Confused about Loops thiazides effect at PCT?

[voicesinmyhead]

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How are the reflex effects of loops and thiazides different at the PCT level?

I think thiazides lead to much more reflex sodium reabsorption at the PCT than Loops, for some reason? why do thiazides cause hyponatremia then?

On another note, sHouldnt loops be having more reflex sodium reabsorption than thiazides since they lose more water?

 

[voicesinmyhead]

i think ive asked you something like this before. but bear with me @tasar1898 🙂

 

[tasar1898]

It prolly has to with the strength of the diuresis.. with loops you lose like 2-3 times more sodium than with thiazides , so the PCT can't overcome that ...Let's say that the PCT can maximally reabsorb 300mg of Na. Imagine taking your thiazide , losing like 100mg of sodium , then your PCT reabsorbs 200 , for a net gain of 100mg . With the loop , you ll lose like 500mg so even if your PCT reabsorbs ''maximally'' , i.e. 300mg due to volume contraction , you still have a net loss of 200mg . And with sodium , there goes the water and you urinate more--> worsen the DI. It's all a numbers game.. ( But the numbers here are completely arbitrary , just to drive the concept home )

I think this explains it pretty well , loops cause more PCT reabsorption ,not less, than thiazides , you prolly got confused due to the net gain of Sodium with low dose thiazide in the case of DI Tx.

Hyponatremia of thiazides has to do with relative concentrations , and not with total amount of sodium , but this is really getting into too much detail , leave it to the nephrologists or something..

 

[voicesinmyhead]

Thanks! medbullets and a few sites here and there say Li toxicity is caused by thiazides and not by loops. Since Li toxicity in thiazides was because of the increased reabsorption at PCT along with Na/instead of Na?, I was wondering if this was an error in those sites? (since loops cause more PCT reabsorption)

 

[tasar1898]

I really don't know about that , maybe it has to do with the specific pumps blocked by thiazides vs loops..

 

[worldbeater]

Li toxicity is caused by thiazides and not by loops. Since Li toxicity in thiazides was because of the increased reabsorption at PCT along with Na/instead of Na

Your close, Lithium's MOA is unknown, but is thought to be related to the mimicking of sodium. So if sodium reabsorption is blocked by a thiazide in the distal convoluted tubule, Lithium is free to be reabsorbed into the serum, leading to your lithium toxicity. There is a question on World about this that I missed, how thiazides cause volume depletion, and leads to Lithium toxicity.

Also, why do you keep talking about/mixing up the drugs acting on different parts of the nephron? The practice questions are really straight forward, you just need to know what drugs act on what sections. For review:

PCT - Carbonic Anhydrase. Normal physio says that 95% of Bicarb absorbed, and 65% of amino acids, glucose, salt, amino acids, water, and potassium absorbed
Thick ascending loop of Henle: Furosemide (among others)
DCT - Thiazides (block reabsorption of sodium and chloride)
(Early) Collecting Duct - Spironolactone (K+ sparing)
(Late) Collecting Duct - Eplernone, Amilonide, Triametriene (K+ Sparing)

 

[voicesinmyhead]

Your close, Lithium's MOA is unknown, but is thought to be related to the mimicking of sodium. So if sodium reabsorption is blocked by a thiazide in the distal convoluted tubule, Lithium is free to be reabsorbed into the serum, leading to your lithium toxicity. There is a question on World about this that I missed, how thiazides cause volume depletion, and leads to Lithium toxicity. Also, why do you keep talking about/mixing up the drugs acting on different parts of the nephron? The practice questions are really straight forward, you just need to know what drugs act on what sections. For review: PCT - Carbonic Anhydrase. Normal physio says that 95% of Bicarb absorbed, and 65% of amino acids, glucose, salt, amino acids, water, and potassium absorbed Thick ascending loop of Henle: Furosemide (among others) DCT - Thiazides (block reabsorption of sodium and chloride) (Early) Collecting Duct - Spironolactone (K+ sparing) (Late) Collecting Duct - Eplernone, Amilonide, Triametriene (K+ Sparing)

Hey thanks, but with the same logic, why not furosemide too causes Li toxicity? why just thiazides?

 

[worldbeater]

It has to do with the MOA of lithium specifically on the DCT, it's not really due to a low volume state in general. Lithium (Li) copies Sodium (Na) on the DCT and are thought to use the same channel; so in this case Li would follow Na, but Na would block some of it. An appropriate portion of Li is absorbed into the serum. Remember that the MOA of Lithium is still unknown at this point, but this is the theory and makes physio sense.

Since furosemide acts on the thick ascending loop of henle, a different part of the nephron, it doesn't affect the absorption of lithium. In this case, we are just worried about the side effect of reversible hearing loss (World Q) that goes away in 2 days, I believe.

 

[tasar1898]

@worldbeater pretty cool explanation! Remember the additive effects of Loops + Aminoglycosides on hearing , they literally blow the ears up . I used to see it all the time on septic pts in the ICU..