The skeleton and metabolism Flashcards
Give the hormones with skeletal effect.
Oestrogen Androgens Cortisol Parathyroid (PTH) Vitamin D (calcitriol) Calcitonin
What Hormones are secreted from the skeleton?
FGF-23 (fibroblast growth factor 23)
Describe the Calcium Distribution.
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
Describe the Intake and Excretion of Calcium.
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
Describe the Bone as a metabolic organ.
Bone turnover serves homeostasis of serum calcium and phosphate in conjunction with:
- parathyroid hormone (PTH)
- vitamin D (1,25- dihydroxy D3)
- calcitonin
- FGF-23
What is the Parathyroid hormone?
84 amino acid polypeptide synthesized by parathyroid chief cells
What is the Half-life of PTH?
short half life (<5 mins)
What is the Role of PTH?
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
Describe the Regulation of PTH secretion.
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
State the Actions of PTH.
- 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
What is the Effect of PTH on bone remodelling?
PTH receptors on osteoblasts and osteoclasts, increasing bone remodelling:
- increased bone formation via osteoblasts
- increased bone reabsorption after activating osteoclasts via RANKL
How does the Concentration of PTH affects bone remodelling
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
What is Vitamin D (calcitriol)?
steroid hormone (not a vitamin) synthesized in skin in response to UV exposure
Describe the Activation of Vitamin D.
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)
What is 1 alpha hydroxylase?
located in the kidney
its activity is increased by:
- PTH
- low phosphate
What are the Actions of Calcitriol?
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)
What is Calcitonin?
32 amino acid peptide hormone secreted by C cells of the thyroid gland
What is the Stimulus for calcitonin secretion?
high blood calcium levels (opposite to PTH)
What is the Action of calcitonin?
Decreases extracellular calcium via:
Kidney
-decreases calcium and phosphate reabsorption
Bone: decreases Ca bone reabsorption/ release by inhibiting osteoclast activity
Give some Clinical uses of synthetic calcitonin.
treatment of Paget’s disease of bone and severe osteoporosis due to inhibition of osteoclast activity
Describe the Lacunar-Canalicular System.
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)
What is FGF-23?
hormone synthesized and secreted by osteocytes which decreases phosphate levels
-also produced by calcitriol
What are Hypophosphatemic rickets?
autosomal dominant rare phosphate wasting disease (excessive phosphate excretion) leading to osteomalacia (bone mineralisation defects)
associated with high levels of FGF-23
What are the Actions of FGF-23?
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)
