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As a molecule, urea is small (molecular weight, 60 Da), is water soluble, and is freely filtered Because of its highly polar nature, it does not permeate lipid bilayers, but a set of uniporters (the UT family) transport urea in various places in the kidney and in other sites within the body (particularly red blood cells) Because urea is freely filtered, the filtrate contains urea at a concentration identical to that in plasma Let us assume a normal plasma level (5 mmol/L) Roughly half the filtered load is reabsorbed in the proximal tubule This occurs primarily by the paracellular route As water is reabsorbed (about two thirds of the filtered water is reabsorbed in the proximal tubule), solutes in the lumen that are not reabsorbed by the transcellular route become concentrated Urea is prominent among these solutes As urea becomes concentrated, it is driven passively through the leaky tight junctions By the time the tubular fluid enters the loop of Henle, about half the filtered urea has been reabsorbed, and the urea concentration has increased to a little more than its value in the filtrate (because proportionally more water than urea was reabsorbed) At this point, the process becomes fairly complicated First, conditions in the medulla depend highly on the individual s state of hydration Second, there is a difference between superficial nephrons, with short loops of Henle that only penetrate the outer medulla, and juxtamedullary nephrons, with long loops of Henle that reach all the way down to the papilla We simplify the issue by considering all nephrons together The interstitium of the medulla has a considerably higher urea concentration than plasma The concentration increases from the outer to the inner medulla (part of the so-called medullary osmotic gradient), and its peak value in the inner medulla depends on hydration status and levels of antidiuretic hormone We explain these variations in 6 in connection with regulation of water excretion For now, we note that the medullary urea concentration is greater than in the tubular fluid entering the loop of Henle, so there is a concentration gradient favoring secretion into the lumen The tight junctions in the loop of Henle are no longer permeable, but the epithelial membranes of the thin regions of the Henle loops express urea uniporters, members of the UT family This permits secretion of urea In fact, the urea secreted from the medullary interstitium into the thin regions of the loop of Henle replaces the urea previously reabsorbed in the proximal tubule Thus, when tubular fluid enters the thick ascending limb, the amount in the lumen is at least as large as the filtered load Because about 80% of the filtered water has now been reabsorbed, the luminal urea concentration is now several times greater than in the plasma Beginning with the thick ascending limb and continuing all the way to the medullary collecting ducts (through the distal tubule and cortical collecting ducts), the luminal membrane urea permeability (and the tight junction permeability) is essentially zero Therefore, a large amount (roughly the filtered load or more) of urea is still within the tubular lumen and flowing from the cortical into the medullary collecting ducts The concentration is now much greater than in the plasma Just how much greater depends on hydration status, because, as is discussed in 6, a variable fraction of the remaining water is reabsorbed in the cortical collecting ducts. vb.net generator pdf417 pdf417 generator vb . net - Barcode SDK
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