Diuretics

Question 1

What is a diuretics?

Answer 1

Substance that promotes the increased formation of urine

By increased renal excretion of water and Na = increased fractional excretion >1% = reduced ECF volume

Question 2

What is a diuretics main mechanism of action?

Answer 2

Block reabsorption of Na/water by the tubule

1) direct blocking of Na transporters
2) antagonising action of aldosterone
3) modification of filtrate content by osmotic diuretics
4) inhibiting carbonic anhydrase in PCT

Question 3

What is Na reabsorption driven by?

Answer 3

Na/K ATPase pump on basolateral membrane = gradient created

Na across apical (luminal) mem by transporters, down conc gradient

Water moves down osmotic gradient created by Na reabsorption

Question 4

Where are Na/K ATPase found in the tubule

Answer 4

All segments

Question 5

What unique pumps are present in the proximal tubule?

Answer 5

Na-H antiporter

Na-Glucose symporters

Na-AA

Question 6

What unique pump is present in the loop on henle?

Answer 6

Na-K 2Cl symporter

Question 7

What unique pumps are present in the early DT?

Answer 7

Na-Cl symporter

Question 8

What unique pumps are present in the late DT and CD?

Answer 8

ENaC

Question 9

What is the function of aldosterone on the kidney?

Answer 9

Increased expression of NA/K ATPase, ENAC and K channels

= more Na reabsorption = increased ECF volume

Question 10

Outline the role of the principle cell in the late DT and CD

Answer 10

Enables tubular reabsorption of Na via ENaC

Question 11

Explain how the hypertonicity of the medulla is created and how this effects water movement

Answer 11

25% Na absorbed via Na/-K-Cl in LoH = hypertonicity in medulla

In late DT and CD, ADH allows water to move from hypotonic tubular fluid into hypertonic medulla

Question 12

Discuss loop diuretics

Answer 12

Act on thick ascending limb - LoH

Block Na/K-2CL cotransporter = Na/Cl not reabsorbed = medullary tonicity less = less water reabsorption further down the tubule

K via K channels back into lumen = +ve potential = drive absorption of Ca2+ and Mg2+

Very potent

Used in heart failure = breathlessness, oedema, vaso/venodilatation reduces after/preload

E.g. Furosemide

Hypokalaemia

Question 13

Describe thiazide diuretics

Answer 13

Act on early DT

Block Na/Cl cotransporter = increases Na loss in urine

Reduces Ca2+ loss in urine

Less potent than loop diuretics

Used in hypertension = vasodilation

E.g. Bendroflumethiazide

Hypokalaemia

Question 14

Describe K sparing diuretics: ENaC

Answer 14

Act on DCT and CD

Block ENaC = also reduces K secretion

Mild diuretic

E.g. Amiloride

Hyperkalaemia

Question 15

Discuss K sparing diuretics: aldosterone antagonists

Answer 15

Competitive inhibition of aldosterone receptor

Reduces expression of Na-K ATPase, ENaC, K channels in principle cells

Decreased Na reabsorption = reduced K secretion

Mild diuretic

Used in heart failure, ascites, cirrhotic oedema, hypertension, hyperaldosteronism

E.g. Spironolactone

Hyperkalaemia

Question 16

Explain the term ‘K sparing effects’

Answer 16

Na reabsorption is linked to K excretion = Na reabsorption creates -ve potential in lumen which favours secretion of K through K channels, blockage of Na channels also reduces K secretion

Question 17

When a pt is on a diuretic, monitoring what is vital?

Answer 17

K+ levels

Question 18

What is nephrotic syndrome?

Answer 18

Nephrotic disease = increase in glomerular basement membrane permeability to protein = proteinuria = low plasma albumin = low plasma oncotic pressure = peripheral oedema

Reduced circulatory vol = RAAS activated = Na/water retention = expansion of ECF = more oedema

Question 19

How does cirrhosis of the liver cause ascites and peripheral oedema?

Answer 19

Damage = fibrous tissue = decreased albumin production = reduced oncotic pressure = peripheral oedema

Portal hypertension = increased venous pressure in GI circulation = transudate moves to peritoneal cavity = ascites

Both = RAAS activation = further expansion of ECF

Question 20

What diuretic is used to treat cirrhosis and ascites?

Answer 20

Spironolactone = K sparing effects

Hypokalaemia exacerbates symptoms of liver failure

Question 21

Outline the possible adverse effects from using diuretics

Answer 21

Potassium abnormalities

Hypovolaemia

Hyponatraemia

Increased uric acid levels in the blood = can precipitate attack of gout