Kidney countercurrent multiplication

Definitions & Key takeaways

Kidney countercurrent multiplication refers to the process in which energy is used to create an osmotic gradient that enables the reabsorption of water from the tubular fluid, so that urine can be concentrated. Countercurrent multiplication creates this gradient by actively moving sodium chloride from the tubular fluid into the interstitial space deep within the kidneys.

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Introduction0:00–0:36

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.

Renal Tubule0:36–1:51

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.

Corticopapillary Gradient1:51–3:15

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 countercurrent multiplication, and let’s start with blood which is coming into the nephron with an osmolarity of 300 mOsm/L, and we’ll use these purple boxes to indicate the osmolarity of the blood.

Countercurrent Multiplication3:15–3:54

As it passes through the proximal tubule, there is almost no osmolarity change so it remains at 300 mOsm/L as it enters the loop of Henle.
We’re going to focus mostly on the loop of Henle so let’s zoom in a bit to show the ascending and descending limbs. Now to start let’s just assume that everything is 300 mOsm/L, both in the tubule and in the interstitium.

Single Effect3:54–5:56

The first step of countercurrent multiplication is called single effect, and it involves the ascending limb so let’s hop over to that side.
Tubule cells along the ascending limb have Na+K+2Cl- cotransporters on the apical surface, and they shuttle one sodium into the cell down its concentration gradient, and that powers the movement of one potassium and two chlorides into the cell as well.
On the basolateral surface of the tubule cell, a Na/K ATPase uses ATP to pump three sodium ions into the interstitial fluid in exchange for letting two potassium ions into the cell.
This helps to maintain the low sodium concentration inside the cell. Finally, both chloride and potassium move from the cell into the interstitial fluid as well, passively through their own channels down their concentration gradients.
So essentially here you have solutes being transported out into the interstitial space, but since we’re in the ascending limb, it’s impermeable to water, so the tubular fluid becomes more dilute as solutes are continuously transported out, going from 300 mOsm/L to 200 mOsm/L.
Now the volume in the tubular fluid is much lower than the volume in the interstitium, but if this process happens over and over, then the interstitial fluid will become more concentrated, and eventually rise from 300 mOsm/L to 400 mOsm/L.
Now in the descending limb, the tubular fluid boxes have an osmolarity of 300 mOsm/L, but unlike the ascending limb, the descending limb is permeable to water and solutes, so that means that the tubule will equilibrate with the interstitium.
By the process of osmosis - water will move from the tubule to the interstitium, and solutes will diffuse in the other direction - from the interstitium into the tubule.
Once equilibrium is reached, osmolarity in the descending limb will go from 300 mOsm/L to 400 mOsm/L. The second step of countercurrent multiplication is called flow of fluid, and it involves new fluid entering the kidney and going through the nephrons.

Flow of Fluid5:56–7:30

To illustrate this, let's push two new boxes of 300 mOsm/L into the descending limb, and shift everything over, and bump two boxes out of the ascending limb into the distal convoluted tubule.
Now that that’s happened, remember there’s also the single effect in the ascending limb, sodium is reabsorbed from the tubular fluid boxes and moved into the interstitial fluid.
So in the two boxes near the bottom of the ascending limb, the osmolarity will drop from 400 mOsm/L to 300 mOsm/L. These solutes will be transported into the interstitial fluid boxes at the bottom, and their concentration rise from 400 mOsm/L to 500 mOsm/L.
In the two boxes at the top of the ascending limb, their osmolarity is 200 mOsm/L from before, and as more solute is pumped out, they’ll drop to 150 mOsm/L.
The reason that they don’t drop all the way to 100 mOsm/L is that as the ion concentration falls, it’s harder and harder for those Na+K+2Cl- cotransporters to find and move ions - there literally aren’t as many of them around.
Now, as those solutes move into the interstitial fluid boxes in the cortex, the concentration might go from 300 mOsm/L to 350 mOsm/L.
You can see that this cycle starts to create a gradient, and If we continue to repeat this cycle over and over again, the corticopapillary gradient basically takes shape with an eventual concentration of 1200 mOsm/L at the inner medulla where there is a very high concentration of sodium ions and very little water, and 300 mOsm/L in the outer cortex where the concentration of sodium and water is similar to the blood.
The size of the gradient depends on the length of the loop, so certain rodents like Kangaroo rats that live in the desert, have a relatively long loop of Henle, allowing the osmolarity at the bend to reach over 3000 mOsm/L!

Countercurrent Exchange7:30–9:20

Now, it’s important to keep in mind that there is an additional process called countercurrent exchange which takes place in the peritubular capillaries that travel alongside the descending and ascending tubule.
The peritubular capillaries are permeable to both water and solutes. Now, blood has an osmolarity of 300 mOsm/L.
Along the descending limb of the tubule, water will diffuse out of the blood into the interstitial fluid while solutes diffuse in, and if this blood simply carry away the solutes, it would destroy the corticopapillary gradient.
To counteract this, the peritubular capillaries also ascend alongside the ascending loop. Since the corticopapillary gradient decreases as we go up the ascending limb, the extra solute in the blood diffuses back out of the vessel and into the interstitium, and water diffuses back into the vessel.
So as the blood exits the Loop of Henle, it has an osmolarity of 325 mOsm/L which is only slightly higher than when it entered.
In other words, water is secreted into the tubule but then reabsorbed and returned to systemic circulation, and solutes are reabsorbed into the circulation but then secreted back into the interstitium, and from that that was reabsorbed only a little solute that form the corticopapillary gradient is lost.
This helps the maintains the gradient that took a lot of energy to create. The amount of solute lost this way depends on the rate of blood flow.
Normally, the blood flows slowly through the peritubular capillaries and that allows time for passive diffusion to maintain the gradient.
But if the blood flow increases there’s less time for the diffusion of solutes out of the peritubular capillaries at the ascending limb and more solutes will be carried back into systemic circulation.
Alright, as a quick recap, countercurrent multiplication is the continual repetition of a single two step process that gradually increases the corticopapillary gradient.

Review9:20–10:01

For the first part, single effect, In the ascending limb, electrolytes move from the urine to the interstitium, while it’s impermeable to water, so the urine becomes more dilute.
In the descending limb, both electrolytes and water can diffuse across, so it comes to equilibrium with the interstitium.
Then the second part is flow of fluid, which pushes fluid of different concentrations through, establishing the corticopapillary gradient where there’s has increasing osmolarity in the medulla, which ultimately helps more and more water to get reabsorbed from the tubules.