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Define diuresis

Increased formation of urine by the kidney

1

Define diuretic

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

2

What are the four main ways diuretics work?

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

3

Briefly, what does aldosterone do?

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

4

Give an example of a loop diuretic

Furosemide
Bumetanide

5

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

25%

6

What normally happens in the thick ascending limb?

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

7

How do loop diuretics work?

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

8

What are loop diuretics used for?

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

9

Where is the site of action of thiazide diuretics?

Distal convoluted tubule

10

Give an example of a thiazide diuretic

Bendroflumethiazide
Metolazone

11

What normally happens in the distal convoluted tubule?

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

12

What is the action of thiazide diuretics?

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)

13

What are thiazide diuretics useful for treating?

Hypertension (causes vasodilation, not understood how)

14

Side effects of thiazide diuretics?

Hypokalaemia
Hypercalcaemia

15

Example of a potassium sparing diuretic?

Amiloride

16

Site of action of potassium soaring diuretics?

Collecting duct (principal cells)

17

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

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

18

Action of potassium sparing diuretics?

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

19

Action of aldosterone antagonists?

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

20

Example of an aldosterone antagonist?

Spironolactone

21

Use of aldosterone antagonists?

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

22

What is Conn's syndrome?

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

23

Uses of K+ sparing diuretics?

Often used with other diuretics eg thiazide to reduce hypokalaemia

24

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

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

25

What does carbonic anhydrase do?

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

26

Action of carbonic anhydrase inhibitors?

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

27

What can carbonic anhydrase inhibitors be useful to treat?

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

28

Side effects of carbonic anhydrase inhibitors?

Metabolic acidosis because HCO3 is lost in the urine

29

How do osmotic diuretics work?

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+

30

Name an osmotic diuretic

Mannitol

31

What can osmotic diuretics be used to treat?

Cerebral oedema
(IV mannitol)

32

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

-drop in cardiac output
-RAAS activation
-Na and H2O retention
-expansion of ECF and oedema

-increase in systemic venous pressure
-oedema

33

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

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

34

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

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

35

Which diuretics can cause hyperkalaemia?

Loop diuretics
Thiazide diuretics

36

Which diuretics can be used to treat hypokalaemia?

K+ sparing diuretics
Aldosterone antagonists

37

How do loop diuretics and thiazide diuretics cause hypokalaemia?

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

38

In what other way do diuretics contribute to hypokalaemia?

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

39

What is hepatic encephalopathy?

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

40

What diseases can cause diuresis?

Diabetes mellitus
Diabetes insipidus (cranial or nephrogenic)
Psychogenic polydipsia

41

What is the difference between cranial and nephrogenic diabetes insipidus?

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

Both lead to diuresis

42

What are some adverse effects of diuretics?

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

43

What does alcohol affect to cause a diuretic effect?

Inhibits ADH release

44

What does coffee do?

Increases GFR
Decreases tubular Na+ reabsorption