Lecture 7: Chemical control of breathing

Question 1

What sets an automatic rhythm for contraction of respiratory muscles?

Answer 1

Automatic centre in brainstem activate respiratory muscles rhythmically and subconsciously
-but respond to changed needs and production of pO2, pCO2, pH

Question 2

What tasks does ventilation need to accomodate?

Answer 2

• maintain adequate oxygen status

- ajust respirations for changing metabolic status/needs reflected by altered pO2, pCO2, pH

Question 3

What are peripheral and central chemoreceptors?

Answer 3

Peripheral chemoreceptors sense pO2, pCO2, pH
Central chemoreceptors sense pCO2, pH
(pH measures hydrogen ions- inverse relationship)

Question 4

What are the types of peripheral chemoreceptors?

Answer 4

Carotid bodies
-located at bifurcation of the common carotid arteries
-near carotid sinus (contain baroreceptors)
Aortic bodies
-located in aortic arch near baroreceptors

Major function: sense hypoxaemia and signal to cells in the medulla to increase ventilation
(also sense high pCO2 and low pH)

Question 5

What is a type 1 glomus cell?

Answer 5

Chemical sensing cells in the carotid body (neurone-like)

-sense pCO2, pO2, pH

Question 6

What does hypercapnia mean?

Answer 6

High levels of CO2

Question 7

What are the afferent sensory nerves from the peripheral carotid bodies to the brainstem?

Answer 7

Carotid: small branch of glossopharyngeal nerve called the carotid body nerve
Aortic: small branch of the vagus nerve
(signals will increase as pO2 falls)

Question 8

When does the carotid body sense oxygen?

Answer 8

When pO2 decreases below 60 mmHg (8kPa)
-this stimulates neurotransmitter and ATP release which activates afferent fibres and sends signals to CNS and stimulate respiration

Question 9

How does increasing minute ventilation compensate for acidosis?

Answer 9

CO2 strongly influences blood pH
CO2 + H2O <> H2CO3 <> HCO3- + H+
-therefore if CO2 levels increase, H+ levels increase
-decreasing CO2, will cause H+ to decrease so pH rises

Question 10

How does hypoxaemia affect the peripheral chemoreceptors?

Answer 10

Hypoxaemia increases the peripheral chemoreceptors’ response to acidosis and hypercapnia

Question 11

What are the first chemoreceptors in the body to respond?

Answer 11

Peripheral chemoreceptors (rapid responders)

Question 12

What are central chemoreceptors?

Answer 12

Specialised neurones located on the brain side of the BBB (bathed in brain extracellular fluid, which is separated from arterial blood by the BBB)

Question 13

What is the role of central chemoreceptors?

Answer 13

Sense increase in arterial PCO2 (slower)
Sense decrease in arterial pH but much more slowly
-when blood-gas parameters are nearly normal, central chemoreceptors are the primary source of feedback to the brainstem respiratory centres for adjustments
-if pCO2 increases suddenly, ventilation increases rapidly due to central chemoreceptors

Question 14

Where are central chemoreceptors located?

Answer 14

Ventral surface of the medulla

-very close to the brainstem respiratory centre

Question 15

How do central chemoreceptors sense changes in pCO2 and pH?

Answer 15

• BBB separates central chemoreceptors in medulla from the arterial blood
• BBB has a low permeability to ions such as H+, HCO3-, but high permeability to CO2
• CO2 diffuses into brain extracellular fluid where central chemoreceptor neuron cells bathe
• CO2 dissociates to form H+ and HCO3-, causing a drop in pH, so central chemoreceptors increase firing so ventilation can increase
• CNS is limited to only the HCO3- buffering capacity, so therefore acidosis develops
• it takes longer for the chemoreceptors to detect changes in pH because the BBB isn’t freely diffusable to H+/HCO3-

Question 16

How do central chemoreceptors respond to hypercapnia?

Answer 16

Many diseases lead to chronic hypercapnia e.g. COPD/emphysematous
-if CO2 remains elevated, pH of CSF recovers over 8-24 hrs because the choroid plexus increases active transport of HCO3- into the CSF
-this resets the sensitivity of central chemoreceptors to CO2
-meaning that higher levels of CO2 is needed to cause acidosis and thereby increase ventilation
(there is also metabolic compensation where the kidneys increase HCO3- reabsorption, but this occurs over 3-5 days rather than hours)

Question 17

What is the sequence of events leading to hyperventilation in diabetic ketoacidosis?

Answer 17

• there is a low pH to start with due to the acidosis
• carotid bodies (as peripheral chemoreceptors are first responders) sense this and cause hyperventilation, this then reduces the CO2 and the pH
• central chemoreceptors decrease firing due to the low CO2 (take a while to respond) to slow breathing
• the central chemoreceptors are over-ridden by the peripheral chemoreceptors but hyperventilation isn’t at maximum (due to chemoreceptors)
• eventually as H+ crosses the BBB, full hyperventilatory drive occurs as it causes the central chemoreceptors to modulate their firing

Question 18

What would be the mechanism in metabolic alkalosis?

high bicarb levels

Answer 18

You can’t compensate

• need to increase CO2 levels to push reaction back to the right= hypoventilate
• oxygen levels will become too low (below 8kPa), so we can’t continually hypoventilate