bone - hormonal control Flashcards
Which dietary requirements are needed for bone growth
Calcium and proteins
which hormones play a role in growth
- insulin - provides glucose energy for growth
- GF and IGF required for protein and cell division
- thyroid hormones - permissive role (play direct role in nervous system developmet
- sex steroids - determines final bone length
Explain bone composition
Calcium phosphate crystals precipitate and attach to a collagen fibre lattice
Two types of bone
Compact/cortical
Trabecular/spongy
What is the important extra role that central bone marrow plays
It is haematopoietic
Osteoblasts are modified what
Fibroblasts
Function of osteoblasts
Bone forming cells - produce enzymes and osteoid to which hydroxyapatite binds to
What extra proteins help osteoblasts in deposition
Osteocalcin
Osteonectin
In what part of the long bone does linear growth occur
The epiphyseal plate
Where are chondrocytes located
Near the epiphyses in children
Function of chondrocytes
Produce collagen - the collagen layer thickens and old chondrocytes disintegrate leaving spaces for osteoblasts to deposit bone
What are osteocytes?
The less active form of osteoblasts
Explain the structure of osteoclasts
Large, mobile, multinucleate cells derived from haematopoietic stem cells
Action of osteoclasts
Secretes acid and protease enzymes to dissolve calcified matrix and collagen support
–> cause calcium to enter the blood
Which organs are involved in the hormonal control of the exchange of calcium
Bone
Kidneys
Intestine
Which hormones are involved in calcium metabolism
Parathyroid hormone
Vitamin d3
Calcitonin
Functions of calcium
- important intercellular signal
- structural functions (physical strength to bone matrix and helps hold cells together at tight junctions)
- cofactor for blood coagulation
- required for normal excitability of neurons and muscles
Where are the three pools of calcium storage
Bone matrix - major -99%
Extracellular fluid - as ionized calcium - 0.1%
Intracellular fluid - as free calcium - 0.9%
Roles of intracellular calcium
Signal in second messenger pathways
Role in muscle contraction
Roles of extracellular calcium
- cement for tight junctions
- role in myocardial and smooth muscle relaxation
- neurotransmitter
- excitability of neurons
- cofactor in coagulation cascade
What is the concentration of calcium in the ECF
2.5mM
What is the intracellular concentration of calcium
0.001mM
Which pool of calcium is free to move to other locations
The calcium in the ECF
How much of our dietary calcium is absorbed
1/3
Most of our calcium is lost how
In the urine and some in the faeces
There are active transporters in the kidney that reabsorb the majority
What are the kidney transporters that actively reabsorb calcium
ECaC
Na-Ca antiport
Ca-ATPase
When is parathyroid hormone released
In response to a decrease in calcium concentration - detected by a Ca sensing receptor in the parathyroid gland
General function of parathyroid hormone
- Increases plasma calcium
- decreases plasma phsophate
What is the action of parathyroid hormone on the kidneys
Increases calcium reabsorption and decreases phosphate reabsorption
How does parathyroid hormone do its function on bones
Drives the actions of OPG and RANKL on osteoblasts to act on osteoclasts to:
- increases calcium and phosphate release from the bone into plasma
- favours bone resorption by osteoclasts
(increases activity of both osteoclasts and osteoblasts)
What is the action of parathyroid hormone on the intestines
Indirectly increases calcium and phosphate reabsorption by vitamin D activation
Transport of parathyroid hormone in the blood
Dissolved in plasma
Explain the biosynthesis of parathyroid hormone
Continuous production with little stored
Absence of parathyroid hormone causes…
Hypocalcemic tetany
Onset of action of parathyroid hormone
- 2-3 hours for bone
- 1-2 days for intestinal absorption
- within minutes for kidneys
What releases calcitonin
C cells of the thyroid gland
When is calcitonin released
In response to high plasma concentrations of calcium (only in extreme hypercalcemia)
How is calcitonin transported in the blood
Dissolved in plasma
General function of calcitonin
Decreases the activity of osteoclasts –> Decreased calcium and phosphate by reducing calcium release from bone, decreasing calcium reabsorption and increasing renal calcium excretion
Target tissues for calcitonin
Bone and kidney
What is the interaction of parathyroid hormone and vitamin d
PTH plays a role in turning on the kidney enzymes to get the second hydroxylation of vitamin D to make it active
Where do the hydroxylations of vitamin D occur
1st - liver
2nd - kidney
What is the action of vitamin D
Promotes intestinal absorption of calcium and phosphate
How is vitamin d transported in the blood
Bound to plasma proteins (steroid hormone)
What other hormone other than parathyroid hormone plays a role in vitamin D
Prolactin - stimulates synthesis
What is the action of vitamin d at a molecular level
Stimulates the production of calbindin (a Ca binding protein) and CaSR in the parathyroid gland
What is the other name for vitamin d
Calcitriol
Where is phosphate predominantly found in the body
Bone
ECF
intracellular
Action of vitamin d on phosphate
- Enhances intestinal phosphate absorption in the intestine
- weakly promotes phosphate reabsorption in the kidney
What is the action of parathyroid hormone on phosphate
- promotes phosphate excretion and reduced phosphate reabsorption in the kidney
- promotes bone phosphate release from the bone
What causes PTH hyposecretion
Autoimmune attack of the glands (rare)
What happens as a result of a deficiency in vitamin d?
PTH maintains calcium levels at the expense of bone causing bone demineralisation –> rickets or osteomalacia
What causes osteoporosis
Long term imbalance of calcium metabolism of bone resorption>bone formation in people of 50 years, predominately in postmenopausal women
What are the high risk factors for osteoporosis
Inactivity Malnutrition Alcoholism Smoking Postmenopausal Old age Endocrine disorders such as Cushing's
how do glucocorticoids affectbone
increases osteoclast activity
decreases osteoblast activity
how does oestrogen affect bone
- decreases osteoclast proliferation, differentiation and activation - promoting osteoclast apoptosis
- increases the life span of osteoblasts and osteocytes
what is the definition of osteoporosis
a reduction in bone mass more than 2.5 standa5 standard rd deviations below the normal for healthy 30 year old women
what is the definition of osteopaenia
a reduction in bone mass 1-2.5 standard deviations below the normal for healthy 30 year old women
which part of the bone mass is lost in osteoporosis
both cells and matrix
how does osteoporosis cause increased risk of fracture
loss of trabeculae and thinning reduce the cross-sectional area so that loads on bone are relatively greater
