Hypomagnesaemia

Note: Davidson's Principles and Practice of Medicine is not available in this library. The following is a detailed, clinically structured account drawn from Rosen's Emergency Medicine, Brenner & Rector's The Kidney, Mulholland & Greenfield's Surgery, and related authoritative textbooks - the clinical content aligns closely with what Davidson's covers.

Definition and Normal Values

• Normal serum magnesium: 1.5 - 3.0 mEq/L (0.75 - 1.0 mmol/L)
• Hypomagnesaemia is defined as serum Mg < 1.5 mEq/L (< 0.75 mmol/L)
• Symptoms typically appear when levels fall below 1.2 mEq/L
• Severe hypomagnesaemia: < 1.0 mEq/L (< 0.5 mmol/L) - requires IV replacement

Magnesium Physiology - Brief Review

1. Ionized (free) - biologically active (~55%)
2. Protein-bound (~30%)
3. Complexed to anions (~15%)

Renal Handling

• 95-97% of filtered magnesium is reabsorbed along the nephron
• Proximal tubule: 5-15% reabsorption
• Thick ascending limb (TAL): 50-70% - passive paracellular pathway (via claudin-16/claudin-19)
• Distal convoluted tubule (DCT): 5-10% - this is the fine-tuning segment via TRPM6 channel (active transcellular)
• In hypomagnesaemia, normal kidneys can reduce urinary excretion to as little as 0.5% of filtered load

Clinical Assessment of Renal Wasting

• Fractional excretion of magnesium (FEMg) normally < 2% in hypomagnesaemia
• FEMg > 4% = renal magnesium wasting
• Formula: FEMg = (urine Mg × serum Cr) / (0.7 × serum Mg × urine Cr) × 100

Causes of Hypomagnesaemia

1. Dietary / Reduced Intake

• Chronic protein-calorie malnutrition
• Prolonged IV fluid replacement without magnesium supplementation
• Starvation, anorexia nervosa
• Foods rich in magnesium: green vegetables, legumes, fruits, shellfish, fresh meat, cocoa

2. Gastrointestinal Losses

• Chronic diarrhoea (most common GI cause)
• Malabsorption syndromes: coeliac sprue, short bowel syndrome
• Inflammatory bowel disease (Crohn's, ulcerative colitis)
• Vomiting
• Pancreatitis
• Nasogastric suction
• Post-operative bowel resection

3. Renal Wasting (most common in hospitalised patients)

Drug-induced:

Non-drug renal causes:

• Post-obstructive polyuria
• Recovery from acute tubular necrosis
• Renal tubular acidosis
• Primary hyperaldosteronism (aldosterone increases renal Mg loss)

4. Endocrine / Metabolic

• Diabetes mellitus (osmotic diuresis)
• Diabetic ketoacidosis (DKA)
• Hyperparathyroidism
• Hyperthyroidism
• Hyperaldosteronism

5. Redistribution

• "Hungry bone" syndrome (after parathyroidectomy)
• Refeeding syndrome
• Insulin therapy
• Acute pancreatitis

6. Alcohol Use Disorder

• Reduced dietary intake
• Alcohol's diuretic effect causing renal wasting
• Episodes of pancreatitis and diarrhoea
• This is a very common and often overlooked cause

7. Genetic / Primary Inherited Disorders

Clinical Features

Neuromuscular (most prominent)

• Muscle cramps and fasciculations
• Tetany - from coexistent hypocalcaemia (Mg deficiency inhibits PTH secretion + causes PTH resistance)
• Trousseau sign - carpal spasm on BP cuff inflation
• Chvostek sign - facial twitch on tapping over facial nerve
• Hyperactive deep tendon reflexes
• Weakness, fatigue
• Seizures (severe cases)
• Ataxia, vertigo
• Dysarthria and dysphagia (oesophageal dysmotility)
• Depression, agitation, confusion

Cardiovascular

• QT interval prolongation (most important ECG change)
• PR interval prolongation
• ST segment depression
• Flattening/widening of T waves
• U waves (often due to coexistent hypokalaemia)
• Decreased deep tendon reflexes (severe)
• Arrhythmias:
  • Atrial fibrillation
  • Multifocal atrial tachycardia
  • Premature ventricular complexes
  • Ventricular tachycardia
  • Torsades de pointes (characteristic and dangerous)
  • Ventricular fibrillation
• Decreased vascular tone
• Impaired cardiac contractility

Metabolic Consequences

1. Hypokalaemia - Mg is needed for Na+/K+-ATPase function; ~50% of hypokalaemic patients are also hypomagnesaemic; hypokalaemia refractory to K+ replacement should prompt Mg check
2. Hypocalcaemia - Mg deficiency inhibits PTH secretion AND causes PTH resistance in target tissues
3. These electrolyte abnormalities worsen each other and must all be corrected together

Investigation / Diagnosis

• Serum magnesium - routine measurement; note: serum level may be normal despite total body deficit because Mg is released from bone
• Urine magnesium or FEMg - to distinguish renal vs. non-renal losses:
  • FEMg < 2%: extra-renal cause (GI losses, poor intake)
  • FEMg > 4%: renal wasting
• Serum calcium - check for coexistent hypocalcaemia
• Serum potassium - check for coexistent hypokalaemia
• ECG - QT prolongation, arrhythmias
• Assess for underlying cause (medications, alcohol history, GI disease, renal function)

Management

1. Mild / Asymptomatic Hypomagnesaemia (Mg > 1.0 mEq/L)

• Oral magnesium supplementation
  • Magnesium oxide 400 mg twice daily
  • Alternatives: magnesium chloride, magnesium gluconate, magnesium hydroxide (milk of magnesia)
  • Note: oral absorption is variable; doses > 80 mEq/day may cause catharsis
• Address underlying cause

2. Moderate Hypomagnesaemia (Mg 0.5-1.0 mEq/L) - Symptomatic

• IV magnesium sulfate
  • Loading dose: 1-2 g IV over 10-60 minutes
  • Maintenance: 0.5-1 g/hr until symptoms resolve
  • 1 g IV magnesium raises serum Mg by ~0.15 mEq/L within 18-30 hours
• Normal renal function required for safe infusion

3. Severe / Life-threatening (Mg < 1.0 mEq/L, haemodynamic instability, or cardiac arrest)

• IV magnesium sulfate bolus - 1-2 g IV push or over 5 minutes
• For Torsades de Pointes: 2 g IV over 5 minutes
• For cardiac arrest: 1-2 g magnesium sulfate IV push
• Maximum safe infusion rate (non-emergency): 150 mg/min

4. Special Considerations

• Magnesium replacement should accompany potassium replacement in hypokalaemia
• In post-transplant patients with severe hypomagnesaemia (<1.0 mg/dL), IV Mg is especially important in those with CAD, arrhythmias, or on digoxin
• Renal impairment: reduce dose and infusion rate; monitor for hypermagnesaemia
• Monitor for adverse effects of rapid IV replacement: decreased deep tendon reflexes, respiratory depression, heart block

5. Monitoring After Replacement

• Serum Mg often falls again after IV replacement because renal excretion increases
• Ongoing supplementation (oral or IV as appropriate) is needed
• Correct any coexisting hypokalaemia and hypocalcaemia simultaneously

Disposition

Key Clinical Pearls

1. Always check Mg in refractory hypokalaemia - replacing K without fixing Mg will fail
2. Hypomagnesaemia and hypocalcaemia often coexist - if tetany doesn't respond to calcium, consider hypomagnesaemia
3. Torsades de pointes - IV magnesium is first-line treatment regardless of serum Mg level
4. Loop and thiazide diuretics are the most common drug causes in outpatients
5. Alcohol use disorder is an extremely common and underrecognised cause
6. PPIs - long-term use, especially with diuretics, can cause significant hypomagnesaemia
7. Serum Mg can be normal despite total body deficit - clinical suspicion in high-risk patients is essential
8. Post-transplant patients on calcineurin inhibitors (ciclosporin, tacrolimus) are a very high-risk group