Calcium Homeostasis

Question 1

What are the roles of calcium in the body?

Answer 1

Signalling
Blood clotting
Apoptosis
Skeletal strength 
Membrane excitability

Question 2

How is calcium involved in signalling?

Answer 2

E.g. - exocytosis of synaptic vesicles (e.g. neurotransmitters/hormones etc.), contraction of muscle fibres, alters enzyme function

Question 3

How is calcium involved in blood clotting?

Answer 3

It is an essential component of the clotting cascade

Question 4

What is apoptosis?

Answer 4

Programmed cell death

Question 5

How does calcium contribute to skeletal strength?

Answer 5

99% of calcium in the body is wrapped up in bone –> gives strength to skeleton

Question 6

How does Ca affect membrane excitability?

Answer 6

Ca decreases Na permeability

Question 7

How does hypocalcaemia affect the membrane excitability of neurons? Clinically what does this mean?

Answer 7

Increases Na permeability –> hyperexcitation of neurons

Can cause tetany, if spreads to larynx + respiratory muscles –> asphyxiation

Question 8

How does hypercalcaemia affect the membrane excitability of neurons? Clinically what does this mean?

Answer 8

Decreases neuronal Na permeability which will reduce excitability + depress neuromuscular activity

May in extreme cases trigger cardiac arrhythmias

Question 9

Describe the calcium distribution in the body

Answer 9

Bones - 99%
Intracellular - 0.9%
Extracellular - 0.1%

Question 10

Where is most of the intracellular Ca stored?

Answer 10

Mitochondria and sarcoplasmic reticulum

Question 11

What is most of the extracellular Ca in the plasma bound to?

Answer 11

Protein

NB: only 0.05% of Ca in the body is free in solution + physiologically active

Question 12

How is Ca stored in bones?

Answer 12

It is calcified into the ECM of bone mostly in the form of hydroxyapatite (Ca10(PO4)6(OH)2)

Question 13

What is the normal range for calcium in the plasma?

Answer 13

2.2-2.6mM

Question 14

What does Ca have a very high affinity for?

Answer 14

Proteins (small positive charge attracted to large negative charge)

NB: 40% protein bound in plasma

Question 15

How much Ca in the blood is actually free ionised?

Answer 15

1.2mM (50% of plasma Ca)

Question 16

What accounts for the other 10% of plasma Ca that is not free nor bound to plasma proteins?

Answer 16

10% bind to plasma anions

Question 17

What Ca is physiologically active?

Answer 17

Only free calcium

Question 18

What two plasma proteins does calcium mostly bind to?

Answer 18

Albumin (80%)

Globulin (20%)

Question 19

What anions can Ca bind to?

Answer 19

HCO3
H2PO4
HPO4
Sulphate
Citrate
Lactate

Question 20

How does plasma pH affect the binding capacity of Ca?

Answer 20

Binding capacity is increased under alkalotic conditions

This may precipitate a hypocalcaemic tetany

Opposite occurs in acidosis, where binding capacity reduces and free Ca rises

Question 21

Why does acidosis lead to more free Ca?

Answer 21

Increased [H+] displaces bound Ca2+ so there is more free Ca

Question 22

Total body calcium =

Answer 22

Ca in (diet) - Ca out (excretion at kidneys + faeces)

Question 23

Bone functions to provide mechanical support for the body but its role in _________________ takes precedence over this.

Answer 23

Maintaining Ca balance

Ca stored in bone can be added to or released as req.

Question 24

What are osteoblasts?

Answer 24

Bone building cells - lay down a collagen extracellular matrix which they calcify

Question 25

What do osteoblasts differentiate into?

Answer 25

Osteocytes in established bone

Question 26

What are the roles of osteocytes?

Answer 26

Appear to regulate the activity of osteoblasts + osteoclasts

Question 27

What is the role of osteoclasts?

Answer 27

Mobilising bone

Question 28

How do osteoclasts mobilise bone?

Answer 28

Secrete H ions to dissolve Ca salts + provide proteolytic enzymes to digests the EC M

Question 29

What are the two main hormones that act to raise plasma Ca levels?

Answer 29

Parathyroid hormone | Calcitriol

Question 30

What kind of hormone is PTH and where is it produced?

Answer 30

Polypeptide hormone | Produced by the parathyroid glands

Question 31

What is calcitriol?

Answer 31

Active form of VitD3, steroid hormone produced from Vit D by the liver + kidneys

Question 32

Where are the parathyroid glands found?

Answer 32

Usually 4 on the posterior surface of the thyroid gland NB: 1 in 10 have aberrant distribution (important for thyroid surgery)

Question 33

True or false: | Parathyroid glands are not essential for life and can be removed during thyroid surgery without complication

Answer 33

FALSE | They are essential for life

Question 34

When is PTH secreted?

Answer 34

In response to low [Ca]plasma

Question 35

What does PTH do?

Answer 35

Increases free [Ca] plasma by: 1. stimulating osteoclasts to increase resorption of Ca + phosphate in bone 2. Inhibit osteoblasts 3. Increasing reabsorption of Ca at kidney tubules 4. Increasing renal excretion of phosphate 5. Stimulating kidneys to make calcitriol

Question 36

How does calcitriol increase free Ca in the plasma?

Answer 36

Binds to nuclear receptors in target tissues (intestine, bone, kidney) to increase absorption of Ca from the gut, facilitate renal absorption of Ca and mobilise Ca stored in bone by stimulating osteoclasts

Question 37

How does increasing renal excretion of phosphate increase free Ca levels?

Answer 37

Prevents it being deposited back into bone, a process that req. phosphate

Question 38

Describe the production of calcitriol

Answer 38

Endogenous precursors are acted upon by sunlight on skin to produce vitamin D or acquired from diet Vit D processed in liver to become vit D3 and then metabolised in the kidneys to become calcitriol

Question 39

What other hormone stimulates the production of calcitriol?

Answer 39

Prolactin in lactating women

Question 40

What foods are high in vit D?

Answer 40

Fatty fish, egg yolks etc.

Question 41

How much dietary calcium is normally absorbed?

Answer 41

30%

Question 42

Why are older individuals at more risk of becoming vit D deficient?

Answer 42

Reduced gut absorption and reduced Ca mobility

Question 43

What does vitamin D3 deficiency result in?

Answer 43

Intestinal malabsorption of Ca --> reduced Ca in plasma --> increased PTH which promotes phosphate deficiency and aggravates Ca loss from bone

Question 44

Why are Asian populations at most risk of vit D3 deficiency?

Answer 44

Chapatti flour contains phytate which binds dietary Ca Dietary deficiency of Vit D3 Pigmented skin less able to make Vit D3 in response to UV light

Question 45

What conditions has vit D deficiency been implicated in?

Answer 45

MS Cancer CVD

Question 46

What hormone decreases [Ca] plasma?

Answer 46

Calcitonin

Question 47

Where is calcitonin produced?

Answer 47

Thyroid gland

Question 48

What stimulates the secretion of calcitonin?

Answer 48

Increased plasma Ca level

Question 49

What is the main action of calcitonin?

Answer 49

Bind to osteoclasts + inhibit bone resorption + increase renal excretion of Ca

Question 50

Why is it thought that calcitonin is not that important?

Answer 50

Where calcitonin levels are really high (e.g. thyroid tumours), plasma Ca levels are normal, so xs calcitonin is overridden by PTH

Question 51

How does cortisol affect Ca balance?

Answer 51

Inhibits osteoblasts, increases renal excretion of Ca+ phosphate + reduces intestinal absorption of Ca --> increased PTH --> increased bone resorption which over time can produce osteoporosis

Question 52

How does insulin affect bone formation?

Answer 52

Increases bone formation + antagonises action of cortisol

Question 53

How does oestrogen affect bone formation?

Answer 53

Promotes bone formation via oestrogen receptor on osteoblasts

Question 54

How does growth hormone affect bone formation?

Answer 54

Constant stimulus for bone formation

Question 55

How does prolactin affect calcium balance?

Answer 55

Promotes calcium absorption from gut via stimulating synthesis of calcitriol