CASE 9 - bone, stress fractures, muscle Flashcards
what is woven bone?
- primary bone
- appears in embryonic development and fracture repair as it can be laid down rapidly
- consists of osteoid (unmineralised ECM), with the collagen fibres arranged randomly
- it is a temporary structure, soon replaced by mature lamellar bone
what is lamellar bone?
- secondary bone — the bone of the adult skeleton
- consists of highly organised sheets of mineralised osteoid — this organised structure makes it much stronger than woven bone
- can be divided into 2 groups — compact and spongy
what is endochondral ossification?
where hyaline cartilage is replaced by osteoblasts secreting osteoid (eg. occurs in femur)
what is intramembranous ossification?
where mesenchymal (embryonic tissue) is condensed into bone. forms flat bones such as the temporal bone and scapula
what are the steps involved in the repair of a bone fracture?
- formation of a haematoma at the site of fracture
- migration of fibroblasts to the fracture site
- bridging of broken ends by a fibrocartilaginous callus
- osteoblast production of trabeculae and bony callus formation
- resorption of remaining bone fragments and remodelling of bone
describe osteogenesis
- osteoblasts secrete collagen molecule and ground substance (extrafibrillar matrix)
- collagen molecules combine to form collagen fibres
- the resultant tissue is called osteoid (non-calcified bone)
- hydroxyapatite crystals form on the collagen fibres. the osteoid is now calcified and this is bone
what produce new bone, secrete osteoid and are responsible for mineral depostition?
osteoblasts
what are mature bone cells located in lacunae and maintain the matrix?
osteocytes
how do osteoclasts work?
- osteoclasts adhere to an area of trabecular bone
- they dig a pit by secretion H+ and proteolytic enzymes (osteolysis)
- this secretes cytokines such as IGF-1 and TGF-B that have been embedded into the osteoid
- these cytokines recruit and activate ostoblasts that have been stimulated to develop from osteoprogenitor cells
- osteoblasts invade the site, synthesising and secreting the organic matrix of the bone (the osteoid) and secreting IGF-1 and TGF-B
- the osteoid is then calcified into bone
- some osteoblasts become embedded in the osteoid, forming terminal osteocytes
where are osteogenic stem cells found?
endosteum and periosteum
what do osteogenic stem cells develop into?
osteoblasts
what is a stress fracture?
= a fracture occurring in normal bone that has been subject to excessive and repeated trauma resulting in cumulative microscopic fractures
- over time, these micro fractures exceed the capacity of the normal healing process, resulting in the development of a macrofracture
micro damage > repair process —> stress response —> stress fractures
where do stress fractures commonly occur?
in poorly vascularised areas eg. 5th metatarsal, navicular, anterior tibia
signs and symptoms of stress fracture
- pain, localised tenderness and swelling gradually develop
- percussion of bone away from fracture may illicit pain
X-RAYS in stress fractures
- initially normal
- plain x-ray is 1st line imaging — initially normal or very subtle with radiolucency and poor definition of the cortex
- later on, thickening and sclerosis of endosteum and periosteum new bone formation
MRI in stress fracture?
- has taken over from bone scan
- can pick up a stress response before a stress fracture
what would be measured in bloods for a stress fracture?
vitamin D levels, bone profile, hormone levels
when is a bone scan good for stress fractures?
if worried about multiple non-continuous stress fractures eg. 2nd or 5th metatarsal fracture in combination with tibial fracture
management of stress fractures?
- rest and immobilisation
- avoid NSAIDs (can slow down bone healing)
- get patient on board
- pulsed ultrasound or extracorporeal shock wave therapy (ESWL)
describe pulsed ultrasound
upregulates chondrocytes and increases endochondral ossification
describe ESWL
induces periosteal detachment and micro trabecular fracture — stimulates fracture healing
what is the indication for surgery for a stress fracture?
the presence of the “dreaded black line” in tibia. surgery is only used when conservative management has failed
what is shin splints caused by?
repeated trauma to the connective muscle tissue surrounding the tibia
what is a common cause of shin splints?
over pronation
- pronation occurs when the ankle bone moves downward and towards the middle to create a more stable point of contact with the ground (ie. the ankle rolls inwards so that more of the arch has contact with the ground)
- this abnormal movement causes muscles to fatigue more quickly and unable to absorb any shock from the foot hitting the ground
pain associated with shin splints is caused from a disruption of what?
Sharpey’s fibres that connect the medial soleus fascia through the periosteum of the tibia where it inserts into the bone
with repetitive stress, impact forces fatigue the ____ and created repeated ___ bending
- soleus
- tibial
the impact causing shin splints is worsened by what?
running uphill, downhill, on uneven terrain or on hard surfaces
also wearing improper footwear
how are shin splints treated?
- rest
- applying ice to shin to reduce blood flow
- elevation of legs reducing swelling and pain killers/anti-inflammatories
why might ACL tears be more common in women?
- physical conditioning
- muscular strength
- neuromuscular control
- pelvis size — females have wider hips and so working their legs will cause the vastus lateralis to develop more than the vastus medialis, thus pushing the patella laterally and causing the tear in the ligament
- lower extremity (leg) alignment
- increased looseness in ligaments
- effects of oestrogen on ligament properties
what are causes of ACL tears?
- changing direction rapidly
- stopping suddenly
- slowing down while running
- landing from jump incorrectly
- direct contact or collision eg. football tackle
what are the symptoms of an ACL tear?
- pain with swelling — within 24 hours the knee swells. swelling and pain may resolve on its own. however if sports resumed, the knee will be unstable and there’s risk of further damage to the cushioning cartilage (meniscus)
- loss of full range motion
- tenderness along joint line
- discomfort while walking
why do you get an over rotated hip and how can it cause knee pain?
- internal rotation of femur due to weak gluteus medius, vastus medialis
- creates shear force in femur
- shear force is moving lateral —> medial around knee
what are 3 major factors contributing to the aetiology of patellofemoral pain syndrome?
- quadriceps muscle imbalance and/or weakness
- lower extremity and patellofemoral malalignment
- physical overload of the patellofemoral joint
what is the Q angle?
- angle between force vector of the quadriceps tendon and the force vector of the patella tendon
- women have a greater Q angle
what exacerbates the Q angle?
- a weak gluteus medius —> internal rotation of femur
- over pronation of ankle
management of patellofemoral pain syndrome?
- recovery
- gait analysis
- strengthening
- avoid running downhill and only uphill in recovery face
- orthotics don’t ultimately cure problem
- needs to not be a heel striker
- retrain to become a midfoot to forefoot striker to alleviate pressure to the heel and force transmission into the left leg and right leg — help running gait
what physical activity is recommended for everyone a week?
- 150 mins moderate intensity activity a week, with muscle strengthening activity at least 2 days a week
- minimise sedentary behaviour
what does the stance phase consist of?
- begins with a heel strike, when the heel hits the ground and begins to assume the body’s full weight (mid stance), and ends with a push off by the forefoot — a result of plantarflexion
what muscles are involved in heel strike?
tibialis anterior and gluteus maximus
what is the loading response?
- foot flat
- part of stance phase
what muscle is used in loading response?
quadriceps
what muscles are used in mid stance?
gluteus medius and minimus
what muscles are used in terminal stance (heel off)?
soleus and gastrocnemius (known together as triceps surae
when does the swing phase begin and end?
begins after push off when the toes leave the ground and ends when the heel strikes the ground
what muscles are used in preswing (toe off)?
rectus femoris
what muscles are used in initial and midswing?
iliopsoas and rectus femoris
what muscles are used in terminal swing?
hamstrings, foot and ankle dorsiflexors (the tibialis anterior, the extensor hallucis longus (EHL), and the extensor digitorum longus (EDL)
what % do the swing phase and stance phase occupy of the walking cycle?
swing = 40%
stance = 60%
what are the stance and swing phases also referred to as?
stance - support phase
swing - unsupported phase
what are the ankle, knee, hip and foot joints like in the heel strike phase?
ankle = neutral
knee = flexed
hip = flexed
foot = supinated
what are the ankle, knee, hip and foot joints like in mid stance phase?
ankle = dorsifelxed
knee = extended
hip = neutral
foot = slight pronation
what are the ankle, knee, hip and foot joints like in the toe off phase?
ankle = plantar flexed
knee = flexed
hip = extended
foot = supinated
what are the ankle, knee, hip and foot joints like in acceleration?
ankle = neutral
knee = flexed
hip = flexed
foot = slight pronation
what are osteophytes?
= bony projections that occur at the sites of cartilage degeneration or destruction near joints and iv discs (= a bony projection associated with the degeneration of cartilage at joints)
- form because of the increase in damage joint’s SA
what are enthesophytes?
bony projections that form at the attachment of a tendon or ligament
what are osteophytes on the fingers or toes known as?
- if on distal interphalangeal joint = Heberden’s nodes
- if in the proximal interphalangeal joints = Bouchard’s nodes
the female athlete triad is a syndrome of what 3 interrelated conditions?
- eating disorders (low energy available)
- menstrual dysfunction (amenorrhoea)
- decreased bone mineral density (osteoporosis/osteopenia)
what are clinical symptoms of the female athlete triad?
- disordered eating and fatigue
- noticeable weight loss
- increased healing time from injuries
- increased incidence of bone fracture
- cessation of menses
- may also struggle with low self-esteem and depression
what are signs of female athlete triad syndrome?
- restrictive eating but not meeting the clinical criteria for an eating disorder
- subtle menstrual disturbances such as a change in menstrual cycle length, an ovulation, or luteal phase defects, but not yet have developed complete amenorrhea
- athletes bone density may decrease, but may not yet have dropped below her age-matched normal range
what are the 2 types of amenorrhoea?
- primary — absence of menstruation by 16
- secondary — absence of menstruation for 3 months in a women who has previously had cycles
what can cause the hypothalamus to stop producing GnRH (needed in menstruation)?
excessive weight loss and exercise, as well as stress
causes of amenorrhoea
- polycystic ovary syndrome, where the ovaries dont release the egg (ovulate)
- hypothalamus stops producing GnRH
- hyperprolactinaemia
- premature ovarian failure
what do gonadotropin hormones do?
- stimulate growth of the gonads and the secretion of sex hormones
- play a role in stimulating oestrogen release from the ovaries
what can lead to decreases in oestrogen?
exercising intensely and not eating enough calories
what happens to osteoclasts in an oestrogen deficiency?
they live longer and resort more bone — loss of bone mineral density
how can exercise affect muscle mitochondria?
exercise can increase muscle mitochondria biogenesis (ie. gives more mitochondria per muscle cell)
—> this is probably via Ca++ signalling pathways in the cell as well as via a chronic imbalance of ATP demand vs ATP production by mitochondria which causes activation of signalling protein kinases
describe adenosine monophosphate-activated protein kinase (AMPK) in exercise
- enzyme that plays a role in cellular energy homeostasis
- ‘fuel gauge of the cell’
- during a bout of exercise, AMPK activity increases while the muscle experiences metabolic stress brought about by an extreme cellular demand for ATP
- upon activation, AMPK increases cellular energy levels by inhibiting anabolic energy consuming pathways (fatty acid synthesis, protein synthesis etc) and stimulating energy producing, catabolic pathways (fatty acid oxidation, glucose transport etc)
hope can a lack of exercise lead to atrophy of muscles?
- skeletal muscle atrophy causes a drop in : protein levels, fibre diameter, force production, and fatigue resistance
- a reduction in protein synthesis coupled with increased protein degradation pathways contribute to muscle loss and disuse
- proteolytic pathways are involved in muscle atrophy
- transcription factor NF-kB and myostatin are important cell signallers for muscel cell atrophy. lack of exercise leads to an increase in these factors in muscle
what does muscle hypertrophy result from?
an increase in the number of actin and myosin filaments in each muscle fibre
describe muscle atrophy
- when a muscle remains unused for many weeks, the rate of degradation of the contractile proteins is more rapid than the rate of replacement — therefore muscle atrophy occurs
- the pathway that seems to account for much of the protein degradation in a muscle undergoing atrophy is the ATP-dependent ubiquitin-proteasome pathway
> proteasomes degrade damaged or unneeded proteins by proteolysis
> ubiquintin is a regulatory protein that labels which cells will be targeted for proteasomal degradation
how is muscle length adjusted?
when muscles are stretched to greater than normal length, new sarcomeres are eventually added at the ends of the muscle fibres, where they attach to the tendons
- this increases the length of msucels
what does loss of innervation to a muscle result in?
atrophy
in the final stage of denervation atrophy, what are the destroyed muscle fibres replaced by?
fibrous and fatty tissue
which of the following proteins links actin filaments in skeletal muscle to the outer cell membrane?
- titin
- vinculin
- desmin
- dystrophin
- nebulin
- alpha-actin in
dystrophin
which of the following is NOT a histological characteristic of skeletal muscle?
- branched
- bundles
- striations
- multi-nucleated
- Z lines
branched
which of the following is NOT a feature of type 2B muscle fibres?
- have the highest myosin ATPase activity
- would be the predominant type in a sprinter
- have a limited blood supply
- have a high SA to volume ratio
- they are pale in colour
have a high SA to volume ratio
the recruitment of which type of cell is essential for fracture repair?
- osteocytes
- osteoblasts
- osteoclasts
- bone lining cells
- all of the above
osteoblasts
which of the following occurs first during ligament repair?
- vascular endothelial growth factor increases vessel formation and blood flow
- collagen fibrils align with the ligaments
- platelets interact with matrix proteins to form a clot
- immune cells are recruited to the area and remove damaged cells
- fibroblasts proliferation initiates rebuilding the tissue matrix
platelets interact with matrix proteins to form a clot
function of vinculin?
actin binding protein involved in cell-matrix adhesion and cell-ell adhesion (regulates mechanical force between the cytoskeleton and adhesion receptors)
function of talin?
Talin is a cytoskeletal protein that is localized at cell junctions, links the cytoskeleton to the cell membrane, by binding directly to both the actin filaments and the integrin cytoplasmic tails, and mediates inside-out signaling and integrin activation.
talin binding activates vinculin
links integrins to actin cytoskeleton
function of alpha-actinin?
- protein encoded by the ACTN1 gene
- necessary for the attachment of actin myofilaments to the Z-lines in skeletal muscle cells
function of desmin?
- helps to maintain the structure of sarcomeres
- links z-discs to each other, hence linking neighbouring sarcomeres
function of titin?
- one end of the titin molecule is elastic and is attached to the Z disc, acting as a spring and changing length as the sarcomere contracts and relaxes
- the other part of the titin molecule tethers it to the myosin thick filament
what do all muscles develop from?
paraxial mesoderm
each somite has how many divisions?
3
the hypomere forms what type of muscle?
hypaxial muscles
(epimere = epaxial muscles)
which of the following plays a role in muscle elongation?
- GATA4
- GATS6
- Kindlin-2
- Kindlin-6
- GABA
Kindlin-2
myoblasts that do not form muscle fibres dedifferentiate back into…..?
satellite cells
myoblasts will proliferate if enough of what substance is present?
FGF
once FGF substance runs out, the myoblasts cease division and secrete what other substance onto their ECM?
fibronectin
which substance is required for the fusion of myogenic precursor cells to either new or previously existing fibres?
- myostatin
- PAX7
- myogenin
- MyoD
- Mox2
myogenin
which protein inhibits muscle differentiation and growth?
myostatin
what is the most peripheral layer of fascia?
- perimysium
- ectomysium
- endomysium
- epimysium
- sarcomysium
epimysium
what are elastic filaments composed of?
titin
what line marks the :
1. boundary of the sarcomere
2. centre of the sarcomere
boundary = z line
centre = m line
what type of muscle contraction is this describing?
the force generated is sufficient to overcome the resistance, and the muscle shortens as it contracts
concentric
what type of muscle contraction is this describing?
holding an object up without moving it; the muscular force precisely matches the load, and no movement results
isometric
what type of muscle contraction is this describing?
the tension in the muscle remains constant despite a change in muscle length — this can only occur when a muscle’s maximal force of contraction exceeds the total load on the muscle
isotonic
what type of muscle contraction is this describing?
the force generated is insufficient to overcome the external load on the muscle and the muscle fibres lengthen as they contract
eccentric contraction
where does calcium bind in muscle?
troponin
where does ATP bind?
myosin filament
a lack of what substance will prevent the release of actin from myosin, resulting in the rigor state and characteristic of rigor mortis?
ADP
which type of muscle has a narrow Z-line width and low resistance to fatigue?
type IIb skeletal muscle
people who have the non-mutants version of the ACTN3 gene are more likely to have a higher proportion of which type of muscle?
slow twitch muscle
what can elevated levels of ghrelin cause?
amenorrhoea
during the reparative stage of fracture repair, periosteal cells closest to the fracture gap develop into chondroblasts which form what?
hyaline cartilage
