In Grant’s case, Dr. Pischel determined that one reason she felt fatigued was anemia of inflammation, formerly called anemia of chronic disease. This type of anemia occurs when chronic illnesses cause a drop in the longevity of red blood cells. Her hematocrit, a measure of the number and size of red blood cells, is 30 (normal is between 36 and 44). With too few or too-small blood cells, her body has too little iron. And too little iron means less energy, because iron is what holds onto oxygen in the red blood cells, and oxygen is vital for energy production.

“Because Grant’s hematocrit is 20 percent lower than normal, her body has to work an extra 20 percent harder whenever she moves,” says Dr. Pischel. When performing normal daily physical activities, the muscles are taxed closer to their maximum capacity – similar to a healthy person working out intensely. Overtaxed muscles result in fatigue after even a short burst of activity.

Loss of Muscle Mass

The loss of muscle tissue means the loss of cells that produce energy. More than half of people with severe RA, according to one study, are affected by a condition called cachexia, in which muscle mass decreases and fatigue increases. Cachexia is linked with overactive immune system cytokines; in fact, tumor necrosis factor-alpha – the cytokine targeted by the biologic medications adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade) – is sometimes called ‘cachectin’ because of its connection with cachexia.

Looking Deeper

What happens when major issues have been sorted through but the source of fatigue cannot be pinpointed? Doctors may order a series of lab tests that can provide clues or uncover an as-yet-undiagnosed condition.

White blood cell (WBC) count. A high level of WBCs, which are the immune system cells that fight bacteria and viruses, usually indicates an underlying infection that may be causing the body to use extra energy in attempts to fight off bacteria or a virus.

The Chem-20 panel. This standard blood test of 20 chemicals measures electrolytes like calcium, potassium and sodium, which help cells produce energy. Abnormal levels of the proteins, enzymes or chemicals, including glucose or carbon dioxide, may indicate problems with metabolism, the liver or kidneys, or it may indicate other chronic conditions, like hypoglycemia, which may reduce energy levels.

Thyroid-stimulating hormone (TSH) test. A TSH level that is too high indicates the pituitary gland is working overtime in an attempt to get the thyroid to pump out enough of the hormones that keep metabolism and energy production at a normal level. If the thyroid gland is not producing enough, the condition is called hypothyroidism. Fatigue is a major symptom of hypothyroidism, sometimes an autoimmune disease in its own right, which occurs at a higher frequency among people with autoimmune diseases like RA.