SODIUM BALANCE

1. بسم الله الرحمن الرحيم SODIUM BALANCE Dr.MohammedSharique Ahmed Quadri Assistant prof. Physiology Al Maarefa College

2. OBJECTIVES • Describe the overall handling of Na+ by nephron. • Discriminate the mechanism of reabsorption of Na+ in different parts of nephron • Describe the tubular reabsorption of water • Explain the concept of tubule glomerular feedback and glomerulo tubular balance • Discuss how various drugs affect the reabsorption of sodium (Diuretics). • Illustrate the renal mechanism of regulation of Na+ excretion.(effect of sympathetic , ANP, Starlings forces,& renin-angiotensin-aldosterone mechanism )

3. Sodium Balance • Na+ is major cation in ECF Amount of sodium in ECF Volume of ECF Plasma volume Blood volume Blood pressure

4. Sodium content VS Sodium concentration • Na+ concentration is determined not only by the amount of Na+ present but also by the volume of water. • For example, • a person can have an increased Na+ content but a normal Na+ concentration (if water content is increased proportionately). • Or, a person can have an increased Na+ concentration with a normal Na+ content (if water content is decreased).

5. OVERALL HANDLING OF NA+

6. Na+ Reabsorption • An active Na+ - K+ ATPase pump in basolateral membrane is essential for Na+ reabsorption • Of total energy spent by kidneys, 80% is used for Na+ transport • Na+ is not reabsorbed in the descending limb of the loop of Henle • Water follows reabsorbed sodium by osmosis which has a main effect on blood volume and blood pressure

7. Cellular mechanisms of Na+ reabsorption in the early proximal tubule Diuretics that act here:- a)Osmotic diuretics – Mannitol,Urea etc b)Carbonic Anhydrase Inhibitors - Azetazolamide

8. Cellular mechanisms of Na+ reabsorption in the late proximal tubule

9. Isosmotic Reabsorption • Na+ enters the cell across the luminal membrane water follows the solute to maintain isosmolarity. • Na+ is pumped out of the cell by the Na+-K+ ATPase, at basolateral membranes, water again follows passively. • Isosmotic fluid accumulates in lateral intercellular space between the proximal tubule cells. • This isosmotic fluid is reabsorbed in peritubular capillary blood due to high oncotic pressure in peritubular capillaries (πc) .

10. Mechanism of isosmotic reabsorption in the proximal tubule

11. Regulation of Tubular ReabsorptionGlomerulotubular Balance • Tubular reabsorption increases/decreases automatically as the filtered load increases/ decreases. • Glomerulotubular balance ensures that a constant fraction of the filtered load is reabsorbed by the proximal tubule, even if the filtered load increases or decreases. • Glomerulotubular balance ensures that normally 67% of the filtered Na+ and water is reabsorbed in the proximal tubule

12. Glomerulotubular Balance Increase in GFR Increase in filtration fraction Increase in concentration of protein in peritubular capillaries Increase in πc Increase reabsorption in proximal tubule

13. Effects of ECF volume expansion & ECF volume contraction on isosmotic fluid reabsorption in the proximal tubule

14. PROXIMAL TUBULEPoints to ponder • Reabsorbs 67% of the filtered Na+. • Reabsorbs 67% of the filtered water. • The tight coupling between Na+ and water reabsorption is called isosmotic reabsorption. • This bulk reabsorption of Na+ and water (the major constituents of ECF) is critically important for maintaining ECF volume. • The site of glomerulotubular balance, a mechanism for coupling reabsorption to the GFR.

15. Cellular mechanism of Na+ reabsorption in the early distal tubule

16. Thick Ascending Limb of Loop of Henle(points to ponder) • Load dependent reabsorption • Electrogenic • The role of lumen possitive potential is driving the reabsorption of Mg & Ca • Impermeable to water

17. Cellular mechanism of Na+ reabsorption in the early distal tubule

18. EARLY DISTAL TUBULE • IMPERMEABLE TO WATER • CORTICAL DILUTING SEGMENT

19. Late distal tubule • Principal cell : Na+ reabsorption & K+ secretion • α- inetercalted cells K+ reabsorption & H+ secretion

21. Late distal tubule(points to ponder) • Na+ reabsorption in these segments is hormonally regulated. Aldosterone is a steroid hormone that acts directly on the principal cells to increase Na+ reabsorption • Water permeability of principal cells is controlled by ADH

22. Regulation of sodium balance • EABV: Portion of ECF that is in arteries & is the volume effectively perfusing the tissues • The renal mechanism to regulate the Na excretion are • Sympathetic nerve activity • Atriopeptin (ANP) • Starling’s forces in peritubular capillaries • Renin-angiotensin aldosterone system

23. Sympathetic nerve activity In response to dec arterial pressure V.C of aff arteriole & inc Na reabsorption in proximal tubule

24. Starlinf forcess in peritubular capillaries • Renin-angiotensin aldosterone system • In respose to decrease in arterial pressure • Angiotensin II inc reabsorption of Na in proximal tubule • Aldosterne inc reabsorption of Na in distal tubule & collecting ducts

25. RAAS

28. Atriopeptin (ANP) • In rsponse to increase in ECF volume • V.D of aff & V.C OF eff arteriol • Incease GFR & dec reabsorption of Na

30. References • Human physiology by Lauralee Sherwood, seventh edition • Text book of physiology by Linda .s contanzo,third edition • Text book physiology by Guyton &Hall,11th edition