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Rhabdomyolysis.pptx
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- 3. What is Rhabdomyolysis? •A serious life-threatening condition due to direct or indirect injury to muscle tissue • Rapid breakdown and death of skeletal muscle fibers, leading to the release of potentially toxic cellular contents into the circulation • Should be distinguished from other causes of pigmentation in urine eg drugs, hemolysis, porphyria
- 4. Rhabdo cont’d • Creatinekinase levels rise to significant levels • Normal range 40-320 U/L. In Rhabdo – CK can rise to x10 as much. Can be as high as 1 million U/L. • Can be a single event or recurrent • If recurrent – genetic disorder more likely
- 6. Causes 1: intenseexercise in healthy subjects 1. An area of litigation in the military 2. Exertional rhabdo occurs as a physiological response to unaccustomed, prolonged, repetitive exercise with eccentric characteristics causing muscle tension, strain and injury 3. In the military there may be a metabolic component – energy depletion since timings of meals/hydration are also tightly controlled 4. This is a real threat to military population especially when training under heat stress
- 7. Causes 2: Ischemiaand Trauma Multiple causes • Falls • Long lasting muscle compression eg after prolonged immobilization after a fall or lying unconscious on a hard surface during illness or after taking drugs or alcohol • Crush injuries • Status epilepticus • Electrical shock injury • Third degree burns • Lightning strike • Venom from snake or insect bite
- 8. Causes 3: Drugsand Toxins Drugs and toxins: Alcohol, carbon monoxide, HIV drugs, herbal remedies, opiates, amphetamines, ask for over the counter remedies Statins Myalgia, Hypercalcemia Necrotizing myopathy – CK around 10,000 with death of muscle fibers and poor prognosis for Recovery HMG CoA reductase antibodies Neuroleptic Malignant Syndrome A rare reaction to anti-psychotics 2/10,000 people
- 9. Causes 4: Autoimmunemyositides • Dermatomyositis
- 10. Causes 5: Endocrinopathiesand Electrolyte disturbances • Thyroid disease • Diabetes • Diabetes insipidus • Pituitary dysfunction • Diabetic ketoacidosis • Profound hyokalemia - in renal tubular dysfunction • Adrenal pathology • Hyponatremia, Hypernatremia
- 11. Causes 6: Infection 1.Influenza A and other types 2. Coxsackie B virus 3. HIV and seroconversion 4. Others…
- 12. Causes 7: Genetic 1.Inherited metabolic myopathies 1. Glycolysis eg McArdle’s, Tarui’s 2. Fatty acid oxidation defect eg carnitine palmitoyl transferase II deficiency, multiple Acyl Co A dehyrogenase deficiency 2. Mitochondrial disorders 3. Malignant hyperthermia (ryanodine mutations RYR1); 4. Dystrophinopathies (eg Becker’s muscular dystrophy, LGMD especially related to ANO5, Dysferlin or Caveolin-3 mutations, Sarcoglycanopathies, FKRP) – giving this pseudometabolic presentation
- 13. Symptoms and complications •Myalgia • Muscle swelling • Muscle Weakness • Dark urine
- 15. Consequences • Sarcolemma injuryresults in Na/K- ATPase and Ca-ATPase pump dysfunction • High intracellular calcium levels enhance activation of calcium dependent proteases and phospholipases with destruction of myofibrillar, cytoskeletal and membrane proteins • K+, PO4-, urate, aldolase, creatine kinase, myoglobin, AST and LDH leak into circulation • Myoglobin in excess precipitates in glomerular filtrate and can cause Acute Renal Failure
- 16. Complications • Renal failurewith anuria • Fever, nausea, anuria, confused/agitated • Hypocalcemia • Hyperkalemia, cardiac arrhythmia and death • Hepatic inflammation can occur as a result of released proteases • Liver failure • Disseminated intravascular coagulation • Compartment syndrome • Death
- 17. The clue canbe in the history and digging for triggers… • Infection and fever • Fasting/Diet • Trauma • Exercise (unaccustomed, intense) • Exercise-induced myalgia • Probing for second wind (McArdle’s) • Anesthesia • Medications including anti-psychotics, herbal remedies, recreational drugs, alcohol, statins • Background of exercise – induced myalgia
- 18. Pathology • Early onin exercise – severe cramp and muscle stiffness with weakness • Higher the intensity – symptoms come on almost immediately • If the intensity is less – symptoms come on later • Second wind: rest/slowing down, allowing blood borne glucose to be delivered to muscle bypassing the myophosphorylase enzyme activity/defect allowing them to continue activity because of increased blood supply (during exercise) but at lower intensity
- 20. How to investigaterhabdomyolysis… • If single episode, individual trains regularly and is of high fitness (+/- occurring in context of unusual exercise) – maybe no investigations required ????? (Difficult!)
- 22. Current Investigations • Baselinebloods • NCS and EMG (generally unhelpful) • Exercise test • Aerobic defects (abnormality in acyl carnitine profile and urine organic acids, ↑ lactate) • Beware ↑ lactate and deconditioning • Glycolytic/glycogen storage defects (flat lactate) • Muscle MRI • This would detect changes in dystrophinopathies, ANO5 etc • But some RYR1 patients can have normal MRI! • Low threshold for testing for • CPT2 deficiency (1 yield over 10 years! – after extended gene testing to detect 2nd mutation) • ETFDH (multiple Acyl CoA dehydrogenase deficiency) – Riboflavin responsive myopathy • Muscle biopsy (at least 1 month after rhabdo) - mitochondrial • Genetic tests (other)
- 23. When to considergenetic testing • R Recurrent (single episode there is an argument for not testing further) • H HyperCK persists • A No unusual exercise (absent) • B Blood CK >50 UMNL • D Drugs (absent) • O Other family members (similar symptoms)
- 24. Management of Rhabdomyolysis •Preserve renal function • Correct metabolic derangement • Iv fluids ideally until CK drops to below 1000 • Alkalinisation of urine to promote myoglobin washout • Bicarbonate corrects metabolic acidosis • Keep an eye out for high K+ • Hemodialysis may be required • DIC and compartment syndrome
- 25. Long term managementof metabolic myopathies • Exercise + Diet • Avoid exercise when running fever, dehydrated or fasting or metabolically stressed • Keep well hydrated • Seek advice immediately if myalgia + dark urine • Carnitine can help with chronic myalgia • If there is a suggestion of Multiple Acyl Co A dehydrogenase deficiency • Caution with persistent hyperemesis/weight loss/nutritional deficiency/pregnancy • Riboflavin
- 26. Conclusions • Many causesfor rhabdomyolysis • Acute management is same for all • Investigation pathway needs some thought given that the current yield of tests is very low • Muscular dystrophies and mitochondrial disorders may rarely cause rhabdo • There are common metabolic disorders to be aware of – correct advice on exercise and diet management