A comprehensive review for deep learners or medical students

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