Thiazides = hypercalcemia, Loop diuretics = hypocalcemia

[loveoforganic]

Can someone please explain the physio behind this? I can't find a good answer anywhere, and I'm talking myself in circles trying to ration it out.

Thanks in advance!

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[johndoe3344]

Loop diuretics inhibit the NKCC. This diminishes the positivity in the lumen, reducing calcium paracellular absorption = more excreted.

Thiazides decrease calcium excretion because they:
1) upregulate NCX due to low intracellular Na concentrations = more calcium reabsorbed
2) volume depletion causes upregulation of Na reabsorption = enhanced paracellular calcium reabsorption

 

[JackShephard MD]

Can someone please explain the physio behind this? I can't find a good answer anywhere, and I'm talking myself in circles trying to ration it out.

Thanks in advance!

To expand what the other poster said:

Loop diuretics like furosemide inhibit NKCC.

Well, as you reabsorb potassium, some will diffuse back into the lumen. This diffusion creates a positive potential in the lumen (K -----> lumen +). Losing this positive potential means that calcium will tend to fill its void, meaning more calcium will be excreted and less will be reabsorbed.

As for thiazides, on the basolateral side (not the apical / lumen side) of the distal convoluted tubule, there is a sodium/calcium exchange transporter. Well, because this diuretic acts to block NaCl reabsorption, there will be a lack of sodium inside the distal tubule cells (as more NaCl is excreted with water). These cells will then tend to use this basolateral exchanger to bring in more Na. Well, that means they will have less calcium in them (and more calcium will be brought into the interstitium). The new lack of calcium inside the cell (and corrected sodium) will tend to increase calcium reabsorption from the lumen into the distal tubule cells. Therefore increasing overall calcium in the body.

The other mechanism described occurs in the proximal tubule, the thiazide-induced volume depletion leads to enhanced sodium reabsorption and passive calcium reabsorption alongside.

 

[loveoforganic]

Thank you both - makes a lot of sense!

I was getting into messing with the medullary interstitium and I can't even remember what else.

 

[lookmanohands]

To expand what the other poster said:

Loop diuretics like furosemide inhibit NKCC.

Well, as you reabsorb potassium, some will diffuse back into the lumen. This diffusion creates a positive potential in the lumen (K -----> lumen +). Losing this positive potential means that calcium will tend to fill its void, meaning more calcium will be excreted and less will be reabsorbed.

As for thiazides, on the basolateral side (not the apical / lumen side) of the distal convoluted tubule, there is a sodium/calcium exchange transporter. Well, because this diuretic acts to block NaCl reabsorption, there will be a lack of sodium inside the distal tubule cells (as more NaCl is excreted with water). These cells will then tend to use this basolateral exchanger to bring in more Na. Well, that means they will have less calcium in them (and more calcium will be brought into the interstitium). The new lack of calcium inside the cell (and corrected sodium) will tend to increase calcium reabsorption from the lumen into the distal tubule cells. Therefore increasing overall calcium in the body.

The other mechanism described occurs in the proximal tubule, the thiazide-induced volume depletion leads to enhanced sodium reabsorption and passive calcium reabsorption alongside.

I'll just expand a bit. Start off with the Na/K pump that is dictating the flow of ions. It makes sure Na concentration is low inside the cell and K concentration is high inside the cell and burns ATP to set up that unique situation so the body can then utilize it for different things

For loops, its not so much that Ca is filling a void in positive charge from K not being in the lumen as it is that you no longer have the strong repelling force in the lumen from that unique K flow to drive Ca and Mg into the cells. With the NKCC pump, you're absorbing a net charge of zero but the high K concentration inside allows K to leave back into the lumen,following its concentration gradient. Now the lumen potential switches charge and the positive charge especially repels 2+ charged ions out of the lumen

For the DCT, the low intracellular Na concentration will allow Na to flow down its concentration gradient into the cell. On the lumen side, its a NaCl cotransporter and on the basolateral side is the NaCa antiporter and both are competing against each other to try to get Na in (the other ions are dragged in their respective direction). If you block one side, the other side will dominate. This part of the tube is also controlled by PTH to decide how much Ca can be absorbed from the lumen side of the cell