bone physiology Flashcards
bone fucntions include:
– support and protection
– movement
– a Ca2+ (and PO4
3-) store
– a bone marrow store
bone is a —- matrix which is mainly —– with some —–
-mineralised organic
- type 1 collagen fibers ( 90-95%)
which provides tensile strength with some proteoglycans ~5% which provides compressive strength
2 types of bones:
1 —- :
– also known as ‘cortical bone’
– dense, stiff structure
– low porosity (5-25%)
– most human bone is compact (~80%)
2- —- :
– also known as ‘cancellous or spongy bone’
– spongy, light structure
– high porosity (up to 70%)
the combination of these 2 types provide —– despite being —-
- compact
- trabecular
- mechanical strength
- lightweight
- in long bones —- from the shaft aka diaphysis
- trabecular bone is found at the — aka —–
- between epiphysis and the metaphysis is the —–
- Growth of the long bones occur at —- the until —– when it fuses w —-
- cortical bone
- ends aka epiphysis/metaphysis
- epiphyseal growth plate
- growth plate until 18
- fuses w metaphysis
1-durig fatal life , bones are modelled in —- and then —- aka —-
2- During childhood/adolescence, cartilage proliferates at the ——- controlled by ——–
3- once laid down the collagen is mineralised with —- during —– and its now —-
- cartlige ( type 1 colagen )
- mineralised
- ossification
- growth plate elongating the long bones
- controlled by: growth hormone and insulin-like growth hormone (IGF-1)
- hydroxipiate
- ossification
-hydroxyapatite formula: Ca10(PO4)6(OH)2
-the —- form around
Haversian canals containing
blood vessels and nerves
- each osteon is formed of —-
- between lamellae are — where —- are located
osteon
concentric rings or lamellae
– separated from the adjacent
osteon by a cement line
- lacunae
- osteocytes
3 mian types of cells bones:
1- —– :
– promote bone formation
– lay down osteoid and initiate mineralisation
2- —– :
– promote bone reabsorption
– remove mineralisation and liberate Ca2+ and PO4
3- —–:
– transfer mineral from inner regions of bone to the growth surfaces
1- osteoblast
2- osteoclast
3- osteocyte
-Osteoblasts are modified ——derived from —— stem cells
- osteoblast can lay down —- and facilitate the ——
- excess osteoblast are —- some get embedded in the lining of the new bone and become become —– -in the lacunae between the lamellae
- fibresblast
-mesenuchimal stem cells - osteoid of type 1 collagen
- ossification of the osteiod
- removed
- osteocytes
-osteocyte are derived from —- which transfers — from —- of the bone to —- surfaces
- osteocytes have —- into the bone and can sense — on the bone
- these projections passes — to —
- osteoblast
- minerals
- inner region
- growth surfaces
- cytoplasmic projections
- mechanical load
- info
- osteoblast
-Osteoclasts are derived from the ——
- attracted to and resorb —- and create —– pits
-Solubilise the mineral at —- , —- the organic matrix ( requires factors from ——- )
-Indirectly stimulated by —- that promotes —- it:
-macrophage lineage of cells
-mineralized bone and create resorption pits
- low pH , phagocytose
- osteoblasts
- PTH
- promotes bone reabsorption
- it:
– remove mineralisation and liberate Ca2+ and PO4
3-
– PTH acts on osteoblasts and their activation ultimately activates osteoclasts
bone remodelling:
From maturity, while bone growth has stopped —- doesnt
– adult skeleton remodelled every 10 years
– 1 million BMUs operating at any one time (3-4 million BMUs initiated each year)
bone turnover
bones are constantly balancing the mineralisation through activation of:
osteoblast and osteoclast which :
– enables adaptation to mechanical loading
– enables fracture healing
– prevents “bone fatigue” by continually renewing bone matrix
in response to: osteocyte signalling, PTH/vitamin D signalling and other
growth factors
Osteocyte detected mechanical strain is relayed to ——
osteoblast and also PTH signalling
-Osteoblasts stimulate —- to activate circulating monocytes
- monocytes become —- and move to region to be —-
- growth factors stimulates —– leading to lat down of new — for mineralisation
NFkB ( – increase NFκB activator RANK-L and decrease NFκB inhibitor osteoprotegrin )
- osteoclast
- reabsorbed
- osteoblast formation
- osteoid
( over the ~120 day cycle there is no net loss of bone)
bone remodelling :
- Resorption phase (2 weeks)
– bone lining cells pull away from bone surfaces to
be resorbed
– osteoclasts are attracted to bone surfaces
– pockets of bone resorbed by osteoclasts, creation
of resorption pits, osteoclast apoptosis - Reversal phase (2 weeks)
– resorbed bone surface prepared for subsequent
bone deposition, formation of cement line] - Formation phase (13 weeks)
– resorption of bone releases stored growth factors
– osteoblasts attracted to resorption sites and
deposit osteoid, which then mineralises
– osteoblasts are trapped in bone matrix and
become osteocytes or become bone lining cells
– cover bone surfaces that are not actively being
remodelled
ca+2 and physiological regulation:
- Ca2+ movement across membranes is important in triggering many physiological mechanisms
- Some examples are :
– neurotransmitter release at a synapse
– smooth muscle contraction
– heart muscle contraction
– secretory mechanisms for hormones
– secretory mechanisms for gut enzymes
-ca+2 is found in 3 forms:
- In general most ohysiolofical fucntions are mediated by —-
- acid base status affects level of —- ca+2 as:
- ionised (free) - about 45%
- bound to protein - about 45%
- bound to small anions - about 10%
(e.g. phosphate, citrate and oxalate) - most mediated by ionised form ca+2
- bound ca+2 as:
– increase [H+] displaces Ca2+ from protein increasing free [Ca2+]
– decrease [H+] promotes Ca2+ binding to protein decreasing free [Ca2+]
(CHECK SLIDE 21 22)
-the —- is a major controller of free ca+2 in the body .
-this hormone is released by — in —- at —-
- ca+2 is detected by —–
- ca +2 decreases —-
- ca+2 inhibits —-
-peptide hormone PTH
- PTH is released from chief cells in the four parathyroid glands at low plasma [Ca2+]
- Ca2+ is detected by a membrane bound G- protein receptor coupled to cAMP
– Ca2+ decreases cAMP and inhibits PTH release
( check slide 26)
-PTH regulates —— by stimulating —–
- PTH indirectly stimulates —– to promote bone reasbpriton
- this is mediated by the — of production of mixture of —-
- The reabsorption of bone minerals increases the —–
- plasma Ca+2 by stimulating bone reabsportion
-PTH indirectly stimulates osteoclasts to promote bone reabsorption
– reabsorption of mineral out of bone: i.e. breakdown - increase
- cytokines
- plasma [Ca2+] but also
plasma phosphate
– bone mineral is hydroxyapatite: Ca10(PO4)6(OH)2
PTH actions on the kidney modulate the raised —– and —–
PTH promotes the reasbprtion of —-
and inhibits —–
PTH also stimulates —–
-plasma ca+2 and phosphate from bone reasbsoption
- Ca+2 ( thick ascending limb of loop of henle )
- inhibits phosphate reabsorption ( proximal and distal tubule which promotes phosphate excretion )
- stimulates 1alpha-hydrolase enzyme which is a key step in the sythesis of active form of vitamin d
-the active form of vitamin d is:
- it undergoes —– in the liver catalysed by — and its – a rate limiting step in production of the active form
- activation is —- in the — which is catalysed by — and the —- is an important regulatory site
- —- is a steroid like structure so acts on intracellular receptors
- 1,25 dihydroxycholecalciferol (DHCC) aka calcitriol
- 25-hydroxylation
- catysled by 25-hydoxylase
- not a rate limiting step
- 1α-hydroxylation in the kidney
- catalysed by 1alpha-hydroxylase
-kidney - vitamin d
( check slide 29 pls)
ca+2 absorption occurs in the — as they are absorbed through —- and binds to —- example: they —- pump out at the —-
- duodenum
- ca+2 channels
- bidning protein as calbindin
- actively pump out at the basolateral side
true or false:
vitamin d promotes the increase in the synthesis of ca+2 channels as well as phosphate absorption in the gut
true
-in —- vitamin d promotes ca+2 and po4 -3 reabsorption
- the overall effect of vitamin d is the increase of the ——- and — in bone
- kidney tubules
- flux of ca+2 and phosphate
-Systemic skeletal disease characterised by low bone mass and
microarchitectural deterioration of bone tissue
– reduced osteoid and mineralisation
– bone fragility and susceptibility to fracture
is known as —-
osteoporosis
in osoteprosis:
- increase – population will increase the risk due to the reduced avativity/loading and the reduced —- function
- — of females will suffer a feature after the age of — . which s compared to — of males will suffer fracture after that age — .
- can be due to :
- females are more likely to suffer a hip fracture than develop —-
- ageing
- anabolic function
- 33%
- 50
-20% - post-menopausal ( importance of estrogen inhibition of osteoclast )
- breast cancer
vitamin d deficiency:
—- in children which is the abnormal amount of unmineralised ostieods, characterised be bowing of log leg bones
—- in adults bone weakens due to unmierlaised osteoid , but longitudinal bone growth has been completed as there is no bowing of legs
- rickets
- osteomalacia
( info: * Circulating [25(OH)D] of <50 nmol/L are said to be deficient
– UV strength at this latitude is too low to generate sufficient Vit D Oct-Mar
– sunblock, covering up in the sun, dark skin colour all decrease UV exposure
– renal disease cannot make enough vitamin D)
-Bone growth stops with the fusing of the ——- in the long bones
- —— continues throughout life and is mediated by osteoblasts, osteoclasts and osteocytes
- —- and — control plasma Ca2+ levels and with it bone mineralisation
- Vitamin D deficiency among other factors can alter —- availability
and —– bone mineralisation
-epiphyseal plate
- bone turnover
- vitamin d and PTH
- ca+2
- decrease
