1. PROF. EMAN EL ETER Diluting and concentrating mechanisms of the kidney

2. Introduction: Urine osmolality varies widely in response to changes in water intake. Following several hours without water intake, such as occurs overnight during sleep, human urine osmolality may rise to ∼ 1,200 mOsm/kg H 2 O, about 4-times plasma osmolality ( ∼ 300 mOsm/kg H 2 O). Conversely, urine osmolality may decrease rapidly following the ingestion of large quantities of water, such as commonly occurs at breakfast, human (and other mammals) urine osmolality may decrease to ∼ 50 mOsm/kg H 2 O

3. Renal mechanisms for excreting a dilute urine Mechanisms: 1. PCT: Solutes & H2O absorbed in equal proportion (tubular fluid =iso-osmotic with plasma). 2. Descending loop: H2o reabsorbed by osmosis (tubular fluid hypertonic in equilibrium with renal medulla interstitium 1200 mOsm/L). 3.Thick Ascending loop of Henle & early distal: tubular fluid diluted due to 1Na-1K-2Cl. This segmnet is impermeable to H2O even in presence of ADH (tubular fluid osmolality =100 mOsm/L). 4. Distal & collecting tubule: Tubular fluid become further diluted due to absence of ADH + additional absorption of solutes (NaCl). Tubular fluid become more diluted (50 mOsm/L) and a diluted urine will be excreted.

4. Urine dilution occurs in absence of ADH Note urine osmolality drops in inner medullary collecting ducts

5. Urinary concentrating mechanisms Introduction: All mammalian kidneys maintain an osmotic gradient that increases from the cortico-medullary boundary to the tip of the medulla (papillary tip). This osmotic gradient is sustained even in diuresis, although its magnitude is diminished relative to antidiuresis. NaCl is the major constituent of the osmotic gradient in the outer medulla, while NaCl and urea are the major constituents in the inner medulla. The cortex is nearly isotonic to plasma, while the inner medullary (papillary) tip is hypertonic to plasma, and has osmolality similar to urine during antidiuresis

6. Urine concentration The basic requirement to form a concentrated urine: 1. High levels of ADH. 2. High osmolarity of renal medullary interstitial fluid to provide the osmotic gradient needed for H2O reabsorption in the presence of ADH.

7. COUNTER CURRENT MECHANISM LOOPS OF HENLE OF JUXTA MEDULLARY NEPHRONS establish hyperosmolality of interstitium of medulla. They are called COUNTER CURRENT MULTIPLIERS. VASA RECTA maintain hyperosmolality established by counter current multipliers. They are called COUNTER CURRENT EXCHANGERS

9. Counter current multiplier mechanism Definition: Countercurrent multiplication refers to the process by which a small osmolality difference (produced by reabsorption of solutes into the medulla), at each level of the outer medulla, between fluid flows in ascending and descending limbs of the loops of Henle, is multiplied by the countercurrent flow configuration to establish a large axial osmolality difference, from 300 mOsm/L by the end of PCT to 1200 mOsm/L at the tip of the loop of Henle. In a counter current system the in flow is parallel to, close to and opposite to the outflow. Adding more solutes to medulla in excess of H2O….TRAP SOLUTES IN MEDULLA and multiplies concentration gradient by active pumping out of thick LH.

10. Loop of Henle: Countercurrent Mechanism Figure 25.14

11. Urine concentrating mechanisms The osmolarity of the interstitial fluid in the medulla of the kidney is much higher, increasing progressively to about 1200 to 1400 mOsm/L in the pelvic tip of the medulla. The major factors creating hyperosmolar medulla: 1. Passive reabsorption of NaCl by the thin acsnding limb of Henle which depends on prior reabsorption of water by the descending limb. 2.Active transport of sodium ions and co-transport of potassium, chloride in thick portion of the ascending limb of the loop of Henle into the medullary interstitium. 3. Facilitated diffusion of large amounts of urea from the inner medullary collecting ducts into the medullary interstitium (ADH). 4. Active transport of Na from the collecting ducts into the medullary interstitium and passive electrogenic reabsorption of Cl.

12. Formation of concentrated urine under ADH

13. Maintenance of hyperosmolar medulla The mechanism responsible for maintaining a hyperosmolar medulla acts through two properties of medullary blood flow: 1. The medullary blood flow is very small (1-2% of the total blood flow of the kidney). Because of this very small and sluggish flow, removal of solutes in minimized.

14. Maintenance of hyperosmolar medulla: The counter current exchanger : vasa recta mechanism 2. Counter current exchanger (vasa recta mechanism): Descending vasa recta loose water and gain solute and while ascending, vasa recta gain water and loose solute. The exchange of water and solute between the descending and ascending vasa recta and the surrounding interstitium is called “countercurrent exchange.” This prevents wash out of solutes from the medulla, thus maintaining its hyperosmolarity.

16. Counter current exchange, cont….. Conditions that decrease medullary blood flow, such as volume depletion, improve urine concentrating ability and the efficiency of countercurrent exchange by allowing more time for blood in the ascending vasa recta to loose solute and achieve osmotic equilibration. Conversely, conditions that increase medullary blood flow, such as osmotic diuresis, decrease urine concentrating ability and impair the efficiency of countercurrent exchange.