calcium

see also:

• phosphate
• magnesium
• vitamin D
• parathyroid hormone (PTH)
• calcitonin
• hypercalcaemia
• hypocalcaemia
• calcium gluconate
• osteoporosis
• bone physiology

• intravenous calcium as either calcium chloride or calcium gluconate is occasionally required in the ED to treat:
  • severe hypocalcaemia
  • severe hyperkalaemia
• calcium gluconate is generally preferred as it causes less tissue damage if inadvertently extravasated
  • as long as equivalent molar doses are used, calcium gluconate works as quickly (and to the same degree) as calcium chloride to raise calcium concentration¹⁾
  • you need 3 grams calcium gluconate to give the same molar dose of calcium (270mg of elemental calcium) as 1 gram calcium chloride

• adults contain 1100g Ca (27.5 mol) ie. l.5% body weight;
• plasma calcium:
  • corrected calcium normal range: 2.10-2.60 mM , if total plasma calcium is 2.5mM then:
    • 54% is diffusible (1.34 mM):
      • l.18 mM free ionised;
      • 0.16 mM complexed HCO3, citrate;
    • 46% protein bound (l.16 mM):
      • 0.92 mM albumin bound;
      • 0.24 mM globulin bound;
• protein binding increased (& thus free ionised calcium is decreased) if:
  • pH increased (eg. hyperventilation) ⇒ increased anion sites;
  • [plasma protein] increased;
• to calculate corrected total calcium level:
  • add 0.1mM calcium for every 4g/L that albumin is below 40g/L, & converse if above 40g/L
  • ie. corrected calcium = measured total calcium + [0.1 x (40 - serum albumen) / 4]
  • NB. this does not correct for other causes of artefactual calcium measurements:
    • presence of other proteins: eg. myeloma, cirrhosis, individual variation
    • poor blood sampling - prolonged tourniquet
  • if in doubt consider ABG or VBG on blood gas machine that measures ionised calcium
• it is the free ionised Ca which is important as a vital 2nd messenger, a decreased [free calcium] in extracellular fluid ⇒ tetany;
• calcium measurements by most blood gas machines measure free ionised calcium and not total calcium!

• for most people, calcium requirements are in the range 800-1500 mg daily.
  • these requirements are best met by consuming at least two or three servings of high calcium foods daily (for example, milk products, calcium-fortified soy products). A serving of dairy food contains 200-300 mg of elemental calcium
  • The recommended daily calcium intake is 800 mg for adults, 1100–1200 mg during pregnancy and lactation and 1500 mg in postmenopausal women.
• when checking the true calcium content of foods and supplements, it is the elemental calcium that matters.
• Daily physiological needs may be at least 1000 mg during growth, in pregnancy and possibly in the late postmenopausal stage of life.
  • Recommended dietary intakes of calcium (under review) indicate an additional 300 mg daily in pregnancy and an additional 400 mg daily for lactation.

• Calcium supplements can be a useful way of helping individuals who are unable to consume sufficient calcium from dietary sources, however, recent studies suggest that those who are not institutionalised, and who take calcium supplements may have 20-30% increased risk of acute myocardial infarction (AMI/STEMI/NSTEMI) and stroke (CVA)²⁾
• An extra 500-700 mg elemental calcium per day will suffice for most people.
• The cheapest, easiest way to achieve this objective is with a single calcium carbonate tablet containing 600 mg elemental calcium.
  • Calcium carbonate contains 40% elemental calcium by weight compared with 21% in calcium citrate. Although calcium citrate is more soluble and its bioavailability may be approximately 25% greater than that of calcium carbonate and it is also more expensive.
• In general, it is recommended to prescribe or advise the use of widely available, major brand-name calcium preparations whose absorbability has been well documented. This is because the absorbability of some marketed products is only 40-60% of that of plain calcium carbonate.
• Calcium supplements are usually well tolerated. Occasional adverse effects include constipation, bloating and flatulence.
• Calcium supplementation is contraindicated in the presence of hypercalcaemia or marked hypercalciuria, and during calcitriol therapy for osteoporosis, because of the risk of inducing hypercalcaemia or hypercalciuria.
• Measurement of the serum calcium, albumin and creatinine should therefore be part of the pre-treatment evaluation of patients presenting with apparent osteoporosis. Caution is also required in renal impairment, sarcoidosis and when there is a history of nephrolithiasis.
• avoid intake during fasting in patients with gastric hypochlorhydria / achlorhydria (eg. on PPI's) as absorption is poor and consider citrate form in these patients, otherwise there is no need for precise timing of intake, although evening intake may reduce the normal nocturnal rise in bone resorption rate, and they should be taken several hours apart from medications which buind calcium such as bisphosphonates.
• absorption of calcium is impaired by:
  • phytates (found in cereals, bran, soybeans, seeds)
  • oxalates (found in spinach, rhubarb, walnuts)
  • vitamin D deficiency
  • long-term corticosteroids treatment
  • achlorhydria and perhaps proton pump inhibitors (PPIs)
  • renal disease

• 30-80% ingested Ca is absorbed;
• Active transport of Ca out of lumen occurs mainly in upper GIT, and there is some absorption by passive diffusion;
• this Ca-depend. ATPase may become saturated if high intake Ca;
• Active transport incr. by:
  • 1,25 dihydroxycholecalciferol - this is incr. if: decr. [Ca]plasma
    • ⇒ incr. Ca binding protein via exposing DNA-binding region;
    • ⇒ incr. basolateral cell Ca pumping out of cell ⇒ ECF;
  • high protein diet (adults);
  • decr. luminal phosphates and oxalates (form insoluble salts);

• see bone physiology

• 98-99% of filtered Ca is reabsorbed, thus only 1% filtrate excreted:
  • 60% reabsorption in prox. tubules;
  • distal tubular reabs. regulated by parathyroid hormone;

• parathyroid hormone ⇒ incr. Ca reabs. distal tubules;
  • ⇒ decr. P reabs. prox. tubules;
• calcitonin ⇒ incr. Ca excretion;
• 1,25 dihydroxycholecalciferol ⇒ incr. Ca reabs.
• there is concern that high intake of phosphate containing beverages such as Diet Coke may lead to increased calcium excretion and thus increase risk of osteoporosis.
• there is no evidence for this currently, but one may theorise that high levels of phosphate will result in increased parathyroid hormone secretion due to the fall in free ionised calcium levels, this may then result in:
  • increased phosphate excretion
  • mobilisation of calcium from bones and thus risk of osteoporosis but the rise in serum calcium will then reduce PTH secretion returning system to normal

increased 1,25 dihydroxycholecalciferol production but this may be minimised by inhibition by raised phosphate levels renal calcium excretion will only increase if the rise in serum calcium is sufficient to cause increased calcitonin secretion thus as long as dietary calcium intake is reasonable, additional risk of osteoporosis may be marginal

• MJA March 2009 - Position statement - Calcium and bone health: position statement for the Australian and New Zealand Bone and Mineral Society, Osteoporosis Australia and the Endocrine Society of Australia
• Aust. Presc 2003 Calcium supplementation: the bare bones