Endocrine Control Of Calcium Balance Flashcards
What is the role of calcium in the body?
- Cell signalling
- Blood clotting
- Apoptosis
- Skeletal strength
- Membrane excitability
What role does calcium play in cell singalling?
Plays a role in the exocytosis of synaptic vesicles e.g. neurotransmitters/hormones.
Contraction of muscle fibres
Alters enzyme function
What would happen is calcium was removed from the plasma?
Blood would stop clotting
RECAP- what is apoptosis?
Programmed cell death
What % of calcium in the body is in the skeleton?
99%
What happens if we are deficient in calcium?
Bones weaken
What role does calcium play in membrane excitability?
Decreases sodium permeability
->this is more critical in short term homeostasis
Hypocalcaemia?
Low levels of calcium in the blood
What does hypocalcaemia lead to in terms of sodium permeability?
Increased sodium permeability leading to hyperexcitation of neurons.
In extreme cases of hypocalcaemia, the hyperexcitation of neurons can causes what to happen?
Tetany (involuntary muscle contraction).
If there is tetany, which ion is low in the blood?
Calcium
How can low calcium levels lead to asphyxiation (being deprived of oxygen, ultimately leading to death)?
The increased sodium permeability causes hyperexcitation of neurons and tetany, as previously discussed.
If this involuntary muscle contraction spreads to the larynx and respiratory muscles, it can cause asphyxiation.
What can hypercalcaemia cause to happen?
Decreases neuronal sodium permeability which reduces excitability.
This depresses neuromuscular activity.
The depressed neuromuscular activity associated with hypercalcaemia can cause what to happen?
Can trigger cardiac arrhythmias
What % of calcium in the body is intracellular?
0.9%
What % of calcium in the body is in the extracellular fluid?
0.1%
-> 99% in bone, 0.9% intracellular, 0.1% in ECF
So, there’s 0.1% of body calcium found in the ECF. Half of these is bound to protein. Therefore, what % of calcium in the body is physiologically active?
0.05%
What form is calcium in the bone found as?
Hydroxyapatite
Which type of homeostasis is important in determining calcium balance?
Phosphate homeostasis
What does calcium has a high affinity for?
Protein
-> in plasma, around 40% of calcium in bound to plasma proteins
How many mM of calcium is found in the plasma?
2.2-2.6 mM
In the plasma, there is 0.1% of our calcium. Explain, in %, what this calcium is found as.
0.1%
40% bound to plasma protein
50% free/ionised, physiologically active
10% in complexes e.g. bicarbonate etc.
What effects the binding of calcium to plasma proteins?
pH
Is binding capacity increased under acidic or alkaline conditions?
Alkaline
If you hyperventilate, what happens to pH?
Blow of CO2, lower hydrogen ions and increase pH, making it more alkaline
If more calcium binds to plasma proteins, the calcium concentration in the plasma would fall. What can this cause again?
Hypo calcaemic tetany
RECAP 1ST YEAR : If you were retaining CO2, if this acidosis or alkalosis:?
Acidosis
If the pH of plasma is more alkaline, what happens?
More calcium becomes bound to plasma proteins
What is the total amount of calcium in the body determined by?
The about of calcium in via the diet and the amount out via excretion
99% of calcium in stored in bones. However, this can fluctuate. Why?
The body can use the stores of calcium in the bones if required
-> calcium needed to provide skeletal strength but it’s role in maintaining calcium balance takes priority
There is continuous turnover of bone, it is continually deposited and resorbed.
What do osteoblasts do?
Bone-building cells, lay down a collagen extracellular matrix which they then calcify
-> think Blasts= Bone-Building
What do osteoclasts do?
Responsible for mobilising bone and dissolve the calcium salts.
They provide proteolytic enzymes to digest the extracellular matrix.
->basically, osteoclasts breakdown bone, osteoblasts build back bone
Which two hormones act to increase calcium levels?
Parathyroid hormone
Calcitriol
What is parathyroid hormone and where is it produced?
Polypeptide hormone produced by parathyroid glands
What is calcitriol the active form of?
Vitamin D
What is calcitriol and where is it produced?
Steroid hormone produced from vitamin D in the liver and kidneys
Which hormone increases calcium levels and is a polypeptide hormone?
Parathyroid hormone
Which hormone increases calcium levels and is a steroid hormone?
Calcitriol
Name the hormone which acts to decrease calcium levels in the plasma.
Calcitonin
What type of hormone is calcitonin?
Peptide hormone
Where is calcitonin released from?
Parafollicular cells of the thyroid gland
Where are the parathyroid glands?
Posterior surface of thyroid gland
How many parathyroid glands do we have?
4
->not all required for survival, can live with one or two. In surgery for removal of thyroid, always tried to keep some of them
When is parathyroid hormone released?
In response to low levels of calcium
How does parathyroid hormone act to increase free calcium levels in the plasma regarding bones?
Stimulates osteoclasts to increase release/resorption of calcium and phosphate in bone
Inhibits osteoblasts which reduce calcium deposition
How else does parathyroid hormone act to increase free calcium levels in the plasma?
Increases reabsorption of calcium from the kidney tubules which decreases it’s secretion in urine
Increases renal excretion of phosphate as prevents calcium being deposited back into bone as this process requires phosphate
Calcium and phosphate are both required to get calcium into bones via hydroxyapatite . Therefore, when there are low plasma levels of calcium, what happens to phosphate?
In order to increase calcium levels in the plasma, phosphate needs to be excreted
How does parathyroid hormone use calcitriol to increase levels of plasma calcium?
Stimulates the kidneys to synthesise calcitriol from vitamin D which promotes calcium absorption at the gut and kidney
Calcitriol complements the actions of which other hormone?
Parathyroid hormone
RECAP- what are all steroid hormones, like calcitriol, derived from?
Cholesterol
Calcitriol is produced in two steps from vitamin D. Where does:
a. Step 1 take place
b. Step 2 take place?
a. Liver
b. Kidneys
What is the name of inactive vitamin D?
Cholecalciferol
How do we get cholecalciferol (inactive vitamin D)
Via diet or sunlight
Name some food sources of vitamin D.
YAY
Oily fish, liver, oils, egg yolks.
->Fat soluble vitamin so good dietary sources are fatty.
When is the formation of calcitriol from cholecalciferol enhanced?
Enhanced in lactating women by the hormone prolactin
Which hormone is the only hormone which can increase calcium absorption from the gut?
Calcitriol
Since calcitriol is a steroid hormone, it binds to intracellular nuclear receptors in the target tissues. What are the target tissues?
Intestine, bone and kidney
What happens when calcitriol binds to the target tissues?
Increases the absorption of calcium from the gut
-> unlike potassium and sodium, which are completely absorbed from the gut, a lot of calcium in the diet is excreted.
Calcitriol controls a system which moves calcium from the intestinal lumen into the blood
If there is low levels of calcium in the plasma, what happens in terms of hormones?
Increases in parathyroid hormones, increase in calcitriol which increases the intestinal absorption of calcium
If there are high levels of calcium in the plasma, what happens in terms of hormones?
Inhibits the release of PTH (negative feedback)
Greater osteoblast deposition and less osteoclast resorption so we can store the excess calcium in bone
How can calcitriol act on the kidneys in order to increase plasma calcium?
Similar to PTH
Increases calcium absorption from the gut and facilitates renal absorption of calcium
What does vitamin D promote the reabsorption of?
Phosphate
Therefore, if you are deficient in vitamin D, what happens?
Weak bones
What % of calcium consumed through the diet is absorbed?
30%
What % of calcium consumed through the diet is absorbed if the individual is deficient in vitamin D?
10-15%
What % of calcium consumed through the diet is absorbed if the individual is pregnant/lactating/having a growth spurt?
45-55%
Below what level does vitamin D levels need to fall below in order to be classed as deficient?
Below 20ng/ml
In which groups of people is vitamin D deficiency more prevalent?
-Those living in northern hemisphere due to lack of sunlight
-Those over 65yrs due to reduced gut absorption
What can vitamin D deficiency lead to in children?
Rickets
What can vitamin D deficiency lead to in adults?
Osteomalacia
What is the direct effect of vitamin D?
To release calcium from bones and increase plasma calcium
What is the net effect of vitamin D?
While increasing calcium in plasma, plasma phosphate levels also increase which means there is an increase in bone strength
Therefore, why do we get weak bones if we are deficient in vitamin D?
PTH works to maintain calcium levels but also excretes phosphorus so calcium cannot join to it and be laid back into bone.
Therefore, weaker bones
What happens in rickets?
Bones bend
What happens in osteomalacia?
Bones are more likely to fracture
So in turn, a deficiency in vitamin D leads to which other deficiencies?
Calcium and phosphate deficiencies
Which populations are at greater risk of vitamin D, calcium and phosphate deficiency?
Asian and Elderly populations
-> this is because chapatti flour contains phytate which binds to dietary calcium, there may be a dietary deficiency and pigmented skin is less able to make vitamin D in response to UV light
In which conditions if vitamin D deficiency more common?
MS, cancer, arthritis and CVD
What type of hormone is calcitonin?
Peptide hormone
Where is calcitonin produced from?
Thyroid gland
When is the secretion of calcitonin increased?
When there is increased calcium levels in the plasma
-> just wanted to say out of interest that there’s little evidence to suggest that humans need calcitonin
How does calcitonin reduce calcium plasma levels?
Binds to osteoclasts and inhibits bone resorption.
Increases renal excretion.
Any effects of excess calcitonin is overridden by what?
PTH
Which condition can calcitonin be useful in and help in the treatment of?
Paget’s disease
What happens in Paget’s disease?
Overactive osteoclasts which break down bone, leading to soft bone
How does cortisol alter calcium balance?
Inhibits osteoblasts and increases renal excretion of calcium.
Over time, this can lead to osteoporosis
How does insulin alter calcium balance?
Increases bone formation and antagonises the action of cortisol
Therefore, those with diabetes can have what effect on bone?
Significant bone loss as lack of insulin which aids in bone formation
How does oestrogen alter calcium balance?
Promotes bone formation via oestrogen receptors on osteoblasts.
-> Post-menopausal osteoporosis is a major problem
How does GH alter calcium balance?
Acts as a constant stimulus for bone formation
How does prolactin alter calcium balance?
Promotes calcium absorption form gut by stimulating the synthesis of calcitriol
