Y khoa, y dược - The respiratory system: Part B

22 The Respiratory System: Part BRespiratory VolumesUsed to assess a person’s respiratory statusTidal volume (TV) Inspiratory reserve volume (IRV) Expiratory reserve volume (ERV) Residual volume (RV) Figure 22.16bRespiratoryvolumesTidal volume (TV) Amount of air inhaled or exhaled with each breath under resting conditions3100 ml Inspiratory reservevolume (IRV) Expiratory reservevolume (ERV)Residual volume (RV) Amount of air remaining in the lungs after a forced exhalation500 ml Amount of air that can be forcefully inhaled after a nor-mal tidal volume inhalationAmount of air that can beforcefully exhaled after a nor-mal tidal volume exhalation1200 ml1200 mlMeasurementDescriptionAdult maleaverage value1900 ml 500 ml 700 ml1100 mlAdult femaleaverage valueRespiratory CapacitiesInspiratory capacity (IC) Functional residual capacity (FRC)Vital capacity (VC) Total lung capacity (TLC) Figure 22.16bRespiratorycapacities(b) Summary of respiratory volumes and capacities for males and femalesFunctional residualcapacity (FRC)Volume of air remaining in the lungs after a normal tidal volume expiration: FRC = ERV + RVMaximum amount of air contained in lungs after a maximum inspiratory effort: TLC = TV + IRV + ERV + RVMaximum amount of air that can be expired after a maxi-mum inspiratory effort: VC = TV + IRV + ERVMaximum amount of air that can be inspired after a normal expiration: IC = TV + IRVTotal lung capacity (TLC)Vital capacity (VC)Inspiratory capacity (IC)6000 ml4800 ml3600 ml2400 ml4200 ml3100 ml2400 ml1800 mlFigure 22.16aInspiratoryreserve volume3100 mlTidal volume 500 ml(a) Spirographic record for a maleExpiratoryreserve volume1200 mlResidual volume1200 mlFunctionalresidualcapacity2400 mlInspiratorycapacity3600 mlVitalcapacity4800 mlTotal lungcapacity6000 mlDead SpaceSome inspired air never contributes to gas exchangeAnatomical dead space: volume of the conducting zone conduits (~150 ml)Alveolar dead space: alveoli that cease to act in gas exchange due to collapse or obstructionTotal dead space: sum of above nonuseful volumesPulmonary Function TestsSpirometer: instrument used to measure respiratory volumes and capacitiesSpirometry can distinguish betweenObstructive pulmonary disease—increased airway resistance (e.g., bronchitis)Restrictive disorders—reduction in total lung capacity due to structural or functional lung changes (e.g., fibrosis or TB)Pulmonary Function TestsMinute ventilation: total amount of gas flow into or out of the respiratory tract in one minuteForced vital capacity (FVC): gas forcibly expelled after taking a deep breathForced expiratory volume (FEV): the amount of gas expelled during specific time intervals of the FVCPulmonary Function TestsIncreases in TLC, FRC, and RV may occur as a result of obstructive disease Reduction in VC, TLC, FRC, and RV result from restrictive diseaseAlveolar VentilationAlveolar ventilation rate (AVR): flow of gases into and out of the alveoli during a particular timeDead space is normally constantRapid, shallow breathing decreases AVRAVR=frequencyX(TV – dead space)(ml/min)(breaths/min) (ml/breath)Table 22.2Nonrespiratory Air MovementsMost result from reflex actionExamples include: cough, sneeze, crying, laughing, hiccups, and yawnsGas Exchanges Between Blood, Lungs, and TissuesExternal respirationInternal respirationTo understand the above processes, first considerPhysical properties of gases Composition of alveolar gasBasic Properties of Gases: Dalton’s Law of Partial PressuresTotal pressure exerted by a mixture of gases is the sum of the pressures exerted by each gas The partial pressure of each gas is directly proportional to its percentage in the mixtureTable 22.4Basic Properties of Gases: Henry’s LawWhen a mixture of gases is in contact with a liquid, each gas will dissolve in the liquid in proportion to its partial pressureAt equilibrium, the partial pressures in the two phases will be equalThe amount of gas that will dissolve in a liquid also depends upon its solubilityCO2 is 20 times more soluble in water than O2Very little N2 dissolves in waterComposition of Alveolar GasAlveoli contain more CO2 and water vapor than atmospheric air, due toGas exchanges in the lungsHumidification of air Mixing of alveolar gas that occurs with each breath Table 22.4External RespirationExchange of O2 and CO2 across the respiratory membraneInfluenced byPartial pressure gradients and gas solubilitiesVentilation-perfusion couplingStructural characteristics of the respiratory membranePartial Pressure Gradients and Gas SolubilitiesPartial pressure gradient for O2 in the lungs is steepVenous blood Po2 = 40 mm HgAlveolar Po2 = 104 mm HgO2 partial pressures reach equilibrium of 104 mm Hg in ~0.25 seconds, about 1/3 the time a red blood cell is in a pulmonary capillaryFigure 22.18Time in thepulmonary capillary (s) P 104 mm HgO2End ofcapillary Start ofcapillaryPartial Pressure Gradients and Gas SolubilitiesPartial pressure gradient for CO2 in the lungs is less steep:Venous blood Pco2 = 45 mm HgAlveolar Pco2 = 40 mm HgCO2 is 20 times more soluble in plasma than oxygenCO2 diffuses in equal amounts with oxygen Figure 22.17Inspired air:P 160 mm HgP 0.3 mm HgBlood leavinglungs andentering tissuecapillaries:P 100 mm HgP 40 mm HgAlveoli of lungs:P 104 mm HgP 40 mm HgO2Heart Blood leavingtissues andentering lungs:P 40 mm HgP 45 mm HgSystemicveinsSystemicarteriesTissues:P less than 40 mm HgP greater than 45 mm HgInternalrespiration Externalrespiration Pulmonaryveins (P100 mm Hg)PulmonaryarteriesCO2O2CO2O2CO2O2CO2O2CO2O2Ventilation-Perfusion CouplingVentilation: amount of gas reaching the alveoliPerfusion: blood flow reaching the alveoliVentilation and perfusion must be matched (coupled) for efficient gas exchangeVentilation-Perfusion CouplingChanges in Po2 in the alveoli cause changes in the diameters of the arteriolesWhere alveolar O2 is high, arterioles dilateWhere alveolar O2 is low, arterioles constrictVentilation-Perfusion CouplingChanges in Pco2 in the alveoli cause changes in the diameters of the bronchiolesWhere alveolar CO2 is high, bronchioles dilateWhere alveolar CO2 is low, bronchioles constrictFigure 22.19Mismatch of ventilation and perfusion ventilation and/or perfusion of alveoli causes local P and PCO2O2Pulmonary arteriolesserving these alveoliconstrictO2autoregulatesarteriole diameterMatch of ventilationand perfusion ventilation, perfusion(a)(b)Mismatch of ventilation andperfusion ventilation and/or perfusion of alveoli causes local P and PCO2O2Pulmonary arteriolesserving these alveolidilateMatch of ventilationand perfusion ventilation, perfusionO2autoregulatesarteriole diameterThickness and Surface Area of the Respiratory MembraneRespiratory membranes0.5 to 1 m thickLarge total surface area (40 times that of one’s skin)Thicken if lungs become waterlogged and edematous, and gas exchange becomes inadequate Reduction in surface area with emphysema, when walls of adjacent alveoli break downInternal RespirationCapillary gas exchange in body tissuesPartial pressures and diffusion gradients are reversed compared to external respirationPo2 in tissue is always lower than in systemic arterial bloodPo2 of venous blood is 40 mm Hg and Pco2 is 45 mm HgFigure 22.17Inspired air:P 160 mm HgP 0.3 mm HgBlood leavinglungs andentering tissuecapillaries:P 100 mm HgP 40 mm HgAlveoli of lungs:P 104 mm HgP 40 mm HgO2Heart Blood leavingtissues andentering lungs:P 40 mm HgP 45 mm HgSystemicveinsSystemicarteriesTissues:P less than 40 mm HgP greater than 45 mm HgInternalrespiration Externalrespiration Pulmonaryveins (P100 mm Hg)PulmonaryarteriesCO2O2CO2O2CO2O2CO2O2CO2O2Transport of Respiratory Gases by BloodOxygen (O2) transportCarbon dioxide (CO2) transportO2 TransportMolecular O2 is carried in the blood 1.5% dissolved in plasma98.5% loosely bound to each Fe of hemoglobin (Hb) in RBCs4 O2 per Hb O2 and HemoglobinOxyhemoglobin (HbO2): hemoglobin-O2 combination Reduced hemoglobin (HHb): hemoglobin that has released O2 O2 and HemoglobinLoading and unloading of O2 is facilitated by change in shape of Hb As O2 binds, Hb affinity for O2 increasesAs O2 is released, Hb affinity for O2 decreasesFully (100%) saturated if all four heme groups carry O2Partially saturated when one to three hemes carry O2 O2 and HemoglobinRate of loading and unloading of O2 is regulated byPo2TemperatureBlood pHPco2Concentration of BPG Influence of Po2 on Hemoglobin SaturationOxygen-hemoglobin dissociation curveHemoglobin saturation plotted against Po2 is not linearS-shaped curve Shows how binding and release of O2 is influenced by the Po2 Figure 22.20O2 unloadedto restingtissuesLungsExercisingtissuesRestingtissuesAdditionalO2 unloadedto exercisingtissuesInfluence of Po2 on Hemoglobin SaturationIn arterial bloodPo2 = 100 mm HgContains 20 ml oxygen per 100 ml blood (20 vol %)Hb is 98% saturatedFurther increases in Po2 (e.g., breathing deeply) produce minimal increases in O2 bindingInfluence of Po2 on Hemoglobin SaturationIn venous bloodPo2 = 40 mm HgContains 15 vol % oxygen Hb is 75% saturatedInfluence of Po2 on Hemoglobin SaturationHemoglobin is almost completely saturated at a Po2 of 70 mm HgFurther increases in Po2 produce only small increases in O2 bindingO2 loading and delivery to tissues is adequate when Po2 is below normal levelsInfluence of Po2 on Hemoglobin Saturation Only 20–25% of bound O2 is unloaded during one systemic circulationIf O2 levels in tissues drop:More oxygen dissociates from hemoglobin and is used by cells Respiratory rate or cardiac output need not increaseFigure 22.20O2 unloadedto restingtissuesLungsExercisingtissuesRestingtissuesAdditionalO2 unloadedto exercisingtissuesOther Factors Influencing Hemoglobin SaturationIncreases in temperature, H+, Pco2, and BPGModify the structure of hemoglobin and decrease its affinity for O2Occur in systemic capillariesEnhance O2 unloading Shift the O2-hemoglobin dissociation curve to the rightDecreases in these factors shift the curve to the leftFigure 22.21O2P (mm Hg) Normal bodytemperature10°C20°C38°C43°CNormal arterialcarbon dioxide(P 40 mm Hg)or H+ (pH 7.4) CO2Increased carbon dioxide(P 80 mm Hg)or H+ (pH 7.2)CO2Decreased carbon dioxide(P 20 mm Hg) or H+ (pH 7.6)CO2(a)(b)Factors that Increase Release of O2 by HemoglobinAs cells metabolize glucosePco2 and H+ increase in concentration in capillary bloodDeclining pH weakens the hemoglobin-O2 bond (Bohr effect)Heat production increasesIncreasing temperature directly and indirectly decreases Hb affinity for O2Homeostatic ImbalanceHypoxiaInadequate O2 delivery to tissues Due to a variety of causesToo few RBCsAbnormal or too little HbBlocked circulationMetabolic poisonsPulmonary diseaseCarbon monoxideCO2 TransportCO2 is transported in the blood in three forms7 to 10% dissolved in plasma 20% bound to globin of hemoglobin (carbaminohemoglobin)70% transported as bicarbonate ions (HCO3–) in plasmaTransport and Exchange of CO2CO2 combines with water to form carbonic acid (H2CO3), which quickly dissociates:Most of the above occurs in RBCs, where carbonic anhydrase reversibly and rapidly catalyzes the reactionCO2+H2OH2CO3H++HCO3–CarbondioxideWaterCarbonic acidHydrogen ionBicarbonate ionTransport and Exchange of CO2In systemic capillariesHCO3– quickly diffuses from RBCs into the plasmaThe chloride shift occurs: outrush of HCO3– from the RBCs is balanced as Cl– moves in from the plasma Figure 22.22aRed blood cellBlood plasmaSlowTissue cellInterstitial fluidCarbonicanhydraseCO2CO2(a) Oxygen release and carbon dioxide pickup at the tissuesCO2 (dissolved in plasma)CO2 + H2OH2CO3HCO3– + H+FastCO2 + H2OH2CO3O2 (dissolved in plasma)CO2 + HbHbCO2HbO2O2 + Hb(Carbamino-hemoglobin)HCO3– + H+HCO3–Cl–Cl–HHbBinds toplasmaproteinsChlorideshift(in) viatransportproteinCO2CO2CO2CO2CO2O2O2Transport and Exchange of CO2In pulmonary capillariesHCO3– moves into the RBCs and binds with H+ to form H2CO3H2CO3 is split by carbonic anhydrase into CO2 and waterCO2 diffuses into the alveoliFigure 22.22bBlood plasmaAlveolusFused basement membranesCO2CO2CO2(b) Oxygen pickup and carbon dioxide release in the lungsCO2O2O2O2 (dissolved in plasma)Cl–SlowCO2 (dissolved in plasma)CO2 + H2OH2CO3HCO3– + H+Red blood cellCarbonicanhydraseFastCO2 + H2OH2CO3CO2 + HbHbCO2O2 + HHbHbO2 + H+(Carbamino-hemoglobin)HCO3– + H+HCO3–Cl–Chlorideshift(out) viatransportproteinHaldane EffectThe amount of CO2 transported is affected by the Po2The lower the Po2 and hemoglobin saturation with O2, the more CO2 can be carried in the bloodHaldane EffectAt the tissues, as more carbon dioxide enters the bloodMore oxygen dissociates from hemoglobin (Bohr effect)As HbO2 releases O2, it more readily forms bonds with CO2 to form carbaminohemoglobinInfluence of CO2 on Blood pHHCO3– in plasma is the alkaline reserve of the carbonic acid–bicarbonate buffer system If H+ concentration in blood rises, excess H+ is removed by combining with HCO3– If H+ concentration begins to drop, H2CO3 dissociates, releasing H+Influence of CO2 on Blood pHChanges in respiratory rate can also alter blood pHFor example, slow shallow breathing allows CO2 to accumulate in the blood, causing pH to dropChanges in ventilation can be used to adjust pH when it is disturbed by metabolic factorsControl of RespirationInvolves neurons in the reticular formation of the medulla and ponsMedullary Respiratory CentersDorsal respiratory group (DRG)Near the root of cranial nerve IX Integrates input from peripheral stretch and chemoreceptorsMedullary Respiratory Centers2. Ventral respiratory group (VRG)Rhythm-generating and integrative centerSets eupnea (12–15 breaths/minute)Inspiratory neurons excite the inspiratory muscles via the phrenic and intercostal nervesExpiratory neurons inhibit the inspiratory neuronsFigure 22.23PonsPonsVentral respiratory group (VRG)contains rhythm generatorswhose output drives respiration.Pontine respiratory centersinteract with the medullaryrespiratory centers to smooththe respiratory pattern.MedullaMedullaTo inspiratorymuscles External intercostalmusclesDiaphragmDorsal respiratory group (DRG)integrates peripheral sensoryinput and modifies the rhythmsgenerated by the VRG.Pontine Respiratory CentersInfluence and modify activity of the VRGSmooth out transition between inspiration and expiration and vice versaGenesis of the Respiratory RhythmNot well understoodMost widely accepted hypothesisReciprocal inhibition of two sets of interconnected neuronal networks in the medulla sets the rhythmDepth and Rate of BreathingDepth is determined by how actively the respiratory center stimulates the respiratory musclesRate is determined by how long the inspiratory center is activeBoth are modified in response to changing body demandsChemical FactorsInfluence of Pco2:If Pco2 levels rise (hypercapnia), CO2 accumulates in the brain CO2 is hydrated; resulting carbonic acid dissociates, releasing H+H+ stimulates the central chemoreceptors of the brain stemChemoreceptors synapse with the respiratory regulatory centers, increasing the depth and rate of breathingFigure 22.25Initial stimulusResultPhysiological responseVentilation(more CO2 exhaled)Arterial P and pHreturn to normalCO2Medullaryrespiratory centersRespiratory muscleAfferent impulsesEfferent impulsesArterial PCO2Central chemoreceptorsin medulla respond to H+in brain ECF (mediate 70% of the CO2 response)Peripheral chemoreceptorsin carotid and aortic bodies (mediate 30% of the CO2response)P decreases pH in brain extracellular fluid (ECF)CO2Depth and Rate of BreathingHyperventilation: increased depth and rate of breathing that exceeds the body’s need to remove CO2Causes CO2 levels to decline (hypocapnia)May cause cerebral vasoconstriction and cerebral ischemiaApnea: period of breathing cessation that occurs when Pco2 is abnormally lowChemical FactorsInfluence of Po2Peripheral chemoreceptors in the aortic and carotid bodies are O2 sensorsWhen excited, they cause the respiratory centers to increase ventilationSubstantial drops in arterial Po2 (to 60 mm Hg) must occur in order to stimulate increased ventilationFigure 22.26BrainSensory nerve fiber in cranial nerve IX(pharyngeal branch of glossopharyngeal) External carotid arteryInternal carotid arteryCarotid bodyCommon carotid arteryCranial nerve X (vagus nerve)Sensory nerve fiber incranial nerve X Aortic bodies in aortic archAortaHeartChemical FactorsInfluence of arterial pHCan modify respiratory rate and rhythm even if CO2 and O2 levels are normalDecreased pH may reflectCO2 retentionAccumulation of lactic acidExcess ketone bodies in patients with diabetes mellitusRespiratory system controls will attempt to raise the pH by increasing respiratory rate and depthSummary of Chemical FactorsRising CO2 levels are the most powerful respiratory stimulantNormally blood Po2 affects breathing only indirectly by influencing peripheral chemoreceptor sensitivity to changes in Pco2Summary of Chemical FactorsWhen arterial Po2 falls below 60 mm Hg, it becomes the major stimulus for respiration (via the peripheral chemoreceptors)Changes in arterial pH resulting from CO2 retention or metabolic factors act indirectly through the peripheral chemoreceptors Influence of Higher Brain CentersHypothalamic controls act through the limbic system to modify rate and depth of respiration Example: breath holding that occurs in anger or gasping with painA rise in body temperature acts to increase respiratory rateCortical controls are direct signals from the cerebral motor cortex that bypass medullary controlsExample: voluntary breath holdingPulmonary Irritant ReflexesReceptors in the bronchioles respond to irritantsPromote reflexive constriction of air passagesReceptors in the larger airways mediate the cough and sneeze reflexesInflation Reflex Hering-Breuer ReflexStretch receptors in the pleurae and airways are stimulated by lung inflation Inhibitory signals to the medullary respiratory centers end inhalation and allow expiration to occurActs more as a protective response than a normal regulatory mechanismFigure 22.24Higher brain centers(cerebral cortex—voluntarycontrol over breathing)Other receptors (e.g., pain)and emotional stimuli actingthrough the hypothalamusPeripheralchemoreceptors O2 , CO2 , H+Receptors inmuscles and jointsIrritantreceptorsStretch receptorsin lungsRespiratory centers(medulla and pons)––++–+–++CentralChemoreceptors CO2 , H+ Respiratory Adjustments: ExerciseAdjustments are geared to both the intensity and duration of exerciseHyperpneaIncrease in ventilation (10 to 20 fold) in response to metabolic needs Pco2, Po2, and pH remain surprisingly constant during exerciseRespiratory Adjustments: ExerciseThree neural factors cause increase in ventilation as exercise beginsPsychological stimuli—anticipation of exerciseSimultaneous cortical motor activation of skeletal muscles and respiratory centersExictatory impulses reaching respiratory centers fromRespiratory Adjustments: ExerciseAs exercise endsVentilation declines suddenly as the three neural factors shut offRespiratory Adjustments: High AltitudeQuick travel to altitudes above 8000 feet may produce symptoms of acute mountain sickness (AMS)Headaches, shortness of breath, nausea, and dizzinessIn severe cases, lethal cerebral and pulmonary edemaAcclimatization to High AltitudeAcclimatization: respiratory and hematopoietic adjustments to altitude Chemoreceptors become more responsive to Pco2 when Po2 declinesSubstantial decline in Po2 directly stimulates peripheral chemoreceptors Result: minute ventilation increases and stabilizes in a few days to 2–3 L/min higher than at sea levelAcclimatization to High AltitudeDecline in blood O2 stimulates the kidneys to accelerate production of EPORBC numbers increase slowly to provide long-term compensationHomeostatic ImbalancesChronic obstructive pulmonary disease (COPD)Exemplified by chronic bronchitis and emphysemaIrreversible decrease in the ability to force air out of the lungsOther common featuresHistory of smoking in 80% of patients Dyspnea: labored breathing (“air hunger”)Coughing and frequent pulmonary infectionsMost victims develop respiratory failure (hypoventilation) accompanied by respiratory acidosisFigure 22.27• Tobacco smoke• Air pollution• Airway obstruction or air trapping• Dyspnea• Frequent infections• Abnormal ventilation- perfusion ratio• Hypoxemia• Hypoventilationa-1 antitrypsindeficiencyContinual bronchialirritation and inflammationBreakdown of elastin inconnective tissue of lungsChronic bronchitisBronchial edema,chronic productive cough,bronchospasmEmphysemaDestruction of alveolarwalls, loss of lungelasticity, air trappingHomeostatic ImbalancesAsthmaCharacterized by coughing, dyspnea, wheezing, and chest tightnessActive inflammation of the airways precedes bronchospasmsAirway inflammation is an immune response caused by release of interleukins, production of IgE, and recruitment of inflammatory cellsAirways thickened with inflammatory exudate magnify the effect of bronchospasms Homeostatic ImbalancesTuberculosisInfectious disease caused by the bacterium Mycobacterium tuberculosis Symptoms include fever, night sweats, weight loss, a racking cough, and spitting up bloodTreatment entails a 12-month course of antibioticsHomeostatic ImbalancesLung cancerLeading cause of cancer deaths in North America90% of all cases are the result of smokingThe three most common typesSquamous cell carcinoma (20–40% of cases) in bronchial epitheliumAdenocarcinoma (~40% of cases) originates in peripheral lung areasSmall cell carcinoma (~20% of cases) contains lymphocyte-like cells that originate in the primary bronchi and subsequently metastasizeDevelopmental AspectsOlfactory placodes invaginate into olfactory pits by the fourth weekLaryngotracheal buds are present by the fifth weekMucosae of the bronchi and lung alveoli are present by the eighth weekFigure 22.28Stomodeum(future mouth)Future mouthEyeTracheaBronchial budsPharynxForegutOlfactoryplacodeEsophagusLiverLaryngotrachealbud(a) 4 weeks: anterior superficial view of the embryo’s head(b) 5 weeks: left lateral view of the developing lower respiratory passageway mucosaeFrontonasalelevation Olfactoryplacode Developmental AspectsBy the 28th week, a baby born prematurely can breathe on its ownDuring fetal life, the lungs are filled with fluid and blood bypasses the lungsGas exchange takes place via the placentaDevelopmental AspectsAt birth, respiratory centers are activated, alveoli inflate, and lungs begin to functionRespiratory rate is highest in newborns and slows until adulthoodLungs continue to mature and more alveoli are formed until young adulthoodRespiratory efficiency decreases in old ageRespiration: Study GuideReview