The document summarizes chemical regulation of respiration. It discusses how carbon dioxide, hydrogen ions, and oxygen levels regulate breathing through central and peripheral chemoreceptors. The central chemoreceptors in the brainstem are stimulated by increased carbon dioxide and hydrogen ions in the bloodstream. The peripheral chemoreceptors in the carotid bodies and aortic arch are stimulated by decreased oxygen levels. Together, the chemoreceptors detect changes in gas levels and stimulate breathing to maintain homeostasis.

1. Chemical Regulation of
Respiration
Dr. Sai Sailesh Kumar G
Associate Professor
Department of Physiology
RDGMC

2. Learning objectives
 List the main types of stimuli for chemical
regulation and their relative importance
 Describe the location and role of the central
and peripheral chemo receptors
 Understand the changes in the respiration
during exercise

3. Introduction
 The ultimate goal of respiration is to maintain proper
concentrations of O2, CO2 and hydrogen ions in the
tissues
 Excess CO2 and excess hydrogen ions acts directly on
respiratory center and increases the inspiratory and
expiratory motor signals to respiratory muscles
 Oxygen does not have significant direct effect. It acts
through peripheral chemo receptors

4. Respiratory center
 Mainly three areas of respiratory center
1. Dorsal Respiratory Group
2. Ventral Respiratory Group
3. Pneumotaxic Center
 It is believed that none of these is effected directly
by changes in the blood CO2 concentration or
hydrogen ion concentration

5. Chemo sensitive area
 Additional neural area
 Lying 0.2 mm beneath the ventral surface of
medulla
 Highly sensitive to changes in blood PCO2 or
hydrogen ion concentration
 It in turn excites the other portions of respiratory
centers

6. Hydrogen ions - primary stimulus
 Hydrogen ions may be the important direct stimulus for
the chemo sensitive neurons
 However, hydrogen ions do not easily cross blood
brain barrier
 For this reason, changes in H+ ion concentration have
less effect in stimulating the chemo sensitive neurons
when compared to CO2

7. CO2 stimulates chemo-sensitive area
 CO2 easily cross Blood brain barrier
 When PCO2 increases in interstitial fluid of medulla
and CSF, the CO2 reacts with water of the tissues and
forms carbonic acid
 Carbonic acid dissociates and releases hydrogen ions
 Hydrogen ions stimulates the chemo sensitive area
and thus respiration

8. CO2 - Mechanism
 Increase in the arterial CO2
 PCO2 increases in interstitial fluid of medulla and CSF
 CO2 reacts with water of the tissues and forms carbonic acid
 Carbonic acid dissociates and releases hydrogen ions
 Hydrogen ions stimulates the chemo sensitive area
 Increase in the firing of inspiratory centers
 Increase in the motor signals to inspiratory muscles
 Increase in the ventilation (how???)

9. CO2 - Mechanism

10. CO2 - Mechanism
 Increase in the concentration of hydrogen ions
 Activates chemo sensitive area
 it activates DRG, PC
 DRG stimulates VRG
 Both DRG and VRG sends signals to inspiratory muscles
 Increase in the frequency of respiratory signals (A.P)
 More frequent contractions of inspiratory muscles
 Increase in the ventilation (rate and depth)

11. CO2 - Mechanism
Story not completed

12. CO2 - Mechanism
 Increase in the ventilation (rate and depth)
 More CO2 moves out
 PCO2 decreases
 H+ ion concentration decreases
 Normal frequency of respiratory signals (A.P)
 Normal contractions of inspiratory muscles
 Normal ventilation (rate and depth) restores

13. What happens if CO2 levels decreases
significantly low
 CO2 levels significantly low (hypo capnia)
 Significant decrease in PCO2
 H+ ion concentration decreases significantly
 No stimulation (inhibition) of chemo sensitive area
 Little signals to DRG, PC (Inhibition of VRG)
 Frequency of signals decreases
 Rate and depth of respiration decreases (hypoventilation)

14. What happens if CO2 levels decreases
significantly low
 Rate and depth of respiration decreases (hypoventilation)
 Little amount of CO2 moves out
 CO2 accumulates in the blood (PCO2 increases)
 H+ ion concentration increases
 more signals to DRG, PC (Inhibition of VRG)
 Frequency of signals increases to inspiratory muscles
 Rate and depth of respiration increases and normal
ventilation restored

15. Changes in O2 concentration
 No direct effect on the respiratory center
 Indirect effect through peripheral chemo receptors

16. Peripheral Chemoreceptors (PCR)
 Peripheral chemoreceptors are neurovascular
structures situated in the carotid body and aortic
body.
 Detects changes in the oxygen in the blood

17. Carotid and aortic bodies
 Carotid bodies are located at the bifurcation of
common carotid artery
 Carotid bodies nerve supply- glossopharyngeal
nerve
 Aortic bodies are located in arch of aorta
 Aortic bodies nerve supply – vagus nerve

18. Carotid and aortic bodies

19. Blood supply to PCR
 Receives blood through a minute artery directly from
adjacent arterial trunk
 Blood flow is extreme ( 20 times the weight of bodies)
 % of oxygen removed from flowing blood is virtually
zero
 They are always exposed to arterial blood not
venous blood

20.  PCR is composed of two types of cells
1. Type I cell or Glomus cell: They are in close
approximation to cuplike endings of afferent nerve fibers of
IX cranial nerve.
2. Type II cells or Glial or Supporting cells: These cells
surround 4-6 glomus cells. Function is protection and
support of glomus cells.

21. Mechanism of action of PCR
 Reduction in the partial pressure of O2 is the most
potent stimulus for PCR
 Decrease in the oxygen concentration below normal
(increased PCO2, H+ concentration to lesser
extent)
 Increase in the firing of aortic and carotid bodies
 Increase in the firing of Inspiratory centers
 Increase in the motor signals to respiratory muscles
 Increase in the ventilation

22. Mechanism of action of PCR
 Glomus cells has oxygen sensitive K+ channels
 When Oxygen concentration decreases below normal,
K+ channels becomes inactive
 Depolarization of cell
 Opening of calcium channels and Influx of calcium
 Release of neurotransmitters
 Stimulation of nerve ending
 Signals to respiratory centers
 Increase in the ventilation

24.  The inspiratory center is stimulated and there is
increase in the rate and depth of respiration. This
brings the blood Po2 normal.
 In the absence of PCR, severe hypoxia depresses
respiration by a direct inhibitory action on
respiratory center (the direct effect of hypoxia on
respiratory center is depression).

25. Factors stimulating PCR
1. Decrease in arterial Po2.
2. Vascular stasis as in circulatory shock (stagnant
hypoxia).
The PCR utilize the dissolved O2 in blood for their
metabolic demands because the blood supply to
PCR is so large. So they respond only to a
reduction in the dissolved O2 in blood.

26. Central chemo receptors
 Located in chemo sensitive
area of medulla
 Stimulated by increase in
the CO2 in the blood
(which increases H+ ion
concentration)
 Slower response when
compared to PCR
Peripheral chemo receptors
 Located in carotid and aortic
bodies
 Decrease in the arterial
oxygen concentration is
primary stimulus and
increased CO2 and H+ also
stimulates but lesser extent
 Response is 5 times fast than
CCR

27. Abnormalities in regulation of respiration
1. Respiratory center depression
 Old age
 Anesthetics
2. Periodic breathing:
It consists of alternate waxing and waning of
respiration or alternate hyper apnea and apnea.

28.  Types of Periodic breathing are:
a) Voluntary hyperventilation
b) Cheyne-Stokes respiration
c) Biot’s Breathing.

29. Voluntary Hyperventilation
 Hyperventilation in normal subjects is followed by
a period of apnea, which in turn is followed by a
few shallow breaths and then by another period of
apnea followed again by a few breaths.
 This is a type of periodic breathing.
 Cycles last for sometime before normal breathing
is resumed.

30. Cheyne-Stokes Respiration
 This type of periodic respiration is seen in both
physiological and pathological conditions.
 In this type, regular alternating periods of
hyperventilation and apnea are seen.
 The change over one to the other occurs
gradually.

31. Cheyne-Stokes Respiration
 Physiological conditions:
 Deep sleep
 Infants
 High altitude
 Pathological conditions:
 Congestive cardiac failure (CCF)
 Morphine poisoning
 Raised intracranial pressure
 Uremia

32. Biot’s Breathing
 This type of breathing is always pathological.
 It consists of irregular periods of apnea and
hyperventilation. The changes are abrupt.
• It is seen in:
 Meningitis
 Medullary lesions

33. Hypercapnia
 It’s a retention of CO2 in the body i.e.; there is an
increase in the concentration of CO2 in blood than
normal
 Hypercapnia initially stimulates respiration, but
retention of large amounts of CO2 produces
depression of CNS and leads to CO2 narcosis,
characterized by:
 Confusion, Paresthesia (altered sensation),
Coma with respiratory depression, Finally death.

34. Hypocapnia
 Decrease in the concentration of CO2 in the arterial
blood below normal is called hypocapnia.
 The arterial Pco2 falls from 40mmHg to as low as
15mmHg.
 It occurs due to hyperventilation especially in
neurotic patients
 The alveolar Po2 rises to 120-140mmHg.

35. Effects of Hypocapnia
1. Cerebral blood flow may be reduced by 30% or
more because of the direct constrictor effect of
hypocapnia on cerebral vessels.
2. Cerebral ischemia produces headache,
dizziness, visual blackouts, etc;

36. Asphyxia
 It is a condition where acute hypoxia and
hypercapnia occur together.
 Causes- obstruction to respiratory passage as in:
 Strangulation
 Choking
 Drowning where there is reflex laryngeal spasm.

37. THANK YOU