Ionized Calcium (Ca)

What sample is needed for Ionized Calcium?

1. Collect blood anaerobically and draw it without applying pressure or causing stasis.
2. The sample is stable for 6 hours at 4 °C.
3. Plasma or serum can be stored for a longer period at -20 °C.
4. The non-fasting sample is acceptable.
   1. The prolonged use of a tourniquet should be avoided because it lowers pH and increases calcium levels.

What are the indications for Ionized Calcium?

1. This test determines physiologically active or free Calcium in patients with altered proteins, e.g, in chronic renal failure, nephrotic syndrome, malabsorption, and multiple myeloma.
2. Ionized calcium values reflect calcium metabolism better than total calcium.
3. A significant decrease in ionized calcium, regardless of total calcium, may lead to increased neuromuscular irritability and tetany.
4. This is also recommended in cases of parathyroid disease.
5. Patients with hypocalcemia or hypercalcemia have borderline serum calcium and altered serum proteins.
6. Patients are receiving an intravenous blood transfusion.
7. In case of major surgery.
8. In case of abnormal blood proteins.

What are the precautions for calcium?

1. Magnesium affects ionized calcium, so it is essential to measure magnesium levels in cases of hypocalcemia.
2. A fasting specimen is preferred.
3. The prolonged use of a tourniquet should be avoided because it lowers pH and increases calcium levels.
4. Serum pH can affect the calcium level. A decreased pH can cause an increased level of calcium.
5. Venous stasis or erect posture increased the calcium level by 0.6 mg/dL.
6. Diurnal variation is higher in PM (about 9 PM) than in AM (lowest level).
7. Separate immediately from RBCs to avoid calcium uptake by these cells (RBCs).
8. Excessive milk intake leads to increased calcium levels.
9. Vitamin D intoxication also increases the calcium level.
10. Check the albumin level because hypoalbuminemia leads to an artificial decrease in the calcium level.
11. Drugs like calcium salts, alkaline antacids, thiazide diuretics, vitamin D, parathyroid and thyroid hormones, and androgens may increase the serum calcium level.
12. Drugs like aspirin, anticonvulsants, heparin, laxatives, diuretics, magnesium salts, and oral contraceptives may decrease the calcium level.

How will you define ionized calcium (Free calcium)?

1. Ionized calcium (Free calcium) is the physiologically active form of calcium.
2. The parathyroid glands, bone, kidneys, and intestine regulate ionized calcium homeostasis.
3. There is a small diurnal change in ionized calcium, with the peak level occurring around 9 p.m. and the lowest level at 9 a.m.
4. Ionized calcium level is not affected by changes in serum albumin.

What do you know about Ionized Calcium (free calcium)?

1. The routine serum calcium measures the total serum calcium value.
2. 99% of the calcium is present in the bones.
   1. It is present in soft tissue = 1%
   2. It is present in the extracellular fluid = 0.2%.
3. Calcium in serum is:
   1. 50% Non-Bound calcium, also known as ionized or free dialyzable calcium. The free or ionized form is the active form.
      1. Only the ionized fraction is biologically active.
   2. 40% is bound to protein. The protein-bound fraction of calcium is bound to albumin (70% to 80%).
   3. 10% is complexed with non-protein compounds (ions), such as citrate, phosphate, sulfate, and bicarbonate.

4. The most valuable clinical information is provided by a knowledge of the concentration of Free (ionized) Ca⁺⁺ rather than of total Ca⁺⁺ in primary hyperparathyroidism.
5. In some patients with primary hyperparathyroidism, there is an increase in ionized calcium, but total calcium is normal.
6. Ionized calcium (hypercalcemia) may be seen in:
   1. Multiple myeloma.
   2. Sarcoidosis.
   3. Hypervitaminosis D.
   4. Metastatic carcinoma infiltrates the bone.
7. Most of the labs have no facility to measure ionized calcium.
   1. The ion-selective electrode can measure ionized calcium.
   2. There are formulas by which you can calculate the ionized calcium from the total serum calcium.
8. In critically ill patients, an increased total serum calcium level usually indicates ionized hypercalcemia.
   1. Normal total serum calcium is evidence against ionized hypocalcemia.
9. Ionized calcium is preferred over total serum calcium in some conditions:
   1. The liver transplantation.
   2. Rapid or large transfusion of citrated blood.
   3. In these conditions, the total serum calcium interpretation is almost impossible.
10. The increase of ions to which calcium is bound is:
    1. Bicarbonate (HCO3).
    2. Citrate during a blood transfusion.
    3. Phosphate level. In the case of phosphate therapy in diabetic ketoacidosis, rhabdomyolysis, and chemotherapy (tumor lysis syndrome).
    4. Radiographic material containing calcium chelators.

What are the functions of Ionized calcium or free (dialysable) calcium?

1. It exerts its physiological effects upon:
   1. The neuromuscular junction.
   2. Membranes.
   3. Bone deposition.

What is the normal Ionized Calcium (Free calcium)?

Source 1

• Ionized calcium:
  • Whole blood adult = 4.65 to 5.28 mg/dL (1.175 to 1.375 mmol/L)
  • Newborn = 4.20 to 5.58 mg/dL.
  • The ratio of ionized Ca⁺⁺ to total Ca⁺⁺ = 48 to 56%.

Source 2

• Newborn = 4.20 to 5.58 mg/dL  (1.05 to 1.37 mmol/L).
• 2 months to 18 years = 4.80 to 5.52 mg/dL  (1.20 to 1.38 mmol/L).
• Adult = 4.5 to 5.6 mg/dL (1.05 to 1.3 mmol/L).

• To convert into an SI unit, the multiplying factor is x 0.25 = mmol/L

How will you measure ionized calcium?

1. It can be measured by the ion-selective electrode method.
   1. The above method is more accurate.
2. A less accurate method to calculate serum calcium:
   1.  Adjusted calcium = (Total serum calcium – serum albumin) + 4.0
      1. (Calcium in mg/dL and albumin in g/dL).
3. In SI unit formula = Adjusted calcium = (calcium – 0.025 albumin) + 1.0
   1. (Calcium in mmol/L and albumin in g/L).
4. Ionized calcium values are affected by the blood pH level.
   1. A decrease of 0.1 pH = an increase in ionized calcium by 1.5% to 2.5%.
   2. If serum is exposed to air and stands for a long time.

What are the causes of an increased level of ionized calcium?

1. Primary hyperparathyroidism. In 25% of patients, it is observed that total serum calcium is normal, while ionized calcium is elevated.
2. PTH-producing tumors.
3. Various malignancies.
4. Excess intake of vitamin D.
5. Acidosis.
6. Neonatal total serum calcium associated with hypoalbuminemia may indicate ionized hypercalcemia.

What are the causes of a decreased level of ionized calcium?

1. Primary hypoparathyroidism. It is also seen in secondary hypoparathyroidism.
2. Alkalosis.
3. Vitamin D deficiency.
4. After a blood transfusion.
5. After major surgery.
6. Trauma, burns, and sepsis.
7. Fat embolism.
8. Pancreatitis.
9. After hemodialysis.
10. Multiple organ failures.
11. Toxic shock syndrome.
12. Increased calcium-binding to albumin in conditions like:
    1. Drugs like heparin, epinephrine, norepinephrine, alcohol, and isoproterenol.
    2. Acute pancreatitis.
    3. Diabetic ketoacidosis.
    4. Sepsis.
    5. AMI.

• Please see more details on the Calcium level (total) in part 1.

What is the Critical value of ionized calcium?

• Ionized calcium level <2 mg/dL (life-threatening).
• Ionized calcium level <3 mg/dL in multiple blood transfusions is the indication for calcium therapy.

What are the natural foods that are a good source of calcium?

Questions and answers: