Rhabdomyolysis

1. Rhabdomyolysis Deanna Caldwell, Alaina Charlton, Suzanne Lynch, Anh Nguyen September 25, 2013 PHM 142 Metabolic Biochemistry and Immunity PHM142 Fall 2013 Instructor: Dr. Jeffrey Henderson

2. What is Rhabdomyolysis A form of myopathy that is associated with acute renal failure and disseminated intravascular coagulation • Destruction and lysis of muscle cells • Cell content is released into the blood stream • Impaired kidney function

3. What causes muscle cell lysis? • Athletes • Accident victims • Abusive drug addicts • Adults taking prescription drugs (ex. statins)

4. Who’s at Risk? • No disease-specific hereditary component • Most common in adults • No particular demographic is more susceptible

5. KidneyOverview

6. Filtration • nephrons (functional unit of the kidney) filter the blood • the nephron consists of the glomerulus, which is enclosed by the Bowman’s capsule Resorption • water and solutes are resorbed into the bloodstream Secretion • wastes are secreted and removed from the bloodstream

7. Acute Renal Failure (ARF) - Vasoconstriction • the breakdown of muscle tissue causes extreme fluid accumulation at the site of injury • this generates a loss of fluid in the renal system • vasoconstriction of kidneys is one of three contributing factors to ARF

8. ARF - Free Radical Damage • Myoglobin reabsorbed into proximal tubular cells • Inside the cell, myoglobin is metabolized yielding a free Fe2+ • Free Fe2+ can donate electrons creating hydroxy radicals

9. ARF - Free Radical Damage • Free radicals cause lipid peroxidation in the cell membrane

10. Ÿ ARF - Free Radical Damage OH

11. ARF - IntratubularCast Formation • Myoglobin co-precipitates with the renal tubular secretory protein, Tamm-Horsfell protein (THP) • Acidic pH favors formation of precipitate • Occurs in the distal nephrons causing intra-tubular obstruction and pressure resulting in ARF

12. Diagnosis • Physical examination • Tender or damaged skeletal muscles • Muscle stiffness weakness or aching • Fatigue and joint pain • Blood test • CBC, including hemoglobin, hematocrit, and platelets • Serum chemistries: creatinine, glucose, potassium, uric acid, phosphate, calcium, uric acid • Electrolyte imbalance • Low plasma pH • Large quantities of muscle enzymes creatine kinase (CK), aspartate transaminase (AST), aldolase, lactate dehydrogenase (LDH)

13. Diagnosis • Urinalysis • Abnormal color (dark, red, or cola colored) • Low urine pH • Decreased production • Urine myoglobin test • Urinary myoglobin concentration >20mg/L: renal impairment • <18 mg/L: no renal failure

14. Treatment • FluidResuscitation • Increases glomerular filtration rate, oxygen delivery, and dilutes myoglobin and other toxins • Prevention of ARF • Urinary alkalization, mannitol, loop diuretics • Correction of Electrolyte, Acid-Base, and Metabolic Imbalances • High K+: NaHCO3, glucose, and insulin; hemodialysis • Low Ca2+: oral or IV repletion • High uric acid and high phosphate: diuretics • Kidneydialysis • Unresponsive to above treatments, life-threatening arrhythmias

15. Summary • Rhabdomyolysis: condition occurs when striated (skeletal) muscle is injured, releasing myoglobin and other muscle cell enzymes into bloodstream • Excess of myoglobin is the main contributing factor which leads to acute renal failure (ARF) • Mostly affects adults taking specific prescription drugs or cases of muscle ischemia (arterial blockage, etc.) • No hereditary component • Causes of ARF: kidney vasoconstriction, lipid membrane free radical damage, intratubular cast formation • Diagnosed via physical exam, blood test and urine analysis • Treatment include fluid resuscitation, prevention of ARF, correction of electrolyte abnormalities, and possibly kidney dialysis

16. References • Holt, S.G., and Moore, K.P., (2001) Pathogenesis and treatment of renal dysfunction in rhabdomyolysis, Intens Care Med, 27, 803-811 • Huerta-Alardin, A.L., Varon, J., Marik, P.E., (2005) Bench-to-bedside review: Rhabdomyolysis – an overview for clinicians, Crit Care, 9,158-169 • Marieb, EN, Wilhelm, PB and Mallatt JB. (2012) The Urinary System, in Human Anatomy & Physiology 7th ed., pp 1007-1021, Pearson, New York. • Paller, M.S. (1988) Hemoglobin- and myoglobin-induced acute renal failure in rats: role of iron in nephrotoxicity, Am. Phys. Soc. 88, F539-F544. • Rosenson, R.S. and Baker, S.K. Statin myopathy. In: UpToDate, Freeman, M.W. (Ed), UpToDate, Rind, D.M., 2013. • Sanders, P.W., Booker, B.B., Bishop, J.B., Cheung, H.C., (1990) Mechanism of Intranephronal Proteinaceous Cast Formation by Low Molecular Weight Proteins, J Clin Invest, 85, 570-576 • Visweswaran, P. and Guntupalli, J., (1999) Rhadomyolysis, Crit Care Clin, 15, 415-428 • Zager, RA. (1996) Rhabdomyolysis and myohemogloburinic acute renal failure, Kidney Int. 49, 314-326. • Image adapted from: Holt, S.G., and Moore, K.P., (2001) Pathogenesis and treatment of renal dysfunction in rhabdomyolysis, Intens Care Med, 27, 803-811 • Image retrieved from: http://www.biochemsoctrans.org/bst/029/bst0290358.htm • Image retrieved from: http://en.wikipedia.org/wiki/Dialysis • Image retrieved from: http://en.wikipedia.org/wiki/Intravenous_therapy • Image retrieved from: http://en.wikipedia.org/wiki/Rhabdomyolysis • Image retrieved from: http://www.expresscheapgeneric.com/generic-mevacor-lovastatin-tablet-p-347.html • Image retrieved from: http://www.fairview.org/healthlibrary/Article/40544 • Image retrieved from: http://www.hospira.com/products_and_services/drugs/MANNITOL_20 • Image retrieved from: http://lifeinthefastlane.com/education/investigations-tests/urinalysis/ • Image retrieved from: http://www.nlm.nih.gov/medlineplus/ency/article/002338.htm • Image retrieved from: http://www.pharmacology2000.com/Cardio/CHF/CHF2/CHF_3.htm