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1 By Adam Hollingworth Table of Contents Oxygen Cascade... 2 Diffusion... 2 Laws of Diffusion... 2 Diffusion & Perfusion Limitations... 3 Oxygen Uptake Along Pulmon Capillary... 4 Measurement of Diffusing Capacity... 5 Factors Affecting Diffusion Capacity for CO... 5 Overall Diffusion Resistance... 6 CO 2 Transfer Across Pulmon Capillary... 7 Different O2 Cascades... 7 Summary... 7

2 Oxygen Cascade = stepwise decrease in PO2 starting from dry room air all the way to the site of consumption (ie mitochondria) typical values in a health person on room air: Diffusion Laws of Diffusion under norm conditions PO2 difference between alveolar gas and end capillary blood should be immeasurable small. Difference is due to incomplete diffusion as defined by Fick: (not same as Fick principle) Must diffuse across blood-gas barrier: o Alveolar epithelium o Interstitial fluid o Pulmonary capillary epithelium Ficks Law: Diffusion rate is: o to the area o inversely to the thickness o to partial pressure difference o to the solubility of the gas in the tissue but inversely proportional to the square root of the molecular weight! = the diffusion constant

3 Can define Ficks law mathematically: A = area (~300 million alveoli with surface area of m 2 for the lung) P = partial pressure difference across membrane (P1 P2) T = thickness of blood gas barrier (~0.3um in lung) D = diffusion constant of gas Can define diffusion constant mathematically also: Dgas = diffusion constant MW = molecular weight = Grahams Law Figures for both equations as prev: o D CO2 ~ x20 that of D O2! means CO2 diffuses 20x faster than o2 because Co2 highly soluble but with same molecular weight o P for:! O2 = PAo2 PvO2 = 100mmhg 40mmHg = 60mmHg! CO2 = PvCO2 PACO2 = 46 40mmHg = 6mmHg Overall diffusion: o O2 = ~ 250mlO2/min o CO2 = ~ 200ml CO2/min! because of the power of solubility stronger that P difference or MW Diffusion & Perfusion Limitations At resting cardiac output rbc spends ~0.75secs in pulmonary capillary! during exercise transit time to ~0.25secs Equilibrium of partial pressures occurs within 0.25secs ie 1/3 transit time Carbon Monoxide = diffusion limited o CO rapid across blood-gas barrier CO content of rbc

4 o But CO binds so tightly to Hb that it leads to hardly any in pp of CO! affinity for Hb x250 that of O2 & rate of combination is faster o pp gradient remains ( P remains high) & CO can continue to rapidly diffuse across alveolar wall o amount of CO that gets into blood is limited by diffusion properties of barrier and not amount blood available Nitrous Oxide = perfusion (or flow) limited o Into blood, no reaction with Hb ppn2o rapidly o eg pp N20 in blood same as alveolar gas within 0.10 secs ( P = 0) o amount N20 taken up depends on blood flow O2 = usually perfusion limited under norm circumstances: o O2 combines with Hb but not as strong as CO o Resting condition : Po2 of blood reach alveolar level ~1/3 through cap transit time! perfusion limited o Abnormal conditions eg damage/thickening of blood gas barrier equilibrium not obtained in transit time! diffusion limitation Diffusion vs perfusion limitation depends on comparison of solubility of gas in the: o blood-gas barrier compared with blood! = dissociation curve! eg N20 = same; CO = very different Oxygen Uptake Along Pulmon Capillary PO2 of blood in pulmon art entering alveoli = 40mmHg Alveolar PO2 = 100mmHg Diffusion across large pressure gradient; equilibrium within ~1/3 cap transit time Diffusion reserves of normal lung are enormous with severe exercise: o cap transit time of blood o in normal people equilibrium still achieved grossly abnormal blood-gas barrier: o thickened barrier o rise in Po2 in blood much slower & equilibrium ± not achieved alveolar hypoxia: o marked in pressure gradient slower diffusion o also influenced by o2 dissociation curve as at low Po2 have hit steep slope! eg diseased lung or high altitude diffusion process is challenged by: o exercise

5 o alveolar hypoxia eg high altitude/lung disease o thickened blood-gas barrier Measurement of Diffusing Capacity Carbon monoxide (CO) is gas of choice for measuring diffusion properties as is entirely diffusion limited In living person the area & thickness of blood/gas barrier cannot be measured! Fick equation can be re-written Gas flow = D L x ΔP D L = o the diffusing capacity of the lung ie:! area! thickness! diffusion properties of b/g barrier & gas involved thus rearrange above equation to find D L = D L = V CO ΔP V CO = gas flow for CO because PaCO is so small it can be ignored leaving PACO2 only: V CO D L = P A CO! VCO and PaCO can both be measured diffusing capacity of the lung for CO = volume CO transferred in ml/min/mmhg of alveolar partial pressure Single breath method: o Single insp of dilute CO o Rate of disappearance of CO from alveolar gas during 10second breath hold is calculated o Measure inspired & expired conc of CO before & after breath hold o Helium is added to give measurement of lung volume by dilation Norm rest = 25ml/min/mmHg! this s 50-70ml/min/mmHg on exercise due to ed recruitment & distension of pulmon capillaries Factors Affecting Diffusion Capacity for CO measured diffusion capacity for CO depends on o lung surface area most common! body size: height lung volume D L! V/Q mismatch: interface for transfer D L! Posture: D L in supine! Pathology: eg emphysema alveolar septae interface D L o blood gas barrier changes:! APO: 2 methods of disruption: length of diffusion pathway through plasma or interstitial oedema

6 ed capillary pressure damaged epithelium & endothelial cells prolif of type II alveolar cells thickened membrane o factors affecting uptake of gases by Hb:! Hb concentration influences rate & amount of O2 uptake! ed capillary transit time eg exercise: causes capillary recruitment D L causes transit time: if <0.25secs o other causes of D L :! ing age! women! black Americans! smoking o exercise can double D L o in diseased lung also:! diffusion properties! alveolar volume! capillary blood Overall Diffusion Resistance Ficks law assumes all resistance to movement of O2 & Co2 resides in the alveolar wall! 2 other factors exist: Distance from alveolar wall to centre of rbc Reaction rate of O2 with Hb inside rbc! = a finite rate (for O2 & CO2 = 0.2 secs) uptake of gas effectively in 2 stages: o diffusion of gas through blood gas barrier, plasma and rbc membrane o reaction of O2 with Hb! known as θ, = mlo 2 /min that combine with 1ml of blood per mmhg of PO 2 the 2 stages can be added together = overall diffusion resistance MATHS: Ohm equation for resistance : P R = Q inverse of resistance is known as conductivity 1 = Q R P Gas flow diffusion capacity actually = conductivity: D L = P inverse of D L (1/D L) = total resistance: D L = D M + θ.v C 1/Dm = resistance of b/g barrier ie incl plasma & distance to centre of rbc θ = reaction rate of O2 with Hb analogue to diffusing capacity of 1ml of blood multiply it with total volume of pulm capillary blood (Vc) = effective diffusing capacity of rate of reaction with Hb! 1/V C.θ describes the resistance of this reaction

7 CO 2 Transfer Across Pulmon Capillary CO2 diffusion being x20 faster than o2 means (due to ed solubility) any in transfer of CO2 v unlikely will be a diffusion problem But reaction of CO2 with blood is complex it is possible any difference between end capillary blood and PACO2 can develop if b/g barrier is diseased Norm conditions: time for PaCO2 = PACO2 (40mmHg) ~ 0.25 secs (similar to O2)! good reserves for diffusion! need diffusing capacity 1/4 of normal value to see non equilibrium PACO2:PaCO2 Different O2 Cascades Partial Pressure cascade: O2 content (concentration) cascade for Hb 14g/dl: FiO2 21% FiO2 100% Dry room air = 159 mmhg Dry room Air = 760 FiO2 21% FiO2 100% Dry room air = 159 mmhg Dry room Air = 760 humidification of dry gas Saturated room air = 149 Saturated room air = 711 gas exchange in alveoli (alv gas equation) Alveolar gas = 100 Alveolar Gas 661 Incomplete diffusion ( immeasurably small) End-capillary blood ~ 100 End capillary blood ~ 661 venous admixture (shunt, V/Q mismatch) Arterial blood = 97 Arterial blood ~ 600 diffusion of O2 to cells humidification of dry gas Saturated room air = 149 Saturated room air = 711 gas exchange in alveoli (alv gas equation) Alveolar gas = 100 Alveolar Gas 661 Incomplete diffusion ( immeasurably small) End-capillary blood ~ 20 (mlo2/dl for Hb14g/dl) End capillary blood ~ 21,5 venous admixture (shunt, V/Q mismatch) Arterial blood = 20 Arterial blood ~ 21,3 diffusion of O2 to cells End-tissue capillary blood = 40 End-tissue capillary blood ~48-50 consumption in cells(mainly mitochondria) End-tissue capillary blood = 15 End-tissue capillary blood ~16,3 consumption in cells(mainly mitochondria) Mitochondria = 4 22 Mitochondria ~4-22 Mitochondria = 4 22mmHg Mitochondria ~4-22mmHg Nb: o A-a difference is different on RA compared to 100% O2:! 21% = ~4mmHg! 100% = ~61mmHg! this is due to shape of OHDC see VQ mismatching Summary Ficks law Diffusion & perfusion limited gases O2 transfer normally perfusion limited but may become diffusion limited under some circumstances Diffusing capacity of lung measured using inhaled CO. Value on exercise Finite reaction of rate of O2 with Hb transfer rate into blood

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