I'm reading up on kidney function but all the mechanisms are confusing me and making my head hurt to be frank.
I keep reading that the urine at the top of the ascending limb is dilute as the thick section of the ascending limb actively removes solutes. Where has this urine come from? Is the urine essentially the  filtrate and ions have been added and removed as well as water and urea throughout all the parts of the nephron (PCT, Loop of Henle, DCT, collecting duct)? I also read that 50 percent of the urea is reabsorbed from the PCT, why? What does your body need to keep urea, isn't it supposed to get rid of it all?

This is honestly driving me insane, I must lack a certain amount of sense so that renal function is gibberish to me. I have no idea whatsoever where this urine is from!!!!!

G'Day Alicia:

Don’t get too bogged down with this - yes, the urine is essentially a filtrate travelling through the nephron as you say! Very simply, urine formation involves removing waste from the blood and reabsorbing/secreting substances, especially water and inorganic ions, to maintain homeostatic balance. It begins with the process of filtration - as blood flows through the glomerulus various chemicals (ions like Na+, K+ and others, glucose, and water with them) are filtered out into the Bowman’s capsule by diffusion and osmosis.

The composition of the filtrate is then altered by reabsorption from the tubules into the surrounding tissue fluid. In the PCT, loop of Henle and DCT (closely apposed to the glomerulus at a point called the macula densa) this includes reabsorption of substances like water (passively reabsorbed from PCT and descending, but not ascending limb of the loop of Henle), glucose (actively reabsorbed from PCT) and Na+, K+ and H+ ions (actively reabsorbed from the tubular fluid, e.g., K+ ions are mainly reabsorbed from PCT). In the DCT Na+ and water reabsorption occurs.

Then we have secretion of substances like H+ and K+ ions by active transport from the DCT and collecting ducts. Water reabsorption in the distal nephron and the collecting ducts (mainly inner medullary collecting duct (IMCD)) allows concentration of the filtrate and is regulated by the hormone vasopressin (or arginine vasopressin, or antidiuretic hormone) binding to the V2 receptor - without vasopressin these structures are impermeable to water (an anagram of vasopressin is “**** saver on”).

With respect to urea, although its principal role is in nitrogen excretion, it is critical in urine concentration (see below) and there is some speculation that urea catabolized by bacteria in the gut may benefit the host by obtaining nitrogen for building amino acids (e.g., implied but not successfully tested long ago in the article “Urea as a source of nitrogen for the biosynthesis of amino acids” by Rose WC & Dekker EE. J biol Chem 223: 107-121, 1956; downloadable via google).

Yes, 50% of urea is passively reabsorbed in the PCT. I ran your question past a couple of colleagues who have done some seminal work on urea transport in the kidney. The best evidence is that the uncharged urea ‘simply’ diffuses down its concentration gradient until the urea concentration in the PCT filtrate and blood are equal. This can occur despite the hydrophilic nature of urea largely because the membrane surface area of the PCT is so vast. The key to understanding urea and the kidney is that urea acts as an osmotic diuretic (inhibits reabsorption of water). To quote my colleagues -

“That is a good question. Of course some caution about teleology is in order but I suppose the student means "... urea is reabsorbed from the PCT, what would be the evolutionary pressure that would make this advantageous for animals and humans?

As the student no doubt knows, the urea concentration in the proximal tubule increases with distance along the tubule as salt and water is reabsorbed (typically from 5mM in the glomerular filtrate to 8-10mM downstream). This generates a favourable gradient for passive reabsorption. Prof. Roger Green (U. of Manchester) working with renowned Prof. Gerhard Giebisch a number of years back showed that the osmotic gradient that drives water reabsorption (via aquaporin-1) in the proximal tubule is only on the order of 6-16 mOsm/kg-water (ref. Green R, Giebisch G. Osmotic forces driving water reabsorption in the proximal tubule of the rat kidney. Am J Physiol. 1989 Oct; 257(4 Pt 2):F669-75. PubMed PMID: 2801964). So if too much urea accumulates, it could substantially 'cut into' this small gradient and impair water (and secondarily salt) reabsorption in the proximal tubule.”

AND -

“some of the solute transporters, in particular SGLT1 have been reported to transport urea. SGLT1 and SGLT2 are strongly expressed in the PCT. They are the major conduits for glucose reabsorption from the primary urine.”

So ‘atypical’ transporters may contribute to urea reabsorption in the PCT.

The specific urea transporters are mainly found in the IMCD, thin descending limb of the loop of Henle and in specialized blood vessels called vasa recta in the medulla. Urea is recycled in the kidney, being reabsorbed in a number of places including the IMCD (urea transport here is facilitated by the urea transporters which allow urea to move extremely fast across membranes, a process regulated by vasopressin and other hormones/factors), and secreted in the thin limb of the loop of Henle. Urea recycling causes the build up of high levels of urea in the inner medulla which helps create the osmotic gradient at the loop of Henle so water can be reabsorbed, i.e., the urea in the interstitial fluid helps ‘pull out’ the water from the filtrate, an essential feature in producing a concentrated urine. Work on urea transporter knockout mice (e.g., see - http://www.ncbi.nlm.nih.gov/pubmed/17264985) showed that if the transporters are not present in the IMCD, urea can’t equilibrate across the IMCD epithelium and hence water reabsorption is reduced. About 40% of filtered urea is excreted in urine.

To quote one colleague again -
“Urea is totally a bad guy with respect to water conservation. That is, we could conserve water even better if we did not have to excrete urea. Typically, humans on a western diet can expect to excrete 0.5-1 mole of urea, a huge osmotic load. The urea accumulation in the inner medulla is an evolutionary adaptation allowing this huge amount of urea to be nearly invisible osmotically.”

I hope this helps. There are loads of articles via google on the concentration/formation of urine, some very simple and even formulated as flash cards for students if you prefer (e.g., http://quizlet.com/6143079/urine-format … h-cards/), describing what substances are secreted and/or reabsorbed along the nephron and collecting ducts.

P.S. the collecting duct connects the nephron to the ureter - strictly speaking, it is not part of the nephron.

Last edited by Steve Lolait (6th Dec 2011 21:17:32)