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Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve after rest or sleep, or occurs independently of physical or mental exertion, it may be a symptom of a medical condition that may become severe or progressive. Fatigue can be a feature of a mental disorder such as depression; may be associated with conditions of chronic pain such as fibromyalgia; it may also feature in conditions of chronic low-level inflammation, and be a disease-related symptom in many other conditions. Fatigue often has no known cause, and is recognised as being very complex in nature. Fatigability describes a susceptibility to fatigue. Physical fatigue results from muscle fatigue brought about by intense
physical activity Physical activity is defined as any voluntary bodily movement produced by skeletal muscles that requires energy expenditure.Global Recommendations on Physical Activity for Health, 2009. World Health Organization. Geneva, Switzerland. Accessed 13/ ...
. Mental fatigue results from prolonged periods of cognitive activity which impairs cognitive ability. Mental fatigue can manifest as sleepiness,
lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...
, or directed attention fatigue. Mental fatigue can also impair physical performance.


Classification


Physical

Physical fatigue, or muscle fatigue, is the temporary physical inability of muscles to perform optimally. The onset of muscle fatigue during physical activity is gradual, and depends upon an individual's level of physical fitness – other factors include sleep deprivation and overall health. Physical fatigue can be caused by a lack of energy in the muscle, by a decrease of the efficiency of the neuromuscular junction or by a reduction of the drive originating from the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
, and can be reversed by rest. The central component of fatigue is triggered by an increase of the level of
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...
in the central nervous system. During motor activity, serotonin released in synapses that contact motor neurons promotes
muscle contraction Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such a ...
. During high level of motor activity, the amount of serotonin released increases and a spillover occurs. Serotonin binds to extrasynaptic receptors located on the axonal initial segment of motor neurons with the result that
nerve impulse An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, c ...
initiation and thereby muscle contraction are inhibited. Muscle strength testing can be used to determine the presence of a neuromuscular disease, but cannot determine its cause. Additional testing, such as electromyography, can provide diagnostic information, but information gained from muscle strength testing alone is not enough to diagnose most neuromuscular disorders. People with multiple sclerosis experience a form of overwhelming lassitude or tiredness that can occur at any time of the day, for any duration, and that does not necessarily recur in a recognizable pattern for any given patient, referred to as "neurological fatigue", and often as "multiple sclerosis fatigue".


Mental

Mental fatigue is a temporary inability to maintain optimal cognitive performance. The onset of mental fatigue during any cognitive activity is gradual, and depends upon an individual's cognitive ability, and also upon other factors, such as sleep deprivation and overall health. Mental fatigue has also been shown to decrease physical performance. It can manifest as
somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
,
lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...
, directed attention fatigue, or disengagement. Research also suggests that mental fatigue is closely linked to the concept of
ego depletion Ego depletion is the idea that self-control or willpower draws upon a limited pool of mental resources that can be used up (with the word "ego" used in the psychoanalytic sense rather than the colloquial sense). When the energy for mental activ ...
. For example, one pre-registered study of 686 participants found that after exerting mental effort, people are likely to disengage and become less interested in exerting further effort. Decreased attention can also be described as a more or less decreased
level of consciousness An altered level of consciousness is any measure of arousal other than normal. Level of consciousness (LOC) is a measurement of a person's arousability and responsiveness to stimuli from the environment. A mildly depressed level of consciou ...
. In any case, this can be dangerous when performing tasks that require constant concentration, such as operating large vehicles. For instance, a person who is sufficiently somnolent may experience
microsleep A microsleep is a sudden temporary episode of sleep or drowsiness which may last for a few seconds where an individual fails to respond to some arbitrary sensory input and becomes unconscious.International Classification of Sleep Disorders, , pa ...
. However, objective cognitive testing can be used to differentiate the neurocognitive deficits of brain disease from those attributable to tiredness. The
perception Perception () is the organization, identification, and interpretation of sensory information in order to represent and understand the presented information or environment. All perception involves signals that go through the nervous syste ...
of mental fatigue is believed to be modulated by the brain's
reticular activating system The reticular formation is a set of interconnected nuclei that are located throughout the brainstem. It is not anatomically well defined, because it includes neurons located in different parts of the brain. The neurons of the reticular formati ...
(RAS). Fatigue impacts a driver's reaction time, awareness of hazards around them and their attention. Drowsy drivers are three times more likely to be involved in a car crash and if they are awake over 20 hours, is the equivalent of driving with a blood-alcohol concentration level of 0.08%.


Primary vs secondary

In some areas it has been proposed that fatigue be separated into primary fatigue, caused directly by a disease process, and secondary fatigue, caused by more general impacts on the person of having the disease.


Causes

Fatigue is a normal result of work, mental stress,
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, overstimulation and understimulation, jet lag, active
recreation Recreation is an activity of leisure, leisure being discretionary time. The "need to do something for recreation" is an essential element of human biology and psychology. Recreational activities are often done for enjoyment, amusement, or plea ...
, boredom, lack of sleep or disease.


Acute

Causes of acute fatigue include depression; chemical causes, such as
dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
,
poison Poison is a chemical substance that has a detrimental effect to life. The term is used in a wide range of scientific fields and industries, where it is often specifically defined. It may also be applied colloquially or figuratively, with a broa ...
ing, low blood sugar, or
mineral In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid chemical compound with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed. (2 ...
or vitamin deficiencies. Fatigue is different from drowsiness, where a patient feels that sleep is required. Temporary fatigue is likely to be a minor illness like the common cold as one part of the sickness behavior response that happens when the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
fights an
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
.


Prolonged

Prolonged fatigue is a self-reported, persistent (constant) fatigue lasting at least one month.


Chronic

Chronic fatigue is a self-reported fatigue lasting at least six consecutive months. Chronic fatigue may be either persistent or relapsing. Chronic fatigue is a symptom of many diseases and conditions. Some major categories of conditions that feature fatigue include: *
Autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
s, such as celiac disease, lupus, multiple sclerosis, myasthenia gravis, Sjögren's syndrome, and
spondyloarthropathy Spondyloarthropathy or spondyloarthrosis refers to any joint disease of the vertebral column. As such, it is a class or category of diseases rather than a single, specific entity. It differs from spondylopathy, which is a disease of the verteb ...
*
Anxiety disorder Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause phy ...
s such as generalized anxiety disorder * Blood disorders such as
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
and
hemochromatosis Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatosi ...
*
Cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
, in which case it is called
cancer fatigue Cancer-related fatigue is a symptom of fatigue that is experienced by nearly all cancer patients. Among patients receiving cancer treatment other than surgery, it is essentially universal. Fatigue is a normal and expected side effect of most for ...
* Chronic fatigue syndrome (CFS) * Substance use disorders including
alcohol use disorder Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomin ...
* Depression and other mental disorders that feature
depressed mood Depression is a mental state of low mood and aversion to activity, which affects more than 280 million people of all ages (about 3.5% of the global population). Classified medically as a mental and behavioral disorder, the experience o ...
* Developmental disorders such as autism spectrum disorder * Eating disorders, which can produce fatigue due to inadequate nutrition * Endocrine diseases or metabolic disorders:
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
,
hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as ...
and Addison’s disease * Fibromyalgia * Gulf War syndrome *
Heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
* HIV *
Idiopathic chronic fatigue Idiopathic chronic fatigue (ICF), is characterized by unexplained fatigue that lasts at least six consecutive months. It is widely understood to have a profound effect on the lives of patients who experience it. ICF is a common illness of unkno ...
(ICF), which is chronic fatigue with no known cause that does not meet chronic fatigue syndrome criteria *
Inborn errors of metabolism Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances ( substra ...
such as fructose malabsorption. *
Infectious diseases An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
such as infectious mononucleosis or
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, ...
* Irritable bowel syndrome *
Kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...
s e.g. acute renal failure, chronic renal failure *
Leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
or
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include en ...
* Liver failure or liver diseases e.g.
Hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ( jaundice), poor appetite, vomiting, tiredness, abdominal ...
*
Lyme disease Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the '' Borrelia'' bacterium, which is spread by ticks in the genus '' Ixodes''. The most common sign of infection is an expanding red rash, known as erythema ...
* Neurological disorders such as narcolepsy,
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
, Postural Orthostatic Tachycardia Syndrome and post-concussion syndrome * Physical trauma and other
pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
-causing conditions, such as arthritis * Sleep deprivation or sleep disorders, e.g. sleep apnea *
Stroke A stroke is a disease, medical condition in which poor cerebral circulation, blood flow to the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemorr ...
*
Thyroid disease Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning ...
such as
hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as ...
Fatigue may also be a side effect of certain
medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...
s (e.g., lithium salts,
ciprofloxacin Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin i ...
); beta blockers, which can induce
exercise intolerance 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 ...
; and many cancer treatments, particularly
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...
and
radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...
.


Inflammation

Inflammation has been linked to many types of fatigue. Findings implicate neuroinflammation in the etiology of fatigue in autoimmune and related disorders.


Diagnosis

One study concluded about 50% of people who have fatigue receive a diagnosis that could explain the fatigue after a year with the condition. In those people who have a possible diagnosis, musculoskeletal (19.4%) and psychological problems (16.5%) are the most common. Definitive physical conditions were only found in 8.2% of cases. If a person with fatigue decides to seek medical advice, the overall goal is to identify and rule out any treatable conditions. This is done by considering the person's
medical history The medical history, case history, or anamnesis (from Greek: ἀνά, ''aná'', "open", and μνήσις, ''mnesis'', "memory") of a patient is information gained by a physician by asking specific questions, either to the patient or to other peo ...
, any other symptoms that are present, and evaluating of the qualities of the fatigue itself. The affected person may be able to identify patterns to the fatigue, such as being more tired at certain times of day, whether fatigue increases throughout the day, and whether fatigue is reduced after taking a nap. Because disrupted sleep is a significant contributor to fatigue, a diagnostic evaluation considers the quality of sleep, the emotional state of the person, sleep pattern, and stress level. The amount of sleep, the hours that are set aside for sleep, and the number of times that a person awakens during the night are important. A sleep study may be ordered to rule out a sleep disorder. Depression and other psychological conditions can produce fatigue, so people who report fatigue are routinely screened for these conditions, along with substance use disorders, poor diet, and lack of physical exercise, which paradoxically increases fatigue. Basic medical tests may be performed to rule out common causes of fatigue. These include blood tests to check for infection or
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
, a
urinalysis Urinalysis, a portmanteau of the words ''urine'' and ''analysis'', is a panel of medical tests that includes physical (macroscopic) examination of the urine, chemical evaluation using urine test strips, and microscopic examination. Macroscopic e ...
to look for signs of liver disease or
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
, and other tests to check for
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
and
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
function, such as a
comprehensive metabolic panel The comprehensive metabolic panel, or chemical screen (CMP; CPT code 80053), is a panel of 14 blood tests that serves as an initial broad medical screening tool. The CMP provides a rough check of kidney function, liver function, diabetic and par ...
. Other tests may be chosen depending on the patient's social history, such as an HIV test or pregnancy test.


Comparison with sleepiness

Fatigue is generally considered a more long-term condition than sleepiness (somnolence). Although sleepiness can be a symptom of a medical condition, it usually results from lack of restful sleep, or a lack of
stimulation Stimulation is the encouragement of development or the cause of activity generally. For example, "The press provides stimulation of political discourse." An interesting or fun activity can be described as "stimulating", regardless of its physic ...
. Chronic fatigue, on the other hand, is a symptom of a greater medical problem in most cases. It manifests in mental or physical weariness and inability to complete tasks at normal performance. Both are often used interchangeably and even categorized under the description of 'being tired.' Fatigue is often described as an uncomfortable tiredness, whereas sleepiness is comfortable and inviting.


Measurement

Fatigue can be quantitatively measured. Devices to measure medical fatigue have been developed by Japanese companies, among them Nintendo (cancelled). Nevertheless, such devices are not in common use outside Japan.


Management

Medications are reviewed as some have side effects that may contribute to fatigue and the interactions of medications are complex. Psychostimulants such as
methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...
, amphetamines, and modafinil have been used in the treatment of fatigue related to depression, chronic fatigue syndrome, and medical illness such as
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
. They have also been used to counteract fatigue in sleep loss and in
aviation Aviation includes the activities surrounding mechanical flight and the aircraft industry. ''Aircraft'' includes airplane, fixed-wing and helicopter, rotary-wing types, morphable wings, wing-less lifting bodies, as well as aerostat, lighter- ...
.


See also

* Affect *
Cancer-related fatigue Cancer-related fatigue is a symptom of fatigue that is experienced by nearly all cancer patients. Among patients receiving cancer treatment other than surgery, it is essentially universal. Fatigue is a normal and expected side effect of most for ...
* Combat stress reaction * Directed attention fatigue * Effects of fatigue on safety * Feeling * Gaucher's disease *
Heat illness Heat illness is a spectrum of disorders due to increased body temperature. It can be caused by either environmental conditions or by exertion. It includes minor conditions such as heat cramps, heat syncope, and heat exhaustion as well as the mo ...
* Malaise *
Microsleep A microsleep is a sudden temporary episode of sleep or drowsiness which may last for a few seconds where an individual fails to respond to some arbitrary sensory input and becomes unconscious.International Classification of Sleep Disorders, , pa ...
* Museum fatigue * Presenteeism * Sleep-deprived driving *
Pacing (activity management) Pacing is an activity management technique for managing a long-term health condition or disability, aiming to maximize what a person can do while reducing, or at least controlling, any symptoms that restrict activity. Pacing is commonly used to hel ...
* Zoom fatigue


References


Further reading

* Byung-Chul Han: ''Müdigkeitsgesellschaft''. Matthes & Seitz, Berlin 2010, . (Philosophical essay about fatigue as a sociological problem and symptom). ** Danish edition: Træthedssamfundet. Møller, 2012, . ** Dutch edition: De vermoeide samenleving. van gennep, 2012, . ** Italian editions : La società della stanchezza. nottetempo, 2012, . ** Korean edition: 한병철 지음 , 김태환 옮김. Moonji, 2011, . ** Spanish edition: La sociedad del cansancio. Herder Editorial, 2012, .


External links


Fatigue – Information for Patients
U.S. National Cancer Institute {{Authority control Exercise physiology Symptoms Subjective experience