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آخر تعديل 20 يناير 2010 |
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Pathophysiology of physical fatigue Study of fatigue in the clinical setting is complicated by its multifactorial etiology, psychological factors, and patient perceptions. The Patho-physiology of physical fatigue experienced by most cancer patients. Pathophysiology is the science that studies the bodily responses and adaptations to physical activity, exercise or sports. Physiological fatigue is also a complex process that can be originated in one or more steps in a chain of interactive events between the central nervous system (CNS) and the skeletal muscle fiber (Lucia et al., 2003). a- CNS Fatigue sometimes originates at the CNS level. Some neuro-modulators such as ammonia or cytokines secreted by immune cells can act on the CNS to alter the psychic or perceptual state and decrease ability to exercise. Besides the side effects of the anticancer drugs on the CNS, the concentration of cytokines increases in individuals with cancer as a result of the interaction between the tumor and the host defence system (Lucia et al., 2003 and Dimeo,1998). b- Insufficient oxygen transport to muscles patients suffering from cancer may have several specific problems that make oxygen supply insufficient to meet the oxygen demands of their muscles. This lack can be help to explain the severe fatigue that patients experience even during normal activities requiring little oxygen consumption by working muscles. Anemia occurs in over 30%of cancer patients at any time and the frequency increases with progressive disease and treatment. Chemotherapy can damage bone marrow and produce renal toxicity. Erythropoietin, the hormone that stimulates the production and maturation of red blood cells, is mainly secreted by kidney. As a result, anemia is further aggravated (Lucia et al., 2003 and Dimeo et al.,1999). c-Insufficient blood pumping to muscles Anticancer therapy can affect central cardiac dynamics and thus blood supply to body tissues particularly exercising muscles. Cardiac atrophy due to long term bed rest further reduces cardiac output (Lucia et al., 2003 and Dimeo et al.,1999). d-Severe impairment of skeletal muscle function Severe muscle-mass atrophy is common problem that results from the catabolic effects that long term bed rest induce in skeletal muscle tissue. In cancer, this problem is further aggravated both by the production by tumors of factors that elicit an inflammatory (prostaglandin E2) in muscle tissue and result in muscle wasting. After discharge, patients consequently need to make greater efforts to carry out normal activities. Furthermore, treatment with high dose corticoids results in a substantial loss of muscle mass. Finally, immuno-suppression with cyclosporine may result in mitochondrial myopathy and loss of capillary density and exercise ability. These last phenomena are clinically indistinguishable from the changes generated by physical deconditioning. According to the latest knowledge, muscle fatigue in human beings is mainly caused by a failure of excitation contraction (E-C) coupling process. E-C coupling is mechanism by which the electrical discharge on the muscle fiber membrane brought about by nerve impulses initiates chemical events inside the fiber-release of intracellular calcium from the sarcoplasmic reticulum. Calcium release is the signal for immediate contractile activity. It t is followed by calcium reuptake to initiate the relaxation process. Coupling (contraction) and uncoupling (relaxation) continuously operate during any type of exercise or physical activity. Despite common belief lactate accumulation and lactic acidosis do not alter E-C coupling are thus are not major determinants of muscle fatigue. Metabolically active molecules such as tumor necrosis factor released from tumor or mast cells can necrotise muscle membranes and thus impair E-C coupling (Lucia et al., 2003). REFERENCES
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