L6: tubular function 2 - LoH

Question 1

What is the loop of henle?

Answer 1

• looped region of the nephron that has countercurrent flow inside it - going in opposite directions.
• absorbed water is taken up by specialised blood vessels called the vasa recta

Question 2

Varying filtrate osmolality in the nephron

Answer 2

• 285 in BC
• 285 in PCT
• 1200 at bottom of LoH
• 90 at top of LoH/start of DCT
• 60 at end of DCT
• 400-1000 in urine - varies but always hypertonic with respect to plasma

Question 3

Role of the loop of henle

Answer 3

• create a hyperosmotic medullary interstitium
• makes the fluid of the medullary interstitium surrounding the LoH and also surrounding the collecting ducts have a very high solute osmolality
• moving from the outer renal cortex to the inner renal medulla, interstitium of medullary region becomes progressively more concentrated, from 300, 400, 600, 900, 1200 = corticomedullary or corticopapillary osmotic gradient

Question 4

How does the thick ascending LoH extrude solutes

Answer 4

• ascending LoH actively extrudes solutes into surrounding interstitium - will increase interstitial osmolality but decrease that of the filtrate making it hyperosmotic
• removal of sodium/chloride from filtrate into interstitium requires a lot of energy - hence a lot of sodium potassium ATPases found on tubular cells here.
• Na+, 2Cl- and K+ enter the tubular cells via a channel. Sodium moves out using the energy by ATPase, and chloride follows down an EC gradient by diffusion.
• water does not follow because this part of the LoH is impermeable to water and only permeable to solutes, so water stays in the filtrate.
• so hypotonic fluid to enter the DCT

Question 5

How does the thin descending LoH extrude water?

Answer 5

• isotonic fluid enters from the PCT
• passively reabsorbs water by osmosis, filtrate in descending LoH surrounded by hyperosmotic medulla. Water enters the medullary interstitium and is picked up by vasa recta. Lots of aquaporins on the descending limb of LoH.
• NOT obligatory. Filtrate becomes hyperosmotic as it equilibrates with the interstitium.
• this part of the LoH is impermeable to solutes and only permeable to water so solute stays in the filtrate.
• hypertonic fluid will go to the ascending part

Question 6

How is osmolality varied within the loop of henle?

Answer 6

Cortico-medullary interstitial gradient:
- ultimately extrusion of sodium/chloride from ascending and water reasborption from descending LoH leads to an increasing vertical hyperosmotic gradient in the medullary interstitium. The LoH, DCT and collecting ducts are thus bathed in a very concentrated interstitium. This means water can be reabsorbed by osmosis from the descending LoH - as well as DCT and collecting ducts.
The outer cortex is less hyperosmotic and the inner medulla is more so there is a vertical corticomedullary gradient.

Watch video at minute 28.

Question 7

What is the difference in osmolality between ascending and descending limb?

Answer 7

There is a 200mOsm difference in osmolality between the ascending and descending limb at the horizontal level.
Energy is required to pump the sodium out and uses ATPases. Although there are millions of these on the basolateral side of each cell, they have their limits and can only do this until 200mOsm/Kg H2O is created.

Question 8

Role of the LoH as a countercurrent multiplier

Answer 8

• even though a different of only 20pmOsm/Kg H2O can be generated at each horizontal level, this ability to create a hyperosmolar medullary interstitium is multiplied into a very large vertical gradient because of the counter-current flow mechanism.
• the role of the LoH or countercurrent multiplier is to establish an osmotic gradient (30l-1200mOsm) from the renal cortex through to the medulla. Water can be removed from the collecting ducts by osmosis, thus concentrating urine from cortex to medulla.

Question 9

What happens to urea in the loop of henle?

Answer 9

The corticomedullary gradient can be made even stronger and more hyperosmotic, especially in the inner medullary region, by extrusion of urea which is very osmoticallt active.
Interstitial urea presence contributes approx half of the osmotic gradient (~500mOsm/Kg H2O).

Question 10

Urea recycling

Answer 10

Urea is reabsorbed passively from the inner medullary region of the collecting duct and accumulates in the medullary interstitium. As water is reabsorbed from the collecting duct filtrate, the concentration of urea increases, so it can move out of these urea-permeable areas of the nephron by diffusion.
Urea is then secreted into/diffuses back into the nephron via the descending LoH and thus is recycled. It cannot leave from the DCT or the cortical region of the collecting ducts as these areas are not permeable to urea.

Question 11

Loop diuretics

Answer 11

• blocks sodium potassium chloride channels in ascending LoH
• so no reabsorption/extrusion of sodium and chloride into medullary interstitium
• prevent generation of a corticomedullary-medullary gradient
• no hypertonic interstitium surrounding LoH, DCT and CDs
• decreases the osmotic driving force to pull water out of CDs
• increased urine production means less fluid in body - diuretic
• decreased sodium reabsorption at ascending LoH means more sodium excretion
• decreased blood volume
• decreased blood pressure