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
Lecture
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
2
20
CO2 generated H+ through
the central chemoreceptors
10
20
40
60
2.7
5.3
8
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+ 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 noncarbonic 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