Magnesium

Magnesium: the forgotten electrolyte

Joyce Wu, Registrar, and Andrew Carter,
Director, Department of Chemical Pathology,
Queensland Health Pathology Service,
Brisbane (Aust Prescr 2007;30:102–5)
 Units of measurement
● the valence of Mg = +2
● mol weight of Mg = 24.3
● mmol = mol weight in mg
● mEq = mmol : valence
● 1 mmol Mg = 24.3 mg
● 1 mEq Mg = 0.50 mmol
● 1L = 10 dL

1 meq/L Mg = 0.50 mmol/L = 12.15 mg/L

= 1.215 mg/dL
The normal range of plasma Mg concentration
= 1.4 to 1.7 meq/L
= 0.70 to 0.85 mmol/L
= 1.7 to 2.1 mg/dL
 Magnesium balance
● Mg dietary sources : whole grain cereals, green
leafy vegetables, legumes, soybeans, nuts, dried
fruit, animal protein and seafood
● The average daily magnesium intake 360 mg
(15 mmol)
● One-third absorbed in the small bowel through
saturable transport system and passive
diffusion
● The intestinal secretion ± 40 mg (1.7 mmol)
● The large bowel absorption ± 20 mg (0.8 mmol)
● Hypomagnesemia stimulates absorption and
hypermagnesemia inhibits
● Daily net uptake balance by the urinary
excretion of ± 100 mg (4.1 mmol)
Magnesium absorption pathways in intestine
Magnesium balance
 Magnesium homeostasis
 The body contains 21–28 grams of Mg (0.864–
1.152 mol); 53% is located in bone, 19% in non-
muscular tissue, and 1% in extracellular fluid
 Normal plasma Mg = 1.7–2.3 mg/dl (0.69–
0.94 mmol/l); majority of serum Mg bound to :
ATP; ADP; proteins (33 %) and citrate; 5–10%
"free" Mg - essential in regulating IC Mg
 The total intracellular Mg content ± 8 to 10
mmol/L (10 to 20 meq/L); most bound to ATP
and other IC nucleotides and enzyme complexes
 Mg homeostasis comprises 3 systems: kidney,
small intestine, and bone
 Renal handling of magnesium
● ± 80 percent of total plasma Mg (± 2400 mg ) is
filtered at the glomerulus daily; 5% (120 mg)
excreted through urine
● 15 to 25 % of the ultrafiltrable Mg reabsorbed
passively in the proximal tubule; 5 to 10
percent in the distal tubule
● The major site of reabsorbtion is in the thick
ascending limb of the loop of Henle (60 to 70
percent)
● Transport occurring by paracellular diffusion
and electrical gradient
Magnesium reabsorption along the nephron
Mg2+ transport pathways in the loop of Henle
 Ion transport pathways
in the distal covoluted tubule
 Regulation of plasma Mg concentration
● Mg is treated by the body as an orphan
● No hormones that modulate urinary Mg excretion
● Bone (the principal reservoir of Mg), does not readily
exchange with circulating Mg
● Plasma magnesium is the main regulator; hyper-
magnesemia inhibits, while hypomagnesemia
stimulates
● Plasma Mg falls rapidly with negative Mg balance,
leading to a marked reduction in Mg excretion
● In acute phase of Mg deficiency, absorption in the
distal small intestine and resorption in the kidneys
tubular are increase; when condition persists, serum
Mg corrected with Mg from bone tissue
● No protection against hypermagnesemia with loss of
renal function; continued intake leads to Mg
retention
 Factors alter magnesium transport
● Calcium concentration : hypercalcemia inhibits
Mg (and Ca) reabsorption, leading to hyper-
magnesuria and hypercalciuria
● Hormones : PTH, calcitonin, glucagon, AVP and
the beta-adrenergic agonists
● Other factors : Metabolic alkalosis - stimulates;
metabolic acidosis, hypokalemia and
phosphate depletion - inhibit reabsorption
 Magnesium function (1)
 Cofactor in more than 300 enzyme-regulated
reactions (most importantly ATP reactions)
 Direct effect on Na, K and Ca channels
 Inhibit K channel efflux; hypomagnesemia
resulting hypokalaemia
 Inhibit release Ca from the sarcoplasmic
reticulum; hypomagnesemia results increased IC
Ca level – inhibits PTH -- hypoparathyroidism –
hypocalcemia; skeletal and muscle receptors
less sensitive to PTH
 Needed for the adequate function of the
Na+/K+-ATPase pumps in cardiac myocytes
 Lack of Mg increases K loss – increase IC K loss --
decrease IC K – tachycardia
 Magnesium function (2)
 Indirect antithrombotic effect upon platelets
and endothelial function
 Increases prostaglandins, decreases
thromboxane, and decreases angiotensin II
 Microvascular leakage and vasospasm through
its function similar to Ca channel blockers
 Convulsions are the result of cerebral
vasospasm
 Exerts a bronchodilatatory effect, probably by
antagonizing Ca-mediated bronchoconstriction
Magnesium imbalance

● Hypomagnesemia
● Hypermagnesemia
 Hypomagnesemia
● Occurring in up to 12 % of hospitalized
patients
● Rises to 60 - 65 % in ICU patients
● Induced by gastrointestinal or renal
losses
● Often associated with hypokalemia and
hypocalcemia
 Gastrointestinal losses
● Dietary deprivation
● Acute or chronic diarrhea
● Malabsorption and steatorrhea
● Small bowel bypass surgery
● Familial disorder (defect in magnesium
absorption)
● Acute pancreatitis
● Chronic use of proton pump inhibitors
(i.e. Omeprazole)
 Renal losses
● Medications : loop and thiazide diuretics,
aminoglycoside, amphotericin B, cyclo-
sporine
● Volume expansion
● Alcohol
● Uncontrolled diabetes mellitus
● Hypercalcemia
● Other acquired tubular dysfunction
● Familial renal magnesium wasting : i.e.
Gitelman syndrome, etc
 Miscellaneous
● Intravascular chelation
● “Hungry bone” syndrome
(parathyroidectomy)
● High-fat diet to induce ketogenesis
(therapy of intractable epilepsy)
● Leptospirosis
 Evaluation
 The cause can usually be obtained from the
history
 Measuring the 24-hour urinary mg excretion or
the fractional excretion of Mg on a random urine
specimen

 A 24-hour Mg excretion > 10 to 30 mg, or FEMg >

2 % and normal renal function - indicates renal
Mg loss
 A 24-hour excretion < 10, or FEMg < 2 % -
indicates extra renal Mg loss (gastrointestinal)
 The major clinical manifestations of
hypomagnesemia
Major Clinical manifestations
Neuromuscular neuromuscular hyperexcitability (eg,
tremor, tetany, convulsions), weakness,
apathy, delirium, and coma
Cardiovascular widening of the QRS and peaking of T
waves with moderate magnesium
depletion, and widening of the PR
interval, diminution of T waves, and
atrial and ventricular arrhythmias with
severe depletion
Calcium metabolism hypocalcemia, hypoparathyroidism,
parathyroid hormone (PTH) resistance,
and decreased synthesis of calcitriol
Potassium Hypokalemia
 Treatment
 Oral repletion
 Intravenous repletion in severe symptoms
 Intravenous repletion in stable patients
 Correction of the underlying disease
 Oral repletion
● Hypomagnesemic patient with no or minimal
symptoms
● Side effects : GI discomfort and diarrhea
● Daily dose (in normal renal function) : 240 to
1000 mg (20 to 80 meq [10 to 40 mmol]) of
elemental Mg in divided doses
● Sustained release preparations : Mg chloride and
Mg L-lactate
● Mg oxide 800 to 1600 mg (20 to 40 mmol [40 to
80 meq]) daily in divided doses may be used for
moderate to severe hypomagnesemia
● Diarrhea frequently occurs with Mg oxide
therapy
 Intravenous repletion in
severe symptoms
● Hemodynamically unstable : 1 to 2 g Mg sulfate (8 to
16 meq [4 to 8 mmol]) given initially over 2 to 15 min
● Hemodynamically stable : 1 to 2 g of Mg sulfate (8 to
16 meq [4 to 8 mmol]) in 50 to 100 mL of D5W given
initially over 5 to 60 min followed by an infusion
● In patients with renal insufficiency (creatinine
clearance less than 30 mL/min/1.73m2), reduce the iv
dose by 50 percent or more and closely monitoring
Mg concentrations
● In children, use a slow infusion of Mg sulfate 25 to 50
mg/kg (0.2 to 0.4 meq/kg [0.1 to 0.2 mmol/kg]) with
a maximum single dose of 2 g (16 meq [8 mmol])
 Intravenous repletion in stable
hospitalized patients
Plasma Mg Regimen
< 1.0 mg/dL (0.4 4 to 8 grams (32 to 64 meq [16 to 32
mmol/L or 0.8 meq/L) mmol]) over 12 to 24 hours, and
repeat as needed
1.0 to 1.5 mg/dL (0.4 2 to 4 grams (16 to 32 meq [8 to 16
to 0.6 mmol/L or 0.8 to mmol]) over 4 to 12 hours
1.2 meq/L)
1.6 to 1.9 mg/dL (0.7 1 to 2 grams (8 to 16 meq [4 to 8
to 0.8 mmol/L or 1.4 to mmol]) over one to two hours
1.6 meq/L)
 Correction of the underlying disease
● The underlying disease should be corrected if
possible
● Hypomagnesemia induced by a thiazide or loop
diuretic : add Amiloride, potassium-sparing
diuretic; decrease Mg excretion by increasing
reabsorption in the distal nephron
● Amiloride also helpful in persistent urinary
magnesium wasting such as Bartter or Gitelman
syndrome
Hypermagnesemia
 Causes of hypermagnesemia (1)

Renal Hypermagnesemia can be seen in 10 to

insufficiency 15 percent of hospitalized patients,
usually in the setting of renal failure
Magnesium Parenteral Mg is commonly used to
infusion decrease neuromuscular excitability in
pregnant women with severe
preeclampsia or eclampsia
Oral ingestion accidental poisoning with Epsom salts
(almost 100 percent Mg sulfate), in
laxative abusers, during treatment drug
overdoses using Mg as a cathartic,
antacid >>, Dead Sea water poisoning
 Causes of hypermagnesemia (2)

Oral ingestion accidental poisoning with Epsom salts

(almost 100 percent Mg sulfate), in
laxative abusers, during treatment drug
overdoses using Mg as a cathartic,
antacid >>, Dead Sea water poisoning
Magnesium absorbed from the large bowel
enemas following a Mg enema; 400 to 800
mmol of Mg sulfate per rectum can raise
the plasma Mg to 6 - 16 meq/L (7.2 to
19.2 mg/dL or 3 to 8 mmol/L)
Miscellaneous primary hyperparathyroidism, familial
(mild) hypocalciuric hypercalcemia, diabetic
ketoacidosis, hypercatabolic states,
lithium ingestion, milk-alkali syndrome,
adrenal insufficiency
 Hypermagnesemia effects (1)
Effects Clinical manifestation
Neuromuscular : Diminished/loss deep tendon
Decreases impulse reflexes, somnolence, muscle
transmission across the paralysis, flaccid quadriplegia,
neuromuscular junction decreased respiration, apnea,
producing a curare-like effect fixed and dilated pupils
mimicking a central brain–stem
herniation syndrome
Cardiovascular : Bradycardia and hypotension,
Ca channel blocker both ECG changes : prolongation of
extracellularly and the P-R interval, increase QRS
intracellularly; intracellular duration, increase Q-T interval.
Mg blocks several cardiac K Complete heart block and
channels cardiac arrest
 Hypermagnesemia effects (2)
Effects Clinical manifestation
Hypocalcemia : Transient and no symptoms;
Inhibit the secretion ECG abnormalities associated
parathyroid hormone, with hypocalcemia
reduction plasma Ca
concentration
Other : Nausea, vomiting, and flushing,
Non-specific symptoms hyperkalemia and decreased
urinary K excretion due to Mg-
induced blockade of renal K
channels
 The relation between clinical manifestations and
the degree of hypermagnesemia
Plasma magnesium Clinical manifestations
concentration
4 to 6 meq/L (4.8 to 7.2 nausea, flushing, headache,
mg/dL or 2 to 3 mmol/L) lethargy, drowsiness, and
diminished deep tendon reflexes
6 to 10 meq/L (7.2 to 12 somnolence, hypocalcemia,
mg/dL or 3 to 5 mmol/L) absent deep tendon reflexes,
hypotension, bradycardia, and
ECG changes
> 10 meq/L (12 mg/dL or 5 muscle paralysis, respiratory
mmol/L) paralysis, complete heart block,
and cardiac arrest; in most cases,
respiratory failure precedes
cardiac collapse
 Hypermagnesemia treatment (1)
● Most symptomatic cases can be
prevented by anticipation
● Patients in renal failure should not
receive Mg-containing medication
● Patients receiving parenteral Mg should
be monitored at least daily
● If renal function is normal, cessation of
Mg therapy will allow prompt
restoration of normal Mg levels
● Loop (or even thiazide) diuretics can be
used to increase renal excretion of Mg
 Hypermagnesemia treatment (2)
● In CKD (eGFR between 15 and 45
mL/min/1.73 m2) and mild AKI, initial
treatment : iv isotonic fluids (eg, NS) plus
a loop diuretic (eg, furosemide)
● Dialysis often required for severe or
symptomatic hypermagnesemia in
advanced CKD or in moderate AKI
patients
● Give 100 to 200 mg of elemental Ca (iv)
over 5 to 10 min, as Mg antagonist to
reverse the neuromuscular and cardiac
effects of hypermagnesemia