Calcium homeostasis Flashcards
5 important roles of calcium in the body
signalling eg exocytosis, muscle contraction blood clotting apoptosis skeletal strength membrane excitability
What does calcium do to sodium permeability?
decrease it
What function of calcium is most important in the short term for homeostasis?
membrane excitability - sodium permeability
Hypocalcaemia - sodium permeability and the result
increases sodium permeability
hyperexcitation of the neurons
tetany - spread to larynx and strap muscles can cause asphyxiation
hypercalcaemia - sodium permeability and the result
decreases sodium permeability
decrease neuromuscular activity
can lead to arrhythmias
How much of calcium is stored in bone?
99%
Explain the remaining 1% of calcium in body
- 9% intracellular fluid stored in mitochondria and SR
0. 1% extracellular fluid although half is bound to carrier proteins
Is calcium in bone or ECF/ICF tightly regulated?
ICF/ECF
What % of calcium in the body is free? what is the result of this?
0.05%
physiologically active
How is calcium stored in bone and what does this mean?
hydroxyapatite - phosphate homeostasis important in calcium balance
Does calcium have a high or low affinity to proteins and why?
high
small positive charge to large negative charge
What happens to the plasma calcium ions neither bound to protein or free in solution?
bind to anions eg sulphate
Is calcium binding to plasma proteins increased under acidic or alkalotic conditions?
alkalotic
Explain what happens to calcium binding in hyperventilation
blow off more CO2
pH rises
more calcium bound to proteins
less plasma calcium = hypocalcaemic tetany
total body calcium =
calcium in (diet) - calcium out ( excreted at kidneys and faeces)
Is mechanical support or calcium balance more important in terms of the bones?
calcium balance
Osteoblasts
bone building, active
actively lay down collagen extracellular matric which can later calcify
Osteocytes
osteoblasts differentiate to form these, less active
regulate osteoblast and osteoclast activity
Osteoclasts
mobilise bone by secreting H+ (pH4) to dissolve calcium salts and also provide proteolytic enzymes to digest extracellular matrix
What are the 2 key endocrine hormones in calcium homeostasis?
PTH
calcitriol
What type of hormone is PTH and where is it released from?
polypeptide
parathyroid glands
What type of hormone is calcitriol? what is it the active form of? where is it produced?
steroid
vitamin D3
from vitamin D in liver and kidneys
Where are parathyroid glands found and why are they important?
4 on posterior surface of thyroid gland - variable
essential for life so must know if they are elsewhere when removing thyroid gland
What is PTH released in response to and what is its general action?
low plasma calcium
increase free calcium in the plasma
What are some ways in which PTH works?
stimulate osteoclasts
inhibit osteoblasts
increase phosphate excretion
increase reabsorption of calcium from kidney tubules to reduce calcium in urine
stimulate kidney to synthesise calcitriol
What does calcitriol promote?
kidney and gut absorption of calcium
Does calcitriol complement or antagonise the action of PTH?
complement
How is vitamin D activated?
dietary/precursors activated by sunlight
How is calcitriol stimulated in pregnancy?
prolactin
Explain the negative feedback loop of PTH and calcitriol
As plasma Ca rises this switches off PTH which then switches off calcitriol synthesis in the kidneys
What does calcitriol bind to on target tissues?
nuclear receptors in intestine, bones, kidney
How does calcitriol increase absorption of calcium from gut?
calcium from intestinal lumen to blood: calcitriol controls this active transport
low plasma calcium - increase PTH, increase calcitriol and increase intestinal absorption
3 actions of calcitriol
increase intestinal absorption
facilitate renal absorption
mobilise calcium stores by stimulating osteoclasts
Why does prolactin stimulate calcitriol synthesis?
increased demand for calcium for milk production in lactation
Value of circulating vitamin D in deficiency
less than 20ng/ml
Where is vitamin D extensively stored?
in fat
Risk factors for vitamin D deficiency
age, lack of sunlight, diet
What is the net effect of vitamin D?
increase plasma calcium and mineralisation of bone
What happens to bones in vitamin D deficiency?
PTH works hard to release calcium
soft and weak bones
Children and adults vitamin D deficiency presentation
children = rickets adults = osteomalacia
If you are vitamin D3 deficient what else will you be deficient in and why?
calcium and phosphate
intestinal malabsorption leads to decreased plasma calcium which increases PTH which promotes phosphate deficiency and aggravates calcium loss from bone
Who is most at risk of vitamin D deficiency?
Asian and elderly
chapatti flour, pigmented skin
What diseases is Vitamin D deficiency implicated in?
arthritis, MS, cancer and CVD
What is the 1 key hormone acts to decrease plasma calcium
calcitonin
What type of hormone is calcitonin and where is it produced from?
peptide hormone
thyroid gland
How does calcitonin work?
increased calcium in plasma
binds osteoclasts and inhibits bone resorption
increase renal excretion and prevent further increase in calcium
Why is calcitonin seen as unimportant?
in people with calcitonin tumours or not enough they still have stable calcium levels as PTH overrides it
When may calcitonin be used in a clinical setting?
Pagets disease = overactive osteoclasts
List 5 other endocrine hormones which alter calcium balance
cortisol insulin oestrogen GH prolactin
How does cortisol work to alter calcium balance?
inhibit osteoblasts and increase renal excretion of calcium and phosphate
reduce intestinal resorption
decrease plasma calcium which increases PTH and increases bone resorption
osteoporosis
Insulin effect on calcium
increase bone formation and antagonise cortisol
diabetics have significant bone loss
oestrogen effect on calcium
promotes bone formation via oestrogen receptors on osteoblasts. Post menopausal osteoporosis
GH effect on calcium
constant stimulus for bone formation
Prolactin effect on calcium
promotes calcium absorption from the gut by calcitriol synthesis