Calcium homeostasis Flashcards
Role of Ca2+ in the body (5)
Signalling
Blood clotting - essential component of clotting cascade
Apoptosis
Skeletal strength
Membrane excitability
Ca2+ involvement with signalling
Ca2+ = important signalling molecule
exocytosis of synaptic vesicles e.g. neurotransmitters/ hormones etc
contraction of muscle fibres
alters enzyme function
What % of calcium in the body is wrapped up in bone? and what form is it in?
99%
Ca10(PO4)6(OH)2
Calcium phosphate hydroxyapatite
How is Ca2+ involved with membrane excitability?
Ca2+ decreases Na+ permeability
Which of Ca2+ roles is the most critical in short term homeostasis?
Membrane excitability
Effect of Hypocalcaemia
increases neuronal Na+ permeability leading to hyperexcitation of neurons.
In extreme cases causes tetany, if spreads to larynx and respiratory muscles – asphyxiation.
Effect of Hypercalcaemia
Decreases neuronal Na+ permeability which will reduce excitability of nerves and depress neuromuscular activity and in extreme cases, trigger cardiac arrhythmias.
Calcium distribution within the body excluding the Ca2+ in bone
- 9% intracellular
0. 1% extracellular fluid - 2.2-2.6 mM in plasma
Where is intracellular Ca2+ stored?
inside mitochondria and sarcoplasmic reticulum
very low levels of free calcium in the cytoplasm
How is Extracellular Ca2+ further divided?
nearly half (40%) ECF Ca2+ is bound to protein (small + charge attracted to large - charge of proteins)
so only 0.05% of Ca2+ in the body is free in solution and physiologically active
What % of Ca2+ is physiologically active in the body?
0.05%
Other than Ca2+ itself, what else needs to be carefully controlled to determine calcium balance?
Phosphate homeostasis
What are the 3 forms ca2+ exists in in the blood?
Protein bound (40%)
Free (ionised) - active (50%)
Complexed (10%) - free +anion =complexed e.g CaCO3 etc (not active)
How does pH affect Ca2+ binding
the binding capacity of plasma proteins changes with pH
Binding capacity is increased under alkalotic conditions
Opposite occurs with acidosis where binding capacity reduces and free [Ca2+]plasma rises (hypercalcaemia)
If you hyperventilate what happens to plasma pH
plasma pH rises as you blow off CO2 so becomes less acidic
plasma proteins bind more Ca2+ causing plasma concentration to fall and therefore may precipitate hypocalcaemic tetany
Summary of pH and Ca2+ binding
low pH - acidic environment - lower binding capacity of plasma proteins - more Ca2+ in plasma - hypercalcaemia
high pH - alkaline environment - better higher binding capacity of plasma proteins - less Ca2+ in plasma - hypocalcaemic tetany
What happens to Ca2+ in bone if plasma need more Ca2+
Bone will be sacrificed despite important functions in order to maintain plasma calcium levels
Function of osteoblasts
bone-building cells - blast out new bone
They are highly active cells which lay down a collagen extracellular matrix which they then calcify
Function of osteocytes
Osteocytes are much less active than osteoblasts but appear to regulate the activity of osteoblasts and osteoclasts
Function of Osteoclasts
Cells that are responsible for mobilizing bone.
They secrete H+ ions to dissolve the calcium salts and also provide proteolytic enzymes to digest the extracellular matrix.
2 hormones that act increase plasma concentration of Ca2+
Parathyroid hormone - (dominant) peptide
Calcitriol - steroid
What produces calcitriol
produced from vitamin D by the liver and kidneys
What is the active form of calcitriol in
Vitamin D3
Describe the secretion of PTH - released in response to a decrease in free plasma Ca2+
Stimulating osteoclasts to increase resorption (release) of Ca2+ and phosphate in bone
Inhibiting osteoblasts to reduce Ca2+ deposition in bone.
Increasing reabsorption of Ca2+ from the kidney tubules, therefore decreasing its excretion in the urine.
Increasing renal excretion of phosphate. This elevates free [Ca2+ ] by preventing it from being deposited back into bone, a process that requires phosphate.
Stimulates the kidney to synthesise calcitriol from vitamin D which promotes calcium absorption at the gut and kidney.
Calcitriol
Complements action of PTH - increase plasma Ca2_
A steroid hormone produced in two steps (1. liver, 2. kidneys) from dietary vitamin D or from precursors activated by sunlight on skin.
Formation is also stimulated by hormone prolactin in lactating women.
Active vit D3 is formed from cholesterol derivatives by the light on the skin but vit D can also be gained from the diet
How does calcitriol increase absorption of Ca2+ from the gut
Unlike many substances, such as water, Na+ and K+ which are completely absorbed from the gut, much of the Ca2+ in the diet passes straight through and is excreted in the faeces.
The active transport system which moves Ca2+ from the intestinal lumen to the blood is under the control of calcitriol.
low plasma Ca2_+ - increased PTH - increased Calcitriol - increase in intestinal absorption of ca2+
Actions of calcitriol (3)
Increase absorption of Ca2+ from the gut.
Facilitates renal absorption of Ca2+
Mobilises calcium stores in bone by stimulating osteoclast activity.
Collectively these actions, complement those of PTH and increase [Ca2+ ]plasma
What are calcitriol’s target tissues
intestine
bone
kidney
What happens when there is an increased demand for Ca2+ for milk production in lactation?
Prolactin stimulates Calcitriol synthesis
Define vit D deficiency
when vit D levels in the blood fall less than 20 ng/ml
What is rickets?
Common in children
Soft bones due to vit d deficiency
PTH works hard to maintain plasma [Ca2+] and in doing so continually removes Ca2+ from bone resulting in bones which are soft and, if still growing, become bent.
Osteomalacia
bones become easily fractured due to vit D deficiency
Vit D3 deficiency - what happens? who is most at risk?
leads to intestinal malabsorption of Ca2+ which decreases [Ca2+]plasma
this increases PTH which then promotes phosphate deficiency - aggravates Ca2+ loss from bone
elderly and asian populations are 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.
What is the only hormone that decreases plasma concentration of Ca2+
Calcitonin
Peptide hormone produced by thyroid gland - released when [Ca2+]plasma increases
Main action of calcitonin
Binds to osteoclasts and inhibits bone resorption as well as increasing renal excretion so preventing a further increase in Ca2+
however, little evidence it is of much importance in humans - can have high calcitonin levels (due to tumours etc) and still have normal Ca2+ levels
any excess of calcitonin is overridden by PTH
Other endocrine hormones altering ca2+ balance
5
Cortisol
Insulin
Oestrogen
GH
Prolactin
Cortisol
inhibits osteoblasts, increases renal excretion of Ca2+ and phosphate and reduces intestinal absorption of Ca2+
decreases plasma [Ca2+ ] which increases PTH and increases bone resorption.
over time - can produce osteoporosis
Insulin and Ca2+
Insulin increases bone formation, and antagonises the action of cortisol.
Diabetics may have significant bone loss.
