- Clinical science
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.
Total and ionized calcium concentrations
Total calcium: the total amount of calcium circulating in the serum, comprising protein-bound, anion-bound, and
- Approx. 40% of the total serum calcium is bound to proteins (mostly albumin) and is physiologically inactive.
- (due to, e.g., nephrotic syndrome, liver cirrhosis, severe malnutrition, malabsorption) → ↓ total Ca2+ level but ionized Ca2+ level is unaffected →
- pH influences the binding of calcium to serum proteins.
- Ionized calcium: the calcium fraction that is not bound to any proteins but is physiologically active
The physiological role of calcium 
Ionized Ca2+ is responsible for stabilizing the resting membrane potential of cells.
- ↓ Serum Ca2+ → ↑ membrane excitability
- ↑ Serum Ca2+ → ↓ membrane excitability
- Acts as a second messenger in signaling pathways
- Cofactor for several enzymes (e.g., phospholipase A, gamma-glutamyltransferase)
- Required for the promotion of coagulation pathways
|Effect on serum [calcium]||Effect on serum [phosphate]||Mechanism of action||Regulation|
|Parathyroid hormone||↑|| |
|Calcitriol (vitamin D3)||↑||↑|
|Calcitonin||↓||↓|| || |
To remember that calcitonin keeps the calcium in the bones, think: Calci-bone-in!
|Types of hypocalcemia||Etiology||Pathophysiology|
|High PTH ()||Vitamin D deficiency|
|Chronic Kidney disease|
Hyperphosphatemia (see )
|Acute necrotizing pancreatitis (see )|| |
|Multiple blood transfusions and hemolysis|| |
|Hypomagnesemia (see )|
|Renal tubular disorders|| |
|Hungry bone syndrome|
Tetany: increased neuromuscular excitability (when caused by respiratory alkalosis = hyperventilation-induced tetany)
- Paresthesias: typically tingling or pins-and-needles sensation in extremities and/or in the perioral area
- Muscle spasms, such as carpopedal spasm; and cramps (possible in any muscle)
- Maneuvers to elicit tetany in physical exam
- Chvostek sign: short contractions (twitching) of the facial muscles elicited by tapping the facial nerve below and in front of the ear (approx. 2 cm ventral to the ear lobe)
- Trousseau sign: ipsilateral carpopedal spasm occurring several minutes after inflation of a blood pressure cuff to pressures above the systolic blood pressure
- Cardiac arrhythmias (typically ventricular tachyarrhythmias) 
- Myocardial depression
- Biliary colic
- Abdominal cramping and diarrhea
Evaluate calcium imbalance
- Initial test: serum calcium concentration
- Confirm true hypocalcemia: Measure or use serum albumin to calculate .
- Differentiate between low PTH and high PTH: to determine the underlying cause of hypocalcemia (see above)
- 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|
|Malabsorption or alcoholism|
Calcium supplementation (see calcium repletion)
- IV calcium (1–2 g calcium gluconate; in 50 mL of 5% dextrose infused over 10–20 mins): indicated in severely symptomatic patients (e.g., tetany, seizures), those with a prolonged QT interval, and asymptomatic patients with an acute decrease in serum corrected calcium to ≤ 7.5 mg/dL (≤ 1.9 mmol/L)
- Oral calcium: indicated in patients with mild neuromuscular irritability (e.g., paresthesias), and those with serum corrected calcium > 7.5 mg/dL (> 1.9 mmol/L)
- Treat any underlying conditions
Loop diuretics Lose calcium. Discontinue them in hypocalcemia.