Biology of Bone and Extracellular Calcium

Question 1

intracellular calcium concentration is

Answer 1

low (< 1 micro mole/L)

Question 2

extracellular calcium concentration is

Answer 2

higher (~1 mmol./L)

Question 3

extracellular calcium allows for

Answer 3

bone mineralisation

acitivity of excitable tissue

Question 4

intracellular calcium allows

Answer 4

calcium protein binding

Question 5

extracellular calcium is measured

Answer 5

in liquid (serum or plasma)
albumin and total calcium both measured

Question 6

calcium is made of how many components?

Answer 6

2
ionised - active
albumin-bound - non-active

Question 7

aging usually marked by

Answer 7

slow phase of negative calcium balance (leads to loss of bone density –> osteoporosis)

Question 8

What are the functions of bone?

Answer 8

support, protection, leverage, RBC production, enocrine function, mineral homeostasis

Question 9

What is the morphology of bone?

Answer 9

trabecular - mesh

cortical - dense edges

Question 10

What do osteoblasts do?

Answer 10

make bone by mineralising osteoid collagen fibres with hydroxyapatite crystals

Question 11

What does mineralisation of osteoids achieve?

Answer 11

rigidity, compression resistance

Question 12

What happens if there is calcitriol deficiency?

Answer 12

failed mineralisation - Rickets, osteomalacia

Question 13

What is the role of ALP in mineralisation?

Answer 13

expressed on differentiated osteoblast surface and released into ECF
promotes mineralisation of hydroxyapatite by increasing local phosphate and hydrolysing pyrophosphate (mineralisation inhibitor)

Question 14

What are osteoclasts?

Answer 14

multinucleate, motile, bone-resorbing cells

Question 15

What does the ‘ruffled border’ of osteoclasts secrete?

Answer 15

H+ and enzymes

Question 16

What is the role of RANK and RANKL?

Answer 16

RANK on osteoclast precursor binds RANKL on bone marrow stromal cell to activate NFkB in the precursor which leads to maturation

Question 17

how do osteoclasts resorb bone?

Answer 17

degrade the matrix

Question 18

What do osteocytes do?

Answer 18

mechanosensory

Question 19

What is Paget’s disease?

Answer 19

overactive osteoclasts lead to bone loss, increased bone resorption –> osteoporosis

Question 20

Which 2 hormones regulate plasma calcium?

Answer 20

parathyroid hormone (peptide) and calcitriol (steroid)

Question 21

How does PTH regulate calcium?

Answer 21

falling calcium leads to PTH secretion, stimulate efflux, renal absorption of calcium, formation of calcitriol by intestinal absorption of calcium, loss of phosphate and bicarbonate from the kidney

Question 22

What is the source of calcitriol?

Answer 22

vitamin D (fat-soluble)

Question 23

How is calcitriol produced?

Answer 23

UV light action on 7-dehydroxycholesterol
in liver 25-hydroxylase converts to 25(OH) vitamin D
in kidney 1alpha-hydroxylase converts to 1,25(OH)2 vitamin D or calcitriol

Question 24

What is calcitriol?

Answer 24

active form of vitamin D, hormone made at kidney and is required for long-term calcium (and phosphate) maintenance, bone growth and mineralisation

Question 25

How is vitamin D produced?

Answer 25

UV light action on precursor 7-DHC in skin

Question 26

What is the mechanism of action of calcitriol?

Answer 26

binds vitamin D receptor
new protein synthesis stimulated - intestine makes calbindin-D9k (promotes absorption)
stimulates osteoblast differention - RANKL formation (stimulates osteoclast activation)

Question 27

How does PTH cooperate with calcitriol?

Answer 27

promotes 1alpha-hydroxylase activity (promotes calcitriol formation)

Question 28

What are the limitations of action between PTH and calcitriol?

Answer 28

switch off PTH gene transcription - limits PTH action

Question 29

What is the key difference between PTH and calcitriol calcium regulation?

Answer 29

PTH - short term (min-by-min)

calcitriol - long term