Biochem: Calcium homeostasis and bone Flashcards
Name as many physiological functions of calcium
Bone mineralisation Tooth formation Muscle contraction Enzyme co-factor First extracellular messenger Second intracellular messenher Secretion and exocytosis Stabilistion of membrane potentials Regulation of cellular division, proliferation and apoptosis
How much of the 1.2kg of Ca2+ is stored in the skeleton?
What is the mineral component?
99%
Hydroxyapatite
1% intracellular
0.1% extracellular
Where is the calcium intracellular
Sequested in intracellular organelles (endoplasmic reticulum, mitochondria, skeletal muscle sarcoplasmic reticulum)
What id the intracellular concentration of calcium
Serum concentration
100nmol/l
Serum: 2.5mmol/l
How does serum calcium circulate?
Effect of albumin levels
Effect of acidosis
45% free ionised form (free calcium)
55% bound (45% to albumin) - changes in albumin changes rain free to bound calcium, in acidosis H+ competes for albumin binding sites
How efficient is the absorption of Ca from the diet.
Where does it mostly occur?
Poor only 20-30% absorption
From the small intestine
Depends on Vit D availability
How does the Calcium balance change throughout a woman lifetime
Child positive
Adult neutral
Post menopausal negative
What are the 3 main hormones that control calcium levels
Parathyroid hormone (increases levels)
Vitamin D/Calcitriol (increase levels)
Calcitonin (decrease levels)
Where is parathyroid hormone produced. Which receptors does it act on?
Chief cells in parathyroid
G protein coupled receptor (PTHR1)
Where does PTH act? What changes does it illicit?
Bone: Activate osteoclasts resorb bone - release Ca and phos
Kindey: Increased phosphate excretion
Kindey: Decreases Calcium excretion
Kidney: Activated Vitamin D
What causes primary hyperparathyroidism?
What happens to levels of Ca/phos/vit d/PTH
Excess of PTH from parathyroid (often benign tumour) High Ca Low phos High Vit D High PTH
What causes secondary hyperparathyroidism?
What happens to levels of Ca/phos/vit d/PTH
Defect in kidneys (CKD), unable to respond to PTH, renal reabsorption Ca not promoted and Vit D not reactivated.
Lead to bone demineralisation (osteomalacia)
What causes tertiary hyperparathyroidism?
Complication of secondary PTH continously excreted leading to parathyroid hyperplasia and appears similar to primary hyperparathyroidism.
Seen in end stage renal failure
Which hormone is released by malignant cells leading to hypercalcaemia
Parathyroid hormone related peptide (PTHrP) (no effect on active vitamin D)
How much vitamin D is from dietary intake vs synthesised in the skin?
10-20% diet
80-90% skin
What is the role of vitamin D
Normal bone remodelling
Increases levels of Ca2+ and phosphate by increasing intestinal absorption
What is considered the active metabolite
Calcitriol
Describe the synthesis of vitamin d in humans
7-dehydrocholesterol in kertinocytes is actived into vitamin D3 (cholecalciferol) mediated by ultraviolet light. It is then activated by i) hydroxylated in the liver ii) hydroxylated in the PCT of kidney to calcitriol.
Where can inactive metabolites of vitamin D be stored?
Body fat, released in winter