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Hypocalcemia

Summary

Hypocalcemia is a state of low calcium levels (total Ca2+< 8.5 mg/dL or ionized Ca2+< 4.65 mg/dL) in the blood serum. Total calcium comprises the ionized calcium, which is the physiologically active ion, as well as 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. Symptoms of hypocalcemia include tetany, which indicates neuromuscular excitation (e.g., carpopedal spasm, “pins and needles” sensation, other paresthesias) as well as prolongation of the QT interval, and abdominal pain. Management consists primarily of treating the underlying disorder and, if necessary, calcium supplementation.

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]

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 [2]

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)
  • A decrease in serum Ca2+ indirectly calcitriol via PTH.
Calcitonin
  • Opposes the effects of PTH
  • Inhibits bone resorption, decreasing serum Ca2+
  • An increase in serum Ca2+ results in calcitonin secretion.

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:[3][1][4][5][6][7]

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)
  • HypomagnesemiaPTH secretion or induces PTH resistance → hypocalcemia
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).

References:[8][1][5][9]

Clinical features

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

References:[11]

Diagnostics

Approach [12]

  1. Evaluate calcium imbalance
  2. Differentiate between low PTH and high PTH: to determine the underlying cause of hypocalcemia (see differential diagnosis of hypocalcemia above)
  3. Further tests

PTH levels in hypocalcemia

PTH level Conditions Laboratory findings
Low PTH Hypoparathyroidism (e.g., postsurgical)
High PTH Vitamin D deficiency
Chronic kidney disease
Pseudohypoparathyroidism
Hyperphosphatemia
Malabsorption or alcoholism

The typical laboratory findings of vitamin D deficiency are ↓ calcium, ↓/↔︎ phosphate, and PTH.

References:[12]

Treatment

Because of adverse cardiac effects, cardiac monitoring is recommended in patients receiving simultaneous cardiac glycosides (digoxin and digitoxin) and IV calcium.

Loop diuretics Lose calcium. Discontinue them in hypocalcemia.

References:[14]