Diuretics

Question 0

Define diuretic

Answer 0

Substance or drug that promotes a diuresis by increased renal excretion of water and sodium to decrease extra cellular fluid volume

Question 1

Define diuresis

Answer 1

Increased formation of urine by the kidney

Question 2

What are the four main ways diuretics work?

Answer 2

Direct action on cells to block sodium transporters on the luminal membrane of the nephron
Antagonise action of aldosterone
Modify filtrate content
Inhibit carbonic anhydrase

Question 3

Briefly, what does aldosterone do?

Answer 3

Acts on principal cells of the late DT and CD to increase expression of epithelial Na channels (ENaC)

Question 4

Give an example of a loop diuretic

Answer 4

Furosemide

Bumetanide

Question 5

What percentage of sodium is reabsorbed in the thick ascending limb?

Answer 5

25%

Question 6

What normally happens in the thick ascending limb?

Answer 6

Na-K-2Cl does reabsorption
K+ drifts back into lumen -> positive lumen potential
Drives paracellular absorption of Ca2+ and Mg2+

Question 7

How do loop diuretics work?

Answer 7

Secreted into PCT
Travel downstream to thick ascending limb
Block Na-K-2Cl transporter
Blocks ability to reabsorb sodium, potassium and chloride, and also calcium and magnesium
Segments downstream have limited capacity to reabsorb flood of Na+ and water

Question 8

What are loop diuretics used for?

Answer 8

Heart failure due to vaso/venodilatation effect
Kidney failure
Acute pulmonary oedema caused by left heart failure
Hypercalcaemia
Fluid retention and oedema due to nephrotic syndrome or kidney failure

Question 9

Where is the site of action of thiazide diuretics?

Answer 9

Distal convoluted tubule

Question 10

Give an example of a thiazide diuretic

Answer 10

Bendroflumethiazide

Metolazone

Question 11

What normally happens in the distal convoluted tubule?

Answer 11

Sodium-chloride transporter reabsorbs sodium and chloride
Calcium is reabsorbed and transported across basolateral membrane via NCX
3Na-2K-ATPase drives the whole thing

Question 12

What is the action of thiazide diuretics?

Answer 12

Block the Na-Cl transporter in the DCT
Increases Na and water loss in urine
Increases calcium reabsorption (because there is a greater sodium gradient for NCX on basolat. because Na-Cl no longer working)

Question 13

What are thiazide diuretics useful for treating?

Answer 13

Hypertension (causes vasodilation, not understood how)

Question 14

Side effects of thiazide diuretics?

Answer 14

Hypokalaemia

Hypercalcaemia

Question 15

Example of a potassium sparing diuretic?

Answer 15

Amiloride

Question 16

Site of action of potassium soaring diuretics?

Answer 16

Collecting duct (principal cells)

Question 17

What normally happens in the principal cells of the collecting duct?

Answer 17

Na+ reabsorbed via ENaC, takes water with it
Driven by Na-K-ATPase
K+ into cell via Na-K-ATPase on basolateral and secreted into lumen

Question 18

Action of potassium sparing diuretics?

Answer 18

Directly block the ENaC in principal cells
Na no longer reabsorbed
Less of a gradient for Na-K-ATPase so less potassium is secreted

Question 19

Action of aldosterone antagonists?

Answer 19

Block the action of aldosterone
Aldosterone normally increases expression of ENaC on apical membrane of principal cells
Less sodium reabsorption and less potassium secretion

Question 20

Example of an aldosterone antagonist?

Answer 20

Spironolactone

Question 21

Use of aldosterone antagonists?

Answer 21

Treat hypertension due to primary aldosteronism
Ascites and oedema in cirrhosis
In addition to loop diuretics in heart failure

Question 22

What is Conn’s syndrome?

Answer 22

Adrenal hyperplasia or a tumour leading to increased aldosterone secretion. Causes hypertension

Question 23

Uses of K+ sparing diuretics?

Answer 23

Often used with other diuretics eg thiazide to reduce hypokalaemia

Question 24

When should K+ sparing diuretics and aldosterone antagonists not be used?

Answer 24

If patient is on ACE-inhibitors or K+ supplements | Patients with renal impairment

Question 25

What does carbonic anhydrase do?

Answer 25

Does the reaction HCO3- + H+ -> H2O + CO2 H2O and CO2 then absorbed into PCT cell and goes back to HCO3- by action of carbonic anhydrase HCO3- can then be absorbed into the blood

Question 26

Action of carbonic anhydrase inhibitors?

Answer 26

Inhibit carbonic anhydrase in the brush border and in PCT cells Prevents reabsorption of HCO3

Question 27

What can carbonic anhydrase inhibitors be useful to treat?

Answer 27

Glaucoma | Reduces formation of aqueous humour of the eye by 50%

Question 28

Side effects of carbonic anhydrase inhibitors?

Answer 28

Metabolic acidosis because HCO3 is lost in the urine

Question 29

How do osmotic diuretics work?

Answer 29

Small inert molecules which increase the plasma osmolarity Causes fluid to be drawn out from rises and cells They are freely filtered in the glomerulus but not reabsorbed to increase osmolarity of filtrate Cause loss of H2O, Na+ and K+

Question 30

Name an osmotic diuretic

Answer 30

Mannitol

Question 31

What can osmotic diuretics be used to treat?

Answer 31

Cerebral oedema | IV mannitol

Question 32

How does congestive heart failure lead to an expansion of ECF and oedema?

Answer 32

- drop in cardiac output - RAAS activation - Na and H2O retention - expansion of ECF and oedema - increase in systemic venous pressure - oedema

Question 33

How does nephrotic syndrome lead to an increase in ECF expansion?

Answer 33

- protein loss in urine - decreased plasma albumin - decreased oncotic pressure - oedema - reduced circulatory volume - RAAS activation - Na+ and H2O retention - expansion of ECF - oedema

Question 34

How does cirrhosis of the liver lead to expansion of the ECF?

Answer 34

- decreased albumin production - decreased plasma albumin - decreased oncotic pressure - oedema - reduced circulatory volume - RAAS activation - Na and H2O retention - expansion of ECF - oedema

Question 35

Which diuretics can cause hyperkalaemia?

Answer 35

Loop diuretics | Thiazide diuretics

Question 36

Which diuretics can be used to treat hypokalaemia?

Answer 36

K+ sparing diuretics | Aldosterone antagonists

Question 37

How do loop diuretics and thiazide diuretics cause hypokalaemia?

Answer 37

Block Na+ and H2O reabsorption in PCT Increased Na+ and H2O to late DT and CD Increased sodium absorption by principal cells Favourable electrical gradient for K+ excretion Faster flow rate in lumen so K+ excreted is washed away faster More K+ lost in urine

Question 38

In what other way do diuretics contribute to hypokalaemia?

Answer 38

Diuretics reduce ECF volume Activation of RAAS Aldosterone increases Na+ reabsorption and K+ excretion Hypokalaemia

Question 39

What is hepatic encephalopathy?

Answer 39

A reversible syndrome of impaired brain function which occurs in cirrhosis with advanced liver failure Caused by elevated ammonia in the blood

Question 40

What diseases can cause diuresis?

Answer 40

Diabetes mellitus Diabetes insipidus (cranial or nephrogenic) Psychogenic polydipsia

Question 41

What is the difference between cranial and nephrogenic diabetes insipidus?

Answer 41

Cranial - less ADH released from posterior pituitary Nephrogenic - poor response of collecting ducts to ADH Both lead to diuresis

Question 42

What are some adverse effects of diuretics?

Answer 42

``` Potassium abnormalities Hypovolaemia Hyponatraemia Increased uric acid in blood leading to gout (loop and thiazide) Metabolic effects (loop and thiazide) -glucose intolerance -raised LDLs Thiazides can cause erectile dysfunction ```

Question 43

What does alcohol affect to cause a diuretic effect?

Answer 43

Inhibits ADH release

Question 44

What does coffee do?

Answer 44

Increases GFR | Decreases tubular Na+ reabsorption