Control 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?

What is
This
Lectur
e
About?

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?

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
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 PreBrotzinger 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 >>1litre tidal
volumes
Maybe important in new born babies
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 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-

Hypercapnia and Ventilation

Ventilation (l/min)

40

The system is very

responsive to PCO

30

20

CO2 generated H+ through

the central chemoreceptors

10

20

2.7

40

5.3

60

Pco2 (kP) (mmHg)

80

10.6

Hypoxia and Ventilation

Ventilation (l/min)

50
40

Peripheral
Chemoreceptors
Stimulated

30
20
10
0
0

8.0 13.3

Arterial Po2 (kPa)

% Haemoglobin Saturation

Neuron depressed
when hypoxia so severe

5.3

8.0

13.3

Blood PO2 (kPa)

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+ doesnt 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