Gas transfer - perfusion limited vs diffusion limited

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)

Perfusion limitation vs diffusion limitation

Solubility determines the limitation to the rate of gas diffusion:

1. Diffusion limited

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.

2. Perfusion limited

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]

Determinants of gas diffusion

1. characteristics of gas
2. characteristics of tissue
3. partial pressure gradient

Characteristics of gas

1.1. Molecular weight

Graham's law - relative rate of diffusion are inversely proportional to the square root of the gas molecular weight.

• Lighter molecules travel faster given the same energy
• Thus O2 diffuse more rapidly than CO2 in the gas phase (1.17:1)
• Only relevant in the gaseous form (i.e. from ambient gas to blood)

1.2. Solubility coefficient

• Relative solubility of CO2 and O2 in water = 24:1
• Combining with MW (Graham's Law),
  => relative rate of diffusion of CO2:O2 = 20.7:1
  => diffusion of CO2 is rarely a problem.

Transfer of O2

Transfer of O2 lies between CO and N2O.

Overall resistance to diffusion of O2 is made up of:

• diffusion of O2 through blood-gas barrier (including plasma and RBC interior)
• reaction time of O2 with haemoglobin

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.

Role of Haemoglobin

Combination of O2 with Hb means content is increased with small increase in PO2

=> partial pressure gradient maintained

=> diffusion continues

=> more O2 taken up

Gas characteritics

Diffusion rate is much slower than CO2, assuming same partial pressure difference.

Equilibrium for O2 may never be reached when

• transit time decrease (due to higher CO)
  e.g. with exercise, transit time can be 0.25 seconds
• decreased PaO2
• impairment of diffusion (alveolar-capillary block)

[See diagram 20050305(3) - Transfer of O2]

=> O2 becomes diffusion-limited.

At lower PAO2

1. PaO2 is decreased
2. Equilibrium of PO2 take longer because
   • reduced partial pressure difference
   • on the steep part of dissociation curve
     => changes in CaO2 leads to relatively small changes in PaO2

Transfer of CO2

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

 

Measuring diffusion capacity

Carbon monoxide is used because the transfer of CO is diffusion limited.

DL = VCO/PACO

Single breath method

• Single aspiration of CO mixture
• Measurement of CO concentration in inspired and expired gas (with infrared analyzer)
• 10 seconds of breath holding

Helium added to mixture to measure lung volume and thus dilutional effect.

=> DL for CO = 25mLmin^-1mmHg^-1

Effects of increased cardiac output

When cardiac output increases due to e.g. exercise,

=> perfusion increases

=> recruitment and distension

=> increased surface area for gas exchange

=> diffusion capacity increases

Summary

Gas transfer rate is affected by

• characteristics of the gas
  => directly - solubility coefficient
  => inversely - square root of MW
• characteristics of the tissue
  => directly - surface area
  => inversely - thickness,
• partial pressure difference (directly)
• Cardiac output
  => via effect on surface area

In the case of O2, additional factors include

• transit time
• diffusion into and within the RBC
• reaction with haemoglobin

 

Additional notes

Diffusion

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

Examiner's comment

• Definition and explanation of perfusion limitation and diffusion limitation
• Fick's law of diffusion
• need to state that diffusion limitation implies that the equilibrium of gas between alveolus and pulmonary capillary is incomplete.
• Need to include in relevant factors: partial pressure gradient, transit time of blood through alveoli, solubility of gas
• (extra) significance of binding of gas to haemoglobin
• (extra) effect of increase cardiac output, altitude
• graph
• (extra) transfer of CO, and its use in measuring gas transfer
• MUST discuss O2 and CO2, not just N2 and CO.

99A03

• Fick's law of simple diffusion (diffusion constant, surface area, membrane thickness, partial pressure gradient)
• effects of solubility and MW - use CO2 and O2 for comparison.
• effects of exercise, altitude, pathology, on O2 transfer
• role of haemoglobin

To be added later

Can CO2 be called diffusion limited?