Diuretics

Question 1

Define the following

a) natriuresis
b) kaliuresis
c) aquaretics

Answer 1

a) Increased sodium excretion
b) Increased K+ excretion
c) Substances that cause increased net excretion of water

Question 2

How does aldosterone increase the resorption of water and Na+?

Answer 2

Increases expression of Na/K ATPase, ENaC channels, and K+ channels

Question 3

What kinds of diuretics can you use on the PCT, LOH, DCT and CT?

Answer 3

PCT: carbonic anhydrase inhibitors, osmotic diuretics

LOH: loop diuretics; furosemide

DCT: Thiazide diuretics; metolazone

CT: Amiloride; blocks ENaC channels

Aldosterone antagonists

Question 4

Give an example of a carbonic anhydrase inhibitor and their mechanism of action

Answer 4

Acetazolamide:

No H+ and HCO3 produced - no H+ into filtrate and HCO3 into blood

Question 5

What is one consequence of carbonic anhydrase inhibitors?

Answer 5

Reduced amount of bicarbonate production

-> metabolic acidosis

Question 6

What do osmotic diuretics do and name one example

Answer 6

Mannitol:

Increases plasma osmolarity by drawing fluid out of tissues/cells -> solutes filtered at glomerulus but not reabsorbed -> ions lost in the urine

Question 7

How does a loop diuretic impact other ions? What is the mechanism of loop diuretics?

Answer 7

Inhibits Na/K/2Cl cotransporter on luminal LOH:

Less K+ in filtrate (ROMK) - filtrate more -ve -> ca2+ and Mg2+ less likely to leave filtrate -> more water/solutes are excreted

Question 8

What is the mechanism of thiazide diuretics? What are two consequences?

Answer 8

Targets luminal NCC channels: Na+, Cl- and water stay in filtrate

Basolateral Na+/Ca2+ exchanger: pumps more Na+ into cell and reabsorbs more Ca2+ = hypercalcemia

Less Cl- reabsorption means less K+ follows = hypokalemia

Question 9

Describe the mechanism of action of aldosterone antagonists and K+ sparing diuretics do.

Are they potent? Name one example of an aldosterone antagonist

Answer 9

Mild diuretics:

Aldosterone antagonists, i.e spironolactone: Less Na reabsorption -> less NA/K ATPase action on basolateral

K+ sparing diuretics, i.e amiloride: decrease ENac channels

=hyperkalemia for both!

Question 10

Why would diuretics be used in congestive heart failure? Which diuretics would you prescribe?

Answer 10

High systemic venous pressure leads to edema, hypotension activates RAAS -> more retention of Na+ and water - need diuretic to reduce extra volume

1st choice: LOOP diuretics
Thiazide diuretics used alongside

Question 11

What is the primary goal of diuretics other than losing more fluid?

Answer 11

Symptomatic relief

Question 12

What happens in nephrotic syndrome and which diuretics should you use?

Answer 12

Hydrostatic>oncotic

1. protein in the urine (gets pushed out)
2. edema
3. Lower circulating volume: Reduced CO
4. RAAS:
   Loop diuretics with thiazide diuretics

Question 13

Why do you need diuretics in liver cirrhosis?

Answer 13

Less albumin produced - reduces oncotic pressure

Hydrostatic>oncotic

Question 14

Two clinical scenarios where you might use spironolactone (aldosterone inhibitor)

Answer 14

Portal hypertension:
*increased venous pressure -> ascites -> reduced CO and worsening RAAS

Primary aldosteronism/Conn’s syndrome

Question 15

What comprises the splanchnic circulation?

Answer 15

GI circulation, superior and inferior mesenteric artery

Question 16

When would you prescribe mannitol?

Answer 16

Cerebral edema

Question 17

Which diuretic works best for glaucoma? Why?

Answer 17

Carbonic anhydrase inhibitors, (decrease intraocular pressure)

Question 18

Which diuretics can lead to hypokalemia?

Answer 18

Thiazide diuretics: Less cl- being resorbed means K+ unlikely to follow

LOOP: Inhibiting Na/K/Cl- cotransporter means K+ stays in the filtrate

Question 19

Which diuretic can lead to hypovolemia? How would you monitor this?

Answer 19

LOOP diuretics are most potent and can therefore lead to excessive water and ion loss,

*monitor weight, BP, postural drop

Question 20

Which diuretic can give you erectile dysfunction?

Answer 20

Thiazide diuretics

Question 21

Explain how alcohol and coffee can have a diuretic effect

Answer 21

Alcohol: inhibits ADH

Coffee: Increases GFR and lowers Na+ resorption

Question 22

How can diuretics lead to gout?

Answer 22

Diuretics concentrate blood, (can crystallize solutes and increase the concentration of uric acid)

Question 23

What’s the difference between diabetes insipidus and Mellitus? How do they have a diuretic effect?

Answer 23

Mellitus: insulin intolerance or deficiency -> glucose in filtrate (draws water in)

Insipidus: decreased production of ADH (retain less water/ions and pee more)

Question 24

What are the two types of diabetes insipidus?

Answer 24

Cranial: reduced ADH secretion from posterior pituitary

Nephrogenic: CTs have a poor response to ADH (aquaporins)

Question 25

Which diuretics can lead to hyperkalemia?

Answer 25

Aldosterone antagonists and K+ sparing diuretics, as both increase Na+ excretion and K+ resorption

Question 26

Which part of the kidney is most targeted by aldosterone antagonists

Answer 26

Principal cells in DCT and CT