Muscle atrophy
Encyclopedia
Muscle atrophy, or disuse atrophy, is defined as a decrease in the mass of the muscle; it can be a partial or complete wasting away of muscle. When a muscle atrophies, this leads to muscle weakness
, since the ability to exert force is related to mass. Muscle atrophy results from a co-morbidity of several common diseases, including cancer
, AIDS
, congestive heart failure
, COPD
(chronic obstructive pulmonary disease), renal failure
, and severe burn
s; patients who have "cachexia
" in these disease settings have a poor prognosis
. Moreover, starvation eventually leads to muscle atrophy. Disuse of the muscles will also lead to atrophy.
mass, known as atrophy
, including: Dejerine Sottas syndrome
(HSMN Type III), inactivity, as seen when a cast is put on a limb, or upon extended bedrest (which can occur during a prolonged illness); cachexia
- which is a "the dark side" syndrome that is a co-morbidity of cancer
and Congestive Heart Failure
; Chronic Obstructive Pulmonary Disease
; burns, liver failure, etc. Other syndromes or conditions which can induce skeletal muscle atrophy are liver disease, and starvation.
". The exact cause of sarcopenia
is unknown, but it may be due to a combination of the gradual failure in the "satellite cells
" which help to regenerate skeletal muscle fibers, and a decrease in sensitivity to or the availability of critical secreted growth factors which are necessary to maintain muscle mass and satellite cell survival.
In addition to the simple loss of muscle mass (atrophy
), or the age-related decrease in muscle function (sarcopenia
), there are other diseases which may be caused by structural defects in the muscle (muscular dystrophy
), or by inflammatory reactions in the body directed against muscle (the myopathies).
-dependent ubiquitin
/proteasome
pathway. In this system, particular proteins are targeted for destruction by the ligation of at least four copies of a small peptide called ubiquitin
onto a substrate protein. When a substrate is thus "poly-ubiquitinated", it is targeted for destruction by the proteasome
. Particular enzymes in the ubiquitin/proteasome pathway allow ubiquitination to be directed to some proteins but not others - specificity is gained by coupling targeted proteins to an "E3 ubiquitin ligase
". Each E3 ubiquitin ligase
binds to a particular set of substrates, causing their ubiquitination.
, or an increase in muscle size. Therefore one way in which exercise induces an increase in muscle mass is to downregulate the pathways which have the opposite effect.
One important rehabilitation tool for muscle atrophy includes the use of functional electrical stimulation
to stimulate the muscles. This has seen a large amount of success in the rehabilitation of paraplegic patients.
Since the absence of muscle-building amino acids can contribute to muscle wasting (that which is torn down must be rebuilt with like material), amino acid therapy may be helpful for regenerating damaged or atrophied muscle tissue. The branched-chain amino acids or BCAA
s (leucine
, isoleucine
, and valine
) are critical to this process, in addition to lysine
and other amino acids.
Fast loss of muscle tissue (relative to normal turnover), can be approximated by the amount of urea
in the urine. The equivalent nitrogen content (in gram
) of urea (in mmol
) can be estimated by the conversion factor 0.028 g/mmol. Furthermore, 1 gram of nitrogen is roughly equivalent to 6 gram of protein, and 1 gram of protein is roughly equivalent to 4 gram of muscle tissue. Subsequently, in situations such as muscle wasting, 1 mmol of excessive urea in the urine (as measured by urine volume in litres multiplied by urea concentration in mmol/l) roughly corresponds to a muscle loss of 0.67 gram.
Muscle weakness
Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
, since the ability to exert force is related to mass. Muscle atrophy results from a co-morbidity of several common diseases, including cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
, congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
, COPD
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
(chronic obstructive pulmonary disease), renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
, and severe burn
Burn
A burn is an injury to flesh caused by heat, electricity, chemicals, light, radiation, or friction.Burn may also refer to:*Combustion*Burn , type of watercourses so named in Scotland and north-eastern England...
s; patients who have "cachexia
Cachexia
Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite in someone who is not actively trying to lose weight...
" in these disease settings have a poor prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
. Moreover, starvation eventually leads to muscle atrophy. Disuse of the muscles will also lead to atrophy.
Clinical settings of atrophy
There are many diseases and conditions which cause a decrease in muscleMuscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
mass, known as atrophy
Atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
, including: Dejerine Sottas syndrome
Dejerine Sottas Syndrome
Dejerine–Sottas disease, also Dejerine–Sottas syndrome or Dejerine–Sottas neuropathy is an autosomal dominant or autosomal recessive neuropathy.-Causes:It has been associated with MPZ, PMP22, PRX, and EGR2.-Symptoms:It is usually characterized...
(HSMN Type III), inactivity, as seen when a cast is put on a limb, or upon extended bedrest (which can occur during a prolonged illness); cachexia
Cachexia
Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite in someone who is not actively trying to lose weight...
- which is a "the dark side" syndrome that is a co-morbidity of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
and Congestive Heart Failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
; Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
; burns, liver failure, etc. Other syndromes or conditions which can induce skeletal muscle atrophy are liver disease, and starvation.
Quality of life
Muscular atrophy decreases quality of life as the sufferer becomes unable to perform certain tasks or worsen the risks of accidents while performing those (like walking). Muscular atrophy increases the risks of falling in conditions such as IBM (inclusion body myositis). Muscular atrophy affects a major number of elderly.Other muscles diseases, distinct from atrophy
During aging, there is a gradual decrease in the ability to maintain skeletal muscle function and mass. This condition is called "sarcopeniaSarcopenia
Sarcopenia is the degenerative loss of skeletal muscle mass and strength associated with aging...
". The exact cause of sarcopenia
Sarcopenia
Sarcopenia is the degenerative loss of skeletal muscle mass and strength associated with aging...
is unknown, but it may be due to a combination of the gradual failure in the "satellite cells
Satellite cells
Myosatellite cells or satellite cells are small mononuclear progenitor cells with virtually no cytoplasm found in mature muscle. They are found sandwiched between the basement membrane and sarcolemma of individual muscle fibers, and can be difficult to distinguish from the sub-sarcolemmal nuclei...
" which help to regenerate skeletal muscle fibers, and a decrease in sensitivity to or the availability of critical secreted growth factors which are necessary to maintain muscle mass and satellite cell survival.
In addition to the simple loss of muscle mass (atrophy
Atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
), or the age-related decrease in muscle function (sarcopenia
Sarcopenia
Sarcopenia is the degenerative loss of skeletal muscle mass and strength associated with aging...
), there are other diseases which may be caused by structural defects in the muscle (muscular dystrophy
Muscular dystrophy
Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...
), or by inflammatory reactions in the body directed against muscle (the myopathies).
Pathophysiology
Muscle atrophy occurs by a change in the normal balance between protein synthesis and protein degradation. During atrophy, there is a down-regulation of protein synthesis pathways, and an activation of no this don't happen. The particular protein degradation pathway which seems to be responsible for much of the muscle loss seen in a muscle undergoing atrophy is the ATPAdenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
-dependent ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
/proteasome
Proteasome
Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria. In eukaryotes, they are located in the nucleus and the cytoplasm. The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...
pathway. In this system, particular proteins are targeted for destruction by the ligation of at least four copies of a small peptide called ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
onto a substrate protein. When a substrate is thus "poly-ubiquitinated", it is targeted for destruction by the proteasome
Proteasome
Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria. In eukaryotes, they are located in the nucleus and the cytoplasm. The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...
. Particular enzymes in the ubiquitin/proteasome pathway allow ubiquitination to be directed to some proteins but not others - specificity is gained by coupling targeted proteins to an "E3 ubiquitin ligase
Ubiquitin ligase
A ubiquitin ligase is a protein that in combination with an E2 ubiquitin-conjugating enzyme causes the attachment of ubiquitin to a lysine on a target protein via an isopeptide bond; the E3 ubiquitin ligase targets specific protein substrates for degradation by the proteasome...
". Each E3 ubiquitin ligase
Ubiquitin ligase
A ubiquitin ligase is a protein that in combination with an E2 ubiquitin-conjugating enzyme causes the attachment of ubiquitin to a lysine on a target protein via an isopeptide bond; the E3 ubiquitin ligase targets specific protein substrates for degradation by the proteasome...
binds to a particular set of substrates, causing their ubiquitination.
Potential treatment
Muscle atrophy can be opposed by the signaling pathways which induce muscle hypertrophyMuscle hypertrophy
Muscle hypertrophy is an increase in the size of muscle cells. It differs from muscle hyperplasia, which is the formation of new muscle cells.-Hypertrophy stimuli:A range of stimuli can increase the volume of muscle cells...
, or an increase in muscle size. Therefore one way in which exercise induces an increase in muscle mass is to downregulate the pathways which have the opposite effect.
One important rehabilitation tool for muscle atrophy includes the use of functional electrical stimulation
Functional electrical stimulation
Functional electrical stimulation is a technique that uses electrical currents to activate nerves innervating extremities affected by paralysis resulting from spinal cord injury , head injury, stroke and other neurological disorders. FES is primarily used to restore function in people with...
to stimulate the muscles. This has seen a large amount of success in the rehabilitation of paraplegic patients.
Since the absence of muscle-building amino acids can contribute to muscle wasting (that which is torn down must be rebuilt with like material), amino acid therapy may be helpful for regenerating damaged or atrophied muscle tissue. The branched-chain amino acids or BCAA
Branched-chain amino acids
A branched-chain amino acid is an amino acid having aliphatic side-chains with a branch...
s (leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
, isoleucine
Isoleucine
Isoleucine is an α-amino acid with the chemical formula HO2CCHCHCH2CH3. It is an essential amino acid, which means that humans cannot synthesize it, so it must be ingested. Its codons are AUU, AUC and AUA....
, and valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
) are critical to this process, in addition to lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
and other amino acids.
Quantification
A CT scan can distinguish muscle tissue from other tissues and thereby estimate the amount of muscle tissue in the body.Fast loss of muscle tissue (relative to normal turnover), can be approximated by the amount of urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
in the urine. The equivalent nitrogen content (in gram
Gram
The gram is a metric system unit of mass....
) of urea (in mmol
Mole (unit)
The mole is a unit of measurement used in chemistry to express amounts of a chemical substance, defined as an amount of a substance that contains as many elementary entities as there are atoms in 12 grams of pure carbon-12 , the isotope of carbon with atomic weight 12. This corresponds to a value...
) can be estimated by the conversion factor 0.028 g/mmol. Furthermore, 1 gram of nitrogen is roughly equivalent to 6 gram of protein, and 1 gram of protein is roughly equivalent to 4 gram of muscle tissue. Subsequently, in situations such as muscle wasting, 1 mmol of excessive urea in the urine (as measured by urine volume in litres multiplied by urea concentration in mmol/l) roughly corresponds to a muscle loss of 0.67 gram.
See also
- Brown atrophy of the heartBrown atrophy of the heartBrown atrophy of the heart is atrophy of the heart muscle commonly found in the elderly . It is described as brown because fibers become pigmented by intracellular lipofuscin deposits a type of lipochrome granule.It has no known effect on function , and is described as being expected or normal in...
- Muscle weaknessMuscle weaknessMuscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
- Muscular dystrophyMuscular dystrophyMuscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...
- Myotonic dystrophyMyotonic dystrophyMyotonic dystrophy is a chronic, slowly progressing, highly variable inherited multisystemic disease. It is characterized by wasting of the muscles , cataracts, heart conduction defects, endocrine changes, and myotonia. Myotonic dystrophy can occur in patients of any age...