Weakness, is a symptom used to describe a number of different conditions including: lack of muscle strength, malaise Malaise is a feeling of general discomfort or uneasiness, an "out of sorts" feeling, often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell", dizziness Dizziness refers to an impairment in spatial perception and stability. It is considered imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or for a non-specific feeling such as giddiness or foolishness or fatigue.^[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 of skeletal muscle diseases, including muscular dystrophy Muscular dystrophy refers to a group of hereditary muscle diseases that weaken the muscles that move the human body. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue. Nine diseases including Duchenne, Becker, limb girdle, congenital, and inflammatory myopathy. It occurs in neuromuscular junction A neuromuscular junction is the synapse or junction of the axon terminal of a motoneuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract. In vertebrates, the signal passes through the disorders, such as myasthenia gravis Myasthenia gravis is a neuromuscular disease leading to fluctuating muscle weakness and fatiguability. It is an autoimmune disorder, in which weakness is caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine.

Definition

Weakness is used to describe a number of symptoms including: loss of muscle strength Muscle is the 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 produce force and cause motion. Muscles can cause, malaise Malaise is a feeling of general discomfort or uneasiness, an "out of sorts" feeling, often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell", dizziness Dizziness refers to an impairment in spatial perception and stability. It is considered imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or for a non-specific feeling such as giddiness or foolishness or fatigue.^[1] The term can be divided into two other more specific states, true weakness and perceived weakness.^[1]

• True weakness (or neuromuscular) describes a condition where the force exerted by the muscles is less than would be expected, for example muscular dystrophy Muscular dystrophy refers to a group of hereditary muscle diseases that weaken the muscles that move the human body. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue. Nine diseases including Duchenne, Becker, limb girdle, congenital,.

• Perceived weakness (or non-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 example chronic fatigue syndrome Сhronic fatigue syndrome is the most common name given to a variably debilitating disorder or disorders generally defined by persistent fatigue unrelated to exertion and not substantially relieved by rest, and accompanied by the presence of other specific symptoms for a minimum of six months. The disorder may also be referred to as post-viral.^[2]

In some conditions, such as myasthenia gravis Myasthenia gravis is a neuromuscular disease leading to fluctuating muscle weakness and fatiguability. It is an autoimmune disorder, in which weakness is caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine muscle strength is normal when resting, but true weakness occurs after the muscle has been subjected to exercise. This is also true for some cases of CSI, 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 (Greek Greek , an independent branch of the Indo-European family of languages, is the language of the Greeks. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. In its ancient form, it is the language of classical ancient Greek literature and the New Testament of: ασθένεια, lit. lack of strength but also disease) is a medical term denoting symptoms of physical weakness Muscle weakness, also known as muscle fatigue, refers to the inability to exert force with one's skeletal muscles. Weakness often follows muscle atrophy and a decrease in activity, such as after a long bout of bedrest as a result of an illness and loss of strength.

A condition in which the body lacks or has lost strength either as a whole or in any of its parts. General asthenia occurs in many chronic wasting diseases, such as anemia and cancer, and is probably most marked in diseases of the adrenal gland. Asthenia may be limited to certain organs In biology and anatomy, an organ is a collection of tissues joined in structural unit to serve a common function or systems of organs, as in asthenopia Asthenopia or eye strain is an ophthalmological condition that manifests itself through nonspecific symptoms such as fatigue, pain in or around the eyes, blurred vision, headache and occasional double vision. Symptoms often occur after reading, computer work, or other close activities that involve tedious visual tasks, characterized by ready fatiguability.

Asthenia is also a side effect of some medications and treatments, such as Ritonavir Ritonavir, with trade name Norvir , is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS (a protease inhibitor Protease inhibitors are a class of medications used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new virons used in HIV Human immunodeficiency virus is a lentivirus (a member of the retrovirus family) that causes acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or treatment), vaccines such as the HPV vaccine Gardasil Gardasil , also known as Gardisil or Silgard, is a vaccine alleged to prevent certain types of human papillomavirus (HPV), specifically HPV types 16, 18, 6, and 11. HPV types 16 and 18 are currently associated with about 70% of cervical, 26% of head and neck and many vulvar, vaginal, penile, and anal cancer cases. HPV types 6 and 11 are associated^[9] and fentanyl Fentanyl is a synthetic primary μ-opioid agonist and a potent narcotic analgesic with a rapid onset and short duration of action. Historically it has been used to treat chronic breakthrough pain and is commonly used pre-procedures patches (an opioid An opioid is a chemical that works by binding to opioid receptors, which are found principally in the central nervous system and the gastrointestinal tract. The receptors in these organ systems mediate both the beneficial effects and the side effects of opioids used to treat pain).

The condition is also commonly seen in patients suffering from chronic fatigue syndrome, sleep disorders or chronic disorders of the heart, lungs or kidneys.

Differentiating between psychogenic asthenia and true asthenia with muscular weakness is often difficult, and in time apparent psychogenic asthenia accompanying many chronic disorders is seen to progress into a primary weakness.

Differential diagnosis

Weakness can be central, neural and peripheral. Central muscle weakness manifests as an overall, bodily or systemic, sense of energy deprivation, and peripheral weakness manifests as a local, muscle-specific incapacity to do work.^[10].^[11] Neural weakness can be both central and peripheral.

Central

The central component to muscle fatigue is generally described in terms of a reduction in the neural The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous system contains the brain, spinal cord, and retina drive 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 although there has been a great deal of interest in the role of serotonergic pathways.^[17][18][19]

Neural

Nerves A peripheral nerve, or simply nerve is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system. In the central nervous system, the analogous structures are known as tracts 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 in potential generate, and barring pathology In medicine, pathology is the study and diagnosis of disease. The related scientific study of disease processes is called "general pathology". Medical pathology is divided into two main branches, anatomical pathology and clinical pathology. Medical pathologists work through examination of organs, tissues, bodily fluids, and whole bodies nervous fatigue is seldom an issue. For extremely powerful contractions that are close to the upper limit of a muscle's ability to generate force, nervous fatigue can be a limiting factor in untrained individuals. In novice strength trainers Strength training is the use of resistance to muscular contraction to build the strength, anaerobic endurance and size of skeletal muscles. There are many different methods of strength training, the most common being the use of gravity or elastic/hydraulic forces to oppose muscle contraction. See the resistance training article for information, 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 move, often going backwards Muscle fiber generates tension through the action of actin and myosin cross-bridge cycling. While under tension, the muscle may lengthen, shorten or remain the same. Although the term 'contraction' implies shortening, when referring to the muscular system it means muscle fibers generating tension with the help of motor neurons. As there is insufficient stress on the muscles and tendons, there will often be no delayed onset muscle soreness Delayed onset muscle soreness , also called muscle fever, is the pain and stiffness felt in muscles about 24 to 72 hours after unaccustomed and/or strenuous exercise. It is a symptom of muscle damage caused by eccentric exercise. After such exercise, the muscle adapts rapidly to prevent muscle damage, and thereby DOMS, in repeated bouts following 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 myofibrilar or sarcoplasmic hypertrophy Muscle hypertrophy is the increase of the size of muscle cells. It differs from muscle hyperplasia, which is the formation of new muscle cells and metabolic fatigue becomes the factor limiting contractile force.

Peripheral

Peripheral muscle fatigue during physical work is considered 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 fatigue—affecting a national average of 72% of adults in the work force in 2002. This causes contractile dysfunction that is manifested 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-optimal aerobic metabolism Cellular respiration, also known as 'oxidative metabolism', is one of the key ways a cell gains useful energy. It is the set of the metabolic reactions and processes that take place in organisms' cells to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration, generally results in the accumulation of lactic acid Lactic acid , also known as milk acid, is a chemical compound that plays a role in several biochemical processes. It was first isolated in 1780 by a Swedish chemist, Carl Wilhelm Scheele, and is a carboxylic acid with a chemical formula of C3H6O3. It has a hydroxyl group adjacent to the carboxyl group, making it an alpha hydroxy acid (AHA). In and other acidic An acid is any chemical compound that, when dissolved in water, gives a solution with a hydrogen ion activity greater than in pure water, i.e. a pH less than 7.0 in its standard state. That approximates the modern definition of Johannes Nicolaus Brønsted and Martin Lowry, who independently defined an acid as a compound which donates a hydrogen anaerobic 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 is therefore dependent on the localised 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 the muscle fiber Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system. It is one of three major muscle types, the others being cardiac and smooth muscle. As its name suggests, most skeletal muscle is attached to bones by bundles of collagen fibers known as tendons. This can occur through a simple lack of energy to fuel contraction, or interference with the ability of Ca²⁺ to stimulate actin Actin is a globular, roughly 42-kDa protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans. Actin is the monomeric subunit of two types of filaments in cells: microfilaments, one of and myosin Myosins are a large family of motor proteins found in eukaryotic tissues. They are responsible for actin-based motility to contract.

Lactic acid

It was once believed that lactic acid Lactic acid , also known as milk acid, is a chemical compound that plays a role in several biochemical processes. It was first isolated in 1780 by a Swedish chemist, Carl Wilhelm Scheele, and is a carboxylic acid with a chemical formula of C3H6O3. It has a hydroxyl group adjacent to the carboxyl group, making it an alpha hydroxy acid (AHA). In build-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 of fermentation Lactic acid fermentation is a biological process by which sugars such as glucose, fructose, and sucrose, are converted into cellular energy and the metabolic byproduct lactate. It is the anaerobic form of respiration that occurs in some bacteria and animal cells, such as muscle cells, in the absence of oxygen. If oxygen is present in the cell,, lactic acid can increase intracellular acidity of muscles. This can lower the sensitivity of contractile apparatus to Ca²⁺ but also has the effect of increasing cytoplasmic The cytoplasm is the part of a cell that is enclosed within the cell membrane. In eukaryotic cells, the contents of the cell nucleus are not part of the cytoplasm and are instead called the nucleoplasm. Also in eukaryotic cells, the cytoplasm contains organelles, such as mitochondria, which are filled with liquid that is kept separate from the Ca²⁺ concentration through an inhibition of the chemical pump The sodium-calcium exchanger is an antiporter membrane protein which removes calcium from cells. It uses the energy that is stored in the electrochemical gradient of sodium (Na+) by allowing Na+ to flow down its gradient across the plasma membrane in exchange for the countertransport of calcium ions (Ca2+). The NCX removes a single calcium ion in that actively transports Active transport is the mediated process of moving particles across a biological membrane against a concentration gradient. If the process uses chemical energy, such as from adenosine triphosphate , it is termed primary active transport. Secondary active transport involves the use of an electrochemical gradient. Active transport uses energy, calcium out of the cell. This counters inhibiting effects of 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 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 Ca²⁺.

Associated conditions

Many different conditions can cause weakness. In 2010 DiagnosisPro listed 464 possible cause.^[22] True weakness may be due to problems with the nerves A peripheral nerve, or simply nerve is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system. In the central nervous system, the analogous structures are known as tracts, neuromuscular junction A neuromuscular junction is the synapse or junction of the axon terminal of a motoneuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract. In vertebrates, the signal passes through the or with muscles Muscle is the 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 produce force and cause motion. Muscles can cause.

• Amyotrophic lateral sclerosis Amyotrophic lateral sclerosis is a form of motor neuron disease. ALS is a progressive, fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement. The condition is often called Lou Gehrig's disease in North America, after the famous New York
• Botulism Botulism also known as botulinus intoxication is a rare but serious paralytic illness caused by botulinum toxin, which is produced by the bacterium Clostridium botulinum under anaerobic conditions
• Centronuclear myopathy Centronuclear myopathies are a group of congenital myopathies where cell nuclei are abnormally located in skeletal muscle cells. In CNM the nuclei are located at a position in the center of the cell, instead of their normal location at the periphery
• Myotubular myopathy
• Muscle Atrophy Muscle 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 is a co-morbidity of several common diseases, including cancer, AIDS, congestive heart failure, COPD ,
• Sarcopenia
• Dysautonomia Dysautonomia is a broad term that describes any disease or malfunction of the autonomic nervous system. This includes postural orthostatic tachycardia syndrome (POTS), vasovagal syncope, mitral valve prolapse dysautonomia, pure autonomic failure, neurocardiogenic syncope (NCS), neurally mediated hypotension (NMH), autonomic instability and a
• Charcot-Marie-Tooth
• Hypokalemia Hypokalemia , hypokalaemia (British English), or hypopotassemia (ICD-9) refers to the condition in which the concentration of potassium (K+) in the blood is low. The prefix hypo- means low (contrast with hyper-, meaning high). Kal refers to kalium, the Neo-Latin for potassium, and -emia means "in the blood."
• Motor neurone disease The motor neurone diseases (MND) are a group of neurological disorders that selectively affect motor neurones, the cells that control voluntary muscle activity including speaking, walking, breathing, swallowing and general movement of the body
• Muscular dystrophy Muscular dystrophy refers to a group of hereditary muscle diseases that weaken the muscles that move the human body. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue. Nine diseases including Duchenne, Becker, limb girdle, congenital,
• Myotonic dystrophy
• Myasthenia gravis
• Progressive muscular atrophy
• Spinal muscular atrophy
• Cerebral palsy
• Infectious mononucleosis
• Herpes zoster
• Vitamin D deficiency
• Fibromyalgia
• Celiac disease
• Hypercortisolism (Cushing's syndrome)
• Hypocortisolism (Addison's disease)
• Primary hyperaldosteronism (Conn's syndrome)
• Ehlers-Danlos syndrome
• Diarrhea
• McArdle's Disease
• Ross River Fever
• Barmah Forest Fever
• Conn's Syndrome

Pathophysiology

Muscle cells work by detecting a flow of electrical impulses from the brain which signals them to 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. New research from scientists at Columbia University suggests that muscle fatigue is caused by calcium leaking out of the muscle cell. This causes there to be less calcium available for the muscle cell. In addition an enzyme is proposed to be activated by this released calcium which eats away at muscle fibers. ^[23]

Substrates within the muscle generally serve to power muscular contractions. They include molecules such as adenosine triphosphate (ATP), glycogen and creatine phosphate. ATP binds to the myosin head and causes the ‘ratchetting’ that results in contraction according to the 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 once intramuscular creatine stores are exhausted, producing lactic acid as 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

1. ^ ^{a b c} Marx, John (2010). Rosen's emergency medicine: concepts and clinical practice 7th edition. Philadelphia, PA: Mosby/Elsevier. p. Chapter 11. ISBN 9780323054720.
2. ^ Enoka RM, Stuart DG (1992). "Neurobiology of muscle fatigue". J. Appl. Physiol. 72 (5): 1631–48. PMID 1601767.
3. ^ Paul L, Wood L, Behan WM, Maclaren WM; Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. European Journal of Neurology 1999 Jan;6(1):63-69 PMID: 10209352
4. ^ McCully K K, Natelson B H; Impaired oxygen delivery to muscle in chronic fatigue syndrome. Clinical Science 1999:97:603-608
5. ^ Pascale De Becker, PhD; Johan Roeykens, PT; Masha Reynders, PT; Neil McGregor, MD, PhD; Exercise Capacity in Chronic Fatigue Syndrome. Archives of Internal Medicine Vol. 160 No. 21, November 27, 2000
6. ^ De Becker P, McGregor N, De Meirleir K. A definition-based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome. J Intern Med 2001;250:234-240.
7. ^ Bruce M Carruthers, Anil Kumar Jain, Kenny L De Meirleir, Daniel L Peterson, Nancy G Klimas et al., Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Guidelines, A Consensus Document Journal of Chronic Fatigue Syndrome 11(1):7-115, 2003. ISBN 0-7890-227-9
8. ^ Jammes Y, Steinberg JG, Mambrini O, Bregeon F, Delliaux S; Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. J Intern Med., 2005 Mar;257(3):299-310.
9. ^ Loris McVittie, Ph.D.. "Information from CDC and FDA on the Safety of Gardasil Vaccine". June 12, 2008. Office of Vaccines Research and Review at the US FDA. http://www.fda.gov/cber/approvltr/gardasil061208L.htm. Retrieved 2008-07-21. "We have approved your supplement to your biologics 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."
10. ^ Gandevia SC, Enoka RM, McComas AJ, Stuart DG, Thomas CK (1995). "Neurobiology of muscle fatigue. Advances and issues". Adv. Exp. Med. Biol. 384: 515–25. PMID 8585476.
11. ^ Kent-Braun JA (1999). "Central and peripheral contributions to muscle fatigue in humans during sustained maximal effort". European journal of applied physiology and occupational physiology 80 (1): 57–63. doi:10.1007/s004210050558. PMID 10367724.
12. ^ Gandevia SC (2001). "Spinal and supraspinal factors in human muscle fatigue". Physiol. Rev. 81 (4): 1725–89. PMID 11581501.
13. ^ 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 (1-2): 115–21. doi:10.1007/s004210000340. PMID 11394239.
14. ^ 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 biophysique 99 (1): 89–93. PMID 1713492.
15. ^ Bigland-Ritchie B, Woods JJ (1984). "Changes in muscle contractile properties and neural control during human muscular fatigue". Muscle Nerve 7 (9): 691–9. doi:10.1002/mus.880070902. PMID 6100456.
16. ^ Noakes TD (2000). "Physiological models to understand exercise fatigue and the adaptations that predict or enhance athletic performance". Scandinavian journal of medicine & science in sports 10 (3): 123–45. doi:10.1034/j.1600-0838.2000.010003123.x. PMID 10843507.
17. ^ Davis JM (1995). "Carbohydrates, branched-chain amino acids, and endurance: the central fatigue hypothesis". International journal of sport nutrition 5 Suppl: S29–38. PMID 7550256.
18. ^ 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. ^ Newsholme EA, Blomstrand E (1995). "Tryptophan, 5-hydroxytryptamine and a possible explanation for central fatigue". Adv. Exp. Med. Biol. 384: 315–20. PMID 8585461.
20. ^ R. Robergs, F. Ghiasvand, D. Parker (2004). "Biochemistry of exercise-induced metabolic acidosis". Am J Physiol Regul Integr Comp Physiol 287 (3): R502–16. doi:10.1152/ajpregu.00114.2004. PMID 15308499.
21. ^ Muscle fatigue and lactic acid accumulation. abstract
22. ^ "Differential Diagnosis for Weakness". http://en.diagnosispro.com/differential_diagnosis-for/weakness/40602-154.html. Retrieved Feb 16, 2010.
23. ^ Finding May Solve Riddle of Fatigue in Muscles - New York Times

External links

• MedlinePlus Encyclopedia 003174
• Jun Mapili's Muscle Weakness Coding Checklist
• AllRefer
• Unexplained Muscle Weakness - Information About McArdle's Disease

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