Skeleton and metabolism Flashcards

1
Q

Hormones with skeletal effects

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

Hormones secreted from the skeleton

A

• FGF-23 (fibroblast growth factor 23)

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3
Q

Bone as 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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4
Q

Daily calcium turnover

A

Daily intake recommended 1000-1200mg (25-30 mmol)
Extracellular: plasma Ca 2.2-2.6 mmol L-1
About half is free [Ca2+] (physiologically active), half protein bound (mainly albumin)
AW Ca = 40, 40 mg = 1 mmol. 900/40 = 22.5 mmol in ECF.

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5
Q

Parathyroid glands

A
  • PTH synthesised by parathyroid chief cells
  • Secreted as 84 AA polypeptide
  • Short half-life in circulation (<5 min)
  • Parathyriod. 80K cells continuously monitoring blood Ca, and increasing or decreasing PTH secretion accordingly.
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6
Q

Parathyroid hormone (PTH)

A
  • Major role is defence against hypocalcaemia
  • Plasma Ca is maintained 2.2 – 2.6 mM (free, ionized Ca2+ is approximately half)
  • Free Ca sensed by GPCR on chief cells
  • Ca binding supresses PTH release
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7
Q

Vitamin D

A
  • Calcitriol (really a steroid hormone, not a vitamin!)
  • Synthesised in skin in response to exposure to UV (‘sunshine vitamin’)
  • Activated by 2 metabolic steps
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8
Q

Actions of PTH

A

Site of regulation is chief cells of PT gland
• Secretion increases as plasma [Ca2+] decreases
Actions:
• Promotes release of Ca from bone
• Increases renal Ca reabsorption
• Increases renal Pi excretion
• Upregulates 1α hydroxylase activity

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9
Q

Actions of calcitriol

A

Site of regulation is control of 1α hydroxylase in kidney
Increased by
• PTH
• Low phosphate
Actions:
• Increase absorption of Ca and Pi from GI tract
Little absorption in absence
• Inhibits PTH secretion (transcription)
• Complex effects on bone, generally in synergy with PTH
• The only way to increase the body’s Ca reservoir is via absorption from the gut, and little takes place in the absence of vitamin D.

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10
Q

Calcium homeostasis

A
  • 99% of body calcium is in bone
  • Remaining 1% is mainly intracellular
  • Hormonal control of the tiny (<0.1%) extracellular fraction is what maintains Ca balance
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11
Q

Actions of PTH on bone

A

• PTH receptors on osteoblasts and osteoclasts
• Promotes bone formation
• Activates osteoclasts via RANKL
• Promotes bone remodelling
Effect depends on concentration dynamics
• Intermittent low doses are anabolic
• Persistent high concentration leads to excess resorption over formation – bone loss

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12
Q

Lacunar-Canalicular network

A

• Allows communication between osteocytes and from osteocytes to surface cells and systemic circulation

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13
Q

FGF-23: a hormone secreted by osteocytes

A
  • Hypophosphatemic rickets: rare phosphate-wasting conditions leading to bone mineralization defects (osteomalacia)
  • Consortium investigating autosomal-dominant HR (ADHR) traced mutation in gene that turned out to be FGF-23
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14
Q

Actions of FGF-23

A
  • Expressed and secreted by osteocytes
  • Increases renal Pi excretion (by reducing Na-Pi reabsorption from proximal tubule)
  • Increased by calcitriol and Pi
  • Inhibits calcitriol synthesis
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15
Q

Disorders of calcium

A
  • Normal range 2.2 – 2.6 mM
  • Hypocalcaemia
  • Hypercalcaemia
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16
Q

Clinical features of hypercalcemia

A
  • Depression, fatigue, anorexia, nausea, vomiting,
  • Abdominal pain, constipation
  • Renal calcification (kidney stones)
  • Bone pain
  • Severe: cardiac arrhythmias, cardiac arrest
  • The deleterious effects are partly due to the fact that ionic Ca is near saturation and rises can lead to precipitation (calcification). There may also be direct neurological effects.
17
Q

Hypercalcemia saying

A

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

18
Q

Causes of hypercalcaemia

A
Most common causes:
•	In ambulatory patients: primary hyperparathyroidism
•	In hospitalized patients: malignancy 
Less common causes include:
•	Hyperthyroidism
•	Excessive intake of vitamin D
19
Q

Primary hyperparathyroidism

A
  • Usually due to a benign adenoma in one or more PT glands
  • Often detected on screening – many patients asymptomatic
  • ~10% of patients present with clinical evidence of bone disease
  • 10 - 20% of patients present with kidney stones
  • Resolved by surgical removal of affected gland(s)
20
Q

Hypercalcaemia of malignancy

A
  • Common problem of advanced malignancy

* Tumour may secrete PTH-related peptide, binds and activates PTH receptor

21
Q

Site of regulation of PT gland

A

Is Chief cells

• Secretion increases as plasma [Ca2+] decreases