Understanding Ionized Calcium

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The difference between corrected calcium and ionized calcium has always confused me. Understanding where calcium is in our body, the units we use to measure each, and how they interact really helps me keep it straight. - A Thread - #MedEd #MedTwitter #FOAMed

Only 1% of total body calcium is outside your bones and teeth. Of the ~0.1% (~350mg) that circulates in plasma: - 40% is bound to protein (albumin) - 10% complexed with anions - 50% is "free" ionized calcium (iCal) Only iCal is physiologically active.

We think of "normal" calcium levels as ~10 because the total is reported as mg/dL This equates to 2.5 when reported as mmol/L As above, Ionized calcium is 50% of the total, and is reported as mmol/L This is why "normal" iCal is ~1.25 mmol/L

What do we mean that iCal is "physiologically" active? A few examples: - iCal is what parathyroids and kidneys respond to; regulates PTH and calcitriol (active form of VitD) - co-factor in the coagulation cascade - critical for muscle contraction and nueronal signaling

The usefulness of total calcium in clinical scenarios is based on the assumption that it reflects iCal activity. So why use iCal over total calcium? 2 Key Scenarios: - Abnormal serum protein concentration - Abnormal Acid-Base status

First, protein concentration: If serum protein (albumin) increases, there is a proportional increase in the amount of calcium that binds to it. But the iCal stays the same Taken together, the TOTAL calcium increases but no longer reflects the more important iCal level.

This is why we use the "modified" Orrell correction: = Serum Ca + 0.8 x (4 - albumin) This correction is good for getting a gut check, but can still be inaccurate, especially in critically ill patients.

Second, acid-base status: Hydrogen ions compete with calcium for protein-binding sites. Acidosis decreases calcium binding and increases the proportion of total calcium that is ionized. In general, every 0.1 decrease in pH leads to an increase of 0.05 mmol/L of iCal

However, since this is simply a change in the proportion of bound vs unbound calcium, the total calcium is unchanged. This can cause problems where calcium seems normal, but iCal is actually abnormal.

So why don't we always report iCal in a BMP? Measurement of iCal requires more complex preservation of the blood sample (maintaining a certain pH, temperature, etc). However, it's easy to measure immediately at the point of care (think VBG in the ICU).

If you remember nothing else: - Total calcium reported as mg/dL; iCal as mmol/L - iCal is ~50% of total calcium - Corrected calcium is an imperfect attempt to correlate with iCal - iCal preferred in critically ill patients, especially those with acid-base disturbances