Wednesday, September 30, 2015

Why does thiazide, a diuretic, cause a paradoxical anti-diuretic effect in Diabetes insipidus?

Hey everyone!

I have explained this before (In one of my earlier posts on free water clearance) but someone found my language too complicated to understand. So I decided to write this post.. An explanation which is "free" of complicated terms like free water clearance. Yaay! :D

ADH absorbs water. In nephrogenic diabetes insipidus, the kidney is unresponsive to ADH.

What do you then?

You use a drug called thiazide.

Thiazide diuretics inhibit the NaCl co-transporter  in the renal distal convoluted tubule (DCT).
The DCT is water impermeable.. So the DCT action is NOT how thiazides preserve water.

Then what is preserving water?

The antidiuretic action of thiazides is secondary to increased renal sodium excretion. The renal sodium loss causes extracellular volume contraction leading to lowered GFR and increased proximal tubular sodium and water reabsorption. Hence, less water and solutes are delivered to the distal tubule and collecting duct and are lost as urine.

Also, there are other mechanisms that may come into play, like upregulation of aquaporin channels and ENaC subunits, which you can read on Ryan's blog, here.

That's all!


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