Myoglobinuria (myoglobin bodies in the urine)

 

Types and Causes of Myoglobinuria (Rhabdomyolysis)

Myoglobinuria is a direct consequence of rhabdomyolysis (skeletal muscle breakdown). Numerous conditions and events can lead to rhabdomyolysis and subsequent myoglobinuria. These can be broadly categorized:

 

Traumatic Causes

• Crush Injuries: Severe trauma causing direct muscle damage (e.g., from accidents, building collapse, natural disasters). This is a classic cause, sometimes leading to "crush syndrome."
• Electrical Injury: High-voltage electrical shock or lightning strike can cause extensive muscle damage.
• Severe Burns: Deep and extensive burns.
• Compartment Syndrome: Increased pressure within a muscle compartment restricting blood flow and causing muscle ischemia and necrosis.
• Prolonged Immobilization with Pressure: Lying unconscious in one position for an extended period.

 

Non-Traumatic Exertional Causes

• Extreme Physical Exertion (Exertional Rhabdomyolysis / March Myoglobinuria): Particularly in untrained individuals, in hot/humid conditions, or with underlying susceptibility (e.g., sickle cell trait, metabolic myopathies). "March myoglobinuria" specifically refers to exertional rhabdomyolysis in soldiers or athletes.
• Seizures: Prolonged or intense convulsive activity.
• Severe Dystonia or Agitation.

 

Non-Traumatic Non-Exertional Causes

• Drugs and Toxins (Toxic Myoglobinuria):
  • Statins (HMG-CoA reductase inhibitors): Especially in high doses or with interacting drugs.
  • Alcohol Abuse (Acute or Chronic): Can cause direct muscle toxicity or rhabdomyolysis due to immobilization or seizures.
  • Illicit Drugs: Cocaine, amphetamines, heroin, ecstasy (MDMA).
  • Venoms: Snakebites (e.g., rattlesnake), wasp or bee stings (massive envenomation).
  • Chemical Poisoning: E.g., carbon monoxide, ethylene glycol, certain herbicides.
  • Certain Medications: Colchicine, zidovudine, fibrates (when combined with statins), some antipsychotics (neuroleptic malignant syndrome).
• Infections:
  • Viral infections (e.g., influenza, HIV, coxsackievirus, Epstein-Barr virus).
  • Bacterial infections (e.g., Legionella, Streptococcus, Salmonella, Clostridium causing gas gangrene).
• Metabolic and Electrolyte Abnormalities:
  • Hypokalemia (severe)
  • Hypophosphatemia (severe)
  • Diabetic ketoacidosis or hyperosmolar hyperglycemic state
• Genetic Muscle Diseases (Muscular Dystrophy and Metabolic Myopathies):
  • Duchenne muscular dystrophy, Becker muscular dystrophy.
  • Disorders of glycogen metabolism (e.g., McArdle's disease).
  • Disorders of lipid metabolism (e.g., carnitine palmitoyltransferase II deficiency).
  • Mitochondrial myopathies.
• Ischemia of Muscle Tissue: Due to arterial occlusion (thrombosis, embolism), prolonged vascular surgery (e.g., aortic cross-clamping), or compartment syndrome. A myocardial infarction (heart attack) involves cardiac muscle, and while troponin is the primary marker, severe cardiac muscle damage could theoretically contribute to myoglobinemia, though skeletal muscle is the more common source for significant myoglobinuria.
• Inflammatory Myopathies: Polymyositis, dermatomyositis.
• Hyperthermia/Hypothermia: Malignant hyperthermia, heat stroke, severe hypothermia.
• Idiopathic Myoglobinuria: Cases where no clear cause is identified.
• Paroxysmal Myoglobinuria: Recurrent episodes, often triggered by exertion or infection, may suggest an underlying metabolic myopathy. "Paralytic myoglobinuria" is an older term, sometimes referring to equine exertional rhabdomyolysis, or in humans, severe rhabdomyolysis leading to weakness.

Massive myoglobinuria, regardless of the cause, poses a significant risk of damage to the renal nephrons (particularly the tubules), potentially leading to oliguria/anuria and the development of acute kidney injury (AKI), formerly known as acute renal failure.

Myoglobin and hemoglobin are structurally very similar chromoproteins (both containing a heme group). Therefore, many chemical reactions designed to detect hemoglobin (e.g., urine dipstick tests for blood) will also give a positive result for myoglobin, which can sometimes make differentiation challenging without further testing.

 

Clinical Manifestations and Associated Symptoms

The clinical presentation of myoglobinuria is largely dominated by the symptoms of the underlying rhabdomyolysis and any associated complications. The classic triad of rhabdomyolysis symptoms includes:

• Muscle pain (Myalgia): Often severe, affecting large muscle groups (e.g., thighs, calves, lower back, shoulders).
• Muscle Weakness: Can range from mild to profound.
• Dark Urine: Reddish-brown, "tea-colored," or "cola-colored" urine due to myoglobinuria.

However, not all three symptoms are always present; some patients may have minimal muscle symptoms or only present with dark urine.

Other associated symptoms and signs can include:

• Muscle swelling and tenderness.
• Malaise, fatigue.
• Fever (especially if an infectious cause or severe inflammation).
• Nausea and vomiting.
• Abdominal pain.
• Symptoms of dehydration (thirst, dry mouth, decreased urine output before AKI onset).
• Symptoms related to the specific cause (e.g., neurological changes with certain toxins or infections, crush injury signs).
• Signs of acute kidney injury: decreased urine output (oliguria), swelling (edema), electrolyte imbalances, rising creatinine.

 

Diagnosis of Myoglobinuria and Rhabdomyolysis

Diagnosing myoglobinuria and the underlying rhabdomyolysis involves laboratory tests and clinical assessment:

1. Urinalysis:
   • Appearance: Red to dark brown urine.
   • Dipstick for Blood (Heme): Positive.
   • Microscopic Examination: Crucially, shows few or no red blood cells (to differentiate from hematuria). Pigmented "heme" casts (myoglobin casts) may be present.
   • Urine Myoglobin Test: Specific immunoassays can confirm the presence of myoglobin in urine.
2. Blood Tests:
   • Serum Creatine Kinase (CK or CPK): Markedly elevated (often >5-10 times the upper limit of normal, and can be >100,000 U/L). This is the most sensitive indicator of muscle damage. The MB fraction should be checked to rule out significant cardiac muscle injury, though some CK-MB can be released from skeletal muscle.
   • Serum Myoglobin: Elevated, but clears from the blood more rapidly than CK, so levels may have returned to normal if testing is delayed.
   • Electrolytes: To check for hyperkalemia (released from damaged muscle), hyperphosphatemia, hypocalcemia (initially, then potentially hypercalcemia during recovery), and metabolic acidosis (elevated anion gap).
   • Renal Function Tests: Serum creatinine and BUN to assess for acute kidney injury.
   • Liver Function Tests: AST and ALT can be elevated due to release from damaged muscle, not necessarily liver injury.
   • Uric Acid: May be elevated due to release from muscle cells.
3. Additional Investigations: To determine the underlying cause:
   • Toxicology screen if drug/toxin exposure is suspected.
   • Infectious disease workup if infection is likely.
   • Genetic testing or muscle biopsy if an inherited myopathy is suspected (usually after the acute episode).
   • Electromyography (EMG) for suspected neuromuscular disorders.

 

Differential Diagnosis: Myoglobinuria vs. Hemoglobinuria vs. Hematuria

Differentiating these conditions is crucial as they have different underlying causes and implications. All can cause a positive dipstick test for blood (heme).

Feature	Myoglobinuria	Hemoglobinuria	Hematuria (Intact RBCs)
Primary Source	Damaged skeletal (or cardiac) muscle (Rhabdomyolysis)	Lysis of red blood cells within the bloodstream (Intravascular Hemolysis)	Bleeding from any point in the urinary tract (kidneys, ureters, bladder, urethra)
Plasma Appearance	Usually clear (myoglobin is rapidly cleared by kidneys or has a normal plasma color)	Pink or red (due to free hemoglobin in plasma, as haptoglobin is saturated)	Usually clear (unless bleeding is massive and causes systemic effects)
Urine Color	Red, reddish-brown, "tea-colored," or "cola-colored." Quickly turns brownish-brown (metmyoglobin).	Pink, red, or reddish-brown. May remain cherry-red for a longer time ("meat slops" color).	Pink, red, or brown (depending on amount of blood and urine pH). Can have visible clots.
Urine Microscopy (Sediment)	Few or no RBCs. Myoglobin (pigmented) casts may be present. Corpuscular elements usually absent on the first day.	Few or no RBCs. Hemoglobin (pigmented) casts may be present. From the first day, hemosiderin, some erythrocytes (if also glomerular damage), may appear.	Numerous RBCs present. RBC casts if glomerular origin.
Hemosiderin in Urine	Typically absent (myoglobin does not contain iron in a form that readily leads to hemosiderinuria directly from myoglobin breakdown products in urine).	Present in chronic intravascular hemolysis (Hemosiderinuria - iron from hemoglobin breakdown stored in shed renal tubular cells).	Absent (unless there is also chronic intravascular hemolysis).
Serum Creatine Kinase (CK/CPK)	Markedly elevated.	Usually normal or only slightly elevated (unless muscle injury coexists).	Usually normal.
Serum Haptoglobin	Usually normal.	Decreased or absent (consumed by binding free hemoglobin).	Usually normal.

 

Management and Treatment of Myoglobinuria

The primary goals of managing myoglobinuria (and the underlying rhabdomyolysis) are:

1. Treat the Underlying Cause: Addressing the specific trigger for muscle breakdown (e.g., discontinuing offending drugs, treating infection, managing metabolic abnormalities, rehydration for exertional rhabdomyolysis).
2. Preserve Kidney Function and Prevent Acute Kidney Injury (AKI): This is a critical aspect of management.
   • Aggressive Intravenous Hydration: Early and vigorous fluid resuscitation with isotonic saline is essential to maintain high urine output (aiming for 1-2 ml/kg/hr or more), dilute myoglobin in the renal tubules, and help flush it out.
   • Urine Alkalinization (Controversial): Administration of sodium bicarbonate to alkalinize the urine (target pH >6.5) has been used with the theory that it reduces myoglobin precipitation in tubules and its nephrotoxicity. However, evidence supporting its benefit over aggressive hydration alone is limited, and it carries risks (e.g., metabolic alkalosis, hypocalcemia).
   • Diuretics (with caution): Mannitol (an osmotic diuretic) or loop diuretics (e.g., furosemide) may be considered if adequate urine flow is not achieved with hydration alone, but only after intravascular volume is restored. They are not routinely recommended.
3. Correct Electrolyte Imbalances: Monitor and correct hyperkalemia, hyperphosphatemia, and hypocalcemia.
4. Manage Complications: Such as compartment syndrome (may require fasciotomy) or DIC.
5. Dialysis: May be necessary if severe AKI develops with anuria, persistent hyperkalemia, or severe acidosis.

 

Potential Complications, Especially Acute Kidney Injury

The most significant complication of myoglobinuria is **Acute Kidney Injury (AKI)**, also known as myoglobinuric acute renal failure. This occurs because filtered myoglobin can cause renal tubular obstruction (by forming casts), direct tubular cell toxicity, and renal vasoconstriction.

Other potential complications of rhabdomyolysis and myoglobinuria include:

• Hyperkalemia: Release of potassium from damaged muscle cells can lead to life-threatening cardiac arrhythmias.
• Hypocalcemia: Initially, due to calcium deposition in damaged muscle.
• Hyperphosphatemia.
• Metabolic Acidosis.
• Compartment Syndrome: Swelling of damaged muscle within a confined fascial compartment can compromise circulation and nerve function, requiring emergency fasciotomy.
• Disseminated Intravascular Coagulation (DIC): In severe cases.
• Liver Dysfunction: Elevated liver enzymes can occur.
• Long-term muscle weakness or pain in some individuals.

 

When to Seek Urgent Medical Attention

Myoglobinuria is a sign of significant muscle injury and requires prompt medical evaluation. Seek urgent medical attention if you experience:

• Dark red, brown, or "cola-colored" urine, especially after intense exercise, trauma, or illness.
• Severe muscle pain, swelling, or weakness.
• Decreased urine output.
• Symptoms of dehydration.
• Fever, confusion, or significant malaise associated with muscle symptoms or dark urine.
• Known exposure to toxins or drugs associated with rhabdomyolysis.

Early recognition and aggressive management, particularly intravenous hydration, are crucial to prevent or mitigate acute kidney injury and other serious complications.