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.