Hypocalcemia
Hypocalcemia is the state in which the serum ionized calcium level drops below the normal range of 1.0 to 1.3 mmol/L. This corresponds, under normal conditions, to a total serum calcium level of 2.1 to 2.5 mmol/L (8.5-10.5 mg/dL).
2. How are serum calcium and serum albumin levels related?
Approximately 50% of serum calcium is bound to albumin, other plasma proteins, and related anions, such as citrate, lactate, and sulfate. Of this, 40% is bound to protein, predominantly albumin, and 10% to 13% is attached to anions. The remaining 50% is unbound or ionized calcium. The total serum calcium level reflects both the bound and the unbound portions with a normal range of 2.1 to 2.5 mmol/L (8.5-10.5 mg/dL).
3. How is the total serum calcium corrected for a low serum albumin level?
Total serum calcium levels are corrected for hypoalbuminemia by the addition of 0.8 mg/dL to the serum calcium level for every 1.0 g/dL that the albumin level is below 4.0 g/dL. The adjusted level of total serum calcium correlates with the level of ionized calcium, which is the physiologically active form of serum calcium.
4. What is the most common cause of low total serum calcium?
Hypoalbuminemia. The ionized calcium concentration is normal. Low serum albumin is common in chronic illness and malnutrition.
5. What factors other than albumin influence the levels of serum ionized calcium?
Serum pH influences the level of ionized calcium by causing decreased binding of calcium to albumin in acidosis and increased binding in alkalosis. As an example, respiratory alkalosis, seen in hyperventilation, causes a drop in the serum ionized calcium level. A shift of 0.1 pH unit is associated with an ionized calcium change of 0.04 to 0.05 mmol/L (0.16-0.20 mg/dL). Increased levels of chelators, such as citrate, which may occur during large-volume transfusions of citrate-containing blood products, also may lower the levels of ionized calcium. Heparin may act similarly.
6. How is serum calcium regulated?
Three hormones maintain calcium homeostasis: parathyroid hormone (PTH), vitamin D, and calcitonin. PTH acts in three ways to raise serum calcium levels: (1) stimulates osteoclastic bone resorption, (2) increases conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, increasing intestinal calcium absorption, and (3) increases renal reabsorption of calcium. Calcitonin decreases the level of serum calcium by suppressing osteoclast activity in bone. The interplay of these hormones maintains calcium levels within a narrow range in a normal individual. Calcium levels are also influenced by the presence or absence of hyperphosphatemia.
7. What steps in vitamin D metabolism may influence serum calcium levels?
Vitamin D is obtained through the diet or is formed in the skin in the presence of ultraviolet light. Vitamin D is converted to 25-hydroxyvitamin D in the liver and finally to 1,25-dihydroxyvitamin D, the most active form of vitamin D, in the kidney. 1,25-dihydroxyvitamin D acts directly on intestinal cells to increase calcium absorption. Deficiency in any of these steps may cause hypocalcemia.
8. What are the major causes of hypocalcemia?
The multiple organ and hormonal regulatory systems involved in calcium homeostasis create the potential for multiple causes of hypocalcemia. The etiology of hypocalcemia must be considered in relation to the level of serum albumin, the secretion of PTH, and the presence or absence of hyperphosphatemia. Initially, hypocalcemia may be approached by a search for failure in one or more of these systems. The systems primarily involved are the parathyroid glands, bone, kidney, and liver; the following list shows the clinical entities followed by their mechanisms:
Hypoparathyroidism: decreased PTH production
Hypomagnesemia: decreased PTH release, responsiveness, and action
Citrate toxicity from massive blood transfusion: complexing of calcium with citrate
Pseudohypoparathyroidism: PTH ineffective at target organ
Pancreatitis: sequestration of calcium in the pancreas; other
Toxic shock syndrome, other critical illness: decreased PTH production or PTH resistance
9. What physical signs suggest hypocalcemia?
The hallmark sign of acute hypocalcemia is tetany. This is characterized by neuromuscular irritability, which is usually seen when the serum ionized calcium concentration is less than 4.3 mg/dL (total serum calcium < 7-7.5 mg/dL).
Mild tetany: perioral numbness, acral paresthesias, and muscle cramps
Severe tetany: carpopedal spasms, laryngospasm, and focal or generalized seizures
