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Muscle atrophy is defined as a decrease in the mass of the muscle; it can be a partial or complete wasting away of muscle, and is most commonly experienced when persons suffer temporary disabling circumstances such as being restricted in movement and/or confined to bed as when hospitalized. When a muscle atrophies, this leads to muscle weakness, since the ability to exert force is related to mass. Modern medicine's understanding of the quick onset of muscle atrophy is a major factor behind the practice of getting hospitalized patients out of bed and moving about as active as possible as soon as is feasible, despite sutures, wounds, broken bones, and pain.

Muscle atrophy
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Prisoner of war exhibiting muscle loss as a result of malnutrition
SpecialtyRheumatology, Neurology Edit this on Wikidata

Muscle atrophy results from a co-morbidity of several common diseases, including cancer, AIDS, congestive heart failure, chronic obstructive pulmonary disease, renal failure, and severe burns; patients who have "cachexia" in these disease settings have a poor prognosis. Moreover, starvation eventually leads to muscle atrophy.

Disuse of the muscles, such as when muscle tissue is immobilized for even a few days – when the patient has a primary injury such as an immobilized broken bone (set in a cast or immobilized in traction), for example – also leads rapidly to disuse atrophy. Minimizing such occurrences as soon as possible is a primary mission of occupational and physical therapists employed within hospitals working in co-ordination with orthopedic surgeons.

Neurogenic atrophy, which has a similar effect, is muscle atrophy resulting from damage to the nerve that stimulates the muscle, causing a shriveling around otherwise healthy limbs. Also, time in a near-zero g environment without exercise leads to atrophy, partially due to the smaller amount of exertion needed to move about, and because muscles are not used to maintain posture. In a similar effect, patients with a broken leg joint undergoing as little as 3 weeks of traction can lose enough back and buttocks muscle mass and strength as to have difficulty sitting without assistance, and experience pain, stress, and burning even after a short 10-minute exposure, when such positioning is contrived during recovery.

Contents

Signs and symptomsEdit

Muscular atrophy decreases qualities of life as the sufferer becomes unable to perform certain tasks or worsens the risks of accidents while performing those (such as walking). Muscular atrophy increases the risks of falling in conditions such as inclusion body myositis. Muscular atrophy affects a high number of the elderly.

CausesEdit

Many diseases and conditions cause a decrease in muscle mass, known as atrophy, including inactivity, as seen when a cast is put on a limb, or upon extended bed rest (which can occur during a prolonged illness); cachexia, which is a syndrome that is a co-morbidity of cancer and congestive heart failure; chronic obstructive pulmonary disease; burns, liver failure, etc., and the wasting Dejerine-Sottas syndrome (HMSN Type III). Glucocorticoids, a class of medications used to treat allergic and other inflammatory conditions, can induce muscle atrophy by increasing breakdown of muscle proteins.[1] Other syndromes or conditions that can induce skeletal muscle atrophy are liver disease and starvation.

PathophysiologyEdit

 
Muscle mass is reduced as muscles atrophy with disuse.

Muscle atrophy occurs by a change in the normal balance between protein synthesis and protein degradation. During atrophy, a down-regulation of protein synthesis pathways occurs, and an activation of protein degradation.[2] The particular protein degradation pathway that seems to be responsible for much of the muscle loss seen in a muscle undergoing atrophy is the ATP-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.

DiagnosisEdit

QuantificationEdit

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 in the urine. The equivalent nitrogen content (in grams) of urea (in mmol) can be estimated by the conversion factor 0.028 g/mmol.[3] Furthermore, 1 g of nitrogen is roughly equivalent to 6 g of protein, and 1 g of protein is roughly equivalent to 4 g 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 g.

Differential diagnosisEdit

During aging, a gradual decrease in the ability to maintain skeletal muscle function and mass occurs, called "sarcopenia". 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 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), other diseases may cause structural defects in the muscle (muscular dystrophy), or by inflammatory reactions in the body directed against muscle (the myopathies).

TreatmentEdit

Muscle atrophy can be opposed by the signaling pathways that induce muscle hypertrophy, or an increase in muscle size. Therefore, one way in which exercise induces an increase in muscle mass is to downregulate the pathways that have the opposite effect.

β-Hydroxy β-methylbutyrate (HMB), a metabolite of leucine which is sold as a dietary supplement, has demonstrated efficacy in preventing the loss of muscle mass in several muscle wasting conditions in humans, particularly sarcopenia.[4][5] It seems that HMB is able to act on three of the four major mechanisms involved in muscle deconditioning (protein turnover, apoptosis, and the regenerative process), whereas it is hypothesized to strongly affect the fourth (mitochondrial dynamics and functions). Moreover, HMB is cheap (about US$30–50 per month at 3 g per day) and may prevent osteopenia [6] and decrease cardiovascular risks. [7] For all these reasons, HMB should be routinely used in muscle-wasting conditions, especially in aged people.}}</ref>[8] A growing body of evidence supports the efficacy of HMB as a treatment for reducing, or even reversing, the loss of muscle mass, muscle function, and muscle strength in hypercatabolic disease states such as cancer cachexia;[9][10][11] consequently, as of June 2016 it is recommended that both the prevention and treatment of sarcopenia and muscle wasting in general include supplementation with HMB, regular resistance exercise, and consumption of a high-protein diet.[9][10] Based upon a meta-analysis of seven randomized controlled trials that was published in 2015, HMB supplementation has efficacy as a treatment for preserving lean muscle mass in older adults.[note 1][8] More research is needed to determine the precise effects of HMB on muscle strength and function in this age group.[8]

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 (leucine, isoleucine, and valine) are critical to this process, in addition to lysine and other amino acids.[citation needed]

In severe cases of muscular atrophy, the use of an anabolic steroid such as methandrostenolone may be administered to patients as a potential treatment.

A novel class of drugs, called selective androgen receptor modulators, is being investigated with promising results. They would have fewer side effects, while still promoting muscle and bone tissue growth and regeneration. These claims are, however, yet to be confirmed in larger clinical trials.[citation needed]

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.[12]

HibernationEdit

Inactivity and starvation in mammals lead to atrophy of skeletal muscle, accompanied by a smaller number and size of the muscle cells as well as lower protein content.[13] In humans, prolonged periods of immobilization, as in the cases of bed rest or astronauts flying in space, are known to result in muscle weakening and atrophy. Such consequences are also noted in small hibernating mammals like the golden-mantled ground squirrels and brown bats.[14]

Bears are an exception to this rule; species in the family Ursidae are famous for their ability to survive unfavorable environmental conditions of low temperatures and limited nutrition availability during winter by means of hibernation. During that time, bears go through a series of physiological, morphological, and behavioral changes.[15] Their ability to maintain skeletal muscle number and size during disuse is of significant importance.

During hibernation, bears spend 4-7 months of inactivity and anorexia without undergoing muscle atrophy and protein loss.[14] A few known factors contribute to the sustaining of muscle tissue. During the summer, bears take advantage of the nutrition availability and accumulate muscle protein. The protein balance at time of dormancy is also maintained by lower levels of protein breakdown during the winter.[14] At times of immobility, muscle wasting in bears is also suppressed by a proteolytic inhibitor that is released in circulation.[13] Another factor that contributes to the sustaining of muscle strength in hibernating bears is the occurrence of periodic voluntary contractions and involuntary contractions from shivering during torpor.[16] The three to four daily episodes of muscle activity are responsible for the maintenance of muscle strength and responsiveness in bears during hibernation.[16]

See alsoEdit

NotesEdit

  1. ^ The estimated standard mean difference effect size for the increase in muscle mass in the HMB treatment groups relative to controls was 0.352 kilograms (0.78 lb) with a 95% confidence interval of 0.11–0.594 kilograms (0.24–1.31 lb).[8] The studies included in the meta-analysis had durations of 2–12 months and the majority of studies lasted 2–3 months.[8]

ReferencesEdit

  1. ^ Seene T (July 1994). "Turnover of skeletal muscle contractile proteins in glucocorticoid myopathy". J. Steroid Biochem. Mol. Biol. 50 (1–2): 1–4. doi:10.1016/0960-0760(94)90165-1. PMID 8049126.
  2. ^ Sandri M. 2008. Signaling in Muscle Atrophy and Hypertrophy. Physiology 23: 160-170.
  3. ^ Section 1.9.2 (page 76) in: Jacki Bishop; Thomas, Briony (2007). Manual of Dietetic Practice. Wiley-Blackwell. ISBN 978-1-4051-3525-2.
  4. ^ Phillips SM (July 2015). "Nutritional supplements in support of resistance exercise to counter age-related sarcopenia". Adv. Nutr. 6 (4): 452–460. doi:10.3945/an.115.008367. PMC 4496741. PMID 26178029.
  5. ^ {{cite journal | vauthors = Brioche T, Pagano AF, Py G, Chopard A | title = Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention | journal = Mol. Aspects Med. | volume = 50| issue = | pages = 56–87| date = April 2016 | pmid = 27106402 | doi = 10.1016/j.mam.2016.04.006 | quote = In conclusion, HMB treatment clearly appears to be a safe potent strategy against sarcopenia, and more generally against muscle wasting, because HMB improves muscle mass, muscle strength, and physical performance.
  6. ^ (Bruckbauer and Zemel, 2013; Tatara, 2009; Tatara et al., 2007, 2008, 2012)
  7. ^ (Nissen et al., 2000).
  8. ^ a b c d e Wu H, Xia Y, Jiang J, Du H, Guo X, Liu X, Li C, Huang G, Niu K (September 2015). "Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis". Arch. Gerontol. Geriatr. 61 (2): 168–175. doi:10.1016/j.archger.2015.06.020. PMID 26169182. RESULTS: A total of seven randomized controlled trials were included, in which 147 older adults received HMB intervention and 140 were assigned to control groups. The meta-analysis showed greater muscle mass gain in the intervention groups compared with the control groups (standard mean difference=0.352kg; 95% confidence interval: 0.11, 0.594; Z value=2.85; P=0.004). There were no significant fat mass changes between intervention and control groups (standard mean difference=-0.08kg; 95% confidence interval: -0.32, 0.159; Z value=0.66; P=0.511).
    CONCLUSION: Beta-hydroxy-beta-methylbutyrate supplementation contributed to preservation of muscle mass in older adults. HMB supplementation may be useful in the prevention of muscle atrophy induced by bed rest or other factors. Further studies are needed to determine the precise effects of HMB on muscle strength and physical function in older adults.
  9. ^ a b Brioche T, Pagano AF, Py G, Chopard A (April 2016). "Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention". Mol. Aspects Med. 50: 56–87. doi:10.1016/j.mam.2016.04.006. PMID 27106402. In conclusion, HMB treatment clearly appears to be a safe potent strategy against sarcopenia, and more generally against muscle wasting, because HMB improves muscle mass, muscle strength, and physical performance. It seems that HMB is able to act on three of the four major mechanisms involved in muscle deconditioning (protein turnover, apoptosis, and the regenerative process), whereas it is hypothesized to strongly affect the fourth (mitochondrial dynamics and functions). Moreover, HMB is cheap (~30– 50 US dollars per month at 3 g per day) and may prevent osteopenia (Bruckbauer and Zemel, 2013; Tatara, 2009; Tatara et al., 2007, 2008, 2012) and decrease cardiovascular risks (Nissen et al., 2000). For all these reasons, HMB should be routinely used in muscle-wasting conditions especially in aged people. ... 3 g of CaHMB taken three times a day (1 g each time) is the optimal posology, which allows for continual bioavailability of HMB in the body (Wilson et al., 2013).
  10. ^ a b Argilés JM, Campos N, Lopez-Pedrosa JM, Rueda R, Rodriguez-Mañas L (June 2016). "Skeletal Muscle Regulates Metabolism via Interorgan Crosstalk: Roles in Health and Disease". J. Am. Med. Dir. Assoc. 17 (9): 789–96. doi:10.1016/j.jamda.2016.04.019. PMID 27324808. Studies suggest dietary protein and leucine or its metabolite b-hydroxy b-methylbutyrate (HMB) can improve muscle function, in turn improving functional performance. ... These have identified the leucine metabolite β-hydroxy β-methylbutyrate (HMB) as a potent stimulator of protein synthesis as well as an inhibitor of protein breakdown in the extreme case of cachexia.65, 72, 76, 77, 78, 79, 80, 81, 82, 83, 84 A growing body of evidence suggests HMB may help slow, or even reverse, the muscle loss experienced in sarcopenia and improve measures of muscle strength.44, 65, 72, 76, 77, 78, 79, 80, 81, 82, 83, 84 However, dietary leucine does not provide a large amount of HMB: only a small portion, as little as 5%, of catabolized leucine is metabolized into HMB.85 Thus, although dietary leucine itself can lead to a modest stimulation of protein synthesis by producing a small amount of HMB, direct ingestion of HMB more potently affects such signaling, resulting in demonstrable muscle mass accretion.71, 80 Indeed, a vast number of studies have found that supplementation of HMB to the diet may reverse some of the muscle loss seen in sarcopenia and in hypercatabolic disease.65, 72, 83, 86, 87 The overall treatment of muscle atrophy should include dietary supplementation with HMB, although the optimal dosage for each condition is still under investigation.68 ...
    Figure 4: Treatments for sarcopenia. It is currently recommended that patients at risk of or suffering from sarcopenia consume a diet high in protein, engage in resistance exercise, and take supplements of the leucine metabolite HMB.
  11. ^ Mullin GE (February 2014). "Nutrition supplements for athletes: potential application to malnutrition". Nutr. Clin. Pract. 29 (1): 146–147. doi:10.1177/0884533613516130. PMID 24336486. There are a number of nutrition products on the market that are touted to improve sports performance. HMB appears to be the most promising and to have clinical applications to improve muscle mass and function. Continued research using this nutraceutical to prevent and/or improve malnutrition in the setting of muscle wasting is warranted.
  12. ^ D.Zhang et al., Functional Electrical Stimulation in Rehabilitation Engineering: A survey, Nenyang technological University, Singapore
  13. ^ a b Fuster G, Busquets S, Almendro V, López-Soriano FJ, Argilés JM; Busquets; Almendro; López-Soriano; Argilés (2007). "Antiproteolytic effects of plasma from hibernating bears: a new approach for muscle wasting therapy?". Clin Nutr. 26 (5): 658–61. doi:10.1016/j.clnu.2007.07.003. PMID 17904252.CS1 maint: Multiple names: authors list (link)
  14. ^ a b c Lohuis TD, Harlow HJ, Beck TD; Harlow; Beck (2007). "Hibernating black bears (Ursus americanus) experience skeletal muscle protein balance during winter anorexia". Comp. Biochem. Physiol. B, Biochem. Mol. Biol. 147 (1): 20–8. doi:10.1016/j.cbpb.2006.12.020. PMID 17307375.CS1 maint: Multiple names: authors list (link)
  15. ^ Carey HV, Andrews MT, Martin SL; Andrews; Martin (2003). "Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature". Physiol. Rev. 83 (4): 1153–81. doi:10.1152/physrev.00008.2003. PMID 14506303.CS1 maint: Multiple names: authors list (link)
  16. ^ a b Harlow, H. J.; Lohuis, T.; Anderson-Sprecher, R. C.; Beck, T. D I. (2004). "Body Surface Temperature Of Hibernating Black Bears May Be Related To Periodic Muscle Activity". Journal of Mammalogy. 85 (3): 414–419. doi:10.1644/1545-1542(2004)085<0414:BSTOHB>2.0.CO;2. ISSN 1545-1542.

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