CVPR Week 8: CVPR Week 8: Renal handling of P Flashcards
How much Magnesium does the body typically store?
24g
Where does the body have magnesium?
99% is intracellular
What is the normal magnesium concentration?
1.7-2.6 mg/dL
How is magnesium structured in the body
- only 70% of serum magnesium is free
- the other 30% is complexed to albumin
Describe Mg flux between body compartments
Similar to calcium!
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Mechanisms of intestinal Mg absorption
- Paracellular
- Transcellular
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Describe renal handling of Mg
PCT 10-20%
TALH 70%
DCT 10%
CD 0%
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What is the major site of Mg reabsorption in the kidney?
TALH
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Loop diuretics effects on Mg
Inhibit NKCC2 and cause hypomagnesemia
Bartter syndrome and Mg
mutations in ROMK, NKCC2, CIC-Kb, Barttin and CaSR
cause
- metabolic alkalosis
- hypokalemia
- normo-hypomagnesemia
- hypercalciuria
Describe Familial hypomagnesemia
- with hypercalciuria and nephrocalcinosis
- mutations in Claudin 16 and 19
Describe Mg handling in TALH
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Main mechanism of Mg handling in the DCT
Transcellular route
Describe Mg handling in the DCT
- The process is coupled to potassium and sodium transport
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The transcellular route of magnesium transport in the DCT is in part controlled by
Mg and loop diuretics
Loop diuretics inhibit NKCC2 and cause hypomagnesemia
Bartter syndrome and Mg
mutations in ROMK, NKCC2, CIC-Kb, Barttin and CaSR
- Metabolic alkalosis
- hypokalemia
- normo-hypomagnesemia
- hypercalciuria
Familial hypomagnesemia etiology
Mutations in Claudin 16 and 19
Familial hypomagnesemia manifestation
hypomagnesemia with hypercalciuria and nephrocalcinosis
Main mechanism for Mg handling in the DCT
Transcellular root
Describe Mg handling in the DCT
- Process is coupled to potassium and sodium transport
- Epidermal growth factor is an important controller of the process
- Anti-EGF drugs in oncology are associated with hypomagnesemia
Thiazide diuretics and Mg
Thiazide diuretics act on the NCC channel and produce hypomagnesemia
Anti-EGF drugs and Mg
Since EGF is an important controller of the transcellular reabsorption route in the DCT, Anti-EGF drugs used in oncology are associated with hypomagnesemia
Factors that increase Mg absorption
9 listed
- Dietary restriction
- PTH
- Glucagon
- Calcitonin
- Vasopressin
- Aldosterone
- Amiloride
- Metabolic alkalosis
- EGF
Factors that decrease Mg absorption
8 listed
- Hypermagnesemia
- metabolic acidosis
- Phosphate depletion
- Loop diuretics and thiazides
- Aminoglycosides and amphotericin
- Chemotherapy (cisplatin)
- Immunosuppressants
Dietary restriction of Mg result on Mg absorption
Increase
PTH result on Mg absorption
Increase
Glucagon result on Mg absorption
Increase
Calcitonin result on Mg absorption
increase
Vasopressin result on Mg absorption
Increase
Aldosterone result on Mg absorption
increase
Amiloride result on Mg absorption
Increase
Metabolic alkalosis result on Mg absorption
Increase
EGF result on Mg absorption
Increase
Hypermagnesemia result on Mg absorption
decrease
Metabolic acidosis result on Mg absorption
Decrease
Phosphate depletion result on Mg absorption
decrease
Loop diuretics and thiazides result on Mg absorption
decrease
Aminoglycosides result on Mg absorption
decrease
Loop diuretics result on Mg absorption
decrease
Thiazides result on Mg absorption
decrease
Amphotericin result on Mg absorption
decrease
Chemotherapy (cisplatin) result on Mg absorption
decrease
Cisplatin result on Mg absorption
Decrease
Immunosuppressants result on Mg absorption
decrease
Clinical disorders of magnesium
- Hypermagnesemia
- Hypomagnesemia
Hypermagnesemia etiology
- increased intake such as by antacids (milk of magnesia), enemas, IV therapy with magnesium sulfate (pre-eclampsia)
- decreased renal filtration
Hypomagnesemia etiology
- Reduced intake
- Redistribution
- Reduced absorption (proton pump inhibitors)
- Renal magnesium wasting (drug-induced losses, hormone-induced magnesuria, ion or nutrient-induced tubular losses)
Common causes of hypomagnesemia
- if on diuretics blame diuretics
- If on Proton pump inhibitors blame PPIs
- not on diuretics or PPI then look for alcohol
Common causes of hypermagnesemia
- Will have pre-eclampsia and you will be asked to either give or withhold magnesium
- If not pregnant will have kidney disease
- If they are taking antacids they may have milk-alkali syndrome
Milk-Alkali Syndrome
- MAS: consists of hypercalcemia, various degrees of renal failure and metabolic alkalosis due to ingestion of large amounts of calcium and absorbate alkali.
- Magnesium may be elevated either because of renal impairment OR because the “alkali” was Milk of Magnesia
Hypermagnesia 5-7 mg/dL
- Nausea
- vomiting
- Lethargy
- diminished reflexes
Hypermagnesia 7-12 mg/dL
- Somnolence
- hypocalcemia
- absent reflexes
- bradycardia
- ECG changes (wide QRS, 1st-degree AVB)
Hypermagnesia > 12 mg/dL
- muscle paralysis
- respiratory muscle paralysis
- complete heart block
- cardiac arrest
Manifestations of hypomagnesemia
- Neuromuscular hyper-excitability
- Cardiovascular manifestations
- abnormalities of calcium metabolism
- Hypokalemia (in patients with preserved renal function or moderate renal insufficiency one cannot correct hypokalemia without replacing concurrent magnesium deficit (EXAM RELEVANT POINT))
Tx of hypermagnesemia: normal or near normal renal function (eGFR>45)
- Normal/near normal renal function (eGFR>45) (stop Mg and give furosemide)
Tx of hypermagnesemia: moderate renal function (eGFR: 15-45)
Stop Mg and give furosemide and IV fluids
Tx of hypermagnesemia: Severe renal impairment GFR: <15
may require dialysis
Tx of Mg associated arrhythmias
Give IV 100-200mg elemental calcium
Question 1
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Question 2
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Question 3
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Question 4
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Question 6
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Question 7
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Question 8
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Carters vs Gitelman’s
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Question 9
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Question 10
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Question 11
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Question 12
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