Content Reviewers:Rishi Desai, MD, MPH
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.
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.
Now, zooming in on this nephron’s tubule, each one’s 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.
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.
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.
- "Medical Physiology" Elsevier (2016)
- "Physiology" Elsevier (2017)
- "Human Anatomy & Physiology" Pearson (2018)
- "Principles of Anatomy and Physiology" Wiley (2014)
- "Urea" Subcellular Biochemistry (2014)
- "Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion" Clinical Journal of the American Society of Nephrology (2014)
- "High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation" Journal of Clinical Investigation (2017)