Calcium homeostasis
Dr. Ahmed Jabbar Abbas
PhD. Clinical Biochemistry
Calcium
• Calcium is the most abundant mineral in the human body.
• The average adult body contains ∼25000 mmol (1 kg), of
which 99% is bound in the skeleton.
• The total calcium content of the extracellular fluid is only
22.5 mmol, of which about 9 mmol is in the plasma .
• About 25 mmol (1 g) of calcium is ingested per day, of which
there is a net absorption of 6–12 mmol (0.25–0.5 g).
• Calcium is lost in urine and faeces.
• Faecal calcium is derived from the diet and that portion of the
large amount of intestinal secretions that has not been
reabsorbed.
• Calcium in the intestine may form insoluble, poorly absorbed
complexes with oxalate, phosphate or fatty acids.
• An excess of fatty acids in the intestinal lumen in steatorrhoea
may contribute to calcium malabsorption.
Effect of protein concentration
• Changes in plasma protein concentration, particularly of albumin
alter the most commonly measured concentration, that of plasma
total calcium, but not that of the free ionized fraction.
• The plasma total calcium concentration is lower in the supine than in
the erect position because of the effect of posture on fluid
distribution and therefore on plasma protein concentration.
• The direct measurement of the physiologically active free calcium
ionized fraction is, for technical reasons, confined to special cases
such as acid–base disturbance.
Effect of pH
• Changes in plasma hydrogen ion concentration ([H+]) affect the binding of
calcium to plasma proteins because H+ competes with Ca2+ for binding sites.
• The plasma total calcium concentration is unaltered by changes in [H+].
• If [H+] falls, as in an alkalosis, tetany may occur, despite a normal plasma total
calcium concentration.
• Conversely, an acidosis decreases binding and so increases the proportion of
plasma calcium in the free ionized form.
• Also, it increases the rate of release of calcium from bones into the extracellular
fluid .
• The increased load reaching the kidneys increases the renal calcium loss.
• Prolonged acidosis may cause osteomalacia, partly due to the buffering effect of
bone .
Parathyroid Hormone
• The parathyroid gland secretes parathyroid hormone in response to low calcium levels
detected in the blood.
• PTH facilitates the synthesis of active vitamin D in the kidneys.
• In conjunction with calcitriol, PTH regulates calcium and phosphate.
• PTH effects are present in the bones, kidneys, and small intestines.
• As serum calcium levels drop, the secretion of PTH by the parathyroid gland increases.
• Increased calcium levels in the serum serve as a negative-feedback loop signaling
the parathyroid glands to stop the release of PTH.
• The mechanism of PTH in the body is intricate, and the clinical ramifications of irregularities
are significant.
• The understanding of PTH is of paramount relevance and importance
Vitamin D
It is a group of fatsoluble secosteroids responsible for
increasing intestinal absorption of calcium, magnesium,
and phosphate, along with numerous other biological
functions.
• In humans, the most significant compounds within this
group are vitamin D3 (cholecalciferol) and vitamin D2 (
ergocalciferol).
Calcitonin
• Calcitonin (produced in the C cells of the thyroid gland)
• It decreases osteoclastic activity, slows calcium release from bone
and has the opposite effect on plasma concentrations of PTH.
• It is probably less important than PTH in physiological homeostasis.
• Plasma concentrations may be very high in patients with medullary
carcinoma of the thyroid, although hypocalcaemia is not usually
reported in this condition.
• However, exogenous calcitonin has been used to treat
hypercalcaemia and Paget’s disease of bone.
Hypocalcaemia
■ Vitamin D deficiency. This may be due to malabsorption, or an
inadequate diet with little exposure to sunlight. It may lead to the
bone disorders, osteomalacia in adults and rickets in children .
■ Hypoparathyroidism.
■ Magnesium deficiency. This is a common cause in hospital
patients.
■ Renal disease. The diseased kidneys fail to synthesize 1,25 DHCC.
Increased PTH secretion in response to the hypocalcaemia may lead
to bone disease if untreated.
■ Hungry bone syndrome. There can be severe and potentially fatal
hypocalcaemia with accompanying hypophosphataemia after
parathyroidectomy, due to rapid remineralization of bone (after sudden
decrease in PTH), especially after long-standing primary
hyperparathyroidism with severe bone disease.
■ Pseudohypoparathyroidism. PTH is secreted but there is failure of
target tissue receptors to respond to the hormone.
■ Rarer causes such as malignancy, acute rhabdomyolysis, acute
pancreatitis, ethylene glycol poisoning or bone marrow transplantation.
Hypercalcemia
■ Inappropriate dosage of vitamin D or metabolites, e.g. in the treatment
of hypoparathyroidism or renal disease or due to self-medication.
■ Granulomatous diseases (such as sarcoidosis or tuberculosis) or certain
tumours (such as lymphomas) synthesize 1,25-dihydroxycholecalciferol.
■ Thyrotoxicosis very occasionally leads to increased bone turnover and
hypercalcaemia.
■ Thiazide therapy: the hypercalcaemia is usually mild.
■ Immobilization: especially in young people and patients with Paget’s
disease.
■ Renal disease. Long-standing secondary hyperparathyoidism may lead to
PTH secretion becoming independent of calcium feedback. This is termed
tertiary hyperparathyroidism.
■ Calcium therapy. Patients are routinely given calciumcontaining solutions
during cardiac surgery, and may have transient hypercalcaemia afterwards.
■ Diuretic phase of acute renal failure or in the recovery from severe
rhabdomyolysis.
■ Milk alkali syndrome: the combination of an increased calcium intake
together with bicarbonate, as in a patient self-medicating with proprietary
antacid, may cause severe hypercalcaemia, but the condition is very rare.
