The Skeleton And Metabolism Flashcards
What are the 6 hormones that have skeletal effects?
→ Estrogens
→ Androgens
→ Cortisol
→ PTH
→ Vitamin D
→ Calcitonin
What is a hormone secreted from the skeleton?
→ FGF-23
How is the calcium distributed in the body?
→ most is intracellular
→ the remaining 0.1% is in the plasma
→ half of the 0.1% is free calcium ions
→ the other half is protein bound
What is the only way to increase Ca2+?
→ Increase calcium absorption through the gut
What does bone turnover contribute to?
→ Homeostasis of serum calcium
→ phosphate
→ and PTH, vit D, calcitonin, FGF-23
What is PTH synthesized from?
→ Parathyroid chief cells
What is PTH secreted as?
→ 84 AA polypeptide
Where is free Calcium sensed?
→ by GPCR on chief cells
What are the endocrine hormones involved in the regulation of bone?
→PTH →TH →GH →IGF →Oestrogen
How is TH involved in bone regulation?
→controls rate at which chondrocytes differentiate into growth plate
→In adults, excess results in activity of osteoclasts
How is GH involved in bone regulation?
→regulates osteoclasts differentiation
How is IGF involved in bone regulation?
chondrocyte differentiation and linear growth, also osteoblast differentiation
Describe calcitriol synthesis
→ 7dehydrocholesterol is in the skin
→ UV light turns it into cholecalcitriol (CCF)
→ 25 hydroxylase adds an OH group in the liver
→ it becomes 25 hydroxyCCG
→ 1a hydroxylase stimulated by PTH in the kidney adds another OH group
→ 1,25 dihydroxyCCF is formed or calcitriol
Where is the regulation site for calcitriol?
→ control of 1a hydroxylase in the kidney
What is calcitriol increased by?
→ PTH - upregulates 1a hydroxylase
→ Low phosphate
What is the function of calcitriol?
→ Increase absorption of Ca and Pi from the GI tract
→ inhibits PTH
What are the 4 actions of PTH?
→ Promotes release of Ca from bone
→ Increases Ca reabsorption
→ increases renal Pi excretion
→ upregulates 1a hydroxylase activity
Describe how PTH works
→ hypocalcaemia stimulates PTH
→ PTH binds to osteoblasts and stimulates RANK ligand
→ RANK ligand binds to RANK receptors on osteoclasts
→ Bone breaks down and Ca2+ and phosphate are released into the blood
→
What are the effects of PTH release on the kidney?
→increased reabsorption of Ca
→increased 1,25-dihydroxy vit D formation
→reduced phosphate reabsorption
What are the effects of PTH on the gut?
increased calcium absorption via D3
What do high Ca and D3 do?
D3 inhibit PTH production
What is phosphate important for?
→for nerve function
What does high serum phosphate do?
→stimulates FGF23 synthesis in osteocytes
→ to decrease phosphate by increase phosphate excretion in the kidney.
What is FG23?
→Fibroblast Growth Factor-23
→
What are the effects of FG23 on the kidneys and parathyroid?
→Decreases phosphate reabsorption in kidneys
→Inhibits PTH production
Decrease release of phosphate via bone resorption
→Inhibits active vitamin D3 production
Decrease phosphate absorption in gut
What is Rickets?
→Defective mineralisation of normally synthesized bone matrix
→Osteoid are laid down normally but can’t be mineralised into mature bone and remains organic portion of bone
What are the two types of Rickets?
→Deficiency of vitamin D3 (causing hypocalcemia)
→Deficiency of Phosphate
What is oncogenic oesteomalacia?
→ mesenchymal tumours producing excess FGF23
Causing excess phosphate excretion
What are the outcomes of oesteomalacia?
→bonepain/tenderness
fracture
→proximal weakness- upper legs and arms are weak
→bone deformity
What are x-ray presentations of oesteomalacia?
→Bowing of long bones
→Widening of growth plates
→Looser’s Zones
What is looser’s zone?
→fracture through one side of bone at 90 degrees to the cortical bone
→ band of bone material of decreased density
What are the effects of excess PTH?
→Hypercalcemia
→Hypophosphatemia
What are primary causes of hyperparathyroidism?
→parathyroid adenoma (85-90%)
→chief cell hyperplasia
What are the secondary causes of hyperparathyroidism?
→chronic renal deficiency
→vit D deficiency
What is Osteitis fibrosa cystica?
→results from hyperparathyroidism
→bone pain
Mnemonic for hyperparathyroidism?
Stones (Kidney stones)
Bones (Pain from osteitis fibrosa cystica and excess bone resorption)
Abdominal Moans (acute pancreatitis)
Psychic Groans (psychosis & depression)
What are the clinical features of hypercalcaemia?
→ Depression, fatigue, anorexia, nausea vomiting
→ Abdominal pain
→ Renal calcification
→ Bone pain
How is primary hyperparathyroidism resolved?
→ removal of the affected gland
