1、5.4 Control of Respiration,Breathing 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,2018/7/18,1,Basic Requirements for Respiratory Regulation,2018/7/18,2,It must be automatic Maintenance of CO2 and
2、O2 levels should not depend on levels of consciousness or alertnessIt must be adaptable to the needs of the organismThere must be mechanisms to compensate for changes in oxygen uptake or CO2 production.It must be subject to voluntary controlThere must be mechanisms to voluntarily override the respir
3、atory control mechanisms at least for brief periods of time,Respiratory Centers and the Basic Respiratory Center,Respiratory centerBrain regions or the spinal cord that involve in the generation of rhythmic respiratory pattern and the regulation of respiratory movement; they are located in the spina
4、l cord, brainstem, cortex, thalamus etc.Basic respiratory centerBrain parts that are responsible for generation of basic respiration patternsIt is located in the brainstem,The Experiment Done by Lumsden in the Cat,ConclusionsUpper pons-pneumotaxic center; lower pons-apneustic center (not accepted);
5、Spinal cord-Basic respiratory center; spinal cord:,2018/7/18,5,Respiratory-Related Neurons in the Basic Respiratory Center,Dorsal respiratory group (DRG)Located in the dorsal region of the nucleus tractus solitariiMainly contain inspiratory neuronsGenerate basic rhythmVentral respiratory group (VRG)
6、A column of cells in the general region of the nucleus ambiguus. It houses both inspiratory and expiratory neuronsMost neurons are silent during normal quiet respiration,Pneumotatic center It acts to limit inspiration. As a result, it increases the rate of breathing,Is the Pre-Btzinger Complex Essen
7、tial for the Generation of Basic Respiratory Pattern?,Modified from Brain 2011:134; 2435,Medulla 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 3,Multiple Systems Atrophy vs. Spinocerebellar Ataxia 3,Pa
8、tients 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-Btzinger
9、 Complex neurons are preserved, whereas ambigual motoneurons are diminished.,Neural Mechanisms underlying the Generation of Rhythmic Respiration,Two Hypotheses Oscillatory theory or the pacemaker hypothesis (起步细胞学说)Network theory (神经网络学说),Oscillatory Theory,Pacemaker neurons generate the respiratory
10、 rhythm (Smith et al., Science, 1991).,Neurons in pre-Btzinger can Burst spontaneously,Regular firing induced by current injection in a hippocampal granule cell,Spontaneous bursting In a rat pre-Btzinger neuron,Neurons in pre-Btzinger can Burst spontaneously,Regular firing induced by current injecti
11、on in a hippocampal granule cell,Spontaneous bursting In a rat pre-Btzinger neuron,2018/7/18,12,Basic respiratory center(Medulla and pons),Voluntary control(Cerebrum),Spinal motor neurons,IntercostalsDiaphragm &accessory musclesMuscles of respiration,CentralChemoreceptors,PeripheralChemoreceptors,Ch
12、emoreceptors,Stretch receptorsIrritant receptorsJ Receptors,Muscle proprioceptors,Mechanoreceptors,Phrenic nerves,other nerves,Voluntary control of respiration is needed in suckling, swallowing, sniffing, chewing, coughing, vomiting and vocalization.Voluntary control over pulmonary ventilation origi
13、nates in the motor cortex of cerebral frontal lobe. The 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 Respiration,Peripheral Chemoreceptor systemCen
14、tral Chemoreceptor system,Respiratory Activity is Sensitive to Oxygen, Carbon Dioxide, and Hydrogen Ions in the Blood,The overall goal of respiration is to maintain proper concentrations of oxygen, carbon dioxide, and hydrogen ions in the tissues.Respiratory activity is highly sensitive to changes i
15、n each of these. Excess carbon dioxide or excess hydrogen ions in the blood mainly act on the central chemoreceptor system whereas hypoxia acts entirely on the peripheral chemoreceptor system.,Peripheral Chemosensory Receptor System,2018/7/18,16,Afferent PathwaysCarotid bodies Carotid sinus nerve gl
16、osopharyngial (IX CN) medulla near nucleus tractus solitarius (NTS)Aortic bodies Join the vagus (X CN) medulla near nucleus tractus solitarius (NTS),Peripheral Chemoreceptors should be Distinguished from Baroreceptors,Carotid artery bodies and aortic bodies: chemoreceptorsCarotid bodies are at the d
17、ivision of the common carotid artery into the external and internal carotid. The aortic body is on the aortic archCarotid artery sinus and aortic arc: baroreceptors (they are within the walls of the blood vessels)Baroreceptors sense the tension of blood vessels,Functions of Peripheral Chemoreceptors
18、,Sense PO2, PCO2 and H+ in the arterial bloodPrimarily sensitive to arterial PO2 hyperventilationIn the absence of peripheral chemoreceptors, hypoxia results in CNS neuronal depression and depressed ventilationPaCO2 and increased H+ concentration stimulate these receptors to a lesser extent but make
19、 them more responsive to hypoxemia,Central Chemoreceptor System,Location: Ventral lateral surface of the medullaStimuli: Increased H+ or high CO2 in CSF or extracellular space,2018/7/18,20,Arterial PCO2 is the most Important Factor in Regulation of Respiration,The arterial CO2 is held within 2-3 mmH
20、g.The arterial CO2 is the most important factor in controlling 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 remai
21、ning 80% from central chemoreceptors (slow).,Mechanisms Underlying Hyperventilation following PaCO2 Increase,Direct stimulationStimulation of peripheral chemoreceptprsStimulation of central chemoreceptorsIndirect stimulation CO2 Arterial H+ Peripheral chemoreceptors,The Effects of Lower PaO2 on Resp
22、iration,No effect of ventilation when PaO2 is above 100 mm HgVentilation is up once PaO2 is below 70 mmHg and is doubled when PaO2 falls to 60 mmHgHyperventilation following decrease in PaO2 is solely made by stimulating peripheral chemoreceptorsSevere hypoxia suppresses respiration through acting o
23、n respiratory centers of brain stem,2018/7/18,23,The Effects of Hydrogen Ions on Respiration,An increase in H+ concentration in arterial blood, CSF or the local tissue of brain stem stimulates respiration. Increased H+ stimulates both peripheral and central chemoreceptors with stimulation of the per
24、ipheral chemoreceptor playing the main role.As H+ cannot pass through the brain-blood barrier, increased H+ in arterial blood stimulates central chemoreceptors through CO2.At both peripheral and central chemoreceptors, H+ mediates increased respiration by CO2 accumulation. Central chemoreceptors are
25、 more sensitive to H+ than peripheral chemoreceptors.,2018/7/18,24,How Does Increased Arterial H+ Act on the Central Chemoreceptors,Significances of Hydrogen Ions on Respiration,Coordinates metabolic needs and respiration.Maintains pH homeostasis.,2018/7/18,26,Ondines Curse,2018/7/18,The Oath by Ond
26、ines husband: My every waking breath shall be my pledge of love and faithfulness to you.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
27、, then that breath will be taken from you and you will die!The end: Ondines husband died.,Central Alveolar Hypoventilation (Ondines Curse),Central alveolar hypoventilation is a rare disease in individuals who are born without ventilatory chemosensitivityBreathing adequate when awake, but not when as
28、leep or during sleepingNo response to hypercapnia and hypoxia,Exercise and Ventilation,Exercise Is Associated with Hyperventilation,Rest Maximal Exercise Intensity,Minute Ventilation (L/min),6,100,Acute Respiratory Response to Graded Dynamic Exercise,ConclusionHyperventilation during exercise is pri
29、marily 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 Reflexes,Several mechanical reflexes that arise from the chest wall and lungs affect ve
30、ntilation and ventilatory patterns.,Receptors Are Localized in Lung Tissue and Airways,Pulmonary receptors can be divided into 3 groups: pulmonary stretch, irritant and J receptors. Afferent fibers of all three types lie predominantly in the vagal nerves.,Pulmonary Stretch Receptors,The stretch rece
31、ptors are sensory terminals of myelinated afferent fibers that lie within the smooth muscle layer of conducting airways. The stretch receptors sense changes in lung volume.The stretch receptors mediate lung inflation refelx (Hering-Breuer reflex).,Lung Stretch Reflexes,Pulmonary inflation reflex (He
32、ring-Breuer inspiratory-inhibitory reflex)Inflation of lungs or stretch of airways switches from inspiration to expiration. As a result, inspiration is shortened with increased breathing rate. Pulmonary deflation reflex: Deflation of lungs promotes inspiration is called pulmonary deflation reflex.Bo
33、th 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 Reflex,The Hering-Breuer inspiratory-inhibitory reflex (pulmonary inflation reflex) is stimulated by increases in l
34、ung volume.This stretch reflex is mediated by vagal fibers; its receptors are located in airway smooth muscles.This reflex results in the cessation of inspiration by stimulating the off-switch neurons in the medulla.It is inactive during quiet breathing and it plays a role only in ventilatory contro
35、l in adults when VT is great than 1 L.It may be more important in newborns.,Irritant Receptors,The irritant receptors are sensory terminals of myelinated afferent fibers that are found in the larger conducting airways.They are rapid adapting receptors.They are involved in coughing, gasping, and prolonged inspiration time.,J Receptors,These receptors are called juxtapulmonary capillary receptors or J receptors.They are C-fiber endings.,
