Cause of nephrocalcinosis in granulomatous ds aEUR'
Increased calcium absorption [Ref: Robbin's 7/e p. 2387; Harrison 17/e p. 23871 Hypercalcemia associated with sarcoidosis The predominant mechanism for the development of hypercalcemia and hypercalciuria is the increased intestinal absorption of calcium induced by elevated calcitriol (1,25 hydroxyvitamin D). Sarcoidosis is associated with ectopic and unregulated synthesis of calcitriol by steroid tissue in response to sunlight or ingestion of vitamin D. The macrophage monocyte line of immune cells express the enzyme la hydroxylase which is identical to the I a hydroxylase present in kidney. - 1 a hydroxylase conves 25 hydroxyvitamin D to 1,25 hydroxy vitamin D. (calcitriol) la hydroxylase 25 hydroxy vitamin D > 1,25 dihydroxy vitamin D (Calcitriol) - (Normally this conversion takes place in kidney) 1,25 hydoxyvitamin D in turn causes increased absorption of calcium in intestine. Activity of I a hydroxylase enzyme is under negative feedback control in normal tissues. - However, in granulomatous disorder normal feed hack inhibition is abolished, probably by the effects of interferon gamma. - Interferon gamma induces the activity of la hydroxylase this leads to increased production of calcitriol (1,25 hydroxyvitamin D). - Increased production of calcitriol causes augumented intestinal absorption of calcium. Hypersensitivity to vitamin D remains despite b/I nephrectomy indicating that increase in serum calcitriol is not mediated by renal I a hydroxylase.
Increased absorption
Increased conversion to 1,25 OH
Dystrophic calcification
Mutation in calcium sensing receptor