Control of Respiration Dr Shihab Khogali Ninewells Hospital

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

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

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

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 is major rhythm generator

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

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

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

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

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

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 >>1 litre tidal volumes Maybe important in new born babies May prevent over-inflation lungs during hard exercise?

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

Factors That May Increase Ventilation During Exercise q Reflexes originating from body movement q Increase in body temperature q Adrenaline release q Impulses from the cerebral cortex q Later: accumulation of CO 2 and H+ generated by active muscles

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

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

Central Chemoreceptors q Situated near the surface of the medulla of the brainstem q Respond to the [H+] of the cerebrospinal fluid (CSF) q CSF is separated from the blood by the blood-brain barrier q. Relatively impermeable to H+ and HCO 3 q. CO 2 diffuses readily q CSF contains less protein than blood and hence is less buffered than blood CO 2 + H 2 O H 2 CO 3 H+ + HCO 3 -

Hypercapnia and Ventilation (l/min) 40 The system is very responsive to PCO 30 2 20 CO 2 generated H+ through the central chemoreceptors 10 20 2. 7 40 5. 3 60 8 Pco 2 (k. P) (mm. Hg) 80 10. 6

Hypoxia and Ventilation (l/min) 50 40 Peripheral Chemoreceptors Stimulated 30 20 10 0 0 8. 0 13. 3 Arterial Po 2 (k. Pa) % Haemoglobin Saturation Neuron depressed when hypoxia so severe 5. 3 8. 0 13. 3 Blood PO 2 (k. Pa)

Hypoxic Drive of Respiration q The effect is all via the peripheral chemoreceptors q Stimulated only when arterial PO 2 falls to low levels (<8. 0 k. Pa) q Is not important in normal respiration q May become important in patients with chronic CO 2 retention (e. g. patients with COPD) q It is important at high altitudes

The + H Drive of Respiration q The effect is via the peripheral chemoreceptors q H+ doesn’t readily cross the blood brain barrier (CO 2 does!) q The peripheral chemoreceptors play a major role in adjusting for acidosis caused by the addition of noncarbonic acid H+ to the blood (e. g. lactic acid during exercise; and diabetic ketoacidosis) q Their stimulation by H+ causes hyperventilation and increases elimination of CO 2 from the body (remember CO 2 can generate H+, so its increased elimination help reduce the load of H+ in the body) q This is important in acid-base balance

Influence of Chemical Factors on Respiration