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Old 03-25-2010
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Question Dehydration in sickle cell disease?

Its known that dehydration causes sickle cell crisis .... But why patient with sickle cell disease usually remain dehydrated ?
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Old 03-25-2010
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Default Ion channels

I think it has something to do with disturbed ion channels on the surface of HbS red blood cells making them dehydrated all the time. Of course when have those billions of RBCs dehydrated the whole body is going to be dehydrated.

But am not sure of this explanation, let's wait and see if somebody gives us another explanation.
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Old 03-25-2010
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You're absolutely right (once again!) dr. YoramFishke!

"All red cells contain Gardos channel proteins in their membranes. Sickle cells accumulate excessive quantities of calcium, that activate the Gardos channel (illustrated as the blue circle on the red cell membrane.) The Gardos channel is a protein "pump" that expels intracellular potassium when activated by calcium. The red cells loose water along with calcium. The result is a higher intracellular hemoglobin concentration. This promotes polymerization of deoxygenated HbS."

source: http://sickle.bwh.harvard.edu/clt.html
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Old 03-25-2010
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... and, by the way, very nice remark, Dr. FSUSTC!
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Old 03-25-2010
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Thank for ur replies ...
In Sickle cell disease there is dehydration due to excessive water loss thru kidney ...
Normally urine concentrate in papilla of renal medulla ...
But in sickle cell disease there is papillary necrosis as due to inadequate blood flow in vasa recta which mainly supplies renal papilla ... And there is also partial ischemia of tubular cell ..... due to papillary necrosis papilla cant concentrate urine with help of ADH causes excessive urinary water excretion causes dehydration ....
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Old 03-26-2010
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@ Dr. FSUSTC, on the role of renal papillary necrosis in the manifestation of dehydration in sickle cell disease.

This is a very interesting remark! However I am not so sure of the actual contribution of this mechanism in the context of dehydration in SCD. I mean, yes you are right that renal papillary necrosis is evident in SCD patients. But the major site of action of ADH, with regard to its water regulatory properties, is the collecting duct (through the down-regulation of water channels and the urea countercurrent mechanism), and to a lesser extent the thick ascending limb of Henle's loop (action on the Na-K-2Cl co-transporter). The renal papilla is where the collecting system ends up, but I think the major work of water reabsorption has already been accomplished in the collecting tubules themselves, before they reach the papilla. Of course, the relatively ischemic tubular cell is not functioning properly, but is this the main reason of dehydration in SCD pt's? Am I missing something on this mechanism?
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Old 03-26-2010
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Default It makes sense

I think papillary necrosis is the reasonable explanation. The RBC membrane channel mechanism mentioned above explains how sickling develops but does not explain why we have contracted ECF in Sicklers even without the crisis.
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Old 03-26-2010
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Actually in sickle cell disease there is decrease blood flow in vasa recta causes
1. ischemia in renal medullary papilla later papillary necrosis .. where urine concentrate
2. ischemic damage of renal tubule .. restrict fluid reabsorption ....
Both of these condition together causes large amount of fluid loss thru urine .... thus dehydration ensue ..
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Old 12-21-2011
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this is what i found in basis pg. 646.
this severe derangement in membrane structure causes the influx of Ca2+ ions, which induces the cross linking of the membrane proteins and activate an ion channel that permits an efflux of K+ and H2O. with repeated episodes of sickling, red cells become increasingly dehydrated, rigid and dense.

i know someone said this up there and here it is with the source.
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