S4) Chemical Control of Breathing

Question 1

What is the concentration of bicarbonate in the blood?

Answer 1

22–26mmol/L

Question 2

What is the average PaO₂ in the blood?

Answer 2

9.3–13.3kPa

Question 3

What is the average PaCO₂ in the blood?

Answer 3

4.7–6.0kPa

Question 4

Identify 2 functions of the respiratory system

Answer 4

• Maintain oxygen and carbon dioxide partial pressure gradients to optimise transfer
• Regulate pH of ECF

Question 5

What is hypoxia?

Answer 5

Hypoxia is a fall in pO₂

Question 6

What is hypercapnia?

Answer 6

Hypercapnia is a rise in pCO₂

Question 7

What is hypocapnia?

Answer 7

Hypocapnia is a fall in pCO₂

Question 8

What is hyperventilation?

Answer 8

Hyperventilation is when ventilation increases without change in metabolism

Question 9

What is hypoventilation?

Answer 9

Hypoventilation is when ventilation decreases without change in metabolism

Question 10

How is hypocapnia caused?

Answer 10

• pO₂ changes without a change in pCO₂
• correction of pO₂ will cause pCO₂ to drop

Question 11

Why does a control system need to avoid marked hypoxia?

Answer 11

• Oxygen-Haemoglobin dissociation curve is flat from approx. 8kPa
• Hence, pO₂ can fall considerably before saturation is markedly effected

Question 12

What equation is used to make calculations in the carbonic acid-bicarbonate buffer system?

Answer 12

pH = pK + log [HCO₃^-] / [H₂CO₃^-]

Question 13

Demonstrate the effect of pCO₂ on plasma pH if bicarbonate concentration doesn’t change

Answer 13

If [HCO₃^-] remains unchanged:

• pCO₂ increase = pH falls (notably)
• pCO₂ decrease = pH rises (notably)

Question 14

What happens if the pH rises above 7.6?

Answer 14

Free calcium concentration drops which leads to tetany

Question 15

What happens if the pH falls below 7.0 ?

Answer 15

Enzymes become denatured

Question 16

In two steps, explain how respiratory acidosis occurs

Answer 16

⇒ Hypoventilation leads to an increase in pCO₂

⇒ Hypercapnia leads to a fall in plasma pH

Question 17

In two steps, explain how respiratory alkalosis occurs

Answer 17

⇒ Hyperventilation leads to a decrease in pCO₂

⇒ Hypocapnia leads to a rise in plasma pH

Question 18

How do the kidneys compensate for respiratory acidosis?

Answer 18

Respiratory acidosis is compensated by the kidneys increasing [HCO₃^-]

Question 19

How do the kidneys compensate for respiratory alkalosis?

Answer 19

Respiratory alkalosis is compensated by the kidneys decreasing [HCO₃^-]

Question 20

How long does it take the kidney to compensate for pH changes?

Answer 20

2-3 days

Question 21

In two steps, explain how metabolic acidosis occurs

Answer 21

⇒ Tissues produce acid & this reacts with HCO₃^-

⇒ The fall in [HCO₃^-] leads to a fall in pH

Question 22

How can metabolic acidosis be compensated for?

Answer 22

Change ventilation:

• Increased ventilation lowers pCO₂
• pH is restored to normal

Question 23

In two steps, explain how metabolic alkalosis occurs

Answer 23

⇒ If plasma [HCO₃^-] rises e.g. after vomiting

⇒ Plasma pH rises

Question 24

How can metabolic alkalosis be compensated for?

Answer 24

Compensated to a degree by decreasing ventilation

Question 25

State 3 principles which allow compensation for pH changes to happen?

Answer 25

• Plasma pH depends on the ratio of [HCO₃^-] to pCO₂ and not their absolute values
• Respiratory driven changes in pH compensated by the kidney
• Metabolic changes in pH compensated by breathing

Question 26

Compare and contrast the pH, pCO₂ and HCO₃^- in the following conditions:

• Metabolic acidosis
• Respiratory acidosis
• Metabolic alkalosis
• Respiratory alkalosis

Answer 26

Question 27

Where are the peripheral chemoreceptors located?

Answer 27

• Carotid bodies
• Aortic bodies

Question 28

Explain how peripheral chemoreceptors are sensitive to large changes in pO₂

Answer 28

Stimulates:

• Increased breathing
• Changes in heart rate
• Changes in blood flow distribution (increasing flow to brain & kidneys)

Question 29

Compare and contrast peripheral and central chemoreceptors in terms of pCO₂ sensitivity

Answer 29

• Peripheral chemoreceptors will detect changes but are relatively insensitive to pCO₂
• Central chemoreceptors in the medulla of the brain are much more sensitive to pCO₂

Question 30

What do the central chemoreceptors do?

Answer 30

Detect changes in arterial pCO₂:

• Small rises in pCO₂ increase ventilation
• Small falls in pCO₂ decrease ventilation

Question 31

Ilustrate the negative feedback control of breathing by central chemoreceptors

Answer 31

Question 32

Central chemoreceptors respond to changes in the pH of cerebro-spinal fluid (CSF).

Explain the pH control of the CSF

Answer 32

CSF separated from blood by the blood-brain barrier:

• CSF [HCO₃^-] controlled by choroid plexus cells
• CSF pCO₂ determined by arterial pCO₂

Question 33

What determines the pH of CSF?

Answer 33

CSF pH is determined by ratio of [HCO₃^-] to pCO₂

Question 34

Why is [HCO₃^-] constant in the short term?

Answer 34

Blood Brain Barrier is impermeable to HCO₃^-

Question 35

What is the signficance of this fixed [bicarbonate]?

Answer 35

• Falls in pCO₂ lead to rises in CSF pH (decreases ventilation)
• Rises in pCO₂ lead to falls in CSF pH (increases ventilation)

Question 36

What is the role of [HCO₃^-] in pH of CSF?

Answer 36

• CSF [HCO₃^-] determines which pCO₂ is seen as ‘normal’ CSF pH (‘sets’ the control system)
• It can be ‘reset’ by changing CSF [HCO₃^-] (choroid plexus cells)

Question 37

Describe the events that lead to persistent hypoxia

Answer 37

• Hypoxia detected by peripheral chemoreceptors which increases ventilation
• But pCO₂ falls further which decreases ventilation
• So, CSF composition compensates for the altered pCO₂ and choroid plexus cells selectively add H⁺ / HCO₃^- into CSF
• Central chemoreceptors “accept” pCO₂ as normal

Question 38

Describe the events that lead to persistent hypercapnia

Answer 38

• Hypoxia and hypercapnia lead to respiratory acidosis
• Decreased pH of CSF cause both chemoreceptors to stimulate breathing
• Acidic pH is undesirable for neurons so choroid plexus adjusts pH of CSF by adding HCO₃^-
• Central chemoreceptors “accept” the high pCO₂ as normal