Weakness

Last updated
Weakness
Other namesAsthenia
Specialty Neurology

Weakness is a symptom of many different medical 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 of skeletal muscle diseases, including muscular dystrophy and inflammatory myopathy. It occurs in neuromuscular junction disorders, such as myasthenia gravis.[ citation needed ]

Contents

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 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. [2]

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 felt when people exhaust their 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.[ citation needed ]

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.[ citation needed ]

Differential diagnosis

True vs. perceived weakness

In some conditions, such as myasthenia gravis, 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 chronic 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. [4] [5] [6] [7] [8] [9]

Asthenia vs. myasthenia

Asthenia or asthaenia (Greek : ἀσθένεια, literally lack of strength but also disease) 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 is a poorly defined condition that can include true or primary muscle weakness or perceived muscle weakness. [10] For perceived muscle weakness, asthenia has been described as the feeling of weak or tired muscles in the absence of muscle weakness, that is the muscle can generate a normal amount of force but it is perceived as requiring more effort. [11] [12]

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 certain organs or systems of organs, as in asthenopia, characterized by ready fatiguability. Asthenia is also a side effect of some medications and treatments, such as Ritonavir (a protease inhibitor used in HIV treatment). [13]

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.[ citation needed ]

Myasthenia or myasthaenia (my- from Greek : μυο meaning "muscle" + -asthenia [ἀσθένεια] meaning "weakness"), or simply muscle 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 in neuromuscular diseases, such as myasthenia gravis. Perceived muscle weakness occurs in diseases such as sleep disorders, and depression. [11]

Types

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. [14] [15] Neuromuscular fatigue can be either central or peripheral.[ citation needed ]

Central fatigue

The central fatigue is generally described in terms of a reduction in the neural drive or nerve-based motor command to working muscles that results in a decline in the force output. [16] [17] [18] 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. [19] [20] The exact mechanisms of central fatigue are unknown, though there has been considerable interest in the role of serotonergic pathways. [21] [22] [23]

Neuromuscular fatigue

Nerves control the contraction of muscles by determining the number, sequence, and force of muscular contraction. When a nerve experiences synaptic fatigue it becomes unable to stimulate the muscle that it innervates. Most movements require a force far below what a muscle could potentially generate, and barring pathology, neuromuscular fatigue is seldom an issue.[ citation needed ]

For extremely powerful contractions that are close to the upper limit of a muscle's ability to generate force, neuromuscular fatigue can become a limiting factor in untrained individuals. In novice strength trainers, the muscle's ability to generate force is most strongly limited by nerve's ability to sustain a high-frequency signal. After an extended 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 lengthening. As there is insufficient stress on the muscles and tendons, there will often be no delayed onset muscle soreness 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 myofibrillar or sarcoplasmic hypertrophy and metabolic fatigue becomes the factor limiting contractile force.

Peripheral muscle fatigue

Peripheral muscle fatigue during 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 fatigue—affecting 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-optimal aerobic metabolism, generally results in the accumulation of lactic acid and other acidic 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. [24]

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.[ citation needed ]

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 myocytes. This can occur through a simple lack of energy to fuel contraction, or through interference with the ability of Ca2+ to stimulate actin and myosin to contract.

Management

Related Research Articles

<span class="mw-page-title-main">Myasthenia gravis</span> Autoimmune disease resulting in skeletal muscle weakness

Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, drooping eyelids, and difficulties in talking and walking. Onset can be sudden. Those affected often have a large thymus or develop a thymoma.

Neuromyotonia (NMT) is a form of peripheral nerve hyperexcitability that causes spontaneous muscular activity resulting from repetitive motor unit action potentials of peripheral origin. NMT along with Morvan's syndrome are the most severe types in the Peripheral Nerve Hyperexciteability spectrum. Example of two more common and less severe syndromes in the spectrum are cramp fasciculation syndrome and benign fasciculation syndrome. NMT can have both hereditary and acquired (non-inherited) forms. The prevalence of NMT is unknown.

<span class="mw-page-title-main">Adenosine monophosphate deaminase deficiency type 1</span> Medical condition

Adenosine monophosphate deaminase deficiency type 1 or AMPD1, is a human metabolic disorder in which the body consistently lacks the enzyme AMP deaminase, in sufficient quantities. This may result in exercise intolerance, muscle pain and muscle cramping. The disease was formerly known as myoadenylate deaminase deficiency (MADD).

The muscular system is an organ system consisting of skeletal, smooth, and cardiac muscle. It permits movement of the body, maintains posture, and circulates blood throughout the body. The muscular systems in vertebrates are controlled through the nervous system although some muscles can be completely autonomous. Together with the skeletal system in the human, it forms the musculoskeletal system, which is responsible for the movement of the body.

<span class="mw-page-title-main">Glycogen storage disease type V</span> Human disease caused by deficiency of a muscle enzyme

Glycogen storage disease type V, also known as McArdle's disease, is a metabolic disorder, one of the metabolic myopathies, more specifically a muscle glycogen storage disease, caused by a deficiency of myophosphorylase. Its incidence is reported as one in 100,000, roughly the same as glycogen storage disease type I.

<span class="mw-page-title-main">Skeletal muscle</span> One of three major skeletal system types that connect to bones

Skeletal muscles are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle tissue, and are often known as muscle fibers. The muscle tissue of a skeletal muscle is striated – having a striped appearance due to the arrangement of the sarcomeres.

<span class="mw-page-title-main">Post-polio syndrome</span> Human disease

Post-polio syndrome is a group of latent symptoms of poliomyelitis (polio), occurring at about a 25–40% rate. These symptoms are caused by the damaging effects of the viral infection on the nervous system. Symptoms typically occur 15 to 30 years after an initial acute paralytic attack. Symptoms include decreasing muscular function or acute weakness with pain and fatigue. The same symptoms may also occur years after a nonparalytic polio (NPP) infection.

<span class="mw-page-title-main">Neuromuscular junction</span> Junction between the axon of a motor neuron and a muscle fiber

A neuromuscular junction is a chemical synapse between a motor neuron and a muscle fiber.

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 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 signal ; and the reduced ability of the muscle fiber to contract.

<span class="mw-page-title-main">Anaerobic exercise</span> Physical exercise intense enough to cause lactate formation

Anaerobic exercise is a type of exercise that breaks down glucose in the body without using oxygen; anaerobic means "without oxygen". In practical terms, this means that anaerobic exercise is more intense, but shorter in duration than aerobic exercise.

Hypotonia is a state of low muscle tone, often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength. Hypotonia is a lack of resistance to passive movement, whereas muscle weakness results in impaired active movement. Central hypotonia originates from the central nervous system, while peripheral hypotonia is related to problems within the spinal cord, peripheral nerves and/or skeletal muscles. Severe hypotonia in infancy is commonly known as floppy baby syndrome. Recognizing hypotonia, even in early infancy, is usually relatively straightforward, but diagnosing the underlying cause can be difficult and often unsuccessful. The long-term effects of hypotonia on a child's development and later life depend primarily on the severity of the muscle weakness and the nature of the cause. Some disorders have a specific treatment but the principal treatment for most hypotonia of idiopathic or neurologic cause is physical therapy and/or occupational therapy for remediation.

<span class="mw-page-title-main">Exercise intolerance</span> Medical condition

Exercise intolerance is a condition of inability or decreased ability to perform physical exercise at the normally expected level or duration for people of that age, size, sex, and muscle mass. It also includes experiences of unusually severe post-exercise pain, fatigue, nausea, vomiting or other negative effects. Exercise intolerance is not a disease or syndrome in and of itself, but can result from various disorders.

<span class="mw-page-title-main">Mitochondrial myopathy</span> Medical condition

Mitochondrial myopathies are types of myopathies associated with mitochondrial disease. Adenosine triphosphate (ATP), the chemical used to provide energy for the cell, cannot be produced sufficiently by oxidative phosphorylation when the mitochondrion is either damaged or missing necessary enzymes or transport proteins. With ATP production deficient in mitochondria, there is an over-reliance on anaerobic glycolysis which leads to lactic acidosis either at rest or exercise-induced.

Muscle weakness is a lack of muscle strength. Its 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 in neuromuscular junction disorders, such as myasthenia gravis. Muscle weakness can also be caused by low levels of potassium and other electrolytes within muscle cells. It can be temporary or long-lasting. The term myasthenia is from my- from Greek μυο meaning "muscle" + -asthenia ἀσθένεια meaning "weakness".

<span class="mw-page-title-main">Neuromuscular disease</span> Medical condition

A neuromuscular disease is any disease affecting the peripheral nervous system (PNS), the neuromuscular junctions, or skeletal muscles, all of which are components of the motor unit. Damage to any of these structures can cause muscle atrophy and weakness. Issues with sensation can also occur.

Acute muscle soreness (AMS) is the pain felt in muscles during and immediately, up to 24 hours, after strenuous physical exercise. The pain appears within a minute of contracting the muscle and it will disappear within two or three minutes or up to several hours after relaxing it.

Neuromuscular junction disease is a medical condition where the normal conduction through the neuromuscular junction fails to function correctly.

<span class="mw-page-title-main">Metabolic myopathy</span> Type of myopathies

Metabolic myopathies are myopathies that result from defects in biochemical metabolism that primarily affect muscle. They are generally genetic defects that interfere with muscle's ability to create energy, causing a low ATP reservoir within the muscle cell.

Central nervous system fatigue, or central fatigue, is a form of fatigue that is associated with changes in the synaptic concentration of neurotransmitters within the central nervous system which affects exercise performance and muscle function and cannot be explained by peripheral factors that affect muscle function. In healthy individuals, central fatigue can occur from prolonged exercise and is associated with neurochemical changes in the brain, involving serotonin (5-HT), noradrenaline, and dopamine. The roles of dopamine, noradrenaline, and serotonin in CNS fatigue are unclear, as pharmacological manipulation of these systems has yielded mixed results. Central fatigue plays an important role in endurance sports and also highlights the importance of proper nutrition in endurance athletes.

References

  1. Marx, John (2010). Rosen's Emergency Medicine: Concepts and Clinical Practice (7th ed.). Philadelphia, PA: Mosby/Elsevier. p. Chapter 11. ISBN   978-0-323-05472-0.
  2. Kolata, Gina (February 12, 2008). "Finding May Solve Riddle of Fatigue in Muscles". The New York Times.
  3. Ropper, Allan H.; Samuels, Martin A. (2009). Adams and Victor's Principles of Neurology, Ninth Edition. McGraw-Hill. ISBN   978-0071499927.
  4. 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): 63–9. doi:10.1046/j.1468-1331.1999.610063.x. PMID   10209352. S2CID   33480143.
  5. McCully KK, Natelson BH (November 1999). "Impaired oxygen delivery to muscle in chronic fatigue syndrome". Clin. Sci. 97 (5): 603–8, discussion 611–3. doi:10.1042/CS19980372. PMID   10545311.
  6. 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): 3270–7. doi:10.1001/archinte.160.21.3270. PMID   11088089. Archived from the original on 2011-08-12. Retrieved 2011-03-12.
  7. 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): 234–40. doi: 10.1046/j.1365-2796.2001.00890.x . PMID   11555128.
  8. 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. Vol. 11. pp. 7–115. doi:10.1300/J092v11n01_02. ISBN   978-0-7890-2207-3. ISSN   1057-3321.{{cite book}}: |journal= ignored (help)
  9. Jammes Y, Steinberg JG, Mambrini O, Brégeon 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): 299–310. doi: 10.1111/j.1365-2796.2005.01452.x . PMID   15715687.
  10. Kauffman, Timothy L.; Kemmis, Karen (2014-01-01), Kauffman, Timothy L.; Scott, Ron; Barr, John O.; Moran, Michael L. (eds.), "Chapter 16 - Muscle weakness and therapeutic exercise", A Comprehensive Guide to Geriatric Rehabilitation (Third Edition), Oxford: Churchill Livingstone, pp. 112–119, ISBN   978-0-7020-4588-2 , retrieved 2023-11-19
  11. 1 2 Saguil, Aaron (2005-04-01). "Evaluation of the Patient with Muscle Weakness". American Family Physician. 71 (7): 1327–1336. PMID   15832536. Asthenia is a sense of weariness or exhaustion in the absence of muscle weakness.
  12. "Muscle Weakness and Fatigue | Causes and Treatment". patient.info. 2021-06-28. Retrieved 2023-11-19. Muscle tiredness: This is sometimes called asthenia. It is a sense of weariness or exhaustion that you feel when using the muscle. The muscle isn't genuinely weaker, it can still do its job but it takes you more effort to manage it.
  13. "PubChem Compound Summary for CID 392622, Ritonavir". NCBI. 28 November 2022. Retrieved 28 November 2022.
  14. Gandevia SC, Enoka RM, McComas AJ, Stuart DG, Thomas CK (1995). "Neurobiology of Muscle Fatigue". Fatigue. Advances in Experimental Medicine and Biology. Vol. 384. pp. 515–25. doi:10.1007/978-1-4899-1016-5_39. ISBN   978-1-4899-1018-9. PMID   8585476.
  15. 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. S2CID   22515865.
  16. Gandevia SC (2001). "Spinal and supraspinal factors in human muscle fatigue". Physiol. Rev. 81 (4): 1725–89. doi:10.1152/physrev.2001.81.4.1725. PMID   11581501.
  17. 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. S2CID   25906759.
  18. 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. doi:10.3109/13813459109145909. PMID   1713492.
  19. 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. S2CID   13606531.
  20. 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. S2CID   23103331.
  21. Davis JM (1995). "Carbohydrates, branched-chain amino acids, and endurance: the central fatigue hypothesis". International Journal of Sport Nutrition. 5 (Suppl): S29–38. doi:10.1123/ijsn.5.s1.s29. PMID   7550256.
  22. 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.
  23. Newsholme EA, Blomstrand E (1995). "Tryptophan, 5-Hydroxytryptamine and a Possible Explanation for Central Fatigue". Fatigue. Advances in Experimental Medicine and Biology. Vol. 384. pp. 315–20. doi:10.1007/978-1-4899-1016-5_25. ISBN   978-1-4899-1018-9. PMID   8585461.
  24. 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. S2CID   2745168.