Calcium Haemostasis Flashcards
Roles of calcium
Signalling Blood clotting Apoptosis Skeletal strength Membrane excitability
What does Ca2+ decrease the permeability of?
Na+
Hypocalcaemia effect on membrane excitability
Increases neuronal Na+ permeability leading to hyperexcitation of neurones
In extreme cases what can hypocalcaemia lead to (in respect to membrane excitability)?
Tetany - if spreads to larynx and resp muscles - asphyxiation
Hypercalcaemia effect on membrane
Decreases neuronal Na+ permeability which will reduce excitability and depress neuromuscular activity
What can hypercalcaemia trigger in extreme cases?
Cardiac arrhythmias
Distribution of calcium in the body
99% bones (1g)
- 9% intracellular fluid
- 1% extracellular fluid
Where is the calcium found in intracellular fluid?
Mostly stored in the mitochondria and sarcoplasmic reticulum.
Free [Ca2+]ic very low
Where is calcium found in the extracellular fluid?
Nearly half ECF Ca2+ is bound to protein
How much of calcium in the body is free in solution and physiologically active?
0.05%
What is most of the calcium stored in bone stored in the form of? And what does this mean is also important in determining calcium balance?
Hydroxyapatite
Phosphate homeostasis is also important
Level of calcium in the plasma
2.2 - 2.6mM (0.1%)
What does calcium have a high affinity for?
Proteins
How much of calcium is bound to plasma proteins in the plasma?
40%
Remaining 10% of plasma calcium ions that are neither bound to plasma proteins nor free are bound to what?
Plasma anions
How much of the calcium in the plasma is freely ionised and therefore physiologically active?
50%
What is the amount of calcium that is bound to protein dependent on?
pH of the ECF
What conditions does binding capacity of Ca2+ increase under?
Alkalotic conditions
What happens to calcium binding in acidosis?
Binding capacity reduces
Free [Ca2+] rises
Total body calcium = ?
Ca2+ from diet - Ca2+ excretion at kidney and faeces
Main function of bone
Role in maintaining Ca2+ balance
What does the bone do when calcium levels are low? What does this lead to?
Release calcium at the expense of bone strength
Leads to brittle and weak bones
Function of osteoblasts
BONE BUILDING CELLS
Lay down a collagen extracellular matrix which they then calcify
Function of osteocytes
Regulate the activity of osteoblasts and osteoclasts
What do osteoblasts differentiate to form?
Osteocytes
Function of osteoclasts
Secrete H+ ions to dissolve the calcium salts and also provide proteolytic enzymes to digest the extracellular matrix
What are the two key hormones that act to increase [Ca2+]plasma?
Parathyroid hormone (PTH) Calcitriol
What is parathyroid hormone produced by?
Parathyroid glands
What is calcitriol and active form on?
Vit D3
What type of hormone is parathyroid hormone (PTH)?
Polypeptide hormone
What type of hormone is calcitriol?
Steroid hormone
What is calcitriol produced from and by?
From vitamin D
Liver and kidneys
How many parathyroid glands are there?
4
Where do the parathyroid glands lie?
On the posterior surface of the thyroid gland
What is parathyroid hormone (PTH) released in response to?
A decrease in free [Ca2+] in the plasma
What is done to increase free [Ca2+] by PTH?
Stimulates osteoclasts to release Ca2+ and phosphate from bone
Inhibiting osteoblasts to reduce Ca2+ deposition in bone
Increasing reabsorption of Ca2+ from the kidney tubules, therefore decreasing its excretion in the urine
Increases renal excretion of phosphate.
Stimulates the kidney to synthesise calcitriol from vitamin D
How long does it take for the effects to be seen from PTH stimulating osteoclasts to release Ca2+ and phosphate into bone?
12 - 24 hours
How does increasing the renal excretion of phosphate lead to an increased free [Ca2+] in the plasma?
It prevents Ca2+ from being deposited back into the bone, a process requiring phosphate
Where does calcitriol promote calcium absorption?
Gut
Kidney
What does calcitriol complement the action of and what does this do?
PTH
Increases [Ca2+] plasma
Sources of Vitamin D3
Cholesterol derivatives from UV sunlight on the skin
Fatty fish e.g. tuna
Fish liver oils
Egg yolks
Formation of calcitriol from Vit D3 is stimulated by what?
Prolactin in lactating woman
Functions of calcitriol
Increase absorption of Ca2+ from the gut
Facilitates renal absorption of Ca2+
Mobilises calcium stores in bone by stimulating osteoclast activity
What controls the active transport system which moves Ca2+ from the intestinal lumen to the blood?
Calcitriol
What does prolactin stimulate the synthesis of? Why?
Calcitriol
Increased demand for Ca2+ for milk production in lactation
The circulating level of what controls the proportion of dietary calcium absorbed from the intestine?
Calcitriol
What is the level of vitamin D to be classified as Vitamin D deficiency?
< 20ng/ml
Over what age is vitamin D deficiency more common in and why?
> 65 y/o
Reduced gut absorption, reduced Ca2+ mobility
Pathology of Vit D deficiency leading to weak bones (rickets/osteomalacia)?
Vit D deficiency Intestinal malabsorption of Ca2+ Decreases [Ca2+] plasma Which promotes PTH Which promotes phosphate deficiency Aggravates Ca2+ loss from bone
What two populations are most at risk of Vit D deficiency?
Elderly
Asian
Pigmented skin and vit D relationship
Pigmented skin less able to make vit D3 in response to UV light
What is vit D deficiency implicated in?
MS
Cancer
Arthritis
CVD
What is the key hormone which acts to decrease [Ca2+] plasma?
Calcitonin
What type of hormone is calcitonin?
Peptide hormone
Where is calcitonin produced from?
Thyroid gland
What is the secretion of calcitonin stimulated by?
Increased [Ca2+] plasma
What is any excess of calcitonin overridden by and what does this mean?
PTH
Not important to humans really
Cortisol effects on bone formation
Inhibits osteoblasts, increases renal excretion of Ca2+ and phosphate and reduces intestinal absorption of Ca2+
This over time can produce osteoporosis
Insulin effect on bone formation
Increases bone formation
Antagonises effects of cortisol
Oestrogen effect on bone formation
Promotes bone formation via oestrogen receptors on osteoblasts
GH on bone formation
Constant stimulus for bone formation
Prolactin effect on bone formation
Promotes calcium absorption from the gut by stimulating synthesis of calcitriol
