Chemical control of
respiration
By,Dr.M.B.Bhat.
Significance of chemical regulation
 Helps
in Homeostasis of
 PO2
 PCO2
&
 H+ ions
 Achieved through Chemoreceptors
Chemo receptors
Two types
 Peripheral chemoreceptors
 Central chemoreceptors
 Hypoxia stimulate respiration through
peripheral chemoreceptor; but hypoxic
direct effect on center is inhibition
 Through central chemoreceptors PCO2 aids
in determination of normal respiratory
rhythm; since it is more sensitive to
central than peripheral chemoreceptors
 H+ ions has got stimulatory effect on both
central & peripheral chemoreceptors

Peripheral chemoreceptors
Peripheral chemoreceptors
Location: Carotid body & Aortic body
Nerve supply – (called as Buffer nerves)
 For carotid body –Carotid sinus nerve (Herring
nerve), a branch from Glossopharyngeal (IX)
nerve
 For aortic body – a branch from vagus (X) nerve

Stimulus for Peripheral
chemoreceptors
 Arterial
blood level - Hypoxia (more potent)
 Hypercapnea
 Increased H+ ions (Decrease pH)
 Carotid
body weight – 2 mg
 Blood flow to carotid body –
0.04ml/min
 Equivalent to 2000 ml/min/100gm
tissue
 Metabolic need of carotid body is
supplied by dissolved oxygen itself
 So these receptors are stimulated,
whenever O2 delivery per unit time
is decreased
 O2 delivery per unit time depend
upon Oxygen tension (PO2)
Factors decreasing O2 delivery per unit time
& thereby stimulating these receptors
1.
2.
3.
4.
5.
6.
Low PO2
Vascular stasis –leads to Low PO2
(which also increase PCO2 & H+
ions)
Cyanide (prevents utilization of O2)
Infusion of K+ ions
Sufficient dose of drugs –nicotine &
lobeline
BP <70 mm Hg up to 40 mm Hg
Conditions not stimulating
chemoreceptors
 Anemia
 CO
poisoning
 In both these conditions –
 O2 content in the blood is decreased
 But PO2 level in the blood is normal
 Hence O2 delivery per unit time is
not affected
Effect of removal of peripheral
chemoreceptors
 Ventilatory
response to hypoxia is
completely lost
 Ventilatory response to Hypercapnea
reduced by 30%
 Ventilation at rest is not affected
Central chemoreceptors
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Located on the ventral surface of medulla near
inspiratory center (these receptors contain
carbonic anhydrase enzyme)
Mechanism of stimulus – by H+ ion conc. In CSF;
(these receptors are H+ ion sensitive receptors)
Normal stimulus – CO2 (As blood level H+ ions
cannot cross the blood-brain barrier); CO2 which
enter brain hydrated by CSF to form H2CO3,
dissociates to give HCO3 & H+ ions –stimulates
chemoreceptors
Effect: Stimulation of central chemoreceptors –
stimulate inspiratory center located near by.
Significance –
Normally also have slight but definite ‘CO2 drive’
on respiratory center through these receptors
keeps the PCO2 level at 40 mm Hg
Also helps in the rhythmicity of respiration

Note – the threshold value for PCO2 on
ventilation is below normal alveolar
PCO2 level
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Summary:
1. Role of CO2:
As long as arterial PCO2 is elevated
hyperventilation persists till to bring back PCO2 to
normal
As long as arterial PCO2 more; hyperventilation
persists even with high arterial PO2 level
When inhalation of gas contain >7% of CO2,the
arterial PCO2 rises in spite of hyperventilation -Leads to hypercapnia – which depresses CNS,
produce headache, confusion & even coma (CO2
narcosis)
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2. Role of Hypoxia:
Hypoxia acts mainly through peripheral
chemoreceptors
Stimulation is slight when PO2 in mm Hg
declines from 100 up to 60; below 60 it is
marked
Reason – Stimulatory effect of hypoxia will
manifest only when it is strong enough to
override the inhibitory effect of
1. fall in H+ ions (as Hb is weaker acid than
HbO2)
2. low PCO2 (due to hyperventilation) on
respiration
–which is possible onlywhen PO2 is below
60 mm Hg.
Effect of Hypoxia & Hypercapnia:
 When alveolar PCO2 is above normal,
there is an inverse relationship
between ventilation & PO2 at any level
 When alveolar PCO2 is below normal,
the stimulatory hypoxic effect appears
only below PO2 of 60 mm Hg
 When alveolar PO2 is held constant,
there is linear relationship between
ventilation & CO2 concentration.
 Hypoxia makes more sensitive to
increases of arterial PCO2
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 3.
Role of H+ ions:
 Stimulatory effects of H+ ions &
CO2 on ventilation is additive.
 Each nanomole rise of H+ ions is
equivalent to rise of 0.8 mm Hg
of CO2
 About 40% of ventilatory
response to CO2 is lost if H+ ions
increase due to CO2, is prevented.
(loss of H+ ions effect through
peripheral chemoreceptors)
Role of respiration on acid-base balance:
 Hypoventilation –retention of CO2 –
Respiratory acidosis
 Hyperventilation –wash out of CO2 –
Respiratory alkalosis
 Metabolic acidosis – pronounced respiratory
stimulation (Kussmaul’s breathing)—blow of
CO2 –produce compensatory rise in blood pH.
 Metabolic alkalosis –Respiratory depression
 leads to accumulation of CO2 –decrease blood
pH
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Effect of hormone on respiration
Adrenaline – injection of adrenaline
produce apnea
 –not direct action on respiratory center
 – but through baroreceptors due to
increase BP
 Thyroid hormone –stimulate both rate &
depth of respiration (secondary due to its
effect on metabolism)
 Progesterone –directly stimulate
respiration
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Pulmonary arterial chemo-reflex
Similar to coronary chemo-reflex (BezoldJarisch reflex)
 Stimulus – Injections of drugs such as
serotonin, capsaicin, veratridine and
related drugs into the pulmonary artery
and so called pulmonary chemo reflex.
 Afferent – ‘C’ fibers goes through vagal
afferent
 Center – Respiratory & CVS centers
 Effect -- on respiration as well as CVS
 On respiration --Apnea followed by rapid
breathing,
 On CVS -- bradycardia, and hypotension
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Voluntary Breath holding
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2.
3.
Time varies up to only few minutes
Breaking point – at which voluntary
breath holding is no longer possible is
due to –hypercapnia & hypoxia of blood.
Time can be prolonged –
By removal of peripheral chemoreceptors
Breathing 100% oxygen or
hyperventilation before breath holding
Psychological factors
End
Thank you