Rhabdomyolysis

Learning objectives

Rhabdomyolysis occurs when damaged skeletal muscle breaks down rapidly and releases its content in the bloodstream
Characterized by skeletal muscle disintegration and the release of myoglobin and other intercellular proteins and electrolytes into the circulation
Hyperkalemia, hyperuricemia, and hyperphosphatemia can all develop rapidly
This can lead to heart- or kidney failure and can even be fatal
Rhabdomyolysis ranges from an asymptomatic illness with elevation in the CK level to a life-threatening condition associated with extreme elevations in CK, electrolyte imbalances, acute kidney injury, and disseminated intravascular coagulation
Most often caused by direct traumatic injury, however, can also result from a wide array of other causes

Myoglobin interacts with the Tamm-Horsfall protein in the renal tubules to form brown granular casts which lead to tubular obstruction
This process is favoured when the urine is acidic
The heme group of myoglobin could lead to lipid peroxidation
Myoglobin also scavenges nitrous oxide leading to renal vasoconstriction
Renal blood flow is furter reduced by hypovolemia, activation of the RAAS system and other vascular mediators

Endogenous Risks	Exogenous Risks
Advanced age (> 80 years) Small body frame and frailty Multisystem disease - Renal dysfunction - Hepatic dysfunction Thyroid disorders, especially Hypothyroidism Hypertriglyceridemia Metabolic muscle disease - Carnitine palmitoyltransferase II deficiency - McArdle disease Myoadenylate deaminase deficiency	Alcohol consumption Heavy exercise Surgery with severe metabolic demands Agents affecting the cytochrome P450 system, especially - Fibrates - Nicotinic acid - Cyclosporine - Azole antifungals - Macrolide antibiotics - HIV protease inhibitors - Nefazodone - Verapamil - Amiodarone - Warfarin - Consumption of > 1 quart daily of grapefruit juice

Blood test: creatine kinase (CK) > 5000 U/L
- Note that myoglobin levels peak before increases in CK
- However, myoglobin is metabolized rapidly at sites outside of the kidney
- This makes CK a more reliable marker of rhabdomyolysis

A metabolic acidosis with a high anion gap is commonly reported in rhabdomyolysis with associated AKI