Control of RespirationControl of Respiration

Dr Shihab Khogali

Ninewells Hospital & Medical School, University of Dundee

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 LectureAbout?

See blackboard for detailed learning objectives

The Neural

&

Chemical

Control of Respiration

To answer these questions we need to understand:

Neural control of Respiration

Fairly normal ventilation retained if section above medulla

Ventilation ceases if section below medulla

medulla is major rhythm generator

The Rhythm: inspiration followed by expiration

anterior

Neural control of RespirationUntil 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?

PONS

MEDULLA

SPINAL CORD

Dorsal respiratory group neurones (inspiratory)

Fire in bursts

Firing leads to contraction of inspiratory muscles - inspiration

When firing stops, passive expiration

What about “active” expiration during hyperventilation?

Increased firing of dorsal neurones excites a second group:

Ventral respiratory group neurones

Excite internal intercostals, abdominals etc Forceful expiration

In normal quiet breathing, ventral neurones do not activate expiratory muscles

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

Unlikely - only activated at large >>1litre tidal volumesMaybe important in new born babies

Do they switch off inspiration during normal respiratory cycle?

May prevent over-inflation lungs during hard exercise?

Joint receptors

Impulses from moving limbs reflexly increase breathing

Probably contribute to the increased ventilation during exercise

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

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

Peripheral Chemoreceptors

Carotid bodies

Aortic bodies

Sense tension of oxygen and carbon dioxide; and [H+] in the blood

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 barrierRelatively 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-

Hypercapnia and Ventilation

10

20

30

40

Ven

tila

tion

(l/

min

)

20 40 60 80

Pco2 (kP) (mmHg)

2.7 5.3 8 10.6

The system is very responsive to PCO2

CO2 generated H+ through the central chemoreceptors

O2 c

on

cen

trat

ion

ml/

100

ml

5.3 13.3

Blood PO2 (kPa)

% H

aem

og

lob

in S

atu

rati

on

8.0Arterial Po2 (kPa)

0

Ven

tila

tion

(l/m

in)

50

40

30

20

10

0 8.0 13.3

Neuron depressed when hypoxia so severe

PeripheralChemoreceptorsStimulated

Hypoxia and Ventilation

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

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

Influence of Chemical Factors on Respiration