Respiratory Physiology Gas Diffusion...

Gas Diffusion

The goal of this section will be to describe the process of
pulmonary gas exchange at the alveolar-capillary surface.
Lecture Outline
Diffusion of gases at the alveolar-capillary surface:
 Fick’s Law
 oxygen time course (normal and abnormal)
 carbon dioxide time course (normal and abnormal)
1. Diffusion of gases
Diffusion is the rate at which a gas can transfer across a
tissue bed. All gases move across the alveolar wall by
passive diffusion. The blood/gas interface in the lung has
a large surface area (50-100 mm2) and is thin ( ~ 0.5 µm)
so it is ideal for diffusion. The diffusive process for a
gas through a tissue sheet is described by Fick's law:
Vgas= A x D x (P1-P2)
T

Vgas= volume of diffusion gas per unit time, ml/min

P1 - P2= partial pressure difference across barrier
A= surface area of barrier
D= diffusion coefficient of particular gas in the
Objectives barrier
 Describe the process of diffusion of gases across the T= Thickness of the barrier
alveolar-capillary membrane, using Fick’s law.
 Describe the time course for the diffusion of oxygen
DLgas = diffusing capacity of the lung for a specific gas
across the alveolar-capillary membrane.
(volume of gas/min/mmHg)
 Describe the time course for the diffusion of carbon
= Area x Dgas
dioxide across the alveolar-capillary membrane. Thickness

 Compare the diffusion coefficient of carbon dioxide
to the diffusion coefficient of oxygen.
Diffusing capacity is a conductance term (the reverse of a
resistance term). The higher the DLgas the more gas that
can be transferred down a specified pressure gradient per
unit of time. This is what is measured clinically.
Respiratory Physiology Gas Diffusion...

2. Diffusion of oxygen  normal transit time of a RBC of 0.75 second may be

cut to 0.25 second but still normal end-capillary PO2

FIGURE 1: is still about equal to alveolar PO2. Again, ,minimal

Oxygen time courses in the pulmonary capillary when A-a gradient.

diffusion is normal and abnormal, and with normal

and low PAO2. Diseased, thickened membrane
 mean capillary PO2 does not reach that of alveolar
gas before transit time is over, therefore a diffusion
normal alveolar PO2 limitation for oxygen arises (end-capillary PO2 will
A-a oxygen be abnormal with an elevated alveolar to arterial
oxygen (A-a O2) gradient.
 a diffusion limitation for oxygen would be greater
with a lower PAO2 and with a higher transit time

low alveolar PO2

Note:
Healthy, breathing room air, at rest
 The mean capillary PO2 virtually reaches that of
alveolar gas when RBC is one- third along capillary
therefore normal end-capillary PO2 is about equal to
alveolar PO2. Minimal A-a gradient.

Healthy, breathing room air, at exercise

 Pulmonary blood flow increases
Respiratory Physiology Gas Diffusion...

3. Diffusion of carbon dioxide Question

Compare the diffusion coefficient of carbon dioxide to
FIGURE 2: the diffusion coefficient of oxygen.
Carbon dioxide time course in the pulmonary capillary
when diffusion is normal and abnormal.
Answer
P v CO 2 exercise The diffusion coefficient of a gas in the substance (tissue
45 and water) of the membrane (Dgas) depends on the
abnormal solubility of the gas within the membrane and inversely
normal
mmHg on the square root of its molecular weight:

40 Dgas = The diffusion coefficient for O2

P ACO 2
0.25 0.5 0.75 = 0.0042
Time in capillary - 0seconds

The diffusion coefficient for CO2

= 0.0860

Therefore, for a given pressure difference, the diffusion

of CO2 across the respiratory membrane is 0.0860/0.0042
or ~ 20 times as rapid as O2! CO2 diffuses through the
respiratory membrane so fast that the average PcCO2 in
the pulmonary blood is almost identical to the PACO2 in
the alveoli (< 1 mm Hg difference).
Respiratory Physiology Gas Diffusion...

4. Diffusion capacity of the lung (DL)

for any gas

DLgas = Area x Dgas

Thickness

Factors that affect the DL for any gas

1. the thickness of the respiratory membrane, or the
length of the diffusion pathway
2. the size of surface area of the respiratory membrane
3. the time available for gas pressure equilibrium to
occur
4. the diffusion coefficient of the gas in the substance of
the membrane (Dgas)

Causes of a decrease in DL for any gas

Increased Distance for Diffusion: (thickened interstitium)
 excess collagen (pulmonary fibrosis)
 interstitial fluid (pulmonary edema)
 inflammatory cells (viral pneumonia)

Decreased Surface Area for Diffusion:

 less alveolar surface (emphysema, surgical resection)
 less capillary surface (pulmonary embolism)
Respiratory Physiology
Gas Transport in the Blood
Lecture Outline
1. Transport of Oxygen
 O2 carriage
 O2 dissociation curve
 total O2 transport to the tissues
 significance of O2 dissociation curve
 factors affecting O2 dissociation curve
2. Transport of Carbon Dioxide
 CO2 carriage
 CO2 dissociation curve
Gas Transport...
Objectives
 Draw the oxygen dissociation curve.
 Describe the factors influencing the arterial
oxygen content.
 Describe the effect of pH, PCO2,
temperature, and 2,3 DPG on the position
of the oxygen dissociation curve.
 List and discuss the forms in which carbon
dioxide is carried by the blood.
 Draw the CO2 dissociation curve.
 List the differences between oxygen and
carbon dioxide transport by the blood.
 Describe the effects of changes in blood
oxygen on the CO2 dissociation curve.
Respiratory Physiology Gas Transport...

1. Transport of Oxygen
O2 Carriage
Oxygen is carried in the blood in two forms -
dissolved in plasma and bound to hemoglobin.
1. Dissolved O2 in Solution
Remember Henry’s Law (see Basic Gas Laws)!
Gases are carried in physical solution in the
blood in proportion to their partial pressure.
O2 forms an easily reversible combination with
hemoglobin (Hb + O2 --> HbO2). The potential
O2 content (capacity) of a blood sample is the
maximum amount of oxygen that will combine
with the available hemoglobin at high PO2. On
the other hand, the % saturation of hemoglobin
(SO2), indicates the portion of the total oxygen
binding sites that are actually occupied by O2.

% saturation = x 100
However, very little O2 is carried in the blood in
the dissolved form at normal partial pressures
As illustrated in Figure 2.1, the relationship
of O2. For example, at a normal PaO2 of 100
between PaO2 and SaO2 or CaO2 is nonlinear.
mmHg, only 3 mL of O2/L of blood is stored in
The curve is S-shaped which has great
physical solution. A blood flow of 1000
physiologic advantages. It has a steep slope
L/minute would be necessary to carry O2 to the
between 20 and 40 mmHg and becomes flatter
tissues with strenuous exercise, if this was the
at PaO2 greater than 70 mmHg.
only form of O2 in the blood!

2. Hemoglobin (Hb) Question

The presence of hemoglobin in the blood Arterial blood gases reveal the following

greatly increases the O2 carrying capacity of information: PaO2 = 60 mmHg, pH = 7.40,

the blood. Hemoglobin is a complex protein PaCO2 = 40 mmHg, and SaO2 =0. 90 (90%).

consisting of 4 polypeptide chains (2 alpha and Calculate the CaO2. Remember with the

2 beta) with 4 iron-porphyrin groups for the reduced PaO2 the Hb is only 90% saturated.

binding of O2. One mole of hemoglobin can

carry 4 moles of O2, or 1.34 mL of O2 per gram
of hemoglobin.

Normal hemoglobin concentration in the blood

is ~150 grams/L of blood. Therefore, ~ 200 mL
of O2/L of blood can be potentially carried by
oxyhemoglobin or HbO2. This is > 70 times the
amount of O2 that can be carried dissolved in
solution.
Respiratory Physiology Gas Transport...

Figure 2.1:
The Oxygen Dissociation Curve
Respiratory Physiology Gas Transport...

Oxygen Transport to the Tissues of O2 for Hb increases ( P50) the curve is

Total oxygen transport to the tissues (DO2) can shifted to the left and less O2 is released to the
be calculated as the oxygen content of arterial tissues at low PaO2’s.
blood times the total blood flow (cardiac
output). Rightward Shift P50)
1.  H+ (called the Bohr effect)
DO2 = CaO2 x CO 2. PaCO2
3. temperature
4. 2,3-diphosphogylcerate in the RBC
Biologic Significance of the Oxygen
increases in chronic hypoxemia)
Dissociation Curve
Leftward Shift ( P50)
1.  H+
1. At a normal PaO2 (100 mmHg), the Hb is
2.  PaCO2
97.5% saturated with oxygen. 3.  temperature
4.  2,3-diphosphogylcerate in the RBC

2. On the flat upper portion of the curve, at

PaO2’s between 75-100 mmHg, there is little
change in the SaO2, and hence, little change in
CaO2 and O2 delivery. This is important
because in lung disease a drop in PaO2 within
this range will minimally affect CaO2 and tissue
oxygen delivery.

3. The steep lower part of the curve aids in the

release of O2 to the tissues. As tissue PO2 is
low (10 mmHg), large amounts of O2 will be
released to the tissues with only a small drop
in blood PO2.

Factors Affecting the Oxygen

Dissociation Curve
The position of the curve may be described by
the PO2 at which the available Hb is 50%
saturated. This is called the P50 and is 26.6
mmHg in human blood at 37oC. When the
affinity of O2 for Hb decreases (P50) the curve
is shifted to the right and more O2 is released
to the tissues at low PaO2’s. When the affinity
Respiratory Physiology Gas Transport...

Question

When his/her patient is ill with pneumonia,

why does the physician wish to maintain the
PaO2 above 60 mmHg with supplemental
oxygen?

Question

How do the factors, affecting the oxygen

dissociation curve, aid in the release of O2 to
an exercising muscle ? Consider what an
exercising muscle would release into its
environment.

Clinical Note

Carbon monoxide (CO) binds very avidly with

hemoglobin and has an affinity for hemoglobin
that is 240 times that of oxygen! Therefore, the
presence of a small amount of CO significantly
decreases the O2 carrying capacity of the blood
by ‘removing’ binding sites for O2. The result is
a ‘functional anemia’. As well, CO does further
harm by shifting the oxygen dissociation curve
to the left.

Question

A victim of CO poisoning presents to the

emergency department with headaches and
confusion. The COHb level in his blood is 50%.
Arterial blood gases on room air reveal a PaO2
of of 95 mmHg, a PaCO2 of 40 mmHg, and a pH
of 7.20. Hemoglobin level is 150 grams/L.
Calculate his CaO2. Why is the pH low?
Respiratory Physiology
2. Transport of Carbon Dioxide
CO2 Carriage
Carbon dioxide is continuously produced by all
metabolizing cells and diffuses from the regions
of high PCO2 in the cells to the regions of lower
PCO2 in the venous capillaries. Once the CO2
has diffused into the blood it is carried towards
the lungs in three forms:
1. Dissolved CO2
CCO2 = K x PCO2
Remember Henry’s Law, where:
CCO2 = content of CO2 in venous blood
K = solubility CO2 in the blood (20 times > O2)
PCO2 = partial pressure in venous blood
Therefore:
CCO2
= (0.71 mL CO2/L blood ò mmHg) x 46 mmHg
= 33 mL CO2/ L blood
~5% of the total CO2 in the mixed venous blood
is in the dissolved form
2. CO2 as bicarbonate
H2O + CO2  H2CO3  HCO3- + H+
The presence of carbonic anhydrase in the RBC
catalyzes the first reaction. The second
reaction is fast without an enzyme. Reduced
hemoglobin (deoxygenated Hb) has the ability
to accept the H+ ions, thereby allowing the
formation of bicarbonate to proceed.
Bicarbonate diffuses out of the RBC’s into the
plasma. Since H+ ions do not easily cross the
Gas Transport...
cell membrane a chloride shift occurs to
maintain electrical neutrality (Cl- moves into
the cell). (see Figure 2.3)
In the peripheral blood:
 O2 is unloaded into the tissues
 the amount of reduced Hb increases
(deoxygenated Hb)
 this aids the loading of CO2 into the
peripheral blood from the tissues
 this is called the Haldane effect
In the mixed venous blood:
 the reverse occurs, i.e., the oxygenation of
Hb helps with the unloading of CO2 into
lungs
 most of the CO2 in the mixed venous blood
is carried in the form of bicarbonate (~90%
of the total), 1/3 in RBC’s and 2/3 in the
plasma
3. CO2 combined with proteins
Some of theáCO2 combines with the terminal
amine groups in the blood proteins, especially
the globin of Hb, to form carbaminohemoglobin.
Once again reduced hemoglobin, can bind more
CO2 as carbaminohemoglobin, than can
oxyhemoglobin.
 although ~5% of the total CO2 in the mixed
venous blood is carried in this from, the
carbamino bound CO2 makes up ~30% of
the PCO2 that is exchanged.
Respiratory Physiology Gas Transport...

Figure 2.2
CO2 Dissociation Curve

The relationship between the PCO2 and the total CO2 concentration in the blood is known as the
carbon dioxide dissociation curve (Figure 2.2).

Note the following:

1. the CO2 dissociation curve is more linear than the O2 dissociation curve
2. the position of the curve is influenced by the state of oxygenation of the hemoglobin
(Haldane effect)
Respiratory Physiology Gas Transport...

Figure 2.3
Scheme of the uptake of CO2 and the release of O2 in the systemic capillaries. Opposite
reactions occur in the pulmonary capillaries.

CO2 transport in the blood illustrating the formation of bicarbonate ions and carbamino compounds,
chloride shift, and buffering of hydrogen ions.

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