Weakness
Overview
"Asthenia" redirects here. The tortrix moth genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...

 is nowadays considered a junior synonym of
Epinotia
Epinotia
Epinotia is a very large genus of tortrix moths . It belongs to the tribe Eucosmini of subfamily Olethreutinae.-Species:166 species of Epinotia were considered valid as of 2009...

.

Weakness is a symptom represented, medically, by a number of different conditions, including: lack of muscle strength, malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", 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
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....

, or fatigue. 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
Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...

 and inflammatory myopathy
Inflammatory myopathy
Inflammatory myopathy is a form of myopathy that involves inflammation of the muscle.Inflammatory myopathy is generally synonymous to the term dermatopolymyositis, which, according to ICD-10 encompasses three related diseases: polymyositis, dermatomyositis, and inclusion-body...

.
Quotations

All cruelty springs from weakness.

Seneca the Younger

Although men are accused of not knowing their own weakness, yet perhaps few know their own strength. It is in men as in soils, where sometimes there is a vein of gold which the owner knows not of.

Jonathan Swift

As you simplify your life, the laws of the universe will be simpler; solitude will not be solitude, poverty will not be poverty, nor weakness weakness.

Henry David Thoreau

Credulity is the man's weakness, but the child's strength.

Charles Lamb

Do you really think it is weakness that yields to temptation? I tell you that there are terrible temptations which it requires strength, strength and courage to yield to.

Oscar Wilde

Get it into your head once and for all, my simple and very fainthearted fellow, that what fools call humanness is nothing but a weakness born of fear and egoism; that this chimerical virtue, enslaving only weak men, is unknown to those whose character is formed by stoicism, courage, and philosophy.

Marquis De Sade

I believe the most solemn duty of the American president is to protect the American people. If America shows uncertainty and weakness in this decade, the world will drift toward tragedy. This will not happen on my watch.

George W. Bush

If thou wouldn't conquer thy weakness thou must not gratify it.

William Penn

If we resist our passions, it is more due to their weakness than our strength.

François de La Rochefoucauld

Insincerity is always weakness; sincerity even in error is strength.

George Lewes

Encyclopedia
"Asthenia" redirects here. The tortrix moth genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...

 is nowadays considered a junior synonym of
Epinotia
Epinotia
Epinotia is a very large genus of tortrix moths . It belongs to the tribe Eucosmini of subfamily Olethreutinae.-Species:166 species of Epinotia were considered valid as of 2009...

.

Weakness is a symptom represented, medically, by a number of different conditions, including: lack of muscle strength, malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", 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
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....

, or fatigue. 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
Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...

 and inflammatory myopathy
Inflammatory myopathy
Inflammatory myopathy is a form of myopathy that involves inflammation of the muscle.Inflammatory myopathy is generally synonymous to the term dermatopolymyositis, which, according to ICD-10 encompasses three related diseases: polymyositis, dermatomyositis, and inclusion-body...

. It occurs in neuromuscular junction
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron 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...

 disorders, such as myasthenia gravis
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...

.

Definition

Weakness describes a number of symptoms, including: loss of muscle strength, malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", 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
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....

 or fatigue. The term can be divided into two other more specific states, true weakness and perceived weakness.
  • 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
    Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...

    .

  • 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
    Chronic fatigue syndrome
    Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...

    .


In some conditions, such as myasthenia gravis
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...

 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 CFS, where objective post-exertion muscle weakness with delayed recovery time has been measured and is a feature of some of the published definitions.

Asthenia

Asthenia (Greek
Greek language
Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...

: ασθένεια, 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
Muscle weakness
Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...

. General asthenia occurs in many chronic wasting diseases (such as anemia 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
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...

, characterized by ready fatiguability. Asthenia is also a side effect of some medications and treatments, such as Ritonavir
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 inhibitor (pharmacology)
Protease inhibitors are a class of drugs used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of proteases, e.g.HIV-1 protease, enzymes used by the viruses to cleave nascent proteins for final assembly of new...

 used in HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

 treatment), vaccines such as the HPV vaccine Gardasil
Gardasil
Gardasil , also known as Gardisil or Silgard, is a vaccine for use in the prevention of certain types of human papillomavirus , specifically HPV types 6, 11, 16 and 18. HPV types 16 and 18 cause an estimated 70% of cervical cancers, and are responsible for most HPV-induced anal, vulvar, vaginal,...

 and fentanyl patches (an opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...

 used to treat pain).

Differentiating between psychogenic (perceived) asthenia and true asthenia with muscular weakness
Muscle weakness
Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle 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. 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
Nervous system
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...

 drive or nerve-based motor command to working muscles that results in a decline in the force output. 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. The exact mechanisms of central fatigue are unknown although there has been a great deal of interest in the role of serotonergic pathways.

Neural

Nerve
Nerve
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...

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 in potential generate, and barring pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....

 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
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...

, 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. As there is insufficient stress on the muscles and tendons, there will often be no delayed onset muscle soreness
Delayed onset muscle soreness
Delayed onset muscle soreness , also called muscle fever, is the pain and stiffness felt in muscles several hours to days after unaccustomed or strenuous exercise. The soreness is felt most strongly 24 to 72 hours after the exercise. It is caused by eccentric exercise...

 following the workout. Part of the process of strength training is increasing the nerve's ability to generate sustained, high frequency signals that 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 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
Cellular respiration is the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration are catabolic reactions that involve...

, generally results in the accumulation of lactic acid
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...

 and other acid
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...

ic 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.

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. This can occur through a simple lack of energy to fuel contraction, or interference with the ability of Ca2+ to stimulate actin
Actin
Actin is a globular, roughly 42-kDa moonlighting 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...

 and myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...

 to contract.

Lactic acid

It was once believed that lactic acid
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...

 build-up was the cause of muscle fatigue. 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
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 an anaerobic fermentation reaction that occurs in some bacteria and animal cells, such as muscle cells, in the...

, 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 cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

ic Ca2+ concentration through an inhibition of the chemical pump
Sodium-calcium exchanger
The sodium-calcium exchanger is an antiporter membrane protein that removes calcium from cells. It uses the energy that is stored in the electrochemical gradient of sodium by allowing Na+ to flow down its gradient across the plasma membrane in exchange for the countertransport of calcium ions...

 that actively transports
Active transport
Active transport is the movement of a substance against its concentration gradient . In all cells, this is usually concerned with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. If the process uses chemical energy, such as from adenosine...

 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
DiagnosisPro
DiagnosisPro is a medical expert system. It provides exhaustive diagnostic possibilities for 11,000 diseases and 30,000 findings. It is supposed to give the most appropriate differential however this is not always the case. Between Oct 2008 and Oct 2009 the site averaged 61,000 visits per month....

 listed 464 possible cause. True weakness may be due to problems with the nerves, neuromuscular junction
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron 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...

 or with muscles.
  • Amyotrophic lateral sclerosis
    Amyotrophic lateral sclerosis
    Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...

  • Botulism
    Botulism
    Botulism also known as botulinus intoxication is a rare but serious paralytic illness caused by botulinum toxin which is metabolic waste produced under anaerobic conditions by the bacterium Clostridium botulinum, and affecting a wide range of mammals, birds and fish...

  • Centronuclear myopathy
  • Myotubular myopathy
  • Muscle Atrophy
    Muscle atrophy
    Muscle atrophy, or disuse 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...

  • Sarcopenia
    Sarcopenia
    Sarcopenia is the degenerative loss of skeletal muscle mass and strength associated with aging...

  • Dysautonomia
    Dysautonomia
    Dysautonomia is a broad term that describes any disease or malfunction of the autonomic nervous system. This includes postural orthostatic tachycardia syndrome , inappropriate sinus tachycardia , vasovagal syncope, mitral valve prolapse dysautonomia, pure autonomic failure, neurocardiogenic...

  • Charcot-Marie-Tooth
  • Hypokalemia
    Hypokalemia
    Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...

  • Motor neurone disease
    Motor neurone disease
    The motor neurone diseases 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. They are generally progressive in nature, and can cause...

  • Muscular dystrophy
    Muscular dystrophy
    Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...

  • Myotonic dystrophy
    Myotonic dystrophy
    Myotonic dystrophy is a chronic, slowly progressing, highly variable inherited multisystemic disease. It is characterized by wasting of the muscles , cataracts, heart conduction defects, endocrine changes, and myotonia. Myotonic dystrophy can occur in patients of any age...

  • Myasthenia gravis
    Myasthenia gravis
    Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...

  • Progressive muscular atrophy
    Progressive muscular atrophy
    Progressive muscular atrophy is a rare subtype of amyotrophic lateral sclerosis or motor neurone disease which affects only the lower motor neurones. PMA is thought to account for around 4% of all ALS/MND cases...

  • Spinal muscular atrophy
    Spinal muscular atrophy
    Spinal Muscular Atrophy is a neuromuscular disease characterized by degeneration of motor neurons, resulting in progressive muscular atrophy and weakness. The clinical spectrum of SMA ranges from early infant death to normal adult life with only mild weakness...

  • Cerebral palsy
    Cerebral palsy
    Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....

  • Infectious mononucleosis
    Infectious mononucleosis
    Infectious mononucleosis is an infectious, widespread viral...

  • Herpes zoster
    Herpes zoster
    Herpes zoster , commonly known as shingles and also known as zona, is a viral disease characterized by a painful skin rash with blisters in a limited area on one side of the body, often in a stripe...

  • Vitamin D deficiency
  • Fibromyalgia
    Fibromyalgia
    Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...

  • Celiac disease
  • Hypercortisolism (Cushing's syndrome
    Cushing's syndrome
    Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...

    )
  • Hypocortisolism (Addison's disease
    Addison's disease
    Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...

    )
  • Primary hyperaldosteronism (Conn's syndrome
    Conn's syndrome
    Primary aldosteronism, also known as primary hyperaldosteronism, is characterized by the overproduction of the mineralocorticoid hormone aldosterone by the adrenal glands., when not a result of excessive renin secretion. Aldosterone causes increase in sodium and water retention and potassium...

    )
  • Ehlers-Danlos syndrome
    Ehlers-Danlos syndrome
    Ehlers–Danlos syndrome is a group of inherited connective tissue disorders, caused by a defect in the synthesis of collagen . The collagen in connective tissue helps tissues to resist deformation...

  • Diarrhea
    Diarrhea
    Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

  • McArdle's Disease
  • Ross River Fever
    Ross River Fever
    Ross River Fever is a mosquito-borne infectious disease caused by infection with the Ross River virus. The illness is typically characterised by an influenza-like illness and polyarthritis...

  • Barmah Forest Fever


Pathophysiology

Muscle cells work by detecting a flow
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...

 of electrical impulses from the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

, which signals them to contract
Muscle contraction
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...

 through the release of calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 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.

Substrates
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...

 within the muscle generally serve to power muscular contractions. They include molecules such as adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 (ATP), glycogen
Glycogen
Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...

 and creatine phosphate
Phosphocreatine
Phosphocreatine, also known as creatine phosphate or PCr , is a phosphorylated creatine molecule that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle and brain.-Chemistry:...

. ATP binds to the myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...

 head and causes the ‘ratchetting’ that results in contraction according to the sliding filament model
Sliding filament mechanism
The sliding filament theory describes a process used by muscles to contract. It was independently developed by Andrew F. Huxley and Rolf Niedergerke and by Hugh Huxley and Jean Hanson in 1954.-Process of movement:...

. Creatine phosphate stores energy so ATP can be rapidly regenerated within the muscle cells from adenosine diphosphate
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

 (ADP) and inorganic phosphate ions, allowing for sustained powerful contractions that last between 5–7 seconds. Glycogen is the intramuscular storage form of glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

, used to generate energy quickly once intramuscular creatine stores are exhausted, producing lactic acid
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...

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.

External links

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