1. Control of Respiration
Dr Shihab Khogali
Ninewells Hospital & Medical School, University of Dundee

2. See blackboard for detailed learning objectives
What makes the inspiratory muscles contract and relax rhythmically?
How could the respiratory activity be modified?
How could the expiratory muscles be called on during active expiration?
How could the arterial PO2 and PCO2 be maintained within narrow limits?
What is the role of the respiratory system in regulating blood H+ concentration?
What is
This
Lecture
About?
See blackboard for detailed learning objectives

3. The Neural & Chemical Control of Respiration
To answer these questions we need to understand:
The Neural
&
Chemical
Control of Respiration

4. Neural control of Respiration
anterior
The Rhythm: inspiration followed by expiration
Fairly normal ventilation retained if section above medulla
Ventilation ceases if section below medulla
 medulla is major rhythm generator

5. Neural control of Respiration
Until recently, it was thought the Dorsal respiratory group of neurons generate the basic rhythm of breathing
It is now generally believed that the breathing rhythm is generated by a network of neurons called the Pre-Brotzinger complex. These neurons display pacemaker activity. They are located near the upper end of the medullary respiratory centre

6. What gives rise to inspiration?
Dorsal respiratory group neurones (inspiratory)
PONS
Fire in bursts
Firing leads to contraction of inspiratory muscles - inspiration
MEDULLA
SPINAL CORD
When firing stops, passive expiration

7. What about “active” expiration during hyperventilation?
Increased firing of dorsal neurones excites a second group:
In normal quiet breathing, ventral neurones do not activate expiratory muscles
Ventral respiratory group neurones
Excite internal intercostals, abdominals etc
Forceful expiration

8. The rhythm generated in the medulla can be modified by neurones in the pons:
“pneumotaxic centre” (PC) +
Without PC, breathing is prolonged inspiratory gasps with brief expiration - APNEUSIS
Stimulation terminates inspiration -
PC stimulated when dorsal respiratory neurones fire
Inspiration inhibited

9. The “apneustic centre”
Conclusion?
Impulses from these neurones excite inspiratory area of medulla
Rhythm generated in medulla
Rhythm can be modified by inputs from pons
Prolong inspiration

10. Reflex modification of breathing
Pulmonary stretch receptors
Activated during inspiration, afferent discharge inhibits inspiration - Hering-Breuer reflex
Do they switch off inspiration during normal respiratory cycle?
Unlikely - only activated at large >>1litre tidal volumes
Maybe important in new born babies
May prevent over-inflation lungs during hard exercise?

11. Joint receptors Impulses from moving limbs reflexly increase breathing
Probably contribute to the increased ventilation during exercise

12. Factors That May Increase Ventilation During Exercise
Reflexes originating from body movement
Increase in body temperature
Adrenaline release
Impulses from the cerebral cortex
Later: accumulation of CO2 and H+ generated by active muscles

13. Chemical Control of Respiration
An example of a negative feedback control system
The controlled variables are the blood gas tensions, especially carbon dioxide
Chemoreceptors sense the values of the gas tensions

14. Peripheral Chemoreceptors
Carotid bodies
Aortic bodies
Sense tension of oxygen and carbon dioxide;
and [H+] in the blood

15. Central Chemoreceptors
Situated near the surface of the medulla of the brainstem
Respond to the [H+] of the cerebrospinal fluid (CSF)
CSF is separated from the blood by the blood-brain barrier
Relatively impermeable to H+ and HCO3-
CO2 diffuses readily
CSF contains less protein than blood and hence is less buffered than blood
CO2 + H2O  H2CO3  H+ + HCO3-

16. Hypercapnia and Ventilation40
The system is very responsive to PCO2 30
Ventilation (l/min) 20
CO2 generated H+ through
the central chemoreceptors 10 20 40 60 80
2.7
5.3 8
10.6
Pco2 (kP) (mmHg)

17. Hypoxia and Ventilation
Neuron depressed
when hypoxia so severe
O2 concentration ml/100 ml
5.3
13.3
Blood PO2 (kPa)
% Haemoglobin Saturation
8.0 50 40
Peripheral
Chemoreceptors
Stimulated 30
Ventilation (l/min) 20 10
8.0
13.3
Arterial Po2 (kPa)

18. Hypoxic Drive of Respiration
The effect is all via the peripheral chemoreceptors
Stimulated only when arterial PO2 falls to low levels (<8.0 kPa)
Is not important in normal respiration
May become important in patients with chronic CO2 retention (e.g. patients with COPD)
It is important at high altitudes

19. The H+ Drive of Respiration
The effect is via the peripheral chemoreceptors
H+ doesn’t readily cross the blood brain barrier (CO2 does!)
The peripheral chemoreceptors play a major role in adjusting for acidosis caused by the addition of non-carbonic acid H+ to the blood (e.g. lactic acid during exercise; and diabetic ketoacidosis)
Their stimulation by H+ causes hyperventilation and increases elimination of CO2 from the body (remember CO2 can generate H+, so its increased elimination help reduce the load of H+ in the body)
This is important in acid-base balance

20. Influence of Chemical Factors on Respiration