AN OUTLINE OF
PULMONARY FUNCTION
AND

PULMONARY EMPHYSEMA

An Outline of
PULMONARY FUNCTION
AND

PULMONARY EMPHYSEMA

By

EUGENE HOSENMAN, M.D.

At»«tdn/ Clinical Profetsor of Medicine (Thorocie)

Loma Linda Unlcenitv, School of Medicine
Los Angeles, California

CHARLES C THOMAS

Springfield • IHinot*

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PREFACE

T his monograph is ^vritten in outline form because, in the ex-
perience of the writer, it is the best approach in introducing
such a complicated subject as dinical pulmonary physiology to
students and clinicians. So muth has been written on the various
aspects of research and clinical studies in this field, that it is diffi-
cult for a student or busy clim'cian to get a proper perspective of
the entire subject to enable him to apply it in his clinical practice,
\mless a bird’s eye view in the form of an outline is presented to
him.

Only our basic present day knowledge of pulmonary function
and the principles of the essentia) lalwratory procedures used in
the determination of the pulmonary function in health and disease
are presented. Greater attention is given to the clinical studies of
abnormal pulmonary physiology and the clinical application of
the various pulmonary function tests.

The material presented here is based on a review of the litera*
ture of the past fifteen or twenty years witten by authorities in
rile field of pulmonary physiology and its clinical applicarion.
Various views, some of which are controversial, have been pre-
sented, especially those pertainmg to the therapeutic application
of the physiologic principles.

The monograph is divided into three parts:

Part I, pulmonary function and function tests, in which the
basic principles of pulmonary physiology and the application of
these principles in the various function tests, are outlined.

Part II, pulmonary emphysema, in which the discussion of the
abnormal pulmonary physiology of this disease and the thera-
peutic measures undertaken to correct it, are presented.

Part UI, the syllabus, is a concise outline review of the whole
siihject and serves as an aid in the reWew of the entire sub/eet
matter, after the principles outlined in Parts I and n have been
mastered.

Eugene Rosenman, M.D.

CONTENTS

Fage

Preface vii

PART I

PULMONARY FUNCTION AND FUNCTION TESTS
Chapter I. Puiaionaby FxntcnON 5

A. Ventilation 5

1. Lung Volumes and Capacib'es 5

2. Ventilation Volumes 6

3. Velodty of Ventilation 12

4. Mechanics of Breathing 13

5. Control of Breathing 15

B. Perfusion 17

1. Cardiac Output 17

2. Distribution of Blood Flow 17

C. Diffusion 18

1. Solubility 18

2. Difference in Pressure of Gas on Both Sides of the

Membrane 20

3. Permeability of Membrane 21

Chapter 11. Pulmonary iNsuFFiOENcy

A. Ventilatory Insufficiency

1. Restrictive Ventilatory Insuffidency

2. Obstructive Ventilatory Insufficiency

B. Respiratory Insufficiency

1. Uneven Perfusion

2. Impaired Diffusion

Chapter III. Hypoxia

A. Shunts of Venous to Arterial Blood

J. CoBgcaits} Heart Disease ^ ,

2. Pulmonary Arteriovenous Pistulae

B. Pulmonary Insufficiency

1. Hypoventilation

ix

Pulmonary Function and Pulmonary Emphysema

Page

2. Uneven VA/Qc Ratios 33

3. Impaired Diffusion 36

4. Differentiation between Different Causes of Hypoxia . 41

Chapter IV. Tests of VENnLATonr Function 43

1. Ratio of Residual Volume to Total Lung Capacity ... 43

2. Timed Vital Capacity 43

3. Maximum Breathing Capadty. Ventilation Factor ... 43

4. Minute Ventilation 44

5. Alveolar Ventilation 44

6. Index of Intrapulmonary Mixing 4S

7. Air Velocity Index 45

8. Percentage Breathing Reserve 46

9. Walking Index 48

10. Spirogram 47

11. Expirogram 48

IS. Bronchospirometry 50

Chapter V. Tests OF Respiratobv (Gas Excbance) Function . 51

1. Arterial O2 Saturation 51

2. Os Uptake after Exercise 52

3. Ventilation Equivalent 53

4. Ventllation/Blood Flow Ratio Variations 54

5. Arterial Blood CO2 Tension ......... 55

6. Arterial Blood pH . 59

7. Cardiac Catheriration 61

8. Tests of Diffusion 61

9. Hb and BBC Determination 61

10. Exercise Tests 61

PART n

PULMONARY EMPHYSEMA

Chapter I. Pathophysiolcxxt 67

A. Classification 67

1. Non-Obstructive 67

2. Obstructive 67

B. Etiology 67

1. Chronic Bronchitis 67

2. Crenshaw's Theory— Obliterative Vascular .... 68

Contents xi

Page

C. Pathology 68

1. Infianunatory Changes in Mucosa 68

2. Dilatation and Distortion of Alveoli 68

3. Sclerosis and Narrowing of Pulmonary Arteries ... 68

D. Correlation of Abnormal Physiology %vith PaUiology

in Pulmonary Emphysema 68

1. Bronchitis and Brondiiolitis 68

2. Alveolar Changes 69

3. Arteriolar Changes and Destruction of Capillaries . 70

Chapter II. Function Tests in PoiAfONARY Emphysema ... 73

A. Ventilatory 73

B. Gas Exchange 75

Chapter III. Diagnosis 77

1. Clinical Course 77

2. Physical Signs and Laboratory Findings 80

3. Boentgenologic Findings* 81

4. Differentiation from Bronchial Asthma 81

5. Physiological ClassiScation 82

Chapter IV. TnEAi^tENT 86

PART m
SYLLABUS

Chapter I. Pulmonary Funchon 97

A. Ventilation 97

B. Respiration or Gas Exdiange 100

Chapter 17. Pulmonary iKsumciENcy 101

A. Ventilatory 101

B. Respiratory 103

Restrictive Diseases 106

Obstructive Diseases 107

Dyspnea 103

Arterial Hypoxia 109

Pulmonary Hypertension Caused by Hypoxia 110

Hypercapnia Ill

Respiratory Acidosis 112

Chapter III. Pulmonary FuNcnON Tests 113

A. Ventilatory 113

B. Respiratory •

xii PtilmoncTy Funcfion and Pulmonary Emphysema

Page

Chapter IV. 'Treatment oE Pclmonaby Emphysema .... 119

References and Suggested Reading 121

Index 133

AN OUTLINE OF
PULMONARY FUNCTION
AND

PULMONARY EMPHYSEMA

PART I

PULMONARY FUNCTION
and

FUNCTION TESTS

Chapter I

PULMONARY FUNCTION

T he chief function of Ae lung is to oxygenate the blood and
to rid it of excess CO 2 , This is being accomph'shed by:
Ventilation— geiihig the air in and out of the chest and its dis-
tribution to the alveoli.

Per/uston— circulation or blood flow in the lung and its distribu-
tion to the capillaries throughout the lung.

Diffusion— the passage of gases through die alveolo-^apillary
membrane.

A. Ventilation

1, Lung Volumes and Copacftics (See Fig. 1 )

1) Volumes

a) Tidal Volume (TV). Volume of air expired at rest in a sin-
gle breath. Normal about 500 ml.

b) Inspiratory Reserve Volume (IRV). Maximal amount in-
spired beyond a normal inspiration. Normal about 3000 ml.

c) Expiroforj/ Rcseroc Volume (ERV). Maximal amount ex-
pired above a normal expiration. Normal about 1000 ml. in men,
and 700 in young women (approx. 252 of vital capacity).

d) Residual Volume (RV), Volume of air remaining in die
lung after a maximal expiration. Normal about 2500 ml. in elderly
men and women, and 1200 ml. in young men and women (approx.
25 to 352 of total lung capacity. In elderly people up to 502).
Measured by obtaining FRC (v.i.) and substracting from it the
ERV.

2) Capacities

a) Inspiratory Capacity (IRV + TV). Normal about 3500 ml.
(approx. 752 of vital capacity).

b) Functional Residual Capacity (ERV + RV). Normal about
3500 ml, in elderly men, or 2000 ml. in young men and women. It
is measured by two methods:

5

6 Pulmonary Function and Pulmonary Emphysema

Open Circuit or Nitrogen Wasftouf Method of Darling (1940) .

The N 2 of the lungs is washed out by breathing 100% Os for
seven minutes and collecting all the expired air in a spirometer.
FRC = Volume of Ns washed out from lungs (minus Ns washed
out from tissues into the lungs as a result of lowering alveolar Ns
tension)/80% (which is % of Ns in the lungs), (minus terminal
alveolar Ns).

Closed Circuit Helium Method of Mcneelt/‘ (1949).

A known concentration of He (O 2 added to prevent asphyxia)
in a known volume is rebreathed until equilibrium of He con-
centration behveen Iimgs and spirometer is obtained. FRC -
Spirometer volume, times (initial He concentration, minus final
He concentration)/final He concentration,

c) Vital Capacity (IC + ERV). Normal about 3000 ml. ± 20%
in young women. 3500 ml. ± 20% in elderly men, and 4800 ml.
± 20% in young men (approx. 65 to 75% of total lung capacity).
West’s Formula for adult men: VC - 25 ml. x height in cm. For
adult women : 20 ml. x height in cm.

d) Total Lung Capacity. Normal about 5000 to 6000 ml. in
men of all ages, and 4500 ml in young women.

2. VentilatianVolumes

1) Minute Ventilation

Volume of gas expired in one minute at rest. It equak Tidal
Volume X frequency of respiration at rest. Normal about 6 to 8
T./min or about 3 to 4 L/roin/M* of body surface area. On exer-
cise, it is 8 to 10.5 L/min/M* BSA or may go up to 70
L/min/M® on strenuous exercise.

2) Dead Space

That part of tidal volume which is not engaged in gas exchange
—either because it fills the conducting air^vays and doesn’t reach
the alveoli— the Anatomic Dead Space, or it returns from venti-
lating alveoli which are poorly perfused or not perfused with
blood. “Distribution Dead Space” or “Alveolar Dead Spaced The
Anatomic dead space and the “Alveolar Dead Space” are grouped
together under the name Physioio^ail Dead Space. In health the

Pulmonary Function 7

physiological dead space is almost the same as the anatomic dead
space and should be no more than 302 of tidal air. It is only in
pulmonary disease feat fee physiological dead space is increased
due to increase in “Alveolar Dead Space” causing the so called
"Dead Space Ventilation.'*

It is conceivable, however, that in some disease, e.g., bron-
chiectasis, fee anatomic dead space is also increased. The ana-
tomic dead space has been calculated from measurements of casts
taken of fee oropharynx, trachea and major bronchi of different
age groups. The measurement for adult is about 150 ml. Anatomic
dead space may also be obtained from the CO 2 concentration in
end tidal (alveolar) air, and in expired air, measured by rapid gas
analyzer according to Fowlers method and calculated by Bohr’s
equation feus;

dead space =

(conc'n COj alveolar air minus conc'n COj expired air)

X dda! volume

ddaTv^ume condn^Os alveolar ah

However, this equation can be applied only if all fee aveoli are
in contact with perfused blood. If alveolar dead space is present,
the air from non-perfused alveoli will contain no COs and will
dilute fee CO^ concentration of fee total alveolar air. We are,
therefore, using a modified Bohr’s equation, substituting fee COj
tension of arterial blood for fee alveolar CO 2 concentration (since
fee arterial CO3 tension is in equilibrium wife fee CO2 tension
of fee alveoli which this blood has perfused). The equation feus
reads:

j , PaCXDa — • PECO 2 X b'dal volume

dead space = —

(PaC 02 = arterial CO 2 tension)

( PECO 2 = CO- tension in expired air)

This actually measures fee physiological dead space.

Increase in physiological dead space is found in all conditions
in which pulmonary capillaries have been obliterated but fee
alveoli are still aerated, e.g., pulmonary embolism, emphysema,
or in conditions which fee ventilation in some parts of fee lung is
greater than fee corresponding capillary blood flow, e.g., emphy-
sema. (If fee alveolar ventilation in fee areas \vife diminished

8 Pulmonary Function and Pulmonary Emphysema

blood flow is decreased in proportion-there is no dead space, of
course.)

Dead Space Ventilation leads to Arterial Hypoxia and Hyper-
capnia, because there is a compensatory increase in blood flow
in other parts of the lung to take care of the cardiac output, and
if the ventilation in these areas is not increased in proportion to
the increased blood flow, a relative alveolar hypoventilation is the
result.

3) Alveolar Ventilation or Effective Alveolar Ventilation, VA

That part of the tidal volume actually reaching the alveoli and
engaging in the gas exchange with the capillaries. It equals tidal
volume minus dead space. Normally, it should be about 70® of
the tidal volume.

4) Alveolar Ventilation per Minute, VA

VA equals (Tidal Volume— Dead Space) x Frequency of Res-
piration. A good way of determining alveolar ventilation per
minute Is by formula:

Normal alveolar ventilation per minute is about 4 to 5 L/min
or 2 to 2.5 L/min/M* BSA.

From the above equab'on VA = (TV-DS) x Frequency, it can
be seen that VA is decreased when either the tidal volume or
frequency or both are decreased. (There is, however, a greater
decrease with decrease in tidal volume than with decrease in
frequency, because with a decrease in tidal volume there is a
relative increase in dead space which is multiplied by the fre-
quency of respiration.) It is also evident from this equation that
VA is decreased when there is an increase in physiological dead
space. This decrease in VA is a decrease in amount of alveolar air
taking part in gas exchange in the areas with dead space ventila-
tion due to the fact that the bbod flow in these areas is decreased
but not due to a decrease in volume of air entering the alveoli.
The alveoli in fact are ventilating normally and the minute venti-
lation is normaL

Pulmonary Function 9

The above is an example of the fact that minute ventilation
may be normal but effective alveolar ventilation could be sub-
normal. Another instance of normal minute ventilation \nth de-
creased alveolar ventilation is tlie case of decreased tidal volume
and proportionately increased frequency of respiration— the min-
ute volume would be normal, but the alveolar ventilation would
be decreased. For example, if the tidal volume be decreased from
500 to 300 ml. and the frequency be increased from 12 to 20,
the minute ventilation would still remain 6£X)0 ml. But the VA
in the first case is (500 ~ 150) x 12 - 4200 (normal), whereas in
the second case it would be (300 - IS)) x 20 - 3000.

5) Uypoccntilation of the Whole Lung

Decreased minute ventilation. Th«, of course, always means
also alveolar hypoventilation. The reverse, however, is not always
true— in the example cited above alveolar hypoventilation may be
present but minute ventilation may be normal.

Hypoventilation alwTiys leads to arterial Hypoxia and Hyper-
capnia.

Hipoventilation occurs in all conditions restricting chest ex-
pansion and strobe volume, so called resfrictioe diseases. These
arc:

a) Depression of the respiratory centers by anesthesia, nar-
cotics, cerebral trauma, increased intracranial pressure, cerebral
ischemia and narcotic concentration of CO 3 and cases of idio-
pathic Alveolar Hypoventilation,” presumably caused by damage
to the respirator)’ center ( Ricliler, T.» cf at, 1957).

b) Restriction of bellows action of thorax or lung.

a. Interference with neural conduction, e.g.. Polio, My-
asthenia Gravis, Traumatic spinal cord lesions.

b. Limitation of movement of Ae lliorax by Artliritis, by
chest deformity, e.g.. Kyphoscoliosis, by obesity, c.g.,
Pickwickian SjTidrome, by paralj'sis of the diaphragm,
and ascites.

c. Limitation of movement of the lungs by thickened
pleura, by pleural effusion and by pneumothorax.

c) Decreased disicnsiblUty of the lung by generalized pulmo-
nary fibrosis or by pulmonary congestion.

10 Pulmonary Function and Pulmonary Emphysema

d) Decreased lung columet e-g-, pneumonectomy, pneumonia,
tumor, atelectasis or complete occlusion of many bronchioles.
Latter occurs as a restrictive defect in obstructive disease.

Hyperventilation •will correct both the hypo.'da and hyper-
capnia. Inhalation of high O 2 on the other hand will correct the
hypoxia but not the hypercapnia. It may even precipitate respira-
tory acidosis (because of the elimination of the hypoxic stimu-
lant to the chemo-receptor centers). Thus, in anesthesia, if O 2 is
given without hyperventilation, the hypoxia wll be corrected but
the patient may develop respiratory acidosis.

6) Uneven Ventilation

Uneven Distribution of Alveolar Air, so called Uneven Intra-
pulmonary Mixing. Result: some alveoli have decreased ventila-
tion, others— normal or increased ventilation. This is present to a
slight degree even in healthy individuals, especially older people.
It may increase in certain positions of the body, viz. lateral incum-
bent. It becomes marked in certain cardiopulmonary diseases,
e.g., asthma, bronchiectasis, congestive heart disease, pulmonary
carcinoma and in post pneumonectomy patients. It becomes most
marked in pulmonary emphysema. In the latter, all the causes of
uneven ventilation are present, e.g. 1) regional changes in elas-
ticity; 2) regional bronchial obstruction; 3) regional check valves
in the bronchial tree; 4) regional disturbance in expansion, as in
fibrosis.

Uneven ventilation always leads to arterial hypoxia unless the
blood flow is reduced in the hypoventilating area in proportion
to the decrease in ventilation. This h)poxia persists even if the
remaining areas of the lung are hyperventilating, thus raising
the minute ventilation and total alveolar ventilation to normal or
even above normal. Thus, in contradistinction to hypoventilation
of the whole lung, in uneven ventilation hypoxia is not corrected
even if the minute ventilation and total alveolar ventilation are
increased to normal or above normal. Hyperventilation succeeds
in increasing the ventilation only in the normally ventilating
alveoli, the Oj pressure in these alveoli is raised to about 116 to
122 mm. Hg. (normal is about 100 to 104). This rise in Oj pres-
sure can increase the O 2 saturation in the capillaries of these areas

Pulmonartf Function 11

but very little and the blood coming from these areas cannot thus
correct the hypoxia in the blood coming from the areas with
poorly ventilated alveoli. The reason for this hes in the peculiar
S shaped curve of oxyhemoglobin dissociation curve, see Figure
2. Even a rise in alveolar Oa pressure to 150 mm. Hg. produced
by administration of 27.8% Oj (as reported by Motley*®’ in a case
of pneumoconiosis), fails to correct the hypoxia in such a case.
Only inhalation of 100% O^, which raises the partial pressure of
alveolar O 2 to above 400 mm. Hg., will succeed to correct the
hypoxia produced by uneven ventilation, because this higher
partial pressure of O 2 will cause a marked increase of O 2 dissolved
in the plasma of the capillaries returning from the normally ven-
tilating alveoli and will raise the O 2 saturation to normal in the
blood from tbe hypoventilating alveoli.

Hyperventilation produced by intermittent positive pressure
breathing may, however, alleviate the hypoxia even though the
partial pressure of O 2 in alveolar air is not higher dian 120 mm.
Hg. This is so because the high flow rate succeeds to ventilate
even the hypoventilating alveoli. In like manner, a mild case of
uneven ventilation may be able to alleviate the hypoxia during
exercise which causes a much higher ventilation tlian hyperven-
tilation at rest (as high as 20 to 100 L/min.). Uneven ventilation
also leads to hypercapnia and consequent respiratory acidosis.
Hyperventilation of the normally ventilating areas of tlie lung,
will blow off the excess C02 and correct the hypercapnia. (Un-
like the oxyhemoglobin dissociation curve which is S shaped with
a flat upper part, the C 02 dissociation curve is a slightly curved
strai^t line with the CO 2 content of the blood being proportional
to the PCOa of the arterial blood. )

7) Hyperventilation of the Whole Lung

Increased Minute Ventilation. Hyperpnea occurs in: a) ner-
vous or emotional hyperventilation— "Ht/peroenfilafion St/n-
drome" resulting in respiratory alkalosis; b) exercise (interest-
ingly, maximal ventilatory re^onse to severe exercise is never
as great as tliat in maximum voluntary ventilation, i.e., MBC.
Exception— occasionally in emphysema, MBC is so low that it
is less than exercise ventilation); c) high altitudes, caused by

12 Pulmonary Function and Pulmonary Emphysema

low O 2 ; d) A-A Block Syndrome; e) early stages of many diffuse
fibrotic diseases of the lung; f) congestive ventilatory insuffi-
ciency; g) dead space ventilation and stimulation by hypercap-
nia, e.g., emphysema; h) metabolic acidosis.

3. Velocity of Ventilation

1) Maximum Breathing Capacity

Maximum amount of air breathed in one minute, the subject
breathing as deeply and rapidly as he can for hvelve seconds.
Normal— 120 to 170 L/min. Diminished in obstructive diseases
(bronchoconstriction) but not necessarily in restrictive diseases,
i.e., having restricted expansion without obstruction.

2) Timed Vital Capacity

A normal individual can e^ire 832 of his vital capacity (actual,
not predicted) in one second, 942 in rivo second, and 972 in
three seconds. (Gaensler).^ Of same significance as MBC, i.e.,
it is reduced in obstructive disease, but may not be in restrictive
disease.

Vital Capacity, on the other hand may not be decreased in ob*
stiuctive disease, but is decreased in restrictive diseases, see
p. 25. Because of it being reduced in so many non-pulmonary
diseases and being often normal in pulmonary disease of obstruc-
tive nature and in pulmonary disease uith impaired diffusion,
vital capacity is not reliable as an isolated test in diagnosis of
pulmonary ^ease. Furthermore, the normal figure of vital ca-
pacity (4000 to 5000) varies as much as 202 in healthy individ-
uals and may even vary in die same individual at various times.
Nevertheless, changes in Vital Capaci^ are important, especially
an increase follo\ving therapy to overcome pulmonary congestion
and in some cases following therapy to overcome bronchial con-
striction (where originally some bronchioles were completely oc-
cluded, thus decreasing the vital capacity).

3 ) Maximal Inspiratory and Expiratory Air Flow

The first is obtained by a forcefal and rapid inspiration after
a regular maximal expiration. The latter is obtained by forceful

Tulmonttry Function 13

and rapid ejcpiration after a regular maximal inspiration. The
normal values are 300 L/min. and 400 L/min., respectively.
(Comroe).*®

4. Mechanics of Breathing

Forces involved in inspiration and expiration.

1) The Force to Overcome Elastic Resistance of the Lvmgs
During Inspiration. At the end of a tidal expiration, a force is
needed to overcome the elastic resistance of the lung to e:qjan-
sion. This force, **Elastance^ is produced by the increased nega-
tive mtrapleural pressure created by the active contraction of
the mm. of the diaphragm and the expanding thorax. (The stored
elastic energy at the end of inspiration causes the lungs to return
rapidly to the resting expiratory level even though eviration is
passive.) Elastance is expressed as the change in pressure (in cm.
of water) necessary to produce a unit volume change (1 liter).
The normal is 5 cm. H 2 O/IL. The inverse of elastance, ^'CompU-
ance" (more commonly used) is expressed as volume change (in
liters) per \mit pressure gradient (1 cm. HjO). Normal is 0.2
L/cm. H 2 O (Comroe).*® This relationship of pressure diange to
volume change varies wth the size of the lung— for a given totra-
pleural pressure change the small lung changes its volume less
than the large lung. This means that the smaller the lung volume
the smaller the compliance; conversely the larger the lung vol-
ume the larger the compliance. In emphysema the lung volume
is increased, consequently compliance is increased, provided the
emphysema is not complicated by fibrosis or congestion, and
provided true static conditions are attained— v.i. It should be
noted that this increase in compliance may be due not only to
the increase in lung volume but also due to the decrease in elas-
tic forces in emphysema which decreases elastance and increases
compliance (distensibility). In the same manner, decreased com-
pliance in such conditions as pulmonary fibrosis, congestion, ede-
ma, pneumonia, tumors, atelectasis may be due to die decrease
in lung volume, but it may also be due to changes in elastic prop-
erties of these lungs— “stiff lung.” According to Marshall, if a
patients compliance is less than the compliance calculated from

14 Fulmonanj Function and Fulmonary Emphysema

his functional residual capacity on the basis of Marshall’s formula,
compliance equals 0.03 x FRG (in liters)— we may assume that
he has changes in elasticity in his lungs.

Compliance should he obtained under static conditions, i.e.,
at points of no air flow when airway resistance and non-dastic
tissue resistance (v.i.) are zero and only the force to overcome
elastic resistance is obtained. These points are at the end of ex-
piration and the end of inspirab'on, and the compliance obtained
is Static Compliance. It is best to interrupt breadiing for a second
or t^^'o to reduce respiratory rate and to insure equilibration of the
intrathoracic pressure and truly static condition. If this equilibra-
tion is not attained, the pressure gradient may represent a flow
resistance element in addition to the elastance. The compliance
obtained thus is a Functional Compliance rather than a true
static compliance. In patients wdi uneven ventilation; e.g,, pul-
monary emphysema, it may be impossible to attain equilibration
of presstire at zero points, and a flow resistance element in addi-
tion to elastance is obtained (functional compliance). Thus we
often get a diminished compliance in these cases, especially if
taken during rapid breathing; whereas if a true static compliance
is obtained it is increased. (In normal individuals static and func-
tional compliance are equal. Even with fast breathing there is
only a slight decrease in compliance.)

2) The Force to Move the Non-elastic Tissues, i.e., force to
overcome friction (“viscosity”) within the tissues that move dur-
ing inspiration and expiration. Value obtained for this and air
flow resistance combined is 1.7 cm. H-O/L/sec. (Comroe).'*®

3) The Force to Overcome Resistance to Air Flow through
the Tracheobronchial Tree during inspiration and expiration. Re-
sistance to air-flow (hence the force to overcome it) is equal to;

pressure difference in cm. H2O
volume flmv in L/sec.

Conversely, Conductance, equals;

volume flow in L/sec.
pressure difference in cm. HjO

Aiiw’ay resistance in the tracheobronchial tree depends on the
rate and nature of air flow and on die number, length and cross

Tulmonaiy Function 15

sectional area of the tracheobrondiial tree (it is inversely pro-
portional to the 4th or 5th power of the internal diameter of the
tube). In normal persons the resistance at rest is the same on in-
spiration and expiration, but may increase markedly on forced
expiration. In patients with obstructive pulmonary disease, e.g.,
pulmonary emphysema, bronchitis, asthma, expiratory resistance
is usually increased more than the inspiratory resistance due to
compression of the bronchioles by the increased intrapulmonary
pressure during expiration. It is also due to check valve action,
closing the bronchioles at tl)e alveolobronchiolar junction during
expiration. Normal value i s 1.6 cm . HaO/L/scc. (Comroe).^® In
emphysema and asthma values may increase to as much as 11 cm.
HnO/L/sec.

It can be seen from the above that a patient with restrictive
disease who has decreased compliance, \vill decrease his tidal
volume to diminish the force necessary to overcome the elastic
resistance of his lungs and thorax. He wU, therefore, breathe
more rapidly in order to keep his alveolar ventilation per minute
at a normal level. On the other hand, a patient with obstructive
disease who has increased resistance to air foto, will tend to
breathe slowly and will increase his tidal volume to have a nor-
mal alveolar ventilation per minute. However, excessive tidal
volume will produce increasing turbulence of flow, which in turn
produces an increasing constricling influence— (the vicious circle
of hyperventilation of nervous origin). In normal individuals 60
to 70% of the work of breathing is done to overcome elastic re-
sistance and 30 to 40% to overcome npn-elastic resistance, chiefly
airflow resistance. In obstructive disease, the reverse is true.

5. Control of Breathing

Respiration has a dual control mechanism; netirogenic and
chemical.

The neurogenic control lies in die respiratory center in the
pons and medulla. This control is both a spontaneous activity
of the respiratory center and a reflex control, the Hering-Breuer
reflexes, mediated through the afferent fibers of the pulmonary
vagi. There is also a reflex control from afferent nerves from other
parts of the body, e.g., pain stimuli, heat and cold stimuli, re-

16 Pulmonary Function and Pulmonary Emphysema

flexes from skeletal muscles during exercise and other reflexes.

The chemical control lies in the respiratory center and in the
chemoreceptor bodies of the aorta and the carotids.

Under ordinary physiological conditions the chemical control
of respiration is carried out through the action of CO^ on the
respiratory center which is very sensitive to any changes in CO 3
concentration. Any increase in the arterial CO« pressure will
cause hyperventilation whidr will blow off the excess COj and
prevent respiratory acidosis. (In some conditions, such as enu-
merated on page 26, in whidr there is hyperventilab'on present
nnthout elevation of arterial CO-, we assume that the Hj’per-
ventilation is due to hypersensitive Hering-Breuer reflexes.)

The responsiveness of the respiratory center to the chemical
stimulation of CO- is lost with depression of the center by anes-
thesia, drugs, cerebral lesion or injury and by narcotic concen-
tration of CO 2 itself. We can test for presence of depression of
the center by letting the patient inhale 7.5% COs- If ventilation
is not appreciably increased (an adequate response is about
50 L/min.), we may assume presence of depression of the respir-
atory center (provided there is no mechanical limitation to res-
piration, as evidenced by normal maximum breathing capacity
and by ability to hyperventilate voluntarily).

Respiration is also controlled by changes in pH. A rise in pH
depresses respiration, a drop in pH stimxdates respiration. Thus,
in metabolic acidosis ventilation is increased even though there
is no increase in CO».

Another diemical stimulus to respiration is anoxemia, but the
center for this action is chiefly in the chemoreceplors of the aortic
and the carotid bodies. These chemoreceplors appear to function
only as an emergencj' mechanism when anoxemia becomes severe
as in serious depression of the respiratory center by any of die
above causes. Should a patient in such a condition be ^ven O 3
injudiciously, his anoxemia will be corrected, but the chemo-
leceptors (which are now the only mechanism functioning to
increase ventilation) ^vill cease to function adequately and, since
the respiratory center is in a depressed state, ventilation will he
decreased markedly, CO- retention will increase greatly and
respiratory acidosis ^viII ensue. All the chemical stimuli to res-

Pulmonary Function 17

piration do so only to a certain critical level beyond which res-
piration is depressed. For example, hypoxia \vill depress respira-
tion when PaOs falls below 30 mm. Hg. pressure; a drop in pH
below 7 in metabolic acidosis will depress respiration, and a rise
of PaC02 above 70-80 mm. Hg. will likewise depress respiration.

B. Perfusion and DistribudoR of Blood Flow

1. Cardiac Output and Ot Vptalcc

Output of each ventricle per beat, or Stroke Volume— about
70 to 80 ml. Output of each ventricle per minute or Minute Vol-
ume— about 5 L.

Tins means that the lungs are perfused with 70 to 80 ml. of
blood with each heart beat or with S)00 ml. per minute.

During e.xerdse, when the 0« consumption is increased, the
tissues are supplied with the extra Oa by: (1 ) a greater coefBcient
of Oa consumption, i.e., by the tissues being able to take up more
Oa and by (2) an increase in minute volume output of the heart
to as much as 32 L. The latter is accomplished by an increase in
stroke volume to almost threefold the volume at rest, i.e., to as
much as 200 ml and by an increase in heart rate to as much as
^ times. The increase in stroke volume can take place, ^vithout
an increase in right ventricular pressure and pulmonary artery
pressure, due to the fact that the pulmonary vascular bed is ca-
pable of a manifold increase by the high distensibility of its ves-
sels and by the opening up of new vessels. This means that a
person can stand a reduch’on in his lung vascular bed by disease
or surgery to as much as half its volume, and is able to accom-
modate his cardiac output at rest, without a rise in pulmonary
artery pressure, provided he does not exercise, and his remaining
vascular bed is capable of dilatation.

Og uptake at Rest: 120-145 (about 250 ml/min}.

Oj uptake during (Baldwin Platform) exercise: 500-600 ml/min/
M2 (about 1000-1200 ml/min).

2. Distribution of Blood Flow — Capillary Perfusion, Qc

The right ventricular minute volume of 5 L/min. should be
distributed evenly througliout die lung capillaries to exchange

18 Pulmonary Function and Pulmonary Emphysema

gases with the 4 L/min, of alveolar air ventilation. However, it,
like alveolar ventilation, is probably not distributed in perfect
uniformity even in health. In disease, imeven distribution of
blood flow occurs in the following conditions:

A) Begional Decrease in Pulmonary Vascular Bed Without
Associated Lung Disease. This may be in only one lung, e.g.,
Pulmonary Artery Thrombosis; or in scattered regions in both
lungs, e.g., recurrent multiple Pulmonary Emboli, or Primary
Pulmonary Arteriosclerosis.

B ) Scattered Begional Decrease in Pulmonary Vascular Bed
occurring in some pulmonary diseases, e.g.. Pulmonary Emphy-
sema or Pulmonary Fibrosis.

Begional changes in blood flow may occur in many pulmonary
or cardiopulmonary conditions, e.g., brondiiectasis, beman^oma,
bronchopneumonia, congestive heart failure, compression of
areas of lung by masses or pneumothorax, and chest deformities.

In all of the conditions enumerated above, there may be also
an associated uneven ventilation with resultant derangement of
the normal alveolar/perfusion ratio of 4 to 5 or 0.8 (4 L/min
alveolar ventilation to 5 L/min blood flow), some areas having
a decreased ratio (less than 0.8) and some an increased ratio.
See also “Uneven Ventilation/Perfusion Ratios."

C. Diffusion

The passage of oxygen from the alveoli to the capillary blood
through the alveolocapillary membrane; likewise the passage of
COa through this membrane in the leveise direction.

Diffusion of a gas through a membrane depends on (1) its solu-
bihty, (2) the difference in pressure levels on both sides of the
membrane and (3) the permeabih’ty of the membrane itself.

I. Solubility

Gas ^vill diffuse from where its partial pressure is hi^er to
where it is lower and Avill dissolve in a h'qm'd imtil an equilibrium
in die partial pressure of the gas in the liquid and outside it is
established. Thus, Oa ^vill diffuse from the alveolus to the capil-
lary because its pressure in the alveolar air is about 100 imn. Hg.,
whereas in the venous blood at die begi nni ng of the pulmonary

Tulmonary Function 19

capillary its pressure is 40. However, the diffusion depends not
only on the difference between the partial pressure of the gas
in the liquid and outside it, but also on the solubility of the gas
in the liquid. For example, the partial pressure of CO 2 in the
venous blood at the beginning of the capillary is 46 mm. Hg. and
in the alveolar air it is 40— a difference of only 6 mm. Hg., yet
CO 2 diffuses out of the blood into the alveolus twenty times fast-
er than Os in the reverse direction. This is so because the solu-
bility of CO 2 in the blood is so much greater than that of O 2 .
Both of these gases are absorbed in the blood in a much greater
quantity than in physical solution, due to their property of com-
bining with certain substances in tlie blood (O 2 with Hb.; CO 2
with Na as bicarbonate, and with Hb. as Carbaminohemo^obin).
Because of its property of combining with Hb., O 2 diffusion from
the alveolar air into the venous blood of the lung and from the
arterial blood of the systemic circulation into the tissues, though
dependent on the partial pressure of O 2 , is not, however, directly
proportional to its partial pressure. Its association with Hb. in
the lung and its dissociation from Hb. in tbe tissues is not linearly
related to its partial pressure; instead, it forms an S shaped curve,
with a steep slope from 0 to 60 mm. Hg. reaching a saturation of
89% at 60 mm. Hg., and a flat upper part where it takes a pressure
rise from 60 to 100 to increase tbe saturation from 89% to 97.4%
(see Fig. 2). This, of course, is to tbe patient's advantage in that
even if O 2 pressure should drop to 80 mm. Hg., the O 2 saturation
would only drop to 94.5% and his tissues would not suffer from
anoxia.

The amount of Hb. in the blood is about 15 Gm. per 100 ml.
of blood. Each Gra. of Hb. can combine witli 1.34 ml. of O 2 .
Thus, 100 ml. of blood containing 15 Gm. of Hb. can combine
with 20 ml. of O 2 . It does not follow, however, that if the blood
contains 15 Gm. of Hb. it %viH necessarily contain 20 ml. O 2 ,
for the combination of Hb. vtith ©2 is dependent on the partial
pressure of O- in the blood albeit not in direct proportion to this
partial pressure. Only with partial pressure of O 2 being 400
mm. Hg. in alveolar air and arterial blood, on breathing high
70% O 2 , will the O 2 saturation become 100%. With partial pres-
siue of O 2 being 100 mm. Hg., as it is normally in the alveolar

20 Tulmonary Function and PuJmofiary EmphyscTna

air and arterial blood (on breathing air), the Hb. saturation
with O 2 is only 97.45 and the volume in the arterial blood is
only 19 ml. per 100 ml. of blood. Og capacity of the blood is
the volume of O 2 in 100 ml. of blood when Hb. is fully 1005
saturated by exposing the sample of blood to air or O,. (If fiie
blood has 15 Gm. Hb. per 100 mb and the Hb. is fully saturated,
the O 2 capacity will be 20 mb)

O 2 content of the blood is d\e volume of O- in 100 ml. of
blood. (To measure this, the blood is obtained taldog precau-
tion not to expose it to air.)

Og scturafion % is the ratio of Oj content to O 2 capacity X
100. In anemic anoxia, where the gaseous exchange in the lung
is normal and the O 2 tension in the arterial blood is normab O 2
saturation % will be normal (O 2 content will be equal to the
O 2 capacity), but both the content and capacity will be below
normal due to decrease in Hb.

2. Difference in Pressure of the Gas on Both Sides of the
Membrane

As mentioned above, the gas will diffuse from where its partial
pressure Is higher to where it is lower until a pressure equilibrium
is established on both side of the membrane. The difference in
pressure determines the rate of diffusion. In the diffusion of ©2
£rom the alveoli to the capillaries, therefore, the rate of diffusion
depends on the difference between the pressure of O. in the
alveolar air and that in the blood at every point along the capil-
lary. The alveolar PO 2 is about 101 mm. Hg. The PO 2 at the be-
ginning of the capillary (venous blood) is 40 mm. Hg. The dif-
ference at that point, therefore, is about 60. The transfer of O 2
there is very rapid (high head pressure) and within the first 0.35
seconds most of the O 2 is transferred from the alveolus to the
capillary. As the O 2 is being transferred across the alveolocapil-
lary membrane, the capillary PO 2 rises and the difference be-
tween the alveolar and capillary PO 2 becomes smaUer, and the
rate of diffusion is slowed down during the ensuing 0.4 seconds
of the total of 0.75 seconds required for the blood to pass through
the capillaiies, until at the arterial end of the capillary, the par-
tial pressure of O 2 is about the same as in the alveolar air.
Diftisiou also depends on the total surface area for diffusion.

Vulmonary Function 21

Tlius, diffusion is decreased in all cases in which there is a de-
crease in capillary bed, e.g., pneumonectomy, multiple pulmo-
nary emboli and emphysema. Increase in blood flow rate will also
decrease the diffusion rate because of decrease of exposure time
of the blood to the O2. However, when increase in blood flow
rate is caused by exercise, diffiision is increased because of dila-
tation and Opening up of new capillaries.

3, Permeability of the Membrane

A slight increase in thickness of the membrane, such as by
edema or by thickening of either the alveolar membrane by fi-
brosis or the capillary membrane by vascular sclerosis, \vill cause
impairment of diffusion.

Diffusion rate can be determined by tlie amount of gas passing
through a membrane in a unit of time per unit of head pressure,
i.e., per imit of difference in partial pressure of the gas on both
sides of the membrane, as measured in mm. Hg.

Krogh's Constant for gas diffusion in the lung is: D -

D • Diffusion constant. V - Volume of the gas passed per minute.
PA - Mean partial pressure of the gas in mm. Hg. in tlie alveolar
air. Pc - Mean partial pressure of the gas in mm. Hg. in the pul-
monary capillary.

For convenience of laboratory tests, the three processes of pul-
monary function (ventilation, perfusion and diffusion) are
grouped in the following manner:

A. Ventilatory Function. Getting the air in and out of the cljcst
and distributing it to the alveoli. Ventilatory function is best
measured by the following tests: minute ventilation, alveolar
ventilation, vital capacity, timed vital capacity, maximum breath-
ing capacity, residual volume, distribution of inspired air, spiro-

etc.

B. Alccolocapillary Gas Exchange, Respiratory Function, AU
ceolar Respiratory Function, (grouping together diffusion and
perfusion). Alveolocapillar)’ gas exchange is best measured by ar-
terial O3 pressure and saturation, total O- uptake at rest and after
exercise, CO- pressure of arterial blood, pH of arterial blood, O3
diffusion capacity, etc.

22 Pulmonary Function and Pulmonary Emphysema

Glossary of Various Gradients (i.e., of various differences in
partial pressures of O 2 in inspired air, alveolar and arterial blood).

“Aeration Gradient” The difference behveen 0. pressure in
inspired air (158 mm. Hg.) and in alveolar air (104 mm. Hg.),
equals 54 mm. Hg. This is increased by a high residual volume,
by hypoventilation, by retained secretions impairing alveolar ven-
tilation and by bronchospasm. All diese cause lowering of alveolar
O 2 pressure with consequent lowering of arterial blood 0^ pres-
sure and O 2 saturation. Hyperventilation, such as effected by
intermittent positive pressure breathing, increases the alveolar
PO 2 by improving the distribuUon of the air, thus reducing the
aeration gradient and increasing the arterial blood O* saturation.

“Transfer Gradient” or Alveolar-Arterial Gradient, “A-a Gra-
dient” or Alveolar-Arterial PO 2 Difference. The difference be-
tween O 2 pressure in alveolar air (about 104 mm. Hg.) and ar-
terial blood in systemic artery (ab. 95 mm. Hg.) equals 9 mm.
Hg. (Motley states this to be 5 mm. Hg.). It consists of two com-
ponents:

a) “Membrane Component” of 1 mm. Hg., the difference in
O 2 pressure between that in the alveolar air and in the end capil-
lary, which are in equilibrium (hence, such a small difference in
pressure).

b) “Venous Admixture Component" of 8 mm. Hg., the differ-
ence in O 2 pressure between that in the end capillary and in the
pulmonary vein (systemic arterial blood). The lowering of PO 2
in the pu^onary vein is due to admixture of venous blood. (See
anatoim'c V-A shimts in Chapter HI. )

“Alveolar—Beginning Capillary Gradient.” The difference be-
tween O 2 pressure in alveolar air (about 104 mm. Hg.) and in
beginning capillary (systemic venous blood) which is 40 mm.
Hg., equals about 60 mm. Hg. This is so-called head pressure de-
termining the rate of diffusion.

“Alveolar— End Capillary Gradient” The difference between
O 2 pressure in alveolar air (ab. 104 mm. Hg.) and end capillary
blood (presumably 103 mm. Hg.) equals 1 mm. Hg. (the Mem-
brane Component” of the a-a gradient).

“Mean Aheolo-Capillary Gradient.” The difference betw’een
the mean alveolar PO 2 and mean capillary POj. (This latter has
to be calculated by Bohr’s Integration Procedure.)

Fulmonary Futvtion

23

Fig. 1

DIAGRAM OF LUNG VOLUMES & CAPACITIES

AppnomiAtE Values

Total Luag Capacity ab. 6000 ml.

Inspiratory Reserve Volume ab. 3000 mL

Tidal Volume (TV) . . . ab. 500 ml

Inspiratory Capacity ab. 3500 mL ab. 60S o( TLC

Expiratory Reserve Volume . . . ab. 1000 mL ab. 25S of VC

Vi^ Capacity . ... ab. 4500 ml. ab 7SS of TLC

Residual Volume .... . ■ • • ■ ab. 1500 ml. ab, 25S of TLC

Functional Residual Capacity . . . ab. 2500 xoL ab. 40S of TLC

Pofmonars Function oml Fuimononj Emphysema

Fig. 2

OXYHEMOGLOBIN DISSOCIATION CURVE

Note: At low Os ssturatioD a rise of 10 mm. In pressure (froiQ 30 mm. to
40 mm.) causes an increase of 181 in saturatioa ({rom 57S to 75Z); whereas, at
hi^ level of saturaboo, a rise of 20 mm. in pressure (from 80 mm. to 100 mm.)
causes an increase in satoratioii of only 32 (from &1.52 to 97.42).

A rise la partial pressure of Ot ia artnial blood from 100 nun. to abcat
120 (as produced by bypcrveslilation or by positive pressure breathins of am-
bient air), will cause only an inaKwedaWe rise ia Or saturaUoa above 97.42. An
increase in pressure to about 150 nun. Hg. (obtained by breathing 302 Oi) will
cause a rise in Ot saturation to an average of 98 82, and an increase in pressure
to about 250 mm. Hg. (obtained by breathing 402 0»), will raise the O* satura-
tion to an average of 99.62. Only a pressure of 400 mnu Hg. (obtained by breath-
ing 702 0>), w^ raise the Oj saturation to 1002 level.

Chapter II

PULMONARY INSUFFICIENCY;
VENTILATORY AND RESPIRATORY

V ENTILATORY insufficienaj or impaired ventilatory func-
tion, may be caused by lestrictive diseases or by obstructiv’e
diseases.

The first effect of ventilatory insufficiency may be dyspnea, i.e.,
pulmonary disability. This is due to the mechanical difficulties in
ventilating the lungs. The ultimate effect of ventilatory insuffi-
ciency is respiratory insufficiency (v-i.).

Ventilatory insufficiency in both restrictive and obstructive dis-
ease may be manifested as hypoventilation or an uneven ventila-
tion, with some alveoli hypoventilating and some hyperventilat-
ing. The ultimate effect of hypoventilation is arterial hypoxia,
hypercapnia and acidosis. The ultimate effect of uneven ventila-
tion is the same, except that the ventilating areas of the lung often
blow off the excess COj. To sum this up: the ultimate effect of
ventilatory insufficiency is respiratory insufficiency.

Respiratory insufficiency or impaired gas exchange function
may occur as end result of ventilatory insufficiency or as a primary
derangement in gas exchange function, viz. uneven perfusion or
impaired diffusion.

A. Ventilatory Insufficiency

This is far more common than gas exchange insuffidenc)’.
Ventilatory insufficiency occurs quite commonly alone, whereas
major distribution (perfusion) and diffusion defects are usually
accompanied by some ventilatory defect as well.

1. Restrictive Ventilatory Itmifficicnaj

Occurs in all the diseases enumerated on page 9, viz. all the
diseases in which there is restriction of expansion of the chest or
lungs, thus decreasing ingress of air into the lungs and decreasing
the stroke volumes, c.g., vital capacity (and consequently, total
25

26 Pulmonary Function and Pulmonary Emphysema

lung capacity) and tidal volume. Restrictive ventilatory defects
may occur also in obstructive disease, e.g., emphysema, if it is
complicated by fibrosis or by complete occlusion of many bron-
chioles, thus causing a decreased vital capacity in addition to a
decreased timed vital capacity in such patients. The ventilatory
insufficiency in restrictive conditions is roughly proportional to
the loss of aerating tissue. Hence, usually these conditions are not
disabling, i.e., there is very little dyspnea present and the only ab-
normal findings may be decreased vital capacity and total lung
capacity. When the restricUon is very severe, causing a “stiff lung”
and greatly increased elastic work to expand such a lung, dyspnea
will occur. In such a case there is an appreciable decrease in tidal
volume with resultant alveolar hypoventilation and consequent
arterial hypoxia and hypercapnia.

Hypoventilation may occur in any of the restrictive diseases.
There are Uvo exceptions, however: Cases Nvilh diffuse fibrosis of
the lungs and cases with pulmonary congestion. In these condi-
tions there is hyperventilation present. Hence, they may be classi-
fied as subdivisions of the heading restrictive ventilatory insufi-
ciency.

1 ) Restrictive Ventilatory Imuf^ciency With Btjperpnea
(Coumand)

In diffuse pulmonary fibrosis and all conditions causing '"Alveo-
lar Capillary Block Syndrome.” In these conditions hyperventila-
tion is a characteristic finding, the cause of which is not adequate-
ly e3q)lamed— there is no hypercapnia in these conditions; perhaps
it is due to hypersensitive Hering-Breuer reflexes or to hypoxia?
This hyperventilation is of unusual severity in the cases with
alveolar capillary block. The marked dyspnea is related to the
hyperpneic state in addition to the increased elastic ^vork.

2 ) Congestive Ventilatory Insufficiency

In congestion of the lungs due to left ventricular failure or
mitral disease, there is also hyperventilation present, thou^ not
as marked as in diffuse pulmonary fibrosis. This hyperventilation
prevents retention of CO- (except in some cases of severe pul-
monary edema). Hence, these patients do not have respiratory
acidosis-a point of differentiation from pulmonary insufficiency

Vulmonarxj Insufficiency: Ventilatory and Respiratory 27

in pulmonary diseases widi respiintory acidosis, e.g. severe pul-
monary empliysema.

2. Obstructive Ventilatory Insufficiency

In diseases of the bronchial lumen, e.g., bronchial asthma,
obstructive pulmonary emphysema and some cases of fibrosis
v-ath bronchial obstruction— all causing impaired egress of air due
to a decrease in diameter of the bronchus by spasm or edema,
and in case of emphysema, also due to loss of elasticity causing
impaired egress of air. In contrast to restrictive ventilatory insuf-
ficiency, air flow obstruction of even minor degree may seriously
reduce the maximal ventilatory capacity because resistance to air
flow increases in inverse proportion to the 4lh or 5th power of the
internal diameter of the bronchus.

In obstructive disease “three different situations may exist:
(1) some airways are obstructed completely, while others are
normal; (2) all air^vays are obstructed to a certain extent but
none is completely closed off; and (3) some are dosed off com-
pletely, while others are nanowed or partially obstructed. In the
first and third situations, the vital capacity will be reduced,
whereas in the second it \viU be normal if sufficient time is al-
lowed to complete the test; in die second and third, maximal ex-
piratory flow rate will be reduced whereas in the first it will
remain normal”— Gander & Comroe.

Bestrktive Disease Obstructive Disease

(1) Vital capacity diminished. (1) Vital capacity may or may not be

diminisbed.

(2) Timed vital capadty % oF patients (2) Timed vitj capacity diminished,
total (actual, not jjredicted)— not

diminished.

(3) ^rBC dini<TitsTi>.d, hut not muds (3) K!BC markedly diminished,
more than in a nonnal person fail'

ing to employ full Inspiratory ca-
paa'fy.

(4) MBG usually performed in normal (4) MBC is performed in Inspiratoiy

mid-position. position.

(5) Maximum expiratory flow rate not (5) MEFR markedly decreased,
decreased.

(6) Air velocity index — 1 or more. (6) AVI — less than 1.

(7) Index of intrapulmonary mixing (7) IIM always greater than 2.5.
rarely greater than 2.5.

(8) Besidu^ volume usually reduced (8) RV always Increased,
or may be normal.

(9) RV/TLG normal (increased only (9) RV/TLC always increased,
if TLC is markedly decreased).

28 PulTnofUJTtf Function and Pulmonary Emphysema

Increased RV means hyperinflah'on. H>'perinflation may be due
to (1) compensatory overinflation of the lung following resection
of lung tissue, or compensatory adjustment of the lung to de-
formity of the thorax; (2) decreased lung elasticity, e.g., "Senile
Lung” ; (3) Bronchial obstruction, e.g,, asthma and (4) structural
decrease of elastic tissue of the lung and destruction of alveolar
septa together with partial obstruction of bronchi, e.g., obstruc-
tive pulmonary emphysema. Only in (3) and (4) is there pul-
monary disability and this is due not to the increased RV but to
the brondual obstruction and other pathophysiologic changes.

Because of the bronchial obstruction, groups (3) and (4) may
be grouped imder obstructive disease with the istlnction that
(3) may be reversible, since some asthma cases revert to normal
physiological status after therapy or during the interval behveen
attacks. However, many cases of bronchial asthma have abnormal
findings (increased RV, increased IIM, increased timed VC,
diminished MBC, etc. ) even during the inter^’a! between attacks,
and may fail to revert to normal even after administration of
bronchodilator drugs. One may then surmise that these cases
have irreversible structural dianges of early obstructive emphy-
sema. Beal et al, however, “do not beb’eve that such a conclusion
is justified." They say that “it is possible that more persistent,
thorough and varied therapy is required to restore to normal
state.” For e.xample, “aerosolized bronchodilators may not reach
completely occluded areas of the lung and exert their effect only
on partiaUy obstructed bronchi." They may, however, become
“more effective when the completely occluded bronchi are acted
upon by systemically administered bronchodilators.” Snider
et consider a rise of 20J in timed vital capacity, following
administration of bronchodilator drugs, as significant of reversible
obstruction.

According to Williams, M. H., Jr. et ol., "the only test which
consistently distinguished between bronchial asthma and pulmo-
nary emphysema svas the diffusing capacity, which is alwa)’S
severely reduced in emphysema, but normal or only moderately
reduced in asthma.” This test, of course, loses its value in dis-
tinguishing between these two diseases in a case of an asthmatic
patient developing emphysema.

For differentiation see Chapter HI in Part 11.

Fiihnonanj Jnsufficienof: Vcnlilatonj onrf /les;>irfl/ory 29

B.Rcspjralor>’ (CasExdtangc) Insunjciency or
AIvcolar-Kcsprralor)’ Insufllncnc)*

May be specific in a sense that the insullicicncy is primarily in
the gas cxcljangc mechanism (even though, ns usually is the case,
the disease in widch this ocairs, has palliological clianges caus-
ing also ventilalorj' dyshincUon), such as uneven perfusion or
Impaired diffusion— or it may be non-specific, trii. Impaired gas
exchange as a result of ventilator)' insullicicncy, c.g., liNTpoxia and
COa retention as a result of h>'povenliiation or uneven ventilation.

1. Uncccii Perfusion

Uneven Distribution of Blood Flow is due to regional decrease
in pulmonai)* \*ascular bed in primar)* vascular disease; or regional
decrease and compression of pulmonar)- sxiscular bed occurring
in certain pulmonary or cardiopulmonary disease~(see "distri-
bution of blood Dow" in preceding cliaplcr).

Tlic diminished blood 0ow in some areas of the lung has to be
rompensated l>y capillar)' dilatation and increased Wood flow in
other areas of the lung to accommodate the cardiac output, espe-
cially during exercise. If this falls to lahe place, pulmonar)' h)'pcr-
tension witli eventual cor pulmonale will ensue.

Tflie direct result of regional decrease in pulmonary blood flow
is increased physiological dead space (provided, of course, that
the ventilation in these areas is not decreased) so called "dead
space ventilation.'’ Dead space ventilation causes d)'spnca— a
volume of air, greater than the volume necessary for gas cx-
cliange, has to l>c ventilated.

An indirect result of regional decrease in pulmonar)’ blood flow,
i.e., of dead space %vnti}ation, may he h}-po.va and h}pcTcapn}<7.
In the areas in whicli compensator)' inaease in blood flow is tak-
ing place, there is a relative alveolar h)'povcnlilalion with result-
ant arterial h)’poxia and h>’pcrcapnia. If, however, ventilation is
increased in the areas with increased blood flow, llicrc will be no
hypoxia and no h)'pcrcapnia. (Venocapillar)' hypoxia may be
present, however.) D)’spnea, on lire oilier hand, w'ill be further
increased because of h)’pcrvcnlilation. See Figure 5a.

30 Palmonary Function and Fulmonanj Emphysema
Uneven Veniilathn/Perftision Eattos

Uneven ventilation/perfusion ratio may be present in cases
of uneven perfusion with even ventilation, as discussed above.
Conversely, it be present in cases of uneven ventilation with
normal perfusion. In cases of uneven perfusion associated with
pulmonary or cardiopulmonary disease, both alveolar ^'entilation
and capillary perfusion are uneven Nvith various possible com-
binations of relationship of ventilation wth perfusion. The fol-
lowing are the two chief categories of this deranged relationship:

A) Areas of decreased Vcntilation/Ferftision Eatio, viz, poorly
ventilating or non-ventilating alveoli wth normal regional blood
flow— "physiological shunt" or "venous admixture" is the result

B) Areas of increased VentUation/Perfusion Rofio, viz. normal-
ly ventilating alveoli wth regionally diminished or absent blood
flow— increased physiological dead space or “dead space ventila-
tion" is the result (Normally, dead space ventilation should be
not more than 30% of tidal volume.)

2. Impaired Diffusion

A specific impairment of diffusion, hnovvn as "Alveolar Capil-
lary Block Syndrome” or “A-A Block” (Alveoloarterial
occurs in any disease involving the alveolocapillary membrane,
e.g.. Diffuse Pulmonary Fibrosis, Sarcoidosis, Berylliosis, Pulmo-
nary Scleroderma (and other collagen diseases). Miliary Tuber-
culosis and Alveolar Cell Carcinoma. Motley,^** however, states
that with the exception of Berylliosis, all the other above men-
tioned diseases do not have A-A Block. According to him, the
principal cause of lowering of arterial blood O 3 in these diseases
(except Berylliosis) is due to perfusion of blood through non-
ventilated or poorly ventilated areas and not to A-A block-

Diminished diffusion will also occur non-speoifically in. de-
creased vascular bed, e.g., multiple pulmonary emboli or destruc-
tion of alveoli, e.g., pulmonary' emphysema. In both cases this is
due to the decreased surface area for diffusion.

Austrian et cl., describe the “pattern of pulmonary dysfunction”
of "alveolar capillary block syndrome" (a term coined by them)
as consisting of:

Tulmomry Insufficiency: VentUatonj and Respiratory ^

1. Reduced lung volumes.

2. Maintenance of a large MBC.

3. Hyperventilation at rest and during exercise.

4. Normal or nearly normal arterial Oj saturatioa at rest, but a
marked reduction of the arterial Os saturation after exercise.

5. Normal alveolar O- tension.

6. A reduced Os diffusion capacity.

7. Pulmonary artery hypertension.

Since patients with pulmonary emphysema may also have re-
duced Os diffusion capacity, it is necessary to rule out the presence
of that disease by ventilatory function tests, which show marked
obstructive defects.

Clinically, the significant finding in the patients with a-a block
syndrome is dyspnea, absence of appreciable obstructive defects
and presence of only slight restrictive defects ( except in the termi-
nal stage of the disease when there is a decrease in the tidal
volume).

The result of impaired difinision is arterial hypoxia. (One must
remember, however, that Oj saturation may not drop appreciably
in case of unpaired diffusion until Uie diffusion capacity drops to
below 9 ml./min./mm. Hg.). COj retention, however, does not
occur, because COj diffuses bventy times as readily as Oj through
the alveolocapillary membrane. Hypoxia due to impaired diffusion
is aggravated during exercise because the velocity of blood flow
through the pulmonary capillaries is increased and this shortens
the time the blood remains in contact wth the diffusion surfaces.
In the normal individual, on the other hand, exercise increases the
rate of diffusion (see p. 62),

He hypoxia caused by impaired diffusion is also aggravated
by inhalation of low which caxises a slowing of diffusion, even
in the normal individual, because of a decrease in bead pressure
between alveolar and be^nning capillary. Breathing high O 2 , on
the other hand, corrects the hypoxia caused by impaired diffusion
by increasing the head pressure, thus increasing the rate of dif-
fusion with resultant lowering of Uie membrane component of the
A-A gradient to 0.

Chapter HI

HYPOXIA

C YANOSIS does not become evident until Oj saturation is de-
creased to 8TO, but some may not have cyanosis even at 75
or 80%. On the other hand, about 49% of patients Nvill show cya-
nosis between 81 and 852.

Besides the anemic hypoxia discussed on page 20 (which is
due to deficiency of 0- carrying capacity of the blood due to
decrease in Hb. ) , the hypoxia due to circulatoiy' disturbances that
prevent the rapid circulation of oxygenated blood in the capil-
laries (the so called “stagnant anoxia” caused by cardiac insuffi-
ciency or by circulatory collapse) and the hypoxia due to low O-
pressure in the inspired air as in high altitude— the two chief
causes of hypoxia are shunts of venous blood into the arterial
blood and pulmonary insufficiency.

A. Shunts of Venous to Arterial Blood

A most common cause of cyanosis. There is some V-A shunt
present in healthy individuals, the normal ANATOMIC V-A
SHUNT, which causes the POj in the arterial blood of the pul-
monary vein to drop as compared with that in the end capillary
blood— the so called “Venous admixture component” of the alveo-
lar arterial PO 2 difference. Normally this should not be more than
of the cardiac output. This normal anatomic V-A shunt is due
to:

1) Thebesian veins emptying uito the left ventricle.

2) Pulmonar>' veins arising from bronchial artery capillaries in
the pleura. (Miller, William S.: TheLung.)

3) Pulmonary veins arising from plexuses of bronchial veins
at dividing places of brondii and bronchioles— “Bronchopulmo-
nary Veins.” (Miller, William S.: The Lting.) Note: There is also
normally present an anastomosis bebveen the capillaries of the
bronchial arteries and pulmonary arteries. \Vhen these are en-
larged as in the case of bronchiectasis, for example, a true signifi-
32

Hypoxia 33

cant A-V (not V-A) shunt takes place, which may correct the
hypoxia in the diseased area of the lung caused hy poorly venti-
lated alveoli.

Pathological Anatomic V-A Shunts

1) Congenital Heart Disease having a right to left shunt.

2) Pulmonary Arteriovenous Aneurysm and Fistula (causing
shunt between pulmonary artery and vein) in Hemangioma.

i. Complete

The only hypoxia not relieved by high O 2 breathing.

1) Anatomic. (COj retention in anatomic shunt is slight be-
cause the lungs are normal and are capable of hyperventilation to
compensate for the venous blood of higher PCOj shunted to the
arterial circulation.)

2) Complete Physiologic— Areas of lung ^vith normal perfusion
without ventilation, e.g., atelectasis of the lobe or a segment or
a completely fibrotic portion of a lung.

2. Incomplete Physiologic

Areas of lung poorly ventilated but with normal perfusion.

B. Pulmonary Insufficiency

Arterial hypoxia occurring in patients with pulmonary disease
may be the result of any or a combination of the following;

I. Hypoventilation

Leads to arterial hypoxia, CO 2 retention and pulmonary acido-
sis. If patient is breathing 100!? O 2 there ^viIl be no anoxia, but
CO 2 retention will persist. Thus, a patient under anesthesia re-
ceiving O 3 but hypoventilating because of the deep anesthesia
will have no hypoxia but will have hypercapnia and may go on to
respiratory acidosis.

2, Uneven Ventilation/Perfusion Ratios Throughout the Lungs

The most frequent cause of hypoxia in patients with pulmo-
nary disease.

34 Fulmonary Function and Pulmonary Emphysema

The normal ratio of 0.8 (4L. to 5L.) between alveolar ventila*
tion per minute and pulmonary blood flow per minute must exist
in all parts of the lungs (see Fig. 3). If not-hypoxia will
result, so that even if the total ventilation and total blood flow
were normal but most of the blood perfused the hypoventilating
alveoli, and the hyperventilating areas would receive decreased
blood flow— the patient will suffer hypoxia. On the other hand,
if the hypoventilating areas receive decreased blood supply, e.g.,
in some cases of tuberculosis or in PNX, there %vill be no hypoxia
in the blood coming from these areas, and, if the remaining nor-
mal areas have a compensatory increase in blood flow with pro-
porUonate increase in ventilation, there will be no hypoxia in the
combined blood from these areas. Thus, there will be no hypoxia
even if there is regional decrease or increase in blood flow or
ventilation as long as there is a corresponding proportionate de-
crease or increase in ventilation or blood flow with preservation of
the Va/Qc ratio of 0.8 in each region.

Of the various possible combinations of relationship of ventila-
tion with perfusion, the following are the two chief categories of
deranged relationship, l.e., of uneven Ventilation/Perfuslon
Ratios:

1 ) Areas of Decreased Ventilation/Perfusion Ratio, viz. poorly
ventilating alveoli with normal regional blood flow causing Ve-
nous Admixture or Physiological V-A Shunt (see Fig. 4). This
may be of two types:

A) Those in which there is no ventilation at all, wth normal
perfusion, e.g., atelectatic or completely fibrotic area— "Complete
Physiological V-A Shunt.”

B) Those in which there is decreased (but not completely
absent) ventilation, ^vith normal perfusion— “Incomplete Physio-
lopcalV-A Shunt.”

Areas of decreased ventilation/perfusion ratio always cause
hypoxia and hypercapnia. However, hyperventflation (which suc-
ceeds in hyperventilating the alveoli in the normal areas only)
will blow off the excess CO. but will not correct the hypoxia, for
the reason given on page 11 (see also Fig. 4a).

2) Arm of Increased VeniihHon/Perfusion Ratio, viz. normal-

Hypoxia 35

ly ventilating alveoli \vith regionally diminished or absent blood
flow. Increased Physiological Dead Space or Dead Space Ventila-
tion is the result,

“Pure” dead space ventilation, i.e., increased ventilation/per-
fusion throughout both lungs is not likely to occur. Even in pure-
ly circulatory disturbance, such as pulmonary arteriosclerosis and
pulmonary hypertension caused by multiple pulmonary emboli,
some arterioles and capillaries are capable of dilatation to accom-
modate the right ventricular output, at least at rest. It is in the
areas where the compensatory increase in blood flow is taking
place (see Fig. 5) that a relative decreased ventilation/perfusion
ratio occurs wth resultant arterial hyposia and hypercapnia (if
ventilation is not increased in these areas in proportion to the
increased blood flow). In such a case the patient will have hyper-
capnia with a normal minute ventilation. Such dead space venti-
lation is the only derangement kno^vn in which there is hyper-
capnia with normal minute ventilation (see Fig. 5).

If ventilation in the areas with increased blood flow is in-
creased proportionately (see Fig. 5a), both the hypercapnia and
hypoxia will he corrected (the former by blowing off the excess
CO-; the latter, by virtue of fact that the blood coming from the
area of dead space ventilation is not desaturated) and the blood
coming from the area of increased perfusion and proportionately
increased ventilation (i.e., an area of normal ventilation-perfu-
sion ratio) %viU have a normal O 2 saturation.

The above type of dead space ventilation is likely to occur in
pulmonary vascular disease, such as multiple pulmonary em-
bolism, etc. In the usual uneven VA/Qc ratios occurring in pul-
monary disease complicated by vascular destruction or obstruc-
tion, all three possible combinations of ratios occur, viz. increased,
decreased and even ventflation/perfusion ratios. The hypoxia ia
such uneven VA/Qc is not corrected by hyperventilation imless
the hyperventilation is accomplished by means of Intermittent
Positive Pressure Breathing with ambient air, which produces a
more uniform ventilation, thus ventilating also the areas \vith de-
creased VA/Qc ratio (imless there is complete V-A Shunt there).
High O 2 breathing will correct the hypoxia. The hypercapnia.

36 Pulmonary Funrfs’on and Pulmonary Emphysema

on the other hand, is cxirrected by any hyperventilation, except
in severe cases where there are few areas left capable of hyper-
ventilation. In these cases intermittent positive pressure is needed
to blow off the excess CO 2 and prevent respiratory acidosis.

3. Impaired Diffusion

This, like the hypoxia of anatomic V-A Shunt, is the only hy-
poxia unaccompanied by hypercapnia.

A combination of any of these types of hypo.'da may occur in
the same individual, e.g,, a patient with severe emphysema may
have hypoventilation, uneven ventilation/perfusion ratios and
impaired diffusion. Hence, a diagnosis of true alveolar capillary
block has to be made wth caution. In the differential diagnosis
behveen these types of hj'poxia we try to establish which is the
predominant type.

Fig. 3

NORMAL VENTILATION/TERrUSION RATIOS
THROUGHOUT BOTH LUNGS

Alveolar ventilation per minute in of total lung area. Diameter
represents alveolar venlflation— 1 cm. = 1 L/min.

= Blood flmv in a of the total lung area. Cross section represents
amout of blood flow — 1 cm. 1 L/min.

Note: Tbe scale and volmnes pven in this and the subsequent diagrams arc
merely a scbemalic presentation of normal and deranged "VA/Qc ratios.

(H)

The entire lung area (of both hmgs) is schematically divided into 4 equal
areas. The total alveolar ventilation of 4L/in is divided evenly between
the 4 areas. The total blood flo>v of 5L/min. is like^vise divided evenly
into 4 parts. The total ventilation/perfusion ratio is 4L/5L or 0.8. The
ratio in each repon is lAewise OA (l/liZS).

38 TulTnonary Function and Tulmonary Emphysenvi

Fig. 5

UNEVEN VENTILATION/PERFUSION RATIOS THROUGHOUT
BOTH LUNGS. INCREASED VENTILATION/TERFUSION RATIOS
(“DEAD SPACE VENTILATION")

Dead space Dead space locreased blood Increased blood
ventilatioa vendbtioD fio^v causing flow causing

relative alveolar relati\'e alv*coIar
hypoventilatioQ hypoventilation

Hotel Even though minute veotilattoQ is nonnah the alveoli in areas c and
d are having relative bypoventilatioD because of increased blood flow in
these areas. Hence, hypoxia and hypercapnia.

Hotel This is the only derangement taw^vn to have hypercapnia wth nor-
mal minute ventUadon. Compare \vilh Fipue 4a.

Hotel If in areas a and b, the ventilation should be decreased (as it hap-
pens when infarcdon follows pulmonary embolus) there will be no dead
space vendlatioD in these areas, of course. Thus, dead space ventilation in
pulmonary embolism must be determined early before infarction occurs. —
Robin. See p. 54.

Hgpoxia

39

Fig. 5a

EFFECT OF HYPERVENTILATION ON DEAD SPACE
VENTILATION

Area a

Area b

Area c

Area d

Dead space

Dead space

Ventilation in-

Ventilation in-

ventilatioo. No

ventilatioD

creased propor-

creased propor-

hypoxia and no

tionate to

tionate to

hypercapnia in

increased blood

increased blood

blood from this

flow. Nonnal

flow. Normal

area.

ratio, therefore

ratio (app)

no hypoxia and

therefore no

no hypercapnia

hypoxia and no

hypercapnia

Remilt; Both hypoxia and hypercapnia in Figure 5 ore corrected here by
hyperventilatioii.

Note: This type of dead space ventilation is likely to occur in pulmonary
vascular disease. In pulmonary disease compL’cated by destrucUon or ob-
struction of vessels, and having imeven ventdation/perfusion ratios — all
three possible combinations of ratios are present, \'iz. areas with increased
ratio, nonnal ratio and decreased ratio. Hence, in these cases there is no
correction of hypoxia by hyperventilatieai- See Figure 6.

40 Pulmonary Function and Pulmonary Emphysema

Fig. 8

USUAL TYPES OF ❖A/QC RATIOS CONTAINING AREAS WITH
INCREASED, DECREASED AND NORMAL RATIOS

Fig. 6a

PREDOMINANT DEAD SPACE VENTILATION

0

(0O.5L^

( ) 0.75L/m ( )

miiiifiiJf/itnu /
No perfusion 1

jl.75L/m[ j

[ j25L/mj j

Area a

Areab

Areae

Aread

Increased ratio

^naeased ratio"

Nonnal

Decreased ratio,

dead space
ventilation

dead space
ventilation

ratio

incomplete
physiologic A-V
shunt

Fig. 6b

PREDOMINANT VENOUS ADMIXTURE

(~) 0.SL/I11

Area a

Area b Area c

Area d

Decieased ratio Decreased ratio Normal Increased ratio

incomplete complete ratio dead space

shunt shunt ventilatibn

Note: In both of these types, there is hypoxia even rvilh h>perventiIation.
Hypercapnia is usually corrected by hyperventilation unless there are very
few areas left capable of hyperventilation.

Hypaaa 41

4. Differentiation Between Htjpoaa Caused by V-A Sftunfs,

Impaired Diffusion and Uneven Ventilation/Perfusion Baths

1. Complete V*A Shunt (i.e., ei&er anatomical V-A Shunt or
shunt due to venous admixture from non-ventilating areas of the
lung) is differentiated from all above hypoxias (including in-
complete V-A shunt) by the fact that complete V-A Shunt hy-
poxia cannot be corrected by inhalation of 1002 Og (an exception
being an anatomic V-A shunt of small vessel size as in a case of
multiple small V-A fistulae in both lungs which had O 2 saturation
of 97.22 on 1002 O- inhalation at rest, reported by Motley in
Diseases of the Chest, June, 1958). This is due to the fact that the
blood flowing through the shunted area is not exposed to the
high alveolar PO 2 . (In incomplete V-A shiml on high O 2 breath-
ing the alveolar POj is increased even In poorly ventilated alveoli,
hence, the hypoxia is corrected by 1002 Oj inhalation. )

2. Anatomical V-A Shunt and Impaired Diffusion. The only
ones of the above hypoxias not accompanied by CO- retention.
Anatomical shunt— because the Itmg is not diseased and is capa-
ble of hyperventilation to compensate for the venous blood of
higher PCOs shunted to the arterial circulation; impaired diffusion
—because CO 2 diffuses 20 times more readily than Og tlxrough
the alveolocapillary membrane. (In uneven ventilation/perfu-
sion ratios, hyperventilation takes place in some of the areas of
the lung, which wU succeed in blowing off excess CO- in mild
and moderate cases, but may f^l to accomplish it in advanced
cases.)

3. Uneven Venlilalion/Ferfusion Batios can be differentiated
from Impaired Diffusion by inleimittenl positive pressme breath-
ing xvith compressed air otdy, at rest, according to Motley.^*'
This relieves the hypoxia in uneven VA/Qc ratios hy producing
a more uniform alveolar VCTtilation due to better inflation of the
hypoventilating alveoli but it does not relieve the hypoxia caused
by impaired diffusion.

4. According to Motley (ibid.). Uneven Ventilalion/Perfusion
Batios can also be differentiated from Impaired Diffusion by in-
halation of 322 O 2 with exercise (which elevates the PO- in the
inspired air to above 200 mm. Hg. and, consequently, above 150

42 Pulmonary Function and Pulmonary Emphysema

in the alveolar-'-airjL This will correct the drop of Oj saturation
with exercise in case of impaired diffusion by increasing the al-
veolar O 2 head pressure, thus increasing the rate of di^sion. It
will not, however, correct the drop of Oj saturation with exercise
in case of \meven VA/Qc ratios because some of the blood of the
increased ri^t ventricular output is shunted through areas of
nonventilating alveoli to which the hi^ O 2 does not reach.

5. Uneven VA/Qc Bados with predominant Dead Space Ven-
tilation may be assumed to be present in a patient having hyper-
capnia xvith normal minute ventilation, since the other cause of
hypercapnia, viz., hypoventilation, is not present (patient is hav-
ing normal minute ventilation). In predominantly decreased
VA/Qc ratios, there is also hypercapnia; but as soon as the pa-
tient increases his ventilation to normal minute ventilation, the
increased ventilation in the normal areas of the lung will blow
off the excess CO 2 at least in the mild and moderate cases.

Chapter IV

TESTS OF VENTILATORY FUNCTION

1. Ratio of Residual Volume to Total Lung Capacity

Normal is 25 to 355?. However, it may be as high as 502 in
older people. Furthermore, it may be increased relatively in
cases wth decreased TLC, sudh as in restrictive disease. Hence,
of greater value in determining presence of obstructive disease
is the presence of absolute increase in residual volume.

2. Timed Vital Capacity

Normally one exhales in the first second 832 (lowest limit—
722) of one’s total (actual, not predicted) vital capacity, Gaens-
lei®® (1951). In two seconds one eHiales 942 and in three seconds
972 (lowest limit— 922). Vital capacity may be normal but timed
vital capacity is always diminished in obstructive disease while
the reverse is true in restrictive disease.

3. Maximum Breathing Capacity— MBC or Maximum Voluntary

Ventilation— MW, British Nomenclature

Maximum amotmt of air breathed in 12 seconds and multiplied
by 5 to obtain volume for one minute— the patient breathing as
deeply and rapidly as he can. Normal; 120 to 170 L/m ± 352.
A maximal ventilation per minute can only be obtained by volun-
tary effort. Even strenuous exercise ^vill not produce maximal
ventilation (see No. 4 below). Since MBC depends on the pa-
tient’s effort, it is not a reliable test. It depends on the depth and,
especially, the rate of breathing the patient chooses. Thus, a pa-
tient with severe emphysema, if he breathes too fast with a low
tidal volume, may have an MBC ventilation even lower than on
exercise. MBC is also a “needlessly exhausting test”— Comroe.*’
For ffiese reasons, the timed vital capacities and maximum expira-
tory flow rate, as obtained on the expirogram, are replacing this
test as an evaluation of air flow resistance.

43

44 Pulmonary Fttncffon end Pulmonary Emphysema

MBC measures botli stroke volume and rate of ventilation, the
latter depending on the air flow resistance. Hence, reduced MBC
does not indicate where the defect is restrictive or obstructive.
However, MBC is markedly reduced in obstructive disease,
whereas in restrictive disease it may be relatively unaffected.
Reason: As slated above MBC measures both stroke volume and
rate of ventilation, i.e., it measures inspiratory capacity in addi-
tion to the rate of ventilation. However, even a healthy person
does not use the full inspiratory capacity in performing MBC.
Hence, a decrease of this component of the MBC (as occurs in
restrictive disease) does not reduce the hlBC as much as a de-
crease in rate of ventilation (as occurs in obstructive disease)
woiJd. This relatively greater decrease of MBC in obstructive
disease and relatively greater decrease of VC in restrictive dis-
ease, led Gaensler to express this relationship by the air velocity
index.

From the average of the above three, a numerical Ventilation
Factor (VF) has been worked out by Motley,”® by adding the
percentages of the predicted three second VC, the predicted
MBC and the ratio of the normal residual volume per cent of
TLC over the observed RV5? of TLC. The sum of these tiiree fig-
ures divided by three, gives the VF. If the VF is decreased to as
low as 25% of predicted normal, dyspnea is usually present at rest.
A low VF is considered a poor anesthetic risk.

4. Minute Ventilation

Resting tidal volume/min/M* B.S.A. Normal about 3 L/min/
M* B.S.A,, or about 6 to 8 L/min. On exercise, it is 8 to 10.5
L/min/M® B.S.A. or may go up to 140 L/min, or 40 to 70 L/
min/M® on strenuous exercise.

Minute ventilation measurement is of value only if it is below
normal, for then we are sure that the alveolar veritilation is also
decreased. A normal minute ventilation, on the other hand, is no
guarantee that alveolar v^tilation is adequate.

5. AlpeoIorVcnfilotion

Normal-ab.2 to 2.5 L/min/M* B.S.A. or 4 to 5 L/min.

45

Tests of Ventilatory Function

6. Test of Distribution of Inspired Atr or Index of Intrapuh

monary Mixing "or Pulmonary Ns Emptying Rote" (CoumandJ

Forced expiration after breathing 100? Oo for 7 min.— Nj con-
tent of this expired air (supposedly pure alveolar) should not
exceed 2.5? (in some laboratories, the upper limit is 1.5?). If it
is more, it signifies poor distribution of inspired O 2 which, there-
fore, could not u’ash out the N- sufficiently. This usually is the
case in emphysema. At times, however, in the presence of effec-
tive hyperventilation, a normal index of intrapulmonary mixing
may be obtained despite the presence of an abnormal residual
volume.

Allhougli poor distribution occurs in the great majority of em-
physema patients, Coumands test is not sensitive enough, how-
ever, and therefore, it was found positive in only 32? of cases.**
For this reason Comroe devised Oie following method—

Single Breath of 0. Method of Detection of Uneven Al-
veolar Ventilation or Abnormal Intrapulmonary Gas Distribu-
tion. (Comroe)**

By continuous measurement of Ng concentration (by a rapid
gas analyzer) and volume flow of alveolar gas expired slowly
and deeply after a single breath of Oj, it is possible to detect
uneven distribution of inspired gas in die lungs. Normally, die
first 150 cc. expired air (dead space) AviU contain no Ng. The
following 600 cc, which is alveolar but which may contain some
dead space gas show a gradual rise of N- to the level of 40?
(half of die normal SO? since it ^\’as diluted by the breath of
pure O 2 ). The followng 500 cc, expired gas should show a level
concentration of 40? Nj wUi only a slight rise of no more than
1.5? throughout the expiration of these 500 cc. A rise above 1.5?
(in emphysema as much as 12?), denoles uneven distribution of
the gas during inspiration and also unequal ratio of flow from dif-
ferent regions of the lungs during expiration. Tests proved posi-
tive in 77? of cases, whereas Coumand’s test was positive in only
32?.

7. Air Velocity Index (Gaenslcr, E, A.)**

8 of predicted MBC ^ Normal...!

% of predicted vital capaaty

46 Pulmonan/ Function and Pulmonary Emphysema

"Chief value is in differentiatmg obslrucUve emphysema from
lesMcUve disease”-GaensIer. (Less than l-obstructive; Restric-
tive— 1 or more.)

8. Percentage of Breathing Beseme (Cournand, A. and Richards,

D.W,Jr.)«

(ventilatotY reserve) ^

MBC

Ventilatory Reserve or Breathing Reserve is MBC minus minute
ventilation. Normal percentage given by Baldwin, Cournand and
Richards^® is 91 to 95. This test is an attempt to determine pre-
operatively when a patient will become dyspneic. However, the
level at which dyspnea occurs varies so much with different in-
dividuals, that this test is of no great practical value. Comroe”
reasons that since a reduction in breathing reserve could be due
either to a reduction in MBC or an increase in minute ventila*
tiOD, and since minute ventilation in resting patients with pub
monary disease rarely rises above 20 L/min. it foUows that re-
duction in breathing reserve merely indicates a reduced MBC.

9. Walking Index (Warring)

Ratio between walking ventilation (^W) and MBC.

Walking ventilation is the volume of gas expired during one
minute while walking at the rate of 180 ft/min., for three min-
utes. It ranges from 8 to 30 L/min., usually 11 to 19 L/min. The
important fact is that it is constant in the same individual in
health and disease and it remains constant in the patient with
pulmonary disease in progression or regression of the disease and
it remains the same after collapse therapy. On the other hand,
MBC svill decrease after collapse therapy. Warring found that
if the MBC is 4 times the walking ventilation (IW) or more, i.e.,
if the walking index is 0.25 or less, the patient will have no
dyspnea. If, however, the MBC is twice the volume of ^W (i.e.,
the walking index is 0.50), the patient will have severe d>'sp-
nea. Thus, this test is of value in evaluating the extent of surgery
a patient will tolerate.

Tests of VentOatory Function

47

10, Spirogram

Tracings of normal breathing, VC and MBC show character-
istics of breathing pattern;

1) Times for Normal Inspiration and Expiration

Expiration is prolonged in obstructive diseases.

2) Time for Return to Resting Expirafort/ Level

If a normal individual inspires maximally and then permits his
chest to return passively to the resting expiratory level, all of the
inspired air is e:qaelled before the next inspiratory occurs. In
patients with obstruction that is predominantly expiratory, the
maneuver is followed by a slow step-like return to the normal
baseline during which several breaths may occur before the test-
ing expiratory level is reached— “air trapping.”

3) One and Two Stage VC

(The “two-stage” VC refers to the procedure in which the in-
spiratory capacity and expiratory reserve volumes are determined
separately and then added.) In asthma and emphysema, the two-
stage value may exceed the one-stage by as much as a liter. If
the two-stage value is smaller than the one-stage, it is likely that
the subject is not cooperating fully.

4) Timed Vital Capacity

See above.

5 ) Maximal Inspiratory and Expiratory Flow Rates

The first is obtained by a forceful and rapid inspiration after a
regular maximal expiration. The latter is obtained by a forceful
and rapid expiration after a regular maximal inspiration. Normal-
ly, maximal inspiratory flow rate is 300 L/min., maximal e;5)ira-
tory flow rate is 400 L/min. In emphysema, the rate of air flow is
slowed throughout, particularly during the latter half of expira-
tion; as much as 20 seconds may be required to expel the VC. Air

48 Pulmonary Function and Pulmonary Emphysema

flow is also slower than normal at end of inspiration. In asthma,
flow is retarded especially in expiration. In congestive heart fail-
ure, flow is slower for the last 200 cc. of both inspiration and ex-
piration.

6)MBC

See above.

11. Expirogram

Record of the expiratory volume of a single forced expiration
(Forced Expiratory Vital Capacity) on a rapidly moving Kymo-
graph. Because of the fast rale of the Kymograph, it is possible
to obtain the measurement of the first part of the vital capacit)'
tracing where the flow rate is greatest.

(a) Shape of Curve

In obstructive disease, expiration is greatly slowed from the
beginning, whereas in restrictive disease iind in chronic heart
failure, a pronounced decrease in slope occurs only at the terminal
portion of the curve.

(bj Timed Fractions of the Curve Used in Estimate ofMBC
( Or MW —Maximum Voliinf ary Ventilation)

Since an individual utilizes only a portion of his Vital Capacity
as the tidal volume of his MBC, this portion being the first rapid
portion representing the maximum depth of breathing or the
maximum air flow— it follows that we could estimate the MBC
from the volume of the first rapid portion of the forced expiratory
capacity (FEC) curve, if we know the respiratory rate taken by
the individual having such tidal volume.

Tiffeneau in France (Paris Med., 1949) found the one second
segment of the FEC curve to be the portion utilized in perform-
ing the MBC at the breathing rale of 30 per minute, and he esti-
mated the MBC by multiplying Uie volume of this segment by 30.

Kennedy, M. S., in England (1949) assumed the 0.75 second
segment to be the representative portion utilized in performing
the MBC at the breathing rate of 40 per minute and he estimated
the MBC by multiplying the volome of this segment by 40.*®*

Tests of Ventilatory function 49

Miller et (1959) consider the 0.5 second segment as a
more representative portion because maxiinal ventilation is per-
formed better at the respiratory rate of 60 assumed at the tidal
volume of that segment. Hence, diey estimate the MBC by multi-
plying the volume of this segment by 60. (They also consider the
0.5 sec. timed capacity, FECos—comroittee on nomenclature, to
be the “most satisfactory estimate of the e:^iratory flow rate.”)'*®
By establishing that FEC05 is equal to 60% of the individual’s
total VC (regardless of his age) they worked out tlie following
method of establishing the presence of obstructive or restrictive
disease: If the total vital capacity is 80% of the predicted or more,
and FECo 5 is less than 60% of the total VC— the patient has ob-
structive disease; if the total VC is less than 80% of predicted, and
the FECfl 8 is more than 60% of die total VC— the patient has re-
strictive disease; if both are decreased— patient has both obstruc-
tive and restrictive defects. (The total VC in these measurements
should be forced & fast VC. )

(e) Maximum Expiratory Floto Rate^ MEFR

Comroe considers the best estimate to be calculated from the
time taken to exhale the Uter of air between the first 200 and 1200
ml. of the FEC (MEFRsooisoo). John A. Akins et al (1960)
found the lowest limit of normal to be about 458 L/min. in young
men and 360 in older men; 294 in young women and 192 in older
women. Comroe considers important to measure the inspiratory
flow rate as well as the expiratory flow rate. This gives “more
complete information on whether the obstruction is indeed ex-
piratory, inspiratory, or due to insufficient muscular effort”—
(personal communication). In his book The Lting, he gives the
normal value for MEFR as 400 L/min. and the inspiratory as
300 L/min.

Leuallen, E. C, and Fowler, \V. S. ( 1955 ) use the middle half of
the total volume of the FEC for determination of MEFR for two
reasons: first, because the large acceleration of volume during
the first several tenths of a second flow make accurate recording
by spirometer imcertain; second, they found that patients with
emphysema have a relatively greater retardation of air flow dur-

50 Pulmonary Function and Pulmonary Emphysema

ing the middle half than during either the first or last quarter of
the total expired vital capacity. Normal values of Maximum Mid-
Expiratory Flow Rate for young men was 264 L/min. and for old
men— 174 L/min. The time required to expire the midvolume was
found to be about 0.6 second in normal male, 0.5 second in nonnal
female and 2.5 seconds in patients with emphysema.

Miller and Johnson^* consider the 0.5 second expiratory capaci-
ty (FECos) as the best estimate of MEFR (see above). Thus,
for example, if the 0.5 second volume is 3L, Ae MEFR is 3 x 2
(to get the volume in one second) x 60 (to get the volume in one
minute) »> 360 L/min.

12. Bronchospirometry

Done to measure tidal air, minute volume, vital capacity and
Oa uptake of each lung separately (O 2 uptake evaluates the rela-
tive circulation of each lung). Chief value of bronchospirometry
is to determine the extent of surreal removal of lung tissue per-
missible.

Cbapler V

TESTS OF RESPIRATORY
(GAS EXCHANGE) FUNCTION

i. Arterial Os Saturation

Normal 97.4% (96 to 98%). (O, saturation of venous blood-
average about 75%. ) The patients disability does not parallel the
degree of O 2 desaturation, A patient with an anatomic shunt may
have a saturation below 80% without disability. On the other
hand, a patient wth asthma or emphysema may have an O 2
saturation of 90-95% and yet be disabled because he needs in-
creased effort to maintain adequate alveolar ventilation and nor-
mal Or near normal Oj saturation.

Arterial Og Tension, PoOg

(Normal about 95 mm. Hg.) is a more sensitive test when the
Oa saturation is on the near nonnal level, i.e., on the 8 at part of
the O 3 Hb. dissociation curve, where a drop of Og tension from
100 to 90 mm. Hg. will result in Og saturation decrease of only
1 % which cannot be measured accurately, since this is wthin
range of laboratory error. Thus, in emphysema, O 2 saturation at
rest may be normal in mild cases, but PaOg is decreased. How-
ever, since it is more difficult to determine PaOg than O 2 satura-
tion, and since in cardiopulmonary disease O- saturation is usually
appreciably reduced (especially after e-rercise) and thus will
correspond to the PaO- reduction, O 2 sahjration determiniation is
usually used.

1) 02 Saturation Following Og Breathing

Differentiates hypoxia due to complete V-A shunt from all

other causes of hypoxia (see differentiation of hypoxia in Chapter
HI).

2) Oxygen Saturation Foffoictng Exercise

Normally the O 2 saturation does not change after exercise.
See page 62. The hypoxia caused by anatomic shunt or by pulmo-
51

52 Pulmonary Function and Pulmonofy Emphysema

nary insufficiency is aggravated after exercise, so that if the
oxygen saturation in pulmonary insufficiency should be only
sli^tly decreased or even normal at rest, it \vill invariably de-
crease following exercise. In some cases of xmeven ventilation/
perfusion ratios, in which incomplete venous admixture rather
than complete venous admixture predominates, hyperventilation
wth exercise may succeed in ventilating the poorly ventilating
areas (in same manner as intermittent positive pressure breathing
would) and increase the O 2 saturation. See differentiation be-
tween the different causes of hypoxia discussed in Chapter III.

The folIo^ving three tests (2, 3, 4) are an effort to establish a
dysfimction due to poor perfusion and to differentiate it from
pulmonary insufficiency.

2. Total O 2 Uptake After Exercise as Compared to That at Rest

Oj Uptake at rest is normal (about 250 ml/min) in most in-
stances of pulmonary disease regardless of the degree of de-
creased perfusion or degree of pulmonary insufficiency.

Exercise, on the other hand, causes in these cases marked re-
duction from the predicted normal of 1000 to 1200 ml. If the O 3
uptake is norma! during exerdse, it denotes normal ability to in-
crease right ventricular output, normal ability to dilate the pul-
monary capiDaries to accommodate the increased blood flow and
of course normal alveolar ventilation.

A reduction from the predicted O- uptake on exercise indicates
a decrease in alveolar ventilation, or an inability of the heart to
increase its output, or a decreased pulmonary vascular Bed, i.e.,
increased pulmonary vascular resistance. The latter is assumed
by Motley, H. L.”* to be present if the O. uptake on exercise is
reduced "in the presence of an adequate minute ventilation,
especially so, ^ '‘&eie is no decrease in Os saturation during the
exercise,” which denotes an inability to increase the pulmonary
blood flow adequately during exercise, although “the blood that
goes through comes in contact with aerated alveoli and is there-
fore normally saturated.””*

Motley”* considers the O 2 uptake on exercise as very helpful
in measuring the mean pulmonary artery pressure wlhout cathe-
terization.

53

Tests of Respiratory (Gas Exchange) Function
3. Veniilaiion Equicalenty VE

Number of b'ters of air breathed per minute per deciliters of O 2
consumption. In other words, number of liters of air ventilated
in order to consume 100 ml. of O^. For example, if minute volume
of breathing is 5 L/min. and the O* consumption is 2.5 dl
(250 ml,), the VE is = 2. Normal is 2.2 to 2.5. If expressed as
L/min. ventilation per LO 2 uptake, e,g., 5/0.25 - 20, normal
value is 25 to 30.

3/ Kutio of O 4 Rcmocal

The reciprocal of the VE x 100, i.e., x 100; or, in other
svords, no. of ml. Oj consumption per minute (250) divided by
no. of liters of air ventilated (5). Normal is 40 to 50, "On standard
exercise, rate of pulmonary circulation probably increases at first
much more rapidly than the pulmonary ventilation, which ex-
plains in part tlic notable increase in the ratio of 0 - removal ob-
served from av. of 40.8 to av. of 54"~Coumand and Richards**
(1941).

3.^* Percentage of O 3 Extracted From Inspired Air, i.e. x 100.

Normal is 4 to 53.

Baldwin, Coumand and Richards** (1948) discuss O* removal
ratio as foUoNvs— "Reduction in the ratio of O 3 removal at rest
implies a slate of hyperv’cntiJation from whatever the cause may
be. An analysis of the causes of reduced ratio of O 2 removal dur-
ing exercise must consider in addition to all the factors which may
result in hyperventilation” (c.g., reflex hyperventilation in pulmo-
nary fibrosis, A-A Block s>'ndrome and congestive ventilatory in-
sufficiency), "those causing an inadequate increase in cardiac
output” (or those occurring where large areas of the lungs are
ventilated during exercise but not perfused). "On the other hand,
in patients unable to increase their ventilation during exercise,
it is sometimes observed tliat a relatively hi^ rale of O 3 removal
is maintained in the presence of severe pulmonary and cardiac
physiological disturbances. The correct interpretation of variation
in the ratio of Oa removal during exercise is tlms difficult in
pathological cases and requires information obtained from other

54 Pulmonary Function and Pulmonary Emphysema

tests. The use of this ratio as a means of differentiating circulatory
from pulmonary insufficiency would appear to be completely
imwarranted.”

4. Ventilation/Blood Flow Itntio Variations

Several tests are employed to get the variations in ventilation/
blood flow ratios throughout the lungs. One, has been by obtaining
the O 2 uptake in each lung by bronchospirometry. ‘‘Normally 552
of the total O 2 uptake is from the ri^t lung and 45% from the left.
Since O 2 can be taken up only by pulmonary capillary blood
flow, deviations from these values may signify imeven blood flow
(if other factors, such as ventilation and diffusion, are normal).
A more recent technique employs a rapid analyzer for the con-
tinuous analysis of CO 2 in expired alveolar air. If die last part
of the expired air contains only a slightly greater concentration
of CO 2 than the first, the ratios are nearly uniform throughout the
lungs; if the last part is much higher in CO 2 than the first part,
ventilation/blood flow ratios must vary (the first part coming
from a region with an increased ratio, i.e., from a hyperventilating
region or a region ivith decreased perfusion and tlie last part from
a region wth a decreased ratio; i.e., from a hypoventilating re-
gion)'* (Comroe*®). The reason for this is that the PCO 2 in the
alveolus is the same as in its end capillary. Therefore, in a region
wth hyperventilating alveoli where the PCO 2 in the end capillary
blood is low, the alveolar PCOj likewise is low. Similarly in a re-
gion with h>’poventiIating alveoli the PCOj in the end capillary
blood is increased with a likewise increase in alveolar FCO 2 .

The presence of areas with increased VA/Qc raUos can be
determined by measuring the physiological dead space by the
modified Bohr's equation (see p. 7). Indeed, one need not go
througli with calculations of dus equalion-lhe mere presence of
an appreciable difference between die arterial PCO 2 and die
alveolar PCO 2 (>5mm. Hg.) denotes presence of areas of poorly
perfused alveoli, i.e., dead space ventilation— (E. D. Robin ct ah,
1960^”-®®*). These investigators have even derived a formula
from Bohr's equation which can be used to estimate the percent-
age of lung that has lost its perfusion, and used it in estimating
the extent of pulmonary embolism.

55

Tests of Resplraton/ (Gas Excliange) Fanctlon
S. Arterial Blood CO™ Tension — VaCOg

PaCOj can be measured directly by bubble equilibrium tech-
nique or by the Severinghaus PCO2 electrode or, indirectly by
determining the pH of the arterial blood, its CO2 content in vol-
ume % and reading the PaCOj from a graph based on calculation
from Henderson-Hasselbalch*s Equation, Thus, as sho\vn in the
nomogram of F. McLean (in physiolo^cal Reviews, 18:493, 1938;
modified in this book for simplification, see page 60), wth a pH of
7.3 (acidosis) and CO* content of 60J, the PaCO- is 55 mm. Hg.
(Respiratory acidosis, since PaC02 is above 40 mm. Hg. ); whereas
with the same pH but a COj content of 45%, the PaCOa is 40 mm.
Hg. (Metabolic acidosis). If we find a pH of 7.5 (alkalosis) and
tlie CO2 content is 34%, the PaCOa is 20 mm. Hg. (Respiratory
alkalosis, since the PaCOj is less than 40 mm. Hg.); with same
pH and CO2 content of 68%, the PaCO. is 40 mm. Hg. {Metabolic
alkalosis). If we find a normal pH of 7.43 and CO. content of
55% the PaCOj is 40 mm. Hg. (normal). On the other hand, with
the same pH but a CO2 content of 83%, the PaCOs is 60 mm. Hg.
(Respiratory acidosis compensated, since the PaCOj is above
40 mm. Hg. and the pH is normal); whereas lire same pH but
witli a COj content of 27%, the PaCOj is 20, Hg. (Respiratory
alkalosis compensated, since the PaCOj is less than 40 mm. Hg.
and tlie pH is normal) . The total CO. content of the plasma is the
sum of the combined CO. (B.HCOj) and the dissolved CO. (the
latter being the sum of the CO. dissolved in the plasma and the
H.HCO3 u’hich is in equilibrium with it.) Tlje total CO* is
measured by releasing die CO. from the B.HCOj by adding a
strong acid. The total thus obtained is 59.6 ml. CO2/IOO ml.
plasma.

Of the tliree buffer systems maintaining the normal pH of
the blood, viz., the hicarhonatc system ( Carbonic Acid and Bi-
carbonates), the phosphate system (NaH.PO^ and Na-HPO^)
and the plasma proteins and hemoglobin (IIHb and KHb)— tlie
bicarbonate system is the most important one in neutralization
of strong base and strong acid, (Carbonic acid itself, which is the
acid formed in largest quantity in the body, is being kept at the
proper level by respiration. However, in respiratory failure, the
excess CO3 cannot be efficiently dealt Nvitb by tlie bicarbonate

56 Pulmonary Function and Pulmonary Emphysema

system. Hemoglobin, which has the greatest capacity for base, is
the most important source of base necessary for the neutralization
of carbonic acid, and thus could be considered the most important
buffer s>'stem,) The bicarbonate system consists of the proper
ratio bet^veen B.HCOa and H.HCOj which determines the pH of
the blood. In the Hendersoa-Hasselbalch equation, this ratio is
expressed as follows:

Ti _ Q t I 1 BHCOj

= WxyT

BHCO,

^ dissolved COj

(The HiCOj is in equilibrium >vith the dissolved COj
in a ratio of IrlOOG-ieiice the substitution.)

- - , , total COj — dissolved COs

+ dtoa; : ^co.

(BHCOj — total COi minus dissolved CO 3 .}

= 6.1 + log total COa (volume 3^1 — 0.07 PaCOa (ram. Hg.)
0.07 PaCO,

(The concentration of a gas in a liquid is directly pro-
portional to the partial pressure of the gas. ( 0.07 is the
proportionality constant for dissolved CO* in volume

S).f

, 59.6 - 0.07 X 40 (normal PaCOa)

= + 6.07X40

59.6-2B 50.8

= 6 . 1 -I- log 00 = 6 . 11 og-^

= 6.1 + log 20 = 6.1 + 1.3 = 7.4

It is apparent from this equation that it is the ratio of 20:1 of
B.HCO, to H.HCOs that determines the pH of the blood and
not the absolute amounts of each.

If the numerator be doubled, the pH ''vill remain undianged
as long as the denominator is also doubled and the ratio thus re-
mains the same. It can also be seen that the partial pressure of
the CO 2 is proportional to the HJHCOj, which together with the
CO 2 dissolved in the plasma, constitutes the “Dissolved CO 2 ,
since the concentration of a dissolved gas is directly proportional

57

Tests of 'Respxratonj (Gas Exchange) Function

to its partial pressure. Hence, an increase in H.HCOa will cause
a rise in PaCOj (whereas, an increase in B.HCOa has no effect
onthePaCOj).

ResptVflfort/ Alhalosxs

PaCOa is decreased in hyperventilation because of decrease in
dissolved CO2 or H.HCO3. This leads to Respiratory Alkalosis.
(Because of the decrease in dissolved CO2, the total CO3 content
is also decreased, but the pH becomes high because of decrease
of H.HCOs— hence alkalosis.) Most common cause of hyperventi-
lation is a neurosis causing “Hyperventilation Syndrome.'* Hyper-
ventilation also occurs in metaboh'c acidosis— v.i. Decreased
PaCOj may occur also in V-A shunt and in impaired diffusion,
because of hyperventilation.

Jlcipiratori/ Acidosis

PaCOj is increased in hypoventilation and in uneven ventila-
tion. However, in the latter, in the early stage, hyperventilating
regions in the lung will bring PaCOs doNvn to normal or even
below normal; but in the later stage, PaCOs rises (see discussion
on respiratory acidosis in Part II). Increased PaCOj leads to
respiratory acidosis in which, the dissolved COj is increased and
hence, the total CO2 content is increased, and the pH is low be-
cause of the increased dissolved COj.

Mefaholtc Acidosis

In Metabolic Acidosis, the pH is of course low because of de-
crease of alkali reserve. The B.HCO3 is decreased, hence tlie total
CO2 content is decreased (contrary to respiratory acidosis) and,
because the change is primarily in the combined CO2 (B.HCO3),
the PaCOa is not affected and remains normal. Metabolic acidosis
is compensated by a respiratory mechanism as follo\vs: The de-
creased pH stimulates the respiratory center and causes hyper-
ventilation, thus blowng off CO- and decreasing the H-COa.

iletaholic Alkalosis

In metabolic alkalosis tlie pH is, of course high. The B.HCO3 is
increased, hence the total CO3 content is increased (contrary to

58 Pulmonary Function and Pulmonary Emphysema

respiratory alkalosis), and because the change is primarily in the
B.HCO 3 , the PaCOa is not affected and remains normal. Compen-
sation for the metabolic alkalosis by the respiratory mechanism
of shallow breathing (by hypoventilation) with subsequent rise
in CO 2 in the blood (thus, increasing the HjCOa), is not as effec-
tive as the respiratory compensation for metabolic acidosis. Hence,
PaCOa is usually normal in metaboh'c alkalosis.

PaCO,

TofalCOtConient

Pli

Bespiratory Addosis

.. High

Higb+

Low

Metabolic Acidosis

. N'ottnal*

Low

Low

Respiratory Alkalosis

Low

Ldw+

High

Metabolic Alkalosis

. . Normal

High

Hi^

• TlieQredeally so, for reason stated attove. Actually, howwer, becanse of the
compensatory allcalosis produced by die hyperventilalion (caused by die low pH),
PaCOi fs Usually Low.

■f \VIiile the total COi content is inoreased in respiratory addosls and decreased
io respiratory alkalosis by the large increase and decrease of ILCO^ respectively,
there is also a snutU increase and decrease respectively of KaHCOi in compeiua-
tory shift of base from or to the alk. or add Hb respectively (compensatory
metabolic alkalosis and compensatory metabolic addosls respectii'ely).

It can be readily seen that PaCO* determination is helpful only
in determining presence of respiratory acidosis, but not metabolic
acid— base derangements. On the other hand, total CO 2 content
cannot aid us in determining whether the patient has respiratory
acidosis or metaboh'c alkalosis, unless we are sure the derange-
ment is primarily respiratory or metaboh'c or unless we know the
pH of the blood.

In respiratory acidosis (i.e., in CO- narcosis, when the respii-
alory mechanism of compensation, viz., hyperventilation, fails)
an attempt is being made at first to neutralize the excess H.HCOj
%vith base from B.Hb (H.HCOj + B.Hb B.HCO3 + H.Hb) —
compensatory metabolic alkalosis. As CO- retention increases,
renal compensation occurs in an attempt to keep the ratio of
B.HCO3/H.HCO3 at 20;1. It does this by excreUng the H of
H.HCOa as HCl or NH4CI and retaining Na as NaHCOj in the
foUowng manner: 1 ) H.HCO3 + NaCi NaHCOs + HCl.
2) H.HCOs + NH3 (formed by the kidney) + NaCl NaHCO, +
NH4CI.

59

Tests of Respiratoty (Gos Exchange) •Function
6 . Arterial Blood pH

Normal 7.38 to 7.4. The best single measurement of the status
of acid base balance. However, the full evaluation of a patients
acid base status can be accomplished only by determining any
two of the following: PaCOj, pH and CO. content. Astrup, P.
et al. (1960 and 1962)’'* determine the capillary pH, and base
excess (BE). The latter is the amount in mEq/L of strong base
in excess of 45 mEq/L of the total buffer anions in the blood,
which consist chiefly of the bicarbonate and proteinate (Hb)
anions. If there is an excess of strong acid (metabolic acidosis),
the BE is expressed as negative amount in mEq/L below the
mean normal value. They obtain all Uiree values in one proce-
dure by an equipment devised by them (Siggaard Andersen, O.
et el. (1960).^*’ The)' determine die actual pH of the capillar}’
blood by a capillary glass electrode, calculate the pCO* by the
“equilibration method,” i.e., by determining the pH of the blood
after equilibrating it \Wlh two known CO* tensions, and obtain
the BE by a nomogram worked out by Siggaard Andersen and
Engel. K. (1960).”*

Vulmonary Function and Pulmonary Emphysema

Fig. 7

McLean’S nomogram

(Modified)

COt Cora.

pH

COt Tenrlon

60

7.3

55

Respiratory Acidosis

45

7.3

40

Metabolic Addosis

34

7.5

20

Respiratory Alkalosis

6S

7.5

40

Metabolic Alkalosis

55

7.4

40

NORMAL

83

7.4

60

Besp. Addos. Compensated

27

7.4

20

Resp. Alkalos. Compensated

61

Tcsf^ of Respiratory (Gas Exchange) Function

7. Cardiac Catheterization
To measure the pressure in the right heart, pulmonary arterj’,

wedge pressure (pulmonary capillaries) and to determine cardiac
output. Normal Values (Comroe, J. H. et Right Ventricle
Pressure 30/2; Pulmonary Artery Pressure 25/8; Pulmonary Cap-
illary Pressure (end pulm. artery pressure) (wedge pressure)
(P.P.C.) 8.

8. Tests of Diffusion

Appl>'ing &ogh’s Constant to Oj, the Diffusion Capacity for O*
or the Rate of Diffusion of O3 is:

DO. = = — —

PAO, - PcO,

DO. s Diffuilon capacity for O. or diffusion coefficient oi Ot
^0« sa Volume of O. uptake/min.

PAO, =s Mean alveolar pressure of Oi
FcOa s Kleaa capUIazy pressure of Oi

CO, a gas which like 0« has the property of combinbg witli
Hb., is also used for measuring the rate of diffusion. Since O3 is
1^ more diffusible than CO, figures obtained by CO have to
be multiplied by 1.23 to get the diffusing capacity for Oj. Com*
roe gives the Diffusing Capacity for CO as 17 ml/min./mm. Hg.
at rest. The Diffusion Capacity for Oj as 20 ml/min./mm. Hg.
at rest and 60 ml/min./mm. Hg. on exercise. The increase dur-
ing exercise is presumably due to the dilatation of patent vessels
and to opening of additional vessels.

Only a few careful studies have been made of the diffusion
capacity in patients with pulmonary disease.

Uncomplicated impairment of diffusion never leads to FCO.
elevation, because CO3 diffuses 20 times as rapidly as Oj.

0. Jib and RBC Determination

The latter to End presence or absence of polycyllicmia (see
discussion on polycythemia at the end of Chapter II in Fart II).

10. Exercise Tests

BaId^vins mediod of stepping up and down a platform 20 cm.
high 30 times in one minute is one commonly accepted, because

62 Pulmonart/ Function and Pulmonary Emphysema

even a patient wth severe pulmonary disease can perform it.
The treadmill has the advantage that it, in contradistinction to
the platform method, allows the pab'ent to reach a steady state.
Pulse; B.P.; Minute Volume of Breathing; Frequency of
Respiration: O2 ConsumpUon, CO2 Elimination: Arterial O2
Saturation and Subjective Reactions (Dyspnea, palpitation,
fatigue)— May all be measured and recorded during and
after exercise.

Effect of Exercise on O2 Uptake, O2 Saturation and
Diffusion Capacity

Normal Indwidual

Cardiac Stroke Volume is increased. Pulmonary vascular bed
is increased to take care of the increased stroke volume. The heart
rate is increased thus increasing further the minute volume. The
diffusion capacity is increased because of the increase in vas-
cular bed thus increasing the diffusion siufaces. This more than
compensates for the decrease in diffusion due to the increased
velocity of blood flow with shortening of the time the blood re-
mains in contact with the diffusion surface. The O2 uptake is
thus increased. The O, saluraOon remains normal because both
the volume of blood flow and ventilaUon are increased adequate-
ly to keep the O2 saturation at the normal level it has been be-
fore the exercise.

Hypocentilating Indwidual

O2 uptake fails to rise to predicted level and Hyporia is in-
creased due to inability to increase ventilation proportionately
to the increased blood flow, thus further decreasing the VA/Qc
ratio. If the individual succeeds to increase his ventilab’on ade-
quately by exercise, the O2 saturab'on may be improved.

Impaired Diffusion

Diffusion capacity is markedly decreased during exercise and
the O2 uptake and O- saturation are markedly decreased. (At
rest O- saturation is usually normal, though the Pa 02 is decreased.
Reason-PaOj change is on the flat part of the ox>’hemoglobin
dissociation curve.)

TcsU of Be^ratory (Gas Exchange) Function

63

Uneven VentUatton/Perfusion Ratios With Predominant
Decreased Ratios (Venous Admixture)

Hie effect of exercise is tbe same as in hj’poventilation and, as
in hypoventilation, exercise may in mild cases relieve tlie lij'poxia
if tlie h>'perventi]aUon caused by the exercise increases tlie venti-
lation in the poorly ventilating areas (by increasing the diameter
of the obstructed airways because of the hyperinflated state of the
lung during exorcise— Knowles) especially if intermittent posi-
tive pressure breathing is given. If complete V-A shunts predomi-
nate, no hyperventilation can improve tlie hypoxia; furthermore,
some of the blood from the increased output from the right ven-
tricle will be shunted and further decrease tlie O. saturation. If
increased VA/Qc ratios are predominant, dyspnea and pulmo-
nary hypertension are increased.

Anatomic Shtmt

Hypoxia is aggravated because die Oj content of the shunted
venous blood is lower during exercise owing to an increased re-
moval of O2 by the muscles. The O3 uptake may be increased
adequately.

PART n

PUUHONARY ESIPHVSeU

Chapter I

PATHOPHYSIOLOGY

A. Classification

1. Non*Obstructive (“Expansion”), (“Suction”--WesterTnark).

1) Compensator}’.

2) Kountz-Alexander (Chest deformity causing non^obstnict*
ing or senile emphysema); (“Atrophic Emphysema" of Howell);
(“Senile Lung” of Mayer)~nol an emphysema, according to
Mayer, but merely an atrophy of disuse,

2. Obstructive (“Direct”— Blowing Up of Alveoli— Westermark).

1) Acute Vesicular. In childhood. Reversible, though may be-
come chronic.

2) Localized, e.g., tumor (true ball-valve obstruction).

3) Associated wiA Bron^ial Asthma. (In early cases it is
merely hyperinflation and is reversible), pneumonoconiosis and
Tbc,

4) Chronic Obstructive Substantial or Idiopathic Emphysema.
Also called “Hypertrophic” (a misnomer). Crenshaw calls it "De-
generative Lung Disease.” Most important and more common
type of emphysema.

B. Etiology
Theories

1. Chronic Bronchitis— most commonly considered cause. In-
creased pressure caused by cough and destructive changes in
elastic fibers was tliought to be the cause. Gordon and Fleischner
consider bronchiolar obstruction as the chief mechanism in pro-
duction of emphysema.

Gordon's Theory; Alternating transient obstruction of bron-
cliioles ^v^th compensatory dilatation of adjacent alveoli whose
bronchioles may temporarily not be obstructed and allow more
air in ingress during inspiration. This process is intermittent so
tljat no permanent bronchial obstruction is found,

Fleischner proved decrease in size of bronchioles on expiration
67

68 Pulmonanj Function and Pulmonary Emphysema

—thus it is not necessary to assume a ball valve mechanism as
in case of localized emphysema caused by obstruction in a major
bronchus. Swelling of mucosa and bronchospasm ^vill narrow
bronchial lumen suflSciently so that it will close completely on
e:^iration.

McLean, K. H., postulates that broncluolar obstruction by a
plug of mucus \vill cause trapping of air in alveoli supplied by
the obstructed bronchiole in the following manner: The alveoli
of the obstructed bronchiole receive the air from the adjacent
alveoli through normally existing pores bet%veen adjacent alveoli.
These pores are enlarged during inspiration and are smaller dic-
ing expiration, hence trapping.

2. Obh’terarive vascular changes similar to those occurring in
Burger’s disease, perhaps caused by tobacco. Bronchospasm and
bronchiolar obstruction are complications ra&er &an etiological
factors.— Crenshaw’s Theory.

He calls this— “Degenerative Lung Disease.”

C. Pathology

1. Inflammatory changes in mucosa and walls of bronchi and
bronchioles with mucous plugs in many of the bronchioles. All
these catue narTO^ving of bronchioles AAoth trapping of air in the
alveoli on expiration. During or following upper respiratory in-
fections, inspissated mucous plugs may completely obstruct the
bronchioles causing segmental atelectasis and patchy pneumo-
nitis. Bronchiectasis often develops in areas of atelectasis. Diffuse
fibrosis may be present in some cases.

2. Dilatation and distortion of alveoli W’ith resultant thinning
of interalveolar septa, rupture of elastic tissue fibers and alveolar
walls, with formation of bullae and blebs.

3. Sclerosis and narrowing of pulmonary arteries and arteri-
oles. Destruction of many arterioles and capiUsrics. Compression
of many arterioles and capillaries by the surrounding distended
alveoli.— D. Spain.*’®

D. Correlation of Abnormal Physiology with Pathology in Pul-
monary Emphysema

1. Bronchitis and Bronchiolitis: The bronchi and bronchioles
show inflammatory changes in die mucosa and walls, thickening

Pathophysiologrj 69

of the walls ivith narrowing of the lumina and partial obstruc-
tion of many bronchi and brondiioles causing ball valve trapping
of air in the alveoli during expiration. (This occurs because of
(i) further narrowing of the broncliial lumen during expiration
and (2) its closure by compression of tire bronchus by the sur-
rounding distended alveoli having a greater air pressure at the
onset of expiration tlian the bronchus. ) This bronchial obstruc-
tion on expiration causes; (1) dyspnea because of the increased
resistance to air flow; (2) prolonged expiration, and slowing of
expiratory flow rate >vith step-like return to the resting e.tpiratory
level (“air trapping"), as shown on tJie spirogram; (3) decrease
of percentage of one’s limed vital capacity to 85 or less in three
seconds (normal is 972); and (4) decreased maximal breathing
capacitj’— (hJBC) to as low as 40 Uters per minute (normal is
100 to 120).

2. Alveolar Changes, including Disruption of Elastic Fibers:
Tlie alveoli are distended (because of the bronchial obstruction
and ball valve trapping of air during expiration), and the inter-
alveolar septa vitli their elastic fiben arc ruptured, with resultant
formation of bullae and blebs, and decrease in pulmonary elas-
ticity. This causes increased residual volume and uneven distri-
bution of inspired air or uneven inlrapultnonary air mixing. The
increased residual volume, measured in relation \vidi the total
lung capacity and expressed as a ratio of the residual volume to
the total lung capacity— nV:TLC), is greater than 352 (top
nonnal is 352). The uneven distribution of inspired air, expressed
as index of intrapulmonary mbdng by determining the nitrogen
content of the expired air after breatliing 1002 oxygen for seven
minutes (thus \%'ashing out almost all of the alveolar nitrogen),
is above the normal value of 2.52.

The increased residual volume causes arterial hypoxia by: (a)
causing a functional arteriovenous shunt— the blood perfusing the
non-ventilating bullae and distended alveoli is poorly oxygen-
ated or not oxygenated at all; (b) by causing impaired difftxsion
due to the decrease of diilusiag surface area (the surface area
of a bulla is much smaller than die sum of the surface areas of
the alveoli occupying the same ^ace).

The uneven distribution of inspir^ air causes an uneven al-
veolar ventilation (uneven VA)— some alveoli ventilating nor-

70 Pulmonary Function and Pulmonary Emphysema

mally and some having hypoventilation. The alveolar hypoventi-
lation causes arterial hypoxia and hypercapnia. The degree of
hypoxia is best measured by the partial pressure of tlie arterial
oxygen. However, determination of oxygen saturation is easier
to perform and is quite satisfactory. In mild and moderate em-
physema it may be normal (97.4S) or sh’ghtly decreased during
rest. During exercise, however, it is decreased considerably.

The increased CO, in the blood coming from the hypoventilat-
ing areas of the lung causes hyperventilation by stimulating the
respiratory center in the medulla. This hyperventilation tends to
correct the hypercapnia by “blowing off” the excess COj. Thus,
a balance is obtained during the benign clinical course of the
disease. When this balance is disturbed, during respirator)' in-
fection or as the disease progresses and the residual volume is
further increased until it reaches a ratio of 45!J to tlie total lung
capacity, hyperventilation becomes ineffective to blow off the
COj and hypercapnia will persist. The partial pressure of arterial
CO 2 will then rise to above the normal of 40 mm. Hg. witli ulti-
mate development of CO 2 narcosis, when the PaCOj rises above
60 mm. Hg. and respiratory acidosis when tlie pH drops from
the normal to 7.43 to as low as 7.3 or lower. DeaUi will ensue, if
this is not corrected.

3. Arteriolar Changes and Destruction of Capillaries: Tlie
pulmonary arteries and arterioles show sclerosis and narrowing
of the lumina \vith resultant obliteration of many arterioles and
destruction of many capillaries as well as their compression by
the surrounding distended alveoli, thus reducing the total pul-
monary vascular bed. This leads to (a) diminished blood flow to
the lungs, inadequate to cope with increased cardiac output dur-
ing exercise, hence manifested by decreased oxygen uptake after
exercise, and (b) to uneven distribution of blood flow to the lung.
Tins together wi^ the uneven aivedhxT venthation causes xmeven
vendlation/perfusion ratios (VA/Qc ratios) throughout tlie lung
which contributes further to the dyspnea and arterial hypoxia.
The former (dyspnea) is caused by the increased physiological
dead space in the areas of diminished blood flow causing in-
creased alveolar ventilation; the latter (hj’poxia) is caused by

Pathophysiology 71

the poor oxygenation in the areas where the blood flow is normal
but the alveolar ventilation is diminished.

The diminished total blood flow to the lung causes an increase
in pulmonary vascular resistance and results in pulmonary arterial
hypertension, the pressure rising to an average height of 50/20
mm. Hg. or higher (the normal is 25/10). The pulmonary hyper-
tension is furtlier aggravated by hypoxia, especially when oxy-
gen saturation drops to 80%. The final result of the pulmonary
hypertension is cor pulmonale.

The foUo\ving table shows diagrammatically the events de-
scribed above.

Chapter n

FUNCTION TESTS IN
PULMONARY EMPHYSEMA

A. Ventilatory

1. Ratio of Residual Volume to Total Lung Capacity is above
35%. Motley’s classification of degree of emphysema; 35 to 45%
—Moderate. 45 to 55^Severe. Above 5555— Very Severe. (How-
ever, this ratio can be relatively increased also if TLC is de-
creased Vrithout any increase in residual volume, e.g., in restric-
tive disease or, if vital capacity is decreased %vith the TLC re-
maining normal, as in senile lung. )

John Curtis** states: “The ratio of residual air over total lung
cajpacity x 100 was greater than 3S% in only 17 severely emphy-
sematous patients and failed to indicate emphysema in the early
stages. The timed vital capacity, the maximal breathing capacity
and tlie single breath of 0} tests measure somewhat diEerent
functions of the lung and, therefore, in combination tend to ex-
clude false positive findings. When all three tests are abnormal,
it becomes more certain that anatomically significant emphysema
is present A combination of prolonged timed VC, diminished
maximal breathing capacity, spirogram elevated to hyperinflation,
and a rising curve of alveolar N 2 after a single breatli of O*— pro-
vided a sensitive indication of early emphysema.”

2. Tlirce Seconds Vital Capacity is decreased to less than 972

(of patient’s vital capacity). Vital capacity may be normal but
timed vital capacity is always decreased, a point of differentiation
from restrictive disease. — ^

3. Maximum Brcatlnng Cap«riy is diminished to 103—22 L/
min. According to Motley, if it is 120, the degree of emphysema
is insufficient; if less than 40, it is significant. Between 120 and
40— indeterminate.

Ventilatory Factor (Motley) Is decreased to 702 of predicted
normal in moderate cases of emphysema and to less llian 402
in severe cases.

73

74 Pultnonanj Punction and Pulmonary Emphysema

4. Minute Ventilation. Resting tidal voItime/min/M® of body
surface is increased to about twice or more of the normal of 3
L/min/M* of 6 L/min.

5. Alveolar Ventilation. Hyperventilation in the patient with
emphysema maintains effective alveolar ventilation. However,
when the ratio of residual volume to total lung capacity is higher
than 45%, hyperventilation is no longer sufficient to maintain nor-
mal gas exchange.

6. Test of Distribuh'on of Inspired Air or Index of Intra-pul-
monary Mixing.— Coumand.

(Na content of expired air after breathing 1(X)2 O- for 7 min-
utes) is more than 2.5%. At times, however, in the presence of
effective hyper\’enUlation, a nonnal index of intra-pulmonary
mixing may be obtained despite the presence of an abnormal
residual volume.

Although poor distribution occurs in tl^e great majority of em-
physema patients, Coumands test is not sensitive enough, how-
ever, and, therefore, it was found positive in only 32% of cases.
For this reason Comroe devised the follon’ing method:

6. * Single Breath of Oa Method of Detection of Uneven Alveo-
lar Ventilation or Abnormal Intra-pulmonary Gas Distribution
(Comroe). An increase of as much as 12% Ns may be found in the
500 cc. air expired after the first 750 cc. expired. Proved positive
in 77% of cases of emphysema.

7. Air Velocity Index
% of predicted MBC

% of predicted VC
is less than 1.

8. Percentage Breathing Reserve Is decreased to below 91%
(see discussion under 8— “Tests of Ventilatory Function,” Part I).

9. Walking Index (see 9 “Tests of Ventilatory Function ” Part
I).

10. Spirogram (see 10. “Tests of Ventilatory Function,” Part I).

11. Exptrogram (see 11. Parti),

12. Bronchospirometry— Helps evaluating risk of pulmonary
lesection in a patient having pulmonary emphysema in addition
to the pathology requiring resection, e.g., huge bulla.

Function Tests in Pulmonary Emphysema 75

B. Gas Exchange

1. Arterial O 2 Saturation. In mild or moderately advanced em-
physema, it may be normal at rest and decrease only after exer-
cise. In some of these cases having O 2 desaturalion, exercise may
correct it. See “Oxygen Saturation Following Exercise,” Ch. V, Part
I. In severe emphysema, it is decreased even at rest. If it drops
to below 60?, cor pulmonale may ensue. (Hypoxia increases pul-
monary vasoconstriction and elevates pulmonary artery pressure,
thus increasing load on the right ventricle whici may eventually
lead to cor pulmonale. ) If exercise saturation is 5 to 10? below
rest level, the patient should be restricted in walking up stairs.

See “Diagnosis— Clinical Course” and physiological classifica-
tion of emphysema based on O 2 saturation.

Hypoxia occurs earher in the course of disease than hyper-
capnia, inasmuch as CO 2 is easily blown ofiF by the hyperventila-
tion. When severe hypoxia develops, COa retention may also oc-
cur. (See discussion on CO 2 retention in “Diagnosis— Clinical
Course.’’)

2. Total O 2 Uptake After Exercise as compared with that at
rest. Indirectly indicates the degree of pulmonary vascular resist-
ance. (See 2, in “Tests of Respiratory Function,” Part I.)

3. Ventilation Equivalent. VE and

3. * Ratio of O 2 Removal. This also provides an estimate of
adequacy of pulmonary blood flow. (See 3* in 'Tests of Respira-
tory Function,” Part I. )

4. Ventilalion/Blood Flow Ratio through all parts of the lungs.
The ratio will vary in different areas of the lungs. In the areas
where perfusion is decreased the ratio is increased, whereas in
areas where ventilation is ineffective the ratio is decreased.

5. Arterial Blood CO 2 Tension. A rise above 40 mm. Hg. is seen
in the severe cases. ( See 5 in “Tests of Respiratory Function.” Part
I.) This rise in CO 2 tension may help us in differentiating this
condition from respiratory insufficiency of cardiac origin (see Part

I).

6. pH of Arterial Blood. Pulmonary acidosis is commonly seen
in the final stages of the disease.

7. Cardiac Catheterization. Patients ^vith advanced pulmonary

76 Pulmonary Function and Pulmonary Emphysema

emphysema frequently luive pulmonary arterial hypertension
(for discussion of other causes of pulmonary h>’pertcnsion see
page 110). The earliest sign of cor pulmonale in patients with
chronic pulmonary emphysema is a rise in puImonar>' arterial
pressure. Average for these cases is 50 s>'stolic, 22 diastolic. ^Vhen
congestive failure develops, pressure rises hi^er. Cardiac output
is usually normal, thou^ it may be in the higher normal range;
some may be even above normal, as high as 10 L/min., but sooner
or later, the output drops below normal. The important point,
how'ever, is that even if the output is hi^, exercise doesn’t in*
crease it appreciably, as it would in a normal individual.

8. Difiusion Capacity is decreased because of decrease in sur-
face area for diffusion (decreased capiUarj’ bed).

9. Polycythemia. “Secondaij'.” Caused by arterial hypoxia. (In-
crease in Hb. concentratioD, however, is inconstant.) Some casK
may not have polycythemia even if the hypoxia is severe. Pres-
ence of poij'cythemia is a good evidence that cor pulmonale has
developed. On the other band, absence of polycythemia is no
proof that the patient does not have cor pulmonale.

Qiaptcr in

DIAGNOSIS

I. Clinical Course

a. Dyspnea. Slowly progressing, exertional at first, later occur-
ring even at rest and is aggravated by respiratory infection dur-
ing which time the symptoms of acute bronchial obstruction may
resemble bronchial asthma.

The causes of dyspnea in pulmonary emphysema are:

a) Broncho-obstruction by thickened mucosa, by thick mucus
filling the bronchi and by compression of some bronchioles by
the surrounding distended alveoli at the beginning of ej^Jiration.

b) Arterial hypoxia.

c) Hyperventilation caused by dead space ventilah'on, and by
increased CO2 concentration in the arterial blood. Hyper\’entila*
Uon is also caused by the patient’s anxiety and nervousness.

d) Inefficient function of the diaphragm with consequent em-
ployment of tlie accessory muscles of respiration,

e) Mechanical muscle disadvanlage—marked inspiratory po-
sition.

b. Chronic Bronchitis. It often precedes dyspnea. However, in
many cases the dyspnea precedes the bronchitis. In some patients
the chain of events starts following a severe respiratory infection
or pneumonia. Pulmonary emphysema can be differentiated from
chronic bronchitis wthout emphysema, according to Barach,^®
by administration of O2 which will cause a substantial decrease
in ventilation (relief of dyspnea) in pulmonary emphysema. The
reason for this is given by him to be the fact that the emphysema
patient has hyperventilation and dyspnea because of hypoxia
which causes stimulation of the diemoreceptor centers in the
carotid and aortic bodies even thou^ tlie hypoxia may be slight
wth little or no O- desaturation. It appears that the chemorecep-
tor centers of an emphysema patient (also of a patient with con-
gestive failure) have an increased sensitivity to hypoxia. The
same degree of hypoxia in a nonnal individual \vill cause much

77

78 Pulmonary Fundfon and Pulmotviry Emphysema

less dyspnea than in the emphysema patient or in the patient
with congestive failure. Relief of the hypoxia in these patients
will, therefore, relieve the dyspnea considerably.

c. Recurring episodes of pneumonitis, due to poor ciliary ac-
tion, ineffective cough (compression of bronchioles by tlie dis-
tended surrounding alveoli at beginning of e.xpiration) and re-
tention of sputum. Brondiieclasis may be present.

d. CO 2 Retenh'on and Respiratory Acidosis. In the mild and
moderate cases of emphysema the increased CO., concentration
in the blood, coming from the diseased areas of tbe lung having
decreased VA/Qc ratios, is being “bloum off” in the alveoli hav-
ing normal ventilation. These patients have chiefly ventilatory’
insuflScfency with little or no arterial hyporia and no hjpercapnia.
As the disease progresses, with resultant decrease in lung areas
capable of hyperventUation and elimination of tlie excess CO.,
retention of the latter tabes place xvilh an increase in its partial
pressure above the normal level of 40 mm. Hg. During this stage
the body’s adaptive (“homeostasis”) mechanisms (Riley, R.
and Barach, A.**' prevent further increase in PaCO* and pre-
cipitation of respiratory acidosis by two processes: 1) a greater
than ordinary concentration of COs can be blown off per unit of
alveolar ventilation, thus allowing the patient to get rid of some
of the excess CO 2 \vithout having to increase further his venti-
lation and his work of breathing. 2) An increase of compensatory
bicarbonate base.

With failure of the adaptive roechanisms due to further pro-
gression of the disease or due to iolercurrent respiratory infection
when the compensatory processes are overwhelmed, the CO 2
tension rises to the narcotic level of 70 mm. Hg. or higher (CO 2
narcosis), the response of the medullary respiratory center to the
CO 2 is decreased, ventilation diminishes and the pH may drop to
below the normal level of 7.38. With the decrease in ventilation
hypoxia increases, the auxiliary chemoreceptor centers in the
carotid and aortic bodies “take over" the regulation of breathing
from the depressed medullary center. If O 2 is then administered
suddenly in high concentration without assisting the ventilation
by positive pressure breathing, apnea and death may ensue.

A fairly common complication of respiratory acidosis is periph-
eral vascular collapse which is aggravated by the impeded return

Diagnosis 79

of the Hood to the right auride caused by the increased intra-
thoracic pressure in these patients. Another complication is
potassium depletion which may occur in tliese patients. Right
ventricular failure may be precipitated by respiratory acidosis.

Respiratory acidosis may be precipitated suddenly by anes-
thesia; by deep sedation or by administration of narcotics; by
cor pulmonale; and, as mentioned above, by intercurrent respira-
tory infection; and by injudicious administration of O2.

The early symptoms of respiratory acidosis are headache, rest-
lessness and delirium. Later, somnolence supervenes followed by
coma and eventually death. Death may occur suddenly and un-
expectedly. These symptoms are thought by some to be due to
the narcotic effect of the high COn concentration, so called CO2
narcosis or CO2 intoxication; others tliinlc it to be due to the in-
creased H ion concentration (low pH). Perhaps botli produce
or augment each other’s effect on the central nervous system.

Respiratory acidosis may occur not only in the obstructive dis-
eases, such as pulmonary emphysema and bronchial asthma. It
occurs also in any of the restrictive diseases (see p. 106 ) whether
they are caused by pulmonary disease or are of non-pulmonary
origin. However, it is not likely to occur in the group of restric-
tive diseases accompanied by hyperventilation, e.g., a) the a-a
block syndrome group of pulmonary fibroses; b) congestive heart
failure. (In the latter, however, respiratory acidosis may occur
in the severe cases wth pulmonary edema.)

e. Cor Pulmonale. Among chronic lung diseases, pulmonary
emphysema is the most frequent cause of right ventricular hyper-
trophy. The pulmonary vascular bed, already reduced in extent
by the anatomic nanowng or actual obliteration of many of the
pulmonary arterioles, is diminished even further as a result of
hypoxia which causes further vasoconstriction. (The exact mech-
anism for this effect of hypoxia has not been clearly defined. ) In-
asmuch as the vasoconstriction can be somewhat reversed by cor-
recting the hypoxia, the cardio-pulmonary changes due to this
factor may also be partially reversed. However, the changes due
to anatomical narrowing cannot be reversed by correcting the
hypoxia. This fact may be utilized to distinguish pulmonary
hypertension of hypoxic origin from primary arteriosclerosis of
the pulmonary vascular bed.

80 Pulmonary Funcffon and Palmoncry Emphysema

In the early stage of right VMitricular hypertrophy, right ven-
tricular failure is rare. As the pulmonary disease progresses, wth
a) an increase in the pulmonary hypertension; b) development
of polycythemia (in about 402 of the cases); and c) h>pervo.
lemia— the cardiac output is increased by the combined eifect of
these factors.

Should cardiac failure occur at such a stage (i.e., when the
cardiac output is increased) the output %vill drop, but it ^vill still
be above the normal—the paradox of “high output failure.” How-
ever, when pulmonary arterial resistance rises to three times the
normal, cardiac output will actually be below normal. These pa-
tients are not able to hyperventilate and are thus prone to de-
velop pulmonary acidosis. In the last stages, the pulmonary
hypertension is irreversible and is accompanied by intractable
heart failure. The cardiac output may then be below nonnal. As
a rule these patients never recover full compensation and suc-
cumb in a few months.

The early diagnosis of cor pulmonale can be confirmed only by
cardiac catheterization and finding an elevated pressure in the
pulmonary artery. Changes in the electrocardiogram^ roentgeno-
gram, venous pressure and circulation time usually appear only
when the disease is clinically well established.

2. Physical Signs and Laboratory Findings

a. Chest in inspiratory position, having diminished movements
and showing active participation of the accessory muscles of
respiration. The expiratory phase is prolonged. The chest is hyper-
resonant. Breath sounds are markedly diminished. "Wheezing may
not be heard on quiet breathing, but may be heard on forced
expiration.

b. Polycythemia maybe present.

c. "Ventilatory function tests— most important in definitive
diagnosis,

d. Respiratory function tests*— important in determining pres-
ence and degree of hypoxia and hypercapnia, presence of respira-
tory acidosis and possible presence of pulmonary hypertension.

e. Blood pressure response to Valsalva maneuver. Important
in differentiation from congestive failure in which the response
is abnormal, whereas it is nonnal in pulmonary emphysema. If

Diagnosis 81

it is abnormal in emphysema it denotes presence of complication
of congestive failure.

f. Cardiac catheterization— -to detect pulmonary hypertension.
Electrocardiogram to look for presence of P. Pulmonale, or R.V.H.

3. Bcntgcnologic Findings

(The findings are really those of hyperinfialion and not neces-
sarily due to emphysema.)

a. Flattened low diaplu-agm.

b. Limitation of movement of diaphragm on fluoroscopy.

c. Digitation of muscular attachment of diaphragm to the
chest cage.

d. Hyperacrated lungs— not reliable— fibrosis and congestive
failure may mask radiability; on the odier band, lung may appear
hyperaerated in a thin person.

e. Bullae and cysts.

f. Hyperaeration and widening of anterior and posterior chom*
bers on laterial view.

g. Positive sniff test on fluoroscopy. In emphysema, the several
quick short descents of the diaphragm, occurring in the normal
individual, are not seen; also, in emphysema, a flattening of the
diaphragm occurs after a sniff.

4. Differentiation from Bronchial Asthma

BRONctoAi. Asthma

a) Attacks of dyspnea usually noctur-
nal and precipitated by allergens or
respiratory infection.

b) During periods of remission, patient
is symptom free, albeit pt^onaiy
function testa may not Ik normiL

c) Even in case having chrotdc severe
dyspnea, a history of acute asth-
matic attadrs can be obtdned.

d) Eoslnophllia— blood or sputum.

e) Iminovement following bronchodi*
lator drugs Is usually greater (more
than 20%).

f) Diffusion capacity is decreased only
slightly or none.

PUIWONAHY EMPITTSEMA

a) Dyspnea In eady cases Is brought
on by exercise. Later, It becomes
cfaroiiic and aggravated by respira-
tory infection.

b) There is usually no dcffnlte remis-
sion. CbiDidc cough and some dysp-
nea are usually present at all times.

c) Acute exacerbations ore always pre-
cipitated by respiratory Infection.
Episodes of pneumonitis are com-
mon.

d) No eosinopbllia.

e) flcsponse to bronchodilators Is usu-
ally not great

f) Diffusion capacity Is al»'8>'s severe-
ty reduced.

82 Pulmonary Fundfon end Tulmonaiy Emphysema

DiCFusion capacity is the only function test that consistently
distinguishes between bronchial asthma and pulmonary emphy-
sema. In a case of bronchial asthma with secondary pulmonary
emphysema it is of no help, of course. It is indeed difficult to
differentiate such a case from primary pulmonary’ emphysema
except perhaps by eosinophih'a, past history of asthmatic attacks
\vith remissions and presence of nasal polyps or sinusitis. Bedell”
states that the "patient with bronchial astluna responds well to
steroid therapy, whereas Ae patient %viA primary emphysema
responds poorly.” He even suggests Aat cases of emphysema re-
ported responding to steroids were most likely cases of emphy-
sema secondary to bronchial asthma.

5. Physiological Classification of Patients WiA
Pulmonary Emphysema

Baldwin, Coumand, Richards et aU* (1949).

Category I.

“Uncomplicated Pulmonary Insufficiency,” i.e., wiAout chronic
cardiopulmonary failure. Acute episodes of cardiac failure may
occur in this category by acute anoxia following pneumonia, and
may even terminate in deaA, or on Ae oAer hand, may end
favorably wiA Ae patient returning to his previous state ui Aout
sequelae.

Croup J.

WiA an arterial Oj saturation above 92S following exercise.
These patients have ventilatory insufficiency only, as evidenced
by an increased RV/TX.C, a mean index of intrapulmonary mixing
(IIM) greater Aan 5.5 and a decreased MBC. There is no alveolo-
respiratory insufficiency, as evidenced by a normal O 3 uptake
during rest and exercise, a normal O 2 saturation at rest and fol-
lo^ving exercise. ( Some of Ae patients in this series had O 2 satura-
tion below 92% at rest which rose to normal followang exercise.)

Group 2.

WiA an arterial O- saturation below 92% but wiA an arterial
CO 2 tension below 48 mm. Hg. following exercise, i.e., this group
has some alveolorespiratory insufficiency in addition to Ae venlil-

83

Diagnosis

atory insufficiency. The ventilatory insufficiency in this group is
of a greater degree tlian in Group 1, as evidenced by a greater
RV, a greater decrease in breathing reserve and a higher mean
IIM, viz. 6.8. Os consumption during e.'rercise is reduced but is
normal at rest. Arterial anoxia is present at rest in majority of
cases and is increased greatly following exercise.

Group 3.

With an arterial O* saturation below 922 and a COj tension
above 48 mm. Hg. following standard exercise. The ventilatory
insufficiency is greater than in Group 1, as evidenced by a still
greater RV. Tire other ventilatory measurements, however, were
about the same. The mean Oj consumption and arterial satura-
tion at rest and following exercise is the same as in Group 2. The
chief diaractcristic of this group is the CO 2 retention and a defi-
nite tendency for respiratory acidosis to develop following exer-
cise.

Category 11.

"Combined Cardiopulmonary Insufficiency,” or

Group 4.

With pulmonary insufficiency complicated by cbronle cor pul-
monale and congestive failure. The pulmonary insufficiency is the
same as in Group 2 and 3. The Oj consumption during exercise
^vas even more reduced tlian in Group 3, and the CO- retention
and pH reduction was even greater than in Group 3. Polycythemia
was present in this group only.

Lately (1960), Richards"® dassifies Groups 1 and 2 into one
group and 3 and 4 into another. He finds that the patients falling
into his Group 1 usually run riieir whole clinical course without
moving into Group 2, except transiently or terminally.

C. Physiological Classification of Patients Witli Large Pulmonary
Air Cysts orBulIae

Baldwin cf ni." (1930).

Group J,

Large air cj’sts communicating freely wtlj the bronchial tree
(hence normal TLC), and assr^aled Nvitlr re-

84 FuJmonary Function and Pulmonary Emphysema

maining lungs. Although these patients have hyperventilation and
may have dyspnea, there is no evidence of any ventilator)' insulB-
ciency— (normal MBC and HM and only slight increase in RV).
The primary physiological disturbance of this group is overventi-
lation of pulmonary areas (cysts) which are poorly or not per-
fused with blood, i.e., considerable dead space ventilation. There
is no ventilatory nor respiratory insufficiency in this group. Sur-
gical resection is optional in this group.

Croup 2.

Large air cysts with poor or intermittent bronchial communica-
tion (hence diminished TLC and, because of the poor bronchial
communication, the ventilation is decreased in these bullae and
there is no dead space ventilation, e\’en though the perfusion is
decreased), and associated with apparently normal remaining
lungs. Although these patients have severe dyspnea and dimin-
ished MBC, and may even have increased IIM.— The HV, how-
ever, is not increased, denoting absence of diffuse pulmonary
emphysema. In this group a varying degree of ventilatory insuf-
ficiency develops— caused by the mechanical interference with
the bellows action of the diest by the tension cyst-depending on
the size of the cyst or cysts and the pressure within them, which
eventually may result in collapse of the remaining normal lung
and considerable mediastinal displacement. Surgical resection is
mandatory in this group.

Groups.

Air cysts \vith poor or intermittent bronchial communication
(hence diminished TLC), and associated with varying degrees of
emphysema in the remaining lun^, as evidenced by increased
RV.

Group 3a.

Ventilatory insufficiency but no alveolorespiratory insufficiency.
These cases can be differentiated from Group 1 and some of
Group 2 of diffuse pulmonary einph>'sema only by the reduced
TLC (unless the cyst happens to communicate freely wlh a
bronchus) and by the somewhat less elevated IIM. However, this

Diagnosis 85

differentiation may often be impossible. Surgical resection may
be well tolerated in this group.

Group 3b.

In addition to the ventilatory insu£Bdency these patients also
have chronic respiratory insufficiency as evidenced by arterial
anoxia following exercise in all cases and on rest in most cases.
There is usually no CO 2 retenUon, howm'er. These patients can be
distinguished from Group 3 of diffuse pulmonary emphysema by
die reduced TLC (unless the cyst happens to communicate freely
with a bronchus), by the somewhat less elevated UM and by the
usual absence of CO 2 retention. Surgical resection in tbis group
is too dangerous and not justified. However, Sato et al., think that
“emphysema, although advanced should not necessarily be re-
garded as a contraindication to surgery. These patients improved
despite a stormy postoperative course.”

From the vic^vpo^lt of surgical feasibility and prognosis, bullae
maybe classified thus:

Resection optional Avith expected favorable postoperative
course— Group 1.

Besection Mandatory with expected favorable postoperative
course— Group 2.

Besection Mandatory ^vith expected fair postoperative course
—Group 3a.

Besection Needed but expected stormy postoperative course
makes surgical intervention hardly justifiable— Group 3b.

Chapter IV

TREATMENT

1. Infection and Secretion

a. Postural Drainage.

b. Antibiotics.

c. Inhalation of Detergent and Mucol>'tic Drugs, best by
IPPB/I.

d. Hydration and Expectorants (KI). Pancreatic Domaso by
aerosal inhalation for purulent thick sputum. Anticholinergics by
aerosal inhalation for copious watery sputum.

e. Avoid oversedation, especially Narcotics. If sedation is nec-
essary, tranquilizers or Demerol (in small dosage) are preferable
to barbiturates.

2. Bronchospasm and BronchoK>bstruction (the major causes of
dyspnea and imeven ventilation).

a. Inhalation of Bronchodilator Drugs, preferably with
IPPB/I. (Intennittent Positive Pressure Breathing on Inspira-
tion.) Distilled water must be added to any medication given by
inhalation.

b. Steroids in severe cases. To be used wth caution, especially
if patient has peptic ulcer, which appears to be fairly common in
pulmonary emphysema.

3. Low Poorly Moving Diaphragm

(It m\ist be remembered that the loss of diaphragmatic func-
tion is not due to any involvement of the diaphragm, but only
due to loss of elastic recoil of the lung.)

a. Kespiralory Exercises, with manual compression of lower
chest and adjoining upper abdomen upward and inw’ard during
expiration.

b. AbdominalBelt (Gordon Barach Type).

86

Treatment

87

c. Pncumoperiloneum— enough to maintain a small space be-
tween the peritoneum and the abdominal viscera to remove the
weight of the latter. If a considerable rise in venous pressure
occurs following induction of pnp., the latter should be discon-
tinued.

d. Tilting head of bed down.

e. Bending body over forward almost horizontally reduces
visceral pull on diaphragm.

4. Dyspnea

Barach*® stresses the importance of hypoxia as a cause of
dyspnea in emphysema and hence advocates administration of
O 3 as an early measure in these patients. (In those cases in whidi
bronchoconslrictlon and broncho-obstruction is an important fac-
tor in production of dyspnea, it is advisable to give the Og with
heliiim and with a brontiodilator drug). Most workers advocate
giving Og by IPPB/I to combat hypercapnia. Barach, however,
is not concerned about COg retention unless it is accompanied by
a drop of pH, in which case IPPB/I must be given to combat the
acidosis. During moderate hypercapnia imaccompanied by acido-
sis, there is an advantageous adaptive mechanism, according to
RUey®®‘ and Barach/** whereby too great an accumulation of
CO 2 is prevented by a greater elimination of COj per unit of
ventilation, thereby allo%ving the patient to handle a greater pro-
duction of CO 2 without having to increase greatly his ventilation
and his work of breathing. This ‘Tiomeostatic” mechanism is aided
also by an increase of compensatory bicarbonate base. Should a
patient with moderate hypercapnia be hyperventilated, he will
lose his bicarbonate base and will be unable to compensate any
increase in CO 3 occurring as a result of exercise and will con-
sequently rapidly develop respiratory acidosis.

5. Hypoxia

To relieve dyspnea and to prevent pulmonary hypertension.
Baradi'* advocates the use of even in absence of O- desatura-
tion, since PaO^ may be below normal and will cause dyspnea be-
cause of hypersensitivity of the dhemoreceptor centers in these pa-
tients. He also advocates administration of O- duringxvalking exer-

88 Fuhnonanj Vunctian and Ptilmonary ’Emphysema

cise*^' *® to increase cardiopuImoDary reserve and to improve the
physical fitness of the patient, as manifested by less dyspnea and
a decrease in tachycardia on exertion following such treatment.

Most workers prefer to give Oj via IPPB/I. If, however, the
latter is not available, should be given starting with 1 L/min
flow and inaeasing gradually to 6 L/min. This gives a concentra-
tion not higher than 4055 Oj and does not depress the respiratory
center. As stated previously, Baradi” prefers to give Oj in this
manner and reserves its administration via IPPB to cases with
respiratory acidosis. Oj via IPPB/I is also given usually in a con-
centration of 40^, but 100% may be given in severe hypoxia (with-
out die danger of precipitating respiratory acidosis, since IPPB
is given). It is best to start with a low pressure, 5-10 cm. HjO and
increase it progressively to 1S20 cm. Some patients tolerate the
low pressure better. Treatments are given for 15-20 minutes U.d.
or q.i.d. and are decreased, with the improvement of the patient’s
condition, to once or twice weekly as necessary. In severe cases
treatment is given for 15 to 20 minutes every hour or continuously,
if necessarj’, with interruption, however, for 30 minutes at the end
of each hour.

Effects of IPPB/I

a) It increases the ddal volume and depth of respiration,
dilates the bronchi and bronchioles and may open up some
bronchi which w'ould remain closed under ordinary breathing.
This results in more uniform distribution of inspired air, dius cor-
recting an essential defect of emphysema, ois, uneven distribution
of inspired air. This alleviates the h>’poxia in these patients, even
if only ambient air and no addib'onal O. is given. It is advisable,
however, to give O-, 40 to 100%, with P.P.B. This beneficial effect
is more likely to occur if bronchodilator and detergent drugs are
given simultaneously by inhalation.

b) It promotes bronchial drainage by developing hi^er peak
flow rates during expiration as compared with inspiration because
of the rapid release of pressure at the start of expiration. This also
is more effective if bronchodilator and detergent drugs are ad-
ministered simultaneously. Barach states that this is entirely due
to the bronchodilator drug effect The expiratory flow rate of
IPPB/I is not high enough to be close to that of a cough.

Treatment

c) It eliminates excess COj, thus preventing and combating
respiratory acidosis. This, furthermore, makes it a safer method of
administering Oj to a patient with respiratory acidosis.

d) Most eCBcient way to administer bron^odilator and deter-
gent drugs by aerosal.

e) Causes more efficient diaphragmatic excursions.
Disadvantages of IPPB/I

a) Compression of hronchioles by the increased pressure
gradient between the bronchioles and the surrounding alveoli at
the beginning of expiration.

One of the difficulties in pulmonary emphysema is the com-
pression of some bronchioles during expiration by the increased
transpulmonary pressure gradient between the high pressure of
the surrounding alveoli and the lower intrahronchial pressure at
the beginning of expiration with collapse of bronchioles occurring
if the intrapulmonary pressure exceeds the intrahronchial pres-
sure plus the lung tension. (The latter, or elastic resistance, aids
to keep the bronchiolar lumen patent by giving “architectural sup-
port” to the bronchiole.) Administration of IPPB/I aggravates
this difficulty. This especially is apt to occur in the severe cases,
and is the reason for the therapeutic failure of IPPB/I in about
50% of the cases in acute respiratory failure.

Jones, R. H., Macnamara, J., and Gaensler, E. R.** are suggest-
ing the advisability of designing “a patient cycled respirator
wliich can deliver very high peak flow rates (in excess of 80 L per
minute), ^vhich has a decreasing— rather than an increasing— pres-
sure during the inspiratory cycle, thus leaving the alveoli with a
low end inspiratory pressure.”

Administration of low positive pressure on expiration may pre-
vent compression of the brondiioles, by raising the intrahronchial
pressure thus decreasing the pressuie gradient between the alveoli
and the bronchi. (This is what the patient himself tries to accom-
plish by pursing his lips. ) Tliis, however, cannot be used in llie
apneic patient.

According to F. M. Bird (personal communication), the chief
difficulty encountered by Ae patient using positive pressure
breatliing is the increased fiowrale which increases the turbulence
of the airflow in the narrowed bronchi and bronchioles of tlie pa-

90 Pulmonary Function ard Pulmonary Emphysema

tient, thus increasing the already increased resistance to airflow
which these patients are having. This increased resistance to air-
flow in the narrowed bronchi diminishes further the decreased
airflow to the areas of the lung having bronchial obstruction, and
diverts it to the normal areas, thereby increasing the over
expansion of these areas. Thus, the uneven distribution of in-
spired air, which these patients are having, is aggravated instead
of being corrected. Furthermore, because of the rapid airflow, the
normal areas of the lung are filled up fast, the peak pressure is
reached rapidly, causing cycling of the machine before comple-
tion of inspiration, thus leaving the patient end up with a de-
creased tidal volume and increased dyspnea. To correct this diffi-
culty, Bird designed in 1937 a machine in which the flo\vrale is
not fixed as it is in the other machines for positive pressure breath-
ing. In his equipment, the florvrate is controlled independently of
the pre-set pressure and can be adjusted to allow a slow filling of
the lung, thereby avoiding all the faults enumerated above.

Recently, a ‘‘cuirass'* respirator has been introduced which is
based on same principle as an “iron lung," uith the diflercnce
diat the extrathoracic pressure in this marine is responsive to
slight inspiratory efforts by the patient, hence it is paUent cycled.
Expiration is passive and retarded by a gradual pressure drop
within the respirator, thus producing a prolonged expiratory’
phase and a type III Coumand mask pressure curve.** Marks, A.
et found this respirator very effective in improving ventila-
tion and correcting the CO- and pH abnormality in respiratory
acidosis. They also found that this machine produced less air
trapping and a more favorable inspiratory-expiratory time relation
♦Tian several other positive pressure machines on the market.

b) Impairment to the venous return to the riglit auricle by the
increased intratboracic pressure. The resultant decreased right
auricular filling causes a drop in cardiac output Tliis is advanta-
geous in pulmonary edema in that it decreases the blood flow to
the lungs thus relieving the pulmonary congestion. FPB further
relieves the pulmonary edema by' the compression of the capil-
laries by the increased intrapulmonary pressure of the surround-
ing alveoli. In patients svith pulmonary emphysema, however, the

Treatment

91

impaired venous return to the ri^t auricle produced by the PPB
further aggravates the already existing decreased right auricular
filling due to the increased intrathoracic pressure in this disease.
Tliis disadvantage of IPPB/I becomes even more deleterious, if
the patient has peripheral vascular collapse (as some patients
wth respiratory acidosis have).

In most cases of pulmonary emphysema it is possible to over-
come the disadvantage of decreased right auricular filling during
DPPB/I by prolonging the expiratory phase (Type III curve of
Coumand et al., 1948“). The eflFect of the increased intrapulmo-
nary pressure on the right auricular filling depends not on the
peak pressure but on the mean pressure of the inspiratory and e.x-
piratory phases. Since the pressure during the expiratory phase is
near 2 ero, prolongation of expiration lowers the mean pressure to
a low positive and allows adequate venous return during that
phase.

Contraindications to the Vae of IPPB

B. M. Cohen^^ lists the following situations as contraindications
to the use of IPPB

a) Beceot hemoptysis.

b) Becent mediastinal emphysema.

c) Bccent spontaneous pneumothorax.

d) Patients "on brink of, or in, peripheral vascular collapse
xvith myocardial infarction or coronary insufficiency.” The in-
creased intrapulmonary pressure impedes the flow of blood into
the right auricle thus decreasing the cardiac output whicli would
aggravate the shock. Cohen also recommends caution (use 12-15
Cm. water pressure instead of 15-20) in patients with cardiac
disease, past history of spontaneous pnx or mediastinal emphy-
sema, also in presence of giant bullae or mediastinal emphysema.
Levine, E. on the other hand, belittles the possibility of rup-
ture of a bullae or of spontaneous pnx. Reason: Pressures as high
as 100 to 150 cm. of v’aler are produced during coughing spells
and yet such incidents do not occur. In IPPB "the maximum pres-
sure of 20 cm. of water is exerted for only a fraction of a second
at the mouth, and only a small degree is transmitted to alveoli

92 Fulmonary Fanciion and Pulmonary Emphysema

through the compressible column of air in the bronchi before ex-
piration begins.”

Ejects of IPPB/N/E or EWNP (Exsufflatwn With
"Negative Fressure)

With this machine ^ere is a peak inspiratory rise of pressure
to 20 to 40 mm. Hg. produced gradually over a period of 2.5
seconds, to avoid developing very high velocities which mi^t
blow bronchial secretions deeper into the lung. This is followed
by a sudden drop in pressure to 40 mm. Hg. below atmospheric
pressure, attained in 0.04 seconds and kept up for 1.5 seconds.
The mean pressure thus obtained is 0.54 mm. Hg. The sudden
drop in pressure at the beginning of expiration causes a very rapid
air flow, greater than that of a natural vigorous cough, especially
in a patient vrith obstructive disease (ufs. 11 L/sec. as against
3 to 6 L/sec.), xvithout producing the unduly high intragaslric
(hence intra-abdominal) pressure of a natural cough, viz, 40 mm.
Hg. as against 90 mm. Hg.

EWNP produces the same effects as IPPB/I ^vith three addi-
tional advantages:

a) It promotes bronchial drainage even more than IPPB/I by
producing an expiratory flow rate similar to that of a natural vig-
orous cough.

b) It produces more effective diaphragmatic excursions.

c) It does not have the disadvantage of decreased right auric-
ular filling and decreased cardiac output that IPPB/I may have
(since it has a high negative pressure on expiration resulting in
a mean intrapuhnonar)’’ pressure of near zero w’hich does not
impede the venous return to the right auricle).

However, E^VNP has its DISADVANTAGES:

a) It can only be given in short courses of treatments— 8 or
10 applications (“coughs”) for each course of treatment, whicli
is given before meals and at bedtime, preferably preceded by ad-
ministration of a bronchodilalor inhalant.

b) It has the disadvantage of compressing the bronclnoles
during expiration as IPPB/I has, even more so (because of the
high pressure gradient between bronchioles and tlic surrounding
alveoli during e.xpiration).

Treatment

93

6. CO 2 IntoxicaOon and Respiratory Acidosis
A A^on-Coma/osc Patient

a) IPPB/1, 60 to loos O 2 , preferably 60:40 Helium O 2 murfure.
(Pressure should be set at 5 cm. water and increased gradually to
15-20 cm.) If prolonged treatment is required in a critically ill
patient, it should be interrupted at the end of each hour for 30
minutes rest period. Bronchodilalor and detergent drugs should
be given.

b) 1/6 Molar Lactate 1000 cc. i.v. (This contains 167 mEq
Na), or 50 cc. NaHCOa i.v. (Contains 44.6 mEq Na.)

c) Treatment of respiratory infection.

d) Treatment of cor pulmonale. If present.

e) Steroids. To be used with caution, especially if patient has
peptic ulcer which appears to be fairly common in pulmonary
emphysema— 20-30% of cases. (In general population, 5-10%.)

f) Tracheotomy as emergency measure, beeping in mind that
it decreases the efficiency of cou^.

g) Shock, when present, should be treated \vith vasopressor
agents— i.v. glucose with Levophed. However, the effectiveness
of the vasopressors is decreased in acidosis and they become effec-
tive only after pH is raised. (Incidentally, the bronehodilator
effect of epinephrine in brondiial asthma is also improved after
administration of Sod. Lactate.) One must remember to use pre-
caution in use of IFF in the presence of shock since the entrance
of blood into the right auricle is already decreased by the shock
and IPPB ^vill impede it further by the increased inlrathoracic
pressure.

h) The following medications have been recommended by
some:

a. Carbonic Anhydrase Inhibitors, e.g., Diamox, Daranide.
(There does not seem to be sound physiological basis
for these.)

b. Organic b\iffers, e.g., Tham. However, may produce
hypoglycemia and anoxemia.

o. Respirator)' Center Stimulant, e.g., EtLami^'an (Emivan).

i) Avoid barbiturates and narcotics.

Note: Since CNS sj-mptoms may be absent even with high

94 Pulmonary Tuncfion and Pulmonary Emphysema

PaCOa and low pH, and conversely, symploms may penist for
some time after above xetum to noimal-tieatinent should be
guided by both laboratory and symptoms.

B. Comatose Tatient

Rx. is same as above, except that tracheotomy is mandatory and
O 2 should be given via an automatic cycling respirator.

7. Cot Pulmonale

a. Treatment of underlying Lung Disease.

b. As a prevenlah've treatment Barach advocates administra*
tion of O 2 10 L/min. flow during walldng exercise. This is a
therapeutic exercise calculated to build cardiopulmonary reser>'e
as well as to relieve dyspnea and hypoxia (see above).

c. Aminophyllin— lowers resistance in pulmonary circulab’on
in addition to its bronchodilator effect.

d. Digitalis. To be used with caution-arrhythmias are prone
to occur,

e. Diuretics. To be used with caution-may cause potassium
depletion.

f. Phlebotomy for polycythemia is recommended by some and
condemned by others.

8. Surgery

a. Excision of large bullae and cysts.

b. Partial Pleureclomy — to increase collateral circulation—
Crenshaw, G. L.®*

c. Denervation (Vagectomy) to reheve bronrfiospasm— recom*
mended only on patients sbowng response to bronchodilating
drugs. A concomitant dorsal sympathectomy may be done when
severe pulmonary vasculai sderosis is present— Abbot ct al.,* also
Waterman, D. H.”^

PART m
SYLLABUS
OF

PARTS I AND n

Qiapter I

PULMONARY FUNCTION

A. Ventilation
1. Mcc/mnics

Forces involved in inspiration and expiration.

1) Force to overcome elastic resistance of the lungs during
inspiration is called ELASTANCE. It is expressed as change in
pressure in cm. of water, necessary to produce a unit volume
change (1 liter). Normal is about 5 cm. H-O/IL.

COMPLIANCE, or distensibility, is the inverse of elastance.
It is expressed as volume change per unit pressure change. Nor-
mal is about 0.2 L/cm. HjO (Comroe). It depends on the lung
volume at the end of quiet expiration (FRC). According to Mar-
shall's formula, compliance - FRC x 0.05. It follows that a larger
lung with a larger FRC (a large normal lung, or a lung with a
large FRC as in emphysema or bronchial asthma) will have a
greater compliance. Conversely, a small lung with a small FRC
(a child’s lung or a small adult lung, or a pneumonectomy or
atelectasis case, or a fibrotic lung) xvill have a smaller compliance.

Resume: The larger the lung volume is at the end of quiet ex-
piration, the more distensible it is during inspiration, i.e., tlie
greater the compliance. The smaller the lung, the lesser the com-
pliance.

Compliance also depends on the elastic properties of the lung.
In emphysema, where the lung elasticity is decreased, compli-
ance is increased even more than the increase due to the large
FRC (provided, of course, static conditions are obtainable dur-
ing measurements— see discussion on mechanics of breathing in
Parti, and provided the emphysema is not complicated by fibro-
sis). On tire other hand, in the "stiff” lung of pulmonary fibrosis
or pulmonary congestion, the compliance is decreased due to the
change in tlie elastic properties of these lungs— (increased elas-
tance). In the case of pulmonary fibrosis tire decrease in compli-
ance is in addition to the decrease due to the small FRC.

97

98 "PulTnonanj Function and Tuhnonanj Emphysema

2) Force to overcome airflow resistance through the tracheo-
bronchial tree during inspiration and ejcpirab'on. Normal: 1.6 cm.
HjO/L/second (Comroe). In obstructive disease tb?g force is
increased more markedly on expiration.

3) Force to move the non-elastic tissues. Normal for this and
for airflow resistance combined is 1.7 cm. H.O/L/second f Corn-
roe).

Fig. 9

SCHEMATIC DIAGRAM OF CO.MPLIANCE AND ELASTANCE
IN LARGE AND SMALL NORMAL LUNG, PULMONARY
EMPm’SE.MA AND PULMONARY HBROSIS

Note

1. A large normal lung, having a FRC of 4L, has s compliance of 0.2L/cm.
HjO. See Marshall's formula. Also, note that a diange in pressure from
20 to 30 cm. is required to increase the lung volume from 4 to 6L Divid-
ing 2L by 10 cm., we gel 0.2L/cTn.

2. A small normal lung, having a FRC of 2L has a compliance of O.lL/cm.:
Volume change -r- pressure change (IL -5- 10 cm.) = O.lL/cm.

3. Emphysema having same FRC as a large normal lung, has a greater com-
pliance (3L -J- 8 cm. = ab. 0.4L/coi.). This is due to loss of clastidt)’,
in addition to the large lung volume.

4. Fibrosis having same FRC as the small normal lung, has a lesser com-
pliance (IL -T- 13 cm. = ab. 0.08L/cm.). This is due to changes in the
elasticity (stiffness), in addition to Ae small lung volume. Note also that
in fibrosis, the elastic tension at the position of maximum inspiration, may
reach the level of 40cm.HjO— dangerously close to causing rupture of
the pleura.

Pulmonary Function 99

2, Control

1 ) Medullary Centers.

a) Neurogenic, a spontaneous activity of the respiratory cen-
ters and a reflex control— the Hering-Breuer reflexes.

b) Chemical:

a') pH— a drop, e.g., in metabolic acidosis, stimulates respira-
tion. However, a drop below 7 will depress respiration. A rise in
pH, e.g., in metabolic alkalosis, depresses respiration.

b') CO 2 concentration— stimulates respiratory center. Rise in
CO 2 concentration above nonnal of 40 mm. Hg. partial pressure,
causes hyperventilation, (However, a rise above 70 mm. Hg.
pressure will depress respiration). Decrease in pressure below
40 mm. Hg. (as in respiratory alkalosis) will decrease ventilation.

2) Aortic and Carotid Bodies — “diemoreceptor centers.” Fimc-
tion to stimulate respiration only as an emergency mechanism in
case of anoxemia, e.g., drop of O 3 saturation to 901? or less. (Se-
vere hypoxia, however, will depress the medullary respiratory
center.) In tissue hypoxia without arterial O 3 desaturation, e.g.,
in toxic hypoxia of CO poisoning or in moderate anemia, the
"chemoreceptor centers” are not stimulated.

3. Normal Values

a) Minute Ventilation — Tidal Volume times frequency, 6 to 10
h/znin, mean— 7.4 L/min.

b) Alveolar Ventilation — That part of the tidal volume actu-
ally engaged in gas exchange (Tidal volume minus dead space
air).

c) Dead Space (Anatomic) air in nose, oropharynx, trachea,
and major bronchi. 150 ml. (See also p. 104.)

d) Alveolar Ventilation per minute— VA/min. (Tidal volume
minus dead space) x frequency = 4 L/min. This is distributed
evenly throughout both lungs, although not in perfect uniform-
ity. Decreased minute ventilation always means also decreased
alveolar ventilation.

Converse— not true:

a) Decreased tidal volume with correspondingly increased fre-
quency will have a normal minute ventilation, but the alveolar
ventilation will be decreased.

100 Tulmonary Function and Pulmonary Emphysema

b) Increased dead space in a normal minute ventilation will
likewise have a decreased alveolar ventilaUon.

B. Respiration or Gas Exchange

1. Diffusion
Depends

a) On head pressure, i.e., pressure di£Ference behveen Oj in
the alveolar air (higher) and that in the venous blood (lower);
likewise, bet\veen CO 2 in the venous blood (higher) and that in
the alveolar air (lower), the gas diffusing from the higher par-
tial pressiire solution into the lower one.

b) On the solubility of the gas, and, in the case of Oj and CO.,
on their chemical combination with Hemoglobin (to form Ox}'-
hemoglobin and Carbaminohemoglobin respectively), COa in
addition combming with strong base of plasma to form BHCOj.
The solubility and chemical combinations of COa is linearly pro-
portional to the partial pressure of CO-, whereas that of O* with
Hb. is not linearly related to the partial pressure of O 2 (see Fig. 2,
O.xyhemoglobin Dissociation curve. Part I).

c) On the penneabllity of the alveolocapillary membrane. Dif-
fusion also depends on total sxirface area available for diffusion.

2. Perfusion

The right ventricular minute volume of 5 L/min. is distributed
evenly throughout both lungs, although not in perfect uniformit)'.

Chapter H

PULMONARY INSUFFICIENCY

A. Ventilator)’ Insufficiency

1 . Total Hypoventilation

(Predominantly in Restrictive Diseases.)

Ends in Respiratory Insufficiency, viz., Arterial Hypoxia and
Hypercapnia; the former leading to Pulmonary Hypertension (re«
versible), the latter to Respiratory Acidosis. Effect of High
Inhalation on Total Hypoventilation— Hi/poric is corrected.

Hypercapnia is not corrected, since patient continues hypovem
tilating; CO2 will accumulate to narcotic level and cause respira-
tory acidosis. In fact, administration of O2 will hasten acidosis
by the removal of the anoxic stimulus to the aortic and carotid
bodies.

Effect of Induced Hyperventilation on Total Hypoventilation—
Both Hypoxia and Hypercapnia are corrected. However, in cases
ivith a-a block, the hypoxia is not corrected.

2 , Regional Hypoventilation, Uneven Ventilation

(Predominantly in Obstructive Disease.)

Ends in Respiratory Insufficiency, vis.. Arterial Hypoxia and
Hypercapnia with ultimate Pulmonary Hypertension and Respir-
atory Acidosis. How’ever, since diese patients have some areas
in their lungs capable of hyperventilation, tlie excess CO2 is blo%vn
off and there is no hypercapnia, unless disease is advanced or
complicated by infection. The reason tliat the h>percapnia is cor-
rected but the hypoxia is not corrected by the hyperventilating
areas is that COa concentration in tlie blood is linearly propor-
tional to its partial tension, whereas O2 association with Hb. is
not linearly proportional to the partial pressure of O2.

Effect of Hyperventilation on Uneven Ventilation— Hi/pcrcap-
nfa is corrected hut not Hypoxia.

However, hyperventilation by IPPB will alleviate hypoxia be-
cause it may succeed in ventilating some poorly ventilating al-
101

102 Pultnonanj Function and Pulmonary Emphysema

veoli. Similarly, hyperventilation by exercise may aUeviale hy-
poxia in mild cases.

Efect of High Os Inhalation on Uneven Ventilation-Same as
in total hypoventilation.

2. Hyperventilation (Increased Minute Ventilation)

Cannot be considered a ventilatory insufficiency, since it does
not lead to hypoxemia and hypercapnia. On the contrary, it usu-
ally corrects these conditions. It may, however, cause pulmonary
disability— dyspnea and fatigue, because it ventilates a volume of
air greater than necessary for gas exchange. It may also, as in
the case of “Hyperventilation Syndrome,” result in respiratory
alkalosis.

Causes of Hyperventilation

1. Nervous or emotional— “Hyperventilation Syndrome.”

2. Hypercapnia, e.g., in obstructive disease (Hyperventilation
thus blows off the excess COs and conects the hypercapnia; how-
ever, this has its limitation— too great an increase in Ventilation
causes an increased melaboh'c production of CO- by the respira-
tory muscle, and this offsets the lowering of CO- by the hyper-
ventilation). Minute ventilation varies from 9 to 20 L/min.

3. Metabolic Acidosis. Mean minute ventilation— 30 L/mtn.

4. Hypoxia. Mean minute ventilation— 32 L/min.

5. Pulmonary Fibrosis, especially “A-A Block Syndrome.”
Cause of hyperventilation unkno^vn-hypersensitive Hering-
Breuer reflexes?

6. Exercise. Minute ventilation— 16 to 20 L/min. Severe exer-
cise— 100 L/min. to 140 L/min.

7. Maximum Voluntary Ventilation (MBC). Minute ventila-
tion— 120 to 160 L/min.

Ill Effects of Respiratory Alkalosis Produced hy Excessive
Hyperventilation

1. Decreased cardiac output.

2. Decreased blood flow to the brain and heart, witli conse-
quent symptoms of ischemia of these organs.

Pulmonary Insufficiency 103

3. Increased cerebrovascular and coronary resistance.

4. Decreased availability of Oj to the tissues because of de»
creased dissociation of oxyhemoglobin in alkalosis. (On the otlier
band, the greater alBnity of hemoglobin for O 2 in presence of
alkalosis helps the blood to lake up more O 2 in the lung. )

B. Respiratory or Gas Exchange Insufficiency
J. End EesuU of Ventilatory Imufjicicncy

2. Coexistent With Ventilatory Insufficiency

1) Impaired Diffusion, e.g., in pulmonary emphysema, due
to decrease in diffusing surface. (The disrupted alveoli and de-
stroyed capillaries in a buUa result in less alveolocapillary sur-
face for diffusion.) Impaired diffusion may also occur in pul-
monary congestion because of loss of diffusion surface.

2 ) Uneven Perfusion, e.g., in pulmonary emphysema} in bron-
chopneumonia; congestive heart failure; compression of areas of
lung by neoplasm or pneumothorax and compression of blood ves-
sels by granulomata. In all of these there may be of course Im-
paired diffusion due to the decrease in diffusion surface.

3. ‘‘Specific Derangement” of Gas Exchange

(Not coexistent %vith ventilatory insufficiency. )

1) Primary Decreased Perfusion wlhoul pulmonary disease,
e.g., multiple pulmonary emboli or a large pulmonary embolus
or thrombosis; primary pulmonary arteriosclerosis or hyperten-
sion. Decreased perfusion is usually regional since there are usu-
ally some capillaries left capable of vasodilatation.

2 ) Specific Impaired Diffusion, e.g., in A-A Block Syndrome—
e.g., in some cases of pulmonary fibrosis, granulomatosis, colla-
gen diseases; lymphogenous carcinomatosis, berylliosis. Result:
Hypoxia on exercise. (Decreased Pa02 is present even at rest,
though not detectable on O- saturation determination— changes
in PaOa on flat part of oxyhemoglobin dissociation curve result
in very slight changes in O 2 saturation.) There is no hypercapnia.
There are no finding of ventilatory insufficiency either, though
the patients do have marked pulmonary disability, ois., marked

104 Pulmonary Funciion and Pulmonary Emphysema

dyspnea and hyperventilah’on. chiefly tachypnea. The cause of
the hyperventilation is not Jaaown— hypersensitive Hering-Breuer
reflexes caused by the decreased compliance (stiff lung)? Strobe
volumes and lung \'oIumes are decreased.

The impaired diffusion in all these cases is presumably due to
a change in the permeability of the alveolocapillar>' membrane.
However, it may very well be due merely to a decrease in dif-
fusion surface caused by the obliteration of many blood vessels
by the interstitial disease. In many of the cases in which there is
an improvement following steroid therapy manifested by dis-
appearance of dyspnea, increase in lung volumes and e\'en roent-
genological clearing, the diffusion capacity remains low, suggest-
ing that this is due to irreversible loss of diffusion surface due to
loss of blood vessels.

4, Uneven Ventilaiion/Perfusion Ratios^Uncccn VA/Qc liaiios

Total alveolar ventilation of 4 L/min. and total cardiac output
of 5 L/min. has to be distributed evenly throughout both lungs
for proper e.xchasge of gases. This means that this ratio of 4/5
or 0.8 has to be present in every part of the lung, otherwise there
will be a gas ex^ange insufBciency, even though the total alveo-
lar ventilation and the total perfusion should be normal. Of all
possible variations of disturbance in ventilation perfusion rela-
tionship, the following are the two chief derangements:

1) Decreased VA/Qc Ratio, causing PHYSIOLOGICAL V-A
SHUNT.

a) Complete— a area has no ventilation, e.g., in complete oc-
clusion of a bronchus by mucous plug or by flbrosis. This is
physiologically indistinguishable from an anatomic V-A shunt,
e.g., pulmonary arteriovenous aneurysm or hemangioma.

b) Incomplete— a area has decreased ventilation.

2) Increased VA/Qc Ratio, causing DEAD SPACE VENTILA-
TION. (This is “alveolar dead space” ventilation, not “anatomic
dead space” mentioned on p. 99. Alveolar dead space + anatomic
dead space is called Physiolo^c Dead Space.)

Decreased VA/Qc Ratio. The blood coming from such an area
is low in O 2 saturation and hi^ in COj tension, and will act as
a V-A SHUNT lowering the O. saturation and raising the CO-

Pulmonary Inmfficicnaj 105

tension in the blood of the pulmonary vein into which the nor-
mal blood, from the areas with norrntd "VA/Qc ratio, is returned.
Should the area ^vith decreased ventilation have a corresponding
decrease in perftision, it vinll have a normal VA/Qc ratio and die
blood cximing from this area will be normal in O 2 saturation and
CO. tension. Thus, there is no hypoxia and hypercapnia in pneu-
monectomy, in PNX, in bronchogenic Ca and in many cases of
pulmonary tuberculosis, even though the disease may be far ad-
vanced. Such is also the case in mild pulmonary emphysema of
Groups 1 and 2 (see Part II), who even though are having ven-
tilatory insufficiency with uneven distribution of inspired air with
imderventilation of as much as 70% of their lung, are neverthe-
less having little or no gas exchange insufficiency due not only
to the fact that they have 30% of dieir lung capable of hyperven-
tilation, but also to the fact that the underventilated areas are
also xmderperfused. On the other hand, the patients in Groups
3 and 4 have marked gas exchange insufficiency due not only to
the fact that they have about 90% of tbeir lung underventilated,
but also due to the fact that the diseased areas happen to be “not
particularly underperfused" (Richards, 1960).“*

Hyperventilation in the areas of the lung with normal VA/Qc
ratios ^vill succeed in correcting the hypercapnia caused by the
blood coming from the area wi& the decreased \^A/Qc ratio, but
it will not correct the hypoxia (reason; see Fig. 2).

However, hyperventilation by positive pressure breathing (IPPB)
or by exercise, often alleviates hypoxia in mild cases of physio-
logical V-A shunts, by succeeding to increase the ventilation even
in the hypoventilating areas (unless such areas have many com-
plete physiological V-A shunts).

Increased VA/Qc Hafio. "Dead Space VenfiVafion**

Unlike total hypoventilation, decrease in perfusion thrau^oiit
both lungs is not likely to occur. Even in purely vascular disturb-
ances, e.g., pulmonary arteriosclerosis, multiple pulmonary em-
boli, some arterioles and capillaries remain which are capable
of dilatation to accommodate the right ventricular output, at
least at rest

The blood coming from the area of dead space ventilation \vill

106 Tulmonary Function and Pulmonanj Emphysema

be nonnal in O 2 saturation and CO 2 tension (albeit the O. up-
take is decreased in this area). However, in the areas with com-
pensatory increase in perfusion there will be a relative decrease
in VA/Qc ratio, i.e., a nonnal alveolar ventilation \vith an in-
creased perfusion (unless the ventilation there is increased corre-
spondingly). The result is arterial hypoxia and hypercapnia in
this area. Such a case ^viII have nonnal alveolar ventilation wth
hypoxia and hypercapnia caused by decreased VA/Qc ratio due
to a regional compensatory increase in perfusion. Tliis is the only
derangement known to have hypercapnia with normal alveolar
ventilation. Should this patient hyperventilate, he wU, of course,
have no hypercapnia (and he will have no hypoxia either, since
he would have no more areas with relatively decreased VA/Qc
ratios). Such a patient, even though having normal arterial 0.
saturation, will nevertheless have episodic cyanosis because of
the Oj unsaturation of the venocapiUary blood due to decreased
O 3 uptake in a case with many areas of decreased perfusion.

On the other hand, in pulmonary disease having dead space
ventilation (e.g., emphysema), there are also areas present hav-
ing decreased VA/Qc ratios, but these are due to actual decrease
in alveolar ventilation in these areas, and the hypoxia and hyper-
capnia are associated with a decreased total alveolar ventilation
due to a decreased regional alveolar ventilation. Should the dead
space and normal areas hyperventilate vith resultant normal
total alveolar ventilation, the hypercapm'a \vill be corrected, hut
not the hypoxia.

If in the areas with decreased perfusion there is a correspond-
ing decrease in ventilation, there will, of course, he no dead space
ventilation. This is what happens in pulmonary embolism after
infarction takes place. Hence, to detect dead space ventilation
in pulmonary emboL'sm, one must test for it before Infarction
takes place.

Restrictive Diseases

Decreased strohe volume, i.c., decreased vital capacity and
inahility to increase tidal volume tohen called for, as in exercise.
In severe cases this leads to respiratory insufficiency, i.e., hypoxia.

Fulmonary Insuficiency 107

hypercapnia wth further sequelae of pulmonary hypertension
and respiratory acidosis. Restrictive disease is caused by:

1. Depression of the respiratory centers by anesthesia, nar-
cotics, cerebral trauma, increased intracranial pressure, cerebral
ischemia and narcotic concentration of CO* and cases of idio-
pathic Alveolar Hypoventilation caused by damage to the respir-
atory center.

2. Restriction of bellows action of thorax or lung,

a. Interference with neural conduction, e.g., poL’o; myasthenia
gravisj traumatic spinal cord lesions.

b. Limitation of movement of the thorax by arthritis; by chest
deformity, e.g., kyphoscoliosis; by obesity, e.g., Pickwickian Syn-
drome; by paralysis of the diaphragm and by ascites,

c. limitation of movement of the lungs by thickened pleura;
by pleural effusion and by pneumothorax.

3. Decreased lung volume, e.g., pneumonectomy; pneumonia;
tumor; atelectasis; complete oedusion of many bronchioles.

i. Decreased distensibility of the lung, e.g., diffuse pulmonary
fibrosis, granulomatosis, lymphogenous carcinomatosis, and pul-
monary congestion. This group has hyperventilation (hence, no
hypercapnia) and dyspnea. Many in this group have A-A Block
Syndrome.

Obstructive Diseases

1. Bronchial Asthma

2. Pulmonary Emphysema

Obstructive disease is more disabling, i.e,, causing more dj^
nea than restrictive disease (wlb exception of Group 4 above)—
Resistance to airflow increases in inverse proportion to the 4lh
power of the diameter of the broodjus.

Patient ^vith obstructive disease may have restrictive defect in
addition to the predominant, obstructive defects, e.g., he may
have complete obstruction of many brondiioles \vith decrease in
stroke volume (vital capacity). Conversely, a patient wth re-
strictive disease may also have obstructive defects if he had par-
tial obstrucrion of some bronchioles by mucus or by external com-

108 Tulmonary Function and Pulmonary Emphysema

pression by fibrosis or granulomata. Such may be the case in tlie
alveolar block syndrome group of diseases, or in pneumoconiosis
or in some cases of pulmonary tuberculosis.

The ventilatory insufficiency in both restrictive and obstructive
disease (total hypoventilation in former, uneven ventilation in
the latter) lead to respiratory insufficiency, ois., hj’poxia \rith
ultimate puhnonar)' hypertension; and hypercapnia, which may
end in respiratory acidosis. In the uneven ventilation of obstruc-
tive disease, however, hyperventilating areas of the lung may
blow off the excess COj.

Dyspnea, a Manifestation of Pulmonary Disabih'ty

Fulmonary disability should not be confused wth pulmonary
insufficiency. Some patients (in group 2 or 3 above) with mod-
erate restrictive disease who have ventilatory insufficiency (de-
creased stroke volumes and lung volumes) and some respiratory
insufficiency (mild hypoxia) may have very httle d>’spnea. On the
other hand, a patient, such as one having pulmonary fibrosis with
impaired diffusion, may have no respiratory insufficiency (no hy-
poxia—at least no appreciable hypoxia at rest, and no h>’percap-
nia), yet he suffers marked dyspnea, and even though he does
have ventilatory insuffidency (decreased stroke volumes and limg
volumes), his severe dyspnea is out of proportion to his ventila-
tory defect.

Causes of Dyspnea

1, Increased resistance to airflow on expiration, due to broncho-
obstruction and bronchoconslricUon.

2. Hypoxia

1) Hypoxic— Low PaOj, stimulates the chemoreceptor centers,
thus causing hyperventilation and dyspnea.

2) Anemic

3) Circulatory

a. Ischemic

b. Stagnant

c. T ^ e.g., hyperth)Toid{sm.

2 and 3) ' •' ' v ability of respiratory

Pulmonary Insufficiency 109

3. Hyperventilation, whatever its cause may be: physiological
dead space, or increased PaCOsi or hypoxia, or patient’s anxiety.

4. Inefficiently functioning diaphragm.

5. Abnormal sensitive Hering-Breuer reflex is postulated as the
cause of dyspnea in pulmonary fibrosis with impaired diffusion,
and in pulmonary congestion. Batach, however, thinks that it is
the hypoxemia in these conditions that causes the dyspnea.

6. Decreased Ability of Respiratory Muscles

1) Muscular weakness or paralyse, e.g., myasthem'a gravis,
thjTOtoxicosis, polio.

2) Mechanical muscle disadvantage, e.g., marked inspiratory
posih'on in emphysema or marked expiratory position in obesity.

3) Anemic and circulatory hypoxia—see above.

Arterial Hypoxia

1. Anemic. This includes tine one caused by CO poisoning.

2. Stagnant, due to cardiac insufficiency or circulatory collapse.

3. Histotoxic— alcohol, cyanide.

4. Hypoxemic

1) High altitude.

2) V*A shunt-anatomic.

3) Pulmonary Insufficiency.

a. Total Hypoventilation.

b. Regional Hypoventilation— uneven ventilation.

c. Impaired Difiusion, espedally on exercise.

Effects of Hypoxia

The brain and the heart are die most vulnerable of all body
tissues to hypoxia.

The clinical pictiure of acute hypoxia simulates drunkenness;
and of chronic hypoxia-fatigue (Barcroft).

The result of hypoxia is a homeostasis beUveen the ill effects
of file hypoxia and the compensatory medranisms.

in Ejects

1. Damage to tissue by the hypoxia may be aggravated further
by the ischemia caused by the vasoconstriction produced by
stimulation of the vasomotor center through the sino-aortic

no PtiltnoTuiry Ftinctton ond Pulmonofy EtnpJiyscma

chemoreceptors (however, this vasoconstriction is counteracted
by the local vaso^tation— vJ.).

2. HI e£Fects of the respiratory alkalosis produced by excessive
hyperventilation.

3. Pulmonary vasoconstriction and hypertension.

4. Pulmonary capillary damage ■wiA an increase in permea-
bility to serum. When this is combined wth a high negative
pleural pressure the occurrence of pulmonary edema is enhanced.

Compensatory Mechanisms

1. Hyperventilation— Depth of breathing rather than rate is
increased. An increase in resting ventilation of only 50% \vill in-
crease Oj saturation by 10 to 20% (provided there is no uneven
ventilation present). However, since stimulation of the respiratory
center by hypoxia (which occurs through the chemoreceptor
centers) begins to take effect only when the O* saturation drops
to 90%, "this stimulation caimot succeed to keep the respiratory
center in a state of optimum reactivity” (Schmidt’” in clinical
physiology by Bard ) .

2. Increased pulse rate.

3. Ixical dilatation of most blood vessels (however, this is
counteracted by the central vasoconstriction— see above).

4. Increased cardiac output.

5. Polycythemia (however, a great increase in viscosity of the
blood may cause a decreased cerebral blood flow).

6. Increased cerebral and coronary blood flow.

7. Decreased cerebrovascular resistance.

Note: All above effects occur ako in hypercapnia.

The iJtimate result in acute hypoxia depends primarily on the
severity and duration of the hypoxia and secondarily on the bal-
ance between tbe local vssodSatathn and central vasoconstricUve
action and on the degree of hyperventilation. In chronic hypoxia
these mechanisms as well as polyQ’themia and renal buffering
action on tbe alkalosis are of primary importance.

Arterial Hypoxia Causing Pulmonary Hypertension

Arterial Hypoxia causes pulmonary hypertension in the follow-
ing manner:

Pulmonary Insuffideivy 111

1. It causes increased cardiac output which causes pulmonary
hypertension.

2. It causes pulmonary vascular constriction which causes in-
creased resistance to pulmonary blood Bow and pulmonary hyper-
tension.

3. It stimulates polycythemia which causes hypervolemia, in-
creased cardiac output and pulmonary hypertension.

4. It causes redistribution of blood from the systemic to the
pulmonary vascular bed, thus increasing pulmonary residual
blood, reducing pulmonary vascular distensibility leading to
pulmonary hypertension.

Hypercapnia

Increased PaCOj stimulates the respiratory center, thus causing
hyperventilation which "blows off” excess COj.

However, failure to hyperventilate may occur—

1) If areas capable of hi'perventilation are decreased by the
progression of the disease having uneven VA/Qc ratios, Nvith
residtant greatly increased residual volume.

2) If areas capable of hyperventilation are decreased by inter-
current bronchopulmonary infection.

3) If the stimulating effect of the coexistent hypoxemia on the
respiratory center is depressed by injudicious a^inistration of
sedatives or narcotics.

4) If the “chemoreceptor centers" in the Carotid and Aortic
Bodies are depressed by inj'udicious administration of high ©2
(without accompanying it by hyperventilation, e.g., by adminis-
tration of IPFB, which would blow off the excess COa), thus re-
moving the only stimulant to rcspirab'on these patients may have,
viz. hypoxia.

Result

Narcotic accumulation of CO 3 — “CO* Narcosis" leading to res-
piratory acidosis.

Respiratory acidosis may be precipitated by decompensated
cor pulmonale. Respiratory acidosis may occur also in non-pul-
monary disease, e.g., improper anesthesia, cerebral lesion or in-
jury. It may occur as end result of any of the restrictive diseases
other than those having hyperventilation.

112 FulmonoTy Function and Fulmonanj Emphjscma

Kespiralory Acidosis

pH<7.4

pH determination per se doesn’t indicate whether acidosis is
respiratory, metabolic, or both (post surgical respiratory' acido-
sis may be complicated by metabohc acidosis caused by anoxemia
and improper glucose combustion during anesthesia). Furtlier-
more, when respiratory acidosis becomes compensated, the pH
xvill be normal but the PaCOj would still be high.

Only by pH and PaC 02 delerminab'on do we get a true picture
of respiratory acidosis. PaCO- can be determined indirectly by
getting the pH of the arterial blood, its total CO 4 content in
volume % and reading off the PaCOj from a nomogram based on
calculation from Henderson-Hasselbalch’s equation (see Fig. 7).
Astrup, P. et aW' * determine the PaCOj, pH and Tjase excess"
in one procedure. Severin^aus*** determines the PaCOj directly
by a modified pH electrode.

TotoTCO. pit PaCO,

Betpiratory Acidosis High Low High

hfetabolic Acidosis . . . Low Low Kormal or low

(Latter because of
b>l)erventiLition)

Combined Respiratory and Mela-

bob'c Acidosis Normal or be- Very low Sb'ghtly eIe^ated

lowDonnnl

Early Symptoms of Respiratory Acidosis

Restlessness; Headache; Confusion; Somnolence.

Later Symptoms

Stupor; Coma; Tremors; Peripheral Vascular Collapse may oc-
cur; Cyanosis; Ri^t heart failure may occur xvith sy’stemic venous
en gorgement and peripheral edema; Increased intracranial pres-
sure xvith increased CSF pressure and papilledema may occur,
latter presumably due to vasodilatation caused by increased
PaCOj.

It must be remembered that onset may be insiduous u-ithout
symptoms and signs, with a precipitous critical situation arising
xvithout w'aming.

Chapter III

PULMONARY FUNCTION TESTS

A. Tests of Ventilatorj' Function
1. LungVolumes and Stroke Volumes

Are estimates of the static elastic forces of the mechanical func-
tion, hence increases and decreases of these volumes correspond
to increases and decreases of compliance. These volumes axe de-
creased in restrictive diseases and defects, and are normal or in-
creased in obstructive diseases and defects.

o. Lung Volumes

a) Total Lung Capacity, TLC. Normal about 5000 ml. to 6000
ml. in men of all ages. In elderly individuals it is not increased
even though the residual volume is increased. This is so because
their vital capacit)' is decreased. TLC is decreased in all restrictive
diseases and in case of cysts or bullae with poorly communicating
bronchi. TLC is increased (usually) in pulmonary emphysema
even in cases with decreased vital capacity. It may, however, be
decreased, along %vith an increased residual volume, in pulmonary
emphysema having bullae with poorly communicating bronchi.

b) Hesidual Volume, RV. Normal, about 1200 ml. in young men
and women, and about 2500 ml. in elderly people. Increased in
obstnicti^'e disease, e.g. pulmonary emphysema and bronchia]
asthma. It is also increased in overinflation of the lung compensa-
tory to loss of some lung tissue or as an adjustment to chest de-
formity; and in decreased elasticity of the senile lung and pulmo-
nary emphysema. (Residual volume may thus be an estimate of
the static elastic forces as well as of air flow resistance ) . RV is de-
creased in most restrictive diseases. In mild and moderate cases
of congestive heart failure, however, RV may be increased, al-
thou^ the other volumes such as inspiratory capacity, total lung
capacity and vital capacity are decreased, as in other restrictive
diseases. This increased RV is due to a decrease in expiratory
reserve volume (Knowles).

113

114 Fulmonary Function and Pulmonary Emphysema

b. Stroke Volumes

a) Vital Capacity, VC. Normal, about 3000 ml. ± 20% in >-oung
women; 4800 ml. ± 2055 in young men (about 75‘? of TLC) and
3500 ml. ± 202 in elderly men. West’s Formula for men: VC •
25 ml. X height in cm. For Women: 20 ml. x height in cm. De*
crease denotes restrictive disease or restrictive defect in obstruc-
tive disease (completely occluded bronchi).

b) Tidal Volume, TV. Normal, about 500 ml. Minute ventila-
tion on exercise is increased in restrictive disease by means of in-
crease in rate of breathing rather than in tidal volume (tachy-
pnea). In severe cases of restrictive disease tidal volume may be
decreased even at rest On the other hand, in obstructive disease,
minute ventilation on exercise is increased by means of increase in
tidal volume rather than in rate.

2. Velocity of Ventilation — Velocity of Air Flow

An estimate of air flow resistance in the bronchial tree, mani-
fested chiefly on expiration (and to a lesser c.xtent, an estimate of
non-elastic tissue resistance), and having an inverse relationship
to these resistances. Thus, a decrease in velocity denotes increased
resistance.

a. Timed Vital Capacities, TVe or VCt.

a) 3 second. Normal, 972 of actual forced (fast) vital ca-
pacity. Lowest limit, 922.

b) 1 second. Normal, 832 of actual forced (fast) utal ca-
pacity. Lowest limit, 722,

b. Maximum Breathing Capacity, MBC or Maximum Volun-
tary Ventilation, MW (English terminology). This measures
stroke volume in addition to velocity of ventilation. Normal, 120
to 170 L/min. ± 352.

c. Maximum Inspiratory Flow Rate, MIFR, Normal, 300 L/min.
(Comroe).

d. Maximum Expiratory Flow Hate, MEFH. Normal, 400
L/min. (Comroe).

3. Air Velocity Index, AVI,

2 of IVedicted MDC
% of Predicted VU '

Pulmonary Function Tests 115

Differentiates between obstructive and restrictive disease.
Ratio is less than one in obstructive disease and one or more in
restrictive disease.

4. Index of Intrapulmonary Infixing, IlM

See Part I. Increase denotes uneven ventilation.

5. Spirogram

Sho^vs breathing pattern in addition to obtaining above meas-
urements.

a. “Air trapping” in obstructive disease.

K One and Two Stage VC. In obstructive disease, two stage
value exceeds one stage (see Part I).

6 . Expirogram

Record of expiratory volume of a single forced expiration
(Forced Expiratory Vital Capacity— FEC) on a rapidly moving
kymograph.

a. Forced Vital Capacity. (Forced and rapid maximal expira-
tion). FVC.

b. Timed Forced Expiratory Capacity (FECt), i.e., timed frac-
tions or segments of the forced expiratory curve. Because of the
rapidly moving kymograph one can measure not only the 3 and 1
second segments but also fractions of the 1 second segment, vis.
0.75 second (Kennedy) and 0.5 second (FECo e. Miller). Miller found
that the FECo 5 normally is 60J or more of one’s FVC, and the
normal FVC is 80% or more of the predicted VC. He worked out
the following method of establishing the presence of obstructive
or restricrive disease: If the FVC is 80% or more of the predicted
VC, and the FECo a is less than 60% of one’s FVC-the patient has
obstructive disease. If the FVC is less than 80% of the predicted,
and the FECo 5 is more than 60% of one’s FVC-the patient has
restrictive disease. If bodi are decreased— the patient has both
obstructive and restrictive- defects.

c. MEFR in Liters per mioule.

a) 200-1200mI.portionofFVC— (Comroe)

b) Middle half volume portion— (Leuallen & Fowler)

116 Pulmonary Function and Pulmonary Emphysema

c) Calculated from FEQ, 5 , by multiplying that volume by
120 to getL/inin.~(MilIer& Johnson)

d. MBC may be estimated, according to Miller, from FECos,
by multiplying that A-olume by 60. (Since a person using the
FECos volume as his tidal volume in performing MBC, wll
breathe at a rate of 60 per minute. )

Expirogram is valuable for office use for differentiation between
obstructive and restrictive disease and for follow up of the effect
of treatment in obstructive disease.

B. Tests of Respiratory Function
1. Determination of Presence and Degree of Hypoxia
(Hypoxic) and Differentiation Bcttcccn Its Causes: Uneven VA/
Qc Ratios; Total Bypoceniilation; V~A Shunts and Impaired Dif-
fusion.

a. Oj Saturalioa at Rest. Decreased in V-A shunt; in total h)^©-
ventilation: in severe and moderate Va/Qc disturbances.

It may or may not be decreased in mild 'Va/Qc disturbances
and in impaired diffusion. (PaOj is decreased, however, even If
O 2 saturarion may be normal (reason-See O.t)’hemoglobin dis-
sociation curv'e]),

b. O 2 Saturah'on after Exerdse. Decreased in all above. In a
mild case of Va/Qc disturbance having O- desaturation, exercise
may correct the desaturation by the increased ventilation on e.rer-
cise.

c. O 2 Saturation on Breathing 100% O 2 — 0. Desaturation is
corrected in all above except in complete V-A shunts— anatomic,
and some cases of physiological (alveolar) shunts. Latter can
then be differentiated from the former by the injection of a dye
in a peripheral vein and noting the time of its appearance in a
peripheral artery. The appearance time is carlj' in an anatomic
shunt and normal in a phj’siological shunt (Chemiack & Chemi-
ack).»’

d. O 2 Saturation on Breathing 30 to 40% O 3 following Exercise.
Desaturation corrected in impaired diffusion, but not corrected
in Va/Qc ratio disturbance (Motiey).

e. O. Saturation on IPPB/I with ambient air. Desaturation
alleviated in Va/Qc disturbances but not in impaired diffusion
(Motley).

Pulmomry Function Tests 117

2. Determination of Presence of Decreased Perfusion and Dead
Space Ventilation

A difference greater than 5 mm. Hg. between COj tension in
arterial blood and in alveolar air (higher in llie former), denotes
dead space ventilation.

3. Attempt to Detect Pulmonary Hypertension

a. O 2 Uptake. Normal at rest, 250 ml/min. On exercise, it is
increased to 1“2 L/min.

In most pulmonary diseases it is normal at rest, but decreased
(i.e., not elevated) on exercise. Decreased O 2 uptake means; a)
Decreased cardiac output, or b) Diminished pulmonary vascular
hed with resultant Pulmonary Hypertension, or c) Decreased
Ventilation. In the presence of evidence of no decrease in cardiac
ou^ut, and in the presence of evidence of adequate ventilation
which may be assumed to be present if there is no decrease in Oa
saturation foUo\ving e.xercise, a decrease in Oa uptake denotes
inability to dilate the pulmonar>' vascular bed to accommodate
the increased blood fio^v during exereise, i.e., it denotes presence
of pulmonary hypertension.

b. Kalio of Oj removal, i.e., ratio of O 2 uptake to ventilation
in L/min. (250 divided by 5). Normal at rest, 40 to 50. After ex-
ercise it is about 54 (due to an initially greater increase in pulmo-
nary circulation than in ventilation). Decreased ratio may mean:
a) Hyperventilation, e.g., in piffmonary fibrosis or pulmonary
congestion, or b) Decreased cardiac output, or c) Pulmonary
Hypertension. Some patients with severe pulmonary or cardiac
disease may be unable to increase their ventilation during exer-
cise to such an extent that their O 2 removal ratio may be relatively
increased, even though they have a decreased O 2 uptake.

4. Determination of Presence of fmpaircii Diffusion

By Krogh’s constant for diffusion of Oa or CO. See Part I, p. 61.
Normal DO 2 (Diffusion Capacity for Oj) at rest is 20 ml/min/
mm.Hg. On exercise it is 60 L/min./mm.Hg.

5. Determination of FaCO^

Normal range 40 to 48 mm. Hg, Determined directly by tlie
Severinghaus electrode or indirectly by Astrup’s method.

118 Fulmorumj Function and Tulmonary Emphysema

Increased in:

a. Uneven Ventilation.

b. Total Hypoventilation.

Not Increased in:

a. Impaired DiSusion, because of tbe hyperventilation present
in these cases and because of the fact that COj is 20 times as
diffusible as O 2 .

b. Anatomic V-A Shunts, because tlie lung is not diseased and
is capable of hyperventilation. (In uneven ventilation causing
physiological V-A shunts, the normal areas of the lung are also
capable of hyperventilation. However, as the disease progresses,
there are less and less of these areas present.)

c. Pulmonary Congestion, because these patients are hyper-
ventilating.

6. Arterial pH

Normal 7.4.

Both pH and FaCOj should be determined for full evaluation of
die status of respiratory acidosis and presence or absence of
compensation.

7. Hb, end RBC Determination

The latter, to determine presence or absence of polycythemia.

Polycythemia. "Secondary.” Caused by hypoxia (increase in
Hb. concentration, however, is inconstant). Some cases may not
have polycythemia even if the hypoxia is severe. Presence of
polycythemia is a good evidence that cor pulmonale has de-
veloped. On the other hand, absence of polycythemia is no proof
that the patient does not have cor pulmonale, as for example,
cases of hypoxia not having polycythemia (as mentioned above),
or cases of cor pulmonale caused not by hypoxia but by pulmo-
nary vascular involvement, such as pulmonary emboli.

S, Cardiac Catheterization

To ascertain presence of pulmonary hypertension.

Normal, 30/15. In hypertension of clinical significance it is
50/25.

Chapter IV

TREATMENT OF PULMONARY
EMPHYSEMA

The chief physiological disturbances and clinical manifestations
of the disease are:

a. Bronchiolar disease: infection; bronchiolar obstruction by
thickened mucosa and by mucus; air trapping with distention of
the alveoli during expiration. All these disturbances cause uneven
distribution of inspiratory air— Uneven Ventilation svith regional
alveolar hypoventilation and dyspnea, hypoxia and hypercapnia
(the latter, in advanced cases).

b. Ix)ss of elasticity, disruption of alveoli and capillaries with
formation of bullae, impairment of diffusion and decrease in
vascular bed, latter causing structural pulmonary hypertension
which is ineversible.

c. Hypoxia caused by the uneven Va/Qc ratios, the result of
a & b above. The hypoxia aggravates the dyspnea and causes
functional pulmonary hypertension which is reversible.

d. Low, poorly functioning diaphragm, aggravating dyspnea
and causing ineffective ventilation.

e. Pulmonary Hypertension and Cor Pulmonale.

f. Hypercapnia in advanced cases, and respirator)’ acidosis.

Treatment is directed toward correction of these clinical mani-
festations and physiological disturbances;

a. &b. Antibiotics to combat infection; Expectorant drugs and
detergents to promote bronchial drainage; bronchodilator drugs,
including aminopliyllin and, when necessary, corticosteroids, to
alleviate bronchospasm and edema of the mucosa, also to relieve
dyspnea; positive pressure breathing on inspiration to correct
uneven distribution of inspiratory air.

c. Oxygen to correct the hypoxia and to prevent the reversible
pulmonary hypertension.

d. Bespiratory exercises; abdominal belt and, when indicated,
pneumoperitoneum to improve diaphragmatic function.

U9

120 Pulmonary Function and Pulmonary Emphysema

e. Oxygen and aminophyllin to relieve pulmonary vasospasm
in pulmonary h>'pertension; digitalis and diuretics in cor pul-
monale.

f. The treatment of hj'percapnia and prevention of respiratory
acidosis is accomplished best by improving the ventilation in tlie
poorly ventilating areas of the lung through the administration
of intermittent positive pressure breathing on inspiration, IPPB/I.

IPPB/I

IPPB/I is the best v’ay known to us at tlie present time of
correcting most of the physiological disturbances of pulmonary
emphysema by one apparatus:

1. It corrects uneven distribution of inspiratory air by opening
up closed off bronchioles.

2. It is fl good way of administering O. in these patients, ^v’ith•
out precipitating respiratory acidosis.

3. It is an efficient way of fldminisfen'ng bronchodilotor and
detergent aerosols.

4. It promotes bronchial drainage.

5. It improves diaphragmatic excursions.

Disadvantages of IPPBfl

1. It may cause compression of bronchioles by the increased
pressure gradient between the high pressure in the alveoli at the
end of inspiration and the low pressure in the bronchioles at the
beginning of expiration.

2. It impedes venous return to the right auricle and decreases
cardiac output by the increased intrathoracic pressure during
inspiration.

For further discussion of IPPB/I and also of E^VNP see Part II.

REFERENCES AND SUGGESTED
READING

1. Abbot^ O. A. et al.: Vagus nerve in pulm. emphysema of the hy-

pertrophic type. /. Med. A. Georgia, 46:58, 1958.

2. Abbott, O. A: Bullons emphysema and pulmonary cysts. Clinical

Cardioputmonanj Physiology, 2nd edition, Grune & Stratton,
New York, 1960.

3. Atidns, J. et al.i The Maximal Expiratory Flow Rate. Dis. Chest,

37:496, 1960.

4. Altschule, M. D.: Physiology in Diseases of the Heart and Lungs.

Cambridge, Harvard Univ. Press, 1948.

5. Andrews, A. H.: Bronchial Obstruction, brondiitis and bron-

chiolitis. C/inIcfll Cardiopulmonary Physiology, 2nd edition,
Gnme & Stratton, New York, 1960.

6. Aronovitch, M. et nl.: Vanilic diethylamide (Emivan) in the

management of acute resp. insufficiency. Canad. Med. Assoc.,
55:875, 1961.

7. Astnip, P. et al: The acid-base metabolism. The Lancet, 1:1035,

1960.

8. Astrup, F.: Acid-base problems in clinical medicine. Scand. /.

Clin. Med., 3I:A-26. March, 1962; 3I:A-34, April, 1962.

9. Attinger, E. O., and Segal, M. S.: Mechanics of breathing. Am.

Rev. of Resp. Dis., 80:38, 1959.

10. Austrian, R. et al,: Clinical and physical features of some types

of pulm. diseases with impairment of alveolar capillary dif-
fusion. The SjTidroine of "Alveolar Capillary Block." Am. J.
Med., 11:667, 1951.

11. Baldwin, E. de F. cf al.: Pulm. Insufficiency II. A study of 39

cases of pulm. fibrosis. Medicine, 28:1, 1949.

12. Bald\vin, E. de F. et al.: Pulm. insuff. L physiol, in normal sub-

jects. Medicine, 27:243, 1948.

13. Baldwin, E. de F. et al.: Pulra. insufficiency III. A study of 122

cases of chr. pulm. emphysema. Medicine, 28:201, 1949.

14. Baldwin, E. de F. et ah: Pulm. insufficiency IV. A study of 16

cases of large pulm. air cysts or bullae. Afedicinc, 29:169, 1950.

121

122 Pulmonary Function and Pulmonary Emphysema

15. Banyai, A.: So called hypertrophic emphysema. Dls. Chest 23-25

1954. ' ' ’

16. Barach, A.: Regulation of pulm. ventilation in pulm. emph)'sema.

Arch. Int. Med., 203:0, 1959.

17. Barach, A.; Ambulatory O* thera0r. Dis. Chest, 35:229, 1959,

18. Baradi, A. L., and Biclcerroan, H. A.: Pulmonanj Emphysema.

The Williams & Willdns Co.. Baltimore, 1958.

19. Barach, A.: Possibilities of prevention of cardiac failure in pulm.

emphysema. Dis. Chest, 37:6S7, 1960,

20. Baradi, A.: A contribution to the mechanism of dj'spnea, based

on the response to therapeutic procedures. Clinical Ccrdio-
pulmonary Physiology, 2nd edib'on, Grune & Stratton, New
York, 1960.

21. Barach, A. et ah: Mechanical production of exp. flow rates sur-

passing the capacity of the human lung. Am. /. Med. Sc.,
226:241. 1953.

22. Beal, B. S., Comroe, J, H., Jr. et ah: Pulm. function studies in 20

asthmatic patients in the symptom-free interval. J. Allergy,
23:1, 1932.

23. Beck, G. J., and Scairone, J. A.: Pb)*siol. effect of c.xsufllation mth

negative pressure (E.W.NJ*.). Dis. Chest, 29:80, 1956.

24. Bedell, G. N, et al.j Treatment of pulm. emphysema. ]A.Mu\.,

169:1699, 1959.

25. Bedell, G. N.: Alveolar Hypoventilation. Clinical Cardiopulmo-

nary Physiology, 2nd edition, Grune edition. Grune & Stratton,
Nmv York, 1960.

26. Best, C. H., and Taylor, N. B.: Physiological Basis of Medical

Practice. 6th edition. Williams & Wilkins, 1955.

27. Bickennan, H. A.: Bronchial drainage and the phenomena of

cough. Clinical Cardiopulmonary Physiology, 2nd edition,
Gnme & Stratton, New York, 1960.

28. Birath, G. et al.: Pulm. function after pneumonectomy. J. Tho-

racic Surg., 16:492, 1947.

29. Brinkman, G, L. et cl,: The treatment of respiratory acidosis with

Tham. Am. J. Med. Sci., 239:341, 1960.

30. Broftnan, B. L. cf al.: Unilateral pulmonary artcr>' occlusion in

man. J. Thoracic Surg., 34:200, 1957.

31. Butler, J. et oh: Pressure volume relationship of the chest in the

completely relaxed patient. Clin. Sci., 16:125, 1957.

32. Gander, L., and Comroe, J. H, Jr.: A method for the ohiecti>-e

e\’aluation of bronchodilator drugs. /. Allergy, 26:210, 1955.

References and Suggested Reading 123

33. Cantarow, A., and Trumper, M.: Clinical Biockemistiy chapter

on Acid-Base Balance. W. B. Saunders Co., 1949.

34. Garden, L. et al.x Acute suppurative brondiitis and bronchiolitis

in chronic pulm. disease. Ann. Inf. Med., 34:559, 1931.

35. Carter, M. G. et a!.: Fneumoperitoneuni in the treatment of pulm.

emphysema. New England J. Med., 243:549, 1950.

36. Charms, B. L. et al.i Differential pulm. artery occlusion in pa-

tients with chronic pulm. disease. Am. /. Med., 26:527, 1959.

37. Cherniack, R. M., and Chemiack; L.: Respiration in Health and

Disease. W. B. Saunders Co., Philadelphia, London, 1961.

38. Cherniack, R,s The physical fwoperties of the lung in chronic

obstructive emphysema. /. Clin. Incest., 35:394, 1956.

39. Christie, R. V.; The elastic properties of the emphysematous

lung and their clinical significance. J. CUn. Incest., 13:295,
1934.

40. Clowes, H. A,, Jr. et al.i The relationship of postoperat. acidosis

to pulm. and cardiovascular function. /. Thoracic c> CardiO’
case. Sufg., 39:1, 1960.

41. Cohen, B. M.: Intennittent Positive Pressure Breathing in In-

spiration. A lecture delivered at the meeting of Am. College
of Chest Phys., Oct., 1959. Reprint

42. Cohn, J. E. et ol.: Resp. Acidosis in emphysema. Am. /. Afed.,

October, 1954.

43. Comroe, J. H., Jr.: Interpretation of commonly used pulm. func-

tion tests. Am. J. Med., 10:356, 1951.

44. Comroe, J. H., Jr. et al.: Mental changes occurring in chemically

anoxemic patients during O 2 therapy. JA.MA., 243:1044,
1950.

45. Comxoe, ]. H. et al: The Lung, Clinical Physiology and Pul-

monary Function Tests. The Year Book Publishers, Chicago,
1955.

48. Comroe, J. H., Jr. cf al.: Mental changes occurring in chronically
anoxemic patients during Oz &^py. JA.MA., 143:1044,
1950.

47. Cory, R. C., and Smith, J. R.: The compartments of the lung vol-

ume and their physiol, significance. Clinical Cardiopulmonary
Physiology, 2nd edition, Gnine & Stratton, New Yorl^ 1960.

48. Coumand, A., and Richards, D. W, Jr.: Pulm. insufficiency. Am.

Reo. The., 44:20, 1941.

49. Coumand, A. et at: Physiolo^cal studies of the effects of inter-

124 Pulmonary Function and Pulmonary Emphysema

mittent Positive Pressure Breathing on cardiac output in man.
Am. }. Physiology, 152:162, 1948.

50. Coumand, A. et al.i Pulm. circulation and alveolar ventilation-

perfusion relationships after pneumonectomy. /. Thoracic
Sufg., 19:80, 1950.

51. Coumand, A. et ah: Physiological studies of the elfects of inter-

mittent positive pressure breathing on cardiac output in man.
Am. /. Physiol, 152:162, 1948.

52. Crenshaw, G. L.: Degenerative lung disease. Dis. Chest, 25:427,

1954.

53. Crenshaw, G. L.: Surgical management of pulm. emphysema.

/. Thoracic Surg., 24:398, 1952.

54. Cmtis, J. K.: Recognition of early emphysema by pulm. function

tests. Dis. Chest, 33:285, 1960.

55. Cushing, I. E., and Miller, \Vm. F.: Considerations in humidifica-

tion by nebulizab'on. Dis. Chest, v. 34, Oct., 1938.

56. Daly, J. J. ct al: Circulatory effect of the valsalva maneuver in

emphysema and the influence of ganglionic blockade. Dis.
Chest, 41:34. 1962.

57. Darling, R. C. cf al: Studies on intrapulmonary mining of gases.

III. An open circuit method of measuring residual air. J. Clin.
Invest.. 19:609, 1940.

58. Davenport, H. W.: The ABC cf Add Chemistry. The Univ. of

Chicago Press. 1952.

59. Dayman, H.: Mechanics of airflow in health and disease. /. CUn.

Invest., 31:1175, 1951.

60. Dexter, L. et al: Chronic cor pulmonale witliout hypo.tia. Bull.

Uew England Med. Can., 14:69, 1952.

61. Diclde, Helen A., and RanJdn, J.: Interstib'al diseases of the lung:

The Alveolar CapUkry Block Syndrome. Clinical Cardiopul-
monary Physiology, 2nd cdib'on, Grune & Stratton, New York,
1960.

62. Donald, K. W. et al: Analysis of factors affecting concentrah'on

of O 2 and CO- in lung gas and blood. /. Applied Physiol.
4:497, 1952.

63. Dorman, P. J.: The renal response to acute respiratory addosis.

/. Ch’n. Incest., 33:82, 1954.

Ebert, R. V., and Pierce, J. A.: Pathogenesis of pulm. emphy-
sema, A.M>A. Arch. Int. Med~, p. 80, July, 1962.

65. Eliaser, hf.. Jr.; Motley, H. L.; Pearce, M. L., and Selzcr, A.:
Pulm. heart disease. A symposium. Calif. Med., 84:217, 1937.

References and Siiggesfed Reading 125

68. Ehvell, L. B.: The successful treatment of dis. of resp. tract by
continuous postural drainage. Vis. Chest, 26:338, 1954.

67. Farber, S. M., and Wilson, R. H. L.: The rational approach in the

use of broachodilators in dir. resp. dis. Ann. Int. Med., 50:
1241, 1959,

68. Fenn, W. O.: Mechanics of respiration. Am. J. Med., 10:77, 1951.

69. Ferris, B. G.: Studies of palm, functioa. New Enghnd J. Med.,

262:552 and 610, 1960.

70. Fleischner, F. G.: The pathogenesis of chronic substantial em-

physema. Am. Rev. The., 62;45, 1950.

71. Fowler, N. O.; Impairment of the pulm. circulation. Clinical

Cardiopulmonary Physiology, 2nd edition, Grune & Stratton,
New York, i960.

72. Fowler, W. S., and Miller, R. D.: Clinical applications of labora-

tory evaluation of pulm. function. Med. Clin. No. America,
38:1227, 1934.

73. Fowler, W. S.: Intrapulm. distribution of inspired gas. Physiol.

Rct>ieu>,32:l, 1952.

74. Fowler, W. S.: Lung function studies 111. Uneven pulm. venti-

lation in normal subjects and in patients with puhn. disease.
J. Applied Physiol, 2:283, 1949.

75. Fraimow, Wm. et at: The use of Intermittent Positive Pressure

Breathing in the prevention of COa narcosis associated with
O 2 therapy. Am. Rco. Resp, Dis., 81:8151, i960.

76. Frank, N. R. at al: Measurements of pulmonary compliance in

seventy young adults. J. Appl. Physiol., 9:38, 1936.

77. Frank, N. R. et al: The effect of pulm. resection on the compli-

ance of human lungs. J. Thoracic if Cardiovasc. Surg., 38:215,
1959.

78. Freimanis, A. K., and Molnar, Wm.; Chronic bronchitis and em-

physema at bronchography. Radiology, 74:194, 1960.

79. Friedman, P.: Fluoroscopy and roentgenology. Clinical Cardio-

pulmonary Physiology, Gnme & Stratton, New York, 1957.

80. Fry, D. L. et al: The mechanics of pulm. ventilation in normal

subjects and in patients with emphysema. Am. /. Med., 16:80,
1954.

81. Fulton, J. F.: Text Book of Physiology, 17th edition, W. B. Saun-

ders, 19^,

82. Gaensler, E. A.; Air Velocity Index. Am, Rev. The., 62:17, 1950.

83. Gaensler, E. A.: Analysis of die Ventilatory Defect by Timed Ca-

pacity Measurements. Am. Rev. The., 64:256, 1951.

126 Pulmonart/ Function and Pulmonary Emphysema

84. Gaensler, E. A.: Clinical Pulm. Ph>-siology. New Enabnd J. Med

252:177,1955.

85. Galland, F.: Chr. cor pulmonale or chr. pulm. hypertension? Dis.

Chest, 43:82, 1963.

86. Gamble, J. H.: Chemical Anatomy, Physiology and Pathology of

Extracellular Fluid. Harvard Uaiv. Press, 1954.

87. Geschickter, Ch., and Popo^'id. A.: Postemphj-sematous h>per-

tension. Arch. Jnt. MerL, 92:167, 1953.

88. Gordon, B. et al.i Considerations of clinical and physiological

factors in the treatment of chr. pulm. conditions. Dis. Chert,
19:271, 1951.

89. Grollman, A.: Clinical Physiology, Part III. The Respiratory Syr-

tern. McGraw-Hill Book Co., 1957.

90. Hackney, J. D., and Collier, C. R.: Simplified rebreathing test

for estimating ventilatory function. The Physiologirt, V. 2,
Aug., 1959.

91. Harper, H. A.: Review of Physiological Chemistry. 7th edition.

Lange Medical Publications, Los Altos, Calif., 1959.

92. Harvey, R. M. et al.i Infiuence of chr. pulm. dis. on the heart and

circulation. Am. /. Med., 10:719, 1951.

93. Hirschfus, J. A. et ah Pulm. function studies in bronchial asthma.

Am. J. Med., 14:23, 1953.

94. Horton, G. E., and Phillips, S.: The Expiratory Ventilogram. Am.

Rev. Resp. Dis., 80:724, 1959.

95. Hurst, A., and Cohen, B. M.: Physiologic therapy of broncho-

pulmonary diseases. Clinical Cardiopulmonary Physiology,
2nd edition, Grune & Stratton, Neiv York, 1960.

96. Hussay, B. A.: Human Physiology. 2nd edition, McGraw-Hill,

New York, 1955.

97. Irvin, C. W., Jr.: Valsalva maneuver as a diagnostic aid. JA.MJl,

113:7811, 1959.

98. Jones, R. W.; Macnamara, J., and Gaensler, R. A,: The elFects of

intermittent positive pressure breathing in simulated pulmo-
nary obstruction. Am. Rev. Resp. Dir., 82:164, 1960.

99. Kountz, W. B., and Alexander, H. L.: Non-obstructive emphy-

sema. JA.MA.. 100:551, 1903.

100. Kelsey, J. E. et ah Expiratory CO. concentration curve, a lest

of pulm. function. Dis. Ch^, 41:498, 1962.

101. Kennedy, M. S.: The brondiodilator action of Khellin. Thorax,

6:44, 1952.

References and Su^esied Reading 127

102. Kennedy, M. S.; Measure of Maximum Ventilatory Capacity.

Thorax, 8:73, 1953.

103. Kiowles, J. H.: Respiratory Physiology and Its Clinical Applica-

tion. Harvard Univ. Press, 1959.

104. Levine, E. R.: A more direct liquefaction of bronchial secretion

by aerosol therapy. Dir. Chest, 31:155, 1957.

105. Levine, E. R.: Emphysema. Clinical Cardiopulmonary Physiology,

2nd edition, Grune & Stratton, New Yorls I960.

106. Leonhardt, K. 0.; Resuscitation of the moribund asthmatfe and

emphysematous patient. Note England /. Med., 264:785, 1961.

107. Leuallen, E. C., and Fowler, W. C.: Maximal Midexpiratory

Flow. Am. Reu. The., 72:783, 1959.

108. Ullington, G. A. et al.i The cardiorespiratory syndrome of obeS'

ity. Dir. Chest, 32:1, 1957.

109. Luchsinger, P. C. et at.: Cardioresp. studies in Hamman Rich

Syndrome. Dis. Chest, 35:50, 1959.

110. LuJsada, A. A. et al: Colloquium on therapy of right heart fail-

ure. Sixth International Congress, Am. College Chest Riysi-
dans, Dis. Chest, 41:260, 1962.

111. Mack, I.: Cor Pulm. Clinical Cardiopulmonary Physiology, 2nd

eition, Grune 4c Stratton, New York, 1960.

112. Mack, 1. et at: Chr. Cor Pulmonale, a symposium at annual meet-

ing of College of Chest Phys. Dis Chest, 41:477, 1962.

113. Maloney, J. V., Jr., and Whitlenberger, J. G.: Clinical implica-

tions of pressures used in respiration. Am. /. Med. Sc., 221:
425, 1951.

114. March, J. W., and Lyons, H. A.; A Stud)' of Maxim. Flow Rate

in health and disease. Dis. Chest, 37:600, 1060.

115. Marks, A. et al.: A new ventilatory assister for patients with re-

spiratory acidosis. New England J. Med., 265:61, 1963.

116. Marshall, R.: The physical properties of the lungs in relation to

the subdivisions of lung volumes. Clin. Sc., 16:507, 1957.

117. Mayer, E., and Rappaport, I.: Bronchitis and emphysema.

J.A.MA., 165:1227, IQSl.

118. McIIroy, M. D., and Bales, D. V.: Respiratory Function after

pneumonectomy. Thorax, 11:303, 1956.

119. McLean, F.: Application of fte law of chemical equilibrium to

biological problems. Physiol. Revieios, 18:495, 1938.

120. McLean, K. H.: Pathogenesis of pulm. emphysema. Am. 1. Med.,

25:62, 1958.

128 Pulmonary Function and Pulmonary Emphysema

121. Meneely, G. R.: Pulmonaiy Rinction testing. Dis. Chest 31-125

1937.

122. Meneely, G. R. ei al: The volume of the lung determined by

helium dilution. ]. Clin. Inwst.. 2S;129, 1949.

123. Miller, Wm. F., and Sproule, B. J.: Studies on role of IPPB/I-0,

in the treatment of pulm. edema. Dis. Chest, 35, May, 1959.

124. Miller, Wm. F.; Severe tesp. depression. Role of a resp. stim-

ulant, Elhamivan, in the treatment JAMA., 1S0:9(S, 1962.

125. Miller, Wm. F.: Chr. inflammatory bronchopulm. disease. A.MA.

Arch. Int. Med., 109:169, 1961.

126. hiiUer, W. F. et al.: The Half Second Expiratorj' Capacity Test

Dis. Chest, 30:33, 1956.

127. Miller, W. F. et al.: Relationship between Maxima! Breathing Ca-

pacity and Timed Expiratory Capadties. J. Applied Physiol,
14:215, 1959.

128. Miller, Wm. S.: The Lung, 2nd edition. Thomas, Springfield,

1947.

129. Mithoefer, J. C.: Inhibition of carbonic anhydrase. Its effect on

COj elimination by the lungs. /. Appl Physiol., 14;109, 1959.

130. Motley, H. L.: Use of pulm. function tests for disability appraisal.

Dis, Chert. 24:387. 1933.

131. hfotley, H. L., and TomashefsJd, J. F.: Treatment of chr. pulm.

dis. ivilh Intermittent Positive Pressure Breathing. Arch. In-
dust Hygiene, 5:1, 1952.

132. Motley, H. L.: Pulm. emphysema, cardio-resp. disturb. Dis. Chest,

29:292, 1956.

133. Motley, H. L.: Physiol, research in chr. pulm. disease. Dis. Chest,

38:250, 1960.

134. Motley, H. L.: The mechanics of chr. pulm. heart disease. Prog.

Cardiovasc. Dis., 1:326, 1959.

135. Motley, H. L.: Studies on the nature of the art. blood orygen

unsaturation in pulm. disease. Dis. Chest, 32:501, 1958.

136. Motley, H. L.: Studies on the nature of hypoxia with and with-

out cyanosis in chronic pulm. disease. Geriatrics, 13:617, 19^.

137. Motley, H. L.: Pulmon. function in the pneumoconioses. Cardio-

pulmonary Function, Crane & Stratton, 1957.

138. Motley, H. L.: Physiology of respiration with reference to pulm.

disease. Am. J. Surgery* SSjlOO, 1055.

139. Nahas, G. G.: O- Dissoc. curve of arterial blood in man breath-

ing high 0- concentrations, J. Applied Physiol., 5:169, 1952.

129

References and Suggested Reading

140. Naimark, A. et al.i The effect of a new carbonic anhydrase inhibi-

tor (Daranide) in respiratory insufficiency. Am. J. Med., 2S:
368, 1960.

141. National Academy of Sciences. Handbook of Physiology. \V. B.

Saunders Co., 1958.

142. O’Reilly, R. J.: The clinical recognition of CO 2 intoxication. Dis.

Chest. 37x185, mo.

143. Raab, W.: Laxyngoptosis, an easily detectable sign of pulm.

emphys. Dis. Chest, 26:703, 1954.

144. Rappaport, I., and Mayer, E.: Emphysema and the senile lung.

J. Am. Geriat. Soc., 2:581, 1934.

143. Rato, O. et ah: Anoxemia secondary to polycythemia and poly-
cythemia secondary to anoxemia. Am. /. Med., 19:958, 19^.

146. Read, J., and Williams, R. Pulm. Ventilation. Am. /. Med.,

27:545, 1939.

147. Richards, D. W., Jr.; The nature of cardiac and pulm. dyspnea.

Circulation, 7:15, 1953.

148. Richards, D. W.: Pulmonary emphysema: etiological factors and

clinical forms. AnnoZs 0 / Jnt. Med., 53:1105, 1960.

149. Richter, T.; l^'est, J. R., and Fishman, A. P.r The Syndrome of

Alveolar Hypoventilation and diminished sensitivity of the
respiratory center. New England J. Med., 256:1185, 1957.

150. Riley, R. L. ct al.x Studies of pulm. circulation at rest and during

exercise in normal individuals and patients with chronic pulm.
disease. Am. J. PhyHol., 152:372, 1948.

151. Riley, R. L.: The work of breafliing and its relation to resp. aci-

dosis. Am. Inf. Med.. 41:172, 1954.

152. Rimini, R. et ah: Unilateral positive pressure breathing as a

means of partial shift of the pulm. blood flow. Dis. Chest,
31:643, 1957.

153. Robin, E. D. et ah: A physiologic approach to the diagnosis of

acute pulm. embolism. New England /. Med., 260:586, 1959.

154. Robin, E. D. et ah: Alveolar gas ex<diange in clinical pulm. em-

bohsm. New England J. Med., 262:283, 1960.

155. Rockey, E. E. et ah: Four and one-half years’ experience in the

treatment of emphysema and offier respiratory insufficiencies
by tracheal fenestration. Dis. Chest, 39:117, 1961.

156. Roosenburg, J. G., and Deeostra, H.; Bronchial-pulmonary vas-

cular shunts in chr. pulm. affections. Dis. Chest, 26:664, 1954.

157. Sato, R. et ah: Pre- and postoperative cardiopuhn. djmamics of

130 Vulrnonory Function end Pulmonary Emphysema

the emphysematous bulla. J. Thor. Cardiovasc. Sure. 39-516
1960.

158. Saxton, G. A., Jr.: Distrib. of gas and blood in the lungs. Clinical

Cardiopulmonary Physiology, 2nd edition, Grune & Stratton
New York, 1960.

159. Schmidt, C. F.; The respiration in P. Bard edition Medical Physi-

ology. 10th edition, St. Louis, Mosby, 1936.

160. Segal, M. S., and Dulfano, M. J.: Chronic Pulmonary Emphysema.

Grime & Stratton, New York, 1^.

161. Segal, M, S. et ah: Alternating Positive-Negative Pressures In

mechanical respirations. Dis. Chest, 25:ft40, 1954.

162. Segal, M. S., and Attinger, E. O.: Bronchial asthma; pathophysi-

ology pulm. function tests and therapeutic aspects. Clinical
Cardiopulmonary Physiology, 2nd edition, Grune & Stratton,
New York, 1960.

163. Selzer, A.: Chronic cyanosis. Am. /. Med., J0:334, 1951.

164. Severinghaus, J. W., and Bradley, A. F.: Electrodes for blood

pOa and pCOa determination. /. Appl. Physiol, J3;5I5, 1058.

165. Sieker, H. 0., and Hickam, J. B.: Carbon dioxide intoxication.

The clinical syndrome, its etiology and management with par-
ticular reference to the use of mechanical respirators. Medi-
cine, 35:389, 1956.

166. Sieker, H. O. et ah: The treatment of carbon dioxide narcosis by

the use of an air automatic positive-negative resuscitator. Am.
Rev. of The., 74:309, 1936.

167. Sigaard Anderson, O. et ah: A micromethod for determination of

pH, CO 2 tension, base excess and standard bicarbonate in
capillary blood. Scand. J. Clin. Med.. 12:172, 1960.

168. Sigaard Anderson, O., and Engel, K.; A neiv acid-base nomo-

gram. Scand. J. Clin. Med., 12:177, 1960.

169. Simmons, P. H.: Evaluation of cUnical acid-base disturbances.

Current concepts in Chest Diseases, published by Tuberculo-
sis and Heart Assn, of Los Angeles, June, 1962.

170. Singer, R. B., and Hastings, A. B.; Improved clinical method for

the estimation of disturbances of the add-base balance of
human blood. Medicine, 27:223, 1948,

171. Smith, G. A. et al.: Preoperativc and postoperative cardiopulm.

function studies in bronchiectasis. Am. Rev. The., 69:869,
1954.

172. Snider, G. L. et al: The evaluation of brondiodilator drugs ^in

the treatment of asthma. J. Lob. O Clin. Med., 45:348, 1955.

References and Suggested Rcodtng 131

173. Snider, G. L., and Badner, D.r The clinical appL'cation of pulm.

function testing. Med. CUn. No. America, 43;445, 1959.

174. Snider, T. H. et al.i Simple bedside test of re^. function.

M.MA, 179:1631, 1959.

175. Spain, D.; Chr. cor pulmonale. Arch. Int. Med., 77:37, 1946.

176. Spain, D. M., and Kaufman, G.: The basic lesion in clonic pulm.

emphysema. Am, Ret), of The., 6S;29, 1953.

177. Spain, D.: Anatomy and pathology of the lungs as related to

physiologic disturbances. Clinical Cardiopulmonary Physi-
ology, 2nd edition, Grune & Stratton, New York, 1960.

178. Spenser, F. C. et oL: The use of a mechanical respirator in the

management of resp. insufBciency follo%ving trauma or opera-
tion for cardiac or pulm. disease, h 77iorflc. 6- Cardiov. Surg.,
38:758. 1959.

179. Stein, M., and Colp, Ch. R.j Simple method for the measurement

of the alveolar COj. /jtJlfA, 173:671, 1960.

180. Stone, D. J. et al.i Preapitation by pulm. infection of acute

anoxia, cardiac failure and respiratory acidosis in chr. pulm.
disease. Am. J. Med., 14:14, 1953.

181. Swan, H. J, C., and McLean, K. H.: The dynamics of normal

pulm. circulation, Clinicol Cardiopulmonary Physiology, 2nd
edition, Grune & Stratton, New York, 1960.

182. Swanson, A. G.: Potential harmful effect of treating pulm. en-

cephalopathy with a CO- buffering agent. Am. J. 5fcd. Sc.,
240:433, 1960.

183. Theodos, P. A.: Physiological interpretations from history, physi-

cal signs and roentgenography. Clinical Cardiopulmonary
Physiology, 2nd edition, Grune & Stratton, New York, 1960.

184. Tomashefsky, }. F.: Normal pulm. physiol. Clinicol Cardiopul-

monary Physiology, 2nd edition, Grune & Stratton, New York,
1960.

185. Trimble, H. G.: Pulm. emphysema treated by Intermittent Posi-

tive Pressure Breathing. /. Am. Ceriatric Society, 2:102, 1954.

186. Vance, J. \V., and Fowler, W. S.; Adjustments of stores of COj

during voluntary hyperventilation. Dis. Chest, 37:302, 1960.

187. Vance, J. VV.: Respiratory exchange during exercise in patients

%vith diffuse obstructive pulm. emphysema. Dis. Chest, 42;
191, 1962.

188. Waldman, S.; Triamcinolone in asthma and secondary bronchosp.

pulm. emphysema. Dis. Chest, 38:522, 1960.

132 Pulmonoiy Furtcilon and Pulmonary Emphysema

189. Wairen, C. I., Jr.: Valsalva Maneuver as a diagnostic aid

JAMA., 170:787, 1959.

190. Warring, F. C., Jr.: Ventilatory function (in patients wth pulm.

the.). Am. Ret). Tic., 52:432, 1945.

191. Waterman, D. H.: Surgical treatment of obstructive emphysema.

Clinical Cardiopulmonary Physiology, Grune & Stratton, Ncav
Y ork, 1957.

192. Wes^ J. R. et al.: Physiopathologic aspects of chr. pulm. omphy*

sema. Am. J. Med., 20:481, 1951.

193. West, J. R., and Alexander, J. R.: Studies on resp. mechanics

and the work of breathing in pulmonary fibrosis. Am. J. A/cd.,
27:529, 1959.

194. Westcott, R. N. et al.i Anoxia and human pulmonary vascular

resistance. J. Clin. Incest., 30:957, 1951.

195. Williams, M. H., Jr. ct al.: Cardiopulm. function in bronchial

asthma. A comparison with dir. pulmonary emphysema. Am.
Reo. of Resp. Dis., 82:173, I960.

196. Wolff, B. P.: Resp. att:alosis wth especial reference to diest pain.

Dis. C/icrt, 28:337, 1955.

197. Wood, P.: Pulm. Hypertension. Modem Concepts of Cardiopos.

Dis., 28:513, 1959.

198. Woodruff et al: Decisions in thoradc surgery as influenced by

the knowledge of pulm. physiology. J. Thor. Surg., 26:156,
1953.

199. Wright, G. W., and Filley, G. F.: Pulm. fibrosis and respiratory

fuDctiOD. Am. /. Med., 20:642, 1951.

200. Zasly, L. et al: A study of gastric secretions in dir. obstruct

pulm. emphysema. Dis. Chest, 38:69, 1960.

201. Zimmerman, H.: A study of pulm. circulation. Dis. Chest, 20:48,

1951.

202. Zoltan, M.: Effect of lateral recumbency on pulm. function. Dis.

Chest. 33:550, 1958.

INDEX

Addosis
ine(aboII<^ 57

combined r&spiratory and metabcdic,
112

respiratory, 57, 112
in emphysema, 7&-79
treatment of, 93
Aeration gradient 22
Air, inspired, distribution of, 10, 45
m emphysema, 74

Air cysts, large, in emphysema, 83^
Air flow, resistance to, 14-15
Air velocity Index, 45, 114
in emphysema, 74
Alhalosis
metabolic, 57*55
respiratory, 57, 102
Alveolar-arterUl gradleot, 22
Alveolar capiBaiy block syndrome, 30-
31. 103

Alveolar changes in emphysema, 69-70
Alveolar-respiratory (gas exchange) in-
suSdency, 29-31, 103-106
Alveolar venblatian, 8-9, 44, 99
In emphysema, 74
Alveolo-capillary gradient, 22
Arterial blood

carbon dioxide tension in, 55-58
in emphysema, 75, 78
hydrogen ion concentration in, 59,
118

in emphysema, 75
Oxygen saturation, 51-52, 110
in emphysema, 75

Arteriolar changes in emph>5eina, 70
Asthma, bronchial, differentiated from
emphysema, 81-82

Base excess, BE, 59
Blood flow distribution, 17-18
uneven, 29, 103

Bobr s equation, 7
Breadting Reserve, 46
Biondiitis, and empb^ema, 67, 68-69,
77

BfondKJspirometiy, 50
Bullae, in emphysema, 83-85

Capacities, lung, 5, 23
functional residual, 5
ifispiratojy, 5

maximum breathing, 12, 43-44, 73,
114

in emphysema, 73
total lung, 6, 113
ratio of residual ^‘oIume to, 43
in emphysema, 73
vital, 6, 114
in emphysema, 73
timed. 12.43,48,114
Capillaries
in emphysema, 70
perfusion of, 17-18
Carbon dioxide

arterial blood tension, 55-58
in emphysema, 75
retention in emphysema, 78
treatment of, 93

Cardiac output and Oi uptake, 17
Catheterization, cardiac. 61, 118
in emphysema. 75-76
Chemoreceptor centen of respiration,
16,99

Conqiliance, 13, 97, 98
functional, 14
Static, 14
Conductance, 14

Congestive ventilatory Insuffidency, 26
Cor pulmonale and emphysema, 79-80
treatment of, 94
Cyaimsis. See Hypoxia

134 Mmonmy Function end Pulmonmj Emphuseme

Dead space
anatomic, 6

alveolar, physiological, 8
Dead space ventilation, 6-8, 35, 38
hyperventilation affecting, 35, 39
Di&ffl'oa, 38-21 , 100

capacity in emphysema. 76
impair^, 30-31, 103
exercise affecting, 82
and hypoxia, 38, 41
tests of, 61
Disability
pulmonary, 108
Dyspnea, 25, 26, 108-109
in emphysema, 69, 70, 72, 77
treatment of, 87
in impaired diffusion, 31

Elastance, 13, 97
Emphysema, 67-94, 107-108
acidosis in, respiratory, 78
treatment of, 93
alveolar changes in, 69-70
arteriolar changes In, 70
and bronchitis, 67, 68-69, 77
capiUaiy destruction in, 70
carbon dioxide retention In, 78
treatment of, 93
classification of, €7
clinical coune of, 77-80
cor pulmonale in, 79-80
treatment of, 94
diagnosis of, 77-85
differentiated from asthma, 81-82
dyspnea in, 72, 77
treatment of, 87
etiology of, 67-68
function tests in, 73-76
hypoxia in, treatment of, 87-88
non-obstructive, 67
obstructive, 67
pathophysiology of, 67-72
physical signs in. 80
roentgenology in, 81
Exercise

effects on Oj uptake, Oi saturation and
diffusion capacity, 62-63
in anatomic V-A shunt case, 63

in bypoventllatiag case, 62
In Impaired diffusion case, 62
in norma] case, 62
la uneven venlilation/peifurion
case, 63

oxygen saturation after, 51, 116
oxygen uptake after, 52, 117
In emphysema, 75
tests. 60

Expiratory flow rate, maximum, 12. 49-
50

Expiratory reserve volume, 5
Expirogram, 48-50, 115
Exsefflation with negalis’e pressure,
E\VNP, 92

Fluoroscopy
in emphysema, 81

Cas diffusion, 18-21

Gas exchange /unction tests. See 3?es-
plntory function tests
Cas exchange insuifideney, 29-31, 103-
112
Cndient
aeration, 22
alveolar-arterial. 22
alveolar-beginning capiDaiy, £2
alveolar-end capillary, 22
alveolo-capillaiy, 22
transfer, 22

Hydrogen ion concentration In arterial
blood. 56, 59,118
in emphysema, 75
IlyperoapDia, 78, HI
Hyperinflation, causes of, 23
Hypeipaea, in restrictive \-entihtOTy in-
suSdeucy, 26
Hypertension, pulmonary
detection of, 52, 01, 117, 118
horn hypoxia, 110-111
in emphysema, 71, 72, 76
IIyper>’entilaUon, 11, 102-103
effect on dead space ventilation, 35,
39

Index

135

effect on hypoventilation, 10, 101
effect on uneven ventilation, 10, 37,
101

Hypoventilation, 9-10, 101
exercise affecting, 62
hypoxia in, 33
Hypoxia, 32-42. 109-111
causing pulmonary hypertension, 110,
111

differentiation between different
causes of, 41-42, 116
effects of. 109, 110
in pulmonary Insufficiency, 33-42
in hypoventilation, 33
in impaired diffusion, 31, 36
in uneven ventilatlon/pcifusion
ratios, 33-38, 41

in shunts of venous to arterial blood.
32-33

treatment of, in emphysema. 87-92
types of, 109

Inspitatory ait flow, maxima], 12. 49
iBsplratory capacity, 5
losplratoty reserve volume, 5
Inspired ait, distribution of, 45
In emphysema, 74

Insufficiency, pulmonary, 25-31, 101-
112

respiratory, 29-31, 103-112
ventilatory, 25-28, 101-103

Lung

capadUes, 5, 23, 113-114
volumes, 5, 23, 113-114

MasimuJD breathing capacity, 12, 43-
44, 48, 114
in emphysema, 73

Medullary centers of respiration, 10, 99
Membrane

component of A-a gradient, 22
difference in pressure of gas on both
sides of, 20
permeability of, 21

Minute ventilation, 6, 44, 99
in emphysema, 74

Nomogram, McLean's, 60

Obstructive ventilatory insufficiency
(obstructive diseases), 27-28, 107-
106
Oxygen

arterial saturation, 51-52, 116
in emphysema, 75
ratio of removal, 53
in emphysema, 75

uptake at rest and after exerdse, 17,
52

to emphysema. 75

Oxyhemoghhin dissociation curves 24

Perfusion and distribution of blood
flow, 17-18, 100
uneven, 29, 103

ventilation/perfusion ratios. See Ven-
Ulation/perfusion ratios
Peripheral vascular collapse to emphy-
sema, 91, 93

Permeability of membrane, 21
Physical signs to pulmonary emphy-
sema, 80

Polycythemia, 76, 118
Pressure breathing
iKgaUve. with exsufflatioii, 92
positive, intermittent, 11, 41, 88-92,
120
pulmonary
disability, 108
fibrosis, 28, 107
insufficiency, 25-31, 101-112

Residual volume, 5, 113
ratio to total lung capacity, 43
to wnphysema, 73
Resistance to air flow, 14-15, 08
Respiration or gas exchange. 21, 100
Respirators
automatic cycling, 9-4

136 Tulmonaty Tunction and

patient cycled, 89, 90
Respiratory function tests, 51-83, 116-
118

arterial Wood pH, 59, 75, 118
arterial oxygen saturation, 51-52, 7^
118

arterial COa tension, 55, 75, 117
diffusion tests, 61
In emphysema, 75-76
exercise tests, 81-63
oxygen uptake after exercise and rest,
52, 75. 117

percentage of oxygen extracted from
inspired air, 53

ratio of oxygen removal, 53, 75, 117
ventilation/blood flow variations. Si,
75, 117

ventilation equivalent, 53, 75
Respiratory insufBdency, 29-31, 103-
112

Roentgenology In emphysema, 81
Restrictive ventilatory insufficiency (re-
strictive diseases), 25-27, 106-107

Shock in emphysema, 91. 93
Shunts of venous to arterial blood, 32-
34

anatomic, 32-33, 104, 116
differentiation between anatomic and
physiological, 116
physiological, 33-34, 131, 116
exercise affecting, 63
Shunts of arterial to venous blood. 33
Spirogram, 47-48, 115
Stroke volumes
cardiac, 17
lung, 114

Tests

of diffusion, 61
in emphysema, 73-76
exercise, 61-63

of pulmonary function, 113-118
of respiratory function. 51-63, 116-
118

of ventilatory function. 43-50, 113*
118

Futmonary Emphysema

Tidal volume, 5, 114
Transfer gradient, 22

Valsalva maneuver
Wood pressure response to, in em-
physema, 80
Velodly

air velocity index, 45, 1 14
In emphysema, 74
of ventilation, 12, 114
Ventilation. 5-17, 97-100
alveolar, 8-9, 44, 99
in emphysema. 74
control of, 15-17, 99
dead space, 6-8, 99, 105-106
hyperventilation affecting, 35, 39
and hypoxia, 35
eqiuvalent, 53
in emphysema, 75
factor in emphysema, 73
hyperventilatfoD, 11, 102-103
effect on dead space ventilaUoD,
35,39

hypoventilation, 9-10, 101
exercise affecting, 63
and hypoxia, 33

maximum \-oIuntaiy or maximum
breathing capacity, 12, 43-41,
73,114

mechanics of, 13-15, 97, 93
minute, 6, 44, 99
In emphysema, 74
Increased, 102
uneven, 10-11, lOl
velocity of, 12, 114
volumes, 6-12
walking. 46

Ventflatton/blood flow ratio variations,
54

in emphy'sema, 75

VentUation/perfusion ratios normal, 36
exercise affecting. 63
hypoxia In, 33-36, 41, 104-106
uneven, 30, 37-40, 101, 104-105
decreased, 37, 104-106
Increased, 38-39, 104-106
increased and decreased, 40, 104-
106

Index

Ventilatory {unction tests, 43-50, 113-
116

air velocity inder, 45, 74, 114
alveolar ventilation, 8*9, 44, 74, 99
bronchospirometry, 50
dbtribution of impired air, 45, 74,
115

in emphysema, 73-74
expirogram, 48-50, IIS
maximum breathing capacity, 12, 43-
44, 73, 114

maTirrmm inspiratory and expiratory
floAV rates. 47, 114

minute ventilation, 6, 44, 74, 99, 102
percentage of breathing reserve. 46
ratio of residual volume to total lung
capacity, 43, 73
residual volume, 43, 73, 113
spirogram, 47-48, 115
timed vital capacity, 12. 43, 73, 114
timed fractiess of vital capacity, on
expirogram, 48, 115

137

vdocity of ventilation (of air flow),
114

walldng index, 46

Ventflatoty insufficiency, 25-28, 101-
103

congestive, 26
ob^iuctive, 27-28, 107-108
restrictive, 25-27, 106-107
Vital capacity, 6, 12 , 114
in emphysema, 73
timed, 12. 43, 73, 114
timed fractions of, on expirogram,
48, 115

Volumes, lung, 5, 23, 113-114
expiratory reserve, S
inqarotory reserve, 5
residual, 5, 113
ratio to total lung capacity, 43
in anjAyseroa, 73
tidal 5, 114

Walking ventilation, 46