The skeleton and metabolism Flashcards
Describe the effects of various hormones on the skeleton
- Oestrogen – promoting and maintaining bone formation
- Androgens – promoting and maintaining bone formation
- Cortisol – this promotes bone resorption (stress hormone – releases digested amino acids into circulation which is used for gluconeogenesis to maintain glucose levels.) High cortisol can lead to loss of bone mass e.g glucocorticoid medicines
- Parathyroid hormone (PTH)
- Vitamin D (calcitriol)
- Calcitonin
What hormone is secreted from the skeleton?
FGF-23 (fibroblast growth factor 23)
What does parathyroid hormone do?
Why is vitamin D needed?
What does calcitonin do?
What does FGF do?
Bone turnover serves homeostasis of serum calcium, phosphate, in conjunction with
• Parathyroid hormone (PTH) – raise extracellular calcium, levels
• Vitamin D (1,25-dihydroxy D3) – needed for absorption of calcium from the diet
• Calcitonin – lowers extracellular calcium levels. Has a minimal physiological role.
• FGF-23 – fibroblast growth factor 23 – new hormone – synthesised and secreted by osteocytes, bone acting as an endocrine organ
What does bone remodelling release?
In the short term, bone remodelling releases minerals, notably calcium, into the circulation, and therefore can be controlled in the short-term in the service of calcium homeostasis.
How much calcium do we consume?
What is the conc of calcium in our body?
What is calcium bound ti?
Lets consider calcium in the extracellular fluid:
• 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)
Where is PTH synthesised?
What is it secreted as?
- PTH synthesised by parathyroid chief cells in the parathyroid glands
- 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.
What do PTH do and how is calcium serum levels detected?
- 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
What is calcitriol?
How is it synthesed?
What does it do?
• Calcitriol (really a steroid hormone, not a vitamin!)
• Synthesised in skin in response to exposure to UV (‘sunshine vitamin’)
• Activated by 2 metabolic steps
25 hydroxylation in liver to form 25OH D3, major circulating metabolite
1α hydroxylation of 25 OH D3 in kidney produces 1,25(OH)2 D3, or calcitriol, the active hormone
• Needed for Ca absorption from gut (why is vitamin D needed?)
• It binds to nuclear receptors
When do we get PTH release?
When calcium levels are low
What are the actions of PTH
- Promotes release of Ca from bone
- Increases renal Ca reabsorption
- Increases renal Pi excretion
- Upregulates 1α hydroxylase activity in kidney for converting vitamin D into its active form: calcitriol
What controls calcitriol release
Site of regulation is control of 1α hydroxylase in kidney
How is calcitriol increased?
Increased by:
- PTH
- Low phosphate
Describe the actions of calcitrol
• Increase absorption of Ca and Pi from GI tract
Little absorption in absence of calcitriol
• Inhibits PTH secretion (transcription)
• Complex effects on bone, generally in synergy with PTH
What effects does PTH have on the bone?
What are these effects dependant on?
- 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
Describe the structure of the lacunocanalicular network
On image
