MSK Flashcards
What are the 7 key functions of bones?
- Storage of minerals (e.g. calcium)
- Transmission of body weight
- Protection of vital organs and structures
- Anchorage - lever system for movement
- Determination of body shape
- Raises body from ground against gravity
- Houses bone marrow to facilitate haematopoeisis
What are the two skeletons?
- Appendicular (126 bones) = green one
- Axial (80 bones) = white one
What are the five types of bone classification by shape?
- Long bones = tubular shape with hollow shaft and ends expanded for articulation, e.g. femur
- Short bones = cuboidal in shape, e.g. carpal bones
- Flat bones = plates of bones, often curved, protective function, e.g. sternum
- Irregular bones = shapes vary, often specific to function, e.g. mandible
- Sesamoid bones = round, contain nodules for tendon attachment, e.g. patella
What are the two types of bone structure macroscopically?
- Cortical/compact = dense, solid, incorporates spaces for blood vessels and cells
- Trabecular/spongy = formed from a network of struts (trabeculae), spongy appearance, many spaces filled with bone marrow
What are the two types of bone classification microscopically?
- Primary/woven = made quickly, disorganised, no clear structure
- Secondary/lamellar = made slower, organised, clearly structured
How does the bone structure contribute to function?
- Hollow long bone = keeps mass away from neutral axis, minimises deformation
- Trabecular bone = gives structural support while minimising mass
- Wide ends = spreads load over weak, low friction surface
- Flat bones = protective
What is bone composed of?
- 50-70% mineral (mainly hydroxyapatite)
- 20-40% organic matrix = collagen (type 1) is 90%, non-collagenous proteins = 10%
- 5-10% water
What are the cells of the bone?
- Osteoclasts = multinucleated
- Osteoblasts = plump, cuboidal
- Osteocytes = stellate, entombed in bone
- Bone lining cell = flattened, lining the bone
What is the origin of osteoblasts?
Mesenchymal stem cells
What do osteoblasts do?
- Blast = build, so form bone in the form of osteoid
- Produce type 1 collagen
- Make non-collagenous proteins
- Secrete factors that regulate osteoclasts
What are osteoclasts formed from?
Haematopoeitic stem cells
What are the functions of osteoclasts?
- Resorb bone
- Dissolve the mineralised matrix
- Break down collagen in the bone
What is the difference between bone modelling and bone remodelling?
- Bone modelling = gross shape is altered, bone added or taken away
- Bone remodelling = all the bone is altered, new bone replaces old bone
Why does bone remodelling occur?
- Forming bone shape
- Replacing woven bone with lamellae
- Reorientation of fibrils and trabeculae to reinforce mechanical strength
- Response to load
- Calcium release
- Damage repair
What are the 5 steps of bone remodelling?
- Activation = monocytes on bone surface differentiate to become osteoclasts
- Reabsorption = osteoclasts secrete acid to dissolve the bone mineral
- Reversal = osteoblasts are stimulated/recruited
- Formation = osteoblasts secrete osteoid to form bone matrix
- Quiescence = without stimulation there is no action
How many amino acids does one collagen fibre contain? What is every third amino acid?
- One collagen fibre = around 1000 amino acids
- Every third amino acid is glycine
What are the stages of collagen synthesis?
- 3 collagen models come together to form a triple helix called tropocollagen
- It is secreted from a fibroblast, here its polypeptides are removed
- Tropocollagen molecules then form covalent cross links between one molecule’s lysine and another’s hydrolysine - this process forms microfibrils
- Microfibrils combine forming fibrils
- Fibrils combine to form fibres
- Fibres form fascicles which are enclosed in endotendon
- The tendon is enclosed in the epitendon
Which bonds join collagen together?
- Covalent cross-links = within and between tropocollagen
- Hydrogen bonds = between hydroxyproline molecules, within tropocollagen
- Between the tropocollagen molecules
What is collagen broken down by?
Enzymes called proteinases, especially collegenases and cathepsin K
What is the process of bone formation known as? What are the two main types?
- Ossification
- Endochondral = bone forms from a hyaline cartilage precursor, occurs during foetal development, long bone formation, and fracture healing
- Intermembranous = bone forms directly from mesenchyme, occurs during foetal development to form flat and irregular bones
What happens in endochondral ossification?
- Chondrocytes produce a cartilaginous precursor
- Primary ossification centre is formed as osteoblasts lay bone onto the cartilage
- Osteoclasts break down the cartilage
- POC is vascularised as blood vessels invade
- Periosteum collar is formed outside the bone as perichondrium is broken down
- Parts of the spongy bone making up the POC are broken down to form the medullary cavity
- Process repeats at ends of long bones to form the secondary ossification centre
- Some layers of cartilage remain between SOC and POC, known as the epiphyseal (growth) plate
What happens in intermembranous ossification?
- Mesenchymal stem cells replicate, forming clusters called nidus
- Stem cells in nidus become osteoprogenitor cells
- Osteoprogenitor cells differentiate into osteoblasts
- Osteoblasts produces extracellular matrix containing T1 collagen fibres
- Some osteoblasts become trapped in matrix, forming osteocytes
- Bond spicules form via mineralisation
- Spicules grow and fuse to form trabeculae, around which periosteum is now formed
What does the epiphyseal plate allow? What does the size of the growth plate increase with?
- Epiphyseal (growth) plate = allows continued growth of long bones in childhood and adolescence
- Size of growth plate increases with constant chondrocyte division
- Some chondrocytes simultaneously degenerate - they are then ossified by osteoblasts
- This process continues throughout growth, after puberty the epiphyseal plate is completely ossified (fused) and growth ceases
What are the 3 general aspects of bone growth?
- Mineralisation = hydroxyapatate crystals being deposited into the bone fibrous matrix, hardens bone, vitamin D and PTH mediated
- Modelling = occurs during growth, osteoblasts building and osteoclasts breaking down to form overall shape
- Remodelling = occurs after growth, alteration and replacement of old bone with new, occurs via blast and clast activity similar to modelling
What stimulates PTH (parathyroid hormone) secretion? What does PTH do?
- Decreased serum calcium results in increased PTH secretion
- PTH increases bone remodelling rates and calcium RESORPTION
- Presence of PTH leads to the conversion of 25-hydroxyvitamin D (calcidiol) to the active 1,25-dihydroxyvitamin D (calcitriol = active vitamin D)
- Combined effect leads to an increase in serum Ca2+ levels
Can Vitamin D be directly consumed? What does active vitamin D cause?
- Vitamin D cannot be directly consumed, and we don’t actually absorb it from the sun
- Active vitamin D increases calcium absorption and is fundamental in maintaining bone mineral density
How is vitamin D synthesised?
- 7-dehydroxycholesterol is synthesised directly from ingested cholesterol
- This is converted to Vitamin D3, facilitated by UVB radiation from the sun
- Vitamin D3 is converted to 25-hydroxyvitamin D (CALCIDIOL) in the liver, via the cytochrome p450 system
- Calcidiol is converted to 1-25-dihydroxyvitamin D (CALCITRIOL) in the presence of PTH
- The presence of calcitriol can then go on and promote gut calcium ion absorption
What is calcitonin produced by? What is its function?
- Calcitonin is produced by C cells (parafollicular cells) in the thyroid gland
- Action not really known, however is secreted in response to serum calcium ion increase, so it is potentially involved in the negative feedback mechanism to reduce bone reabsorption
Where is dietary calcium sourced from? How is extracellular calcium accumulated? How is extracellular calcium used?
- Dietary calcium sources included dairy, vegetables, and oily fish
- Extracellular calcium accumulated via bone resorption, reabsorption in the kidney or absorption in the small intestine
- Extracellular calcium used in bone deposition, kidney filtration and secretion in the small intestine
Draw out calcium homeostasis.
What is the most important regulator of serum phosphate concentration? What is produced by in response to?
- FGF-23
- Produced by osteocytes in response to:
- Rise in serum PO4-
- Presence of PTH
- Presence of calcitriol
What does FGF-23 bind to? What does this result in? What is it inhibited by?
- Binds to Klotho-FGF receptors, resulting in decreased expression of Na+ cotransporters in renal tubules
- It also decreases calcitriol formation
- Resulting in increased PO4- excretion + decreased reabsorption
- FGF-23 secretion by PHEX when serum phosphate levels fall
Where is dietary phosphate sourced from? Where is extracellular phosphate accumulated from? Where is extracellular phosphate used?
- Dietary phosphate is sourced from meat, diary, nuts, and seeds
- Extracellular phosphate is accumulated via bone resorption, gut absorption, or renal reabsorption
- Extracellular phosphate is either used in bone formation, or is excreted (urine/faeces)
Should there be any difference between osteoblast and osteoclast activity? What do they usually communicate via?
- Osteoblast and osteoclast activity is balanced in health - a loss of balance is pathological
- They usually communicate via cytokines, with some OPG (osteoprotegerin) and RANK signalling
What two qualities do cytokines possess?
- REDUNDANT = many different types can perform one job
- PLEIOTROPIC = can initiate effect on many different tissues
What is the role of the RANK ligand? How does it achieve this?
- RANK ligand stimulates increased osteoclast activity, increasing bone reabsorption:
- Secreted by osteoblasts
- Binds to RANK receptors on monocytes
- Monocytes differentiate to osteoclasts which actively reabsorb bone
- Osteoblasts secrete more RANK ligands in the presence of oestrogen (as well as other hormones, GFs, and cytokines)
What is the role of osteoprotogerin (OPG)? How does it achieve this?
- Osteoprotogerin (OPG) inhibits osteoclast activity, allowing increased bone formation:
- Produced by osteoblasts and stromatolites cells
- Binds to RANK ligands, preventing osteoclast activation
- Decreases reabsorption rates
What is Wolff’s law?
- Wolff’s law: in a healthy individual, bone will remodel itself to become more resistant to loading
- If bone loading increases, bone will remodel itself to become more resistant to loading
- These changes result in responsive variation of bone density in appropriate areas
What are actin and myosin made up of?
- Actin:
- Thin filament comprising two g-strands, forming an f-actin helix
- Globular protein + has troponin and tropomyosin incorporated
- Interacts with myosin
- Myosin:
- Thick filament comprising 2 heavy chains and 4 light chains
- Hydrolyses ATP
- Interacts with actin
What are tropomyosin and troponin made up of?
- Tropomyosin:
- Thin filament made up of 2 helical peptide chains
- Occupies each of the longitudinal grooves between 2 actin strands
- Regulates muscle contraction
- Troponin = 3 types, all thin filaments:
- Troponin C = binds to calcium ion
- Troponin I = inhibits myosin and actin action
- Troponin T = binds to tropomyosin
What happens in contraction coupling?
- An impulse reaches the neuromuscular junction
- Presynaptic membrane depolarises, opening voltage-gated Ca2+ channels, enabling Ca2+ influx
- Vesicles migrate and fuse with the presynaptic membrane, releasing ACh into the synaptic cleft via exocytosis
- ACh binds to receptors on the sarcomere, depolarising the sarcomere (through LGSICs and Na+ influx)
- This results in T-tubule depolarisation, and subsequent depolarisation of the sarcoplasmic reticulum
- Sarcoplasmic reticulum releases Ca2+ - this initiates sarcomere contraction
What happens in molecular sarcomere contraction?
- Ca2+ ions from the sarcoplasmic reticulum bind to troponin C, resulting in a conformational change of troponin
- Troponin moves, exposing actin filament binding sites
- Myosin head binds to actin, forming cross links - power stroke is formed, shortening the sarcomere
- ATP binds to myosin head and is hydrolysed, this releases energy, breaking the cross links, resulting in the detachment of actin and myosin
- Myosin head reattached to the next actin binding site and the cycle is repeated, continuing sarcomere shortening and muscle contraction
What are the differences between ligaments and tendons?
- Ligaments = bone to bone, low Type I collagen levels, high elastin content, random organisation, blood supply for prom insertion points
- Tendons = bone to muscle, high Type I collagen levels, low elastin content, highly organised, many are avascular, but some receive blood from surrounding sheath
What are the types of attachment (enthuses)?
- Fibrous = formed vis intramembranous ossification, tendon or ligament attached to bone via Sharpey’s fibres
- Fibrocartilagenous = formed by endochondral ossification, tendon or ligament attached to the bone through a gradual change from collagenous ligament, to fibrocartilage, to mineralised bone
Explain the shape of the load-elongation graph in tendons and ligaments
- Phase 1 = “toe” region of graph, increase in load results in crumpled collagen fibres
- Phase 2 = linear region, fibres straighten and stiffness rapidly increases with loading
- Phase 3 = maximum deformation and ultimate tensile strength, at this point, progressive fibre failure occurs
- Phase 4 = yield point, beyond this point there is complete failure of connective tissue to support loads
What does a hip joint consist of an articulation between? What are these two structures covered in?
- The head of the femur and the acetabulum of the pelvis
- Covered in articular cartilage
What is the blood supply of the hip?
What is the blood supply of the thigh?
What is the nerve supply of the thigh?
- Femoral nerve
- Sciatic nerve
- Obturator nerve
Where are the common sites for intramuscular injections? Why?
Upper lateral quadrant of the gluteus is the most common site for intramuscular injections as it avoids all major nerves and blood vessels
How do we classify joints by degree of movement?
- Immobile, slightly mobile, freely mobile
- Mostly fibrous, mostly cartilaginous, mostly synovial
How do we classify joints by structure?
- Held together by fibrous tissue
- Held together by cartilage
- Held together by a synovial fluid filled capsule. All have articulations cartilage, a joint capsule, a joint cavity, synovial fluid, and reinforcing ligaments
What are the characteristics of:
a) ball & socket joint
b) condyloid
c) hinge joint?
a) - ball within a socket
- wide range of movement in all planes
- shoulder and hip joint
b) - oval sitting within an oval cavity
- movement in two planes
- metacarpophalyngeal
c) - elongated oval in a curved socket
- large range of movement in a single plane
- elbow
What are the characteristics of:
a) pivot joint
b) saddle
c) gliding joint?
a) - bone pivots around an axis
- allows a large amount of rotation
- C1/C2
b) - two saddle shaped surfaces articulating
- movement in two planes
- thumb
c) - two flat surfaces articulating
- limited movement in 2 planes
- carpal joints
What are the ligaments, bursae and meniscus of the knee?
- Ligaments:
- patella ligament
- collateral ligaments (medial + lateral)
- cruciate ligaments (anterior and posterior)
- Bursae = sac filled with synovial fluid that acts to reduce wear and tear
- Menisci:
- C-shaped fibrocartilage
- Acts as shock absorbers
- Deepen the articular surface thus increasing the stability of the joint
What is the largest sesamoid bone in the body? What do the ACL and PCL prevent?
- Largest sesamoid bone = patella, allows quadriceps to be able to extend the knee better
- ACL prevents anterior dislocation of the tibia into the femur and the PCL prevents posterior dislocation
What are the attachments, innervation and actions of deltoid and teres major?
Which features of the shoulder joint provide it with motility?
- Type of joint - ball and socket
- Bony surfaces - shallow glenoid fossa and large numeral head
- Laxity of the joint capsule
Which features of the shoulder provide stability?
- Rotator cuff muscles = surround shoulder joint, attaching to the tubercles of the humerus and fuse with joint capsule, resting tone of these muscles pulls the numeral head into the glenoid fossa
- Glenoid labrum = fibrocartilagenous ridge surrounding + deepening the glenoid fossa
- Ligaments = reinforce joint capsule, form the coraco-acromial arch
What is the ‘socket’ of the shoulder called?
Glenoid fossa
What is the olecranon an important attachment for? Which nerve does it run alongside?
- Attachment site for the triceps tendon
- Known as the ‘funny bone’, runs alongside the ulnar nerve
What is gout caused by?
- High uric acid levels in the blood cause urate/uric acid crystals to deposit in the joints
- The crystals cause inflammation, which then causes the swelling, pain + redness
How does uric acid leave the body?
- Excreted in the urine
- Breakdown in the gut
What is rickets caused by?
- Rickets is a skeletal disorder that’s caused by a lack of vitamin D, calcium, or phosphate
- People with rickets may have weak and soft bones, and, in severe cases, skeletal deformities
What is osteoporosis?
Disease characterised by low bone mass and microarchitectural deterioration of bone tissue in the absence of mineralisation defect, with a consequent increase in bone fragility and susceptibility to bone fracture
What is a fracture? When do fractures occur?
- Fracture = breach in continuity of the bone
- Fractures occur when:
- non-physiological loads are applied to normal bone
- physiological loads are applied to abnormal bone
What are the questions asked during a fracture assessment?
- Which bone and which section? E.g. proximal 1/3 of the tibial shaft
- What is the nature of the fracture (aka what type)? E.g. transverse, comminuted etc.
- What angle is the displacement in the most distal section of the break?
- Is it intra-articular (involving the joint) or extra-articular (outside the joint)?
- Is the fracture open (breaks the skin) or closed (doesn’t break the skin)
What are the three ways to describe the site of a fracture?
What are the 8 types of fracture?
- Transverse
- Linear
- Oblique, non-displaced
- Oblique, displaced
- Spiral
- Greenstick
- Comminuted
- Avulsion
Describe the first two stages of fracture healing.
- Haematoma formation:
- Traumatic rupture of blood vessels at the fracture site
- Bleeding –> haematoma formation
- Reduced blood supply to bone cells, starving them of nutrients - Fibrocartilage (soft) callus formation:
- New capillaries grow at the fracture site, supplying nutrients for repair
- Dead tissues undergo phagocytosis
- Connective tissues (collagen and fibrocartilage) form a repair tissue (soft callus)
Describe the last two stages of fracture healing.
- Bony Callus formation:
- Osteoblasts and osteoclasts migrate to the fracture site and divide
- They replace soft fibrocartilage with spongy bone to form a hard callus
- Forms a bulge at fracture site - Bone remodelling
- Bony callus is remodelled in response to mechanical stress (see Wolff’s law)
- Strong, permanent patch at the fracture site is formed
- New bond is stronger and more compact
