Week 2: Concentrating and diluting urine

Question 1

Explain why active NaCl transport in thick ascending Loop of Henle is critical to both hypotonic and hypertonic urine formation.

Answer 1

• TALH is the diluting segment
• NaCl is reabsorbed via NaK2Cl transporter. Impermeable to water
• interstitial fluid of renal medulla becomes concentrated with NaCl, creates osmotic gradient
• Apical K+ channels recycle K+.
• ADH increases activity of salt transporters
• NaCl reabsorption without water starts process of diluting urine
• the NaCl gradient in medulla interstitial drives water reabsorption from collecting duct in presence of high ADH

Question 2

Contrast the roles of the collecting ducts in the formation of hypotonic (low ADH) vs hypertonic (high ADH) urine.

Answer 2

The distal tubule and cortical and medullary portion of collecting duct actively reabsorb NaCl

• low ADH (dilute urine): these segments not permeable to water. Osmolality of tubule fluid in these segments is reduced further because NaCl is reabsorbed without water. Fluid leaving cortical portion of collecting duct is hypo osmotic with respect to plasma. Some water reabsorbed in medullary collecting duct.
• High ADH (concentrated urine): stimulates NaCl reabsorption by TALH, maintains interstitial gradient while water is reabsorbed. Fluid reaching collecting duct is hypo osmotic relative to interstitial fluid. ADH increases water permeability in last half of distal tubule and in collecting duct by increasing AQP2. Water diffuses out of lumen and tubule fluid osmolality increases.

Question 3

Summarize the importance of urea recirculation to hypertonic urine formation.

Answer 3

• urea is high in IMCD due to water reabsorption without urea previously
• with ADH: IMCD becomes permeable to urea, transported out into interstitial fluid
• Urea re-enters ascending and to lesser degree descending limb, and descending vasa recta
• in the cortical and OMCD, water is reabsorbed but impermeable to urea in presence of ADH
• in the IMCD: urea is transported down its concentration gradient via UT-1
• urea recycling contributes to hypertonicity of inner medulla
• high concentration of urea in ISF prevents diffusion of urea out of IMCD, and allows excretion of urea in urine

Question 4

Evaluate how the counter current arrangement of vasa recta contributes to the process of hypertonic urine formation.

Answer 4

• the vasa recta removes water and solute that is added to the medullary interstitium
• slow flow, loop arrangement, allows equilibration of blood with interstitium. prevents medullary solute gradient washout.
• an increase in blood flow rate dissipates the medullary gradient
• decreased flow rate limited oxygen deliver, which limits active transport

Question 5

Summarize two general mechanisms used by cells in the inner medulla to survive ECF osmolalities of 1200 mOsm.

Answer 5

1. expression of enzymes that produce inert osmolytes such as sorbitol
2. increase production of small molecule transporters to take up osmolytes from ECF
   The ICF osmolality=ECF osmolaity up to 1200 mOsm and cells retain cell volume

Question 6

Vasa recta and countercurrent exchange.

Answer 6

• countercurrent exchange is different from the countercurrent multiplication system (which establishes the corticopapillary osmotic gradient)
• the counter current exchange helps maintain the gradient
• vasa recta is permeable to small solutes and water
• as blood flows down descending limb, exposed to interstitial fluid with increasingly higher osmolarity. Small solutes diffuse into descending limb of vasa recta
• in ascending limb, opposite occurs
• the result is that although the blood leaving the medulla has higher osmolarity than when it entered, it is Less hypertonic than it would be if the vessel were a straight tube instead of hairpin loops