Calcium and its control

Question 1

What is normal serum calcium conc.?

Answer 1

2.2 - 2.6 mM

Question 2

What are the different forms of serum calcium?

Answer 2

Free ionised calcium

Bound to plasma proteins

Bound to citrate

Question 3

What is the concentration of free ionised calcium in the blood?

Answer 3

1 - 1.3mM

Question 4

Which form of serum calcium is the biologically active one?

Answer 4

Free ionised calcium is biologically active

Question 5

What is the mass of calcium in a human adult?

Answer 5

1kg = 1000g

Question 6

Where is most of the calcium in the human body contained?

Answer 6

Bones forming the skeleton

Question 7

In what form is calcium stored in bones?

Answer 7

Calcium hydroxyapatite crystals

Question 8

What is the function of the skeleton? Which function is more improtant?

Answer 8

Structural support

Reserve of calcium - priority

Question 9

How does the skeleton act as a reserve of calcium?

Answer 9

Exchange of calcium phosphate between the bones and the interstitial fluid

• bones release it
• bones take it up

Question 10

What is the normal daily intake of calcium?

Answer 10

1g

Question 11

How is calcium lost from the body? How much?

Answer 11

Urinary loss - 175mg

GI loss - 825mg

altogether 1g is lost

Question 12

What are the molecules involved in the regulation of calcium levels?

Answer 12

Parathyroid hormone

Vitamin D

Calcitonin

Question 13

What types of cells is the parathyroid gland made up of? Which cells form most of it?

Answer 13

Chief cells - form most of parathyroid gland

Oxyphil cells

Question 14

What do chief cells look like?

Answer 14

Darker pink
Visible nuclei
Less cytoplasm

Question 15

What do oxyphil cells look like?

Answer 15

Lighter pink

More cytoplasm

Question 16

What additional structures do the parathyroid glands have?

Answer 16

Outer capsule

Inner adipose tissue

Question 17

What is the function of chief cells?

Answer 17

Produce PTH

Question 18

How often is PTH synthesised?

Answer 18

Continuously

Question 19

How often is PTH stored?

Answer 19

Not stored

Question 20

What type of hormone is PTH?

Answer 20

Polypeptide hormone

Question 21

What is the structure of PTH?

Answer 21

Straight chain

Question 22

Briefly outline how PTH is produced

Answer 22

Pre-pro-PTH is produced
cleaved twice to remove signal peptide, remove other parts of it
to give PTH

Question 23

How is PTH carried in the blood?

Answer 23

Is water-soluble

dissolves in plasma

Question 24

What is the half life of PTH?

Answer 24

Approx 5 mins - relatively short

Question 25

What are the target organs of PTH?

Answer 25

Bone Gut Kidney

Question 26

How does PTH affect bone?

Answer 26

Increases resorption of bone

Question 27

How does PTH give resorption of bone?

Answer 27

Stimulates osteoblasts to produce cytokines - cytokines cause osteoclasts to differentiate and increase in activity - cytokines protect osteoclasts from apoptosis Decreases activity of osteoblasts

Question 28

How long goes it take for PTH to give bone resorption?

Answer 28

1-2 hours

Question 29

What effect does PTH have on the gut?

Answer 29

Indirect effects on the gut because stimulates second hydroxylation reaction 25-hydroxyvitamin D -----> calcitriol and calctriol increases calcium absorption in the gut

Question 30

How is calcium normally absorbed in the gut?

Answer 30

Paracelullar uptake

Question 31

Is paracellular uptake of calcium in the gut effective?

Answer 31

No, is ineffective

Question 32

How does calcitriol give increased calcium absorption in the gut?

Answer 32

Increases transcellular uptake

Question 33

How does PTH affects the kidneys?

Answer 33

Stimulates reabsorption of calcium from the ascending limb and distal convoluted tubule Gives excretion of phosphate Affects magnium reabsorption, excretion

Question 34

What is the purpose of PTH increasing phosphate excretion?

Answer 34

To prevent calcium phosphate forming in the kidneys | would form stones in the kidneys

Question 35

How is secretion of PTH controlled?

Answer 35

Serum calcium levels

Question 36

What type of receptor is the parathyroid gland calcium receptor? What cascade of events does it cause?

Answer 36

GPCR Gaq Increased intracellular calcium

Question 37

How do high serum calcium levels affect PTH secretion?

Answer 37

``` Increased GPCR activation increase in intracellular calcium decreases PTH secretion -decrease gene transcription -inhibit release of PTH ```

Question 38

How do low serum calcium levels affect PTH secretion?

Answer 38

Decreased GPCR activation decrease in intracellular calcium increases PTH secretion -increases survival of mRNA

Question 39

How is PTH degraded?

Answer 39

PTH in parathyroid gland cleaved by chief cells Released PTH is cleaved by the liver

Question 40

How do serum calcium levels affect PTH degradation?

Answer 40

High serum calcium levels | increases PTH cleavage by chief cells in parathyroid gland

Question 41

What are the inactive forms vitamin D?

Answer 41

D3 cholecalciferol D2 ergocalciferol

Question 42

What is the body's source of D3 cholecalciferol?

Answer 42

Exposed to sunlight | cholesterol used to synthesise D3 cholecalciferol

Question 43

What is the body's source of D2 ergocalciferol?

Answer 43

D2 ergocalciferol from yeast and fungi added to foods e.g. margarine, butter, cheese

Question 44

What is the active form of vitamin D?

Answer 44

Calcitriol

Question 45

What are D3 cholecalciferol and D2 ergocalciferol converted into?

Answer 45

Calcitriol

Question 46

How are D3-cholecalciferol/D2-ergocalciferol converted into calcitriol?

Answer 46

Two hydroxylation reactions D3-choleciferol/D2-ergocalciferol -----> 25-hydroxyvitamin D 25-hydroxyvitamin D ------> calcitriol

Question 47

Where does the first hydroxylation reaction D3-cholecalciferol/D2-ergocalciferol -----> 25-hydroxyvitamin D occur?

Answer 47

Liver

Question 48

How long can 25-hydroxyvitamin D stay in the liver?

Answer 48

2 weeks

Question 49

Where does the second hydroxylation reaction | 25-hydroxyvitamin D -----> calcitriol occur?

Answer 49

Kidney | proximal convoluted tubule

Question 50

How does 25-hydroxyvitamin D reach the PCT in the kidneys?

Answer 50

Bound to carrier protein | small enough to be filtered by glomerulus

Question 51

What enzyme catalyses the reaction 25-hydroxyvitamin D -----> calcitriol?

Answer 51

1alpha-hydroxylase

Question 52

What is the half life of calcitriol?

Answer 52

6 hours

Question 53

How do serum calcium levels affect vitamin D formation?

Answer 53

High serum calcium levels inhibit second hydroxylation reaction 25-hydroxyvitamin D -----> calcitriol

Question 54

How does PTH affect calcitriol formation?

Answer 54

High PTH levels stimulate second hydroxylation reaction | 25-hydroxyvitamin D -----> calcitriol

Question 55

How is active vitamin D3 transported in the blood?

Answer 55

Bound to carrier protein transcalciferin Small amount is free

Question 56

What are the target organs of active vitamin D? How does it affect them?

Answer 56

Bone - stimulates resorption of bone Kidneys - stimulates reabsorption of calcium GI - stimulates absorption of calcium by transcellular uptake

Question 57

What produces calcitonin?

Answer 57

Parafollicular cells in the thyroid gland

Question 58

What is the function of calcitonin?

Answer 58

Reduces serum calcium conc.

Question 59

How effective is calcitonin in humans?

Answer 59

Has limited effect

Question 60

How fast or slow does calcitonin have effects?

Answer 60

Rapid acting

Question 61

How is calcitonin used clinically?

Answer 61

In hypercalcaemia, to rapidly lower serum calcium concs.

Question 62

What effect does calcitonin have in pregnancy?

Answer 62

Maintains maternal bones of skeleton maybe