BARTER’S and GITELMAN’s SYNDROMES:
(Congenital Salt Losing Nephropathies).
Barter is a genetic defect in Na/K/2Cl channel in the loop of Henle, leading to loss of Na, K and Chloride in urine. As calcium and magnesium’s absorption is Na dependent, hence they lose Calcium n magnesium too.
Loss of Na absorption at Loop of Henle affects concentrating ability of tubules (ADH can’t work if the loop doesn’t absorb Na to maintain medullary interstitial hypertonicity), so, leading to dilute urine and polyuria.
Loss of Na and water leads to high renin-aldosterone production which causes further loss of K and H-ions with consequent metabolic alkalosis.
Net clinical issues are;
1: Low serum level of Na,K, Cl, Mg and Calcium.
2: Metabolic alkalosis with dehydration
3: Hypovolemia and hypotension
4: Polyuria (dilute urine) with increased urinary electrolytes including Na,K,Cl, Ca and Mg. Increased Calcium loss in urine can cause nephrocalcinosis.
5: High serum renin-aldosterone level.
Loop dietetics also block the same channels and cause acquired Barter’s syndrome. Hence it’s mandatory to exclude their abuse.
Treatment of Barter:
Na,K, Mg etc & water replacement (dietary, oral supplements etc when possible, otherwise IV).
Spironolactone or other K-sparing diuretics to control secondary hyperaldosteronism which help treat metabolic alkalosis and low K.
Family screening and genetic advice.
(Thiazide diuretics can control urinary calcium loss and make urine bit concentrated but worsen Na, K, Mg and water deficiency, so they are not used).
GITELMAN:
It can thought of as a milder form of Barter (as loop handles 25% Na and DCT handles 5% of Na). It has few difference from Barter, so will discuss those (rest will be similar).
1: It’s genetic defect in DCT Na/K channel (not loop).
2: Electrolyte loss is milder than Barter (DCT reabsorbs only 5% of Na).
3: Urinary concentrating ability is not affected (Loop of Henle, collecting tubules and ADH are needed to make urine concentrated. Please note DCT isn’t needed for this purpose and this is one reason why Thiazide can be used in Nephrogenic DI).
4: Hypercalcemia with low urine Calcium- this is a diagnostic difference from Barter’s. DCT is only place where Ca and Na are not coupled with each other, rather they move opposite to each other. Losing Na at DCT cause increased Calcium reabsorption- a fact making thiazide diuretics an option to treat hypercalciuria. Also explains how thiazide diuretics cause hypercalcemia).
5: Thiazide diuretics also block the same channels and cause acquired Gitelman, hence their abuse should be excluded.
6: Low Calcium In diet is needed.
Rest of the facts for Gitelman are quite similar to Barter