Frustrated with FA errata! - Hydrochlorothiazide

[Zzmed]

FA pg 526: Hydrochlorothiazide reduces diluting capacity of nephron

FA errata: Hydrochlorothiazide reduces concentration capacity of nephron

BRS phys: Hydrochlorothiazide decreases ability to dilute urine, while has no effect on ability to concentrate urine

Which one is correct?
I believe it's what BRS physio says.. (predominates on the internet also..)

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[Phloston]

The early-DCT (i.e. where the Na/Cl symporters are) is a location of dilution. Water is not absorbed proportionally to NaCl the same way that it is in the PCT.

So thiazides prevent dilution directly at the early-DCT.

Now, the concentration/dilution capacity of the nephron refers to the ability of distal segments to carry out those functions.

Normally, ADH, at the medullary collecting duct, is responsible for the concentration capacity of the nephron. This capacity is dependent on an osmolarity gradient at this segment of the nephron.

Keep in mind that the early-DCT is cortical, not medullary, so preventing NaCl reabsorption at this segment would not affect the interstitium at the medullary collecting duct where ADH acts. Only loops affect the interstitium because the ascending limb is medullary.

**Therefore, if you use a thiazide, thereby making the urine more concentrated, ADH, despite not losing its ability to concentrate the urine based on a reduction of the medullary interstitial osmolarity (as seen with loops), it instead loses its concentration ability because the tubular fluid is already less dilute.**

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Bottom line:

Thiazides directly reduce dilution of the urine; capacity for dilution is unchanged because in no way are nephron segments distal to the early-DCT unable to dilute concomitant to thiazide administration.

Concentration capacity is in fact decreased. In contrast to loops, where the medullary interstitial osmolarity is decreased, in the presence of thiazides, the tubular fluid has experienced augmented osmolarity; in both cases, the gradient needed by ADH to induce passive water flow is diminished.

 

[Zzmed]

I see... So we are talking about two different functions in two different sites of the nephron.
I admit that this concept wasn't so clear in my head. This is why i got confused.

Thanks for clarifying man.

 

[Phloston]

I think one of the major turning points in terms of getting renal phys down is distinguishing between the cortical and medullary segments, and how ADH's function is affected by proximal alterations.

 

[Zzmed]

Thanks for the note Phloston. Appreciate it.

I wish you a nice outcome on your exam.

 

[Zzmed]

Guys just an update here...

FA 2013 now says that thiazide diuretics reduce diluting capacity of the nephron.

I am confused. I had really grasped the concept with Phloston's explanation but now everything is messed up.

 

[CassieBagley]

Basic mechanisms:
-To dilute means to add water into the lumen (or reabsorb ions from the lumen).
-To concentrate means to reabsorb water from the lumen (or retain ions in the lumen).
-As you know, both loops and thiazides work on the latter by retaining ions within the lumen.
-The key difference is the the location of the diuretics: loops act in TAL in medulla where the interstitiual gradient is developed, whereas thiazides work on DCT in cortex.
-Loops will blocks 2Cl/K/Na reabsorption in the medulla, which not only keep ions within the lumen (concentrates it), but also reduces the ions in the medullary insterstitium (because less ions reabsorbed into the medulla interstitium). It is this medullary interstitium which has the osmotic dragging power to pull water out of the lumen when the urine comes back around through the collecting ducts. Loops thus reduce the ability to dilute (because ions remain within the lumen) and also reduce the ability to concentrate (because less ions in the medullary interstitium means less water can be extracted).
-Thiazides work at the DCT which is in the cortex, not the medulla. The concentrating ability is not affected because the medullary interstitum is generated down by the TAL in the medulla. Here, thiazides can only reduce dilution by keeping ions within the lumen.

 

[Zzmed]

Thanks!

One last thing: diluting ability=diluting capacity???

 

[CassieBagley]

Thanks!

One last thing: diluting ability=diluting capacity???

Diluting ability (the physical mechanisms present to dilute the lumen) vs. diluting capacity (the degree to which your ability is exercised) is almost synonymous here. Both diuretics LIMIT your ability to lower the lumen's osmolality, but only loops limit the ability to also reabsorb water from the lumen. When ADH binds to the V2 receptors and opens up the passive aquaporin channels in the collecting ducts, water will only passively flow back into the interstitium if thiazides were used, but not if loops were used.

 

[Zzmed]

Ok i think i got it.
Thanks!
I will hopefully test the concept in Qbanks.

 

[MaryAnn1]

what is the diluting segment of nephron?
TAL or DCT/Cd

 

[CherryRedDracul]

what is the diluting segment of nephron?
TAL or DCT/Cd

TAL and early DCT. They're both impermeable to water and the dilution is performed by reabsorbing the ions.

 

[MedicineN'Jazz]

Sorry to revive an old thread. Just wanted to say thank you to all the responses on here. I was nearly pulling my hair out in frustration over this. Much love from yours truly!