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Old 04-18-2011
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Kidney Need Clarification of Loop diuretics mechanism in FA2010?

pg 473 in the renal section in FA2010 under Furosemide there's this line thats been bugging me and I just wanted to clarify the concept as I've looked all throughout to understand this and nothing lists it in such a way as FA....

"abolishes hypertonicity of medulla, preventing concentration of urine"

now for the first part of the sentence i understand of how a loop diuretic inhibiting the na, k, 2cl cotransporter would make the lumen more hypertonic than the medulla aka they abolish the hypertonicity of the medulla by inhibiting solutes from reabsorption, thus lumen = hypertonic (less hypotonic) than medulla, and medulla = less hypertonic (or hypotonic) than the lumen.

but i don't quite understand what they mean when they say "preventing the concentration of urine"....shouldn't it be the [Further] concentration of urine? since TAL is impermeable to H20 and in the each subsequent part of the nephron the reabsorption of water requires fH20, and since due to the mechanism of inhibition of na,k,2cl the water remains as obligate h20 and thus wouldn't be reabsorbed by the distal tubule or the collecting ducts, also that the Ca and Mg are not being reabsorbed......and the other part of the story of dec back diffusion of K thus dec +ive potential and decreased anions that follow K out? so what is it when they say "preventing the concentration of urine"

so shouldn't that statement read further concentration of urine? as ADH reabsorbs fH20 and since the water remains Obligate (and with the ions) thus is the mechanism for diuresis?

could someone clarify this stupid statement please! its just making me nuts, lol....i just feel like crossing it out! Thanks guys
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Old 04-19-2011
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Step back for a second and think about the physiology that you already know.

Normally, the Ascending LOH is the "diluting segment" where solutes leave the lumen and water remains, thus decreasing osmolality in the lumen and increasing osmolality in the medulla. When the tubular fluid reaches the distal tubule and collecting duct, water leaves the lumen to go to the medulla and the tubular fluid becomes more concentrated. This leads to a concentrated urine.

When a loop diuretic is used, the osmolarity of the medulla is greatly reduced because essentially all electrolytes are prevented from being absorbed. In the tubular fluid, no electrolytes or water are lost so the osmolality of the tubular fluid remains the same. Now, when the tubular fluid reaches the distal tubule and collecting duct, the medulla cannot pull water out of the tubules so you end up with a dilute urine.

Note the concentrating ability that this statement refers to is that of the distal tubules and collecting ducts (of the medulla).

Hope that cleared things up.
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Old 04-19-2011
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Exactly! the main function of the hypertonic medulla is to concentrate the urine
so loss of hypertonicity = loss of urine concentrating ability of the kidney which is why diuresis occurs
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Old 04-19-2011
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The hyperosmolarity is working on the parts that come before as well (descending limb), not just what comes after - isn't it the salts that the ascending limb pumps into the interstitium that give the descending limb its concentrating power?
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Old 04-20-2011
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yeah thanks guys.....so i did have the right concept then eh? good to know i was on the right track!
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