magnasium

1. Magnesium Disorders
Md. Kamruzzaman
Resident, Phase A
GHPD

2. Over view
 Physiology of Mg
 Hypomagnesemia
Cause of Hypomagnesemia
Approach to Hypomagnesemia
Renal and extrarenal Magnesium wasting
Clinical feature of Hypomagnesemia
Treatment of Hypomagnesemia
 Hypermagnesemia
Cause
Clinical feature
Management

3. Physiology
 Mg is 2nd most abundant intracellular ion
 Bone – 50-60% (reservoir for maintaining extracellular and
intracellular Mg) Circulation <1%
 Most intracellular Mg found in nucleus, mitochondria,
endoplasmic/sarcoplasmic reticulum and the cytoplasm.
 Serum concentration is between 1.5 and 2.3 mg/dl
 Total Mg = Ionized and bound (albumin)
 Ionized Magnesium ~70% of total
 kidneys excrete about half the daily intake of magnesium, which is
about 125 to 150 mg/day.

4. Function of Magnesium
 Magnesium is a cofactor in more than 300 enzyme systems that
regulate diverse biochemical reactions in the body
 It helps to maintain normal nerve and muscle function.
 Supports a healthy immune system,
 Helps bones remain strong.
 It also helps adjust blood glucose levels.
 Helps in blood pressure regulation.
 Magnesium is required for energy production, oxidative
phosphorylation, and glycolysis.
Guyton and Hall Textbook of Medical Physiology 12th Ed

5. Dietary Source
* Most dietary Mg absorption occurs in the ileum and jejunum (upto 65%)

6. Hypomagnesaemia
 Hypomagnesaemia is defined as existing when plasma
magnesium concentrations are below the reference range of
0.75–1.0 mmol/L (1.5–2.0 mEq/L).
Davidson's Principles and Practice of Medicine 24th Edition

7. Davidson's
Principles and
Practice of Medicine
24th Edition

8. Approach to Hypomagnesemia
 Renal magnesium excretion should be reduced in patients with
plasma magnesium depletion. Thus, measurement 24-hour urinary
magnesium excretion or the fractional excretion of magnesium
(FEMg) on a random urine specimen.
 A daily excretion of more than 10 to 30 mg (in a 24-hour urine specimen) or a
fractional excretion of magnesium above 3 to 4 percent in a person with
hypomagnesemia and normal kidney function indicates renal magnesium
wasting.
 By contrast, a 24-hour urinary magnesium excretion less than 10 mg or a
fractional excretion of magnesium less than 2 percent usually indicates an
extrarenal source of magnesium losses (typically gastrointestinal).
UpToDate

9. Renal magnesium wasting
Polyuria
 Osmotic diuresis
 Diabetic ketoacidosis
 Polyureic phase of recovery from acute renal failure
 Recovery from ischemic injury in a transplanted kidney
 Post obstructive diuresis
Diuretics
 Hypomagnesemia is a frequent finding in patients receiving long-term loop
diuretic therapy.
 Loop diuretics' inhibition of the NaK2CI co transporter abolish the
transepithelial potential differences a result, magnesium resorption is
inhibited.
UpToDate

10. Renal magnesium wasting
Extracellular Fluid Volume Expansion
 Mg reabsorption is passive and is driven by the reabsorption of
sodium and water in the PCT.
 Decreases proximal sodium and water reabsorption - hence
reducing magnesium reabsorption.
Hypercalcemia
 Elevated serum ionized Ca levels (malignant bone metastases)
directly induce renal Mg wasting.
UpToDate

11. Renal magnesium wasting
Inherited Renal
Magnesium-
Wasting Disorders

12. Renal magnesium wasting
Inherited Renal Magnesium-Wasting Disorders.
Familial hypercalciuric hypomagnesemia with nephrocalcinosis
 FHHNC is a rare autosomal recessive tubular disorder
 The primary defect-impaired tubular reabsorption of magnesium and
calcium in the thick ascending limb.
Familial Hypomagnesemia with Secondary Hypocalcemia (HSH)
 Rare autosomal recessive
 Mutations in TRPM6 gene
UpToDate

13. Renal magnesium wasting
Drugs
 Aminoglycosides
 Aamphotericin B
 Diuretics
 Antineoplastic drugs (cisplatin and cetuximab)
 Calcineurin inhibitors (tacrolimus)

14. Extrarenal Causes
Nutritional Deficiency
 Severe dietary insufficiency is extremely difficult - nearly all
foods contain significant amounts of Mg.
 Mg deficiency of nutritional origin occurs particularly in two
clinical settings: alcoholism and parenteral feeding
 20% to 25% of alcoholic patients are hypomagnesemic
UpToDate

15. Extrarenal Causes
Intestinal Malabsorption & Diarrhea
 Generalized malabsorption syndromes (Celiac disease,
Whipple's disease, IBD) - associated with intestinal Mg wasting
and Mg deficiency
 In fat malabsorption (steatorrhea) - the fatty acids in the stools
combine with magnesium to form non-absorbable soaps
(saponification).
 Mg deficiency was a common complication of bariatric surgery
by jejunoileal bypass.
 Proton pump inhibitors have been reported to cause
hypomagnesemia in some patients, the evidence suggests
toward intestinal Mg malabsorption.
UpToDate

16. Extrarenal Causes
Cutaneous Losses
 Sweat contains up to 0.5 mg/dL of Mg.
 Prolonged intense exertion can result in a fall of serum Mg
 Hypomagnesemia occurs in 40% of patients with severe burn
injuries.
Redistribution to Bone Compartment
 Hypomagnesemia may accompany profound hypocalcemia of
hungry bone syndrome in hyperparathyroidism.
UpToDate

17. Clinical feature
Neuromuscular manifestations
including neuromuscular hyperexcitability tremor, tetany, convulsions,
weakness, apathy, delirium and coma.
Tetany – Patients may develop positive Trousseau and Chvostek signs,
muscle spasms, and muscle cramps.
Seizures – Hypomagnesemic patients can develop seizures that may be
generalized and tonic clonic in nature or multifocal.
Involuntary movements – Patients with hypomagnesemia can manifest
athetoid or choreiform movements.
UpToDate

18. Clinical feature
Cardiovascular manifestations
 including widening of the QRS and peaking of T waves with
moderate magnesium depletion, and widening of the PR
interval, inversion of T waves, atrial and ventricular arrhythmias
with severe depletion.
 Frequent atrial and ventricular premature systoles may be
present, and sustained atrial fibrillation may also develop.
UpToDate

19. Clinical feature
Skeletal System
 Hypomagnesemia decreased skeletal growth and increased
fragility.
 Mg is mitogenic for bone cell growth, deficiency may directly
result in a decrease in bone formation.
 Mg deficiency may result in a fall in both serum PTH and
Vitamin D levels.
UpToDate

20. Clinical feature
Electrolyte Imbalance
 Patients with hypomagnesemia are frequently also hypokalemic.
 Hypomagnesemia by itself can induce hypokalemia (release of
inhibition of ROMK channels)
 Hypocalcemia occurs in 50% pts - impairment of PTH secretion
by Mg deficiency.
UpToDate

21. Treatment
Patients with severe symptoms: Symptomatic patients, such as those
with tetany, arrhythmias, or seizures should receive intravenous (IV)
magnesium. Such patients should have continuous cardiac monitoring.
 In the acute setting, hemodynamically unstable patients (including
those with arrhythmias) 1 to 2 grams of magnesium sulfate can be given
initially over 2 to 15 minutes . If the patient remains hemodynamically
unstable after this initial bolus, a repeat bolus can be administered.
UpToDate

22. Treatment
 Patients with no or minimal symptoms — If available and
tolerable, oral replacement should be given to the hypomagnesemic
patient with no or minimal symptoms. However, many patients are
unable to take oral magnesium or have side effects such as
gastrointestinal discomfort and diarrhea. Thus, many hospitalized
patients with hypomagnesemia are given IV rather than oral
magnesium supplementation even if symptoms are minimal or
absent.
UpToDate

23. Treatment
For routine IV repletion or maintenance in the inpatient setting
 If the plasma magnesium is less than 0.4 mmol/L, give 4 to 8
grams of magnesium sulfate over 12 to 24 hours and repeat as
needed.
 If the plasma magnesium is 0.4 to 0.6 mmol/L, give 2 to 4 grams
of magnesium sulfate over 4 to 12 hours.
 If the plasma magnesium is 0.7 to 0.8 mmol/L, give 1 to 2 grams
of magnesium sulfate over 1 to 2 hours.
 In stable hospitalized patients receiving magnesium therapy, the
plasma magnesium concentration should be measured daily or
more frequently if indicated. Repeat doses are given based upon
the follow-up measurement.
UpToDate

24. Treatment
Patients with renal function impairment
 Creatinine clearance less than 30 mL/min/1.73 m2 are at risk for
severe hypermagnesemia. Thus, reduction of IV magnesium dose is
needed in such patients by 50 percent or more and closely monitoring
magnesium concentrations.
 Patient who has reduced kidney function (ie, estimated glomerular
filtration rate of 15 to 30 mL/min/1.73 m2) and severe
hypomagnesemia should be treated with 2 to 4 grams of IV
magnesium sulfate given slowly over 4 to 12 hours. The plasma
magnesium should be checked prior to subsequent doses and daily.
UpToDate

25. Treatment
Things to be consider
 If GFR is reduced, the infusion rate should be lowered by 50–75%.
 It is important to consider the need for calcium, potassium,
and phosphate supplementation in patients with hypomagnesemia.
 Vitamin D deficiency frequently coexists and should be treated with
oral or parenteral vitamin D.
 If hypomagnesaemia is caused by diuretic treatment, adjunctive use of a
potassium-sparing agent such as amiloride or triamterene can also help by
reducing magnesium loss into the urine.
 In severely hypomagnesemic patients with concomitant hypocalcemia and
hypophosphatemia, administration of IV magnesium alone may worsen
hypophosphatemia, provoking neuromuscular symptoms or rhabdomyolysis,
due to rapid stimulation of PTH secretion. This is avoided by administering
both calcium and magnesium.
Harrison’s principles of internal medicine, 20th edition

26. Duration of therapy
 Serum magnesium levels usually rise quickly with therapy, but
intracellular stores take longer to replete. It is therefore advisable
in patients with normal kidney function to continue magnesium
repletion for at least one to two days after the serum magnesium
concentration normalizes.
UptoDate

27. Hypermagnesemia
 This is a much less common abnormality than hypomagnesaemia.
 Hypermagnesemia is rarely seen in the absence of renal insufficiency, as
normal kidneys can excrete large amounts of magnesium.
 Predisposing conditions include acute kidney injury, chronic kidney disease and
adrenocortical insufficiency.
 Extensive soft tissue injury or necrosis can also deliver large amounts of
magnesium into the ECF in patients who have suffered trauma, shock, sepsis,
cardiac arrest or severe burns.
 The condition is generally precipitated in patients at risk from an increased
intake of magnesium, or from the use of magnesium-containing medications,
such as antacids, laxatives and enemas.
Davidson's Principles and Practice of Medicine 24th Edition
Harrison’s principles of internal medicine, 20th edition

28. Causes
Harrison’s principles of internal medicine, 20th edition

29. Clinical features

30. Clinical features
 The most prominent clinical manifestations of hypermagnesemia are
vasodilation and neuromuscular blockade, which may appear at serum
magnesium concentrations
>2 mmol/L
 Nausea, lethargy, and weakness may progress to respiratory failure,
paralysis, and coma, with hypoactive tendon reflexes, at serum
magnesium levels >4 mmol/L.
 Hypotension that is refractory to vasopressors or volume expansion
may be an early sign.
 Other findings may include gastrointestinal hypomotility or ileus; facial
flushing; pupillary dilation; paradoxical bradycardia; prolongation of PR,
QRS, and QT intervals; heart block; and, at serum magnesium levels
approaching 10 mmol/L.
Harrison’s principles of internal medicine, 20th edition

31. Management
 It involves ceasing all magnesium-containing drugs and reducing dietary
magnesium intake, improving renal function if possible, and promoting
urinary magnesium excretion using a loop diuretic with intravenous
hydration, if residual renal function allows.
 Calcium gluconate may be given intravenously to ameliorate cardiac effects.
 Use of magnesium-free enemas may be helpful in clearing ingested
magnesium from the gastrointestinal tract. Vigorous IV hydration should be
attempted, if appropriate.
 Dialysis may be necessary in patients with poor renal function. (Severe
hypermagnesemia (>2 mmol/L, Serious cardio-vascular or neuro-musclar
symptoms)
Davidson's Principles and Practice of Medicine 24th Edition
Harrison’s principles of internal medicine, 20th edition

32. Source
 Davidson's Principles and Practice of Medicine 24th Edition
 Harrison’s principles of internal medicine, 20th Edition
 Guyton and Hall Textbook of Medical Physiology 12th Edition
 UpToDate

33. Thank You