Calcium Homeostasis Flashcards
What are some roles of calcium in the body?
Signalling
Blood clotting
Apoptosis
Skeletal strength
Membrane excitability
How does calcium have a signalling role?
Important for exocytosis of vesicles such as neurotransmitters and hormones
Or contractile muscle fibres
Or altering enzyme function
How does calcium have a membrane excitability role?
Calcium decreases sodium permeability
What effect does hypocalcaemia have on neuronal sodium pereability?
Increases Na permeability leading to hyperexcitation of neurons, in extreme cases tetany
If spreads to larynx and respiratory muscles causes asphyxiation
What effect does hypercalcaemia have on sodium permeability?
Decreases Na permeability which will reduce excitability and depress neuromusculae activity
In extreme cases will trigger cardiac arrhythmias
How is calcium distributed in the body?
Bone 99%
Intracellular 0.9%
Extracellular 0.1%
What does the weight of calcium in bone weigh?
About 1kg
How is calcium stored in bone?
Stored in calcified extracellular matrix mostly in the form of hydroxyapatite, so phosphate homeostasis is also important in determining calcium balance
Where is most of the intracellular calcium stored?
Inside mitochondria and sarcoplasmic reticulum
What percentage of extracellular calcium is bound to protein?
Nearly 50%
What calcium in the body is free and physiologically active?
The 50% of extracellular calcium that is not attached to proteins (0.05% of total body calcium)
Why does calcium have a very large affinity for proteins?
Small positive charge attrached to large negative charge
So in plasma 40% is bound to proteins
Explain the distribution of extracellular calcium stores?
Protein bound 40%
Free (ionised) 50%
Complexed 10%
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What proteins is extracellular calcium bound to?
Albumin 80%
Globulin 20%
What changes the binding capacity of calcium to plasma proteins?
pH
Binding capacity is increased under alkalotic conditions
How does hyperventilation impact the binding of calcium to plasma proteins?
Hyperventilation raises plasma pH
Less calcium binds to proteins
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Why do alkalotic conditions increase binding capacity of calcium to plasma proteins?
Less hydrogen ions to complete with for negative binding spots of plasma protein
What is increased pH known as?
Alkalosis
What is decreased pH known as?
Acidosis
What is the total body calcium determined by?
Calcium from diet and calcium excreted at kidneys and faeces
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What is more important, calciums role in bone to provide mechanical support or maintaining calcium balance for physiological activites?
Maintaining calcium balance
What are osteoblasts?
Bone building cells, highly active cells which lay down a collagen extracellular matrix which will then calcify
What do osteoblasts differentiate into?
Osteocytes in established bone, which are much less active but appear to regulate the activity of osteoblasts and osteoclasts
What are osteoclasts?
Cells that mobilise bone, secrete H+ ions (pH about 4) to dissolve the calcium salts and produce proteolytic enzymes to digest extracellular matrix
What are the 2 key hormones that act to increase [Ca2+]plasma?
Parathyroid hormone (PTH)
Calcitol
What does PTH stand for?
Parathyroid hormone
What class of hormone of PTH?
Peptide hormone produced by parathyroid glands
What is calcitol?
Active form of vitamin D3
What class of hormone is caltisol?
Steroid hormone produced from vitamin D by liver and kidneys
What is caltisol produced from?
Vitamin D by liver and kidneys
How many parathyroid glands are there?
Usually 4 but can vary
What is parathyroid hormone released in response to?
Decrease in free [calcium]plasma
Explain the effects of PTH?
- Stimulating osteoclasts to increase resorption (release) of calcium and phosphate in bone (effects seen within 12-24 hours)
- Inhibiting osteoblasts to reduce calcium deposition in bone
- Increasing reabsorption of calcium from kidney tubules, therefore decreasing its excretion in urine
- Increasing renal excretion of phosphate, elevating free calcium by preventing it from being deposited back into bone (a process that requires phosphate)
- Stimulates kidney to synthesis calcitriol from vitamin D which promotes calcium absorption at the gut and kidney
What effect does PTH have on bone?
Stimulate osteoclasts to increase resorption (release of calcium)
Stimulates osteoblasts to reduce calcium deposition in bone
What effect does PTH have on the kidneys?
Increase reabsorption of calcium from kidney tubules, decreasing its excretion in urine
Increase renal excretion of phosphate, elevating free calcium by preventing it from being deposited back into bone (process that requires phosphate)
Stimulates synthesis of calcitrol form vitamin D which promotes calcium absorption at the gut and kidney
What is calcitriol also known as?
Also known as active vitamin D3 or 1, 25 dihydroxycholecalciferol (1,25(OH)2D3)
What is the ultimate effect of calcitriol?
Compliments the action of PTH, so increases calcium in plasma
Where does each stemp of calcitirol formation take place?
Step 1 in liver
Step 2 in kidneys
What is formation of calcitriol stimulated by?
Sunlight on skin
Hormone prolactin in lactating woman
What is active vitamin D3 formed from?
Cholesterol deriviatives from UV action on skin
Also from diet
Is vitamin D a fat soluble vitamin?
Yes
What are some diatery sources of vitamin D?
Fatty fish such as mackeral or tuna
Fish liver oils
Egg yolks
What does calcitriol bind to?
Nuclear receptors in target tissues (intestine, bone and kidneys)
What is the effect of calcitriol?
Increase absorption of calcium from gut
Facilitate renal absorption of calcium
Mobilises calcium stores in bone by stimulating osteoclast activity
What are the active transport systems in the gut that moves calcium from intestine lumen to blood under the control of?
Calcitriol
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Why does prolactin stimulate calcitriol synthesis?
Increased demand for calcium for milk production in lactation
What controls the proportion of dietary calcium absorbed from intestine?
Circulating levels of calcitriol
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When does vitamin D deficiency occur?
When circulating levels fall less than 20ng/ml
Where is vitamin D normally stored?
Extensively in fat
What percentage of Scots are vitamin D deficient?
75% in summer, rising to 92% in winter
Is vitamin D deficiency more prevalent in older or younger people, and why?
People over 65 due to reduced gut absorption and reduced calcium mobility
What impact does vitamin D3 deficiency have on bone?
PTH works hard to miantian plasma calcium and in doing so continually removes calcium from bone resulting in soft bone, and if still growing can become bent
What bone conditions are caused by vitamin D3 deficiency in adults and children?
Adults - osteomalacia
Children - rickets
How does vitamin D3 deficiency lead to phosphate deficiency?
Vitamin D3 deficiency -> intestinal malabsorption of calcium, lowering calcium in plasma which increases PTH -> which promotes phosphate deficiency – aggravating calcium loss from bone:
Who is most at risk of vitamin D deficiency?
Asian populations and elderly:
- chapatti flour contains phytate which binds to dietary calcium
- pigmented skin is less able to make vitamin D3 in response to UV light
What is the one key hormone that acts to decrease calcium plasma levels?
Calcitonin
What class of hormone is calcitonin and what is it produced by?
Peptide hormone produced by thyroid gland
What is secretion of calcitonin stimulated by?
Increased calcium in plasma
What is the main action of calcitonin?
Bind to osteoclasts and inhibit bone resorption as well as increase renal excretion preventing further build up of calcium
What can calcitonin be used to treat?
Paget’s diseae (overactive osteoclasts)
Is calcitonin important in humans?
Research suggests not as its effects are overridden by PTH
Other than PTH, calcitriol and calcitonin, what other hormones act to alter calcium balance?
Cortisol
Insulin
Oestrogen
Growth hormone
Prolactin
How does cortisol affect calcium balance?
Inhibits osteoblasts, increases renal excretion of calcium and phosphate and reduces intestinal absorption of calcium (decreasing serum calcium, increasing PTH and increasing bone resorption)
Together with reduce bone formation over time can produce osteoporosis
How does insulin affect calcium balance?
Increase bone formation and antagonises the action of cortisol
Diabetes have significant bone loss
How does oestrogen affect calcium balance?
Promotes bone formation via oestrogen recceptors on osteoblasts
Post-menopausal osteoporosis is a major problem
How does growth hormone impact calcium balance?
Constant stimulus for bone formation
How does prolactin affect calcium balance?
Promotes calcium absorption from gut by stimulating synthesis of calcitriol