Weakness

This article is about the medical condition. For other uses, seeWeakness (disambiguation)."Asthenia" redirects here. Thetortrix mothgenusis considered ajunior synonymofEpinotia.ICD-10R53

ICD-9728.87(728.9before 10/01/03); alternatively,780.79

DiseasesDB22832

MedlinePlus003174

MeSHD018908

Weaknessorastheniais asymptomof a number of different conditions.[1]The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety ofskeletal muscle diseases, includingmuscular dystrophyandinflammatory myopathy. It occurs inneuromuscular junctiondisorders, such asmyasthenia gravis.Contents[hide] 1Diagnostic Distinctions 1.1True weakness vs. perceived weakness 1.2Asthenia vs. myasthenia 2Differential diagnosis 2.1Central fatigue 2.2Neuromuscular fatigue 2.3Peripheral muscle fatigue 2.4Lactic acid hypothesis 3Pathophysiology 4References 5External linksDiagnostic Distinctions[edit]True weakness vs. perceived weakness[edit] True weakness(orneuromuscular) describes a condition where the force exerted by the muscles is less than would be expected, for examplemuscular dystrophy. Perceived weakness(ornon-neuromuscular) describes a condition where a person feels more effort than normal is required to exert a given amount of force but actual muscle strength is normal, for examplechronic fatigue syndrome.[2]In some conditions, such asmyasthenia gravis, muscle strength is normal when resting, buttrue weaknessoccurs after the muscle has been subjected to exercise. This is also true for some cases ofchronic fatigue syndrome, where objective post-exertion muscle weakness with delayed recovery time has been measured and is a feature of some of the published definitions.[3][4][5][6][7][8]Asthenia vs. myasthenia[edit]Asthenia(Greek:, lit.lack of strengthbut alsodisease) is a medical term referring to a condition in which the body lacks or has lost strength either as a whole or in any of its parts. It denotes symptoms of physical weakness andloss of strength. General asthenia occurs in many chronic wasting diseases (such as tuberculosis and cancer), sleep disorders or chronic disorders of the heart, lungs or kidneys, and is probably most marked in diseases of the adrenal gland. Asthenia may be limited to certainorgansor systems of organs, as inasthenopia, characterized by ready fatiguability. Asthenia is also a side effect of some medications and treatments, such asRitonavir(aprotease inhibitorused inHIVtreatment), vaccines such as the HPV vaccineGardasil[9]andfentanylpatches (anopioidused to treat pain).Differentiating psychogenic (perceived) asthenia and true asthenia from myasthenia is often difficult, and in time apparent psychogenic asthenia accompanying many chronic disorders is seen to progress into a primary weakness.Myasthenia(my- from Greek meaning "muscle" + -asthenia meaning "weakness"), or simplymuscle weakness, is a lack of muscle strength. The causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, including muscular dystrophy and inflammatory myopathy. It occurs inneuromuscular diseases, such as myasthenia gravis.Differential diagnosis[edit]Muscle fatigue can be central, neuromuscular, or peripheral muscular. Central muscle fatigue manifests as an overall sense of energy deprivation, and peripheral muscle weakness manifests as a local, muscle-specific inability to do work.[10][11]Neuromuscular fatigue can be either central or peripheral.Central fatigue[edit]Thecentral fatigueis generally described in terms of a reduction in theneuraldrive or nerve-based motor command to working muscles that results in a decline in the force output.[12][13][14]It has been suggested that the reduced neural drive during exercise may be a protective mechanism to prevent organ failure if the work was continued at the same intensity.[15][16]The exact mechanisms of central fatigue are unknown, though there has been a great deal of interest in the role ofserotonergicpathways.[17][18][19]Neuromuscular fatigue[edit]Nervescontrol the contraction of muscles by determining the number, sequence, and force of muscular contraction. When a nerve experiencessynaptic fatigueit becomes unable to stimulate the muscle that it innervates. Most movements require a force far below what a muscle could potentially generate, and barringpathology, neuromuscular fatigue is seldom an issue.For extremely powerful contractions that are close to the upper limit of a muscle's ability to generate force,neuromuscular fatiguecan become a limiting factor in untrained individuals. In novicestrength trainers, the muscle's ability to generate force is most strongly limited by nerves ability to sustain ahigh-frequency signal. After an extended period of maximum contraction, the nerves 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 move, oftenlengthening. As there is insufficient stress on the muscles and tendons, there will often be nodelayed onset muscle sorenessfollowing the workout. 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 their greatest force. It is this "neural training" that causes several weeks worth 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 sarcoplasmichypertrophyand metabolic fatigue becomes the factor limiting contractile force.Peripheral muscle fatigue[edit]Peripheral muscle fatigueduring physical work is considered[by whom?]an inability for the body to supply sufficient energy or other metabolites to the contracting muscles to meet the increased energy demand. This is the most common case of physical fatigueaffecting a national[where?]average of 72% of adults in the work force in 2002. This causes contractile dysfunction that manifests in the eventual reduction or lack of ability of a single muscle or local group of muscles to do work. The insufficiency of energy, i.e. sub-optimalaerobic metabolism, generally results in the accumulation oflactic acidand otheracidicanaerobic metabolic by-products in the muscle, causing the stereotypical burning sensation of local muscle fatigue, though recent studies have indicated otherwise, actually finding that lactic acid is a source of energy.[20]The fundamental difference between the peripheral and central theories of muscle fatigue is that the peripheral model of muscle fatigue assumes failure at one or more sites in the chain that initiates muscle contraction. Peripheral regulation therefore depends on the localized metabolic chemical conditions of the local muscle affected, whereas the central model of muscle fatigue is an integrated mechanism that works to preserve the integrity of the system by initiating muscle fatigue through muscle derecruitment, based on collective feedback from the periphery, before cellular or organ failure occurs. Therefore the feedback that is read by this central regulator could include chemical and mechanical as well as cognitive cues. The significance of each of these factors will depend on the nature of the fatigue-inducing work that is being performed.Though not universally used, "metabolic fatigue" is a common alternative term for peripheral muscle weakness, because of the reduction in contractile force due to the direct or indirect effects of the reduction of substrates or accumulation of metabolites within themyocytes. This can occur through a simple lack of energy to fuel contraction, or through interference with the ability of Ca2+to stimulateactinandmyosinto contract.Lactic acid hypothesis[edit]It was once believed thatlactic acidbuild-up was the cause of muscle fatigue.[21]The assumption was lactic acid had a "pickling" effect on muscles, inhibiting their ability to contract. The impact of lactic acid on performance is now uncertain, it may assist or hinder muscle fatigue.Produced as a by-product offermentation, lactic acid can increase intracellular acidity of muscles. This can lower the sensitivity of contractile apparatus tocalcium ions(Ca2+) but also has the effect of increasingcytoplasmicCa2+concentration through an inhibition of thechemical pumpthatactively transportscalcium out of the cell. This counters inhibiting effects ofpotassium ions(K+) 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 K+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 Ca2+.Pathophysiology[edit]Main article:muscle contractionMuscle cells work by detecting aflowof electrical impulses from thebrain, which signals them tocontractthrough the release ofcalciumby thesarcoplasmic reticulum. Fatigue (reduced ability to generate force) may occur due to the nerve, or within the muscle cells themselves. New research from scientists at Columbia University suggests that muscle fatigue is caused by calcium leaking out of the muscle cell. This makes less calcium available for the muscle cell. In addition, the Columbia researchers propose that an enzyme activated by this released calcium eats away at muscle fibers.[22]Substrateswithin the muscle generally serve to power muscular contractions. They include molecules such asadenosine triphosphate(ATP),glycogenandcreatine phosphate. ATP binds to themyosinhead and causes the ratchetting that results in contraction according to thesliding filament model. Creatine phosphate stores energy so ATP can be rapidly regenerated within the muscle cells fromadenosine diphosphate(ADP) and inorganic phosphate ions, allowing for sustained powerful contractions that last between 57 seconds. Glycogen is the intramuscular storage form ofglucose, used to generate energy quickly once intramuscular creatine stores are exhausted, producinglactic acidas a metabolic byproduct. Contrary to common belief, lactic acid accumulation doesn't actually cause the burning sensation we feel when we exhaust our oxygen and oxidative metabolism, but in actuality, lactic acid in presence of oxygen recycles to produce pyruvate in the liver, which is known as the Cori cycle.Substrates produce metabolic fatigue by being depleted during exercise, 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.References[edit]1. Jump up^Marx, John (2010).Rosen's Emergency Medicine: Concepts and Clinical Practice(7th ed.). Philadelphia, PA: Mosby/Elsevier. p.Chapter 11.ISBN978-0-323-05472-0.2. Jump up^Ropper, Allan H.; Samuels, Martin A.(2009).Adams and Victor's Principles of Neurology, Ninth Edition. McGraw-Hill.ISBN978-0071499927.3. Jump up^Paul L, Wood L, Behan WM, Maclaren WM (January 1999)."Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome".Eur. J. Neurol.6(1): 639.doi:10.1046/j.1468-1331.1999.610063.x.PMID10209352.4. Jump up^McCully KK, Natelson BH (November 1999)."Impaired oxygen delivery to muscle in chronic fatigue syndrome".Clin. Sci.97(5): 6038; discussion 6113.doi:10.1042/CS19980372.PMID10545311.5. Jump up^De Becker P, Roeykens J, Reynders M, McGregor N, De Meirleir K (November 2000)."Exercise capacity in chronic fatigue syndrome".Arch. Intern. Med.160(21): 32707.doi:10.1001/archinte.160.21.3270.PMID11088089.6. Jump up^De Becker P, McGregor N, De Meirleir K (September 2001)."A definition-based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome".J. Intern. Med.250(3): 23440.doi:10.1046/j.1365-2796.2001.00890.x.PMID11555128.7. Jump up^Carruthers, Bruce M.; Jain, Anil Kumar; De Meirleir, Kenny L.; Peterson, Daniel L.; Klimas, Nancy G. et al. (2003). "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols".Journal of Chronic Fatigue Syndrome11(1): 7115.doi:10.1300/J092v11n01_02.ISBN0-7890-2207-9.ISSN1057-3321.8. Jump up^Jammes Y, Steinberg JG, Mambrini O, Brgeon F, Delliaux S (March 2005)."Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise".J. Intern. Med.257(3): 299310.doi:10.1111/j.1365-2796.2005.01452.x.PMID15715687.9. Jump up^Loris McVittie, Ph.D. (June 12, 2008)."Information from CDC and FDA on the Safety of Gardasil Vaccine". Office of Vaccines Research and Review at the US FDA. Retrieved2008-07-21.We have approved your supplement to yourbiologics license application(BLA) for Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant (GARDASIL), to include arthralgia, myalgia, asthenia, fatigue, and malaise in the Adverse Reactions section of the package insert to reflect reports received during post-marketing surveillance, to include corresponding changes to the patient package insert, and to include additional minor editorial changes to the package insert.[dead link]10. Jump up^Gandevia SC, Enoka RM, McComas AJ, Stuart DG, Thomas CK (1995). "Neurobiology of muscle fatigue. Advances and issues".Adv. Exp. Med. Biol.384: 51525.PMID8585476.11. Jump up^Kent-Braun JA (1999). "Central and peripheral contributions to muscle fatigue in humans during sustained maximal effort".European journal of applied physiology and occupational physiology80(1): 5763.doi:10.1007/s004210050558.PMID10367724.12. Jump up^Gandevia SC (2001). "Spinal and supraspinal factors in human muscle fatigue".Physiol. Rev.81(4): 172589.PMID11581501.13. Jump up^Kay D, Marino FE, Cannon J, St Clair Gibson A, Lambert MI, Noakes TD (2001). "Evidence for neuromuscular fatigue during high-intensity cycling in warm, humid conditions".Eur. J. Appl. Physiol.84(12): 11521.doi:10.1007/s004210000340.PMID11394239.14. Jump up^Vandewalle H, Maton B, Le Bozec S, Guerenbourg G (1991). "An electromyographic study of an all-out exercise on a cycle ergometer".Archives internationales de physiologie, de biochimie et de biophysique99(1): 8993.doi:10.3109/13813459109145909.PMID1713492.15. Jump up^Bigland-Ritchie B, Woods JJ (1984). "Changes in muscle contractile properties and neural control during human muscular fatigue".Muscle Nerve7(9): 6919.doi:10.1002/mus.880070902.PMID6100456.16. Jump up^Noakes TD (2000). "Physiological models to understand exercise fatigue and the adaptations that predict or enhance athletic performance".Scandinavian journal of medicine & science in sports10(3): 12345.doi:10.1034/j.1600-0838.2000.010003123.x.PMID10843507.17. Jump up^Davis JM (1995). "Carbohydrates, branched-chain amino acids, and endurance: the central fatigue hypothesis".Int J Sport Nutr5(Suppl): S2938.PMID7550256.18. Jump up^Newsholme, E. A., Acworth, I. N., & Blomstrand, E. 1987, 'Amino acids, brain neurotransmitters and a functional link between muscle and brain that is important in sustained exercise', in G Benzi (ed.), Advances in Myochemistry, Libbey Eurotext, London, pp. 127-133.19. Jump up^Newsholme EA, Blomstrand E (1995). "Tryptophan, 5-hydroxytryptamine and a possible explanation for central fatigue".Adv. Exp. Med. Biol.384: 31520.doi:10.1007/978-1-4899-1016-5_25.PMID8585461.20. Jump up^R. Robergs, F. Ghiasvand, D. Parker (2004). "Biochemistry of exercise-induced metabolic acidosis".Am J Physiol Regul Integr Comp Physiol287(3): R50216.doi:10.1152/ajpregu.00114.2004.PMID15308499.21. Jump up^Sahlin K (1986). "Muscle fatigue and lactic acid accumulation".Acta Physiol Scand Suppl556: 8391.PMID3471061.22. Jump up^Kolata, Gina (February 12, 2008)."Finding May Solve Riddle of Fatigue in Muscles".The New York Times.