Lecture 10 - Calcium Balance Flashcards
why is calcium critical for normal physiology? (6)
- Intracellular signaling
- Hormone secretion
- Blood clotting (calcium is a cofactor here)
- Neural excitability
- Muscle contraction
- Building & maintaining bone
what are three locations of calcium?
1) extracellular matrix
2) extracellular fluid
3) intracellular Ca 2+
what is the calcium travel pathway in our body?
ingest, displace, secrete pathways
ingest calcium:
dietary intake –> small intestine –> ECF (0.1% concentration of Ca2+) –> bones (99% of calcium is stores in bones)
however if we need to displace some calcium from our bones then:
bones –> ECF –> cells with free Ca2+ (0.9% of calcium is stored in cells)
if we want to secrete calcium:
cells –> ECF –> Kidneys –> urine
explain the anatomy of bones a bit
- what is in bones
- what is constantly happening to it in the body
- how is calcium stores in the bone
- living tissue that has nerves and blood vessels running through
- it is constantly being formed and reabsorbed in the body
- calcium in bones is maining in the form of crystals (hydroxyapatite (calcium and phosphate))
- a small fraction is ionized and exchangeable
what are the three cells that make up bone?
- Osteoblasts: Bone forming cells (b for building)
- Osteoclasts: Break down bone - much bigger than blasts - usually multinucleated- made by a fusion of cells
- Osteocytes: Maintain bone. (These are previously
osteoblasts that are completely surrounded by bone matrix that they’ve been building –> Therefore just maintain bone in its immediate vicinity.
what is making bone scientifically mean
Making bone = creating calcium phosphate complexes
(calcium crystallization)
what is the calcium turnover in infants vs adults
100% infants
18% adults
constantly remodelling bone
how do osteoclasts actually resorb bones?
- they attach to the bone matrix like a suction cup
- they secrete HCl which is of very low pH that essentially eats away at the bone underneath
- also releases proteases which are enzymes that also act under low pH to eat away the bone
- acid and enzymes dissolve the bone matrix and the calcium thats released goes to the ionized calcium pool which can then enter the blood stream
what is the chemical reaction that occurs in osteoclasts to aid their function
CO2 + H2O –> (carbonic anhydrase CA enzyme) –> H+ + HCO3-
- HCO3- and Cl- from osteoclast enter the blood stream to make HCl and lower the pH of the environment so that the bone can be resorbed
describe the timeline of the bone dynamics/remodelling cycle
- in normal bone remodelling, bone is very dynamic and is constantly being built and resorbed in a cycle (every abt 100 days)
- osteoclasts eat the cell within 3 weeks
- osetoblats repair the bone in abt 3 months
why does the bone remodelling cycle occur?
- repair
- microfracture repair
- address changed in calcium
- address needs in our body
- repairing the old tissue with new
- when new bone is being made for example when its fractured, its not perfect. there r bumps and imperfect dips. the osteoblasts and clasts come in to edit the bone to the correct morphology
how do osteoblasts promote inactive precursor osteoclasts to turn into their active version
how do osteoblasts inhibit the formation of active osteoclasts as well
- osteoclast precursors have a membrane receptor called RANK (receptor activator of nuclear factor kappa B)
- osteoblasts have a ligand attached to its membrane called RANKL (RANK ligand)
- when the RANK and RANKL bind, it promotes differentiation and fusion of the osteoclast precursors to become their large multinucleated active osteoclast
- osteoblasts inhibit the formation of active osteoclasts by secreteing Osteoprotegerin (OPG) which binds to its own RANKL (ligand), thus blocking the RANKL/RANK interaction
thus osteoblasts and clasts work together to promote osteoclast formation
how is denosumab drug used to prevent osteoporosis
osteoporosis = more bone resorption than building, thus. more active osteoclasts than blasts
- denosumab is a monoclonal antibody drug that mimics the effect of OPG by binding to RANKL and thus inhibiting the ability for RANK/RANKL to interact and form more active osteoclasts
Which three hormones control plasma Ca2+
levels? and what sites do they act on
- Parathyroid hormone (PTH)
- Calcitriol (aka 1,25-dihydroxycholecalciferol)
- Calcitonin
Act on three target sites:
– Bones
– Kidneys
– Digestive tract
these are the areas that was described in card 3
Parathyroid hormone (PTH):
- where is it released
- what is its stimulus
- what is its function
- how fast and sensitive is the hormone
Released from the parathyroid glands (chief cells)
Stimulus: Low plasma Ca2+
Function: Increases plasma
Ca2+ concentration
sensitivity: very sensitive. as soon as free calcium falls under its normal range, PTH concentration shoots up to fix this mishap
- the glands are essential for life because calcium is essential for life
