Physiology of Bone Calcium and Phosphate Homeostasis

Question 1

What is the most common calcium phosphate?

Answer 1

Hydroxyapatite

Question 2

What are osteoblasts?

Answer 2

Modified fibroblasts involved in forming bone

Question 3

How do osteoblasts build bone?

Answer 3

Produces enzymes and osteoid to which hydroxyapatite binds

Question 4

What is osteoid?

Answer 4

Collagen and protein mix

Question 5

Which proteins aid in deposition of bone?

Answer 5

Osteocalcin and osteonectin

Question 6

What are chondrocytes and where in the developing bone are they found?

Answer 6

Collagen-producing cells of the cartilage located near the epiphysis

Question 7

How are chondrocytes involved in lengthening bone?

Answer 7

Continuously dividing and laying down columns of collagen; as the collagen layer thickens, the old chondrocytes die and leave spaces for osteoblasts to lay down bone on the collagen base

Question 8

What are osteocytes?

Answer 8

Less active osteoblasts

Question 9

What are osteoclasts?

Answer 9

Large, mobile, multinucleate cells derived from haematopoietic stem cells involved in bone resorption

Question 10

How do osteoclasts resorb bone?

Answer 10

Secrete acid and proteases to dissolve the calcified matrix and collagen support

Question 11

What hormones are involved in Ca2+ metabolism?

Answer 11

PTH
Vitamin D3 (calcitriol)
Calcitonin

Question 12

List 4 physiological roles of Ca2+

Answer 12

Intracellular signalling
Structural functions (e.g. bone matrix, tight junctions)
Cofactor in coagulation
Neuronal and muscle excitability

Question 13

What are the 3 pools of Ca2+ in the body and in what form does Ca2+ exist in each? What % of total Ca2+ does each account for?

Answer 13

Bone matrix (99%)
Extracellular (ionised; 0.1%)
Intracellular (free; 0.9%)

Question 14

Which of the 3 pools of Ca2+ in the body is carefully regulated?

Answer 14

ECF (moves freely in and out of plasma)

Question 15

How does Ca2+ get in and out of cells?

Answer 15

In: down the electrochemical gradient (from ~2.5mM to 0.001mM)
Out: active transport

Question 16

How and where is Ca2+ reabsorbed in the kidney?

Answer 16

Reabsorption occurs in the distal nephron via the following transporters:
ECaC
Na+-Ca2+ antiport
Ca2+-ATPase

Question 17

What is the effect of PTH on serum Ca2+ and phosphate?

Answer 17

Increases Ca2+

Decreases phosphate

Question 18

What are the actions of PTH on bone?

Answer 18

Increases Ca2+ and phosphate release into plasma

Favours bone resorption

Question 19

What are the actions of PTH on the kidney distal tubule?

Answer 19

Increases Ca2+ reabsorption

Decreases phosphate reabsorption (and increases excretion)

Question 20

What are the actions of PTH on the intestine?

Answer 20

No direct actions (actions mediated by vitamin D3)

Question 21

What is the result of the absence of PTH?

Answer 21

Hypocalcaemic tetany leading to death

Question 22

Where is calcitonin produced?

Answer 22

C cells of the thyroid (parafollicular cells)

Question 23

What is the stimulus for calcitonin release?

Answer 23

Increased plasma Ca2+

Question 24

What are the effects of calcitonin?

Answer 24

Decreased release of Ca2+ from bone
Decreased bone resorption
Increased renal Ca2+ excretion

Question 25

When is calcitonin relevant?

Answer 25

Only in extreme hypercalcaemia (no role in normal homeostasis) May play be protective for bone Ca2+ during pregnancy and lactation

Question 26

What are calcitonin's effects on the gut?

Answer 26

No effect

Question 27

Describe the pathway of vitamin D activation

Answer 27

Precursor in skin (dehydrocholesterol) is converted by UV light to vitamin D3 (cholecalciferol), or D3 is ingested directly Vitamin D3 is hydroxylated in the liver to produce 25-OH D3 25-OH D3 is further hydroxylated in the kidney to produce the active form, 1,25-(OH)2 D3 1,25-(OH)2 D3 acts mainly on the intestine

Question 28

What factors affect the 2nd hydroxylation of vitamin D3 in the kidney?

Answer 28

PTH stimulates kidney enzymes to increase conversion to the activated form, as does decreased plasma phosphate Prolactin also stimulates synthesis

Question 29

Will kidney and gut dysfunction affect Ca2+ homeostasis?

Answer 29

Yes

Question 30

Which of the 3 organ systems responsible for modulating Ca2+ homeostasis act quickest? Which takes longest?

Answer 30

Kidneys quickest Intestine longer Bone resorption longest

Question 31

What hormone controls epiphyseal closure?

Answer 31

Oestrogen

Question 32

What are the 3 main physiological roles of phosphate?

Answer 32

Energy transfer and storage (ATP, cAMP) Control of enzymes, transporters, ion channels Part of DNA and RNA backbone

Question 33

What is a possible cause of hyperparathyroidism? What are the biochemical findings?

Answer 33

Tumour | Hypercalcaemia, hypophosphataemia (but effects variable)

Question 34

What are some possible causes of hypoparathyroidism? What are the biochemical findings and what are some possible effects?

Answer 34

Autoimmune attack of glands or inadvertent parathyroidectomy during thyroid surgery Hypocalcaemia, hyperphosphataemia Causes neuromuscular excitability (hypocalcaemic tetany) and is ultimately fatal

Question 35

What disorders result from a vitamin D deficiency in childhood and adulthood?

Answer 35

Childhood: rickets Adulthood: osteomalacia

Question 36

What are the effects of a vitamin D deficiency?

Answer 36

Impaired intestinal Ca2+ absorption | Plasma Ca2+ is maintained at the expense of bones

Question 37

What causes osteoporosis?

Answer 37

Long term imbalance of bone resorption and bone formation (loss of protective role of oestrogen may influence)

Question 38

In what population is osteoporosis most common?

Answer 38

Postmenopausal women >50

Question 39

List some risk factors for osteoporosis

Answer 39

``` Inactivity (especially lack of weight-bearing exercise) Malnutrition Alcohol Smoking Endocrine disorders (e.g. Cushings) Low dietary Ca2+ ```

Question 40

What is the effect of cortisol on bone?

Answer 40

Causes increased bone resorption

Question 41

Where is most phosphate reabsorbed?

Answer 41

Proximal tubule

Question 42

What are the physiological effects of 1,25-(OH)2 D3?

Answer 42

Increases intestinal Ca2+ and phosphate absorption Increases calbindin Increases Ca2+-sensing receptors Weakly increases phosphate resabsorption in the kidney)