Sunday, June 26, 2011

Hypercalcaemia induced polyuria

So Leo’s post got me thinking about the pathophysiology of hypercalcaemia-induced polyuria. I wanted to share what I have learned in relation to the mechanisms of this phenomenon.


Calcium-sensing receptors (CaSR) are found on the basolateral membrane of the cells of the thick ascending limb of the loop of Henle. Binding of calcium, with subsequent receptor activation, appears to induce a downstream message to close off the luminal K channel. This in turn inhibits potassium recycling and thereby shuts off the NKCC2 cotransporter, leading to decreased reabsorption of sodium, potassium and chloride in this segment.


Following on from this, the medullary concentration gradient is diminished, leading to an inablility to concentrate urine and subsequent polyuria.


CaSR are also found on the luminal surface of cells in the inner medullary collecting duct. Activation of these, in the setting of increased distal calcium delivery, down-regulates AQP2 expression, again resulting in an inability to concentrate the urine.


Finally, there may be hypercalcaemia-induced PGE2 production in the thick ascending limb, which can further inhibit sodium chloride reabsorption.


Thankfully, the polyuria and concentrating defects associated with hypercalcaemia tend to regress with correction of the calcium levels. One caveat to this may be patients who have developed an interstitial nephritis (secondary to calcium deposition in the medulla ) from prolonged hypercalcaemia.

2 comments:

  1. Sir, can you please describe the difference between loop diuretics and thiazides when it comes to the inhibition of the concentrating and diluting mechanism? And why thiazides cause more often hyponatremia than loop diuretics? Thanks in advance!

    ReplyDelete
  2. Check out this post http://renalfellow.blogspot.com/2010/03/endocrine-and-thiazide-induced.html

    ReplyDelete

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