PHM142 Fall 2015 Instructor: Dr. Jeffrey Henderson

 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.

 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

 Trauma  Exertion  Body temperature change: heat stroke, hypothermia  Genetic defects:metabolic disorders  Drugs and toxins: statins, OTC, illicit drugs

 conversion of HMG-CoA to mevalonate inhibited  depletion of GGPP  mitochondrial dysfunction and energy depletion

 Various causes, but common pathway  2 important factors: › ATP depletion › Calcium concentration  Malfunction of ATP dependent pumps  An increase in intracellular calcium

 Source: Adapted from Landau et al

 Physical Test: tense, swollen lower extremities  Creatine Kinase (CK) level: 160,000 IU/L  Normal CK level: IU/L  Urinalysis: Myoglobin present

 Balanced diet & exercise  Risk: statin & fibrate medications for high cholesterol  Don’t: exercising in extreme heat conditions, take drugs & alcohol  Keep hydrated – electrolytes

 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

 Poels, P., & Gabreëls, F. (2009). Rhabdomyolysis: A review of the literature. Clinical Neurology and Neurosurgery,  Zhang, M. (2012). Rhabdomyolosis and its pathogenesis. World J Emerg Med World Journal of Emergency Medicine,  Bosch, X., Poch, E., & Grau, J. (2009). Rhabdomyolysis and Acute Kidney Injury. New England Journal of Medicine N Engl J Med,  Vanholder, R., Sever, M., Erek, E., & Lameire, N. (2000). Rhabdomyolysis. Journal of the American Society of Nephrology, 11(8),  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),  Hamer, R. “When Exercise Goes Awry: Exertional Rhabdomyolysis.” Southern Medical Journal. May Web 28 July  Criddle, L. “Rhabdomyolysis: Pathophysiology, Recognition, and Management.” Critical Care Nurse Journal. December Web. 28 July  Sakamoto, K., & Kimura, J. (n.d.). Mechanism of Statin-Induced Rhabdomyolysis. J Pharmacol Sci Journal of Pharmacological Sciences,  Chatzizisis, Y., Misirli, G., Hatzitolios, A., & Giannoglou, G. (2008)The syndrome of rhabdomyolysis: Complications and treatment. European Journal of Internal Medicine,  Han, F. (2009). Rhabdomyolysis: A review of the literature. The Netherlands Journal of Medicine, 67(9),