Hi Dr. Topf,
I hope you are well. I have a clarification question regarding milk alkali syndrome. In this disease mechanism, since you have a loop diuretic like effect on the NKCC2 transport proteins, will you have both hypercalcemia AND hypercalciuria?
Best,
XXXXXXXX
MS2
This question asks about the urine calcium level and yes in this conditionyou will have both hypercalcemia and hypercalciuria.
The elevated calcium binds the calcium sensing receptor on the basal lateral side of the thick ascendig loop of Henle tubule cell. This signals a decrease in activity of the ROM-K channel on the apical side of the tubular epithelial cell.
The Na-K-2 Cl channel (NKCC) of the thick ascending limb depends on ROM-K to allow potassium to be recycled. Sodium and chloride are found at way higher concentrations in the tubular fluid than potassium, so without recycling the potassium, the NKCC would grind to a halt for want of K. Since the K that is reabsorbed by the NKCC is able to leave the cell via ROM-K there is always plenty of K available to keep the NKCC turning. It does however make the seemingly electroneutral NKCC (2 cations and 2 anions) become electrogenic, because the potassium just leaks out down its concentration gradient so there is only 1 net cation reabsorbed compared to 2 anions. This makes the tubule electropositive and provides the energy to drive the paracellular reabsorption of magnesium and calcium (and probably some sodium as well).
Following the Ca sensing receptor shuting down ROM-K, the NKCC slows for want of K, and the tubule loses its positive charge. This prevents calcium and Mg reabsorption leading to increased urinary calcium as well as loss of Na in the urine.
Note that this is an appropriate change in calcium handling to help restore a normal calcium level. The high calcium itself shuts down calcium reabsorption. However this is inadequate to normalize calcium in milk-alkali syndrome since the acute kidney injury lowers the GFR so far that not enough calcium escapes to normalize the serum calcium.
