Hypokalemia and Alkalosis?

[phoenix89]

Can anyone tell me why we see Hypokalemia a/c with Alkalosis; and Hyperkalemia with Acidosis?

I know that because in Alkalosis, the blood PH is too high, so inorder to counter that, the intracellullar H ions go out of the cells into the blood, using the H-K pump, pushing K into the cells, and as such decreasing the serum K levels (vice versa in Acidosis)

But I'm asking this from a renal point of view. Let's say in Heart Failure, the Renin-Angiontensin system becomes active, increases Aldosterone, which retains Sodium and excretes K and body becomes hypokalemic. In this scenario, where does the Alkalosis come from?

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[Phloston]

Can anyone tell me why we see Hypokalemia a/c with Alkalosis; and Hyperkalemia with Acidosis?

I know that because in Alkalosis, the blood PH is too high, so inorder to counter that, the intracellullar H ions go out of the cells into the blood, using the H-K pump, pushing K into the cells, and as such decreasing the serum K levels (vice versa in Acidosis)

But I'm asking this from a renal point of view. Let's say in Heart Failure, the Renin-Angiontensin system becomes active, increases Aldosterone, which retains Sodium and excretes K and body becomes hypokalemic. In this scenario, where does the Alkalosis come from?

Aldosterone not only increases principal cell basolateral Na+/K+-ATPase activity (as you've mentioned), but it also upregulated the intercalated cell apical H+/K+-antiporter. You lose protons there. However, given that K+ is reabsorbed via this latter transporter, you might ask why K+ is still low. It's bc in the hypokalaemic state, the principal cell Na+/K+-antiporter substitutes H+ for K+ in order to reabsorb Na+ (USMLE Rx mentioned this at least thrice). This is why in hypokalaemia (or hypokalaemic volume-contraction), we see paradoxical aciduria; the urine is acidic despite the alkalotic state. On the USMLE, you'll see the lab values and it will get confusing if you haven't encountered the question before, so know about paradoxical aciduria.

Hope that helps,

 

[rocketbooster]

Aldosterone not only increases principal cell basolateral Na+/K+-ATPase activity (as you've mentioned), but it also upregulated the intercalated cell apical H+/K+-antiporter. You lose protons there. However, given that K+ is reabsorbed via this latter transporter, you might ask why K+ is still low. It's bc in the hypokalaemic state, the principal cell Na+/K+-antiporter substitutes H+ for K+ in order to reabsorb Na+ (USMLE Rx mentioned this at least thrice). This is why in hypokalaemia (or hypokalaemic volume-contraction), we see paradoxical aciduria; the urine is acidic despite the alkalotic state. On the USMLE, you'll see the lab values and it will get confusing if you haven't encountered the question before, so know about paradoxical aciduria.

Hope that helps,

And just to be clear, is it correct that you would NOT see a paradoxical aciduria if aldosterone is super increased (i.e. Conn's syndrome or something)? You would get hypokalemia, metabolic alkalosis and aciduria but in this case it is not considered paradoxical but instead considered expected, right? Since in this case the direct cause of the metabolic alkalosis is the aciduria frome excess excretion of H+ due to high aldosterone?

 

[Phloston]

And just to be clear, is it correct that you would NOT see a paradoxical aciduria if aldosterone is super increased (i.e. Conn's syndrome or something)? You would get hypokalemia, metabolic alkalosis and aciduria but in this case it is not considered paradoxical but instead considered expected, right? Since in this case the direct cause of the metabolic alkalosis is the aciduria frome excess excretion of H+ due to high aldosterone?

The paradox is that you've got acid in the urine when you're alkalotic. When your serum pH is elevated, you'd expect for the kidney to retain protons, rather than jettison them.

In Conn's, as serum potassium ebbs, the principal cell basolateral Na+/K+-ATPase will begin secreting protons instead of K+, producing acidic urine, despite the alkalosis. This is still "paradoxical." The intercalated cell proton-K+ antiporter is less relevant.

The "classic" paradoxical aciduria is seen with contraction alkalosis (e.g. vomiting). For the USMLE, they want us to know that the alkalotic state is significant secondary to aldosterone's attempt to restore plasma volume versus just due to the mere loss of protons secondary to emesis. In this case, relative to Conn's, por ejemplo, the pH differential between the plasma and urine is more salient- hence classic.

 

[lucky01]

Can anyone tell me why we see Hypokalemia a/c with Alkalosis; and Hyperkalemia with Acidosis?

I know that because in Alkalosis, the blood PH is too high, so inorder to counter that, the intracellullar H ions go out of the cells into the blood, using the H-K pump, pushing K into the cells, and as such decreasing the serum K levels (vice versa in Acidosis)

But I'm asking this from a renal point of view. Let's say in Heart Failure, the Renin-Angiontensin system becomes active, increases Aldosterone, which retains Sodium and excretes K and body becomes hypokalemic. In this scenario, where does the Alkalosis come from?

The answer to your question about where the Alkalosis comes from in case of aldosterone being activated: When aldosterone is activated, it causes Na+ re absorption, this causes lumen negativity and as a result alpha intercalated cells secret K+ and H+. So it is expected to see hypokalemia and metabolic alkalosis with secretion of aldosterone, or rather i should say "a lot of aldosterone secretion."

ps. i know this is 5 years late, but still in case anyone else is wondering

 

[Rahas]

As far as I'm aware aldosterone on principal cells will activate the basolateral Na/K-ATPase pump, as well as insert Na and K channels on the luminal side. This causes Na absorption and the simultaneous loss of K to maintain electrical neutrality. Some H will also move out; the amount is variable and inversely related to serum K concentration (lower availability allows H to compete for the channel to a greater degree).

Aldosterone will also activate the H-ATPase pump in alpha intercalated cells, which contributes to the alkalosis. As far as I'm aware, the H/K-ATPase in alpha intercalated cells is influenced by dietary K intake / serum K levels, and not by aldosterone.

Hyperkalemia also increases activity of the H/K antiporter. In PCT cells this means lowered intracellular concentration of H, which leads to a reduction in ammoniagenesis, and hence decreased acid secretion from the body. Hypokalemia should do the reverse.

 

[3member]

Hyperkalemia also increases activity of the H/K antiporter. In PCT cells this means lowered intracellular concentration of H, which leads to a reduction in ammoniagenesis, and hence decreased acid secretion from the body. Hypokalemia should do the reverse.

Hi,

I was wondering if you could elaborate on how Hyperkalemia increases H-K activity?
I would think that hyperkalemia (lots of K+ in blood) would decrease H-K activity since it's trying to get rid of the K+ to a lower concentration.

 

[Rahas]

The H/K antiporter moves K into cells and H out.

Hyperkalemia would increase the gradient for K moving in, while simultaneously effecting an efflux of H. This creates intracellular alkalosis in the PCT cells, which decreases ammoniagenesis. (BTW, this is how metabolic acidosis is created in type IV RTA)

 

[3member]

The H/K antiporter moves K into cells and H out.

Hyperkalemia would increase the gradient for K moving in, while simultaneously effecting an efflux of H. This creates intracellular alkalosis in the PCT cells, which decreases ammoniagenesis. (BTW, this is how metabolic acidosis is created in type IV RTA)

Thanks for the reply,

I guess what I am confused is if the HKA is on the apical side (facing the tubule) of the PCT cell, I don't see how an increase in K+ (right side) in the blood would drive this pump.

If you have a lot of K+ in the blood, it would move into the cell (from the right) and seems like it would counteract the HKA pump on the left. I'm probably missing something here.

 

[hsk013]

You can think about it like this (according to Boards and Beyond) and correct me if I am wrong.

Hypokalemia → K+ are moving from lumen to the inside of cells → lumen is more negative than before → H+secreted out to the lumen to make up for the electrical neutrality (now lumen is not negative anymore) → metabolic alkalosis

 

[3member]

You can think about it like this (according to Boards and Beyond) and correct me if I am wrong.

Hypokalemia → K+ are moving from lumen to the inside of cells → lumen is more negative than before → H+secreted out to the lumen to make up for the electrical neutrality (now lumen is not negative anymore) → metabolic alkalosis

Thanks for the reply,

I was actually asking about how hyperkalemia would induce metabolic acidosis via the mechanism of the HKA transporter on the a-intercalated cells.

 

[Rahas]

That diagram doesnt show the H/K antiporter, only the ones that are specific to the alpha intercalated cells. What you're confusing it with is the H/K-ATPase, which is a different channel.

The H/K antiporter is a channel present on every cell of the body. Its distinct from the ones shown in that picture.

If you read the bit in FA about the effect of diuretics on NaCl, potassium, acid base status etc you'll notice the H/K antiporter is mentioned there.

 

[Rahas]

Oh sorry, didnt read your post fully.

The H/K antiporter moving in potassium into PCT cells (you're showing an alpha intercalated cell) creates intracellular alkalosis in PCT cells -> this inhibits ammoniagenesis -> decreases the amount of acid that can be trapped in the filtrate -> decreased acid secretion via urine.

I'm not sure what the effect of the H/K antiporter moving K into the alpha intercalated cell would be. But these are ATPases, so maybe they dont care about concentration gradients.