The skeleton and metabolism Flashcards
What hormones cause a skeletal effect?
-Oestrogen
-Androgens
-Cortisol
-PTH
-Vitamin D
Calcitonin
What hormone is secreted from the skeleton?
FGF-23
What does bone serve homeostasis of?
Bone turnover serves homeostasis of serum calcium, phosphate in conjunction with:
- PTH
- Vitamin D
- Calcitonin
- FGF-23
Where is the parathyroid gland located?
Located behind thyroid gland
What is PTH synthesised by?
Synthesised by parathyroid chief cells
What’s the life of PTH in circulation like?
Short half life in circulaiton
What is PTH secreted as?
Secreted as an 84 amino acid polypeptide
What is PTH’s major role?
Major role in defence against hypocalcaemia
What is free Ca sensed by?
Free Ca sensed by GPCR on chief cells
What happens when Ca binds with GPCR on chief cells?
Ca binding to GPCR on chief cells suppresses PTH release
What is calcitriol actually?
Calcitriol is actually a steroid hormone, not a vitamin
Where is calcitriol synthesised and in response to what/
Synthesised in skin in response to exposure to UV
What are the 2 steps which form the active hormone, calcitriol?
Activated by 2 steps:
- 25 hydroxylation in liver to form 25OH D3 the major circulatory metabolite
- 1alpha hydroxylation of 25OH D3 in kidney produces 1,25(OH)2D3, or calcitriol, the active hormone
What is the site of regulation of calcitriol?
Site of regulation is control of 1alpha hydroxylase in kidney
What is calcitriol increased by?
Increased by:
- PTH
- Low phosphate
What are the actions of calcitriol?
-To increase absorption of Ca and Pi from GI tract
-Inhibits PTH secretion and transcription
Complex effects on bone, generally in synergy with PTH
What are the actions of PTH?
- Promotes release of Ca from bone
- Increases renal Ca reabsorption
- Increases renal Pi excretion
- Upregulates 1alpha hydroxylase activity
What are the actions of PTH on bone?
- PTH receptors on osteoblasts and osteocytes
- Promotes bone formation
- Activates osteoclasts via RANK-L
What does the effect of PTH depend on?
Effect depends on concentration dynamics:
- Intermittent low doses are anabolic
- Persistent high concentration leads to excess resorption over formation-bone loss
How many amino acid long is calcitonin?
32 amino acids long peptide
What is calcitonin secreted by>
Secreted by C cells of thyroid
What is the stimulus for secretion of calcitonin?
Stimulus for secretion is high [Ca2+]
What does calcitonin do in kidneys?
Decreases calcium and phosphate reabsorption
What does calcitonin do in bone?
Decreases bone resorption by inhibiting osteoclast activity
What is synthetic calcitonin used for?
Synthetic calcitonin is used in the treatment of paget’s disease of bone and severe osteoporosis
What is FGF-23?
A hormone secreted by osteocytes
What is the central role of FGF-23?
Central role is in phosphate homeostasis
What are the actions of FGF-23?
- Increased by calcitriol and Pi
- Inhibits calcitriol synthesis
- Increases renal Pi excretion
What is hypophosphatemic rickets?
Rare phosphate wasting condition leading to bone mineralization defects
What is the normal range of calcium>
2.2-2.6mM
What are the clinical features of hypercalcemia?
- Depression, fatigue, anorexia, nausea, vomitting
- Abdominal pain
- Kidney stones
- Bone pain
What are the causes of hypercalcemia in ambulatory patients ?
Causes are primary hyperparathyroidism
What are the causes of hypercalcemia in hospitalised patients?
Causes are Malignancy
What are less common causes of hypercalcemia?
- Hyperthyroidism
- Excessive intake of vitamin D
What is primary hyperparathyroidism usually due to?
Usually due to benign adenoma in one or more PT glands
How is primary hyperparathyroidism resolved?
Resolved by surgical removal
