呼吸科呼吸系統(tǒng)4

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,2024/3/20,1,,Basic Requirements fo

2、r Respiratory Regulation,2024/3/20,2,It must be automatic Maintenance of CO2 and O2 levels should not depend on levels of consciousness or alertnessIt must be adaptable to the needs of the organismThere must be mecha

3、nisms to compensate for changes in oxygen uptake or CO2 production.It must be subject to voluntary controlThere must be mechanisms to voluntarily override the respiratory control mechanisms at least for brief periods

4、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;

5、they are located in the spinal 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

6、Done by Lumsden in the Cat,ConclusionsUpper pons-pneumotaxic center; lower pons-apneustic center (not accepted); Spinal cord-Basic respiratory center; spinal cord:,2024/3/20,5,Respiratory-Related Neurons in the Basic Re

7、spiratory Center,Dorsal respiratory group (DRG)Located in the dorsal region of the nucleus tractus solitariiMainly contain inspiratory neuronsGenerate basic rhythmVentral respiratory group (VRG)A column of cells in

8、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 inc

9、reases the rate of breathing,Is the Pre-Bötzinger Complex Essential for the Generation of Basic Respiratory Pattern?,Modified from Brain 2011:134; 24–35,Medulla oblongata = 延髓Pons = 腦橋Lateral reticular nucleus (LR

10、N) = 外側(cè)網(wǎng)狀核XII = 面神經(jīng)Obex = 栓、門MSA = multiple system atrophySCA3 = spinocerebellar ataxia type 3,Multiple Systems Atrophy vs. Spinocerebellar Ataxia 3,Patients with multiple systems atrophy present with central respira

11、tory deficits but without swallowing problemsPre-Bötzinger Complex neurons are reduced whereas ambigual motoneurons are preserved.Patients with spinocerebellar ataxia 3 has no central respiratory deficits but wit

12、h dysphagia,Pre-Bötzinger Complex neurons are preserved, whereas ambigual motoneurons are diminished.,Neural Mechanisms underlying the Generation of Rhythmic Respiration,Two Hypotheses Oscillatory theory or the p

13、acemaker hypothesis (起步細(xì)胞學(xué)說(shuō))Network theory (神經(jīng)網(wǎng)絡(luò)學(xué)說(shuō)),Oscillatory Theory,Pacemaker neurons generate the respiratory rhythm (Smith et al., Science, 1991).,Neurons in pre-Bötzinger can Burst spontaneously,Regular firi

14、ng induced by current injection in a hippocampal granule cell,Spontaneous bursting In a rat pre-Bötzinger neuron,Neurons in pre-Bötzinger can Burst spontaneously,Regular firing induced by current injection in

15、a hippocampal granule cell,Spontaneous bursting In a rat pre-Bötzinger neuron,2024/3/20,12,Basic respiratory center(Medulla and pons),Voluntary control(Cerebrum),Spinal motor neurons,IntercostalsDiaphragm &

16、;accessory musclesMuscles of respiration,CentralChemoreceptors,PeripheralChemoreceptors,Chemoreceptors,Stretch receptorsIrritant receptorsJ Receptors,Muscle proprioceptors,Mechanoreceptors,Phrenic nerves,other

17、nerves,Voluntary control of respiration is needed in suckling, swallowing, sniffing, chewing, coughing, vomiting and vocalization.Voluntary control over pulmonary ventilation originates in the motor cortex of cerebral

18、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 Re

19、spiration,Peripheral Chemoreceptor systemCentral 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 con

20、centrations of oxygen, carbon dioxide, and hydrogen ions in the tissues.Respiratory activity is highly sensitive to changes in each of these. Excess carbon dioxide or excess hydrogen ions in the blood mainly act on the

21、 central chemoreceptor system whereas hypoxia acts entirely on the peripheral chemoreceptor system.,Peripheral Chemosensory Receptor System,2024/3/20,16,Afferent PathwaysCarotid bodies → Carotid sinus nerve → glosopha

22、ryngial (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 Barorecepto

23、rs,Carotid artery bodies and aortic bodies: chemoreceptorsCarotid bodies are at the division of the common carotid artery into the external and internal carotid. The aortic body is on the aortic archCarotid artery sin

24、us and aortic arc: baroreceptors (they are within the walls of the blood vessels)Baroreceptors sense the tension of blood vessels,Functions of Peripheral Chemoreceptors,Sense PO2, PCO2 and H+ in the arterial bloodPrim

25、arily sensitive to ↓arterial PO2 ? hyperventilationIn the absence of peripheral chemoreceptors, hypoxia results in CNS neuronal depression and depressed ventilation↑PaCO2 and increased H+ concentration stimulate thes

26、e receptors to a lesser extent but make 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,2024

27、/3/20,20,Arterial 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 controlling respiration in physiological cond

28、itions. 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% fro

29、m central chemoreceptors (slow).,Mechanisms Underlying Hyperventilation following PaCO2 Increase,Direct stimulationStimulation of peripheral chemoreceptprsStimulation of central chemoreceptorsIndirect stimulation C

30、O2 Arterial H+ Peripheral chemoreceptors,,,,,,The Effects of Lower PaO2 on Respiration,No effect of ventilation when PaO2 is above 100 mm HgVentilation is up once PaO2 is below 70 mmHg and is doubled when

31、PaO2 falls to 60 mmHgHyperventilation following decrease in PaO2 is solely made by stimulating peripheral chemoreceptorsSevere hypoxia suppresses respiration through acting on respiratory centers of brain stem,2024/3

32、/20,23,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 ch

33、emoreceptors with stimulation of the peripheral 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 b

34、oth peripheral and central chemoreceptors, H+ mediates increased respiration by CO2 accumulation. Central chemoreceptors are more sensitive to H+ than peripheral chemoreceptors.,2024/3/20,24,How Does Increased Arterial

35、 H+ Act on the Central Chemoreceptors,Significances of Hydrogen Ions on Respiration,Coordinates metabolic needs and respiration.Maintains pH homeostasis.,2024/3/20,26,Ondine’s Curse,2024/3/20,The Oath by Ondine’s husba

36、nd: 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 yo

37、u 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: Ondine’s husband died.,Central Alveolar Hypoventilation (Ondine’s Curse),Cent

38、ral alveolar hypoventilation is a rare disease in individuals who are born without ventilatory chemosensitivityBreathing adequate when awake, but not when asleep or during sleepingNo response to hypercapnia and hypoxia

39、,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,Conclusio

40、nHyperventilation 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 bas

41、ic respiratory centers ?,Mechanical Reflexes,Several mechanical reflexes that arise from the chest wall and lungs affect ventilation and ventilatory patterns.,Receptors Are Localized in Lung Tissue and Airways,Pulmonary

42、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 receptors are sens

43、ory 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-

44、Breuer reflex).,Lung Stretch Reflexes,Pulmonary inflation reflex (Hering-Breuer inspiratory-inhibitory reflex)Inflation of lungs or stretch of airways switches from inspiration to expiration. As a result, inspiration is

45、 shortened with increased breathing rate. Pulmonary deflation reflex: Deflation of lungs promotes inspiration is called pulmonary deflation reflex.Both are mediated by the vagal fibers; cutting of vagal nerve either

46、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 i

47、ncreases in lung 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

48、 the medulla.It is inactive during quiet breathing and it plays a role only in ventilatory control in adults when VT is great than 1 L.It may be more important in newborns.,Irritant Receptors,The irritant receptors

49、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 Receptor