1. Tubular Reabsorption and regulation of tubular reabsorption Tortora Ebaa M Alzayadneh, PhD

2. Learning Objectives 1-Describe tubular reabsorption and secretion 2-Describe the specific characteristics of different nephron segments in terms of solutes and water reabsorption capabilities. 3-Understand the hormonal regulation of tubular reabsorption. 4-Describe the mechanism of action of some diuretic drugs in the nephron.

3. The functional unit of the kidney Urine Formation: Ultrafiltration Reabsorption Secretion Excretion  180 L/day fluid is filtered.  less than 1% is excreted. Excretion= Filtration-Reabsorption+ Secretion Filtration Secretion Reabsorption Urinary excretion (1-2 L/day)

4. Reabsorption of Water and Solutes

5. Active Transport The key transporter is the Na, K- ATPase Apical Basolateral

6. Downloaded from: StudentConsult (on 27 May 2011 03:09 PM) © 2005 Elsevier Proximal tubule reabsorption Blood High osmolality of intercellular spaces drives water reabsorption Tubular fluid Solvent drag of K + and Ca ++ Paracellular Transcellular: Aquaporins Water reabsorption

7. Glucose: Proximal Tubules Symporter= transports two or more substances in the same direction Glucose is transported via secondary active transport (facilitated diffusion)

8. Proximal Tubules The proximal tubules reabsorbs about 67% of filtered water, Na +, Cl -, K +, HCO 3 -. The proximal tubules reabsorbs almost all glucose and amino acids filtered by the glomeruli. The key transporter element is the Na, K- ATP ase in the basolateral membrane.

9. Loop of Henle Thin Descending  15% of H 2 O reabsorbed. H2OH2O Na + Cl - Thin Ascending  Passive reabsorption of Na+, K+, Cl-.  Impermeable to H 2 O. Thick Ascending  25% of Na+, K+, Cl- reabsorbed.  Impermeable to H 2 O.  Called = Diluting segment.

10. Loop of Henle Water reabsorption occurs exclusively in the thin descending limb of Henle via AQP1 water channels.( Aquaporins) Reabsorption of NaCl occurs in both thin and thick ascending limb of Henle. In thin ascending limb NaCl is reabsorbed passively. However, in thick ascending limb NaCl is reabsorbed through Na + -K + ATPase in basolateral membrane ans. Ascending limb is impermeable to water. Reabsorption of Ca ++ and HCO3 - occurs also in Loop of Henle.

11. Downloaded from: StudentConsult (on 27 May 2011 03:09 PM) © 2005 Elsevier Thick ascending limb of Henle Blood Furosemide of NaCl Reabsorption:  50% is Transcellular  50% is Paracellular Tubular fluid Voltage Impermeable to water

12. Distal tubule and collecting duct  Reabsorbs 7% NaCl, secrets K+ and H+ and reabsorbs 8-17% H 2 O Impermeable to water ENac Basolateral Thiazides Principal cells Intercalated cells Apical Late distal tubule and Collecting duct Early distal tubule Na-K- ATPase Amiloride permeability to water depends on ADH

13. Distal tubule and collecting duct The early segment of the distal tubule is impermeable to water. Dilution starts in the TAL and continues in the early distal tubule. Variable water amounts are reabsorbed in the late distal tubule and collecting duct depending on ADH levels ( Anti Diuretic hormone activates Aquaporins in the apical and basolateral membranes of principal cells to reabsorb water). In absence of ADH little water is reabsorbed.

14. Clinical Application: Drugs acting on nephron segments Furosemide Diuretic( Lasix): Inhibits 1Na-1K-2Cl symporter in the TAL,thus inhibiting NaCl reabsorption and K reabsorption(decreasing K + in blood= Hypokalemia). Thiazides Diuretics: Inhibit the Na-Cl symporters; reduction of Na reabsorption in early distal tubule.( Hypokalemia) Amiloride Diuretic: Inhibits Na channels (ENac)on the luminal (apical) side of the distal tubule and collecting duct cell membranes reducing Na reabsorption and indirectly inhibiting Cl- reabsorption. It also inhibits K secretion. (Sparing Diuretic)( Hyperkalemia)

15. Hormonal regulation: (Antidiuretics actions) Ang II: stimulates NaCl and water reabsorption, induced by decreased extracellular fluid volume. Aldosterone: stimulates NaCl reabsorption in the TAL, DT and CD. Also stimulates K secretion. Catecholamines: Norepinephrine(Adrenal medulla) and Epinephrine(Sympathetic nerves) stimulate NaCl and water reabsorption by the PT, TAL, DT and CD. ADH: Is the most important regulator of water reabsorption in the kidney. Is secreted by the posterior pituitary gland in response to increase in plasma osmolality or decrease in extracellular fluid volume. It increases water reabsorption across the CD and has little effect on NaCl excretion. (Concentrating urine)

16. Hormonal regulation: (Diuretic actions) Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP): Are released from cardiac ventricles in response to increased pressure and extracellular volume. They stimulate urinary NaCl and water excretion. Also they inhibit function and secretion of ADH hormone. Urodilatin: Is secreted by DT and CD and stimulated by increased pressure and extracellular volume. It inhibits NaCl and water reabsorption. In kidney only. More potent than ANP. Dopamine : is a catecholamine released from dopaminergic nerve endings in PT and synthesized in PT cells. Is stimulated by increased extracellular volume fluid. It inhibits NaCl and water reabsorption.

17. Summary; Exam example: 1- PCT = Active transport of sodium, glucose and amino acids occur; water follows passively. 2-DLH=Passively permeable to water; no solute exchange. 3-Thin ALH= Passively permeable to NaCl; impermeable to water. 4-Thick ALH= Active transport of sodium occur; impermeable to water and called the diluting segment. 4-ThickALH= Where Furosemide diuretic inhibits 1Na-1K-2Cl symporter 5 and 6-DCT and CD= Are passively permeable to water under ADH stimulation..