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Urinary > Diuretics > Flashcards

Diuretics Flashcards

1
Q

What is a diuretic?

A

A substance/drug that promotes a diuresis

By increasing the renal excretion of water AND sodium, thereby resulting in a reduction of the ECF volume

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2
Q

What is diuresis?

A

Increased formation of urine by the kidney

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3
Q

Give some examples of conditions where diuretics would be clinically useful?

A

Heart failure
Cirrhosis
Nephrotic syndrome

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4
Q

How do Diuretics work?

A

Act by blocking reabsorption of sodium and water by the tubule

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5
Q

What is the normal fraction of excretion of Na?

A

usually <1%

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6
Q

What effect do diuretics have on the Fraction Excretion of Na? (usually <1%)?

A

They increase the FE of Na

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7
Q

Briefly describe the tubular reabsorption of Na.

A
  • Na+ is pumped out of the cell across the basolateral membrane by Na+K+ATPase
  • Na+ then moves across the apical membrane down its concentration gradient
  • this movement of Na utilizes a membrane transporter or channel on the apical membrane
    (water moves down conc. gradient created by transport of Na)
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8
Q

Where are the Na+K+ATPpase transporters found?

A

On the basolateral membrane. Common to all segments of the tubule.

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9
Q

What Na+ transporters are present on the apical membrane of the PCT?

A

Na-H antiporter

Also symporters Na-Glucose, Na-AA etc

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10
Q

What Na+ transporters are present on the apical membrane in the loop of henle?

A

Na-K-2Cl symporter

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11
Q

What Na transporters are present on the apical membrane of the early part of the DCT?

A

Na-Cl symporter

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12
Q

What Na+ transporters are available in the later DT and the CD? (principle cells))

A

ENaC (Epithelial Na Channels)

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13
Q

Where in the tubule are principle cells located and what Na+ channel is present on the apical membrane?

A

Late part of the DT and the CD

ENaC

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14
Q

What is the mechanism of Na+ reabsorption and K+ secretion in the principle cells of the late DT and the CD?

A
  • Na+-K+-ATPase in basolateral membrane pump out Na+
  • Na+ enters the cell via ENaC
  • Na+ reabsorption favours K+ secretion by creating a lumen negative potential
  • K+ secreted through K+ channels (down electrochemical gradient)
  • Aldosterone increases expression of Na_K-ATPase, ENaC and K+ channels
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15
Q

What do diuretics block in the pirnciple cells in the late DT and the CD?

A

ENaC

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16
Q

What affect on K+ secretion does blocking ENaC have on K+ secretion?
Why?

A

Reduces K+ secretion

Reabsroption of Na+ into the cell across the apical membrane via ENaC results in secretion of K+ down as it creates a negative potential in the lumen. Blocking of ENaC reduces the Na+ reabsorption and therefore doesnt promote the secretion of K+

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17
Q

What diuretics act on the proximal tubule?

A 
Cabonic anhydrase inhibitors (Acetazolamide)
Osmotic diuretics (also act at other sites of water absorption) (Mannitol)
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18
Q

What diuretics act on the Loop of Henle?

A

Loop diuretics (Furosemide, Bumetanide)

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19
Q

What diuretics act in the DCT?

A

Thiazide diuretics, metalozone, indapamide, others

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20
Q

What diuretics act in the Collecting Duct?

A

Potassium sparing diuretics (ENaC blockers: Amiloride

Aldosterone antagonists: Spironolactone

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21
Q

Where in the kidney do loop diuretics act?

Examples include?

A

Loop of Henle

Furosemide and Bumetanide

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22
Q

Where in the kideny do Thiazide diuretics act?

A

DCT

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23
Q

Where in the kideny does amiloride act?

What type of diuretic is it?

A

CD

Potassium Sparing Diuretic

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24
Q

What Na+ channel does Amiloride act on?

What type of diuretic is it?

A

ENaC

Potassium sparing diuretics

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25
Q

Where do aldosterone antagonists act?

Example includes?

A

CD

Spiranolactone

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26
Q

Where does Spironolactone act?

A

CD

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27
Q

What transporter do Thiazide Diuretics affect?

A

Inhibit Na-Cl co-transporter In the Early DT

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28
Q

What Na+ channels do Loop diuretics inhibit?

A

Na+-K+-2Cl co-transporter in the Loop of Henle

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29
Q

What Na+ channels do K= Sparing Diuretics act on?

A

Inhibit ENaC in the late DT and CD

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30
Q

What are the four mechanisms by which diuretics work?

A

1) By direct action on cells to block Na+ transporters on the apical membrane (luminal membrane)
2) By antagonising the action of aldosterone
3) By modification of filtrate content- osmotic diuretics
4) By inhibiting activity of enzyme Carbonic anhydrase

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31
Q

Where does Aldosterone act?

A

On the principal cells of the Late DT and CD to increase reabsorption via ENaC

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32
Q

What do Aldosterone antagonists do?

A

Competitive inhibition of aldosterone receptor on the principal cells in the late DT and CD resulting in decreased Na+ reabsorption

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33
Q

How do osmotic Diuretics work?

Tip: Modification of filtrate

A

Small molecules freely filtered at glomerulus but not reabsorbed, this increases osmolarity of filtrate reducing water and Na+ reabsorption throughout the tubule

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34
Q

What does Acetazolamide do?

Tip: Acts in PCT

A

Inhibits Carbonic Anhydrase in PCT
increase excretion of bicarbonate with accompanying Na+, K+ ions and water, resulting in an increased flow
of an alkaline urine and metabolic acidosis.

35
Q

Carbonic anhydrase inhibitor Acetazolamide is no longer used as a diuretic, what is is tcommonly used to treat?

A

Glaucoma- to reduce aqueous humour

Infantile epilepsy

36
Q

Why is the diuretic effect of carbonic anhydrase self limiting?

A

The urinary loss of bicarbonate depletes extracellular HCO3-, the diuretic effect of carbonic anhydrase is therefore self limiting

37
Q

What % of Na+ is reabsorbed in the Loop of Henle?

A

25%

Na-K-2Cl transporter

38
Q

Why does the lumen have a positive potential comapred to the blood in the loop of henle?

A

The K+ move back into the lumen via the K+channels (electrochemical gradient created by movement of Na+ into the cell and the NA+-K+ATPase continuously provind the cell with K+)

39
Q

What helps to drive the reabsorption of positively charged ions Ca2+ and Mg2+ in the loop of henle?

A

The positively charged lumen (created by K+)

40
Q

Which diuretics are considered the most potent?

A

Loop Diuretics

41
Q

Where are loop diuretics secreted into the lumen?

A

in the PCT (via the organic anion pathway)

Travel downstream to act of the loop of henle

42
Q

What clinical condition are loop diuretics often used in?

A

Heart failure
Fluid retention and oedema in:
- Nephrotic syndrome
- Renal failure
- Cirrhosis of liver (spironolactone preferred in cirrhosis, loop diuretics added if necessary)
Useful in treatment of hypercalcaemia
- Impairs calcium absorption in the loop henle
- increases urinary excretion of calcium
- Furosemide given together with IV fluids

43
Q

What benefit do loop diuretics have in a patient with heart failure?

A

Diuretic effect

Also effect vascular SMC–> Vaso and Venodilation (decrease after/preload)

44
Q

Loop diuretics are used to treat flui retention and oedama in?`

A

Nephrotic syndrome
Renal Failure
Cirrhosis of liver

45
Q

Spironolactone is perferred in _______ and loop diuretics are added if needed

A

Cirrhosis

46
Q

Why are loop diuretics useful in the treatment of hypercalcaemia?

A

Impairs Ca2+ absorption in the Loop of Henle
Increases urinary excretion of Calcium
Furosemide given together with IV fluids

47
Q

What diuretics act on the early Distal Tubule?

A

Thiazides

48
Q

In relation to Na and Ca what is the difference between the loop of henle and the early diatal tubule?

A

Blocking Na absorption increases Ca absorption

49
Q

Describe the process of Thiazide diuretics

A
  • secreted into the lumen in the PCT
  • Travel downstream to act at the DCT
  • Block Na-Cl transporter in DCT
  • Increases Na+ (and H2O) loss in urine
  • reduced Ca loss in urine (i.e increases Ca absorption)
50
Q

Via what transporter are Na ions reabsorbed in the Early DCT?

A

Na-Cl transporter

51
Q

What transporter do thiazide diuretics block and where?

A

Na-Cl transporter

Early Distal Tubule

52
Q

Which diuretics are less potent; Thiazides or Loop?

A

Thiazides

53
Q

Why are Thiazide diuretics less potent than Loop Diuretics?

A

Only 5% of sodium reabsorption inhibited

In effective in renal failure

54
Q

What are Thiazide diuretics widely used for?

A

Hypertension (vasodilatation)

55
Q

Thiazides have a higher incidence of ____

A

Hyperkalaemia

56
Q

What Diuretics act on the Late DCT and the CD?

A

Potassium sparing diuretics

1) Inhibitors of ENaC – Amiloride
2) Aldosterone antagonsits – Spironlactone

57
Q

How much of Na+ reabsorption do K+ sparing diuretics affect?

A

2% of Na+ reabsorption

58
Q

What life threatening condition can both types of potassium sparing diuretics cause?

A

Hyperkalaemia

59
Q

What drugs/conditions can result in hyperkalaemia when using potassium sparing diuretics?

A
  • Ace inhibitors
  • K+ supplements
  • Patients with renal impairment
60
Q

What drug is best for the treatment of hypertension due to primary hyperalosteronism (Conn’s Syndrome)?

A

Aldosterone antagonists e.g Spironolactone

61
Q

What is Conn’s syndrome?

A

Hypertension due to primary hyperaldosteronism

Adrenal hyperplasia or adrenal tumour –> increased secretion of Aldosterone –> Hypertension

62
Q

What is the preferred drug for Ascites and Oedema in Cirrhosis?

A

Aldosterone antagonists e.g spironolactone

63
Q

What are Acites?

A

accumulation of fluid in the peritoneal cavity

64
Q

What diuretics are used in addition to Loop diuretics in heart failure?

A

Aldosterone antagonists e.g. spironolactone

65
Q

What is used as additional therapy in hypertension which is not controlled by ACEI +CCB+Thiazide

A

Aldosterone antagonists e.g. spironolactone

66
Q

What is usually used in combination with Loop or Thiazide diuretics and why?

A

K+ asparing diuretics; ENaC blockers e.g Amiloride.

Minimise the loss of K+

67
Q

What are the 4 main classes of Diuretics?

A
  • Loop diuretics
  • Thiazide Diuretics
  • K+ sparing Diuretics
  • Aldosterone Antagonists
68
Q

Are inhibitors or carbonic anhydrase used as diuretics?

A

No

69
Q

Are Osmotic Diuretics used as diuretics currently?

A

No

70
Q

Where do Carbonic anhydrase inhibitors act?

A

PCT

71
Q

What is an example of a carbonic anhydrase inhibitor?

A

Acetazolamide

72
Q

Describe the action of Carbonic anhydrase inhibitors

A
  • > Inhibits action of carbonic anhydrase in bursh border and PCT cell
  • > Can cause metaboic acidosis due to loss of HCO3- in urine
  • > Useful in the treatment of Glaucoma
  • > Reduces formation of aqueous humor in eye by about 50%
73
Q

What is Mannitol?

A

Osmotic Diuretic

74
Q

Describe Mannitol

A

Osmotic diuretic:

  • Small molecule
  • Increases plasma osmolarity thus drawing out fluid from tissue and cells
  • In the kideny increases the osmolarityb of filtrate
  • Acts by altering the driving force for renal water absorption, which is osmolarity
  • Causes loss of water, Na+ and K+ in urine
  • Not inhibitors of enzymes or transport proteins
75
Q

What is IV mannitol useful in treating?

A

Cerebral Oedema

76
Q

How is K+ secretion driven in the Distal tubule and Collecting duct?

A

Passive Process driven by electrochemical gradient

77
Q

What does the rate of K+ secretion depend on?

A
  • Concentration gradient across the apical membrane

- Rate of Sodium absorption (inward movement of Na+ ion creates a favourable lumen negative potential for K+ secretion)

78
Q

Why do Loop Diuretics and Thiazides cause hypokalaemia?

A

Block Na+ reabsorption in the LoH or early DT, so increased NA+ and H2O delivery to the late DT and CD

  • increased Na absorption by principal cells –> favourable electrical gradient for K+ excretion
  • fatser flow rate of filtrate in tubuile lume –> washing away K+ maintaining a low conc gradient –> Favourable chemical gradient for K+ secretion
79
Q

In relation to the RAAS how does excess diuresis result in hypokalaemia?

A

Excess Diuresis reduces ECF volume

  • –> Activation of RAAS
  • –> Aldosterone Secretion
  • –> increased Na Absorption and K+ secretion
  • –> Hypokalaemia
80
Q

Which Hypo- or Hyper -Kalaemia may occur with K+ sparing Diuretics?

A

HYPERKalaemia

81
Q

What are the mechanisms behind Hyperkalameia when using K+ sparing diuretics?

A

ENaC inhibitors reduce reabsorption of Na+ which reduces K+ loss in urine
Aldosterone antagonsits block the action of Aldosterone thereby reducing the activty of Na+-K+ATPase reducing Na+ reabsorption and reducing loss of K+ in the urine
= HYPERKALAEMIA

82
Q

Sine diuretics can cause hypo and hyper kalaemia what should be done when treating someone with diuretics?

A

Monitor electrolyte levels during therapy }
Combine loop/thiazide diuretic with a K+ sparing diuretic can be used to minimise changes in K+
or combine with K+ supplements

83
Q

When are diuretics used?

A

Conditions with ECF explansion and Oedema

  • HF
  • Cirrhosis
  • Nephrotic syndrome

Urinary (7 decks)

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