Free water clearance decreased by ?
Furosemide Free water clearance Kidney excretes some solutes in the urine daily. The volume of water in urine, excreted per unit time in excess of that required to excrete the contained solutes isoosmatically with plasma is called free water clearance. Free water clearance is positive dilute urine, negative when concentrated urine is passed and zero when isotonic urine is passed. For example, if 1 lit water is required to excrete the contained solutes per day following three conditions may occur (numerical value are just for example). - If urine output is 1.5 litre than free water clearance will be + (positive) *5 lit/day. - If urine output is 1 litre per day, the free water clearance will be zero. - If urine output is *5 litre per day, the free water clearance will be -- (negative) .5lit/day. Action of diuretics To understand the effect of different diuretics on free water clearance one should know the following facts. The nephron of the kidney is arranged in such a way that some poion of it lies in the coex and some poion of it lies in the medulla. - Pas of nephron in the coex - Proximal convoluted tubule Distal convoluted tubule Thick ascending limb of Henle's loop Coical collecting duct - Pas of nephron in the medulla -9 *Descending thin limb of Henle's loop Ascending thin limb of Henle's loop Medullary collecting duct The coical poion of the nephron are responsible for diluting the urine (i.e., positive free water clearance) The medullary poions of the nephron are responsible for concentrating the urine (i.e.. negative free water clearance) Thus the diuretics which act on both medulla and coex can affect both the positive and negative free water clearance where as diuretics which act on either coex or medulla cannot affect both the negative and positive free water clearance. Furosentide Furosemide is a drug which act on both coex and medulla. It acts on the ascending limb of loop of henle which has both coical and medullary component i.e. the thin ascending pa is situated in the coex and the thicker poion is situated in the medulla. Furosemide acts in the following ways: - In hypovolemia medullary pa of ascending limb concentrate the --) negative free water clearance urine to preserve water --> block negative free water clearance - Furosemide blocks the concentrating ability of the ascending limb pa of medullary pa - In volume overload, coical poion of ascending limb of henle --) positive free water clearance loop dilute the urine to decrease the volume overload - Furosemide blocks this diluting ability as well block positive free water clearance. Thus Furosemide can block positive as well as negative free water clearance. Thiazide diuretics act on DCT and proximal pa of CD, block positive free water clearance but has no effect on negative free water clearance. In hypervolumia DCT dilute the urine to decrease the volume overload -4 positive free water clearance --> blocked by thiazide. As thiazide diuretics no effect on medullary interstitium (in contrast to furosamide) so it does not effect the kidney's ability to concentrate urine during hypovolemia --4 no effect on negative free water. Two more options given in the question block free water clearance Vincristine Vincristine increases the secretion of the hormone A.D.H. Inreased A.D.H blocks free water clearance. Chlorpropamide Chlorpropamide sensitizes the kidney to ADH action. Thus it may impair the free water clearance and in some patients may result in hyponatremia and water intoxication. The impoant point to remember about chlorpropamide is that its action depends on small amount of ADH it won't act in the absence of ADH. Most probably the question should have been framed as "All of the following blocks free water clearance, except" But if you have to choose one answer, go for Furosemide as it will always block free water clearance whereas other drugs will cause them occasionally as their adverse effect.
Vincristine
Vinblastine
Chlorpropamide
Furosemide