CALCIUM

Ola H. Elgaddar

MBChB, MSc, MD, CPHQ,

LSSGB

Lecturer of Chemical

Pathology

Medical Research Institute

Alexandria University

Ola.elgaddar@alexu.edu.eg

ILOs After this lecture you should be able to

Describe bone components

Understand the biochemistry and

physiology of Calcium

Differentiate between hypo and

hypercalcemia; causes, clinical

picture and lab diagnosis

Illustrate pre-analytical and

analytical aspects of serum and

urinary calcium measurement

35 % 65 %

BONE

Most prevalent body cation

M.W ≈ 40 gm

2.5 mmol / L = ?? mg / dL

Mg / dL= 2.5 X 40 / 10 = 10 mg / dL

Biochemistry & Physiology

Exists in the 3 mentioned

states.

The free portion is the active

form.

Tightly regulated by PTH and

Vit D.

Effect of pH??

Plasma calcium regulation

Physiologically:

Intracellular Ca:

- 1/10000 of extracellular

- Physiological functions:

Muscle contraction, glycogen

metabolism & cell division

Extracellular Ca:

- Provides calcium ion for the

maintenance of intracellular calcium

- Bone mineralization, blood

coagulation & plasma membrane

potential.

Clinical Significance:

HYPOCALCEMIA

Clinical Significance:

HYPOCALCEMIA

Causes:

Hypoalbuminemia:…….Causes??

(Why?)

Pseudohypocalcemia???

- Decreased total and normal free

calcium??

1 g / dL of albumin binds

approximately 0.8 mg / dL of

calcium

Adjusted Calcium for

Hypoalbuminemia

Corrected Total Calcium (mg / dL) =

Total Calcium (mg / dL) + 0.8 (4 - Albumin [g / dL])

Clinical Significance:

HYPOCALCEMIA

Causes:

CRF: (Why?)

Hypoproteinemia

Hyperphosphatemia

Low serum 1,25(OH) Vit D

Skeletal resistance to PTH

Hypomagnesemia: (Why?)

Impairs PTH secretion

PTH end-organ resistance

Hypoparathyroidism

&

Pseudohypoparathyroidism

???

Clinical Picture

Clinical Significance:

HYPOCALCEMIA

Lab:

- Serum Calcium (Total and ionized)

- Renal functions

- Albumin

- Magnesium

- PTH

- Vitamin D deficiency

Clinical Significance: HYPERCALCEMIA

Causes:

Hyperparathyroidism:

- Most common cause in out patients

- Due to adenoma, hyperplasia or

cancer.

- Mechanism?

Malignancy:

- Most common cause in hospitalized

patients

- Due to excessive bone resorption

Clinical Picture

Clinical Significance:

HYPERCALCEMIA

Lab:

- Serum Calcium (Total and ionized)

- PTH

- Vitamin D

- PTHrP

• Parathyroid H. related peptide

• Secreted from solid tissue malignancies

• Binds to PTH receptors stimulating

bone resorption

Measuring Plasma Calcium:

Ionized Calcium

Vs

Free Calcium

???

Measuring Plasma Calcium: Pre-analytical considerations:

Tourniquet: venous occlusion, water

efflux & increase protein-bound Ca

Fist Clenching:

Exercise,

Increases

Lactate &

Lowers pH

??

Measuring Plasma Calcium: Pre-analytical considerations:

Posture:

- Main problem in hospitalized

patients (Hypoalbuminemia)

- Standing decreases intravascular

water and increases protein-bound

Albumin

Measuring Plasma Calcium: Pre-analytical considerations:

Prolonged immobilization:

- Increase bone resorption

- Which form of calcium increases?

Hyperventilation:

- Increases pH and so……??

Diurnal variation:

- Both free calcium concentration and

excretion decreases by night

Measuring Plasma Calcium: Pre-analytical considerations:

Specimen

Measuring Plasma Calcium: Analytical Methods:

Total Calcium:

Photometric:

- Cresolphthalein method

(Interference???)

- Arsenazo III Method

Atomic absorption Spectrometry:

Reference method according to CLSI

Ion Selective Electrode

Measuring Plasma Calcium: Total Calcium:

Interference:

Lipemia: Ultracentrifugation

Icterus: + or – interference

(Spectro)

Heamolysis:

+ or – interference (Spectro)

- due to dilution effect??

Magnesium

Measuring Plasma Calcium: Analytical Methods:

Free Calcium:

Measuring Plasma Calcium: Free Calcium:

Increasing the pH of a specimen in

vitro increases the ionization and

negative charge on albumin and

other proteins, leading to an increase

in protein-bound calcium and a

decrease in free calcium, and the

reverse is true.

Measuring Plasma Calcium: Free Calcium:

- Free calcium changes by about 5%

for each 0.1 unit change in pH

- Specimens must be analyzed at the

patient's pH in vivo, requiring that all

specimens be handled to prevent

alterations in pH.

Measuring Plasma Calcium: Reference intervals:

Total Calcium:

8.5 - 10.5 mg / dL

(???? Mmol / L)

Free Calcium:

1.15 – 1.33 mmol / L

(???? Mg / dL)

Assignment:

Which is better, to measure Total

or free calcium? Why?

Clinical significance and

reference range for urinary

Calcium