What is the mechanism behind ventilatory acclimatization?

Question

In my respiratory physiology lectures, my professor explained that hypoxia-induced hyperventilation occurs in 2 stages when people try to acclimate at high altitudes. My question is about the long-term 2nd stage, listed as #2 below:

1. there's an immediate increase in alveolar ventilation triggered by peripheral chemoreceptors, but this only leads to a small increase, and also decreases levels of $p_{CO_2}$.
2. over 8 hrs, there's a slow rise and 2 mechanisms are involved:
   a) bicarbonate ion ($\ce{HCO_3^-}$) in cerebrospinal fluid is shuttled out and chemoreceptors increase their sensitivity to $p_{O_2}$
   b) kidneys excrete more $\ce{HCO_3^-}$ to normalize blood pH

I get that the $\ce{HCO_3^-}$ and $\ce{H^+}$ comes from $\ce{H_2CO_3}$ being broken down through carbonic anhydrase. But she never mentioned where the $\ce{HCO_3^-}$ is shuttled to or which chemoreceptors are increasing their sensitivity to $p_{O_2}$ (I assume peripheral since it's mentioning sensitivity to $\ce{O_2}$). She then says that because of this $\ce{H^+}$ and $\ce{CO_2}$ levels increase, stimulating central chemoreceptors to increase ventilation to help decrease the acidity/$\ce{CO_2}$ levels. I don't understand how $\ce{H^+}$ and $\ce{CO_2}$ levels are even rising because I don't know where the $\ce{HCO_3^-}$ is even going and what it's role is. This professor is terrible at explaining things, and I'm just so confused at this point! Any sort of direction would be so helpful! Thanks!

Answer 1

@Michael Kunh Carbonic anhydrase is used in the human body to tip the balance of the reaction $H_2CO_3\rightleftharpoons H^++HCO_3^-$ to the right side, and is an important player in acidobasic homeostasis.

To answer the question:

$HCO_3^-$ is excreted through the kidneys. This represents the metabolic compensation to respiratory alkalosis that appears in altitude.

To summarize:

1. ascension leaves us in with a lower partial pressure of oxygen. This will stimulate the peripheral chemoreceptors of the carotid bodies and aortic arch to increase ventilation (hypoxic ventilatory response). In consequence, an acute respiratory alkalosis develops.

2. renal adaptation begins after more or less 8 hours, and reestablishes homeostasis after 24-48h. To do that, the kidney will excrete $HCO_3^-$, which will tend to acidify blood (metabolic acidosis to counterbalance respiratory alcalosis). To accelerate this phase, one could take some acetazolamide, a diuretic drug that causes $HCO_3^-$ excretion.