1. RESPIRATION Dr. Zainab H.H Dept. of Physiology Lec.11,12

2. Objectives List the types of respiratory controls List the types of chemoreceptors and the main stimulants for each List the effects of pulmonary receptors on ventilation

3. Neural Control

4. Control of Respiration  The respiratory rate changes: i. When active - respiratory rate goes up ii. When less active or sleeping - the rate goes down.  The respiratory muscles are voluntary BUT you can't consciously control them when you're sleeping.  So, how is respiratory rate altered & how is respiration controlled when you're not consciously thinking about respiration? This is by: A. Neural Control B. Chemical Control

5. Two Neurogenic Systems (both CNS) 1) Involuntary (automatic):  involve medulla and pons  limbic systems (emotional response)  hypothalamus (temperature regulation)  other subcortical structures 2) Voluntary:  initiated by the cerebral cortex

6. Two Neurogenic Systems (both CNS)  Notes:  Systems are independent  Both systems require intact innervation of respiratory muscles (descending pathways and alpha motorneurons)  The muscles of respiratory ventilation are controlled by somatic motor system and not the autonomic system  The autonomic system controls airway smooth muscle contraction and secretion

7. Neural Control  Ventilation is matched to the body’s needs for O 2 uptake and CO 2 removal  Medullary respiratory center receives input  Appropriate signals sent to motor neurons  Rate and depth of ventilation adjusted

8. Reticular Activating System (RAS)  Located in the reticular system of the brain stem  Activity is associated with the “awake” or conscious state  When active, stimulates respiratory ventilation  When RAS activity is reduced, as during sleep, ventilation is reduced and the P CO 2 increases by a few mmHg

9. Sleep Apnea  Ventilation ceases temporarily (10+ seconds) during sleep.  types of sleep apnea  central apnea - reduced CNS respiratory drive  obstructive apnea - increased upper airway resistance (lyryngospasm, bronchospasm, snoring)  In infants - can lead to SIDS (sudden infant Death Syndrome).

10. Other Neural Structures  Hypothalamus - change in inspiration associated with temperature regulation  Limbic system - respiratory changes in emotion  Cerebral cortex - voluntary control

11. Chemical Control  This is achieved through the following stimuli: A. Arterial P O 2 level. B. Arterial P CO 2 level. C. Arterial H + Concentration.  CO 2 & [H + ] act centrally while the O 2 levels act on the peripheral chemoreceptors.

12. Chemoreceptors  2 groups of chemo-receptors that monitor changes in blood P CO 2, P O 2, and pH.  Central:  Highly sensitive to P CO 2 and [H + ]  Located in the medulla oblongata.  Functions by stimulating the respiratory centers  Peripheral:  Monitors P O 2 and arterial H +  Located in the Carotid and aortic bodies.  Control breathing indirectly via sensory nerve fibers to the medulla (X, IX).

13. Central Chemoreceptors  Their input modifies the rate and depth of breathing to maintain arterial P CO 2 of 40 mm Hg.  The primary stimulus is [H + ]  But [H + ] can not cross the Blood Brain Barrier  the blood P CO 2 level has more effect as CO 2 readily crosses the BBB.

14. Effects of Blood P CO 2 on Ventilation  Is not direct.  Even the indirect effect of CO 2 is most potent. Why?  Because CO 2 easily crosses the BBB.  Once it is across the BBB,  CO 2 + H 2 O  H 2 CO 3  H + + HCO 3 -  These increased H + ions in the brain stimulate the medullary chemoreceptors.

15. Effects of Blood P CO 2 on Ventilation  very large effect  sensitive in the normal range of 40 mmHg  low P CO 2 depresses ventilation  very high CO 2 is a respiratory depressant

18. Effects of Blood P CO 2 on Ventilation  The afferent sensory receptors located in the CNS and affected by CSF.  Carotid bodies also have CO 2 receptors, but these are less important than the CNS CO 2 receptors  The main stimulus is H + of CSF, which in turn controlled by PCO 2 of blood and to a smaller extent, blood pH

19. Effects of Blood P CO 2 on Ventilation

20.  Physiological Significance  homeostatic: maintains PCO 2 within the normal range (38-42 mmHg), thus helps to maintain brain pH  synergistic with O 2 : hypercapnia increases sensitivity to hypoxemia

21. Effects of Blood H + on Ventilation  Response as a function of pH  especially marked at acidic pH The afferent endings are carotid body and aortic body H + sensitive receptors (rapid response) CNS medullary H + receptors (slow H + leakage across the BBB, so slow response Stimulus is pH a and pH CSF

22. Quantitative Effect of H + Ions  The stimulatory effect of H + ions increases in the first few hours.  It then decreases in the next 1 to 2 days.  It comes down to about 1/5 th the initial effect.  This is due to Renal readjustment of [H + ] in the circulating blood.

23. Quantitative Effect of H + Ions  The kidneys increase blood HCO 3 -.  This HCO 3 - binds with the free H + ions in the blood & decreases their concentration.  HCO 3 - also diffuses slowly past the BBB and decreases the H + ions in the brain.  Therefore the effect of H + ions is:  Potent: Acutely  Weak: Chronically.

25. Effect of O 2  The partial pressure of O 2 has no effect on the central (medullary) chemoreceptors.  It only has an effect on the peripheral chemoreceptors.

26. Peripheral Chemoreceptors  There are two pairs of O 2 chemoreceptors:  Aortic Bodies: located at the arch of aorta.  Carotid bodies (mainly): located at the branching of the common carotid arteries.  Their functions are:  To detect changes in the P O 2 & H+  To transmit nervous signals to the Respiratory Centers.

28. Peripheral Chemoreceptors  These bodies have two types of special cells called glomus cells.  The type 1 glomus cells have special ion channels sensitive to P O 2.  They fire the nerve endings and send signals via:  Aortic bodies: Vagi.  Carotid bodies: Glossopharyngeal nerve.

29. Peripheral Chemoreceptors  Both these bodies receive their own special blood supply through minute arteries, directly from the trunk.  Their blood flow is roughly 20 times their own weight.  They are all the time exposed only to arterial blood.   P O 2 stimulates these chemoreceptors strongly.

30. Effects of Blood P O 2 on Ventilation  Relatively small effect in the normal range (PO 2 > 70 mmHg)  Only important in pronounced hypoxemia (PO 2 < 60 mmHg)  High PO 2 does not depress ventilation (except for chronic hypercapnia)  Peripheral chemoreceptors respond to the P O 2 and not the total O 2 content.

32. Physiological Significance  helps to maintain PO 2 in conditions of severe hypoxia (homeostatic)  remain when other chemostimulation is lost  synergistic with CO 2 response (hypoxia increases sensitivity to hypercapnia)  NOTE: If PO 2 is very low, then all CNS neurons including respiratory neurons, become depressed, so respiratory ventilation is reduced or ceases activity.

33. Effects of Blood P O 2 on Ventilation  Hypoxic drive:  Emphysema blunts the chemoreceptor response to P CO 2.  Choroid plexus secrete more HCO 3 - into CSF, buffering the fall in CSF pH.  Abnormally high P CO 2 enhances sensitivity of carotid bodies to fall in P O 2.

34. Effect of CO 2 & H +  They also stimulate the peripheral chemoreceptors.  But their effects on the central or medullary chemoreceptors are more powerful.  PCO 2 stimulates the peripheral chemoreceptors 5 times as rapidly as it stimulates the central ones.  So this is responsible for the rapid response to CO 2 at the onset of exercise.

35. Effects of Pulmonary Receptors on Ventilation  Lungs contain receptors that influence the brain stem respiratory control centers via sensory fibers in vagus. i. Pulmonary stretch (mechano-) receptors ii. Lung irritant receptors - airway receptors responding to inhaled irritating substances; cause hyperpnea and bronchoconstriction

36. Effects of Pulmonary Receptors on Ventilation iii. Proprioceptors (Respiratory muscle spindle receptors and joint receptors) may contribute to respiratory drive in exercise.  Along with the chemoreceptors, they send information to the respiratory centers.

37. Factors Influencing Respiratory Rate and Depth A. Physical factors i. Increased body temperature ii. Exercise iii. Talking iv. Coughing B. Volition (conscious control) - emotional factors C. Chemical factors i. CO 2 levels ii. O 2 levels  Chemoreceptors in aorta and carotid arteries

38. Respiratory Rate Changes Throughout Life  Newborns: 40 to 80 respirations per minute  Infants: 30 respirations per minute  Age 5: 25 respirations per minute  Adults: 12 to 18 respirations per minute  Rate often increases somewhat with old age

39. A 36-year-old man visits his doctor because his wife has long complained of his snoring, but recently observed that his breathing stops for a couple of minutes at a time while he is sleeping. He undergoes polysomnography and ventilatory response testing to ascertain the extent and cause of his sleep apnea. The activity of the central chemoreceptors is stimulated by which of the following? a. A decrease in the metabolic rate of the surrounding brain tissue b. A decrease in the PO2 of blood flowing through the brain c. An increase in the PCO2 of blood flowing through the brain d. An increase in the pH of the CSF e. Hypoxemia, hypercapnia, and metabolic acidosis

40. Every day it’s the same old thing: Breathe Breathe Breathe