Regulation of respiration Nervous system:  Normally adjusts the rate of alv. vent. almost exactly to the demands of the body so that arterial P O2 & P CO2 are hardly altered even during respir. Stress (exercise)

Regulation of respiration  Respiratory centre:  neurons in the medulla oblongata and pons of the brain stem  divided into: 1- dorsal respiratory group 2- ventral respiratory group 3- pneumotaxic centre 4- apneustic center & pre-Botzinger complex

Regulation of respiration  Dorsal respiratory group:  extends through most of the length of the medulla  sensory termination of vagal & glossopharyngeal nerves then transmit sensory signals into the respiratory centre  signals received from: 1- peripheral chemoreceptors 2- various receptors in the lungs

Regulation of respiration  Rhythmical inspiratory discharge from the dorsal group  basic respiratory rhythm is generated in the dorsal group (pre-potzinger complex)  this group still emits repetitive bursts of inspiratory neuronal action potentials even if: a- all the peripheral nerves entering the medulla are cut b- the medulla is sectioned from above or below

Regulation of respiration  Inspiratory “ramp” signals :  inspiratory signals to the diaphragm are not instantaneous bursts of action potentials  normally the signal begins weak and increases steadily in a ramp manner for 2 secs.  after that the signal ceases for 3 secs.  this causes steady increase in lungs volume and not inspiratory gasps

Regulation of respiration  “Ramp” is controlled by 2 ways: a- control the rate of increment of “ramp” signals.  during heavy respiration, “ramp” increases rapidly and fills the lungs b- control the limiting point at which the ramp suddenly ceases.  early cease  shorter inspiration  shorter expiration  increased frequency

Regulation of respiration  Pneumotaxic centre:  located dorsally in the nucleus parabrachialis of the upper pons  transmits signals to the inspiratory center  controls the “switch off” point of the inspiratory ramp  controlling the duration of the filling phase  when weak  filling takes 5 secs.  when strong  filling lasts for 0.5 sec.  so the respiratory cycle varies  3-40 breaths/min

Regulation of respiration  Ventral group:  located in each side of the medulla 5mm lateral & anterior to the dorsal group  functions: 1- inactive during normal quite resp. 2- not involved in the basic rhythmical oscillation 3- provides extra resp. drive when ventilation is more than normal 4- contributes in both inspiration & respiration

Regulation of respiration  The Hering-Breuer inflation reflux:  sensory signals from the lungs help in controlling respiration  stretch receptors that are found in the muscular portion of the bronchi & bronchioles send their signals with the vagus to the dorsal group  these signals are: a- sent when the lungs are overstretched b- have similar effect to that of the pneumotaxic centre c- activated when T.V is larger than 1.5L/breath

Regulation of respiration Chemical control  In order to control [O2], [CO2], [H+] in tissues  Control by CO2 & H+:  the chemosensitive respiratory centre is not affected directly by [CO2].  located 0.2mm beneath the surface of the ventral medulla  highly sensitive to changes in blood P CO2 or [H+]

Regulation of respiration  Control by CO2 & H+:  H+ is likely the primary stimulus for these receptors  H+ cannot cross the blood-brain barrier so changes in blood [H+] wont affect these receptors  instead an increment in blood P CO2 will indirectly activate these receptors  when [CO2] ↑ in blood  ↑ in CSF  CO2+H2O Carbonic acid bicarbonate + H+

Regulation of respiration  Effect of CO2 on chemosensitive neurons:  the excitation effects peaks the 1 st hours after the increment in blood [CO2]  after 2 days the effect is decreased because of: a- renal adjustment of [H+]. b- increased bicarbonate ions that enter the CSF and bind to H+

Regulation of respiration  O2 effect:  virtually no direct effect on respiratory centre because: 1- change of P O2 from 60mmHg to 100mmHg has no effect on the amount of [O2] because of Hb buffering 2- [CO2] in blood & tissue is inversely proportional to the ventilation rate  so evolution has made CO2 the major controller instead of O2

Regulation of respiration  Peripheral chemoreceptors:  special nervous chemical receptors for detecting changes in O2 in blood & tissues, and to less extent changes in CO2 & H+  carotid bodies (through glossopharyngeal) & aortic bodies (through vagus)  to the dorsal group  the blood flow supplying these bodies is 20x their weight each minute so the % of removed O2 from the blood flow is virtually zero  those bodies are exposed to arterial blood not venous blood

Regulation of respiration  Peripheral chemoreceptors:  are stimulated by ↓ [O2], and the range of sensitivity is between mmHg (a range in which Hb saturation decreases rapidly)

Regulation of respiration  Effect of CO2 & H+ :  ↑ [CO2], [H+]  excite receptors  ↑ respiration  both have 7x more effect on the central receptors than on the peripheral receptors but 5x as rapid on the peripheral ones.  Effect of O2:  low [O2] excites peripheral receptors “glomus cells” that synapse directly or indirectly with nerve endings.  low PO2 and normal [CO2], [H+] will drive the ventilatory process quite strongly

Regulation of respiration  Acclimatization “Chronic breathing of low O2”:  Mountain climbers ascend slowly over a period of days  causing deep breathing and withstanding low P O2  because after 2 days 4/5th of the sensitivity of receptors to CO2 an H+ is lost  so low [O2]  ↑ ventilation by 400% whereas acute exposure of low [O2] will only ↑ ventilation by 70%

Regulation of respiration  Regulation during exercise:  In exercise O2 consumption and CO2 formation is increased 20x  the ventilation is increased so P O2, P CO2 and pH remain Normal  when the brain sends its signals to the muscles it also send collateral signals to the brain stem to increase ventilation even before exercise  then chemical factors play a significant role to maintain [O2],[CO2]

Regulation of respiration  Other factors affecting respiration: 1- voluntary control : for short period of times 2- irritant receptors: stimulated by many incidents  coughing & sneezing 3- J receptor in alveolar walls lead to edema where the patient has dyspnea 4- brain edema causes res. centre depression 5- anesthesia & narcotic overdose depresses res. centre (halothane, morphine, pentobarbital)

Regulation of respiration  Periodic “Chyne-Stokes” breathing :  person over-breathes  ↑ [O2], ↓ [CO2]  after seconds these [ ] are sensed by the resp. centre  inhibition of excess ventilation  opposite cycle begins  ↓ [O2], ↑ [CO2]  after seconds these [ ] are sensed by the resp. centre  the person is again over-breathing

Regulation of respiration  Periodic “Chyne-Stokes” breathing :  this cycle doesn’t occur normally but can be seen in these conditions: 1- increased neg. feedback gain in resp. control areas  change in [CO2], [H+] causes further great change in ventilation “brain-damage” 2- long delay in transporting blood from the lungs to the brain “severe or chronic heart failure,

Regulation of respiration  Sleep apnea:  episodes of apnea lasting for 10 secs. Or more, occurring times/night  Obstructive sleep apnea:  during sleep the pharynx is relaxed, in some individuals this may lead to complete closure  snoring & labored breathing  apnea  ↓ O2, ↑ CO2  stimulation of resp. center  sudden snorts and gasps

1- elderly, obese, nasal ostruction, large tongue, enlarged tongue 2- Sudden infant death syndrome (SIDS): exaggerated case of sleep apnea, premature baby, smoker pregnant mother

Regulation of respiration  central sleep apnea: 1- damage to resp. center 2- abnormalities of resp. neuromuscular apparatus 3- unknown 4- resp. center is less responsive