Ca/P Metabolism Flashcards
What controls bone remodelling?
A tightly regulated, constant process
Osteoblasts form bone vs. osteoclasts resorb bone
Affected by hormones, vitamins, stress, inflammation, growth factors and cytokines
What effect do glucocorticoids have on bone remodelling?
Inhibit osteoblasts
What disorders and drugs can cause bone resorption and loss?
Decreased sex hormones (menopause, hypogonadism), drugs (GCs), diseases (hyperparathyroidism, Cushing’s) or genetic
What is osteoporosis?
Thinning of the bone tissue and loss of bone density over time
What are the bone mineral density categories for osteopenia and osteoporosis?
Osteopenia: -1 to -2.5
Osteoporosis:
How does Ca exist in the body?
99% as a reservoir in bone
1% dissolved in blood and ECF
Why do Ca levels need to be tightly maintained?
Needed for key cellular processes eg. contraction and nerve conduction, so pumps and transporters are ++ important in maintaining both intracellular and extracellular levels
What are the consequences of hypercalaemia?
Fractures, calculi formation, proximal myopathy, pancreatitis, mental changes (depressed nervous activity)
What are the consequences of hypocalaemia?
Paraesthesia, cramps, tetany, agitations, seizures (excited nervous activity)
What are the main regulators and the main organs involved in Ca homeostasis?
PTH, calcitriol (active vit D)
Organs: intestine, kidney, bone
What is parathyroid hormone?
Most important endocrine Ca/P regulator. Made by the parathyroid gland based on serum Ca levels
How does Ca affect PTH production?
The CaR (Ca-sensing receptor) is GPCR and causes a signalling cascade to inhibit PTH secretion when stimulated. Without this inhibition (ie low plasma Ca), PTH is secreted.
Where is calcitonin produced and what does it do?
Made in thyroid C cells (+ minor in some other tissues)
Calcitonin promotes Ca deposition and prevents bone resorption but is less important than PTH (pharmacological doses not useful for treating osteoporosis)
What is vitamin D?
D2: ergocalciferol
D3: cholecalciferol
Both of these are biologically inactive
How is vitamin D3 produced?
Cholesterol - cholecalciferol by UV in the skin
Cholecalciferol (also from diet) - calcidiol in liver
Calcidiol - calcitriol in kidney (by 1-alpha-hydroxylase)
How is vitamin D/calcitriol transported in blood and how does it act?
Carried by transcalciferin and acts by binding to intracellular vitamin D receptors
What are the 6 functions of calcitriol?
Regulates bone remodelling Increases gut Ca/P absorption Increases muscle strength and growth Increases immune function Reduces inflammation Increases differentiation of epithelial cells
Of all these functions, which is most important for calcitriol and how does it occur?
Increase Ca uptake in the SI
Gene synthesis increases expression of proteins that promote transcellular transport of Ca
What channels does calcitriol use to increase SI Ca uptake?
NCX1: 3Na/Ca channel to ISF (Na in)
PMCA1b: Ca to ISF
How does calcitriol inhibit PTH?
Inhibits transcription of the PTH gene
What is the long-term effect of calcitriol on bone resorption?
Stimlates osteoblasts to release factors that stimulate osteoclast differentiation
What are the consequences of severe vitamin D deficiency?
Body can’t compensate for low Ca, secondary hyperparathyroidism
Phosphorus lost in urine due to PTH so bone mineralisation defects
Where is phosphorous found and what do we get it from?
85% in bone, all cells contain phosphate anions
Found in most unprocessed foods and food additives, deficiencies rare with normal diet
Which part of the nephron absorbs phosphate?
Proximal Na/P cotransporters allow absorption with low dietary intake
