Calcium homeostasis Flashcards
What are the functions of calcium in the body?
Signalling Blood clotting Apoptosis Skeletal strength Membrane excitability
What is the clinical significance of hypocalcaemia?
Hypocalcaemia increases neuronal Na+ permeability leading to hyperexcitation of neurons. In extreme cases causes tetany, if spreads to larynx and respiratory muscles – asphyxiation.
What is the clinical significance of hypercalcaemia?
Hypercalcaemia decreases neuronal Na+ permeability which will reduce excitability and depress neuromuscular activity and in extreme cases, trigger cardiac arrhythmias.
How is calcium distributed in the body?
Bones contain 99% of calcium in the body
Intracellular fluid 0.9% - Mostly stored inside mitochondria and Sarcoplasmic Reticulum. Free [Ca2+ ]ic very low
Extracellular fluid 0.1% - Nearly half ECF Ca2+ is bound to protein.
How is calcium is stored in bones?
~1Kg (99%) calcium is stored in the calcified extracellular matrix of bone, mostly in the form of hydroxyapatite (Ca10(PO4)6(OH)2) so phosphate homeostasis is also important in determining calcium balance.
What % of calcium in plasma is bound?
40% is bound to plasma proteins
In what 3 forms is calcium found in the blood?
40% is protein bound, 80% of this to albumin and 20% to globulin.
How does pH affect calcium binding to plasma proteins?
- An important consideration for Ca2+ is that the binding capacity of plasma proteins changes with pH.
- Binding capacity is increased under alkalotic conditions.
- So e.g. if hyperventilate, then plasma pH rises and plasma proteins bind more Ca2+ causing plasma concentration to fall and therefore may precipitate hypocalcaemic tetany.
What do osteoblasts do?
- Osteoblasts are the bone-building cells. They are highly active cells which lay down a collagen extracellular matrix which they then calcify.
- They differentiate to form osteocytes in established bone. Osteocytes are much less active than osteoblasts but appear to regulate the activity of osteoblasts and osteoclasts.
From what cells do osteocytes differentiate from?
Osteoblasts
What do osteoclasts do?
• Osteoclasts are the cells that are responsible for mobilizing bone. They secrete H+ ions (pH ≈ 4) to dissolve the calcium salts and also provide proteolytic enzymes to digest the extracellular matrix
What two hormones increase plasma calcium concentrations?
Parathyroid hormone (PTH) polypeptide hormone produced by the parathyroid glands
Calcitriol (active form of Vit D3) steroid hormone produced from Vitamin D by the liver and kidneys
How is calcitriol produced?
Calcitriol (active form of Vit D3) steroid hormone produced from Vitamin D by the liver and kidneys
Describe the location of parathyroid glands and how many you have
• There are usually 4 lying on the posterior surface of the thyroid gland, although variations in number and location of are common, 1 in 10 people have aberrant distribution, (important if need to remove overactive thyroid gland!).
What stimulates the secretion of parathyroid hormone?
Decrease in free plasma calcium levels
How does PTH increase free plasma calcium?
o Stimulating osteoclasts to ↑ resorption (release) of Ca2+ and phosphate in bone (effects seen within 12-24hrs)
o Inhibiting osteoblasts to reduce Ca2+ deposition in bone.
o Increasing reabsorption of Ca2+ from the kidney tubules, therefore decreasing its excretion in the urine.
o Increasing renal excretion of phosphate. This elevates free [Ca2+ ] by preventing it from being deposited back into bone, a process that requires phosphate.
o Stimulates the kidney to synthesise calcitriol from vitamin D which promotes calcium absorption at the gut and kidney.
How is calcitriol also called?
Aka active Vitamin D3 or 1,25 dihydroxycholecalciferol (1,25(OH)2D3)
How is calcitriol produced?
A steroid hormone produced in two steps (1. liver, 2. kidneys) from dietary vitamin D or from precursors activated by sunlight on skin. Active vitamin D3 is formed from cholesterol derivatives by the action of UV light on the skin, but Vit D can also be gained from the diet.
What stimulates calcitriol production in pregnant woman?
Formation stimulated by hormone prolactin in lactating women.
How do we get vitamin D from our diet?
Fat-soluble vitamin, dietary sources are fatty fish eg mackerel and tuna, fish liver oils and egg yolks.
Describe the actions of calcitriol?
Binds to nuclear receptors on target cells (fat soluble)
Increases active absorption of calcium from the gut
Facilitates renal absorption of Ca2+
Mobilises calcium stores in bone by stimulating osteoclast activity
Describe how calcium is absorbed from the gut via the influence of calcitriol?
The active transport system which moves Ca2+ from the intestinal lumen to the blood is under the control of calcitriol.
What hormone stimulates calcitriol secretion?
PTH
Define vitamin D deficiency
Circulating vitamin D levels fall to less than 20ng/ml
What can cause vitamin D deficiency?
Clothing UVB sunscreen Diet Low fat Age - >65yo due to reduced gut absorption and Ca mobility
What diseases can vitamin D deficiency?
Rickets in children
Osteomalacia in adults (soft bones)
How does Vitamin D3 deficiency lead to Ca2+ and phosphate deficiency?
Vitamin D3 deficiency → intestinal malabsorption of Ca2+, this ↓ [Ca2+ ]plasma which ↑ PTH which then promotes phosphate deficiency – aggravates Ca2+ loss from bone.
Who is more at risk of vitamin D3 deficiency leading on to Ca2+ and phosphate deficiency, and why?
Elderly and Asian populations are the most at risk
Chapatti flour contains phytate which binds dietary Ca2+.
There may be dietary deficiency of vitamin D3
Pigmented skin is less able to make vitamin D3 in response to UV light.
In what diseases is vitamin D deficiency implicated in?
Vit D deficiency implicated in MS, cancer, arthritis, CVD
What hormone decreases free plasma calcium?
Calcitonin
What type of hormone is calcitriol?
Peptide
What type of hormone is calcitonin, and where is it produced?
Peptide hormone produced by the thyroid gland
What stimulates calcitonin secretion by the thyroid gland?
Increase in free calcium in plasma
How does calcitonin decrease free plasma calcium?
Its main actions are to bind to osteoclasts and inhibit bone resorption as well as ↑ renal excretion so preventing a further ↑ in Ca2+ .
What hormone can be used to treat Pagets disease?
Calcitonin
Paget’s disease (overactive osteoclasts)
How does cortisol affect calcium balance?
Cortisol inhibits osteoblasts, increases renal excretion of Ca2+ and phosphate and reduces intestinal absorption of Ca2+ →↓ plasma [Ca2+ ] →↑ PTH →↑ bone resorption. This together with the reduced bone formation can, over time, produce osteoporosis.
How does insulin affect calcium balance?
Insulin increases bone formation, and antagonises the action of cortisol. Diabetics have significant bone loss.
What hormone antagonises the effect of cortisol on calcium balance?
Insulin
How does oestrogen affect calcium balance?
Oestrogen promotes bone formation via oestrogen receptors on osteoblasts. Post-menopausal osteoporosis a major problem.
How does GH affect calcium balance?
Growth Hormone – constant stimulus for bone formation.
How does prolactin affect calcium balance?
Prolactin – promotes calcium absorption from the gut by stimulating synthesis of calcitriol.
