Renal Physiology L5.pdf

Physiology - Renal Reabsorptive & Secretory Mechanism LECTURE (5) ROLE OF KIDNEY IN WATER BALANCE DR. El-Sawy 0  Physiology - Renal...

Physiology - Renal Reabsorptive & Secretory Mechanism LECTURE (5) ROLE OF KIDNEY IN WATER BALANCE DR. El-Sawy 0  Physiology - Renal Reabsorptive & Secretory Mechanism Water balance (the balance between) Water input Water output  2.5 L/day  2.5 L/day  Controlled mainly by thirst  Controlled mainly by kidney under mechanism control of ADH  Reabsorb 65 % of filtered water In proximal tubules  Passively by osmosis 2ry to reabsorption of solutes.  Reabsorb 15% of filtered water DLH:  passively by osmosis secondary to high medullary osmolarity In loop of Henle  Totally impermeable to water (most ALH: diluting segment of nephron) Early distal  Impermeable to water. tubules Late distal  Reabsorb 10 % of filtered water. In distal tubules tubules &  Permeable to water in the presence and collecting Cortical of ADH. ducts collecting duct  Reabsorb 4% of filtered water. Medullary  So, 1% of filtered water will form collecting duct urine (0.5-1 ml/min). DR. El-Sawy 1  Physiology - Renal Reabsorptive & Secretory Mechanism The kidney can make diluted urine concentrated urine Up to 25-50 m.osmol/L Up to 1200-1400 m.osmol/L. Occur in overhydration Occur in dehydration Decreased ADH secretion increased ADH secretion  For making either diluted or concentrated urine, the kidney must do osmotic work.  Osmotic work is exerted by loop of Henle (specifically by thick ALH).  Fluid enters the loop of Henle is isotonic from PT and leaves it hypotonic to DT.  The excess solutes (NaCl and urea) are entrapped in the medulla making what is called the medullary gradient. How the kidney be able to dilute or concentrate urine? ① Formation of medullary gradient. ② Maintenance of this medullary gradient. ③ Role of ADH. DR. El-Sawy 2  Physiology - Renal Reabsorptive & Secretory Mechanism DR. El-Sawy 3  Physiology - Renal Reabsorptive & Secretory Mechanism  Gradually increasing medullary osmolarity: Definition From 300 mosmol/L at cortico-medullary junction up to 1200-1400 mosmol/L at tip of renal papillae. 1) Counter-current multiplier system. Mechanisms 2) Urea recycling (Between DLH & PCD).  The system in which the inflow runs parallel, in proximity and Definition in counter direction to the outflow. 1) Active transport process by thick ALH. 2) Different water and solutes permeability of the loop of Henle. Requirement 3) Counter-current flow of fluid in DLH, ALH and CD. 4) Water reabsorption from late distal tubule and CCD. 5) Osmotic equilibrating device of the medullary CD. DR. El-Sawy 4  Physiology - Renal Reabsorptive & Secretory Mechanism ① Active transport of NaCl at thick ALH: [key factor = single effect]  By Na-K-2Cl Cotransport  NaCl reabsorption is key factor of development of medullary gradient.  Responsible for horizontal gradient in osmolarity: Between ALH and surrounding interstitium At any level by about 200 mosmol/L.  In presence of ADH: Water is absorbed without urea in connecting tubules, CD Increase urea concentration in inner MCD (papillary CD) → urea is reabsorbed into medullary interstitium → ↑↑ its osmolarity (shift of horizontal to vertical gradient). This makes concentrated fluid at the bend of loop of Henle → helps passive diffusion of NaCl from thin ALH to the medullary interstitium, further increasing its osmolarity. So, the horizontal gradient is shifted indirectly into a vertical one. ② Different water & solute permeability of loop of Henle DR. El-Sawy 5  Physiology - Renal Reabsorptive & Secretory Mechanism ③ Counter-current flow in the loop of Henle: DLH Thin ALH Permeable only to water Permeable only to solutes  Allows water reabsorption by the  Allows NaCl- reabsorption passively surrounding medullary into medullary interstitium. hyperosmolarity.  These features of loop of Henle together with the counter-current flow in loop of Henle shift the horizontal gradient into vertical one. ④ Role of distal tubule and CCD:  About 2/3 of water delivered to connecting tubules and CCD is reabsorbed.  So, little fluid is delivered to medulla → increasing urea concentration → diffusion of urea to medullary interstitium → increasing medullary osmolarity. ⑤ Osmotic equilibrating device of medullary CD:  To help reabsorption of urea & solutes from collecting duct to medullary interstitium, so increasing deep medullary osmolarity. DR. El-Sawy 6  Physiology - Renal Reabsorptive & Secretory Mechanism Factors Determining the Degree of the Gradient:  ↓↓ magnitude of single effect → ↓ gradient ① Magnitude of single effect  As by use of loop diuretics & lack of ADH  ↑↑ flow rate →↓↓ gradient ② Flow rate in loop of Henle  Since there is no enough time for reabsorption. ③ length of loop of  ↑↑ length of loop of Henle → ↑ gradient Henle  ↑↑ percentage number of long loop of Henle as in ④ percentage number of long loop of camels & rodents (up to 30%) → formation of more Henle concentration urine (up to 5000 mosmol/L). ⑤ Rate of medullary blood flow in vasa  High rate → washout of medullary gradient. recta  High protein diet makes more concentrated urine ⑥ Amount of urea available  due to more available urea ⑦ ADH  Presence or absence of ADH DR. El-Sawy 7  Physiology - Renal Reabsorptive & Secretory Mechanism Handling of urea in renal tubules:  Reabsorption of large amount of H2O →↑ conc. of urea Pars recta from 6 to 20 osmol/L. at end of pars recta.  50% of urea is passively reabsorped from pars recta.  H2O only reabsorbed →↑ conc. of urea leaving DLH from DLH: 20 to 40 (in short nephron) and to 80 (in long nephron).  Urea is secreted due to high conc. of urea in interstitium of Thin ALH: inner medulla (600m.osmol/L). Thick ALH  No urea reabsorption.  H2O only absorbed by ADH → increase conc. Of urea Connecting tubule, cortical, outer reaching inner medullary collecting duct → passive medullary reabsorption of urea in inner medullary or papillary collecting duct: collecting duct (PCD) by ADH. urea recycling :  Cycling of urea between inner medullary CD "PCD" ⇨ inner medullary interstitium → thin ALH → thick ALH → DCT → Definition connecting tubules → CCD → MCD → PCD → interstitium again and so on. 1. Entrapping of urea in the interstitium of inner medulla. Significance 2. Augmentation of its concentration in the inner medulla. Both 1 and 2 increase the medullary gradient. DR. El-Sawy 8  Physiology - Renal Reabsorptive & Secretory Mechanism DR. El-Sawy 9  Physiology - Renal Reabsorptive & Secretory Mechanism Vasa recta (VR) is characterized by: 1. Counter-current exchanger system. 2. Capillary wall is permeable to solutes & water:  In DVR: solute enter and water leaves it.  In AVR: solutes leave and water enters it. 3. Long capillaries Causing sluggish blood flow 4. High viscosity of the blood Steady state In dehydration or ↓ ECF In overhydration & ↑ in ( L body water) : volume. ECF volume:  The VR reabsorb more  VR reabsorb more  VR reabsorb equal water than solutes → solutes than water amount of water and building up of (washout of medullary solutes. medullary. gradient is required). DR. El-Sawy 10  Physiology - Renal Reabsorptive & Secretory Mechanism at thick ALH  Stimulation of co-transport of Na+, K+ & Cl- connecting  It increases water permeability tubule, CCD Outer  It increases water permeability medullary C Inner  It increases urea permeability medullary C entrapping of  To share by 50% of medullary osmolarity urea in  (600 mosmol NaCl and 600 mosmol urea). medulla decreases medullary  Helps maintenance of medullary gradient blood flow Mechanism of action of ADH: 1) ADH binds to basolateral border C-AMP. 2) C-AMP activates protein kinase → phosphorylates aquaporin (water channel). 3) Insertion of the phosphorylated aquaporin in the apical membrane of the principal cells. DR. El-Sawy 11  Physiology - Renal Reabsorptive & Secretory Mechanism Types of aquaporin:  Present at apical border of PT & DLH.  Not affected by ADH.  Present in apical border of CD, especially principal cells.  Located at basolateral border of principal cells  To facilitate transport of urea & water.  Located in brain.  Located in salivary & lacrimal glands & respiratory system. Stimuli for thirst: 1- Hyperosmolarity: 2-3% change in plasma osmolarity → strong desire to drink. 2- 2- Blood volume: 10-15% decrease in blood volume evokes thirst as that induced by 2-3% increase in plasma osmolarity. 3- AII by direct action on thirst center. 4- Dryness of the mouth. 5- There may be some kind of water metering in stomach: That sense the need for water. DR. El-Sawy 12