Explain the difference between perfusion limitation and diffusion limitation in the transfer of gas between alveolus and pulmonary capillary. Outline the factors that determine whether gas transfer is perfusion or diffusion limited. (03B12)
Describe the factors that affect the transport of oxygen and carbon dioxide from the alveolus to the blood. (99A3)
Solubility determines the limitation to the rate of gas diffusion:
e.g. carbon monoxide (CO)
CO forms strong bond with Hb
=> increases in CO content result in very minimal increase in partial pressure
=> partial pressure difference still exists (ie. equilibrium is not reached) when blood finishes its passage through the alveoli
=> transfer of CO is limited by the rate of diffusion, not the amount of blood available.
e.g. nitrous oxide (N2O)
N2O doesn't form bond with Hb
=> increase in N2O content results in rapid rise in partial pressure
(equilibrium within 0.075 second)
=> equilibrium is reached very early on
=> transfer of N2O is limited by the amount of blood available.
[See diagram 20050305(2) - Diffusion limited vs Perfusion limited gas transfer]
Graham's law - relative rate of diffusion are inversely proportional to the square root of the gas molecular weight.
Transfer of O2 lies between CO and N2O.
Overall resistance to diffusion of O2 is made up of:
RBC spends about 0.75 seconds in pulmonary capillary.
O2 reacts with haemoglobin within 0.2 seconds.
=> equilibrium for O2 is reached in 0.3 seconds.
=> due the short transit time, reaction time can still be a limiting factor.
Normally O2 is perfusion-limited.
Combination of O2 with Hb means content is increased with small increase in PO2
=> partial pressure gradient maintained
=> diffusion continues
=> more O2 taken up
Diffusion rate is much slower than CO2, assuming same partial pressure difference.
[See diagram 20050305(3) - Transfer of O2]
=> O2 becomes diffusion-limited.
Even though MW of CO2 is heavier, CO2 is highly water soluble than O2
=> diffuse 20 times as fast as O2.
However, CO2 carriage is in the forms of dissolved CO2, bicarbonate, carbamino haemoglobin
=> chemical reactions involved in the latter two can limit rate.
Also, because the PvCO2-PACO2 difference is small (46-40=6mmHg)
=> it is generally assumed by the end of transit time, there is no difference between the PCO2 of alveolar gas and pulmonary end-capillary blood
NB: MCQ exam question stated that "transfer of CO2 is diffusion limited"
=> ? true
Carbon monoxide is used because the transfer of CO is diffusion limited.
DL = VCO/PACO
Helium added to mixture to measure lung volume and thus dilutional effect.
=> DL for CO = 25mLmin-1mmHg-1
When cardiac output increases due to e.g. exercise,
=> perfusion increases
=> recruitment and distension
=> increased surface area for gas exchange
=> diffusion capacity increases
Gas transfer rate is affected by
In the case of O2, additional factors include
Diffusion is defined as "the constant random thermal motion of molecules, in gaseous or liquid phases, which leads to net transfer of molecules from a region of high concentration to a region of low concentration (thermodynamic activity).
Need to add: effect of altitude
Can CO2 be called diffusion limited?