RINGKASAN FAAL PARU

WEST’S RESPIRATORY PHYSIOLOGY

THE ESSENTIALS

John B. West

Penyusun:
dr. Nurul Hazi Putri

Pembimbing : dr. Adrianison,Sp.P(K)

STASE FAAL
DEPARTEMEN PULMONOLOGI DAN ILMU KEDOKTERAN RESPIRASI
FAKULTAS KEDOKTERAN UNIVERSITAS RIAU
2024
T E N T H E D IT IO N

WEST’S
RESPIRATORY
PHYSIOLOGY
T H E E S S E N T IA LS
STRUCTURE AND
FUNCTION
H O W T H E A R C H IT E C T U R E
O F T H E LU N G S U B S E R VE S
IT S F U N C T IO N
1
• Blood-Gas Inter ace
• Airways and Airf ow W e be gin w ith a s hort review o the
re lations hips be twe e n s tructure and unction
• Blood Vessels and Flow in the lung. Firs t, we look at the blood-gas
• Stability o Alveoli inte r ace , w he re the exchange o the re s piratory
gas e s occurs . Next we look at how oxyge n is
• Removal o Inhaled Particles
brought to the inte r ace through the airways
and the n how the blood re m ove s the oxyge n
rom the lung. Finally, two pote ntial proble m s o
the lung are brie f y addre s s e d: how the alve oli
m aintain the ir s tability and how the lung is ke pt
cle an in a pollute d e nvironm e nt.

1
2 CHAPTER 1

T he lung is or gas exchange. Its prime unction is to allow oxygen to move

rom the air into the venous blood and carbon dioxide to move out. T he lung
does other jobs too. It metabolizes some compounds, lters unwanted materi-
als rom the circulation, and acts as a reservoir or blood. But its cardinal unc-
tion is to exchange gas, and we shall there ore begin at the blood-gas inter ace
where the gas exchange occurs.

BLOOD-GAS INTERFACE
O xygen and carbon dioxide move between air and blood by simple di -
usion, that is, rom an area o high to low partial pressure,* much as
water runs downhill. Fick’s law o di usion states that the amount o gas that
moves across a sheet o tissue is proportional to the area o the sheet but
inversely proportional to its thickness. T he blood-gas barrier is exceedingly
thin (Figure 1.1) and has an area o between 50 and 100 square meters. It is
there ore well suited to its unction o gas exchange.
H ow is it possible to obtain such a prodigious sur ace area or di usion inside
the limited thoracic cavity? T his is done by wrapping the small blood vessels (cap-
illaries) around an enormous number o small air sacs called alveoli (Figure 1.2).
T here are about 500 million alveoli in the human lung, each about 1/3 mm in
diameter. I they were spheres,† their total sur ace area would be 85 square meters
but their volume only 4 liters. By contrast, a single sphere o this volume would
have an internal sur ace area o only 1/100 square meter. T hus, the lung generates
this large di usion area by being divided into a myriad o units.
G as is brought to one side o the blood-gas inter ace by airways, and blood
is brought to the other side by blood vessels.

AIRWAYS AND AIRFLOW

T he airways consist o a series o branching tubes, which become narrower,
shorter, and more numerous as they penetrate deeper into the lung (Figure 1.3).
T he trachea divides into right and le t main bronchi, which in turn divide into
lobar, then segmental bronchi. T his process continues down to the terminal

*T he partial pressure o a gas is ound by multiplying its concentration by the total pressure.
For example, dry air has 20.93% O 2. Its partial pressure (P o 2) at sea level (barometric pressure
760 mm H g) is 20.93/100 × 760 = 159 mm H g. W hen air is inhaled into the upper airways, it is
warmed and moistened, and the water vapor pressure is then 47 mm H g, so that the total dry gas
pressure is only 760 − 47 = 713 mm H g. T he P o 2 o inspired air is there ore 20.93/100 × 713 =
149 mm H g. A liquid exposed to a gas until equilibration takes place has the same partial pressure
as the gas. For a more complete description o the gas laws, see Appendix A.
†
T he alveoli are not spherical but polyhedral. N or is the whole o their sur ace available or di -
usion (see Figure 1.1). T hese numbers are there ore only approximate.
 STRUCTURE AND FUNCTION 3

F ig u r e 1 . 1 . Ele ctro n m icro g ra p h s h o w in g a p u lm o n a ry ca p illa ry (C) in th e a lve o la r

wa ll. No te th e e xtre m e ly th in b lo o d -ga s b a rrie r o a b o u t 0.3 µm in s o m e p la ce s .
Th e la rg e a rro w in d ica te s th e d i u s io n p a th ro m a lve o la r ga s to th e in te rio r o th e
e ryth ro cyte (EC) a n d in clu d e s th e la ye r o s u r a cta n t (n o t s h o w n in th e p re p a ra tio n ),
a lve o la r e p ith e liu m (EP), in te rs titiu m (IN), ca p illa ry e n d o th e liu m (EN), a n d p la s m a .
Pa rts o s tru ctu ra l ce lls ca lle d b ro b la s ts (FB), b a s e m e n t m e m b ra n e (BM), a n d a
n u cle u s o a n e n d o th e lia l ce ll a re a ls o s e e n .

bronchioles, which are the smallest airways without alveoli. All o these bronchi
make up the conducting airways. T heir unction is to lead inspired air to the gas-
exchanging regions o the lung (Figure 1.4). T he larger proximal airways have
a lot o cartilage in their walls. As the airways progress distally, the proportion
o cartilage decreases and smooth muscle increases such that the very small
distal airways are composed mostly o smooth muscle. Because the conduct-
ing airways contain no alveoli and there ore take no part in gas exchange, they
4 CHAPTER 1

F ig u r e 1 . 2 . Se ctio n o lu n g s h o w in g m a ny a lve o li a n d a s m a ll b ro n ch io le . Th e
p u lm o n a ry ca p illa rie s ru n in th e wa lls o th e a lve o li (Fig u re 1.1). Th e h o le s in th e
a lve o la r wa lls a re th e p o re s o Ko h n .

constitute the anatomic dead space, where the term “dead space” re ers to areas
o lung that receive ventilation but no blood f ow. Its volume is about 150 ml.
T he terminal bronchioles divide into respiratory bronchioles, which have
occasional alveoli budding rom their walls. Finally, we come to the alveolar
 STRUCTURE AND FUNCTION 5

Fig u r e 1 .3 . Cast o the airways o a hum an lung. The alveoli have been pruned away,
allowing the conducting airways rom the trachea to the term inal bronchioles to be seen.

ducts, which are completely lined with alveoli. T his alveolated region o
the lung where the gas exchange occurs is known as the respiratory zone.
T he portion o lung distal to a terminal bronchiole orms an anatomical unit
called the acinus. T he distance rom the terminal bronchiole to the most distal
alveolus is only a ew millimeters, but the respiratory zone makes up most o
the lung, its volume being about 2.5 to 3 liters during rest.
D uring inspiration, the volume o the thoracic cavity increases and air is
drawn into the lung. T he increase in volume is brought about partly by con-
traction o the diaphragm, which causes it to descend, and partly by the action
o the intercostal muscles, which raise the ribs, thus increasing the cross-
sectional area o the thorax. Inspired air f ows down to about the terminal
bronchioles by bulk f ow, like water through a hose. Beyond that point, the
combined cross-sectional area o the airways is so enormous because o the
large number o branches (Figure 1.5) that the orward velocity o the gas
6 CHAPTER 1

Z
Tra che a
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Bronchi 1
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2
n
i
t
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3
d
n
o
4
C
Bronchiole s
5

Te rmina l
bronchiole s 16
17
Re s pira tory
bronchiole s 18 F ig u r e 1 . 4 . Id e a liza tio n o
s
d
e
19 th e h u m a n a irwa ys a cco rd in g
n
n
a
o
to We ib e l. No te th a t th e rs t
l
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20
a
y
n
16 g e n e ra tio n s (Z) m a ke
r
o
Alve ola r
o
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21
t
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i
ducts
a
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a n d th e la s t 7 m a ke u p th e
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22
a
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T
re s p ira to ry zo n e (o r th e
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Alve ola r 23 tra n s itio n a l a n d re s p ira to ry
s a cs
zo n e s ).

500

400
)
2
m
c
(
a
300
e
r
a
n
o
i
t
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s
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200 Conducting Re s pira tory F ig u r e 1 . 5 . Dia g ra m to s h o w
s
o
zone zone th e e xtre m e ly ra p id in cre a s e
r
c
in to ta l cro s s -s e ctio n a l a re a o
l
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t
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th e a irwa ys in th e re s p ira to ry
T
zo n e (co m p a re Fig u re 1.4). As
100
a re s u lt, th e o rwa rd ve lo city
Te rmina l o th e ga s d u rin g in s p ira tio n
bronchiole s
b e co m e s ve ry s m a ll in th e
re g io n o th e re s p ira to ry
0 5 10 15 20 23 b ro n ch io le s , a n d ga s e o u s
d i u s io n b e co m e s th e ch ie
Airwa y ge ne ra tion m o d e o ve n tila tio n .
 STRUCTURE AND FUNCTION 7

becomes small. D i usion o gas within the airways then takes over as the dom-
inant mechanism o ventilation in the respiratory zone. T he rate o di usion o
gas molecules within the airways is so rapid and the distances to be covered so
short that di erences in concentration within the acinus are virtually abolished
within a second. H owever, because the velocity o gas alls rapidly in the region
o the terminal bronchioles, inhaled dust requently settles out there.
T he lung is elastic and returns passively to its preinspiratory volume dur-
ing resting breathing. It is remarkably easy to distend. A normal breath o
about 500 ml, or example, requires a distending pressure o less than 3 cm
water. By contrast, a child’s balloon may need a pressure o 30 cm water or
the same change in volume.
T he pressure required to move gas through the airways is also very small.
D uring normal inspiration, an air f ow rate o 1 liter·s−1 requires a pressure
drop along the airways o less than 2 cm water. Compare a soda straw, which
may need a pressure o about 500 cm water or the same f ow rate.

A ir w a y s

• Divid e d in to a co n d u ctin g zo n e a n d a re s p ira to ry zo n e

• Vo lu m e o th e a n a to m ic d e a d s p a ce is a b o u t 150 m l
• Vo lu m e o th e a lve o la r re g io n is a b o u t 2.5 to 3.0 lite rs
• Ga s m ove m e n t in th e a lve o la r re g io n is ch ie f y b y d i u s io n

BLOOD VESSELS AND FLOW

T he pulmonary blood vessels also orm a series o branching tubes rom the
pulmonary artery to the capillaries and back to the pulmonary veins. Initially, the
arteries, veins, and bronchi run close together, but toward the periphery o the
lung, the veins move away to pass between the lobules, whereas the arteries and
bronchi travel together down the centers o the lobules. T he capillaries orm a
dense network in the walls o the alveoli (Figure 1.6). T he diameter o a capil-
lary segment is about 7 to 10 µm, just large enough or a red blood cell. T he
lengths o the segments are so short that the dense network orms an almost
continuous sheet o blood in the alveolar wall, a very e cient arrangement or
gas exchange. Alveolar walls are not o ten seen ace on, as in Figure 1.6. T he
usual, thin microscopic cross section (Figure 1.7) shows the red blood cells in
the capillaries and emphasizes the enormous exposure o blood to alveolar gas,
with only the thin blood-gas barrier intervening (compare Figure 1.1).
T he extreme thinness o the blood-gas barrier means that the capillaries
are easily damaged. Increasing the pressure in the capillaries to high levels
or inf ating the lung to high volumes, or example, can raise the wall stresses
8 CHAPTER 1

F ig u r e 1 . 6 . Vie w o a n a lve o la r wa ll (in th e ro g ) s h o w in g th e d e n s e n e tw o rk

o ca p illa rie s . A s m a ll a rte ry (le ft) a n d ve in (rig ht) ca n a ls o b e s e e n . Th e in d ivid u a l
ca p illa ry s e g m e n ts a re s o s h o rt th a t th e b lo o d o rm s a n a lm o s t co n tin u o u s s h e e t.

o the capillaries to the point at which ultrastructural changes can occur.

T he capillaries then leak plasma and even red blood cells into the alveolar
spaces.
T he pulmonary artery receives the whole output o the right heart, but the
resistance o the pulmonary circuit is astonishingly small. A mean pulmonary
arterial pressure o only about 20 cm water (about 15 mm H g) is required
or a f ow o 6 liter·min −1 (the same f ow through a soda straw needs 120 cm
water).

B lo o d -G a s In t e r f a c e

• Extre m e ly th in (0.2 to 0.3 µm ) ove r m u ch o its a re a

• En o rm o u s s u r a ce a re a o 50 to 100 m 2
• La rg e a re a o b ta in e d b y h a vin g a b o u t 50 0 m illio n a lve o li
• So th in th a t la rg e in cre a s e s in ca p illa ry p re s s u re ca n d a m a g e th e
b a rrie r
 STRUCTURE AND FUNCTION 9

F ig u r e 1 . 7 . Micro s co p ic s e ctio n o d o g lu n g s h o w in g ca p illa rie s in th e a lve o la r

wa lls . Th e b lo o d -ga s b a rrie r is s o th in th a t it ca n n o t b e id e n ti e d h e re (co m p a re
Fig u re 1.1). Th is s e ctio n wa s p re p a re d ro m lu n g th a t wa s ra p id ly ro ze n w h ile b e in g
per used.

Each red blood cell spends about 0.75 s in the capillary network and dur-
ing this time probably traverses two or three alveoli. So e cient is the anat-
omy or gas exchange that this brie time is su cient or virtually complete
equilibration o oxygen and carbon dioxide between alveolar gas and capillary
blood.
T he lung has an additional blood system, the bronchial circulation that sup-
plies the conducting airways down to about the terminal bronchioles. Some
o this blood is carried away rom the lung via the pulmonary veins, and some
enters the systemic circulation. T he f ow through the bronchial circulation is
a mere raction o that through the pulmonary circulation, and the lung can
unction airly well without it, or example, ollowing lung transplantation.

B lo o d Ve s s e ls

• Th e w h o le o th e o u tp u t o th e rig h t h e a rt g o e s to th e lu n g .
• Th e d ia m e te r o th e ca p illa rie s is a b o u t 7 to 10 µm .
• Th e th ickn e s s o m u ch o th e ca p illa ry wa lls is le s s th a n 0.3 µm .
• Blo o d s p e n d s a b o u t 0.75 s in th e ca p illa rie s .
10 CHAPTER 1

To conclude this brie account o the unctional anatomy o the lung, let us
glance at two special problems that the lung has overcome.

STABILITY OF ALVEOLI
T he lung can be regarded as a collection o 500 million bubbles, each 0.3 mm
in diameter. Such a structure is inherently unstable. Because o the sur ace
tension o the liquid lining the alveoli, relatively large orces develop that tend
to collapse alveoli. Fortunately, some o the cells lining the alveoli secrete a
material called surfactant that dramatically lowers the sur ace tension o the
alveolar lining layer (see Chapter 7). As a consequence, the stability o the
alveoli is enormously increased, although collapse o small air spaces is always
a potential problem and requently occurs in disease.

REMOVAL OF INHALED PARTICLES

W ith its sur ace area o 50 to 100 square meters, the lung presents the largest
sur ace o the body to an increasingly hostile environment. Various mecha-
nisms or dealing with inhaled particles have been developed (see Chapter 9).
Large particles are ltered out in the nose. Smaller particles that deposit in
the conducting airways are removed by a moving staircase o mucus that con-
tinually sweeps debris up to the epiglottis, where it is swallowed. T he mucus,
secreted by mucous glands and also by goblet cells in the bronchial walls, is
propelled by millions o tiny cilia, which move rhythmically under normal
conditions but are paralyzed by some inhaled toxins.
T he alveoli have no cilia, and particles that deposit there are engul ed
by large wandering cells called macrophages. T he oreign material is then
removed rom the lung via the lymphatics or the blood f ow. Blood cells such
as leukocytes also participate in the de ense reaction to oreign material.

KEY C O N CE P T S
1. T he blood-gas barrier is extremely thin with a very large area, making it
ideal or gas exchange by passive di usion.
2 . T he conducting airways extend to the terminal bronchioles, with a total
volume o about 150 ml. All the gas exchange occurs in the respiratory
zone, which has a volume o about 2.5 to 3 liters.
3 . Convective f ow takes inspired gas to about the terminal bronchioles;
beyond this, gas movement is increasingly by di usion in the alveolar
region.
4 . T he pulmonary capillaries occupy a huge area o the alveolar wall, and a
red cell spends about 0.75 s in them.
VENTILATION
HO W G A S G ETS
T O T H E A LVE O LI
2
• Lung Volumes
• Ventilation W e now look in m ore de tail at how oxyge n
is brought to the blood-gas barrie r by the proce s s
• Anatomic Dead Space o ve ntilation. Firs t, lung volum e s are brie f y
• Physiologic Dead Space reviewe d. The n total ve ntilation and alve olar
ve ntilation, w hich is the am ount o re s h gas
• Regional Differences in
ge tting to the alve oli, are dis cus s e d. The lung that
Ventilation
doe s not participate in gas exchange is de alt w ith
unde r the he adings o anatom ic and phys iologic
de ad s pace . Finally, the uneve n dis tribution o
ve ntilation caus e d by gravity is introduce d.

14
 VENTILATION 15

T he next three chapters discuss how inspired air gets to the alveoli, how gases
cross the blood-gas inter ace, and how they are removed rom the lung by the
blood. T hese unctions are carried out by ventilation, di usion, and blood
ow, respectively.
Figure 2.1 is a highly simplif ed diagram o a lung. T he various bronchi
that make up the conducting airways (Figures 1.3 and 1.4) are now repre-
sented by a single tube labeled “anatomic dead space.” T his leads into the gas-
exchanging region o the lung, which is bounded by the blood-gas inter ace
and the pulmonary capillary blood. W ith each inspiration, about 500 ml o
air enters the lung (tidal volume) and about the same volume leaves. N ote how
small a proportion o the total lung volume is represented by the anatomic
dead space. T he larger the volume o the dead space, the smaller the volume
o resh gas entering the alveoli. Also note the very small volume o capillary
blood compared with that o alveolar gas (compare Figure 1.7).

LUNG VOLUMES
Be ore looking at the movement o gas into the lung, a brie glance at the
static volumes o the lung is help ul. Some o these can be measured with a
classic water-bell spirometer (Figure 2.2). N ote that electronic devices have
now replaced the water spirometer shown in this f gure. D uring exhalation,

VOLUMES FLOWS

Tida l volume Tota l ve ntila tion

500 ml 7,500 ml/ min

Ana tomic de a d s pa ce Fre que ncy

150 ml 15/min

Alve ola r ve ntila tion

5,250 ml/ min
Alve ola r ga s
3,000 ml
–~
–1

P ulmona ry P ulmona ry
ca pilla ry blood blood flow
70 ml 5,000 ml/ min

F ig u r e 2 . 1 . Dia g ra m o a lu n g s h o w in g typ ica l vo lu m e s a n d f o w s . Th e re is

co n s id e ra b le va ria tio n a ro u n d th e s e va lu e s d e p e n d in g o n th e s ize a n d g e n d e r o th e
p a tie n t.
16 CHAPTER 2

8
P a pe r

Tota l
6 lung S pirome te r
ca pa city
Vita l
ca pa city
s
r
4
e
t
i
Tida l Pen
L
volume

2
Functiona l
re s idua l Re s idua l
ca pa city volume
0

F ig u r e 2 . 2 . Lu n g vo lu m e s . No te th a t th e to ta l lu n g ca p a city, u n ctio n a l re s id u a l
ca p a city, a n d re s id u a l vo lu m e ca n n o t b e m e a s u re d w ith th e s p iro m e te r.

the bell goes up and the pen down, marking a moving chart. First, normal
breathing can be seen (tidal volume). N ext, the subject took a maximal inspira-
tion and ollowed this by a maximal expiration. T he exhaled volume is called
the vital capacity. H owever, some gas remained in the lung a ter a maximal
expiration; this is the residual volume. T he volume o gas in the lung a ter a
normal expiration is the functional residual capacity (FRC).
N either the FRC nor the residual volume can be measured with a simple spi-
rometer. H owever, a gas dilution technique can be used, as shown in Figure 2.3.
T he subject is connected to a spirometer containing a known concentration o

C1 C2
V1

V2

Before equilibration After equilibration

C 1 × V1 = C 2 × (V1 + V2 )

F ig u r e 2 . 3 . Me a s u re m e n t o th e u n ctio n a l re s id u a l ca p a city b y h e liu m d ilu tio n .

 VENTILATION 17

helium, which is virtually insoluble in blood. A ter some breaths, the helium
concentrations in the spirometer and lung become the same.
Because no helium has been lost, the amount o helium present be ore
equilibration (concentration times volume) is
C 1 × V1
and equals the amount a ter equilibration:
C 2 × ( V1 + V2 )
From this,
C1 − C 2
V2 = V1 ×
C2
In practice, oxygen is added to the spirometer during equilibration to make
up or that consumed by the subject, and also carbon dioxide is absorbed.
Another way o measuring the FRC is with a body plethysmograph
(Figure 2.4). T his is a large airtight box, like an old telephone booth, in
which the subject sits. At the end o a normal expiration, a shutter closes
the mouthpiece, and the subject is asked to make respiratory e orts. As the
subject tries to inhale, he (or she) expands the gas in the lungs; lung volume
increases, and the box pressure rises because its gas volume decreases. Boyle’s
law states that pressure × volume is constant (at constant temperature).
T here ore, i the pressures in the box be ore and a ter the inspiratory e ort
are P 1 and P 2, respectively, V1 is the preinspiratory box volume, and ∆ V is the
change in volume o the box (or lung), we can write
P1 V1 = P2 ( V1 − V )
T hus, ∆ V can be obtained.
N ext, Boyle’s law is applied to the gas in the lung. N ow,
P3 V2 = P4 ( V2 + V )

P V

F ig u r e 2 . 4 . Me a s u re m e n t o FRC w ith a
PV = K
b o d y p le thys m o g ra p h . Wh e n th e s u b je ct
P V m a ke s a n in s p ira to ry e o rt a ga in s t a clo s e d
a irwa y, h e s lig h tly in cre a s e s th e vo lu m e o
h is lu n g , a irwa y p re s s u re d e cre a s e s , a n d b ox
p re s s u re in cre a s e s . Fro m Bo yle’s la w, lu n g
vo lu m e is o b ta in e d (s e e te xt).
18 CHAPTER 2

where P 3 and P 4 are the mouth pressures be ore and a ter the inspiratory
e ort, and V2 is the FRC. T hus, FRC can be obtained.
T he body plethysmograph measures the total volume o gas in the lung,
including any that is trapped behind closed airways (an example is shown in
Figure 7.9) and that there ore does not communicate with the mouth. By con-
trast, the helium dilution method measures only communicating gas or ventilated
lung volume. In young normal subjects, these volumes are virtually the same, but
in patients with lung disease, the ventilated volume may be considerably less than
the total volume because o gas trapped behind obstructed airways.

Lu n g Vo lu m e s

• Tid a l vo lu m e a n d vita l ca p a city ca n b e m e a s u re d w ith a s im p le

s p iro m e te r.
• To ta l lu n g ca p a city, u n ctio n a l re s id u a l ca p a city, a n d re s id u a l vo l-
u m e n e e d a n a d d itio n a l m e a s u re m e n t b y h e liu m d ilu tio n o r th e b o d y
p le thys m o g ra p h .
• He liu m is u s e d b e ca u s e o its ve ry lo w s o lu b ility in b lo o d .
• Th e u s e o th e b o d y p le thys m o g ra p h d e p e n d s o n Bo yle’s la w, PV = K,
a t co n s ta n t te m p e ra tu re .

VENTILATION
Suppose the volume exhaled with each breath is 500 ml (Figure 2.1) and there
are 15 breaths·min −1. T hen the total volume leaving the lung each minute is
500 × 15 = 7500 ml·min −1. T his is known as the total ventilation or the minute
ventilation. T he volume o air entering the lung is very slightly greater because
more oxygen is taken in than carbon dioxide is given out.
H owever, not all the air that passes the lips reaches the alveolar gas
compartment where gas exchange occurs. O each 500 ml inhaled in
Figure 2.1, 150 ml remains behind in the anatomic dead space. T hus, the vol-
ume o resh gas entering the respiratory zone each minute is (500 − 150) × 15
or 5,250 ml·min −1. T his is called the alveolar ventilation and is o key impor-
tance because it represents the amount o resh inspired air available or gas
exchange (strictly, the alveolar ventilation is also measured on expiration, but
the volume is almost the same). N ote that even though only 350 ml o resh
gas enters the alveoli with each breath, the alveolar volume still expands by
the ull size o the tidal volume as 150 ml o gas le t over in the anatomic dead
space at the end o the previous exhalation is drawn into the alveoli with each
breath be ore the resh gas enters.
T he total ventilation can be measured easily by having the subject breathe
through a valve box that separates the inspired rom the expired gas, and
 VENTILATION 19

collecting all the expired gas in a bag. T he alveolar ventilation is more di f cult
to determine. O ne way is to measure the volume o the anatomic dead space
(see below) and calculate the dead space ventilation (volume × respiratory
requency). T his is then subtracted rom the total ventilation.
We can summarize this conveniently with symbols (Figure 2.5). U sing V
to denote volume, and the subscripts T, D , and A to denote tidal, dead space,
and alveolar, respectively,
VT = VD + VA*
there ore,
VT ⋅ n = VD ⋅ n + VA ⋅ n
where n is the respiratory requency.
T here ore,
&E = V
V &D + V
&A

where V & means volume per unit time, V & is expired total ventilation,
E
& &
and VD and VA are the dead space and alveolar ventilations, respectively
(see Appendix A or a summary o symbols).
T hus,
&A = V
V &E − V
&D

A di f culty with this method is that the anatomic dead space is not easy
to measure, although a value or it can be assumed with little error. N ote
that alveolar ventilation can be increased by raising either tidal volume or
respiratory requency (or both). Increasing tidal volume is o ten more e ective

VD
VT

FI FE
F ig u r e 2 . 5 . Th e tid a l vo lu m e
(VT) is a m ixtu re o ga s ro m th e
a n a to m ic d e a d s p a ce (VD) a n d a
co n trib u tio n ro m th e a lve o la r ga s VA
(VA). Th e co n ce n tra tio n s o CO 2 FA
a re s h o w n b y th e d o ts . F, ra ctio n a l
co n ce n tra tio n ; I, in s p ire d ; E,
e xp ire d . Co m p a re Fig u re 1.4.

*N ote that VA here means the volume o alveolar gas in the tidal volume, not the total volume
o alveolar gas in the lung.
20 CHAPTER 2

because this reduces the raction o each breath occupied by the anatomic
dead space (sometimes called the dead space raction).
Another way o measuring alveolar ventilation in normal subjects is rom
the concentration o CO 2 in expired gas (Figure 2.5). Because no gas exchange
occurs in the anatomic dead space, there is no CO 2 there at the end o inspira-
tion (we can neglect the small amount o CO 2 in the air). T hus, because all the
expired CO 2 comes rom the alveolar gas,

& & %CO 2

VCO 2 = VA ×
100
T he % CO 2/100 is o ten called the ractional concentration and is denoted
by F c o 2.
T here ore,
&CO = V
V &A × F
2 CO 2

and rearranging gives

&C O
V
&A =
V 2

FCO 2

T hus, the alveolar ventilation can be obtained by dividing the CO 2 output

by the alveolar ractional concentration o this gas.
N ote that the partial pressure o CO 2 (denoted P c o 2) is proportional to the
ractional concentration o the gas in the alveoli, or P c o 2 = F c o 2 × K, where
K is a constant.
T here ore,
&C O
V
&A =
V 2
×K
PCO 2

T his is called the alveolar ventilation equation.

Because in normal subjects the P c o 2 o alveolar gas and arterial blood
are virtually identical, the arterial P c o 2 can be used to determine alveolar
ventilation. T he relation between alveolar ventilation and P c o 2 is o crucial
importance. I the alveolar ventilation is halved (and CO 2 production remains
unchanged), or example, the alveolar and arterial P c o 2 will double. CO 2 pro-
duction at rest is usually constant, but it is a ected by metabolic activity and
can be increased by actors such as exercise, ever and in ection.

ANATOMIC DEAD SPACE

T his is the volume o the conducting airways (Figures 1.3 and 1.4). T he
normal value is about 150 ml, and it increases with large inspirations
because o the traction or pull exerted on the bronchi by the surrounding
 VENTILATION 21

lung parenchyma. T he dead space also depends on the size and posture o
the subject.
T he volume o the anatomic dead space can be measured by Fowler’s
method. T he subject breathes through a valve box, and the sampling tube o
a rapid nitrogen analyzer continuously samples gas at the lips (Figure 2.6A).
Following a single inspiration o 100% O 2, the N 2 concentration rises as the
dead space gas is increasingly washed out by alveolar gas. Finally, an almost
uni orm gas concentration is seen, representing pure alveolar gas. T his phase
is o ten called the alveolar “plateau,” although in normal subjects it is not

A S ta rt of
ins pira tion

80

O2
End of
%
e xpira tion
n
o
i
t
a
Re corde r
r
40
t
n
S a mpling
e
c
tube
n
Alve ola r
o
c
pla te a u
2
S ta rt of
N
e xpira tion N2 me te r

0
0 5 10
Time (s )

B
%
40
n
o
i
t
A
a
r
t
n
e
c
n
o
c
2
N
B
0
0 0.2 0.4 0.6 0.8
Expire d volume (lite rs )

F ig u r e 2 . 6 . Fo w le r m e th o d o m e a s u rin g th e a n a to m ic d e a d s p a ce w ith a ra p id N 2
a n a lyze r. A s h o w s th a t o llo w in g a te s t in s p ira tio n o 100% O 2 , th e N 2 co n ce n tra tio n
ris e s d u rin g e xp ira tio n to a n a lm o s t le ve l “ p la te a u ” re p re s e n tin g p u re a lve o la r ga s .
In (B), N 2 co n ce n tra tio n is p lo tte d a ga in s t e xp ire d vo lu m e , a n d th e d e a d s p a ce is th e
vo lu m e u p to th e ve rtica l d a s h e d lin e , w h ich m a ke s th e a re a s A a n d B e q u a l.
22 CHAPTER 2

quite at, and in patients with lung disease it may rise steeply. Expired volume
is also recorded.
T he dead space is ound by plotting N 2 concentration against expired
volume and drawing a vertical line such that area A is equal to area B in
Figure 2.6B. T he dead space is the volume expired up to the vertical line. In
e ect, this method measures the volume o the conducting airways down to
the midpoint o the transition rom dead space to alveolar gas.

PHYSIOLOGIC DEAD SPACE

Another way o measuring dead space is Bohr’s method. Figure 2.5 shows that all
the expired CO 2 comes rom the alveolar gas and none rom the dead space.
T here ore, we can write
V T ⋅ FE CO 2 = VA ⋅ FAC O 2
N ow,
VT = VA + VD
T here ore,
VA = VT − VD
Substituting
VT ⋅ FE CO 2 = ( VT − VD ) ⋅ FAC O 2
W hence

VD PAC O 2 − PE C O 2
= (Bohr equation)
VT PAC O
2

where A and E re er to alveolar and mixed expired, respectively (see Appendix

A). T he normal ratio o dead space to tidal volume is in the range o 0.2 to
0.35 during resting breathing. In normal subjects, the P c o 2 in alveolar gas and
that in arterial blood are virtually identical so that the equation is there ore
o ten written

VD PaC O 2 − PE C O 2
=
VT PaC O
2

It should be noted that the Fowler’s and Bohr’s methods measure some-
what di erent things. Fowler’s method measures the volume o the conduct-
ing airways down to the level where the rapid dilution o inspired gas occurs
with gas already in the lung. T his volume is determined by the geometry
 VENTILATION 23

o the rapidly expanding airways (Figure 1.5), and because it re ects the
morphology o the lung, it is called the anatomic dead space. Bohr’s method
measures the volume o the lung that does not eliminate CO 2. Because this is a
unctional measurement, the volume is called the physiologic dead space. In nor-
mal subjects, the volumes are very nearly the same. H owever, in patients with
lung disease, the physiologic dead space may be considerably larger because
o inequality o blood ow and ventilation within the lung (see Chapter 5).
T he size o the physiologic dead space is very important. T he larger it is, the
greater the total ventilation an individual must generate to ensure an adequate
amount o air enters the alveoli to participate in gas exchange.

Ve n t ila t io n

• To ta l ve n tila tio n is tid a l vo lu m e × re s p ira to ry re q u e n cy.

• Alve o la r ve n tila tio n is th e a m o u n t o re s h ga s g e ttin g to th e a lve o li,
o r (VT − VD) × n .
• An a to m ic d e a d s p a ce is th e vo lu m e o th e co n d u ctin g a irwa ys , a b o u t
150 m l.
• Phys io lo g ic d e a d s p a ce is th e vo lu m e o ga s th a t d o e s n o t e lim in a te
CO 2.
• Th e tw o d e a d s p a ce s a re a lm o s t th e s a m e in n o rm a l s u b je cts , b u t th e
p hys io lo g ic d e a d s p a ce is in cre a s e d in m a ny lu n g d is e a s e s .

REGIONAL DIFFERENCES IN VENTILATION

So ar, we have been assuming that all regions o the normal lung have the
same ventilation. H owever, it has been shown that the lower regions o the
lung ventilate better than do the upper zones. T his can be demonstrated i
a subject inhales radioactive xenon gas (Figure 2.7). W hen the xenon-133
enters the counting f eld, its radiation penetrates the chest wall and can be
recorded by a bank o counters or a radiation camera. In this way, the volume
o the inhaled xenon going to various regions can be determined.
Figure 2.7 shows the results obtained in a series o normal volunteers using
this method. It can be seen that ventilation per unit volume is greatest near the
bottom o the lung and becomes progressively smaller toward the top. O ther
measurements show that when the subject is in the supine position, this di er-
ence disappears, with the result that apical and basal ventilations become the
same. H owever, in that posture, the ventilation o the lowermost (posterior)
lung exceeds that o the uppermost (anterior) lung. Again, in the lateral position
(subject on his or her side), the dependent lung is best ventilated. T he cause o
these regional di erences in ventilation is dealt with in Chapter 7.
24 CHAPTER 2

133 Xe 100
Ra dia tion
counte rs

e
m
80

u
l
o
v
60

t
i
n
u
/
n
40

o
i
t
a
l
i
t
n
20

e
V
Lowe r Middle Uppe r
0 zone zone zone
Dis ta nce

F ig u r e 2 . 7 . Me a s u re m e n t o re g io n a l d i e re n ce s in ve n tila tio n w ith ra d io a ctive

xe n o n . Wh e n th e ga s is in h a le d , its ra d ia tio n ca n b e d e te cte d b y co u n te rs o u ts id e
th e ch e s t. No te th a t th e ve n tila tio n d e cre a s e s ro m th e lo w e r to u p p e r re g io n s o th e
u p rig h t lu n g .

KEY C O N CE P T S
1. Lung volumes that cannot be measured with a simple spirometer include
the total lung capacity, the unctional residual capacity, and the residual
volume. T hese can be determined by helium dilution or the body
plethysmograph.
2 . Alveolar ventilation is the volume o resh (non–dead space) gas entering
the respiratory zone per minute. It can be determined rom the alveolar
ventilation equation, that is, the CO 2 output divided by the ractional
concentration o CO 2 in the expired gas.
3 . T he concentration o C O 2 (and there ore its partial pressure) in
alveolar gas and arterial blood is inversely related to the alveolar
ventilation.
4 . T he anatomic dead space is the volume o the conducting airways and
can be measured rom the nitrogen concentration ollowing a single
inspiration o oxygen.
5 . T he physiologic dead space is the volume o lung that does not elimi-
nate CO 2. It is measured by Bohr’s method using arterial and expired
CO 2.
6 . T he lower regions o the lung are better ventilated than the upper
regions because o the e ects o gravity on the lung.
DIFFUSION
HO W G A S G ETS AC RO S S
T H E B LO O D - G A S B A R R IE R
• Laws of Diffusion
• Diffusion and Perfusion
Limitations
• Oxygen Uptake Along the
Pulmonary Capillary
• Measurement of Diffusing
Capacity
• Reaction Rates with
Hemoglobin
• Interpretation of Diffusing
Capacity for CO
• CO2 Transfer Across the
Pulmonary Capillary
28
3
W e now cons ide r how gas e s m ove acros s
the blood-gas barrie r by di us ion. Firs t, the
bas ic law s o di us ion are introduce d. Next, we
dis tinguis h be twe e n di us ion- and pe r us ion-
lim ite d gas e s . Oxyge n uptake along the
pulm onary capillary is the n analyze d, and the re
is a s e ction on the m e as ure m e nt o di us ing
capacity us ing carbon m onoxide . The f nite
re action rate o oxyge n w ith he m oglobin is
conve nie ntly cons ide re d w ith di us ion. Finally,
the re is a brie re e re nce to the inte rpre tation o
m e as ure m e nts o di us ing capacity and pos s ible
lim itations o carbon dioxide di us ion.
 DIFFUS ION 29

In the last chapter, we looked at how gas is moved rom the atmosphere to the
alveoli, or in the reverse direction. We now come to the trans er o gas across
the blood-gas barrier. T his process occurs by diffusion. Only 80 years ago, some
physiologists believed that the lung secreted oxygen into the capillaries, that is,
the oxygen was moved rom a region o lower to one o higher partial pressure.
Such a process was thought to occur in the swim bladder o sh, and it requires
energy. But more accurate measurements showed that this does not occur in the
lung and that all gases move across the alveolar wall by passive di usion.

LAWS OF DIFFUSION
D i usion through tissues is described by Fick’s law (Figure 3.1). T his states
that the rate o trans er o a gas through a sheet o tissue like a postage stamp
is proportional to the tissue area and the di erence in gas partial pressure
between the two sides, and inversely proportional to the tissue thickness.
As we have seen, the area o the blood-gas barrier in the lung is enormous
(50 to 100 square meters), and the thickness is only 0.3 µm in many places
(Figure 1.1), so the dimensions o the barrier are ideal or di usion. In addi-
tion, the rate o trans er is proportional to a di usion constant, which depends
on the properties o the tissue and the particular gas. T he constant is propor-
tional to the solubility o the gas and inversely proportional to the square root
o the molecular weight (Figure 3.1). T his means that CO 2 di uses about
20 times more rapidly than does O 2 through tissue sheets because it has a
much higher solubility but not a very di erent molecular weight.

P2 Vga s ∝ A . D . (P1 – P 2 )
T

S olubility
Are D∝
O2 a (A) Mol. Wt

P1

CO 2
Thickne s s (T)

F ig u r e 3 . 1 . Diffu s io n th ro u g h a tis s u e s h e e t. Th e a m o u n t o f ga s tra n s fe rre d is

p ro p o rtio n a l to th e a re a (A), a d iffu s io n co n s ta n t (D), a n d th e d iffe re n ce in p a rtia l
p re s s u re (P1 − P2), a n d is inve rs e ly p ro p o rtio n a l to th e th ickn e s s (T). Th e co n s ta n t
is p ro p o rtio n a l to th e ga s s o lu b ility b u t inve rs e ly p ro p o rtio n a l to th e s q u a re ro o t o f
its m o le cu la r w e ig h t. As a re s u lt, ca rb o n d ioxid e d iffu s e s m o re ra p id ly th a n d o e s
oxyg e n .
30 CHAPTER 3

F ic k ’s La w o f D if f u s io n

• Th e ra te o f d iffu s io n o f a ga s th ro u g h a tis s u e s lice is p ro p o rtio n a l to

th e a re a b u t inve rs e ly p ro p o rtio n a l to th e th ickn e s s .
• Diffu s io n ra te is p ro p o rtio n a l to th e p a rtia l p re s s u re d iffe re n ce .
• Diffu s io n ra te is p ro p o rtio n a l to th e s o lu b ility o f th e ga s in th e tis s u e
b u t inve rs e ly p ro p o rtio n a l to th e s q u a re ro o t o f th e m o le cu la r w e ig h t.

DIFFUSION AND PERFUSION LIMITATIONS

Suppose a red blood cell enters a pulmonary capillary o an alveolus that
contains a oreign gas such as carbon monoxide or nitrous oxide. H ow
rapidly will the partial pressure in the blood rise? Figure 3.2 shows the time
courses as the red blood cell moves through the capillary, a process that takes
about 0.75 s. Look rst at carbon monoxide. W hen the red cell enters the

S ta rt of End of
ca pilla ry ca pilla ry

Alve ola r
N2 O
O 2 (Norma l)
e
r
O 2 (Abnorma l)
u
s
s
e
r
p
l
a
i
t
r
a
P
CO

0 0.25 0.50 0.75

Time in ca pilla ry (s )

F ig u r e 3 . 2 . Up ta ke of ca rb o n m o n oxid e , n itro u s oxid e , a n d O 2 a lo n g th e p u lm o n a ry

ca p illa ry. No te th a t th e b lo o d p a rtia l p re s s u re o f n itro u s oxid e virtu a lly re a che s th a t
o f a lve o la r ga s ve ry e a rly in th e ca p illa ry, s o th e tra n s fe r o f th is ga s is p e rfu s io n
lim ite d . By co n tra s t, th e p a rtia l p re s s u re o f ca rb o n m o n oxid e in th e b lo o d is a lm o s t
u n ch a n g e d , s o its tra n s fe r is d iffu s io n lim ite d . O 2 tra n s fe r ca n b e p e rfu s io n lim ite d o r
pa rtly d iffu s ion lim ite d , d e p e n d in g o n th e co n d itio n s .
 DIFFUS ION 31

capillary, carbon monoxide moves rapidly across the extremely thin blood-gas
barrier rom the alveolar gas into the cell. As a result, the content o carbon
monoxide in the cell rises. H owever, because o the tight bond that orms
between carbon monoxide and hemoglobin within the cell, a large amount o
carbon monoxide can be taken up by the cell with almost no increase in partial
pressure. T hus, as the cell moves through the capillary, the carbon monoxide
partial pressure in the blood hardly changes, so that no appreciable back pres-
sure develops, and the gas continues to move rapidly across the alveolar wall.
It is clear, there ore, that the amount o carbon monoxide that gets into the
blood is limited by the di usion properties o the blood-gas barrier and not
by the amount o blood available.* T he trans er o carbon monoxide is there-
ore said to be diffusion limited.
Contrast the time course o nitrous oxide. W hen this gas moves across
the alveolar wall into the blood, no combination with hemoglobin takes
place. As a result, the blood has nothing like the avidity or nitrous oxide that
it has or carbon monoxide, and the partial pressure rises rapidly. Indeed,
Figure 3.2 shows that the partial pressure o nitrous oxide in the blood has
virtually reached that o the alveolar gas by the time the red cell is only one-
tenth o the way along the capillary. A ter this point, almost no nitrous oxide
is trans erred. T hus, the amount o this gas taken up by the blood depends
entirely on the amount o available blood f ow and not at all on the di usion
properties o the blood-gas barrier. T he trans er o nitrous oxide is there ore
perfusion limited.
W hat o O 2? Its time course lies between those o carbon monoxide and
nitrous oxide. O 2 combines with hemoglobin (unlike nitrous oxide) but with
nothing like the avidity o carbon monoxide. In other words, the rise in partial
pressure when O 2 enters a red blood cell is much greater than is the case or
the same number o molecules o carbon monoxide. Figure 3.2 shows that
the P o 2 o the red blood cell as it enters the capillary is already about our-
tenths o the alveolar value because o the O 2 in mixed venous blood. U nder
typical resting conditions, the capillary P o 2 virtually reaches that o alveolar
gas when the red cell is about one-third o the way along the capillary. U nder
these conditions, O 2 trans er is per usion limited like nitrous oxide. H owever,
in some abnormal circumstances when the di usion properties o the lung
are impaired, or example, because o thickening o the blood-gas barrier, the
blood P o 2 does not reach the alveolar value by the end o the capillary, and
now there is some di usion limitation as well.
A more detailed analysis shows that whether a gas is di usion limited or
not depends essentially on its solubility in the blood-gas barrier compared
with its “solubility” in blood (actually the slope o the dissociation curve; see
Chapter 6). For a gas like carbon monoxide, these are very di erent, whereas

*T his introductory description o carbon monoxide trans er is not completely accurate because
o the rate o reaction o carbon monoxide with hemoglobin (see later).
32 CHAPTER 3

or a gas like nitrous oxide, they are the same. An analogy is the rate at which
sheep can enter a eld through a gate. I the gate is narrow but the eld is
large, the number o sheep that can enter in a given time is limited by the size
o the gate. H owever, i both the gate and the eld are small (or both are big),
the number o sheep is limited by the size o the eld.

OXYGEN UPTAKE ALONG THE PULMONARY

CAPILLARY
Let us take a closer look at the uptake o O 2 by blood as it moves through a
pulmonary capillary. Figure 3.3A shows that the P o 2 in a red blood cell
entering the capillary is normally about 40 mm H g. Across the blood-gas bar-
rier, only 0.3 µm away, is the alveolar P o 2 o 100 mm H g. O xygen f oods down

A
Alve ola r
100

Norma l

Abnorma l
g
H
m
50
m
Gros s ly a bnorma l
2
o
P
Exe rcis e

0
0 0.25 0.50 0.75

F ig u r e 3 . 3 . Oxyg e n tim e
B Alve ola r
co u rs e s in th e pu lm o n a ry
50 ca p illa ry w h e n d iffu s io n is
n o rm a l a n d a b n o rm a l (e .g .,
Norma l
Abnorma l b e ca u s e o f th icke n in g o f th e
g
H
b lo o d -ga s b a rrie r b y d is e a s e ).
m
A s ho w s tim e co u rs e s w he n th e
m
Gros s ly a bnorma l a lve o la r Po 2 is n o rm a l. B s h o w s
2
o
s lo w e r oxyge na tio n w h e n th e
P
Exe rcis e
a lve o la r Po 2 is a b n o rm a lly lo w.
0
0 0.25 0.50 0.75 No te th a t in b o th ca s e s , s e ve re
e xe rcis e re d u ce s th e tim e
Time in ca pilla ry (s ) a va ila b le fo r oxyg e n a tio n .
 DIFFUS ION 33

this large pressure gradient, and the P o 2 in the red cell rapidly rises; indeed,
as we have seen, it very nearly reaches the P o 2 o alveolar gas by the time the
red cell is only one-third o its way along the capillary. T hus, under normal
circumstances, the di erence in P o 2 between alveolar gas and end-capillary
blood is immeasurably small—a mere raction o an mm H g. In other words,
the di usion reserves o the normal lung are enormous.
W ith severe exercise, the pulmonary blood f ow is greatly increased, and
the time normally spent by the red cell in the capillary, about 0.75 s, may be
reduced to as little as one-third o this. T here ore, the time available or oxy-
genation is less, but in normal subjects breathing air, there is generally still
no measurable all in end-capillary P o 2. H owever, i the blood-gas barrier is
markedly thickened by disease so that oxygen di usion is impeded, the rate
o rise o P o 2 in the red blood cells is correspondingly slow, and the P o 2 may
not reach that o alveolar gas be ore the time available or oxygenation in the
capillary has run out. In this case, a measurable di erence between alveolar
gas and end-capillary blood or P o 2 may occur.
Another way o stressing the di usion properties o the lung is to lower
the alveolar P o 2 (Figure 3.3B). Suppose that this has been reduced to
50 mm H g, by the subject either going to high altitude or inhaling a low
O 2 mixture. N ow, although the P o 2 in the red cell at the start o the capil-
lary may only be about 20 mm H g, the partial pressure di erence respon-
sible or driving the O 2 across the blood-gas barrier has been reduced rom
60 mm H g (Figure 3.3A) to only 30 mm H g. O 2 there ore moves across
more slowly. In addition, the rate o rise o P o 2 or a given increase in O 2
concentration in the blood is less than it was because o the steep slope o
the O 2 dissociation curve when the P o 2 is low (see Chapter 6). For both o
these reasons, there ore, the rise in P o 2 along the capillary is relatively slow,
and ailure to reach the alveolar P o 2 is more likely. T hus, severe exercise at
very high altitude is one o the ew situations in which di usion impairment
o O 2 trans er in normal subjects can be convincingly demonstrated. By the
same token, patients with a thickened blood-gas barrier will be most likely to
show evidence o di usion impairment i they breathe a low oxygen mixture,
especially i they exercise as well.

D if f u s io n o f O x y g e n A c r o s s t h e B lo o d -G a s B a r r ie r

• Blo o d s p e n d s o n ly a b o u t 0.75 s in th e ca p illa ry a t re s t.

• At re s t, th e Po 2 o f th e b lo o d virtu a lly re a ch e s th a t o f th e a lve o la r ga s
a fte r a b o u t o n e -th ird o f its tim e in th e ca p illa ry.
• On e xe rcis e , th e tim e is re d u ce d to p e rh a p s 0.25 s .
• Th e d iffu s io n p ro ce s s is ch a lle n g e d b y e xe rcis e , a lve o la r hyp oxia ,
a n d th icke n in g o f th e b lo o d -ga s b a rrie r.
34 CHAPTER 3

MEASUREMENT OF DIFFUSING CAPACITY

We have seen that oxygen trans er into the pulmonary capillary is normally lim-
ited by the amount o blood f ow available, although under some circumstances
di usion limitation also occurs (Figure 3.2). By contrast, the trans er o carbon
monoxide is limited solely by di usion, and it is there ore the gas o choice or
measuring the di usion properties o the lung. At one time O 2 was employed
under hypoxic conditions (Figure 3.3B), but this technique is no longer used.
T he laws o di usion (Figure 3.1) state that the amount o gas trans erred
across a sheet o tissue is proportional to the area, a di usion constant, and the
di erence in partial pressure, and inversely proportional to the thickness, or

& = A ⋅ D ⋅ (P P )
Vgas 1 2
T
N ow, or a complex structure like the blood-gas barrier o the lung, it is not
possible to measure the area and thickness during li e. Instead, the equation
is rewritten as
& = D ⋅ (P P )
V gas L 1 2

where D L is called the diffusing capacity of the lung and includes the area, thick-
ness, and di usion properties o the sheet and the gas concerned. T hus, the
di using capacity or carbon monoxide is given by
V&C O
DL =
P1 − P2
where P 1 and P 2 are the partial pressures o alveolar gas and capillary blood,
respectively. But as we have seen (Figure 3.2), the partial pressure o carbon mon-
oxide in capillary blood is extremely small and can generally be neglected. T hus,
&CO
V
DL =
PACO
or, in words, the di using capacity o the lung or carbon monoxide is the
volume o carbon monoxide trans erred in milliliters per minute per mm H g
o alveolar partial pressure.
A requently used test is the single-breath method, in which a single inspira-
tion o a dilute mixture o carbon monoxide is made and the rate o disappear-
ance o carbon monoxide rom the alveolar gas during a 10-s breath-hold is
calculated. T his is usually done by measuring the inspired and expired concen-
trations o carbon monoxide with an in rared analyzer. T he alveolar concen-
tration o carbon monoxide is not constant during the breath-holding period,
but allowance can be made or that. H elium is also added to the inspired gas
to give a measurement o lung volume by dilution.
 DIFFUS ION 35

T he normal value o the di using capacity or carbon monoxide at rest is

about 25 ml·min −1·mm H g−1, and it increases to two or three times this value
on exercise because o recruitment and distension o pulmonary capillaries
(see Chapter 4).

M e a s u r e m e n t o f D if f u s in g C a p a c it y

• Ca rb o n m o n oxid e is u s e d b e ca u s e th e u p ta ke o f th is ga s is d iffu s io n
lim ite d .
• No rm a l d iffu s in g ca p a city is a b o u t 25 m l·m in −1 ·m m Hg −1.
• Diffu s in g ca p a city in cre a s e s o n e xe rcis e .

REACTION RATES WITH HEMOGLOBIN

So ar we have assumed that all the resistance to the movement o O 2 and CO
resides in the barrier between blood and gas. H owever, Figure 1.1 shows that
the path length rom the alveolar wall to the center o a red blood cell exceeds
that in the wall itsel , so that some o the di usion resistance is located within
the capillary. In addition, there is another type o resistance to gas trans er
that is most conveniently discussed with di usion, that is, the resistance
caused by the nite rate o reaction o O 2 or CO with hemoglobin inside the
red blood cell.
W hen O 2 (or CO ) is added to blood, its combination with hemoglobin is
quite ast, being well on the way to completion in 0.2 s. H owever, oxygen-
ation occurs so rapidly in the pulmonary capillary (Figure 3.3) that even this
rapid reaction signi cantly delays the loading o O 2 by the red cell. T hus, the
uptake o O 2 (or CO ) can be regarded as occurring in two stages: (1) di u-
sion o O 2 through the blood-gas barrier (including the plasma and red cell
interior) and (2) reaction o the O 2 with hemoglobin (Figure 3.4). In act, it
is possible to sum the two resultant resistances to produce an overall “di u-
sion” resistance.
We saw that the di using capacity o the lung is de ned as
DL = V & / (P − P ) that is, as the f ow o gas divided by a pressure di erence.
gas 1 2
T hus, the inverse o D L is pressure di erence divided by f ow and is there-
ore analogous to electrical resistance. Consequently, the resistance o the
blood-gas barrier in Figure 3.4 is shown as 1/D M , where M means membrane.
N ow, the rate o reaction o O 2 (or CO ) with hemoglobin can be described
by θ, which gives the rate in milliliters per minute o O 2 (or CO ) that com-
bine with 1 ml o blood per mm H g partial pressure o O 2 (or CO ). T his is
analogous to the “di using capacity” o 1 ml o blood and, when multiplied
36 CHAPTER 3

Alve ola r
wa ll
Re d ce ll

Alve olus
O2 O 2 + Hb → HbO 2
DM θ • Vc
F ig u r e 3 . 4 . Th e d iffu s in g ca p a city
o f th e lu n g (DL) is m a d e u p o f tw o
co m p o n e n ts : th a t d u e to th e d iffu s io n
p ro ce s s its e lf a n d th a t a ttrib u ta b le to
1 1 1 th e tim e ta ke n fo r O 2 (o r CO) to re a ct
= +
DL DM θ • Vc w ith h e m o g lo b in .

by the volume o capillary blood (Vc), gives the e ective “di using capacity”
o the rate o reaction o O 2 with hemoglobin. Again its inverse, 1/(θ·Vc),
describes the resistance o this reaction. We can add the resistances o ered
by the membrane and the blood to obtain the total di usion resistance. T hus,
the complete equation is
1 1 1
= +
D L D M θ ⋅ Vc
In practice, the resistances o ered by the membrane and blood compo-
nents are approximately equal, so that a reduction o capillary blood volume
by disease can reduce the measured di using capacity o the lung. θ or CO
is reduced i a subject breathes a high O 2 mixture, because the O 2 competes
with the CO or hemoglobin. As a result, the measured di using capacity is
reduced by O 2 breathing. In act, it is possible to separately determine D M
and Vc by measuring the di using capacity or CO at di erent alveolar P o 2
values.

R e a c t io n R a t e s o f O 2 a n d C O w it h H e m o g lo b in

• Th e re a ctio n ra te o f O 2 is fa s t, b u t b e ca u s e s o little tim e is a va ila b le in

th e ca p illa ry, th is ra te ca n b e co m e a lim itin g fa cto r.
• Th e re s is ta n ce to th e u p ta ke o f O 2 a ttrib u ta b le to re a ctio n ra te is p ro b -
a b ly a b o u t th e s a m e a s th a t d u e to d iffu s io n a cro s s th e b lo o d -ga s
b a rrie r.
• Th e re a ctio n ra te o f CO ca n b e a lte re d b y ch a n g in g th e a lve o la r P o 2 .
In th is wa y, th e s e p a ra te co n trib u tio n s o f th e d iffu s io n p ro p e rtie s
o f th e b lo o d -ga s b a rrie r a n d th e vo lu m e o f ca p illa ry b lo o d ca n b e
d e rive d .
 DIFFUS ION 37

INTERPRETATION OF DIFFUSING CAPACITY

FOR CO
It is clear that the measured di using capacity o the lung or CO depends not
only on the area and thickness o the blood-gas barrier but also on the volume
o blood in the pulmonary capillaries. Furthermore, in the diseased lung, the
measurement is a ected by the distribution o di usion properties, alveo-
lar volume, and capillary blood. For these reasons, the term transfer factor is
sometimes used (particularly in Europe) to emphasize that the measurement
does not solely ref ect the di usion properties o the lung.

CO2 TRANSFER ACROSS THE PULMONARY

CAPILLARY
We have seen that di usion o CO 2 through tissue is about 20 times aster
than that o O 2 because o the much higher solubility o CO 2 (Figure 3.1). At
rst sight, there ore, it seems unlikely that CO 2 elimination could be a ected
by di usion di culties, and indeed, this has been the general belie . H owever,
the reaction o CO 2 with blood is complex (see Chapter 6), and although
there is some uncertainty about the rates o the various reactions, it is possible
that a di erence between end-capillary blood and alveolar gas can develop i
the blood-gas barrier is diseased.

KEY C O N CE P T S
1. Fick’s law states that the rate o di usion o a gas through a tissue sheet
is proportional to the area o the sheet and the partial pressure di erence
across it, and inversely proportional to the thickness o the sheet.
2 . Examples o di usion- and per usion-limited gases are carbon monoxide
and nitrous oxide, respectively. O xygen trans er is normally per usion
limited, but some di usion limitation may occur under some condi-
tions, including intense exercise, thickening o the blood-gas barrier, and
alveolar hypoxia.
3 . T he di using capacity o the lung is measured using inhaled carbon
monoxide. T he value increases markedly on exercise.
4 . T he nite reaction rate o oxygen with hemoglobin can reduce its trans-
er rate into the blood, and the e ect is similar to that o reducing the
di usion rate.
5 . Carbon dioxide trans er across the blood-gas barrier is probably not di -
usion limited.
 BAB 1
STRUKTUR DAN FUNGSI

Paru berfungsi sebagai pertukaran gas. Fungsi utamanya adalah memasukan oksigen dari
udara ke dalam darah vena dan mengeluarkan karbondioksida. Fungsi paru yang lain adalah
memfiltrasi benda toksik dari sirkulasi, memetabolisme beberapa senyawa dan sebagai
reservoir darah.

SAWAR GAS DARAH

Perpindahan oksigen dan karbondioksida antara udara dan darah terjadi secara difusi dengan
pergerakannya dari daerah dengan tekanan parsial yang tinggi ke rendah. Hukum difusi
Fick’s menyatakan bahwa jumlah gas yang melintasi jaringan adalah berbanding lurus
dengan luas daerahnya tapi berbanding terbalik dengan ketebalannya. Sawar gas darah sangat
tipis dengan luas 50 – 100 m2, oleh karena itu berfungsi dengan baik sebagai pertukaran
gas.Terdapat Sekitar 500 juta kantong udara yang disebut alveoli pada paru, setiap alveoli
mempunyai diameter 1/3 mm dan dibungkus oleh kapiler. Jika dibentangkan total permukaan
daerah tersebut mencapai 85 m2 tetapi volumenya hanya 4 liter. Satu potongan volume ini
hanya memiliki luas permukaan internal 1/100 m2.Oleh karena itu paru memiliki daerah
difusi yang luas. Komponen proses difusi terdiri atas udara yang masuk melalui saluran
pernapasan ke tempat pertukaran gas dan darah yang berada pada pembuluh darah.

SALURAN NAPAS DAN ALIRAN UDARA

Saluran napas merupakan serangkaian tabung bercabang yang ketika berpenetrasi jauh lebih
dalam kedalam paru akan semakin sempit, memendek dan bercabang lebih banyak. Trakea
bercabang menjadi bronkus utama kanan dan kiri lalu bercabang menjadi bronkus lobaris,
kemudian bronkus segmental. Proses ini berlanjut kebawah sampai bronkiolus terminal yang
merupakan saluran napas terkecil tanpa alveoli. Semua bronkus ini merupakan zona konduksi.
Fungsinya sebagai saluran perantara udara inspirasi ketempat pertukaran gas di paru.Saluran
napas proksimal yang lebih besar mempunyai banyak tulang rawan di dindingnya. Ketika saluran
napas menuju ke arah distal, proporsi tulang rawan menurun dan otot polos meningkat sehingga
saluran napas distal yang sangat kecil tersusun sebagian besar oleh otot polos. Karena saluran
napas pada zona konduksi tidak mengandung alveoli dan tidak ada struktur yang ikut serta dalam
pertukaran gas, maka saluran tersebut disebut ruang rugi anatomiyaitu area paru yang menerima
ventilasi tetapi tidak ada aliran darah dengan volume sekitar 150 ml.

Bronkiolus terminal bercabang menjadi bronkiolus respiratori yang mulai memiliki alveoli pada
dindingnya. Daerah alveoli ini merupakan tempat terjadi pertukaran gas, dan dikenal sebagai zona
respirasi. Bagian distal paru sampai bronkiolus terminal dikenal sebagai lobulus primer atau
asinus. Jarak dari bronkiolus terminal sampai ujung distal alveoli hanya beberapa milimeter,
namun zona respirasi menempati sebagian besar paru, volumenya sekitar 2,5 hingga 3 liter saat
istirahat.

1
Gambar 1.1 Mikrograf elektron memperlihatkan kapiler pulmoner (C) pada dinding alveolar.
Sawar gas darah tipis sekali kurang dari 0,5 mikron. Panah menunjukan jalan difusi dari gas
alveolar yang masuk kedalam eritrosit (EC) dan lapisan surfaktan (tidak terlihat pada preparat
ini), epitel alveolar (EP), interstitium (IN) endotel kapiler (EN) dan plasma. Bagian struktur
sel dinamakan fibroblast (FB), membran basal (BM) dan juga terlihat nukleus sel endotel.

Gambar 1.2 Potongan paru yang menunjukkan beberapa alveoli dan bronkiolus kecil. Kapiler
pulmoner melintasi dinding alveoli (gambar 1.1). Lubang pada dinding alveoli adalah pori
pori dari Kohn (Scan mikrograf elektron oleh Nowell, J.A dan W.S Tyler)

2
Gambar 1.3 Saluran napas pada manusia,mulai dari trakea hingga bronkiolud terminalis

Gambar 1.4 saluran napas pada manusia menurut Wiebel. 16 percabangan pertama (Z)
membentuk zona konduksi dan 7 sisanya merupakan zona respirasi.

Gambar 1.5. Diagram ini menunjukan peningkatan total area cross sectional saluran napas
pada zona respirasi.kecepatan gas saat inspirasi menjadi semakin kecil pada daerah
bronkiolus respirasi,dimana difusi gas merupakan proses yang terpenting

Selama inspirasi, volume rongga dada meningkat dan udara masuk kedalam paru.
Peningkatan volume rongga dada terjadi akibat kontraksi dari muskulus interkostal sehingga
iga tertarik kedepan,diafragma turun kebawah kemudian meningkatkan luas penampang

3
 dada,udara inspirasi yang mengalir kedalam saluran napas menuju bronkiolus terminalis
sifat aliran udaranya yang cepat, namun kecepatan gas yang diteruskan menjadi berkurang
saat beralih ke zona respirasi.Laju difusi molekul gas dalam saluran napas terjadi cepat dan
jarak yang ditempuh singkat. Namun, karena kecepatan gas meningkat pesat di daerah
bronkiolus terminal, debu yang terhirup sering kali mengendap. Paru bersifat elastis dan
pengembangannya .tekanan pengembangan kurang dari 3 Cm H20 membutuhkan tekanan
300 cm H2O untuk perubahan volume yang sama. Tekanan untuk menggerakkan udara ke
saluran napas juga sedikit sekali. Selama inspirasi normal,laju aliran udara 1 liter /detik
membutuhkan tekanan kurang dari 2 cmH20

PEMBULUH DARAH DAN ALIRANNYA

Pembuluh darah paru juga membentuk serangkaian tabung bercabang dari arteri pulmonalis
ke kapiler dan kembali ke vena pulmonalis. Pada awalnya, arteri, vena, dan bronkus berjalan
berdekatan, vena bergerak menjauh melewati antara lobulus, sedangkan arteri dan bronkus
berjalan bersama-sama. Kapiler membentuk jaringan di dinding alveoli (Gambar 1.6).
Gambar 1.7 merupakan penampang mikroskopis tipis yang menunjukkan sel darah merah
didalam kapiler dan yang akan berinteraksi dengan gas alveolar ,dengan pembatas.
Sangat tipisnya penghalang gas darah berarti kapiler akan mudah rusak. Sehingga akan,
meningkatkan tekanan di kapiler ke tingkat yang tinggi atau menggembungkan paru ke
volume yang tinggi, misalnya, dapat meningkatkan tekanan dinding kapiler ke titik di mana
perubahan ultrastruktural dapat terjadi. Kapiler kemudian mengeluarkan plasma dan bahkan
sel darah merah ke dalam ruang alveolar. Arteri pulmonalis menerima seluruh darah
keluaran jantung kanan, namun resistensi sirkuit paru sangat kecil. Pada paru yang parah
tekanan arteri hanya diperlukan sekitar 20 cm H20 (sekitar 15 mm Hg), untuk aliran oksigen
6 liter·mnt−1 (aliran yang sama melalui sedotan soda membutuhkan 120 cm H20).

Gambar 1.6 Gambaran dinding alveolar (pada katak) yang menunjukkan jaringan kapiler yang
padat. Arteri kecil (kiri) dan vena (kanan) juga dapat dilihat. Segmen kapiler berukuran sangat
pendek saling bersambungan yang dibentuk oleh darah.

4
Gambar 1.7 Bagian mikroskopis paru anjing menunjukkan kapiler di dinding alveolar.
Penghalang darah-gas sangat tipis sehingga tidak dapat diidentifikasi di sini (bandingkan
Gambar 1.1).
Setiap sel darah merah menghabiskan sekitar 0,75 detik di jaringan kapiler dan melintasi dua
atau tiga alveoli. Efisiensi waktu pada pertukaran gas sangatlah penting,dimana waktu yang
singkat dapat menjaga keseimbangan oksigen dan karbondioksida pada alveolus dan kapiler.

Paru mempunyai sistem peredaran darah tambahan, yaitu peredaran bronkial yang menyuplai
saluran pernafasan sampai ke bronkiolus terminal. Sebagian darah ini dibawa keluar dari paru
melalui vena pulmonalis, dan sebagian lagi memasuki sirkulasi sistemik. Aliran yang melalui
sirkulasi bronkial hanyalah sebagian kecil yang melalui sirkulasi paru masih dengan baik tanpa
sirkulasi ini.

STABILITAS ALVEOLI

Paru dapat dianggap sebagai kumpulan 500 juta gelembung, masing-masing berukuran diameter
0,3 mm. Struktur seperti ini pada dasarnya tidak stabil. Adanya tegangan permukaan cairan yang
melapisi alveoli, timbul gaya yang relatif besar yang cenderung menghancurkan alveoli.
Untungnya, beberapa sel yang melapisi alveoli mengeluarkan bahan yang disebut surfaktan
yang secara drastis menurunkan tegangan permukaan lapisan lapisan alveolar (lihat Bab 7).

ELIMINASI PARTIKEL YANG TERHIRUP

Dengan luas permukaan 50 hingga 100 meter persegi, paru merupakan permukaan tubuh yang
paling luas. Berbagai mekanisme untuk mengatasi partikel yang terinhalasi telah dikembangkan.
Partikel-partikel berukuran lebih kecil yang mengendap di dalam saluran napas dibersihkan oleh
mukus yang terus menerus menggerakkan partikel tersebut hingga ke epiglotis dan akan ditelan.
Mukus yang disekresikan oleh kelenjar mukosa dan sel goblet di dinding bronkus didorong oleh
jutaan silia kecil yang bergerak secara berirama pada kondisi normal.Namun dapat dilumpuhkan
oleh partikel racun yang terhirup. Alveoli tidak memiliki silia dan partikel yang mengendap
disana akan ditelan oleh makrofag. Benda asing tersebut kemudian dikeluarkan dari paru
melalui sistem limfatik atau aliran darah. Sel darah seperti leukosit juga berperan dalam reaksi
pertahanan terhadap bahan asing.

5
 BAB 2
VENTILASI : BAGAIMANA UDARA MENCAPAI ALVEOLI

Gambar 2.1 Diagram paru menunjukkan volume dan aliran udara. Terdapat variasi yang cukup
besar pada komponen ini tergantung pada ukuran dan jenis kelamin pasien.

1. VOLUME PARU

Gambar 2.2 Volume Paru.Pada spirometri, selama ekspirasi bell akan naik dan pen akan
turun yang t e r l i h a t p a d a p e r g e r a k a n g r a f i k .

Dari gambar 2-2, dapat dilihat 4 volume dan/atau kapasitas paru:

1. Volume Tidal (Tidal Volume) : Pernapasan normal
2. Volume yang terekspirasi disebut sebagai Kapasitas Vital (Vital Capacity) :
Inspirasi maksimal dan dilanjutkan oleh ekspirasi maksimal
3. Volume Residu (Residual Volume) : Sejumlah udara masih tersisa di paru setelah
ekspirasi maksimal.
4. Kapasitas Residu Fungsional (Functional Residual Capacity) : Volume udara
yang tersisa di paru setelah ekspirasi normal.
Volume Residu dan Kapasitas Residu Fungsional tidak dapat diukur dengan pemeriksaan
spirometri sederhana, tetapi dapat diukur dengan menggunakan teknik dilusi gas atau
body plethysmograph.

6
a. Teknik Dilusi Gas

Pada teknik dilusi gas, pasien dihubungkan ke spirometri berisi gas Helium (insoluble di
dalam darah). Setelah beberapa kali proses pernapasan, konsentrasi Helium di dalam
spirometri dan paru mencapai nilai yang sama.

Gambar 2.3 Pengukuran Kapasitas Residu Fungsional dengan Teknik Dilusi Helium

Tidak ada Helium yang hilang, sebelum equilibration, jumlah Helium = C1 x V1

Sesudah equilibration, jumlah Helium = C2 x (V1 + V2)

Jumlah Helium pada kedua keadaan diatas sama besar, jadi:

C1 x V1 = C2 x (V1 + V2)
C1 V1 = C2 V1 + C2 V2
C2 V2 = C1 V1 - C2 V1
= V1 (C1 - C2)
V2 = V1 (C1 - C2)
C2

C1 = Konsentrasi gas helium sebelum masuk pernapasan

V1 = Volume gas helium sebelum masuk pernapasan
C2 = Konsentrasi gas helium sisa setelah masuk pernapasan
V2 = Volume gas helium yang masuk toraks

b. Pletismografi Tubuh (Body Plethysmograph)

Pletismografi tubuh (body plethysmograph) adalah teknik lain yang dapat mengukur
Kapasitas Residu Fungsional (KRF).
 Pada pletismografi tubuh, subjek duduk di kotak kedap udara (serupa dengan kotak
telepon umum).
7
  Di akhir ekspirasi normal, shutter akan menutup mouthpiece dan pasien melakukan
usaha pernapasan.
 Subjek melakukan inhalasi, dan akan terjadi ekspansi udara di dalam paru. Volume
dalam paru akan meningkat dan secara bersamaan, tekanan dalam kotak meningkat
karena volume gas dalam kotak menurun.

Hukum Boyle = Tekanan x Volume adalah konstan (dalam suhu yang konstan)
P1 x V1 = P2 (V1 - ∆ V)
P3 x V2 = P4 (V2 + ∆ V)

P1 = Tekanan dalam kotak sebelum inspirasi

P2 = Tekanan dalam kotak sesudah inspirasi
V1 = Volume dalam kotak sebelum
inspirasi
∆V = Perubahan volume dalam kotak (atau paru)
P3 = Tekanan dalam mulut sebelum inspirasi
P4 = Tekanan dalam mulut sesudah inspirasi
V2 = Kapasitas Residu Fungsional (KRF)

Gambar 2.4 Pengukuran KRF dengan Pletismografi Tubuh. Saat subjek melakukan usaha
inspirasi pada jalan napas yang tertutup, subjek akan sedikit meningkatkan volume paru-nya,
tekanan jalan napas berkurang, dan tekanan dalam kotak akan meningkat. Dari Hukum
Boyle, akan didapatkan volume paru

2. VENTILASI

Ventilasi total adalah volume total udara yang keluar dari paru.
 500 ml (volume ekspirasi setiap napas) x 15 napas/ menit = 7.500 ml / menit
 Setiap 500 ml udara yang diekspirasi, 150 ml tetap berada di dalam Ruang Rugi
Anatomis

Ventilasi Alveolar adalah volume udara bebas yang masuk zona respirasi setiap menit
(jumlah udara inspirasi yang tersedia untuk pertukaran gas).
 (500 ml – 150 ml) x 15 napas / menit = 5.250 ml / menit
 Dapat meningkat dengan peningkatan Volume Tidal atau frekuensi pernapasan atau
keduanya.
Cara pengukuran Ventilasi Total :
 Pasien bernapas melalui kotak berkatup yang memisahkan udara inspirasi dengan udara
terekspirasi, dan mengumpulkan semua udara terekspirasi dalam suatu kantong.

8
 Cara pengukuran Ventilasi Alveolar :
 Dengan mengukur volume Ruang rugi anatomidan mengukur ruang rugi ventilation
(Volume x Frekuensi Napas), lalu dikurangi dari ventilasi total.
VT V T = VD + VA VT = Volume Tidal
.n = VD.n+VA.n VD = Dead space
VE = VD + VA VA = Ventilasi alveolar
V A = VE - VD F1 = Konsentrasi fraksi inspirasi
VE = Ventilasi total ekspirasi
FE = Konsentrasi fraksi ekspirasi

Gambar 2.5 Volume VA











9
3. RUANG RUGI ANATOMI

Ruang Rugi Anatomi adalah volume udara pada zona konduksi dengan nilai normal ± 150 ml.
 Ruang rugi anatomi akan meningkat dengan peningkatan inspirasi karena traksi /
tarikan pada bronkus oleh parenkim paru di sekitarnya.
 Ruang rugi anatomi tergantung dari ukuran dan postur pasien.
 Ruang rugi anatomi diukur dengan metode Fowler (menggunakan rapid N2 analyzer) :
— Subjek bernapas melalui kotak berkatup dengan sampling tube dari rapid N2
analyzer secara berkelanjutan melakukan sampling gas pada bibir.
— Dari inspirasi tunggal 100% O2 , konsentrasi N2 meningkat saat udara pada
ruang rugisemakin banyak tercuci atau terhapus oleh gas di alveoli.
— Pada akhirnya, konsentrasi gas yang hampir homogen dapat terlihat (pure
alveolar gas). Fase ini sering disebut fase Alveolar plateau, walaupun pada
subjek normal terlihat gambaran tidak terlalu datar (flat), dan pada pasien
penyakit paru dapat meningkat tajam.

Gambar 2.6 Metode Fowler mengukur Ruang rugi anatomi dengan Rapid N2 Analyzer.
(A) Memperlihatkan bahwa pada uji inspirasi O2 100%, konsentrasi N2 akan meningkat
selama ekspirasi menjadi tingkat mendekati pola “plateau” yang menggambarkan
udara murni.
(B) Memperlihatkan konsentrasi N2 dibandingkan dengan volume udara ekspirasi, dan
ruang rugia dalah volume yang mencapai garis lurus vertikal, sehingga area A dan
B bernilai sama besar.

10
4. RUANG RUGI FISIOLOGI

Cara lain untuk mengukur ruang rugi adalah dengan menggunakan metode Bohr.

Dari gambar 2.5, dapat dilihat bahwa semua CO2 ekspirasi berasal dari gas alveoli dan sama
sekali tidak berasal dari ruang rugi.

VT . FE = VA . FA
VT = V A + VD  VA = VT -
VDVT . FE = (VT - VD) . FA
= (VT . VA) - (VD . FA)
VD . FA = (VT . FA) - (VT . FE) = VT . (FA –
FE)VD = (FA – FE)
VT FA

Tekanan parsial gas  proporsional dengan konsentrasinya

VD = PACO2 – PECO2
(BOHR EQUATION)
VT PACO2

 Nilai rasio normal VD / VT = 0,2 – 0,35 selama pernapasan saat istirahat

 Pada pasien normal, PCO2 di alveoli dan darah arteri adalah identik, sehingga dapat ditulis :
VD = PaCO2 - PECO2

VT PaCO2
 Metode Bohr mengukur volume paru yang tidak mengeliminasi CO 2; karena
merupakan pengukuran fungsional, volume tersebut disebut Ruang Rugi
Fisiologis atau Physiologic Ruang rugi.
 Pada subjek normal, physiologic ruang rugidan anatomic ruang rugi
memiliki volume yang hampir sama.
 Pada pasien penyakit paru, physiologic ruang rugidapat bernilai lebih besar
karena perbedaan aliran darah dan ventilasi pada paru.
5. Perbedaan Regional pada Ventilasi

 Ventilasi paru di area lebih rendah / basal lebih baik dibandingkan dengan pada zona
bagian atas.
 Dapat diperiksa dengan pemeriksaan menggunakan inhalasi gas radioaktif Xenon :
— Xenon – 133 memasuki area pengukuran, radiasi Xenon akan menembus dinding
dada dan direkam oleh pengukur / kamera radiasi.
— Volume Xenon yang terinhalasi dan masuk ke dalam berbagai area dapat ditekan.
— Hasilnya: volume ventilasi per unit paling banyak di bagian yang mendekati basal
paru, dan semakin berkurang di zona bagian atas , Kecuali : pada posisi supine,
perbedaan hasil ini akan hilang dan ventilasi diapeks dan basal menjadi sama.
11
Gambar 2.7 Pengukuran perbedaan daerah dalam ruang ventilasi dengan radioaktif
Xenon. Saat gas dihirup, radiasinya dapat dideteksi oleh counter di luar dada. Perhatikan
bahwa ventilasi berkurang dari daerah bawah ke atas dalam posisi paru tegak.

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 BAB 3
DIFUSI

Difusi adalah proses perpindahan gas melintasi sawar darah-gas. Gas berpindah melintasi
sawar melalui mekanisme difusi pasif.

HUKUM DIFUSI

Difusi melintasi jaringan dideskripsikan dengan Fick’s Law (Hukum Fick). Ada tiga hal
utama pada Hukum Fick:
1. Kecepatan difusi gas melintasi jaringan sebanding dengan luas area difusi namun
berbanding terbalik dengan ketebalan jaringan yang harus dilintasi.
2. Kecepatan difusi berbanding lurus dengan perbedaan tekanan parsial.
Kecepatan difusi berbanding lurus dengan kelarutan gas pada jaringan namun
berbanding terballik dengan akar kuadrat berat molekul yang melintas

Gambar 3-1. Difusi melalui lembaran jaringan. Jumlah gas yang berpindah
berbanding lurus dengan area (A), konstanta difusi (D) dan perbedaan tekanan parsial (P1-
P2) dan berbanding terbalik dengan ketebalan (T). Konstanta berbanding lurus dengan
solubilitas gas (Sol) namun berbanding terbalik dengan akar kuadrat berat molekul (MW).

Area sawar darah-gas sangat luas (50-100 meter2) dan ketebalan sawar hanya 0,3 um,
sehingga dimensi sawar ini ideal untuk proses difusi gas. Kecepatan difusi juga berbanding
lurus dengan konstanta difusi, yang bergantung pada jaringan dan gas yang melintas.
Konstanta berbanding lurus dengan solubilitas gas dan berbanding terbalik dengan akar
kuadrat berat molekul.

Batasan Difusi Perfusi

Sel darah merah bergerak dalam kapiler dalam waktu 0,75 detik. Karbon monoksida
bergerak cepat melintasi sawar darah-gas dari alveolus ke dalam sel darah merah
sehingga kadar karbon monoksida dalam sel meningkat. Ikatan kuat antara karbon
monoksida dan hemoglobin dalam sel darah merah menyebabkan sejumlah besar karbon
monoksida dapat berpindah ke dalam sel darah merah tanpa mengubah tekanan
parsialnya.

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 Saat sel darah merah bergerak dalam kapiler, tekanan parsial karbon monoksida dalam
darah tidak mengalami perubahan sehingga tidak timbul tekanan balik yang berarti dan
gas tetap melintas dinding alveolus dengan cepat. Jumlah karbon monoksida yang masuk
ke pembuluh darah dibatasi oleh sawar darah-gas dan tidak dibatasi oleh jumlah darah
yang ada. Perpindahan karbon monoksida pun dikatakan terbatas difusi.

Ambilan Oksigen pada Kapiler Paru

PO2 normal sel darah merah yang memasuki kapiler 40 mmHg dan pada alveolus, PO2
alveolus 100 mmHg. Gradien konsentrasi di kedua sisi tersebut mengakibatkan oksigen
berpindah dan PO2 pada sel darah merah meningkat cepat, bahkan dapat menyerupai PO 2
alveolus walaupun baru sepertiga jalan di dalam kapiler. Hal ini menunjukkan bahwa
proses difusi oksigen pada paru normal sangat besar.

Gambar 3-2. Waktu oksigen dalam kapiler paru saat difusi berjalan normal dan
abnormal (penebalan sawar darah-gas saat sakit).
A. Waktu saat PO2 alveolus normal. B. Oksigenasi terjadi lebih lambat saat PO2 rendah.
Pada kedua keadaan, aktivitas fisis berat menurunkanwaktu oksigenasi.

Pada aktivitas fisik berat, aliran darah paru sangat meningkat dan kecepatan pergerakan
sel darah merah berkurang dari 0,75 detik menjadi sepertiganya. Peningkatan kecepatan
aliran ini menyebabkan waktu oksigenasi berkurang, namun pada subjek yang normal,
tidak ada penurunan yang berarti pada PO2 di akhir kapiler. Jika terjadi penebalan pada
sawar darah-gas karena suatu penyakit yang menyebabkan penebalan sawar, kecepatan
peningkatan PO2 di sel darah merah akan menurun dan PO2 darah tidak dapat mencapai
PO2 alveolus pada saat waktu oksigenasi di kapiler habis. Pada keadaan ini, dapat terjadi
perbedaan bermakna antara PO2 darah dan PO2 alveolus.

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Pada keadaan subjek berada pada ketinggian atau bernapas pada kadar O2 rendah, PO2
alveolar dapat menurun. PO2 sel darah merah di awal kapiler 20 mmHg, namun
perbedaan tekanan parsial yang dapat mengakibatan perpindahan O2 melewati sawar
darah-gas berkurang dari 60 mmHg menjadi 30 mmHg sehingga perpindahan menjadi
lebih lambat.
Selain itu, sesuai dengan kurva disosiasi O2, kecepatan peningkatan PO2 lebih rendah
karena kemiringan kurva disosiasi saat PO2 rendah. Kegiatan fisik berat pada ketinggian
adalah suatu contoh situasi gangguan transfer O2. Pasien dengan penebalan sawar darah-
gas juga akan menunjukkan gangguan difusi jika pasien bernapas dalam udara berkadar
oksigen rendah, terutama jika mereka melakukan aktivitas fisik.

Pengukuran Kapasitas Difusi

Transfer oksigen umumnya terbatas pada jumlah aliran darah, walapun pada keadaan
tertentuterdapat batasan dalam difusi. Sebaliknya, transfer karbon monoksida terbatas
hanya olehdifusi, sehingga karbon monoksida merupakan gas pilihan untuk mengukur
difusi pada paru. Hukum difusi menyatakan jumlah gas yang berpindah melalui lembaran
jaringan berbanding lurus dengan luas area, konstanta difusi dan perbedaan tekanan
parsial, serta berbandingterbalik dengan ketebalan, dengan rumus:

Pada struktur yang kompleks seperti sawar darah-gas pada paru, tidak mungkin
mengukur area dan ketebalan sepanjang masa hidup. Sehingga rumus dimodifikasi
sebagai berikut:

Pada rumus ini, DL adalah kapasitas difusi pada paru termasuk area, ketebalan dan difusi
pada lembaran jaringan dan gas tertentu. Kemudian, kapasitas difusi karbon monoksida
dihitung dengan:

Pada rumus tersebut, P1 dan P2 adalah tekanan parsial gas alveolus dan darah kapiler.
Namun tekanan parsial karbon monosida pada kapiler darah sangat kecil dan dapat
diabaikan. Sehingga rumus dimodifikasi sebagai berikut:

Atau dengan kata lain kapasitas difusi paru terhadap karbon monoksida adalah volume
karbon monoksida yang berpindah dalam milimeter per menit per mmHg dari tekanan
parsial alveolus.

15
Tes yang umum digunakan adalah single-breath method, satu kali inspirasi gas campuran
karbon monoksida kemudian dihitung kecepatan hilangnya karbon monoksida dalam
menahan napas 10 detik. Umumnya menggunakan infrared analyzer. Konsentrasi karbon
monoksida alveolar tidak konstan sepanjang menahan napas.

Helium juga ditambahkan pada gas inspirasi tersebut untuk membantu penghitungan
volume paru daridifusi.
Nilai normal kapasitas difusi karbon monoksida saat istirahat berkisar antara 25 ml-menit -1
mmHg-1 dan meningkat 2-3 kali lipat saat aktivitas fisis karena pengembangan kapiler paru.

Rasio Reaksi dengan Hemoglobin

Selain hambatan yang disebabkan oleh jarak antara dinding alveolar dengan pusat sel
darah merah, hambatan difusi lain dapat disebabkan oleh kecepatan reaksi O 2 atau CO
dengan hemoglobin dalam sel darah merah.
Saat O2 (atau CO) masuk ke dalam darah, kombinasi dengan hemoglobin cukup cepat
yaitu selesai dalam 0,2 detik. Namun, oksigenasi berlangsung cepat sekali pada kapiler
paru sehingga reaksi cepat ini pun dapat mengurangi kecepatan muat O2 dalam sel darah
merah. Ambilan O2 (atau CO) terbagi dalam dua tahap: (1) difusi O2 menembus sawar
darah-gas (termasuk plasma dan bagian dalam sel darah merah) dan (2) reaksi O 2 dengan
hemoglobin (gambar 3-4). Kedua hambatan ini dapat dijumlahkan untuk mendapat rata-
rata hambatan difusi.

Gambar 3-3. Kapasitas difusi paru (DL) tersusun dari dua komponen: proses difusi itu
sendiri dan waktu yang dibutuhkan oleh O2 (atau CO) untuk bereaksi dengan
hemoglobin.
Pada rumus di bawah ini, 1/DL adalah perbedaan tekanan dibagi aliran dan analog dengan
resisten elektris. Hambatan sawar darah-gas adalah 1/DM dengan M berarti membran.
Kecepatan reaksi O2 (atau CO) dengan hemoglobin dapat dideskripsikan sebagai θ, yaitu
kecepatan pada milimeter per menit O2 (atau CO2) yang dikombinasikan dengan 1 ml
darah per mmHg tekanan parsial O2 (atau CO). Hal ini analog dengan kapasitas difusi 1
ml darah dan jikadikalikan volume kapiler darah (VC), akan didapatan kapasitas difusi
kecepatan reaksi oksigen dengan hemoglobin. Selanjutnya 1/(θ.Vc) menggambarkan
hambatan pada reaksi ini. Rumus lengkapnya sebagai berikut:

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Hambatan membran dan komponen darah kurang lebih sama, sehingga penurunan
volume darah kapiler oleh suatu penyakit dapat menurunkan kapasitas difusi paru.Jika
seseorang bernapas pada udara beroksigen tinggi, θ Co akan menurun karena O 2
berkompetisi dengan CO hemoglobin. Kapasitas difusi akan menurun dengan menghirup
O2.

Interpretasi Kapasitas Difusi Karbon Monoksida (CO)

Kapasitas difusi paru bergantung pada area dan ketebalan sawar darah-gas serta volume
darah pada kapiler paru. Pada paru yang sakit, pengukuran dipengaruhi distribusi difusi,
volume alveolus dan darah kapiler. Istilah faktor transfer kadang digunakan untuk
menekankan bahwa pengukuran tidak selalu menggambaran keadaan difusi paru.

Perpindahan Oksigen Melintasi Kapiler Paru

Difusi CO2 20 kali lebih cepat dari O2 karena solubilitas CO2 lebih tinggi. Reaksi CO2
dengan darah sangat rumit dan jika terjadi kelainan pada sawar darah-gas dapat terjadi
perbedaan antara darah pada akhir kapiler dan gas alveolar.

Kesimpulan

1. Hukum Fick menyatakan bahwa kecepatan difusi gas melintasi lapisan jaringan
sebanding dengan area lapisan jaringan dan perbedaan tekanan parsial pada kedua
sisi, dan berbanding terbalik dengan ketebalan lapisan jaringan yang dilintasi.
2. Contoh gas yang terbatas difusi adalah karbon monoksida dan gas yang terbatas
perfusi adalah nitrogen oksida. Perpindahan oksigen umumnya terbatas perfusi namun
batasan difusi dapat timbul pada keadaan tertentu, termasuk aktivitas fisis berat,
penebalan sawar darah-gas dan hipoksia alveolus.
3. Kapasitas difusi paru diukur menggunakan karbon monoksida yang diinhalasi.
Kapasitas difusi meningkat pada saat aktivitas fisik atau olahraga.
4. Laju reaksi terbatas antara oksigen dan hemoglobin dapat menurunkan kecepatan
perpindahan oksigen ke dalam darah dan efeknya serupa dengan penurunan kecepatan
difusi.
5. Perpindahan karbon dioksida ke dalam darah tidak terbatas difusi.

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