Hypocalcemia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

Overview

Hypocalcemia may develop in disorders associated with insufficient parathyroid hormone or vitamin D production or resistance to hormonal activities. Perturbations of calcium homeostasis can be caused by environmental factors or occur as a result of genetic mutations in the calcium-sensing receptor (as in type 1 autosomal dominant hypocalcemia), Gs α subunit (as in type 1A and 1B pseudohypoparathyroidism), vitamin D hydroxylase (as in type 1 vitamin D-dependent rickets , and calcitriol receptor (as in type 2 vitamin D-dependent rickets).

Pathophysiology

Physiology

The normal physiology of Hypocalcemia can be understood as follows:[1][2]

  • The normal concentrations of calcium in the body is maintained within the narrow range and that is required for the optimal activity of the many extra- and intracellular processes that calcium regulates. 
  • Calcium transport within the blood is mainly via bound to plasma proteins such as albumin (45%), phosphate and citrate (15%) and ionized state (40%).
  • Only the ionized form of calcium is active but most laboratories show report of total serum calcium concentrations.
  • The normal concentration of calcium ranges between 8.5 and 10.5 mg/dL.
  • The normal range of ionized calcium in the plasma is 4.65 to 5.25 mg/dL.

Pathogenesis

It is understood that hypocalcemia may result through any of the following mechanisms:

Vitamin D deficiency

Hypoalbuminemia

  • When there is a fluctuation in serum protein concentrations, especially albumin, total calcium levels in the blood may change.[5][6]
  • Whereas the levels of ionized calcium (free form) remains mostly constant, because it is hormonally regulated.
  • In cases of hypoalbuminemia, total serum calcium levels may not accurately reflect the physiologically important ionized calcium concentration.
  • Therefore, a correction may be required in order to arrive at the corrected calcium levels. (Corrected calcium = Measured calcium + 0.02 x [40 - Albumin])

Hormonal regulation 

Magnesium 

Acid-base disturbances

Alkalosis

  • For an increase in pH of 0.1 unit, there is an approximately 0.05 mmol/L (0.1 mEq/L) fall in the serum level of ionized calcium.

Respiratory alkalosis

Globulin binding

Autoimmune 

Genetics

The development of hypocalcemia is the result of genetic mutations such as

References

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