PERINATAL PULMONARY PATHOLOGY

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PERINATAL

PULMONARY

PATHOLOGY

By J. N. Briggs, M.D., and Georgina Hogg, B.Sc., M.D.

Departments of Pediatrics and Patholog/, University of Manitoba, and the Winnipeg

General Hos-pital

Atebectasis

Hyalirie Membrane

Pneumonia

15 cases 33 cases

20 cases

W

ITHIN recent years there has been

enor-mous interest in the study of

pub-monary factors present in perinatal deaths.

In the last 3 years alone some 40 articles

have been published in the major journals

on this subject. The thorough review on

hyaline membrane syndrome by Tran Dinh

De and Anderson,1 the experimental work

on neonatal respiration by Miller and

Behrle2 and the histochemical studies of

Gitlin3 along with the fundamental work of

Lynch4T have done much to improve our

knowledge of pulmonary pathology in the

newborn.

This study is an attempt to analyze the

natural history of changes seen in the lungs

of infants dying in the first 7 days after

birth.

PATIENT MATERIAL AND METHODS

All the infants in this series were observed

between September, 1954, and February, 1957.

It was felt that the 153 cases which came to

necropsy during this period were a representa-tive group as the necropsy rate during this time

was 92%.

All patients with anomalies of the kidneys,

central nervous system and cardiovascular

sys-tem were excluded. No infant was included

who had received excessive artificial

respira-tion by positive pressure techniques. No data

concerning infants weighing less than 600 gm were reviewed.

Data from 110 of the 153 liveborn infants

were accepted for study and clinical records

and pathologic sections of the lungs of these

infants were reviewed together with those of

26 stillborn infants who were not macerated and

who were delivered during the same period.

Technique of Preparation of Sections

It was felt that it was important to examine considerable areas of lung tissue in each case and not just an isolated segment. With this

in mind all sections were made in a coronal

plane to include the hibum and lateral surfaces

and extending from the base to apex of each

lung. Sections obtained in this way were large

enough to give a representative picture of the

pathologic findings in the lungs. One average

lung section occupied a complete slide

(2.5 x 7.5 cm). All the sections were stained

with hematoxylin, phboxin and saffron stains.

General

RESULTS

Pulmonary factors were considered to be

the chief cause of death in 68 of the cases

(61.9%) in the 110 liveborn infants and these

were classified as follows:

In the remaining 42 cases pulmonary

con-ditions were considered to be contributory

factors rather than the chief cause of death.

The weights of the infants are given in

Table I.

There is an obvious bias in the weights of

the stillborn infants, as smaller fetuses were

usually so autolyzed by the time they were

delivered that they were unsatisfactory for

pathologic examination. The 26 stillborn

in-fants all died shortly before birth and were

not autolyzed.

The types of premedlication and

anes-thesia were reviewed and were similar in all

(Accepted February 11, 1958; submitted October 4, 1957.)

Supported by a Dominion-Provincial Grant from the Department of Child and Maternal Welfare, Canada.

ADDRESS: (J.N.B.) Winnepeg Clinic, St. Mary’s at Vaughn, Winnepeg 1, Manitoba, Canada.

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42 PULMONARY PATHOLOGY

TABLE I

WEIGHT DISTRIBUTION

Weight of Infants Liveborn Stillborn

Lessthanl,000gm 1,000-1,500gm 1,800-2,000gm 2,000-2,500gm Morethan2,SOOgm 24 27 21 18 20 0 3 0 4 19 110 26

respects to the general use of these agents

in this hospital. Only one-third of the

mothers received premedication. The

com-monest anesthetic was combination nitrous

oxide and cycbopropane and this was used

in 40% of all the cases.

Microscopic Findings

Microscopically the lung sections were

di-vided into seven pathologic categories. Each

category represented the major and

gen-eralized finding in the lung sections. Some

overlap did occur in the same lung, but on

the whole these categories were well

de-fined.

1. STILLBORN LUNG (Fics. 1, 2) : In

these lungs the bronchioles and bronchiolar

atria were open. The air spaces were partly

expanded with fluid (amniotic) and often

contained debris and squamous cells. The

36 cases in this category were made up of 26

true stillbirths and 10 livebirths. These lungs

had the typical appearance and it was quite

impossible to separate findings pertaining

to liveborn infants from those of stillborn

infants. Nineteen of the stillborn infants and

seven of the liveborn infants weighed more

than 2,500 gm.

2. IMMATURE LUNG: Findings classified

as immature lung were present in very

small premature infants. Five of six

pre-mature infants weighed less than 700 gm.

Here, because of a relatively large amount

of interstitial tissue and inadequately

de-veloped air spaces the lungs were neither

expanded nor collapsed.

3. ATELECTASIS: Lungs similar to those

of the stillborn infants but from which the

amniotic fluid had been resorbed and many

of the air spaces had collapsed were

classi-fled as atelectatic. The weight range in this

group was from 1,000 to 4,000 gm.

4. COLLAPSE WITH HYALINE MEMBRANE

(Fic. 3) : This occurred uniformly through

the weight range of 1,000 to 2,500 gm. Four

infants weighed more than 2,500 gm. The

microscopic appearance of the dilated

alveolar ducts and atria lined with

acido-philic membrane was seen with or without

hyaline plugs in the bronchi and

bronchi-oles.

5. COLLAPSE WITHOUT HYALINE

MEM-BRANE BUT OF HYALINE TYPE

(

Fic. 4

)

: This is a form of atelectasis considered a separate

category because of the striking resemblance

to that seen in hyaline membrane. However,

no membrane is present. These cases were

found evenly distributed in the weight

ranges, 1,000 to 2,500 gm.

6. PULMONARY HEMORRHAGE: Petechial

hemorrhages were not included; two types

of pulmonary hemorrhage were recognized:

(a) Interstitial hemorrhage, where blood

occurred in the fibrous septal tissues and

pleura.

(b) Intrapulmonary hemorrhage in which

the bleeding occurred into the air spaces.

When moderate, the lung was largely

cob-lapsed; when massive, the lung was actually

expanded by blood. It was noted that

hy-aline membrane and intrapulmonary

hemor-rhage did occur in association (Fig. 3).

7. PNEUMONIA: This was of two types:

(a) Bronchopneumonia with typical

pen-bronchial inflammatory changes and

poly-morphonuclear cells in the alveolar exudate.

(b) Interstitial pneumonia in which most

of the inflammation was confined to the

interstices of the lungs and often there were

mononuclear cells in the alveolar exudate.

Cultures were made from practically all

the lungs in this necropsy series along with

cultures from the spleen, trachea and heart

blood but with little success in isolating

any pathogenic organism frequently, or, in

the few cases that were studied in this

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ARTICLES

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77 F. S

FIG. 1 (Upper). Photomicrograph of stillborn lung.

Fic. 2 (Lower). Photornicrograph of “stillborn type” of lung in early neonatal death.

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PULMONARY PATHOLOGY

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Fic. :3(Upper). Photomicrograph of lung demonstrating ‘collapse with hyaline membrane.”

Ftc. 4 (Lower). Photomicrograph of lung demonstrating “collapse with:nit hyaline

membrane but of hyaline membrane type.”

44

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ARTICLES 45

TABLE II

INCIDENCE OF PATHOLOGIC FINDINGS

No.of

Cases

%of

Cases

Hyaline membrane 37 33.6

Pneumonia 7 24.5

Atelectasis 16 14.5

Stillborn type 10 9.1

Hyaline type (no nieinbrane) 9 .2

Premature lungs 6 5.5

Pulmonary hemorrhage 5 4.5

110 99.9

Table II summarizes the frequency of

these findings in the liveborn infants.

As has been stated, the majority of cases

fell into one category or another. Four cases

of hyaline membrane and mild pulmonary

hemorrhage were grouped under the major

finding of hyaline membrane.

Five infants had both hyaline membrane

and pneumonia. Two of these were

classi-fled in the pneumonia group and three in

the hyaline membrane group.

It was felt that it would be of interest to

relate the pathologic findings to the length

of time the infant had lived, as one might

expect these categories to have different

time relationships. Table III illustrates the

distribution among the 110 liveborn infants.

Within the first 12 hours, as might be

expected, all the patients with “stillborn

type” of lungs died as did the majority of

infants having premature type of lungs or

atelectasis.

In this same period of time it will be seen

that hyaline membrane type of atelectasis

without the membrane was almost as

corn-mon a pulmonary finding as true hyaline

membrane. It will also be noted that a

few cases of pulmonary hemorrhage were

present.

Pneumonic changes were present in the

lungs of the other infants that died within

12 hours of birth. They were the next most

common finding after atelectasis and the

“stillborn type” of lung.

In the 12- to 24-hour period a very

differ-ent pattern was apparent. Hyaline

mem-brane far surpassed the combined total of

all other pathologic findings and pneumonic

inflammation was infrequent.

After 24 hours of life the incidence of

hy-aline membrane rapidly declined and was

present in only four cases in which death

occurred after 60 hours. After 48 hours, the

frequency of pneumonia exceeded that of

all other conditions.

When certain categories were grouped

to-gether, excluding the “stillborn type” of

lungs, the picture was further highlighted

(Table IV).

The group with inadequate expansion

died very early, while a definite time lag

occurred in those cases where some

un-known mechanism or mechanisms produced

the hyaline type of atelectasis, hyaline

mem-TABLE III

NUMBER OF CASES IN EACH PATHOLOGIC Gnou

Pathologic Category

-Duration of Life (hours)

--86-48 48-60 ---60 o-1 --1-L -p5-36

Stillborn type 10

Premature type 5 1

Ateleetatic 14 1 1

Hyaline type ateleetasis without membrane 6 1 2

Ilyaline membrane 7 15 8 1 2 4

Pulmonary hemorrhage 2 2 1

Pneumonia 9 3 1 1 4 9

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Number of Cases

Hours Duraiwn of Life

-(Percentageof Cases)

---.8+

0-12 12-8

Premature lungs+atelectasis 22 81.9 9.0 9.0

Hyaline type of atelectasis+hyaline

mem-brane+pulmonary hemorrhage 51 29.4 60.8 9.8

Pneumonia 27 33.3 18.5 48.2

TABLE IV

PERCENTAGE DISTRIBUTION OF PATHOLOGIC GROUPS

brane and pulmonary hemorrhage. The

group with pneumonia shows a “U” type of

distribution caused in the early hours by

intrauterine infection and in the later period

by infections contracted within the nursery.

Hyaline Membrane

Hyaline membrane was the major

patho-logic finding in 37 cases (33.6%). The

classi-fication of the infants according to weight

may be seen from Table V. These 37 cases

were reviewed and, while the number was

insufficient to draw any conclusions, there

was a definite tendency for the membrane,

when it was graded in severity from 1 to 4+,

to be 1 to 2+ in the first 8 hours after birth,

and thereafter 3 to 4+ until about 60 hours,

when it again was 1 to 2+ . This suggested

a definite sequence of early formation to

a full blown condition and then a gradual

disappearance, a finding which fits well with

the clinical picture of respiratory distress

in infants who suffer from probable hyaline

membrane and survive.

It was interesting to note that the cases

categorized as hyaline type of atelectasis but

TABLE V

WEIGHT DISTRIBUTION OF PATIENTS WITH

HYALINE MEMBRANE

Weight of Infants Number of Cases

Lessthanl,000gm 1,000-1,500gm 1,500-2,000gm 2,000-2,500gm Morethan2,SOOgm 2 12 11 9 3 37

without the hyaline membrane presented a

typical picture of respiratory distress which

was indistinguishable from that seen with

the true hyaline membrane. It was also

note-worthy in the study of time relationships that

the hyaline type of atelectasis without the

membrane definitely appeared to precede

hyaline membrane. On the other hand

pub-monary hemorrhage when it occurred with

hyaline membrane was felt to be a sequel

to the latter condition.8

DISCUSSION

This histologic study emphasized that

elapse of a definite interval from the infant’s

birth appeared to be necessary before

hy-aline-like atebectasis, hyaline membrane,

and pulmonary hemorrhage were likely to

be present in the necropsy material. These

three conditions appeared to be closely

in-terrelated in time and pathogenesis.

There appeared to be a definite sequence

in which hyaline membrane was preceded

by the hyaline-like atelectasis. While the

cases of pulmonary hemorrhage were few,

it was felt from a previous study that

pul-monary hemorrhage appeared to represent

the end result of this triad. Therefore, those

who die early show only the hyaline type

of atelectasis. Those who survive longer

demonstrate true hyaline membrane.

Fi-nally, in some of these the end result is a

massive intrapulmonary hemorrhage which

floods the air spaces.

In this study these three conditions

reached a peak incidence between 8 and 24

hours. The incidence of pneumonia showed

two peaks, the first occurring within 12

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ARTICLES 47

These findings differ from those of

Land-ing9 who noted the histologic findings of

hy-aline membrane to be most frequent from 0

to 36 hours while the incidence of

pneu-monia (acute) reached its peak between 36

and 96 hours. However, this study is based

on a different premise as he was concerned

mainly with the association of several

differ-ent pulmonary findings which might occur

in the same lung. This study was concerned

with the major pathologic condition present

in any given pulmonary section studied.

SUMMARY

A series of 153 necropsies of liveborn

in-fants was reviewed. Data from 110 of these

and 26 stillborn infants were accepted for

study. It was noted that 61.9% of the

chil-dren died from major pulmonary disorders.

Hyaline membrane was present in 33.6% of

the 110 liveborn infants.

The time relationships of the various

con-ditions was reviewed.

A new pathologic appearance-hyaline

type of atelectasis but with the absence

of the true membrane-was noted. This

con-dition is considered to fall into the same

clinical and pathologic group as hyaline

membrane and pulmonary hemorrhage.

REFERENCES

1. Tran Dinh De, and Anderson, G. W. : The

experimental production of pulmonary

hyaline-like membranes with atelectasis. Am.

J.

Obst. & Gynec., 68: 1557, 1954. 2. Miller, H. C., and Behrle, F. C. : The effects

of hypoxia on the respiration of newborn

infants. PEDIATRICS, 14:93, 1954.

3. Gitlin, D., and Craig,

J.

M.: The nature of

the hyaline membrane in asphyxia of the

newborn. PEDIATRICS, 17:64, 1956.

4. Lynch, M.

J.,

and Mellor, L. D.: Hyaline

membrane in the lungs of the newborn.

Lancet, 1:1002, 1955.

5. Idem: Hyaline membrane disease of newborn premature lungs; a new approach.

J.

Pediat., 47:275, 1955.

6. Lynch, M.

J.

C., Melbor, L. D., and Badgery,

A. R.: Hyaline membrane disease.

J.

Pediat., 48:602, 1956.

7. Lynch, M.

J.

G.: Hyaline membrane disease

of lungs; further observations.

J.

Pediat.,

48:165, 1956.

8. Briggs,

J.

N., and Hogg, C. : Pulmonary

haemorrhage in the newborn infant.

Manitoba M. Rev., 36:5, 1956.

9. Landing, B. H. : Pulmonary lesions of

new-born infants; a statistical study.

PsDIA-TIIICS, 19:217, 1957.

SUMMARIO IN INTERLINGUA

Perinatal Pathologia Pulmonar

Le presente studio analysa be histonia natural

del alterationes incontrate in be pulmones de

infantes qui mon intra be prime 7 dies post

nato. Esseva examinate be constatationes

nec-roptic relative a! pulmones de 110 infantes.

Etiam be dossiers clinic esseva studiate. Pro

objectivos de comparation, 26

monte-natos-non-macerate e nascite durante be mesme

pe-riodo-esseva studiate. Factores pulmonar

es-seva considerate como le causa principal del

morte in 61,9% del vive-natos. Esseva notate

que be typos de premedication e de anesthesia

esseva simile in omne respectos a illos in uso

general al hospital ubi be studio esseva

condu-cite. Sectiones microscopic esseva facite in be

plano coronal a includer be hilo e le

super-ficies lateral del pubmon ab be base usque al

apice pro un studio complete del pulmon

in-tegre.

Iste revista justificava be conclusion que

septe categorias pote esser distinguite. Ibbos es:

1. Pulmon “monte-nate” (9,1%).

2. Pulmon immatur (5,5%).

3. Atelectasis (14,5%).

4. Coblapso con membrana hyabin (33,8%).

5. Collapso sin membrana hyalin sed del typo hyabin (8,2%). Iste forma de atebectasis

es-seva considerate como un categoria separate

a causa de su frappante similitate con ver

mem-brana hyalin ben que nulle ver membrana

es-seva presente in iste casos. Iste condition

oc-curreva in individuos del mesme ordine de peso

(1000 a 2500 g) como le casos de membrana

hyalin.

6. Hemorrhagia pulmonar (4,5%). Isto

signi-ficava massive hemorrhagia intrapulmonar.

7. Pneumonia (24,5%). Isto esseva de duo

typos principal, bronchopneumonia e pneu-monia interstitial.

Es constatate que individuos con pulmon

monte-nate e immatur e con atelectasis mon sin

exception durante be prime 12 horas del vita.

Esseva notate que a circa iste tempore

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atelectasis sin be presentia del membrana esseva

quasi tanto commun como le mortes in casos

con presentia del membrana hyalin. Durante

be periodo de plus que 12 usque a 24 horas,

presentia de membrana hyalin excedeva per

multo omne altere causa mortal. Ilbo attingeva

su maximo a! nivello de circa 24 horas e

des-cendeva subsequentemente. A partir de iste

tempore, constatationes pulinonar esseva

rela-tivemente pauco numerose, usque al puncto de

circa 60 horas post nato quando pneumonia

deveniva le plus frequente constatation

mic-roscopic.

Es presentate le conception que le

condi-tiones de atelectasis hyalinoide sin membrana,

de membrana hyalin, e de hemorrhagia

pul-monar es interrelationate tanto in br histobogia como etiam in be tempore de br declaration.

BRONCHIAL OBSTRUCTION Dua TO PULMONARY ARTERY ANOMALIES. I. VASCULAR

SLING, S. Contro et al. (Circulation, 17:418, March, 1958.)

The authors report three cases of respiratory embarrassment in infants from corn-pression of the right bronchus and trachea by a “vascular sling” formed by an

aber-rant left pulmonary artery coursing anterior to the right main-stern bronchus and

posterior to the trachea. Five similar cases have been described in earlier literature.

The embryologic origin of this anomaly appears to be a disturbed time-sequence in

the growth and union of the left pulmonary artery and the left lung bud. The clinical symptoms are those of respiratory distress in the neonatal period produced by

tracheo-bronchial compression, associated with obstructive emphysema of the right lung.

Bronchoscopic examination reveals extrinsic pressure on the right bronchus and

pos-terior wall of the trachea. The esophagram does not reveal any posterior indentation

and is thereby helpful in distinguishing this entity from the more common “vascular

ring” which is a systemic arterial malformation causing constriction of the trachea

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1958;22;41

Pediatrics

J. N. Briggs and Georgina Hogg