Fatigue
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. Mental fatigue results from prolonged periods of cognitive activity which impairs cognitive ability. Mental fatigue can manifest as sleepiness, lethargy, 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 individuals 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, and can be reversed by rest. The central component of fatigue is triggered by an increase of the level of serotonin in the central nervous system. During motor activity, serotonin released in synapses that contact motor neurons promotes muscle contraction. 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 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 individuals 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, lethargy, directed attention fatigue, or disengagement. Research also suggests that mental fatigue is closely linked to the concept of ego depletion. 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. 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. However, objective cognitive testing can be used to differentiate the neurocognitive deficits of brain disease from those attributable to tiredness.The perception of mental fatigue is believed to be modulated by the brains reticular activating system (RAS).Fatigue impacts a drivers 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, overstimulation and understimulation, jet lag, active recreation, boredom, lack of sleep or disease.

Acute
Causes of acute fatigue include depression; chemical causes, such as dehydration, poisoning, low blood sugar, or mineral 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 fights an infection.

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 diseases, such as celiac disease, lupus, multiple sclerosis, myasthenia gravis, Sjögrens syndrome, and spondyloarthropathy
Anxiety disorders such as generalized anxiety disorder
Blood disorders such as anemia and hemochromatosis
Cancer, in which case it is called cancer fatigue
Chronic fatigue syndrome (CFS)
Substance use disorders including alcohol use disorder
Depression and other mental disorders that feature depressed mood
Developmental disorders such as autism spectrum disorder
Eating disorders, which can produce fatigue due to inadequate nutrition
Endocrine diseases or metabolic disorders: diabetes mellitus, hypothyroidism and Addison’s disease
Fibromyalgia
Gulf War syndrome
Heart failure
HIV
Idiopathic chronic fatigue (ICF), which is chronic fatigue with no known cause that does not meet chronic fatigue syndrome criteria
Inborn errors of metabolism such as fructose malabsorption.
Infectious diseases such as infectious mononucleosis or tuberculosis
Irritable bowel syndrome
Kidney diseases e.g. acute renal failure, chronic renal failure
Leukemia or lymphoma
Liver failure or liver diseases e.g. Hepatitis
Lyme disease
Neurological disorders such as narcolepsy, Parkinsons disease, Postural Orthostatic Tachycardia Syndrome and post-concussion syndrome
Physical trauma and other pain-causing conditions, such as arthritis
Sleep deprivation or sleep disorders, e.g. sleep apnea
Stroke
Thyroid disease such as hypothyroidismFatigue may also be a side effect of certain medications (e.g., lithium salts, ciprofloxacin); beta blockers, which can induce exercise intolerance; and many cancer treatments, particularly chemotherapy and radiotherapy.

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 persons medical history, 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, a urinalysis to look for signs of liver disease or diabetes mellitus, and other tests to check for kidney and liver function, such as a comprehensive metabolic panel. Other tests may be chosen depending on the patients 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. 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, amphetamines, and modafinil have been used in the treatment of fatigue related to depression, chronic fatigue syndrome, and medical illness such as cancer. They have also been used to counteract fatigue in sleep loss and in aviation.

See also
References
Further reading
Byung-Chul Han: Müdigkeitsgesellschaft. Matthes & Seitz, Berlin 2010, ISBN 978-3882216165. (Philosophical essay about fatigue as a sociological problem and symptom).
Danish edition: Træthedssamfundet. Møller, 2012, ISBN 978-8799404377.
Dutch edition: De vermoeide samenleving. van gennep, 2012, ISBN 978-9461640710.
Italian editions : La società della stanchezza. nottetempo, 2012, ISBN 978-8874523450.
Korean edition: 한병철 지음 | 김태환 옮김. Moonji, 2011, ISBN 978-8932023960.
Spanish edition: La sociedad del cansancio. Herder Editorial, 2012, ISBN 978-8425428685.

External links

Fatigue –  Information for Patients, U.S. National Cancer Institute