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PHM142 Fall 2015 Instructor: Dr. Jeffrey Henderson
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Disintegration/breakdown of skeletal muscle Leakage of muscle cell contents into vasculature › Creatine kinase › Myoglobin › Electrolytes: potassium & phosphate › Purines › Various enzymes: aldolase, lactate dehydrogenase, etc.
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Coca-cola coloured urine › Results from myoglobinuria Muscle pain, swelling, and tenderness Limb weakness Confusion, unconsciousness Fever, nausea/vomitting Less frequent urination In severe cases: renal failure Laboratory tests : plasma creatine kinase levels, plasma potassium levels, urine myoglobin assay
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Trauma Exertion Body temperature change: heat stroke, hypothermia Genetic defects:metabolic disorders Drugs and toxins: statins, OTC, illicit drugs
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conversion of HMG-CoA to mevalonate inhibited depletion of GGPP mitochondrial dysfunction and energy depletion
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Various causes, but common pathway 2 important factors: › ATP depletion › Calcium concentration Malfunction of ATP dependent pumps An increase in intracellular calcium
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Source: Adapted from Landau et al. 2012.
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Physical Test: tense, swollen lower extremities Creatine Kinase (CK) level: 160,000 IU/L Normal CK level: 0-195 IU/L Urinalysis: Myoglobin present
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Balanced diet & exercise Risk: statin & fibrate medications for high cholesterol Don’t: exercising in extreme heat conditions, take drugs & alcohol Keep hydrated – electrolytes
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Rhabdomyolysis is the breakdown of skeletal muscle, leading to the leakage of cell contents (myoglobin, creatine kinase, electrolystes, etc.) Symptoms include coca-cola coloured urine, muscle pain, naseua, confusion Causes include trauma, overexertion, drugs Rhabdomyolysis depends on 2 important factors: ATP or energy depletion and increased intracellular calcium concentration ATP depletion leads to increase in intracellular Ca2+ which triggers a series proteolytic enzymes to cause myocyte destruction and leakage of cell components in bloodstream - excess myoglobin—> precipitate in glomerular filtrate—> acute renal failure Some prevention strategies include keeping hydrated and well supplemented with electrolytes and carbohydrates, and avoiding drugs, alcohol, excessive heat and over-exercising
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Poels, P., & Gabreëls, F. (2009). Rhabdomyolysis: A review of the literature. Clinical Neurology and Neurosurgery, 175-192. Zhang, M. (2012). Rhabdomyolosis and its pathogenesis. World J Emerg Med World Journal of Emergency Medicine, 11-11. Bosch, X., Poch, E., & Grau, J. (2009). Rhabdomyolysis and Acute Kidney Injury. New England Journal of Medicine N Engl J Med, 62-72. Vanholder, R., Sever, M., Erek, E., & Lameire, N. (2000). Rhabdomyolysis. Journal of the American Society of Nephrology, 11(8), 1553-1561. Paidoussis, D., & Dachs, R. (2013). Severe Rhabdomyolysis Associated With a Popular High-Intensity At-Home Exercise Program. J Med Cases Journal of Medical Cases, 4(1), 12-14. Hamer, R. “When Exercise Goes Awry: Exertional Rhabdomyolysis.” Southern Medical Journal. May 1997. Web 28 July 2014. Criddle, L. “Rhabdomyolysis: Pathophysiology, Recognition, and Management.” Critical Care Nurse Journal. December 2003. Web. 28 July 2014. Sakamoto, K., & Kimura, J. (n.d.). Mechanism of Statin-Induced Rhabdomyolysis. J Pharmacol Sci Journal of Pharmacological Sciences, 289-294. Chatzizisis, Y., Misirli, G., Hatzitolios, A., & Giannoglou, G. (2008)The syndrome of rhabdomyolysis: Complications and treatment. European Journal of Internal Medicine, 568-574. Han, F. (2009). Rhabdomyolysis: A review of the literature. The Netherlands Journal of Medicine, 67(9), 272-283.
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