Diuretics

Question 1

What is diuresis?

Answer 1

Increased formation of urine by the kidney

Question 2

How do diuretics generally act?

Answer 2

By blocking reabsorption of sodium and water by the tubule, blocking the action of aldosterone, modifying filtrate content or inhibiting the activity of carbonic anhydrase

Question 3

What channel pumps Na+ out across the basolateral membrane of the tubule?

Answer 3

Na-K-ATPase

Question 4

True or False:

Na+ moves across the apical membrane of tubules against its concentration gradient

Answer 4

False

Moves down its concentration gradient - set up by Na/K pump on basolateral membrane that pumps sodium out of the cell - therefore tubular cell concentration of sodium is low

Question 5

True or False:

The Na/K pump on the basolateral membrane is common to all segments of the tubule

Answer 5

True

Question 6

What sodium channels are present in the apical membrane of the proximal tubule?

Answer 6

Na-H antiporter
Na-Glucose
Na-AA etc

Question 7

What sodium channels are present in the apical membrane of the loop of henle?

Answer 7

NKCC (Na K 2 Cl)

Question 8

What sodium channels are present in the apical membrane of the early distal tubule?

Answer 8

NaCl symporter

Question 9

What sodium channels are present in the apical membrane of the late distal tubule and collecting duct?

Answer 9

ENaC

Question 10

What do diuretics reducing ENaC activity also reduce?

Answer 10

K+ secretion

Question 11

In which part of the kidney is there a net secretion of K+?

Answer 11

Principal cells in late DT and CD

K+ brought into cell on the basolateral membrane via Na/K pump and leaves via a K+ channel on the apical membrane

Question 12

Does Na+ absorption favour K+ excretion in the principal cells?

Answer 12

Yes

Question 13

Where do loop diuretics act?

Answer 13

Loop of henle

Question 14

What do loop diuretics block?

Answer 14

NaKCC

Question 15

Where do thiazide diuretics act?

Answer 15

Early DT

Question 16

What do thiazide diuretics block?

Answer 16

Na-Cl cotransporter

Question 17

What do K+ sparing diuretics act on?

Answer 17

Late DT and CD

Block ENaC

Question 18

How does aldosterone act on principal cells of the late DT and CD?

Answer 18

Increases Na+ reabsorption via ENaC

Question 19

How do aldosterone antagonists decrease Na reabsorption?

Answer 19

Competitive inhibition of aldosterone receptor - so aldosterone cannot increase reabsorption

Question 20

How do osmotic diuretics work?

Answer 20

Increase osmolarity of filtrate - reduce water and Na+ reabsorption throughout the tubule

Question 21

What are some examples of loop diuretics?

Answer 21

Furosemide, bumetanide

Question 22

What is used in acute pulmonary oedema?

Answer 22

IV Furosemide (loop diuretic)

Question 23

Why are loop diuretics used in heart failure?

Answer 23

For treatment of symptoms (breathlessness, oedema)

• Diuretic effect
• Vaso and venodilation

Question 24

When are loop diuretics used to treat fluid retention and oedema?

Answer 24

In nephrotic syndrome, renal failure, cirrhosis of liveer

Question 25

Why are loop diuretics useful in treatment of hypercalcaemia?

Answer 25

Impairs calcium absorption in loop of henle, increases urinary excretion of calcium

Question 26

What effect does thiazide diuretics have calcium absorption?

Answer 26

Increases Ca2+ absorption - reduces Ca2+ loss in urine

Question 27

What is an example of a thiazide diuretic?

Answer 27

Bendroflumethiazide

Question 28

True or False: Aldosterone antagonists are shown to reduce mortality in HF

Answer 28

True Used in lon term tretment of HF (non diuretic effect)

Question 29

What is the preferred drug for ascites and oedema in cirrhosis?

Answer 29

Aldosterone antagonists (eg spironolactone)

Question 30

What is used to treat hypertension due to primary hyperaldosteronism (Conns syndrome)?

Answer 30

Aldosterone antagonist - spironolactone | Adrenal hyperplasia/tumour -> causes increased secretion of aldosterone -> hypertension

Question 31

What does amiloride block?

Answer 31

ENaC

Question 32

Why are ENaC blockers usually used in combination with loop or thiazide diuretics?

Answer 32

ENaC blockers have a K+ sparing effect | Used to minimise K+ loss

Question 33

What does the rate of K+ secretion in the DT and CD depend on?

Answer 33

Concentration gradien across apical membrane and rate of sodium abdorption (inward movement of Na+ creates a favourable lumen negative potential for K+ secretion)

Question 34

How can loop and thiazide diuretics lead to hypokalaemia?

Answer 34

Block Na+ reabsorption in LoH or early DT Increased Na absorption by principal cells Favourable electrical gradient for K+ excretion More K+ loss in urine leading to hypokalaemia

Question 35

Which diuretics are K+ sparing?

Answer 35

ENaC blockers and aldoserone antagonists

Question 36

Why should spironolactone not be used along with K+ supplements?

Answer 36

Increased risk of hyperkalaemia as spironalactone is an aldosterone antagonist which is K+ sparing

Question 37

How can glomerular disease lead to oedema?

Answer 37

Increase in GBM permeability to protein - proteins filtered and lost in urine Causes low plasma albumin, resulting in a low plasma oncotic pressure -> peripheral oedema Reduced circulatory volume -> RAAS activates

Question 38

What conditions are diuretics used in?

Answer 38

Conditions with ECF expansion and oedema (Congestive HF, nephrotic syndrome, cirrhosis, kidney failure) Acute pulmonary oedema HF Hypertension

Question 39

What are some adverse effects of diuretics?

Answer 39

``` Potassium abnormalities Hypovolaemia Hyponatraemia Increased uric acid levels -> gout attacks Erectile dysfunction (thiazides) Gynaecomastia (spironolactone) ```

Question 40

What is an example of a carbonic anhydrase inhibitor?

Answer 40

Acetazolamide

Question 41

Where do carbonic anhydrase inhibitors act?

Answer 41

Proximal tubule - inhibits action of carbonic anhydrase in brush border + PCT cell

Question 42

What is an example of an osmotic diuretic?

Answer 42

Mannitol

Question 43

What is IV mannitol used to treat?

Answer 43

Cerebral oedema

Question 44

What are some diseases that cause diuresis?

Answer 44

Diabetes mellitus Diabetes insipidus Psychogenic polydipsia

Question 45

What are the two types of diabetes insipidus?

Answer 45

Cranial - decreased ADH release from post pituitary | Nephrogenic - poor response of CD to ADH