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 and aldosterone antagonists (since aldosterone increases the expression of all channels that could increase BP)

Question 4

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

Answer 4

Acetazolamide:

1. If you can’t create carbonic acid, no H+ and HCO3 gets produced.
2. no H+ means the Na/H exchanger is unable to pump Na+ into the cell, so more stays in the filtrate
3. No HCO3- created means less HCO3- goes back into the blood

Question 5

What is one consequence of carbonic anhydrase inhibitors?

Answer 5

The reduced amount of bicarbonate production can mean the body will go into metabolic acidosis

Question 6

What do osmotic diuretics do and name one example

Answer 6

Mannitol:
Increase plasma osmolarity by drawing fluid out from tissues and cells. Solutes are filtered at the glomerulus but not resorbed - more ions are lost in the urine

Question 7

What is the mechanism of loop diuretics?

Answer 7

Inhibits the Na/K/2Cl transporter on the luminal membrane in the LOH:

1. Less resorption of Na+ and Cl-
2. The Na/K ATPase on the basolateral membrane pumps less Na into the blood, and less K+ back into the cell
3. Fewer K+ in the cell means the ROMK channel is unable to transport K+ into the filtrate, this means the filtrate remains more negative and Ca2+ and Mg2+ are less likely to leave by slipping through the cell and epithelium and resorb into the bloodstream. Rather they stay in the filtrate

Overall: more water and solutes are excreted

Question 8

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

Answer 8

Unlike in LOH, Na+ resorption reduces Ca2+ resorption:

1. Since the Na+/Cl- transporter is blocked, there’s Na+ and water loss. BUT since thiazide diuretics are less potent than loop diuretics, only 5% of Na+ resorption is inhibited
2. Less Na+ being resorbed into the cell means the Na/K ATPase on the basolateral membrane will resorb less into the blood
3. Now that there’s less Na+ in the blood, the Na+/Ca2+ exchanger is unable to pump Na+ back into the cell and resorb Ca2+ = less calcium resorption

Less Cl- being resorbed means K+ is less likely to follow, so thiazide diuretics can also lead to hypokalemia

Question 9

What do aldosterone antagonists and K+ sparing diuretics do? Are they potent?

Name one example of an aldosterone antagonist

Answer 9

Both are mild diuretics, only affecting 2% of Na+ resorption. Aldosterone antagonists means less Na+ is resorbed and fewer K+ is excreted, and K+ sparing diuretics (such as amiloride) decrease action of ENac channels. Therefore, the Na/K ATPase is unable to resorb Na+ and pump K+ into the cell, so more K+ is retained in the body.

Normally aldosterone acts on principal cells in DCT and CT to increase expression of ENac, Na/K ATPase and K+ channels. Antagonists inhibit the aldosterone receptor, to prevent resorption of ions. E.g; spironolactone

Question 10

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

Answer 10

You have a high systemic venous pressure which can lead to edema. Since there’s less fluid in circulation, there’s a drop-in CO: this activates the RAAS system which only leads to more retention of Na+ and water - need a diuretic to reduce the 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 and should be used alongside another therapy for full treatment

Question 12

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

Answer 12

The hydrostatic pressure overwhelms the oncotic pressure: leading to

1. protein in the urine
2. edema
3. Lower circulating volume: Reduced CO
4. RAAS: more retention of fluid - worsening hydrostatic pressure

Use loop diuretics with thiazide diuretics

Question 13

Why do you need diuretics in liver cirrhosis?

Answer 13

Less albumin produced by the liver means a reduced oncotic pressure. Therefore hydrostatic pressure&raquo_space; oncotic pressure, and this follows the same pathology as nephrotic syndrome

Question 14

What is portal hypertension?

Which diuretic would you prescribe?

Answer 14

Increased venous pressure in the splanchnic circulation can lead to ascites: fluid buildup in the abdomen, reduced CO, RAAS and worsening ECF volume and edema

Spironolactone

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, since they decrease fluid this can reduce the interocular pressure in the eye and help treat glaucoma

Question 18

Which diuretics can lead to hypokalemia?

Answer 18

Thiazide diuretics: Less cl- being resorbed means K+ is 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 the most potent and can therefore lead to excessive water and ion loss, managed by monitoring weight, BP and 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 anti-diuretic hormone release, so less water and ions are resorbed into the body

Coffee: Increases the GFR and lowers Na+ resorption

Question 22

How can diuretics lead to gout?

Answer 22

Diuretics concentrate the blood, this can make solutes crystallize 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: caused by insulin intolerance or deficiency. Leads to glucose in the filtrate which draws water into the filtrate

Insipidus: caused by decreased production of ADH: means you retain less water/ions and pee more

Question 24

What are the two types of diabetes insipidus?

Answer 24

Cranial: lowers ADH release from the posterior pituitary
Nephrogenic: Collecting ducts have a poor response to ADH

Question 25

Which diuretics can lead to hyperkalemia?

Answer 25

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