Producing A Concentrated Or Dilute Urine

Question 1

Osmolarity

Answer 1

number of osmoles of a solute per litre of solution (Osm/L)

Question 2

Osmolality

Answer 2

number of osmoles of solute per kg of solvent (Osm/kg)

Question 3

Normal osmolality of blood plasma

Answer 3

~290 mOsm/kg

Question 4

How does the kidney deal with excess/lack of water reabsorption as well as solute reabsorption?

Answer 4

The kidney excretes H20 but without compromising reabsorption of solutes. Rapidly increases flow of urine and reduces osmolality, solute excretion does not change much as it is an independent process.

Question 5

Where is the water transported out of the nephron?

Answer 5

• Proximal tubule
• Thin Descending Limb of the Loop of Henle
• (AVP only) Cortical Collecting Duct
• (AVP only) Medullary Collecting Duct
• AVP only - means that they only release water out of the tubule when Arginine Vasopressin (AVP), also known as Anti-Diuretic Hormone (ADH), is released.

Question 6

Where is the solute separated from water in the nephron?

Answer 6

• LOOP of HENLE
• Only H2O reabsorption in Thin Descending Limb
• Only NaCl reabsorption in the Thin Ascending Limb and Thick Ascending Limb.

Question 7

Osmolality of Ultrafiltrate

Answer 7

Approximately 65% of H20 and Na+ is reabsorbed in the Proximal Tubule. This reabsorption is ISO-OSMOTIC (osmolality of tubular fluid/ultrafiltrate is equal to interstitial fluid). This remains true no matter the water excretion requirements.

Question 8

In the Thin Descending Limb of the Loop of Henle, H2O is reabsorbed VIA……

Answer 8

Aquaporin 1 Water Channels in a Transcellular manner. Requires an osmotic gradient despite the channels being open.

Question 9

In the Thin Ascending Limb of the Loop of Henle, NaCl is reabsorbed VIA…..

Answer 9

Paracellular Route.

Question 10

In the Thick Ascending Limb of the Loop of Henle, NaCl is reabsorbed through the epithelial cell to the blood VIA…..

Answer 10

• Basolateral Na+/K+ ATPase - which generates electrochemical gradients. - into interstitium where it will be reabsorbed into blood by vasa recta
• Apical Na+-K+-Cl- Co-Transporter (NKCC2) - into epithelial cell
• Basolateral Cl- Channel - into blood via interstitium
• Na+ can also be reabsorbed via the paracellular pathway - lumen of tubule > interstitium > blood

Question 11

In the Thick Ascending Limb of the Loop of Henle, what transports K+ across??

Answer 11

• Basolateral Na+/K+ ATPase - generates electrochemical gradient - Interstitum > epithelial cell
• Leak K+ Channel in basolateral membrane - epithelial cell > interstitum
• Apical Renal Outer Medullary K+ Channel (ROMK) - epithelial cell > lume of tubule - maintains electrical gradient for paracellular transport
• Apical Na+-K+-Cl- Co-Transporter (NKCC2) - Lumen of tubule > epithelial cell

Question 12

How are Mg2+ and Ca2+ reabsorbed into the interstitum from the Lumen of the Tubule?

Answer 12

Paracellular pathway - due to electrical gradient maintained by ROMK

Question 13

Counter Current Multiplier Mechanism

Answer 13

1. The “first” time the tubular fluid enters the Loop, it will travel all the way to the Thick Ascending Limb, because there are no gradients enabling passive transport.
2. In the Thick Ascending Limb, Na+ and Cl- are reabsorbed into the medullary interstitium via NKCC2, generating an osmotic gradient ~200 mOsm between the tubular fluid and interstitium.
3. The interstitium is now HYPEROSMOTIC (400 mOsm) because of the extra NaCl, and the osmotic gradient enables passive reabsorption of H2O in the earlier Descending Limb. The movement of water out of the tubular fluid, increases the osmolality of the tubular fluid in the descending limb. H2O will move out of the tubule and equilibrate to the osmolality of the medullar interstitium.
4. Tubular fluid moves round the Loop and fresh fluid from the Proximal Tubule (300 mOsm) enters the Loop.
5. NaCl is reabsorbed in both the Thick and Thin Ascending Limbs (due to osmotic gradient established). So there is always a gradient of 200 mOsm from the tubular fluid to the medullary interstitium.
6. The fluid moving down the descending limb willequilibrate to the osmolality of the medullary interstitium.
7. This keeps getting repeated, establishing a greater and greater gradient the further the loop stretches down the medulla

Question 14

Transporters of the Distal Convoluted Tubule

Answer 14

• Na+/K+ ATPase (Na+ to interstitium and K+ into epithelial cell) and leak K+ channel (epithelial cell to interstitium) in the basolateral membrane.
• Na+-Cl- Co-Transporter (NCC) in the apical membrane (lumen of tubule > epithelial cell)
• Cl- channel in basolateral membrane (epithelial cell > interstitium)
• NO WATER TRANSPORT

Question 15

Transporters in the Collecting Duct

Answer 15

• Na+/K+ ATPase (Na+ into cell, K+ into interstitium) and leak K+ channel (K+ into interstitium) in the basolateral membrane.
• ROMK also allows apical K+ exit.
• ENaC (Epithelial Na+ Channel) allows apical entry of Na+ into epithelial cell.
• Osmotic gradient drives H2O reabsorption via Aquaporin 2 (AQP2). ONLY IF AVP/ADH IS RELEASED.
• Cl- moves via a paracellular pathway.

Question 16

Transport of Urea

Answer 16

• Contributes 40-50% of the osmolality (500-600 mOsm/kg) of the renal interstitium when maximally concentrating urine.
• It moves passively down its chemical gradient. Freely filtered.
• PROXIMAL TUBULE - solvent drag through tight junctions, higher concentration in tubule so it moves out into interstitium. ~50%
• THIN DESCENDING LIMB OF THE LOOP OF HENLE - transcellular secretion via UT-A2. Higher concentration of urea in interstitium (from Collecting Duct) so it moves into lumen of tubule. ~50%
• MEDULLARY COLLECTING DUCT - transcellular reabsorption via UT-A1 or UT-A3. Higher concentration of urea in tubule so moves into interstitium and effectively recycles to the Loop of Henle.
• Remainder (~20%) is excreted into urine.

Question 17

Counter Current Exchanger (VASA RECTA)

Answer 17

• Surround juxtamedullary nephron Loop of Henle.
• Gives nutrients, removes waste.
• Becomes viscous as hairpin bend due to lack of H2O & build up of solute and plasma proteins.
• Vasa recta form parallel hairpin bends to the Loop of Henle.
• On left side, H2O will diffuse out and solutes will diffuse in as the vasa recta descends into medulla. The plasma osmolality increases but does not quite match the medullary interstitium.
• The reverse happens on the way back to the cortex , water diffuses into the vasa recta and solutes dissolves out, reduces the osmolality.
• This allows blood supply without washout of the osmotic gradient generated.