Control of Ventilation

Now we're moving onto learning about respiration! Yay...? Also, this lecture has a hell of a lot of aims, so hold onto your hat!

Describe the central generation of respiratory rhythm, including the three common hypothesis.

As mentioned here, generation of respiratory rhythm originates from centres in the medulla of the brain. There are several different hypotheses about how these centres interact:

1. Off-switch model: In this model, inspiratory motor neurons stimulate inspiration. Inspiration then feeds back onto some integrating neurons, which then stimulate an "off-switch" to stop inspiration. Eventually, the lack of inspiration stops the "off-switch" neurons, causing the inspiratory neurons to start up again.
2. Oscillator model: In this model, both inspiratory and expiratory neurons are constitutively activated. Inspiratory neurons can activate interneurons that turn the expiratory neurons off, and vice versa. If the timing is right, they can inhibit each other at the right times, generating a rhythm.
3. Pacemaker kernel model: This model suggests that there are some cells that act as a pacemaker. Indeed, some cells in the pre-Bötzinger complex do show synchronised pacemaker spikes. Glutamate inhibitors can block this synchrony.

The off-switch model and oscillator models are also known as "distributed network models," as they require multiple different groups of cells to work together.

Define apnoea, hyperpnea, hypopnea, gasping, apneusis.

• Apnoea: Lack of breathing. May result from damage to the medulla.
• Hyperpnea: Increased breathing
• Hypopnea: Reduced breathing
• Hyperventilation: Increased breathing that goes beyond what your body actually needs. (Note that hyperpnea and hyperventilation both involve increased breathing, but hyperventilation is inappropriate to the situation, whereas hyperpnea is totally appropriate.)
• Apneusis: Prolonged inspirations with short expirations. May occur due to damage to the pons. (This is where the pneumotaxic centre is, as I'll explain in a bit.)
• Gasping: The opposite of apneusis: prolonged expirations with short inspirations.

Describe the brain regions involved in the respiratory rhythm.

See earlier post: Control of Ventilation

Explain the function of the pneumotaxic centre.

See earlier post: Control of Ventilation. Also, as mentioned earlier in this post, the pneumotaxic centre is located in the pons, so damage to the pons causes apneusis.

Identify simple respiratory patterns and how they arise

I'm not really sure what I'm meant to know for this. Apneusis maybe? But I just wrote about that...

Describe the location of the central and peripheral chemoreceptors.

The central chemoreceptors are located in the ventral medulla, whereas the peripheral chemoreceptors are located in the carotid body and aortic arch.

Describe the stimuli that these receptors respond to.

Central chemoreceptors respond to the pH of the cerebrospinal fluid, which actually allows them to respond to CO₂ in a very roundabout way. CO₂ can diffuse through the blood-brain barrier, where it can form H⁺ and HCO₃^- by reacting with water. An increase in H⁺ decreases the pH, which is detected by the central chemoreceptors. It's unclear exactly how the central chemoreceptors are activated. To add even more confusion, there are many cells in the brain that can detect pH: aside from the chemoreceptors in the ventral medulla, cells in the dorsal and ventral respiratory groups, pons and hypothalamus can all respond to pH. Le sigh.

Peripheral receptors can respond to CO₂, H⁺ and O₂, though to my understanding they respond mostly to O₂. Also, carotid bodies may be better at sensing H⁺ than aortic bodies.

Peripheral receptors can respond more rapidly than central chemoreceptors as they don't have to worry about gases diffusing through the blood-brain barrier and whatnot.

Recall the sensory input into control of ventilation, the effectors controlled and where control occurs.

Not sure what exactly I'm supposed to put here that I haven't put under another heading, so I'm just going to shove a link to my old post on ventilation control here and call it a day.

Explain how the peripheral chemoreceptors sense P_O2 and P_CO2

The cells of the peripheral chemoreceptors that detect O₂, CO₂ and pH are called glomus cells. Glomus cells are excitable and can release neurotransmitters, just like nerve cells.

CO₂ can diffuse into glomus cells and cause a change in pH, just like they do in the brain. The increased H⁺ ions can protonate and close calcium-activated potassium channels in the membrane of these cells. As potassium can no longer leave, the cell becomes more and more depolarised, eventually leading to action potentials.

O₂ is detected via a different mechanism. O₂ can be converted into carbon monoxide by an enzyme called haemoxygenase. Carbon monoxide is usually known as a poisonous gas, but it can also serve as a signalling molecule in the cells. In this case, carbon monoxide causes CO-gated potassium channels to open. This keeps the membrane potential low, inhibiting action potentials. If O₂ levels drop, CO levels also drop, allowing these channels to close. (This usually happens when P_O2 < 60mmHg.) As mentioned before, stopping potassium from leaving causes the cell to depolarise and action potentials to be produced.

Explain the response to changes in blood oxygen, carbon dioxide and pH.

As alluded to before, low levels of oxygen (<60mmHg) cause a large increase in ventilation. Aaaaand I don't really have much else to say here.

Most of the response to carbon dioxide (60-80%) occurs via central chemoreceptors, though peripheral receptors play a part too, as discussed above.

Another interesting phenomenon to take note of is that of "synergistic drives." Essentially, this means that when oxygen levels are low, your cells become more responsive to high CO₂, and vice versa. This is because the detection of oxygen and carbon dioxide occur through similar mechanisms: the opening or closing of potassium channels of glomus cells.