Mineral Homeostasis

• calcium is the most abundant mineral in the body at 25 moles (1kg in a 70kg individual)
• 99% of the body's calcium is in bone and teeth as hydroxyapatite - combined with phosphorus to harden and strengthen the bone and teeth
• 85% of phosphorus is found in the bone
• extracellular fluid calcium concentrations are very small in comparison to total body calcium
• calcium is in a constant stqate of flux
• some bone is reabsorbed every day as it is not a static tissue allowing Ca to be returned to extracellular fluid to maintain balance and create new bone formation
• calcium is absorbed from the diet and secreted into the gut
• net absorption of calcium is the amount lost in urine
• roughly 10% of bone is turned over each year - within 10 years you have a new skeleton
• dietary calcium intake is 25 mmol/day
• 12mmol/day of calcium is absorbed into the ECF and 7mmol/day is excreted from ECF to the GIT to give a net volume of 23mmol with 9mmol in plasma
• 500mmol/day is in flux between bone and ECF
• 20mmol of calcium each day is excreted from GIT in faeces
• 235mmol/day Ca absorbed from kidney and 240mmol/day excreted to the kidney causing a 5mmol/day renal loss - balanced with the net Ca absorption in the GIT
• calcium is present in plasma in 3 forms:

  1. ionised or free - this is active (50-65%)
  2. bound, mostly to plasma albumin (30-45%)
  3. complexed with other ions such as citrate, phosphate, and bicarbonate(5-10%)
• Ca2+ is physiologically active and important in maintaining extracellular Ca within narrow limits by :

  • maintaining skeletal tissue
  • muscle contraction
  • controlling cell functions
  • release of neurotransmitters from neurones
• calcium affects membrane permeability
• calcium activates blood coagulation
• Ca is involved in glandular secretions by bringing Ca into cells due to hormone action
• calcium affects cell adhesion and shape
• Ca is closely regulated by parathyroid hormone (PTH)
• plasma [total Ca] reference range is between 2.2 and 2.6 mmol/L
• protein-binding of Ca is pH dependent:

  • acidosis = Ca is displaced from protein causing an increase in plasma con
  • alkalosis = Ca is bound to protein causing a decrease in plasma con
• it is possible to measure ionised Ca but requires specialized equipment and collection techniques - not available in most labs
• there are problems in interpretation in the measurement of Ca as changes in albumin concentration cause changes in Ca concentration and so an adjusted Ca is calculated
• Adjusted Ca value

  total Ca + 0.02 (47 - [alb] g/L)
• 47 is the midpoint of the plasma albumin concentration reference range
• an increase or decrease by 0.1 mmol/L of [Ca] for every 5g/L of albumin is above or bellow 47g/L
• levels of calcium are controlled by the action of PTH and 1,25 - dihydroxycholecalciferol (1,25-DHCC)
• PTH has a molecular weight of 9,500 and consists of 84 amino acids
• the reference range for PTH is 29-85 pmol/L
• PTH is produced by parathyroid glands and secreted in response to a decrease in the concentration of ionised Ca
• PTH increases calcium levels by:

  1. stimulating osteoclasts to release Ca from bone into the ECF
  2. increase renal absorption preventing loss in urine
  3. increase synth of 1,25-DHCC
• 1,25-DHCC is calcitriol and synthesis is activated by high levels of PTH and low levels of Ca causing increased:

  • Ca uptake in intestines
  • Ca reabsorption from bone and kidneys
• calcitriol is the active version of vitamin D
• hypercalcaemia occurs when the adjusted [Ca]> 2.8 mmol/L - it is life threatening if 3.5mmol/L as that level can cause cardiac arythmias
• clinical features of hypercalcaemia include:

  • lethargy, confusion, irritability and depression
  • abdominal pain, nausea, anorexia, vomiting and constipation
  • renal stones, thirst and polyuria
  • cardiac arythmias
• a common cause of hypercalcaemia is primary hyperparathyroidism
• PTS-secreting adenoma is a benign tumour which synthesizes and secretes PTH with no feed back control causing Ca levels to rise
• with prolonged stimulation of parathyroids due to a secondary condition tertiary hyperparathyroidism can occur where PTH secretion becomes autonomous