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Urinary > Week 7 - Diuretics > Flashcards

Week 7 - Diuretics Flashcards

1
Q

Explain tubular reabsorption of Na and H2O in PCT

A
  • NaKATPase on basolateral membrane sets up an Na gradient
  • Na symporter on apical membrane allows Na to enter the cell down its concentration gradient
  • Water follows by osmosis
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2
Q

Name the Na transporters of the PCT

A
  • Na:glucose
  • Na:a’a
  • NHE
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3
Q

Name the Na transporters of the loop of henle

A

-NaKCC2

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4
Q

Name the Na transporters of the DCT

A

-NCCT

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5
Q

Name the Na transporters of the late DCT and CD

A

-ENaC

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6
Q

Describe Na resorption and K secretion in Late DCT and CD

A
  • Occurs in principle cells
  • NaKATPase on basolateral membrane sets up a Na Gradient
  • Na enters the cell via a channel called ENaC
  • Influx of Na+ produces a lumen negative potential which favours K+ secretion through K channels
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7
Q

What are the effects of aldosterone at a molecular level?

A

-Increases expression of NaKATPase, ENaC and K channel

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8
Q

What is meant by a potassium sparing diuretic?

A

-A diuretic which also decreases potassium secretion in its mechanism of action eg spironolactone

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9
Q

Which diuretics work by direct action? What is meant by this?

A
  • Loop Diuretics
  • Thiazide Diuretics
  • K sparing diuretics
  • > The diuretics work by directly acting on Na transporters to block them and prevent resorption and this water resorption
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10
Q

Which channels do loop diuretics work on?

A

-NKCC2 in LoH

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11
Q

Which channels do thiazide diuretics work on?

A

-NCCT in early DCT

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12
Q

Which channels do K sparing diuretics work on?

A

-ENaC in late DCT and CD

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13
Q

How do direct action diuretics reach their target site?

A

-They are secreted into the lumen in the PCT

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14
Q

Explain how a diuretic would work by antagonising the action of aldosterone? Name an example

A

-Aldosterone increases the expression of NaKATPase, ENaC and K channels in late DCT and CD, thus it works to increase Na and water resorption
-Competitive inhibition of aldosterone would decrease expression of these channels and thus increase renal excretion of Na and water
eg spironolactone

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15
Q

Explain how some diuretics work by modification of filtrate. Give an example

A

-These diuretics are small molecules which are free filtered at the glomerulus but are not reabsorbed
-They increase the osmolarity of the filtrate and thus decrease water resorption
eg mannitol

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16
Q

Explain how inhibiting the activity of carbonic anhydrase would ace as a diuretic

A
  • Inhibition of CA -> decreased CO2 and H20 entering the cell
  • Decreased activity of NHE
  • Decreased Na and H2O resorption
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17
Q

Give an example of a loop diuretic

A

-Furosemide

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18
Q

Give an example of a diuretic which inhbits ENaC

A

-Amiloride

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19
Q

Which diuretics work in PCT?

A

-CA inhibitors

20
Q

What is essential to ensure the continual action of NKCC2 in the loop?

A

-Diffusion of K back into the lumen so it can be used again

21
Q

Which diuretic also helps to drive reabsorption of Ca and Mg?

A

-Loop diuretics

22
Q

Why does decreasing resorption in the loop increase renal excretion?

A

-Segments downstream have limited capacity for reabsorption and thus cannot reabsorp the flodding of Na and water

23
Q

Why are loop diuretics used in HF?

A
  • Diuretic effect

- Vaso and venodilation reduce after/pre load

24
Q

When are loop diuretics used?

A 
To treat fluid retention and oedema in
-HF
-Nephrotic syndrome
-renal failure
To treat hypercalcaemia as impairs Ca resorption in the loop
25
Q

When are thiazide diuretics used?

A

-Hypertension

26
Q

Which diuretics are the least potent at Na resorption?

A

-K sparing

27
Q

In what situations are K sparing diuretics contraindicated and why?

A
  • When pt on ACE inhibitor, K supplements or patients with renal impairment
  • Can lead to life threatening hyperkalaemia
28
Q

Explain why ACE inhibitor and K sparing diuretics can cause hyperkalaemia when used together

A
  • ACE inhibitor blocs angiotensin I to angiotensin II
  • Decrease angiotensin II results in decreased aldosterone
  • Decreased aldosterone increases k retention as K secretion is decreased
  • K aring diuretics also cause K retention
  • Together can lead to hyperkalaemia
29
Q

When is spironolactone used?

A
  • Hypertension due to primary hyperaldosteronism (conn’s syndrome)
  • Ascites and oedema in cirrhosis
  • In addition to loop diuretics in HF
30
Q

What groups of diuretics are not currently used?

A
  • Inhibitors of carbonic anhydrase

- osmotic diuretics

31
Q

What is an adverse effects of carbonic anhydrase inhibitor diuretics?

A

-Metabolic acidosis as it decreases the resorption of HCO3

32
Q

When are carbonic anhydrase inhibitors used?

A

-Glaucoma as reduces aqueous humor formation

33
Q

What is IV mannitol used to treat?

A

-Cerebral oedema

34
Q

Why is there expansion of ECF in congestive heart failure?

A
  • Increased systemic venous pressure -> oedema as fluid moves into ECF due to increased hydrostatic pressure
  • Decreased CO stimulates RAAS which increased Na and H2O retention
35
Q

Why does nephrotic syndrome lead to increased ECF?

A
  • Increase in glomerular basement membrane to protein
  • proteins such as albumin lost in urine
  • Results in a lower oncotic pressure leading to peripheral oedema
  • causes low circulating volume and activation of RAAS
  • Na and water retention leads to more oedema
36
Q

Why does peripheral oedema ensue in liver cirrhosis?

A

-Reduced albumin synthesis in liver ->Low plasma oncotic pressure ->Peripheral oedema -> Decreased CO due to low blood volume activates RAAS -> worsening oedema

37
Q

Why does ascites occur in liver cirrhosis?

A
  • Portal hypertension leads to an increased systemic pressure in GI circulation
  • Increased hydrostatic pressure, coupled with low oncotic pressure, causes fluid to move from peritoneal capillaries to peritoneal cavity
  • Decreased CO due to low blood volume activates RAAS -> worsening ascites
38
Q

What does the rate of K secretion in DCT depend on?

A
  • Concentration gradient of K across apical membrane

- Rate of Na absorption

39
Q

How do loop and thiazide diuretics lead to K loss?

A

1) Increased Na and H2o delivery to late DCT and CD
- Increased Na resorption by ENaC
- Favours K secretion via creating lumen negative potential
2) increased flow rate -> increased removal of K in lumen -> increased conc gradient favours K secretion

40
Q

What can you do when giving diuretics to ensure that hyper/hypokalaemia doesnt develop?

A
  • Monitor electrolyte levels

- Give a K sparing diuretic (amiloride/spironolactone) with a K loosing diuretic (loop/thiazide) to minimise K change

41
Q

Why can loop diuretics cause hypovolaemia?

A
  • Decreases ECF volume by causing excretion of Na and H2O

- Loop diuretics are the most potent as the segments distal do not have capacity to resorb much water

42
Q

List some adverse effects of diuretucs

A
  • Potassium disturbance
  • Hypovolaemia
  • Hyponatraemia
  • Gout
43
Q

Why can loop and thiazide diuretics lead to gout?

A

-Increase uric acid levels in the blood

44
Q

Name some substances with diuretic effects

A
  • Alcohol
  • Coffee
  • Lithium
45
Q

Name some disease which cause diuresis

A
  • Diabetes mellitus

- Diabetes insipidus

46
Q

What is a diuretic? When are they used?

A

-A substance/drug that increases urine formation via promoting renal excretion of water and sodium in order to reduce ECF volume

Urinary (21 decks)

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