Calcium Homeostasis Flashcards
Role of Ca in body?
Signalling Blood clotting Apoptsis Skeletal strength Membrane excitability
How is Ca involved in signalling?
Causes exocytosis of synaptic vesicles - neurotransmitters/hormones
Causes contractions of muscle fibres
Alters enzyme function
How is Ca involved in blood clotting?
Essential componant of clotting cascade
What is apoptosis?
Programmed cell death
How is Ca involved in skeletal strength?
99% of calcium in the body is wrapped up in bone where it gives strength to the skeleton.
How is Ca involved in membrane excitability??
Ca2+ decreases Na+ permeability
Which of these functions is most critical in short term homeostasis?
Membrane excitabilty
How does hypocalcaemia affect membrane excitability?
Increases neuronal Na+ permeability causing hyperexcitation - in extreme cases leads to tetany and if it spreads to larynx and resp. muscles = asphyxiation
How does hypercalcaemia affect membrane excitabilty?
Decreases neuronal Na+ permeability = reduced excitability which depresses neuromuscular activity and in extreme cases triggers cardiac arrhythmias.
How is Ca distrubuted in the body?
Bones = 99%
Intracellular = 0.9% - mostly stored in mitochondria and in sarcoplasmic reticulum
Extracellular fluid = 0.1% - nearly half Ca2+ is bound to protein so only 0.05% of Ca in body in free in solution and physiologically active
How is calcium stored in bones and why is this significant? How much is in bones?
In form of hydroxyapatite meaning phosphate homeostasis is important in determing calcium balance
1 kg
Conc of calcium in cells?
24mM with 0.001mM in solution in the cytosol and rest in mitochondria and SR
Conc of calcium in plasma?
2.2-2.6mM
Conc of calc in ECF is tightly maintained
Since calcium has a very high affinity for proteins, what actual conc of calcium is free ionised and physiologically active in the ECF?
1.2mM
If 40% of calcium is bound to proteins in the ECF and 50% is free, what is the other 10% doing?
Bound to plasma anions
Name some proteins Ca binds to and the % that binds to them.
Albumin - 80%
Globulin - 20%
What type of Ca is physiologically active?
Free calcium
What changes the binding capacity for plasma proteins with Calcium?
pH
Binding is increased under alkalotic conditions and opposite happens with acidosis
What is total body calcium determined by?
Calcium in (diet) - calcium out (exctretion at kidneys and faeces)
The distribution of Ca2+ between BLANk and BLANK is crucial. Explain?
Bone and ECF
99% of total body Ca2+ is stored in bone and this can be added to or released as required
Bone functions to provide mechanical support for the body but its role in maintaining Ca2+ balance takes precedence over this.
What are osteoblasts?
Bone building cells
Highly active - lay down a collagen extracellular matrix which they then calcify
What are esteocytes?
Differentiated osteoblasts in established bone - much less active but regulate activity of osetoblasts and osteoclasts
What is an osteoclast?
Cells responsible for mobilizing bone
They secrete H+ ions (pH ~4) to dissolve the calcium salts and also provide proteolytic enzymes to digest the extracellular matrix.
What hormones act to increase Calcium in the plasma?
Parathyroid hormone
Calcitriol
What type of hormone is parathyroid hormone and where is it made?
Polypeptide hormone
Parathyroid glands
What is calcitriol?
The active form of Vit. D3
A steroid hormone produced from vit. D by liver and kidneys
Are parathyroid glands essential for life? What considerations should be taken clinically about them?
Yes - should be thought about if an overactive thyroid gland needs removed
What is parathyroid hormone (PTH) released in response to?
Decrease in Ca2+ conc in plasma
How does PTH increase free Ca2+ conc?
Stimulate osteoclasts to increase release/resorption of Ca2+ and phosphate in bone
Inhibits osteoblasts to reduce Ca deposition in bone
Increasing re-absorption of Ca from kidney tubules
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.
What hormone helps form calcitriol in lactating women?
Prolactin
How is calcitriol made?
Produced in two steps (1. liver, 2. kidneys) from dietary vitamin D or from precursors activated by sunlight on skin.
Active vitamin D3 is formed from cholesterol derivatives by the action of UV light on the skin, but Vit D can also be gained from the diet.
Where does calcitriol bind?
Receptors in intestine, bone and kidney
What effect does calcitrol have?
Increases absorption of calcium from the gut
The active transport system which moves Ca2+ from the intestinal lumen to the blood is under the control of calcitriol
Also facilitates renal absorption of calcium
Mobilises calcium stores in bone by stimulating osteoclast activity
Summaries what happens when there is low plasma calcium.
Increase in PTH leads to its effects which include an increase in calcitrol which leads to increase in intestinal absorption of Ca2+
What happens when there is high levels of calcium in blood?
PTH release is inhibited causing a shift towards osteoblast deposition and less osteoclast resoprtion/release
In a healthy individual how much dietary calcium should be absorbed?
30%
In a Vit. D deficient individual how much dietary calcium is be absorbed?
10-15%
In a pregnant or lactating individual or someone going through growth spurts. how much dietary calcium should be absorbed? Why is this possible?
45-55%
Higher circulating Vit D3
When is a person vit. d deficient?
When levels fall below 20ng/ml
What does vit D def cause in children and why?
Rickets
In a vit D def PTH works harder to maintain plasma Ca levels by removing calcium from bone = soft bones that are easily fractures and bent
If Vit. D’s direct effect is to release calcium from bone - how does lack of it result in rickets?
Because Vit. D also affects gut absorption and absorption of Ca from kidneys and without it the effects are not balanced and you lack Ca
What is rickets called in adults?
Osteomalacia
Why are asians more prone to Vit D def?
Chapatti flour has phytate which binds dietary Ca
May be dietary def of Ca
Pigmented skin = harded to make D3 from UV light
What diseases is Vit d def implicated in?
MS
Cancer
Arthritis
CV disease
What is the one hormone which acts to decrease blood ca conc?
Calcitonin
What type of hormone is calcitonin, where is it secreted from and how does it work?
Peptide
Thyroid gland
Binds to osteoclasts and inhibits bone resoption/release of Ca2+ as well as increasing renal excretion
Is calcitonin crucial in humans?
Not really - if high its affects are over-ridden by PTH
Patients with high or low levels have no adverse effects
What can calcitonin be used to treat?
Paget’s disease - overactive osteoclasts
Name some other endocrine hormones that alter Ca2+ blanace
Cortisol Insulin Oestrogen GH Prolactin
How does cortisol affect calcium?
Inhibits osteoblasts
Increases renal excretion of Ca2+ and phosphate
Reduced intestinal absorption of Ca2+
This decreases plasma Ca2+ and combined with inhibited osteoblasts can lead to osteoporosis
How does insulin affect calcium?
Increases bone formation - diabetics may have bone loss
What does oestrogen do for calcium?
Promotes bone formation
What does GH do?
A constant stim for bone formation
What does prolactin do?
Stimulating systhesis of calcitriol
