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In healthy lungs, oxygenis equilibrated between blood and alveolar gas by the time bloodhas passed one third of the way through an alveolar capillary.PAO2 = 150 mm Hg − 40 mm Hg/0.8 = 100 mm HgBecause PO2 is also fully equilibrated between alveolar air andblood as it passes through alveolar capillaries, and nearly all ofpulmonary blood flow is exposed to alveolar air, the normalvalue for PaO2 is nearly 100 mm Hg. Partial pressures of oxygenand carbon dioxide in inspired and alveolar air and mixedvenous and arterial blood are illustrated in Figure 13.11.158Respiratory PhysiologyPO2 ⴝ 150 mm HgPCO2 ⴝ 0 mm HgA.
Normal ventilationPCO2 ⴝCO2 productionalveolar ventilationMixed venous bloodPO2 ⴝ 40 mm HgPCO2 ⴝ 46 mm Hginspired airPO2 ⴝ 100 mm HgPCO2 ⴝ 40 mm HgAlveolusCO2O2Arterial bloodPO2 ⴝ 100 mm HgPCO2 ⴝ 40 mm HgCO2 O2TissuesCO2 O2B. Alveolar hypoventilationCO2 production(constant)PCO2 ⴝ(elevated) alveolar ventilation(decreased)Mixed venous bloodPO2 ⴝ 36 mm HgPCO2 ⴝ 66 mm HgPO2 ⴝ 150 mm HgPCO2 ⴝ 0 mm Hginspired airPO2 ⴝ 80 mm HgPCO2 ⴝ 60 mm HgAlveolusCO2O2Arterial bloodPO2 ⴝ 80 mm HgPCO2 ⴝ 60 mm HgCO2 O2TissuesCO2 O2Figure 13.11 Partial Pressures of Oxygen and Carbon Dioxide in Blood and Alveolar AirThe normal partial pressures of gases in mixed venous blood entering the alveolar capillaries are indicatedon the left side of part A. As blood flows through the alveolar capillaries in healthy lungs, oxygen and carbondioxide levels equilibrate between alveolar air and blood.
Thus, partial pressures of oxygen and carbondioxide determined by arterial blood gas (ABG) measurement are approximately equal to the partial pressures in alveolar air in healthy subjects. During hypoventilation (B, indicated by partial blockage of theairway), PO2 is reduced and PCO2 is elevated in arterial blood (the subject is hypoxic and hypercapnic) aswell as in the alveolar gas.Diffusion-Limited Gas TransportDuring very strenuous aerobic exercise in which cardiacoutput is greatly increased, or in some disease states such asinterstitial fibrosis, oxygen transport may be diffusion-limited.In other words, PO2 is not completely equilibrated betweenalveolar air and blood leaving the alveolar capillary.
The classicexample of a diffusion-limited gas is carbon monoxide (CO).When a subject breathes a gas mixture containing CO, COdiffuses from the alveolar air to blood. However, CO is boundto hemoglobin with very high affinity, and as a result, largeamounts of CO can be transferred to blood with little changein blood PCO. Thus, the partial pressures of CO in alveolar airand blood do not fully equilibrate during the transit of bloodthrough the alveolar capillary, and its transport is limited onlyby the diffusion capacity of the alveolar membrane.Diffusion in the lung can be assessed using a measurementknown as diffusion capacity of the lung for CO (DLCO).
COis useful for this purpose because its transport is diffusionlimited. According to Fick’s law,Pulmonary Ventilation and Perfusion and Diffusion of Gases159A. Pathways of O2 and CO2 diffusionO2AlveolusCO2Surface-lining fluidAlveolar epitheliumBasement membranes (fused)Capillary endotheliumPlasmaMembraneRed blood cell Intracellular fluidHemoglobin moleculesPO2 ⫽ 150 mm HgPCO2 ⫽ 0 mm HgAtmospheric air atairway openingB. Transfer of O2 and CO2 betweenalveolar air and capillary bloodO2CO2AlveolusPO2 ⴝ 100 mm HgPCO2 ⴝ 40 mm HgO2CO2PO2 ⴝ 40 mm HgPCO2 ⴝ 46 mm HgPulmonary artery(mixed venous blood)PO2 ⴝ 100 mm HgPCO2 ⴝ 40 mm HgPulmonary vein(arterial blood)Capillariesmm Hg8060Normal4846100PO2PCO280lormaAbn6044PO24042204040Transit timeduring exercise00AbnormalPCO2Normal0.250.50Transit time (sec)2048464442mm Hg100400.75Figure 13.12 O2 and CO2 Exchange Diffusion of carbon dioxide and oxygen between blood andalveolar air occurs by diffusion through the thin alveolar-capillary membrane (A).
Partial pressures of gasesin inspired air, alveolar air, and blood are illustrated in the center panel. At resting cardiac output, bloodnormally traverses the length of the alveolar capillary in 0.75 sec, and O2 and CO2 are equilibrated betweenblood and alveolar air as blood passes through the first third of the capillary (B). When the alveolar-capillarymembrane is thickened by interstitial fibrosis, the resulting diffusion barrier impedes gas exchange (dashedlines).V COPA COA × DCO × ( PCO1 − PCO2 )V CO =TDLCO =DLCO is defined as a transfer factor equal to (A/T) × DCO andis substituted in the above equation, yielding.VCO = DLCO × (PCO1 − PCO2)VENTILATION AND PERFUSION GRADIENTSRearranging and substituting PACO for PCO1 − PCO2 (becausethe concentration of CO in blood is initially zero),Optimal function of the lung requires proper balance betweenventilation and perfusion.
In other words, ventilation shouldbe matched to blood flow for efficient exchange of gases160Respiratory Physiologybetween the environment and the blood. However, neitherventilation nor perfusion of the lung is uniform from apex tobase.CLINICAL CORRELATEDLCO and Interstitial Pulmonary FibrosisInterstitial fibrosis is a type of restrictive lung disease, in whichfunctional lung volume is reduced. It is an inflammatory diseasein which deposition of connective tissue and subsequent scarformation in the interstitial space of the alveolar-capillarymembrane results in thickening of the membrane.
As a consequence, diffusion across the alveolar-capillary membrane isimpeded, and mechanical properties of the lung are altered(resulting in “restriction”; discussed in context in Chapter 14).Changes in the diffusing capacity of the lung in interstitial fibrosis are typically assessed by measurement of DLCO. Beginningat residual volume, the subject takes in a single, large breath ofair containing 0.3% CO and 10% helium, inhaling to total lungcapacity, holds this breath for 10 seconds, and then exhales. Asample of exhaled air is collected after exhalation of dead spacevolume for measurement of the final concentration of gases inalveolarair. DLCO is then determined by the formula DLCO =.VCO/PACO. PACO in this formula is the initial value upon inspiration of the gas mixture and is calculated based.
on CO concentration in inspired air and helium dilution; VCO is calculatedbased on alveolar volume, breath-hold time, and the change inCO concentration in alveolar air.Arterialpressure(mm Hg)Alveolar pressure(mm Hg)02In the standing position, the weight of the lungs stretches thetop portion of the organ, such that the alveoli near the apexhave larger volume than those near the base.
Thus, the smalleralveoli toward the base of the lung have greater compliancethan those that are already stretched by gravitational forces,and as a result, ventilation is greater toward the bottom ofthe lung. In other words, there is an increasing ventilationgradient from top to bottom of the lung.Zones of the LungAn even larger gradient (than the one for ventilation) existsfor pulmonary blood flow (perfusion) in the standing position (Fig. 13.13), whereby greater flow occurs toward thebottom of the lungs. This is the result of gravitational effectson vascular pressures and the relationship between vascularpressure and alveolar pressure as blood flows through alveolarcapillaries.
Perfusion pressure in most regional circulations isthe difference between arterial and venous pressure. However,Venous pressure (mm Hg)Zone 1. Alveolar pressure exceeds arterial pressure, and thereis no blood flow to this area. Occurs only abnormally whenalveolar pressure is increased or arterial pressure is reduced.024620281014022Zone 2. Arterial pressure exceeds alveolar pressure, andalveolar pressure exceeds venous pressure. Blood flow varieswith difference between arterial and alveolar pressure and isgreater at bottom of zone than at top.0216218206222248102Zone 3. Both arterial and venous pressures exceed alveolarpressure. Blood flow depends on arterial-venous pressuredifference, which is constant throughout the zone.
Becausearterial pressure increases down zone, transmural pressurebecomes greater, capillaries distend, and resistance to flow falls.12Figure 13.13 Distribution of Pulmonary Blood Flow As a result of gravity, blood flow through thelungs is not uniformly distributed in the standing position. At the apex of the lungs, hydrostatic pressure isreduced, potentially resulting in collapse of capillaries by alveolar pressure; as a result, flow is reducedtoward the apex, and may cease if alveolar pressure is increased or blood pressure is reduced (zone 1).
Inthe middle of the lungs (zone 2), arterial pressure exceeds alveolar pressure, but alveolar pressure is higherthan venous pressure. Flow in zone 2 is more than that in zone 1, but less than flow in zone 3, where higherhydrostatic pressure causes distension of vessels and therefore reduced vascular resistance.Pulmonary Ventilation and Perfusion and Diffusion of Gasesin the pulmonary system, as blood flows through a capillary,the rate of flow is potentially affected by air pressure in thealveoli on either side of the capillary. Blood enters the lung atthe hilum, approximately midway between apex and base;above this point of entry, hydrostatic pressure in the pulmonary vessels is reduced by the effect of gravity. At the very topof the lung, alveolar pressure may even exceed arterial pressure under some conditions, producing a region of no bloodflow, zone 1.
In regions of the lung in which alveolar pressureis higher than venous pressure but less than arterial pressure,perfusion pressure is equal to arterial pressure minus alveolarpressure. This occurs in zone 2 of the lung (see Fig. 13.13).Thus, as blood passes through alveolar capillaries in zone 2,the pressure gradient for blood flow is the difference betweenpulmonary arterial pressure and the pressure within thealveoli, which exceeds venous pressure. In contrast, in zone 3(lower portions of the lung) pulmonary vascular pressures areelevated by the effect of gravity, and both arterial and venouspressures exceed alveolar pressure. The higher hydrostaticpressure causes distension of vessels and therefore reducedresistance; as a result, blood flow is greatest in zone 3 of thelung.The Ventilation-to-Perfusion RatioAs a resultin ventilation and perfusion, the..
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