MSS: The Skeleton And Metabolism Flashcards
What are the functions of our bones?
- Support and movement: attachment site for muscles
- Protection for internal organs
- provide home for bone marrow
- Acts as mineral reservoir
- Endocrine: Source of some ‘non classical’ hormones
Describe the bone structure
- Cortical (compact) bone
- Trabecular (spongy, cancellous) bone
Describe the composition of the bone
- Protein: Organic osteoid matrix (25%)
- Mineral (75%)
- Cells
Describe the organic osteoid protein matrix in more detail
- Mainly type 1 collagen
- Gives both flexibility and tensile strength
Describe the bone minerals in more detail
- Has a hydroxy apatite
- Calcium and phosphate
- Rigid, brittle: Gives a higher compressive strength
Describe the cells part of the bone composition
Consists of:
- Osteoblasts
- Osteocytes
- Osteoclasts
- Bone marrow cells such as
- Mesenchymal (stromal) stem cells
- Haematopoietic stem cells
How can the bone be seen as a metabolic organ?
Bone turnover serves homeostasis of Serum, Calcium, Phosphates in conjugation with:
- Parathyroid hormone (PTH)
- Vitamin D (1,25 dihydroxy D3)
- FGF-23
What is the daily calcium turnover?
List the Daily intake and Extracellulae plasma conc
- 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)
- And the other half is protein bound (mainly albumin)
Name some hormones that have skeletal effects
- Oestrogen
- Androgens
- Cortisol
- Parathyroid hormone (PTH)
- Vitamin D (calcitriol)
- Calcitonin
What hormone is secreted from the skeleton?
FGF-23 (Fibroblast growth factor 23)
Where are Parathyroid glands synthesised from?
- Parathyroid hormone (PTH) synthesised by parathyroid chief cells
- Function is to increase Serum [Ca]
- Secreted as 84 AA polypeptide
- Short half life in circulation (<5 min)
What is the function of the parathyroid hormone?
To increase Serum [Ca]
How is the Parathyroid hormone related to Calcium?
- Major hormone in calcium homeostasis
- Plasma Ca is maintained 2.2 - 2.6 mM (total Ca; ionised Ca2+ is approximately half)
- Free (ionised) Ca2+ sensed by GPCR on chief cells
- Ca binding suppresses PTH release
Name one type of Vitamin D
Calcitriol (The most active form)
Where is it synthesised?
Synthesised in the skin in response to exposure to UV (Sunshine vitamin)
How is Calcitriol activated?
Activated by 2 metabolic steps:
- 25 hydroxyl action in liver to form 25 OH D3, major circulating metabolite
- 1â hydroxylation of 25 OH D3 in kidney produces 1,25 (OH)2 D3 or calcitriol, the active hormone
- Needed for Ca absorption of the gut
Where are the Parathyroid hormones regulated?
- Regulated at the chief cells of the PT gland
- Secretion increases as plasma [Ca2+] decreases
What activity does PTH carry out?
- Promotes release of Ca from bone
- Increases renal Ca reabsorption
- Increases renal phosphate excretion
- Upregulates 1α hydroxylase activity
Where is Calcitriol regulated?
- Regulated by the control of 1ã hydroxyl in the kidney
- Increased by: PTH, Low phosphate
What are the actions of Calcitriol?
- 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
Describe the calcium homeostasis
- 99% of body calcium is in the bones
- Remaining 1% is mainly intracellular
- Hormonal control of the tiny (0.1%)
- Extracellular fraction is what maintains Ca balance
What are the actions of PTH on the bone?
- PTH receptors on osteoblasts and osteocytes
- Activates osteoclasts via RANKL
- Promotes bone remodelling
What are the effects dependent on?
Depends on concentration dynamics
- Intermittent low doses are anabolic (bone formation)
- Persistent high concentration are catabolic (excess resorption over formation – bone loss)
What are osteocytes also known as?
- as Endocrine cells
- Lacunocanalicular network permits communication between osteocytes and from osteocytes to surface cells and systemic circulation
