Fatigue is one of the most common disease symptoms and drug side effects. What is it? Why can we not treat it?
Excluding cases where the cause is clear, such as poor nutrition, sleep disorders and anemia, what is happening in the huge range of pathologies from autoimmune fatigue, chronic fatigue syndrome, endocrine disorders, etc?
Is it happening on the cellular level or is it do with the chemistry of the brain? Apart from stimulants are there any leads on drugs to target it?
Fatigue in chronic illnesses is extremely common and very poorly understood. In my field of inflammatory bowel diseases many patient complain about fatigue, it is however difficult to measure in routine clinical practice. While it is generally though to be asociated with inflammatory burden in IBD, patients in clinical remission also report fatigue.
but it would be interesting to see how many completely health individuals complain about fatigue too. We could certainly do with more high quality research on fatigue in chronic inflammatory disorders.
Fatigue defined as “a biological drive for recuperative rest”,[7] can be determined by a number of factors, such as circadian and homeostatic effects (e.g., time of day, time awake, and periods of rest and sleep).
7. Williamson A, Lombardi DA, Folkard S, Stutts J, Courtney TK, Connor JK. The link between fatigue and safety. Accid Anal Prev. 2011;34:498–515.
Thanks everyone. David, that definition sounds like tiredness within the normal parameters. I was wondering about pathological fatigue.
Is fatigue real? Is the body incapable of exerting energy or is it a message that the mind signals for the body to shut down?
Hi Juliet,
Fatigue is a multidimensional and subjective concept. It covers both physiological and psychological aspects. Physiological aspects consider fatigue as a bodily phenomenon which has contribution to the perception of fatigue. It is defined as a loss of voluntary force producing capacity during exercise. This can be due to both central and peripheral ( i.e. the muscle tissue) mechanisms. During peripheral fatigue, the accumulation of lactate and extracellular potassium, together with a lowering of pH, affects membrane excitability.
As you mentioned, fatigue (as a chronic syndrome) is a sign
of a number of somatic disorders including MS, Parkinson. But, there
is a group of severely fatigued patients that do not have any
somatic disorders. I think (this is my own idea) that these are related to psychological states of patients or psychological fatigue. There are some ways to quantify psychological fatigue like AFQ or CIS, but I don't have any information about the underlying mechanisms. So, very pleased to know any new information about this issue. Actually this is one of my concerns as well.
Bests,
Fatigue is as dangerous in normal populations as it is among patients.Driver fatigue kills more than drink-driving. As little as 17 hours of continuous wakefulness causes as much performance decline as blood alcohol concentration of .05 (legal limit in most countries). 22 hours continuous wakefulness doubles that damage to the equivalent of .10 blood alcohol. This doesn't make fatigue any easier to capture in research on healthy subjects. Here is my take: as fatigue is manifested in performance decline, feelings of exhaustion and phyiological resource depletion, it is best assessed with multiple measures of behaviour, cognitive appraisals and physiological responses. We routinely employ multi-level assessment that includes self-report (Karolinska Sleepiness Scale; Borg's Perceived Exertion), task performance (PVT, Procedural RT, Go/NoGo tasks), behavioural (e.g., actigraphy) and physiological data (e.g., EEG, eye-blink velocity and heart rate variability). Analysing real-time dynamics becomes a challenge and takes us into time series, autocorrelations and fractals territory. But it seems worth it.
With respect to the underlying fatigue common in many chronic diseases–one of the causes appears to be elevated circulating interleukin-6 or soluble IL-6 receptor. The fatiguing effects of increased IL-6 have been shown in athletes (http://www.ncbi.nlm.nih.gov/pubmed/15317982) and elevated levels are associated with most inflammatory-based illnesses that present with fatigue. Cytokine-blockers are currently being developed (Chugai Pharmacueticals) that block/reduce the sensations of fatigue. The fatigue has been termed 'cytokine sickness'. Have a look at http://www.ncbi.nlm.nih.gov/pubmed/12895132.
In addition to the increase of lactic acid and the reduction of muscular glycogen, the MAIN cause of muscular fatigue is the change of ph in the microenvironment. If we measured the ph level inside the muscle cells, where the myosin head interacts with the actin filament, we would note a physiological ph level. But when the exercise is extreme, that is when too many times the ATP has been hydrolyzed, H+ ions increases and the ph level may low from 7 to 4. Because the myosin head has an optimal conformation at ph 7-7.2, ph 4 levels brakes the contractile event, because each enzyme needs for an optimal ph to act. This is a transitory condition, but it’s sufficient to prevent the exercise continuation.
I have a lot of experience in metabolism, especially lipid metabolism, but I have not worked directly in the field of CFS. My interest in CFS arises because a neighbor suffers from it.
That said, one aspect of CFS biology that is attracting research interest is mitochondrial dysfunction. As with many aspects of CFS, there is, as yet, no consensus on the role of mitochondria, but this 2009 article appears reasonably balanced and thought provoking. It is published in a new journal and I do not know the authors, but your question suggests you'd find it interesting.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680051/
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