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Hannah's Locomotor > Physiology of Bone Calcium and Phosphate Homeostasis > Flashcards

Physiology of Bone Calcium and Phosphate Homeostasis Flashcards

1
Q

What is the most common calcium phosphate?

A

Hydroxyapatite

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2
Q

What are osteoblasts?

A

Modified fibroblasts involved in forming bone

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3
Q

How do osteoblasts build bone?

A

Produces enzymes and osteoid to which hydroxyapatite binds

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4
Q

What is osteoid?

A

Collagen and protein mix

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5
Q

Which proteins aid in deposition of bone?

A

Osteocalcin and osteonectin

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6
Q

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

A

Collagen-producing cells of the cartilage located near the epiphysis

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7
Q

How are chondrocytes involved in lengthening bone?

A

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

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8
Q

What are osteocytes?

A

Less active osteoblasts

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9
Q

What are osteoclasts?

A

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

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10
Q

How do osteoclasts resorb bone?

A

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

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11
Q

What hormones are involved in Ca2+ metabolism?

A

PTH
Vitamin D3 (calcitriol)
Calcitonin

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12
Q

List 4 physiological roles of Ca2+

A

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

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13
Q

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?

A

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

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14
Q

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

A

ECF (moves freely in and out of plasma)

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15
Q

How does Ca2+ get in and out of cells?

A

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

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16
Q

How and where is Ca2+ reabsorbed in the kidney?

A

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

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17
Q

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

A

Increases Ca2+

Decreases phosphate

18
Q

What are the actions of PTH on bone?

A

Increases Ca2+ and phosphate release into plasma

Favours bone resorption

19
Q

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

A

Increases Ca2+ reabsorption

Decreases phosphate reabsorption (and increases excretion)

20
Q

What are the actions of PTH on the intestine?

A

No direct actions (actions mediated by vitamin D3)

21
Q

What is the result of the absence of PTH?

A

Hypocalcaemic tetany leading to death

22
Q

Where is calcitonin produced?

A

C cells of the thyroid (parafollicular cells)

23
Q

What is the stimulus for calcitonin release?

A

Increased plasma Ca2+

24
Q

What are the effects of calcitonin?

A

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

25
Q

When is calcitonin relevant?

A

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

26
Q

What are calcitonin’s effects on the gut?

A

No effect

27
Q

Describe the pathway of vitamin D activation

A

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

28
Q

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

A

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

29
Q

Will kidney and gut dysfunction affect Ca2+ homeostasis?

A

Yes

30
Q

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

A

Kidneys quickest
Intestine longer
Bone resorption longest

31
Q

What hormone controls epiphyseal closure?

A

Oestrogen

32
Q

What are the 3 main physiological roles of phosphate?

A

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

33
Q

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

A

Tumour

Hypercalcaemia, hypophosphataemia (but effects variable)

34
Q

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

A

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

35
Q

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

A

Childhood: rickets
Adulthood: osteomalacia

36
Q

What are the effects of a vitamin D deficiency?

A

Impaired intestinal Ca2+ absorption

Plasma Ca2+ is maintained at the expense of bones

37
Q

What causes osteoporosis?

A

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

38
Q

In what population is osteoporosis most common?

A

Postmenopausal women >50

39
Q

List some risk factors for osteoporosis

A 
Inactivity (especially lack of weight-bearing exercise)
Malnutrition
Alcohol
Smoking
Endocrine disorders (e.g. Cushings)
Low dietary Ca2+
40
Q

What is the effect of cortisol on bone?

A

Causes increased bone resorption

41
Q

Where is most phosphate reabsorbed?

A

Proximal tubule

42
Q

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

A

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

Hannah's Locomotor (10 decks)

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