This document discusses hypomagnesemia and provides information on magnesium. It notes that hypomagnesemia affects 2-20% of hospitalized patients and 50-60% of ICU patients. Symptoms include cardiovascular, neurological, and muscular issues. Causes include low intake, redistribution, gastrointestinal loss, inherited renal defects, drugs, and renal wasting. Treatment involves oral or IV magnesium supplementation depending on severity.

1. A New Perspective on
Hypomagnesemia
Taipei Veterans General Hospital, Hsin-Chu branch
Director of Nephrology
Steve Chen
Mg

2. Magnesium: forgotten cationMagnesium: forgotten cation

3. MagnesiumMagnesium
Reference Range:
1.7 – 2.1 mg/L

4. MagnesiumMagnesium
Hypomagnesemia is magnesium < 1.7
mg/dL

5. The risk of hypomagnesemiaThe risk of hypomagnesemia
2% in the general population
10-20% in hospitalized patients
In a Mayo Clinic review, magnesium levels of
less than 1.7 mg/dl were noted in 13,320 of 65,974
hospitalized adult patients (20.2%)
50-60% in intensive care unit (ICU) patients
30-80% in persons with alcoholism
25% in outpatients with diabetes

7. Hypomagnesemia: S/SHypomagnesemia: S/S
 Cardiovascular:
Coronary artery vasospasm; hyperstenion (HTN);
arrhythmia
 Neuropsychiatrical:
Tetany; tremor, myoclonus, convulsions
Ataxia, vertigo
Apathy, depression, anxiety, chronic fatigue
 Hypocalcemia:
↓PTH ; PTH resistance; ↓1,25(OH)2,vitamin D
 Hypokalemia(40 ~ 60%):
↓ ATP → ATP-inhibitable ROMK ↑; ↓ Na-K
ATPase

8. Hypomagnesemia: HeartHypomagnesemia: Heart
impairment of the membrane sodium-potassium pumpimpairment of the membrane sodium-potassium pump
Epidemiologic studies:
an association between magnesium deficiency and
coronary artery disease (CAD)
Arrhythmia:
intracellular magnesium deficiency + digoxin
excess  ↓ Na+
/K+
-ATPase  ↓ intracellular K
HTN:
↓intracellular magnesium  ↓activation of
calcium channels ↑ intracellular calcium

9. Hypomagnesemia: EKG findingsHypomagnesemia: EKG findings
Nonspecific T-wave changes - U waves
Prolonged QT and QU interval
Premature ventricular contractions -
Monomorphic ventricular tachycardia
Torsade de pointes
Ventricular fibrillation
Enhanced digitalis toxicity

10. Hypomagnesemia: NerveHypomagnesemia: Nerve
Magnesium for stabilization of the axonMagnesium for stabilization of the axon
 Tremor, fasciculations, tetany
 Convulsions
 Vertical and horizontal nystagmus
 Muscle cramps
 Hyperactive deep-tendon reflexes
 Hyperreactivity to sensory stimuli
 Positive Chvostek sign and Trousseau sign
 Acute organic brain syndromes
 Apathy
 Depression

11. ROMK in intracellular magnesiumROMK in intracellular magnesium
Huang et al: JASN 2007 (University of Texas Medical Center)Huang et al: JASN 2007 (University of Texas Medical Center)
CCT
E Na C
ROMK
Na K ATP ase
Depolarize
+
UK 5mM CK 143mM
Aldosterone
+
Na
K
Mg

12. Hypokalemia in magnesium deficiencyHypokalemia in magnesium deficiency
4040~~60%60%
Huang et al: JASN 2007 (University of Texas Medical Center)Huang et al: JASN 2007 (University of Texas Medical Center)
CCT
E Na C
ROMK
Na K ATP ase
Depolarize
+
Urine Blood
Aldosterone
+
Na
K

14. Magnesium metabolismMagnesium metabolism
 Trans-cellular shift:
influx :Na-Mg-Anion co-transporter (↑PKC)
efflux: 2Na-Mg anti-porter(↑cAMP)
 GFR: percent filtrate constant( serum Mg or Ca)
 PCT: 20 ～ 30%; passively by paracellular path
 TALH: 65 ～ 70; passively by paracellular
path(lumen positive from Na-K-2Cl driven)
 DCT:5 ～ 10%; active by transcellular( Na-Mg
exchanger, basolateral; EMgC, apical )

15. TRP M6 knockout mice modelTRP M6 knockout mice model
Transient receptor potential channels
(TRP): Gate-keeper proteins
TRP M6 in kidney: EMgC, apical
Mutations of the epithelial growth factor
(EGF) have been associated with reduced
expression of TRPM6
EGF receptor mutation→TRP M6 ↓→Mg ↓
Colorectal cancer treatment with
cetuximab/panitumumab (EGF receptor
inhibitors) → hypomagnesemia (RR = 8.6).

16. TALH
FHHNC: familial hypomagnesemia with
hypercalciuria and nephrocalcinosis
ADH : autosomal-dominant hypocalcemia
DCT
HSH: hypomagnesemia with secondary
hypocalcemia (AR)
IDH : isolated dominant hypomagnesemia

18. Magnesium assessmentMagnesium assessment
Red cell content
Mononuclear cell content
Skeletal muscle intracellular conten
24-hour urinary excretion
Fractional excretion (FE) of magnesium
Intracellular free magnesium ion
concentration with fluorescent dye or
nuclear magnetic resonance spectroscopy

19. Renal magnesium wastingRenal magnesium wasting
FEMg= Mg clearance/ Cr clearance
= UMg x PCr/﹙0.7x PMg x UCr﹚
The plasma magnesium concentration is multiplied by 0.7, since
only about 70% of the circulating magnesium is free (not bound to
albumin) and therefore capable of being filtered across the glomerulus
24-H UMg
FEMg 3%≧
24-H Umg 24 mg/D ( 2 meq or 1 mmol/D)≧

20. HypomagnesemiaHypomagnesemia
related to decreased magnesium intakerelated to decreased magnesium intake
Starvation
Alcohol dependence
Total parenteral nutrition

21. HypomagnesemiaHypomagnesemia
related to redistribution of magnesiumrelated to redistribution of magnesium
Hungry bone syndrome
Treatment of diabetic ketoacidosis
Alcohol withdrawal syndromes
Refeeding syndrome
Acute pancreatitis

22. HypomagnesemiaHypomagnesemia
related to gastrointestinal magnesium lossrelated to gastrointestinal magnesium loss
Diarrhea
Vomiting and nasogastric suction
Gastrointestinal fistulas and ostomies
Hypomagnesemia with secondary
hypocalcemia (HSH)

23. HypomagnesemiaHypomagnesemia
related to inherited renal tubular defectsrelated to inherited renal tubular defects
 Gitelman syndrome
 Classic Bartter syndrome (type III Bartter
syndrome)
 Familial hypomagnesemia with hypercalciuria and
nephrocalcinosis (FHHNC)
 Autosomal-dominant hypocalcemia with
hypercalciuria (ADHH)
 Isolated dominant hypomagnesemia (IDH) with
hypocalciuria
HSH

24. HypomagnesemiaHypomagnesemia
related to drug renal tubular lossrelated to drug renal tubular loss
 Diuretics - Loop diuretics, osmotic diuretics, and
long-term use of thiazides
 Antimicrobials - Amphotericin B,
aminoglycosides, pentamidine, and foscarnet
 Chemotherapeutic agents - Cisplatin, cetuximab
 Immunosuppressants - Tacrolimus and
cyclosporine
 Proton-pump inhibitors
 Ethanol

25. HypomagnesemiaHypomagnesemia
related to renal tubular lossrelated to renal tubular loss
Hypercalcemia
Chronic metabolic acidosis
Volume expansion
Primary hyperaldosteronism:
Chronic volume expansion, thereby increasing
magnesium excretion
Alcohol-induced tubular dysfunction (which is
reversible within 4 weeks of abstinence)
Hypophosphatemia - Unknown

26. TALH
FHHNC: familial hypomagnesemia with
hypercalciuria and nephrocalcinosis
ADH : autosomal-dominant hypocalcemia
DCT
HSH: hypomagnesemia with secondary
hypocalcemia (AR)
IDH : isolated dominant hypomagnesemia
Ca++

27. TALH DCT
Chronic metabolic acidosis  TRPM6 ↓ Mg wasting
H+

29. IV MgSO4 supplyIV MgSO4 supply
 Severe hypomagnesemia ( < 1.2 mg/dl)
 10% MgSO4 (2000G or 16.2 meq/20cc/1 amp) , 1~2G, IVF for
10~20 minutes
 Maintenance dose:
50 mEq of intravenous magnesium, given slowly over
8-24 hours
 This dose be repeated daily for 3-5 days
 Monitoring of DTR
 25-50% of the normal dose magnesium dose should be
given to patients when plasma creatinine levels are
greater than 2 mg/dL

30. PO MgO supplyPO MgO supply
Mild hypomagnesemia ( > 1.4mg/dl) :
usually asymptomatic
Mg supply:
250mg MgO =150mg Mg( 60% )
2~4 tablets daily may be sufficient
6~8 tablets should be taken daily in divided
doses for severe magnesium depletion
Mg-sparing diuretic: Amiloride use
Monitoring of diarrhea
 Green vegetables (spinach, legumes...), beans, peas , nuts,
seeds, and whole unrefined grains

31. IP MgSO4, dailyIP MgSO4, daily
Bastani et al, NDT 16: 2086-89, 2001Bastani et al, NDT 16: 2086-89, 2001
Osmolality Peritoneal
irritation score
4G in 500cc of
D5W, IVF 20m
411 10/10
2G in 500cc of
D5W, IVF 20m
344 8/10
1G in 500cc of
D5W, IVF 20m
311 1/10