Ajazzy
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How come thiazides cause hypercalcemia when they have no direct influence on the Na ca counter transport of Distal nephron. Doesn't PTH take care of that ?
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| rida
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Thiazides block the Na/Cl cotransporter, which increases their concentrations within the cell. Even though the Na/Ca Antitransporter is under influence of PTH, that transporter is responsible for bringing sodium in and calcium out to the blood, and with thiazides, the activity of that transporter increases further causing more calcium to be reabsorbed by the blood, and sodium in the cell to be excreted in the urine. This causes a hypercalcemia. Hope i did'nt confuse you further. 
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| Sakaki-
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Due to decreased Na+ reabsorption, the intracellular concentration of Na+ (in the DCT) is reduced, which results in an increased concentration gradient across the basolateral membrane. This enhances the reabsorption of calcium through the Na+/Ca2+ countertransporter.
Edit: Hmm, it seems that rida is saying something different; the intracellular conc of Na+ is increased? as a result of decreased reabsorption. But isn't the Na+/Cl- contransporter on the luminal aspect of the DCT cell, so decreased activity should result in decreased Na+ conc?
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| hiwa
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Sakaki
U right but the concentration gradient leads to flow of the Ca from lumen to the cell via Ca pores(specific for DCT) not Na/Ca countertransport which lead to transport of Ca from intracellular to blood, and also replace the intracellular Na deficit caused by Blockage of Na/cl transporter
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| Ajazzy
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well may be the answer is much simpler.Na cl co transporter is on the luminal side right.
The thiazide blocks the transporter therefore increasing the level of Na in the luminal side. The Ca ions leak thru the cl channels on the luminal side into the cell by electrogenic potential generaed by Na just like what happens in the ascending tubule when Increasing K drives the pus of ca and mg into the tubule cell.
The increased calcium inthe cell is then transprted to blood by a Na Ca countertransporter driven by PTH.... what da ya say !!!
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| rida
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I actually got my explanation from the picture in pharm notes for kaplan under thiazides. What i was trying to say is the blockade of na/cl cotransporter causes an increase in the functioning of the na/ca antitransporter which is reabsorbing Ca's and leads to hypercalcemia.
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| Sakaki-
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So the Na/Ca antiporter increases in activity, contrary to what hiwa said?
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| rida
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hmmm, what hiwa is saying is making sense to me too, maybe got the wrong idea from the picture in kaplan, will check it again.
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| Sakaki-
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Thanks for looking into it! 
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