7.6 Flashcards
EC Ca++ conc
Free= 1-1.3 mM Total= 2.2-2.6 mM
IC Ca++ conc
100 nM
How Ca++ travels in the blood?
Ionized form= 45%
Bound to proteins= 45%
Complex with anions= 10%
What happens when there are more Albumin/ Phosphate in the blood?
Less Ca++ is free
What happens when pH goes down?
H+ binds to Albumin -> increasing free Ca
What synthesize PTH
Chief cells in the parathyroid glands
Describe PTH secretion
preproPTH -> proPTH -> PTH (84AA)
What evokes the secretion of PTH?
Ca-Sensing-Receptors (CaSR) present on chief cells
Ca-Sensing-Receptors (CaSR)
Way of action
Gq detect high Ca -> IC Ca signal -> inhibition of vesicle fusion
***also has Gi activity
What is the result of Ca-Sensing-Receptors (CaSR) mutation?
Familial Hypercalemic Hypocalciuria
Decreased affinity of Ca-Sensing-Receptors to Ca
What will higher phosphate cause
Less free Ca
So more PTH secretion
How vit.D affect PTH
Decrease secretion
By increasing CaSR expression
By Direct PTH gene inhibition
Long term vit D def. will cause
Rickets= deformation of long bones bcs there is less Ca and Pi absorption from the GI
What secretes clacitonin
Parafollicular C cells of thyroid
Action of Calcitonin
Decrease Ca levels by inhibiting Osteoclasts so increasing bone formation
What increase secretion of Calcitonin
High Ca
More than 1.3 mM
Which disease can exogenous Calcitonin treat
Paget’s Disease
Disorder of overactive OsteoClasts
2 types of bones
Compact- 80% of the long bones
Spongy- 20% of all bones
Location of spongy bones
Vertebral
Neck of long bones
Bone cavity
Special thing of spongy bones
High surface area so high turnover of formation and resorption of bone
Osteoblast origin
Fibroblasts
Secretory proteins of osteoblasts
Collagen type 1
Osteocalcin
Osteonectin
Alkaline phosphate
Osteolacin job
Binds Ca and hydroxyapetite
Osteonectin job
Same as osteolacin
Alkaline phosphate job
Role in the formation of Hydroxyapetits
Regulatory proteins of Osteoblasts
RANK Ligand
OPG
Catabolic enzymes of Osteoblasts
Collagenase
Gelatinase
Phases of bone formation
Osteoid formation
Mineralization
How much time does osteoid formation takes
10-14 days
What happens during osteoid formation
Creation of protein matrix of bones
What does osteoid gives us
Site for nucleation and precipitation of hydroxyapetite
Duration of mineralization
Couple of weeks
What happens during mineralization
Pi groups are released for the formation of hydroxyapatite
Where do osteoClast comes from
Haematopoietic cell line
What do osteoclast activation requires
M-CSF
RANK Ligand
IL-6 (cytokine)
What regulates bone resorption
- PTH, Calcitriol
- Calcitonin
- Glucocorticoids
- Estrogens
- Tumors
Job of PTH and calcitriol in bone resorption
Act on osteoblasts ->RANK -> osteoclast activation
Job of OPG
Acts on osteoclast and decrease their activity
It blocks the RANK R
What determines osteoclast activity?
RANK/OPG ratio
High- increase osteoclast activity
Low- decreases
Calcitonin acts on osteoclasts?
Inhibition
Glucocorticoids action on bones?
Acts on osteoblasts
Increase RANK/OPG ratio
Estrogens action on bones?
Decrease RANK/OPG ratio
