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MUSCULOSKELETAL > The Skeleton and Metabolism > Flashcards

The Skeleton and Metabolism Flashcards

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1
Q

List the hormones that display skeletal effects?

A
  • Oestrogen = maintains bone health
  • Androgens = maintains bone health
  • Cortisol = detrimental in excess
  • Parathyroid hormone (PTH) = bone maintenance + regulation of extracellular Ca2+ + phosphate
  • Vitamin D (calcitriol) = bone maintenance and regulation of extracellular Ca2+ + phosphate
  • Calcitonin
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2
Q

What hormone is secreted from the skeleton?

A

FGF-23 (fibroblast growth factor 23)

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3
Q

What is extracellular free calcium important for and what does it mean for its regulation?

A

Important for physiological processes e.g electrical signalling

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4
Q

Why does Ca2+ intake and outtake need to be balanced?

A

Maintains Ca2+ homeostasis

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5
Q

What molecule is calcium often bound to?

A
  • Half of the calcium present is free [Ca2+] (physiologically active)
  • Half is protein bound (mainly albumin)
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6
Q

How is bone a metabolic organ?

A

Bone turnover serves homeostasis of serum calcium, phosphate, in conjunction with

  • Parathyroid hormone (PTH)
  • Vitamin D (1,25-dihydroxy D3)
  • Calcitonin
  • FGF-23
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7
Q

What synthesises PTH?

A

PTH is synthesised by parathyroid chief cells on the parathyroid gland

  • Chief cells monitor extracellular calcium and adjust their function
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8
Q

What is the main role of PTH?

A

Major role is defence against hypocalcaemia

  • As free Ca2+ levels are low serum PTH levels rise, as free Ca2+ levels are high serum PTH levels decrease.
  • Linear region = negative feedback homeostatic function
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9
Q

What happens when Ca binds to GPCR on the chief cells?

A

Supresses PTH release

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10
Q

What is calcitriol?

A

Known as vitamin D, is a steroid hormone not a vitamin

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11
Q

What does the calcitriol nuclear receptor do?

A

Synthesised in the skin in response to exposure to UV (‘sunshine vitamin’)

Activated by 2 metabolic steps

  • 25 hydroxylation in the liver to form 25OH D3, which is the major circulating metabolite (not activated form essentially a prohormone)
  • 1α hydroxylation of 25 OH D3 in kidney produces 1,25(OH)2 D3, or calcitriol, the active hormone

Steroid hormone therefore binds to a nuclear receptor activating the transcription of target genes

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12
Q

What is vitamin D increased by?

A
  • PTH
  • Low phosphate in plasma
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13
Q

What are the actions of vitamin D?

A
  • Increase absorption of Ca and Pi from GI tract
    • Little absorption in absence
  • Inhibits PTH secretion (transcription)
    • In a negative feedback mechanism
  • Complex effects on bone, generally in synergy with PTH
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14
Q

What are the actions of PTH?

A
  • Promotes release of Ca from bone (as PTH is the main defence against hypocalcaemia)
  • Increases renal Ca reabsorption
  • Increases renal Pi excretion
  • Upregulates 1α hydroxylase activity which activates vitamin D
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15
Q

What is the action of PTH on bone?

A
  • PTH receptors are present osteoblasts and osteoclasts
  • Promotes bone formation
  • Activates osteoclasts via RANKL
  • Promotes bone remodelling
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16
Q

What is the effect of PTH on bone in regards to calcium

A

Promotes release of Ca from bone (as PTH is the main defence against hypocalcaemia)

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17
Q

What is the effect of PTH on bone in regards to phosphate?

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A

Increases excretion of phosphate, if extracellular Ca2+ drops, reabsorption can be increased to counteract the drop

However, phosphate needs to drop to maintain the homeostasis of minerals

18
Q

Summarise the effect of PTH on bone?

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A
  • Increases reabsorption of Ca2+ and increased excretion of phosphate
    • Maintains homeostasis of minerals
  • More calcium = less phosphate
19
Q

How does PTH increase the absorption of calcium and phosphate from the GI tract?

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A
  • Increases the expression of the 1-alphahydroxylase enzyme in the kidney which increases levels of calcitriol.
  • Calcitriol increases absorption of calcium and phosphate from the GI tract
20
Q

What does the effect of PTH partly depend on?

Study These Flashcards
A

Concentration dynamic

  • Intermittent low doses anabolic - promotes remodelling
  • Persistent high concentration leads to excess resorption over formation leading to bone loss
21
Q

What is calcitonin?

Study These Flashcards
A
  • Secreted by C cells of thyroid
  • Stimulus for secretion is high [Ca2+]
22
Q

What is the effect of calcitonin?

Study These Flashcards
A
  • Opposite effect of PTH
  • The net effect is to decrease extracellular calcium
23
Q

How does calcitonin work?

Study These Flashcards
A
  • Decreases extracellular calcium via renal transporters
  • Inhibits osteoclasts to inhibit calcium release from bone
24
Q

Target organs for calcitonin

Study These Flashcards
A

Kidney - decreases calcium and phosphate

Bone - decreases bone resorption by inhibiting osteoclast activity

25
What can synthetic calcitonin be used for?
Treatment of paget's disease of bone and severe osteoporosis Calcitonin inhibits osteoclasy activity = reduction in bone reabsorption = weakening of bones
26
What is the lacunar-canalicular network?
Allows for the communication between osteocytes and from osteocytes to surface cells and systemic circulation
27
What are the lacunae?
Small cell sized holes where osteocytes live when they intune themselves into bone after terminal differentiation
28
What secretes FGF-23?
Hormone secreted by osteocytes
29
Where does FGF-23 act?
* Expressed and secreted by osteocytes * Increased by calcitriol and Pi * Inhibits calcitriol synthesis * Increases renal Pi excretion
30
What is hypophosphatemic rickets?
Hypophosphatemic rickets: rare phosphate-wasting conditions leading to bone mineralization defects (osteomalacia)
31
What is vitamin D resistant ricketts and give an example?
Normally ricketts would be treated by vitamin D but in rare cases is resistant One example is hypophosphatemic rickets
32
How does the rise in extracellular Pi stimulate FGF-23?
Rise stimulates secretion of FGF-23 from osteoclasts that promote phosphate excretion via kidney FGF-23 interacts with other loops, it inhibits alpha-1 hydroxylase decreasing calcitriol
33
What is hypocalcaemia?
Below normal range of 2.2 - 2.6 mM
34
What is hypercalcaemia?
Above normal range of 2.2-2.6 mM
35
What are the clinical features of hypercalcaemia?
* Depression * Fatigue * Anorexia * Nausea * Vomiting * Abdominal pain * Constipation * Renal calcification * Bone pain Mnemonic = 'painful bones, renal stones, abdominal groans and psychic moans'
36
What is a severe features of hypercalcaemia?
* Cardiac arrhythmias * Cardiac arrest
37
What are common causes of hypercalcaemia?
Ambulatory patients = primary hyperparathyroidism Hospitalized patients = malignancy (secondary release of PTH from tumour cells)
38
Less common causes of hypercalcaemia?
Hyperthyroidism Excessive intake of vitamin D
39
Describe primary hyperparathyroidism
* Excessive secretion of PTH * Due to benign adenoma in one or more of the parathyroid glands
40
How is primary hyperparathyroidism resolved?
Through surgical removal of affected glands
41
What is hypercalcaemia of malignancy?
* Common problem of advanced malignancy * Tumour secretes PTH related peptide activating the PTH receptor * Mimics the effects of excessive PTH * Leads to bone disease, cancer and hypercalcaemia

MUSCULOSKELETAL (3 decks)

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