Calcium Homeostasis Flashcards
What are the roles of calcium in the body?
Signalling Blood clotting Apoptosis Skeletal strength Membrane excitability
How is calcium involved in signalling?
E.g. - exocytosis of synaptic vesicles (e.g. neurotransmitters/hormones etc.), contraction of muscle fibres, alters enzyme function
How is calcium involved in blood clotting?
It is an essential component of the clotting cascade
What is apoptosis?
Programmed cell death
How does calcium contribute to skeletal strength?
99% of calcium in the body is wrapped up in bone –> gives strength to skeleton
How does Ca affect membrane excitability?
Ca decreases Na permeability
How does hypocalcaemia affect the membrane excitability of neurons? Clinically what does this mean?
Increases Na permeability –> hyperexcitation of neurons
Can cause tetany, if spreads to larynx + respiratory muscles –> asphyxiation
How does hypercalcaemia affect the membrane excitability of neurons? Clinically what does this mean?
Decreases neuronal Na permeability which will reduce excitability + depress neuromuscular activity
May in extreme cases trigger cardiac arrhythmias
Describe the calcium distribution in the body
Bones - 99%
Intracellular - 0.9%
Extracellular - 0.1%
Where is most of the intracellular Ca stored?
Mitochondria and sarcoplasmic reticulum
What is most of the extracellular Ca in the plasma bound to?
Protein
NB: only 0.05% of Ca in the body is free in solution + physiologically active
How is Ca stored in bones?
It is calcified into the ECM of bone mostly in the form of hydroxyapatite (Ca10(PO4)6(OH)2)
What is the normal range for calcium in the plasma?
2.2-2.6mM
What does Ca have a very high affinity for?
Proteins (small positive charge attracted to large negative charge)
NB: 40% protein bound in plasma
How much Ca in the blood is actually free ionised?
1.2mM (50% of plasma Ca)
What accounts for the other 10% of plasma Ca that is not free nor bound to plasma proteins?
10% bind to plasma anions
What Ca is physiologically active?
Only free calcium
What two plasma proteins does calcium mostly bind to?
Albumin (80%)
Globulin (20%)
What anions can Ca bind to?
HCO3 H2PO4 HPO4 Sulphate Citrate Lactate
How does plasma pH affect the binding capacity of Ca?
Binding capacity is increased under alkalotic conditions
This may precipitate a hypocalcaemic tetany
Opposite occurs in acidosis, where binding capacity reduces and free Ca rises
Why does acidosis lead to more free Ca?
Increased [H+] displaces bound Ca2+ so there is more free Ca
Total body calcium =
Ca in (diet) - Ca out (excretion at kidneys + faeces)
Bone functions to provide mechanical support for the body but its role in _________________ takes precedence over this.
Maintaining Ca balance
Ca stored in bone can be added to or released as req.
What are osteoblasts?
Bone building cells - lay down a collagen extracellular matrix which they calcify
What do osteoblasts differentiate into?
Osteocytes in established bone
What are the roles of osteocytes?
Appear to regulate the activity of osteoblasts + osteoclasts
What is the role of osteoclasts?
Mobilising bone
How do osteoclasts mobilise bone?
Secrete H ions to dissolve Ca salts + provide proteolytic enzymes to digests the EC M
What are the two main hormones that act to raise plasma Ca levels?
Parathyroid hormone
Calcitriol
What kind of hormone is PTH and where is it produced?
Polypeptide hormone
Produced by the parathyroid glands
What is calcitriol?
Active form of VitD3, steroid hormone produced from Vit D by the liver + kidneys
Where are the parathyroid glands found?
Usually 4 on the posterior surface of the thyroid gland
NB: 1 in 10 have aberrant distribution (important for thyroid surgery)
True or false:
Parathyroid glands are not essential for life and can be removed during thyroid surgery without complication
FALSE
They are essential for life
When is PTH secreted?
In response to low [Ca]plasma
What does PTH do?
Increases free [Ca] plasma by:
- stimulating osteoclasts to increase resorption of Ca + phosphate in bone
- Inhibit osteoblasts
- Increasing reabsorption of Ca at kidney tubules
- Increasing renal excretion of phosphate
- Stimulating kidneys to make calcitriol
How does calcitriol increase free Ca in the plasma?
Binds to nuclear receptors in target tissues (intestine, bone, kidney) to increase absorption of Ca from the gut, facilitate renal absorption of Ca and mobilise Ca stored in bone by stimulating osteoclasts
How does increasing renal excretion of phosphate increase free Ca levels?
Prevents it being deposited back into bone, a process that req. phosphate
Describe the production of calcitriol
Endogenous precursors are acted upon by sunlight on skin to produce vitamin D or acquired from diet
Vit D processed in liver to become vit D3 and then metabolised in the kidneys to become calcitriol
What other hormone stimulates the production of calcitriol?
Prolactin in lactating women
What foods are high in vit D?
Fatty fish, egg yolks etc.
How much dietary calcium is normally absorbed?
30%
Why are older individuals at more risk of becoming vit D deficient?
Reduced gut absorption and reduced Ca mobility
What does vitamin D3 deficiency result in?
Intestinal malabsorption of Ca –> reduced Ca in plasma –> increased PTH which promotes phosphate deficiency and aggravates Ca loss from bone
Why are Asian populations at most risk of vit D3 deficiency?
Chapatti flour contains phytate which binds dietary Ca
Dietary deficiency of Vit D3
Pigmented skin less able to make Vit D3 in response to UV light
What conditions has vit D deficiency been implicated in?
MS
Cancer
CVD
What hormone decreases [Ca] plasma?
Calcitonin
Where is calcitonin produced?
Thyroid gland
What stimulates the secretion of calcitonin?
Increased plasma Ca level
What is the main action of calcitonin?
Bind to osteoclasts + inhibit bone resorption + increase renal excretion of Ca
Why is it thought that calcitonin is not that important?
Where calcitonin levels are really high (e.g. thyroid tumours), plasma Ca levels are normal, so xs calcitonin is overridden by PTH
How does cortisol affect Ca balance?
Inhibits osteoblasts, increases renal excretion of Ca+ phosphate + reduces intestinal absorption of Ca –> increased PTH –> increased bone resorption which over time can produce osteoporosis
How does insulin affect bone formation?
Increases bone formation + antagonises action of cortisol
How does oestrogen affect bone formation?
Promotes bone formation via oestrogen receptor on osteoblasts
How does growth hormone affect bone formation?
Constant stimulus for bone formation
How does prolactin affect calcium balance?
Promotes calcium absorption from gut via stimulating synthesis of calcitriol
