Production of a dilute or concentrated urine

Question 1

What are the major sites of fluid absorption along the nephron?

Answer 1

PCT = 70% - water absorption is secondary to solute absorption, after an osmotic gradient is set up. This stays around 70% during normal, dehydration or over hydration states

LoH = 20% - All reabsorbed in the Descending thin limb. The thin and thick ascending loops are impermeable to water. The reabsorption is driven by the hyper osmotic intersititium

DCT = 4-5% - NaCl reabsorption sets up an osmotic gradient across the apical membrane. Water reabsorption is dependent on the presence of ADH. This is the first site at which water reabsorption is regulated dependent on hydration status

CD = 0-5% - water reabsorption is dependent on ADH. Absence of ADH, the CD is impermeable to water, and a large volume, low osmolality urine is produced. ADH present causes AQ2 channels to make the CD permeable, causing reabsorption into the hyperosmotic interstitium, producing a low volume, high osmolality urine. The CD is the major site in regulation of water reabsorption depending on hydration status.

Question 2

What is the importance of generating a hyperosmotic medullary interstitium to urinary concentration?

Answer 2

• Needed to generate a range of dilute to concentrated urine
• Generated by organisation of the nephron and the blood supply within the medulla
• Medulla has the LoH of midcortical and juxtamedullary nephrons (JM LoH descend deep into papilla)
• Filtrate flows in a counter-current, with it flowing down, then up, then down. This allows interaction between the adjacent nephron segments
• Blood supply to the medulla from the juxtaglomerular efferent arterioles is ~7% of total renal blood flow - important to be low so it doesn’t wash out the osmolytes.
• Due to the blood supply being a loop, there is countercurrent exchange of water and osmolytes

Question 3

What makes the hyperosmolar environment in which the countercurrent flows through?

Answer 3

Build up of NaCl and urea in the medulla, due to selective transport of water and salt in different nephron segments.
- urea ~40% of the osmotically active particles in the medulla

Question 4

How does urea recycling generate the hyperosmotic medulla?

Answer 4

• Urea is a breakdown product of protein metabolism and is freely filtered through the glomerulus
• Around 50% of the filtered load is reabsorbed back into the blood in PCT
• then in the thin ascending limb, about 50% is secreted back in again
• Around 30% is then reabsorbed into the interesitium in the thick ascending limb.
• At the end of the CD, 55% of filtered load is reabsorbed
• therefore 15% is eliminated in urine
• The key is that there is a constant recycling of urea between the CD and thin ascending limb

Question 5

How does salt transport affect urinary concentration?

Answer 5

• Filtrate enters descending limb at 300mOsM (isotonic with plasma)
• Water is abstracted from descending limb (20% filtered load), but is impermeable to NaCl
• Gives very high NaCl concentration
• NaCl is then abstracted from the ascending limb, which is impermeable to water
• Done passively in thin ascending limb, and actively through Na/K/2Cl in thick
• Filtrate leaves LoH at 100mOsM

Question 6

What transporter is the target for loop diuretics?

Answer 6

Na/K/2Cl transporter in thick ascending limb

Question 7

What properties does the THIN DESCENDING limb of the LoH have?

Answer 7

• Impermeable to NaCl and Urea
• Permeable to water
• Water removed, increasing NaCl concentration
• passes through hyperosmotic interstitium
• 20% filtered load of water
• Osmolality increases from 300mOsM to 1200mOsM

Question 8

What properties does the THIN ASCENDING limb of the LoH have?

Answer 8

• Impermeable to water
• Permeable to NaCl and Urea
• Tubular fluid has high [NaCl] due to water abstraction in thin Descending limb
• Concentration gradient between tubular fluid and interstitium, so NaCl diffuses out into intersitium
• This causes the lumen osmolality to decrease, and increase in the intersitium
• This high interstitial osmolality generated by urea and NaCl gives the driving force for water abstraction in the descending loop

Question 9

What properties does the THICK ASCENDING limb of LoH have?

Answer 9

• Impermeable to water, and permeable to NaCl and urea
• NaCl is actively removed by Na/K/2Cl transporter on apical side
• urea absorbed in thick ascending limb
• NaCl concentration rises in intersitium

Question 10

How does ADH work?

Answer 10

• ADH is secreted by posterior pituitary
• Inserts AQ channels into the apical membrane of the DCT - allowing water, along with NaCl reabsorption
• Inserts AQ channels into the apical membrane of the CD, allowing water reabsorption into the CD. This reabsorption is driven by the large osmotic gradient between the tubular fluid and the hyperosmotic interstitium
• Both leads to a marked increase in the osmolality of the tubular fluid, producing a small volume, high osmolality urine.