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1、5.4 Control of Respiration l Breathingisacriticalrobusthomeostaticprocessthatensuresadequatelevelsofoxygeninbloodandprovidesameanstoremovecarbondioxidefromthebody2023/5/26 1Basic Requirements for Respiratory Regulation2023/5/262l Itmustbeautomaticl MaintenanceofCO2andO2levelsshouldnotdependonlevelso
2、fconsciousnessoralertnessl Itmustbeadaptabletotheneedsoftheorganisml TheremustbemechanismstocompensateforchangesinoxygenuptakeorCO2production.l Itmustbesubjecttovoluntarycontroll TheremustbemechanismstovoluntarilyoverridetherespiratorycontrolmechanismsatleastforbriefperiodsoftimeRespiratory Centers
3、and the Basic Respiratory Centerl Respiratory centerl Brainregionsorthespinalcordthatinvolveinthegenerationofrhythmicrespiratorypatternandtheregulationofrespiratorymovement;theyarelocatedinthespinalcord,brainstem,cortex,thalamusetc.l Basic respiratory centerl Brainpartsthatareresponsibleforgeneratio
4、nofbasicrespirationpatternsl ItislocatedinthebrainstemThe Experiment Done by Lumsden in the CatConclusionsUpper pons-pneumotaxic center;lower pons-apneustic center(not accepted);Spinal cord-Basic respiratory center;spinal cord:Cut at Breathing pattern(vagus nerve intact)Breathing pattern(vagus nerve
5、 cut off)Midbr ainandtheponsNear l ynormal Deepandslo wMidpons Near l ynormal Apneusticbr eathingP onsandmedullaIrr egular Che yne-St ok esbr eathingMedullaandthespinalcor dNobr eathing Nobr eathingIs the Pre-Btzinger Complex Essential for the Generation of Basic Respiratory Pattern?Modified from Br
6、ain 2011:134;2435Medullaoblongata=延髓Pons=脑桥Lateralreticularnucleus(LRN)=外侧网状核XII=面神经Obex=栓、门MSA=multiplesystematrophySCA3=spinocerebellarataxiatype3Multiple Systems Atrophy vs.Spinocerebellar Ataxia 3 Patientswithmultiplesystemsatrophypresentwithcentralrespiratorydeficitsbutwithoutswallowingproblems
7、 Pre-BtzingerComplexneuronsarereducedwhereasambigualmotoneuronsarepreserved.Patientswithspinocerebellarataxia3hasnocentralrespiratorydeficitsbutwithdysphagia,Pre-BtzingerComplexneuronsarepreserved,whereasambigualmotoneuronsarediminished.Neural Mechanisms underlying the Generation of Rhythmic Respira
8、tionTwoHypothesesOscillatorytheoryorthepacemakerhypothesis(起步细胞学说)Networktheory(神经网络学说)Neurons in pre-Btzinger can Burst spontaneously RegularfiringinducedbycurrentinjectioninahippocampalgranulecellSpontaneousburstingInaratpre-BtzingerneuronNeurons in pre-Btzinger can Burst spontaneously Regularfiri
9、nginducedbycurrentinjectioninahippocampalgranulecellSpontaneousburstingInaratpre-BtzingerneuronlVoluntary control of respiration is needed in suckling,swallowing,sniffing,chewing,coughing,vomiting and vocalization.lVoluntary control over pulmonary ventilation originates in the motor cortex of cerebr
10、al frontal lobe.lThe impulses are transmitted down the corticospinal tracts to the respiratory neurons in the spinal cord,bypassing the brainstem respiratory centers.Voluntary Control of Breathing Respiratory Activity is Sensitive to Oxygen,Carbon Dioxide,and Hydrogen Ions in the Blood l Theoverallg
11、oalofrespirationistomaintainproperconcentrationsofoxygen,carbondioxide,andhydrogenionsinthetissues.l Respiratoryactivityishighlysensitivetochangesineachofthese.l Excesscarbondioxideorexcesshydrogenionsinthebloodmainlyactonthecentralchemoreceptorsystemwhereashypoxiaactsentirelyontheperipheralchemorec
12、eptorsystem.PeripheralChemosensoryReceptorSystem2023/5/2616Afferent PathwaysCarotid bodies Carotid sinus nerve glosopharyngial(IX CN)medulla near nucleus tractus solitarius(NTS)Aortic bodies Join the vagus(X CN)medulla near nucleus tractus solitarius(NTS)Functions of Peripheral Chemoreceptorsl Sense
13、PO2,PCO2andH+inthearterialbloodl PrimarilysensitivetoarterialPO2hyperventilationl Intheabsenceofperipheralchemoreceptors,hypoxiaresultsinCNSneuronaldepressionanddepressedventilationl PaCO2andincreasedH+concentrationstimulatethesereceptorstoalesserextentbutmakethemmoreresponsivetohypoxemiaCentralChem
14、oreceptorSystemLocation:Ventral lateral surface of the medullaStimuli:Increased H+or high CO2 in CSF or extracellular space2023/5/26 20Arterial PCO2 is the most Important Factor in Regulation of Respiration The arterial CO2 is held within 2-3 mmHg.The arterial CO2 is the most important factor in con
15、trolling respiration in physiological conditions.With increased arterial PCO2,both the rate and the depth of respiration increase.Peripheral chemoreceptor denervation studies showed 20-30%of the response from carotid bodies(rapid);the remaining 80%from central chemoreceptors(slow).Mechanisms Underly
16、ing Hyperventilation following PaCO2 IncreaseDirect stimulationlStimulation of peripheral chemoreceptprslStimulation of central chemoreceptorsIndirect stimulation CO2 Arterial H+Peripheral chemoreceptorsTheEffectsofHydrogenIonsonRespirationl AnincreaseinH+concentrationinarterialblood,CSForthelocalti
17、ssueofbrainstemstimulatesrespiration.l IncreasedH+stimulatesbothperipheralandcentralchemoreceptorswithstimulationoftheperipheralchemoreceptorplayingthemainrole.l AsH+cannotpassthroughthebrain-bloodbarrier,increasedH+inarterialbloodstimulatescentralchemoreceptorsthroughCO2.l Atbothperipheralandcentra
18、lchemoreceptors,H+mediatesincreasedrespirationbyCO2accumulation.l CentralchemoreceptorsaremoresensitivetoH+thanperipheralchemoreceptors.2023/5/2624HowDoesIncreasedArterialH+ActontheCentralChemoreceptorsSignificancesofHydrogenIonsonRespirationl Coordinatesmetabolicneedsandrespiration.l MaintainspHhom
19、eostasis.2023/5/2626CentralAlveolarHypoventilation(OndinesCurse)l Centralalveolarhypoventilationisararediseaseinindividualswhoarebornwithoutventilatorychemosensitivityl Breathingadequatewhenawake,butnotwhenasleeporduringsleepingl NoresponsetohypercapniaandhypoxiaEXERCISE AND VENTILATION Acute Respir
20、atory Response to Graded Dynamic Exercise Exercise IntensityVentilation(L/min)V/Q PAO2(mm Hg)PaO2(mm Hg)PaCO2(mm Hg)Arterial pHRest 5 1 103 100 40 7.40Walking 20 2 103 100 40 7.40Jogging 45 3 106 100 36 7.40Running 75 4 110 100 25 7.32ConclusionHyperventilationduringexerciseisprimarilycausedbymechan
21、ismsbeyondchemicalchangesinthebloodThecortexsendssignalstothebasicrespiratorycenter?Isthereinteractionbetweenthecardiovascularandbasicrespiratorycenters?MECHANICALREFLEXESSeveralmechanicalreflexesthatarisefromthechestwallandlungsaffectventilationandventilatorypatterns.Receptors Are Localized in Lung
22、 Tissue and Airwaysl Pulmonaryreceptorscanbedividedinto3groups:pulmonarystretch,irritantandJreceptors.l Afferentfibersofallthreetypesliepredominantlyinthevagalnerves.Pulmonary Stretch Receptorsl Thestretchreceptorsaresensoryterminalsofmyelinatedafferentfibersthatliewithinthesmoothmusclelayerofconduc
23、tingairways.l Thestretchreceptorssensechangesinlungvolume.l Thestretchreceptorsmediatelunginflationrefelx(Hering-Breuerreflex).Lung Stretch Reflexesl Pulmonaryinflationreflex(Hering-Breuerinspiratory-inhibitoryreflex)l Inflationoflungsorstretchofairwaysswitchesfrominspirationtoexpiration.Asaresult,i
24、nspirationisshortenedwithincreasedbreathingrate.l Pulmonarydeflationreflex:Deflationoflungspromotesinspirationiscalledpulmonarydeflationreflex.l Botharemediatedbythevagalfibers;cuttingofvagalnerveeitherunilaterallyorbilaterallycoulddeepenandprolonginspiration.More about the Hering-Breuer Inspiratory
25、-Inhibitory Reflexl TheHering-Breuerinspiratory-inhibitoryreflex(pulmonaryinflationreflex)isstimulatedbyincreasesinlungvolume.l Thisstretchreflexismediatedbyvagalfibers;itsreceptorsarelocatedinairwaysmoothmuscles.l Thisreflexresultsinthecessationofinspirationbystimulatingtheoff-switchneuronsinthemed
26、ulla.l ItisinactiveduringquietbreathinganditplaysaroleonlyinventilatorycontrolinadultswhenVTisgreatthan1L.l Itmaybemoreimportantinnewborns.Irritant Receptorsl Theirritantreceptorsaresensoryterminalsofmyelinatedafferentfibersthatarefoundinthelargerconductingairways.l Theyarerapidadaptingreceptors.l Theyareinvolvedincoughing,gasping,andprolongedinspirationtime.J Receptorsl ThesereceptorsarecalledjuxtapulmonarycapillaryreceptorsorJreceptors.l TheyareC-fiberendings.