MSS: The Skeleton and Metabolism Flashcards
List some hormones with skeletal effects.
- oestrogen
- androgens
- cortisol
- parathyroid hormone (PTH)
- Vitamin D (calcitriol)
- calcitonin
Hormones secreted from the skeleton
FGF-23 (fibroblast growth factor 23)
Calcium Distribution
the 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
Intake and Excretion of Calcium (daily turnover)
Daily calcium intake is recommended to be at 1000-1200mg (25-30 mmol). 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
Extracellular calcium levels are kept at 2.2-2.6 mmol/L.
About half is free [Ca2+] (physiologically active), and the other half is protein-bound (mainly to albumin).
What is the role of bone as a metabolic organ?
Bone turnover serves the homeostasis of serum calcium and phosphate, in conjunction with:
- parathyroid hormone (PTH)
- Vitamin D (1,25-dihydroxy D3)
- Calcitonin
- FGF-23
Parathyroid hormone
Half-life of PTH
84 amino acid polypeptide synthesized by parathyroid chief cells
short half-life (<5 mins)
Role of PTH regarding calcium
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
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
Actions of PTH
- promotes the 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 are the actions of PTH on the bone?
PTH receptors on osteoblasts and osteoclasts, increasing bone remodelling:
- increased bone formation via osteoblasts
- increased bone reabsorption after activating osteoclasts via RANKL
How do we get the active form of vitamin D?
- we make most of the prohormone for vitamin D3 in our skin through UV exposure
- We also get some from dietary intake
- The liver converts it to 25-hydroxyvitamin D
- The kidneys converted to active form: 1,25 dihydroxy vitamin D
Thus, the site of regulation is control of 1α hydroxylase in the kidney. It is increased by:
- PTH
- low phosphate levels
How Concentration of PTH affects bone remodelling
Intermittent low doses are anabolic (bone formation)
Persistent high concentration leads to excess reabsorption over the formation, causing bone loss due to increased calcium release causing bone de-mineralisation
Vitamin D
- also known as calcitriol
- steroid hormone (not a vitamin) synthesized in the skin in response to UV exposure
1 alpha-hydroxylase
Where is it found?
What regulates it?
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 the 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 the purpose of the Lacunar-canalicular network?
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)
symptoms of osteomalacia
bone pain/tenderness
fracture
proximal weakness
bone deformity
What are the actions of FGF-23?
Decreases phosphate levels:
- expressed and secreted by osteocytes
- increased by calcitriol and phosphate
- inhibits calcitriol synthesis
- inhibits PTH secretion (because PTH increases calcitriol, which in turn increases phosphate)
- inhibits 1⍺ hydroxylase, inhibiting calcitriol synthesis (because calcitriol increases absorption of phosphate)
- increases renal phosphate excretion (by reducing Na-Pi reabsorption from the proximal tubule)
Describe primary hyperparathyroidism.
It is usually due to a benign adenoma in one or more parathyroid glands. It’s often detected on screening - many patients are asymptomatic.
Around 10% of patients present with clinical evidence of bone disease. 10-20% of patients present with kidney stones. It is resolved by the surgical removal of the affected gland(s).
Compare the histology of a normal bone and one with osteomalacia
