1. Hello everyone ? kidneys filter magnesium everyday. Do you want to know how?! #tweetorial #nephtwitter #medtwitter
Keep reading & see our recent post on hypoMg on @RenalFellowNtwk
renalfellow.org
@TheSkeletonKG @NSMCInternship
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Keep reading & see our recent post on hypoMg on @RenalFellowNtwk
renalfellow.org
@TheSkeletonKG @NSMCInternship
??????
2. First answer this question #nephtwitter, do you know how much Mg is filtered by the kidneys?
3. In the kidneys, Mg handling is a filtration-reabsorption process:
- 70-80% of blood Mg is ultrafilterable (free & complexed).
- 2000–2400 mg of magnesium per day (assuming a normal GFR) are filtered by the kidneys
annualreviews.org
- 70-80% of blood Mg is ultrafilterable (free & complexed).
- 2000–2400 mg of magnesium per day (assuming a normal GFR) are filtered by the kidneys
annualreviews.org
4. Control of total body magnesium homeostasis principally resides within the nephron segments of the kidney. Where does the magnesium absorption mainly occur?
5. Mg is handled in different ways along the nephron segments:
- Proximal tubule → 5-15% is reabsorbed by paracellular pathway.
- Na - water reabsorption → ↑ Intraluminal Mg concentration & lumen-positive potential
karger.com
- Proximal tubule → 5-15% is reabsorbed by paracellular pathway.
- Na - water reabsorption → ↑ Intraluminal Mg concentration & lumen-positive potential
karger.com
6. Main site of Mg absorption → thick ascending limb (TAL) of the loop of Henle:
- Reabsorbs ∼70% of the filtered load
- Cortical segment plays a major role in Mg reabsorption.
- Mg cross the epithelium predominantly through paracellular pathway, but also via transcellular
- Reabsorbs ∼70% of the filtered load
- Cortical segment plays a major role in Mg reabsorption.
- Mg cross the epithelium predominantly through paracellular pathway, but also via transcellular
7. Knowing that the greatest absorption of Mg occurs in the TAL, how does furosemide (lasix) lead to HypoMg? ?
8. Loop diuretics inhibit NaCl absorption by NKCC2:
- ↓ basolateral Cl- efflux via ClC-Kb
- ? the back leak of K
- No lumen-positive potential generation
- ↓ the driving force for paracellular Mg reabsorption via claudin-16 and 19
- ↓ basolateral Cl- efflux via ClC-Kb
- ? the back leak of K
- No lumen-positive potential generation
- ↓ the driving force for paracellular Mg reabsorption via claudin-16 and 19
9. Permeability to Mg in the tight junctions resides in transmembrane proteins → claudin-16 & 19.
#NephPearls: Mutations in CLDN16 or CLDN19 cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC).
academic.oup.com
#NephPearls: Mutations in CLDN16 or CLDN19 cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC).
academic.oup.com
10. Only 10-15% of the filtered Mg is delivered to the distal tubule:
- BUT 70 to 80% of what reaches here is reabsorbed actively via TRPM6
- Leaving about 3% of the filtered Mg normally appearing in the urine
cjasn.asnjournals.org
- BUT 70 to 80% of what reaches here is reabsorbed actively via TRPM6
- Leaving about 3% of the filtered Mg normally appearing in the urine
cjasn.asnjournals.org
11. Around 50% of clinically significant HypoK has concomitant HypoMg, this is most frequently observed in loop or thiazide diuretic therapy. Why does magnesium decrease potassium excretion?
jasn.asnjournals.org
jasn.asnjournals.org
12. Mg regulates ROMK (inward-rectifying K channel responsible for basal K secretion) activity:
- Intracellular Mg binds and blocks the pore of the channel from the inside.
- Limits outward K flux.
- Inward K flux displace intracellular Mg from the pore and release the block.
- Intracellular Mg binds and blocks the pore of the channel from the inside.
- Limits outward K flux.
- Inward K flux displace intracellular Mg from the pore and release the block.
13. ? Take home points:
- Healthy Kidneys filter 2000-2400 mg of Mg /day
- Reabsorption mainly occur at TAL (paracellular pathway)
- Loop diuretics can inhibit paracellular Mg absorption
- HypoMg leads to HypoK
- Healthy Kidneys filter 2000-2400 mg of Mg /day
- Reabsorption mainly occur at TAL (paracellular pathway)
- Loop diuretics can inhibit paracellular Mg absorption
- HypoMg leads to HypoK
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