Lecture 16: mechanisms of urinary concentration

Question 1

Describe the what happens to the blood & urine if a person drinks excessive water

Answer 1

• the concentration of the blood becomes hyposmolar, and the kidneys produce hypoosmolar urine
• the waste solutes are excreted in large volumes of dilute urine

Question 2

Describe what happens to the blood and urine if a person if very dehydrated (eg lost in desert)

Answer 2

• If a person isnt drinking enough water, and is loosing excess water to salt (eg through sweating etc) the blood becomes hyperosmolar and therefore the urine also becomes hyperosmolar
• the waste solutes are excreted in small volume of very concentrated urine

Question 3

what is the value of normal plasma osmolality?

Answer 3

• 290mOsm/kg H20

Question 4

In extreme dehydration, what values can plasma osmolality reach?

Answer 4

1200-1440 mOsm/kg H20 which is 4-5 fold higher than normal plasma osmolality

Question 5

recap: what concentration relative to plasma is the** fluid entering the loop of henle**?

Answer 5

• isotonic relative to plasma
• as a proportional amount of water is moving relative to solutes

Question 6

recap: why does water diffuse out of the descending limb?

Answer 6

*the descending thin limb of the loop of henle is relatively impermeable to solutes, therefore the solutes are concentrated in the tubular fluid
the descending limb is permeable to h20, therefore water moves out

Question 7

Recap: what is the concentration of the tubular fluid relative to plasma after the loop of henle?

Answer 7

• the tubular fluid becomes diluted as it passes through the loop of henle
• this is due to the reabsorption of solutes
• water does not passively follow the osmoles because the TAL is impermeable to water

Question 8

what is the hyperosmolar gradient in the medullary interstitium?

Answer 8

• the increasing hyperosmolar gradient from the renal cortex into the inner medulla
• water diffuses passively out of the nephrons (in permeable parts) because of the increasing gradient of osmolality from the cortex to the papillary regions of the kidney

Question 9

In simple words, what must the nephron do to produce hypo-osmotic urine?

Answer 9

• nephrons must reabsorb solutes from tubular fluid and remove (excrete) water

Question 10

In simple words, what must the nephrons do in order to** produce hyper-osmolar urine**?

Answer 10

• the nephrons must reabsorb water from the tubular fluid and remove solutes

Question 11

**which part of the nephron **is essential for generating the hyperosmotic gradient in the medullary interstitium?

Answer 11

• the henle loops
• especially the thick ascending limb (TAL)

Question 12

How is the hyper-osmolar gradient produced?

Answer 12

• the loop of henle acts as a counter current multiplier
• the role of urea cycling in the renal medulla

Question 13

How does the loop of henle act as a counter current multiplier?

Answer 13

• the loops of henle do not concentrate the tubular fluid, but instead they generate a high osmotic concentration in the medullary interstitial fluid
• this then allows water to be removed from the collecting ducts
• the TAL of the loop actively transports Na+ into the** medullary interstitium**, but it is impermeable to water so the water cannot passively follow the osmoles
• as a consequence,** the osmolality of the medullary interstitium is increased** and the osmolality of the tubular fluid in the TAL is decreased (more h2o present)
• as a result of the difference in osmolality, a small trans-epithelial osmotic gradient is generated in the interstitium

Question 14

How does the osmolality of the interstitium increase even further?

Answer 14

• when continous tubular fluid enters the TAL, which actively transports even more solutes into the interstitium, therefore increasing the osmolality

Question 15

what does the progressive transport of solutes from the tubular fluid into the interstitium establish?

Answer 15

• it establishes a longitudinal gradient in the medulla
• the loop of henle produces a small osmotic pressure difference between the ascending and descending limbs of henles loops, this small difference would be multiplied into a large longitudinal gradient

Question 16

what does the progressive transport of solutes from the tubular fluid into the interstitium establish?

Answer 16

• it establishes a longitudinal gradient in the medulla

Question 17

How is the longitudinal gradient established by the loop of henle?

Answer 17

• the loop of henle produces a small osmotic pressure difference between the** ascending and descending limbs** of henles loops, this small difference would be multiplied into a large longitudinal gradient by the counter current arrangement in the 2 limbs of the loops

Question 18

what is the **counter current arrangement **between the 2 limbs of the loops of henle?

Answer 18

• flow of solutes or water in opposite directions

Question 19

Describe the important role of **urea recycling **in producing the hyperosmolar gradient in the medullary interstitium

Answer 19

• a** significant fraction of the osmolality of the interstitium** is **due to urea ** (approx 50%)
• urea is delivered to the LOH from the PCT and passes around the LOH to the CD
• from the TAL to the the inner medullary collecting duct (IMCD), the nephron is impermeable to urea, but reabsorption does occur via the apical UT-A1 and basolateral UT-A3
• at the IMCD, urea diffuses down its conc gradient into the interstitium (as high conc in tubular fluid) and is recycled (secreted) back into the nephron via the UT-A2 channels on the thin ascending loop

Question 20

what does the urea cycling do to the urea conc in the medullary interstitium ?

Answer 20

urea recycling traps urea in the inner medulla which increases the osmolality of the interstitium

Question 21

What **maintains **the hyperosmolar medullary interstitium gradient?

Answer 21

the vasa recta

Question 22

what is the vasa recta?

Answer 22

• the vasa recta are capillaries
• they are derived from the efferent arterioles of the juxtamedullary nephrons which have a hair pin arrangement and dip far down into the medulla

Question 23

How does the vasa recta maintain the gradient?

Answer 23

• the hairpin arrangement of the vasa recta enables them to function as counter current exchangers
• this is different from the counter current multipliers
• as the vasa recta enters the extremely hyperosmolar MI, water is** osmotically removed** from the blood vessel ( so osmolality of the blood is increased- less h20)
• in the ascending limb, water water re-enters the blood vessel
• The hair pin arrangment ensures a low flow rate through the deep parts of the vasa recta and minimises the wash out of medullary solutes

Question 24

How does the release of ADH enhance the countercurrent multiplier system ?

Answer 24

1. it increases NaCl reabsorption in the TAL, DT and CD
2. It also increases the **permeability medullary portion of the collecting duct to urea **