1. 3-Mar-16Control of Respiration1 Neural Mechanisms Chemical Mechanisms

2. 3-Mar-16Control of Respiration2 Introduction  Function of respiration include –Regulation of alveolar ventilation Maintain constant supply of O 2 to tissues –Normal 250 ml O 2 /min –This can increase to 20 times during exercise To eliminate CO 2 from the tissues Thus P O2, P CO2, pH –Maintained at constant values or nearly constant values

3. 3-Mar-16Control of Respiration3 Introduction  Other functions of respiration include –Phonation, singing, laughing, whistling etc  In all these –Extremely complicated respiratory movements are performed –Require coordinated control

4. 3-Mar-16Control of Respiration4 Neural Control of Respiration  Two neural control mechanisms regulate respiration –One responsible for voluntary control –The other one for automatic control Cerebral cortex Pons & medulla Spinal cord Respiratory muscles Corticospinal tract Reticulospinal tract

5. 3-Mar-16Control of Respiration5 Neural Control of Respiration  Voluntary control system –Located in cerebral cortex –Send impulses to respiratory muscles via Corticospinal tracts (CST) Cerebral cortex Pons & medulla Spinal cord Respiratory muscles Corticospinal tract Reticulospinal tract

6. 3-Mar-16Control of Respiration6 Control Systems for Respiration  Automatic system –Located in pons and medulla oblongata –Efferent output from this system to respiratory muscles Located in spinal cord close to CST Cerebral cortex Pons & medulla Spinal cord Respiratory muscles Corticospinal tract Reticulospinal tract

7. 3-Mar-16Control of Respiration7 Control Systems for Respiration  Nerves serving inspiration converge in ventral horns –C3,4,5 (phrenic nerve) –External intercostal motor neurons  Fibres concerned with expiration –Converge on internal intercostals motor neurons Cerebral cortex Pons & medulla Spinal cord Respiratory muscles Corticospinal tract Reticulospinal tract

8. 3-Mar-16Control of Respiration8 Control Systems for Respiration  Reciprocal activity –Motor neurons to expiratory muscles Inhibited when those to inspiratory muscles are activated &vice versa Cerebral cortex Pons & medulla Spinal cord Respiratory muscles Corticospinal tract Reticulospinal tract

9. 3-Mar-16Control of Respiration9 Breathing Pattern  During quite breathing  Inspiration is brought about by –Progressive increase in activation of inspiratory muscles  End of inspiration associated with –Rapid decrease in excitation Inspiration Expiration 2 sec3 sec Electrical activity (diaphragm)

10. 3-Mar-16Control of Respiration10 Breathing Pattern  The progressive activation of inspiratory muscle cause –Lungs to fill at constant rate until tidal vol reached  End of inspiration associated –Rapid decrease in excitation of inspiratory muscles Expiration occurs Inspiration Expiration 2 sec3 sec Electrical activity (diaphragm)

11. 3-Mar-16Control of Respiration11 Respiratory Neurons  Two types of brainstem respiratory neurons  Inspiratory neurons (I-neurons) –Discharge during inspiration  Expiratory neurons(E-neurons) –Discharge during expiration During quite breathing –Remain silent Become active only when ventilation is increased

12. 3-Mar-16Control of Respiration12 Respiratory Centers IX X XI XII D R G V R G Vagus, glosopharyngeal Pneumotaxic center DRG VRG Apneustic center

13. 3-Mar-16Control of Respiration13 Respiratory Centers  Composed of several groups of neurons –Located bilaterally in Medulla oblongata Pons IX X XI XII D R G V R G Pneumotaxic center Apneustic center

14. 3-Mar-16Control of Respiration14 Respiratory Centers  Three major collection of neurons –Dorsal respiratory group (DRG) –Ventral respiratory group (DRG) –Pneumotaxic center –? Apneustic center IX X XI XII D R G V R G Apneustic center Pneumotaxic center

15. 3-Mar-16Control of Respiration15 Respiratory Centers  Dorsal respiratory group (DRG) –Located on the dorsal portion of medulla In or near the Nucleus of Tractus Solitarius(NTS) IX X XI XII D R G V R G

16. 3-Mar-16Control of Respiration16 Respiratory Centers  NTS –Sensory terminal of vagus & glossopharyngeal Transmit sensory signals from –Peripheral chemoreceptors –Baroreceptors –Receptors in the lungs IX X XI XII D R G V R G

17. 3-Mar-16Control of Respiration17 Respiratory Centers  DRG made up –Of I – neurons Some project monosynaptically to phrenic nerve motor neurons (MN) –Cause inspiration IX X XI XII D R G V R G

18. 3-Mar-16Control of Respiration18 Respiratory Centers  VRG  Long column extends through –Nucleus ambiguus –Nucleus retroambiguus in the ventral medulla IX X XI XII D R G V R G

19. 3-Mar-16Control of Respiration19 Respiratory Centers  VRG has both I & E neurons –E – neurons at its rostral end –I-neurons at the mid portion –E-neurons at its caudal end Some of these neurons project to –Respiratory motor neurons IX X XI XII D R G V R G

20. 3-Mar-16Control of Respiration20 Generation of Breathing Pattern  Rhythmic respiratory pattern –Appear to be initiated by the Rhythmic discharges of neurons in the medulla and pons IX X XI XII D R G V R G A D

21. 3-Mar-16Control of Respiration21 Generation of Breathing Pattern  Trans-section of brain –Below medulla Stops respiration –Above the pons Automatic breathing is still present  Neurons in medulla & pons –Responsible for generating the rhythmic respiratory movements IX X XI XII D R G V R G A D

22. 3-Mar-16Control of Respiration22 Generation of Breathing Pattern  The actual mechanism responsible for –Rhythmic respiratory discharge not known  However, –Group of pacemaker neurons have been identified Pre-Böttzinger Complex Area between nucleus ambiguus & lateral reticular nucleus IX X XI XII D R G V R G A D

23. 3-Mar-16Control of Respiration23 Pontine & vagal Influence  The spontaneous rhythmic discharges of medullary neurons is modified by –Neurons in the pons –Afferents in the vagus from receptors in the airways and lungs IX X XI XII D R G V R G

24. 3-Mar-16Control of Respiration24 Pontine & vagal Influence  Pneumotaxic center located in –Nucleus parabrachialis in dorsal lateral pons  Contain both –I-neurons & E-neurons –Also contain neurons that are active in both phases of respiration IX X XI XII D R G V R G Pneumotaxic center

25. 3-Mar-16Control of Respiration25 Pontine & vagal Influence  When this area is damaged –Respiration becomes slower –Tidal volume greater  Pneumotaxic center m ay play a role –Switching between inspiration & expiration IX X XI XII D R G V R G Pneumotaxic center

26. 3-Mar-16Control of Respiration26 Pontine & vagal Influence  Apneustic center –Situated in lower pons  Send signals to DRG –Prevent “switching- off” of respiratory ramp (increase duration of inspiration) –Lungs become completely filled with air IX X XI XII D R G V R G Pneumotaxic center Apneustic center

27. 3-Mar-16Control of Respiration27 Pontine & vagal Influence  Apneustic center is inhibited by –Vagus & pneumotaxic center  Vagotomy & destruction of pneumotaxic center causes –Prolonged period of inspiration Apneusis IX X XI XII D R G V R G Pneumotaxic center Apneustic center

28. 3-Mar-16Control of Respiration28 Chemical Control  Pulmonary ventilation –Regulated to meet different levels of metabolic demands Supply O 2 Elimination of CO 2  Achieved by feed back control of respiratory center activity –In response to chemical composition of blood P CO2, H +, P O2

29. 3-Mar-16Control of Respiration29 Chemical Control  Types of receptors –Central chemo-receptors –Peripheral receptors –Others

30. 3-Mar-16Control of Respiration30 Central Chemoreceptors  Chemosensitive neurons –Bilateral beneath the ventral medulla  Sensitive to changes in P CO2 & H +  H + only important direct stimulus DRG CO 2 + H 2 O ⇌ H 2 CO 3 ⇌ HCO 3 - + H + Chemosensitive neurons

31. 3-Mar-16Control of Respiration31 Central Chemoreceptors  H + crosses the blood- brain –barrier (BBB) very poorly –Changes in H + in blood have less immediate effect on respiration  CO 2 diffuse easily across BBB –It is then hydrated and dissociates to H + & HCO 3 - DRG CO 2 + H 2 O ⇌ H 2 CO 3 ⇌ HCO 3 - + H + Chemosensitive neurons

32. 3-Mar-16Control of Respiration32 Central Chemoreceptors  An increase CSF CO 2 causes chemoreceptors to stimulate respiration  A decrease CSF CO 2 causes chemoreceptors to inhibit respiration DRG CO 2 + H 2 O ⇌ H 2 CO 3 ⇌ HCO 3 - + H + Chemosensitive neurons

33. 3-Mar-16Control of Respiration33 Peripheral Chemoreceptors  Located in the carotid & aortic bodies  These receptors respond to –Lowered arterial O 2 tension –Rise in arterial CO 2 tension –Increase in H + conc in arterial blood

34. 3-Mar-16Control of Respiration34 Peripheral Chemoreceptors  Arterial O 2 tension –Only site in the body that detect changes in O 2 tension of body fluids  Peripheral chemoreceptors –Receive a lot of blood flow for their size 2000 ml/100 gm/min (cf brain = 54 ml/100 gm/min)

35. 3-Mar-16Control of Respiration35 Peripheral Chemoreceptors  Thus they monitor –O 2 tension rather than O 2 content  O 2 cause by anaemia, methaemoglobin, CO poisoning –Do not stimulate peripheral chemoreceptors

36. 3-Mar-16Control of Respiration36 Peripheral Chemoreceptors  When P O2 falls below 60–80 mm Hg –There is an increase in rate of discharge of fibers from the receptors to RC – ↑ Rate and depth of respiration – ↑ Alveolar ventilation Elimination of CO 2

37. 3-Mar-16Control of Respiration37 Peripheral chemoreceptors  Elimination of CO 2 –Respiratory alkalosis ↓ H + conc CSF Inhibition of respiratory drive  Over the course of several days –Ionic pumps (pia matter, choroid plexus) Transfer HCO 3 - from CSF to blood CSF pH returns towards normal Respiratory drive returns

38. 3-Mar-16Control of Respiration38 Peripheral chemoreceptors  Effect of CO 2 tension  Elevation of CO 2 tension also –Stimulate peripheral chemoreceptors –But most of effect of CO 2 is on the central chemoreceptors

39. 3-Mar-16Control of Respiration39 Peripheral chemoreceptors  Effect of H + concentration  ↑ in H + conc –Stimulate peripheral chemorecptors –Increase in ventilation  The increase in alveolar ventilation – ↓ CO 2 tension –pH return towards normal –Ventilatory drive tends to reduce

40. 3-Mar-16Control of Respiration40 Other receptors  Pulmonary stretch receptors –Lie within the walls of airways  They are stimulated by –Inflation of the lung  Initiate inspiratory inhibition –Termination of inspiration –Hering – Breuer reflex

41. 3-Mar-16Control of Respiration41 Other Receptors  Irritant receptors –Lie in large airways Between airway epithelial cells –Stimulated by Noxious gases, smoke, particulates in inhaled air –Initiate reflex that stimulate Coughing, bronchospasm, mucus secretion Breath holding (apnoea)

42. 3-Mar-16Control of Respiration42 Other Receptors  J-receptors –Juxta-capillary –Located in the pulmonary interstitium at the level of pulmonary capillaries –Stimulated by the distension of pulmonary capillaries Caused by ventricular failure, emboli, chemicals

43. 3-Mar-16Control of Respiration43 Other Receptors  J-receptors –Initiate reflex that cause Rapid, shallow breathing, tachypnoea  Nose & upper airway receptors –Upper respiratory pathways contain receptors Respond to mechanical, chemical stimuli –Reflex initiated Sneezing, coughing, bronchoconstriction

44. 3-Mar-16Control of Respiration44 Other Receptors  Joint & muscle receptors –Impulses from moving limbs Are believed to be part of stimuli for ventilation –Early stages of exercises  Baroreceptors –A rise in BP cause Reflex hypoventilation –A fall in BP cause Reflex hyperventilation