Thiazide and sodium

I have always wondered: why does diuretic induced hyponatremia almost always due to thiazides?

To understand this need to go back to physiology.

From Google Image.

Let’s say you use thiazide. What’s the result?

  • Water and NaCl would not be reabsorbed (= concentrated urine).
  • Distal delivery of this urine will lead to more sodium reabsorption in collecting duct via ENaC. But then, there is a limit how much sodium ions can be reabsorbed each time.
  • Meanwhile, ADH acts and water is reabsorbed.
  • So you end up having a very concentrated urine with lots of sodium (high osmolality).
  • The combined effect of too much water being reabsorbed + sodium wasting leads to thiazide induced hyponatremia.

Let’s say you use loop diuretic. What’s the result?

  • You block the TAL of loop of Henle. Na and Cl are blocked from getting reabsorbed.
  • Medullary interstitium depend on Na-Cl reabsorption to restore its hypertonicity. When the interstitium is washed out, urine can no longer be concentrated in medulla.
  • This urine will go on to distal tubule and collecting duct, and without being able to be concentrated, more sodium will be reabsorbed in those parts of nephron.
  • The end result? You probably will have dehydration from losing too much water. And possibly hypernatremia in extreme cases.

But even so, why doesn’t loop diuretic seldom produce any dehydration?

  • Because of tubuloglomerular feedback (TGF) mechanism.
  • When lots of sodium are going through distal tubule, they pass through macula densa and this alerts the TGF system.
  • Vasoactive mediators are release to vasoconstrict the afferent arterioles of glomeruli and you end up having less GFR, and water & sodium are preserved.

From Google Image

Why is thiazide counter-intuitively used in nephrogenic diabetes insipidus (NDI)?

  • NDI is characterized by ADH failing to act in nephrons.
  • By increasing sodium excretion (together with water) distally, in an attempt to preserve water and sodium, nephrons will reabsorb more of these substances in proximal tubules.
  • So less water = less urine.
  • There is newer mechanism eg thiazide may reduce the expression of ENaC and aquaporin channels.


Why Do Thiazides Decrease Polyuria in Diabetes Insipidus?


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