:D Flashcards
what are the two ways can develop bone? [2]
- *intramembranous ossification**: direct bone formation, many skull bones
- *endochondral** ossification: most of skeleton, cartilage first & then bone
what is the name of the inorganic substance that is precipitated over collagen fibres to calcify it? [1]
what is structure of ^ like on collagen fibres? [1]
what is the name of the inorganic substance that is precipitated over collagen fibres to calcify it? [1]
95% calcium hydroxyapatite
what is structure of ^ like on collagen fibres? [1]
- as crystals
what substance is secreted that makes osteoBlasts differentiate into osteoclasts? [1]
RANKL
how does endochondral ossification occur?
- Mesenchymal cells condense and differentiates into chondroblasts to produce hyaline cartilage model extracellular matrix (so they use collagen type 2 rather than collagen type 1).
- the perichondrium forms around cartilage model and holds all the mesenchymal cells next to the condensing bone
- To begin with, ECM is made more from collagen type 2, more proteoglycans: causes cartilage to grow in legnth and width (into the shape of the bone): causes to be further away from nutrient source
- chondrocytes now in the middle will begin to deteriorate as there is no blood supply into this cartilage
- this creates cavities, right in the centre, where the cartilage used to be. When they die, this triggers calcification as it triggers a Ph change: It releases vesicles in the chondrocytes with enzyme like alkaline phosphatase which changes the ph and encourages calcification of the matrix.
At this time, a blood vessel known as the nutrient artery can penetrate the perichondrium and begin to bring in osteoclasts from the haemopoietic cells to start remodelling: break down some of the spongy bone to create a marrow, or medullary, cavity in the centre.
Bone on the inside and bone on the outside grow towards each other to completely replace the cartilage.
what is fate of osteoblasts? [2] become either:
- osteocyte
- lining cell: old osteoblast that are not encased in own matrix to help regulate calcium entry into and out of bone. can be reactivated by PTH
what are the internal [1] and external signals [2] for bone remodelling?
what are the internal and external signals for bone remodelling?
- *internal factors**
- osteocytes processes extend in canaliculi & touch their neighbours
- osteocytes produce sclerostin to indicate bone health ! - stops osteoblasts coming
- when osteocytes stop producing sclerostin: indicates bad bone health
- *external factors**
- serum calcium level: low serum calcium causes the release of parathyroid hormone - causes osteoblasts to make RANK L
- pro-inflam cytokines: IL1, IL6, IL17 & TNF
what do osteoclasts look like? [1]
explain mechanism of bone remodelling occurs xox
osteoclasts - multinucleated macrophage relation
- look for areas of bone that need to be renewed
- make leak proof seal over the area
- secrete enzymes & HCl that will dissolve the calcium hydroxyapatite
- osteoclasts take up calcium & proteins pump into interstitial fluid
- osteoclasts find new area
- osteoblasts come in & fill lacuna with osteoid - firstly NOT MINERALISED
- *-** approx 7-10 days osteoid is mineralised
- osteoblast becomes encased & beomes osteocyte
what do osteoclasts look like? [1]
explain mechanism of bone remodelling occurs xox
osteoclasts - multinucleated macrophage relation
- look for areas of bone that need to be renewed
- make leak proof seal over the area
- secrete enzymes & HCl that will dissolve the calcium hydroxyapatite
- osteoclasts take up calcium & proteins pump into interstitial fluid
- osteoclasts find new area
- osteoblasts come in & fill lacuna with osteoid - firstly NOT MINERALISED
- *-** approx 7-10 days osteoid is mineralised
- osteoblast becomes encased & beomes osteocyte
what is the effect of when low Ca2+ serum causes PTH to be secreted in? [3]
- low serum Ca2+ (below 2.2 mmol/L) stimulates parathyroid hormone (PTH) secretion
- PTH promotes
i) Ca2+ reabsorbtion from kindey and PO4 excretion
ii) @ kindey: synthesis of 1,25 dihydroxyvitamin D -> i_ncreases calcium absorbtion from gut_
iii) **Ca2+ reabsorbtion from bones - increases activity and no. osteoclasts - **PTH binds to osteoblasts; osteoblasts produce RANKL; osteoclasts have RANKL receptor; activates osteoclasts
how does PTH cause Ca2+ reabsorbtion from bones via the increase of activity and no. osteoclasts? [3]
Ca2+ reabsorbtion from bones - increases activity and no. osteoclasts
PTH binds to osteoblasts
osteoblasts produce RANKL
osteoclasts have RANKL receptor
activates osteoclasts
how does body stop cell from producing more Ca2+?
- stop production of PTH
-
calcitonin: released from C cells in thyroid gland
i) inactivates osteoclasts
ii) increases Ca2+ bones can accept
iii) increases renal Ca2+ reabsorb
explain how intramembranous ossificatin occurs xo
- ossification centre appears in fibrous connective tissue membrane: here mesenchymal cells condense and differentiate as osteogenic cells: osteoblasts
- Osteoblasts secrete bone matrix (osteoid) & matrix becomes calcified with calcium hydroxyapatite
- trapped osteoblasts become osteocytes
- Mesenchyme on outside condenses: periosteum
- blood vessels growing to supply the bone with nutrients will bring in osteoclasts, which can then remodel the bone into compact/cortical bone on the outside and trabecular bone on the inside.
what are 5 stages of epiphyseal growth plate?
- Zone of resting cartilage
- Zone of proliferating cartilage
- Zone of hypertrophic cartilage
- Zone of provisional calcifcation
- zone of ossification
how does appositional growth of bone occur? (to the side)
- osteoprogenitors in periosteum differentiate as osteoblasts – secrete new bone matrix to form compact, cortical bone (osteons) and grow on either side of a blood vessel.
- these ridges get bigger and eventually form a tunnel with a blood vessel right in the centre.
- Inside tunnel: Former periosteum becomes endosteum due to being enclosed inside the bone due to bone growth. It still has progenitor cells
- Osteoblasts make new bone lamellae filling tunnel
how does appositional growth of bone occur? (to the side)
- osteoprogenitors in periosteum differentiate as osteoblasts – secrete new bone matrix to form compact, cortical bone (osteons) and grow on either side of a blood vessel.
- these ridges get bigger and eventually form a tunnel with a blood vessel right in the centre.
- Inside tunnel: Former periosteum becomes endosteum due to being enclosed inside the bone due to bone growth. It still has progenitor cells
- Osteoblasts make new bone lamellae filling tunnel
in appositional growth, why is bone must be removed from the inner medullary cavity?
- As new bone added to outside of bone, bone must be removed from the inner medullary cavity so that we maintain the same proportions of cortical:trabecular bone
- Addition of new bone needs to be matched with removal to maintain the thickness
give two reasons why skeleton is renewed before it deteriotes [2]
which type of bone is quicker at remodelling? [1]
give two reasons why skeleton is renewed before it deteriotes [2]
- renews bone before deterioration
- redistributes bone matrix along lines of mechanical stress
which type of bone is quicker at remodelling? [1]
Trabecular bone 3-10 times quicker than cortical bone: Larger surface area, Responds to stresses on the bone quicker
which cell signals bone remodelling? [1]
what hormone does ^ cell secrete? [1]
how does the process occur? [2] (basic)
which cell signals bone remodelling? [1]
-osteocytes
what hormone does ^ cell secrete? [1]
sclerostin
how does the process occur? [2]
- *-sclerostin** secreted: causes inhibition of osteoblast action
- cellular process extend in canaliculi and touch their neighbours
explain mechanism of how osteoclasts resorb bone?
- osteoclasts clamps down onto surface of the bone and forms a leak proof seal [1]
- Release protein-digesting enzymes, and acid (HCL) underneath: this breaks down and digest collagen fibres
- low pH of 5 dissolves the bone minerals
- bone proteins and minerals (mainly Ca2+) cross osteoclast to exit into interstitial fluid so these can be re-used
- once the osteoclasts have moved to the next area to remodel new bone, the area gets covered with osteoblasts: fill lacuna with osteoid (collagen type 1 and proteoglycan). This is UNMINERALISED BONE MATRIX
- takes about 7-10 days for the calcium to be precipitated over the new bone & osteon is reminarlised
explain mechansim of bone metabolsim through PTH secretion
- Low plasma Ca2+ stimulates Parathyroid hormone (PTH) secretion: Parathyroid glands
- Ca2+ reabsorption from kidney and PO4 excretion (at the expense of phosphate as we can make this easily)
- Initiates synthesis of 1,25-dihydroxyvitamin D (1,25 (OH)2 vitamin D3) in kidney, as 1,25 (OH)2 vitamin D3 increases Ca2+ absorption from gut
- Ca2+ reabsorption from bone - increases number and activity of osteoclasts
- Osteoblasts have receptor for PTH - causes expression of RANKL (ligand for RANK)
- Osteoclast precursors have RANK (receptor)
- If osteoblasts produce RANKL it stimulates osteoclasts to produce more, thus mobilising calcium in your skeleton
- RANKL/RANK = Osteoclast proliferation and differentiation
explain mechansim of bone metabolsim through PTH secretion
- Low plasma Ca2+ stimulates Parathyroid hormone (PTH) secretion: Parathyroid glands
- Ca2+ reabsorption from kidney and PO4 excretion (at the expense of phosphate as we can make this easily)
- Initiates synthesis of 1,25-dihydroxyvitamin D (1,25 (OH)2 vitamin D3) in kidney, as 1,25 (OH)2 vitamin D3 increases Ca2+ absorption from gut
- Ca2+ reabsorption from bone - increases number and activity of osteoclasts
- Osteoblasts have receptor for PTH - causes expression of RANKL (ligand for RANK)
- Osteoclast precursors have RANK (receptor)
- If osteoblasts produce RANKL it stimulates osteoclasts to produce more, thus mobilising calcium in your skeleton
- RANKL/RANK = Osteoclast proliferation and differentiation
explain mechanism of how osteoclasts resorb bone?
- osteoclasts clamps down onto surface of the bone and forms a leak proof seal [1]
- Release protein-digesting enzymes, and acid (HCL) underneath: this breaks down and digest collagen fibres
- low pH of 5 dissolves the bone minerals
- bone proteins and minerals (mainly Ca2+) cross osteoclast to exit into interstitial fluid so these can be re-used
- once the osteoclasts have moved to the next area to remodel new bone, the area gets covered with osteoblasts: fill lacuna with osteoid (collagen type 1 and proteoglycan). This is UNMINERALISED BONE MATRIX
- takes about 7-10 days for the calcium to be precipitated over the new bone & osteon is reminarlised
which cell signals bone remodelling? [1]
what hormone does ^ cell secrete? [1]
how does the process occur? [2] (basic)
which cell signals bone remodelling? [1]
-osteocytes
what hormone does ^ cell secrete? [1]
sclerostin
how does the process occur? [2]
- *-sclerostin** secreted: causes inhibition of osteoblast action
- cellular process extend in canaliculi and touch their neighbours
give two reasons why skeleton is renewed before it deteriotes [2]
which type of bone is quicker at remodelling? [1]
give two reasons why skeleton is renewed before it deteriotes [2]
- renews bone before deterioration
- redistributes bone matrix along lines of mechanical stress
which type of bone is quicker at remodelling? [1]
Trabecular bone 3-10 times quicker than cortical bone: Larger surface area, Responds to stresses on the bone quicker
in appositional growth, why is bone must be removed from the inner medullary cavity?
- As new bone added to outside of bone, bone must be removed from the inner medullary cavity so that we maintain the same proportions of cortical:trabecular bone
- Addition of new bone needs to be matched with removal to maintain the thickness
?
rhomboids
supinator
dorsal interossei of hand
dorsal interrossei: abduct fingers (DAB)
