1. Dr. Nisreen Abo-elmaaty Regulation of Respiration

2. Dr. Nisreen Abo-elmaaty The Respiratory system in human performs a critical task That is to regulate & respond to O2 demands Maintaining a constant O2 & CO2 in the blood Therefore, regulation of respiration is critically important for Homeostasis

4. The main are chemosensors sensing changes in CO2, O2 & pH

5. Other contributors: in the lungs, cardiovascular, skeletal muscles, tendons of respiratory muscles,

6. Effector-> respiratory muscles Inspiration; diaphragm &external intercostals Expiration; internal intercostals & abdominal recti

9. The Ventral Expiratory Group (VEG)

10. The 2 groups are bilaterally paired

11. There is cross communication between them

13. Dr. Nisreen Abo-elmaaty Medullary Respiratory NeuronsInput & Output of DRG Pneumotaxic centre Apneustic centre Central chemoreceptors - Peripheral chemoreceptors + DRG + Spinal motoneurons Cervical (3,4,5) & Thoracic (1-12)

14. Dr. Nisreen Abo-elmaaty Medullary Respiratory NeuronsVentral Respiratory Group (VRG) Anterolateral to DRG Activated during heavy breathing; e.g. exercise During such conditions, the increased activity of inspiratory neurons activates the VRG In turn, the activated VRG discharge: - inhibits inspiratory group - stimulates the muscles of expiration; internal intercostals (T6-L3), abdominal recti (T4-L3)

15. Dr. Nisreen Abo-elmaaty Pontine Respiratory Centre 2 pontine centres that modify The rate & The Pattern of respiration

19. Dr. Nisreen Abo-elmaaty The co-ordinated work of neurons of respiratory centre +

21. Dr. Nisreen Abo-elmaaty 1- Central Chemoreceptors Pathway Its receptors: Central chemosensitive area Lying just beneath ventral surface of medulla Relaying most important sensory input about changes in their close environment to respiratory centre in medulla & pons Most sensitive to change in PaCO2 ,H+ conc., but not to PaO2

22. Dr. Nisreen Abo-elmaaty 1- Central Chemoreceptors Pathway Central chemosensitive area Under normal conditions, ~75-85% of respiratory drive is due to stimulation of central chemoreceptors by PaCO2 However, the direct stimulant for neurons of central chemoreceptors is only H+ ions But H+ can not cross blood brain barrier while CO2 can So, how central chemoreceptors are stimulated by an increase in arterial PCO2?

23. Dr. Nisreen Abo-elmaaty More sensitive to changes in CSF than to changes in cerebral blood

24. Dr. Nisreen Abo-elmaaty 2- Peripheral Chemoreceptor PathwayPeripheral (Arterial) Chemoreceptors Peripheral chemoreceptors are the only sensors detecting a fall in PO2

26. an increase in PaCO2 or H+ concentrationThey maximally stimulated when PaO2 decreases below 50-60mm Hg They detect changes in dissolved O2 but not in the O2 that is bound to Hb (e.g. in anaemia there is normal PaO2 but reduced content of O2 bound to Hb)

27. Dr. Nisreen Abo-elmaaty What if Carotid bodies are removed? if there is decreased PaO2 (Hypoxia) with absence of peripheral chemoreceptors Hypoxia would inhibit respiration Why? hypoxia depresses neuronal activity including that of respiratory centre Hypoxia ->VD of cerebral vessels ->↓PaCO2 in CSF ->↓CO2-mediated stimulation of central chemoreceptors -> hypoventilation

28. Dr. Nisreen Abo-elmaaty A). Involuntary Automatic ControlII- Neurogenic Reflexes Hering-Breuer Inflation Reflex Hering-Breuer Deflation Reflex J-receptor Reflex Cough & sneezing Reflexes Baroreceptors Reflex Other influences (mediated via hypothalamus)

29. Dr. Nisreen Abo-elmaaty Neurogenic Reflexes originating from the respiratory system1- Hering-Breuer inflation reflex (inhibito-inspiratory reflex) Over-Inflation of lungs-> stimulation of slowly adapting stretch receptors in smooth muscles of large & small airways ->afferent vagal signals ->inhibitory to medullary and pontine inspiratory network ->termination of inspiration This reflex in not important in normal adults. It is more important & powerful in neonates.

30. Dr. Nisreen Abo-elmaaty Neurogenic Reflexes originating from the respiratory system2- Hering-Breuer deflation reflex (excito-inspiratory reflex) Deep expiration -> Deflation of the lungs ->↓activity of previous slowly adapting stretch receptors or stimulate other propioceptors in respiratory muscle -> decreasing afferent vagal signals to respiratory centres-> increase in the activity of inspiratory neurons ->↑ rate of breathing

31. Dr. Nisreen Abo-elmaaty Neurogenic Reflexes originating from the respiratory system3- J-receptor Reflex Pulmonary emboli or oedema or congestion -> stimulation of juxtapulmonary-capillaries receptors ->impulses along vagal afferent -> respiratory centre -> rapid shallow breathing These receptors are responsible for the sensation of air hunger (Dyspnea; shortness of breath)

32. Dr. Nisreen Abo-elmaaty Neurogenic Reflexes originating from the respiratory system4- Cough, Sneezing reflexes Dust, smoking, irritant substances -> stimulation of irritant receptors in upper airways (nose, larynx, bronchi)->afferent signals via vagus (larynx, cough}) or trigeminal or olfactory (nose, sneezing) -> respiratory centre -> deep inspiration followed by forced expiration against closed glottis ->opening of glottis ->forceful outflow of air (help removal of irritants)

33. Dr. Nisreen Abo-elmaaty Neurogenic Reflexes from other systemsBaroreceptor Reflex Acute ↑in ABP -> stimulation of baroreceptors ->afferent signals via X & IX -> inhibitory to respiratory centre -> decrease rate & depth of respiration ->↓venous return -> ↓COP -> ↓ABP

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35. Dr. Nisreen Abo-elmaaty Neurogenic ReflexesOther Influences from higher centershypothalamus & limbic system Temperature: Increases respiratory rate Pain: Sudden pain decreases, prolonged pain increases rate Alcohol: Decreases rate Exercise; increases breathing rate (higher cortical centers)

36. Dr. Nisreen Abo-elmaaty B). Voluntary Control of BreathingCortical Influence Through descending tracts from the cerebral cortex to motor neurons of the respiratory muscles (dorsolateral corticospinal tracts) This provides CNS the ability to override the automatic regulation of respiration for short time e.g. holding breath but the involuntary control will take over (↑ PCO2, H+), or deliberate hyperventilation (↓PCO2)

37. Dr. Nisreen Abo-elmaaty Now, can U explain what u have read about Luke? His respiratory rate of 22/min His PaO2 was 61 mm Hg His PaCO2 was 31 mm Hg

38. Dr. Nisreen Abo-elmaaty Summary in Figures

39. Dr. Nisreen Abo-elmaaty The Effect of ↑ PaCO2 on ventilation

40. Dr. Nisreen Abo-elmaaty Effect of a decreased PaO2

41. Dr. Nisreen Abo-elmaaty Summary of Chemical Pathways stimulating Ventilation

42. Dr. Nisreen Abo-elmaaty Summary Of the Overall Control of Activity of Respiratory Centre

43. Dr. Nisreen Abo-elmaaty Now, You should ask yourself if you know the followings: General organization of respiratory control system Localization & description of brain stem centres involved in regulation of breathing The sensors that sense changes in PaO2, PaCO2 & H+ The effects of changes in PaO2, PaCO2 & H+ on breathing The list of reflexes that affect the breathing pattern

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45. Dr. Nisreen Abo-elmaaty Mark the following T or F Respiratory chemoreceptors: a). in the carotid and aortic bodies are most important in the ventilatory response to an elevated PCO2 b. in the carotid and aortic bodies are strongly stimulated by the low arterial O2 content in anaemic patients c). in the medulla are responsive to changes in arterial PCO2 d. transducer a chemical changes into electric signals e. may be sensitive to H+

46. Dr. Nisreen Abo-elmaaty Choose the best answer Voluntary apnea for 90 seconds will a. Increase arterial PCO2 b. Decrease arterial PO2 c. Stimulate the arterial chemoreceptors d. Stimulate the central chemoreceptors e. All of the above

47. Dr. Nisreen Abo-elmaaty What is the function of the Apneustic centre in the brain? monitor changes in CO2, O2 & H+ ions sends inhibitory signals to Inspiratory area in medulla sends stimulatory signals to Inspiratory area in medulla monitors changes in blood pressure

48. Dr. Nisreen Abo-elmaaty Stimulation of which of the following receptors should result in decreased ventilation? a. Aortic chemoreceptors b. Carotid chemoreceptors c. Central chemoreceptors d. Hering-Breuer inflation (stretch) receptors

49. Dr. Nisreen Abo-elmaaty THANK U