Loop diuretics and electrolyte loss
Loop diuretics block a transporter in the thick ascending limb of the loop of Henle (the hairpin bend of the kidney tubule), so potassium, calcium and magnesium are lost.
Remember
Loop diuretics make the kidney lose calcium and magnesium as well as potassium, and they typically cause a metabolic alkalosis (blood that has become too alkaline). Loops lose calcium; thiazides (diuretics that act further along the tubule) keep it.
Loop diuretics such as furosemide and bumetanide block the NKCC2 cotransporter in the thick ascending limb of the loop of Henle. This carrier protein moves one sodium, one potassium and two chloride ions together out of the fluid in the tubule and back into the blood. Around a quarter of filtered sodium is reabsorbed at this site, which makes loop diuretics very powerful.
Blocking NKCC2 has a second consequence. A working carrier helps build a positive electrical charge inside the tubule, and that charge helps drive calcium and magnesium back into the blood by passing them between the cells. When the carrier is blocked, the charge falls and the kidney loses calcium and magnesium in the urine. Blood levels of both can drop, giving hypocalcaemia and hypomagnesaemia (low blood calcium and low blood magnesium).
Potassium falls for a different reason. Extra sodium now reaches the collecting duct (the last part of the kidney tubule), which draws potassium and hydrogen ions (acid) out into the urine. Losing potassium means low blood potassium, called hypokalaemia. Losing acid, together with chloride and fluid, leaves the blood too alkaline, which is a metabolic alkalosis.
Thiazides can cause the same pattern of low potassium and metabolic alkalosis, but they make the kidney hold on to calcium. So use the site of action to tell them apart: thiazides act in the distal convoluted tubule (the part of the tubule after the loop of Henle), whereas loop diuretics act in the thick ascending limb.
Key facts
- Site of action
- the thick ascending limb of the loop of Henle, where the NKCC2 cotransporter is blocked.
- Calcium and magnesium
- blocking NKCC2 weakens the positive charge that drives their reabsorption, so calcium and magnesium are lost in the urine.
- Potassium and acid
- more sodium reaches the collecting duct, so potassium and hydrogen ions are lost, and loop diuretics typically cause low blood potassium with a metabolic alkalosis.
- Contrast with thiazides
- thiazides tend to raise calcium, whereas loop diuretics lose it.
- Ear effects
- ototoxicity (damage to the inner ear) is rare, but more likely with rapid intravenous doses or with aminoglycoside antibiotics such as gentamicin.
Exam traps
- Blocking the sodium-chloride cotransporter in the distal convoluted tubule (the segment after the loop of Henle) does not cause calcium loss, because that is the action of thiazides, which increase calcium reabsorption and so tend to raise blood calcium.
- A potassium-sparing diuretic (one that reduces potassium excretion) is not expected to cause low blood potassium, because it tends to cause high blood potassium, the opposite of the loop diuretic picture.
- Indapamide, a thiazide-like diuretic, lowers potassium and magnesium but tends to raise calcium rather than lower it, and ototoxicity is a feature of loop diuretics, so it does not fit low calcium with ear damage.
Read the full notes
Tested in 6 SimpleMed+ questions
Practice it in Pharmacology, with the answer and a full explanation after every question.
Practice these questions