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
What is the function of calcitriol? Where is the hormone produced & from what is it produced?
- To increase plasma [Ca]
- Produced in two steps in 1. Liver & 2. Kidneys
- Steroid hormone produced from either UV sunlight activated endogenous cholesterol precursors OR dietary vitamin D
What are the actions of calcitriol?
- Increase Ca absorption from the gut
- Facilitates renal absorption of Ca
- Mobilizes calcium in bone by stimulating osteoclast activity
Why is a hormone needed to stimulate Ca absorption in the gut?
- Because unlike water, Na and K which are completely absorbed in the gut, much of the Ca in our diet passes straight through and is excreted in faeces
- The transport system moving Ca from the intestinal lumen to the blood is under calcitriol control
- Increase in PTH causes increase in calcitriol causes increase in Ca absorption
How does prolactin accommodate for the increased Ca demands present during lactation?
- Prolactin stimulates calcitriol synthesis to increase Ca absorption in the gut
What is the effect of vitamin D3 on bone mineralization?
- The direct effect is to release Ca from bone via osteoclasts
HOWEVER - The effect of D3 on Ca absorption in the gut / kidneys means the NET affect is an increase in plasma [Ca] and an increase in bone mineralization
- Less D3 = weaker bones
Why does vitamin D deficiency cause reduced bone mineralization?
- Reduced absorption of dietary calcium due to lack of calcitriol (from lack of vitamin D)
- PTH ends up working to maintain plasma [Ca] despite reduced Ca intake, and so continually removes Ca from bone
What bone conditions are associated with reduced bone mineralization? (vit D deficiency)
- Rickets in children
- Osteomalacia in adults
- Causes bone to become soft and weak, and bent if still growing
- elderly more susceptible due to reduced gut absorption and reduced calcium mobilization. Asians also suscpetible due to pigmented skin being less able to make D3 (and dietary differences: chapatti flour)
What are some other conditions is vitamin D deficiency implicated in?
- MS
- Cancer
- Arthritis
- CVD
What is the key hormone functioning to reduce plasma [Ca]? Where is it produced and what triggers its secretion?
- Calcitonin
- Peptide hormone produced by thyroid gland
- Secretion triggered by increase in plasma [Ca]
Describe the actions of calcitonin? How important is this hormone?
- Binds osteoclasts to inhibit bone resorption
- Increases renal excretion of calcium
- Doesn’t appear to be too important, in thyroid disease where calcitonin is very high plasma calcium remains normal so PTH overrides excess calcitonin
- May be used to treat Paget’s disease (overactive osteoclasts)
What effect does cortisol have on calcium balance?
- Inhibits osteoblasts
- Increases renal excretion of Ca and phosphate
- Reduces intestinal absorption of Ca
- Can cause decreased plasma [Ca], causing increased PTH, causing increased bone resorption. May lead to osteoporosis over time
What effect does insulin have on calcium balance?
- Increases bone formation
- Antagonizes effects of cortisol
- Diabetics may develop significant bone loss
What effect does oestrogen have on calcium balance?
- Promotes bone formation via oestrogen receptors on osteoblasts
- Post-menopausal osteoporosis can be a major problem
What effect does growth hormone have on calcium balance?
- Stimulates bone formation
