sendwich

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can anyone clarify how this works? according to uworld, anything that increases proximal tubule Na reaborption will increase the likelihood of Li toxicity. I get this but I thought diuretics (particularly hydrochlorothiazide in uworld) inhibit the Na/K/Cl transporter-->LESS Na reabsorbed in kidney-->less Li toxicity??
 

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Lithium's effects are two-fold: the first effect is that it may be absorbed instead of Na+. This is dangerous in concurrent usage in diuretics like HCTZ because the sodium depletion will cause an initial sodium loss, but the higher sodium concentration at the end of the tubule and the loss of serum sodium will induce aldosterone and ATII to increase sodium reabsorption in the distal collecting tubule and proximal tubule, respectively.

Its second effect is that it is an ADH antagonist and may cause nephrogenic diabetes insipidus with prolonged usage. The increase in Li+ absorption while on diuretics obviously does not help this at all.
 
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Lithium's effects are two-fold: the first effect is that it may be absorbed instead of Na+. This is dangerous in concurrent usage in diuretics like HCTZ because the sodium depletion will cause an initial sodium loss, but the higher sodium concentration at the end of the tubule and the loss of serum sodium will induce aldosterone and ATII to increase sodium reabsorption in the distal collecting tubule and proximal tubule, respectively.

Its second effect is that it is an ADH antagonist and may cause nephrogenic diabetes insipidus with prolonged usage. The increase in Li+ absorption while on diuretics obviously does not help this at all.
so the "increased Na+ in PT increases Li absorption" is what you see as a subsequent result of of volume depletion due to the HCTZ?
 

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so the "increased Na+ in PT increases Li absorption" is what you see as a subsequent result of of volume depletion due to the HCTZ?
Yes. It sounds counter-intuitive at first that a Na/Cl diuretic would lead to salt retention, but think about the physiology: an initial loss in Na/Cl due to HCTZ will result in lowered sodium levels in the serum and a higher concentration at the collecting tubules. The JGA cells will later on see this lowered sodium concentration as a sign of a salt deficiency, so it will activate the renin-angiotensin system. ATII will result in higher salt intake at the prox tubule (Na/H exchange pump) and aldosterone (Na/K & H pump). Since Li+ has similar ion characteristics to Na+, some lithium may get in on some of the action as well. This is why HCTZ can be used to tx nephrogenic diabetes insipidus.

If it still doesn't click try drawing it out. FA has good diagrams of where all the pumps are in the tubule.
 

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Remember on the periodic table that Na and Li are in the same column. So, Li can exchange for Na in the Na transport systems.

So with hyponatremia, more Li is reabsorbed causing higher Li levels and lithium toxicity. This goes for anything that causes lower na levels.