Chemical Control of Breathing DEMO - Forster

Question 1

Define: V_E (V may have a dot over it)

Answer 1

Minute expired ventilation

The volume of air expired from a person’s lungs per minute.

Question 2

Define:

1) FETCO₂ / FETO₂
2) PETCO₂ / PETO₂

Answer 2

1) Fraction of CO₂ / O₂ at the Endof aTidal breath

(unitless / %)

2) **Pressure **of CO₂ / O₂ at the End of a Tidal breath

(mmHg)

Question 3

1) What formula do you use to convert the measured FETCO₂ to PETCO₂ (or likewise for O₂)?
2) What other equation will be used in this calculation?

Answer 3

1) PETCO₂ = FETCO₂ x P_norm

(This should be intuitive: knowing the fraction of a gas within a system, one can calculate the pressure of that gas as a fraction of the total pressure of gas in the system)

2) To calculate the normalized pressure, P_norm, subtract pressure due to water vapor from the atmospheric pressure:

P_norm = P_ATM - P_WV

(For our class example, P_ATM in Milw was 740mmHg and P_WV was 47mmHg)

Question 4

Define: CO₂ sensitivity of V_E

Answer 4

CO₂ sensitivity of V_E:

Change in V_E per 1mmHg increase in CO₂

(In class, the student’s V_E increased by 1.6L/min per 1mmHg increase in CO₂)

Question 5

Describe the ventilatory response of hypercapnia.

1) Which chemoreceptors are largely responsible for the response?
2) What is the response? To what extent?
3) Is the response sensitive or insensitive?
4) What parameters of the response change, and how?

Answer 5

1) Brain chemoreceptors
2) Increased ventilation (aka V_I, in L/min) to reach a new steady state of CO₂
3) Sensitive - Gradual changes in response to small CO₂ changes
4) Tidal volume increases first, and does so substantially. **Frequency **increases second, and less so than V_T (at least to the extent of hypercapnia demonstrated in class)

Question 6

1) Does PETCO₂ increase or decrease when breathing a hypercapnic air mixture? Why?
2) Does PETO₂ increase or decrease when breathing a hypercapnic air mixture? Why?

Answer 6

Hypercapnic air mixture:

1) PETCO₂ inceases - there is more in the air
2) PETO₂ increases - metabolic requirements have not increased, and the subject has increased their ventilation in response to the hypercapnia.

Question 7

How would you characterize a subject’s [H⁺] status while breathing CO₂-enriched air?

Answer 7

Respiratory acidosis

Question 8

What are the effects on breathing and plasma [H⁺] of chronic alveolar hypoventilation?

Answer 8

Loss of baroreceptor CO₂ sensitivity over time, leading to chronically elevated plasma [H⁺].

Question 9

Describe the ventilatory response of hypoxia.

1) Which chemoreceptors are largely responsible for the response?
2) What is the response?
3) Is the response sensitive or insensitive?
4) What parameters of the response change, and how?

Answer 9

1) Peripheral (carotid) chemoreceptors respond to decreased O₂
2) Increase in ventilation (aka V_I, in L/min)
3) Insensitive - a large O₂ drop is required before there is a reponse, but once the drop is sufficient, the response is fast
4) Tidal volume increases suddenly and markedly. Frequency changes more gradually but more significantly than in hypercapnia (at least to the extend of hypoxia demonstrated in class)

Question 10

1) Does PETCO2 increase or decrease when breathing a hypoxic air mixture? Why?
2) Does PETO2 increase or decrease when breathing a hypoxic air mixture? Why?

Answer 10

Hypoxia

1) PETCO₂ decreases because of hypoxia-induced tachypnea without an increase in metabolic rate (more CO₂ is breathed off than produced)
2) PETO₂ decreases because there is less O₂ in the inspired air.

Question 11

How would you characterize a subject’s [H⁺] status during hypoxia?

Answer 11

Respiratory alkalosis

Question 12

How do high-altitude natives maintain a higher PO₂ despite lower V_E (as compared to a visitor to high-altitude)?

Would you say high-altitude natives have a increased or decreased response to hypoxemia?

Answer 12

Increased diffusion capacity due to increased respiratory surface area in the lungs.

Decreased response

Question 13

1) The carotd body is innervated by sensory fibers that originate from what ganglion?
2) What nerve do these fibers constitute?
3) Further back, these fibers originate from what part of the brain?

Answer 13

1) Petrosal ganglion
2) Nucleus Tractus Solitarius
3) Carotid Sinus Nerve

Question 14

What cell types can be found in the carotid body?

Answer 14

1. Chemoreceptor cells
   
   • contain cytoplasmic synaptic vesicles near their interface with:
2. Endings of sensory nerve cells
3. Sustentacular cells
   
   • a type of supportive cell
4. Endothelial cells
   
   • of capillaries that surround the clusters of other cells

Question 15

What is the biochemical origin of the chemoreceptor signal?

Answer 15

Controversial / Not known

Likely involves:

• K⁺ channel conductance
• Intracellular Ca²⁺
• Serotonin
• ACh

Question 16

How does the frequency of the carotid chemoreceptor signal change in response to:

1) Increasing CO₂?
2) Decreasing O₂?

Answer 16

1) Increased CO₂: Increased frequency
2) Decreased O₂: Increased frequency

Because both CO₂ and O₂ can alter the frequency rate, you can think of increased CO₂ as increasing the sensitivity of the chemoreceptors to decreased O₂ and vice versa.

Question 17

Are the carotid chemoreceptors more sensitive to hypoxia or hypercapnia?

Answer 17

Hypoxia

Question 18

What would happen if the carotid chemoreceptors were surgically denervated?

Answer 18

• Pronounced hypoventilation
• Attenuation of CO₂ sensitivity

(I would think attenuation of O₂ sensitivity as well, but it’s not listed…)

Question 19

Why can plasma [H⁺] not stimulate the brain chemoreceptors?

Answer 19

The blood-brain barrier is impermeable to H⁺. CO₂ must diffuse across, reacting with H₂O to form HCO₃^- and H⁺, decreasing pH that way.

Question 20

Where are central chemoreceptors found?

Answer 20

All are found at various spots throughout the brainstem.

• Locus coeruleus
• Pontine & Medullary raphes
• Fastigial nucleus
• Medial & Lateral parapyramidal areas
• Nucleus tractus solitarius
• Retrotrapezoidal area
• pre-Bötzinger complex

Question 21

Is the ventilatory response to **respiratory **or metabolic acidosis greater?

Answer 21

Response to respiratory acidosis is greater

(However, lung pathology may prevent the lungs from adequately responding and neccessitate metabolic compensation via HCO₃^-)

Question 22

What are major excitatory factors for chemoreceptor firing?

Major inhibitory factors?

Answer 22

Excitatory:

• Serotonin
• ACh
• Substance P
• NE
• Orexin

Inhibitory:

• GABA
• Glycine

Question 23

Is chemoreceptor stimulation by CO₂ obligatory to stimulate breathing?

Answer 23

No, CO₂ is not obligatory.

There are experimental models in which breathing does not change when PaCO₂ in increased by increasing inspired CO₂.