Renal (Diuretics)

Front 1

Which of the following does NOT act on the proximal tubules?
Carbonic anhydrase inhibitors
furosemide
Osmotic agents
None of the above
Which of the following does NOT act on the proximal tubules?

a. Carbonic anhydrase inhibitors
b. furosemide
c. Osmotic agents
d. None of the above

Back 1

B. furosemide is a loop diuretic that acts on the thick asc limb of loop of henle

Front 2

what is the class and mechanism of acetazolamide?

Back 2

class = carbonic anhydrase inhibitor

mechanism =
inhibits NaHCO3 reabsorption in the PT (Inhibits conversion of bicarb to H20 and CO2, which keeps these 2 molecules from being able to be reabsorbed into PCT epithelial cells)

Front 3

what are the effects of acetazolamide and what are its clinical uses?

Back 3

Effects:
-NaHCO3 diuresis
-Hyperchloremic metabolic acidosis

Clinical uses:
-urinary alkalinization
-metabolic alkalosis (pushes more H+ back into serum)
-glaucoma (reduces rate of aqueous humor formation)
-acute mountain sickness (reduces CSF formation)

Front 4

toxicity of CAIs

Back 4

1) hyperchloremic metabolic acidosis (bc of the bicarb diuresis, there's more H that's building up intracellularly and moving back into the serum along with Cl)

2) kidney stones (calcium salts are insoluble at alkaline pH)

3) renal K wasting (Anytime you have diuresis and block Na proximally, this will increase Na load down stream and cause Na/K ATPases to be at work more, leading to more K secretion and possibly hypokalemia.)

4) drowsiness/paresthesias (with large doses)

Front 5

contraindication of carbonic anhydrase inhibitors

Back 5

pts with hepatic cirrhosis (can contribute to hyperammonia and hepatic encephalopathy)

Front 6

what is the class and mechanism of mannitol?

what are its uses?

Back 6

class = osmotic diuretics

mechanism =
1. prevent water reabsorption in nephron segments that are freely permeable to water (PT and desc limb of the loop of Henle)
2. oppose ADH action on CDs


SO OSMOTIC DIURETICS INCREASE URINE VOL (rarely used)

USES:
- increase urine volume
- reduce intracranial and intraocular pressure

Front 7

what are the toxicities of osmotic diuretics (like Mannitol)?

Back 7

-ECF volume expansion (bc mannitol extracts water from cells --> vol expansion/hyponatremia)
- chronically: dehydration and hypernatremia

Front 8

what is the class and mechanism of Furosemide?

what are it's effects (think about it!)

Back 8

class= loop diuretic

mechanism = inhibits Na/K/Cl co-transporter in thick asc limb of Henle

effects = induce NaCl diuresis, increase Mg and Ca excretion (by diminishing luminal positive potential), K wasting (from excessive Na diuresis and flow downstream to CT), induce renal prostaglandin synthesis (increasing renal blood flow/vasodilation)

Front 9

what are the clinical uses of loop diuretics?

Back 9

-Acute pulmonary edema (helps get rid of fluids)
-Edematous conditions: heart failure, hepatic cirrhosis, nephrotic syndrome
-Hypercalcemia
-Hyperkalemia
-SIADH
-Acute renal failure: Loop agents can increase the rate of urine flow and enhance K+ excretion

Front 10

how do loop diuretics (like furosemide) help SIADH?

Back 10

SIADH is a condition where there's too much ADH being produced...

In the loop of Henle, Na+ reabsorption without H2O leads to a concentrated medulla.

Kidney concentrating capacity depends on maintaining a hyperosmolar medulla and hence, urine concentrating ability.

Loop diuretics, by blocking Na+ reabsorption in the loop of Henle, block the responses to ADH.

Front 11

toxicities of loop diuretics

Back 11

-metabolic alkalosis (by increasing H excretion)
-hypokalemia (K+ depletion – heavy load of Na+ presented to the distal tubule)
-hypomagnesemia
-hyperuricemia (block uric acid secretion)
-ototoxicity (hearing loss)
-hypokalemic alkalosis

Front 12

class and mechanism of hydrochlorothiazide

what are its effects?

Back 12

class = thiazide diuretic

mechanism = inhibit Na-Cl cotransporter in distal convoluted tubule

effects= induce, NaCl diuresis, increase Ca reabsorption, K wasting

Front 13

clinical uses of thiazide diuretics

Back 13

-HTN
-HF
-nephrolithiasis due to hypercalciuria
-nephrogenic diabetes insipidus

Front 14

toxicities of thiazide diuretics

Back 14

-metabolic alkalosis
-hypokalemia
-hypercalcemia
-hyperglycemia (for pts with DM)
- hyponatremia (due to hypovolemia-induced elevation of ADH and increased thirst)

Front 15

use _______ to decrease urine volume in diabetes insipidus. but you can give ______ and _____ for nephrogenic DI.

Back 15

antidiuretics

thiazide diuretics; low Na diet

Front 16

how does thiazide diuretics help nephrogenic DI?

Back 16

nephrogenic DI is resistanct to ADH actions in the kidney; this causes rapid loss of H2O adn increase in osmolality (bc you can't reabsorb water anymore).

thiazide-induced Na losses will stimulate Na reabsorption in PT and decrease urine formation (bc the only other place where you can really pick up more water is in the PT, and this is a safe place bc ADH doesn't act on these aquaporins)

Front 17

what do potassium-sparing diuretics do?

Back 17

they inhibit the effects of aldosterone (in order to keep Na retention from occuring)...this will lead to increased Na excretion and increased urine volume as well

Front 18

what are the 2 types of potassium-sparing diuretics? provide examples of each.

Back 18

1) direct aldosterone inhibitor via antagonism of mineralcorticoid receptors (MR) = spironolactone

2) inhibit Na entry via ion channels in luminal membrane (ENaC) = amiloride

Front 19

what are the effects of K-sparing diuretics and how are they specifically different from thiazide diuretics in terms of potassium balance?

Back 19

effects: increase urine NaCl excretion, HYPERkalemia, metabolic acidosis

diff from thiazide diuretics in that they don't cause hypokalemia like thiazides do since they bypass the problem of K wasting.

K-sparing diuretics act on the final portion of the nephron in reabsoption of Na and so there's no worry about anything like K wasting downstream taking place.

Front 20

what are the clinical uses of K sparing diuretics (2)

Back 20

1. primary and secondary hyperaldosteronism
2. heart failure

Front 21

toxicities of K sparing diuretics

Back 21

- hyperkalemia
- hyperchloremic metabolic acidosis
- gynecomastia (spironolactone)
- kidney stone (triamterene)

Front 22

tell me about using loop diuretics and thiazides together = the good and bad?

Back 22

good = loop diuretics and thiazides (Combining a loop and a thiazide diuretic to “block” Na+ absorption at two nephron sites can increase Na+ losses.)

bad = K+ wasting (hypokalemia) is extremely common because these patients often have hyperaldostronism.

Front 23

Match diuretic to site of action:
1. furosemide
2. amiloride
3. hydrochlorothiazide
4. mannitol
5. acetazolamide

a. proximal nephron
b. loop of Henle
c. DCT
d. collecting duct

Back 23

1. b
2. d
3. c
4. a, d
5. a

Front 24

2. Why are the loop diuretics more “powerful” than other agents?

Back 24

The loop diuretics not only block TALH sodium, potassium, and chloride absorption, they also prevent the loop from concentrating the medullary interstitium. Thus water absorption in the collecting duct, under the influence of ADH, is also inhibited.

Front 25

3. Why do thiazide, loop, and carbonic anhydrase inhibitor diuretics cause hypokalemia?

Back 25

All of these diuretics increase the amount of sodium excretion. This has two effects: 1) it stimulates the renin-angiotensin-aldosterone and aldosterone is the major determinant of K+ excretion during diuretic therapy. 2) Reabsorption of sodium in the collecting duct stimulates potassium secretion into the tubule lumen by these cells. This occurs at the principal cell (remember the Na channel on the urine side of the principal cell?). Further, the volume of urine flowing through the collecting duct is increased, leading to more rapid elimination of the more electrically positive lumen. This expedites potassium losses.

Front 26

4. In general, how do potassium sparing diuretics work?

Back 26

There are two types of potassium sparing diuretics: 1) one type blocks the effects of aldosterone on principal cells; while 2) the other type blocks the sodium channel found on the luminal side of these cells. The net result is a loss of sodium absorption into the cell via the luminal sodium channel, and a decrease towards zero of the negative lumen voltage. Potassium secretion thus is decreased.

Front 27

5. Which diuretics cause renal calcium retention? Which diuretics cause the kidneys to loose calcium? What are the mechanisms?

Back 27

Calcium is primarily reabsorbed in the proximal tubule (follows sodium) and thick loop of Henle.

Loop diuretics prevent calcium absorption by the loop, and thus increase urinary calcium concentrations. This is offset in part by increased proximal calcium absorption if patient becomes volume depleted. However, if patient is not volume depleted, there will be a net loss of calcium in the urine. Thus, for hypercalcemic patients, both saline and loop diuretics are used in increase renal excretion of calcium.

Thiazide diuretics act on the cortical distal nephron where calcium is not absorbed. Thiazide diuretics do not directly change urinary calcium. Rather, thiazides cause volume depletion which results in increased proximal and loop calcium absorption from the tubule lumen. Thus thiazide diuretics will lower urinary calcium, and sometimes cause hypercalcemia.