Control of Renal Function

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 Ca 2+ levels. Understand the molecular of the diuretics presented in lecture.

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.

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.

Review of ADH Conrols H 2 O reabsorption or excretion. - Acts by increasing the H 2 O permeability of the distal tubule and collecting tubules. - Increase urea permeability in the medullary collecting tubule. Helps conserve H 2 O during dehydration.

Potassium

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

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.

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.

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?

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 H 2 O, but increases the excretion of K +.

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 +

Renal Regulation of Ca 2+ In the kidneys, parathyroid hormone: *Stimulates the reabsorption of Ca 2+ in the thick ascending loop of Henle and distal tubules. *Stimulates the conversion of vitamin D to a more active form (vitamin D increases Ca 2+ absorption from the small intestines.).

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 +, H 2 O, and K + ?

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

Typical Diuretic Response When the intake of Na + is constant. Diuretic causes an increase in Na + excretion. Because of osmosis, the rate of H 2 O excretion is also increased. As a result, the volume of extracellular fluid decreases.

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 +.

“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 H 2 O 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.

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 H 2 O in the tubular lumen. What would chlorothiazide do to the countercurrent mechanism?

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

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