By : Andy Pranata K, dr

BBM : 7D648D4A
Transport of O2 and CO2 between the
alveoli and the tissue cells:
Diffusion: movement of O2 from the alveoli
into the pulmonary blood and diffusion of CO2
in the opposite direction. Gases dissolved in
the fluids and body tissues. Diffusion require
energy which is provided by the kinetic
motion of the molecules of gas themselves.
Partial pressure of gases (in a mixture)

The pressure of gas is caused by the constant

kinetic movement of gas molecules against the
surface. In respiratory physiology, there is a
mixture of gases mainly of O2, N2, and CO2. The
rate of diffusion of each of these gases is directly
proportional with the partial pressure of the gas.

Pressure of gases dissolved in water and tissue:

The pressure of gases dissolved in fluid is similar
to their pressure in the gaseous phase and they
exert their own individual partial pressure.
Dissolved gas molecules

A B
Diffusion of gases through fluids pressure
difference causes net diffusion:

The net diffusion of gas from the area of high

concentration to the area of low concentration = the
number of molecules bouncing in the forward direction
the number of molecules bouncing in the opposite
direction (pressure difference for diffusion).

The solubility of gas, CO2 is more soluble than O2

The relative diffusion rates for different gases:
O2 1.0
CO2 20.3
N2 0.53
 Diffusion of gases through tissues

The gases of respiratory importance are

highly soluble in cell membrane (all are
highly soluble in lipids). Also, diffusion of
gases through the tissue, including through
the respiratory membrane, is equal to the
diffusion of gases through water. CO2
diffusion 20 times more rapidly than O2
because of its high solubility in tissue fluids.
Composition of alveolar air and its
relation to atmospheric air:
Alveolar air is partially replaced by
atmospheric air with each breath.
O2 is constantly absorbed from the
alveolar air.
CO2 constantly diffuses from the
pulmonary blood into the alveoli.
The dry atmospheric air enters the
respiratory passage is humidified
before it reaches the alveoli.
 Partial pressures of respiratory gases as they
enter and leave the lungs (at sea level)

N2 O2 CO2 H2O
Atmospheric Air* 597.0 (78.62%) 159.0 (20.84%) 0.3 (0.04%) 3.7 (0.50%)
(mmHg)

Humidified Air 563.4 (74.09%) 149.3 (19.67%) 0.3 (0.04%) 47.0 (6.20%)
(mmHg)

Alveolar Air 569.0 (74.9%) 104.0 (13.6%) 40.0 (5.3%) 47.0 (6.2%)
(mmHg)

Expired Air 566.0 (74.5%) 120.0 (15.7%) 27.0 (3.6%) 47.0 (6.2%)
(mmHg)
The rate at which alveolar air is
renewed by atmospheric air:

The amount of air remaining in the lungs at

the end of normal expiration ~ 2300ml (FRC).
Only 350ml of air is brought into the alveoli
with each breath. Therefore, the amount of
alveolar air is replaced by new atmospheric
air with each breath is only 1/7th of the total.
This slow replacement of alveolar air is
important in preventing sudden changes in
gaseous concentrations in the blood.
O2 concentration and pressure in the
alveoli:

O2 is continuously absorbed into the blood of

the lungs and replaced from the atmosphere.
So its concentration is lower in the alveoli if
its absorbed more rapidly. Its concentration
is higher in the alveoli if new O2 is breathed
rapidly.
The solid curve represents O2 absorption at a
rate of 250ml/min, and the dotted curve at
1000ml/min. At normal ventilatory rate of 4.2
liters/min and O2 consumption of 250ml/min,
the normal operating point is point A. During
moderate exercise when O2 is absorbed, each
minute 1000ml, the rate of alveolar ventilation
is increase 4-fold to maintain the alveolar PO2
at normal value of 104mmHg. Also marked
increase in the alveolar ventilation never
increase the alveolar PO2 above 149mmHg if
the person breathing normal atmospheric air.
CO2 concentration and pressure in the
alveoli:
CO2 is continuously formed in the body,
discharged into the alveoli, then removed by
ventilation.

The solid curve represents the normal rate of CO2

excretion of 200ml/min, at normal ventilation of 4.2
liters/min, the operating point for alveolar PCO2 is
at point A at 40mmHg. Alveolar PCO2 increases
directly in proportion to the rate of CO2 excretion,
as represented by the dotted curve for 800ml CO2
excretion/min. Alveolar PCO2 decreases in inverse
proportion to alveolar ventilation.
Diffusion of gases through the
respiratory membrane
Respiratory unit is composed of respiratory
bronchiole, alveolar ducts, atria, and alveoli
(about 300 million in the 2 lungs, each
alveolus with an average diameter of 0.2
millimeter). The walls of the alveoli, alveolar
ducts and other parts of the respiratory unit
are extremely thin within, there are
interconnecting capillaries which is called
the respiratory membrane or pulmonary
membrane.
 The total surface area of the
respiratory membrane is ~ 50 to
100 m2 in normal adult. This
large surface area to allow rapid
diffusion of gases through the
respiratory membrane

Respiratory membrane
Factors that affect the rate of gas diffusion
through the respiratory membrane:
1. The thickness of the respiratory membrane.
thickness of the respiratory membrane e.g.,
edema rate of diffusion. The thickness
of the respiratory membrane is inversely
proportional to the rate of diffusion through
the membrane.
2. Surface area of the membrane. Removal of
an entire lung decreases the surface area to
half normal. In emphysema with dissolution
of the alveolar wall S.A. to 5-folds
because of loss of the alveolar walls.
Epithelial basement Capillary basement
membrane Interstitial membrane
space Capillary endothelium
Alveolar epithelium

Fluid and Red

surfactant blood
layer cell

Alveolus Capillary
Diffusion O2

Diffusion CO2
3. The diffusion rate of the specific gas.
Diffusion coefficient for the transfer of
each gas through the respiratory
membrane depends on its solubility in the
membrane and inversely on the square
root of its molecular weight. CO2 diffuses
20 times as rapidly as O2.
4. The pressure difference between the two
sides of the membrane (between the alveoli
and in the blood). The alveolar pressure
represents a measure of the total number of
molecules of a particular gas striking a unit
area of the alveolar surface of the membrane
in unit time. When the pressure of the gas in
the alveoli is greater than the pressure of the
gas in the blood as for O2, net diffusion from
the alveoli into the blood occurs, but when the
pressure of the gas in the blood is greater
than the pressure in the alveoli as for CO2, net
diffusion from the blood into the alveoli
occurs
 Diffusing capacity of the
respiratory membrane
Diffusing capacity: is the volume of a gas that
diffuses through the membrane each minute for
a pressure difference of 1mmHg.
The diffusing capacity for O2: In the average
young male adult, the diffusing capacity for O2
under resting conditions averages
21ml/min/mmHg. The mean O2 pressure
difference across the respiratory membrane
during normal, quiet breathing is ~ mmHg. (11 x
21 = 230 ml) of O2 diffusing through the
respiratory membrane each minute equal to the
rate at which the body uses O2.
Changes in O2 diffusing capacity
during exercise
During strenuous exercise or other
conditions that increase the pulmonary
blood flow and alveolar ventilation, the
diffusing capacity for O2 increases to
65ml/min/mmHg (3 times the diffusing
capacity under resting conditions). This
increase is caused by opening up the
dormant pulmonary capillaries to
increase the surface area of the blood
into which O2 can diffuse.
 It is the ratio of alveolar ventilation to
pulmonary blood flow per minute. The
alveolar ventilation at rest (4.2L/min) and is
calculated as:
Alveolar ventilation = respiratory rate x (tidal volume
dead space air).
The pulmonary blood flow is equal to right ventricular
output per minute (5L/min).
This value is an average value across the
lung.
At the apex, V/Q ratio = 3.
At the base, V/Q ratio = 0.6.
So the apex is more ventilated than perfused, and the
base is more perfused than ventilated.
During exercise, the V/Q ratio becomes
more homogenous among different
Ventilation-perfusion ratio parts of
(V/Q)
the lung.
 Diffusing capacity for CO2

CO2 diffuses through the respiratory

membrane so rapidly that the average PCO2
difference between the alveolar and capillary
blood is 1mmHg. The diffusion capacity for
CO2 is 20 times that of the O2, so we expect
that the diffusion capacity for CO2 under
resting conditions ~ 400 to 450ml/min/mmHg
and during exercise is about 1200 to 1300
ml/min/mmHg.
 Uptake of O2 from the alveoli by the
pulmonary blood
The PO2 in the alveolus is 104mmHg and in the
venous blood entering the capillary is 40mmHg
because large amount of O2 has been removed
from this blood as it has passed through the
peripheral tissues. The initial pressure
difference that causes O2 to diffuse into the
pulmonary capillary is 64mmHg (104-
40=64mmHg). The rapid rise in blood PO2 as the
blood pressure through the capillary, that the
PO2 rises to equal that of the alveolar air by the
time the blood moved a 1/3rd of the distance
through the capillary becoming 104mmHg
 Uptake of O2 by the pulmonary blood
during exercise
During strenuous exercise, the body requires as much as
20 times the normal amount of O2. Also, because of the
increased cardiac output, the time that the blood remains
in the capillary may be reduced to less than half normal.
Therefore, oxygenation of the blood could suffer.
Because of safety factor for diffusion of O2 through the
pulmonary membrane, the blood is almost completely
saturated with O2 when it leaves the pulmonary capillaries
for 2 reasons:
During exercise, the rate of O2 diffusion through the pulmonary
membrane increases to 3 fold, due to the number of capillaries.
During blood flow through the capillary, the blood becomes
almost saturated with O2 by the time it has passed through the
1/3rd of the pulmonary capillary.
 Diffusion of O2 from the tissue
capillaries into tissue fluid

The PO2 in the arterial blood reaching the

capillary is 95mmHg, the PO2 in the interstitial
fluid is 40mmHg and 23mmHg inside the
cells. So there is a tremendous initial
pressure difference that causes O2 to diffuse
very rapidly from the blood into the tissues,
so that the capillary PO2 falls to 40mmHg in
the interstitium. The blood entering the veins
from the tissue capillaries is about 40mmHg.
Effect of rate of blood flow and tissue
metabolism on interstitial fluid PO2
If the blood flow through the tissue is
increased, large quantities of O2 are
transported into the tissue in a given period
of time, and the tissue PO2 is increased. The
upper limit to which the PO2 can rise, even
with maximum blood flow is about 95mmHg
(because this is the O2 pressure in the
arterial blood). Conversely, if the cells utilize
more O2 for metabolism than normal, this
reduce the interstitial fluid PO2.
 Diffusion of O2 from the capillaries
to the tissue cells
O2 is used by the cells. Therefore, the
intracellular PO2 remains lower than the PO2
in the capillaries. The intracellular PO2 is
about 23mmHg (range between 5 to
40mmHg). Because only 1 to 3mmHg of O2
pressure is normally required for full support
of the metabolic processes of the cell, so
that even with this low PO2 of 2mmHg is
more than adequate and safe for the
metabolic processes.
 Diffusion of CO2 from the tissue cells
into the tissue capillaries and from the
pulmonary capillaries into the alveoli
When O2 is used by the cells, most of it becomes CO2 and
this increases the intracellular PCO2. CO2 diffuse from the
cells into the tissue capillaries and then carried by the blood
to the lungs, when it diffuses from the pulmonary capillaries
into the alveoli. CO2 diffuses in opposite direction to the
diffusion of O2. CO2 diffuses 20 times as rapidly as O2.
Therefore, the pressure differences that cause CO2
diffusion are far less than the pressure differences required
to cause O2 diffusion. These pressures are the following:
Intracellular PCO2 is about 46mmHg, the interstitial PCO2 is
about 45mmHg, there is only a 1mmHg pressure difference.
 PCO2 of the arterial blood entering the tissues 40mmHg,
PCO2 of the venous blood leaving the tissue is about
45mmHg. So that tissue capillary blood is in an equilibrium
with the interstitial PCO2 45mmHg.
PCO2 of the venous blood entering the pulmonary capillaries
in the lungs 45mmHg, PCO2 of the alveolar air is 40mmHg,
only 5mmHg pressure difference causes CO2 to diffuse out of
the pulmonary capillary into the alveoli.
The PCO2 of the pulmonary capillary blood falls exactly to
equal the alveolar PCO2 of 40mmHg before it passed more
than about 1/3rd the distance through the capillaries

Effect of tissue metabolism and blood flow on interstitial PCO2:

Increased tissue metabolism increases the CO2 in the tissue,
but increased blood flow carries more CO2 away and
decreases its concentration.
 Function of haemoglobin to
transport O2 in arterial blood
About 97% of O2 is transported in chemical
combination with haemoglobin and 3% is carried
in the dissolved form in the plasma and cells.
Under normal conditions O2 carried to the
tissues almost entirely by haemoglobin. O2
molecule combines loosely and reversibly with
the heme portion of the Hb. When the PO2 is
high (as in the pulmonary capillaries) O2 binds
with the Hb, but when the PO2 is low (as in the
tissue capillaries) O2 is released from the Hb.
 The oxygen-haemoglobin
dissociation curve

It shows the progressive increase in the

percentage saturation of the Hb with the
increase in the PO2 in the blood. The
PO2 in the arterial blood is about
95mmHg and saturation of Hb with O2 is
about 97%. In the venous blood
returning from the tissues, the PO2 is
about 40mmHg and the saturation of Hb
with O2 is about 75%.
Maximum amount of O2 than can
combine with the Hb of the blood

In a normal person, 15gm of Hb in

each 100ml of blood, each gram of
Hb bind with a maximum of about
1.34ml of O2. At 100% saturation,
the Hb in 100ml of blood can
combine with 20ml of O2.
The amount of O2 released from the
Hb in the tissues

In the arterial blood 97/100 x 1.34 x

15gm of Hb = 19.4ml of O2 bound with
Hb.
In the venous blood 75/100 x 1.34 x
15gm = 14.4ml of O2.
So under normal conditions about 5ml
of O2 are transported to the tissues by
each 100ml of blood.
 Transport of O2 during
strenuous exercise
In heavy exercise the muscle cells utilize
O2 rapidly, which causes the interstitial
fluid PO2 to fall to 15mmHg. Only 4.4ml
of O2 remains bound to with Hb in each
100ml of blood (19.4 4.4 = 15ml of O2
are transported by each 100ml of blood).
Also cardiac output can increase to 7
fold. The amount of O2 transported to
the tissue increase to 20 folds (3 x 7 =
21).
Factors affecting the affinity of Hb for O2
3 important conditions
1) The pH or (H+ conc),
2) the temperature,
3) and the concentration of 2,3 diphosphoglycerate
(2,3-DPG).
4) PCO2 concentration (Bohr effect) all shift the
curve to the right.

P50: it is the partial pressure of O2 at which 50%

of Hb is saturated with O2.
P50 means right shift lower affinity for O2.
P50 means left shift higher affinity for O2.
 Metabolic use of O2 by the cells

The figure shows the relationship

between intracellular PO2 and the
rate of O2 usage at different
concentrations of ADP. When the
rate of ADP concentration is altered,
the rate of O2 usage changes in
proportion to the change in ADP
concentration.
 ADP = 1 normal

ADP = Normal resting level

ADP = normal
Transport of O2 in the dissolved state

Only 3% of the total O2 is transported

in the dissolved state composed with
97% transported by Hb.

In the arterial blood, the PO2 is

95mmHg 0.3ml of O2 is dissolved in
dl of blood. In venous blood PO2 is
40mmHg (as in tissue capillaries)
0.12ml of O2 is dissolved in dl of
blood.
The importance of dissolved form

Tissue consume the O2 directly.

It depends on the PO2 (so higher alveolar
PO2 will increase the amount of O2 carried
in the dissolved state e.g., hyperbaric O2
therapy as in CO poisoning).

Combination of Hb with CO
displacement of O2:
CO combines with Hb and it displace O2
from Hb. It binds with about 250 times as
much tenacity as O2.
 Transport of CO2 in the blood

Under normal resting conditions

~ 4ml of CO2 is transported from
the tissue to the lungs in each
100ml of blood.
 1-7% of CO2 is transported in the
dissolved state.
2-70% of CO2 is transported in the
form HCO3. HCO3 diffuses out of the
RBC with Hb and Cl ions diffuse into
the RBC (chloride shift).
3-23% of CO2 is transported in
combination with Hb and plasma
proteins as carbamino-Hb: CO2 reacts
with the amino group of the Hb to form
the carbamino-Hb
Chemical forms in(CO 2HHB).
which COThisis
2
reaction is reversible when CO2 is
transported
released into the alveoli.
Change in blood acidity during
CO2 transport
CO2 H+ pH ( acidity of the blood
stimulate its release from the blood through the
lungs).
The respiratory exchange ratio:
rate of CO2 output 4
R 0.8 (80%)
rate of O 2 uptake 5
R value changes under different metabolic
conditions. If the person is utilizing carbohydrate
for body metabolism. R value rises to 1 and it
decreases to 0.7 if the person is utilizing fat for
metabolism. If the person consume normal diet
(CHO, fat and protein), R value is ~ 0.825.
 Keseimbangan asam-basa pengaturan
konsentrasi ion H+ dalam cairan tubuh
Ion H+ sbg hasil dari metabolisme:
C6H12O6 + O2 CO2 + H2O H2CO3 H+ + HCO3-
[H+] dlm plasma pH plasma darah = 7,4
Sistem dapar (buffer) menghambat
perubahan pH yang besar jika ada
penambahan asam atau basa

Keseimbangan Asam & Basa

60
1. Asam karbonat:Bikarbonat
sistem dapar di CES untuk asam non-
karbonat
2. Protein
sistem dapar di CIS & CES
3. Hemoglobin
sistem dapar di eritrosit untuk asam
karbonat
4. Phosphat
sistem dapar di ginjal dan CIS

Sistem Dapar
61
Keseimbangan ion H+

faal_cairan-asam-basa/ikun/2006 62
faal_cairan-asam-basa/ikun/2006 63
 Sistem dapar hanya mengatasi
ketidakseimbangan asam-basa sementara
Ginjal: meregulasi keseimbangan ion H+
dengan menghilangkan
ketidakseimbangan kadar H+ secara
lambat; terdapat sistem dapar fosfat &
amonia
Paru-paru: berespons scr cepat thd
perubahan kadar H+ dalam darah &
mempertahankan kadarnya sampai ginjal
menhilangkan ketidakseimbangan
tersebut

Mekanisme Regulasi
Keseimbangan Asam-Basa
64
 Kadar CO2 meningkat pH menurun
Kadar CO2 menurun pH meningkat
Kadar CO2 & pH merangsang
kemoreseptor yg kemudian akan
mempengaruhi pusat pernapasan
hipoventilasi meningkatkan kadar CO2
dlm darah
hiperventilasi menurunkan kadar CO2
dlm darah

Regulasi Pernapasan dlm

Keseimbangan Asam-Basa
65
Regulasi Pernapasan dlm
Keseimbangan Asam-Basa
66
 Sekresi H+ ke dalam filtrat & reabsorpsi
HCO3- ke CES menyebabkan pH ekstrasel
meningkat
HCO3- di dlm filtrat diabsorbsi
Laju sekresi H+ meningkat akibat
penurunan pH cairan tubuh atau
peningkatan kadar aldosteron
Sekresi H+ dihambat jika pH urin < 4,5

Regulasi Ginjal dlm

Keseimbangan Asam-Basa
67
1. Asidosis respiratori
hipoventilasi retensi CO2 H2CO3H+
2. Alkalosis respiratori
hiperventilasi CO2 banyak yg hilang
H2CO3 H+
3. Asidosis metabolik
Diare, DM HCO3- PCO2 H+
4. Alkalosis metabolik
muntah H+ HCO3- PCO2

Gangguan Keseimbangan
Asam-Basa
68
Kompensasi Sistem
Pernafasan terhadap Asidosis
Metabolik
71
Kompensasi Ginjal terhadap
Asidosis Respiratorik
72
Nomogram Davenport
INTERPRETASI AGD
Lihat pH darah

pH < 7,35 pH > 7,45

ASIDOSIS ALKALOSIS

Lihat pCO2 Lihat HCO3-

< 40mmHg > 40 mmHg < 24 mM > 24 mM

METABOLIK RESPIRATORIK RESPIRATORIK METABOLIK

 Lihat pH kembali
- jika mendekati kadar normal (7,35-7,45)
terkompensasi
- jika belum mendekati normal
tidak terkompensasi atau terkompensasi
sebagian
Jika asidosis respiratorik dgn HCO3- < 24 mM
terkompensasi sebagian
Jika asidosis metabolik dgn pCO2 < 40 mmHg
terkompensasi sebagian
Jika alkalosis respiratorik dgn HCO3- > 24 mM
terkompensasi sebagian
Jika alkalosis metabolik dgn pCO2 > 40 mmHg
terkompensasi sebagian

TERKOMPENSASI atau TIDAK?