Lecture 13 - Muscle tissue growth and atrophy Flashcards
Increased work demand, metabolic demand, excess endocrine stimulation, persistent tissue injury can lead to
hyperplasia
Hypertrophy
Hypertrophy AND hyperplasia
Hypertrophy without hyperplasia is seen in …
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
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
Hypertrophy - physiological
Adult skeletal muscle shows hypertrophy without hyperplasia as muscle cells cannot divide e.g. skeletal muscle with extra work
Skeletal muscle development
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
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
Myoblasts
Myoblasts are precursors of muscle cells
Myoblasts proliferate during development
These fuse to form muscle cells
Genes can influence degree of proliferation
Myostatin
Myostatin slows myoblast proliferation - gene that slows down myoblast proliferation, so when it is ‘switched on’ it slows down the proliferation
Double muscling of cattle
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)
Hypertrophy and hyperplasia due to gene mutation
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
Child and myostatin mutation
Myostatin mutation associated with gross muscle hypertrophy in a child
Cardiac hypertrophy - physiological
Mice that swim have bigger hearts
Exsisting cardiac muscle cells are increasing in size
Cardiac hypertrophy - pathogloical
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
Hypertrophy of smooth muscle with an example
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)
Hyperplasia with hypertrophy example
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
An increase in functional muscle mass can occur via 2 mechanisms
Increased cell number–HYPERPLASIA(only certain circumstances)
Increase in cell size - HYPERTROPHY
A key feature of hyperplasia and hypertrophy
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)
Disuse, inadequate nutrients, lack of endocrine stimulation, denervation, aging leads to …
reduced cell size - cell atrophy
reduced cell number - involution of tissue
reduced cell size and cell number - cell atrophy and involution
Muscle atrophy examples
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).
- 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
Disuse atrophy occurs from a lack of physical exercise (reversible).
- 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).
Severe type of muscle atrophy is neurogenic atrophy.
- 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
Atrophy
decrease in cell size
If nervous stimulation of muscle ceases, then the muscle fibres decrease in size = atrophy
Muscle atrophy occurs in response to reduced
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)
Ageing also causes
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
Mechanisms underlying atrophy and involution
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
Autophagy in cell atrophy
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
example of autophagy in cell atrophy
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
Macroautophagy
Macroautophagy - breaks down relative large components and whole organelles
Microautophagy
Microautophagy - lysosome can directly eat small molecules in the cell such as proteins
Chaperone-mediated autophagy autophagy
Chaperone-mediated autophagy - specific proteins recognised specific motifs on molecules and break them down in a very selective way
Mitophagy
= breakdown of whole mitochondria
Apoptosis =
programmed cell death
Apotosis explained
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
Phases of apoptosis
Induction/signlling phase
Effect/executioner phase
Degradation phase
Phagocytic phase
Apoptosis examples
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
Apoptosis = induction/signalling phase
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.
Apoptosis = effect/executioner phase
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
Apoptosis = degradation phase
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)
Apoptosis = phagocytic phase
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
Decreased cell mass
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.
Example of physiological muscle hypertrophy
Increase in muscle size in response to exercise
In adulthood there is no increase in the NUMBER of muscle fibres
Example of pathological muscle hypertrophy
Increase in cardiac muscle cells size in response to ateriosclerosis for example
Compensating for the narrowing of the blood vessels
Example of hyperplasia + hypertrophy
Increase in the size of the myometrium during pregnancy
