1. Regulation of respiration
Nervous system:
Normally adjusts the rate of alv. vent. almost exactly to the demands of the body so that arterial PO2 & PCO2 are hardly altered even during respir. Stress (exercise)

2. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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 PCO2 or [H+]

13. 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 PCO2 will indirectly activate these receptors
when [CO2] ↑ in blood ↑ in CSF
CO2+H2O Carbonic acid bicarbonate + H+

14. Regulation of respiration
Effect of CO2 on chemosensitive neurons:
the excitation effects peaks the 1st 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+

16. Regulation of respiration
O2 effect:
 virtually no direct effect on respiratory centre because:
1- change of PO2 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

17. 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

18. 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)

21. 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

24. Regulation of respiration
Acclimatization “Chronic breathing of low O2”: Mountain climbers ascend slowly over a period of days causing deep breathing and withstanding low PO2
 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%

25. Regulation of respiration
Regulation during exercise:
 In exercise O2 consumption and CO2 formation is increased 20x
 the ventilation is increased so PO2, PCO2 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]

29. 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)

30. 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

32. 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,

33. 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

34. 1- elderly, obese, nasal ostruction, large tongue, enlarged tonsils
2- Sudden infant death syndrome (SIDS): exaggerated case of sleep apnea, premature baby, smoker pregnant mother

35. Treatment of obstructive sleep apnea
1-Surgery uvulopalatopharyngoplasty (remove excess fat at back of throat , tonsils, tracheostomy)
2-Continous positive airway pressure CPAP