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Hypocalcaemia

Background Information

Definition

Hypocalcaemia is defined as serum adjusted calcium <2.20 mmol/L

  • Severe hypocalcaemia: serum adjusted calcium <1.90 mmol/L
  • Note the lower limit for ionised calcium is 1.15 mmol/L

Adjusted calcium takes serum albumin into account, it estimates true calcium level when albumin is abnormal.

Ionised calcium directly measures the biologically active form of calcium. This is the best marker of calcium status, typically used when accuracy is critical (e.g. critical illness, acid-base disorders)

Aetiology

Key causes:

Hypoparathyroidism – common Most commonly from surgery (parathyroidectomy / thyroidectomy)

See the Hypoparathyroidism article for more information

Hypomagnesaemia Hypomagnesaemia reduces PTH secretion (magnesium is required for PTH release) and causes PTH resistance in target tissue → hypocalcaemia

*Hypomagnesaemia can cause both hypocalcaemia and hypokalaemia

Vitamin D deficiency – common E.g. CKD, malnutrition, malabsorption, lack of sunlight exposure, dietary insufficiency

See the Vitamin D Deficiency article for more information

Calcium complex formation Severe acute pancreatitis can cause hypocalcaemia
  • The leaked pancreatic lipase breaks down fat, producing free fatty acids
  • Free fatty acids binds to calcium, forming insoluble calcium soaps

 

Rhabdomyolysis and tumour lysis syndrome

  • Both causes hyperphosphataemia (due to massive cell lysis)
  • Phosphate binds to calcium, forming calcium-phosphate complexes
  • *Rhabdomyolysis and tumour lysis syndrome causes hypocalcaemia, hyperkalaemia, and hyperphosphataemia

 

Blood transfusion (esp. massive transfusion)

  • Stored blood contains citrate (an anticoagulant)
  • Citrate can bind to free ionised calcium, forming calcium-citrate complexes
Drugs
  • Loop diuretics (**NOT thiazide diuretics, they causes hypercalcaemia)
  • Osteoporosis drugs (by inhibiting bone resorption)
    • Bisphosphonates
    • Calcitonin
    • Denosumab
  • Steroids (steroids antagonise vitamin D action)
Hyperventilation Hyperventilation → respiratory alkalosis → more ionised calcium bind albumin → less free ionised calcium

Clinical Features

Early / mild hypocalcaemia features [Ref]
  • Paraesthesia (peri-oral and in extremities)
  • Muscle cramps / stiffness / myalgia
  • Signs:
    • Chvostek sign (facial twitching upon tapping the facial nerve)
    • Trousseau sign (carpopedal spasm induced by brachial artery occlusion with a BP cuff)
Features of more severe hypocalcaemia: [Ref]
  • Laryngospasm
  • Tetany
  • Seizures
  • QTc prolongation and torsades de pointes

Hypocalcaemia increases neuromuscular excitability because ionised calcium normally stabilises voltage-gated sodium channels. When calcium levels fall, these channels open more easily, leading to spontaneous depolarisation.

Investigation and diagnosis

Initial biochemical investigations: [Ref]

  • Serum adjusted calcium and phosphate
  • Vitamin D
  • PTH
  • Magnesium
  • U&E

It is important to check magnesium levels when treating hypocalcaemia (and hypokalaemia!). If it is secondary to hypomagnesaemia, the hypocalcaemia (or hypokalaemia) will NOT correct until magnesium is replaced, regardless of how much calcium (or potassium) is given.

Management

Management depends on 1) the severity and 2) whether the patient is symptomatic or not.

Mild Hypocalcaemia (1.9-2.2 mmol/L) and Asymptomatic

Treat with oral calcium supplement (e.g. Calcichew Forte chewable) [Ref]

  • Consider vitamin D supplementation if there is evidence of vitamin D deficiency

If the patient also has magnesium deficiency → correct hypomagnesaemia first and reassess (this might be enough to correct the hypocalcaemia)

Severe Hypocalcaemia (<1.9 mmol/L) or Symptomatic

Initial management: IV calcium gluconate 10% [Ref]

  • ECG monitoring is necessary
  • Followed by a continuous IV infusion of calcium gluconate later on

If the patient also has magnesium deficiency → give IV calcium urgently and also give IV magnesium promptly.

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