Lecture 26

Question 1

What is ischaemia-reperfusion injury?

Answer 1

When blood flow is occluded then returned to the muscle

Question 2

How can muscles be damaged in an experimental setting without causing fibrosis?

Answer 2

myotoxin can be used to damage muscle without damaging the ECM.

Question 3

What is the difference in muscle repair if injury is limited just to the fibers compared to ECM?

Answer 3

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.

Question 4

What happens to nuclei during muscle injury?

Answer 4

Nuclei move from periphery to the inside of the cell

Question 5

What is the sequence of events that happen during muscle injury?

Answer 5

Degeneration -> Inflammation -> Regeneration -> Fibrosis

Question 6

What are the consequences of unsuccessful muscle repair?

Answer 6

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.

Question 7

What is the difference in stretch resposne between haelthy and dystrophic muscle?

Answer 7

Stretching of healthy muscle results in generation of a good amount of force. Stretching dystrophic muscle causes generation of fewer muscle.

Question 8

Which types of contractions generate the most force?

Answer 8

During eccentric contractions greater forces are developed by the muscles (almost 2x greater).

Question 9

What determines magnitude of force decrease associated with stretch-induced injury?

Answer 9

The average force developed during stretch.

The displacement or magnitude of strain.

Question 10

What are the symptoms of muscle injury?

Answer 10

Creatine Kinase

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)

Muscle soreness

Question 11

What happens to muscles after repeated injury?

Answer 11

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)

Question 12

What are the downsides to using CK signalling to understand muscle damage?

Answer 12

CK doesn’t tell us how much damage a muscle has experienced. It only tells us there is damage.

Question 13

What is the best way to measure degree of muscle injury?

Answer 13

The decrease in muscle force is the most valid measure of totality of injury.

Question 14

What happens to muscle fibers during an injury?

Answer 14

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.

Question 15

What are the types of injuries that sarcomeres can experience?

Answer 15

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.

Question 16

What happense to muscle if muscle stress > muscle strength?

Answer 16

If muscle stress > muscle strength the result is structural failure

Question 17

What is Z-line streaming?

Answer 17

Z-line streaming may result causing Z-line to stretch within muscles and this decreases force production considerably

Question 18

What can happen to T-tubules during injury?

Answer 18

Disruptions may occur to the t-tubules leading to failure of EC coupling.

Question 19

What does the sarcomere inhomogeneity hypothesis state?

Answer 19

Injury is initiated when weak sarcomeres are stretched by stronger sarcomeres in series.

Question 20

Can t-tubules be damaged from muscle contraction?

Answer 20

Yes, t-tubules are at the overlap of thick and thin filaments and are also subject to damage.

Question 21

What is secondary injury?

Answer 21

repeat injury 1-3 days after initial injury.

Question 22

What is the result of damage to the t-tubule?

Answer 22

damage to the t-tubule results in decrease in calcium releast at SR and the activation of proteases and phospholipases along with inflammation.

Question 23

What is the best indication of sarcomere damage during secondary injury?

Answer 23

Best indication of sarcomere damage during secondary injury is the force deficit

Question 24

Why is secondary injury soreness a delayed response?

Answer 24

Enzyme CK takes time to be released, nerves take time to be sensitized to the injury, etc

Question 25

What is the response to elevated calcium levels in the muscle?

Answer 25

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.

Question 26

What are some preventative measures to breaking down of the muscle cell?

Answer 26

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.

Question 27

What are the steps of initial muscle injury?

Answer 27

Lengthening muscle actions -> Sarcomere inhmogeneity -> sarcolemmal disruption -> Ca2+ overload? -If yes-> no secondary injury
-If no-> intrinsic mechanisms result in a secondary injury.

Question 28

What happens during a secondary injury response

Answer 28

Increase in protease and phospholipase activity -> actvates myofibrillar and membrane degradation via the phagocytic pathway -> regenerative phase occurs

Question 29

What is the difference in the response to minor damage and major damage?

Answer 29

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.

Question 30

What is the role of macrophages in cell damage?

Answer 30

During degeneration macrophages ‘eat’ the necrotic debris and as a result the injury zone is prepared for regeneration.

Question 31

What is the importance of inflammation in muscle repair?

Answer 31

Inflammamation is essential for regeneration.because it activates satellite cells.

Question 32

How does the muscle avoid damage to healthy fibers?

Answer 32

damaged area being repaired is isolated from the other areas of the muscle.

Question 33

What happens after damaged muscle is broked down and cleared?

Answer 33

Satellite cells then begin proliferating and repairing the muscle.

Question 34

How can muscle injury be prevented?

Answer 34

Repeat bouts of lengthening contractions decrease the force deficit. So continuous exercising of a muscle could decrease chances of strain. Rest between boats is necessary to ensure that muscle has time to condition itself for the next bout.