Calcium homeostasis Flashcards
What are the roles of calcium in the body?
Signalling
Blood clotting
Apoptosis
Skeletal strength
Membrane excitability
What signalling roles does calcium carry out?
- exocytosis of hormones, neurotransmitters etc
- in muscle fibre contraction
- alters enzyme function
What role does calcium play in blood clotting?
Essential component of the clotting cascade - used in conversion of the ‘Factors’
In what way does calcium contribute to membrane excitability?
Ca2+ decreases Na+ permeability
This is a very critical role in short-term homeostasis
Describe the effects of calcium imbalances in the blood on membrane excitability?
Hypocalcaemia leads to increased neuronal permeability which causes hyperexcitation
- Can cause tetany, or asphyxiation
Hypercalcaemia leads to decreased neuronal permeability which reduces the excitability of neurones
- This depresses neuromuscular activity
- May cause cardiac arrhythmias
Describe the distribution of calcium throughout the body
99% - in bones
- 9% - intracellular
- 1% - extracellular fluid
Describe the containment of intracellular calcium
0.9% of total calcium content
Mostly stored inside mitochondria and Sarcoplasmic Reticulum. Free [Ca2+]ic very low
Describe how calcium exists in extracellular fluid
0.1% of total body calcium
Nearly half of ECF Ca2+ is bound to protein
In the entire body, how much Ca2+ is free? (ie not in a molecule and not bound to etc)
So only 0.05% of the calcium in the body is free in solution and physiologically active
How does calcium exist in the bone?
~1Kg (99%) calcium is stored in the calcified extracellular matrix of bone, mostly in the form of hydroxyapatite (Ca10(PO4)6(OH)2)
so phosphate homeostasis is also important in determining calcium balance.
What is the normal concentration of calcium in the plasma?
2.2-2.6 mM in plasma (0.1%)
Why does a lot of the extracellular calcium exist bound to proteins?
Calcium has a very high affinity for proteins - (small positive charge attracted to large negative charge)
in plasma, around 40% is bound to plasma proteins.
Why is [Ca2+]plasma not an accurate measurement of physiologically active calcium?
[Ca2+]plasma does not account for the Calcium that is bound to proteins or in other ways unavailable
free ionised, and therefore physiologically active [Ca2+] is only about 1.2mM and accounts for ~50% of plasma calcium.
What are the reasons for Calcium in plasma not being physiologically available?
Most are bound to plasma proteins (40% of total)
The remaining 10% of plasma calcium ions bind to plasma anions.
What plasma proteins does calcium bind to?
Albumin - 80%
Globulin - 20%
What anions can calcium bind to?
HCO3
H2PO4
HPO4
Sulphate
Citrate
Lactate
What is the effect of pH on the binding capacity for Calcium?
Binding capacity is increased under alkalotic conditions
If someone is hyperventilating - what is the effect on the pH of the blood and what can this precipitate?
(and vice versa)
hyperventilation means that plasma pH rises - becomes more alkaline
Alkaline means increased binding capacity
This means more calcium is bound to - removing Calcium ions from blood
This would precipitate Hypoglycaemic tetany
How does alkalosis increase the binding capacity for plasma proteins?
If a solution becomes more alkaline - then the [H+] decreases
This means less [H+] ions are available to bind to plasma proteins - meaning there are more available to Ca2+
How does calcium leave the body?
Ca2+ excretion at kidney and faeces
What is more important - keeping calcium in the bones or maintaining Ca2+ balance?
Maintaining balance
99% of Calcium stored in bone - but this can be removed when required to maintain said balance
What types of cells are responsible for maintaining our bone turnover?
Osteoblasts - Bone builders
- Lay down collagen Extracellular bone matrix and then calcify it
Osteocytes - Exist in established bone
- less active than osteoblasts but appear to regulate the activity of osteoblasts and osteoclasts
Osteoclasts - Bone removal
- secrete H+ ions (pH » 4) to dissolve the calcium salts
- provide proteolytic enzymes to digest the extracellular matrix.
What are the 2 key hormones related to maintaining calcium homeostasis?
Parathyroid hormone (PTH)
- polypeptide hormone produced by the parathyroid glands
Calcitriol (active form of Vit D3)
- steroid hormone produced from Vitamin D by the liver and kidneys
Where are the parathyroid glands?
Describe their basic anatomy
There are usually 4 lying on the posterior surface of the thyroid gland
(although variations in number and location of are common, 1 in 10 people have aberrant distribution)
Supplied by Left/Right, Superior/Inferior arteries
What stimulates the release of Parathyroid hormone?
Released in response to DECREASE in free [Ca2+]plasma
What is the action of PTH?
Parathyroid hormone acts to increase [Ca2+] by:
BONES:
- Stimulate osteoclast resorption and release of Calcium
- Inhibit Osteoblast deposition in bone
KIDNEYS:
- Increases reabsorption of Ca2+ from kidney tubules - decreasing excretion into urine
- Increases renal phosphate excretion. This elevates free [Ca2+] by preventing it from being deposited back into bone
- Stimulates calcitriol synthesis which promotes calcium absorption at the gut and kidney.
What is Calcitriol?
aka active Vitamin D3 or 1,25 dihydroxycholecalciferol
Complements action of PTH - [Ca2+] plasma
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.
What diet advice would you give to patients to increase their dietary vitamin D intake
fatty fish eg mackerel and tuna
fish liver oils
egg yolks.
Describe the action of calcitriol?
Binds to nuclear receptors in its target tissues - Intestines, bone, kidneys
Actions:
1) - Increase absorption of Ca2+ from the gut
2) - Facilitates renal absorption of Ca2+
3) - Stimulates osteoclast activity to mobilise calcium stores
Describe how calcitriol increases the level of calcium absorption from our food?
The active transport system for Ca2+ absorption from intestinal lumen is under the control of calcitriol
So PTH production - leads to Calcitriol production - leads to increased intestinal absorption of Ca2+
In what states is calcium absorption from the lumen increased?
Normal individual - 30% of Calcium absorbed
Pregnant women, Lactation, growth spurts - 45-55% Ca2+ absorbed from lumen
Due to high levels of circulating Calcitriol - 1,25 (OH)2D3
How common is vitamin D deficiency?
~75% of Scots are Vit D “insufficient” in summer, rising to 92% in the winter
Lack of sunlight and poor diet are the main causes of this
What is the overall effect of vitamin D3 on the body?
(why is it so important)
Direct effect of Vit D3 is to release Ca2+ from bone,
However - its effect on Ca2+ absorption from gut/ reabsoption at kidneys, means the net Vitamin D3 effect is to increase plasma [Ca2+] and mineralization of bone
What are the problems associated with Vitamin D deficiency?
Rickets in children
Osteomalacia in adults (softening of bones)
Vitamin D3 deficiency generates Ca2+ and phosphate deficiency
What endocrine hormone acts the reduce [Ca2+] in the blood?
Calcitonin
Peptide hormone produced by the thyroid gland, its secretion is stimulated by increased [Ca2+]plasma
How does calcitonin work?
Binds to osteoclasts to reduce bone resorption
Stimulates renal Ca2+ secretion
However - its actually pretty arbitrary as a hormone and isnt really necessary to maintain Ca2+
What other endocrine hormones affect Calcium levels in the blood?
Cortisol
Insulin
Oestrogen
Growth hormone
Prolactin
cba writing out how
