Calcium Homeostasis Flashcards
Name five process that calcium is involved in
- Signalling
- Blood clotting
- Apoptosis
- Skeletal strength
- Membrane excitability (important)
Why is Ca important for signalling in the body?
Ca2+ important signalling molecules: exocytosis of synaptic vesicles e.g. neurotransmitters/ hormones etc, contraction of muscle fibres, alters enzyme function.
Why is Ca important for blood clotting?
Essential component of clotting cascade.
Why is Ca important for skeletal strength?
99% of calcium in the body is wrapped up in bone where it gives strength to the skeleton.
Why is Ca important for membrane excitability?
Ca2+ decreases Na+ permeability - most critical to control
What is the most critical process in the body that Ca must control?
Membrane excitability as Ca causes hyper excitation or depression of the NS
How does hypocalcaemia affect membrane excitability?
Hypocalcaemia increases neuronal Na+ permeability leading to hyperexcitation of neurons.
In extreme cases causes tetany, if spreads to larynx and respiratory muscles – asphyxiation.
How does hypercalcaemia affect membrane excitability?
Hypercalcaemia decreases neuronal Na+ permeability which will reduce excitability and depress neuromuscular activity and in extreme cases, trigger cardiac arrhythmias.
Describe the calcium distribution in the body
- Bones - 99%
- Intracellular - 0.9% mostly in mitochrondria and Sarcoplasmic reticulum
- Extracellular fluid - 0.1% with nearly half bound to protein
So only 0.05% of Ca in body is free in solution and physiologically active
How is Ca stored in bone?
Ca is stored int he calcified extracellular matrix of bone, most in the form of hydroxyapatite, so phosphate homeostasis is also important in determining Ca balance (as phosphate groups in hydroxy.).
What is the molecular formula of hydroxyapatite?
Ca10(PO4)6(OH)2
How many mM of Ca is there in bone?
2.2-2.6mM
What are the three forms that Ca exist in the blood
Protein bound:
Ca has a high affinity for proteins (small positive attracted to large negative charge) and in plasma around 40% is bound to plasma proteins
Free (ionised):
So while [Ca2+] plasma is ~2.4mM, free ionised, and therefore physiologically active [Ca2+ ] is only about 1.2mM and accounts for ~50% of plasma calcium.
Complexed:
The remaining 10% of plasma calcium bind to plasma anions.
In what form in the blood in Ca physiologically active?
Free (ionised)
What are the different anions that Ca can bind to in the blood?
HCO3 H2PO4 HPO4 Sulphate Citrate Lactate
What two proteins does Ca bind to in the plasma?
80% to albumin and 20% to globulin
What affects how much Ca is bound to protein?
Plasma pH
How does pH affect binding capacity of plasma proteins?
Binding capacity increases under alkalotic conditions and opposite in acidosis where it reduces and free [Ca]plasma rises
What is the effect of hyperventilation on binding capacity of Ca?
Hyperventilate -> pH rises and plasma proteins bind more Ca causing plasma conc. to fall
This may precipitate hypocalcaemic tetany
What is the physiology of pH rise increasing binding capacity of Ca?
When pH of the plasma increases, as in alkalinosis, protons are deprotonated, and the overall resulting negative charge on the protein allows calcium to bind, thus effectively reducing the amount of ionised calcium whilst total calcium remains constant.
What is the physiology of pH fall decreasing binding capacity of Ca?
Decrease in pH causes the increase in protons displaces Calcium from the protein resulting in increased ionised calcium, again with no effect on total calcium.
How is total body Ca determined?
Total = Ca in from diet - calcium out via excretion in kidneys and faeces
Why is the distribution between bone and ECF crucial?
99% of total body Ca is stored in bone and this can be added or released as required
The bone plays an important role in maintaining Ca balance
What are the different cells in bone responsible for Ca storage in bone?
Continuous turnover in bone due to:
• Osteoblasts
• Osteocytes
• Osteoclasts