Hypocalciuriaoccur in? (PGI Nov 11)
1. Bartter's syndrome and Gitelman’s’ syndrome are characterized by Hypokalemia without hypertension
a. Renal potassium wasting (Can lead to periodic paralysis)
b. Metabolic alkalosis
d. Blood pressure usually is normal or reduced
e. Renin and aldosterone levels are very high.
Genetics and Pathogenesis of Bartter’s syndrome and Gitelman’s syndrome
A. Bartter's syndrome
i. In Bartter's syndrome, the primary defect lies in one of the epithelial transport proteins involved in the reabsorption of sodium chloride, most commonly the furosemide-sensitive Na + -K+ -2CIcotransporter in the ascending limb of Henle's loop.
ii. There is NaCl wasting, hypercalciuria, and mild hypomagnesemia.
iii. The clinical syndrome mimics a state induced by chronic ingestion of a loop diuretic.
B. Gitelman’s syndrome
a. It is due to mutations in the thiazide-sensitive Na-Cl co-transporter (NCCT) in the DCT.
b. Defects in NCCT in Gitelman’s syndrome impair sodium and chloride reabsorption in the DCT and, thus, resemble the effects of thiazide diuretics.
c. Hypomagnesemia&Hypocalciuria is a feature.
Rx Bartter’s Syndrome and Gitelman’s syndrome
1. Both conditions require lifelong therapy with potassium and magnesium supplements and liberal salt intake.
2. High doses of spironolactone or amiloride are necessary to treat the hypokalemia, alkalosis, and magnesium wasting.
3. NSAIDs reduce the polyuria and salt wasting in Bartter’s syndromebut are ineffective in Gitelman’s syndrome. They may be lifesaving in hyper prostaglandin E syndrome.
4. In Gitelman’s syndrome magnesium repletion is essential to correct the hypomagnesemia and control muscle weakness, tetany, and metabolic alkalosis;
Extra Edge: Hyperprostaglandin E syndrome is a particularly severe form of Bartter's syndrome in which neonates present with pronounced volume depletion and failure to thrive, as well as fever, vomiting, and diarrhea from PGE2 overproduction. (H-18thPg- 2361)