Lecture 27 - Muscle injury Flashcards
How do muscles get damaged?
laceration strain Surgery Burning or freezing chemical contusion metabolic motor vehicle accident ishaemia-reperfusion Crush
What is the sequence of msucle injury and repair?
Degeneration
Inflammation
Regeneration
Fibrosis (the enemy, will prevent full functional restoration)
There is overlap between these
Where will the injured muscles nuclei be located?
centrally
The type of injury determines the extent of muscle damage, regeneration and fibrosis
what is the difference in injury to just the muscle fibre vs. damages to ECM as well.
Injury only to muscle fibres:
e.g myotoxic damage with notexin = complete restoration with little (if any) fibrosis
If ECM is compromised:
e.g crush, laceration
-more severe injury
- damage to BVs, nerves
- less complete regeneration
- extensive fibrosis
impaired functional restoration
What are the consequences of unsuccessful muscle repair?
loss of muscle function
re-injury disability loss of independence reduced QOL health care costs
Why do muscles get injured by their own actions?
When the load on the msucle is grataer than the force developed by the muscle the muscle is stretched, producing a lengthening action
greater forces developed during stretch - force is two-fold greater
What are the indirect measures of muscle injury?
CK release from muscle
- delayed, highly variable response (higher with eccentric compared to concentric)
increase calcium influx
decrease in relative maximum force (in the absence of fatigue)
muscle soreness (humans)
What are the problems with a ‘gold standard’ of injury measurement?
problems quantifying structural damage
considerable variability in plasma enzyme levels as indices of injury
the decrease in max. force, although an indirect measure provides the most valid measure of the totality of the injury
What is the concept of the initial injury?
The mechanical initiating event associated with contraction-induced injury is primarily mechanical in nature
occurs when individual sarcomeres are stretched excessively, damaging sarcomeres and t-tubules leading to E-C coupling failure
the injury may involves single or cumulative contractions, any number of fibres within a muscle and within an individuals fibre:
- focal injuries localised to a few sarcomeres in series or in parallel
- more widespread injuries across the entire cross section of the fibre; as observed with electron microscopy
What is the sarcomere inhomogeneity hypothesis?
injury is initiated when weak sacromeres are stretched by stronger sarcomeres that exist in series
due to biological variation, some sarcomeres will be weaker than others
the weakest sarcomeres are randomly distributed throughout the fibre and are usually those on the descending limb of the tension-length curve
when stretched, the weak sarcomeres will yield or ‘‘pop’’
upon relaxation, some of these sarcomeres will fail to reinterdigitate properly and remain at longer lengths
In initial mechanical injury t-tubules are at the overlap of thick and thin filaments and are assumed to be subject to…
shearing stress
where shear stress is greatest rupture occurs
What is the concept and characteristics of the secondary injury?
1-3 days after initial injury - severe morphological damage observed by LM and EM
CK enzyme release
intensity of muscle (DOMS)
quantitative assessment of injury by these methods is not possible
force deficit still provides best assessment of damage and subsequent recovery
although immediately after an exercise protocol the decrease in force may reflect both fatigue and injury, the deficit remaining following recovery from fatigue in the ability of the muscle to develop force provides the most quantitative and reproducible measure of the totality of a muscle injury
What is the effect of Ca2+ homeostasis in msucle injury?
there is an elevation of Ca2+ at the site of damage
cellular necrosis is linked with a loss in Ca2+ homeostasis
disruption of the sarcolemma could allow for loss of ion regulation
SR may become dysfunctional, i.e unable to resequester Ca2+
If the fibre is able to handle Ca2+ influx effectively and maintain relatively low [Ca2+] levels, then the injury sequence may never proceed to the next phase
the dependability of a muscle fibre to survive is dependent on its ability to regulate ___ levels
Ca2+
If the Ca2+ changes cannot be buffered there will be a secondary injury
during secondary injury what is activates that casues myofibrillar and membrane degradation –> phagocytic pathway and the regenerative phase?
Increase in protease and phospholipase activity
What are the characteristics of minor damage?
limited intracellular disruption
minor damage to cell membrane
viability maintained, therefore no degeneration
intracellular repair, membrane resealing
What are the characteristics of major damage?
irreparable intracellular disruption
compromised cell membrane
loss of cell viabilty and cell degeneration
fiber replacement via regeneration
What is the benefits of inflammation?
neutrophils and macrophages recruited to site of injury
remove necrotic debris
prepare injury zine for regeneration
increaase vascular permeability
stimulate monocyte accumulation
inflammatory response critical for successful regeneration
activation of satellite cell
How can we protect our msucles from excessive contractions?
repeat bouts of lengthening contractions shown to decrease force deficit
mechanism possibly involving sarcomere homogeneity
sufficient recovery between sessions –> training
protection lost by ‘‘overtraining’’ or fatigue (lack of sufficient recovery between bouts) - trained is less likely to be injured by a protocol of contractions that previously caused injury
What is the potential mechanism of trained muscle being less likely to injure?
consists of regenerated fibres that have increased sarcomere homogeneity
these fibres are less likely to be pulled onto the descending limb of the length-tension relationship when activated and stretched forcibly
