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Rhabdomyolysis
Ashley Sharifara, Jessie Tong, Nisha Gajaria, Yixin (Angie) Qu
PHM142 Fall 2015 Instructor: Dr. Jeffrey Henderson
What is Rhabdomyolysis? 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.
Symptoms 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
Causes Trauma
Exertion
Body temperature change: heat stroke,
hypothermia
Genetic defects:metabolic disorders
Drugs and toxins: statins, OTC, illicit
drugs
Statin Induced Rhabdomyolysis
conversion of HMG-CoA to
mevalonate inhibited
depletion of GGPP
mitochondrial dysfunction and
energy depletion
General Mechanism of Rhabdomyolysis (1):
Various causes, but common pathway
2 important factors:› ATP depletion› Calcium
concentration Malfunction of ATP
dependent pumps An increase in
intracellular calcium
General Mechanism of Rhabdomyolysis(2):
Source: Adapted from Landau et al. 2012.
Case Study:A dazed looking patient comes into the emergency room, struggling to walk…
A few days later…Test Results
Physical Test: tense, swollen lower
extremities
Creatine Kinase (CK) level: 160,000 IU/L
Normal CK level: 0-195 IU/L
Urinalysis: Myoglobin present
Prevention
Balanced diet & exercise
Risk: statin & fibrate medications for
high cholesterol
Don’t: exercising in extreme heat
conditions, take drugs & alcohol
Keep hydrated – electrolytes
Summary of Rhabdomyolysis 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
References 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.