Question

Some mountain climbers will take a medication, called acetazolamide (trade name Diamox), starting 24 hours prior to ascending to elevation as a preventative to reduce high altitude sickness. To figure out how this alleviates high altitude sickness, answer the following questions.

1. Around 70% of CO2 is transported in the blood as bicarbonate ions. Draw this reaction.
2. Acetazolamide inhibits the enzyme that catalyzes the reaction between CO2 and H2O and the dissociated ions of carbonic acid (bicarbonate and H+). What effect would this have on blood pH, blood PO2, and blood PCO2?
3. Acetazolamide triggers the kidneys to excrete bicarbonate and increase the respiratory rate. What effect would this have on blood pH, blood PO2, and blood PCO2?
4. Based on these answers, how does this help to prevent high altitude sickness?

Answer 1

Acetazolamide inhibits the enzyme (carbonic anhydrase) that catalyzes the reaction between CO2 and H2O and the dissociated ions of carbonic acid. As a result blood pH will decrease do to accumulation of carbonic acid (since forward reaction blocked by enzyme inhibition), pCO2 will increase do to accumulation of CO2 (since forward reaction with H2O blocked by enzyme inhibition). As a consequence of increased pCO2, pO2 will decrease.

Acetazolamide triggers the kidneys to excrete bicarbonate and increase the respiratory rate. As a result blood pH will decrease due to excretary removal of alkaline bicarbonate, pO2 will increase due to increased O2 ventilation by increased respiratory rate and pCO2 will decrease by reducing CO2 retention.

High altitude sickness arises due to decreased O2 tension in the atmosphere at high altitude. So, in order to meet the O2 demand of the body, hyperventilation occurs. This will result in increased removal of CO2 from the body leading to respiratory alkalosis. Acetazolamide administration helps to overcome this respiratory alkalosis by acting as described above (inhibiting carbonic anhydrase, increasing excretion of bicarbonates). In this way, acetazolamide results in an artificial compensatory mechanism to what the body believes to be excess CO2. This compensation result in faster and deeper breathing. The outcome of that is higher levels of oxygen in the body, which improves the ability of the body to adjust itself to higher altitude levels.