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Flashcards in Renal Deck (42):
1

Where is 60-70% of NaCl reabsorbed?

The proximal tubule

2

How much NaCl is reabsorbed in the loop of henle?

20-30%

3

Where is K+ reabsorbed and where is it secreted?

Reabsorbed in the proximal tubule and loop of henle (?)
Secreted in the Distal tubule and collecting ducts

4

Which section of the Nephron do loop diuretics act on?

Ascending loop of Henle

5

What ion channels do loop diuretics act on?

The Na+/K+/2Cl-

6

How do loop diuretics increase urine production?

By acting on the Na+/K+/2Cl- channel loop diuretics keep more ions in the lumen. Ordinarily the movement of ions into the epithelial cells and then into the interstitium creates an osmotic gradient which drives the movement of water into the interstitium which is reabsorbed. The lack of Osmotic pressure keeps water in the lumen and prevents water reabsorbtion. The increased osmotic pressure in the lumen reduces water reabsorbtion downstream as well, further increasing water secretion.

7

Name a common loop diuretic

Furosemide

8

What percentage of Na+ is excreted when furosemide is taken?

15-20%

9

When are loop diuretics used?

Acute pulmonary oedema
Chronic heart failure
Ascites (liver failure)
Renal failure

10

How can loop diuretics cause hypokalaemia?

Decreased reabsorbtion of Na+ in the loop of henle
Increased concentration of Na+ in the distal tubule
Up-regulation of the Na+/K+ATPase pump in the dt = increased K+ secretion
Hypokalaemia

11

What supplement is usually given with loop diuretics?

K+

12

What is secreted when using a loop diuretic that may cause a metabolic alkalosis?

H+

13

What is a potential negative outcome of furosemide in the elderly?

Loss of extracellular fluid volume causing hypovolaemia and hypotension

14

Where do thiazide diuretics act?

The distal convoluted tubule

15

What channels do thiazide diuretics act on?

The Na+/Cl- co-transporter

16

How do thiazide diuretics cause hypokaleamia?

As for loop diuretics except now the process occurs in the collecting duct

17

How long are loop diuretics active for?

3-6 hours

18

Name 2 thiazide diuretics

Bendrofluazide/Hydrochlorothiazide
(thiazides)

19

How long are thiazides active for?

Max effect 4-6 hours but act for 8-12hours (they are excreted in the urine)

20

What are thiazides used for?

Hypertension,
Severe resistant oedema (in combination with a loop diuretic)

21

Side effects of thiazides?

Increased uric acid due to inhibition of secretion - can cause gout
Hypokaleamia - co administered with a K+ supp

22

Name a thiazide like diuretic

Indapamide - reduced side effects

23

Name a potassium sparing diuretic

Spironolactone

24

How do potassium sparing diuretics act?

The potassium-sparing diuretics are competitive antagonists that either compete with aldosterone for intracellular cytoplasmic receptor sites, or directly block sodium channels (specifically epithelial sodium channels (ENaC) by amiloride). The former prevents the production of proteins that are normally synthesized in reaction to aldosterone. These mediator proteins are not produced, and so stimulation of sodium-potassium exchange sites in the collection tubule does not occur. This prevents sodium re-absorption and potassium and hydrogen ion secretion.

25

What is the half life of spironolactone?

It is very short (about 10 minutes) buts its metabolite has a long half life (16 hours) and is still active

26

Is spironolactone fast or slow onset?

Slow onset long duration

27

When in spironolactone used?

In combination with a loop diuretic or thaizide diuretic
Heart failure
Hyperaldosteronism

28

What are some side effects of potassium sparing diuretics?

Hyperkaleamia
Gastrointestinal upset

29

What are triamterene and amiloride?

They are drugs which block epithelial sodium channels (stopping re-absorption) and hence block the secretion of potassium.

30

Describe the pharmacokinetics of Triamterene

Well absorbed, onset after 2 hours and works for a duration of 12-16 hours

31

Describe the pharmacokinetics of Amiloride

Poorly absorbed with a slow onset and a duration of action of about 24 hours

32

What are osmotic diuretics?

They are pharmocologically inert substances which are filtered but not reabsorbed. They act by changing osmolarity and hence reducing passive water reabsorbtion

33

Where do osmotic diuretics act?

They act the water permeable parts of the nephron (proximal tubule, descending loop of henle, collecting tubules)

34

When are osmotic diuretics used

Raised intra-cranial pressure
Intraocular pressure
To prevent acute renal failure
- If GFR is so low/slow that all NaCl and water is being reabsorbed then water retention by osmotic diuretics is effective
These diuretics only have a small impact on Na+ retention

35

Name a heavy metal which damages the nephron

Mercury

36

How does mercury damage the nephron

Direct toxicity and vasoconstriction
binds to the thiol groups in proteins and causes immune glomerulonephritis (inflammation either of the glomeruli or small blood vessels in the kidneys)

37

How can heavy metals damage the nephron?

Loss of brush boarder membranes
Cause mitochondrial changes
Apoptosis

38

Name an antibiotic which can damage the kidney

Gentamicin

39

How does gantamicin damage the nephron

Mechanism
Cationic drug binds to anionic phsopholipids
Altered generation of PIP2
Altered intracellular Ca2+ levels
Impaired mitochondrial respiration
Cell injury

This impairs secretion which in turn increases toxicity and thus generates a vicous cycle

40

Where does gentamicin act on the nephron?

Apical membrane of the proximal tubule

41

Describe how antineoplastic agents can damage the kidney:

These agents are activated inside cells
Form highly reactive species
Binds to the neucleophilic components of cell (eg thiols of proteins)

42

What does cisplatin do

It treats prostate tumours as well as other cancers (it is a cytotoxic agent)
It causes protinuria, increased urea in blood and electrolyte imbalance
thus causing dose limiting side effects