Musculoskeletal System Flashcards
describe the structure of compact bone (3)
- basic unit is an osteon or Haverian system
- layers of concentric circles (lamellae) laid around a central canal (Haversian canals)
- canals contain vessels - blood, nerve and lymphatics
where is compact principally found in long bone?
diaphyses - middle part
what structure makes up cancellous bone?
mesh work of trabeculae - allows space for marrow
where is cancellous bone principally found?
epiphises (ends of bone)
what is the material composition of bone?
- 30% organic - type I collagen (tensile strength + flexibility)
- 70% inorganic - calcium + phosphate salts (compressive strength)
what other structural feature of compact bone provides strength on all sides?
collagen is laid in different directions in each lamella
what is the ground substance of bone ECM mainly composed of? what process do these contribute to?
- glycoproteins and proteoglycans
* calcification - increased ion binding capacity
what are osteoclasts? (2)
- derived from haematopoietic stem cells
* responsible for bone reabsorption
what are osteoblasts? (3)
- responsible for bone formation
- regulate (paracrine action) osteoclastic bone reabsorption
- derived from mesenchymal cells
what are osteocytes? what proportion of bones cells do they represent?
- possibly sense mechanical loads
- have dendritic structure for communication
- responsible for bone remodelling
- form when osteoblasts are entombed within hard, mineralised bone (ie. initially derived from mesenchymal cells)
• 90% of bone cells are osteocytes
what is the structure of a long bone? (5)
- long tube-like diaphysis
- medullary cavity at centre of shaft with cancellous bone
- 2 epiphyses with articulate surfaces for cartilage and joints
- epiphyseal growth plate between diaphysis and epiphysis until fusion (becomes epiphyseal line)
- layer of external and internal connective tissue called the periosteum and endosteum
what is the difference between endochondral ossification and intermembranous ossification? when do these processes occur?
- endochondral is the process of bone gradually replacing a cartilage mould (primary and secondary ossification centres at the diaphysis and epiphyses respectively)
- intermembranous is present in flat bone development in which no cartilage mould is required and bone is laid on top of bone
• primarily occurs during embryogenesis - may also occur during repair
describe the longitudinal growth of bones (6)
1 - cartilage proliferates on epiphyseal side of growth plate
2 - produces columns of chondrocytes embedded in matrix
3 - chondrocytes enlarge and hypertrophy
4 - produce alkaline phosphatase to endure calcification of matrix
5 - osteoblasts add osteoid (organic part of bone) onto calcified matrix
6 - deposited trabecular bone is remodelled and incorporated into diaphysis
at roughly what age does the epiphyseal growth plate fuse?
25 years
describe appositional growth of bone
1 - bone is laid beneath the periosteum
2 - when bone has reached optimal thickness, osteoclasts reabsorb bone
3 - rate of production and absorption is the same, therefore thickness is maintained
what unit carries out bone remodelling?
bone multicellular unit - coupled osteoblasts and osteoclasts activity
what is the composition of cartilage (2)
- large unbranched polysaccharide molecules - glycoaminoglycans
- arranged in association with collagen fibres (mostly CII)
what is the role of GAGs and collagen in cartilage?
- GAGs hydrate the matrix, making it less rigid than bone
* collagen provides mechanical stability (compressive resistance)
what cells are involved with GAGs?
- chondroblasts produce
* chondrocytes maintain
what is the perichondrium? what type of collagen is it made up of?
- covering on most hyaline cartilage (except articulate cartilage)
- collagen I fibrils
from what cells do cartilage cells develop?
mesenchymal stem cells
describe how cartilage forms (5)
1 - mesenchymal cells proliferate and become tightly packed
2 - begin to differentiate into chondroblasts
3 - secrete cartilage matrix
4 - as more matrix is laid down cells become les metabolically active and become chondrocytes
5 - chondrocytes occupy lacunae (small cavities) in matrix to maintain it
how can chondroblasts and chondrocytes be distinguished under the microscope?
• chondroblasts are larger, have darker cytoplasm and increased Golgi
what are the major GAGs in cartilage? what structure can they form?
- hyaluronic acid
- chondroitin sulphate
- keratin sulphate
• joined to aggregate core to form a proteoglycan
what are the features of hyaline cartilage and where is it found? (3)
- collagen II fibres orientated along lines of stress
- resistant to wear
- covers surface of most synovial joints due to increased mechanical stress, also present in the epiphyseal growth plate
what are the features of elastic cartilage and where is it found? (3)
- more elastic fibres and lamellae than hyaline cartilage
- has more resilience and recoil ability
- found in ear and epiglottis
what are the features of fibrocartilage and where is it found? (2)
- mostly collagen I fibres embedded in fibrocollagenous support matrix
- found in discs within joints (eg. knee joint)
what is the definition of the extracellular matrix?
non-cellular component of tissues and organs
what are the 2 types of ECM?
- interstitial - surround cells, structural ‘scaffolding’ for tissues
- basement membrane - separated epithelium from surrounding stroma
what are 4 ways that ECM can support / aid tissue?
- structural support (eg. tensile strength)
- adhesive
- signalling
- chemical environment
what are the 2 parts of interstitial ECM?
- fibres (collagen and elastin)
* ground substance
what are the 5 classes of macromolecules associated with interstitial ECM?
- collagens
- elastin
- proteoglycans
- hyaluronic acid (GAG)
- other glycoproteins
what is the structure of collagen? (amino acid pattern + shape)
- Gly - X - Y repeating pattern
* 3 polypeptide chains forming a triple helix
what are the 2 major arrangements of collagen (+ purpose), and what types form each arrangement?
- fibrillar - I, II, III (strength)
* sheet - IV (support or filter in basement membrane)
where are the 4 major types of collagen found?
I - dermis, tendons, ligaments, bone, fibrocartilage (hard stuff)
II - hyaline cartilage (other hard one)
III - (reticulin) liver, bone marrow, lymphoid organs, granulation tissue (soft stuff)
IV - basement membranes
what other molecule is required to form elastin into functional fibres?
fibrillin
what stain is used to highlight elastin fibres?
van Giessen stain
what are the 4 types of typical elastin arrangements in the ECM? compare their relative ‘strengths’ and where they are located
- loose, irregular - some strength (lymphoid tissue)
- dense, irregular - increased strength (dermis)
- dense regular - max strength (tendons, ligaments)
- super-specialised - max strength (bone, cartilage)
what is ground substance? what is it made up of?
- amorphous, non-fibrous substance surrounding cells
* water and macromolecules (mainly GAGs and proteoglycans)
what are the main GAGs found in 1. synovial fluid, 2. cartilage, 3. basement membrane
1 - hyaluronic acid (max hydration)
2 - chondroitin sulphate + keratin sulphate
3 - heparan sulphate
what are the primary proteoglycan cores in 1. widespread areas (involved in ECM assembly and growth factor regulation), 2. cartilage, 3. basement membrane
1 - decorin
2 - aggrecan + syndecan
3 - perlecan
what special molecules are involved in the basement membrane? (2)
- integrins - in hemidesmosomes on cell surface connect to
* laminins - act as organiser and maintains the basement membrane
how are collagen IV and laminin arranged in the basement membrane?
- assembled separately independent of scaffolds
* links together with indigenous and perlecan
what are the 7 functions of the basement membrane?
- support
- bind to underlying tissue
- mediate signals between cells and connective tissue
- determines cell polarity
- permits flow of nutrients (permeability)
- path for cell migration
- barrier to downward growth
what are 4 disorders of the basement membrane?
- cancer - epithelial tissue are malignant once BM is breached
- diabetes mellitus - thickening of BM in glomerulus changes permeability
- epidermolysis bullosa - attachment of epidermis to BM
- Goodpastures syndrome - autoantibodies to collagen VI destroy BM in glomerulus and lung
describe the synthesis of collagen (2)
1 - initially synthesised as procollagen by fibroblasts
2 - modified by glycosylation and hydroxylation
describe the synthesis of elastin (4)
1 - initially synthesised as tropoelastin by fibroblasts
2 - modified by hydroxylation
3 - has fibrillin scaffold for assembly
4 - made up of cross-linked fibres
what are 4 disorders of the ECM?
- Supravalvular Aortic Stenosis (SVAS) - heart defect resulting from faulty elastin
- Marfan Syndrome - affects connective tissues due to mutations of fibrillin gene: vision problems, aortic defects, abnormally long limbs
- Ehlers-Danlos Syndrome - affects connective tissues due to mutation in collagen genes (particularly collagen I): hypermobility, fragile + stretchy skin, chronic pain
- Alpert Syndrome - chronic kidney disease sue to affected glomerulus structure (collagen IV)
what is an articulation?
where 2 or more bones make contact
describe fibrous joints
bones connected by dense, fibrous connective tissue
what are the functional classifications of fibrous joints? give examples
- synarthrosis: strong and permit almost no movement - sutures, gomphosis (hold teeth in place)
- amphiarthrosis: permit more movement than synarthrosis - syndesmosis (bones connected by ligaments eg. tibia and fibula)
describe cartilaginous joints. what is the difference between primary and secondary?
• bones joined by cartilage - allow more movement than fibrous joints
- primary - united by hyaline cartilage (epiphyseal growth plate, costco sternal joint)
- secondary - known as symphyses, covered by hyaline cartilage but joined by fibrous cartilage (IVD)
what are the functional classifications of cartilaginous joints? give examples
- synarthrosis: synchrondosis (1st sternocostal joint)
* amphiarthrosis: symphysis (articulating bones separated by wedge eg. between pubic bones)
what are synovial joints? what is their functional classification?
- bones are not directly joined
* all synovial joints are diarthrosis
describe the structure of a synovial joint
- articulated capsule encloses the joint and is lined by synovial membrane
- has articulated / synovial cavity containing synovial fluid
what are the 6 types of synovial joint? give the axises they move on and example locations
UNIAXIAL
• pivot: rotation on an axis - atlanto-axial joint
• hinge: flexion and extension - elbow joint
• plane: gliding and sliding motions - acromioclavacular joint
BIAXIAL
• condyloid: permits abduction, adduction, flexion, extension and circumduction - metacarpophalangeal joint
• saddle: saddle-shaped heads with movement in 2 planes - carpometacarpal joints
MULTIAXIAL
• ball and socket - hip and shoulder joint
what is the definition of osteoarthritis?
a progressive disorder of the joints caused by gradual loss of cartilage, resulting in the development of bones spurs and cysts
what are the anatomical features of a joint exhibiting osteoarthritis? (7)
- thickened capsule
- synovial fluid leakage forming cysts in bone
- sclerosis (hardening) of subchondral bone (beneath joint)
- fibrilated cartilage - softening and loss of structure
- osteophytic lipping - boney overgrowth
- synovial hypertrophy
- altered bone contour
what changes are exhibited by articulated cartilage in osteoarthritis? (4)
- swelling
- colour change
- cartilage fibrillation
- erosion down to subchondral bone
what are features of the pathogensis of osteoarthritis? (4)
- initial increase in water content, then decreased with chronicity (ie. longer time)
- decreased proteoglycan synthesis
- decreased collagen cross-linking
- decreased aggrecan, GAG and hyaluronic acid size
what type of joints are most commonly affected by osteoarthritis?
- weight-bearing joints (hip and knee)
* joints of the hand, foot and spine
what is the difference between primary and secondary osteoarthritis?
- primary has an unknown cause but related to degeneration over time
- secondary usually has a traumatic cause
what are the systemic risk factors of primary osteoarthritis? (4)
- age over 45
- being female
- genetics
- nutrition (decreased vit C and D)
what are the bio mechanical risk factors of primary osteoarthritis? (3)
- obesity
- occupation - more wight-bearing labour
- hypermobility
what are 4 common causes of secondary osteoarthritis?
- trauma
- congenital abnormalities
- occupational hazards (eg. knee joint of footballers)
- avascular necrosis (sickle cell) and other bone diseases
what are the key symptoms of osteoarthritis? (3)
- pain - particularly performing weight-bearing activities
- short-lived stiffness in morning - improves in 30 mins or less with movement
- difficulty moving affected joints / doing certain activities
what features of osteoarthritis should be checked for in a history? (5)
- pain
- decreased walking distance
- sleep disturbance
- limp (loose hip abductors)
- stiffness
describe how osteoarthritis initially develops (4)
- balance between cartilage production and degradation is lost (net loss of articular cartilage)
- localised breakdown by chondrocytes
- variable cartilage loss - irregular surface
- inflammation of synovium and joint capsule (debris)
describe how osteoarthritis progresses in later stages? (7)
- secondary bone changes result from cartilage loss
- articulation of bone on bone
- polishing of subchondral bone (eburnation)
- cyst development
- cartilaginous overgrowths (calcified = osteophytes)
- synovial hyperplasia / hypertrophy
- joint immobility
what is the structure of a skeletal muscle fibre?
- multinucleated
- unbranded
- striated
- cells combined to make long continuous fibre
what is the sarcolemma?
a thin membrane surrounding the muscle fibre - also connects to tendons at either end
what 2 proteins primarily make up a myofibril?
- ‘thick’ myosin filaments (dark bands)
* ‘think’ actin filaments (light bands)
what do the ends of the actin filaments attach to? what structure runs along this line?
- Z disc
* T tubules
what is the A band of a sarcomere? what is the I band? what is the H zone? what is the M line?
- A - contains mostly myosin with some part overlapping with actin
- I - contains mostly actin, so are lighter than the A band
- H - brighter central region of the A band where there is no actin overlap (present in relaxed state)
- M - dark line bisecting the H zone (formed by cross-connecting elements of cytoskeleton)
describe how contraction of skeletal muscle is caused (8)
1 - action potential travels along motor neurone to nerve endings on muscle fibre
2 - at endings, acetylcholine is secreted
3 - ACh acts on local area of muscle fibre by opening ligand-gated ion channels
4 - Na+ diffuse through channels into muscle fibre causing depolarisation, and opening voltage-gated Na+ channels to initiate AP
5 - depol. propagated along muscle fibre
6 - AP reaches centre of a fibre (cylinder of myofibrils), causes sarcophagi can reticulum to release Ca2+ ions
7 - Ca2+ ions initiate attractive forces between actin and myosin, causing them to slide alongside each other (decrease distance between Z discs)
8 - Ca2+ ions removed by pumps and returned to reticulum to stop contraction
describe the cellular structure of a skeletal muscle fibre (6)
- sarcoplasma suspends myofibrils
- myofibrils arranged into cylinders around each other
- myonuclei are flattened and pressed against the sarcolemma
- mitochondria lie between myofibrils
- ER replaced with sarcoplasmic reticulum (Ca2+)
- at level of Z discs, there are 2 terminal cisternae with a T tubule between
what are T tubules?
- extensions of the cell membrane that penetrate deep into the muscle cell
- permit rapid transmission of AP into the cell
what are the 3 components of the actin filament?
- G actin - units that make up the double helix
- tropomyosin - molecule that wraps spirally around actin helix -> block myosin binding sites in resting state
- troponin - 3 subunits in 1 complex
what are the 3 subunits of troponin?
- troponin C - receives a conformational change from calcium
- troponin T - amplifies change along tropomyosin
- troponin I - has an inhibitory effect on myosin binding sites -> pulls tropomyosin from binding site when shape changes
describe actin-myosin interactions during contraction (5)
1 - before contraction begins, heads of myosin bind with ATP
2 - heads act as ATPase and energy is stored as head to extends towards actin (ADP and Pi remain bound)
3 - when troponin-tropomyosin complex binds to Ca2+, active sites on actin are uncovered and myosin binds
4 - process of bind causes conformational change in head - tilts towards arm of myosin called power stroke (uses up energy)
5 - ADP and Pi are released from myosin, and new ATP binds, causing myosin head to detach from actin -> new cycle
