.

Acute inflammation and edema of the interlobular septa of the lung with

no suppuration is often found with both lobar and bronchopneumonia and

is occasionally so far advanced that it can be recognized on gross

examination of the lungs. In a small area interlobular septa are

conspicuous as yellowish lines of edematous appearance which may be 1 to

1.5 mm. in thickness and sometimes form a network with rectangular or

polygonal meshes. The gelatinous appearance of the edematous fibrous

tissue does not suggest suppuration. Microscopic examination shows that

the tissue is distended by edema and contains fibrin and polynuclear

leucocytes; the lymphatics are distended and contain a network of fibrin

within which leucocytes are numerous. Inflammatory edema of the

interstitial tissue has been recognized at autopsy four times in

association with bronchopneumonia (Autopsy 253 with Pneumococcus II;

Autopsy 335, with Pneumococcus IV and S. viridans; Autopsy 477 with S.

hemolyticus and Autopsy 498 with S. viridans); twice with lobar

pneumonia (Autopsy 343 with Pneumococcus IV and Autopsy 353 with

atypical Pneumococcus II); twice with combined lobar and broncopneumonia

(Autopsy 273 with S. hemolyticus and Pneumococcus IV and Autopsy 357

with Pneumococcus IV). Edema of interstitial septa was recognized at

autopsy in the immediate neighborhood of an abscess three times

(Autopsies 277 and 278 with hemolytic streptococci and Autopsy 282 with

hemolytic streptococci and Pneumococcus II). In these instances of

inflammation and edema the lymphatics are found distended by fibrinous

thrombi, and it is probable that occlusion of lymphatics determines the

occurrence of inflammatory edema within the surrounding tissue.

Inflammation has not proceeded to suppuration.

With interstitial suppurative pneumonia, interlobular connective tissue

is marked by conspicuous yellow lines, 1 to 3 or even 5 mm. in

thickness, forming a network with polygonal meshes which represent

secondary lobules (Figs. 10 and 11). The distended septa not

infrequently have bead-like enlargements at intervals and from the cut

surface it is often possible to scrape away creamy yellow pus. These

lines of suppuration invariably extend up to the pleura and are often

broadest immediately below it. Adjacent septa which have not undergone

suppuration are much thickened and have the yellowish gray appearance

produced by edema.

[Illustration:

Fig. 10.—Interstitial suppurative pneumonia; interstitial septa are

the site of suppuration and lymphatics are distended with purulent

fluid; empyema. Autopsy 474, left lung. (See right lung) Fig. 9.

]

[Illustration:

Fig 11.—Suppurative interstitial pneumonia; the left lower lobe is the

site of almost uniform consolidation and here interstitial septa and

their lymphatics are distended with pus. There is more extensive

interstitial suppuration in the upper lobe where consolidation is

absent. The cloudy appearance of the consolidated lung is well

shown. Autopsy 452.

]

Suppurative interstitial pneumonia frequently occurs in association with

bronchopneumonic consolidation which may be peribronchiolar, hemorrhagic

or lobular, but there is in addition consolidation of the pulmonary

tissue between the inflamed septa which may affect part of a lobe, an

entire lobe, or parts of several lobes; it does not exhibit the

characters of confluent lobular pneumonia.

In approximately half of the cases consolidation, associated with

interstitial suppuration, has been lobar in distribution (Fig. 11). The

tissue is laxly consolidated, finely granular, and has a cloudy red or

gray appearance. The coarsely granular surface of lobar pneumonia is

absent. The affected lung may weigh 1,500 or 1,650 grams. Occasionally,

interstitial septa of air containing lung tissue is the site of

suppurative inflammation or edema. In Autopsy 452 the lower lobe, save a

small part at the base, is laxly consolidated; interstitial septa in the

consolidated area are yellow, 1.5 to 2 mm. in thickness, beaded and

exude purulent fluid on pressure. In the adjacent part of the upper lobe

there is a patch of consolidation, and a network of yellow thickened

septa extends from it far into the surrounding air containing tissue.

The weight of the right lung is 635 grams; of the left, 1,650 grams.

The distribution of interstitial suppuration in 21 instances, including

4 in which the lesion has occurred in the same lungs with abscess

formation, has been as follows: right upper lobe, 9 instances; middle

lobe, 4; lower lobe, 5; left upper lobe, 7; left lower lobe, 6. In 6 of

these autopsies more than one lobe of the same lung has been affected by

the lesion; in 2 autopsies parts of both lungs have been affected.

Localized abscess of the lung is more common in the lower than in the

upper lobes, but suppuration of the interstitial tissue is more often

found in the upper lobes.

The duration of illness with interstitial suppurative pneumonia has

varied from six days to five weeks. In over half of the cases death has

occurred during the second week of illness.

The bacteriology of these cases is shown in Table XLVIII.

TABLE XLVIII

════════╤════════╤═════════════════╤═════════════════

│ NO. OF │ │ HEMOLYTIC

│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI

────────┼────────┼────────┬────────┼────────┬────────

│ │ NO. │PER CENT│ NO. │PER CENT

│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE

────────┼────────┼────────┼────────┼────────┼────────

Bronchus│ 10│ │ │ 9│ 90.0

Lung │ 20│ 1│ 5.0│ 17│ 85.0

Blood │ 21│ 2│ 9.5│ 17│ 81.0

────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════

│ │

│ STAPHYLOCOCCI │ B. INFLUENZÆ

────────┼────────┬────────┼────────┬────────

│ NO. │PER CENT│ NO. │PER CENT

│POSITIVE│POSITIVE│POSITIVE│POSITIVE

────────┼────────┼────────┼────────┼────────

Bronchus│ 5│ 50.0│ 10│ 100.0

Lung │ 5│ 25.0│ 7│ 35.0

Blood │ │ │ │

────────┴────────┴────────┴────────┴────────

S. hemolyticus has been almost invariably present in lungs, heart’s

blood and bronchi. In 16 of 21 autopsies hemolytic streptococci have

been obtained from the blood in pure cultures, in one instance

associated with pneumococcus. With associated empyema, pericarditis or

peritonitis, the same microorganism has been found in the pleural

cavities, pericardium or peritoneum. Furthermore, microscopic

examination has demonstrated the presence of chains of streptococci in

the affected interlobular tissue and in much greater abundance in the

distended lymphatics.

Nevertheless in 2 instances no streptococci have been found. These cases

are as follows:

=Autopsy 330.=—Illness began with symptoms of influenza ten days

before death; signs of pneumonia were recognized three days before

death. There is firm, gray red consolidation of the entire left

upper lobe; the interlobular septa are here indicated by yellow

lines of obvious suppuration and thick puslike fluid exudes from the

cut surface of the consolidated tissue. The upper half of the left

lower lobe has undergone gray hepatization, but here there is no

distention of the interlobular septa. There is fibrinopurulent

pleurisy on the left side with accumulation of 400 c.c. of fluid.

Pneumococcus IV is obtained from the blood of the heart and from the

lung. In the suppurating tissue diplococci which stain by Gram’s

method are present in large number; there are a few short chains.

=Autopsy 379.=—Illness began seven days before death with influenza;

signs of pneumonia were first recognized the day before death. The

middle lobe of the right lung is firmly consolidated; on section

there is mottling of deep red and pinkish red and the cut surface is

coarsely granular. The interstitial septa are distended by fluid and

are grayish yellow. There is fibrinopurulent pleurisy on the right

side with accumulation of 600 c.c. of fluid. Pneumococcus atypical

II is obtained from the blood of the heart. A large bacillus

unstained by Gram’s method is obtained from the right lung and from

the right main bronchus. In the bronchus are a few influenza

bacilli. In the suppurating and necrotic tissue of the interstitial

septa are found diplococci and chains of 4 to 6 cocci in great

number; a few large Gram-negative bacilli are found.

In both these autopsies consolidation had the characters of lobar

pneumonia, and pneumococci were obtained from the blood of the heart. It

is possible that streptococci failed to grow or while present elsewhere

were absent at the spot where cultures were made.

It is noteworthy that B. influenzæ was found in the bronchi in every

instance (10) in which cultures were made, but was obtained much less

frequently from the lung. In one instance (Autopsy 474) this

microorganism was found in the blood in association with hemolytic

streptococci. There was suppurative interstitial pneumonia in the left

lung and abscess in the right lower lobe with rupture into the cavity

and empyema. Hemolytic streptococci and B. influenzæ were found in the

bronchus, right pleural cavity and blood of the heart.

In 4 instances (Autopsies 251, 259, 295 and 474) interstitial

suppurative pneumonia has been associated with abscess formation. In one

instance (Autopsy 251) the right middle lobe has been the site of

interstitial suppuration and abscess formation; in another (Autopsy 295)

the left lower lobe has been the site of both lesions, but in the other

2 instances suppurative interstitial pneumonia and abscess formation

have occurred in opposite lungs. In all 4 autopsies hemolytic

streptococci have been found in the blood of the heart and in lungs or

bronchi.

Empyema has been present in all but 3 of 21 instances of interstitial

suppurative pneumonia.

[Illustration:

Fig. 12.—Suppurative interstitial pneumonia, showing an immensely

dilated lymphatic containing purulent exudate, a short distance

below the pleura. Autopsy 474.

]

Histologic examination of lungs with interstitial suppuration shows that

the interlobular septa are distended by serum and contain a conspicuous

network of fibrin. Polynuclear leucocytes are present in varying number,

and at times densely infiltrate the distended tissue; it is not uncommon

to find a zone of densely crowded polynuclear leucocytes along each edge

of the septum, whereas the central part contains comparatively few.

Occasionally, there is hemorrhage into the distended connective tissue.

Within the distended septa occur greatly dilated lymphatics filled with

polynuclear leucocytes (Figs. 12 and 13). Thrombosis of the distended

lymphatics has usually occurred, and a conspicuous network of fibrin in

which are polynuclear leucocytes plugs the lumen. Streptococci in chains

of variable length are found in the inflamed interstitial tissue, but

are present in far greater number within the distended lymphatics.

[Illustration:

Fig. 13.—Suppurative interstitial pneumonia showing a dilated

lymphatic. Autopsy 428.

]

Necrosis of the cells which fill the lymphatics occurs in spots, usually

in the center of the thrombus, and occasionally affects the entire

contents of the lymphatic; polynuclear leucocytes have lost their nuclei

or in some the nucleus has undergone fragmentation. In these spots the

network of fibrin has disappeared. Not infrequently the wall of the

lymphatic in a small sector or throughout the circumference has

undergone necrosis, and spots of necrosis may occur in the interlobular

septa distended by inflammatory exudate. Wherever necrosis has occurred,

chains of streptococci are present in immense number.

Accumulation of polynuclear leucocytes, necrosis of these cells,

solution of fibrin at first in the centers of the lymphatic thrombus and

later throughout, occasionally with necrosis of the wall of the vessel,

result in the formation of an abscess at the site of the distended

lymphatic. These lymphatics, dilated by purulent fluid, may have a

diameter from 2 to 3 mm. and may cause considerable compression and

collapse of immediately adjacent alveoli. Lymphangitis, distention of

lymphatics, thrombosis and finally suppuration may occur in the

lymphatic vessels encircling the blood vessels and in those situated in

the adventitia of the bronchi of medium size.

The alveoli adjacent to the distended septa are filled by inflammatory

products; edema is almost invariably present and the alveoli may contain

serum and desquamated epithelial cells; fibrin is often present, but

more frequently polynuclear leucocytes are predominant. Not

infrequently, abscess formation, recognized microscopically, has

occurred in contact with septa most often immediately below the pleura.

Polynuclear leucocytes are present in immense number and alveolar septa

have disappeared; occasionally, with abscess formation there is more or

less widespread necrosis of tissue, cells both of the exudate and of the

alveolar walls having lost their nuclei.

Lymphatics in many places are distended and plugged by fibrinous

thrombi, whereas elsewhere softening of the thrombus has been brought

about by suppuration. Suppuration, both within the lymphatic and in

adjacent alveoli, appears to be secondary to lymphatic obstruction. In

some instances the lymphatic appears to have undergone distention after

the thrombus has formed, for between the thrombus and the wall of the

lymphatic a channel is occasionally found containing uncoagulated lymph.

[Illustration:

Fig. 14.—Endophlebitis occurring in association with suppurative

pneumonia; the intima contains lymphoid cells in great number; at

one spot there is a small thrombus adherent to the intima. Autopsy

325.

]

Acute endophlebitis has been repeatedly observed in association with

interstitial suppurative pneumonia (Fig. 14). The lesion usually occurs

in veins situated within the septa which are the site of intensely acute

inflammation associated with necrosis. The wall of the vein appears to

be so injured by the surrounding changes that polynuclear leucocytes and

small mononuclear cells accumulate below the endothelium. Throughout the

circumference of the veins, often 0.5 to 1 mm. in diameter, the

endothelium is separated from the underlying media by polynuclear

leucocytes which form a conspicuous zone encircling the lumen. Some

cells of lymphoid type are usually present among the polynuclear

leucocytes. Polynuclear leucocytes are often adherent to the endothelial

lining of the vessel and are not infrequently fixed in the process of

passing through the endothelium. The lesion may be more severe (Autopsy

325), so that the endothelium has disappeared, and upon the exposed

surface fibrin is deposited; within this fibrin polynuclear leucocytes

are numerous and nuclear fragmentation has occurred. The middle coat of

the vessel usually contains few cells; some polynuclear leucocytes

within it may be stretched out as if in process of wandering through the

wall.

In other instances the accumulation of cells below the endothelium is

almost wholly mononuclear. Cells of the type of lymphocytes occur, but

more abundant are slightly larger cells with more abundant cytoplasm.

These cells may form a thick zone below the intima throughout the entire

circumference of the lesion. It seems probable that these cells, like

the polynuclear leucocytes, are derived from circulating blood within

the lumen of the vessel, for small cells of the type of lymphocytes are

not infrequently found adherent to the lumen and occasionally one is

fixed in process of passing through the endothelium.

This endophlebitis appears to be the result of changes outside the

vessel; there is usually necrosis of the adjacent tissue and the

production of the lesion is favored by lymph stasis; as the result of

injury to the vessel wall, polynuclear leucocytes in response to

chemotaxis, or with milder irritation, mononuclear cells, wander through

the endothelium and accumulate below it perhaps on account of the

greater impermeability of the middle coat to the passage of cells.

Epidemic Respiratory Disease The pneumonias and other infections of the repiratory tract accompanying influenza and measles · 第 6 / 10 章

Pneumococcus I and II, which are found approximately in two-thirds of