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Total CO₂, calcium, magnesium and phosphate

16 min

Skills you'll build4 skills
  • Recognize CO₂ escape from an uncapped tube behind a low total CO₂
  • Choose between total and ionized calcium when albumin or pH is abnormal
  • Check magnesium when hypokalemia does not correct
  • Tell a phosphate shift into cells from renal or dietary phosphate loss

At the bench: Assess specimen interference before reporting a chemistry result · Review electrolyte results and related calculations for consistency

Try first

Try first

An outpatient's total CO2 is 17 mmol/L. Last month it was 25 mmol/L. Sodium, chloride and potassium match last month's. The handling record shows the separated tube stood uncapped on the bench for 5 hours before testing. What best explains the low total CO2?

Keep going to see the reasoning.

Keep going to see the reasoning.

Right. Keep going to follow the reasoning.

Keep going to see the reasoning.

Get the idea

Use the explanation to check your first decision.

Total CO2 in uncapped tubes

The chemistry panel's total CO2 is mostly bicarbonate, measured enzymatically on serum or plasma. Dissolved CO2 escapes from an uncapped tube, and the result falls with every hour it stands open.1 The calculated anion gap rises as a result. Tubes stay stoppered and are tested promptly. For an isolated fall in total CO2, check the handling record against the assay's stability limits first.1

Total and ionized calcium

About 45 to 50% of blood calcium is ionized. About 40 to 45% is bound to protein, mostly albumin, and the rest is complexed.1 Total calcium changes with albumin. The usual correction estimates total calcium at a normal albumin:

Corrected total calcium (mg/dL) = measured total calcium + 0.8 × [4.0 − albumin (g/dL)]

In 5,055 samples, corrected calcium agreed with measured ionized calcium no better than uncorrected total calcium did.2 Alkalemia increases calcium binding to albumin, and citrate from transfused blood binds it. In acute illness, ionized calcium is measured by ion-selective electrode on an anaerobic specimen.1

Magnesium and refractory hypokalemia

Under 1% of body magnesium circulates, so a serum value within its interval can occur with depleted body stores. Low magnesium causes continued renal potassium loss, and the hypokalemia persists until magnesium is repleted. About 40% of hospital patients with hypokalemia also have hypomagnesemia.1 Hypokalemia that does not correct needs a magnesium measurement.

Phosphate shifts into cells

Insulin-driven glucose uptake during refeeding pulls phosphate into cells. Serum phosphate can fall sharply within days of feeding starting. Acute respiratory alkalosis does the same.1 A falling phosphate is interpreted with the timing of feeding and insulin. Hemolysis and delayed separation raise phosphate in the tube, so an earlier high baseline is checked for them.1

Follow the bench demonstration

Sources for this step
References
  1. Rifai N, Chiu RWK, Young I, Burnham CAD, Wittwer CT, eds. Tietz Textbook of Laboratory Medicine. 7th ed. Elsevier; 2023.
  2. Pekar JD, Grzych G, Durand G, et al. Calcium state estimation by total calcium: the evidence to end the never-ending story. Clin Chem Lab Med. 2020;58(2):222-231. doi:10.1515/cclm-2019-0568

Watch one

Read each decision and its explanation.

An intensive care patient received several units of blood and a bicarbonate infusion today. The morning panel and an arterial gas give these results.

The ward asks whether the corrected calcium can be used. Work through the calcium results in order.

TestResultReference intervalFlag
Total calcium7.6 mg/dL Low8.6–10.2 mg/dL8.6–10.2Low
Albumin2.2 g/dL Low3.5–5.0 g/dL3.5–5.0Low
pH, arterial7.52 High7.35–7.457.35–7.45High
Ionized calcium, whole blood0.98 mmol/L Low1.15–1.27 mmol/L1.15–1.27Low

Specimen: H 10, L 15, I 2. Serum for the panel; balanced-heparin arterial syringe for ionized calcium and pH

  1. Read the total calcium and albumin: 7.6 mg/dL with albumin 2.2 g/dL.

    Total calcium includes the bound fraction, so it is read with albumin.

  2. Calculate the corrected value: 7.6 + 0.8 × (4.0 − 2.2) = 7.6 + 1.44 = 9.0 mg/dL, inside the interval.

    The correction estimates total calcium at a normal albumin.

  3. Check the conditions: pH 7.52 and transfused blood both lower the ionized fraction, so the corrected value cannot be used as an estimate of it.

    The correction assumes stable binding, and alkalemia and citrate change binding.

  4. Read the ionized calcium: 0.98 mmol/L is below 1.15 mmol/L.

    Ionized calcium measures the active fraction directly.

  5. Check the specimen: a balanced-heparin arterial syringe with no air exposure.

    The syringe was capped and anaerobic, so the pH and ionized result reflect the patient.

The ionized calcium of 0.98 mmol/L is low. The corrected total of 9.0 mg/dL is within the interval and does not show the deficit, so the ionized result is reported.

Practice this skill

Your turn

Problem 1 of 3 · Hints available

Which measurement best resolves calcium status during acute shifts in pH and albumin?

Incorrect. The adjustment assumes stable binding. In acute illness, total calcium cannot reliably predict the ionized fraction, and in a large comparison corrected values agreed no better with measured ionized calcium than unadjusted totals.

Correct. An ion-selective electrode measures the active fraction directly. Handle the specimen anaerobically, because CO2 loss raises pH, shifts calcium onto albumin, and lowers the ionized result.

Incorrect. Prompt separation prevents stasis artifacts, but total calcium still includes the protein-bound and complexed fractions that pH and albumin shifts redistribute.

Hint
  1. Ask which fraction of calcium the body uses.
  2. Ask which measurement measures that fraction directly.
  3. An adjustment assumes binding stays the same.

Review Calcium

Problem 2 of 3 · Hints available

Which accompanying deficit can sustain renal potassium wasting and make hypokalemia persist?

Correct. Renal potassium wasting continues until magnesium is repleted, so hypokalemia stays refractory while the deficit lasts. About 40% of hypokalemic hospital patients also have hypomagnesemia.

Incorrect. Hypophosphatemia often accompanies magnesium deficiency. The continuing renal potassium loss is caused by the low magnesium.

Incorrect. Hypocalcemia often accompanies magnesium deficiency because low magnesium suppresses PTH secretion. The continuing renal potassium loss comes from the magnesium deficit itself.

Hint
  1. Ask which deficit keeps the kidney losing potassium.
  2. This deficit is often present with a serum value within its interval.

Review Hypomagnesemia and hypermagnesemia

Problem 3 of 3 · On your own

A patient with severe weight loss starts tube feeding on Monday. Serum phosphate is 3.4 mg/dL on Monday, 2.1 mg/dL on Tuesday and 1.2 mg/dL on Wednesday. Each specimen was separated on time and has no hemolysis. What best explains the fall?

The fall began with feeding and was rapid. Insulin released by feeding moves phosphate into cells, which fits the timing.

Missed a refeeding shift behind a falling phosphate

Insulin-driven glucose uptake during refeeding pulls phosphate into cells, so serum phosphate can fall sharply within days of feeding. Reading the fall as new renal or dietary loss misses the shift. Compare the timing with feeding and insulin, and check whether hemolysis or delayed separation raised an earlier baseline.

Feeding raises insulin, and glucose uptake carries phosphate into cells as phosphorylated intermediates. A sharp fall within days of feeding fits that shift.

The Monday specimen had no hemolysis and was separated on time. Its value of 3.4 mg/dL is valid.

Tube feeding supplies phosphate. Dietary lack also acts over weeks, and this fall took two days.

Review Phosphate

For reference

Sources checked