Hypocalcaemia

Aetiologies

• Increased binding of calcium to protein
• Magnesium is required for the release of PTH ⇒ hypomagnesaemia can precipitate hypocalcaemia

Factor	Effect on Ionised Calcium
Albumin	increased albumin = decreased ionised calcium
pH	increased pH = decreased ionised calcium
Lactate	increased lactate = decreased ionised calcium
Phosphate	increased phosphate = decreased ionised calcium
Bicarbonate	increased bicarbonate = decreased ionised calcium
Citrate	increased citrate = decreased ionised calcium
Heparin	Presence of heparin in the sample = decreased ionised calcium
Free fatty acids	Increase in free fatty acids = decreased ionised calcium

Physiology of Calcium Homeostasis

Parathyroid Hormone

• Secreted by chief cells of the parathyroid glands
• Most regulatory influences on PTH are inhibitory influences (inorganic phosphate is the only proper stimulatory release factor)
• Calcium level and PTH secretion relation is not linear; high calcium can never completely suppress PTH secretion and PTH secretion reaches a peak at calcium concentration of around 0.90 mmol/L
• Effects of PTH
  • Osteoclastic:
    • Direct effect on decreasing osteoblast activity
    • Increased osteoclast activity
    • Thus, increased release of calcium and phosphate from bone, and decreased bone deposition
  • Renal:
    • Decreased reabsorption of inorganic phosphate at the proximal tubule
    • Increased reabsorption of calcium at the thick ascending limb of the loop of Henle
    • Increased production of production of calcitriol in the kidney, through the stimulation of renal 1α-hydroxylase.

Calcitonin

• Secreted from parafollicular cells of the thyroid gland
  • Osteoclastic:
    • Direct effect on decreasing osteoclast activity¹
    • This decreases the resorption of bone, and therefore limits the entry of bone calcium and phosphate into the blood
  • Renal:
    • Calcitonin acts as a weak diuretic, increasing the elimination of sodium, chloride, phosphate and calcium. The effect on calcium is mainly due to inhibited reabsorption.
    • It also increases production of production of calcitriol in the kidney, through the stimulation of renal 1α-hydroxylase.
  • Intestinal:
    • Calcitonin increases gastric acid and pepsin secretion and decreases pancreatic amylase secretion.
    • It has no direct effect on calcium absorption in the intestine, but it can increase it indirectly by stimulating renal calcitriol synthesis

Action of Biphosphonates

• Inhibition of osteoclast and osteoblast activity
  • Osteoclasts:
    • Inhibition of osteoclast recruitment and adhesion
    • Shortening of the life span of osteoclasts
    • Inhibition of osteoclast activity by inhibiting several essential parts of the cholesterol synthesis pathway
  • Inhibition of calcification by inhibiting the formation of calcium phosphate salts
    • Mainly seen in high doses
    • A totally physicochemical effect: they bind to the calcium of calcium phosphate
    • The result is inhibition of formation and aggregation of calcium phosphate crystals and inhibition of the transformation of amorphous calcium phosphate into hydroxyapatite.

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Investigations

• Correcting $\mathrm{Ca}{}^{+}$ for albumin, however evidence demonstrates that formulas actually perform worse than uncorrected calcium levels

$$\mathrm{Corrected}\mathrm{Calcium}=0.8\times (40-\mathrm{Albumin})+\mathrm{Ca}{}^{2+}$$