Editing Muscle fatigue

{{Hatnote| For reduced ability to generate muscle force as a symptom or that does not improve with rest, see [[muscle weakness]]. For the absence of muscle weakness coupled with the feeling that it requires more effort to move the muscle, see [[asthenia]].}}

{{short description|Initially normal, then declining ability of a muscle to generate force}}

'''Muscle fatigue''' is when muscles that were initially generating a normal amount of [[force]], then experience a declining ability to generate force. It can be a result of vigorous [[Physical exercise|exercise]], but abnormal fatigue may be caused by barriers to or interference with the different stages of [[muscle contraction]]. There are two main causes of muscle fatigue: the limitations of a [[nerve]]’s ability to generate a sustained [[Action potential|signal]] (neural fatigue); and the reduced ability of the [[muscle fiber]] to contract (metabolic fatigue).

Muscle fatigue is not the same as muscle weakness, though weakness is an initial symptom. Despite a normal amount of force being generated at the start of activity, once muscle fatigue has set in and progressively worsens, if the individual persists in the exercise they will eventually lose their hand grip, or become unable to lift or push with their arms or legs, or become unable to maintain an isometric position (such as [[Plank (exercise)|plank]]). Other symptoms may accompany such as myalgia (muscle pain), shortness of breath, fasciculations (muscle twitching), myokymia (muscle trembling), and muscle cramps during exercise; muscle soreness may occur afterwards.<ref>{{Cite web |title=Muscle Fatigue |url=https://www.physio-pedia.com/Muscle_Fatigue |access-date=2023-11-19 |website=Physiopedia |language=en}}</ref> An inappropriate rapid heart rate response to exercise may be seen, such as in the metabolic myopathy of McArdle disease (GSD-V), where the heart tries to compensate for the deficit of ATP in the [[skeletal muscle]] cells (metabolic fatigue) by increasing heart rate to maximize delivery of oxygen and blood borne fuels to the muscles for oxidative phosphorylation.<ref>{{Cite journal |last1=Lucia |first1=Alejandro |last2=Martinuzzi |first2=Andrea |last3=Nogales-Gadea |first3=Gisela |last4=Quinlivan |first4=Ros |last5=Reason |first5=Stacey |last6=Bali |first6=Deeksha |last7=Godfrey |first7=Richard |last8=Haller |first8=Ronald |last9=Kishnani |first9=Priya |last10=Laforêt |first10=Pascal |last11=Løkken |first11=Nicoline |last12=Musumeci |first12=Olimpia |last13=Santalla |first13=Alfredo |last14=Tarnopolsky |first14=Mark |last15=Toscano |first15=Antonio |date=December 2021 |title=Clinical practice guidelines for glycogen storage disease V & VII (McArdle disease and Tarui disease) from an international study group |journal=Neuromuscular Disorders |volume=31 |issue=12 |pages=1296–1310 |doi=10.1016/j.nmd.2021.10.006 |issn=0960-8966|doi-access=free |pmid=34848128 }}</ref> The combination of an inappropriate rapid heart rate response to exercise with heavy or rapid breathing is known as an exaggerated cardiorespiratory response to exercise.<ref>{{Cite journal |last1=Noury |first1=Jean-Baptiste |last2=Zagnoli |first2=Fabien |last3=Petit |first3=François |last4=Marcorelles |first4=Pascale |last5=Rannou |first5=Fabrice |date=2020-05-29 |title=Exercise efficiency impairment in metabolic myopathies |journal=Scientific Reports |volume=10 |issue=1 |pages=8765 |doi=10.1038/s41598-020-65770-y |issn=2045-2322 |pmc=7260200 |pmid=32472082|bibcode=2020NatSR..10.8765N }}</ref>  

Due to the confusion between muscle fatigue and muscle weakness, there have been instances of abnormal muscle fatigue being described as exercise-induced muscle weakness.<ref>{{Cite web |title=#254110 - MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 8; LGMDR8 |url=https://www.omim.org/entry/254110 |access-date=2023-11-19 |website=www.omim.org |language=en-us}}</ref><ref>{{Cite web |title=#300559 - GLYCOGEN STORAGE DISEASE IXd; GSD9D |url=https://www.omim.org/entry/300559 |access-date=2023-11-19 |website=www.omim.org |language=en-us}}</ref><ref>{{Cite journal |last1=Das |first1=Anibh M. |last2=Steuerwald |first2=Ulrike |last3=Illsinger |first3=Sabine |date=2010 |title=Inborn errors of energy metabolism associated with myopathies |journal=Journal of Biomedicine & Biotechnology |volume=2010 |pages=340849 |doi=10.1155/2010/340849 |issn=1110-7251 |pmc=2877206 |pmid=20589068 |quote=There are three phenotypes of CPT2 deficiency: the 'classic muscular form' (OMIM 255110) is most frequent and shows onset in childhood or adulthood with exercise-induced muscle weakness and rhabdomyolysis. |doi-access=free }}</ref>  

==Muscle contraction==
{{main|Muscle contraction}}
Muscle cells work by detecting a [[Action potential|flow]] of electrical impulses from the [[brain]] which signals them to [[Muscle contraction|contract]] through the release of [[calcium]] by the [[sarcoplasmic reticulum]].  Fatigue (reduced ability to generate force) may occur due to the nerve, or within the muscle cells themselves.{{cn|date=May 2023}}

==Neural fatigue ==
[[Nerve]]s are responsible for controlling the contraction of muscles, determining the number, sequence and force of muscular contraction.  Most movements require a force far below what a muscle could potentially generate, and nervous fatigue is seldom an issue. But, during extremely powerful contractions that are close to the upper limit of a muscle's ability to generate force, nervous fatigue (enervation)&nbsp;&mdash; in which the nerve signal weakens&nbsp;&mdash; can be a limiting factor in untrained individuals.{{Citation needed|date=April 2022}}

In novice [[strength training|strength trainers]], the muscle's ability to generate force is most strongly limited by nerve’s ability to sustain a high-frequency signal.  After a period of maximum contraction, the nerve’s signal reduces in frequency and the force generated by the contraction diminishes.  There is no sensation of pain or discomfort, the muscle appears to simply ‘stop listening’ and gradually cease to contract, often [[Muscle contraction#Eccentric contraction|going backwards]].  Often there is insufficient stress on the muscles and tendons to cause [[delayed onset muscle soreness]] following the workout.{{Citation needed|date=April 2022}}

Part of the process of strength training is increasing the nerve's ability to generate sustained, high frequency signals which allow a muscle to contract with its greatest force.  This neural training can cause several weeks of rapid gains in strength, which level off once the nerve is generating maximum contractions and the muscle reaches its physiological limit.  Past this point, training effects increase muscular strength through myofibrillar or sarcoplasmic [[Muscle hypertrophy#Strength training|hypertrophy]] and metabolic fatigue becomes the factor limiting contractile force.{{Citation needed|date=April 2022}}

==Metabolic fatigue==
Though not universally used, ‘metabolic fatigue’ is a common term for the reduction in contractile force due to the direct or indirect effects of two main factors:
# Shortage of, or inability to metabolize, fuel ([[Substrate (biochemistry)|substrates]]) within the [[muscle fiber]] causing a low ATP reservoir.
# Accumulation of substances ([[metabolite]]s) within the muscle fiber, which interfere either with the release of calcium (Ca<sup>2+</sup>) or with the ability of calcium to stimulate muscle contraction.

===Substrates===
[[Substrate (biochemistry)|Substrates]] within the muscle serve to power muscular contractions. They include molecules such as [[adenosine triphosphate]] (ATP), [[glycogen]] and [[Phosphocreatine|creatine phosphate]]. ATP binds to the [[myosin]] head and causes the ‘ratchetting’ that results in contraction according to the [[Sliding filament mechanism|sliding filament model]]. Creatine phosphate stores energy so ATP can be rapidly regenerated within the muscle cells from [[adenosine diphosphate]] (ADP) and inorganic phosphate ions, allowing for sustained powerful contractions that last between 5–7 seconds. Glycogen is the intramuscular storage form of [[glucose]], used to generate energy quickly as intramuscular phosphocreatine stores become exhausted, producing [[lactic acid]] as a metabolic byproduct.

Substrate shortage is one of the causes of metabolic fatigue. Substrates are depleted during exercise or are unable to be metabolized (e.g. [[Metabolic myopathy|metabolic myopathies]]), resulting in a lack of intracellular energy sources to fuel contractions. In essence, the muscle stops contracting because it lacks the energy to do so.

===Metabolites===
Metabolites are the substances (generally waste products) produced as a result of muscular contraction.  They include [[chloride]], [[potassium]], [[lactic acid]], [[Adenosine diphosphate|ADP]], [[magnesium]] (Mg<sup>2+</sup>), [[reactive oxygen species]], and [[inorganic phosphate]].  Accumulation of metabolites can directly or indirectly produce metabolic fatigue within muscle fibers through interference with the release of calcium (Ca<sup>2+</sup>) from the sarcoplasmic reticulum or reduction of the sensitivity of contractile molecules [[actin]] and [[myosin]] to calcium.

====Chloride====
Intracellular [[chloride]] partially inhibits the contraction of muscles. Namely, it prevents muscles from contracting due to "false alarms", small stimuli which may cause them to contract (akin to [[myoclonus]]).

====Potassium====
High concentrations of [[potassium]] (K<sup>+</sup>) also causes the muscle cells to decrease in efficiency, causing cramping and fatigue. Potassium builds up in the [[t-tubule]] system and around the muscle fiber as a result of [[action potentials]]. The shift in K<sup>+</sup> changes the membrane potential around the muscle fiber. The change in membrane potential causes a decrease in the release of [[calcium]] (Ca<sup>2+</sup>) from the [[sarcoplasmic reticulum]].<ref name="Silverthorne2009">{{cite book|author=Dee Unglaub Silverthorn|title=Human Physiology: An Integrated Approach|year=2009|publisher= Pearson|edition = 5th|isbn= 978-0321559807|page=412}}</ref>

====Lactic acid====
It was once believed that [[lactic acid]] build-up was the cause of muscle fatigue.<ref name="pmid3471061">{{cite journal | vauthors = Sahlin K | title = Muscle fatigue and lactic acid accumulation | journal = Acta Physiol Scand Suppl | volume = 556 | pages = 83–91 | date = 1986 | pmid = 3471061 }}</ref>  The assumption was lactic acid had a "pickling" effect on muscles, inhibiting their ability to contract.  Though the impact of lactic acid on performance is now uncertain, it may assist or hinder muscle fatigue.

Produced as a by-product of [[lactic acid fermentation|fermentation]], lactic acid can increase intracellular acidity of muscles.  This can lower the sensitivity of contractile apparatus to Ca<sup>2+</sup> but also has the effect of increasing [[cytoplasm]]ic Ca<sup>2+</sup> concentration through an inhibition of the [[sodium-calcium exchanger|chemical pump]] that [[Active transport|actively transports]] calcium out of the cell.  This counters inhibiting effects of potassium on muscular action potentials.  Lactic acid also has a negating effect on the chloride ions in the muscles, reducing their inhibition of contraction and leaving potassium ions as the only restricting influence on muscle contractions, though the effects of potassium are much less than if there were no lactic acid to remove the chloride ions.  Ultimately, it is uncertain if lactic acid reduces fatigue through increased intracellular calcium or increases fatigue through reduced sensitivity of contractile proteins to Ca<sup>2+</sup>.

Lactic acid is now used as a measure of endurance training effectiveness and [[VO2 max|VO<sub>2</sub> max]].<ref name="pmid26136542">{{cite journal | vauthors = Lundby C, Robach P | title = Performance Enhancement: What Are the Physiological Limits? | journal = Physiology | volume = 30 | issue = 4 | pages = 282–92 | date = July 2015 | pmid = 26136542 | doi = 10.1152/physiol.00052.2014 | s2cid = 36073287 }}</ref>

==Pathology==
Muscle fatigue may be due to problems with the [[neuropathy|nerve supply]], [[neuromuscular disease]] (such as [[myasthenia gravis]]), [[inborn errors of metabolism]] (such as [[Metabolic myopathy|metabolic myopathies]]), or problems with muscle itself. The latter category includes [[polymyositis]] and other [[myopathy|muscle disorders]].

==Molecular mechanisms==
Muscle fatigue may be due to precise molecular changes that occur ''in vivo'' with sustained exercise. It has been found that the [[ryanodine receptor]] present in skeletal muscle undergoes a [[conformational change]] during exercise, resulting in "leaky" channels that are deficient in [[calcium]] release. These "leaky" channels may be a contributor to muscle fatigue and decreased exercise capacity.<ref name="pmid18268335">{{cite journal | vauthors = Bellinger AM, Reiken S, Dura M, Murphy PW, Deng SX, Landry DW, Nieman D, Lehnart SE, Samaru M, LaCampagne A, Marks AR | title = Remodeling of ryanodine receptor complex causes "leaky" channels: a molecular mechanism for decreased exercise capacity | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 105 | issue = 6 | pages = 2198–202 | date = February 2008 | pmid = 18268335 | pmc = 2538898 | doi = 10.1073/pnas.0711074105 | bibcode = 2008PNAS..105.2198B | doi-access = free }}</ref>

==Effect on performance==
Fatigue has been found to play a big role in limiting performance in just about every individual in every sport.  In research studies, participants were found to show reduced voluntary force production in fatigued muscles (measured with concentric, eccentric, and isometric contractions), vertical jump heights, other field tests of lower body power, reduced throwing velocities, reduced kicking power and velocity, less accuracy in throwing and shooting activities, endurance capacity, anaerobic capacity, anaerobic power, mental concentration, and many other performance parameters when sport specific skills are examined.<ref name="pmid21425889">{{cite journal | vauthors = Knicker AJ, Renshaw I, Oldham AR, Cairns SP | title = Interactive processes link the multiple symptoms of fatigue in sport competition | journal = Sports Med | volume = 41 | issue = 4 | pages = 307–28 | date = April 2011 | pmid = 21425889 | doi = 10.2165/11586070-000000000-00000  | s2cid = 20840531 | url = http://eprints.qut.edu.au/47248/1/47248_acceptedVersion.pdf }}</ref><ref name="pmid18608847">{{cite journal | vauthors = Montgomery PG, Pyne DB, Hopkins WG, Dorman JC, Cook K, Minahan CL | title = The effect of recovery strategies on physical performance and cumulative fatigue in competitive basketball | journal = J Sports Sci | volume = 26 | issue = 11 | pages = 1135–45 | date = September 2008 | pmid = 18608847 | doi = 10.1080/02640410802104912 | s2cid = 37412777 }}</ref><ref name="pmid9459539">{{cite journal | vauthors = Linnamo V, Häkkinen K, Komi PV | title = Neuromuscular fatigue and recovery in maximal compared to explosive strength loading | journal = Eur J Appl Physiol Occup Physiol | volume = 77 | issue = 1–2 | pages = 176–81 | date = 1998 | pmid = 9459539 | doi = 10.1007/s004210050317 | s2cid = 27621985 }}</ref><ref name="pmid19834352">{{cite journal | vauthors = Smilios I, Häkkinen K, Tokmakidis SP | title = Power output and electromyographic activity during and after a moderate load muscular endurance session | journal = J Strength Cond Res | volume = 24 | issue = 8 | pages = 2122–31 | date = August 2010 | pmid = 19834352 | doi = 10.1519/JSC.0b013e3181a5bc44  | s2cid = 25256350 | doi-access = free }}</ref><ref name="pmid16720888">{{cite journal | vauthors = Girard O, Lattier G, Micallef JP, Millet GP | title = Changes in exercise characteristics, maximal voluntary contraction, and explosive strength during prolonged tennis playing | journal = Br J Sports Med | volume = 40 | issue = 6 | pages = 521–6 | date = June 2006 | pmid = 16720888 | pmc = 2465109 | doi = 10.1136/bjsm.2005.023754  }}</ref>

==Electromyography==
[[Electromyography]] is a research technique that allows researchers to look at muscle recruitment in various conditions, by quantifying electrical signals sent to muscle fibers through motor neurons.  In general, fatigue protocols have shown increases in EMG data over the course of a fatiguing protocol, but reduced recruitment of muscle fibers in tests of power in fatigued individuals.  In most studies, this increase in recruitment during exercise correlated with a decrease in performance (as would be expected in a fatiguing individual).<ref name="pmid21284370">{{cite journal | vauthors = Carneiro JG, Gonçalves EM, Camata TV, Altimari JM, Machado MV, Batista AR, Guerra Junior G, Moraes AC, Altimari LR | title = Influence of gender on the EMG signal of the quadriceps femoris muscles and performance in high-intensity short-term exercise | journal = Electromyogr Clin Neurophysiol | volume = 50 | issue = 7–8 | pages = 326–32 | date = 2010 | pmid = 21284370 }}</ref><ref name="pmid12576411">{{cite journal | vauthors = Clark BC, Manini TM, Thé DJ, Doldo NA, Ploutz-Snyder LL | title = Gender differences in skeletal muscle fatigability are related to contraction type and EMG spectral compression | journal = J. Appl. Physiol. | volume = 94 | issue = 6 | pages = 2263–72 | date = June 2003 | pmid = 12576411 | doi = 10.1152/japplphysiol.00926.2002 | s2cid = 16202462 }}</ref><ref name="pmid23083331">{{cite journal | vauthors = Beneka AG, Malliou PK, Missailidou V, Chatzinikolaou A, Fatouros I, Gourgoulis V, Georgiadis E | title = Muscle performance following an acute bout of plyometric training combined with low or high intensity weight exercise | journal = J Sports Sci | volume = 31 | issue = 3 | pages = 335–43 | date = 2013 | pmid = 23083331 | doi = 10.1080/02640414.2012.733820 | s2cid = 31326593 }}</ref><ref name="pmid10774875">{{cite journal | vauthors = Pincivero DM, Aldworth C, Dickerson T, Petry C, Shultz T | title = Quadriceps-hamstring EMG activity during functional, closed kinetic chain exercise to fatigue | journal = Eur. J. Appl. Physiol. | volume = 81 | issue = 6 | pages = 504–9 | date = April 2000 | pmid = 10774875 | doi = 10.1007/s004210050075 | s2cid = 9033212 }}</ref>

Median power frequency is often used as a way to track fatigue using EMG. Using the median power frequency, raw EMG data is filtered to reduce noise and then relevant time windows are Fourier Transformed. In the case of fatigue in a 30-second isometric contraction, the first window may be the first second, the second window might be at second 15, and the third window could be the last second of contraction (at second 30). Each window of data is analyzed and the median power frequency is found. Generally, the median power frequency decreases over time, demonstrating fatigue. Some reasons why fatigue is found are due to action potentials of motor units having a similar pattern of repolarization, fast motor units activating and then quickly deactivating while slower motor units remain, and conduction velocities of the nervous system decreasing over time.<ref name="pmid22067242">{{cite journal | vauthors = Jakobsen MD, Sundstrup E, Andersen CH, Zebis MK, Mortensen P, Andersen LL | title = Evaluation of muscle activity during a standardized shoulder resistance training bout in novice individuals | journal = J Strength Cond Res | volume = 26 | issue = 9 | pages = 2515–22 | date = September 2012 | pmid = 22067242 | doi = 10.1519/JSC.0b013e31823f29d9  | s2cid = 17445280 | doi-access = free }}</ref><ref name="pmid21986694">{{cite journal | vauthors = Sundstrup E, Jakobsen MD, Andersen CH, Zebis MK, Mortensen OS, Andersen LL | title = Muscle activation strategies during strength training with heavy loading vs. repetitions to failure | journal = J Strength Cond Res | volume = 26 | issue = 7 | pages = 1897–903 | date = July 2012 | pmid = 21986694 | doi = 10.1519/JSC.0b013e318239c38e  | s2cid = 5587233 | doi-access = free }}</ref><ref name="pmid21696871">{{cite journal | vauthors = Cardozo AC, Gonçalves M, Dolan P | title = Back extensor muscle fatigue at submaximal workloads assessed using frequency banding of the electromyographic signal | journal = Clin Biomech (Bristol, Avon) | volume = 26 | issue = 10 | pages = 971–6 | date = December 2011 | pmid = 21696871 | doi = 10.1016/j.clinbiomech.2011.06.001 }}</ref><ref name="pmid23211923">{{cite journal | vauthors = Hollman JH, Hohl JM, Kraft JL, Strauss JD, Traver KJ | title = Does the fast Fourier transformation window length affect the slope of an electromyogram's median frequency plot during a fatiguing isometric contraction? | journal = Gait Posture | volume = 38 | issue = 1 | pages = 161–4 | date = May 2013 | pmid = 23211923 | doi = 10.1016/j.gaitpost.2012.10.028  }}</ref>

==See also==
*[[Asthenia]]
*[[Debility (medical)|Debility]]
*[[Exercise intolerance#Low ATP reservoir in muscles (inherited or acquired)|Exercise intolerance § Low ATP reservoir in muscles (inherited or acquired)]]
*[[Fatigue (medical)]]
*[[Central fatigue]]
*[[Malaise]]
*[[Metabolic myopathy|Metabolic myopathies]]
*[[Uric acid#High uric acid|Myogenic hyperuricemia]] (due low ATP reservoir in muscle cell)
*[[Muscle weakness]]
*[[Paresis]]

==References==
{{reflist|30em}}

==External links==
* {{MeshName|Muscle+Fatigue}}
{{Myopathy}}
[[Category:Neurological disorders]]
[[Category:Muscular disorders]]
[[Category:Exercise physiology]]