Renal System Flashcards

1
Q

What are the five classes of diuretics?

A

1) Carbonic anhydrase inhibitors
2) Loop Diuretics
3) Thiazide Diuretics
4) Potassium-sparing diuretics
5) Osmotic diuretics

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2
Q

How do carbonic anhydrase inhibitors mainly produce their diuretic effect?

A

Reducing reabsorption of bicarbonate in the proximal convoluted tubule.

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3
Q

Describe the mechanism of action for carbonic anhydrase inhibitors

A

1) They inhibit the function of carbonic anhydrase

2) This prevents H2CO3 from being converted into H2O and CO2 (in the lumen)
CO2 and H2O from being converted into H2CO3 in the cell.

3) H2CO3 (bicarbonate) is lost in urine
H+ isn’t available to be pumped out of sodium hydrogen ion exchanger and Na+ is not reabsorbed (Water always follows sodium) so is lost in urine

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4
Q

Why do carbonic anhydrase inhibitors have a mild diuretic effect?

A

Because they act at the proximal convoluted tubule and reabsorption of Na+ and H2O can occur later in the nephron

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5
Q

What are some of the side effects of carbonic anhydrase inhibitors?

A

Hypokalemia - Caused by increased sodium delivery to the distal nephron and its reabsorption there in exchange for potassium

Metabolic acidosis (increased plasma acidity) - H2CO3 is wasted which usually acts as a buffer in the blood

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6
Q

How do loop diuretics produce their diuretic effects?

A

Inhibit sodium-potassium-2-chloride cotransporter in thick ascending limb

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7
Q

Where are 100% of amino acids and glucose reabsorbed in the nephron?

A

The proximal convoluted tubule

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8
Q

Where is 90% of NaHCO3 (Sodium Bicarbonate) reabsorbed?

A

The proximal convoluted tubule

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9
Q

Where are 65% of Na+, K+ and H2O reabsorbed?

A

The proximal convoluted tubule

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10
Q

What is secreted in the descending loop of of henle?

A

H2O

The walls are impermeable to sodium

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11
Q

What is reabsorbed in the thick ascending limb of the loop of henle?

A

Na+ passively (as water is impermeable here so cannot be reabsorbed meaning sodium leaves)

Na+ actively (via sodium-potassium 2 chloride co-transporter)

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12
Q

Describe the mechanism of action of loop diuretics

A

1) The Na+-K+-2Cl- co-transporter is inhibited, reducing the level of these ions in the cell.
2) The concentration of K+ (owing to the co-transporter and ATPase on interstitial side) in the cell decreases.
3) This means K+ does not leak out of the cell, therefore no driving force is created for paracellular reabsorption of Mg2+ and Ca2+.
4) Loss of water owing to Na+ (and other ions) lost

Normally the Na+-K+-2Cl- co-transporter causes reabsorption of these ions in the ascending limb. The Na+ K+ ATPase exchanger allows K+ into the cell and Na+ into the blood, which causes a high level of K+ in the cell. K+ usually leaks out of the cell into the lumen, creating a +++ outside the cell. This electrical driving force = paracellular reabsorption of Mg2+ and Ca2+.

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13
Q

What are the side effects of loop diuretics?

A

Electrolyte imbalance

Acute blood volume loss = acute hypovolemia

Ototoxicity - damage to hearing (the Na+-K+-Cl- co-transporter is also in ear)

Some of them compete with transport of uric acid (blocking secreation) = hyperuricemia and worsening of gout

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14
Q

What hormones act on the principle cell in the collecting duct?

What are their actions?

A

Aldosterone - increased Na+ reabsorption + increased K+ secretion

Antidiuretic hormone - increases water permeability and therefore water reabsorption

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15
Q

What hormones act on intercalated cells in the collecting duct?

What does this hormone cause this cell to do?

A

The primary function of the cell is to recreate H+ and reabsorb K+ - this is regulated by aldosterone

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16
Q

What do all diuretics aim to do?

A

Increase the volume of urine by acting on different parts of the collecting duct

17
Q

How and where do thiazide diuretics act?

A

Thiazide diuretics increase sodium chloride secretion by inhibiting the sodium-chloride co-transporter in the early part of the distal convoluted tubule

18
Q

What are the side effects of thiazide diuretics?

A
Hyperkalemia
Hyperuricemia (interferes with transport of uric acid)

Hypercalcemia
Volume depletion in PCT = compensatory increase in sodium = electrical gradient = passive calcium reabsorption
OR
Na+Ca2+ exchanger - Low Na+ in cell so Ca2+ in cell exchanged for Na+ in blood

Hyperglycaemia
Hyperlipidema

19
Q

What is an unintended effect of thiazide diuretics that the MoA of which is unknown?

A

They cause vasodilation which reduces peripheral vascular resistance

20
Q

Why are thiazide diuretics weak diuretics?

A

Over 90% of sodium is reabsorbed before reaching the distal convoluted tubule

21
Q

What are thiazide-like diuretics?

A

Drugs that share the same mechanism of action as thiazide diuretics but do not have a thiazide ring

22
Q

How and where do potassium sparing diuretics work?

A

They inhibit sodium reabsorption and potassium secretion in the collecting tubule

23
Q

Describe the Mechanism of Action of Potassium sparing diuretics

A
  1. Block sodium channel resulting in decreased sodium/potassium exchange + thus retention of potassium
    e. g. amiloride, triamterene
  2. Antagonising aldosterone
    Prevent reabsorption of sodium and water + secretion of potassium because there is reduced transcription of genes encoding the sodium channel + sodium/potassium ATPase
    e.g. spironolactate + epierenone
24
Q

What are the side effects of potassium sparing diuretics?

A

Hyperkalemia
Spironolactate can cause menstrual irregularities (females) and gynecomastea (males) - stimulate receptors for testosterone and progesterone

25
Q

When are osmotic diuretics used for?

A

Reduction of intracranial pressure
Promotion of urinary excretion of toxic substances
Promotion of urine production in patients with acute kidney failure

26
Q

Why are osmotic diuretics not effective at treating oedema caused by sodium retention?

A

They increase water excretion rather than sodium excretion

27
Q

Give examples of osmotic diuretics

A

Mannitol, Urea

28
Q

What are the side effects of osmotic diuretics?

A

Significant fluid changes e.g. volume overload or dehydration and thus electrolyte imbalances

29
Q

How to osmotic diuretics work?

A

They interfere directly with osmosis.

30
Q

What is the mechanism of action of osmotic diuretics?

A

Water moves across membrane from lower osmolarity or the dilute side to a higher osmolarity or the concentrated side. Osmotic agents are filtered from glomerulus they are very water soluble or hydrophilic and they undergo very limited reabsorption due to their large molecular size this leads to increased osmolarity of the tubular fluid and thus decreased water reabsorption