Lecture 13 - Muscle tissue growth and atrophy

Question 1

Increased work demand, metabolic demand, excess endocrine stimulation, persistent tissue injury can lead to

Answer 1

hyperplasia
Hypertrophy
Hypertrophy AND hyperplasia

Question 2

Hypertrophy without hyperplasia is seen in …

Answer 2

Hypertrophy without hyperplasia seen in skeletal muscle with extra work
So when adult humans undergo exercise and muscles get bigger this occurs because the muscle fibres undergo hypertrophy without hyperplasia (they are post mitotic, no more skeletal muscle fibres can be made) and exercise causes muscle to increase in size due to the existing muscle fibres increasing in size

Adult skeletal muscle cannot produce new muscle cells
Various ways that can increase the size of the existing muscle fibres and their capacity …. Sarcomere expansion, more sarcoplasmic reticulum, more nuclei (muscle fibres can be multinucleate which gives an increased capacity for protein synthesis

Question 3

Various ways that can increase the size of the existing muscle fibres and their capacity

Answer 3

Sarcomere expansion, more sarcoplasmic reticulum, more nuclei (muscle fibres can be multinucleate which gives an increased capacity for protein synthesis

Question 4

Hypertrophy - physiological

Answer 4

Adult skeletal muscle shows hypertrophy without hyperplasia as muscle cells cannot divide e.g. skeletal muscle with extra work

Question 5

Skeletal muscle development

Answer 5

Myoblasts are precursors of muscle cells
Myoblasts proliferate during development
These fuse to form muscle cells
Genes can influence degree of proliferation
Myostatin slows myoblast proliferation - gene that slows down myoblast proliferation, so when it is ‘switched on’ it slows down the proliferation
The number of muscle fibres that we have as an adult is fixed during development - depends on the proliferation of the precursors to muscles during development

Question 6

The number of muscle fibres that we have as an adult is

Answer 6

fixed during development - depends on the proliferation of the precursors to muscles during development

Question 7

Myoblasts

Answer 7

Myoblasts are precursors of muscle cells
Myoblasts proliferate during development
These fuse to form muscle cells
Genes can influence degree of proliferation

Question 8

Myostatin

Answer 8

Myostatin slows myoblast proliferation - gene that slows down myoblast proliferation, so when it is ‘switched on’ it slows down the proliferation

Question 9

Double muscling of cattle

Answer 9

Double muscling in cattle - can get hyperplasia in skeletal muscles in response to change in development but not a as a result to a change in adulthood
Mutated myostatin gene leads to more skeletal muscle fibres being produced during development (mutated sequence inhibits the functionality of myostatin)

Question 10

Hypertrophy and hyperplasia due to gene mutation

Answer 10

Mice purposely made deficient in the myostatin gene also have remarkably big muscles
Mice have more muscle fibres as well as bigger muscle fibres in knockout mouse as the gene is knocked out during development

Question 11

Child and myostatin mutation

Answer 11

Myostatin mutation associated with gross muscle hypertrophy in a child

Question 12

Cardiac hypertrophy - physiological

Answer 12

Mice that swim have bigger hearts

Exsisting cardiac muscle cells are increasing in size

Question 13

Cardiac hypertrophy - pathogloical

Answer 13

Mice with aortic restriction also have bigger hearts (because the heart is working harder for the same amount of output)
Ventricle has hypertrophic wall due to narrowing of the aortic valve (increased workload)

hyperytrophic myocardium due to narrowing of the aortic valve
large often polyploid nuclei
thickened ventricular wall reduces outflow and impairs the relaxation phase

Question 14

Hypertrophy of smooth muscle with an example

Answer 14

Obstructions of bladder lead to hypertrophy of smooth muscle e.g. with prostate cancer
Compensatory increase in smooth muscle cells
For example - when the prostate increases in size it basically reduces the diameter of the urethra so the bladder has to work harder to push urine out so there is an increase in the size of smooth muscle cells
Obstructions of intestines can have similar effects
Mimicking bladder obstructions in animals shows smooth muscle hypertrophy (smooth muscle cells increase in size to compensate)

Question 15

Hyperplasia with hypertrophy example

Answer 15

Both occur together in response to increased functional requirements

Example: pregnant myometrium
Cells in pregnant uterus are enlarged and have larger nuclei reflecting their increased protein synthesis. Number of cells is also increased.
Following pregnancy the uterus returns to normal size by physiological atrophy termed involution.
Pregnant woman - increased mass of smooth muscle in the wall due to both hypertrophy and hyperplasia

Question 16

An increase in functional muscle mass can occur via 2 mechanisms

Answer 16

Increased cell number–HYPERPLASIA(only certain circumstances)
Increase in cell size - HYPERTROPHY

Question 17

A key feature of hyperplasia and hypertrophy

Answer 17

A key feature of these types of increased cell mass is that on removal of the causative environmental stimulus, the altered pattern of cell growth ceases and the tissue reverts to its former state. (Muscles adapt to the amount that you need them because for example bigger muscles require more food etc therefore this needs to be managed to prevent waste of energy)

Question 18

Disuse, inadequate nutrients, lack of endocrine stimulation, denervation, aging leads to …

Answer 18

reduced cell size - cell atrophy
reduced cell number - involution of tissue
reduced cell size and cell number - cell atrophy and involution

Question 19

Muscle atrophy examples

Answer 19

Examples of muscle atrophy:
1. Disuse atrophy occurs from a lack of physical exercise (reversible). Examples: bed-ridden people, astronauts ( do not stimulate the muscle through the normal pressure of gravity in space therefore have to work harder to maintain their muscle mass).

2. Severe type of muscle atrophy is neurogenic atrophy. It occurs when there is injury or disease to a nerve. Tends to occur more suddenly than disuse atrophy. Example: poliomyelitis (polio).
   Loss of neuronal signal that causes the muscle to contract
   In polio, lose the functionality of the motor neurons therefore as a consequence they cannot really use their muscles anymore so undergo severe

Question 20

Disuse atrophy occurs from a lack of physical exercise (reversible).

Answer 20

1. Disuse atrophy occurs from a lack of physical exercise (reversible). Examples: bed-ridden people, astronauts ( do not stimulate the muscle through the normal pressure of gravity in space therefore have to work harder to maintain their muscle mass).

Question 21

Severe type of muscle atrophy is neurogenic atrophy.

Answer 21

2. Severe type of muscle atrophy is neurogenic atrophy. It occurs when there is injury or disease to a nerve. Tends to occur more suddenly than disuse atrophy. Example: poliomyelitis (polio).
   Loss of neuronal signal that causes the muscle to contract
   In polio, lose the functionality of the motor neurons therefore as a consequence they cannot really use their muscles anymore so undergo severe

Question 22

Atrophy

Answer 22

decrease in cell size

If nervous stimulation of muscle ceases, then the muscle fibres decrease in size = atrophy

Question 23

Muscle atrophy occurs in response to reduced

Answer 23

endocrine stimuli

Reductions in anabolic hormones can cause muscle atrophy: Testosterone, Growth hormone, IGF1
Stat5b knockout mice show muscle atrophy! (Smaller due to muscle atrophy)

Question 24

Ageing also causes

Answer 24

muscle atrophy

When the old mouse is treated with an estrogen (17-alpha estradiol), it can actually increase the size of their muscles so the muscle regain their size and strength tests with them such as putting them on a running wheel shows that they have improved functional capacity which shows that the loss of specific hormones specifically oestrogen is involved in the ageing process

Question 25

Mechanisms underlying atrophy and involution

Answer 25

Autophagy in cell atrophy Apoptosis - programmed cell death Autophagy is to break down cell components whereas to get rid of whole cells you use apoptosis

Question 26

Autophagy in cell atrophy

Answer 26

Macroautophagy - breaks down relative large components and whole organelles Microautophagy - lysosome can directly eat small molecules in the cell such as proteins Chaperone-mediated autophagy - specific proteins recognised specific motifs on molecules and break them down in a very selective way The cellular component that you want to degrade is enclosed by a membrane Individual amino acids and molecules can be released back into the cell Mitophagy = breakdown of whole mitochondria Stained for acid phosphatase Stains the cell so you can see where this enzyme is and that it is only in the lysosome One of many lysosomal enzymes Detaches phosphoryl groups when at an optimal pH (<7) A lower lysosomal pH protects the cell in case these enzymes escape Example = uterine involution in mice Increase in size during pregnancy and then decreases Post pregnancy shows that it slowly decreases in size and during this period a lot of lysosomes are formed and become activated, autophagy is switched on just after pregnancy which helps the uterus to revert back to its normal size

Question 27

example of autophagy in cell atrophy

Answer 27

Example = uterine involution in mice Increase in size during pregnancy and then decreases Post pregnancy shows that it slowly decreases in size and during this period a lot of lysosomes are formed and become activated, autophagy is switched on just after pregnancy which helps the uterus to revert back to its normal size

Question 28

Macroautophagy

Answer 28

Macroautophagy - breaks down relative large components and whole organelles

Question 29

Microautophagy

Answer 29

Microautophagy - lysosome can directly eat small molecules in the cell such as proteins

Question 30

Chaperone-mediated autophagy autophagy

Answer 30

Chaperone-mediated autophagy - specific proteins recognised specific motifs on molecules and break them down in a very selective way

Question 31

Mitophagy

Answer 31

= breakdown of whole mitochondria

Question 32

Apoptosis =

Answer 32

programmed cell death

Question 33

Apotosis explained

Answer 33

Apoptosis is an important mechanism in developing and adult tissues for eliminating cells that are no longer needed. Activation is initiated by extracellular or intracellular death signals. Mediated by caspases which exist in all cells as inactive procaspases. Activated by cleavage by other caspases. (Various caspases that mediate apoptosis) Destroys wholes cells that are not needed

Question 34

Phases of apoptosis

Answer 34

Induction/signlling phase Effect/executioner phase Degradation phase Phagocytic phase

Question 35

Apoptosis examples

Answer 35

Elimination of cells after hormonal growth stimulus e.g. oestrogen sensitive tissues. Elimination of cells in tissues with a high cell turnover e.g. lining epithelia in gut. Removal of excess cells in embryogenesis e.g. fingers, gut lumen. Removal of cells for organ remodelling e.g. tadpole to frog, hand webbing to removal of it (need to initially produce a big block of tissue that we later refine down to get a particular shape that we need for our bodies

Question 36

Apoptosis = induction/signalling phase

Answer 36

Normal cells are in close contact and are united by junctions. § Cell receives either an internal or external signal that initiates apoptosis. Cell looks normal at this stage.

Question 37

Apoptosis = effect/executioner phase

Answer 37

Protease enzymes cause severe structural changes: Cell shrinkage Loss of surface specialisations Loses cell junctions and microvilli Condensed chromatin Changes in nucleus in its shape

Question 38

Apoptosis = degradation phase

Answer 38

The cell splits up into smaller fragments called apoptotic bodies. The nucleus also fragments. Each fragment contains viable mitochondria and intact organelles. (Spread between the apoptotic bodies)

Question 39

Apoptosis = phagocytic phase

Answer 39

Apoptotic fragments are recognised and phagocytosed by adjacent cells where they are destroyed. ( by lysosomes for example) Some fragments degenerate extracellularly. Some fragments are ingested by phagocytic cells

Question 40

Decreased cell mass

Answer 40

A reduction in tissue mass is termed atrophy. Mechanisms of atrophy can involve reduction in cell number or cell volume. Autophagy and apoptosis are cellular processes involved in decreased tissue mass. Leads to reduction in organ size unless lost cells are replaced by adipose tissue or fibrous tissue.

Question 41

Example of physiological muscle hypertrophy

Answer 41

Increase in muscle size in response to exercise In adulthood there is no increase in the NUMBER of muscle fibres

Question 42

Example of pathological muscle hypertrophy

Answer 42

Increase in cardiac muscle cells size in response to ateriosclerosis for example Compensating for the narrowing of the blood vessels

Question 43

Example of hyperplasia + hypertrophy

Answer 43

Increase in the size of the myometrium during pregnancy