Ca/P Metabolism

Question 1

What controls bone remodelling?

Answer 1

A tightly regulated, constant process
Osteoblasts form bone vs. osteoclasts resorb bone
Affected by hormones, vitamins, stress, inflammation, growth factors and cytokines

Question 2

What effect do glucocorticoids have on bone remodelling?

Answer 2

Inhibit osteoblasts

Question 3

What disorders and drugs can cause bone resorption and loss?

Answer 3

Decreased sex hormones (menopause, hypogonadism), drugs (GCs), diseases (hyperparathyroidism, Cushing’s) or genetic

Question 4

What is osteoporosis?

Answer 4

Thinning of the bone tissue and loss of bone density over time

Question 5

What are the bone mineral density categories for osteopenia and osteoporosis?

Answer 5

Osteopenia: -1 to -2.5
Osteoporosis:

Question 6

How does Ca exist in the body?

Answer 6

99% as a reservoir in bone

1% dissolved in blood and ECF

Question 7

Why do Ca levels need to be tightly maintained?

Answer 7

Needed for key cellular processes eg. contraction and nerve conduction, so pumps and transporters are ++ important in maintaining both intracellular and extracellular levels

Question 8

What are the consequences of hypercalaemia?

Answer 8

Fractures, calculi formation, proximal myopathy, pancreatitis, mental changes (depressed nervous activity)

Question 9

What are the consequences of hypocalaemia?

Answer 9

Paraesthesia, cramps, tetany, agitations, seizures (excited nervous activity)

Question 10

What are the main regulators and the main organs involved in Ca homeostasis?

Answer 10

PTH, calcitriol (active vit D)

Organs: intestine, kidney, bone

Question 11

What is parathyroid hormone?

Answer 11

Most important endocrine Ca/P regulator. Made by the parathyroid gland based on serum Ca levels

Question 12

How does Ca affect PTH production?

Answer 12

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.

Question 13

Where is calcitonin produced and what does it do?

Answer 13

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)

Question 14

What is vitamin D?

Answer 14

D2: ergocalciferol
D3: cholecalciferol
Both of these are biologically inactive

Question 15

How is vitamin D3 produced?

Answer 15

Cholesterol - cholecalciferol by UV in the skin
Cholecalciferol (also from diet) - calcidiol in liver
Calcidiol - calcitriol in kidney (by 1-alpha-hydroxylase)

Question 16

How is vitamin D/calcitriol transported in blood and how does it act?

Answer 16

Carried by transcalciferin and acts by binding to intracellular vitamin D receptors

Question 17

What are the 6 functions of calcitriol?

Answer 17

Regulates bone remodelling
Increases gut Ca/P absorption
Increases muscle strength and growth
Increases immune function
Reduces inflammation
Increases differentiation of epithelial cells

Question 18

Of all these functions, which is most important for calcitriol and how does it occur?

Answer 18

Increase Ca uptake in the SI

Gene synthesis increases expression of proteins that promote transcellular transport of Ca

Question 19

What channels does calcitriol use to increase SI Ca uptake?

Answer 19

NCX1: 3Na/Ca channel to ISF (Na in)
PMCA1b: Ca to ISF

Question 20

How does calcitriol inhibit PTH?

Answer 20

Inhibits transcription of the PTH gene

Question 21

What is the long-term effect of calcitriol on bone resorption?

Answer 21

Stimlates osteoblasts to release factors that stimulate osteoclast differentiation

Question 22

What are the consequences of severe vitamin D deficiency?

Answer 22

Body can’t compensate for low Ca, secondary hyperparathyroidism
Phosphorus lost in urine due to PTH so bone mineralisation defects

Question 23

Where is phosphorous found and what do we get it from?

Answer 23

85% in bone, all cells contain phosphate anions

Found in most unprocessed foods and food additives, deficiencies rare with normal diet

Question 24

Which part of the nephron absorbs phosphate?

Answer 24

Proximal Na/P cotransporters allow absorption with low dietary intake

Question 25

What increases renal phosphate absorption?

Answer 25

PTH

FGF-23

Question 26

What is FGF-23 and what does it do?

Answer 26

Fibroblast growth factor 23
Decreases expression of renal phosphate transporters and increases phosphate excretion, but decreases calcitriol synthesis (opposite to PTH)

Question 27

What is the clinical significance of FGF23?

Answer 27

Found in patients with chronic kidney disease and causes secondary hyperparathyroidism