METABOLISM AND ENDOCRINE SYSTEM ALTERATIONS Daily human energy needs include basal

metabolic activity, thermogenesis of food, and the need for ADL and locomotion. It is unclear whether
basal metabolism changes during bed rest; this uncertainty stems from inadequate scientific studies on
control of factors that could influence the basal metabolic rate during prolonged bed rest. Lean body
mass decreases during bed rest, and an equal gain in body fat maintains constant body weight (137).
The reduced lean body mass is associated with decreased metabolic activity of muscle, diminished
utilization of oxygen and glucose, increased insulin resistance, and deteriorated musculoskeletal
function directly affecting overall metabolic, endocrine, and immune system functions (138). Electrolyte
Balance Prolonged immobility, especially if associated with posttraumatic electrolyte changes, will alter
balance of sodium, sulfur, phosphorus, and potassium. A decrease in total body sodium occurs in
tandem with the diuresis seen early during bed rest. However, serum sodium levels do not correlate
well with the severity of orthostatic intolerance described earlier. Hyponatremia in the elderly is
manifested by lethargy, confusion and disorientation, anorexia, and seizures. Potassium levels
progressively decrease during the early weeks of bed rest (136). Immobility alone rarely causes serious
electrolyte disturbances, aside from the high calcium levels seen in immobilization hypercalcemia (83).
Nevertheless, patients with multiple medical illnesses may be seriously affected by even slight
electrolyte abnormalities that are caused by immobility. CHAPTER 48 | PHYSICAL INACTIVITY:
PHYSIOLOGICAL AND FUNCTIONAL IMPAIRMENTS AND THEIR TREATMENT 1267 Hormonal Disorders A
lack of physical activity can cause altered responsiveness of hormones and enzymes. Although they may
be clinically undetected during early immobility, numerous changes have been demonstrated to occur in
the endocrine system. Significant carbohydrate intolerance has been noted as early as the third day of
immobility, and peripheral glucose uptake may decline 50% after 14 days (138). The duration of
immobility correlates proportionally with the degree of carbohydrate intolerance. The glucose
intolerance induced by bed rest can be improved by isotonic, but not isometric, exercises of the large
muscle groups (139). The reason for this intolerance is not lack of insulin but rather increased resistance
to the action of insulin, resulting in hyperglycemia and hyperinsulinemia. Possible explanations include a
reduction in number or affinity of insulin receptors or postreceptor changes in the target cells. Inactivity
appears to cause a reduction in insulin-binding sites, predominantly on the muscle membrane (140).
There are several other hormonal effects, including an increase in serum parathyroid hormone, which is
related to hypercalcemia from immobility, although its precise mechanism is unknown (141).
Triiodothyronine (T3) blood levels are also elevated during immobility (142). In addition, a variety of
alterations have been reported in androgen levels and spermatogenesis, in growth hormone response to
hypoglycemia, in levels of adrenocorticotropic hormone, and in catecholamine secretion from the
sympathomedullary system (143,144). Serum corticosteroid levels during bed rest are increased,
accompanied with increased excretion of urinary cortisol. Studies on bed rest for periods of 1 month or
more have found that adrenocorticotropic hormone levels were three times higher than baseline and
required about 20 days of physical activity of returning to normal (144). By contrast, prolonged exercise
has been shown to increase plasma hydrocortisone levels and decrease plasma norepinephrine levels.
Free Radicals and Oxidative Stresses Free radicals are highly reactive compounds that cause oxidation of
a number of molecules, inducing inflammation in a number of organs. Free radicals produced in muscles
have been implicated as a cause of muscular fatigue as well for a decline in mobility in the elderly
population. To counteract their negative effects, the body must produce or ingest antioxidants.
Antioxidants are enzymes, vitamins, or other types of compounds that are capable of reducing or
preventing the harmful effects of free radicals. Vitamins E, C, and A (i.e., retinol) and nonvitamin
compounds like glutathione peroxidase and superoxide dismutase are important antioxidants that are
reduced in older adults and, possibly, in chronic immobility. Whether free radicals interfere with
metabolic processes in muscle and its contractility, causing functional limitation in mobility and ADLs, is
not entirely known. It has been theorized that increased free radicals in elderly subjects may indeed
cause decline in mobility function (145). However, there are no studies to prove that free radicals
contribute to disuse atrophy and reduced endurance in subjects on bed rest. On the other hand, there is
ample evidence that free radicals cause inflammatory conditions such as in atherosclerosis. For example,
oxidized low-density lipoprotein (oxLDL) plays a major role in the development of artherosclerosis and
subsequent blood vessel inflammation, which is a leading cause of endothelial dysfunction,
thromboembolic events, and ultimately to physical limitations and disability (146). Regular exercises
reduce LDL levels, improve insulin sensitivity, and reduce body weight and subsequent risks for
cardiovascular disease. Furthermore, moderate-intensity regular exercise can reduce free radicals and
positively affect the balance between antioxidants and free radicals reducing oxidative stress and
therefore producing beneficial effects on morbidity and mortality of CAD. Very high intensity, long
duration, or sudden onset of strenuous eccentric exercises can cause muscle damage and trigger release
of inflammatory cytokines, that is IL-6, and precursors of C-reactive protein, which are associated with
development of chronic low-grade inflammatory conditions. However, regular exercise of gradually
progressive intensity does not produce elevation of inflammatory markers such as C-reactive protein
and actually can reduce their levels (37,145). Study by Tanasescu et al. further elucidated the difference
in types of exercises. They found that aerobic exercises, walking and running or aerobic dancing, were
associated with a lower risk of fatal or nonfatal myocardial infarctions, while swimming and bicycling
were not (146). The mechanism of how physical activity prevents cardiovascular disease is not fully
understood although it has a beneficial effect on its risk factors, for example, on cholesterol, HDL,
triglycerides, hypertension, and diabetes mellitus. IMMUNE SYSTEM ALTERATION Chronic physical and
psychological stresses may alter immune system functions such as a reduction of tumor rejection and
increase in tumor growth factors and protection against upper respiratory infection or worsening of
some autoimmune conditions. In animal studies, exposure to long periods of physical restraint resulted
in a significant decrease in number of lymphocytes, T-lymphocytes response, and mononuclear splenic
cells as well as increase in plasma corticosteroid levels (147). Initially, it was believed that these
alterations are due to immunosuppressive effects of increased corticosterone levels; however,
adrenalectomy did not prevent these changes. On the other hand, improvement in immune system
function has been found in subjects after moderate types of exercises or physical activities. For example,
randomized studies revealed that daily brisk walking of moderate intensity enhances the host protective
immune system function and reduces days of illness in half when compared to nonexercising subjects
(41). Longterm highly intensive exercises like marathons actually produce immunosuppression and
increased susceptibility to upper respiratory infections in these athletes. These effects are not 1268
PART IV | SECONDARY CONDITIONS AND COMPLICATIONS ameliorated with vitamin C, glutamine, or
zinc, although carbohydrates given before or after running a marathon have been partially successful in
reducing this infection through unclear mechanisms. It is currently believed that very intensive
longduration exercise may cause striated muscle damage releasing a preponderance proinflammatory
cytokines and suppression of immune function as demonstrated in marathon runners and cyclists (148).
In immunosuppressed patients with advanced age and HIV infection, moderate exercise has shown to
provide an enhancement in amount of immune system function. THE NERVOUS SYSTEM AND
IMMOBILITY Sensory deprivation is a silent hazard of prolonged bed rest. Healthy subjects placed on
strict bed confinement for 3 hours and required to wear gloves, goggles, and earplugs to reduce sensory
input experience hallucinations and disorientation. During prolonged bed rest, exposure to social and
chronological cues, such as time of day and movement through space, are reduced causing emotional,
cognitive, and intellectual declines (149). Social isolation alone with preserved mobility can cause
emotional lability and anxiety but usually does not cause any intellectual alterations. However,
prolonged bed rest and social isolation together produce much greater alterations in mental
concentration, orientation to space and time, and other intellectual functions. Restlessness, anxiety,
decreased pain tolerance, irritability, hostility, insomnia, and depression may occur during 2 weeks of
recumbency and social isolation. Furthermore, judgment, problem-solving and learning ability,
psychomotor skills, and memory all may be impaired. Perceptual impairment can be altered even after 7
days of immobility (150). Lack of concentration and motivation, depression, and reduced psychomotor
skills may drastically affect the patient’s ability to maintain optimal level of functioning and
independence. These behavioral effects of immobility may result in a lack of motivation and diminish the
patient’s ability to attain optimal healing and restoration of function. Balance and coordination also are
impaired after prolonged immobility, and this effect appears to be due to altered neural control rather
than muscle weakness (151). An important strategy in the prevention and treatment of these
complications is to apply appropriate physical and psychosocial stimulation early in the course of illness.
Options for the treatment of these effects include group therapy sessions, attention to socialization,
encouragement of family interaction, and avocational pursuits during evenings and weekends, as well as
participation in regular physical activity and exercise. In a multicenter prospective study of older,
noninstitutionalized women tested over 6 to 8 years, greater intensity of physical activity was associated
with smaller declines in cognitive function, even when controlling for age, estrogen use, and
comorbidities. The authors concluded that physical activity prevents decline in cognitive function in
older women (152).