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What are the types of calcium and how can we measure it?

Extracellular Calcium

Ca outside of cells is available in either diffusible or non-diffusible form

  • Diffusible calcium is called as such because it is small enough to cross cell membranes. This includes Ca that is free and therefore ionized, or complexed (electrically neutral) to small negatively charged molecules like oxalate and phosphate
  • Non-diffusible calcium includes Ca that is bound to negatively charged proteins like albumin which prevent it from crossing cell membranes

Ionized Calcium and Albumin

Ionized Ca has been shown to be the more physiologically important component of blood Ca. Unfortunately it is expensive to directly measure it and is reserved only if the diagnosis of hypocalcemia is in doubt. In most cases, we can estimate free ionized Ca through formulas that help us to adjust for levels of albumin.

Generally, because a large portion of serum Ca is bound to albumin, changes in albumin can result in changes in the total Ca concentration without actually affecting the physiologically important ionized calcium concentration.

In other words, if you have hypo- or hyper-albuminemia, it will not cause you to have any change in your physiologically important free ionized Ca.

The reason why is because albumin or any protein for that matter do not serve as easily accessible Ca resevoirs. So consider free ionized Ca as completely independent from Ca bound to albumin. Free ionized Ca is more so controlled by hormonal controls like PTH than by the level of albumin in the body.

Each 10 g/L decrease in albumin will decrease the serum Ca by 0.2 mmol/L without affecting ionized Ca

The formula to calculate albumin-adjusted Ca is

  • Corrected total calcium (mmol/L) = total serum Ca (mmol/L) + 0.02 [40 (g/L) – albumin (g/L)])
  • Represented another way
    • Corrected total = total serum Ca + {2 x [40 (g/L) – albumin (g/L)])} / 100