Calcium Homeostasis Flashcards
What are some of the roles of Calcium in the body?
- Signalling (vesicle exocytosis / muscle contraction etc.)
- Blood clotting
- Apoptosis
- Skeletal Strength
- Membrane Excitability (Ca decreases Na permeability)
What are the neuronal consequences of hypocalcaemia?
- Low Ca increases Na permeability leading to hyperexcitation of neurones.
(can cause tetany and asphyxiation if spreads to laryngeal / respiratory muscles)
What are the neuronal consequences of hypercalcaemia?
- High Ca reduces Na permeability which reduces nerve excitability and depresses neuromuscular activity
- Can lead to cardiac arrhythmias
Describe the distribution of calcium in the body
- 99% in Bones
- 0.9% Intracellular (mostly sarcoplasmic reticulum and mitochondria)
- 0.1% in ECF (half bound to protein /anions, only 0.05% of Ca free and physiologically active)
In what form is most of calcium present in bone?
- As hydroxyapatite
- Ca10(PO4)6(OH)2
So phosphate homeostasis is also important in regulating calcium balance
Describe the distribution of extracellular Ca
- 40% bound to proteins (large negative charge attracts small positive charge) (20% globulin, 80% albumin)
- 10% bound to plasma anions
- 50% (~1.2mM) as free ionized calcium, the physiologically active portion
What is a significant factor determining the amount of Ca bound to proteins in the plasma?
- The plasma pH
- Alkaline conditions precipitate increase Ca - protein binding
Describe the effect of a raise and drop in plasma pH on free ionized calcium concentration
- Raise in pH: more Ca binds to plasma proteins, reduces free ionised [Ca}, may precipitate hypocalcaemic tetany
- Drop in pH: less Ca bound to protein, increased free ionised [Ca], more physiologically active calcium
Why does a drop in pH cause an increase in free ionized Ca in the plasma?
- Because when pH drops the amount of free H+ ions in plasma increases, these are also attracted to negative charge and so displace some of the calcium bound to proteins
- When pH rises, less H+, more space for calcium to bind proteins
What is the biggest accessible reserve of calcium in the body?
- Bone
- Bone isn’t static, constantly being deposited and then resorbed, its role in maintaining Ca balance takes precedence over providing mechanical support to the body
What are osteoblasts? How do they mature?
- Osteoblasts are the bone building cells, lay down a collagen ECM around bone which they then calcify
- They differentiate into osteocytes in established bone, which are much less active but seem to regulate osteoblast and osteoclast activity
What is the function of osteoclasts? How do they achieve this?
- Responsible for breakdown / mobilization of bone
- They secrete H+ ions to dissolve calcium salts and provide proteolytic enzymes to breakdown the ECM
Which two key hormones function to increase plasma [Ca]? Where is each produced?
- Parathyroid Hormone (PTH): polypeptide hormone produced by parathyroid glands
- Calcitriol (active form of vitamin D3): steroid hormone produced from vitamin D by the liver and kidneys
Brief description of parathyroid gland anatomy?
- 4 glands located on the posterior thyroid
- Variations in number and location common though, can be important clinically if surgery is needed to remove overactive thyroid
Describe the actions of parathyroid hormone (PTH)?
- Stimulate osteoclasts to increase Ca resorption
- Inhibit osteoblasts
- Decrease excretion of Ca in urine by increasing reabsorption by kidney tubules
- Increase renal excretion of phosphate, elevates free [Ca] by preventing it from being deposited in bone, a process that requires phosphate
- Stimulates the kidney to synthesize calcitrol from vitamin D which promotes Ca absorption at the gut and kidney
