MK - Diuretics I

Question 1

What is the functional unit of the kidney?

Answer 1

Nephron

Question 2

What effect does sympathetic stimulation have on the kidneys?

Answer 2

Sympathetic stimulation causes vasoconstriction of alpha 1 afferent arterioles, reducing the glomerular filtration rate

Question 3

Mechanism of urine formation (2)

Answer 3

1. Na+ gradient generated by Na+/K+ pump of proximal tubule epithelial cell walls is used to drive reabsorption of glucose, amino acids
2. Osmotic gradient leads to H2O reabsorption – ca. 50%
   Mainly paracellular H2O in proximal tubule

Question 4

How are ions reabsorbed into the blood? (3)

Answer 4

1. Na+ reabsorbed into blood from epithelial cell via Na/K pump ATPase
2. 2Cl- and K+ and Na+ move from lumen into epithelial cells via Na-K-2Cl cotransporter (secondary active transport)
3. Cl reabsorbed into blood

Question 5

How does loop of henle alter the concentration of urine? (2)

Answer 5

• The countercurrent mechanism driven by the active extrusion of Na produces hypertonic conditions in medulla
• This can be used to create hypertonic urine by regulating water permeability of collecting duct – regulated by ADH

Question 6

What 4 things do Na+ ions aid with?

Answer 6

• Nerve function
• Fluid balance
• Muscle function
• Blood pressure and volume

Question 7

What is the action of Osmotic diuretics (On the PCT)? (3)

Answer 7

E.g. Mannitol

• Non-metabolisable enters the tubule and via osmotic effects prevents reabsorption of water
• Water movement largely paracellular in the proximal tubule

Used in the treatment of cerebral oedema and raised intra-ocular pressure

Question 8

How do Carbonic Anhydrase Inhibitors act on the PCT? (5)

Answer 8

1. Na gradient drives H+ efflux into tubule,
2. Combines with HCO3- via Carbonic anhydrase to produce CO2 and H20 (lost)
3. CO2 into epithelial cell combines with H20 in cell to produce HCO3- and H+ via Carbonic anhydrase
4. HCO3- plus Na+ via cotransporter to blood
5. Therefore reduce Na+ reabsorption into blood

Hence, normally reabsorb Bicarb and H2O

E.g. Acetazolamide, reduces reabsorption of bicarbonate

Weak diuretic and used mainly in the treatment of glaucoma, prophylaxis against mountain sickness and epilepsy.

Question 9

What is a common loop diuretic? (on the LOH)

Answer 9

Na-K-2Cl co-transporter blocked

E.g. Furosemide

• Act on the thick ascending limb
  Block Na-K-2Cl co-transporter preventing Na gradient-driven reabsorption of K+.
  Therefore lose K+ and H2O

Result in increased osmolarity in the ascending limb (more salt)

Question 10

Thiazide diuretics on the DCT (3)

Answer 10

Na-Cl co-transporter blocked

Eg. bendrofluazide

• Act on distal convoluted tubule
• Block Na-Cl co-transporter
• Increase Na and K loss

Question 11

Potassium Sparing Diuretics
on the collecting duct

Answer 11

Collecting duct normally:

• Impermeable to water in the absence of ADH (aquaporins)
• Impermeable to Na in the absence of Aldosterone (eNaC)

eNaC blocked by amiloride (mineralocorticoid aldosterone increases eNaC and Na/K pump retain Na+)

Question 12

What do alsoterone blockers and eNaC blockers do?

Answer 12

Aldosterone Blockers
(K+ sparing but weaker diuresis)
e.g. Spironolactone

• limited action via blocking intracellular Aldosterone receptors prevents upregulation of eNaC

eNaC Blockers
Antagonise Aldosterone effects (K+ sparing)
e.g. Amiloride

• reduces Na reabsorption and K+ loss