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2. A system in which the inflow runs parallel to, counter to, and in close proximity to the outflow for some distance. Conditions to be fulfilled, 2 tubes in parallel movement in opposite direction in close proximity & selectively permeable 3. Maintenance of air temperature in a furnace Countercurrent mechanism helps Penguin to stand on ice for long time. 4. Skin (heat conservation) Scrotum (exchange of heat & testosterone) Kidney ability to concentrate urine, a critical adaptation of life on land through evolution 5. Depends upon maintenance of a gradient of increasing osmolality along the medullary pyramids. Counter current multiplication system- Loop of Henle Counter current exchange system Vasa recta 6. long loop of Henle establishes a vertical osmotic gradient (Countercurrent multiplier) their vasa recta preserve this gradient while providing blood to renal medulla ( Countercurrent exchanger) collecting ducts of all nephrons use the gradient in conjunction with the hormone vassopressin, to produce urine of varying concentration (osmotic equilibrating device) Collectively this entire functional organization is known as medullary countercurrent system 7. A large, vertical osmotic gradient is established in the interstitial fluid of the medulla (from 100 to 1200 mosm/liter) This osmotic gradient exists between the tubular lumen and the surrounding interstitial fluid. 8. Process in which small osmotic gradient established at any level of LOH is multiplied in to larger gradient. Single effect Active transport of Na & Cl out of thick ascending limb High permeability of thin descending limb to water Solute deposition in medulla & removal of water from descending limb 9. PCT Water reabsorption follows solute reabsorption Descending limb of loop of Henle Highly permeable to water Relatively impermeable to solutes Thick Ascending limb Impermeable to water Solute reabsorption occurs 10. Hypothetical case Assume glomerular filtrate to be 300 mOsm/L Assume Medullary interstitium to be at 300 mOsm/L 300 300 300 300 300 300 300 300 300 300 300 300 300 300 300 300 300 300 11. Transporters create a gradient of 200 mOsm/L 300 300 300 300 300 300 300 300 300 300 300 300 300 300 300 300 300 300 12. The osmolarity in the medullary intersitium increases to 400 mOsm/L 300 300 300 300 300 300 200 200 200 200 200 200 400 400 400 400 400 400 13. The descending limb loses water and reaches the same osmolarity 400 400 400 400 400 400 200 200 200 200 200 200 400 400 400 400 400 400 14. New fluid enters the loop of Henle300 300 300 400 400 400 200 200 200 400 400 400 400 400 400 400 400 400 15. Upper interstitium equilibrates 300 300 300 400 400 400 200 200 200 400 400 400 300 300 300 400 400 400 16. 300 300 300 400 400 400 200 200 200 400 400 400 300 300 300 400 400 400 Transporters pump out sodium and chloride again into interstitium 17. Until a gradient of 200 mosm is attained 300 300 300 400 400 400 150 150 150 300 300 300 350 350 350 500 500 500 18. Descending limb equilibrates350 350 350 500 500 500 150 150 150 300 300 300 350 350 350 500 500 500 19. Inflow of fresh filtrate and equilibration with the medullary interstitum 300 300 350 350 500 500 150 150 300 300 500 500 300 300 350 350 500 500 20. Tranporters work again to reach a gradient of 200 mosm Process is repeated again and again Thus a single effect gets multiplied 300 300 350 350 500 500 125 125 225 225 400 400 325 325 425 425 600 600 21. Axial gradient Magnitude depends on, Rate of fluid flow Strength of single effect Length of LOH 22. Descending limb is highly permeable to water but impermeable to solutes Thin ascending limb is passively permeable to solutes In thick ascending limb, Na & Cl are actively transported (Na/K/2Cl) 23. Solute gradient created by LOH in medulla is maintained by vasa recta Decrease solute dissipation In descending limb, solutes diffuse into vessels In ascending limb, solutes diffuse out of vessel Thus solutes keep circulating Water diffuses out of descending limb and into ascending limb While solutes recirculate in medulla, water is removed from it 24. Descending vasa recta Loses water Gains solutes Ascending vasa recta Gains water Loses solutes 25. Acts as osmotic equilibrating device, by its permeability to water & urea use the gradient, created by LOH & maintained by vasa recta, in conjunction with the hormone vasopressin, to produce urine of varying concentration 26. Vasopressin-controlled, variable water reabsorption occurs in the final tubular segments. 65% of water reabsorption is obligatory in the proximal tubule. In the distal tubule and collecting duct it is variable, based on the secretion of ADH. The secretion of vasopressin increases the permeability of the tubule cells to water. An osmotic gradient exists outside the tubules for the transport of water by osmosis. Vasopressin works on tubule cells through a cyclic AMP mechanism. During a water deficit, the secretion of vasopressin increases. This increases water reabsorption. During an excess of water, the secretion of vasopressin decreases. Less water is reabsorbed. More is eliminated. 27. Every time tubular fluid passes through LOH, Water comes out of descending limb into interstitium, which is removed by ascending limb of vasa recta Solutes come out of ascending limb into interstitium Thus, high osmolality is maintained in medulla This causes movement of water out of the Collecting Duct & makes the urine concentrated 28. DIURETICS drugs that increase the rate of urine flow their clinical applications aim to reduce ECF volume by decreasing total body NaCl content 29. TYPE Site of Action Examples 1. Inhibitors of Carbonic Anhydrase PCT Acetazolamide, Methazolamide 2. Osmotic diuretics LOH Glycerine, Isosorbide, Mannitol,Urea 3. Inhibitors of Na-K-2Cl symport (Loop diuretics /High ceiling diuretics Thick AL of LOH Furosemide, Bumetamide, Torsemide 30. TYPE Site of Action Examples 4. Inhibitors of Na-Cl symport (Thiazide-like diuretics) DCT Chlorothiazide, Hydrochlorothiaz ide, 5. Inibitors of renal epithelial Na channels (K-sparing diuretics) Late DCT & CD Amiloride, Triamterene 6. Antagonists of mineralocorticoid receptors (Aldosterone antagonists/ K-sparing diuretics) Late DCT & CD Spironolactone 31. Diuretic Braking Compensatory Mechanisms: Activation of sympathetic nervous system Activation of R-A-A axis Decreased arterial BP Hypertrophy of renal epithelial cells Increased expression of renal epithelial transporters