mitochondria | medical plaintalk

Imagine the way you felt the last time you had the flu. You were flattened, devoid of all energy. Staying upright to get dressed was more than you could handle. You slept – and slept – and slept – and still experienced none of the normal refreshment that a good night’s sleep provides. A fog descended on your mind and fuzzed up memory, destroyed drive and made your head ache. You could not concentrate on simple mental tasks like reading. Though you were doing nothing physical, your muscles ached. Then it all went away and you forgot about it.

But now imagine that it didn’t go away. The same misery persists and dramatically alters your life. You cannot work. You move from bed to couch and back to bed. You go to doctor after doctor and they find nothing wrong. Routine blood tests, X-ray and scan results are normal. Someone prescribes an antidepressant, confirming the suspicions of family, friends, and some doctors that your debilitating physical symptoms are “all in your head.” Eventually, you find your way to a doctor who makes a diagnosis. You have CFS which stands for chronic fatigue syndrome, and which, as of early 2015, has been renamed system exertion intolerance disease or, in our acronym-laden age, CFS/SEID.

A long history, with different names

CFS/SEID has probably been around for more than 200 years, making its appearance in the medical literature as “neurasthenia,” a term applied to patients who were lacking in physical, emotional and cognitive energy without any discernible disease to account for their malaise, without any improvement over time and without any progression that brought them to a worsened state. They were mostly ladies, whose frail constitutions prevented them from exerting themselves and who mysteriously took to their beds for weeks at a time.

The Yuppie flu

British doctors in the 1950s christened the symptom complex myalgic (painful muscles) encephalitis (inflammation of the brain), even though there was no evidence for inflammation to account for the headaches, difficulty concentrating and memory problems patients experienced. In the US in the 1980s, the syndrome was dubbed the Yuppie Flu because it seemed to follow viral infections like infectious mononucleosis and occurred in cities where young urban professionals (“yuppies”) congregated. When reported from other settings as well, the name was changed to chronic fatigue syndrome.

No apparent cause, but a real illness

Because no single infectious, hormonal or immunologic cause for CFS emerged from many attempts to identify its cause, because it was impossible to measure the subjective complaints constituting the syndrome, and because some improvements occurred when antidepressants were prescribed, CFS was, for decades, viewed as a psychological disorder. But this view became more and more untenable as it became clear that the illness hit people who had no history of depression or inability to cope with life. Many CFS patients continued to be very productive, learning how to manage their lives within the limitations of their fatigue and mental fog. Laura Hillenbrand, author of Seabiscuit and Unbroken is one outstanding example. Though no cause has yet been identified for the illness, the name change from chronic fatigue syndrome to systemic exertion intolerance disease signals that the illness is one rooted not in psychology but in an, as yet, unidentified physical cause.

Epidemiology and diagnostic criteria

It is estimated that there are about 1 million patients with CFS/ SEID in the US at any given time. There is no evidence that its incidence is increasing, but it is quite possible that some cases are hidden on among the legions of people who have been diagnosed only with depression. CFS/SEID is more common in women than in men. Sometimes it follows directly upon an acute flu-like illness, but at other times appears out of nowhere. The diagnostic criteria at this time include 6 months of unexplained, life-altering fatigue and orthostatic intolerance, which means the inability to stand for more than very short periods. Four of eight other symptoms are also required and these include disturbances in memory and concentration, persistent sore throat, tender lymph nodes, muscle pain, joint pain, headache, disturbed sleep patterns, and malaise following even minimal exertion. Additional symptoms may include increased sensitivity to tastes, odors, temperature and noise.

A relapsing illness

A small minority of CFS/SEID patients get completely better and never suffer a relapse. The majority suffer relapses for prolonged periods of time, perhaps the rest of their lives. Relapses are triggered by infections, surgery, temperature extremes and stressful events. Another minority are severely affected from the beginning of their illness and require support in the activities of daily living for the rest of their lives. Deterioration, though, is unusual and suggests the diagnosis of CFS is wrong and further attempts to find the correct diagnosis are indicated.

Problems in mitochondrial energy production?

While there is no identifiable single cause for CFS/SEID, poor energy production seems to be at the root of the many symptoms in this illness, which has focused some researchers’ attention on mitochondria – the powerhouses of all cells in the body. Mitochondria must continuously recycle the molecules they use to produce energy and there is some indication that this process is impaired in people with CFS/SEID. Perhaps this is why experience has taught many CFS/SEID patients to pace their lives, always allowing significant time for recovery from exertion.

Boosting energy production

In addition to pacing life to allow recovery time, lifestyle alterations that seem to help CFS/SEID patients minimize relapses also happen to be useful in maximizing mitochondrial function. These include avoidance of drugs and environmental toxins, avoidance of processed foods with high carbohydrate and sugar concentrations, addition of whole foods containing plenty of antioxidants and high quality protein, correction of hormonal problems, especially of the thyroid gland, and decreasing chronic inflammation associated with obesity and allergies. Gradual and graded programs of exercise, outdoors with some sun exposure help prevent the loss of muscle associated with inactivity and improve Vitamin D levels, with positive effects on immune function. Continued research will most likely show that CFS/SEID has many causes, all of which result in impaired mitochondrial function.

As Supreme Court Justice Potter Stewart famously said, when confronted with a decision about what constituted pornography, the definition is hard, but “I know what it is when I see it.” An all-encompassing definition of fatigue is similarly difficult, but everyone knows what fatigue feels like. The profound lassitude that signals an oncoming flu is a gluey, mesmerizing state of mind and body that renders one incapable of remembering ever feeling good, of imagining ever feeling energetic again, or of conceiving of a desire to participate in any physical, social or mental activity beyond crawling beneath the bedcovers.

The perception of energy failure

Where there is life, there is fatigue. All plants and animals run on energy produced in little chemical factories (mitochondria) in every cell. The ultimate source of biologic energy is the sun’s nuclear energy, converted to usable form by plants and transferred to animals as food. The more complex the living thing, the more obvious the need for periods of rest and recovery to replenish energy. When the demand energy use outpaces the time needed for recovery, or when normal function is derailed by illness, drugs or toxins, fatigue is the name we give to what we feel, mentally and physically. To the research scientist, fatigue is a by-product of numerous little proteins (cytokines) produced by the immune system to protect us from outside invaders and internal disorders like cancer. How these proteins create the feeling of fatigue is a mystery, but there is admirable logic in a system that commandeers a patient’s energy, drive and ambition and sends him packing off to bed while an internal battle rages.

Voluntary fatigue

Less admirable is our ability to override the biology that produces tiredness, and to become passive, cranky and sleep-deprived. In fact, most complaints of fatigue reflect the deliberate choice to ignore the symptom and would and yield to simple lifestyle changes – if one were willing and able to sleep more, lose weight, eat regular, well-balanced meals, exercise enough, manage time wisely, avoid smoking, excess alcohol, and junk food, and engage in satisfying work. In our culture these are tall orders, and a background level of fatigue is often accepted as normal.

Evaluation of fatigue

New, unexpected and persistent tiredness, however, may signal underlying illness or environmental stress and warrants a serious evaluation, with clear communication about exactly what fatigue means to the patient. First, a description of the patient’s normal “background energy” is important. Some people are full of energy from the day they are born. Others are inveterate couch potatoes, happy to sit and watch life go by. The feeling of fatigue that prompts one to see a doctor is, by definition, different from the patient’s normal state, but the doctor sees only a snapshot in time. Patients and families should never be shy about volunteering information about what life used to be like.

Defining the symptom

Next, the language used by patients to describe fatigue needs to be clear. “I’m tired” sometimes means “I’m weak,” and “I’m weak” sometimes means “I’m tired,” but in the jargon of medicine, weakness means loss of muscle strength. Provided that they exert full effort, tired people can generate normal muscle power upon request, but people with strokes or nerve and muscle diseases cannot. Separating weakness from fatigue is the doctor’s first job – otherwise he may head off on the wrong diagnostic road. Description of the activities affected by tiredness and/or weakness, and characterization of changes fatigue brings to daily life are crucial to the process of diagnosis.

Finding the source

Once a doctor understands the way fatigue affects life for a patient, he moves on to a “review of systems” – a top to bottom list of questions ranging over all the body’s organs, looking for clues to the presence of heart, kidney or liver disease, diabetes, cancer, sleep apnea, restless leg syndrome, insomnia, degenerative neurologic diseases like Parkinson’s, autoimmune illnesses like lupus or MS, chronic infections, eating disorders and problems of the thyroid, adrenal and pituitary glands. A good doctor will then delve into the lifestyle and life events surrounding the appearance of fatigue. Tiredness is a complex, high level symptom that may also originate in the mind – it is one of the cardinal symptoms of depression.

Is it the drugs

Next comes a careful inventory of all medicines in use, prescription and non-prescription. New fatigue symptoms may parallel the addition of new drugs (even antibiotics can cause fatigue). An inventory of potential toxins and hazards in the environment may turn up a faulty furnace producing carbon monoxide or exposure to toxins such as volatile hydrocarbons that can damage the part of the brain called the cerebellum – a major player in energy balance.

Following the clues

Following a good, inquisitive medical history, a complete physical exam (the kind that requires undressing) may turn up other clues that suggest the need for more than “routine” tests. Fatigue is messenger bringing information about conditions ranging from minor to mortal. When not readily explained, fatigue warrants the best of our medical tools to ferret out the source of trouble. The first step though, is still a careful history and physical examination. Without these, advanced medical technological evaluation of fatigue is little better than a fishing expedition sent to sea with no information about where the fish hang out.

The Chronic Fatigue Syndrome

Definition:

Profound, life-altering fatigue lasting more than 6 months.

May follow a viral infection, but no test abnormalities persist along with the fatigue.

Physical and mental activities both worsen symptoms.

Variety of accompanying symptoms: weakness, muscle and skeletal aches and pains, impaired memory, lack of drive, poor sleep.

Diagnosis:

No specific tests, other than exclusion of other illnesses that produce these symptoms, among others. CFS is a “diagnosis of exclusion.”

Conditions to be excluded:

Chronic infections, mononucleosis, autoimmune disorders (lupus, M.S.), hypothyroidism, low adrenal function, sleep apnea, cancer (particularly pancreatic), obesity, eating disorders, drug and alcohol abuse, major psychiatric disturbances: schizophrenia, depression.

Posted by medical plaintalk

Posted by medical plaintalk