Urine Formation Variation Dr. Wasif Haq

Osmolarity Osmolarity: Measure of solute concentration. Total concentration of solutes in extracellular fluid. Determined by amount of solutes divided by volume of extracellular fluid. Human blood osmolarity= 300 mOsm/L

Osmolarity Effect on Type of Urine Produced Hyper Osmolarity: Concentrated Urine (ADH released) Hypo Osmolarity: Diluted Urine. (ADH not released)

ADH/Vasopressin; Main Determinant Hyperosmolarity ∝ ADH secretion ∝ Reabsorption of water by distal tubules & collecting ducts ∝ Concentrated, small volume urine. Hypo-osmolarity 1/ ∝ ADH secretion 1/ ∝ Permeability of distal tubules & collecting ducts to water 1/ ∝ Dilute, large volume urine.

Dilute Urine Formation General principle: The more a segment of Nephron is impermeable to water, the more dilute urine it would produce. Electrolyte reabsorption but no reabsorption of water. Steps: 1. Isosmoticity in proximal tubular fluid & Descending limb. 2.Dilution in Ascending limb and distal tubule

Steps for Dilution of Urine 1. Isosmotic fluid in Proximal tubule & Descending limb Equal reabsorption of water & electrolytes in proximal tubules, hence no difference of osmolarity between plasma osmolarity and the fluid passing in proximal tubules. Water reabsorption occurs in descending limb of Loop of Henle making the fluid ‘hypertonic’. However here the renal medullary interstital fluid is also very concentrated (hypertonic), therefore the osmolarity still remains constant and same.

Steps for Dilution of Urine 2. Dilution in Ascending limb & Distal tubule Ascending limb: Impermeable to water but high Na +, K + Cl - reabsorbtion. This diluted fluid flows to ‘Diluting segment’ DISTAL CONVOULATED TUBULE. Osmolarity drop: 100 mOsm/L. Independently of ADH, fluid in early distal tubule is “Hypo-osmolar”. If ADH absent: Further dilution in late distal tubule & collecting ducts because of impermeability to water, solutes reabsorption occurs. Osmolarity drop: 50 mOsm/L.

Urine Concentration Requirements for forming concentrated urine: 1. High level of ADH (greater water reabsorption in distal tubules and collecting ducts) 2. High osmolarity of renal medullary interstital fluid creating osmotic gradient that promotes water reabsorption. Renal Medullary Interstitum( Tissues surrounding Loop of Henle in renal medulla) Increased ADH levels cause water absorption as Vasa recta transport water back to blood.

Hyperosmolar Renal Medulla 1. Active transport of Na + & co-transport of K +, Cl - from Ascending limb & collecting ducts into medullary interstitum along with other ions. 2. Diffusion of urea from medullary collecting ducts into medullary interstitum along with small quantities of water.

Counter Current Multiplier Responsible for producing concentrated urine by Loop of Henle Step 1. Isosmoticity between Loop of Henle fluid & Proximal tubule: Same osmolarity of fluid entering Loop of Henle & Proximal fluid & in medullary interstitum.

Counter Current Multiplier Step 2: Active pump on Ascending limb of Loop of Henle creates 200 mOsm/L concentration gradient: Active pump transports Na + & co-transports K + & Cl - & other ions out of ascending limb into medullary interstitum creating osmotic gradient of 200 mOsm/L that increases osmolarity to 400 mOsm/L.

Counter Current Multiplier Step 3: Osmosis of water out of descending limb balances osmolarity difference between the descending limb and interstital fluid: Movement of fluid from descending limb into medullary interstitum to balance the osmolarity difference. Osmolarity rises to 400 mOsm/L in descending limb.

Counter Current Multiplier Step 4. Hyperosmolar fluid reaches Ascending limb: Further flow of fluid from Proximal tubule to Loop of Henle now pushes the already present hyperosmolar fluid from Descending limb to Ascending limb rising it’s osmolarity to 400 mOsm/L.

Counter Current Multiplier Step 5. Active pump at Ascending limb (same as Step 2): Further transportation of ions from Ascending limb to renal medullary interstitum rising it’s osmolarity now to 500 mOsm/L. Ions transported till 200 mOsm/L difference established between interstitum & Ascending limb.

Counter Current Multiplier Step 6. Balance of osmolarity between Descending limb & medullary interstitum : (Same as step 4) Osmosis of water out of the Descending limb to balance the osmotic gradient. All steps repeated till urine osmolarity reached till mOsm/L.

Influence of ADH ADH increases water reabsorption in cortical collecting ducts & distal tubules. Water reabsorption occurs in cortex and not in medulla, therefore osmolarity of medullary interstitum in maintained.

Urea Recirculation 40% of total renal medullary interstitum is contributed by Urea. Thick limb, distal tubules & cortical collecting tubules impermeable to Urea, only medullary collecting duct permeable to Urea. From here, Urea diffuses to renal medullary interstitum and rises osmolarity. Some Urea can diffuse later to recirculate in Loop of Henle, distal tubules & cortical collecting tubules several times thereby rising medullary interstital fluid hyperosmolarity.

Counter Current Exchange Maintains the renal medullary interstitum osmolarity by Vasa recta. Vasa recta also has a descending and ascending limb. 1. Slow medullary blood flow which minimizes soulte dissipation. 2. U-shaped Vasa recta: Reabsorption of substances possible preventing the solute loss.

Counter Current Exchange 1.Hypertonic medulla causes increased reabsorption of salt and Urea in descending limb of vasa recta followed by water secretion. Net result: Increased osmolarity. 2.Towards the cortex, the osmolarity is less; therefore the salt diffuses from ascending limb of vasa recta into the medullary interstitum along with water reabsorption. Net effect: Decreased osmolarity.

If NaCl & Urea reabsorbed in blood, water will be secreted into interstitum & vice versa.