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
What is the daily calcium intake?
→ 1000-1200
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
Where are the parathyroid glands located?
→ behind the thyroid
What is PTH secreted as?
→ 84 AA polypeptide
What is the role of PTH?
→ Defend against hypocalcaemia
What is the concentration of plasma Ca2+?
→ 2.2-2.6 mM
Where is free Calcium sensed?
→ by GPCR on chief cells
What is the stimulus for PTH release?
→ Low calcium
Where is calcitriol synthesized and in response to what?
→ in the skin
→ in response to UV
What is calcitriol?
→ Vitamin D
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
Where are PTH receptors found?
→ osteoblasts
How does PTH promote bone remodelling?
→ Activates osteoclasts via RANKL
→ promotes bone remodelling
What does intermittent low dosage of PTH lead to?
→ favoring formation over reabsorption
What does a persistent high concentration of PTH lead to?
→ excess resorption over formation
Where is calcitonin secreted from?
→ C cells of the thyroid
What stimulates calcitonin secretion?
→ high Ca2+
What is the effect of calcitonin?
→ to lower Ca2+ by inhibiting osteoclasts
What does calcitonin do in the kidney?
→ Decreases calcium and phosphate reabsorption
What does calcitonin do in the bone?
→ Decreases bone resorption by inhibiting osteoclast activity
What is used to treat Paget’s?
→ Synthetic calcitonin
What is the lacunar-canalicular system for?
→ Communication between osteocytes
→ communication from osteocytes to surface cells and systemic circulation
What is hypophosphatemic rickets?
→ Rare phosphate wasting conditions leading to bone mineralization defects
What is the role of FGF-23?
→ to decrease phosphate
What is FGF-23 expressed and secreted by?
→ osteocytes
What is FGF-23 stimulated by?
→ Calcitriol and Pi
What does FGF-23 do?
→ inhibits calcitriol synthesis
→ Increases renal Pi excretion (by reducing Na-Pi reabsorption from the proximal tubule)
What are the clinical features of hypercalcaemia?
→ Depression, fatigue, anorexia, nausea vomiting
→ Abdominal pain
→ Renal calcification
→ Bone pain
What are causes of hypercalcaemia in ambulatory patients?
→ Primary hyperparathyroidism
What are causes of hypercalcaemia in hospitalised patients?
→ Malignancy
What is primary hyperparathyroidism due to?
→ Benign adenoma in one or more PT glands
How is primary hyperparathyroidism resolved?
→ removal of the affected gland
What is hypercalcaemia of malignancy?
→ Tumor can secrete PTH related peptide
→ Binds and activates PTH receptor
