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î Basic principles of diffusion

î Diffusion of oxygen / carbon dioxide /
carbon monoxide in the lung
î Factors affecting diffusion
î Diffusion of gases in tissues
  
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î xet transfer of molecules by random movement

from a zone of higher to lower partial gas
pressure
î Partial P of gas = Total P x [fract.] (Dalton)
î May be from gas- gas, gas - liquid, liquid- liquid
î Dynamic equilibrium exists for O2 between
alveolus and mitachondria (reverse for CO2)
î Static equilibrium for gases that are not
metabolised
± All tissue partial pressures approach inspired over time
± Eg. x2 and volatile agents
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î Depends on:
± Gas properties
‡ Molecular size / temperature
‡ Density:
Graham¶s Law: Rate of diffusion  1 / ¥MW
± Length of diffusion path
± Inversely related to area of interface
î Diffusing capacity = net rate of gas transfer
partial pressure gradient
± Units: ml.min-1. mmHg-1
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î PP of gas in solution = PP of same gas in a gas

mixture that is in equilibrium with the liquid
± pO2 of blood is independent of Hb concentration
î With more soluble gases, more molecules of
the gas are present in the liquid for a given PP
î Gas diffusion in solution always follows
pressure gradients
± PP exerted is inversely related to solubility
± Eg. Same concentration of x20 in water and oil
(oil: water solubility = 3:1)
‡ PP of x2O in oil is 1/3 PP in water
‡ If mixed together, x2O concentration oil: water = 3:1
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î Equilibrium between alveolar O2 and
pulmonary capillaries nearly achieved at
rest
± Uptake of O2 limited by PBF, not diffusing capacity
î Diffusing capacity may limit O2 uptake
with exercise / decreased FiO2, PiO2
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î Alveolar surfactant
î Tissue barrier (~0.5µm)
± Alveolar epithelium + basement membrane
± Interstitial space
± Pulmonary capillary epithelium + basement membrane
î Plasma layer
± Pulmonary capillary diameter ~ 7µm (= RBC diameter)
î Diffusion into RBC
± O2 diffusing capacity of free Hb is 40% greater than in RBC
± Depends on µdeformability¶ of RBC
î Time taken for combination of O2 and Hb
 'uantification of the diffusing
capacity for oxygen
oxygen uptake
O2 diffusing capacity = (alveolar - mean pul. capillary) pO2

Difficulty lies in estimating mean pulmonary capillary pO2

î Rate of O2 transfer is not solely proportional to PP
gradient
± Rate of transfer limited by rate of combination of O2 with Hb
‡ Major part of total resistance to O2 transfer
‡ Rate of combination of 4th O2 molecule with Hb >> first 3
± Rate of transfer also slows as capillary saturation rises
‡ Due to law of mass action
‡ Depends on shape of Hb dissociation curve
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î Used to measure diffusing capacity of lung

because affinity of CO for Hb is so high that
pulmonary capillary PCO remains ~ zero
î Hence: Ñ 



 

 
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Ñ
î Diffusion pathway for CO is very similar to O2
± Rate of diffusion of O2 up to entry into RBC = 1.25 x CO
± But affinity of Hb for CO = 250 x for O2
± Rate of HbCO formation reduced if high HbO2 saturation
 Pulmonary capillary transit time

= Most important determinant of pulmonary end-

capillary pO2 and diffusing capacity
± xormal value ~ 0.8s
± wide range: 0.1 -3.0s
± If < 0.25s, increased alveolar - end capillary pO2 gradient
î Mean transit time = mean Pcap. BV / PBF
î Desaturated blood from fast - transit capillaries
contribute to intrapulmonary shunt
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î CO2 is > 20 times as soluble as O2 in water

î Diffusing capacity¶ for CO2 is limited by:
1) Rate of release of CO2 from carbamino carriage
2) carbonic acid (H2CO3) CO2+ H2O

 


î Hypercapnia is never due to decreased
diffusing capacity¶
±  carbonic anhydrase is inhibited by acetazolamide
î Usual assumption is that PCO2:
2
 

 2 

 2
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X
 2
2 

1) Change in effective surface area of gas

exchange membrane
2) Change in the physical properties of the
gas exchange membrane
3) Change in the uptake of gas by the RBC
Effect of change in membrane
surface area on diffusing capacity
î Lung volume
± Maximal at TLC
± Body size
î V / ' mismatch
± Only adequately ventilated alveoli will contribute to gas
exchange
î Posture
± DLCO increased when supine despite decreased lung
volume
‡ Due to increased pulmonary blood volume and more
uniform distribution of perfusion
î Pathology
± Eg. alveolar septal destruction in emphysema
Factors influencing the membrane
diffusion barrier
î Most likely causes are chronic heart failure and
pulmonary oedema
î Pulmonary capillary congestion:
± increases diffusion path
± Produces endothelial and epithelial cell damage
± Leads to proliferation of Type II alveolar cells
î Interstitial oedema increases membrane
thickness
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î Hb concentration
± Affects rate of uptake of O2 and CO
± Measurements of diffusing capacity must be corrected for
Hb
î Decreased capillary transit time
± Anaemia / exercise
î Change in O2 disociation curve
± Eg. shift to left by hypothermia / metabolic alkalosis
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î Age
± Linear decrease in DLCO occurs with age
î Exercise
± Mechanism is reduced capillary transit time
± Hypoxaemia due to diffusion limitation can occur in athletes
î Race
± DLCO is lower in black Americans cf. White (?)
î Smoking
± DLCO is reduced in proportion to pack - year history
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î Released O2 diffuses to its site of utilisation in
the mitachondria
± PO2 of mitachondria < 10mmHg
î Diffusion paths are much longer than in lung
± fat >> muscle >> brain
î Problems with mean tissue¶ PO2:
± Varies between organs
± Varies within tissues / cells
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î ? Magnitude of PCO2 gradient between mitachondria and
tissue capillaries
î Tissue - venous PCO2 gradient can be increased by:
± Inhibition of carbonic anhydrase
‡ Blocks uptake of CO2 by blood
± Hyperoxygenation of arterial blood (PO2 of 2250mmHg)
‡ Reduces amount of reduced Hb
‡ Reduced Hb is more efficient for carbamino carriage of
CO2 than is HbO2
 

î Gas diffusion depends on properties of the gas,

the length and area of the diffusion pathway
î Gas diffusion in solutions follow pressure (
concentration) gradients
î xo significant diffusion barrier to oxygen
normally exists at rest
î The major component of resistance to O2
transfer is the time taken to form HbO2
î There is no diffusion barrier for CO2
î DLCO can be used to estimate O2 diffusing
capacity