Monitoring Metabolic Status Predicting Decrements in Physiological and Cognitive Performance (2004) / Chapter Skim
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4 Physiological Biomarkers for Predicting Performance
4 Physiological Biomarkers for Predicting Performance
Pages 85-158
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From page 85... ...
Therefore, appropriate groupings of biomarkers can be selected from this list, depending on specific conditions and goals. BIOMARKERS OF BONE HEALTH Healthy bone is essential to minimize fracture incidence, including stress fractures that decrease the availability of combat military personnel for training and combat action (Burr, 1997; IOM, 19984.
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Bone health is related to both adult peak bone mass and the rate of bone loss after peak bone mass (Reeker et al., 1992~. Peak bone mass occurs in individuals between 20 and 30 years of age (Bass and Myburgh, 20004.
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From page 87... ...
As a measure of change in bone resorption status, these early markers could be used in clinical assessment of decreases in bone resorption after therapy or after a return to health. Endocrine markers of bone resorption are important for understanding the balance between bone loss and bone formation.
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From page 88... ...
Increases in stress indicators have been shown to correlate with increases in bone resorption. However, a clinical prediction of bone health using these stress markers cannot yet be made because often stress indicators appear over a limited time and may not result in significant bone loss and an increase in fracture risk.
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From page 89... ...
had increased plasma cortisol levels immediately upon entry into space. These levels remained above baseline during space flight, but all levels were within their normal ranges with considerable variation between crew members.
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From page 90... ...
and group 2 (dashed lines) over an 8-week Ranger training course.
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From page 91... ...
Because increased cortisol levels did not occur in Rangers until their fourth week of training, it may be expected that after training, cortisol levels would return to pretraining levels and, similar to astronauts, their bone formation would increase. BIOMA:RKERS OF MUSCLE METABOLISM AND FATIGUE Skeletal muscle structure is highly adaptable in that the individual muscle cells (myocytes)
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From page 92... ...
Local fatigue originates within the muscle, whereas central fatigue is secondary to alterations within the brain. Several neurological and biochemical changes may cause local muscle fatigue, including the following (Fists, 1994~: · inability of the sodium-potassium pump to maintain the membrane excitability necessary for contraction, · inability of the muscle fiber to maintain normal contractility because calcium ions are not efficiently removed from the intermyofibrillar space into the sarcoplasmic reticulum, · inability to provide oxygen to the muscle cell for energy metabolism (oxidative phosphorylation)
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From page 93... ...
(Fists, 1994; Westerblad et al., 1991~. Muscle fatigue may relate to the process by which free calcium ions are removed from the intermyofibrillar space back into the sarcoplasmic reticulum (Westerblad et al., 1991~.
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From page 94... ...
Muscle fibers store energy as glycogen. It is estimated that 2,000 muscle fiber contractions may be required to deplete muscle glycogen stores, suggesting that this is a good source of energy for muscle contractions, particularly during quick-burst activities.
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From page 95... ...
Ultimately, muscle fatigue is accompanied by cessation of contraction, which restores capillary blood flow with the consequent removal of lactic acid and the recovery of normal intracellular pH. Regeneration of AMP is then possible from inosine monophosphate through a guanosine-triphosphatemediated reaction (Meyer and Foley, 1996~.
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From page 96... ...
One subjective measure of muscle fatigue is self perception, as described previously in Chapter 3; however, predictors of fatigue at an earlier state have been proposed (see following sections)
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From page 97... ...
Cortisol Stress causes increased muscle protein breakdown that results in loss of muscle mass and potentially in muscle atrophy (Wolfe and B0rsheim, 20034. The most common stress indicator is increased blood or urinary cortisol levels (IOM, 19994.
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From page 98... ...
Therefore, blood amino acids are not considered good markers of muscle changes (Wolfe and B0rsheim, 20034. Neutrophil Infiltration and Cytokines Other markers of muscle damage include neutrophil infiltration into the muscle cells and increased concentrations of the cytokines IL-1 and tumor necrosis factor.
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From page 99... ...
It is a relatively low-cost and noninvasive way to measure muscle oxidative metabolism that has found wide application in sports medicine (Puente-Maestu et al., 2003; Xu et al., 2003~. Among the other important variables that would be valuable to assess noninvasively would be tissue pH, redox potential, hydration, extracellular sodium and glucose concentration, osmolality, and evidence of inflammation.
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From page 100... ...
The ratelimiting step in the synthesis of 5-HT is the transport of free TRP across the blood-brain barrier as it competes for a barrier carrier system with other large neutral amino acids, especially BCAAs. Thus an increase in free TRP and a reduction in BCAAs favors uptake of TRP across the blood-brain barrier and increased 5-HT synthesis.
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From page 101... ...
of total body weight, depending on an individual's body composition (Sawaka and Pandolf, 1990~. Individuals with more muscle mass have a higher percentage of body water than individuals with more body fat since water comprises about 72 percent of muscle and organ weight, but only about 20 to 30 percent of fat weight.
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From page 102... ...
Dehydration of greater than 3 percent of body weight increases the risk of developing exertional heat illness and of producing significant reductions in cardiac output since the reduction in stroke volume can be greater than the increase in heart rate (ACSM, 1996; Casa et al., 20004. Table 4-1 provides a general overview of the effect that continued dehydration has on thirst, on the ability to perform work, and on physiological functions.
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From page 103... ...
This in turn decreases the body's ability to cool itself, which leads to an increased core body temperature and the risk of heat illness and collapse and, in rare situations, life-threatening heat stroke (Sutton, 1990~. Various types of heatrelated disorders and factors that increase risk for heat illness are outlined in Table 4-2.
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From page 104... ...
The causes of heat exhaustion may be as sociated with a combination of heavy sweating, dehydration, sodium losses, and energy deple tion. Symptoms include elevated or normal core body temperature, dizziness, lightheadedness, headache, syncope, nausea, decreased urine output, persistent muscle cramps, pallor, pro fuse sweating, chills, intestinal cramps, weak ness, and hyperventilation.
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From page 105... ...
Along with an increased core body temperature (2 1 04°F or 40°C) and hot, dry skin, altered mental status is the uni versally accepted sign that distinguishes exer tional heat stroke from heat exhaustion.
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From page 106... ...
The sports medicine staff identified those football players with a history of whole-body muscle cramp during practices and competition. During two 2.5-hour training practices, sodium and fluid intakes and losses were measured.
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From page 107... ...
Under these conditions, consumption of plain or bottled water may not provide enough electrolytes to maintain good fluid and electrolyte balance. Measurement of Total Body Water In general, assessment of TBW requires a laboratory setting and uses the dilution principle, which states that the volume of the compartment is equal to the amount of the tracer added to the compartment divided by the concentration of the tracer in the compartment (Schoeller, 19964.
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From page 108... ...
deserves attention because of the role of the kidney in maintaining protein status, electrolyte balance, and hydration status. Acute renal failure may occur within hours, and without proper kidney functioning, death ensues within a few weeks to a month (Kopple, 19994.
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Renal damage ~ FIGURE 4-4 Procedure for renal function assessment. Yes Yes 1 Urinary Tract Infection
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From page 110... ...
High blood urea nitrogen or high serum creatinine suggests that protein intake is very high, protein catabolism is very high, the individual is very dehydrated, or kidney function is abnormal. The problem with these measures is that multiple processes and factors, not simply hydration status, influence all of them.
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From page 111... ...
. Hydration Status Measures The maintenance of proper hydration status is a critical issue facing combat military personnel in the field, especially in hot environments (IOM, 1994~.
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Although the measurement of first-morning urine specific gravity in the field may be feasible, individuals could also be trained to associate a urine specific gravity that represents dehydration with their urine color (urine color charts are available)
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From page 113... ...
Individuals should drink until their urine color is either a "very pale yellow" or "pale yellow." However, this may not be the best measure of hydration status within 6 hours of physical activity-caused dehydration (Kovacs et al., 1999~. Urine Volume Urine volume is difficult and impractical to track, but it may corroborate other measures of dehydration.
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From page 114... ...
Sweat rate is calculated as follows: Sweat rate = preexercise body weight - postexercise body weight + fluid intake - urine volume/exercise time in hours Although the measurement of sweat rate and changes in body weight may be easy in a sport setting where locker rooms are available, this becomes more difficult in a field setting. It might be easier to determine an individual's sweat rate in a controlled setting and then use this rate to estimate sweat losses in the field.
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From page 115... ...
Considering the interactions between these systems, monitoring of biomarkers of stress and immune function should ideally include monitoring the immune system and the neuronal and hormonal arms of the stress response at multiple levels. This includes monitoring the expression of immune and nervous system genes, receptors, and maturation or activation markers in accessible cells and tissues (Wed et al., 2003~.
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From page 116... ...
The Stress Response The HPA axis and the sympathetic adrenomedullary system are the primary neuroendocrine components of the stress response (Chrousos, 1998; Eskandari and Sternberg, 2002; Goldstein, 1995; Sternberg, 1998) and are further described below.
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From page 117... ...
The prolonged state of alarm associated with negative emotions likewise places an excessive energy demand on the system. On the way to death, however, premature aging and disease characterize a system dominated by negative effect and autonomic imbalance.
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From page 118... ...
have been shown to attenuate release of these proinflammatory cytokines, and sympathetic hyperactivity is associated with their increased production (Des, 2000~. Thus autonomic imbalance may be a final common pathway to increased morbidity and mortality from a host of conditions and diseases.
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From page 119... ...
In fact, the therapeutic effectiveness of smoking cessation, reduced alcohol consumption, and increased physical activity rest in part on their ability to restore autonomic balance and increase parasympathetic tone. In sum, autonomic imbalance, and decreased parasympathetic tone in particular, may be the final common pathway linking negative effective states and dispositions, including the indirect effects of poor lifestyle, to numerous diseases and conditions associated with aging and increased morbidity and mortality.
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From page 120... ...
Glucocorticoids regulate a wide variety of immune cell expressions and function, including production of cytokines, adhesion molecular expression, immune cell traff~cking, immune cell maturation and differentiation, expression of chemoattractants and cell migration, and production of inflammatory mediators and other inflammatory molecules (Webster et al., 20024. Exposure to physiological concentrations of stress hormones exerts biphasic effects on immune function, that is, they are immunomodulatory rather than simply immuno
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From page 121... ...
At physiological concentrations, glucocorticoids inhibit Thl and enhance Th2 cytokine production, thus causing a shift in immune responses from a cellular immune to a humoral pattern of response. Such glucocorticoid-induced shifts may protect against some forms of autoimmune disease (Sternberg, 2001)
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From page 122... ...
, and transient increases in leukocyte count (Mills et al., 1995~. During chronic stress, high levels of glucocorticoids suppress most aspects of the immune responses, including humoral, cellular, and innate immunity; immune cell trafficking out of the blood and into tissues (Dhabhar and McEwen, 1997~; and the ability to fight infection and mount an antibody response (Dhabhar, 20024.
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From page 123... ...
Thus systemically, an over-reactive immune response, through activation of the stress system, stimulates an important negative feedback mechanism that protects the organism from "overshoot" of proinflammatory cytokines and other products of activated macrophages with tissue damaging potential. Conversely, a blunted hormonal stress response may enhance immune responses and susceptibility to autoimmune disease as a consequence of inadequate responsiveness of this negative feedback loop.
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From page 124... ...
are seen. This pattern of immune responses an up-regulation of the Th2 humoral response and suppressed Thl cellular responses—would be consistent with reported higher levels of stress hormones (cortisol and catecholamine)
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From page 125... ...
Monitoring Stress and Immune Function This section outlines general categories of biomarkers that are currently used to measure both physiological stress responses and immune responses, but they are neither comprehensive nor exhaustive. Monitoring biomarkers of the stress response should include molecular and functional measures of the HPA axis, the adrenergic response systems, and the immune system at multiple levels.
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From page 126... ...
Second, as mentioned above, body odors often directly reflect physiological processes. For example, odors associated with stress have been suggested to arise from the action of stress hormones (e.g., cortisol)
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From page 127... ...
Female mice can be trained to distinguish the odor of mice that vary genetically from themselves (Yamaguchi et al., 1981; Yamazaki et al., 1979~. This discrimination has also been demonstrated in untrained MHC-mutant mouse strains differing in only five amino acids (Carroll et al., 2002~.
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, a B-type retrovirus that is tightly linked to immune responses. MMTV can be acquired either through infection (when newborn pups suckle on infected mothers that shed the virus into milk)
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From page 129... ...
These experiments need to be repeated with stimuli that arouse more intense emotions, although ethical considerations may limit the conduct of some extreme study designs. Recognition and Detection of Human Odor Profiles Studies reviewed here suggest there is a rich potential for monitoring human physical and psychological states using body odors.
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From page 130... ...
It is encouraging that the Defense Advanced Research Projects Agency has an interest in funding studies to identify individuals based on their body odors. Information Conveyed in Humar' Body Odors Current evidence suggests that genetically based odor profiles play a role in individual identity and immune and stress responses and may be useful for monitoring a variety of physical and emotional states in humans.
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From page 131... ...
Odor Sensors One strategy to desinging odor sensors is to develop devices that mimic or even use biological principles to detect specific body odors. Particularly attractive is the idea that one might be able to express olfactory receptors in a device that monitors receptor activity using, for example, fluorescence to express overall patterned activity.
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From page 132... ...
Over the next 5 to 10 years, major strides are likely to be made in understanding the molecular mechanisms of olfaction and the relationship between gene expression and individual odor profiles and their links with emotion and cognitive states. Development of sensor technology are ongoing and are likely to yield smaller, more automated devices that reduce analysis time and increase reliability two factors critical for field applications.
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From page 133... ...
Tear concentrations of valproic acid were directly correlated to cerebrospinal fluid concentrations as strongly as were plasma concentrations, and more so than were salivary concentrations (Monaco et al., 1982~. Further, tear concentrations of valproic acid were correlated with plasma concentrations among adults and among children under 3 years of age (Nakajima et al., 2000; Monaco et al., 1982, 19844.
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From page 134... ...
The development of sensors and applicability in the field remains at different stages; some of them, such as the monitoring of renal function by dipstick strips, are ready for field use, while others, such monitoring methods for bone health or muscle fatigue, still need validation in the field. Maintaining a healthy bone to minimize the incidence of fracture is predicted by measuring bone mineral density.
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From page 135... ...
Med Sci Sports Exerc 28:)
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From page 136... ...
Med Sci Sports Exerc 25:543-549. Armstrong LE, Herrera Soto JA, Hacker FT, Casa DJ, Kavouras SA, Maresh CM.
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From page 137... ...
1988. Changes in plasma concentrations of aromatic and branched-chain amino acids during sustained exercise in man and their possible role in fatigue.
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From page 138... ...
Pro c Natl Acad Sci USA 99:2187-2192. Carter R
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From page 139... ...
Med Sci Sports Exerc 24:512-520. Cocke R
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From page 140... ...
Pro c Natl Acad Sci USA 96:10591064. Dhabhar FS, McEwen BS.
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1996. Prolonged bed rest decreases skeletal muscle and whole body protein synthesis.
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Med Sci Sports Exerc 24:645-656.
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From page 143... ...
1988. Plasma cortisol and natural killer cell activity during bereavement.
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From page 144... ...
1997. Immune responses to final exams in healthy and asthmatic adolescents.
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From page 145... ...
1999. Urine color, osmolality and specific electrical conductance are not accurate measures of hydration status during postexercise rehydration.
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From page 146... ...
Med Sci Sports Exerc 23:1028-1034. Manore M, Thompson J
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From page 147... ...
2003. Major histocompatibility complex heterozygote superiority during coinfection.
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From page 148... ...
Med Sci Sports Exerc 20:408-414. Moynihan JA.
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From page 149... ...
Med Sci Sports Exerc 23:1055-1061. Oh MS, Uriba~Ti J
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From page 150... ...
1990. Cellular and molecular diversities of mammalian skeletal muscle fibers.
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From page 151... ...
Elects of Exercise. Presented at the Institute of Medicine, Committee on Metabolic Monitoring Technologies for Military Field Applications Workshop on Metabolic Monitoring Technologies for Military Field Applications, San Antonio, Texas, January 8-9.
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From page 152... ...
Med Sci Sports Exerc 23:542-551. Smith LL.
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From page 153... ...
Med Sci Sports Exerc 35:S48. Strachan AT, Maughan RJ.
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From page 154... ...
In: Lamb DR, Gisolfl CV, eds. Perspectives in Exercise Science and Sports Medicine.
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From page 155... ...
1998. Effect of mild acute stress on immune cell distribution and natural killer cell activity in breast cancer patients.
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From page 156... ...
Proc Natl Acad Sci USA 97:325-330. Wysocki CJ, Preti G
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From page 157... ...
Pro c Natl Acad Sci USA 99:5612-5615. Yehuda R
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