Lecture 7: Bone Physiology Flashcards
Describe the calcium distribution in bone:
- 99% of calcium in bone is tied up in bone mineralization
- 1% is able to be rapidly accessed for release extracellularly
Describe the concentration of calcium in the blood and ECF?
- Plasma Ca2+ concentration ~ 2.4 mM half bound to proteins
- Free concentration is ~1.2 mM (~10-3 M)
Describe the concentration of intracellular calcium?
- Ca2+ concentration inside cells is ~10-7 M, MUCH less than the ECF - huge conc. gradient
- Cells have intracellular calcium stores in the mitochondria and the endoplasmic reticulum
What happens if calcium levels drop too low?
Nerves and muscles can become hyperexcitable
What happens if calcium levels increase?
Can develop cardiac arrythmias
How can we gain calcium in the body?
Through our diet - absorption from gut
How do we lose calcium from the body?
Kidneys - reabsoprtion
Where is calcium mainly contained?
99% contained in bone - resorption
Describe the structure of a bone:
Epiphysis
Epiphyseal growth plate (in children)
Shaft with medullary cavity
What are the 2 types of bone?
Cortical - Outer 80% strong
Cancellous - Inner 20% highly vascular
What are osteoblasts?
New bone formation - synthesise and secrete collagen fibres
What do osteocytes do?
Mature bone cells - exchange Ca2+ between bone exchangeable calcium and ECF
What are osteoclasts?
Bone destruction - resorption of bone to release Ca2+ and phosphate from non-exchangeable pool (99%)
What is the overall role of the parathyroid hormone?
Increase plasma Ca2+
What is the overall role of calcitriol?
Active form of vitamin D
Increases plasma Ca2+
What is the overall role of calcitonin?
Decreases plasma Ca2+
What is the parathyroid hormone?
- Peptide hormone
- Secreted by chief cells of parathyroid gland as preprohormone, cleaved in the liver and kidney
- Chief cells have Ca2+ receptors - stimulated by decreased Ca2+
What occurs in chief cells when Ca2+ levels are high?
- Gq and Gi are activated
- Gq: PLC is activated leading to Ca2+ release from ER, and PKC activation: Inhibiting PTH secretion
- Gi: Adenylyl cyclase is inhibited, decreasing cAMP, decreasing active PKA: Inhibiting PTH secretion
What occurs in chief cells when Ca2+ levels are low?
- Gq and Gi are inactivated
- Gq: Decrease intracellular Ca2+ and PKC activation: Allowing PTH secretion
- Gi: Acetyl choline will be active, increasing cAMP, increasing active PKA: Allowing PTH secretion
What occurs if Ca2+ is high for a long period of time?
Transcription of the gene for PTH will decrease, decreasing production of PTH
What occurs if Ca2+ is low for a long period of time?
Transcription of the gene for PTH will increase, increasing production of PTH
Describe the actions of PTH:
- Increase bone Ca2+ resorption
- Increase Ca2+ kidney reabsorption
- Increase conversion of vitamin D to calcitriol
- Increase plasma Ca2+
What is calcitriol?
- Active form of vitamin D
- Hormone as it is synthesised
- Steroid hormone
How is calcitriol made?
- Eat or make vitamin D from sunlight
- Liver and kidneys synthesise calcitriol from vitamin D
Describe the actions of calcitriol:
- Increase bone resorption
- Increase intestinal absorption of calcium
- Increase kidney calcium reabsorption
How do PTH and calcitriol increase bone resorption?
- Stimulate osteoblasts to secrete factors which cause osteoclast proliferation
- Osteoclasts resorb bone, releasing calcium to the blood
What is calcitonin?
- Peptide hormone
- Made in C cells of thyroid gland
- Released when Ca2+ levels are high - only under pathological conditions
Describe the action of calcitonin:
- Inhibits osteoclasts to reduce bone resorption
- Increase urinary Ca2+ excretion to decrease plasma Ca2+
Describe bone loss with age and sex:
- As we age we lose bone mass
- Sex hormones inhibit bone resorption and stimulate bone formation
- Following menopause estradiol drops - reduction in bone density
What is osteoporosis?
Abnormal loss of bony tissue resulting in fragile bone
What is rickets and osteomalacia?
Deficiency of vitamin D/calcitriol - bones become soft
* Rickets in children - bowing of legs and increase fracture risk
* Osteomalacia in adults - increase risk of fractures
