Download Diffusion - Dr James Mitchell

B. 5 Diffusive transfer of respiratory gases
a. Describe and explain the oxygen cascade.
The partial pressure of oxygen falls at each stage of its transport from air to
peripheral tissues.
Dry air
Air at BTPS
Alveolar gas
Pulmonary capillary blood
Mean capillary blood
Interstitial fluid
Intracellular fluid
159 mmHg
149 mmHg
100 mmHg
40 → <100 mmHg
40 mmHg
15-40 mmHg
≥1 mmHg for normal metabolism
The fall from dry to saturated air results from the increase in the partial
pressure of water from 0 to 47 mmHg. The pressure in inspired gas also depends upon
barometric pressure.
The difference between inspired gas and ideal alveolar gas depends on ventilation
and oxygen useage. With high alveolar ventilation, alveolar PO2 approaches inspired PO2
asymptotically. Alveolar PO2 is also reduced by oxygen uptake and CO2 release in the
alveoli.
The gradient between alveolar gas and pulmonary capillary blood depends on the
factors affecting diffusion described below. In addition it is increased by shunt and V/Q
scatter. A high inspired PO2 increases the pressure gradient because the content gradient
remains constant while the content/pressure graph becomes very flat at high PO2. A fall in
cardiac output causes a rise in the proportion of shunted blood as well as a fall in mixed
venous PO2 due to constant tissue oxygen uptake. A very marked rise in cardiac output can
also increase the A-a gradient by reducing transit time in the pulmonary capillaries to the
extent that oxygen uptake becomes diffusion-limited. Factors which influence the shape of
the oxygen dissociation curve also affect A-a gradient: pH, temperature, and 2,3-DPG. An
increase in haemoglobin concentration also reduces A-a gradient.
An increase in ventilation can cause a rise in A-a gradient both due to the rise in
alveolar PO2 and the fall in cardiac output which accompanies the fall in PCO2. If there is
more than 3% shunt, increasing ventilation starts to cause a fall in arterial PO2 because of
the fall in cardiac output.
The gradient from blood to interstitial fluid to intracellular fluid differs markedly
from tissue to tissue and regionally within any tissue. It is dependent on perfusion,
haemoglobin concentration and oxygenation of blood. In most tissues passive diffusion
carries oxygen down the concentration gradient from capillary blood to the mitochondria.
Some tissues such as muscle have specialized oxygen carrying proteins (myoglobin) to
improve oxygen transport and storage.
b. Explain the capillary exchange of oxygen and carbon dioxide, and the
relationship of erythrocyte transit to oxygen
and carbon dioxide transfer.
100
Respiratory diffusion
1.B.5.1
PO2 (mmHg)
O2 and CO2 cross the blood-gas barrier by
passive diffusion. The distance from alveolar
lumen to erythrocyte cytoplasm is about 0.3 µm.
O2 diffuses rapidly across this barrier,
equilibrating with blood in about 0.25 s. At rest,
erythrocyte transit time in alveolar capillaries is
about 0.75 s, however in exercise it falls to as little
as 0.25 s. The time taken for diffusion can be
greatly increased by lung disease which results in
Normal
Diseased
50
0
.25
.5
Time (s)
.75
James Mitchell (December 24, 2003)
thickening of the blood-gas barrier and consequent diffusion-limitation of oxygen transport.
A reduction in the pressure gradient driving diffusion will also slow diffusion. This is seen
at high altitude, where PAO2 is reduced by a greater amount than the fall in venous PO2.
CO2 is much more soluble than O2, however the pressure gradient driving its
diffusion is only 5 mmHg. In healthy lungs the time taken for alveolar gas to equilibrate
with pulmonary capillary blood is about the same as with O2: 0.25 s.
c. Explain perfusion-limited and diffusion-limited transfer of gases.
In gas exchange at the blood-gas barrier, the rate-limiting step differs according
to the gas being examined. In the case of oxygen, as described above, the partial pressure
equilibrates in much less time than the blood spends in alveolar capillaries. Thus transport
of oxygen is limited by the total alveolar blood flow at rest; it is perfusion-limited. N2O is an
extreme case of perfusion-limitation as it reaches equilibrium with blood in around 0.1 s.
Perfusion-limitation is a characteristic of gases and anaesthetic vapours which are roughly
equally soluble in the blood-gas barrier and in blood.
In exercise, when the transit time for blood is reduced substantially and if the
diffusion capacity for oxygen is reduced by lung disease, the partial pressure of oxygen in
pulmonary venous blood may still be much lower than in alveolar gas. CO diffuses much
less readily than O2, with a very gradual rise in blood partial pressure. Its transport is thus
almost entirely dependent on the rate of diffusion through the blood-gas barrier, hence its
use in measuring diffusion capacity. This is a case of diffusion-limited gas transport and is
characteristic of gases which have widely differing solubilities in the blood-gas barrier and
in blood.
d. Define diffusion capacity and its measurement.
Diffusion capacity is a measure of the rate at which a gas can diffuse across the
blood-gas barrier. It is described by Fick’s law of diffusion. The rate of diffusion is
proportional to the area (A) and pressure gradient and inversely proportional to the
thickness (T) of the sheet. It is proportional to the diffusion constant which is equal to the
solubility of the gas (Sol) divided by the square root of its molecular weight (MW):
˙ ∝ A ⋅Sol(P1 − P2 )
V
gas
T MW
Because area and thickness of the blood-gas barrier are not readily measurable,
an empirical “diffusing capacity” for each gas is defined such that:
˙ = D ⋅ (P − P )
V
gas
L
1
2
where DL is the diffusion capacity for the gas being tested. In the case of O2 and CO, uptake
is also limited by reaction with haemoglobin. This is also included in DL. DL can then be
split into two components, with DM representing the conductance of the blood-gas
membrane, VC the capillary blood volume, and θ representing the rate of reaction with Hb
(in ml/min/ml blood/mmHg):
1
1
1
=
+
D L D M θ ⋅ VC
Diffusion capacity is conventionally measured using CO as its transport across
the blood-gas barrier is diffusion-limited and its normal blood concentration is nearly zero.
This can be done with a 10s single breath-hold of a 0.3% CO and 10% He containing
mixture to measure both lung volume and DLCO or using a steady-state technique with
measurement of CO uptake over several breaths.
At rest DLCO is typically 25 ml/min/mmHg. With exercise it increases by a factor
of three or more due to pulmonary vasodilatation and alveolar recruitment.
e. Describe the physiological factors that alter diffusion capacity.
Increase
Respiratory diffusion
1.B.5.2
James Mitchell (December 24, 2003)
blood-gas barrier area
lung size
alveolar recruitment
alveolar gas concentration
pulmonary vasodilatation
uptake of CO or O2 by Hb or buffering of CO2
Decrease
blood-gas barrier thickness
systemic venous blood gas concentration
temperature (reduces solubility)
functional dead space
Respiratory diffusion
1.B.5.3
James Mitchell (December 24, 2003)