Renal 2 Flashcards
What is the function of the distal convoluted tubule?
- relatively impermeable to water
- reabsorb 5-10% of filtered Na+
List all the transporters/channels on the apical side of the distal tubule. Which way do the ions flow?
- Na/Cl cotransporter (NCC); Na and Cl go into tubule cells
- Ca2+ selective channel (TRPV5); Ca goes into tubule cells
List all the transporters/channels on the basolateral side of the distal tubule? Which way do the ions flow?
- Na/Ca exchanger (NCX); Na into cell, Ca into interstium/blood
- Ca2+/H+ antiport (ATP driven); Ca out of cell into interstium
which diuretic drug targets the distal convoluted tubule? What class?
hydrochlorothiazide; class: thiazides
What is the mechanism of thiazides?
inhibit NCC (apical) –> decrease Na and Cl reabsorption –> increase Ca reabsorption via NCX (basolateral)
What are the therapeutic uses of thiazides?
hypertension, mild HF, severe resistant edema, reduce kidney stone formation in idiopathic hypocalciuria
What are the adverse effects of thiazides?
hypokalemia, metabolic alkalosis, impaired glucose tolerance (due to decrease in in insulin release)
What is the most important site for K+ excretion?
collecting tubules
What are the 2 cell types in the collecting tubules?
principal and intercalated
Describe the path of Na reabsorption in the principal cells. (use channels)
1) apical Na+ entry via epithelial Na+ channels (ENaC)
2) Na+ into interstitium via Na/K ATPase
How does aldosterone affect ENaC and Na/K ATPase?
increase activity
What drives K+ excretion into the lumen in the collecting tubules, in principal cells?
- lumen (-) potentials from Na+ exit from lumen via ENaC
- high [K+] inside cell (due to basolateral Na/K ATPase)
What are the 2 types of intercalated cells in the collecting tubules?
type A (alpha) and type B (beta)
Describe the events that occur at type A intercalated cells.
1) H+ excretion into lumen via apical proton pump
2) HCO3- reabsorption into interstitium via basolateral HCO3-/Cl- exchanger
What enhances/drives H+ secretion in type A intercalated cells?
- lumen (-) potential (due to Na influx via ENaC)
- aldosterone increases number of apical proton pumps
Which type of intercalated cells dominate in acidemia? alkalemia?
acidemia: type A - secrete excess H+
alkalemia: type B - secrete excess HCO3-
Describe the events that occur at type B intercalated cells.
1) HCO3- excretion into lumen via apical HCO3-/Cl- exchanger
2) H+ reabsorption into interstitium via basolateral proton pump
Which class of diuretic drugs targets the collecting tubules?
K+ sparing diuretics
What are the different types of K+ sparing diuretics?
- inhibitors of Na+ influx through ENaC
- competitive antagonist of aldosterone
What is the mechanism and function of amiloride? What class of diuretic is this?
- class: K+ sparing diuretic
- mech: inhibit Na+ influx through ENaC
- fxn: decrease in Na+ exit from lumen –> reduce (-) luminal potential –> less K+ excretion
What is the mechanism and function of eplerenone? What class of diuretic is this? What receptor is this drug selective for?
- class: K+ sparing diuretic
- receptor: mineralocorticoid receptors
- mech: competitive antagonist of aldosterone
- fxn1: reduce activities of ENaC and Na/K ATPase in principal cells
-fxn2: reduce proton pumps in type A intercalated cells
How can eplerenone cause metabolic acidosis?
reduce proton pumps in type A intercalated cells –> less proton secretion
What are the therapeutic uses of K+ sparing diuretics?
- use with K+ losing diuretics to prevent K+ loss in HF and hypertension treatment
- hyperaldosteronism (aldosterone antagonists)
What is the adverse effect of K+ sparing diuretics?
hyperkalemia
What is the role of ADH (antidiuretic hormone) on the collecting tubules?
1) ADH acts on basolateral V2 receptors
2) increase cAMP
3) increase insertion of AQP2 in apical membrane
4) increase water reabsorption
5) concentrated urine
What is the function of a V2 receptor antagonist? What class of diuretic is this?
- inhibit effect of ADH in collecting tubules
- reduce water reabsorption
- increase plasma Na concentration
class: antidiuretic hormone (ADH)antagonist
What are the therapeutic uses of V2 receptor antagonists?
- syndrome of inappropriate ADH secretion (water retention die to excessive ADH secretion)
- hyponatremia
What are the adverse effects of V2 receptor antagonists?
- hypernatremia
- hypotension
What are the edamatous states that diuretics can clinically treat?
- heart failure
- kidney disease and renal failure
- liver disease
- idiopathic edema
What are the non-edematous states that diuretics can clinically treat?
- hypertension
- nephrolithiasis (kidney stone)
- hypercalcemia
