Chemical control of breathing

Question 1

How is ventilation controlled?

Answer 1

• Automatic centres in brainstem activate respiratory muscles rhythmically and subconsciously

Question 2

Which tasks does ventilation need to accommodate?

Answer 2

• Maintain adequate oxygen status
• Adjust respiration for changing metabolic status/needs reflected by altered pO2, pCO2, pH

Question 3

Where is the the respiratory control centre located?

Answer 3

Medulla, pons

Question 4

What are the sensors for respiration?

Answer 4

• Peripheral chemoreceptors
• Central chemoreceptors
• Pulmonary mechanoreceptors

Question 5

What are the effectors for respiration?

Answer 5

• Respiratory muscles
• Diaphragm

Question 6

What are the different types of respiratory peripheral chemoreceptors?

Answer 6

• Carotid bodies
• Aortic bodies

Question 7

Where are carotid bodies located?

Answer 7

• Bifurcation of common carotid arteries
• Do not confuse with carotid sinus

Question 8

Where are aortic bodies located?

Answer 8

• Located in aortic arch of thorax

Question 9

What is the major function of the peripheral chemoreceptors?

Answer 9

• Sense hypoxaemia
• Signal cells in medulla to increase ventilation
• Both carotid and aortic bodies primarily sensitive to decreases in arterial pO2
• Also stimulated by hypercapnia and acidosis

Question 10

Describe glomus cells

Answer 10

• Derived from ectoderm
• Neuron-like characteristics
• Excitable cells (depolarisation generates action potentials)

Question 11

What is the function of glomus cells?

Answer 11

• When pO2 is low, membrane depolarises
• Causes release of intracellular vesicles of neurotransmitters
• Neurotransmitter release from glomus cells triggers action potentials in carotid body nerve afferent fibres
• This signals low paO2 to medulla

Question 12

What do carotid body glomus cells do?

Answer 12

• When PO2 decreases below ~8kPa
• Stimulates neurotransmitter and ATP release which activates afferent fibres (carotid sinus nerve)
• Signals sent to CNS and respiration stimulated
• Similar mechanism for PCO2 and H+ - alveolar ventilation increased

Question 13

What effect does paO2 have on carotid body afferent nerves?

Answer 13

• Alters nerve impulse firing rate from carotid body
• Firing rate increases significantly after paO2 drops from 8-4 kPa
• I.e. when Hb saturation with O2 decreases rapidly

Question 14

What happens when peripheral chemoreceptors sense low paO2 and/or high paCO2?

Answer 14

• They feed back to medulla respiratory centres to increase minute ventilation
• Leads to increase in paO2 and decrease in paCO2
• Limited response in people with lung disease

Question 15

How does increasing minute ventilation compensate for acidosis?

Answer 15

• CO2 strongly influences blood pH
• If CO2 levels increase, H+ increases - pH falls
• If CO2 levels decrease, H+ decreases - pH rises

Question 16

What is the sensory innervation for the carotid body?

Answer 16

• Branch of CN IX

Question 17

What is the sensory innervation for the aortic body?

Answer 17

• Branch of CN X

Question 18

What increases peripheral chemoreceptors’ sensitivity to acidosis and hypercapnia?

Answer 18

• Hypoxaemia

Question 19

What are the first chemoreceptors to respond to hypoxaemia?

Answer 19

• Carotid and aortic bodies

Question 20

What are central chemoreceptors?

Answer 20

• Anatomical collection of neuronal chemoreceptors (specialised neurones)
• Located just beneath ventral surface of medulla on brain side of blood brain barrier
• Bathed in CSF
• Few hundred microns away from brainstem respiratory centres

Question 21

What is the function of the central chemoreceptors?

Answer 21

• Sense increases in paCO2
• Also senses decreases in arterial pH but much more slowly
• Does not detect changes in pO2

Question 22

When are central chemoreceptors the primary source of feedback to respiratory centres?

Answer 22

• When blood gas parameters are nearly normal

Question 23

What happens if pCO2 increases suddenly?

Answer 23

• Ventilation increases rapidly
• Augments minute ventilation

Question 24

How do central chemoreceptors sense changes in pCO2 and pH?

Answer 24

• BBB separates central chemoreceptors in medulla from arterial blood
• BBB has low permeability to ions (H+ and HCO3-) but high permeability to small molecules (CO2)
• CO2 diffuses into CSF bathing central chemoreceptors
• CNS receives very limited HCO3- buffering capacity
• Acidosis develops
• Even small decreases in pH raise firing rate of central chemoreceptor neurones
• Ventilation increases

Question 25

What happens to the pH of CSF if CO2 remains elevated?

Answer 25

• Slowly recovers and rises over 8-24 hours
• Because choroid plexus increases active transport of HCO3- into CSF (buffers H+ ions)
• This is CNS metabolic compensation to respiratory acidosis

Question 26

What happens when the CNS compensates for respiratory acidosis?

Answer 26

• The adjustment means that a higher level of CO2 is needed to cause acidosis and thereby increase ventilation
• CO2 drive for ventilation has been ‘reset’ at a higher level

Question 27

What does an increase in ventilation cause?

Answer 27

• Raises pO2
• Lowers pCO2
• Normalises pH
• Corrects imbalance