Rhabdomyolysis Im Morning


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Rhabdomyolysis Im Morning

  1. 1. IM Morning ConferencesRenal Section<br />Antonio L. Diaz-Hernandez, MD<br />PGY-5 Renal section<br />
  2. 2. Reason for consult: <br />“Please evaluate pt with rhabdomyolysis related to statin/gemfibrozil combination”<br />
  3. 3. History of present illness<br />Patient is a 72 year old man, with pertinent medical Hx of hypertension and hypercholeterolemia who was in his usual state of health consisting of free ambulation and self care until the day before admission when he was unable to even stand up. Patient was referring this progressive weakness since last April. He use to walk long distance from his home and had been felling more tired needing to take breaks every few blocks or so. The Monday before admission he started to have muscular pain in his extremities, more prominent in legs, and reproduce with palpation.<br />
  4. 4. History of present illness<br />The symptoms keep getting worse until yesterday when he felt extreme weakness. Patient also complains of tiredness and dizziness. As per interview reveals, signs and symptoms correlate in time with recent optimization of simvastatin treatment, form 40 mg to 80 mg day.<br />
  5. 5. Active medical problems<br />Active medication<br />Atenolol 50 mg day<br />Gemfibrozil 600 mg BID<br />Simvastatin 80 mg day<br />ASA 81 mg day<br />HCTZ12.5/<br /> irbesartan150 mg day<br />Active Medical Problems<br />Hyperlipidemia<br />Hypertension<br />Arthritis<br />BPH<br />
  6. 6. Past Medical History<br />Occupation - pension<br /> Habits <br />Alcohol:1 liter of alcohol for 20 years, quit 18 years ago<br />Tobacco: 40 packs/years, quit 18 years ago<br />Drugs: marijuana<br />Family history<br />Father: HBP<br />Allergies: NKA<br />Transfusions: denies<br />Travels: EEUU, Las Vegas, Oct 2007<br /> Surgeries: tonsilectomy<br />
  7. 7. Active Medications<br />0.9% sodium chloride inj, 150 ml/hr@0 IV<br />sodium bicarbonate 150 meq in 5% dextrose/water 100 ml/hr@0 IV<br />Ceftriaxone/azythromycin; suspected CAP<br />
  8. 8. Physical exam:<br />Vital Signs: <br /> DATE/TIME TEMP PULSE RESP BP PAIN <br /> 8/30/08 @ 1528 98.6 82 20 110/75 0 <br />General: Alert and oriented times three. Free of chest pain, no in acute distress. <br />HEENT: Atraumatic, No JVD at 45*, no carotid bruits. <br />Heart: RRR, S4(-), S3(-) no murmur. <br />Chest/lungs: bilateral clean auscultation <br />Abd: Bowel sounds audible. Soft and depressible, no rebound, no tenderness. <br />Extremities: +1 bilateral pitting edema no cyanosis. Bilateral lower extremities pain to palpation, bilateral extremities weakness, more evident lower extremities.<br />
  9. 9. Admission Labs<br />CBC<br />HGB 12.2<br />Htc 35.6 <br />WBC 15.5<br />Plat 253<br />Serum Chemistry<br />BUN 47<br />Creat2.4 (1.1; 2007)<br />Na 140<br />K 5.2<br />Cl 103<br />HCO3 20<br />Glu 106<br />Ca 9.3 <br />PO4 XX<br />CPK &gt;20,000<br />
  10. 10. Admission Labs<br />U/A<br />Sg 1.015<br />Blood large<br />pH 5.5<br />RBC 0-5<br />WBC 0-5<br />Protein 100 <br />Cast none<br />Bacteria none<br />
  11. 11. Initial Clinical Impression<br />AKI<br />Rhabdomyolysis; statin induces<br />
  12. 12. Rhabdomyolysis<br />
  13. 13. Rhabdomyolysis<br />Backgrounds: <br />First describe 1940-1941 during WW II<br />Commonly to the victims of crush injury in London during blitzkrieg  bombing raids <br />Bywaters and Beall describe pathologic change of four patient who die during blitz operations, change were similar to the previews describe in mismatch blood transfusion<br />
  14. 14. Rhabdomyolysis<br />Epidemiology<br />World wide <br />5-20% of AKI<br />United State <br />8-15% of AKI<br />Estimated 2 cases per 10,000 person-years 26,000 total cases per year<br />85% of patients with major traumatic injuries will experience some degree of rhabdomyolysis <br />
  15. 15. Rhabdomyolysis<br />Pathogenesis<br />Three principal mechanism:<br />ATP demand that outstrip ATP supply<br />Sustained increase in sarcoplasmatic calcium concentration<br />Sarcolema increase permeability<br />
  16. 16. Rhabdomyolysis<br />Na+<br />Ca+<br />Ca+<br />Ca+<br />Na+<br />Ca+<br />Ca+<br />Ca+<br />Na+<br />Na+<br />Ca+<br />Na+<br />ATPase<br />K+<br />K+<br />K+<br />Na+<br />Ca+<br />Na+<br />Na+<br />K+<br />K+<br />K+<br />K+<br />Na+<br />K+<br />K+<br />Ca+<br />K+<br />ATPase<br />Na+<br />K+<br />K+<br />Na+<br />K+<br />K+<br />Na+<br />K+<br />K+<br />Ca+<br />K+<br />K+<br />K+<br />
  17. 17. Rhabdomyolysis<br />↓ATP<br />Increase intracellular [Ca+] <br />Activation proteolytic and cytotoxic enzymes<br />Na+ with associate cellular swelling and injury<br />ATP maintain [Ca+] by<br />Sequestration sarcoplasmic reticulum<br />Promote outflow to extracellular spaces<br />
  18. 18. Rhabdomyolysis<br /><ul><li>Cell swelling</li></ul>Swelling restricted by surrounding fascia<br />Trauma or toxin<br />Sarcoplasmatic permeability<br />compartment pressure<br />ischemia, necrosis and compartment syndrome<br />
  19. 19. Hereditary Etiologies<br />Deficiencies of glyco(geno)lytic enzymes <br />myophosphorylase (McArdle&apos;s disease)<br />phosphorylasekinase<br />phosphofructokinase (Tarui&apos;s disease)<br />phosphoglyceratemutase<br />phosphoglyceratekinase l <br />actatedehydrogenase<br />Abnormal Lipid Metabolism <br />carnitinepalmitoyltranferase deficiency I and II <br />carnitine deficiency<br />
  20. 20. Acquires Etiologies<br />Excessive muscle exercise <br />sports and military training <br />status epilepticus<br />status asthmaticus<br />prolonged myoclonus<br />Metabolic disorders<br />diabetic ketoacidosis<br />nonketotichyperosmolar coma <br />hypothyroidism<br />hypophosphatemia<br />hyponatremia<br />hypokalemia<br />Ischemic injury <br />compression <br />vascular occlusion <br />sickle cell trait<br />Infections <br />bacterial <br />viral<br />Heat-related syndromes <br />heat stroke<br />Inflammatory myopathies<br />polymyositis<br />dermatomyositis<br />Direct muscle injury <br />crush <br />burning/ freezing <br />electric shock<br />lightning stroke<br />
  21. 21. Associate drugs<br />Drug<br />Barbiturates<br />Amphetamines<br />Heroin <br />Methadone <br />Phencyclidine (PCP)<br />Phenylpropanolamine<br />Chlorpromazine <br />Morphine <br />Diazepam <br />Dihydrocodeine<br />LSD<br />Lithium<br />Salicylates<br />Amoxapine<br />Clofibrate/Bezafibrate<br />Phenelzine<br />Isoniazid<br />Loxapine<br />Antihistamines<br />Theophyllin<br />Oxprenolol<br />Pentamidine<br />Ethanol <br />Vasopressin <br />Statins<br />
  22. 22. Statin Induce Myopathies<br />Muscle injury by <br />↓sarcolema cholesterol <br />↓Ubiquinone (coenzyme Q10)<br />Impairs oxidative phosphorilation<br />Presentations<br />Asymptomatic CPK elevations<br />Myalgia with normal CPK<br />Frank rhabdomyolysis<br />
  23. 23. Rhabdomyolysis<br />Increase risk if:<br />Large dose<br />Kidney disease<br />Hepatic disease<br />Hypothyroidism<br />Amiodarone<br />Gemfibrozil<br />Erythromycin<br />Warfarin<br />Cyclosporine<br />Itraconazole<br />
  24. 24. Rhabdomyolysis<br />
  25. 25. Rhabdomyolysis<br />Cocaine<br />Direct myotoxicity<br />Indirect effect<br />Vasoconstriction<br />Seizures<br />Agitation<br />Delirium<br />Hyperthermia<br />Muscle compression in obtunded patient<br />Ethanol<br />Direct myotoxicity<br />Indirect effect<br />Poor caloric intake<br />Malnutrition<br />Potassium/phosphate depletion<br />Hyperactivity<br />Deliriums tremens<br />Associate trauma<br />Muscle compression due to coma<br />
  26. 26. Systemic Effects<br />
  27. 27. Rhabdomyolysis<br />Possible kidney manifestation<br />Asymtomatic normal renal function with discrepancy of blood vs RBC presence<br />Ex: Blood= large/RBC=2-5<br />Pigment nephropathy<br />ATN<br />Oliguric <br />Non oliguric<br />
  28. 28. Kidney Vulnerability<br />↓renal vasodilatation<br />Nitric oxide<br />Heme proteins<br />↓[NO]<br />+<br /> Heme proteins<br />production of vasoconstrictors (endothelin, isoprostanes)<br />Glomerular filtration/ ultrafiltration<br />Concentrate and internalize heme proteins<br />oxidizes<br />Hydrogen peroxyde<br />+<br />urine heme protein<br />Increasing toxicity<br />denaturate heme<br /> protein<br />Acidic urine pH<br />interaction with Tamm-Horsfall protein<br /> urine cast formation<br />
  29. 29. Pigment Nephropathy<br />Vasoconstriction<br />Cytokines activity<br />Heme toxic effect<br />Cast formation<br />
  30. 30. Rhabdomyolysis<br />Diagnosis <br />Wide range of presentation<br />Muscle pain<br />Swelling weakness<br />Bruising<br />Compartment syndrome features<br />Largely asymtomatic with dark urine, decrease urine output and abnormal electrolytes <br />
  31. 31. Rhabdomyolysis<br />Laboratory evaluation<br />Myoglobinuria<br />Dark urine<br />50% positive heme proteins with 0-5 RBC/hpf<br />Acidic urine pH<br />Tubular epithelial cells<br />Granular cast<br />Dark pigment cast<br />Proteinuria 50% case<br />May reach nephrotic range<br />Myoglobinuria; transitory finding<br />
  32. 32. Rhabdomyolysis<br />Patient serum<br />CPK<br />Peaks 48 hr after event<br /> ½ life 48 hr<br />Range could vary from 1,000 to 100,000 IU/L<br />Fivefold greater than upper limits or &gt; 500 IU/L<br />Second wave elevation rise suspicious of possible compartment syndrome<br />
  33. 33. Rhabdomyolysis<br />Patient serum<br />Hyperkalemia<br />Hyperphosphatemia<br />Hypocalemia<br />Hyperuricemia<br />Hypoalbuminemia?<br />Low BUN/creatinine<br />
  34. 34. Rhabdomyolysis<br />Treatment options: <br />Crush syndrome: <br />1-1.5 L 0.9 NSS 1 Hr<br />+/- 10 L first 24 Hr<br />Non traumatic:<br />High rate 0.9 NSS infusion<br />Correct intravascular volume depletion<br />
  35. 35. Rhabdomyolysis<br />Treatment options: <br />Urine alkalinization?<br />May reduce risk of pigment nephropathy<br />1L 0.45 NSS + NaHCO3 75 mmol<br />Mannitol in isotonic solution<br />100 meqq NaHCO3 + mannitol 100mL(25%) + D5% 800 mL; 1 L in 4 Hr, if no improve in urinary output (&lt; 20mL/Hr) stop treatment<br />May worse hypocalcemia<br />
  36. 36. Rhabdomyolysis<br />Treatment options:<br />Hemodialysis!<br />
  37. 37. Be carful of simvastatin 80 mg! (and also from alcohol + exercise)<br />
  38. 38. Clostridium septicum<br />
  39. 39.
  40. 40. Human renal biopsy showing proximal tubule injury. This image is a representative sample of a kidney biopsy for ARF, kindly provided by Dr. James Hasbargen, following exercise-induced rhabdomyolysis. The biopsy, obtained within 24 hours of the event, revealed significant proximal tubule cell damage with intraluminal accumulation of apical membrane fragments and a detached cell (*), thinning of proximal tubular cells to maintain monolayer tubule integrity (arrowhead), and dividing cells and accumulation of white cells within the microvascular space in the peritubular area (arrow). The patient required renal replacement therapy but did regain complete renal function.<br />
  41. 41. Pathogenesis of Pigment Nephropathy<br />Myoglobin Release<br />Intravascular volume depletion<br />Systemic acidosis<br />