MSK-physiology Flashcards
what do ligaments link?
bone to bone
what do tendons link?
bone to muscle
what is the type I collagen arrangement of ligaments?
- non-parallel
- ‘wavy bundles’
what is the type I collagen arrangement of tendons?
-parallel bundles of collagen
what are the physical properties of ligaments?
elastic and strong
what are the physical properties of tendons?
non-elastic and tough
what type of cartilage present in tendons and ligaments?
fibrocartilage
what is a sprain?
an over-stretched or torn ligament
what is a strain?
an over-stretched or torn tendon
what is the composition of tendons?
- fibroblasts-tenocytes
- fibrous connective tissue
- type I collagen
- proteoglycans
- elastin
what is the composition of ligaments?
- fibroblasts-ligamentocytes
- fibrous connective tissue
- type I collagen
- proteoglycans
- elastin
what is the difference in composition of ligaments and tendons?
- ligament less compact, more mixed cell morphology, more proteoglycan and elastin fibres
- ligament also has more cartilaginous proteins: aggrecan and collagen type I
- different ECM organisations
what does formation of tendons and ligaments in foetus is dependent on?
use muscle as a template/ axis
where are tendons and ligaments of the head formed from?
neural crest cells
where are the tendons and ligaments of axial body are formed?
somites
where are tendons and ligaments of the limbs formed?
limb buds/ lateral limb plate
what is scleraxis?
a marker for development of tendons and ligaments
what influences tendon and ligament development?
growth factors
- TGFbeta
- TGF8
what makes ligaments and tendons viscoelastic?
- Elastic-cross links between collagen fibrils
- Viscous-ability of collagen fibrils to slide over each other
describe the creep effect on ligaments and tendons
when applying a constant load, deformation of tendon/ligament primarily occurs at the moment of loading –> deformation continues to increase with time
describe the stress effect on ligaments and tendons
once a load is applied onto a ligament/tendon, it initially relaxes rapidly –> rate of relaxation decreases with application of a constant load over time
what is the hysteresis effect on ligaments and tendons
when the rate at which tendon/ligament elongates during loading is not the same rate at which it shortens during unloading
when the rate at which it lengthens is faster than the rate that it shortens by.
what happens to ligaments and tendons beyond 2% stress?
collagen fibres in ligaments and tendons straighten out
what happens to ligaments and tendons beyond 4% stress?
collagen fibres might be experiencing small ruptures as fibres slide past one another and cross-links start to fail but will ultimately return to normal length/ structure when the load is taken off-microscopic failure
what happens to ligaments and tendons beyond 8% stress?
macroscopic failure of tendon/ ligament will occur
what does the toe region of the stress-strain curve represent?
the un-crimping of the collagen fibrils
what does the shear rate refer to?
how quickly collagen fibrils slide over when a load is applied to the tendon/ ligament
describe the steps in the synthesis of collagen
1-3 alpha-helix chains are hydroxylated and glycosylated-these are called propeptides
2-then wound together to form a triple helical structure-procollagen (Vit C is cofactor for this reaction)
3-procollagen leaves the cell, entering extra-cellular space-becomes part of ECM
4-there is cleavage of N 7 C terminal telopeptides—->makes 1 collagen fibril
5-many collagen fibrils can be cross-linked together-using pyridinium cross-links-when lots are cross-linked it forms 1 collagen fibre
where is collagen I located?
bone, tendons, ligaments, skin
where is collagen II located in ECM?
cartilage
where is collagen III located in the ECM?
- found alongside type I collagen, in smaller amounts
- also found in higher abundance in healing ligaments and cartilage
where is collagen VI located?
muscle tissue
where is collagen IX located in the ECM?
- found alongside type II collagen in smaller amounts
- found in higher abundance in articular cartilage
where is collagen X located in the ECM?
ossifying cartilage
-it is a marker for new bone formation in articular cartilage
what are the components of cartilage?
- collagen (mainly type II)-gives structural strength
- Elastin-allows flexibility
- Proteoglycan-provides large osmotic effect
what cells are found in cartilage?
chondrocytes are embedded in ECM and it’s the matrix that provides cartilage with its unique characteristics
Name the 3 types of cartilage.
- fibrocartilage
- hyaline cartilage
- elastic cartilage
where is fibrocartilage found?
- pubic symphysis
- intervertebral disc
where is hyaline cartilage found?
most common type of cartilage-found in synovial joints
where is elastic cartilage found?
- epiglottis
- outer ear
- larynx
which is the strongest type of cartilage and why?
fibrocartilage due to high amounts of collagen II
what does fibrocartilage lack?
a true perichondrium
what are the main components in the ECM of hyaline cartilage?
- hyaluronan
- aggrecan
- negatively charged polysaccharide side chains-this attracts water
- 20% ECM and chondrocytes
- 80% cartilage
what is the most flexible cartilage and why?
elastic cartilage
-due to high amounts criss-crossed elastin
does elastic cartilage have a perichondrium?
yes
which types of cartilage always remain as cartilage?
- fibrocartilage
- elastic cartilage
what is hyaline cartilage that stays as cartilage called?
articular cartilage
what is hyaline cartilage that develops into bone called?
epiphyseal growth plate
what gives hyaline cartilage its weight bearing properties?
its water content-attracted negatively charged proteoglycans
what is the structure of articular cartilage?
1- Tangential (superficial) zone 2-Transitional (middle) zone 3- Radial (deep) zone Tide mark 4-Calcified cartilage
describe the tangential zone of articular cartilage
- fibres of type II collagen are parallel to the articular surface
- chondrocytes are flattened
- in contact with synovial fluid and tangential zone of articular cartilage of the bone it is articulating with
describe the transitional zone of articular cartilage
- collagen arranged into Arcades of Benninghoff
- abundant proteoglycans
what are the tide marks in articular cartilage?
the boundary between that which is and isn’t calcified
where is the calcified cartilage in articular cartilage?
transition zone between articular cartilage and bone
what is lambda ratio?
minimum film thickness in relation to the composite surface roughness
what is lubricin?
mucinous glycoprotein, which covers articular cartilage at synovial joints
what produces lubricin?
chondrocytes in superficial zone of articular cartilage
when do you need more lubricin?
If the surfaces coming into contact are very rough (e.g. bone ends), then you need more lubricin
-eg in osteoarthiritis
why do you normally not need a lot of lubricin?
as articular cartilage is smooth and it protect our bone ends
what does higher lubricin mean in terms of lambda ratio?
higher lambda ratio
describe the process of endochondral ossification?
1-mesenchyme clusters together in shape of bone
2-mesenchyme cells differentiate into chondroblasts- cartilage model is formed
3-perichondrium encapsulates the model
4-chondrocytes proliferate
5-cartilage calcifies
6-osteoprogenitor cells turn into osteocytes
7-bone is now replacing cartilage in the diaphysis
8-perichondrium is replaced by periosteum
9-there is now an artery supplying the bone
10-osteoclasts breakdown bone in centre to form cavity for marrow
11-the epiphyses of bones also calcify and are replaced by bone
12-articular cartilage will stay and protect articulating bone
13-growth plate will grow and over time develop into bone
what cartilage type is involved in endochondral ossification?
hyaline
what happens to the epiphyseal growth plate once a person has stopped growing?
it turns completely to bone
what is the AER in the embryology of limb development?
structure that forms from ectodermal cells at distal end of each limb bud
what is the proximal to distal elongation produced by?
AER
what does the AER act as in limb development?
major signalling centre to ensure proper development of a limb
what induces AER formation and what occurs after this?
limb buds induce AER formation
-the AER and limb mesoderm continue to communicate with each other to direct further limb development
what is the initiation of limb development driven by?
- fibroblast growth factors FGFs
- Hox and TBx genes/ T-Box transcription factors
describe the initiation of limb development using fibroblasts
- The mesoderm releases FGF10
- FGF10 causes cells overlying the AER to proliferate
- The AER releases FGF8 in response
- FGF8 causes the underlying mesoderm to proliferate
- positive feedback loop is formed-called reciprocal induction
what happens in limb development as the mesoderm and AER both thicken?
limb gets longer
what is the role of sonic hedgehog (SHH) in limb development?
acts in the zone of polarisation to differentiate the anterior-posterior axis-width of limb
what secretes SHH?
ZPA
describe the initiation of limb development using Hox and TBx genes
- Somites release retinoic acid and express Hox genes
- This causes TBx genes to express T-Box transcription factors
(Tbx-2, Tbx-3, Tbx-4 and Tbx-5) - Tbx-2 and Tb-x3 make all 4 limbs grow
- Tbx-4 makes lower limbs grow
- Tbx-5 makes upper limbs grow
what are SOX9 and GDF5 essential for?
allowing chondrocytes to grow
and for cartilage to form
what ere the 4 types of bone cells?
- osetocytes
- osteoblasts
- osteoprogenitor
- osteoclasts
which bone cell is the most common and why?
osteocytes-they are mature bone cells so most common
what is the role of osteocytes?
- mechanoreceptors
- ->monitors loading on bone and maintains bone metabolism accordingly (by activating osteoblast and osteoclasts)
what is the role of osteoblasts?
- bone building cells
- ->synthesise and secrete ECM
what has to happen before osteoblasts can become osteocytes?
become surrounded in their own ECM
What is the role of osteoprogenitor cells?
-will form osteoblasts (precursors)
why are osteoprogenitor cells the only bone cell type to undergo mitosis?
These are mesenchymal, unspecialised cells so can undergo mitosis
where are osteoprogenitor cells found?
inner side of periosteum
what is the role of osteoclasts?
-bone resorbing cells
what are osteoclasts derived from?
fusion of 50 monocytes
mulitnucleated
what type of cell are osteoclasts and how does it help with its function?
A polarised cell – it has a ‘ruffled border’ on one side which secretes enzymes and acid which acts on bone tissue to break it down
what is interstitial growth?
growth in length involving hyaline epiphyseal cartilage
what does the zone of resting cartilage do?
keeps epiphyses anchored
what occurs in the zone of proliferation?
chondrocytes are making more cartilage and are arranged into columns
what occurs in the zone of hypertrophy?
chondrocyte hypertrophy-chondrocytes mature and enlarge
what occurs in the zone of calcification?
-ECM cartilage calcifies and then the chondrocytes are starved of nutrients–> chondrocytes die
what does the calcified cartilage turn into and where is it in the bone?
ossified bone-closest to diaphysis
what is appositional growth?
bone width growth
what is appositional growth indirectly derived from?
hyaline cartilage
describe the steps of appositional bone growth
1-A periosteal blood vessel lies in a groove in the periosteum
2-periosteum starts peaking around the vessel (periosteal ridges) –>This periosteum now termed the endosteum.
3-Periosteal ridges close around vessel, creating a (Haversian) canal with vessel inside. Osteoblasts build inwards, towards canal to form an osteon.
4-process repeats on top of the osteon that was just formed
why does appositional growth not directly involve chondrocytes?
it occurs around the bone that was formed in the primary ossification centre-so requires no chondrocytes
what are interstitial and appositional growth examples of?
endochondral ossification
how is intramembranous ossification different from endochondral ossification?
bone develops straight from clustered mesenchyme-there is no cartilage involved
what bones does intramembranous ossification form?
- flat bones of skull and face
- clavicles
- mandible
outline the steps of intramembranous ossification
1-ossification centre: mesenchymal cells–>osteoprogenitor–>osteocytes-secrete ECM
2-calcification-ECM hardens and calcifies
3-formation of trabeculae–>ECM forms into trabeculae
-red marrow fills space in between trabeculae–>forms spongey bone
4-development of periosteum-at the periphery, periosteum covers the bone
is the complete process of mineralisation/ osteoid formation a quick one?
no it takes months
outline the steps of osteoid formation
1-osteoblasts synthesis and secrete type I collagen fibrils (ECM)
2-collagen fibrils polymerise, forming collagen strands
3-osteoblasts secrete alkaline phosphatase (ALP) which cleaves pyrophosphate into phosphate which is required for mineralisation
4-calcium and phosphate precipitate crystals on collagen in vesicles-forms hydroxyapatite which forms the osteoid
5-the vesicles on top of the collagen strands rupture and the crystals grow
describe the process of bone reabsorption
- Osteoblasts release RANK-Ligand (RANK-L) protein
- RANK-L binds to RANK receptors onto osteoclast precursors. The binding causes them to differentiate into mature osteoclasts
- The mature osteoclasts also express RANK receptors – RANK-L binds to them and activates the mature osteoclasts
- The mature activated osteoclast secretes enzymes and acid to reabsorb bone – eventually, they deactivate or die
how is bone metabolism regulated?
by Sclerostin-a regulatory factor and is secreted by the osteocytes and inhibits the osteoblast
precursors from maturing
how does bone building occur?
Osteoblasts secrete collagen fibres which are then mineralised
what are 2 classifications of bone?
- macroscopic
- microscopic
what can macroscopic bone be split into?
- spongy/ trabecular
- compact/ cortical
what can microscopic bone be split into?
- lamellar
- woven
where is spongy bone located?
in the interior of a bone covered by a layer of compact bone
how are the lamellae organised in spongey bone?
into irregular thin columns—>trabeculae
-organistaion is irregular but not random
where are trabeculae formed along and why?
-lines of stress placed on bone -to increase its strength and weight-bearing ability
what are the spaces in trabeculae filled with?
- red bone marrow-produces blood cells
- yellow bone marrow (adipose tissue)
which bones in adults does red bone marrow exist?
- hip bones
- ribs
- sternum
- spinal vertebrae
- proximal ends of femur and humerus (bony sites of haematopoiesis in adults)
what is compact bone organised into?
osteons
what are osteons?
concentric lamellae around a Haversian canal (vasculature)
what is situated between osteons?
interstitial lamellae
what is situated around all osteons?
circumferential lamellae
what lies within lamellae?
osteocytes that lie in spaces-lacunae-and canaliculi that radiate outwards
how do Haversian and Volkmann’s canals differ?
Haversian canals run along the long axis of the bone, whereas Volkmann’s canals connect the Haversian canals to each other by running horizontally.
which type of bone is mechanically weaker lamellar or woven?
woven
-due to haphazard organisation of collagen
where is woven bone produced?
in all foetal bone
what happens to woven bone?
gets replaced by lamellar bone
when does woven bone appear in adults?
only after a fracture or in Paget’s disease
how is woven bone produced?
when osteoblasts produce osteoid rapidly as complete mineralisation in lamellar bone takes too long
what doe lamellar bone require for its production?
a relatively flat surface to lay collagen fibres down in parallel or concentric fibres-increasing their strength
which 3 calcium-relating hormones play important roles in producing healthy bone?
- sex hormones
- parathyroid hormone
- calcitriol
what is the effect of low estrogen or testosterone on bones?
-bones weaken
what is the effect of parathyroid hormone on bones?
maintains level of calcium and stimulates both resorption and formation of bone
what is the effect of calcitriol on bones?
stimulates osteoclastic bone resorption by inducing RANKL and increasing the number and activity of osteoclasts
