Loop of Henle

Definitions & Key takeaways

The loop of Henle is a part of the Nephron in the kidneys, which helps to reabsorb water and salt from the kidney tubules. It has three main parts, the thin descending limb which is where water moves out of the tubule through aquaporin proteins, the thin ascending limb which is where sodium and chloride move out of the tubule through channel proteins, and the thick ascending limb which is where sodium, potassium, and chloride move out of the tubule through a carrier protein and channel proteins.

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Introduction0:00–0:25

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 tubes called nephrons which go from the outer cortex down into the medulla and back out into the cortex again.
Nephrons filter out harmful substances in the blood so that we can excrete them into the urine. Each nephron is made up of the glomerulus, or a tiny clump of capillaries, where blood filtration begins.

Nephron0:25–1:18

These capillaries have very thin walls and they act like a coffee filter. Red blood cells and proteins are large and stay in the capillaries whereas blood plasma and smaller particles get filtered out.
This filtrate, called tubular fluid, collects in a cup shaped structure containing the glomerulus called the Bowman's capsule.
Together, the glomerulus and the Bowman’s capsule make up the renal corpuscle. The Bowman’s capsule is connected to the renal tubule which has a few segments: the proximal convoluted tubule, the U- shaped loop of Henle with a thin descending, a thin ascending limb and a thick ascending limb, and finally the distal convoluted tubule which empties into the collecting duct, which collects the urine.
Zooming in on the U shaped loop of Henle, it’s lined by epithelial cells. On one side is the apical surface which faces the tubular lumen, and on the other side is the basolateral surface, which faces the interstitium between the tubule and the peritubular capillaries.

Loop of Henle1:18–1:48

The peritubular capillaries run alongside the nephron, and the capillaries that run along the loop of henle are called vasa recta.
Solutes and water that are reabsorbed into the interstitium go into the vasa recta and re-enter circulation. Now, when tubular fluid leaves the proximal tubule, it has an osmolarity of around 300 mOsm/L which is the same as the osmolarity of the interstitial fluid around the tubule.

Tubular Fluid Osmolarity1:48–3:10

The tubular fluid mainly contains water, sodium, potassium, chloride, calcium, and urea. When it travels down the descending limb, the osmolarity in the medullary interstitium increases rapidly, from 300 mOsm/L at the top to 1200 mOsm/L at the bottom, where the loop bends.
Most of that osmolarity in the interstitium is due to the large quantities of sodium as well as some urea. Now the squamous epithelial cells that line the thin descending loop have a lot of aquaporin proteins on the apical and basolateral sides.
These aquaporin proteins are channels that only allow water to pass through. So in the thin descending limb, water diffuses from the lumen into the tubular cells and from the tubular cells into the interstitial fluid where the water gets reabsorbed into the vasa rectas and returned to circulation.
The epithelial cells have very few channels for solutes so solutes don’t leave the tubular fluid in significant quantities.
Since water leaves but solutes remain in the tubular fluid, it quickly becomes concentrated and at the end of the descending limb, the tubular fluid has an osmolarity of 1200 mOsm/L, just like the interstitial fluid.

Thin Ascending Limb3:10–3:56

Now the thin ascending limb is also made of squamous epithelial cells. These cells don’t have any aquaporin proteins, so the thin ascending limb is impermeable to water.
Instead, the thin ascending limb has lots of sodium and chloride channels on the apical and basolateral surface of the cells.
These sodium and chloride channels allows those ions to diffuse from the tubular fluid into the epithelial cells, and then from the epithelial cells into the interstitium, all of it down their concentration gradient.
Since water remains in the tubule, but solutes move out - as we travel up the thin ascending loop, the interstitial fluid starts decreasing in osmolarity, reaching around 600 mOsm/L at the top of the thin ascending loop.
After the thin ascending limb, there’s the thick ascending limb which is made up of cuboidal epithelium. These cells are much bigger than the squamous cells so that’s what makes this portion of the loop of henle “thick.” These cells also don’t contain aquaporins so the thick ascending limb is impermeable to water.

Thick ascending Limb3:56–5:50

Epithelial cells along the thick 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.
Think of it as a revolving door where sodium is the guy doing all the pushing and one potassium and two chlorides just follows him in.
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.
Now the volume in the tubular fluid is much lower than the volume in the interstitium, but if sodium is pumped into the interstitial fluid over and over, then the interstitial fluid will become more concentrated and we end up with this highly concentrated intersitum in the medulla.
And since solutes keep moving out - as we travel further up the thick ascending loop, the tubular fluid starts decreasing in osmolarity, reaching around 325 mOsm/L at the top of the thick ascending loop.
The process of creating this gradient is called countercurrent multiplication. It uses ATP to build up the concentration gradient but in return we get to reabsorb water into the interstitial fluid for free since it can diffuse passively via osmosis!
Importantly, the thick ascending loop is the target of loop diuretics. Specifically, they attach to the Cl- binding site of the Na-K-2Cl cotransporter and inhibit the transport protein.

Loop Diuretics5:50–6:13

Diuretics are medications that help the body lose water by inhibiting the reabsorption of sodium. Water follows sodium so if more sodium is excreted in the urine, more water is lost in the urine as well.
Alright, as a quick recap, the loop of henle has three main parts, the thin descending limb which is where water moves out of the tubule through aquaporin proteins, the thin ascending limb which is where sodium and chloride move out of the tubule through channel proteins, and the thick ascending limb which is where sodium, potassium, and chloride move out of the tubule through a carrier protein and channel proteins.

Review6:13–6:37