Endocrine Control of Calcium Balance Flashcards
What are the rolls of calcium in the body?
Signalling Blood clotting Apoptosis Skeletal strength Membrane excitability
What is the signalling role of Ca2+?
Exocytosis
Contraction of muscle fibres
Altering enzyme function
What is the blood clotting role of Ca2+?
Part of clotting cascade
What is the membrane excitability role of Ca2+?
Ca2+ decreases Na+ permeability
What effect does hypocalcaemia have?
Increased neuronal Na+ permeability causing hyper-excitations
- Tetany
What effect does hypercalcaemia have?
Decreased neuronal Na+ permeability
Reduced excitability
Depressed neuromuscular activity
Arrhythmias!!
What is the distribution of calcium in the body?
Bones 99%
Intracellular 0.9%
Extracellular fluid 0.1%
Where is intracellular calcium stored?
Inside mitochondria, sarcoplasmic reticulum
How is calcium stored in the extracellular fluid?
~50% bound
How much calcium in the body is free in solution?
0.05%
How much calcium is stored in bones? How is it stored?
99% - 1kg
Calcified extracellular matrix in hydroxyapatite with PO4
What other factor is also important in determining calcium balance?
Phosphate homeostasis
Calcium is stored with what in the bones?
Ca10(PO4)6(OH)2
Hydroxyapatite
What is the normal range of plasma Ca2+?
2.2-2.6mM in plasma
Calcium has a high affinity for what? Why?
Proteins
they have a large -ve charge
Which part of [Ca2+]plasma is physiologically active?
~50%, unbound, 1.2mM
What happens to the 10% of calcium ions not bound to plasma protein, nor free in solution?
Bound to plasma anions
What proteins, and to what proportion, is calcium bound?
Albumin - 80%
Globulin - 20%
Which anions is calcium typically bound to?
HCO3 H2PO4 HPO4 Sulphate Citrate Lactate
What is the calcium distribution in blood?
40% protein bound
10% complexed
50% free
The binding capacity of Ca2+ is dependent on what?
pH
When is binding capacity increased?
Alkalotic conditions
What is the effect on plasma pH of hyperventilation?
Increased pH
How can hyperventilation precipitate hypocalcaemic tetany?
Decreased CO2
Increased pH
Increased bound [Ca2+]
Hypocalcaemia
What is the effect of acidosis on protein bound calcium?
Decreased pH increases plasma [H+] which displaces bound Ca2+, increasing free [Ca2+]
Total body calcium = ?
Calcium in - Calcium out
What is the most important role of bone?
Calcium balance maintenance
What are osteoblasts?
Bone building cells
How do osteoblasts work/
Highly active
Lay down collagen extracellular matrix which they then calcify
Differentiate into osteocytes in established bone
What do osteocytes do?
Regulate osteoblast/osteoclast activity
What is the function of osteoclasts?
Secrete H+ (pH 4) to dissolve calcium saltes
Provide proteolytic enzymes to digest extracellular matrix
Which hormones increase [Ca2+]plasma?
Parathyroid hormone
Calcitriol
What is parathyroid hormone?
Polypeptide hormone produced by the parathyroid gland
What is calcitrol?
Active form of Vitamin D
Steroid hormone produced by liver and kidneys
Where are the parathyroid glands located?
Lying on the posterior surface of the thyroid gland
When is parathyroid hormone secreted?
Response to ↓[Ca2+]plasma
How does parathyroid hormone increase [Ca2+]?
- Stimulate osteoclasts to resorb Ca and Phosphate
- Inhibit osteoblasts to reduce Ca deposition
- Increase reabsorption of Ca2 from kidney tubules
- Increase renal phosphate excretion
- Stimulate kidney calcitrol synthesis promoting calcium absorption
How does increasing renal excretion of phosphate increased [Ca2+]?
Prevents Ca2+ from being deposited back into bone
What is calcitriol?
Active vitamin D3
What type of hormone is calcitriol?
Steroid hormone
What also stimulates formation of calcitriol?
Prolactin (lactating women)
How does sunlight form vitamin D3?
Action of UV light on the skin causing cholesterol –> vitamin D3
What are the dietary sources of vitamin D3?
Fatty fish
Fish liver oils
Egg yolks
How is calcitrol produced?
Vitamin D
Processed by liver, then kidneys
OR
Steroid precursors activated by UV light
Which actions of calcitrol complement PTH?
Increased Ca2+ absorption in gut
Facilitates renal absorption of Ca2+
Mobilises calcium stores in bone
How does calcitrol mobilise calcium stores in bone?
Stimulating osteoclast activity
How does calcitriol control intestinal intake of Ca2+?
Controlling active transport system
What is the effect of low plasma [Ca2+]?
↑ in PTH –> ↑calcitriol –> ↑intestinal Ca2+ absorption
What is the effect of prolactin in relation to Calcium?
Stimulation of calcitriol synthesis by kidneys to supply increased demand
What is the amount of dietary Ca2+ absorbed in a healthy individual?
30%
What is the amount of dietary Ca2+ absorbed in a vitamin D deficient individual?
10-15%
What is the amount of dietary Ca2+ absorbed in a pregnant/lactating/growing individual?
45-55%
What is the amount of calcitriol in a vitamin D deficient individual?
Low
What is the amount of calcitriol in a pregnant/lactating/growing individual?
High
When is Vitamin D considered ‘deficient’?
Circulating vitamin D <20ng/ml
What % of scots are vitamin D insufficient?
Summer - 75%
Winter - 92%
When does Vitamin D deficiency become more prevalent?
> 65 years due to reduce absorption
How does vitamin D deficiency present?
Children - Rickets
Adults - Osteomalacia
If calcitriol causes Ca release from bone, how does it make bones stronger?
Greater effect on gut absorption/kidney reabsorption, which increases bone mineralization
Vitamin D3 deficiency leads to what?
Ca2+ and Phosphate deficiency
How does vitamin D3 deficiency lead to phosphate deficiency?
Intestinal malabsorption means low [Ca2+], this increases PTH
Increased PTH aggravated Ca loss from bone .’. loss of phosphate
Why are asians at risk of Ca deficiency?
Chapatti flour contains phytate
Phytate binds dietary Ca2+
Pigmented skin less able to respond to UV light
Vitamin D deficiency is implicated in what?
MS
Cancer
Arthritis
CVD
Which hormone decreases [Ca2+]
Calcitonin
What type of hormone is calcitonin?
Peptide hormone
What stimulates calcitonin secretion?
↑ [Ca2+]
Where is calcitonin produced?
Thyroid gland
What are the main actions of calcitonin?
Bind to osteoclasts and inhibit bone resorption
Increase Ca2+ excretion by kidneys
When is calcitonin used as a treatment?
Paget’s Disease
overactive osteoclasts
What is the effect of Cortisol on Ca2+ balance?
Inhibit osteoblasts
Increase Ca2+ and phosphate
Reduce intestinal absorption
Increase PTH .’. ↑bone resorption
What can increased cortisol lead to over time?
Osteoporosis
What is the effect of insulin on Ca2+ balance?
Inhibit cortisol
Increase bone formation
What is the effect of oestrogen on Ca2+ balance?
Promote bone formation via oestrogen receptors on osteoblasts
What is the effect of growth hormone on Ca2+ balance?
Constant stimulus for bone formation
What is the effect of prolactin on Ca2+ balance?
Promotes calcium absorption by the gut, stimulating synthesis of calcitriol
When are osteoclasts stimulated?
When calcium is low
Where is Calcitriol activated?
Kidneys
What causes the inhibition of PTH?
Increased plasma [Ca2+]
Calcitriol binds to what?
Target tissue nuclear receptors
Intestine
Bone
Kidney
What is the primary action of vitamin D?
Get calcium out of the gut