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duced output of work (work decrement) or a lack of endurance; and (3) a subjective feeling of tiredness and discomfort As to the biochemical and physiologic changes, continuous muscular work leads to depletion of muscle adenosine triphosphate (ATP), the supply of which is derived from creatine phosphate via phosphorylation of adenosine diphosphate (ADP) With continued and more intense exercise, a further supply of ATP becomes available as a result of the anaerobic breakdown of glycogen When all the muscle glycogen has been consumed, exercise at a maximal level cannot be continued However, mild to moderate exercise is still possible, since fatty acids provide an increasing share of muscle fuel Gradually there is an accumulation of lactic acid and other metabolites, which in themselves reduce the power of muscular contraction and delay the recovery of muscle strength Even in normal persons, extreme degrees of muscular effort, in which activity exceeds the provision of substrates, may result in necrosis of bers and a rise in serum concentrations of creatine kinase (CK) (this effect is much more evident in individuals with one of the hereditary metabolic diseases of muscle described in Chap 51) The decreased productivity and capacity for work, which is a direct consequence of fatigue, has been investigated by industrial psychologists Their ndings clearly demonstrate the importance of motivational factors on work output, whether the work be of physical or mental type More striking are individual constitutional differences in energy, which vary greatly, just as do differences in physique, intelligence, and temperament It should be emphasized that in the majority of persons complaining of fatigue, one does not nd true muscle weakness This may be dif cult to prove, for many such individuals are disinclined to exert full effort in tests of peak power of muscle contraction or in endurance of muscular activity A disinclination to make an effort is also an essential characteristic of the fatigued mind.

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Patients experiencing lassitude and fatigue have a more or less characteristic way of expressing their symptoms They say that they are burned out, all done in, tired all the time, weary, exhausted, or pooped out or that they have no pep, no ambition, or no interest They manifest their condition by showing an indifference to the tasks at hand, by talking much about how hard they are working and how stressed they are by circumstances; they are inclined to sit around or lie down or to occupy themselves with trivial tasks On closer analysis, one observes that many such patients have dif culty in initiating activity and also in sustaining it ie, their endurance is diminished This condition, of course, is the familiar aftermath of sleeplessness or prolonged mental or physical effort, and under such circumstances it is accepted as a normal physiologic reaction When, however, similar symptoms 433

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Fatigue has both explicit and implicit effects, grouped under (1) a series of biochemical and physiologic changes in muscles and a reduced capacity to generate force manifest as weakness, or asthenia; (2) an overt disorder in behavior, taking the form of a re-

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appear without relation to such antecedents, they should be suspected of being the manifestations of disease The physician s task is initially to determine whether the patient is merely suffering from the physical and mental effects of overwork without realizing it Overworked, overwrought people are observable everywhere in our society Their actions are both instructive and pitiful Their behavior in this regard is said to be irrational in that they will not listen to reason; they seem to be impelled by certain notions of duty and refuse to think of themselves In addition to fatigue, such persons frequently show irritability, restlessness, sleeplessness, and anxiety, sometimes to the point of panic attacks and a variety of somatic symptoms, particularly abdominal, thoracic, and cranial discomforts Formerly, society accepted this state in responsible individuals and prescribed the obvious cure a vacation Even Charcot made time for regular cures during the year, in which he retired to a spa without family, colleagues, or the drain of work Nowadays, the need to contain this type of stress, to which some individuals are more prone than others, has spawned a small industry of meditation, yoga, and similar therapies Individuals with strong hobbies and athletic interests seem to be less subject to this problem A common error in diagnosis, however, is to ascribe fatigue to overwork when actually it is a manifestation of a neurosis or depression, as described below

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tendency is to improve as the day wears on, and they may even feel fairly normal by evening It may be dif cult to decide whether the fatigue is a primary manifestation of the disease or secondary to a lack of interest Among chronically fatigued individuals without medical disease, not all deviate enough from normal to justify the diagnosis of neurosis or depression Many persons, because of circumstances beyond their control, have little or no purpose in life and much idle time They are bored with the monotony of their routine Such circumstances are conducive to fatigue, just as the opposite, a strong emotion or a new enterprise that excites optimism and enthusiasm, will dispel fatigue As mentioned, one must be aware of striking individual differences in energy potential Some persons are born low in impulse and energy and become more so at times of stress; they have a lifelong inability to play games vigorously, to compete successfully, to work hard without exhaustion, to withstand illness or recover quickly from it, or to assume a dominant role in a social group a constitutional asthenia (Kahn)

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