1. Na + Homeostasis

2. Sodium reabsorption by the nephron 1% 3% 6% 65% 25% Percentages give the proportion from filtered load reabsorbed Normally, only 1% or less is excreted But this 1% is a significant quantity

3. Na + Balance Na + balance will be maintained if the following is true Intake = Excretion OR If Na + content is high, increase excretion If Na + content is low, increase reabsorption

4. Na + Content of the Body Na + content of the body can not be detected What can be measured are:  Concentration of in ECF, strongly correlated to ECF osmolality as it is the main solute in ECF  ECF volume, which correlated with blood volume and arterial blood pressure

5. Na + Content of the Body Would changes in Na+ content of the body primarily result in changes in: ? Osmolality of ECF ? Volume of ECF

6. Mechanisms of Na + Homeostasis These mechanisms are responsive mostly to Change in ECF volume and its consequences which are  Change in blood volume  Change in blood pressure Response of Na+ regulatory mechanisms to change is osmolality is minimal Na + Homeostatic are directed towards regulateing blood volume and arterial blood pressure

7. Total Vs Effective Blood Volume Effective blood volume – volume of blood available for perfusion, the blood volume contained in the arterial system Total blood volume – volume of blood in the whole circulatory system Na+ homeostatic mechanisms are linked to the effective blood volume

8. Total Vs Effective Blood Volume Can the effective blood volume change when the total blood volume remains the same? Yes, due to changes in venous capacity Example: “septic shock” blood vessels are dilated, effective blood volume decreased but total blood volume is normal

9. Glomerular Mechanisms Raised Blood VolumeRaised Blood Pressure Increased Renal Blood Flow Increased Glom Capillary Hydrostatic Pressure Increased GFR Trend Towards Increased Na + and H 2 O excretion Increased Glom Capillary Oncotic Pressure,

10. Glomerular Mechanisms Raised Blood VolumeRaised Blood Pressure Increased Renal Blood Flow Increased Glomerular Capillary Hydrostatic Pressure Increased GFR Trend Towards Increased Na + and H 2 O excretion Baroreceptor mechanism Glomerular arteriolar dilatation (mostly afferent) Decreased Glomerular Capillary Oncotic Pressure

11. Glomerular Mechanisms Raised Blood Volume Atrial Distention Atrial Natriuretic Peptide Increased GFR – dilatation of afferent arteriole

12. Proximal Tubular Mechanisms 1.Increased delivery of Na + to the proximal tubule  Proximal tubular reabsorption of Na + is on a percentage basis  Total reabsorbed in increased but the total unabsorbed by the proximal tubule is also increased  More Na leaves the proximal tubule and enters the loop of Henle

13. Proximal Tubular Mechanisms 2.Status of the peritubular capillaries  Higher hydrostatic pressure in peritubular capillaries  Lower oncotic pressure in the peritubular capillaries Reabsorption is inhibited Minor decrease in the percentage of Na + absorbed in the proximal tubule But constitutes a significant decrease in quantity if Na + reabsorbed

14. Proximal Tubular Mechanisms 3. Increased interstitial pressure  Higher arterial pressure results in higher medullary interstitial pressure  Reabsorption is inhibited – mediated by a reduction of Na + K + ATPase activity

15. Proximal Tubular Mechanisms 4. Flow rate (minor effect only)  Higher GFR will increase flow rate in the tubule  Less Na + reabsorption takes place

16. Loop of Henle No significant Na + regulatory mechanism in Loop of Henle

17. JGA & Distal Tubule Major contributor to Na+ homeostasis 1.JUXTAGLOMERULAR APPARATUS  Sensor function  renal arteriolar pressure  distal tubular flow  Secretion of renin 2.DISTAL TUBULE  Modulation of Na+ reabsorption

18. Juxtaglomerular Apparatus Sensory function 1.Granular cells of afferent arteriole – sensitive to pressure within the arteriole  High pressure – renin secretion is inhibited 2. Macula Densa – sensitive to fluid flow rate NaCl flow rate  High flow rate – renin secretion is reduced

19. Renin Secretion Renin secretion is by afferent arteriolar granular cells STIMULI 1.Granular cells themselves 2.Macula densa 3.Renal sympathetic nerves (through beta 1 receptors)

21. Renin Secretion High blood volumeHigh blood pressure Distension of afferent arteriole Raised GFR & reduced proximal tubular reabsorption High distal tubular flow rate Inhibition of sympathetic nerves Inhibition of renin secretion

22. Renin Secretion Renin secretion is  Inhibited by high effective blood volume and high blood pressure  Increased when effective blood volume and blood pressure are low

23. Renin Angiotensin Aldosterone System Angiotensinogen Angiotensin I Angiotensin II Arteriolar constriction Aldosterone secretion Renin Increase distal tubular Na+ reabsorption Decrease GFR Renin activates mechanisms that increase Na+ and water retention ADH secretion Angiotensin converting enzyme

24. Overview of Na+ Homeostasis Changes in effective blood volume and blood pressure Arteriolar changes, hydrostatic & oncotic pressure changes, endocrine responses Responses by glomerulus, proximal tubule and distal tubule Modulation of Na+ excretion Compensation of changes in effective blood volume and blood pressure