8_HST110 Diuretics 2017

Question 1

What are diuretics good for?

Answer 1

Increased urine output

Both solute and water excretion are increased

Decreased ECF volume

Question 2

All diuretics inhibit Na+ reabsorption by the nephron

Increase urinary excretion of (X) (natriuresis)
Decrease (Y) volume

Answer 2

X = Na+
Y = ECF

Question 3

Diuretics are useful in the treatment of what 2 conditions?

Answer 3

volume overload and hypertension

Question 4

The site of action of a diuretic determines how much (X) excretion will be achieved

Depends partly on how much (X) are reabsorbed at the site

Determines what effects on other solutes (K+, Ca2+, HCO3-) will be seen

Answer 4

X = sodium and water

Question 5

Effect on other nephron segments: Inhibition of Na+ reabsorption at one site of the nephron (X) delivery of Na+ and water to more distal segments. The ability of distal segments to handle the increased solute and water load determines the overall effect of the diuretic

Answer 5

X = increases

Question 6

Action of diuretics depends on delivery in sufficient quantities to the site of action. Most diuretics act at the (X)

Answer 6

X = lumen of the tubule (filtered or secreted by PT)

Question 7

Name 5 classes of diuretics

Answer 7

1. Carbonic anhydrase inhibitors
2. Osmotic diuretics
3. Loop diuretics
4. Thiazide diuretics
5. Potassium-sparing diuretics (Aldosterone antagonists, Na+ channel blockers)

Question 8

Carbonic Anhydrase Inhibitors:

Site of action:
(X)

Prototype:
(Y)

Mechanism:
Inhibit carbonic anhydrase

Rationale for use:
~1/3 of Na+ reabsorbed in PCT is via (Z) antiporter, which depends on CA

Rarely used as a diuretic

Answer 8

X = Proximal tubule
Y = Acetazolamide
Z = Na+-H+

Question 9

Net effect of Carbonic Anhydrase Inhibitors on Na+

Answer 9

Downstream nephron segments increase Na+ reabsorption (aka not super effective)
Only 5-10% of filtered Na+ excreted

Question 10

Osmotic Diuretics:
Site of action:
(X)

Prototype:
Mannitol

Mechanism:
Freely filtered by glomerulus, not reabsorbed
Increase luminal (Y) and inhibit reabsorption of (Z)

Rationale for use: bulk of fluid and ion reabsorption takes place in PCT

Answer 10

X = Proximal tubule, TDL
Y = osmolality
Z = water

Question 11

Net effect of Osmotic agents on Na+

Answer 11

Downstream nephron segments increase Na+ reabsorption
Only 10% of filtered Na+ excreted

Bottom line:
Rarely used as a diuretic

Question 12

Loop Diuretics
Site of action:
(X)

Prototype:
(Y)

Mechanism:
Inhibit (Z) symporter
Abolishes medullary interstitial gradient
Blocks tubuloglomerular feedback at (A)

Rationale for use:
Loop of Henle is vital to urinary concentration

Answer 12

X = Thick ascending limb
Y = Furosemide
Z = Na+-K+-2Cl-
A = macula densa

Question 13

Net effect of Loop Diuretics on Na+

Answer 13

Downstream segments have limited ability to absorb Na+
Up to 25% of filtered Na+ excreted

Bottom line:
Most potent diuretic

Question 14

Thiazide Diuretics
Site of action:
(X)

Prototype:
Hydrochlorothiazide (HCTZ)

Mechanism:
Inhibit (Y) symporter

Rationale for use:
Increased urinary Na+ loss

Answer 14

X = Distal convoluted tubule
Y = Na+-Cl-

Question 15

Net effect of Thiazie Diuretics on Na+

Answer 15

Downstream segments have limited ability to absorb Na+
5-10% of filtered Na+ excreted

Bottom line:
Used for treatment of hypertension and edema

Question 16

K+sparing diuretics
Site of action:
Sites of K+ secretion: (X)

Prototype:
Aldosterone antagonist: (Y)
Na+ channel blocker: amiloride

Mechanism:
Aldosterone antagonists: block mineralocorticoid receptor and decrease activity and number of (Z) channels
Na+ channel blockers: block (Z)

Rationale for use:
Avoid (A)

Answer 16

X = late distal tubule, cortical collecting duct
Y = spironolactone
Z = ENaC
A = hypokalemia

Question 17

Net effect of K+ sparing diuretics on Na+

Answer 17

3-5% of filtered Na+ excreted

Bottom line:
Weak diuretics
Can be used with other diuretics for HTN and edema
Can be used to prevent/treat hypokalemia caused by other diuretics

Question 18

Diuretics: Effects on K+

1. Blocking Na+ reabsorption increases delivery of Na+ and water to the (X) nephron
2. K+ secretion increases due to:
   * Increased Na+ reabsorption (via (Y))
   * Increased tubular flow (via (Z) K+ channels)
   * Increased (A) (stimulated by volume depletion)

Answer 18

X = distal
Y = ROMK
Z = flow-sensitive
A = aldosterone

Question 19

Diuretics: Effects on Ca+

Ca2+ reabsorption (paracellular) is normally coupled to Na+ reabsorption in the (X)

Thus, diuretics that impair (Y) reabsorption at these sites also inhibit Ca2+ reabsorption

Answer 19

X = proximal tubule and thick ascending limb
Y = Na+

Question 20

What is the 1 exception for diuretics effects on Ca2+?

Answer 20

Thiazide diuretics STIMULATE Ca2+ reabsorption at the distal tubule

Question 21

Diuretics: Effects on HCO3-

Primary sites of HCO3- reabsorption and H+ secretion

• Proximal tubule: HCO3- reabsorption coupled to (X) reabsorption
• CCD: (Y) secretion coupled to (X) reabsorption

Answer 21

X = Na+
Y = H+

Question 22

Diuretics: Effects on HCO3-

Carbonic anhydrase inhibitors
*Directly inhibit HCO3- reabsorption -> increase HCO3- excretion -> metabolic (X)

Answer 22

X = acidosis

Question 23

Diuretics: Effects on HCO3-

Loop and thiazide diuretics decrease ECF volume and cause (X)

Stimulate proximal Na+ reabsorption and H+ secretion (via (Y)) -> more HCO3- reabsorbed

Stimulate (Z) activity -> increase H+ secretion in CCD -> increase (A) reabsorption

Answer 23

X = metabolic alkalosis
Y = NHE3
Z = aldosterone
A = HCO3-

Question 24

Diuretics: Effects on HCO3-

K+-sparing diuretics:
Inhibit Na+ reabsorption in distal tubule and CCD -> decrease H+ secretion -> (X)

Answer 24

X = metabolic acidosis