Flashcards in Lecture 26 Deck (34)
What is ischaemia-reperfusion injury?
When blood flow is occluded then returned to the muscle
How can muscles be damaged in an experimental setting without causing fibrosis?
myotoxin can be used to damage muscle without damaging the ECM.
What is the difference in muscle repair if injury is limited just to the fibers compared to ECM?
If injury is limited to just the muscle fibers the muscle is completely restored.
If ExtraCellular Matrix is compromised this results in muscles having less complete regeneration and extensive fibrosis. Functionally the muscles are impaired.
What happens to nuclei during muscle injury?
Nuclei move from periphery to the inside of the cell
What is the sequence of events that happen during muscle injury?
Degeneration -> Inflammation -> Regeneration -> Fibrosis
What are the consequences of unsuccessful muscle repair?
Depending on the injury it can lead to short-term or long term disability, loss of independence, reduced quality of life, and increase in health care costs.
What is the difference in stretch resposne between haelthy and dystrophic muscle?
Stretching of healthy muscle results in generation of a good amount of force. Stretching dystrophic muscle causes generation of fewer muscle.
Which types of contractions generate the most force?
During eccentric contractions greater forces are developed by the muscles (almost 2x greater).
What determines magnitude of force decrease associated with stretch-induced injury?
The average force developed during stretch.
The displacement or magnitude of strain.
What are the symptoms of muscle injury?
Delayed, variable response
Calcium influx (loss of calcium regulation in the muscle is a sign of muscle injury)
Decrease in relative maximum force (in absence of fatigue)
What happens to muscles after repeated injury?
If muscle is subject to repeat boats the magnitude of injury on the muscle is decreased. (CK levels decrease significantly after first boat of exercise)
What are the downsides to using CK signalling to understand muscle damage?
CK doesn't tell us how much damage a muscle has experienced. It only tells us there is damage.
What is the best way to measure degree of muscle injury?
The decrease in muscle force is the most valid measure of totality of injury.
What happens to muscle fibers during an injury?
Initial injury is primarily mechanical in nature and occurs when individual sarcomeres are stretched excessively, damaging structural components within or between sarcomeres.
The injury may involve any number of fibers within a muscle and within an individual fiber.
What are the types of injuries that sarcomeres can experience?
Focal injuries are localized to a few sarcomeres in series or in parallel.
More widespread injuries are accross the entire cross section of the fiber as observed with electron microscopy.
What happense to muscle if muscle stress > muscle strength?
If muscle stress > muscle strength the result is structural failure
What is Z-line streaming?
Z-line streaming may result causing Z-line to stretch within muscles and this decreases force production considerably
What can happen to T-tubules during injury?
Disruptions may occur to the t-tubules leading to failure of EC coupling.
What does the sarcomere inhomogeneity hypothesis state?
Injury is initiated when weak sarcomeres are stretched by stronger sarcomeres in series.
Can t-tubules be damaged from muscle contraction?
Yes, t-tubules are at the overlap of thick and thin filaments and are also subject to damage.
What is secondary injury?
repeat injury 1-3 days after initial injury.
What is the result of damage to the t-tubule?
damage to the t-tubule results in decrease in calcium releast at SR and the activation of proteases and phospholipases along with inflammation.
What is the best indication of sarcomere damage during secondary injury?
Best indication of sarcomere damage during secondary injury is the force deficit
Why is secondary injury soreness a delayed response?
Enzyme CK takes time to be released, nerves take time to be sensitized to the injury, etc
What is the response to elevated calcium levels in the muscle?
Elevated Calcium can flood into the cell through the damaged membrane. Disruption of sarcolemma could allow for loss in calcium homeostasis. SR may become unable to resequester calcium.
As a result proteases and phospholipases can be released and cell debris is removed and regeneration is initiated.
What are some preventative measures to breaking down of the muscle cell?
To prevent calcium induced breakdown of the cell, the sarcoplasmic reticulum can buffer some of the effect as well as the the mitchondria and the Ca2+ ATPases in the membrane.
What are the steps of initial muscle injury?
Lengthening muscle actions -> Sarcomere inhmogeneity -> sarcolemmal disruption -> Ca2+ overload? -If yes-> no secondary injury
-If no-> intrinsic mechanisms result in a secondary injury.
What happens during a secondary injury response
Increase in protease and phospholipase activity -> actvates myofibrillar and membrane degradation via the phagocytic pathway -> regenerative phase occurs
What is the difference in the response to minor damage and major damage?
Minor damage involves limited intracellular disruption and minor damage to cell membrane.
Viability is maintained with no degeneration occuring.
Intracellular repair occurs with membrane being resealed.
Major damage to muscle fibers results in irreplaceable disruption of cell membrane, and proteins. The cell is then degenerated and muscle fibers are replaced.
What is the role of macrophages in cell damage?
During degeneration macrophages 'eat' the necrotic debris and as a result the injury zone is prepared for regeneration.
What is the importance of inflammation in muscle repair?
Inflammamation is essential for regeneration.because it activates satellite cells.
How does the muscle avoid damage to healthy fibers?
damaged area being repaired is isolated from the other areas of the muscle.
What happens after damaged muscle is broked down and cleared?
Satellite cells then begin proliferating and repairing the muscle.