Urea recycling

Definitions & Key takeaways

Urea recycling is a process in kidneys that involves the reabsorption and secretion of urea several times, which contributes to the high concentration of solutes in the renal medulla and helps to establish and maintain the corticopapillary gradient. This gradient is important for water conservation and urine concentration, allowing the kidney to produce concentrated urine and conserve water.

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Introduction0:00–1:21

If we take a cross-section of the kidney, there are two main parts, the outer cortex and the inner medulla. If we zoom in, there are millions of tiny functional units called nephrons which go from the outer cortex down into the medulla and back out into the cortex again.
These nephrons perform the major function of the kidney, which is to clear harmful substances from the body by filtering the blood.
Each nephron is made up of the glomerulus, or a tiny clump of capillaries, where blood filtration begins. The stuff that gets filtered into the tubule is called the filtrate, and the rest of it leaves the glomerulus through the efferent arteriole.
interestingly, the blood that leaves these glomeruli does not enter into venules. Instead the efferent arterioles divide into capillaries a second time.
These peritubular capillaries then reunite and at that point the blood enters venules and eventually drains back into the venous system.
Now, The renal tubule is a structure with several segments: the proximal convoluted tubule, the U- shaped loop of Henle with a descending and ascending limb and the distal convoluted tubule, which winds and twists back up again, before emptying into the collecting duct, which collects the final urine.

Nephron1:21–1:49

Now, zooming in on this nephron’s tubule, each one’si lined by brush border cells which have two surfaces. One is the apical surface which faces the tubular lumen and is lined with microvilli, which are tiny little projections that increase the cell’s surface area to help with solute reabsorption.
The other is the basolateral surface, which faces the peritubular capillaries, which run alongside the nephron. The urine osmolarity is the concentration of urine, and is measured in Osmoles per liter,which is the solute particles that exist in a liter of urine.

Urine Osmolarity1:49–2:54

To concentrate urine, or increase its osmolarity, nephrons rely on the corticopapillary gradient, which is a concentration gradient that spans from the cortex to the papilla which is the innermost tip of the medulla.
In other words there are a lot of solutes in the interstitium with more solutes down here then up here. So as a tubule dives deeper down into the medulla, the surrounding interstitium gets more and more hypertonic relative to the lumen of the tubule, and that drives more and more water out of the tubule, the deeper it goes.
So you can see how important the corticopapillary gradient is - it prevents us from unnecessarily losing water - like a water recycling mechanism.

Urea Recycling2:54–5:27

Establishing the corticopapillary gradient takes a lot of work - specifically, it relies on two key mechanisms - urea recycling which helps bring urea into the interstitium and countercurrent multiplication which helps bring electrolytes into the interstitium.
Let’s focus on urea recycling, and let’s start with urea itself which is one of the blood’s waste products. Urea is continually formed within the body as a by-product of amino acid or protein breakdown and it’s dumped into the bloodstream.
So urea molecules in the blood get freely filtered across the glomerular capillaries, and make their way through the renal tubule.
In general, urea moves along its concentration gradient, meaning that it passively diffuses from areas of high to low concentration.
In the initial filtrate, its concentration is identical to that in the blood, so at first, there is no concentration gradient and there’s 100% of the urea filtered still in the tubule.
But in the proximal tubule, both urea and water get reabsorbed. Proportionally, more water is reabsorbed than urea, and that causes the urea concentration in the tubular lumen to become higher than its concentration in the blood.
By the end of the proximal convoluted tubule, about half or 50% of the initial filtered urea is in the tubule, and the other half is reabsorbed, and what remains goes into the thin descending limb of the loop of Henle.
Now, deep in the inner medulla, the concentration of urea in the interstitium is much higher than the urea concentration within the tubule, so urea diffuses into the lumen.
In fact, typically, more urea is secreted into the lumen than what was reabsorbed in the proximal tubule, so at the bottom of the U-shaped bend in the loop of Henle, there’s more urea than what was present in the initial filtrate.
Specifically, there’s about 110% of the filtered load of urea. Now, next is the thick ascending limb of Henle’s loop and the early distal convoluted tubule, but these are all totally impermeable to urea, so no urea reabsorption or secretion goes on here.
These segments are also impermeable to water, so urea’s concentration coming out of these is going to stay the same—110% of the filtered load.

Antidiuretic Hormone (ADH)5:27–7:15

Finally, there’s the late distal convoluted tubule, cortical and outer medullary collecting ducts, and that’s where antidiuretic hormone or ADH from the posterior pituitary gland can help increase water reabsorption.
The way it does that is by making the cells lining these tubules incorporate water protein channels called aquaporins in their luminal membrane.
More ADH in the blood, means that there are more aquaporins around to facilitate water diffusion through the cells and into the interstitium.
But what causes water to move in the first place is that the osmolarity in the surrounding interstitium is much higher than that within the lumen.
And that high interstitial osmolarity is the result of having a bit of urea and a whole lot of other solutes, like sodium chloride NaCl.
In other words, most of that high osmolarity is due to solutes other than urea. So, by the process of osmosis, water moves from areas of low solute concentration like the lumen to areas of high solute concentration like the interstitium.
But as water leaves, remember you still have 110% of the filtered urea in the tubule, so the concentration of urea in the tubular fluid gets even higher than its concentration within the interstitium.
So you have a big concentration gradient now for urea. In the very last part of the nephron, in the inner medullary collecting ducts, ADH increases the urea transporter UT1 on the apical surface, which actually allows urea to diffuse down its concentration gradient as well, so both water and urea start move from the tubular fluid into the interstitial fluid.
In fact, in the presence of ADH, about 70% of the filtered urea is reabsorbed through UT1, leaving behind 40% of the filtered urea to be excreted in the urine.

Urea Reabsorption7:15–7:55

So, in the end, water diffuses into the interstitium, but doesn’t stay there a lot, since it’s reabsorbed right back into the blood of the peritubular capillaries.
At the same time, some of the urea that moves into the interstitial space is secreted back into the bottom of the U-shaped bend in the loop of Henle.
And this urea is going to go up again and then make its way down back into the collecting duct. And from here some of it will be reabsorbed again in the interstitium and on and on.
So, this circular travel of urea, known as urea recycling, is what maintains kind of a “pool” of urea in the medullary interstitial fluid.

Corticopapillary Gradient7:55–8:33

This, together with the high concentration of sodium chloride NaCl within the interstitium, helps to establish the corticopapillary gradient, which remember is a concentration gradient with a low solute concentration in the cortex and a high solute concentration in the papilla, which is the innermost tip of the medulla.
And This corticopapillary gradient drives the movement of water from the lumen into the interstitium, allowing that water to get reabsorbed back into the blood instead of getting lost in the urine.

Review8:33–9:22

All right, as a quick recap, in the nephron, urea is freely filtered, and 50% is reabsorbed in the proximal convoluted tubule, but in the loop of henle urea is secreted back in, and by the bottom it’s 110% of the filtered load.
Urea can’t move across the tubule in the ascending limp and first part of the collecting duct, and doesn’t get reabsorbed until the last part, leaving 40% to be excreted in the urine.
A part of that reabsorbed urea is secreted into the loop of henle, called urea recycling, which helps establish the corticopapillary gradient, which helps us reclaim water that was filtered into the nephron!