1、2023-1-415.4 Control of Respiration 5.4 Control of Respiration lBreathing is a critical robust homeostatic process that ensures adequate levels of oxygen in blood and provides a means to remove carbon dioxide from the body 2023-1-42Basic Requirements for Respiratory RegulationlIt must be automatic l
2、Maintenance of CO2 and O2 levels should not depend on levels of consciousness or alertnesslIt must be adaptable to the needs of the organismlThere must be mechanisms to compensate for changes in oxygen uptake or CO2 production.lIt must be subject to voluntary controllThere must be mechanisms to volu
3、ntarily override the respiratory control mechanisms at least for brief periods of timeRespiratory Centers and the Basic Respiratory CenterlRespiratory centerRespiratory centerlBrain regions or the spinal cord that involve in the generation of rhythmic respiratory pattern and the regulation of respir
4、atory movement;they are located in the spinal cord,brainstem,cortex,thalamus etc.lBasic respiratory centerBasic respiratory centerlBrain parts that are responsible for generation of basic respiration patternslIt is located in the brainstemThe Experiment Done by Lumsden in the CatConclusionsUpper pon
5、s-pneumotaxic center;lower pons-apneustic center(not accepted);Spinal cord-Basic respiratory center;spinal cord:Cut atBreathing pattern(vagus nerve intact)Breathing pattern(vagus nerve cut off)Midbrain and the pons Nearly normalDeep and slowMid ponsNearly normal Apneustic breathingPons and medullaIr
6、regularCheyne-Stokes breathingMedulla and the spinal cordNo breathingNo breathing2023-1-45Respiratory-Related Neurons in the Basic Respiratory Center lDorsal respiratory group(DRG)lLocated in the dorsal region of the nucleus tractus solitariilMainly contain inspiratory neuronslGenerate basic rhythml
7、Ventral respiratory group(VRG)lA column of cells in the general region of the nucleus ambiguus.lIt houses both inspiratory and expiratory neuronslMost neurons are silent during normal quiet respirationPneumotatic center It acts to limit inspiration.As a result,it increases the rate of breathingIs th
8、e Pre-Btzinger Complex Essential for the Generation of Basic Respiratory Pattern?Modified from Brain 2011:134;2435Medulla oblongata=延髓Pons=脑桥Lateral reticular nucleus(LRN)=外侧网状核XII=面神经Obex=栓、门MSA=multiple system atrophySCA3=spinocerebellar ataxia type 3Multiple Systems Atrophy vs.Spinocerebellar Ata
9、xia 3Patients with multiple systems atrophy present with central respiratory deficits but without swallowing problemsPre-Btzinger Complex neurons are reduced whereas ambigual motoneurons are preserved.Patients with spinocerebellar ataxia 3 has no central respiratory deficits but with dysphagia,Pre-B
10、tzinger Complex neurons are preserved,whereas ambigual motoneurons are diminished.Neural Mechanisms underlying the Generation of Rhythmic RespirationTwo Hypotheses Oscillatory theory or the pacemaker hypothesis(起步细胞学说)Network theory(神经网络学说)Oscillatory TheoryPacemaker neurons generate the respiratory
11、 rhythm(Smith et al.,Science,1991).Neurons in pre-Btzinger can Burst spontaneously Regular firing induced by current injection in a hippocampal granule cellSpontaneous bursting In a rat pre-Btzinger neuronNeurons in pre-Btzinger can Burst spontaneously Regular firing induced by current injection in
12、a hippocampal granule cellSpontaneous bursting In a rat pre-Btzinger neuron2023-1-412Basic respiratory center(Medulla and pons)Voluntary control(Cerebrum)Spinal motor neuronsIntercostalsDiaphragm&accessory musclesMuscles of respirationCentralChemoreceptorsPeripheralChemoreceptorsChemoreceptorsStretc
13、h receptorsIrritant receptorsJ ReceptorsMuscle proprioceptorsMechanoreceptors Phrenic nervesother nerveslVoluntary control of respiration is needed in suckling,swallowing,sniffing,chewing,coughing,vomiting and vocalization.lVoluntary control over pulmonary ventilation originates in the motor cortex
14、of cerebral 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 CHEMICAL CONTROL OF RESPIRATIONPeripheral Chemoreceptor systemCentral Chemoreceptor systemResp
15、iratory Activity is Sensitive to Oxygen,Carbon Dioxide,and Hydrogen Ions in the Blood lThe overall goal of respiration is to maintain proper concentrations of oxygen,carbon dioxide,and hydrogen ions in the tissues.lRespiratory activity is highly sensitive to changes in each of these.lExcess carbon d
16、ioxide or excess hydrogen ions in the blood mainly act on the central chemoreceptor system whereas hypoxia acts entirely on the peripheral chemoreceptor system.2023-1-416Peripheral Chemosensory Receptor SystemAfferent PathwaysCarotid bodies Carotid sinus nerve glosopharyngial(IX CN)medulla near nucl
17、eus tractus solitarius(NTS)Aortic bodies Join the vagus(X CN)medulla near nucleus tractus solitarius(NTS)Peripheral Chemoreceptors should be Distinguished from BaroreceptorslCarotid artery bodies and aortic bodies:chemoreceptorslCarotid bodies are at the division of the common carotid artery into th
18、e external and internal carotid.The aortic body is on the aortic archlCarotid artery sinus and aortic arc:baroreceptors(they are within the walls of the blood vessels)lBaroreceptors sense the tension of blood vesselsFunctions of Peripheral ChemoreceptorslSense PO2,PCO2 and H+in the arterial bloodlPr
19、imarily sensitive to arterial PO2 hyperventilationlIn the absence of peripheral chemoreceptors,hypoxia results in CNS neuronal depression and depressed ventilationlPaCO2 and increased H+concentration stimulate these receptors to a lesser extent but make them more responsive to hypoxemiaCentral Chemo
20、receptor SystemLocation:Ventral lateral surface of the medullaStimuli:Increased H+or high CO2 in CSF or extracellular space2023-1-420Arterial 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 contr
21、olling 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 Underlyin
22、g Hyperventilation following PaCO2 IncreaseDirect stimulationlStimulation of peripheral chemoreceptprslStimulation of central chemoreceptorsIndirect stimulation CO2 Arterial H+Peripheral chemoreceptors2023-1-423The Effects of Lower PaO2 on RespirationlNo effect of ventilation when PaO2 is above 100
23、mm HglVentilation is up once PaO2 is below 70 mmHg and is doubled when PaO2 falls to 60 mmHglHyperventilation following decrease in PaO2 is solely made by stimulating peripheral chemoreceptorslSevere hypoxia suppresses respiration through acting on respiratory centers of brain stem2023-1-424The Effe
24、cts of Hydrogen Ions on RespirationlAn increase in H+concentration in arterial blood,CSF or the local tissue of brain stem stimulates respiration.lIncreased H+stimulates both peripheral and central chemoreceptors with stimulation of the peripheral chemoreceptor playing the main role.lAs H+cannot pas
25、s through the brain-blood barrier,increased H+in arterial blood stimulates central chemoreceptors through CO2.lAt both peripheral and central chemoreceptors,H+mediates increased respiration by CO2 accumulation.lCentral chemoreceptors are more sensitive to H+than peripheral chemoreceptors.How Does In
26、creased Arterial H+Act on the Central Chemoreceptors2023-1-426Significances of Hydrogen Ions on RespirationlCoordinates metabolic needs and respiration.lMaintains pH homeostasis.2023-1-4Ondines CurseThe Oath by Ondines husband:My every waking breath shall be my pledge of love and faithfulness to you
27、.The Curse made by Ondine(on-deen):You swore faithfulness to me with every waking breath,and I accepted your oath.So be it.As long as you are awake,you shall have your breath,but should you ever fall asleep,then that breath will be taken from you and you will die!The end:Ondines husband died.Central
28、 Alveolar Hypoventilation(Ondines Curse)lCentral alveolar hypoventilation is a rare disease in individuals who are born without ventilatory chemosensitivitylBreathing adequate when awake,but not when asleep or during sleepinglNo response to hypercapnia and hypoxiaEXERCISE AND VENTILATION Exercise Is
29、 Associated with HyperventilationRest Maximal Exercise IntensityMinute Ventilation(L/min)6100Acute Respiratory Response to Graded Dynamic Exercise Exercise IntensityVentilation(L/min)V/QPAO2(mm Hg)PaO2(mm Hg)PaCO2(mm Hg)Arterial pHRest51103100407.40Walking202103100407.40Jogging453106100367.40Running
30、754110100257.32ConclusionHyperventilation during exercise is primarily caused by mechanisms beyond chemical changes in the bloodThe cortex sends signals to the basic respiratory center?Is there interaction between the cardiovascular and basic respiratory centers?MECHANICAL REFLEXESSeveral mechanical
31、 reflexes that arise from the chest wall and lungs affect ventilation and ventilatory patterns.Receptors Are Localized in Lung Tissue and AirwayslPulmonary receptors can be divided into 3 groups:pulmonary stretch,irritant and J receptors.l Afferent fibers of all three types lie predominantly in the
32、vagal nerves.Pulmonary Stretch ReceptorslThe stretch receptors are sensory terminals of myelinated afferent fibers that lie within the smooth muscle layer of conducting airways.l The stretch receptors sense changes in lung volume.lThe stretch receptors mediate lung inflation refelx(Hering-Breuer ref
33、lex).Lung Stretch ReflexeslPulmonary inflation reflex(Hering-Breuer inspiratory-inhibitory reflex)lInflation of lungs or stretch of airways switches from inspiration to expiration.As a result,inspiration is shortened with increased breathing rate.lPulmonary deflation reflex:Deflation of lungs promot
34、es inspiration is called pulmonary deflation reflex.lBoth are mediated by the vagal fibers;cutting of vagal nerve either unilaterally or bilaterally could deepen and prolong inspiration.More about the Hering-Breuer Inspiratory-Inhibitory ReflexlThe Hering-Breuer inspiratory-inhibitory reflex(pulmona
35、ry inflation reflex)is stimulated by increases in lung volume.lThis stretch reflex is mediated by vagal fibers;its receptors are located in airway smooth muscles.lThis reflex results in the cessation of inspiration by stimulating the off-switch neurons in the medulla.lIt is inactive during quiet bre
36、athing and it plays a role only in ventilatory control in adults when VT is great than 1 L.lIt may be more important in newborns.Irritant ReceptorslThe irritant receptors are sensory terminals of myelinated afferent fibers that are found in the larger conducting airways.lThey are rapid adapting receptors.lThey are involved in coughing,gasping,and prolonged inspiration time.J ReceptorslThese receptors are called juxtapulmonary capillary receptors or J receptors.lThey are C-fiber endings.
