May24 M1-Histo 3 Flashcards
def of bone remodelling
balance between
- bone adding by osteoblasts
- bone resorption by osteoclasts
balance of bone remodelling during skeletal growth
bone deposition exceeds bone resorption
balance of bone remodelling during adulthood
bone deposition = bone resorption
balance of bone remodelling during during old age
bone resorption exceeds bone deposition. this also occurs earlier in osteoporosis
end result of bone resorption exceeding bone deposition
loss of skeletal mass
what induces bone remodelling
fatigue damage in the bone. resulting in these events:
- accumulation of microcraks in the mineralized ECM
- osteocytes mechanosensory network senses this damage
- osteocytes signal for bone remodelling to replace these microcracks with new bone
why bone remodelling is needed to repair microcracks
too many microcracks lead to bone fracture
skeletal cell types involved in bone remodelling and in initiating it
- initiated by osteoclasts
- involves all cell types
2 mechanisms of bone remodelling
- stochastic process (random): prevent bone age from exceeding an acceptable level. = random bone replacmeent
- directed process: removes bone that is in some way defective from a specific location (OSTEOCYTES SENSING MICROCRACKS AND REPLACING DEFECTIVE PARTS)
in the adult skeleton, what creates the demand for osteoblasts
bone resorption
in the adult skeleton, what creates the demand for osteoclasts
the different purposes of bone remodelling
what allows growth of long bones during endochondral bone formation (endochondral ossification)
cartilage. it persists in
- articular surface (hyaline cartilage and perichondrium)
- epiphyseal plate (perichondrium on both sides so will be persistent perichondrium, the one responsible for bone growth)
what happens to woven bone in the diaphysis of long bones during development
developmental remodelling
- woven bone is replaced by compact lamellar bone (the epiphyseal plate is responsible for this growth in length)
- during adulthood, growth continues as a radial growth
why woven bone in diaphysis of long bones initially (first in development)
bcause first step in endochondral bone formation is intramembranous ossification
longitudinal growth vs radial growth of bone
- longitudinal growth = on bone length
- radial growth = on bone diameter (deposition on periosteal surface and resorption on endosteal surface)
4 stages of RADIAL growth of the diaphysis of long bone
- early foetal life (formation of woven trabecular bone)
- late foetal life (last step where you see woven trabecular immature bone with disorganized collagen)
- childhood
- adulthood
composition of bone in early and late fetal life + where osteoblasts and osteocytes are found in this bone
- trabecules of primary bone only (woven) formed by periosteal intramembranous ossification
- osteoblasts on periphery of the trabecules
- osteocytes within the trabecules
in early and late fetal bone, what is between the trabecules
CT and blood vessels
early and late fetal bone origin + structure
trabecules + CT lined on one side by periosteum (the origin of this intramembranous ossification) and on the other side by endosteum definitive, organizing endosteum.
diff things happening to bone between late foetal life and childhood
- woven bone replaced by lamellar bone
- Volkman’s canals penetrate through the periosteum and and get through the endosteum
- Volkman’s canals have blood vessels and osteoprogenitor cells, osteoblasts and osteoclasts with them
how can Volkman’s canal tunnel through the bone as you transition into childhood
bone resorption
what do Volkman’s canals do after they penetrated through woven bone perpendicularly
- will eventually turn 90 degrees and follow the direction of bone
- this creates big cavities occupied by osteoclasts
cells that Volkman’s canals (and anything penetrating through endostium and periostium) bring with them
- osteoprogenitor cells
- osteoblasts
- osteocytes
what happens to cavities created by Volkman’s canals in woven bone of late foetal life
replaced by lamellar bone and Haversian systems. these will replace woven bone
histology of bone in childhood
- concentric bone lamellae (Hav systems) formed in spaces between the woven bone trabecules
- primary bone progressively disappears because of OSTEOCLASTS
histology of COMPACT bone in adulthood
- is lamellar bone only
- this lamellar bone is constantly restructured by dissolution and replacement of osteons (by osteon reconstruction)
example of pattern you may expect to see in adult compact bone
- some big canals originating from Volkman’s canal turning and following bone length eventually
- these canals had osteoblasts which produced all the lamellar bone.
- this concentric production of lamellar bone by osteoblasts near the canal creates Haversian systems
charact of immature Haversian system
- wider middle canal
- surrounded by dividing osteoblasts which produce ECM and lamellar bone
- osteocytes getting trapped between the lamella
- osteoblasts and osteocytes continue to grow towards the center and system being formed layer by layer
- the Haversian canal is becoming smaller with less vessels in it
charact of mature Haversian system
- small Hav canal with one only blood vessel (capillary) in it for nutrition
- a cementing line surrounding the Hav system is produced (seals the whole thing)
- divison of osteoblasts, grow to the center, formation of Hav system and lamella
when does the formation of the circumferential lamellae occur
near the end of skeletal growth
how formation of circumferential lamellae occurs
- periosteum adds sheets of bone wrapping outside
- they have the form of concentric lamellae that encircle the bone (and surround the compact Hav bone layer (cortical bone))
- surrounding = outer circumferential lamellae
- endosteum does the same thing to do the inner circumferential lamellae
at the end of skeletal growth, what happens to the central mixed spicules formed by endochondral ossification and that are present near the metaphysis and the epiphysis
- remodeled to form a spongy trabecular cancellous bone network with trabecules (spicules) of lamellar bone only with no cartilage core (initially had core remnant from growth plate)
- this bone replaces the cartilaginous epiphyseal plate to make an EPIPHYSEAL SCAR that persists in adult bone
in the adult bone, where do you find hyaline cartilage
ONLY at the extremities of the bone as articular cartilage
directions of bone growth and shaping after late fetal life in the epiphyseal plate
- growth in length (chondrogenesis)
- radial growth at the level of the metaphysis (due to addition of hyaline cartilage to the perichondrium). funnel formation.
what is the cause of growth in length in epiphyseal plate at end of fetal life
- addition of chondrocytes in epiphyseal plate
- cells dividing at the epiphyseal plate and pushing the epiphysis of the bone out of the way
- chondrogenic activity*
in late foetal life, 3 things happening in bone in the METAPHYSIS at the same time as the growth in length + radial growth of the epiphyseal plate
- osteoblasts add bone on endosteal (inner) surface
- osteoclasts resorb bone on the periosteal surface (remodelling of the funnel)
- formation of new spicules by lateral invasion of blood vessels (MAKES TRABECULAR BONE)
what do we mean by remodelling of the funnel by osteoclasts (removing bone in periosteum) and by funnel formation (from hyaline cartilage addition from perichondrium for radial growth at epiphyseal plate)
funnel = the part of the bone where the epiphysis and metaphysis (head) becomes narrower to transition into the less thick epiphysis (shaft). funnel = the curve there where the bone becomes less wide
what is responsible for the funnel shape of the bone (not a tube but rather a shaft which is less wide than the heads)
osteoclastic activity right under the periosteum at the level of the metaphysis
how the formation of new spicules in bone metaphysis at end of fetal life by lateral invasion of blood vessels occurs
- these blood vessels are bringing in osteoblasts
- these osteoblasts form the mixed spicules (TRABECULAR BONE)
consequence of formation of new spicules in bone metaphysis at end of fetal life by lateral invasion of blood vessels
the bone finds support to push the epiphysis away from the center (bc this happens most superficially in the metaphysis, near bone surface) where spicules can be SUPPORTED ON ENDOSTEUM UNDER THE EPIPHYSEAL PLATE
consequence of osteoblasts adding bone on endosteal (inner) surface of metaphysis
endosteal surface (endosteal zone) gets thicker
diff layers of the periosteum at the level of the metaphysis (when periosteum is being remodelled by osteoclasts to make the funnel shape)
- fibrous periosteum
- osteogenic periosteum underneath
- layer of multinucleated cells (osteoclasts) underneath the osteogenic periosteum
during bone dev at end of fetal life, what happens in the diaphysis + what happens to the bone spicules previously there
opposite of metaphysis
- osteoclastic activity on endosteal surface
- osteogenesis on periosteal surface
- this results in radial, lateral growth of bone and in a bigger cavity of marrow*
- when this happens, all the bone spicules have been dissolved*
how body reacts to accumulation of microcracks in bone matrix (bone fatigue) (which may lead to bone fracture)
sensed by osteocyte mechanosensory network.
-signals for bone remodelling to replace the microcracked bone
what is the bone remodelling that we refer to when we say that osteocytes call for bone remodelling to repair microcracks (what is exactly happening)
- Volkmann’s canals penetrate from periphery perpendicularly and then go up parallel to bone axis
- form a big tunnel, hole.
- interstitial systems (bad, old Hav systems)
- then new addition and formation of bone
first step when a bone is fractured
- bone matrix is destroyed
- bones adjoining the fracture die
- damaged blood vessels produce a localized hemorrhage that forms a blood clot
fracture repair: what happens to initial blood clot formed
removed during repair by macrophages
steps of the repair of a fracture
- periosteum and endosteum around the fracture proliferate
- periosteum produces hyaline cartilage at the end of the fracture that is unstable
- primary woven bone is formed by endochondral ossification
- periosteum and endosteum produce more bone by intramembranous ossif
- a CALLUS persists for some time
fracture healing takes how long
1.5 months
what happens during fracture repair between hyaline cartilage at end of fracture (unstable. produced by periosteum) and formation of primary woven bone
- the chondrocytes in this hyaline cartilage receive no more blood bc no more blood vessels so they hypertrophy and die
- ECM calcifies because of that*
- osteoblasts come in and form woven bone
- later bone replaced by compact bone (similar to fetal life bone replaced by lamellar bone)
what happens to the bone callus with time
eventually is resorbed and you’re left with compact bone only
what’s Wolff’s law
- increased P on bone leads to bone resorption by osteoclasts
- increase bone tension leads to bone formation by osteoblasts
Wolff’s law is used where
- orthodontics
- distraction osteogenesis for bone lengthening
- create tension to terminal part of dental arch and osteogenesis occurs on bone that is root of teeth*
bone lengthening is done for who
children whose bones are skeletally immature (still growing**)
what does distraction osteogenesis mean
- bone cut during surgery and gradually distracted (pulled apart)
- bone osteogenesis at site of lengthening occurs
- break bone, attach pins to the bone, the pins pull the bone 1 mm every day
bone regions involved in distraction osteogenesis
- create a fracture = periosteum naturally responds by creating hyaline cartilage
- the daily separation of the gap destroys the periosteum
- periosteum produces more and more hyaline cartilage
- hyaline cartilage eventually heals like in a fracture. (primary bone produced then replaced by secondary lamellar bone)
other name of distraction osteogenesis
bone destruction
bone struction most important conceps
- create fracture
- allows formation of cartilage
- then pull on both ends
- more cartilage added
- cartilge replaced by woven bone
- woven bone replaced by lamellar bone
how does high Ca in the blood happen
bone resorption. a normal process in the bone, regulated by PTH indirectly
PTH secreted by what + function
- by parathyroid glands
- increase conc. of Ca in the blood
PTH acts on what receptor and R is where
parathyroid hormone 1 receptor (PTH1R). most concentrated in
- bone (on osteoblasts. NOT OSTEOCLASTS)
- kidney
what happens when PTH bind PTH1R on osteoblasts
- stimulates osteoblasts to increase their expression of RANKL
- inhibits osteoblast expression of OPG (osteoprotegerin)
what does the reduced OPG expression by osteoblasts due to PTH help bone resorption
- OPG binds RANKL normally and blocks it from interacting with RANK (the receptor for RANKL)
- this usually stimulates osteoclasts precursors to fuse forming new osteoclasts which enhances bone resorption
how does higher RANKL expression and lower OPG expression by osteoblasts due to PTH promote bone resorption
- more RANKL so more RANKL binding RANK to stim osteoclasts formation
- less OPG to block the RANKL-RANK interaction (by binding to RANKL) so more stimulation of osteoclast production can occur
PTH is involved in the metabolism of what 2 things
- calcium (Ca2+)
- phosphorus
hormone that counteracts PTH
calcitonin
calcitonin produced by what + its function
- by parafollicular cells (C cells) of the thyroid gland
- lowers blood Ca
4 ways by which calcitonin lowers blood Ca
- inhibit Ca absorption by the intestines
- inhibit renal tubular cell reabsorption of Ca so it is excreted in the urine
- inhibits osteoclast activity in bones
- stimulates osteoblast activity in bones
calcitonin is especially useful at what times?
- during periods of calcium mobilization (bc it protects from ca loss from skeleton)
- pregnancy
- lactation - prevents postprandial hypercalcemia resulting from absorption of Ca2+
estrogen effect on bone + consequence of menopause
inhibits bone resorption
- menopause = stop secreting estrogen so possibly more bone resorption
- consider estrogen replacement therapy
growth hormone (GH) secreted from where + effect
- anterior lobe of pituitary gland
- makes liver produce somatomedin
effect of somatomedin
overall growth effect on the epiphyseal plate + other structures of the bone
consequence of lack of GH during the growing years
pituitary dwarfism
consequence of excess of GH during the growing years
gigantism (excessive growth of long bones): excessive cartilage and bone formation at the epiphyseal plate of LONG bones
consequence of excess of GH in the adult
acromegaly (increase in the width of bones due to periosteal growth)
achondroplastic dwarfism is what
genetic defect caused a deficient or improper growth of the epiphyseal plate
causes of pituitary dwarfism
anything that affects GH secretion
- low GH
- genetics
- trauma to pituitary gland
- surgical injury to pituitary
- CNS trauma or tumor or radiation
- often unknown*
treatment of pituitary dwarfism
GH replacement therapy if child lacking GH
- to be done before bone growth plates have fused or joined. once the growth plates have fused, GH replacement therapy is rarely effective
- WINDOW OF THERAPY*
achondroplasia vs pituitary dwarfism
- pituitary dwarfism = proportions of the body reamin the same
- achondroplastic dwarfism = proportions of the body are abnormal
achondroplasia is what + meaning of the word
short limbed DWARFISM. achondroplasia means without cartilage formation
COMMON CAUSE OF DWARFISM
cause of achondroplasia
- gain of function (TM, transmembrane specifically in achondroplasia) mutation in fibroblast growth factor receptor 3 (FGFR3)
- the protein is excessive
- need 1 allele defect (autosomal dominant)
- 2 bad alleles = lethal
normal function of FGFR3
negative regulatory effect on bone growth during normal development of person or child
what happens in mutated FGFR3 (transmembrane mutation)
- mutated form of R is constitutively active
- severely shortened bones
exact function of FGFR3 on cell signaling and bone ossification specifically
- represses the number of chondrocytes that proliferate and mature into bone at the growth plate
- gain of function and ossification is repressed even more
- epiphyseal plate is disorganized, with a much smaller cartilage
- gain of function = it accomplishes its function of repression cartilage maturation into bone too much*
long bones growth takes how long in humans + regulated by what hormone
- 20 years
- GH
does the thickness of the epiphyseal plate change with time
- no. because rate of chondrocyte prolif and bone formation = rate of destruction of spicules
- the epiphyseal plate is simply displaced away from the middle of the diaphysis with time (resulting in net growth in length)
