Weakness

This article is about the medical condition. For other uses, see Weakness (disambiguation).
"Asthenia" redirects here. The tortrix moth genus is considered a junior synonym of Epinotia.
ICD-10

R53

ICD-9

728.87 (728.9 before 10/01/03);

alternatively, 780.79

DiseasesDB

22832

MedlinePlus 003174
MeSH

D018908

Weakness or asthenia is a symptom of 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 of skeletal muscle diseases, including muscular
dystrophy andinflammatory myopathy. It occurs in neuromuscular junction disorders, such
asmyasthenia gravis.
Contents
[hide]

1 Diagnostic Distinctions
o 1.1 True weakness vs. perceived weakness
o 1.2 Asthenia vs. myasthenia

2 Differential diagnosis
o 2.1 Central fatigue
o 2.2 Neuromuscular fatigue
o 2.3 Peripheral muscle fatigue

o 2.4 Lactic acid hypothesis

3 Pathophysiology

4 References

5 External links

Diagnostic Distinctions[edit]
True weakness vs. perceived weakness[edit]

True weakness (or neuromuscular) describes a condition where the force exerted by the
muscles is less than would be expected, for example muscular dystrophy.

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.[2]

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.[3][4][5][6][7][8]
Asthenia vs. myasthenia[edit]
Asthenia (Greek: , lit. 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
denotes symptoms of physical weakness and loss 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 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), vaccines such as the HPV
vaccine Gardasil[9] and fentanyl patches (an opioid used 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 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.
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]
The central fatigue is generally described in terms of a reduction in the neural drive or nervebased 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 of serotonergic pathways.[17][18][19]
Neuromuscular fatigue[edit]
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.
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 nerves
ability to sustain a high-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 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[edit]

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 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-optimal aerobic metabolism,
generally results in the accumulation of lactic acid and other acidic anaerobic metabolic byproducts 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 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.
Lactic acid hypothesis[edit]
It was once believed that lactic acid 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 can increase intracellular acidity of
muscles. This can lower the sensitivity of contractile apparatus to calcium ions (Ca2+) but also
has the effect of increasing cytoplasmic Ca2+concentration through an inhibition of the chemical
pump that actively transports calcium out of the cell. This counters inhibiting effects
of potassium 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 contraction
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.[22]
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 57 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[edit]
1. Jump up^ 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. Jump up^ Ropper, Allan H.; Samuels, Martin A. (2009). Adams and Victor's
Principles of Neurology, Ninth Edition. McGraw-Hill.ISBN 978-0071499927.
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.14681331.1999.610063.x.PMID 10209352.

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. PMID 10545311.
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. PMID 11088089.
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.13652796.2001.00890.x. PMID 11555128.
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
Syndrome 11 (1): 7115. doi:10.1300/J092v11n01_02. ISBN 0-7890-22079.ISSN 1057-3321.
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.PMID 15715687.
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.PMID 8585476.
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 physiology 80 (1): 57
63.doi:10.1007/s004210050558. PMID 10367724.

12. Jump up^ Gandevia SC (2001). "Spinal and supraspinal factors in human muscle
fatigue". Physiol. Rev. 81 (4): 172589.PMID 11581501.
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): 115
21.doi:10.1007/s004210000340. PMID 11394239.
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 biophysique 99 (1): 89
93.doi:10.3109/13813459109145909. PMID 1713492.
15. Jump up^ Bigland-Ritchie B, Woods JJ (1984). "Changes in muscle contractile
properties and neural control during human muscular fatigue". Muscle
Nerve 7 (9): 6919.doi:10.1002/mus.880070902. PMID 6100456.
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 sports 10 (3): 123
45. doi:10.1034/j.1600-0838.2000.010003123.x. PMID 10843507.
17. Jump up^ Davis JM (1995). "Carbohydrates, branched-chain amino acids, and
endurance: the central fatigue hypothesis". Int J Sport Nutr 5 (Suppl): S29
38. PMID 7550256.
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, 5hydroxytryptamine and a possible explanation for central fatigue". Adv. Exp. Med.
Biol. 384: 31520.doi:10.1007/978-1-4899-1016-5_25. PMID 8585461.
20. Jump up^ R. Robergs, F. Ghiasvand, D. Parker (2004). "Biochemistry of
exercise-induced metabolic acidosis". Am J Physiol Regul Integr Comp
Physiol 287 (3): R50216.doi:10.1152/ajpregu.00114.2004. PMID 15308499.
21. Jump up^ Sahlin K (1986). "Muscle fatigue and lactic acid accumulation". Acta
Physiol Scand Suppl 556: 8391.PMID 3471061.
22. Jump up^ Kolata, Gina (February 12, 2008). "Finding May Solve Riddle of
Fatigue in Muscles". The New York Times.