Fatigue

Introduction

Risk factors

Major sources of chronic fatigue

Managing fatigue

Resources

Introduction

Fatigue may be defined as a subjective state in which one feels tired or exhausted, and in which the capacity for normal work or activity is reduced. There is, however, no commonly accepted definition of fatigue when it is considered in the context of health and illness. This lack of definition results from the fact that a person’s experience of fatigue depends on a variety of factors. These factors include culture, personality, the physical environment (light, noise, vibration), availability of social support through networks of family members and friends, the nature of a particular fatiguing disease or disorder, and the type and duration of work or exercise. For example, the experience of fatigue associated with disease will be different for someone who is clinically depressed, socially isolated, and out of shape compared to another person who is not depressed, has many friends, and is aerobically fit.

Fatigue is sometimes characterized as normal or abnormal. For example, the feeling of tiredness or even exhaustion after exercising is a normal response and is relieved by resting; many people report that the experience of ordinary tiredness after exercise is pleasant. Moreover, this type of fatigue is called “acute” because the onset is sudden and the desired activity level returns after resting. On the other hand, there is a kind of fatigue that is not perceived as ordinary and that may develop insidiously over time. This type of fatigue is unpleasant or seriously distressing and is not resolved by rest. Fatigue of this nature is abnormal and referred to as “chronic.”

Some researchers regard fatigue as a defense mechanism that promotes the effective regulation of energy expenditures. According to this theory, when people feel tired, they take steps to avoid further stress (physical or emotional) by resting or by avoiding the stressor. They are then conserving energy. Because chronic fatigue is not normal, however, it is an important symptom of some mental disorders, a variety of physical diseases with known etiologies (causes), and some medical conditions that have no biological markers although they are recognizable syndromes (patterns of symptoms and signs).

Fatigue is sometimes described as being primary or secondary. Primary fatigue is a symptom of a disease or mental disorder and may be part of a cluster of such symptoms as pain, fever, or nausea. As the disease or disorder progresses, however, the fatigue may be intensified by the patient’s worsening condition, other disease symptoms, or surgical or medical treatment. This subsequent fatigue is called secondary.

Risk factors

Fatigue is a common experience. It is one of the top ten symptoms that people mention when they visit the doctor. Some people, however, are at higher risk for developing fatigue. For example, the risk for women is about 1.5 times the risk for men, and the risk for people who do not exercise is twice that of active people. Some researchers question whether women really are at higher risk: they are more likely than men to go to the doctor with health problems, and men are less likely to admit feeling fatigued. Other risk factors include obesity , smoking, use of alcohol, high stress levels, depression, anxiety , and low blood pressure. Having low blood pressure is usually considered desirable in the United States but is regarded as a treatable condition in other countries. Low blood pressure or postural hypotension (sudden lowering of blood pressure caused by standing up) may cause fatigue, dizziness, or fainting.

Major sources of chronic fatigue

Disease

There are many diseases and disorders in which fatigue is a major symptom. These include cancer, cardiovascular disease, emphysema, multiple sclerosis, rheumatic arthritis, systemic lupus erythematosus, HIV/AIDS, infectious mononucleosis, chronic fatigue syndrome, and fibromyalgia. The reasons for the fatigue, however, vary according to the organ system or body function affected by the disease. Physical reasons for fatigue include:

• circulatory and respiratory impairment. When the patient’s breathing and blood circulation are impaired or when the patient has anemia (low levels of red blood cells), body tissues do not receive as much oxygen and energy. Hence, the patient experiences a general sense of fatigue. Fatigue is also an important warning sign of heart trouble because it precedes 30-55% of myocardial infarctions (heart attacks) and sudden cardiac deaths.
• infection. Microorganisms that disturb body metabolism and produce toxic wastes cause disease and lead to fatigue. Fatigue is an early primary symptom of chronic, nonlocalized infections found in such diseases as AIDS, Lyme disease, and tuberculosis.
• nutritional disorders or imbalances. Malnutrition is a disorder that promotes disease. It is caused by insufficient intake of important nutrients, vitamins, and minerals; by problems with absorption of food through the digestive system; or by inadequate calorie consumption. Protein-energy malnutrition (PEM) occurs when people do not consume enough protein or calories; this condition leads to wasting of muscles and commonly occurs in developing countries. In particular, young children who are starving are at risk of PEM, as are people recovering from major illness. In general, malnutrition damages the body’s immune function and encourages disease and fatigue. Taking in too many calories for the body’s needs, on the other hand, results in obesity, which is a predictor of many diseases related to fatigue.
• dehydration. Dehydration results from water and sodium imbalances in body tissues. The loss of total body water and sodium may be caused by diarrhea, vomiting, bed rest, exposure to heat, or exercise. Dehydration contributes to muscle weakness and mental confusion; it is a common and overlooked source of fatigue. Once fatigued, people are less likely to consume enough fluids and nutrients, worsening the fatigue and confusion.
• deconditioning. This term refers to generalized organ system deterioration resulting from bed rest and lack of exercise. In the 1950s and 1970s, the National Aeronautics and Space Administration (NASA) studied the effects of bed rest on healthy athletes. The researchers found that deconditioning set in quite rapidly (within 24 hours) and led to depression and weakness. Even mild exercise can counteract deconditioning and has become an important means of minimizing depression and fatigue resulting from disease and hospitalization.
• pain. When pain is severe enough, it may disrupt sleep and lead to the development of sleep disorders such as insomnia or hypersomnia. Insomnia is the term for having difficulty falling and/or staying asleep. Hypersomnia refers to excessive sleeping. In general, disrupted sleep is not restorative; people wake up feeling tired, and as a result their pain is worsened and they may become depressed. Furthermore, pain may interfere with movement or lead to too much bed rest, which results in deconditioning. Sometimes pain leads to social isolation because the person cannot cope with the physical effort involved in maintaining social relationships, or because family members are unsympathetic or resentful of the ill or injured person’s reduced capacity for work or participation in family life. All of these factors worsen pain, contributing to further sleep disruption, fatigue, and depression.
• stress. When someone experiences ongoing pain and stress, organ systems and functional processes eventually break down. These include cardiovascular, digestive, and respiratory systems, as well as the efficient elimination of body wastes. According to the American Psychiatric Association, various chronic diseases are related to stress, including rheumatoid arthritis, cardiac angina, and secondary dysmenorrhea (painful menstruation).
• sleep disorders. There are a variety of sleep disorders that cause fatigue, including insomnia, hypersomnia, sleep apnea, and restless legs syndrome. For example, hypersomnia may be the result of brain abnormalities caused by viral infections. Researchers studying the aftermath of infectious mononucleosis proposed that exposure to viral infections might change brain function with the effect of minimizing restorative sleep; hence, some people developed hypersomnia. Another common disorder is sleep apnea, in which the patient’s breathing stops for at least ten seconds, usually more than 20 times per hour. Snoring is common. People may experience choking and then wake up gasping for air; they may develop daytime hypersomnia to compensate. Sleep apnea is associated with aging, weight gain, and depression. It is also a risk factor for stroke and myocardial infarctions. Restless legs syndrome is a condition in which very uncomfortable sensations in the patient’s legs cause them to move and wake up from sleep, or keep them from falling asleep. All of these disorders reduce the quality of a person’s sleep and are associated with fatigue.

Fibromyalgia and chronic fatigue syndrome

Fibromyalgia (also known as myofascial syndrome or fibrositis) is a syndrome characterized by pain and achiness in muscles, tendons, and ligaments. There are 18 locations on the body where patients typically feel sore. These locations include areas on the lower back and along the spine, neck, and thighs. A diagnostic criterion for fibromyalgia (FM) is that at least 11 of the 18 sites are painful. In addition to pain, people with FM may experience sleep disorders, fatigue, anxiety, and irritable bowel syndrome. Experts have suggested that FM and chronic fatigue syndrome (CFS) are manifestations of the same pain and fatigue syndrome. The care that patients receive for FM or CFS depends in large measure on whether they were referred to a rheumatologist (a doctor who specializes in treating diseases of the joints and muscles), neurologist, or psychiatrist.

A few doctors may still not accept CFS (also known as myalgic encephalomyelitis in Great Britain) as a legitimate medical problem. This refusal is stigmatizing and distressing to the person who must cope with disabling pain and fatigue. It is not uncommon for people with CFS to see a number of different physicians before finding one who is willing to diagnose CFS. Nevertheless, major health agencies, such as the Centers for Disease Control (CDC) in the United States, have studied the syndrome. As a result, the CDC has developed a case definition for CFS that lists major and minor criteria for diagnosis. The major criteria of CFS include the presence of chronic and persistent fatigue for at least six months; fatigue that does not improve with rest; and fatigue that causes significant interference with the patient’s daily activities. There are also eight other characteristic symptoms that include fever, sore throat, swollen lymph nodes, myalgia (muscle pain), difficulty with a level of physical exercise that the patient had performed easily before the illness, sleep disturbances, and headaches. Additionally, people often have difficulty concentrating and remembering information, and they experience extreme frustration and depression as a result of the limitations imposed by CFS. Full recovery from CFS is rare, occurring in only 5% to 10% of cases, although a 2005 report found that 8% to 63% of patients may experience improvement.

Psychological disorders

While fatigue may be caused by many organic diseases and medical conditions, it is a chief complaint for several mental disorders, including generalized anxiety disorder and clinical depression. Moreover, mental disorders may coexist with physical disease. When there is considerable symptom overlap, the differential diagnosis of fatigue is especially difficult.

GENERALIZED ANXIETY DISORDER

People are diagnosed as having generalized anxiety disorder (GAD) if they experience overwhelming worry or apprehension that persists, usually daily, for at least six months, and if they also experience some of the following symptoms: unusual tiredness, restlessness and irritability, problems with concentration, muscle tension, and disrupted sleep. Stressful life events such as divorce, unemployment, illness, or being the victim of a violent crime are associated with GAD, as is a history of psychiatric problems. Some evidence suggests that women who have been exposed to danger are at risk of developing GAD; women who suffer loss are at risk of developing depression; and women who experience danger and loss are at risk of developing a mix of both GAD and depression.

While the symptoms of CFS and GAD overlap, the disorders have different primary complaints. Patients with CFS complain primarily of tiredness, whereas people with GAD describe being excessively worried. In general, some researchers believe that anxiety contributes to fatigue by disrupting rest and restorative sleep.

DEPRESSION

In the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), the presence of depressed mood or sadness, or loss of pleasure in life, is an important diagnostic criterion for depression. Daily fatigue, lack of energy, insomnia, and hypersomnia are indicators of a depressed mood. The symptoms of depression overlap with those of CFS; for example, some researchers report that 89% of people with depression are fatigued, as compared to 86-100% of people with CFS. The experience of fatigue, however, seems to be more disabling with CFS than with depression. Another difference between CFS and depression concerns the onset of the disorder. Most patients with CFS experience a sudden or acute onset, whereas depression may develop over a period of weeks or months. Also, while both types of patients experience sleep disorders, CFS patients tend to have difficulty falling asleep, whereas depressed patients tend to wake early in the morning. It is possible for CFS and depression to be comorbidities.

Some researchers believe that there is a link between depression, fatigue, and exposure to too much REM sleep. There are five distinct phases in human sleep. The first two are characterized by light sleep; the second two by a deep restorative sleep called slow-wave sleep; and the last by rapid eye movement or REM sleep. Most dreams occur during REM sleep. Throughout the night, the intervals of REM sleep increase and usually peak around 8:30 A.M. A sleep deprivation treatment for depression involves reducing the patient’s amount of REM sleep by waking him or her around 6:00 A.M. Researchers think that some fatigue associated with disease may be a form of mild depression and that reducing the amount of REM sleep will reduce fatigue by moderating depression.

Managing fatigue

The management of fatigue depends in large measure on its causes and the person’s experience of it. For example, if fatigue is acute and normal, the person will recover from feeling tired after exertion by resting. In cases of fatigue associated with influenza or other infectious illnesses, the person will feel energy return as they recover from the illness. When fatigue is chronic and abnormal, however, the doctor will tailor a treatment program to the patient’s needs. There are a variety of approaches that include:

• aerobic exercise. Physical activity increases fitness and counteracts depression.
• hydration (adding water). Water improves muscle turgor or tension and helps to carry electrolytes.
• improving sleep patterns. The patient’s sleep may be more restful when its timing and duration are controlled.
• pharmacotherapy (treatment with medications). The patient may be given various medications to treat physical diseases or mental disorders, to control pain, or to manage sleeping patterns.
• psychotherapy. There are several different treatment approaches that help patients manage stress, understand the motives that govern their behavior, or change maladaptive ideas and negative thinking patterns.
• physical therapy. This form of treatment helps patients improve or manage functional impairments or disabilities.

KEY TERMS

Biological marker —An indicator or characteristic trait of a disease that facilitates differential diagnosis (the process of distinguishing one disorder from other, similar disorders).

Deconditioning —Loss of physical strength or stamina resulting from bed rest or lack of exercise.

Electrolytes —Substances or elements that dissociate into electrically charged particles (ions) when dissolved in the blood. The electrolytes in human blood include potassium, magnesium, and chloride.

Metabolism —The group of biochemical processes within the body that release energy in support of life.

Stress —A physical and psychological response that results from being exposed to a demand or pressure.

Syndrome —A group of symptoms that together characterize a disease or disorder.

In addition to seeking professional help, people can understand and manage fatigue by joining appropriate self-help groups , reading informative books, seeking information from clearinghouses on the Internet, and visiting Web sites maintained by national organizations for various diseases.

See alsoBrain; Breathing-related sleep disorder; Caffeine and related sleep disorders; Circadian rhythm sleep disorder; Pain Disorder; Self-help groups; Somatization and somatoform disorders.

Resources

BOOKS

Beers, Mark H., and Robert Berkow, eds. The Merck Manual of Diagnosis and Therapy, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

Glaus, A. Fatigue in Patients with Cancer: Analysis and Assessment. Recent Results in Cancer Research, No. 145. Berlin, Germany: Springer-Verlag, 1998.

Hubbard, John R., and Edward A. Workman, eds. Handbook of Stress Medicine: An Organ System Approach. Boca Raton, FL: CRC Press, 1998.

Natelson, Benjamin H. Facing and Fighting Fatigue: A Practical Approach. New Haven, CT: Yale University Press, 1998.

Winningham, Maryl L., and Margaret Barton-Burke, eds. Fatigue in Cancer: A Multidimensional Approach. Sud-bury, MA: Jones and Bartlett Publishers, 2000.

PERIODICALS

Natelson, Benjamin H. “Chronic Fatigue Syndrome.” JAMA: Journal of the American Medical Association 285.20 (May 23-30 2001): 2557–59.

ORGANIZATIONS

MEDLINE plus Health Information, U.S. National Library of Medicine. 8600 Rockville Pike, Bethesda, MD 20894. Telephone: (888) 346-3656. <http://www.medlineplus.gov>.

National Chronic Fatigue Syndrome and Fibromyalgia Association. P.O. Box 18426, Kansas City, MO 64133. Telephone: (816) 313-2000. <http://www.4woman.gov/nwhic/references/mdreferrals/ncfsfa.htm>.

WEB SITES

Centers for Disease Control. “Chronic Fatigue Syndrome”. (2006) <http://www.cdc.gov/cfs/cfsbasicfacts.htm>

Davis, Caralyn. “What’s In a Name: Fibro vs. CFS.” Arthritis Foundation. <http://www.arthritis.org/resources/news/news_fibro_cfs.asp>

Tanja Bekhuis, PhD
Emily Jane Willingham, PhD

Fatigue

Introduction

Fatigue may be defined as a subjective state in which one feels tired or exhausted, and in which the capacity for normal work or activity is reduced. There is, however, no commonly accepted definition of fatigue when it is considered in the context of health and illness. This lack of definition results from the fact that a person's experience of fatigue depends on a variety of factors. These factors include culture; personality; the physical environment (light, noise, vibration); availability of social support through networks of family members and friends; the nature of a particular fatiguing disease or disorder; and the type and duration of work or exercise. For example, the experience of fatigue associated with disease will be different for someone who is clinically depressed, is socially isolated, and is out of shape, as compared to another person who is not depressed, has many friends, and is aerobically fit.

Fatigue is sometimes characterized as normal or abnormal. For example, the feeling of tiredness or even exhaustion after exercising is a normal response and is relieved by resting; many people report that the experience of ordinary tiredness after exercise is pleasant. Moreover, this type of fatigue is called acute since the onset is sudden and the desired activity level returns after resting. On the other hand, there is a kind of fatigue that is not perceived as ordinary; that may develop insidiously over time; is unpleasant or seriously distressing; and is not resolved by rest. This kind of fatigue is abnormal and is called chronic.

Some researchers regard fatigue as a defense mechanism that promotes the effective regulation of energy expenditures. According to this theory, when people feel tired they take steps to avoid further stress (physical or emotional) by resting or by avoiding the stressor. They are then conserving energy. Since chronic fatigue is not normal, however, it is an important symptom of some mental disorders; of a variety of physical diseases with known etiologies (causes); and of medical conditions that have no biological markers although they have recognizable syndromes (patterns of symptoms and signs).

Fatigue is sometimes described as being primary or secondary. Primary fatigue is a symptom of a disease or mental disorder, and may be part of a cluster of such symptoms as pain, fever, or nausea. As the disease or disorder progresses, however, the fatigue may be intensified by the patient's worsening condition, by the other disease symptoms, or by the surgical or medical treatment given to the patient. This subsequent fatigue is called secondary.

Risk factors

Fatigue is a common experience. It is one of the top ten symptoms that people mention when they visit the doctor. Some people, however, are at higher risk for developing fatigue. For example, the risk for women is about 1.5 times the risk for men, and the risk for people who don't exercise is twice that of active people. Some researchers question whether women really are at higher risk, since they are more likely than men to go to the doctor with health problems; also, men are less likely to admit they feel fatigued. Other risk factors include obesity ; smoking; use of alcohol; high stress levels; depression; anxiety; and low blood pressure. Having low blood pressure is usually considered desirable in the United States, but is regarded as a treatable condition in other countries. Low blood pressure or postural hypotension (sudden lowering of blood pressure caused by standing up) may cause fatigue, dizziness, or fainting.

Major sources of chronic fatigue

Disease

There are many diseases and disorders in which fatigue is a major symptom— for example, cancer, cardiovascular disease, emphysema, multiple sclerosis, rheumatic arthritis, systemic lupus erythematosus, HIV/AIDS, infectious mononucleosis, chronic fatigue syndrome, and fibromyalgia. The reasons for the fatigue, however, vary according to the organ system or body function affected by the disease. Physical reasons for fatigue include:

• Circulatory and respiratory impairment. When the patient's breathing and blood circulation are impaired, or when the patient has anemia (low levels of red blood cells), body tissues do not receive as much oxygen and energy. Hence, the patient experiences a general sense of fatigue. Fatigue is also an important warning sign of heart trouble because it precedes 30%–55% of myocardial infarctions (heart attacks) and sudden cardiac deaths.
• Infection. Microorganisms that disturb body metabolism and produce toxic wastes cause disease and lead to fatigue. Fatigue is an early primary symptom of chronic, nonlocalized infections found in such diseases as acquired immune deficiency syndrome (AIDS), Lyme disease, and tuberculosis.
• Nutritional disorders or imbalances. Malnutrition is a disorder that promotes disease. It is caused by insufficient intake of important nutrients, vitamins, and minerals; by problems with absorption of food through the digestive system; or by inadequate calorie consumption. Protein-energy malnutrition (PEM) occurs when people do not consume enough protein or calories; this condition leads to wasting of muscles and commonly occurs in developing countries. In particular, young children who are starving are at risk of PEM, as are people recovering from major illness. In general, malnutrition damages the body's immune function and thereby encourages disease and fatigue. Taking in too many calories for the body's needs, on the other hand, results in obesity, which is a predictor of many diseases related to fatigue.
• Dehydration. Dehydration results from water and sodium imbalances in body tissues. The loss of total body water and sodium may be caused by diarrhea, vomiting, bed rest, exposure to heat, or exercise. Dehydration contributes to muscle weakness and mental confusion; it is a common and overlooked source of fatigue. Once fatigued, people are less likely to consume enough fluids and nutrients, which makes the fatigue and confusion worse.
• Deconditioning. This term refers to generalized organ system deterioration resulting from bed rest and lack of exercise. In the 1950s and 1970s, the National Aeronautics and Space Administration (NASA) studied the effects of bed rest on healthy athletes. The researchers found that deconditioning set in quite rapidly (within 24 hours) and led to depression and weakness. Even mild exercise can counteract deconditioning, however, and has become an important means of minimizing depression and fatigue resulting from disease and hospitalization.
• Pain. When pain is severe enough, it may disrupt sleep and lead to the development of such sleep disorders as insomnia or hypersomnia . Insomnia is the term for having difficulty falling and/or staying asleep. Hypersomnia refers to excessive sleeping. In general, disrupted sleep is not restorative; people wake up feeling tired, and as a result their pain is worsened and they may become depressed. Furthermore, pain may interfere with movement or lead to too much bed rest, which results in deconditioning. Sometimes pain leads to social isolation because the person cannot cope with the physical effort involved in maintaining social relationships, or because family members are unsympathetic or resentful of the ill or injured person's reduced capacity for work or participation in family life. All of these factors worsen pain, contributing to further sleep disruption, fatigue, and depression.
• Stress. When someone experiences ongoing pain and stress, organ systems and functional processes eventually break down. These include cardiovascular, digestive, and respiratory systems, as well as the efficient elimination of body wastes. According to the American Psychiatric Association, various chronic diseases are related to stress, including regional enteritis (intestinal inflammation); ulcerative colitis (a disease of the colon); gastric ulcers; rheumatoid arthritis; cardiac angina, and dysmenorrhea (painful menstruation). These diseases deplete the body's levels of serotonin (a neurotransmitter important in the regulation of sleep and wakefulness, as well as depression), and endorphins (opiate-like substances that moderate pain). Depletion of these body chemicals leads to insomnia and chronic fatigue.
• Sleep disorders. There are a variety of sleep disorders that cause fatigue, including insomnia, hypersomnia, sleep apnea, and restless legs syndrome. For example, hypersomnia may be the result of brain abnormalities caused by viral infections. Researchers studying the aftermath of infectious mononucleosis proposed that exposure to viral infections might change brain function with the effect of minimizing restorative sleep; hence, some people developed hypersomnia. Another common disorder is sleep apnea, in which the patient's breathing stops for at least ten seconds, usually more than 20 times per hour. Snoring is common. People may experience choking and then wake up gasping for air; they may develop daytime hypersomnia (daytime sleepiness) to compensate. Sleep apnea is associated with aging, weight gain, and depression. It is also a risk factor for stroke and myocardial infarctions. Restless legs syndrome is a condition in which very uncomfortable sensations in the patient's legs cause them to move and wake up from sleep, or keep them from falling asleep. All of these disorders reduce the quality of a person's sleep and are associated with fatigue.

Fibromyalgia and chronic fatigue syndrome

Fibromyalgia (also known as myofascial syndrome or fibrositis) is characterized by pain and achiness in muscles, tendons, and ligaments. There are 18 locations on the body where patients typically feel sore. These locations include areas on the lower back and along the spine, neck, and thighs. A diagnostic criterion for fibromyalgia (FM) is that at least 11 of the 18 sites are painful. In addition to pain, people with FM may experience sleep disorders, fatigue, anxiety, and irritable bowel syndrome. Some researchers maintain, however, that when fatigue is severe, chronic, and persistent, FM is indistinguishable from chronic fatigue syndrome (CFS). The care that patients receive for FM or CFS depends in large measure on whether they were referred to a rheumatologist (a doctor who specializes in treating diseases of the joints and muscles), neurologist, or psychiatrist .

Some doctors do not accept CFS (also known as myalgic encephalomyelitis in Great Britain) as a legitimate medical problem. This refusal is stigmatizing and distressing to the person who must cope with disabling pain and fatigue. It is not uncommon for people with CFS to see a number of different physicians before finding one who is willing to diagnose CFS. Nevertheless, major health agencies, such as the Centers for Disease Control (CDC) in the United States, have studied the syndrome. As a result, a revised CDC case definition for CFS was published in 1994 that lists major and minor criteria for diagnosis . The major criteria of CFS include the presence of chronic and persistent fatigue for at least six months; fatigue that does not improve with rest; and fatigue that causes significant interference with the patient's daily activities. Minor criteria include such flu-like symptoms as fever; sore throat; swollen lymph nodes; myalgia (muscle pain); difficulty with a level of physical exercise that the patient had performed easily before the illness; sleep disturbances; and headaches. Additionally, people often have difficulty concentrating and remembering information; they experience extreme frustration and depression as a result of the limitations imposed by CFS. The prognosis for recovery from CFS is poor, although the symptoms are manageable.

Psychological disorders

While fatigue may be caused by many organic diseases and medical conditions, it is a chief complaint for several mental disorders, including generalized anxiety disorder and clinical depression. Moreover, mental disorders may coexist with physical disease. When there is considerable symptom overlap, the differential diagnosis of fatigue is especially difficult.

GENERALIZED ANXIETY DISORDER. People are diagnosed as having generalized anxiety disorder (GAD) if they suffer from overwhelming worry or apprehension that persists, usually daily, for at least six months; and if they also experience some of the following symptoms: unusual tiredness, restlessness and irritability, problems with concentration, muscle tension, and disrupted sleep. Such stressful life events as divorce, unemployment, illness, or being the victim of a violent crime are associated with GAD, as is a history of psychiatric problems. Some evidence suggests that women who have been exposed to danger are at risk of developing GAD; women who suffer loss are at risk of developing depression, and women who experience danger and loss are at risk of developing a mix of both GAD and depression.

While the symptoms of CFS and GAD overlap, the disorders have different primary complaints. Patients with CFS complain primarily of tiredness, whereas people with GAD describe being excessively worried. In general, some researchers believe that anxiety contributes to fatigue by disrupting rest and restorative sleep.

DEPRESSION. In the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSMIV ), the presence of depressed mood or sadness, or loss of pleasure in life, is an important diagnostic criterion for depression. Daily fatigue, lack of energy, insomnia and hypersomnia are indicators of a depressed mood. The symptoms of depression overlap with those of CFS; for example, some researchers report that 89% of people with depression are fatigued, as compared to 86%–100% of people with CFS. The experience of fatigue, however, seems to be more disabling with CFS than with depression. Another difference between CFS and depression concerns the onset of the disorder. Most patients with CFS experience a sudden or acute onset, whereas depression may develop over a period of weeks or months. Also, while both types of patients experience sleep disorders, CFS patients tend to have difficulty falling asleep, whereas depressed patients tend to wake early in the morning.

Some researchers believe that there is a link between depression, fatigue, and exposure to too much REM sleep. There are five distinct phases in human sleep. The first two are characterized by light sleep; the second two by a deep restorative sleep called slow-wave sleep; and the last by rapid eye movement or REM sleep. Most dreams occur during REM sleep. Throughout the night, the intervals of REM sleep increase and usually peak around 8:30 a.m. A sleep deprivation treatment for depression involves reducing the patient's amount of REM sleep by waking him or her around 6:00 A.M. Researchers think that some fatigue associated with disease may be a form of mild depression and that reducing the amount of REM sleep will reduce fatigue by moderating depression.

Managing fatigue

The management of fatigue depends in large measure on its causes and the person's experience of it. For example, if fatigue is acute and normal, the person will recover from feeling tired after exertion by resting. In cases of fatigue associated with influenza or other infectious illnesses, the person will feel energy return as they recover from the illness. When fatigue is chronic and abnormal, however, the doctor will tailor a treatment program to the patient's needs. There are a variety of approaches that include:

• Aerobic exercise. Physical activity increases fitness and counteracts depression.• Hydration (adding water). Water improves muscle turgor or tension and helps to carry electrolytes.
• Improving sleep patterns. The patient's sleep may be more restful when its timing and duration are controlled.
• Pharmacotherapy (treatment with medications). The patient may be given various medications to treat physical diseases or mental disorders; to control pain; or to manage sleeping patterns.
• Psychotherapy. There are several different treatment approaches that help patients manage stress; understand the motives that govern their behavior; or change maladaptive ideas and negative thinking patterns.
• Physical therapy. This form of treatment helps patients improve or manage functional impairments or disabilities.

In addition to seeking professional help, people can understand and manage fatigue by joining appropriate self-help groups ; reading informative books; seeking information from clearinghouses on the Internet; and visiting web sites maintained by national organizations for various diseases.

See also Brain; Breathing-related sleep disorder; Caffeine and related sleep disorders; Circadian rhythm sleep disorder; Pain disorder; Self-help groups; Somatization and somatoform disorders

Resources

BOOKS

Beers, Mark H., and Robert Berkow, eds. The Merck Manual of Diagnosis and Therapy. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

Glaus, A. Fatigue in Patients with Cancer: Analysis and Assessment. Recent Results in Cancer Research, no. 145. Berlin, Germany: Springer-Verlag, 1998.

Hubbard, John R., and Edward A. Workman, eds. Handbook of Stress Medicine: An Organ System Approach. Boca Raton, FL: CRC Press, 1998.

Natelson, Benjamin H. Facing and Fighting Fatigue: A Practical Approach. New Haven, CT: Yale University Press, 1998.

Winningham, Maryl L., and Margaret Barton-Burke, eds. Fatigue in Cancer: A Multidimensional Approach. Sudbury, MA: Jones and Bartlett Publishers, 2000.

PERIODICALS

Natelson, Benjamin H. "Chronic Fatigue Syndrome." JAMA: Journal of the American Medical Association 285, no. 20 (May 23-30 2001): 2557-59.

ORGANIZATIONS

MEDLINEplus Health Information. U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda, MD 20894. (888) 346-3656. <http://www.medlineplus.gov>.

National Chronic Fatigue Syndrome and Fibromyalgia Association. P.O. Box 18426, Kansas City, MO 64133. (816)313-2000. <http://www.4woman.gov/nwhic/references/mdreferrals/ncfsfa.htm>.

Tanja Bekhuis, Ph.D.

Fatigue

Definition

Fatigue may be defined as a subjective state in which one feels tired or exhausted, and in which the capacity for normal work or activity is reduced. There is, however, no commonly accepted definition of fatigue when it is considered in the context of health and illness. This lack of definition results from the fact that a person's experience of fatigue depends on a variety of factors. These factors include culture, personality, the physical environment (light, noise, vibration), availability of social support through networks of family members and friends, the nature of a particular fatiguing disease or disorder, and the type and duration of work or exercise . The experience of fatigue associated with disease will be different for someone who is clinically depressed, is socially isolated, and is out of shape, as compared to another person who is not depressed, has many friends, and is aerobically fit.

Description

Fatigue is sometimes characterized as normal or abnormal. For example, the feeling of tiredness or even exhaustion after exercising is a normal response and is relieved by resting; many people report that the experience of ordinary tiredness after exercise is pleasant. Moreover, this type of fatigue is called "acute" since the onset is sudden and the desired activity level returns after resting. On the other hand, there is fatigue that is not perceived as ordinary, that may develop insidiously over time, is unpleasant or seriously distressing, and is not resolved by rest. This kind of fatigue is abnormal and is called "chronic."

Some researchers regard fatigue as a defense mechanism that promotes the effective regulation of energy expenditures. According to this theory, when people feel tired they take steps to avoid further stress (physical or emotional) by resting or by avoiding the stressor. They are then conserving energy. Since chronic fatigue is not normal, however, it is a common symptom of some mental disorders, a variety of physical diseases with known etiologies (causes), and medical conditions that have no biological markers although they have recognizable syndromes (patterns of symptoms and signs).

Fatigue is sometimes described as being primary or secondary. Primary fatigue is a symptom of a disease or mental disorder, and may be part of a cluster of such symptoms as pain , fever, or nausea. As the disease or disorder progresses, however, the fatigue may be intensified by the patient's worsening condition, by the other disease symptoms, or by the surgical or medical treatment given to the patient. This subsequent fatigue is called secondary.

Risk factors

Fatigue is a common experience. It is one of the top ten symptoms that people mention when they visit the doctor. Some people, however, are at higher risk for developing fatigue. The risk for women is about 1.5 times the risk for men, and the risk for people who do not exercise is twice that of active people. Some researchers question whether women really are at higher risk, since women are more likely than men to go to the doctor with health problems; also, men are less likely to admit they feel fatigued. Other risk factors include obesity, smoking, use of alcohol, high stress levels, depression , anxiety, and low blood pressure. Having low blood pressure is usually considered desirable in the United States, but is regarded as a treatable condition in other countries. Low blood pressure or postural hypotension (sudden lowering of blood pressure caused by standing up) may cause fatigue, dizziness , or fainting .

Major sources of chronic fatigue

Disease

There are many diseases and disorders in which fatigue is a major symptom—for example, cancer, cardiovascular disease, emphysema, multiple sclerosis , rheumatic arthritis, systemic lupus erythematosus, HIV/AIDS, infectious mononucleosis, chronic fatigue syndrome, and fibromyalgia. The reasons for the fatigue, however, vary according to the organ system or body function affected by the disease.

Physical reasons for fatigue include:

• Circulatory and respiratory impairment. When the patient's breathing and blood circulation are impaired, or when the patient has anemia (low levels of red blood cells), body tissues do not receive as much oxygen and energy. Consequently, the patient experiences a general sense of fatigue. Fatigue is also an important warning sign of heart trouble; it precedes 30–55% of myocardial infarctions (heart attacks) and sudden cardiac deaths.
• Infection. Microorganisms that disturb body metabolism and produce toxic wastes cause disease and lead to fatigue. Fatigue is an early primary symptom of chronic, nonlocalized infections found in such diseases as acquired immune deficiency syndrome (AIDS ), Lyme disease , and tuberculosis.
• Nutritional disorders or imbalances. Malnutrition is a disorder that promotes disease. It is caused by insufficient intake of important nutrients, vitamins, and minerals; by problems with absorption of food through the digestive system; or by inadequate calorie consumption. Protein-energy malnutrition (PEM) occurs when people do not consume enough protein or calories; this condition leads to wasting of muscles and commonly occurs in developing countries. In particular, young children who are starving are at risk of PEM, as are people recovering from major illness. In general, malnutrition damages the body's immune function and thereby encourages disease and fatigue. Taking in too many calories for the body's needs, on the other hand, results in obesity, which is a predictor of many diseases related to fatigue.
• Dehydration. Dehydration results from water and sodium imbalances in body tissues. The loss of total body water and sodium may be caused by diarrhea, vomiting, bed rest, overexposure to heat, or exercise. Dehydration contributes to muscle weakness and mental confusion; it is a common and overlooked source of fatigue. Once fatigued, people are less likely to consume enough fluids and nutrients, which makes the fatigue and confusion worse.
• Deconditioning. This term refers to generalized organ system deterioration resulting from bed rest and lack of exercise. In the 1950s and 1970s, the National Aeronautics and Space Administration (NASA) studied the effects of bed rest on healthy athletes. The researchers found that deconditioning occurred rapidly (within 24 hours) and led to depression and weakness. Even mild exercise can counteract deconditioning, however, and it has become an important means of minimizing depression and fatigue resulting from disease and hospitalization.
• Pain. When pain is severe enough, it may disrupt sleep and lead to the development of such sleep disorders as insomnia or hypersomnia . (Insomnia is the term for having difficulty falling and/or staying asleep. Hypersomnia refers to excessive sleeping.) In general, disrupted sleep is not restorative; people wake up feeling tired, and as a result their pain is worsened and they may become depressed. Furthermore, pain may interfere with movement or lead to too much bed rest, which results in deconditioning. Sometimes pain leads to social isolation because the person cannot cope with the physical effort involved in maintaining social relationships, or because family members are unsympathetic or resentful of the ill or injured person's reduced capacity for work or participation in family life. All of these factors worsen pain, contributing to further sleep disruption, fatigue, and depression.
• Stress. When someone experiences ongoing pain and stress, organ systems and functional processes eventually break down. These include cardiovascular, digestive, and respiratory systems, as well as the efficient elimination of body wastes. According to the American Psychiatric Association, various chronic diseases are related to stress, including regional enteritis (intestinal inflammation), ulcerative colitis (a disease of the colon), gastric ulcers, rheumatoid arthritis, cardiac angina, and dysmenorrhea (painful menstruation). These diseases deplete the body's levels of serotonin (a neurotransmitter important in the regulation of sleep and wakefulness, as well as depression), and endorphins (opiate-like substances that moderate pain). Depletion of these body chemicals leads to insomnia and chronic fatigue.
• Sleep disorders. There are a variety of sleep disorders that cause fatigue, including insomnia, hypersomnia, sleep apnea , and restless legs syndrome . For example, hypersomnia may be the result of brain abnormalities caused by viral infections. Researchers studying the aftermath of infectious mononucleosis proposed that exposure to viral infections might change brain function with the effect of minimizing restorative sleep. Another common disorder is sleep apnea, in which the patient's breathing stops for at least 10 seconds, usually more than 20 times per hour. Snoring is common. People may experience choking and then wake up gasping for air; they may develop daytime hypersomnia (daytime sleepiness) to compensate. Sleep apnea is associated with aging, weight gain, and depression. It is also a risk factor for stroke and myocardial infarctions. Restless legs syndrome is a condition in which very uncomfortable sensations in the patient's legs cause them to move and wake up from sleep, or keep them from falling asleep. All of these disorders reduce the quality of a person's sleep and are associated with fatigue.

Fibromyalgia and chronic fatigue syndrome

Fibromyalgia (also known as myofascial syndrome or fibrositis) is characterized by painful and achy muscles, tendons, and ligaments. There are 18 locations on the body where patients typically feel sore. These locations include areas on the lower back and along the spine, neck, and thighs. A diagnostic criterion for fibromyalgia (FM) is that at least 11 of the 18 sites are painful. In addition to pain, people with FM may experience sleep disorders, fatigue, anxiety, and irritable bowel syndrome. Some researchers maintain, however, that when fatigue is severe, chronic, and persistent, FM is indistinguishable from chronic fatigue syndrome (CFS). The care that patients receive for FM or CFS depends in large measure on whether they were referred to a rheumatologist (a doctor who specializes in treating diseases of the joints and muscles), neurologist , or psychiatrist.

Some doctors do not accept CFS (also known as myalgic encephalomyelitis) as a legitimate medical problem. This refusal is stigmatizing and distressing to the person who must cope with disabling pain and fatigue. Many people with CFS may see a number of different physicians before finding one who is willing to diagnose CFS. Nevertheless, major health agencies such as the Centers for Disease Control (CDC) in the United States have studied the syndrome. As a result, a revised CDC case definition for CFS was published in 1994 that lists major and minor criteria for diagnosis. The major criteria of CFS include the presence of chronic and persistent fatigue for at least six months; fatigue that does not improve with rest; and fatigue that causes significant interference with the patient's daily activities. Minor criteria include such flu-like symptoms as fever, sore throat, swollen lymph nodes, myalgia (muscle pain), difficulty with a level of physical exercise that the patient had performed easily before the illness, sleep disturbances, and headaches. Additionally, people often have difficulty concentrating and remembering information and they experience extreme frustration and depression as a result of the limitations imposed by CFS. The prognosis for recovery from CFS is poor, although the symptoms are manageable.

Psychological disorders

While fatigue may be caused by many organic diseases and medical conditions, it is a chief complaint for several mental disorders, including generalized anxiety disorder and clinical depression. Moreover, mental disorders may coexist with physical disease. When there is considerable symptom overlap, the differential diagnosis of fatigue is especially difficult.

GENERALIZED ANXIETY DISORDER

People are diagnosed as having generalized anxiety disorder (GAD) if they suffer from overwhelming worry or apprehension that persists, usually daily, for at least six months, and if they also experience some of the following symptoms: unusual tiredness, restlessness and irritability, problems with concentration, muscle tension, and disrupted sleep. Such stressful life events as divorce, unemployment, illness, or being the victim of a violent crime are associated with GAD, as is a history of psychiatric problems. Some evidence suggests that women who have been exposed to danger are at risk of developing GAD; women who suffer loss are at risk of developing depression, and women who experience danger and loss are at risk of developing a mix of both GAD and depression.

While the symptoms of CFS and GAD overlap, the disorders have different primary complaints. Patients with CFS complain primarily of tiredness, whereas people with GAD describe being excessively worried. In general, some researchers believe that anxiety contributes to fatigue by disrupting rest and restorative sleep.

DEPRESSION

In the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), the presence of depressed mood or sadness, or loss of pleasure in life, is an important diagnostic criterion for depression. Daily fatigue, lack of energy, insomnia, and hypersomnia are indicators of a depressed mood. The symptoms of depression overlap with those of CFS; for example, some researchers report that 89% of people with depression are fatigued, as compared to 86–100% of people with CFS. The experience of fatigue, however, seems to be more disabling with CFS than with depression. Another difference between CFS and depression concerns the onset of the disorder. Most patients with CFS experience a sudden or acute onset, whereas depression may develop over a period of weeks or months. Also, while both types of patients experience sleep disorders, CFS patients tend to have difficulty falling asleep, whereas depressed patients tend to wake early in the morning.

Some researchers believe that there is a link between depression, fatigue, and exposure to too much REM sleep. There are five distinct phases in human sleep. The first two are characterized by light sleep; the second two by a deep restorative sleep called slow-wave sleep; and the last by rapid eye movement, or REM, sleep. Most dreams occur during REM sleep. Throughout the night, the intervals of REM sleep increase and usually peak around 8:30 a.m. A sleep deprivation treatment for depression involves reducing patients' amount of REM sleep by waking them around 6:00 a.m. Researchers think that some fatigue associated with disease may be a form of mild depression and that reducing the amount of REM sleep will reduce fatigue by moderating depression.

Managing fatigue

The management of fatigue depends in large measure on its causes and the person's experience of it. For example, if fatigue is acute and normal, the person will recover from feeling tired after exertion by resting. In cases of fatigue associated with influenza or other infectious illnesses, the person will feel energy return as they recover from the illness. When fatigue is chronic and abnormal, however, the doctor will tailor a treatment program to the patient's needs. There are a variety of approaches that include:

• Aerobic exercise. Physical activity increases fitness and counteracts depression.
• Hydration (adding water). Water improves muscle turgor, or tension, and helps to carry electrolytes.
• Improving sleep patterns. The patient's sleep may be more restful when its timing and duration are controlled.
• Pharmacotherapy (treatment with medications). The patient may be given various medications to treat physical diseases or mental disorders, to control pain, or to manage sleeping patterns.
• Psychotherapy. There are several different treatment approaches that help patients manage stress, understand the motives that govern their behavior, or change maladaptive ideas and negative thinking patterns.
• Physical therapy. This form of treatment helps patients improve or manage functional impairments or disabilities.

In addition to seeking professional help, people can understand and manage fatigue by joining appropriate self-help groups, reading informative books, seeking information from clearinghouses on the Internet, and visiting websites maintained by national organizations for various diseases.

Resources

BOOKS

Beers, Mark H., and Robert Berkow, eds. The Merck Manual of Diagnosis and Therapy, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

Glaus, A. Fatigue in Patients with Cancer: Analysis and Assessment. Recent Results in Cancer Research, no. 145. Berlin, Germany: Springer-Verlag, 1998.

Hubbard, John R., and Edward A. Workman, eds. Handbook of Stress Medicine: An Organ System Approach. Boca Raton, FL: CRC Press, 1998.

Natelson, Benjamin H. Facing and Fighting Fatigue: A Practical Approach. New Haven, CT: Yale University Press, 1998.

Winningham, Maryl L., and Margaret Barton-Burke, eds. Fatigue in Cancer: A Multidimensional Approach. Sudbury, MA: Jones and Bartlett Publishers, 2000.

PERIODICALS

Natelson, Benjamin H. "Chronic Fatigue Syndrome." JAMA: Journal of the American Medical Association 285, no. 20 (May 23–30 2001): 2557–59.

ORGANIZATIONS

MEDLINEplus Health Information. U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda, MD 20894. (888) 346-3656. <http://www.medlineplus.gov>.

National Chronic Fatigue Syndrome and Fibromyalgia Association. P.O. Box 18426, Kansas City, MO 64133. (816) 313-2000.

Tanja Bekhuis, PhD

Rosalyn Carson-Dewitt, MD

fatigue

Not a simple topic

‘Fatigue is multifactorial’ — it has diverse causes and many components, and expresses itself in varied ways. Even if we postpone discussion of mental fatigue, the purely physical dimensions of the word will prove more flexible than the first-time enquirer probably suspects. A hockey or rugby winger, after sprinting 60 metres, has to stop; but the fatigue experienced is of a palpably different kind from that at the end of a day's hill walking, yet alone a marathon race. Another sprint down the wing is possible within 1–2 minutes; another marathon is not possible that day. We will take these two extremes of sports fatigue, and related experiences, in that order. The entry on skeletal muscle should, however, be read first, and that on exercise may also be helpful.

‘Sprint’ fatigue

Very intensive exercise, such as that involved in sprinting, is powered predominantly by anaerobic metabolism. This form of metabolism produces lactic acid, and it is normally considered to be the acidity of this which stops muscles working. No form of fatigue has a single cause, but very intensive dynamic exercise probably comes nearer to being brought to an end by one mechanism than any other form of activity.

Degrees of acidity are expressed scientifically in terms of ph units, lower values indicating greater acidity. The pH within resting muscle cells is about 7.2. If it falls to around 6.4, which can happen after about a minute of really intensive activity in mammals and humans, the great majority of experiments indicate that both force-generation and further metabolism will be severely inhibited. (The musculature of salmon, after 30 seconds' swimming flat-out up a salmon ladder or striving to jump a weir, has been reported to touch pH 6.0; warm-blooded animals cannot tolerate this value.) Recovery from the major part of the fatigue is almost as rapid as onset. One of the few anomalies in the account is that the recovery of pH within the cells is not as quick. Also the inhibition of force-production by acidity is much more marked in experiments done on isolated muscles at the salmon's body temperature than at our own. So the mechanisms involved may be less direct than has long been thought, but the association between acidity and fatigue remains very strong.

Decline of speed and power

It is never more obvious than towards the end of a burst of sprinting that fatigue consists not only in loss of the force that muscles can produce but in impairment of their shortening speed. Since many actions in life depend not on either force or speed alone, but on power, which involves both, the effect of fatigue is redoubled. Power is the essence of such varied actions as a high jump, a javelin throw, a tennis serve, an axe-stroke, or work with a saw.

Isometric fatigue

Intensive isometric (static) exercise produces no power at all, since it causes no movement. Nevertheless, isometric fatigue has about the same time-scale as that of intense dynamic exercise, and near-complete recovery is also comparably fast. Build-up of acidity is part of the mechanism here, too, but there are other factors. Muscles exerting more than about a third of their maximum static force squeeze the intramuscular blood vessels so hard that they cut off their own blood supply: effectively they operate under a self-imposed tourniquet. This produces a more profound loss of force than sprinting. Our fit hockey winger, if she slowed down by 20–30% after her 60 metre dash, could go on running for many minutes. A maximal isometric contraction falls to half or less in the first minute, and starting at 70–80% maximum force retards the subsequent decline only a little. (Try applying your utmost effort to undoing a recalcitrant jar-top; maintaining it for more than 3–5 seconds is impossible.) Only when force has fallen to 10–15% of the original maximum does a steady state ensue which can be maintained for long periods, because only then has the muscle's self-tourniquet been fully released. Fortunately it is this level of force which muscles involved in posture need to maintain, when a guardsman stands to attention for long periods.

During self-tourniquet, muscles trap within themselves many products of contractile effort in addition to lactic acid. Perhaps the most important other product is potassium. Potassium ions come out of all electrically-active cells, including muscle fibres, in the second half of each electrical impulse (‘action potential’). Outside the muscle cells they probably contribute to fatigue in at least three ways. Firstly, they may lead to failures of impulse transmission down the finer motor nerve branches within the muscle, so fewer muscle fibres receive the instructions to go on contracting. Secondly, by accumulating particularly in the narrow ‘transverse tubules’, which have the function of conveying activation from the surface to the depth of each muscle fibre, they can block propagation of further impulses at that point; consequently the centre of the fibre may cease to produce force, even when the surface is still doing so. Thirdly, by depolarizing sensory nerve endings embedded in the interstitial spaces between muscle fibres, potassium ions are thought to contribute to the pain of sustained contraction, and to a number of other effects such as increased respiration and elevated blood pressure. An organic product of metabolism, adenosine, also probably contributes to the pain, and contrary to a common assumption it is almost certainly more significant in this than lactic acid.

Long-lasting activity

At the end of a day in the hills, or even a marathon race, muscle pH is not significantly lowered; the metabolism has been aerobic not anaerobic, so negligible lactic acid has been produced. The main causes of fatigue in these ‘endurance activities’ appear to be microscopic muscle damage, and simply running out of fuel.

The fuel concerned is glycogen, the animal body's stored carbohydrate. Untrained people have only enough glycogen for perhaps 6–10 km at a racing pace; athletes who are highly trained, and have loaded themselves with carbohydrate food for the last few days before a race, will normally reach the finish with just a little left. Without glycogen one is not immobile, but maximum speed drops severely. The explanation for this hinges on the fact that muscles are composed of different types of fibre. The fastest fibres can utilize only carbohydrate, and many others — perhaps, in human beings, all others — can work faster on carbohydrate than on their alternative fuel, fat. Ultramarathons, channel swims, and other competitive events lasting many hours have traditionally been performed almost entirely on fat. However, technology can alter this situation to some extent, and cyclists on such events as the Tour de France (who can carry drinking bottles easier than runners) take high-carbohydrate drinks throughout the day to ward off total depletion of their carbohydrate stores as long as possible; the drink keeps blood glucose concentration high, and the muscles can use the glucose direct or turn it into glycogen.

As to the micro-damage, this is often marked enough to see in electron micrographs of endurance runners' leg muscles, and might prove even more severe after strenuous climbs. However, a form of damage on a yet smaller scale probably affects the internal activating mechanism of every fibre in a profoundly fatigued muscle. Experimentalists have called this ‘low frequency fatigue’, for it shows as substantially subnormal force when the muscle is artificially stimulated at fairly low frequencies (mimicking gentle voluntary activation). High-frequency stimulation overcomes the shortfall, and voluntary ‘superhuman effort’ has the equivalent effect: presumably high rates of natural or artificial stimulation release, even from a somewhat damaged system, enough of the required agent, calcium ions, to activate the contraction fully.

Intermediate intensities

In running races from 1500 to 10 000 metres and cycling, swimming, or rowing events of similar duration, many of the mechanisms described thus far probably mingle. Lactic acid builds up, but more slowly than in a sprint; glycogen depletion may be significant in some of the fastest fibres, though not generally; calcium release is probably impaired in more than one way; and so on. One additional mechanism, however, may have its greatest importance in activities lasting from a few minutes to half an hour. The key biological energy-molecule, adenosine triphosphate (ATP), is broken down to adenosine diphosphate (ADP), hydrogen ions, and phosphate ions in the process of force-generation and then must be reconstituted by metabolism. Reconstitution seems to lag increasingly behind breakdown as exercise proceeds; significant concentrations of the breakdown products thus build up in intensively working muscle. In the events we are now considering this is especially true of phosphate ions. Hydrogen ions, when not also being released at great rate by the additional mechanism of anaerobic metabolism, are better ‘buffered’. The effects the two ions can have are discussed in the next section.

Action of ATP breakdown products

If two water tanks are linked at the bottom by a pipe, and one starts empty while the other is full, water at first flows into it rapidly; gradually, however, the build-up of water in the receiving tank slows down further flow between them. In rather the same way the build-up of the products of any chemical reaction weakens its forward drive. This is a key mechanism by which both hydrogen ions (acidity) and phosphate ions are generally thought to contribute to muscle fatigue. No doubt ADP would do so too, did not metabolism ensure that ADP concentration never rises far.

Muscle contraction is brought about by the concerted action of submicroscopic structures called ‘cross bridges’. Their power-generating strokes are weakened, and may also be individually slowed, when hydrogen and phosphate ions accumulate. In addition, in the majority of experimental conditions, hydrogen ions inhibit the amount of calcium released from intracellular stores by electrical excitation — which has the consequence that fewer cross-bridges are even active.

Notice that ‘running out of ATP’ does not appear among the mechanisms inducing fatigue. ATP concentrations are maintained quite close to resting value by muscle metabolism; evolution has ensured this, since to let them fall far could be fatal. The fatality would not be due to weakened contractions but to a single over-strong one: not fatigue but ‘rigor mortis’, the rigidity of death, is what sets in when ATP concentrations fall seriously low! So muscle fatigue is not due to an energy crisis in a direct, simple way, though some of the fatigue mechanisms we have discussed could be said to represent energy crises in broader senses.

Systemic fatigue

So far, all the mechanisms discussed have been of ‘muscle fatigue’, but the body can tire of prolonged work in other ways. Fluid loss, notably in sweat, is a major factor. Even 2–3% loss (1–2 litres, according to one's size) impairs performance. Thus sportspeople competing in hotter countries than their own should check themselves each morning for weight loss, which is likely to occur even without their being active. Heat in fact presents a double challenge, for blood is diverted from muscles to skin, so that it may be cooled there by evaporating sweat; when there is less fluid circulating, due to sweating, circulation in both regions is compromised. Furthermore if core temperature rises more than about 3°C, bodily and mental functions are seriously impaired, and heat stroke may set in. Thus the importance of maintaining fluid intake during prolonged activity, even in temperate climates and more so in hot ones, cannot be overstated; and it is unfortunate that thirst is an insufficient guide — in these circumstances we always need more fluid than the thirst mechanism indicates.

At the other extreme, cold is (in a purely arithmetical sense) even more dangerous than heat, for in many people core temperature need only fall 2°C to produce the severe impairments of physical and mental function characterizing hypothermia. This is a thermal risk associated with exercise in exposed conditions, though not due to it, and involving fatigue-like symptoms rather than fatigue itself. Furthermore, the best preventive on land, however wet the conditions, is to maintain activity; so hypothermia in these circumstances becomes not a cause but a consequence of fatigue. (In cold water, however, attempts to swim are counterproductive, for stirred water extracts body heat faster than muscle activity can generate it).

Irrespective of temperature, though more challenged by cold than heat, blood glucose must be maintained. If it is not, the organ that suffers worst is the brain, which can only operate on glucose fuel. About one fifth of the glycogen in a rested body is stored in the liver, not the muscles, and it is from there, as exercise goes on, that it is released into the blood as glucose. When this mechanism fails and blood glucose (‘blood sugar’) falls below about half its resting value, mental functions become seriously impaired.

The heart is a muscle, and both it and the muscles of breathing can in principle be subject to fatigue. When healthy people exercise at ordinary altitudes, however, neither of these categories of muscle fatigues sufficiently to impair the body's performance — though either heart or lung disease can alter this situation profoundly.

Central nervous fatigue

This may be regarded as the physiologist's name for what others would term ‘mental fatigue’; however, it carries the specific implication that a physical mechanism can be identified, which is not (or not yet?) the case in all mental fatigue.

A particularly interesting mechanism has recently been proposed, which would make central nervous fatigue a direct consequence of prolonged muscle activity. Muscles running short of carbohydrate fuel instead take up increased amounts of certain amino acids, notably the branched chain amino acids (BCAA) such as valine. Consequently, after a while, less of these remain in the blood than were present when the exercise began. Now, there is a transport mechanism across the walls of brain capillaries which normally shares out its services between BCAA and other large, uncharged amino acids — the most prominent being tryptophan. As muscle demands continue, less BCAA and instead more tryptophan is taken into the brain. The neurotransmitter substance serotonin (‘5-HT’) is made from tryptophan, so the consequence of the shift in uptake is that more serotonin is synthesized. The crux underlying all this is that increased brain concentrations of serotonin appear to promote the symptoms and sensation of fatigue.

Inverting the direction of brain–muscle interaction, every sports coach knows that psychology has profound effects on the most physical of performances; even shouts of encouragement can be crucial. Fatigue, however, occurs in more situations than those involving muscular effort. Can anything be said about the others? We all know that, when tired, we perform less well at both motor and mental tasks — indeed, the mental ones are often impaired earlier and more severely, so that physical exercise can be a fruitful way of throwing off mental fatigue. That there are physical aspects even to mental fatigue is strongly suggested when we recall that hunger or severe thirst, extremes of cold or heat, oxygen lack, alcohol, and other drugs can all increase fatigue — while drugs with the opposite effect, such as caffeine or amphetamines, can help ward it off. Altered levels of brain transmitters, particularly in regions of the brain stem — increased serotonin and acetylcholine, decreased noradrenaline — have been demonstrated in certain experimental studies of fatigue. But it is probably fair to say that scientific investigation is still only scratching the surface of the problem, as the most universal and ultimately irresistible cause of mental fatigue is lack of sleep. Despite the best efforts of committed researchers, we do not yet really understand sleep. Until we do, there seems little hope of comprehending what happens when we have had too little.

Neil Spurway

Bibliography

Gandevia, S. C. et al. (1996). Fatigue: neural and muscular mechanisms. Plenum, New York.
Newsholme, E. A.,, Blomstrand, E.,, and and Ekblom, B. (1992). Physical and mental fatigue: metabolic mechanisms and importance of plasma amino acids. British Medical Bulletin, 48, 477–95.
Wilmore, J. H. and and Costill, D. L. (2000). Physiology of sport and exercise. 2nd ed. Human Kinetics, Champaign, Illinois.

Fatigue

Definition

Fatigue is physical and/or mental exhaustion that can be triggered by stress, medication, overwork, or mental and physical illness or disease.

Description

Everyone experiences fatigue occasionally. It is the body's way of signaling its need for rest and sleep. But when fatigue becomes a persistent feeling of tiredness or exhaustion that goes beyond normal sleepiness, it is usually a sign that something more serious is amiss.

Physically, fatigue is characterized by a profound lack of energy, feelings of muscle weakness, and slowed movements or central nervous system reactions. Fatigue can also trigger serious mental exhaustion. Persistent fatigue can cause a lack of mental clarity (or feeling of mental "fuzziness"), difficulty concentrating, and in some cases, memory loss.

Causes and symptoms

Fatigue may be the result of one or more environmental causes such as inadequate rest, improper diet, work and home stressors, or poor physical conditioning, or one symptom of a chronic medical condition or disease process in the body. Heart disease, low blood pressure, diabetes, end-stage renal disease, iron-deficiency anemia, narcolepsy, and cancer can cause long-term, ongoing fatigue symptoms. Acute illnesses such as viral and bacterial infections can also trigger temporary feelings of exhaustion. In addition, mental disorders such as depression can also cause fatigue.

A number of medications, including antihistamines, antibiotics, and blood pressure medications, may cause drowsiness as a side-effect. Individuals already suffering from fatigue who are prescribed one of these medications may wish to check with their healthcare provider about alternative treatments.

Extreme fatigue which persists, unabated, for at least six months, is not the result of a diagnosed disease or illness, and is characterized by flu-like symptoms such as swollen lymph nodes, sore throat, and muscle weakness and/or pain may indicate a diagnosis of chronic fatigue syndrome. Chronic fatigue syndrome (sometimes called chronic fatigue immune deficiency syndrome), is a debilitating illness that causes overwhelming exhaustion and a constellation of neurological and immunological symptoms. Between 1.5 and 2 million Americans are estimated to suffer from the disorder.

Diagnosis

Because fatigue is a symptom of a number of different disorders, diseases, and lifestyle choices, diagnosis may be difficult. A thorough examination and patient history by a qualified healthcare provider is the first step in determining the cause of the fatigue. A physician can rule out physical conditions and diseases that feature fatigue as a symptom, and can also determine if prescription drugs, poor dietary habits, work environment, or other external stressors could be triggering the exhaustion. Several diagnostic tests may also be required to rule out common physical causes of exhaustion, such as blood tests to check for iron-deficiency anemia.

Diagnosis of chronic fatigue syndrome is significantly more difficult. Because there is no specific biological marker or conclusive blood test to check for the disorder, healthcare providers must rely on the patient's presentation and severity of symptoms to make a diagnosis. In many cases, individuals with chronic fatigue syndrome go through a battery of invasive diagnostic tests and several years of consultation with medical professionals before receiving a correct diagnosis.

Treatment

Conventional medicine recommends the dietary and lifestyle changes outlined above as a first line of defense against fatigue. Individuals who experience occasional fatigue symptoms may benefit from short term use of caffeine-containing central nervous stimulants, which make people more alert, less drowsy, and improve coordination. However, these should be prescribed with extreme caution, as overuse of the drug can lead to serious sleep disorders, like insomnia.

Another reason to avoid extended use of caffeine is its associated withdrawal symptoms. People who use large amounts of caffeine over long periods build up a tolerance to it. When that happens, they have to use more and more caffeine to get the same effects. Heavy caffeine use can also lead to dependence. If an individual stops using caffeine abruptly, withdrawal symptoms may occur, including headache, fatigue, drowsiness, yawning, irritability, restlessness, vomiting, or runny nose. These symptoms can go on for as long as a week.

Alternative treatment

The treatment of fatigue depends on its direct cause, but there are several commonly prescribed treatments for non-specific fatigue, including dietary and lifestyle changes, the use of essential oils and herbal therapies, deep breathing exercises, traditional Chinese medicine, and color therapy.

Dietary changes

Inadequate or inappropriate nutritional intake can cause fatigue symptoms. To maintain an adequate energy supply and promote overall physical well-being, individuals should eat a balanced diet and observe the following nutritional guidelines:

• Drinking plenty of water. Individuals should try to drink 9 to 12 glasses of water a day. Dehydration can reduce blood volume, which leads to feelings of fatigue.
• Eating iron-rich foods (i.e., liver, raisins, spinach, apricots). Iron enables the blood to transport oxygen throughout the tissues, organs, and muscles, and diminished oxygenation of the blood can result in fatigue.
• Avoiding high-fat meals and snacks. High fat foods take longer to digest, reducing blood flow to the brain, heart, and rest of the body while blood flow is increased to the stomach.
• Eating unrefined carbohydrates and proteins together for sustained energy.
• Balancing proteins. Limiting protein to 15-20 grams per meal and two snacks of 15 grams is recommended, but not getting enough protein adds to fatigue. Pregnant or breastfeeding women should get more protein.
• Getting the recommended daily allowance of B complex vitamins (specifically, pantothenic acid, folic acid, thiamine, and vitamin B₁₂). Deficiencies in these vitamins can trigger fatigue.
• Getting the recommended daily allowance of selenium, riboflavin, and niacin. These are all essential nutritional elements in metabolizing food energy.
• Controlling portions. Individuals should only eat when they're hungry, and stop when they're full. An overstuffed stomach can cause short-term fatigue, and individuals who are overweight are much more likely to regularly experience fatigue symptoms.

Lifestyle changes

Lifestyle factors such as a high-stress job, erratic work hours, lack of social or family support, or erratic sleep patterns can all cause prolonged fatigue. If stress is an issue, a number of relaxation therapies and techniques are available to help alleviate tension, including massage, yoga, aromatherapy, hydrotherapy, progressive relaxation exercises, meditation, and guided imagery. Some individuals may also benefit from individual or family counseling or psychotherapy sessions to work through stress-related fatigue that is a result of family or social issues.

Maintaining healthy sleep patterns is critical to proper rest. Having a set "bedtime" helps to keep sleep on schedule. A calm and restful sleeping environment is also important to healthy sleep. Above all, the bedroom should be quiet and comfortable, away from loud noises and with adequate window treatments to keep sunlight and streetlights out. Removing distractions from the bedroom such as televisions and telephones can also be helpful.

Essential oils

Aromatherapists, hydrotherapists, and other holistic healthcare providers may recommend the use of essential oils of rosemary (Rosmarinus officinalis ), eucalyptus blue gum (Eucalyptus globulus ), peppermint, (Mentha x piperata ), or scots pine oil (Pinus sylvestris ) to stimulate the nervous system and reduce fatigue. These oils can be added to bathwater or massage oil as a topical application. Citrus oils such as lemon, orange, grapefruit, and lime have a similar effect, and can be added to a steam bath or vaporizer for inhalation.

Herbal remedies

Herbal remedies that act as circulatory stimulants can offset the symptoms of fatigue in some individuals. An herbalist may recommend an infusion of ginger (Zingiber officinale ) root or treatment with cayenne (Capsicum annuum ), balmony (Chelone glabra ), damiana (Turnera diffusa ), ginseng (Panax ginseng ), or rosemary (Rosmarinus officinalis ) to treat ongoing fatigue.

An infusion is prepared by mixing the herb with boiling water, steeping it for several minutes, and then removing the herb from the infusion before drinking. A strainer, tea ball, or infuser can be used to immerse loose herb in the boiling water before steeping and separating it. A second method of infusion is to mix the loose herbal preparation with cold water first, bringing the mixture to a boil in a pan or teapot, and then separating the tea from the infusion with a strainer before drinking.

Caffeine-containing central nervous system stimulants such as tea (Camellia senensis ) and cola (Cola nitida ) can provide temporary, short-term relief of fatigue symptoms. However, long-term use of caffeine can cause restlessness, irritability, and other unwanted side effects, and in some cases may actually work to increase fatigue after the stimulating effects of the caffeine wear off. To avoid these problems, caffeine intake should be limited to 300 mg or less a day (the equivalent of 4-8 cups of brewed, hot tea).

Traditional Chinese medicine

Chinese medicine regards fatigue as a blockage or misalignment of qi, or energy flow, inside the human body. The practitioner of Chinese medicine chooses acupuncture and/or herbal therapy to rebalance the entire system. The Chinese formula Minot Bupleurum soup (or Xiao Chia Hu Tang) has been used for nearly 2,000 years for the type of chronic fatigue that comes after the flu. In this condition, the person has low-grade fever, nausea, and fatigue. There are other formulas that are helpful in other cases. Acupuncture involves the placement of a series of thin needles into the skin at targeted locations on the body known as acupoints in order to harmonize the energy flow within the human body.

Deep breathing exercises

Individuals under stress often experience fast, shallow breathing. This type of breathing, known as chest breathing, can lead to shortness of breath, increased muscle tension, inadequate oxygenation of blood, and fatigue. Breathing exercises can both improve respiratory function and relieve stress and fatigue.

Deep breathing exercises are best performed while laying flat on the back on a hard surface, usually the floor. The knees are bent, and the body (particularly the mouth, nose, and face) is relaxed. One hand should be placed on the chest and one on the abdomen to monitor breathing technique. With proper breathing techniques, the abdomen will rise further than the chest. The individual takes a series of long, deep breaths through the nose, attempting to raise the abdomen instead of the chest. Air is exhaled through the relaxed mouth. Deep breathing can be continued for up to 20 minutes. After the exercise is complete, the individual checks again for body tension and relaxation. Once deep breathing techniques have been mastered, an individual can use deep breathing at any time or place as a quick method of relieving tension and preventing fatigue.

Color therapy

Color therapy, also known as chromatherapy, is based on the premise that certain colors are infused with healing energies. The therapy uses the seven colors of the rainbow to promote balance and healing in the mind and body. Red promotes energy, empowerment, and stimulation. Physically, it is thought to improve circulation and stimulate red blood cell production. Red is associated with the seventh chakra, located at the root; or base of spine. In yoga, the chakras are specific spiritual energy centers of the body.

Therapeutic color can be administered in a number of ways. Practitioners of Ayurvedic, or traditional Indian medicine, wrap their patients in colored cloth chosen for its therapeutic hue. Individuals suffering from fatigue would be wrapped in reds and oranges chosen for their uplifting and energizing properties. Patients may also be bathed in light from a color filtered light source to enhance the healing effects of the treatment.

Individuals may also be treated with color-infused water. This is achieved by placing translucent red colored paper or colored plastic wrap over and around a glass of water and placing the glass in direct sunlight so the water can soak up the healing properties and vibrations of the color. Environmental color sources may also be used to promote feelings of stimulation and energy. Red wall and window treatments, furniture, clothing, and even food may be recommended for their energizing healing properties.

Color therapy can be used in conjunction with both hydrotherapy and aromatherapy to heighten the therapeutic effect. Spas and holistic healthcare providers may recommend red color baths or soaks, which combine the benefits of a warm or hot water soak with energizing essential oils and the fatigue-fighting effects of bright red hues used in color therapy.

Prognosis

Fatigue related to a chronic disease or condition may last indefinitely, but can be alleviated to a degree through some of the treatment options outlined here. Exhaustion that can be linked to environmental stressors is usually easily alleviated when those stressors are dealt with properly.

There is no known cure for chronic fatigue syndrome, but steps can be taken to lessen symptoms and improve quality of life for these individuals while researchers continue to seek a cure.

Prevention

Many of the treatments outlined above are also recommended to prevent the onset of fatigue. Getting adequate rest and maintaining a consistent bedtime schedule are the most effective ways to combat fatigue. A balanced diet and moderate exercise program are also important to maintaining a consistent energy level.

Resources

BOOKS

Davis, Martha, et al. The Relaxation & Stress Reduction Workbook. 4th ed. Oakland, CA: New Harbinger Publications, Inc., 1995.

Hoffman, David. The Complete Illustrated Herbal. New York: Barnes & Noble Books, 1999.

KEY TERMS

Aromatherapy— The therapeutic use of plantderived, aromatic essential oils to promote physical and psychological well-being.

Guided imagery— The use of relaxation and mental visualization to improve mood and/or physical well-being.

Hydrotherapy— Hydrotherapy, or water therapy, is use of water (hot, cold, steam, or ice) to relieve discomfort and promote physical well-being.