A 69-year-old male with a history of previous pneumonectomy for lung carcinoma, is admitted with confusion. There are no focal neurological signs on clinical examination. Neck stiffness is not present. Contrast CT brain scan is normal. His initial plasma biochemistry is shown below:

Parameter

Patient Value

Adult Normal Range

Na+

148 mmol/L*

134 – 145

K+

3.7 mmol/L

3.5 – 5.0

Cl-

109 mmol/L*

97 – 107

HCO3-

33 mmol/L

24 – 34

Albumin

15 g/L*

35 – 40

Urea

12.8 mmol/L*

3.1 – 8.1

Creatinine

36 µmol/L*

60 – 100

Total calcium

2.59 mmol/L*

2.20 – 2.55

Phosphate

0.86 mmol/L

0.78 – 1.05

a)    What is the most likely cause of the confusion in this patent, based on the above information? Justify your response.    (10% marks)

b)    List four therapies for the cause stated in a).    (20% marks)
 

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College answer

a)    Hypercalcemia (When corrected for albumin the true calcium is higher).

b)    Calciuresis (saline +/- frusemide)
•    Bisphosphonates
•    Calcitonin
•    Corticosteroids
•    NSAIDS
•    Mithramycin
 

Discussion

a)

To use a formula  first described by Payne et al (1973):

Corrected calcium = (0.02 × (normal albumin - patient's albumin)) + serum calcium

Thus, (0.02 × (40 - 15)) + 2.59 = 3.09mmol/L.

However, one needs to seriously question this value, and the use of the term "true calcium" to describe it. This 3.09 mmol/L is not the One True Calcium. The patient's actual serum calcium level is still the one reported in the blood results; it's not as if hypoalbuminaemia causes your blood sample to magically hide 0.50 mmol/L of calcium, and only to reveal them when the intensivist chants the appropriate incantations. The calcium value corrected for low albumin is a mathematical workaround from an era when calcium ion-selective electrodes were not widely available. Payne's formula calculates the calcium level your patient would have if their albumin were normal, so you can decide whether their ionised calcium might be high. Again, this is not a "true" calcium by any means. The patient's blood does not actually contain this much calcium. A much better calculation would have been to use an equation such as the ones tested by Mateu-de Antonio (2016), which use albumin and total calcium measurements to predict the ionised calcium value:

Ca2+ =  0.813 × CaTot0.5 - 0.006 × Alb0.75 + 0.079

(where albumin is represented in g/L).
Thus, in this case, ionised calcium would be (0.813 × 2.590.5 - 0.006 × 150.75 + 0.079) = 1.34 mmol/L, which is a mild hypercalcemia- elevated but potentially asymptomatic.

b)

In brief, these are the physiological aims for management of hypercalcemia, and the means to achieve them:

  • Dilute serum calcium
    • Rehydration with IV fluids
  • Decrease calcium resportion from bone
    • Calcitonin
    • Bisphosphonates
    • Gallium nitrate
    • Mithramycin (for malignant disease)
  • Decrease calcium resportion from renal tubule
    • Loop diuretics (this has fallen out of favour)
    • Calcitonin
  • Decrease calcium absorption from the gut
    • Corticosteroids (also they decrease the 1,25-dihydroxyvitamin D production by monocytes within granulomae)
  • Forcibly remove excess calcium from the circulation
    • Haemodialysis
    • EDTA administration (as chelating agent)

References

References

Mateu-de Antonio, Javier. "New predictive equations for serum ionized calcium in hospitalized patients." Medical Principles and Practice 25.3 (2016): 219-226.

Payne, R. B., et al. "Interpretation of serum calcium in patients with abnormal serum proteins." British medical journal 4.5893 (1973): 643.

Stewart, Andrew F. "Hypercalcemia associated with cancer." New England Journal of Medicine 352.4 (2005): 373-379.

Zawada Jr, E. T., D. B. Lee, and C. R. Kleeman. "Causes of hypercalcemia."Postgraduate medicine 66.4 (1979): 91-7.