Loop diuretics acidify urine and lose potassium - please explain in English

[TexasTriathlete]

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First of all, I suck at renal. If I had to pick my one real weakness, I would say "medicine". But if I had to be more specific, I would say "renal".

So here's what I understand with my completely fried brain: potassium and h+ are going to be inverse to one another. That is, if you're dumping potassium into the urine, then I would think that you'd be retaining protons, and vice-versa. Is this the paradoxical aciduria thing?

What am I missing here? I read the explanation on USMLERx, and I don't seem to get it. Someone put it in bullet points or something please.

 

[PokerDoc]

First of all, I suck at renal. If I had to pick my one real weakness, I would say "medicine". But if I had to be more specific, I would say "renal".

So here's what I understand with my completely fried brain: potassium and h+ are going to be inverse to one another. That is, if you're dumping potassium into the urine, then I would think that you'd be retaining protons, and vice-versa.

What am I missing here? I read the explanation on USMLERx, and I don't seem to get it. Someone put it in bullet points or something please.

well a loop diuretic is completely inhibiting the Na/K/Cl transporter (and also as a result inhibiting Ca and Mg reabsorption as well) causing a diuresis. However, in response to that, your aldosterone levels will increase reflexively to try to preserve that sodium that you are now not reabsorbing in the thick ascending limb.

There is the missing link, you will get alkalosis systemically and urine acidosis because there is more activity in the collecting duct (meaning more exchange of K+ and H+ for Na+) in an attempt to retain more sodium.

Remember that aldosterone acts both on principle and intercalated cells; and when its trying to maximize Na+ reabsorption in the collecting duct, it will excrete BOTH K+ and H+ in exchange for Na+ by the typical mechanism aldosterone works.

do you follow?


also, FWIW, remember that loop and thiazide diuretics will both cause metabolic alkalosis, and acetezolamide which acts on the proximal tubule and prevents HCO3- reabsorption will cause metabolic acidosis (due to HCO3- loss)

 

[TexasTriathlete]

Got it. Thanks.

It makes sense when you think about it, but I hate thinking about this ****.

 

[otacon88]

an easy way i remember it is the way aldosterone affects the two: with metabolic alkalosis, you get hypokalemia.

-you have an alkalotic environment in your serum
-the cells secrete acid to make it less alkalotic
-there is an H/K exchanger, and so when you secrete H, you take in K
-so with an alkalosis, you get hypokalemia in order to exchange H with K and switch to a metabolic acidosis

at least that's what my understanding is.

 

[NRAI2001]

well a loop diuretic is completely inhibiting the Na/K/Cl transporter (and also as a result inhibiting Ca and Mg reabsorption as well) causing a diuresis. However, in response to that, your aldosterone levels will increase reflexively to try to preserve that sodium that you are now not reabsorbing in the thick ascending limb.

There is the missing link, you will get alkalosis systemically and urine acidosis because there is more activity in the collecting duct (meaning more exchange of K+ and H+ for Na+) in an attempt to retain more sodium.

Remember that aldosterone acts both on principle and intercalated cells; and when its trying to maximize Na+ reabsorption in the collecting duct, it will excrete BOTH K+ and H+ in exchange for Na+ by the typical mechanism aldosterone works.

do you follow?


also, FWIW, remember that loop and thiazide diuretics will both cause metabolic alkalosis, and acetezolamide which acts on the proximal tubule and prevents HCO3- reabsorption will cause metabolic acidosis (due to HCO3- loss)

You re definitely right about Thiazides blocking NKCC transporter leading to overactivity of the collecting ducts... but I didnt realize that there is actually a measurabe increase in aldosterone? I thought Aldo goes up due to changes in RBF?? Diuretics do not change RBF... but it also makes sense eventually you may loose enough salt to kick start the RAS..

So do loop diuretics officially lead to a measurable increases in Aldoesterone?? Never really so this in any UW question or pharm text. Maybe I missed it??

 

[aashkab]

yes, they increase aldosterone.

diuretics decrease plasma volume and decrease renal plasma (blood) flow. you get increased aldosterone like you just said.

i'm not sure if they have "overactivity of the collecting ducts." I thought that the sodium channels are always fully saturated in that part (late DCT/collecting duct) to begin with so it can't become "overactive" because it is already maximally active.

 

[NRAI2001]

yes, they increase aldosterone.

diuretics decrease plasma volume and decrease renal plasma (blood) flow. you get increased aldosterone like you just said.

i'm not sure if they have "overactivity of the collecting ducts." I thought that the sodium channels are always fully saturated in that part (late DCT/collecting duct) to begin with so it can't become "overactive" because it is already maximally active.

The "overactivity" was stressed during renal physio and during pharm... basically more salt is reaching the DCT -> greater activity of the Na/K exchangers in that region bc there is more "substrate" to act on. Not that there is some biochemical change in the DCT transporters... just simply more "substrate" to act on --> increased activity.

 

[PokerDoc]

The "overactivity" was stressed during renal physio and during pharm... basically more salt is reaching the DCT -> greater activity of the Na/K exchangers in that region bc there is more "substrate" to act on. Not that there is some biochemical change in the DCT transporters... just simply more "substrate" to act on --> increased activity.

the term overactive should be used relatively.. its just compared to the patient if they were not on the diuretic. also I want to clarify, you said 'thiazide', we were talking about loops.. they both sort of have the same effect on aldo, but loops are more potent and there are definitely differences and different indications for each drug. so dont confuse the two or group them together for too many purposes.

 

[Ableton]

The "overactivity" was stressed during renal physio and during pharm... basically more salt is reaching the DCT -> greater activity of the Na/K exchangers in that region bc there is more "substrate" to act on. Not that there is some biochemical change in the DCT transporters... just simply more "substrate" to act on --> increased activity.

This was my understanding as well. Also, with the resultant hypokalemia, wouldn't you have suppression of aldosterone synthesis in order to conserve potassium?

 

[PokerDoc]

This was my understanding as well. Also, with the resultant hypokalemia, wouldn't you have suppression of aldosterone synthesis in order to conserve potassium?

No, hence the problem of hypokalemia with diuretic use.. Osmolality dictates movement and if you're hyponatremic your body will fix that over hypokalemia, even though hypokalemia can be more life threatening acutely.

I dont have a full understanding on the mechanism but as far as I know you don't have direct control over K+ conservation w/o the use of a K+ sparring diuretic. Your body can only directly control Na+, K+ movement is indirectly related to the actions around it..


can someone else expand on this or correct me?

 

[drizzt3117]

There's also the effect of hypokalemia on prostaglandin synthesis and JG hypertrophy, if you take them long enough.

 

[NRAI2001]

There's also the effect of hypokalemia on prostaglandin synthesis and JG hypertrophy, if you take them long enough.

I m sorry.. I didn't quite understand what your comment meant? Are you revering to prostaglandins and their effects on RBF and GFR?