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Hypocalcemia

Summary

Hypocalcemia is a state of low serum calcium levels (total Ca2+ < 8.5 mg/dL or ionized Ca2+ < 4.65 mg/dL). Total calcium comprises physiologically-active ionized calcium as well as anion-bound and protein-bound, physiologically-inactive calcium. Calcium plays an important role in various cellular processes in the body, such as stabilizing the resting membrane potential of cells, cell signaling, coagulation, and hormone release. In addition to hormonal control by parathyroid hormone (PTH) and calcitriol, calcium homeostasis is also influenced by serum protein levels and acid-base status, both of which impact the ratio of protein-bound Ca2+ to ionized Ca2+ in the serum. Severity and chronicity of calcium deficiency in addition to the patient's age and comorbidities contribute to the overall clinical presentation of hypocalcemia. Symptoms are variable; the most characteristic features include prolongation of the QT interval and signs of neuromuscular excitation (e.g., tetany, carpopedal spasm, paresthesias). Management consists of calcium supplementation and identifying and treating the underlying cause.

Definition

  • Hypocalcemia: total serum calcium concentration < 8.5 mg/dL (< 2.12 mmol/L), or ionized (free) calcium concentration < 4.65 mg/dL (< 1.16 mmol/L) [1]
  • Severe hypocalcemia: total serum calcium concentration ≤ 7.5 mg/dL (< 1.9 mmol/L), or ionized (free) calcium concentration < 3.6 mg/dL (< 0.9 mmol/L) [2]
  • Factitious hypocalcemia: an asymptomatic decrease in total calcium with a normal ionized Ca2+ level (typically occurs due to low serum protein levels)

Calcium homeostasis and calcium physiology

Total and ionized calcium concentrations

To remember the changes in PTH depending on pH, think: pH = PTH and pH = PTH

The physiological role of calcium [3]

Calcium homeostasis

Calcium homeostasis is a complex process, involving many organs (kidneys, gastrointestinal tract, bones, liver, and skin) and hormones (PTH, calcitonin, vitamin D).

Hormone
Effect on serum [calcium] Effect on serum [phosphate] Mechanism of action Regulation
Parathyroid hormone

Calcitriol (vitamin D3)
Calcitonin
  • Opposes the effects of PTH
  • Inhibits bone resorption, decreasing serum Ca2+

The acronym “PTH” describes the action of parathyroid hormoneP = Phosphate T = Trashing H = Hormone

To remember that calcitonin keeps the calcium in the bones, think: Calci-bone-in!

References:[4][5][6][7][8][9]

Etiology

Types of hypocalcemia Etiology Pathophysiology
Low PTH Hypoparathyroidism
High PTH (secondary hyperparathyroidism) Vitamin D deficiency
Chronic kidney disease
Pseudohypoparathyroidism
  • PTH resistance

Hyperphosphatemia (see phosphate)

Acute necrotizing pancreatitis (see acute pancreatitis)
  • Calcium soap precipitation in the abdomen

Other Medications
Multiple blood transfusions and hemolysis
  • Citrate in blood products chelates serum calcium.
Hypomagnesemia (see magnesium)
Hyperventilation
  • Redistribution of calcium
Osteoblastic metastases
Renal tubular disorders
  • See RTA type 1.
Pseudohypocalcemia
Neonatal hypocalcemia
Hungry bone syndrome


Hypocalcemia is most often due to hypoparathyroidism or vitamin D deficiency (e.g., malabsorption, chronic kidney disease).

Suspect hypocalcemia in the postoperative thyroidectomy patient with new-onset paresthesias and muscle spasms or cramping.

References:[10][5][7][11]

Clinical features

Manifestations of hypocalcemia are influenced by the severity and chronicity of the hypocalcemia as well as by the patient's age and comorbidities.

Neurological manifestations [12][13][14][1]

Signs of neuromuscular irritability (e.g., paresthesias, spasms and cramps) are the most characteristic features of hypocalcemia.

Cardiovascular manifestations [12][13][14][1]

Manifestations of chronic hypocalcemia [12][13][14][1]

Diagnostics

Approach

Acute symptomatic hypocalcemia is a medical emergency that is potentially fatal, diagnostics should not delay treatment.

Laboratory studies [12][2]

Routine studies

Additional studies

Interpretation of laboratory findings in hypocalcemia [1]
PTH level Additional findings Conditions
Low PTH
High PTH

The typical laboratory findings of vitamin D deficiency are ↓ calcium, ↓ (or normal) phosphate, and PTH.

Additional diagnostics

Treatment

The mainstay of therapy of hypocalcemia consists of calcium supplementation and the treatment of the underlying cause.

Calcium supplementation [2]

Calcium supplementation; should be provided based on severity. See “Repletion regimens for hypocalcemia” for more details on calcium supplementation with specific dosages.

  • Severe and/or symptomatic hypocalcemia: e.g., tetany, seizures, prolonged QT interval, serum calcium ≤ 7.5 mg/dL (< 1.9 mmol/L)
    • IV calcium supplementation: calcium gluconate or calcium chloride
    • Continuous telemetry [2]
    • Consider transfer to critical care unit
  • Mild and/or chronic hypocalcemia: no symptoms or only mild neuromuscular irritability (e.g., paresthesias), serum calcium 7.6–8.4 mg/dL (1.9–2.12 mmol/L)
    • Oral calcium supplementation: calcium citrate, calcium carbonate

IV calcium can trigger life threatening arrhythmias in patients simultaneously receiving cardiac glycosides (digoxin or digitoxin). [1]

Treatment of the underlying condition

Loop diuretics Lose calcium. Discontinue them in hypocalcemia.