week 5 Flashcards
cellular differentiation
process of one cell type changing to another cell type
how does differentiation affect a cell
size shape membrane potential metabolic activity responsiveness to signals
when do limbs start to form
week 4
mesenchyme
connective tissue found in embryo development
arises from mesoderm
contains loosely packed cells which are non specialised
mesenchymal cells are highly migratory
limb development stages
at the end of week 4 - limb buds first become visible
upper limb buds appear first as ridges from ventrolateral body wall
lower limb as small bulges
limb morphogenesis takes place between weeks 4 and 8
lower limbs lag slightly behind
no nerves in early limb bud
where is mesenchyme derived from
dorsolateral mesoderm cells of the somites
components of mesenchymal connective tissue
matrix of collagen fibres
hyaluronic acid
glycoproteins
structure of a limb bud
mesenchymal core - from somatic layer of lateral plate mesoderm
covered by a layer of cuboidal ectoderm
apical ectodermal ridge at distal border
what is the AER
apical ectodermal ridge
it is thickened ectoderm at the distal border of a limb bud
has an inductive relationship with mesoderm
remains undifferentiated
key signalling centre in limb development - limbs fail to develop without AER
limb development after AER has formed
as limb grows, cells furthest from the AER begin to differentiate into cartilage and muscle
limb outgrowth initiated by secretion of FGF10
position of AER corresponds to border between dorsal and ventral ectoderm
role of FGF10 in limb development
signalling molecule first seen in the limb bud
paracrine signalling molecule
FGF family known for mitogenic activity - induce a cell to begin division via triggering a signal transduction pathway
where is radical fringe expressed
expressed by dorsal ectoderm
its a signalling molecule
what does the ventral ectoderm express
transcription factor called engrailed1
function of FGF 4 and 8 in limb development
at distal end keep cells undifferentiated
function of engrailed1 and radical fringe in limb development
RF - in dorsal limb it restricts AER to the distal tip
engrailed does the same on the ventral side
function of retinoic acid in limb development
at the proximal end starts differentiation into prox components - signals from AER to not reach to prox
what are the factors designating UL and LL
t-box family TFs
TBX-5 expressed in the UL
TBX-4 expressed in the LL
mesoderm and ectoderm relationship in AER
AER is ectoderm and is acting on mesoderm but its own existence is controlled by mesoderm
week 6 of limb development
terminal portion of buds becomes flattened - handplates and footplates
seperated from the proxmal segements by constriction (wrist)
second constriction further divides proximal portion into 2 segments (elbow)
3 components of limb in development
stylopod - humerus and femur
zeugopod - radius/ulna and tibia/fibia
autopod - carpels, metacarpals, digits, tarsals/metatarsals
function of HOX genes in limb development
regulates positioning of limbs along craniocaudal axis
expressed in overlapping patterns
mis expression will alter limb position
polydactylyl
extra digits due to a defect in mesoderm - mutation in HOX genes, Shh or Wnt
what happens after cells start to die in AER
cell death in AER separates ridges into 5 parts - 5 digits grow out under influence of 5 ridge parts
mesenchyme condense to form cartilaginous digits
by d56, digit separation is complete
describe limb rotation after development
LL develops 1-2 days later
limb development over week 7
UL and LL rotate in opposite directions
rotation occurs from from coronal to the parasaggital plane, then along the long axis
which way does UL rotate in development
UL rotates 90 degrees laterally
extensor muscles lie lateral ad posterior side
which way does LL rotate in development
rotates 90degrees medially
extensors on anterior surface
appositional growth
increase in girth/width
chondroblasts deposit collagen matrix on cartilage beneath the periosteum which initiates growth
interstitial growth
increase in length
achieved by growth plate up until puberty - cartilage can do this not bone
endochondral ossification
cartilage model laid down as a precursor to bone
mainly in long bones
intramembranous ossification
cartilage not involved
condensation of mesenchyme which is converted straight to bone
see this in flat bones
stages of limb bone development
part 1
as external shape is being established, mesenchyme in the buds becomes condensed
cells differentiate to chondrocytes - driven by expression of BMPs
at week 6 - hyaline cartilage models can be seen
areas where chondrogenesis is arrested makes joints - cell proliferation, increased density, differentiation then cell dealth - induced by WNT 14
bones formed by week 8
centres of ossification form in diaphyses and epiphyses
primary centres of ossification present in all long bones by week 12
growth plates of cartilage remain
stages in limb bone development
part 2
cells in centre of cartilage model proliferate, enlarge, make new kind of matrix - can be calcified
calcified cartilage matrix does not allow diffusion of nutrients so cartilage cells die
left with spicules of calcified cartilage matrix - acts as a scaffolding on which bone can be deposited
periosteum is vascular connective tissue around model where blood vessels grown in - BVs bring in progenitor cells
osteoprogenitor cells become osteoblasts - line up on spicules and start producing bone matrix
core of calcified cartilage matrix removed by osteoclasts
trapped osteoblasts become osteocytes
during growth period, what remodels bone to maintain overall shape and proportion
osteoclasts
achondroplasia
disorder of bone growth that affects endochondral ossification via cartilage
achondroplasia mutation
mutation in FGFR3 - normally down regulates cartilage and bone growth and it inhibits cell proliferation and differentiation
mutation in receptor results in permanent expression so protein is overactive - results in reduced chondrocyte activity
examples of where hyaline cartilage is located in the body
skeletal - articular, costal, growth plate
trachea
larynx
nose
examples of where elastic cartilage is located in the body
ear
epiglottis
examples of where fibrocartilage is located in the body
meniscus
IVDs
describe articular cartilage
smooth lubricated surface for articulation
facilitate load transmission and create low friction environment
cells - chondrocytes
ECM - collagen, water, proteoglycans/proteins - hyaluronan and aggrecan
it is avascular, aneural, non-immunogenic
function of chondrocytes and ECM in articular cartilage
c - synthesise and maintain ECM
ECM - protects chondrocytes from loading forces
what is involved in the degradation part of cartilage turnover
MMPs - degrade collagen/proteoglycans
TIMPs prevent degradation of MMPs
what is involved in the synthesis part of cartilage turnover
collagen, proteoglycans and proteins
increase in GFs, IGF-1 and TGF-beta
decrease in cytokines
issue with cartilage healing
injury must penetrate subchondral bone to allow bleeding - inflammatory cells, platelets, mesenchymal cells to synthesise collagen type I (not as good as II)
stages of cartilage healing
inflammation
repair
remodelling
issue with meniscal tears
cant heal as no blood supply
composition of fibrocartilage
cells - fibrocartilage
ECM - collagen type I, water, proteoglycans, glycoproteins, elastin
acute and chronic cartilage injuries
a - trauma, sports, infection
c - osteoarthritis, previous injury
diagnosis of cartilage injury
xray
mri
arthroscopy
treatment of cartilage injury
physiotherapy medical - paracetamol, NSAIDs arthroscopy cartilage transplantation joint replacement
two types of bone
mature/lamellar: all cortical and cancellous bone osteoblasts lay bone matrix in sheets - lamellae parallel, organised collagen fibres immature/woven: randomly aligned collagen fibres
cortical bone
mature bone laid down in concentric rings
80% of the skeleton
slow turnover rate/metabolic activity
cancellous bone
spongy or trabecular bone
high turnover rate and undergoes greater remodelling
inorganic part of bone matrix
calcium and phosphorus
organic part of bone matrix
collagen, mucopolysaccharides, non-collagenous proteins
3 blood supplies of bone
periosteum blood supply is most important supply in children
nutrient artery enters centre of diaphysis - high pressure
vessels enter at metaphysis and epiphysis - communicate with nutrient artery but enter separately
two types of fracture healing
indirect and direct
indirect fracture healing process
haematoma: haemopoetic cells secrete GFs fibroblasts, osteoprogenitor cells, mesenchymal cells, immune cells granulation tissue forms soft callus: 1 week - 1 month 10% strain at failure hard callus: soft callus becomes mineralised disorganised woven bone remodelling: stable bridge with low strain environment osteoclasts go across and dissolve mineralised bone, osteoblasts form new bone
direct fracture healing
unique ‘artificial’ surgical situation - forms low strain environment
direct formation of bone without formation of callus - via osteoclastic absorption and osteoblastic formation
fracture stable - no movement under physiological load
relies upon compression of the bone ends - osteoblasts and osteoclasts can cut across gap that has been compressed
which fractures are prone to problems with union or necrosis bc of blood supply problems
proximal pole of scaphoid fractures
talar neck
intracapsular hip
surgical neck of humerus
inhibition of fracture healing factors
increasing age diabetes anaemia malnutrition peripheral vascular disease hypothyroidism smoking alcohol
why are there increasing numbers of people with a disability
population growth
increase in chronic disease
medical advances which extend and prolong life
a disabled person
someone with a physical or mental impairment that has a long term effect on his/her ability to carry out normal daily activities
even if condition is controlled by medication etc it still counts as a disability - except eyesight controlled by glasses
impairment
is due to an injury, illness or congenital condition that causes or is likely to cause a loss or difference of physiological or psychological function
causes of disability in young people
prenatal premature birth injury - cerebral palsy congenital - downs syndrome accident infection - meningitis violence disease
barriers children with disabilities experience
physical disability locomotor disability - movement cosmetic disability sensory eg blind, deaf cognitive impairment
promoting factors for young disabled people in the work participation
male education level parental education level higher level of psychosocial functioning lower scores on depression scales
hindering factors for young disabled people in the work participation
lower educational factors female inpatient treatment - can affect education motor impairment wheelchair use functional limitations multiple health problems low mental health perception, dependent coping strategy
adjustments to work with a disability
adjustments to equipment, work station - voice activated software
support - supervision
change in duties
modification of hours and place
absence due to treatment or rehabilitation
may involve moving to lower grade job if that is what they are competent of now
embryonic folding
occurs in 2 directions:
lateral folding - driven by somites - creates embryo body - creates tube with endoderm in the middle
cephalocaudal/head to tail folding - driven by CNS - creates c shape as tube bends
the folds happen simultaneously and somatic LPM fuses to close the body wall to create tube like structure
what does the dermomyotome form
becomes dermis and skeletal muscle
what does the sclerotome form
vertebrae and ribs
process of intramembranous ossification
begins with condensation of the mesenchymal stem cells - they undergo proliferation and undergo morphological changes and differentiate into osteoprogenitor cells which will develop into osteoblasts
osteogenic cells start to deposit bone matrix which are arranged in bony spicules
differentiating osteoblasts arrange themselves along the spicules and begin to secrete more bone matrix
as more matrix gets laid down, the spicules increase in size and will fuse together
as these grow, they will fuse with more and more spicules and this results in the formation of trabeculae
