L6. Bone Physiology Flashcards
Calcium in the bone?
99% of calcium in bone is tied up in bone mineralisation
1% is able to be rapidly accessed for release extracellularly
Calcium in blood and ECF?
Plasma Ca2+ concentration is approximately 2.4mM (half bound to proteins and half floating around plasma of blood)
Free concentration is approximately 1.2mM
Intracellular calcium?
Ca2+ concentration in ICF is less than that of the ECF
Cells have intracellular calcium stores in the mitochondria and the endoplasmic reticulum
Body calcium balance?
- Gut is absorption
- Kidneys reabsorption
- Bones is resorption
- 99% of total body Ca2+ is contained in bone
What is special about cancellous bone?
It’s highly vascular and contains red bone marrow
Of bone structure =
- Cortical bone (outer): 80%
- Trabecular bone (inner): 20%
Osteoblasts?
Synthesise and secrete collagen fibres and promote Ca2+ phosphate deposition (new bone formation)
Osteocytes?
Exchange Ca2+ phosphate between the bone exchangeable calcium pool (1%) and extracellular fluid
Osteoclasts?
Cause resorption of bone to release Ca+ and phosphate from the non-exchangeable pool (99%)
Hormonal control of calcium?
Parathyroid hormone = increases plasma Ca2+
Calcitriol = active form of vitamin D, increases plasma Ca2+
Calcitonin = decreases plasma Ca2+, levels low or undetectable under most physiological conditions
Parathyroid hormone (PTH)?
- Peptide hormone
- Secreted by chief cells of the parathyroid glands as a preprohormone, cleaved in the liver and kidney
Chief cells have Ca2+ receptors
- Secretion stimulated by decreased plasma Ca2+
- Secretion inhibited by increased plasma Ca2+
- Removal of the parathyroid glands reduces plasma Ca2+ by 50%
When Ca2+ is high?
Calcium sensing receptor is linked to:
Gq and Gi protein coupled receptors
When levels are high, Gq and Gi will both be activated;
- Phospholipase C (PLC) is activated, leading to Ca2+ release, and PKC activation: inhibiting PTH secretion
- Adenylyl cyclase is inhibited, decreasing cAMP, decreasing activated PKA (which is needed for secretion): inhibiting PTH secretion
When Ca2+ is low?
Gq and Gi will both be inactive
- Decreased intracellular calcium concentration and PKC activation: allowing PTH secretion
- Acetylcholine will be active, increasing cAMP, increasing activated PKA, allowing PTH secretion
When Ca2+ is high over a long period of time?
Transcription of the gene for parathyroid hormone will decrease, decreasing production of PTH
When Ca2+ is low over a long period of time?
Transcription of the gene for parathyroid hormone will increase, increasing production of PTH
Calcitriol?
- Is hormonally active metabolite of vitamin D which is made in the body
- Is a hormone because it can be synthesised, but vitamin D may have been ingested
- Is a steroid hormone that acts on intracellular receptors to change gene expression
Increases plasma Ca2+ by:
- Increases Ca2+ absorption by epithelial cells in the small intestine
- Stimulates osteoclast proliferation, increasing bone resorption and release of calcium
Bone resorption?
PTH and calcitriol stimulate osteoblasts to secrete factors which cause osteoclast proliferation
Osteoclasts resorb bone, releasing calcium to the blood
Calcitonin?
- Peptide hormone
- Made in C cells of the thyroid gland
- Released when Ca2+ levels are high, may only be recruited under pathological conditions
They work to:
- Inhibit osteoclasts to reduce bone resorption
AND
- Increases urinary Ca2+ excretion to decrease plasma Ca2+
Bone loss with age?
- Estradiol and testosterone (sex steroids) inhibit bone resorption and stimulate bone formation
- Following menopause there is a dramatic reduction in estradiol levels
- Estradiol deficiency following menopause causes a rapid reduction in bone mineral density
Osteoporosis?
- Abnormal loss of bony tissue resulting in fragile porous bones, so it is a loss of minerals AND bone matrix
- About 50% of women and 25% of men are expected to have osteoporosis in their lifetime
- Increases risk of bone fractures - can lead to other medical complications
Rickets?
Vitamen D deficiency in children resulting in;
- Bowing of the legs
- Increased fracture risk
Which is due to soft bones and mineral deficiency
Osteomalacia?
Vitamen D or Ca2+ deficiency in adults resulting in;
- Increased risk of fractures
Which is due to soft bones and mineral deficiency
True or false?
Calcitriol stimulates osteoclasts, increasing bone resorption
True
Choose the CORRECT statement
A. Calcitonin is secreted when plasma calcium is within the normal homeostatic range
B. Calcitriol is a steroid hormone
C. Vitamin D deficiency causes an increase in bone density in children
D. Bone mass peaks at approximately 15
B
Women have a higher risk of developing osteoporosis as they age BECAUSE testosterone inhibits bone resorption
A. If both statements are true, and the second causes the first
B. If both statements are true, but the second does not cause the first
C. If the first is true and the second is false
D. If the first is false and the second is true
E. Both statements are false
B
The extracellular calcium concentration is much lower than the cytoplasmic calcium concentration BECAUSE calcium is stored intracellularly in the endoplasmic reticulum
A. If both statements are true, and the second causes the first
B. If both statements are true, but the second does not cause the first
C. If the first is true and the second is false
D. If the first is false and the second is true
E. Both statements are false
D
