Control of Renal Function

1. Control of Renal Function

2. Learning Objectives • Know the effects of aldosterone, angiotensin II and antidiuretic hormone on kidney function. • Understand what happens when extracellular K+ becomes elevated and how this is regulated. • Know how the kidneys help regulate Ca2+ levels. • Understand the molecular of the diuretics presented in lecture.

3. Review of Aldosterone Acts primarily on the principle cells of the cortical collecting tubules. Stimulates Na+/K+-ATPase. This increases Na+reabsorption and K+ secretion.

4. Review of Angiotensin II • Powerful Na+-retaining hormone. - Stimulates aldosterone - Constricts efferent arterioles. - Reduces peritubular capillary hydrostatic pressure. - Increase the filter fraction. - Stimulates Na+/K+-ATPase in the proximal tubules, loops of Henle, distal tubules, and the collecting tubules. • As discussed last time, angiotensin II is important in pressure diuresis and natriuresis.

5. Review of ADH • Conrols H2O reabsorption or excretion. - Acts by increasing the H2O permeability of the distal tubule and collecting tubules. - Increase urea permeability in the medullary collecting tubule. Helps conserve H2O during dehydration.

6. Potassium

7. Changing K+ It is very important to keep extracellular K+ regulated

8. Regulating K+ • The intracellular fluid can act as a buffer, by taking up or releasing K+. • Some factors that increase the uptake of K+ into cells are: insulin, aldosterone and alpha-adrenergic stimulation • Some factors that increase the release of K+ from cells are: Strenuous exercise (release for muscle), cell lysis and blocking the actions of insulin, aldosterone, alpha-adrenergic stimulation.

9. Renal Control of K+ • Proximal tubule and ascending loop of Henle reabsorb large amounts of K+. This level of reabsorption does not normally change much. • Most regulation of K+ is done in the late distal tubule and cortical collecting tubule. There, K+ can be reabsorbed or secreted at varying degrees.

10. K+ Secretion in the Principal Cells • Principal cells make up ~ 90% of the epithelial cells in the late distal tubule and cortical collecting tubule. • These cells can secrete a large amount of K+. • When K+ is high, the rate of K+ secretion in the principal cells is high. • When K+ is low, the rate of secretion is low. Then, the rate of K+reabsorption by the intercalated cells can exceed the secretion rate by the proximal cells. • What hormone controls the rate of K+ secretion in the principal cells?

11. Regulation of K+ Secretion • Increased extracellular K+ causes: - An increase in Na+/K+-ATPase activity in the principal cells. - An increase in aldosterone. - This further increases Na+/K+-ATPase activity and increases permeability of the luminal membrane of epithelial cells. - Aldosterone increases reabsorption of Na+ and H2O, but increases the excretion of K+.

12. Acidosis and K+ Levels • Acute increases in H+ inhibits the Na+/K+-ATPase in the principal cells. • What does this do to K+ secretion? - Decreases secretion • What does decreased secretion do to extracellular K+ levels? - Increases extracellular K+

13. Renal Regulation of Ca2+ In the kidneys, parathyroid hormone: *Stimulates the reabsorption of Ca2+ in the thick ascending loop of Henle and distal tubules. *Stimulates the conversion of vitamin D to a more active form (vitamin D increases Ca2+ absorption from the small intestines.).

14. Practice Question • If a person does not secrete enough aldosterone (Addison’s Disease), what do you expect to happen to the body’s level of Na+, H2O, and K+?

15. Diuretics • Diuretics increase the rate of urine output. • Most act by decreasing the rate of Na+reabsorption.

16. Typical Diuretic Response • When the intake of Na+ is constant. • Diuretic causes an increase in Na+ excretion. • Because of osmosis, the rate of H2O excretion is also increased. • As a result, the volume of extracellular fluid decreases.

17. Typical Diuretic Response • Why does the rate of Na+ excretion decrease after a few days? • Other mechanisms are activated, e.g., a decreased arterial pressure (from less blood volume) would cause an increase in angiotensin II. This would increase the GFR and reabsorption of Na+.

18. “Loop” Diuretics • “Loop” diuretics (e.g., furosemide (Lasix)) inhibit the Na+/2Cl-/K+cotransporter in the thick ascending loop of Henle. • This decreases the reabsorption of Na+, Cl-, and K+. The extra ions in the tubular lumen osmotically increase the amount of H2O in the tubular lumen. • What would Lasix do to the countercurrent mechanism? • - Decrease the reabsorption of ions into the medullary interstitial fluid and thus decrease the effectiveness of the countercurrent mechanism. Know how this would affect renal function.

19. Thiazide Diuretics • Thiazide diuretics, e.g., chlorothiazide, inhibit the Na+/Cl-cotransporter in the early distal tubule. • This decreases the reabsorption of Na+ and Cl-. The extra ions in the tubular lumen osmotically increase the amount of H2O in the tubular lumen. • What would chlorothiazide do to the countercurrent mechanism?

20. Competitive Inhibitors of Aldosterone • Competitive inhibitors of aldosterone, e.g., spironolactone, inhibit aldosterone’s Na+/K+-ATPasein the cortical collecting tubule. • This decreases the reabsorption of Na+ and the secretion of K+. • Hence, these are called “K+-sparing” diuretics.

21. Na+ Channel Blockers • Inhibition of Na+ channels in cortical collecting tubule, e.g., amiloride, decrease the reabsorption of Na+.