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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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x2 and volatile agents . gas .|   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.gas. 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.] (Dalton) î May be from gas.liquid.

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mmHg-1 .min-1.|   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.

|      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. 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 . 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.

PiO2 . |       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.

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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 .      î Alveolar surfactant î Tissue barrier (~0.

'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 .

|  Ñ`   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    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 .

BV / PBF î Desaturated blood from fast .end capillary pO2 gradient î Mean transit time = mean Pcap.transit capillaries contribute to intrapulmonary shunt .8s ± wide range: 0.1 -3.25s.0s ± If < 0. increased alveolar . Pulmonary capillary transit time = Most important determinant of pulmonary end- capillary pO2 and diffusing capacity ± xormal value ~ 0.

|  Ñ`   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   .

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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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White (?) î Smoking ± DLCO is reduced in proportion to pack .  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.year history .

|       ` 2 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 .

|         Ñ  2 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 .