SM 199a - IVF and Diuretics

Question 1

How do loop diuretics lead to hypocalcemia?

Answer 1

Loop duretics (ex: furosemide) block the Na+/K+/2Cl- cotransporter

• -> Decreased Na+/K+ ATPase activity on the basolateral membrane
  
  • Less Na+ reabsorption = less drive to pump it into the interstititum = less K+ into the cell
• -> Less intracellular K+
• -> Less K+ pumped out into the tubular lumen (less recycling)
• -> Decreased lumen positivity
• -> Decreased electric gradient driving paracellular Ca2+ reabsorption through claudin 16
• -> hypocalcemia

Note: This is the same mechanism by which loop diuretics may cause hypomagnesemia

Question 2

Describe the mechanism of action of proximal tubule diuretics

Answer 2

PCT Diuretic = Acetazolamide

Inhibits carbonic anhydrase

• Normally carbonic anhydrase promotes the absorption of Na+ with bicarbonate
• Inhibiting carbonic anhydrase causes less Na+ reabsorption, less bicarbonate reabsorption, and less H+ secretion

Note: not often used because not very effective - distal Na+ reabsorption mechanisms compensate

Question 3

What are the side effects of loop diuretics?

Answer 3

• Volume depletion
• Electrolyte imbalances
  
  • Hypocalcemia
  • Hypomagnesmia
  • Hypokalemia
• Ototoxicity, hyperuricemia, hyperglycemia, increased LDL and triglycerides

Use primarily for volume overload. Only used for HTN in patients with CKD

Question 4

How does acetazolamide cause acidosis?

Answer 4

Acetazolamide inhibits carbonic anhydrase in the PCT

This results in:

• -> Decreased Na+ reabsorption
• -> Decreased HCO3- reabsorption
• -> Decreased H+ secretion

Decreased HCO3- = Acidosis
(Non-anion gap, implying that the decereased reabsorption of HCO3- plays a larger role than the retention of H+)

Question 5

What are the side effects of thiazide diuretics?

Answer 5

• Electrolyte imbalances
  
  • Hypokalemia
  • Hyponatremia
  • Hypercalcemia
• Impotence, impaired glucose tolerance, increased cholesterol