Physiology_Levy

Physiology_Levy. 0.3 0.2 •Fig. 21.2 Changes in Alveolar and Pleural Pressure During Quiet Breathing (Tidal Volume). Inspirationisrepresentedtotheleftofthevertical dotted line, andexhalationisrepresentedtotherightofit.Positive(inrelationtoatmospheric)pressuresarerepresentedabovethehorizontal dotted line, andnegativepressuresarerepresentedbelowit.Seetextfordetails.Atpointsofnoairflow(pointsAandC),alveolarpressureis0.FRC,functionalresidualcapacity. 2 1.2 •Fig. 21.3 The Various Lung Volumes and Capacities. ERV,expiratoryreservevolume;FRC,functionalresidualcapacity;FVC,forcedvitalcapacity;IC,inspiratorycapacity;IRV,inspiratoryreservevolume;RV,residualvolume;TLC,totallungcapacity;VC,vitalcapacity;VT,tidalvolume.


Physiology_Levy

Physiology_Levy. and play a major role in the work of breathing (see ). All lung volumes are subdivisions of total lung capacity (TLC), the total volume of air that is contained in the lung at the point of maximal inspiration. Lung volumes are reported in liters either as volumes or as capacities. A capacity is composed of two or more volumes. Many lung volumes are measured with a spirometer. The patient is asked to first breathe normally into the spirometer, and the volume of air (the tidal volume [VT]) that is moved into and out of the lungs with each quiet breath is measured. The patient then inhales maximally and exhales forcefully and completely, and the volume of exhaled air is measured. The total volume of exhaled air, from a maximal inspiration to a maximal exhalation, is the vital capacity (VC). Residual volume (RV) is the air remaining in the lungs after a complete exhalation. TLC is the sum of VC and RV; it is the total volume of air contained in the lungs at the end of maximal inspiration,


Physiology_Levy

Physiology_Levy. volume (RV) is the air remaining in the lungs after a complete exhalation. TLC is the sum of VC and RV; it is the total volume of air contained in the lungs at the end of maximal inspiration, and it includes the volume of air that can be moved (VC) and the volume of air that is always present (trapped) in the lungs (RV). Functional residual capacity (FRC) is the volume of air in the lungs at the end of exhalation during quiet breathing and is also called the resting volume of the lungs. FRC is composed of RV and the expiratory reserve volume (the volume of air that can be exhaled from FRC to RV).


Physiology_Levy

Physiology_Levy. Measurement of Lung Volumes RV and TLC can be measured in two ways: by helium dilution and by body plethysmography. Both methods are used clinically and provide valuable information about lung function and lung disease. The helium dilution technique is the older and simpler method, but it is often less accurate than body plethysmography, which requires sophisticated and expensive equipment. 21.1 Pulmonaryfunctiontestsareoftenusedtodiagnoseabnormalitiesinlungfunctionandtoassesstheprogressionoflungdisease.Theycandistinguishthetwomajortypesofpulmonarypathophysiologicprocesses:obstructivelungdiseasesandrestrictivelungdiseases.Forexample,innormalindividuals,theratioofRVtoTLCislessthan 0.25.Thusinahealthyindividual,approximately25%ofthetotalvolumeofairinthelungistrapped.Inobstructive pulmonary diseases, anelevationinRV/TLCratioissecondarytoanincreaseinRVoutofproportiontoanyincreaseinTLC.Incontrast,inrestrictive lung diseases, theelevationintheRV/TLCratioiscausedbyadecreaseinTLC.


Physiology_Levy

Physiology_Levy. In normal individuals, the FRC measured by helium dilution and the FRC measured by plethysmography are the same ( Table 21.1 ). This is not true in individuals with lung disease. The FRC measured by helium dilution is the volume of gas in the lung that communicates with the •Fig. 21.4 Measurement of Lung Volume by Helium Dilution. C1,knownconcentrationofaninertgas;C2,new(previouslyunknown)concentrationofthegas;V1,knownvolumeofabox;V2,lungvolume(initiallyunknown). airways, whereas the FRC measured by plethysmography is the total volume of gas in the lungs at the end of a normal exhalation. If a significant amount of gas is trapped in the lungs (because of premature airway closure; see ), the FRC determined by plethysmography is considerably higher than that determined by helium dilution.


Physiology_Levy


Physiology_Levy

Physiology_Levy. •Fig. 21.5 The Body Plethysmograph. Notethattheboxinwhichthepatientsitsisnotdepicted. Determinants of Lung Volume


Physiology_Levy

Physiology_Levy. Determinants of Lung Volume What determines the volume of air in the lung at TLC or at RV? The answer lies in the properties of the lung parenchyma and in the interaction between the lungs and the chest wall. The lungs and chest wall always move together as a unit in healthy individuals. The lung contains elastic fibers that (1) stretch when stress is applied, which results in an increase in lung volume, and (2) recoil passively when this stress is released, which results in a decrease in lung volume. The elastic recoil of the lung parenchyma is very high. In the absence of external forces (such as the force generated by the chest wall), the lungs become almost airless (10% of TLC). Similarly, chest wall volume can increase when the respiratory muscles are stretched and decrease when respiratory muscle length is shortened. In the theoretical absence of the lung parenchyma, the resting volume of the chest wall increases and is approximately 60% of TLC.


Physiology_Levy

Physiology_Levy. Lung volumes are determined by the balance between the lung’s elastic properties and the properties of the muscles of the chest wall. The maximum volume of air contained within the lung and the chest wall (i.e., TLC) is controlled by the muscles of inspiration (see ). With increasing lung volume, the chest wall muscles lengthen progressively. As these muscles lengthen, their ability to generate force decreases. TLC occurs when the inspiratory chest wall muscles are unable to generate the additional force needed to further distend the lung and chest wall. Similarly, the minimal volume of air in the –40–20 0 20 40 Pressure (cm H2O) (PL, P , or P ) •Fig. 21.6 Relaxation Pressure-Volume Curve of the Lung, Chest Wall, and Respiratory System. Thecurvefortherespiratorysystemisthesumoftheindividualcurves.Thecurveforthelungisthesameastheoneforthenormallungin


Physiology_Levy

Physiology_Levy. Fig.21.1 .FVC,forcedvitalcapacity;PL,transpulmonary(ortranslung)pressure(PL);Prs,thepressureacrosstherespiratorysystem;Pw,thetransmuralpressureacrossthechestwall;RV,residualvolume;TLC,totallungcapacity. lung (i.e., RV) is controlled by the expiratory muscle force. Decreasing lung volume results in shortening of the expiratory muscles, which, in turn, results in a decrease in muscle force. The decrease in lung volume is also associated with an increase in the outward recoil pressure of the chest wall. RV occurs when expiratory muscle force is insufficient to further reduce chest wall volume.


Physiology_Levy

Physiology_Levy. FRC, or the volume of the lung at the end of a normal exhalation, is determined by the balance between the elastic recoil pressure generated by the lung parenchyma to become smaller (inward recoil) and the pressure generated by the chest wall to become larger (outward recoil). When the chest wall muscles are weak, FRC decreases (lung elastic recoil > chest wall muscle force). In the presence of airway obstruction, FRC increases because of premature airway closure, which traps air in the lung (see


Physiology_Levy

Physiology_Levy. A number of important observations can be made from an examination of the pressurevolume curves of the lung, chest wall, and respiratory system (Fig. 21.6 ). At the resting volume of the lung (FRC), the elastic recoil of the lung acts to decrease lung volume, but this inward recoil is offset by the outward recoil of the chest wall, which acts to increase lung volume. At FRC, these forces are equal and opposite, and the muscles are relaxed. As a result, the transmural pressure across the respiratory system (Prs) at FRC is 0. At TLC, both lung pressure and chest wall pressure are positive, and both require positive transmural distending pressure. The resting volume of the chest wall, in the absence of the lungs, is the volume at which the transmural pressure for the chest wall is 0, and it is approximately 60% of TLC. At volumes greater than 60% of TLC, the chest wall recoils inward and positive transmural pressure is needed, whereas at volumes below 60% of TLC, the chest wall tends to


Physiology_Levy

Physiology_Levy. is approximately 60% of TLC. At volumes greater than 60% of TLC, the chest wall recoils inward and positive transmural pressure is needed, whereas at volumes below 60% of TLC, the chest wall tends to recoil outward.


Physiology_Levy

Physiology_Levy. The lungs alone are smallest when transpulmonary pressure is 0. The lungs, however, are not totally devoid of air when transpulmonary pressure is 0 because of the surface tension–lowering properties of surfactant (see the section “ ”). The transmural pressure for a healthy lung alone flattens at pressures higher than 20 cm H2O because the elastic limits of the lung have been reached. Thus further increases in transmural pressure produce little change in volume, and compliance (see the section ”) is low. Further distention is limited by the connective tissue (collagen, elastin) of the lung. If further pressure is applied, the alveoli near the lung surface can rupture, and air can escape into the pleural space. This is called a pneumothorax. In a pneumothorax or when the chest is opened, as during thoracic surgery, the lungs and chest wall no longer function as a single unit. The lungs recoil until transpulmonary pressure is 0; the chest wall then increases in size until trans chest


Physiology_Levy

Physiology_Levy. as during thoracic surgery, the lungs and chest wall no longer function as a single unit. The lungs recoil until transpulmonary pressure is 0; the chest wall then increases in size until trans chest wall pressure is 0.


Physiology_Levy

Physiology_Levy. The relationship between transpulmonary pressure and pleural, alveolar, and elastic recoil pressures is depicted in Fig. 21.7 . Alveolar pressure is the sum of the pleural pressure and elastic recoil pressure (Pel) of the lung: Equation 21.4 Because transpulmonary pressure (PL) = PA + Ppl, Equation 21.5 •Fig. 21.7 Relationshipbetweentranspulmonarypressure(PL)andthepleural(Ppl),alveolar(PA),andelasticrecoil(Pel)pressuresofthelung.Alveolarpressureisthesumofpleuralpressureandelasticrecoilpressure.Transpulmonarypressureisthedifferencebetweenalveolarpressureandpleuralpressure. In general, PL is the pressure distending the lung, whereas Pel is the pressure that tends to collapse the lung. Lung elastic recoil increases as the lung inflates.


Physiology_Levy

Physiology_Levy. In general, PL is the pressure distending the lung, whereas Pel is the pressure that tends to collapse the lung. Lung elastic recoil increases as the lung inflates. Lung compliance (CL) is a measure of the elastic properties of the lung. It reflects how easily the lung is distended. Lung compliance is defined as the change in lung volume resulting from a 1–cm H2O change in the distending pressure of the lung. The units of compliance are in milliliters (or liters) per centimeter of water. When lung compliance is high, the lung is readily distended. When lung compliance is low (“stiff” lung), the lung is not easily distended. The compliance of the lung (CL) is expressed as Equation 21.6 where ΔV is the change in volume and ΔP is the change in pressure. Graphically, lung compliance is the slope of the line between any two points on the deflation limb of the pressurevolume loop (


Physiology_Levy

Physiology_Levy. Fig. 21.8 ). The compliance of a normal human lung is approximately 0.2 L/cm H2O, but it varies with lung volume. Note that the lung is less distensible at high lung volumes. For this reason, compliance is corrected for the lung volume at which it is measured (specific compliance; Fig. 21.9 ). Compliance is not often measured for clinical purposes because it requires placement of an esophageal balloon. The esophageal balloon, which is connected to a pressure transducer, is an excellent surrogate marker for pleural pressure, which is very difficult to measure directly. The change in pleural pressure (Ppl) is measured as a function of the change in lung volume; that is, CL =ΔV/ΔPplor .ΔPpl =ΔCL.


Physiology_Levy

Physiology_Levy. In addition to the elastic properties of the lungs, another major determinant of lung compliance is surfactant and its •Fig. 21.8 Deflation Pressure-Volume Curve. Thepatientinhalestototallungcapacity,andtranspulmonarypressureismeasuredwiththeuseofanesophagealballoon(whichmeasurespleuralpressure).Thepatientthenexhalesslowly,andpressureismeasuredatpointsofnoairflow,whentherespiratorymusclesarerelaxed.Thepressure-volumecurveofthelungisnotthesameininspiration(notshown)andexhalation.Thisdifferenceiscalledhysteresis, anditiscausedbytheactionofsurfactant.Inaccordancewithconvention,thedeflationpressure-volumecurveisusedformeasurements.Complianceatanypointalongthiscurveisthechangeinvolumeperchangeinpressure.Thecurvedemonstratesthatlungcompliancevarieswithlungvolume.Alinecanbedrawnbetweentwodifferentvolumesonthecurve,andtheslopeofthislinerepresentsthechangeinvolume(ΔV)forachangeinpressure(ΔP).Comparethecomplianceatline1versusline


Physiology_Levy

Physiology_Levy. 1 liter = 0.2 0.5 liter = 0.1 0.1 liter = 0.02 = 0.2 5 cm H2O 0.1 liter 0.2 = 0.2 0.1 = 0.2 0.5 liter 0.02 •Fig. 21.9 Relationship Between Compliance and Lung Volume. Imaginelungsinwhicha5–cmH2Ochangeinpressureresultsina1-Lchangeinvolume(situation1).Ifonelungisremoved(situation2),thecompliancedecreases,butwhencorrectedforvolumeofthelung,thereisnochange(specificcompliance).Evenwhentheremaininglungisreducedby90%(situation3),thespecificcomplianceisunchanged.


Physiology_Levy

Physiology_Levy. effect on surface tension. Surface tension is a force caused by water molecules at the airliquid interface that tends to minimize surface area, which makes inflating the lungs more difficult. The effect of surface tension on lung inflation is illustrated by a comparison of the volumepressure curves of a salinefilled lung and of an airfilled lung. Higher pressure is necessary to fully inflate the lung with air than with saline because of the higher surface tension forces in airfilled lungs than in salinefilled lungs. Surface tension is a measure of the attractive force of the surface molecules per unit length of material to which they are attached. The units of surface tension are those of a force applied per unit length. For a sphere (such as an alveolus), the relationship between the pressure within the sphere (Ps) and the tension in the wall is described by the law of Laplace: Equation 21.7 where T is the wall tension (in dynes per centimeter) and r is the radius of the sphere.


Physiology_Levy

Physiology_Levy. Equation 21.7 where T is the wall tension (in dynes per centimeter) and r is the radius of the sphere. The alveoli are lined with a predominantly lipidbased substance called surfactant. Pulmonary surfactant serves several physiological roles, including (1) reducing the work of breathing by decreasing surface tension forces; (2) preventing collapse and sticking of alveoli on exhalation; and (3) stabilizing alveoli, especially those that tend to deflate at low surface tension. In the absence of surfactant, the surface tension at the airliquid interface would remain constant, and the transalveolar pressure needed to keep it at that volume would be higher when alveolar volumes are lower (


Physiology_Levy

Physiology_Levy. Fig. 21.10A ). Therefore, higher transalveolar pressure would be necessary to produce a given increase in alveolar volume at lower lung volumes than at higher lung volumes. Surfactant stabilizes the inflation of alveoli because it allows the surface tension to increase as the alveoli become larger (see Fig. 21.10B ). As a result, the transalveolar pressure necessary to keep an alveolus inflated increases as lung volume and transpulmonary pressure increases, and it decreases as lung volume decreases. In the presence of surfactant, surface tension is increased at high lung volume and decreased at low lung volume. The result is that the lungs can maintain alveoli at many different volumes. Otherwise, the gas in small alveoli would empty into large alveoli.


Physiology_Levy

Physiology_Levy. Pulmonary surfactant is synthesized by alveolar type II cells, stored in the cell in lamellar bodies, and secreted into the alveolar space in a precursor form (tubular myelin), from where it spreads throughout the entire alveolar surface and attains its ability to decrease surface tension. Surfactant is 85% to 90% lipids, predominantly phospholipids, and 10% to 15% proteins (


Physiology_Levy

Physiology_Levy. Table 21.2). The major phospholipid is phosphatidylcholine, approximately 75% of which is present as dipalmitoyl phosphatidylcholine (DPPC). DPPC decreases surface tension and is the major surfaceactive component in surfactant. The second most abundant phospholipid is phosphatidylglycerol, which accounts for •Fig. 21.10 Surface Forces in a Sphere Attempt to Reduce the Area of the Surface and Generate Pressure Within the Sphere. ByLaplace’slaw,thepressuregeneratedisinverselyproportionaltotheradiusofthesphere.A, Intheabsenceofsurfactant,surfaceforcesinthesmallerspheregeneratehigherpressure(heavier purple arrows) thandothoseinthelargersphere(lighter purple arrows). Asaresult,airmovesfromthesmallsphere(higherpressure)tothelargersphere(lowerpressure;black arrow).Thiscausesthesmallspheretocollapseandthelargespheretobecomeoverdistended.B, Surfactant(shaded layer)


Physiology_Levy


Physiology_Levy

Physiology_Levy. 1% to 10% of total surfactant. These lipids are important in formation of the monolayer on the alveolarair interface, and phosphatidylglycerol is important in the spreading of surfactant over a large surface area. Surfactant protein A, which is the protein most studied, is expressed in alveolar type II cells and in Clara cells in the lungs. Surfactant protein A is involved in the regulation of surfactant turnover, in immunoregulation within the lungs, and in the formation of tubular myelin.


Physiology_Levy

Physiology_Levy. Surfactant is secreted into the airway through exocytosis of the lamellar body by constitutive and regulated mechanisms. Numerous agents, including βadrenergic agonists, activators of protein kinase C, leukotrienes, and purinergic agonists, stimulate the exocytosis of surfactant. The major routes of clearance of pulmonary surfactant within the lung are reuptake by type II cells, absorption into the lymphatic vessels, and clearance by alveolar macrophages. Surfactant is readily inactivated by hypoxia, infection, and edema fluid, which results in a decrease in lung compliance.


Physiology_Levy

Physiology_Levy. In addition to surfactant, another mechanism, interdependence, contributes to stability of the alveoli. Alveoli, except for those on the pleural surface, are surrounded by other alveoli. The tendency of one alveolus to collapse is opposed by the traction exerted by the surrounding alveoli. Thus collapse of a single alveolus causes stretching and distortion of the surrounding alveoli, which in turn are connected to other alveoli. Small openings (pores of Kohn) in the alveolar walls connect adjacent alveoli, whereas the canals of Lambert connect the terminal airways to adjacent alveoli. The pores of Kohn and the canals of Lambert provide collateral ventilation and prevent alveolar collapse (atelectasis).


Physiology_Levy

Physiology_Levy. In1959,AveryandMeaddiscoveredthatinprematureinfantswhodiedofhyalinemembranedisease(HMD),thelungsweredeficientinsurfactant.HMD,alsoknownasinfantrespiratory distress syndrome, ischaracterizedbyprogressiveatelectasisandrespiratoryfailureinprematureinfants.Itisamajorcauseofmorbidityandmortalityintheneonatalperiod.Themajorsurfactantdeficiencyinpremature 1. Gas flows from areas of higher pressure to areas of lower pressure. Positive transpulmonary pressure is needed to increase lung volume. The pressure across the respiratory system is 0 at points of no airflow (end inspiration and end exhalation). At functional residual capacity (FRC), the pressure difference across the respiratory system is 0, and lung elastic recoil pressure, which operates to decrease lung volume, and the pressure generated by the chest wall to become larger are equal and opposite. 2.


Physiology_Levy

Physiology_Levy. 2. Pressure gradients in the respiratory system are created by the active contraction and subsequent relaxation of the muscles of respiration. 3. Lung volumes are determined by the balance between the lung’s elastic recoil properties and the properties of the muscles of the chest wall. Gibson GJ, Pride NB. Lung distensibility: the static pressurevolume curve of the lungs and its use in clinical assessment. Br J Dis Chest. 1976;70:143184. Jobe AH. The alveolar lining layer: a review of studies on its role in pulmonary mechanics and in the pathogenesis of atelectasis, by Mary Ellen Avery, MD, Pediatrics, 1962:30:324330. Pediatrics. 1998;102(S1):234235. infantsislackofphosphatidylglycerol.Ingeneral,asthelevelofphosphatidylglycerolincreasesinamnioticfluid,theinfantmortalityratedecreases.ResearchinthisfieldhasculminatedinsuccessfulattemptstotreatHMDinprematureinfantswithsurfactantreplacementtherapy.Today,surfactantreplacementtherapyisstandardcareforprematureinfants. 4.


Physiology_Levy

Physiology_Levy. 4. Total lung capacity (TLC) is equal to the total volume of air that can be exhaled after a maximal inspiration (vital capacity [VC]) and the air remaining in the lung after a maximal exhalation (residual volume [RV]). 5. Lung compliance is a measure of the elastic properties of the lung. Elastic recoil is lost in patients with emphysema, and this loss is associated with an increase in lung compliance, whereas in diseases associated with pulmonary fibrosis, lung compliance is decreased. 6. The surface tensionreducing and antisticking properties of surfactant increase lung compliance, decrease the work of breathing, and help stabilize alveoli of different size. Lumb AB. Nunn’s Applied Respiratory Physiology. 8th ed. St. Louis: Elsevier; 2016. Mead J, Macklem PT, vol eds. American Physiological Society Handbook of Physiology: The Respiratory System, vol. 3: Mechanics. Bethesda, MD: American Physiological Society; 1986.


Physiology_Levy

Physiology_Levy. Mead J, Macklem PT, vol eds. American Physiological Society Handbook of Physiology: The Respiratory System, vol. 3: Mechanics. Bethesda, MD: American Physiological Society; 1986. Otis AB. A perspective of respiratory mechanics. J Appl Physiol. 1983;54:11831187. Otis AB, Fenn WO, Rahn H. Mechanics of breathing in man. J Appl Physiol. 1950;2:592607. Upon completion of this chapter the student should be able to answer the following questions: 1. Describe air flow in the airways. 2. Define resistance and its affect upon airflow in the airways. 3. List and describe two categories of factors that contribute to airway resistance. 4. List the features of a spirogram and flow volume curve. 5. Describe how flow limitation occurs at the equal pressure point and the role of dynamic airway compression in flow limitation. 6. Define the components of work of breathing. 7. Understand how dynamic compliance is different from static compliance and its contribution to work of breathing.


Physiology_Levy

Physiology_Levy. 6. Define the components of work of breathing. 7. Understand how dynamic compliance is different from static compliance and its contribution to work of breathing. In this chapter, the principles that control air movement into and out of the lungs are examined. Dynamic mechanics is the study of physical systems in motion, and for the respiratory system it is the study of the properties of a lung whose volume is changing with time. Air flows into and out of an airway when there is a pressure difference at the two ends of the airway. By way of review, during inspiration the diaphragm contracts, pleural pressure becomes more negative, and gas flows into the lung (see


Physiology_Levy

Physiology_Levy. Fig. 21.2 ). To meet the changing metabolic needs of the body, gas exchange depends on the speed at which fresh gas is brought to the alveoli and the rapidity with which the metabolic products of respiration (i.e., CO2) are removed. Two major factors determine the speed at which gas flows into the airways for a given pressure change: the pattern of gas flow and the resistance to airflow by the airways. Patterns of Airflow There are two major patterns of gas flow in the airways— laminar and turbulent. Laminar flow is parallel to the airway walls and is present at low flow rates. As the flow rate increases and particularly as the airways divide, the flow stream becomes unsteady and small eddies develop. At higher flow rates the flow stream is disorganized and turbulence occurs.


Physiology_Levy

Physiology_Levy. The pressure-flow characteristics of laminar flow were first described by the French physician Poiseuille and apply to both liquids and air. In straight circular tubes the flow rate (V̇ ) is defined by the following equation: Equation 22.1 where P is the driving pressure, r is the radius of the tube, η is the viscosity of the fluid, and l is the length of the tube. It can be seen that driving pressure (P) is proportional to the flow rate (V̇ ); thus the greater the pressure, the greater the flow. The flow resistance (R) across a set of tubes is defined as the change in driving pressure (ΔP) divided by the flow rate, or: Equation 22.2


Physiology_Levy

Physiology_Levy. The flow resistance (R) across a set of tubes is defined as the change in driving pressure (ΔP) divided by the flow rate, or: Equation 22.2 The units of resistance are cm H2O/L•sec. This equation is for laminar flow and demonstrates that the radius of the tube is the most important determinant of resistance. If the radius of the tube is reduced by half, the resistance will increase 16-fold. If, however, tube length is increased twofold, the resistance will increase only twofold. Thus the radius of the tube is the principal determinant of resistance. Stated another way, resistance is inversely proportional to the fourth power of the radius, and it is directly proportional to the length of the tube and to the viscosity of the gas.


Physiology_Levy

Physiology_Levy. In turbulent flow, gas movement occurs both parallel and perpendicular to the axis of the tube. Pressure is proportional to the flow rate squared. The viscosity of the gas increases with increasing gas density, and therefore the pressure drop increases for a given flow. Overall, gas velocity is blunted because energy is consumed in the process of generating eddies and chaotic movement. As a consequence, higher driving pressure is needed to support a given turbulent flow than to support a similar laminar flow. Whether flow through a tube is laminar or turbulent depends on the Reynolds number. The Reynolds number (Re) is a dimensionless value that expresses the ratio of two dimensionally equivalent terms (kinematic/viscosity), as seen in the equation:


Physiology_Levy

Physiology_Levy. Equation 22.3 where d is the fluid density, v is the average velocity, r is the radius, and η is the viscosity. In straight tubes, turbulence occurs when the Reynolds number is greater than 2000. From this relationship it can be seen that turbulence is most likely to occur when the average velocity of the gas flow is high and the radius is large. In contrast, a low-density gas such as helium is less likely to cause turbulent flow. This is clinically relevant in states of increased airway resistance where a decrease in gas density (e.g., substituting helium for nitrogen in inspired air) can improve airflow.


Physiology_Levy

Physiology_Levy. Although these relationships apply well to smooth cylindrical tubes, application of these principles to a complicated system of tubes such as the airways is difficult. As a result, much of the flow in the airways demonstrates characteristics of both laminar and turbulent flow. In the trachea, for example, even during quiet breathing the Reynolds number is greater than 2000. Hence turbulent flow occurs in the trachea even during quiet breathing. Turbulence is also promoted by the glottis and vocal cords, which produce some irregularity and obstruction in the airways. As gas flows distally the total cross-sectional area increases dramatically, and gas velocities decrease significantly. As a result, gas flow becomes more laminar in the smaller airways even during maximal ventilation. Overall the gas flow in the larger airways (nose, mouth, glottis, and bronchi) is turbulent, whereas the gas flow in the smaller airways is laminar. Breath sounds heard with a stethoscope reflect turbulent


Physiology_Levy

Physiology_Levy. the gas flow in the larger airways (nose, mouth, glottis, and bronchi) is turbulent, whereas the gas flow in the smaller airways is laminar. Breath sounds heard with a stethoscope reflect turbulent airflow. Laminar flow is silent, which is why it is difficult to “hear” small airway disease with a stethoscope.


Physiology_Levy

Physiology_Levy. Airflow resistance is the second major factor that determines rates of airflow in the airways. Airflow resistance in the airways (Raw) differs in airways of different size. In moving from the trachea toward the alveolus, individual airways become smaller while the number of airway branches increases dramatically. Raw is equal to the sum of the resistance of each of these airways (i.e., Raw = Rlarge + Rmedium + Rsmall). From Poiseuille’s equation, one might conclude that the major site of airway resistance is in the smallest airways. In fact, however, the major site of resistance along the bronchial tree is in the first eight generations of airways. .08 .06 Respiratory zoneConducting zone Airway generation .02 .04 0 0 5 10 15 20 Resistance (cm H2 O/L/sec) •Fig. 22.1 Airwayresistanceasafunctionoftheairwaygeneration.Inanormallung,mostoftheresistancetoairflowoccursinthefirsteightairwaygenerations.


Physiology_Levy

Physiology_Levy. The smallest airways contribute very little to the overall total resistance of the bronchial tree (Fig. 22.1 ). The reason for this is twofold: (1) airflow velocity decreases substantially as the effective cross-sectional area increases (i.e., flow becomes laminar), and (2) most importantly, the airway branches in each generation exist in parallel rather than in series. The resistance of airways in parallel is the inverse of the sum of the individual resistances; therefore the overall contribution to resistance of the small airways is very small. As an example, assume that each of three tubes has a resistance of 3 cm H2O. If the tubes are in series, the total resistance (Rtot) is the sum of the individual resistances: Equation 22.4 If the tubes are in parallel (as they are in small airways), the total resistance is the sum of the inverse of the individual resistances: Equation 22.5


Physiology_Levy

Physiology_Levy. Equation 22.4 If the tubes are in parallel (as they are in small airways), the total resistance is the sum of the inverse of the individual resistances: Equation 22.5 This relationship is in marked contrast to the pulmonary blood vessels, in which most of the resistance is located in the small vessels (see ). Thus as airway diameter decreases, the resistance offered by each individual airway increases, but the large increase in the number of parallel pathways and cross-sectional area reduces the resistance at each generation of branching.


Physiology_Levy

Physiology_Levy. During normal breathing, approximately 80% of the resistance to airflow at functional residual capacity (FRC) of efferent vagal fibers, either directly or reflexively, increases ) secondary to airway constriction (recall that the vagus nerve innervates airway smooth muscle). In con trast, stimulation of sympathetic nerves and release of the postganglionic neurotransmitter norepinephrine inhibits airway constriction. Reflex stimulation of the vagus nerve by inhalation of smoke, dust, cold air, or other irritants can also result in airway constriction and coughing. Agents such as histamine, acetylcholine, thromboxane A2, prostaglandin F2, and leukotrienes (LTB4, LTC4, and LTD4) are released by resident cells (e.g., mast cells, airway epithelial cells) and recruited cells (e.g., neutrophils, eosinophils) in response to various triggers such as allergens and viral infections. These agents act directly on airway smooth muscle to cause constriction and an increase in airway resistance.


Physiology_Levy

Physiology_Levy. eosinophils) in response to various triggers such as allergens and viral infections. These agents act directly on airway smooth muscle to cause constriction and an increase in airway resistance. Inhalation •Fig. 22.2 Airwayresistance(AWR)andconductance(Cond.)asafunctionoflungvolume.


Physiology_Levy

Physiology_Levy. occurs in airways with diameters greater than 2 mm. Because the small airways contribute so little to total lung resistance, measurement of airway resistance is a poor test for detecting small airway obstruction. Factors That Contribute to Airway Resistance In healthy individuals, airway resistance is approximately 1 cm H2O/L • sec. One of the most important factors affecting resistance is lung volume. Increasing lung volume increases the caliber of the airways because it creates a positive transairway pressure. As a result, resistance to airflow decreases with increasing lung volume and increases with decreasing lung volume. If the reciprocal of resistance (i.e., conductance) is plotted against lung volume, the relationship between lung volume and conductance is linear (Fig. 22.2 ). Other factors that increase airway resistance include airway mucus, edema, and contraction of bronchial smooth muscle, all of which decrease the caliber of the airways.


Physiology_Levy

Physiology_Levy. 22.2 ). Other factors that increase airway resistance include airway mucus, edema, and contraction of bronchial smooth muscle, all of which decrease the caliber of the airways. The density and viscosity of the inspired gas also affect airway resistance. When scuba diving, gas density rises and results in an increase in airway resistance; this increase can cause problems for individuals with asthma and obstructive pulmonary disease. Breathing a low-density gas such as an oxygen-helium mixture results in a decrease in airway resistance and has been exploited in the treatment of status asthmaticus, a condition associated with increased airway resistance due to a combination of bronchospasm, airway inflammation, and hypersecretion of mucus. Neurohumoral Regulation of Airway Resistance


Physiology_Levy

Physiology_Levy. Neurohumoral Regulation of Airway Resistance In addition to the effects of disease, airway resistance is regulated by various neural and humoral agents. Stimulation of methacholine, a derivative of acetylcholine, is used to diagnose airway hyperresponsiveness, which is one of the cardinal features of certain asthma phenotypes. Although everyone is capable of responding to methacholine, airway obstruction develops in individuals with asthma at much lower concentrations of inhaled methacholine. Measurement of Expiratory Flow Measurement of expiratory flow rates and expiratory volumes is an important clinical tool for evaluating and monitoring respiratory diseases. Commonly used clinical tests have the patient inhale maximally to total lung capacity (TLC) and then exhale as rapidly and completely as possible to residual volume (RV). The test results are displayed either as a spirogram ( Fig. 22.3A ) or as a flow-volume curve/ loop (


Physiology_Levy

Physiology_Levy. Fig. 22.3A ) or as a flow-volume curve/ loop ( Fig. 22.3B ). Results from individuals with suspected lung disease are compared with results predicted from normal healthy volunteers. Predicted or normal values vary with age, sex, ethnicity, height, and to a lesser extent, weight ( Table 22.1 ). Abnormalities in values indicate abnormal pulmonary function and can be used to predict abnormalities in gas exchange. These values can detect the presence of abnormal lung function long before respiratory symptoms develop, and they can be used to determine disease severity and the response to therapy. The Spirogram A spirogram displays the volume of gas exhaled as a function of time (see Fig. 22.3A ) and measures: (1) forced vital capacity (FVC), (2) forced expiratory volume in 1 second (FEV1), (3) the ratio of FEV1 to FVC (FEV1/ FVC), and (4) the average midmaximal expiratory flow (FEF25-75).


Physiology_Levy

Physiology_Levy. The total volume of air that is exhaled during a maximal forced exhalation from TLC to RV is called the FVC. The volume of air that is exhaled in the first second during the maneuver is called the FEV1. In normal individuals, 70% to 85% (depending on age) of the FVC can be exhaled in the first second. Thus the normal FEV1/FVC ratio is greater than 70% in healthy adults. A ratio less than 70% suggests •Fig. 22.3 Theclinicalspirogram(A)andflow-volumeloop(B).Theindividualtakesamaximalinspirationandthenexhalesasrapidly,asforcibly,andasmaximallyaspossible.Thevolumeexhaledisplottedasafunctionoftime.Inthespirogramthatisreportedinclinicalsettings,exhaledvolumeincreasesfromthebottomofthetracetothetop(A).Thisisincontrasttothephysiologist’sviewofthesamemaneuver(see


Physiology_Levy

Physiology_Levy. Fig.21.3 ),inwhichtheexhaledvolumeincreasesfromthetoptothebottomofthetrace.Intheflow-volumeloop(B),exhaledvolumeisplottedasafunctionoftheinstantaneousflowrate,whichismeasuredusingapneumotachometer.Themaximalexpiratoryflowrateachievedduringthemaneuveriscalledthepeak expiratory flow rate. NotethelocationsofTLCandRVonbothtracings. difficulty exhaling because of obstruction and is a hallmark of obstructive pulmonary disease. One expiratory flow rate—the average flow rate over the middle section of the VC—can be calculated from the spirogram. This expiratory flow rate has several names, including MMEF (midmaximal expiratory flow) and FEF25-75 (forced expiratory flow from 25%–75% of VC). Although it can be calculated from the spirogram, today’s spirometers automatically calculate FEF25-75.


Physiology_Levy

Physiology_Levy. Another way of measuring lung function clinically is the flow-volume curve or loop. A flow-volume curve or loop is created by displaying the instantaneous flow rate during a forced maneuver as a function of the volume of gas. This instantaneous flow rate can be displayed both during exhalation (expiratory flow-volume curve) and during inspiration (inspiratory flow-volume curve) (see


Physiology_Levy

Physiology_Levy. Fig. 22.3B ). Expiratory flow rates are displayed above the horizontal line, and inspiratory flow rates are displayed below the horizontal line. The flow-volume loop measures: (1) the FVC, (2) the greatest flow rate achieved during the expiratory maneuver, called the peak expiratory flow rate (PEFR), and (3) multiple expiratory flow rates at various lung volumes. When the expiratory flow-volume curve is divided into quarters, the instantaneous flow rate at which 50% of the VC remains to be exhaled is called the FEF50 (also known as the V̇ max50), the instantaneous flow rate at which 75% of the VC has been exhaled is called the FEF75 (V̇ max75), and the instantaneous flow rate at which 25% of the VC has been exhaled is called the FEF25 (V̇ max25). •Fig. 22.4 Isovolumecurves.Threesuperimposedexpiratoryflowmaneuversaremadewithincreasingeffort.Notethatpeakinspiratoryandexpiratoryflowratesaredependentoneffort,whereasexpiratoryflowrateslaterinexpirationareindependentofeffort.


Physiology_Levy


Physiology_Levy

Physiology_Levy. Determinants of Maximal Flow The shape of the flow-volume loop reveals important information about normal lung physiology that can be altered by disease. Inspection of the flow-volume loop reveals that the maximum inspiratory flow is the same or slightly greater than the maximum expiratory flow. Three factors are responsible for the maximum inspiratory flow. First, the force generated by the inspiratory muscles decreases as lung volume increases above RV. Second, the recoil pressure of the lung increases as the lung volume increases above RV. This opposes the force generated by the inspiratory muscles and reduces maximum inspiratory flow. However, airway resistance decreases with increasing lung volume as the airway caliber increases. The combination of inspiratory muscle force, recoil of the lung, and changes in airway resistance causes maximal inspiratory flow to occur about halfway between TLC and RV.


Physiology_Levy

Physiology_Levy. During exhalation, maximal flow occurs early (in the first 20%) in the maneuver, and flow rates decrease progressively toward RV. Even with increasing effort, maximal flow decreases as RV is approached. This is known as expiratory flow limitation and can be demonstrated by asking an individual to perform three forced expiratory maneuvers with increasing effort.


Physiology_Levy

Physiology_Levy. Fig. 22.4 shows the results of these three maneuvers. As effort increases, peak expiratory flow increases. However, the flow rates at lower lung volumes converge; this indicates that with modest effort, maximal expiratory flow is achieved. No amount of effort will increase the flow rates as lung volume decreases. For this reason, expiratory flow rates at lower lung volumes are said to be effort independent and flow limited because maximal flow is achieved with modest effort, and no amount of additional effort can increase the flow rate beyond this limit. In contrast, events early in the expiratory maneuver are said to be effort dependent; that is, increasing effort generates increasing flow rates. In general the first 20% of the flow in the expiratory flow-volume loop is effort dependent. Flow Limitation and the Equal Pressure Point


Physiology_Levy

Physiology_Levy. Flow Limitation and the Equal Pressure Point Why is expiratory flow limited and reasonably effort independent? Factors that limit expiratory flow are important because many lung diseases affect these factors and thus affect the volume and speed with which air is moved into and out of the lung. Flow limitation occurs when the airways, which are intrinsically floppy distensible tubes, become compressed. The airways become compressed when the pressure outside the airway exceeds the pressure inside the airway. How and when this occurs is important to understanding lung disease. Fig. 22.5 shows the events that TLC, no flow •Fig. 22.5 Flowlimitation.A,Endinspiration,beforethestartofexhalation.B,Atthestartofaforcedexhalation.C,Expiratoryflowlimitationlaterinaforcedexhalation.Expiratoryflowlimitationoccursatlocationswhereairwaydiameterisnarrowedasaresultofnegativetransmuralpressure.Seetextfordetails.


Physiology_Levy

Physiology_Levy. occur during expiratory flow limitation at two different lung volumes. The airways and alveoli are surrounded by the pleural space and the chest wall. The airways are shown as tapered tubes because the total or collective airway cross-sectional area decreases from the alveoli to the trachea. At the start of exhalation but before any gas flow occurs, the pressure inside the alveolus (PA) is zero (no airflow) and pleural pressure (in this example) is −30 cm H2O. Transpulmonary pressure is thus +30 cm H2O (PL = PA − Ppl). Because there is no flow, the pressure inside the airways is zero and the pressure across the airways (Pta, transairway pressure) is +30 cm H2O [Pta = Pairway − Ppl = 0 − (−30 cm H2O)]. This positive transpulmonary and transairway pressure holds the alveoli and airways open.


Physiology_Levy

Physiology_Levy. When an active exhalation begins and the expiratory muscles contract, pleural pressure rises to +60 cm H2O (in this example). Alveolar pressure also rises, in part because of the increase in pleural pressure (+60 cm H2O) and in part because of the elastic recoil pressure of the lung at that lung volume (which in this case is 30 cm H2O). Alveolar pressure is the sum of pleural pressure and elastic recoil pressure (i.e., PA = Pel + Ppl = 30 cm H2O + 60 cm H2O = 90 cm H2O in this example). This is the driving pressure for expiratory gas flow. Because alveolar pressure exceeds atmospheric pressure, gas begins to flow from the alveolus to the mouth when the glottis opens. As gas flows out of the alveoli, the transmural pressure across the airways decreases (i.e., the pressure head for expiratory gas flow dissipates). This occurs for three reasons: (1) there is a resistive pressure drop caused by the frictional pressure loss associated with flow (expiratory airflow resistance); (2) as the


Physiology_Levy

Physiology_Levy. gas flow dissipates). This occurs for three reasons: (1) there is a resistive pressure drop caused by the frictional pressure loss associated with flow (expiratory airflow resistance); (2) as the cross-sectional area of the airways decreases toward the trachea, gas velocity increases and this acceleration of gas flow further decreases the pressure; and (3) as lung volume decreases, the elastic recoil pressure decreases.


Physiology_Levy

Physiology_Levy. Thus as air moves out of the lung, the driving pressure for expiratory gas flow decreases. In addition, the mechanical tethering that holds the airways open at high lung volumes diminishes as lung volume decreases. There is a point between the alveoli and the mouth at which the pressure inside the airways equals the pressure that surrounds the airways. This point is called the equal pressure point. Airways toward the mouth but still inside the chest wall become compressed because the pressure outside is greater than the pressure inside (dynamic airway compression). As a consequence the transairway pressure now becomes negative [Pta = Paw − Ppl = 58 − (+60) =−2 cm H2O] just beyond the equal pressure point. No amount of effort will increase the flow further because the higher pleural pressure tends to collapse the airway at the equal pressure point, just as it also tends to increase the gradient for expiratory gas flow. Under these conditions, airflow is independent of the total driving


Physiology_Levy

Physiology_Levy. tends to collapse the airway at the equal pressure point, just as it also tends to increase the gradient for expiratory gas flow. Under these conditions, airflow is independent of the total driving pressure. Hence the expiratory flow is effort independent and flow limited. It is also why airway resistance is greater during exhalation than during inspiration. In the absence of lung disease, the equal pressure point occurs in airways that contain cartilage, and thus they resist collapse. The equal pressure point, however, is not static. As lung volume decreases and as elastic recoil pressure decreases, the equal pressure point moves closer to the alveoli.


Physiology_Levy

Physiology_Levy. One additional measurement of dynamic lung mechanics should be mentioned, and this is the measurement of dynamic compliance. A dynamic pressure-volume curve can be created by having an individual breathe over a normal lung volume range (usually from FRC to FRC +1 L). The Whathappensinindividualswithlungdisease?Imagineanindividualwithairwayobstructionsecondarytoacombinationofmucus accumulationandairwayinflammation(Fig.


Physiology_Levy

Physiology_Levy. mean dynamic compliance of the lung (dyn CL) is calculated as the slope of the line that joins the end-inspiratory and end-expiratory points of no flow ( Fig. 22.7 Dynamic compliance is always less than static compliance, and it increases during exercise. This is because during tidal volume breathing, a small change in alveolar surface area is insufficient to bring additional surfactant molecules to the surface, and thus the lung is less compliant. During exercise the opposite occurs; there are large changes in Mucus, Edema, Bronchoconstriction PL = 90˜60 = 30 cm H2O Fig. 22.6 A,Flowlimitationinthepresenceofincreasedairwayresistance.B,Flowlimitationinthepresenceofalossofelasticrecoil.


Physiology_Levy

Physiology_Levy. Mucus, Edema, Bronchoconstriction PL = 90˜60 = 30 cm H2O Fig. 22.6 A,Flowlimitationinthepresenceofincreasedairwayresistance.B,Flowlimitationinthepresenceofalossofelasticrecoil. Fig. 22.7 Inflation-deflationpressure-volumecurve.Thedirectionofinspirationandexhalationisshownbythearrows.Thedifferencebetweentheinflationanddeflationpressure-volumecurvesisduetothevariationinsurfacetensionwithchangesinlungvolume.Notetheslopeofthelinejoiningpointsofnoairflow.Thisslopeislesssteepthantheslopefromthedeflationpressure-volumecurveatthesamelungvolume. tidal volume, and more surfactant material is incorporated into the air-liquid interface. Therefore the lung is more compliant.


Physiology_Levy

Physiology_Levy. tidal volume, and more surfactant material is incorporated into the air-liquid interface. Therefore the lung is more compliant. Sighing and yawning increase dynamic compliance by increasing tidal volume and restoring the normal surfactant layer. Both of these respiratory activities are important for D maintaining normal lung compliance. In contrast to the 1000 lung, the dynamic compliance of the chest wall is not significantly different from its static compliance. EF Insp. Exp. B Work of Breathing


Physiology_Levy

Physiology_Levy. EF Insp. Exp. B Work of Breathing Breathing requires the use of respiratory muscles (diaphragm, intercostals, etc.), which expends energy. Work is required to overcome the inherent mechanical properties of the lung (i.e., elastic and flow-resistive forces) and to move both the lungs and the chest wall. This work is known as the work of breathing. Changes in the mechanical properties of the lung or chest wall (or both) in the presence of disease result in an increase in the work of breathing. Respiratory muscles can perform increased work over long periods. However, the body. In the respiratory system, the work of breathing is calculated by multiplying the change in volume by the pressure exerted across the respiratory system:


Physiology_Levy

Physiology_Levy. Work of breathing (W) = Pressure (P) DC like other skeletal muscles they can fatigue, and respiratory failure may ensue. Respiratory muscle fatigue is the most common cause of respiratory failure, a process in which gas exchange is inadequate to meet the metabolic needs of Although methods are not available to measure the total amount of work involved in breathing, one can estimate the mechanical work by measuring the volume and pressure changes during a respiratory cycle. Analysis of pressure-volume curves can be used to illustrate these points. Fig. 22.8A represents a respiratory cycle of a normal lung. The static inflation-deflation curve is represented by line ABC. The total mechanical workload is represented by the trapezoidal area OAECD. In restrictive lung diseases, such as pulmonary fibrosis, lung compliance is decreased and the pressure-volume curve is shifted to the right. This results in a significant increase in the work of breathing (see


Physiology_Levy

Physiology_Levy. Fig. 22.8B ), as indicated by the increase in the trapezoidal area of OAECD. In obstructive lung diseases, such as asthma during an exacerbation or chronic bronchitis, airway resistance is elevated (see Fig. 22.8C ) and greater negative pleural pressure is needed to maintain normal inspiratory flow rates. In addition to the increase in total inspiratory work (OAECD), individuals with obstructive lung disease have an increase in positive pleural pressure during exhalation because of the increase in resistance and the increased expiratory workload, which is visualized as area DFO. The stored elastic energy, represented by area ABCF of


Physiology_Levy

Physiology_Levy. Fig. 22.8A , is not sufficient, and additional energy is needed for exhalation. With time or disease progression, these respiratory muscles can fatigue and result in respiratory failure. The work of breathing is also increased when deeper breaths are taken (an increase in tidal volume requires more elastic work to overcome) and when the respiratory rate increases (an increase in minute •Fig. 22.8 Mechanicalworkdoneduringarespiratorycycleinanormallung(A),alungwithreducedcompliance(B),andalungwithincreasedairwayresistance(C).Breakdownofthetrapezoidalareasenablesonetoappreciatetheindividualaspectsofthemechanicalworkload,whichincludethefollowing:OABCD,worknecessarytoovercomeelasticresistance;AECF,worknecessarytoovercomenonelasticresistance;AECB,worknecessarytoovercomenonelasticresistanceduringinspiration;ABCF,worknecessarytoovercomenonelasticresistanceduringexhalation(representsstoredelasticenergyfrominspiration). ventilation requires more flow resistance force to overcome) (


Physiology_Levy

Physiology_Levy. ventilation requires more flow resistance force to overcome) ( Fig. 22.9 ). Normal individuals and individuals with lung disease adopt respiratory patterns that minimize the work of breathing. For this reason, individuals with pulmonary fibrosis (increased elastic work) breathe more shallowly and rapidly, and those with obstructive lung disease (normal elastic work but increased resistive work) breathe more slowly and deeply. 60 50 40 Total work Elastic work Nonelastic work 20 10 30 10 20 30 40 Mechanical work (kg-m/min) Respiratory rate (no./min)


Physiology_Levy

Physiology_Levy. 60 50 40 Total work Elastic work Nonelastic work 20 10 30 10 20 30 40 Mechanical work (kg-m/min) Respiratory rate (no./min) Chronic obstructive pulmonary disease (COPD)isageneraltermthatincludesdiseasessuchasemphysemaandchronicbronchitis.COPDmostcommonlyoccursinindividualswhosmoke,inwhompathologicchangesinthelungconsistentwithbothemphysemaandchronicbronchitiscancoexist.ForindividualswithCOPDinwhomemphysemaisamajorcomponent,theelastictissueinthealveolarandcapillarywallsisprogressivelydestroyed,whichresultsinincreasedlungcomplianceanddecreasedelasticrecoil.Thedecreaseinelasticrecoilresultsinmovementoftheequalpressurepointtowardthealveolusandprematureairwayclosure.ThisproducesairtrappingandincreasesinRV,FRC,andTLC.Airwayresistanceisalsoincreased.Theseincreasesinlungvolumesincreasetheworkofbreathingbystretchingtherespiratorymusclesanddecreasingtheirefficiency.


Physiology_Levy


Physiology_Levy

Physiology_Levy. 1. There are two major patterns of gas flow in the airways: turbulent and laminar. 2. Resistance to airflow is the change in pressure per unit of flow. Airway resistance varies with the inverse of the fourth power of the radius and is higher in turbulent than in laminar flow. The major site of airway resistance is the first eight airway generations. Airway resistance decreases with increases in lung volume and with decreases in gas density. Airways resistance is also regulated by neural and humoral agents. 3.


Physiology_Levy

Physiology_Levy. 3. Pulmonary function tests (spirometry, flow-volume loop, body plethysmography) can detect abnormalities in lung function before individuals become symptomatic. Test results are compared with results obtained in normal individuals and vary with sex, ethnicity, age, and height. COPD is characterized by increases in lung volumes and airway resistance and by decreases in expiratory flow rates. Emphysema, a specific type of COPD, is further characterized by increased lung compliance. Restrictive lung diseases are characterized by decreases in lung volume, normal expiratory flow rates and resistance, and a marked decrease in lung compliance. 4.


Physiology_Levy

Physiology_Levy. 4. The equal pressure point is the point at which the pressure inside and surrounding the airway is the same. The location of the equal pressure point is dynamic. Specifically, as lung volume and elastic recoil decrease, the equal pressure point moves toward the alveolus in normal individuals. In individuals with chronic obstructive pulmonary disease (COPD), the equal pressure point at any lung volume is closer to the alveolus. Expiratory flow limitation occurs at the equal pressure point. 5. Energy is expended during breathing to overcome the inherent mechanical properties of the lung. Respiratory muscle fatigue is the most common cause of respiratory failure. Individuals breathe at a respiratory rate to minimize work. For individuals with increased airway resistance, work is minimized by breathing at lower frequencies. For individuals with restrictive lung diseases, work is minimized by shallow breathing at high frequencies. 6.


Physiology_Levy

Physiology_Levy. 6. The dynamic compliance of the lung is always less than the static compliance and increases during exercise, sighing, and yawning. Calverley PMA, Koulouris NG. Flow limitation and dynamic hyperinflation: key concepts in modern respiratory physiology. Eur Respir J. 2005;25:186-199. Crapo RO, et al. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis. 1981;123:659-664. Otis AB. A perspective of respiratory mechanics. J Appl Physiol. 1983;54:1183-1187. Otis AB, et al. Mechanics of breathing in man. J Appl Physiol. 1950;2:592-607. Leff AR, Schumacker PT. Respiratory Physiology: Basics and Applications. Philadelphia: Saunders; 1993. Lumb AB. Nunn’s Applied Respiratory Physiology. 8th ed. St. Louis: Elsevier; 2016. Mead J, MacKlem PT. Mechanics of breathing. In: Handbook of Physiology. Section 3, The Respiratory System. Bethesda, MD: American Physiological Society; 1986. Wiley Online Library doi:10.1002/cphys.cp0303fmo1.


Physiology_Levy

Physiology_Levy. Ventilation, Perfusion, and Ventilation/ Perfusion Relationships Upon completion of this chapter, the student should be able to answer the following questions: 1. Define two types of dead space ventilation, and describe how dead space ventilation changes with tidal volume. 2. Describe the composition of gas in ambient air, the trachea, and the alveolus, and understand how this composition changes with changes in oxygen fraction and barometric pressure. 3. Use the alveolar air equation to calculate the alveolar-arterial difference for oxygen (AaDO2). 4. Understand the alveolar carbon dioxide equation and identify how it changes with alterations in alveolar ventilation. 5. Compare the distribution of pulmonary blood flow to the distribution of ventilation. 6. List and define the four categories of hypoxia and the six causes of hypoxic hypoxia. 7. Distinguish the causes of hypoxic hypoxia on the basis of the response to 100% O2. 8. Describe the two causes of hypercapnia.


Physiology_Levy

Physiology_Levy. 7. Distinguish the causes of hypoxic hypoxia on the basis of the response to 100% O2. 8. Describe the two causes of hypercapnia. he major determinant of normal gas exchange and thus the level of PO2 and PCO2 in blood is the relationship between ventilation (V̇ ) and perfusion (Q̇ ). This relationship is called the ventilation/perfusion (V̇ /Q̇ ) ratio. Ventilation is the process by which air moves in and out of the lungs. The incoming air is composed of a volume that fills the conducting airways (dead space ventilation) and a portion that fills the alveoli (alveolar ventilation). Minute (or total) ventilation (V̇ E) is the volume of air that enters or leaves the lung per minute:


Physiology_Levy

Physiology_Levy. Equation 23.1 where f is the frequency or number of breaths per minute and VT (also known as TV) is the tidal volume, or volume of air inspired (or exhaled) per breath. Tidal volume varies with age, sex, body position, and metabolic activity. In an average-sized adult at rest, tidal volume is 500 mL. In children, it is 3 to 5 mL/kg. Dead Space Ventilation: Anatomical and Physiological Dead space ventilation is ventilation to airways that do not participate in gas exchange. There are two types of dead space: anatomical dead space and physiological dead space. Anatomical dead space (VD) is composed of the volume of gas that fills the conducting airways: Equation 23.2 where V refers to volume and the subscripts T, D, and A refer to tidal, dead space, and alveolar. A “dot” above V denotes a volume per unit of time (n): Equation 23.3


Physiology_Levy

Physiology_Levy. Equation 23.2 where V refers to volume and the subscripts T, D, and A refer to tidal, dead space, and alveolar. A “dot” above V denotes a volume per unit of time (n): Equation 23.3 Equation 23.4 where V̇ E is the total volume of gas in liters expelled from the lungs per minute (also called exhaled minute volume), V̇ D is the dead space ventilation per minute, and V̇ A is alveolar ventilation per minute. In a healthy adult, the volume of gas contained in the conducting airways at functional residual capacity (FRC) is approximately 100 to 200 mL, in comparison with the 3 L of gas in an entire lung. The ratio of the volume of the conducting airways (dead space) to tidal volume represents the fraction of each breath that is “wasted” in filling the conducting airways. This volume is related to tidal volume (VT) and to exhaled minute ventilation (V̇ E) in the following way: Equation 23.5 CHAPTER 23 Ventilation, Perfusion, and Ventilation/Perfusion Relationships


Physiology_Levy

Physiology_Levy. Equation 23.5 CHAPTER 23 Ventilation, Perfusion, and Ventilation/Perfusion Relationships If the dead space volume is 150 mL and tidal volume increases from 500 to 600 mL for the same exhaled minute ventilation, what is the effect on dead space ventilation? = 0 3. × VE and, similarly, Increasing tidal volume is an effective way to increase alveolar ventilation (and thus normal blood gas values), as might occur during exercise or periods of stress. As tidal volume increases, the fraction of the dead space ventilation decreases for the same exhaled minute ventilation.


Physiology_Levy

Physiology_Levy. Dead space ventilation (VD) varies inversely with tidal volume (VT). The larger the tidal volume, the smaller the proportion of dead space ventilation. Normally, VD/VT is 20% to 30% of exhaled minute ventilation. Changes in dead space are important contributors to work of breathing. If the dead space increases, the individual must inspire a larger tidal volume to maintain normal levels of blood gases. This adds to the work of breathing and can contribute to respiratory muscle fatigue and respiratory failure. If metabolic demands increase (e.g., during exercise or with fever), individuals with lung disease may not be able to increase tidal volume sufficiently.


Physiology_Levy

Physiology_Levy. The second type of dead space is physiological dead space. Often in diseased lungs, some alveoli are perfused but not ventilated. The total volume of gas in each breath that does not participate in gas exchange is called the physiological dead space. This volume includes the anatomical dead space and the dead space secondary to perfused but unventilated alveoli. The physiological dead space is always at least as large as the anatomical dead space, and in the presence of disease, it may be considerably larger. Both anatomical and physiological dead space can be measured, but they are not measured routinely in the course of patient care. Composition of Air Inspiration brings ambient or atmospheric air to the alveoli, where O2 is taken up and CO2 is excreted. Ambient air is a


Physiology_Levy

Physiology_Levy. Composition of Air Inspiration brings ambient or atmospheric air to the alveoli, where O2 is taken up and CO2 is excreted. Ambient air is a In individuals with certain types of chronic obstructive pulmonary disease (COPD), such as emphysema, physiological dead space is increased. If dead space doubles, tidal volume must increase in order to maintain the same level of alveolar ventilation. If tidal volume is 500 mL and VD/VT is 0.25, then If VD increases to 250 mL in this example, tidal volume (VT) must increase to 625 mL to maintain a normal alveolar ventilation (i.e., VA = 375 mL): gas mixture composed of N2 and O2, with minute quantities of CO2, argon, and inert gases. The composition of this gas mixture can be described in terms of either gas fractions or the corresponding partial pressure.


Physiology_Levy

Physiology_Levy. Because ambient air is a gas, the gas laws can be applied, from which two important principles arise. The first is that when the components are viewed in terms of gas fractions (F), the sum of the individual gas fractions must equal one: Equation 23.6 1 0. = FN2 + FO2 + Fargon and other gases It follows, then, that the sum of the partial pressures (in millimeters of mercury) of a gas, also known as the gas tension (in torr), must be equal to the total pressure. Thus at sea level, where atmospheric pressure (also known as barometric pressure [Pb]) is 760 mm Hg, the partial pressures of the gases in air are as follows: Equation 23.7 Three important gas laws govern ambient air and alveolar ventilation. According to Boyle’s law, when temperature is constant, pressure (P) and volume (V) are inversely related; that is, Boyle’s law is used in the measurement of lung volumes (see


Physiology_Levy

Physiology_Levy. Boyle’s law is used in the measurement of lung volumes (see Fig. 21.4 ). Dalton’s law is that the partial pressure of a gas in a gas mixture is the pressure that the gas would exert if it occupied the total volume of the mixture in the absence of the other components. Eq. 23.7 is an example of how Dalton’s law is used in the lung. According to Henry’s law, the concentration of a gas dissolved in a liquid is proportional to its partial pressure. The second important principle is that the partial pressure of a gas (Pgas) is equal to the fraction of that gas in the gas mixture (Fgas) multiplied by the atmospheric (barometric) pressure: Equation 23.8 Ambient air is composed of approximately 21% O2 and 79% N2. Therefore, the partial pressure of O2 in inspired ambient air (PO2) is calculated as follows:


Physiology_Levy

Physiology_Levy. Equation 23.8 Ambient air is composed of approximately 21% O2 and 79% N2. Therefore, the partial pressure of O2 in inspired ambient air (PO2) is calculated as follows: Equation 23.9 where (FiO2) is the fraction of oxygen in inspired air. The partial pressure of O2, or oxygen tension, in ambient air at the mouth at the start of inspiration is therefore 159 mm Hg, or 159 torr. The O2 tension at the mouth can be altered in one of two ways: by changing the fraction of O2 in inspired air (FiO2) or by changing barometric pressure. Thus ambient O2 tension can be increased through the administration of supplemental O2 and is decreased at high altitude.


Physiology_Levy

Physiology_Levy. The partial pressure of O2 in ambient air varies with altitude. The highest and lowest points in the contiguous United States are Mount Whitney in Sequoia National Park/ Inyo National Forest (14,505 feet; barometric pressure, 437 mm Hg) and Badwater Basin in Death Valley National Park (282 feet; barometric pressure, 768 mm Hg). On Mount Whitney, the partial pressure of O2 in ambient air is calculated as follows: . = 92 mm Hg whereas in Death Valley Badwater Basin, the partial pressure of oxygen is calculated as follows: . = 161mm Hg Note that the FiO2 does not vary at different altitudes; only the barometric pressure varies. These differences in oxygen tension have profound effects on arterial blood gas values.


Physiology_Levy

Physiology_Levy. Note that the FiO2 does not vary at different altitudes; only the barometric pressure varies. These differences in oxygen tension have profound effects on arterial blood gas values. As inspiration begins, ambient air is brought into the nasopharynx and laryngopharynx, where it becomes warmed to body temperature and humidified. Inspired air becomes saturated with water vapor by the time it reaches the glottis. Water vapor exerts a partial pressure and dilutes the total pressure in which the other gases are distributed. Water vapor pressure at body temperature is 47 mm Hg. To calculate the partial pressures of O2 and N2 in a humidified mixture, the water vapor partial pressure must be subtracted from the total barometric pressure. Thus in the conducting airways, which begin in the trachea, the partial pressure of O2 is calculated as follows: Equation 23.10 = . = 150 mm Hg and the partial pressure of N2 is calculated similarly:


Physiology_Levy

Physiology_Levy. Equation 23.10 = . = 150 mm Hg and the partial pressure of N2 is calculated similarly: Equation 23.11 = 563 mm Hg Note that the total pressure remains constant at 760 mm Hg (150 + 563 + 47 mm Hg) and that the fractions of O2 and N2 are unchanged. Water vapor pressure, however, reduces the partial pressures of O2 and N2. Note also that in the calculation of the partial pressure of ambient air ( Eq. 23.9), water vapor is ignored, and ambient air is considered “dry.” The conducting airways do not participate in gas exchange. Therefore, the partial pressures of O2, N2, and water vapor remain unchanged in the airways until the air reaches the alveolus.


Physiology_Levy

Physiology_Levy. When the inspired air reaches the alveolus, O2 is transported across the alveolar membrane into the capillary bed, and CO2 moves from the capillary bed into the alveolus. The process by which this occurs is described in . At the end of inspiration and with the glottis open, the total pressure in the alveolus is atmospheric; thus, the partial pressures of the gases in the alveolus must equal the total pressure, which in this case is atmospheric. The composition of the gas mixture, however, is changed and can be described as follows:


Physiology_Levy

Physiology_Levy. Equation 23.12 1 0. = FO2 + FN2 + FH2O + FCO2 + Fargon and other gases where N2 and argon are inert gases, and therefore the fraction of these gases in the alveolus does not change from ambient fractions. The fraction of water vapor also does not change because the inspired gas is already fully saturated with water vapor and is at body temperature. As a consequence of gas exchange, however, the fraction of O2 in the alveolus decreases, and the fraction of CO2 in the alveolus increases. Because of changes in the fractions of O2 and CO2, the partial pressures exerted by these gases also change. The partial pressure of O2 in the alveolus (PAO2) is given by the alveolar gas equation, which is also called the ideal alveolar oxygen equation: Equation 23.13 CHAPTER 23 Ventilation, Perfusion, and Ventilation/Perfusion Relationships PO2 159 150 102 90 40 PCO2 0 040 40 46 PH2O, 37°C 0 47 47 47 47 PN2 601 563 571


Physiology_Levy

Physiology_Levy. Equation 23.13 CHAPTER 23 Ventilation, Perfusion, and Ventilation/Perfusion Relationships PO2 159 150 102 90 40 PCO2 0 040 40 46 PH2O, 37°C 0 47 47 47 47 PN2 601 563 571 PCO2, partial pressure of carbon dioxide; PH2O, partial pressure of water; PN2, partial pressure of nitrogen; PO2, partial pressure of oxygen; PTOTAL, partial pressure of all parameters; R, respiratory quotient. *PN2 is increased in alveolar gas by 1% because R is normally less than 1. †Ptotal is less in venous than in arterial blood because PO2 has decreased more than PCO2 has increased.


Physiology_Levy

Physiology_Levy. where PiO2 is the partial pressure of inspired O2, which is equal to the fraction of O2 (FiO2) multiplied by the barometric pressure (Pb) minus water vapor pressure (PH2O); PACO2 is the partial pressure of alveolar CO2; and R is the respiratory exchange ratio, or respiratory quotient. The respiratory quotient is the ratio of the amount of CO2 excreted (V̇ CO2) to the amount of O2 taken up (V̇ O2) by the lungs. This quotient is the amount of CO2 produced in relation to the amount of O2 consumed by metabolism and is dependent on caloric intake. The respiratory quotient varies between 0.7 and 1.0; it is 0.7 in states of exclusive fatty acid metabolism and 1.0 in states of exclusive carbohydrate metabolism. Under normal dietary conditions, the respiratory quotient is assumed to be 0.8. Thus the quantity of O2 taken up exceeds the quantity of CO2 that is released in the alveoli. The partial pressures of O2, CO2, and N2 from ambient air to the alveolus at sea level are shown in Table 23.1


Physiology_Levy

Physiology_Levy. Table 23.1 A similar approach can be used to calculate the estimated PACO2. The fraction of CO2 in the alveolus is a function of the rate of CO2 production by the cells during metabolism and the rate at which the CO2 is eliminated from the alveolus. This process of elimination of CO2 is known as alveolar ventilation. The relationship between CO2 production and alveolar ventilation is defined by the alveolar carbon dioxide equation: Equation 23.14 where V̇ CO2 is the rate of CO2 production by the body, V̇ A is alveolar ventilation per minute, and FACO2 is the fraction of CO2 in dry alveolar gas. This relationship demonstrates that the rate of elimination of CO2 from the alveolus is related to alveolar ventilation and to the fraction of CO2 in the alveolus. Like the partial pressure of any other gas (see Eq. 23.8 ), PACO2 is defined by the following: Equation 23.15 Substituting for FACO2 in the previous equation yields the following relationship: Equation 23.16


Physiology_Levy

Physiology_Levy. Eq. 23.8 ), PACO2 is defined by the following: Equation 23.15 Substituting for FACO2 in the previous equation yields the following relationship: Equation 23.16 This equation demonstrates several important relationships. First, there is an inverse relationship between the partial pressure of CO2 in the alveolus (PACO2) and alveolar ventilation per minute (V̇ A), regardless of the exhaled CO2. Specifically, if ventilation is doubled, PACO2 decreases by 50%. Conversely, if ventilation is decreased by half, the PACO2 doubles. Second, at a constant alveolar ventilation per minute (V̇ A), doubling of the metabolic production of CO2 (V̇ CO2) causes the PACO2 to double. The relationship between V̇ A and PACO2 is depicted in Fig. 23.1


Physiology_Levy

Physiology_Levy. Fig. 23.1 In normal lungs, PaCO2 is tightly regulated and maintained at 40 ± 2 mm Hg. Increases or decreases in PaCO2, particularly when associated with changes in arterial pH, have profound effects on cell function, including enzyme and protein activity. Specialized chemoreceptors monitor PaCO2 in the brainstem ( ), and exhaled minute ventilation ( Eq. 23.1 ) varies in accordance with the level of PaCO2. An acute increase in PaCO2 results in respiratory acidosis (pH < 7.35), whereas an acute decrease in PaCO2 results in respiratory alkalosis (pH > 7.45). Hypercapnia is defined as an elevation in PaCO2, and it occurs when CO2 production exceeds alveolar ventilation (hypoventilation). Conversely, hyperventilation occurs when alveolar ventilation exceeds CO2 production, and it decreases PaCO2 (hypocapnia).


Physiology_Levy

Physiology_Levy. • Fig. 23.1 The Alveolar Partial Pressure of Carbon Dioxide (PCO2; y-axis) as a Function of Alveolar Ventilation per Minute (VA; x-axis) • Fig. 23.2 Regional Distribution of Lung Volume, Including in the Lung. Each line corresponds to a given metabolic rate asso- Alveolar Size (Circles) and Location on the Pressure-Volume ciated with a constant production of CO2 CO2 isometabolic line).


Physiology_Levy

Physiology_Levy. Alveolar Size (Circles) and Location on the Pressure-Volume ciated with a constant production of CO2 CO2 isometabolic line). Curve of the Lung at Different Lung Volumes. Because the lungs are suspended in the upright position, the pleural pressure (Ppl) and translung pressure (PL) of lung units at the apex are greater than those at the base. These lung units are larger at any lung volume than are those at the base. The effect is greatest at residual volume (RV), less so at functional residual capacity (FRC), and absent at total lung capacity (TLC). Note also that because of their “location” on the pressure-volume curve, inspired air is differentially distributed to these lung units; those at the apex are less compliant and receive a smaller Normally, alveolar ventilation is controlled to maintain an alveolar PCO2 of approximately 40 mm Hg. Thus at rest, when VCO2 is approximately 250 mL/minute, alveolar ventilation of 5 L/minute results in an alveolar


Physiology_Levy

Physiology_Levy. PCO2 of 40 mm Hg. A 50% decrease in ventilation at rest (i.e., from 5 to 2.5 L/minute) results in doubling of alveolar PCO2. During exercise, CO2 production is increased (V̇ CO2 = 750 mL/min), and to maintain normal alveolar PCO2, ventilation must increase (in this case, to 15 L/ minute). Again, however, a 50% reduction in ventilation (from 15 to 7.5 L/minute) results in doubling of the alveolar PCO2. proportion of the inspired air than do the lung units at the base, which are more compliant (i.e., are represented at a steeper part of the Distribution of Ventilation


Physiology_Levy

Physiology_Levy. proportion of the inspired air than do the lung units at the base, which are more compliant (i.e., are represented at a steeper part of the Distribution of Ventilation Ventilation is not uniformly distributed in the lung, largely because of the effects of gravity. In the upright position, at most lung volumes, alveoli near the apex of the lung are more expanded than are alveoli at the base. Gravity pulls the lung downward and away from the chest wall. As a result, pleural pressure is lower (i.e., more negative) at the apex than at the base of the lung, and static translung pressure (PL = PA − Ppl) is increased; this results in an increase in alveolar volume at the apex. Because of the difference in alveolar volume at the apex and at the base of the lung (Fig.


Physiology_Levy

Physiology_Levy. 23.2 ), alveoli at the lung base are represented along the steep portion of the pressure-volume curve, and they receive more of the ventilation (i.e., they have greater compliance). In contrast, the alveoli at the apex are represented closer to the top or flat portion of the pressure-volume curve. They have lower compliance and thus receive proportionately less of the tidal volume. The effect of gravity is less pronounced when a person is supine rather than upright, and it is less pressure-volume curve). Alveolar units with long time constants fill and empty slowly. Thus an alveolar unit with increased airway resistance or increased compliance takes longer to fill and longer to empty. In adults, the normal respiratory rate is approximately 12 breaths per minute, the inspiratory time is approximately 2 seconds, and the expiratory time is approximately 3 seconds. In normal lungs, this time is sufficient to approach volume equilibrium (


Physiology_Levy

Physiology_Levy. Fig. 23.3 ). In the presence of increased resistance or increased compliance, however, volume equilibrium is not reached. Adults with COPD have a very long time constant as a result when a person is supine rather than prone. This is because the diaphragm is pushed in a cephalad direction when a person is supine, and it affects the size of all of the alveoli. In addition to gravitational effects on the distribution of ventilation, ventilation in alveoli is not uniform. The reason for this is variable airway resistance (R) or compliance (C), and it is described quantitatively by the time constant (τ):


Physiology_Levy

Physiology_Levy. Equation 23.17 of an increase in resistance and, in the case of individuals with emphysema, an increase in compliance. As a result, such affected adults tend to breathe at a low respiratory rate. Imagine now what happens when individuals with COPD climb a flight of stairs. The increase in respiratory rate does not allow sufficient time for a full exhalation, and a process called dynamic hyperinflation occurs ( Fig. 23.4 ); lung volumes, which are already increased, increase further, the lung becomes less compliant, and the work of breathing is very high.


Physiology_Levy

Physiology_Levy. Fig. 23.4 ); lung volumes, which are already increased, increase further, the lung becomes less compliant, and the work of breathing is very high. CHAPTER 23 Ventilation, Perfusion, and Ventilation/Perfusion Relationships ˛=0.28 ˛=0.56 C=0.4 Decreased compliance C=0.8 Increased resistance R=0.7 R=1.4 R=0.7 ˛=1.12 • Fig. 23.4 Dynamic Hyperinflation. The total time for respiration (Ttot) is composed of the time for inspiration (Ti) and the time for exhalation (Te). When the respiratory rate increases (e.g., during exercise), Ttot decreases. In individuals with chronic obstructive pulmonary disease


Physiology_Levy

Physiology_Levy. C=0.8 Normal (COPD), the effect of the increase in Ttot on Te may not allow for complete emptying of the alveoli with a long time constant, and with each succeeding breath, there is an increase in the lung volume (air trapping). This increase in lung volume eventually results in such a degree of hyperinflation that the affected person is no longer able to do the work needed to overcome the decreased compliance of the lung at this high lung volume. In such individuals, it is a major cause of shortness of breath with activity. FRC, functional residual capacity.


Physiology_Levy

Physiology_Levy. • Fig. 23.3 Examples of Local Regulation of Ventilation as a Result of Variation in the Resistance (R) or Compliance (C) of Individual Lung Units. Top, The individual resistance and compliance values of three different lung units are illustrated. Bottom, The graph illustrates the volume of these three lung units as a function of time. In the upper schema, the normal lung has a time constant (τ) of 0.56 second. This lung unit reaches 97% of final volume equilibrium in 2 seconds, which is the normal inspiratory time. The lung unit at the right has a twofold increase in resistance; hence its time constant is doubled. That lung unit fills more slowly and reaches only 80% volume equilibrium during a normal inspiratory time (see graph); thus this lung unit is underventilated. The lung unit on the left has decreased compliance (is “stiff”), which acts to reduce its time constant. This lung unit fills quickly, reaching its maximum volume within 1 second, but receives only half the ventilation


Physiology_Levy

Physiology_Levy. left has decreased compliance (is “stiff”), which acts to reduce its time constant. This lung unit fills quickly, reaching its maximum volume within 1 second, but receives only half the ventilation of a normal lung unit.


Physiology_Levy

Physiology_Levy. Blood flow in the pulmonary circulation is pulsatile and influenced by pulmonary vascular resistance (PVR), gravity, alveolar pressure, and the arterial-to-venous pressure gradient. PVR is calculated as the change in pressure from the pulmonary artery (PPA) to the left atrium (PLA), divided by the flow (QT), which is cardiac output: Equation 23.18 Under normal circumstances, Equation 23.19 This resistance is about 10 times less than that in the systemic circulation. The pulmonary circulation has two unique features that allow increased blood flow on demand without an increase in pressure: (1) With increased demand, as during exertion or exercise, pulmonary vessels that are normally closed are recruited; and (2) the blood vessels in the pulmonary circulation are highly distensible, and their diameter increases with only a minimal increase in pulmonary arterial pressure.


Physiology_Levy

Physiology_Levy. Fig. 23.5). At end inspiration, the air-filled alveoli compress the alveolar capillaries and increase PVR. In contrast to the capillary beds in the systemic circulation, the capillary beds in the lungs account for approximately 40% of PVR. The diameters of the larger extra-alveolar vessels increase at end inspiration because of radial traction and elastic recoil, and their PVR is lower at higher lung volume. During exhalation, the deflated alveoli apply the least resistance to the alveolar capillaries and their PVR is diminished, whereas the higher pleural pressure during exhalation increases the PVR of extra-alveolar vessels. As a result of these opposite effects of lung volume on PVR, total PVR in the lung is lowest at FRC.


Physiology_Levy

Physiology_Levy. • Fig. 23.5 Schematic Representation of the Effects of Changes in Vital Capacity on Total Pulmonary Vascular Resistance and the Contributions to the Total Afforded by Alveolar and Extra-Alveolar Vessels. During inflation from residual volume (RV) to total lung capacity (TLC), resistance to blood flow through alveolar vessels increases, whereas resistance through extra-alveolar vessels decreases. Thus changes in total pulmonary vascular resistance are plotted as a U-shaped curve during lung inflation, with the nadir at functional residual capacity (FRC). Distribution of Pulmonary Blood Flow


Physiology_Levy

Physiology_Levy. Distribution of Pulmonary Blood Flow Because the pulmonary circulation is a low-pressure/lowresistance system, it is influenced by gravity much more dramatically than is the systemic circulation. This gravitational effect contributes to an uneven distribution of blood flow in the lungs. In normal upright persons at rest, the volume of blood flow increases from the apex of the lung to the base of the lung, where it is greatest. Similarly, in a supine individual, blood flow is least in the uppermost (anterior) regions and greatest in the lower (posterior) regions. Under conditions of stress, such as exercise, the difference in blood flow in the apex and base of the lung in upright persons becomes less, mainly because of the increase in arterial pressure.


Physiology_Levy

Physiology_Levy. On leaving the pulmonary artery, blood must travel against gravity to the apex of the lung in upright people. For every 1-cm increase in location of a pulmonary artery segment above the heart, there is a corresponding decrease in hydrostatic pressure equal to 0.74 mm Hg. Thus the pressure in a pulmonary artery segment that is 10 cm above the heart is 7.4 mm Hg less than the pressure in a segment at the level of the heart. Conversely, a pulmonary artery segment 5 cm below the heart has a 3.7–mm Hg increase in pulmonary arterial pressure. This effect of gravity on blood flow affects arteries and veins equally and results in wide variations in arterial and venous pressure from the apex to • Fig. 23.6 Model to Explain the Uneven Distribution of Blood Flow in the Lung According to the Pressures Affecting the Capillaries.


Physiology_Levy

Physiology_Levy. PA, pulmonary alveolar pressure; Pa, pulmonary arterial pressure; Pv, pulmonary venous pressure. (From West JB, et al. J Appl Physiol. 1964;19:713.) the base of the lung. These variations influence both flow and ventilation/perfusion relationships. In addition to the pulmonary arterial pressure (Pa) to pulmonary venous pressure (Pv) gradients, differences in pulmonary alveolar pressure (PA) also influence blood flow in the lung. Classically, the lung has been thought to be divided into three functional zones (


Physiology_Levy

Physiology_Levy. Fig. 23.6 ). Zone 1 represents the lung apex, where Pa is so low that it can be exceeded by PA. The capillaries collapse because of the greater external PA, and blood flow ceases. Under normal conditions, this zone does not exist; however, this state could be reached during positive-pressure mechanical ventilation or if Pa decreases sufficiently (such as might occur with a marked decrease in blood volume). In zone 2, or the upper third of the lung, Pa is greater than PA, which is in turn is greater than Pv. Because PA is greater than Pv, the greater external PA partially collapses the capillaries and causes a “damming” effect. This phenomenon is often referred to as the waterfall effect. In zone 3, Pa is greater than Pv, which is greater than PA, and blood flows in this area in accordance with the pressure gradients. Thus, pulmonary blood flow is greater in the base of the lung because the increased trans-mural pressure distends the vessels and lowers the resistance.


Physiology_Levy

Physiology_Levy. Active Regulation of Blood Flow Blood flow in the lung is regulated primarily by the passive mechanisms described previously. There are, however, several active mechanisms that regulate blood flow. Although the smooth muscle around pulmonary vessels is much thinner than that around systemic vessels, it is sufficient to affect vessel caliber and thus PVR. Oxygen levels have a major effect on blood flow. Hypoxic vasoconstriction occurs in arterioles in response to decreased PAO2. The response is local, and the result is the shifting of blood flow from CHAPTER 23 Ventilation, Perfusion, and Ventilation/Perfusion Relationships


Physiology_Levy

Physiology_Levy. CHAPTER 23 Ventilation, Perfusion, and Ventilation/Perfusion Relationships AT THE CELLULAR LEVEL • BOX 23.1 Factors and Hormones That Regulate Pulmonary Blood Flow hypoxic areas to well-perfused areas in an effort to enhance gas exchange. Isolated, local hypoxia does not alter PVR; approximately 20% of the vessels must be hypoxic before a change in PVR can be measured. Low inspired O2 levels as a result of high altitude have a greater effect on PVR because all vessels are affected. High levels of inspired O2 can dilate pulmonary vessels and decrease PVR. Other factors and some hormones (


Physiology_Levy

Physiology_Levy. Box 23.1 ) can also influence vessel caliber, but their effects are usually local, brief, and important only in pathological conditions. Pulmonary capillaries lack smooth muscle and are thus not affected by these mechanisms. In some individuals, as a consequence of chronic hypoxia or collagen vascular disease, or for no apparent reason, pulmonary artery vascular resistance and subsequently pulmonary artery pressures rise (pulmonary artery hypertension).


Physiology_Levy

Physiology_Levy. Both ventilation (V̇ ) and lung perfusion (Q̇ ) are essential components of normal gas exchange, but a normal relationship between the two components is insufficient to ensure normal gas exchange. The ventilation/perfusion ratio (also referred to as the V̇ /Q̇ ratio) is defined as the ratio of ventilation to blood flow. This ratio can be defined for a single alveolus, for a group of alveoli, or for the entire lung. At the level of a single alveolus, the ratio is defined as alveolar ventilation per minute (V̇ A) divided by capillary flow (Q̇ c). At the level of the lung, the ratio is defined as total alveolar ventilation divided by cardiac output. In normal lungs, alveolar ventilation is approximately 4.0 L/min, whereas pulmonary blood flow is approximately 5.0 L/min. Thus


Physiology_Levy

Physiology_Levy. Endothelin-1 is an amino acid peptide that is produced by the vascular endothelium. Endothelin regulates the tone of pulmonary arteries, and increased expression of endothelin-1 has been found in individuals with pulmonary artery hypertension. Endothelin-1 also decreases endothelial expression of nitric oxide synthase, which reduces levels of nitric oxide, an endothelial vasodilator. Endothelin-1 antagonists (e.g., bosentan, sitaxentan) have been produced and are important drugs in the treatment of pulmonary arterial hypertension.


Physiology_Levy

Physiology_Levy. in a normal lung, the overall ventilation/perfusion ratio is approximately 0.8, but the range of V̇ /Q̇ ratios varies widely in different lung units. When ventilation exceeds perfusion, the ventilation/perfusion ratio is greater than 1 (V̇ /Q̇ > 1), and when perfusion exceeds ventilation, the ventilation/ perfusion ratio is less than 1 (V̇ /Q̇ < 1). Mismatching of pulmonary blood flow and ventilation results in impaired O2 and CO2 transfer. In individuals with cardiopulmonary disease, mismatching of pulmonary blood flow and alveolar ventilation is the most frequent cause of systemic arterial hypoxemia (reduced PaO2). In general, V̇ /Q̇ ratios greater than 1 are not associated with hypoxemia.


Physiology_Levy

Physiology_Levy. A normal ventilation/perfusion ratio does not mean that ventilation and perfusion of that lung unit are normal; it simply means that the relationship between ventilation and perfusion is normal. For example, in lobar pneumonia, ventilation to the affected lobe is decreased. If perfusion to this area remains unchanged, perfusion would exceed ventilation; that is, the ventilation/perfusion ratio would be less than 1 (V̇ /Q̇ < 1). However, the decrease in ventilation to this area produces hypoxic vasoconstriction in the pulmonary arterial bed supplying this lobe. This results in a decrease in perfusion to the affected area and a more “normal” ventilation/perfusion ratio. Nonetheless, neither the ventilation nor the perfusion to this area is normal (both are decreased), but the relationship between the two could approach the normal range.


Physiology_Levy

Physiology_Levy. The ventilation/perfusion ratio varies in different areas of the lung. In an upright individual, although both ventilation and perfusion increase from the apex to the base of the lung, the increase in ventilation is less than the increase in blood flow. As a result, the normal V̇ /Q̇ ratio at the apex of the lung is much greater than 1 (ventilation exceeds perfusion), whereas the V̇ /Q̇ ratio at the base of the lung is much less than 1 (perfusion exceeds ventilation). The relationship between ventilation and perfusion from the apex to the base of the lung is depicted in


Physiology_Levy

Physiology_Levy. Fig. 23.7 • Fig. 23.7 Ventilation/Perfusion Relationships in a Normal Lung in the Upright Position. Only the apical and basal values are shown for clarity. In each column, the number on top represents values at the apex of the lung, and the number on the bottom represents values at the base. PCO2, partial pressure of carbon dioxide; PN2, partial pressure of nitrogen; PO2, partial pressure of oxygen; Q̇ , perfusion per minute; VA, alveolar ventilation per minute.


Physiology_Levy

Physiology_Levy. PACO2 and PaCO2 are equal because of the solubility properties of CO2 (see ). The same is not true for alveolar and arterial O2. Even in individuals with normal lungs, PAO2 is slightly greater than PaO2. The difference between PAO2 and PaO2 is called the alveolar-arterial difference for oxygen (AaDO2). An increase in the AaDO2 is a hallmark of abnormal O2 exchange. This small difference in healthy individuals is not caused by “imperfect” gas exchange, but by the small number of veins that bypass the lung and empty directly into the arterial circulation. The thebesian vessels of the left ventricular myocardium drain directly into the left ventricle (rather than into the coronary sinus in the right atrium), and some bronchial and mediastinal veins drain into the pulmonary veins. This results in venous admixture and a decrease in PaO2. (This is an example of an anatomical shunt; see the section .”) Approximately 2% to 3% of the cardiac output is shunted in this way.


Physiology_Levy

Physiology_Levy. To measure the clinical effectiveness of gas exchange in the lung, PaO2 and PaCO2 are measured. PAO2 is calculated from the alveolar air equation ( Eq. 23.13 ). The difference between the calculated PAO2 and the measured PaO2 is the AaDO2. In individuals with normal lungs who are breathing room air, the AaDO2 is less than 15 mm Hg. The mean value rises approximately 3 mm Hg per decade of life after 30 years of age. Hence, an AaDO2 lower than 25 mm Hg is considered the upper limit of normal. Assume that an individual with pneumonia is receiving 30% supplemental O2 by face mask. Arterial blood gas pH is 7.40, PaCO2 is 44 mm Hg, and PaO2 is 70 mm Hg. What is the patient’s AaDO2? (Assume that the patient is at sea level and the patient’s respiratory quotient is 0.8.) According to the alveolar air equation ( Eq. 23.13 R 44PAO2 = [0 3. × (760 − 47)] − 0 8. = 159 mm Hg Therefore, This high AaDO2 suggests that the patient has lung disease (in this case, pneumonia).


Physiology_Levy

Physiology_Levy. Eq. 23.13 R 44PAO2 = [0 3. × (760 − 47)] − 0 8. = 159 mm Hg Therefore, This high AaDO2 suggests that the patient has lung disease (in this case, pneumonia). Abnormalities in PaO2 can occur with or without an elevation in AaDO2. Hence, the relationship between PaO2 and AaDO2 is useful in determining the cause of an abnormal PaO2 and in predicting the response to therapy (particularly to supplemental O2 administration). Causes of a reduction in PaO2 (arterial hypoxemia) and their effect on AaDO2 are listed in Table 23.2 . Each of these causes is discussed in greater detail in the following sections. Arterial Blood Hypoxemia, Hypoxia, and Hypercarbia


Physiology_Levy

Physiology_Levy. Table 23.2 . Each of these causes is discussed in greater detail in the following sections. Arterial Blood Hypoxemia, Hypoxia, and Hypercarbia Arterial hypoxemia is defined as a PaO2 lower than 80 mm Hg in an adult who is breathing room air at sea level. Hypoxia is defined as insufficient O2 to carry out normal metabolic functions; hypoxia often occurs when the PaO2 is less than 60 mm Hg. There are four major categories of hypoxia. The first, hypoxic hypoxia, is the most common. The six main pulmonary conditions associated with hypoxic hypoxia—anatomical shunt, physiological shunt, decreased FiO2, V̇ /Q̇ mismatching, diffusion abnormalities, and hypoventilation—are described in the following sections and in


Physiology_Levy

Physiology_Levy. Table 23.2 . A second category is anemic hypoxia, which is caused by a decrease in the amount of functioning hemoglobin as a result of too little hemoglobin, abnormal hemoglobin, or interference with the chemical combination of oxygen and hemoglobin (e.g., carbon monoxide poisoning; see the following “ In the Clinic” box). The third category is hypoperfusion hypoxia, which results from low CHAPTER 23 Ventilation, Perfusion, and Ventilation/Perfusion Relationships AaDO2, alveolar-arterial difference for oxygen; FiO2, fraction of inspired oxygen; PaO2, partial pressure of arterial oxygen. blood flow (e.g., decreased cardiac output) and reduced oxygen delivery to the tissues. Histotoxic hypoxia, the fourth category of hypoxia, occurs when the cellular machinery that uses oxygen to produce energy is poisoned, as in cyanide poisoning. In this situation, arterial and venous PO2 are normal or increased because oxygen is not being utilized.


Physiology_Levy

Physiology_Levy. Carbon monoxide can be generated from a malfunctioning space heater, from car exhaust, or from a burning building. Individuals exposed to carbon monoxide experience headache, nausea, and dizziness, and if it is not recognized, such individuals may die. They often have a cherry-red appearance, and oxygen saturation as measured with an oximeter is high (approaching 100%). Even on an arterial blood gas, the PAO2 may be normal. Nevertheless, the tissues are depleted of O2. Thus it is imperative that the clinician recognize a potential case of carbon monoxide poisoning and order an oxygen saturation measurement with the use of a carbon monoxide oximeter. If a patient has carbon monoxide poisoning, there will be a marked difference between the measurement of oxygen saturation by oximetry and that measured with a carbon monoxide oximeter. A useful way to examine the relationship between ventila tion and perfusion is with the two–lung unit model (Fig.