Pulmonary 5: Diffusion and Perfusion

Question 1

Draw a basic diagram to outline how CO2/O2 exchange occurs across the body. Provide metabolic CO2 and O2 levels.

Answer 1

Slide 4.

Question 2

Describe the process by which gas is transferred across the blood gas barrier.

What are factors that facilitate this process in the respiratory system?

Answer 2

Transfer of gas across the blood gas barrier occurs by diffusion (passive)

transfer of gas follows basic gas diffusion laws

Factors facilitating gas diffusion in respiratory system:

• large surface area (alveoli: 70m^2)
• short distances (0.2-5 micrometers)
• gases w advantageous diffusion properties

Question 3

Describe the following factors pertaining to alveolar-capillary network gas exchange:

-capillary diameter
-erythrocyte diameter
(describe how erythrocytes pass through capillaries and the average transit time)

Answer 3

Capillary diameter: less than 10 micrometers

erythrocyte diameter: 7 micrometers

pass through cap. in single file.
avg. transit time less than 1 sec.

Question 4

Describe Fick’s Law and how it relates to diffusion through tissues. Describe the principles.

Answer 4

• The amount of gas transferred is proportional to the area (A), a diffusion constant, and the difference in partial pressure

• The amount of gas in indirectly proportional to the thickness (T).

Vgas proportional to A/T x D x (P1-P2)

Question 5

Describe Graham’s Law and how it relates to diffusion through tissues.

Answer 5

rate of diffusion is proportional to solubility coefficient of the gas/ square root of molecular weight

Solubility coefficient O2=1
Solubility Coefficient for CO2=22

Rate of diffusion:
O2= 1/(square root of 32) =0.176
CO2=20/(square root of 44)=3.01

Question 6

Describe diffusion and perfusion limitations in regards to insoluble gases.

Answer 6

Insoluble gases (N2O)
- do not chemically combine 
 with proteins
- equilibrate rapidly
→ perfusion limited
gas transfer is limited by the
amount of blood perfusing the alveolus

Perfusion is the process by which deoxygenated blood
passes through the lung and becomes reoxygenated.

Question 7

Describe diffusion and perfusion limitations in regards to soluble gases.

Answer 7

Soluble gases:

CO: diffuses rapidly into erythrocytes,
high affinity for hemoglobin,
no or little increase in partial pressure
→ diffusion limited

because of the tight bond that forms between carbon monoxide and hemoglobin within the cell, a large amount of carbon monoxide can be taken up by the cell with almost no increase in partial pressure. Thus, as the cell moves through the capillary, the carbon monoxide partial pressure in
the blood hardly changes, so that no appreciable back pressure develops, and the
gas continues to move rapidly across the alveolar wall. It is clear, therefore, that the amount of carbon monoxide that gets into the blood is limited by the diffusion properties of the blood-gas barrier and not by the amount of blood available.*
The transfer of carbon monoxide is therefore said to be diffusion limited.

Question 8

Describe perfusion of O2 and CO2. How does their affinity for hemoglobin compare to CO?

Answer 8

O2 and CO2: bind to hemoglobin, but with lower affinity than CO;
→ normal transfer is perfusion limited

Question 9

Draw a graph that shows the uptake of nitrous oxide (N2O), CO, and O2 in blood relative to their partial pressures and the transit time of the RBC in the capillary.

Describe the gases that are perfusion limited or diffusion limited, how does this affect whether or not they reach equilibrium with the capillary?

Answer 9

Slide 9.

For gases that are perfusion limited (N2O and O2), their partial pressures have equilibrated with alveolar pressure before exiting the capillary.

In contrast, the partial pressure of CO, a gas that is diffusion limited, does not reach equilibrium with alveolar pressure.

O2 and CO2: normal transfer is perfusion limited.

Question 10

Graph oxygen uptake along the pulmonary capillary (transit time on horizontal axis and PO2 mmHg on vertical axis). How does this change with exercise?

At a diffusion reserve of greater than 0.5 sec…
at t=0 what is PO2?
at t=.2 sec what is PO2?

How does blood flow and transit time change during exercise?

Answer 10

Slide 10.

at t=0sec, PO2 is 40mmHg
t= 0.2 sec, PO2 is 100mmHg

Exercise:
Increased blood flow
Reduced transit time (down to 1/3)

• At rest, the PO 2 of the blood virtually reaches that of the alveolar gas after about one-third of its time in the capillary

With severe exercise, the pulmonary blood flflow is greatly increased, and the time normally spent by the red cell in the capillary, about 0.75 second,
may be reduced to as little as one-third of this. Therefore, the time available for oxygenation is less, but in normal subjects breathing air, there is generally
still no measurable fall in end-capillary Po2

Question 11

How might fibrosis or edema affect oxygen uptake? Why?

Answer 11

Increased thickness of
blood-gas barrier (fibrosis, edema)
→ oxygen uptake may become
diffusion limited

• The diffusion process is challenged by exercise, alveolar hypoxia, and thickening of the blood-gas barrier

Question 12

At lower alveolar PO2 (high altitude or low?), what can severe exercise lead to?

Answer 12

At low alveolar PO2, such as in high altitude, however, severe exercise can lead to diffusion impairment of oxygen transfer in healthy individuals.

Slide 11.

Another way of stressing the diffusion properties of the lung is to lower the alveolar PO2 (slide 11). Suppose that this has been reduced to 50 mm Hg, by the subject either going to high altitude or inhaling a low O2 mixture. Now, although the PO2 in the red cell at the start of the capillary may only be
about 20 mm Hg, the partial pressure difference responsible for driving the O2 across the blood-gas barrier has been reduced from 60 mm Hg (slide 10) to only 30 mm Hg. O2 therefore moves across more slowly. In addition, the
rate of rise of PO2 for a given increase in O2 concentration in the blood is less than it was because of the steep slope of the O2 dissociation curve when
the Po2 is low (see Chapter 6). For both of these reasons, therefore, the rise in PO2 along the capillary is relatively slow, and failure to reach the alveolar
Po2 is more likely. Thus, severe exercise at very high altitude is one of the few situations in which diffusion impairment of O2 transfer 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 of diffusion impairment if they breathe a low oxygen mixture, especially if they exercise
as well.

Question 13

Since area and thickness cannot be measured in vivo, how can you determine the rate of diffusion?

Answer 13

We have seen that oxygen transfer into the pulmonary capillary is normally
limited by the amount of blood flow available, although under some circumstances
diffusion limitation also occurs. By contrast, the transfer
of carbon monoxide is limited solely by diffusion, and it is therefore the gas of choice for measuring the diffusion properties of the lung

Rate of diffusion (V)= diffusion capacity of the lung (DL) x (P1-P2)

DL= V/(P1-P2)

partial pressure of CO in capillary blood an be neglected

DL= V(CO)/PalveolarCO

single breath method (dilute CO) to calculate DL (normal: 25mL/min/mmHg)

Question 14

Which are the only arteries in the body that carry deoxygenated blood?

What is the total blood volume in body? In alveolar network? How does this change in rest/exercise?

Answer 14

pulmonary arteries

total blood volume- 500 mL

in alveolar network: 70mL under resting, 150-200mL during exercise

Question 15

What is the driving force in the systemic circuit? (Refer to slide 14 for reference on pressures if needed)

What is the driving force in the pulmonary circuit?

Answer 15

driving pressure in systemic circuit is Pa-Pra = 90- 3= 87mmHg

driving pressure in pulmonary circuit is Ppa-Pla = 14-8= 6mmHg

CO must be seam in both circuits in the steady state bc they are in series. Resistance to flow through the lungs is less than 10% of that of rest of body.

Question 16

Describe pulmonary arteries:

Answer 16

Only arteries in the body
that carry deoxygenated blood

thin wall, minimal smooth muscle
7 x more compliant than 
systemic arteries
easily distensible –> low pressure circulation

Question 17

What are some factors influencing lung perfusion?

Calculate PVR.

Answer 17

pulmonary vascular resistance (PVR)
gravity
alveolar pressure
arterial-venous pressure gradient

PVR= change in pressure/blood flow (Q) = P(PA)-PLA/ Q(T) = 14-8 mmHg/6L/m = 1 mmHg/L.min

(Slide 16)

Question 18

Draw on a graph the relationship between PVR and changes in vascular pressures. (arterial or venous pressure on horizontal axis, pulmonary vascular resistance on vertical axis)

Explain why.

Answer 18

Slide 17.

With increasing venous or arterial pressure there is a drop in PVR (more dramatic response in arterial system)

(As arterial or venous pressure drops, increase in PVR)

The lung responds to an increase in vascular pressure with a decrease in pulmonary vascular resistance (PVR).

This behavior can be explained by the recruitment of alveolar capillaries that are closed or not perfused under normal conditions and by distension of perfused capillaries (recruitment and distension).

Question 19

Describe the pressures around pulmonary blood vessels in alvelolar and extra-alveolar vessels during FRC and TLC.

Answer 19

During inspiration from FRC to TLC, extra-alvelolar blood vessels are pulled open by radial forces of surrounding parenchyma.

Alveolar vessels are exposed to alveolar pressure and are compressed if this increases.

Slide 18/19
Alveolar vessels are exposed
to alveolar pressure
and are compressed if this increases

Alveolar” and “extra-alveolar” vessels. The first are mainly the capillaries and are exposed to alveolar pressure. The second are pulled open by the radial traction of the surrounding lung parenchyma, and the effective pressure around them is therefore lower than alveolar pressure.

Question 20

Describe how resistance to blood flow through alveolar and extra-alveolar vessels changes during inflation from RV to TLC.

Graph alveolar, extra alveolar and total (vital capacity against PVR) At what point is PVR the lowest?

(Explain graph on slide 20)?

Answer 20

Slide 20.
inflation from RV to TLC, resistance to blood flow through alveolar vessels increases, whereas resistance through extra-alveolar vessels decreases.

Thus changes in total pulmonary vascular resistance form a U shaped curve during inflation with the nadir at FRC (lowest point)

Question 21

Describe the difference between alveolar and extra-alveolar vessels. What determines their caliber?

Answer 21

Alveolar vessels are exposed to alveolar pressure and include the capillaries and the slightly larger vessels in the corners of the alveolar walls. Their caliber is determined by the relationship between alveolar pressure and the pressure within them.

Extra-alveolar vessels include all the arteries and veins that run through the lung parenchyma. Their caliber is greatly affected by lung volume because this determines the expanding pull of the parenchyma on their walls. The very large vessels near the hilum are outside the lung substance and are exposed to intrapleural pressure.

Question 22

Explain the second graph on slide 20.
Describe the effect of lung volume on PVR when transmural pressure of capillaries is held constant.

Describe extra-alveolar vessels. When is their vascular resistance low? Why? When do they have a high resistance?

Answer 22

At low lung volumes, resistance is high because the extra-alveolar vessels become narrow. At high volumes, the capillaries are stretched, and their caliber is reduced.

The caliber of the extra-alveolar vessels is determined by a balance between various forces. As we have seen, they are pulled open as the lung expands. As a result, their vascular resistance is low at large lung volumes. On the other hand, their walls contain smooth muscle and elastic
tissue, which resist distension and tend to reduce the caliber of the vessels. Consequently, they have a high resistance when lung volume is low. Indeed, if the lung is completely collapsed, the smooth muscle
tone of these vessels is so effective that the pulmonary artery pressure has to
be raised several centimeters of water above downstream pressure before any
flow at all occurs. This is called a critical opening pressure

(If alveolar pressure rises with respect to capillary pressure, the vessels tend to be
squashed, and their resistance rises. This usually occurs when a normal subject takes a deep inspiration, because the vascular pressures fall

An additional factor is that the caliber of the capillaries is reduced at large lung volumes because of stretching and consequent thinning of the alveolar walls. Thus, even if the transmural pressure of the capillaries is not changed
with large lung inflations, their vascular resistance increases_

Question 23

Describe the distribution of pulmonary blood flow. (Graph distance up lung on horizontal axis and blood flow/unit volume on vertical axis)

What does blood flow distribution depend on?

Will difference between apex and base become more or less during exercise?

Answer 23

(Like the distribution of inspired air into the vertical lung is not uniform, so is the distribution of pulmonary blood flow to the lung non-uniform.

Blood flow distribution depends on posture (upright, supine)
Difference between apex and base becomes less during exercise.

Question 24

In which zone of the lung is blood flow the greatest? What are two reasons for this?

Answer 24

3 zones are distinguished according to blood flow w the highest flow being in the base (Zone 3) and the lowest flow being in the apex (zone 1).

There are two reasons for blood flow to be higher in the lung base than apex:

1) more lung tissue (more capillaries) at the base than apex due to the triangular shape of the vertical lung.
2) since blood is much more massive than air, gravity pulls blood into the base of the lung more easily

Question 25

What determines the upper boundary between zones 1 and 2?

The lower boundary between zones 2 and 3

Answer 25

between zones 1 and 2- pressure in pulmonary artery

between zones 2 and 3 -pressure in pulmonary vein

(for blood to flow through the lung, the RV must supply sufficient pressure to overcome pulmonary vascular resistance as well as gravitational forces to push blood “up hill”

Question 26

Describe Zone 1. (Flow, pressures present, why…)

Answer 26

Zone 1 represents the lung apex, where Pa is so low that it can be exceeded by PA. The capillaries collapse because of the greater external PA, and blood flow
ceases. Under normal conditions this zone does not exist; however, this state could be reached during positive pressure mechanical ventilation or if Pa
decreased sufficiently (such as might occur with a marked decrease in blood volume)

the “no-flow” zone in the apex of the lung
No blood can reach this region bc the RV is not that strong. Both pulmonary arterial and pulmonary venous pressures are subatmospheric. This is a pathological situation due to a low RV CO and hypotension in the pulmonary circuit.
The normal lung has no zone 1 flow bc the pulmonary arterial pressure pushed the boundary between zone 2 and zone 1 several cm above the shoulders. Hence, zone 1 may still exist at very low blood pressures, such as shock.

Question 27

Describe Zone 2.

Why is this zone known also as a “compressive flow”?

Answer 27

Zone 2 is “waterfall zone” in the middle/top of the lung

Blood can flow through this region bc pulmonary arterial pressure exceeds atmospheric pressure, but blood “falls down” through the capillaries since the pulmonary venous pressure is subatmospheric. The flow in this zone functions like a Starling resistor where the alveolar pressure controls the flow, not the pressure gradient between pulmonary artery and vein. For this reason it is also known as a “compressive flow” since alveolar pressure in this zone compresses the vessels and increases their vascular resistance.

In zone 2, or the
upper third of the lung, Pa is greater than PA, which is
also greater than Pv. Because PA is greater than Pv, the
greater external PA partially collapses the capillaries
and causes a “damming” effect. This phenomenon is
often referred to as the “waterfall” effect

Question 28

Describe Zone 3.

Answer 28

“normal zone” or “continuous flow” at the base of the lung.
both pulmonary arterial and venous pressure are above atmospheric pressure and alveolar pressure has no effect on vascular resistance.

Question 29

Describe what determines hypoxic vasoconstriction. Where does it occur? How does this come into play at birth?

What effect do local vasoconstrictors/vasodilators have?

Answer 29

Hypoxic vasoconstriction occurs in small arterial
vessels in response to decreased alveolar PO2. Determined by PO2 
in alveolar gas (PAO2), but 
not by ParterialO2

Shifts blood from hypoxic areas 
to well-ventilated areas
 (graph slide 23)

Important at birth:
 First breath 
→ dramatic decrease in PVR
→ increase in pulmonary blood flow
 (from 15% of CO before birth)

Local vasoconstrictors (alpha agonist)/vasodilator (B1 agonist) effects are usually short lived and important only in pathological conditions.

Hypoxic vasoconstriction has the effect of directing blood flow away from hypoxic regions of lung. These regions may result from bronchial
obstruction, and by diverting blood flow, the deleterious effects on gas exchange are reduced. At high altitude, generalized pulmonary vasoconstriction occurs, leading to a rise in pulmonary arterial pressure. But probably
the most important situation in which this mechanism operates is at birth. During fetal life, the pulmonary vascular resistance is very high, partly because of hypoxic vasoconstriction, and only some 15% of the cardiac
output goes through the lungs (see Figure 9-5). When the first breath oxygenates the alveoli, the vascular resistance falls dramatically because of relaxation of vascular smooth muscle, and the pulmonary blood flow
increases enormously.

Question 30

What does water balance inside and outside the lung depend on? Explain.

Describe filtration and what can occur with excessive filtration into alveolar walls or pleural space.

Answer 30

depends on Starling forces (hydrostatic and oncotic pressures) on either side of capillary. Normally there is net flux of fluid out of the vessels into the interstitum, which is drained from the interstitial space by lymphatic system. If drainage rates are exceeded, interstitial lung edema develops and leads to alveolar lung edema.

Plasma water is filtered from pulmonary capillaries into alveolar walls and is eventually picked up by lymphatic, excessive filtration can lead to engorgement of the alveolar walls and even alveolar flooding (internal drowning).

plasma water is filtered from systemic capillaries into pleural space and is eventually picked up by lymphatic vessels, but excessive filtration leads to engorgement of the pleural space resulting in pleural effusions at the expense of loss of lung volume (decreased FRC)

Question 31

How does hypoxia affect PVR?

How do high levels of O2 affect PVR?

Answer 31

Isolated, local hypoxia does not alter PVR; approximately
20% of the vessels need to be hypoxic before a change
in PVR can be measured. Low inspired O2 levels as a
result of exposure to high altitude will have a greater
effect on PVR because all vessels are affected. High
levels of inspired O2 can dilate pulmonary vessels and
decrease PVR.