Loop of Henle TPRH passage

[Postictal Raiden]

This is from TPRH SW passage 69, Q7

The drug acetazolamide inhibits the action of carbonic anhydrase in the kidney, which catalyzes the reaction:

CO2 + H2O --> H2CO3

What effects would the drug have on kidney function?

A. Decreased plasma pH
B. Increased plasma CO2 concentration
C. Increased urine osmolarity
D. Increased H+ secretion


The answer is A. Why it's not B? My rationale is that once you inhibit the above reaction from happening, CO2 level will increases and H2CO3 decreases.

The solution says "It can be inferred that without carbonic anhydrase, the proximal tubule's ability to secrete H+ is inhibited; increased urine pH results. Another consequence is that if H+ is not secreted into urine, then it will remain in the plasma, thereby decreasing plasma pH at the same time that urine pH increases."

Their explanation makes sense, except that carbonic anhydrase would be inhibited from catalyzing the above reaction, which in turn causes a decrease in the H+ produced.

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[sdm33]

carbonic anhydrases catalyze the rapid interconversion so the reversible reaction that occurs rather slowly in the absence of a catalyst.

 

[Meredith92]

So I thought of it like lechateliers principle you would have a build up of CO2 in the plasma like you said which would then cause a shift to the right in the plasma (carbonic anhydrase is only inhibited in the kidney not the blood cells)

Maybe totally wrong on that though!!

 

[Postictal Raiden]

So I thought of it like lechateliers principle you would have a build up of CO2 in the plasma like you said which would then cause a shift to the right in the plasma (carbonic anhydrase is only inhibited in the kidney not the blood cells)

Maybe totally wrong on that though!!

Perhaps this is the key statement

 

[image187]

Just to make it clear, this is taking place in the proximal tubule, not the loop of henle.

The tubular cell secretes out H+ to the lumen, which combines with HCO3- to form CO2 and H2O, which then freely moves back into the tubular cell. This CO2 and H2O combine back together to form HCO3- and H+ in the tubular cell. The bicarb is saved, and the acid is recycled to grab more bicarb. If carbonic anhydride is blocked, H2CO3 builds up in the tubule and H+ is not able to be secreted for HCO3 absorption, leading to a metabolic acidosis. There will be a decreased pH

 

[Meredith92]

Just to make it clear, this is taking place in the proximal tubule, not the loop of henle.

The tubular cell secretes out H+ to the lumen, which combines with HCO3- to form CO2 and H2O, which then freely moves back into the tubular cell. This CO2 and H2O combine back together to form HCO3- and H+ in the tubular cell. The bicarb is saved, and the acid is recycled to grab more bicarb. If carbonic anhydride is blocked, H2CO3 builds up in the tubule and H+ is not able to be secreted for HCO3 absorption, leading to a metabolic acidosis. There will be a decreased pH

But if carbonic anhydrase is blocked h2co3 wouldn't build up... Cuz co2 and o2 wouldn't be able to be converted into h2co3

Unless I'm misunderstanding something?

 

[Meredith92]

Ah just read this wiki page and completely get when you're saying now
Look at the mechanism of action section
http://en.m.wikipedia.org/wiki/Acetazolamide#section_1