1. Fatigue is one of the least understood symptoms of cancer treatment,
and we still don’t know exactly what causes it. The specific
physiological/biological factors underlying persistent cancer related
fatigue are unclear, and there appear to be a number of other factors
which contribute to and maintain fatigue including behaviour,
thinking, emotion and the environment.

2. Biological factors:
There is some evidence for
biological factors to fatigue.
Changes in the way the
nerves function may
contribute to fatigue as well
as auto-immune factors such
as cytokine production.
Cancer and cancer treatments, treatment side-effects and
comorbidities can result in a variety of biochemical and
physiological changes that have been linked to fatigue (e.g.
thyroid and cardiac dysfunction, vomiting, nausea,
diarrhoea, weight loss, pain and psychological distress)
Fatigue may be linked to dysregulation of neuroimmune,
and endocrine systems. These include the hypothalamic-
pituitary (HPA) axis, circadian rhythms, vagal afferent nerve
activation and neuroimmune system transmitter secretion
and function.
The way your immune system functions may also
contribute to fatigue. Cytokines are cells produced by the
immune system in times of an actute infection. They are
very important in the fight against infection but they cause
fatigue in doing so. Cancer treatment and stress are also
linked to cytokine production.

3. Behaviour:
It is difficult to cope with unexpected,
prolonged and/or severe fatigue.
Alternatively they may push
themselves to do as much as
possible when they can and rest
more when symptoms get worse
(what we call all-or-nothing
behaviour).
People who suffer from prolonged
and/or severe fatigue often try to
manage it by either resting more
and avoiding or reducing activity in
the hope of feeling better and to
prevent the fatigue from getting
worse.
These are natural, understandable
attempts to manage the fatigue, and
sometimes seem to be the only possible
course of action.
However, such behaviours and its
consequences can accidentally maintain
the vicious cycle of symptoms and
disability.

4. Behaviour
Consequences of too much rest.
Faced with prolonged, severe fatigue and pain, a
natural response is to rest more, and significantly cut
back or modify activity levels. Rest is a very effective
way of reducing tiredness and bringing symptom
relief in the short term, but in the long term it may
be less helpful.
Rest reduces exercise tolerance and muscle
strength. It can produce increased weakness, muscle
wasting, cardiac and respiratory difficulties, and
increased sensitivity to activity. This means that
increased symptoms of pain and fatigue will occur at
progressively lower levels of activity.
Therefore, while rest may seem helpful initially, its
negative consequences will become increasingly
apparent whenever activity is next attempted. These
include an immediate or delayed increase in
symptoms which worsen with continued activity.
Not surprisingly, one may become sensitised by
repeated experiences of exhaustion, pain and failure,
and wish to avoid, reduce or control such
experiences. As a result, increases in symptoms are
often interpreted as a signal to cut back on activity,
and life can become progressively more restricted as
prolonged rest seems to be the only way to prevent
symptoms from worsening.
Consequences of all-or-nothing behaviour.
Many people try to control and manage
their symptoms by trying to fight through
and ignore the fatigue: of necessity, such
attempts are usually short-lived, as people
are left feeling even more exhausted and
unwell.
Since neither excessive rest nor activity
seem to help, patients learn to cope with
their symptoms by doing as much as
possible when they can (often over-tiring
themselves in the process), and resting
more when the symptoms get worse.
Alternating between over activity on a
good day and under-activity on a bad day
may prevent extremes of disability, but
often results in fatigue and disability
plateauing rather than improving.
Since any activity undertaken is "paid for
later", this can be as demoralising and
restricting in its own way as complete rest.

5. Thinking:
Another factor which may impact on
fatigue is the way people think about
their illness and themselves. For
example, someone might continually
think they will never cope with their
symptoms. It is easy for a chronic
illness to get on top of us, and it can
bring on unhelpful ideas and thoughts
which in turn can influence the way
we make sense of our symptoms. Unhelpful ideas can also contribute to
lower mood or anxiety, and lead to less
helpful behaviour. Unhelpful thoughts
can trap us in a vicious cycle where the
more fatigued we become the more
unhelpful thoughts we might have, the
more we believe them and the more
tired we might become.

6. Emotion:
The emotional consequences of cancer can be severe, and should not be
under-estimated. Depression, fear/anxiety, and embarrassment/shame can
perpetuate fatigue, and are common in most chronic illnesses.
These emotional reactions can have an impact on symptoms itself. Most
negative mood states produce physiological changes such as increased fatigue
and muscle pain, impaired memory and concentration, and reduced activity
and motivation. The condition and symptoms can be complicated.
People may worry that symptoms are a warning sign of a recurrence; or that
continued or repeated activity may be harmful. All of this can leave individuals
feeling helpless and uncertain.
Given the often unpredictable nature of chronic illness, anxiety about coping
and performance of certain activities or achievement of goals are also
common. As with depression, the specific symptoms of these mood states can
overlay and intensify the symptoms of fatigue, and affect how you cope with
it: depression and demoralisation will make you more likely to reduce activity
while frustration is more likely to propel you into doing too much too quickly.
Embarrassment and shame has been found to be linked with fatigue, and can
cause people to socially withdraw, reduce activity and may contribute to
lowered mood.

7. Environment A person’s experience of cancer and fatigue is likely to
also be influenced by environmental factors such as
stress and reactions from those around them.
Stress can have an effect on fatigue. Controllable
stressors such as your work environment can be dealt
with or changed in some way. Uncontrollable stressors,
such as how your illness might progress, are more
difficult to manage and trying too hard to do so can lead
to increased fatigue.
Another environmental factor which could impact on
fatigue is the advice and reactions from others.
Considerable distress can be caused by unhelpful or
inappropriate reactions from others; particularly those
who do not understand, do not take the fatigue seriously,
or are over solicitous. The support of family, friends,
doctors and colleagues is invaluable. However, it can
sometimes be difficult for others to understand what is
wrong, especially when there are few directly observable
signs of illness, or if they see a person on a "good" day
(“You’re looking well!”).
Social attitudes to any chronic illness can be ambivalent,
geared towards seeing illness as being either
physical/real or psychological/"all in the mind". This is an
artificial and unhelpful divide, since all illnesses involve a
mixture of physical and psychological factors. People may
have had some negative reactions from others and this
can significantly add to emotional distress and may have
an impact on fatigue.