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Musculo-Skeletal System > The skeleton and metabolism > Flashcards

The skeleton and metabolism Flashcards

1
Q

Give the hormones with skeletal effect.

A 
Oestrogen
Androgens
Cortisol
Parathyroid (PTH)
Vitamin D (calcitriol)
Calcitonin
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2
Q

What Hormones are secreted from the skeleton?

A

FGF-23 (fibroblast growth factor 23)

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3
Q

Describe the Calcium Distribution.

A

mineral content of bone (99%)

intracellular (1%)

Extracellular (<0.1%)

  • free or albumin bound
  • this fraction is monitored by the chief cells of parathyroid glands
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4
Q

Describe the Intake and Excretion of Calcium.

A

Daily intake: 1000-1200mg (25-30mmol) and therefore a similar amount will be excreted:
-about 80% of calcium intake is lost via the gut and the remainder is excreted by the kidney

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5
Q

Describe the Bone as a metabolic organ.

A

Bone turnover serves homeostasis of serum calcium and phosphate in conjunction with:

  • parathyroid hormone (PTH)
  • vitamin D (1,25- dihydroxy D3)
  • calcitonin
  • FGF-23
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6
Q

What is the Parathyroid hormone?

A

84 amino acid polypeptide synthesized by parathyroid chief cells

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7
Q

What is the Half-life of PTH?

A

short half life (<5 mins)

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8
Q

What is the Role of PTH?

A

defence against hypocalcaemia via negative feedback homeostatic function

-parathyroid glands contain 80,000 chief cells continuously monitoring blood Ca, and increase or decrease PTH secretion accordingly

Plasma Ca is maintained at 2.2-2.6mmol/L (free, ionised Ca2+ is ~half):

  • low plasma Ca, increased PTH secretion
  • high plasma Ca, PTH secretion suppressed
  • in between, roughly linear relationship between extracellular plasma and PTH release
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9
Q

Describe the Regulation of PTH secretion.

A

Increase in extracellular Ca, activation of G-protein coupled receptor, PTH secretion falls

Decrease in extracellular Ca, no activation of G-protein coupled receptor, PTH secretion rises

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10
Q

State the Actions of PTH.

A
  • promotes release of Ca from bone
  • increases renal Ca reabsorption via actions on specific renal tubular transporters
  • increases renal phosphate excretion via actions on specific renal transporters
  • upregulates 1⍺ hydroxylase activity to activate vitamin D
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11
Q

What is the Effect of PTH on bone remodelling?

A

PTH receptors on osteoblasts and osteoclasts, increasing bone remodelling:

  • increased bone formation via osteoblasts
  • increased bone reabsorption after activating osteoclasts via RANKL
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12
Q

How does the Concentration of PTH affects bone remodelling

A

Intermittent low doses are anabolic (bone formation)

Persistent high concentration leads to excess reabsorption over formation, causing bone loss due to increased calcium release causing bone de-mineralisation and loss

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13
Q

What is Vitamin D (calcitriol)?

A

steroid hormone (not a vitamin) synthesized in skin in response to UV exposure

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14
Q

Describe the Activation of Vitamin D.

A

1) 25 hydroxylation of Vitamin D3 in liver to form 25OH D3, major circulating metabolite
2) 1α hydroxylation of 25OH D3 in kidney produces 1,25 (OH)2 D3, or calcitriol, the active hormone (binds nuclear receptor to affect transcription)

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15
Q

What is 1 alpha hydroxylase?

A

located in the kidney

its activity is increased by:

  • PTH
  • low phosphate
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16
Q

What are the Actions of Calcitriol?

A

Increase absorption of calcium and phosphate from GI tract

Inhibits PTH secretion (by inhibiting PTH transcription in chief cells in parathyroid glands)

Complex effects on bone in synergy with PTH (essential in normal bone mineralisation)

17
Q

What is Calcitonin?

A

32 amino acid peptide hormone secreted by C cells of the thyroid gland

18
Q

What is the Stimulus for calcitonin secretion?

A

high blood calcium levels (opposite to PTH)

19
Q

What is the Action of calcitonin?

A

Decreases extracellular calcium via:

Kidney
-decreases calcium and phosphate reabsorption

Bone: decreases Ca bone reabsorption/ release by inhibiting osteoclast activity

20
Q

Give some Clinical uses of synthetic calcitonin.

A

treatment of Paget’s disease of bone and severe osteoporosis due to inhibition of osteoclast activity

21
Q

Describe the Lacunar-Canalicular System.

A

Lacunae are small sized cavities filled with osteocytes and are connected to other lacunae and to the bone surface via minute channels called canaliculi

allows communication between osteocytes and from osteocytes to surface cells and systemic circulation (between systemic circulation and bone)

22
Q

What is FGF-23?

A

hormone synthesized and secreted by osteocytes which decreases phosphate levels

-also produced by calcitriol

23
Q

What are Hypophosphatemic rickets?

A

autosomal dominant rare phosphate wasting disease (excessive phosphate excretion) leading to osteomalacia (bone mineralisation defects)

associated with high levels of FGF-23

24
Q

What are the Actions of FGF-23?

A

Decreases phosphate levels:

  • increases renal phosphate excretion (by reducing Na-Pi reabsorption from proximal tubule)
  • inhibits PTH secretion (because PTH increases calcitriol, which in turn increases phosphate)
  • inhibits 1⍺ hydroxylase, inhibiting calcitriol synthesis (because calcitriol increases absorption of phosphate)
25
Q

What are the Clinical Features of hypercalcaemia?

A

Depression, fatigue, anorexia, nausea, vomiting

Abdominal pain, constipation

Renal calcification (kidney stones)

Bone pain

“Painful bones, renal stones, abdominal groans and psychic moans”

Severe: cardiac arrhythmias and cardiac arrest

26
Q

What are the Most common causes of hypercalcaemia?

A

In ambulatory patients
-primary hyperparathyroidism (benign adenoma of parathyroid gland)

In hospitalised patients:
-malignancy

27
Q

What are the Less common causes of hypercalcaemia?

A

Hyperthyroidism

Excessive intake of vitamin D (inhibits PTH secretion)

28
Q

What is Primary hyperparathyroidism?

A

Excessive secretion of PTH due to a benign adenoma in one or more parathyroid glands

Resolved by surgical removal of affected gland(s)

Musculo-Skeletal System (4 decks)

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