eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Myoglobinuria

Author: Prasad Devarajan, MD, Louise M Williams Endowed Chair in Pediatrics, Professor of Pediatrics and Developmental Biology, Director of Nephrology and Hypertension, Director of Clinical Nephrology Laboratories, Chief Executive Officer of Dialysis Unit, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine
Coauthor(s): Watson C Arnold, MD, Director, Department of Pediatric Nephrology, Cook Children's Medical Center
Contributor Information and Disclosures

Updated: Jul 27, 2009

Introduction

Background

Myoglobinuria is usually the result of rhabdomyolysis or muscle destruction. Any process that interferes with the storage or use of energy by muscle cells can lead to myoglobinuria. The release of myoglobin from muscle cells is often associated with an increase in levels of creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), serum glutamic-pyruvic transaminase (SGPT), and other enzymes. When excreted into the urine, myoglobin, a monomer containing a heme molecule similar to hemoglobin, can precipitate, causing tubular obstruction and acute renal insufficiency.

A clinician caring for a patient with crush injuries or other causes of muscle destruction must recognize the presence and severity of myoglobinuria and initiate aggressive hydration to prevent acute renal insufficiency.

The most common causes of myoglobinuria in adults are alcohol and drug abuse, usually in relation to muscle necrosis from prolonged immobilization and pressure by the body weight. Prolonged ethanol consumption and seizure activity, similar to excessive physical activity, can produce an imbalance between muscle energy consumption and production, resulting in muscle destruction.  In children and adolescents, the most common causes of rhabdomyolysis and myoglobinuria are viral myositis, trauma, excessive exercise, drug overdose,¹ seizures, metabolic disorders, and connective tissue disease.

Pathophysiology

Myoglobin is released from muscle tissue by cell destruction or alterations in the permeability of the cell membrane.

Frequency

United States

The frequency of myoglobinuria varies with the incidence of natural disasters and environmental trauma. Epidemics of viral myositis may temporarily increase the incidence in local areas. In urban areas with a high incidence of drug and alcohol abuse, many patients with myoglobinuria may present to emergency departments. Hot weather increases the incidence of stress induced rhabdomyolysis, especially in young athletes.

International

Crush injuries related to earthquakes and other natural disasters are the major cause of cases reported internationally. Any person dug from the rubble of such disasters should be considered to have rhabdomyolysis, myoglobinuria, and potential acute renal failure and, therefore, should be given rapid fluid resuscitation.

Mortality/Morbidity

Myoglobinuria causes little or no morbidity or mortality unless it is associated with the secondary complications of rhabdomyolysis, including hyperkalemia, hypocalcemia, and acute renal failure.² However, when it is associated with severe rhabdomyolysis, myoglobinuria-induced acute renal failure is a potentially lethal complication.

In adults, rhabdomyolysis can be complicated by acute renal failure in approximately 30% of patients, with about 5% of those requiring hemodialytic support. In the pediatric age group, although previous small case series reported acute renal failure rates of 40-50%, a large retrospective review indicates that only about 5% of subjects with rhabdomyolysis develop acute renal failure.³  In both adults and children, the overall mortality rate of acute severe rhabdomyolysis is reported to be 7-8% and is primarily related to acute renal failure and multiorgan failure.

Race

Race is a factor only when natural disasters and economic shortfalls increase the rates of drug and alcohol abuse and the mortality rate among certain racial groups.

Sex

Myoglobinuria tends to affect males more than females because of the former group's predisposition to trauma and participation in strenuous physical exercise. Persons who exercise and have increased muscle mass have an increased intracellular myoglobin content.

Age

In a recent large retrospective review, the median age was 11 years.³  The leading cause of rhabdomyolysis in the 0-9 year age range was viral myositis, whereas the leading diagnosis in the 9-18 year age range was trauma.

Clinical

History

The classical triad of symptoms of rhabdomyolysis includes myalgia, muscle weakness, and dark urine. The typical history may include drug use, coma, trauma, or strenuous exercise. Patients who use diuretics and develop severe potassium deficiency may be predisposed to rhabdomyolysis.

• Some patients may provide a history of viral illnesses, fever, convulsions, electric shock, burns, crush injuries, or trauma of any type. Patients may have a history of sepsis, especially sepsis that affects muscle tissue, such as gas gangrene. Others may give a history of participation in organized athletics during the summer or in strenuous exercise during athletic events, such as bicycle races or mountain climbing.
• The use of some prescription drugs, such as azidothymidine (AZT) or lovastatin, or the ingestion of ethylene glycol may predispose individuals to myoglobinuria. Other drugs associated with myoglobinuria include heroin, codeine, barbiturates, amphetamines, licorice, diazepam, amphotericin-B, phencyclidine, and some dietary supplements.
• Acute tumor lysis syndrome may be associated with myoglobinuria.
• Snakebites, bites from recluse spiders, and multiple insect stings can cause muscle necrosis.
• Ingestion of quail can precipitate myoglobinuria.
• Autoimmune vesiculitis, such as dermatomyositis, may destroy muscle tissue.
• Recurrent myoglobinuria was reported in a 14-year-old girl with Becker muscular dystrophy.⁴

Physical

• Physical examination reveals generalized muscle weakness, often with painful muscle groups, trauma, and/or areas of ischemic pressure necrosis when the patient has laid down for extended periods.
• Expect any patient with extensive trauma to have some myoglobinuria.
• The volume status of the patient should be carefully and quickly determined because volume depletion necessitates rapid correction in order to prevent acute renal failure.

Causes

• Trauma and compression: Trauma is the most common cause of myoglobinuria. Patients who experience crush injuries, such as those that occur when individuals are buried after earthquakes, have rhabdomyolysis and myoglobinuria. Volume depletion from fluid sequestration in damaged tissues and poor fluid intake accentuate the possibility of acute renal insufficiency. Electric shock can cause enough muscle damage to precipitate myoglobinuria.
• External myolysis: Exertional myoglobinuria occurs in most athletes but rarely becomes symptomatic unless combined with poor training, inadequate oral intake, dehydration, and heat exhaustion. Trauma from repeated blows to the muscle always releases myoglobin into the system. The treatment is prevention, which includes plentiful fluid, limited exercise during particularly hot periods, and avoiding muscle trauma. Athletes have more myoglobin in their muscles than other individuals and are prone to symptoms when small amounts of muscle tissue are damaged.
• Viral myositis: Viral infections from a wide variety of organisms can cause myositis and myoglobinuria. The patient usually presents with generalized weakness and myalgias, particularly in the back and proximal extremities. Children with influenza A and influenza B viral infections can present with tenderness in calves and lower extremities. Treatment is generous hydration to facilitate myoglobin excretion.
• Electrolyte disorders: Metabolic diseases, particularly those involving muscle metabolism, may be associated with myoglobinuria. Males are affected more often, and symptomatology is exacerbated by exercise and heat injuries. Potassium depletion has been particularly associated with myoglobinuria.
• Toxins, drugs, and diet
  • Snakebites and other venoms can cause muscle necrosis and myoglobinuria.
  • Some drugs predispose individuals to rhabdomyolysis, including AZT (used to treat acquired immunodeficiency syndrome [AIDS]) and lovastatin (used to treat hypercholesterolemia). However, statin-induced rhabdomyolysis is rare and occurs in less than 0.1% of all users.
  • Alcohol, cocaine, amphetamines, phencyclidine, ecstasy, and some dietary supplements can lead to myoglobinuria.⁵
  • Ingestion of ethylene glycol, isopropyl alcohol, and phencyclidine has been associated with myoglobinuria.
  • Overindulgence in quail can also cause myoglobinuria in some patients.
• Infection or sepsis syndromes: Syndromes involving muscle destruction include gas gangrene, tetanus, Legionnaire disease, or shigellosis. Coxsackie viral infections with myositis may be the most common cause of mild myoglobinuria.
• Endocrine disorders: Diabetic ketoacidosis, myxedema, and nonketotic hyperosmolar comas can disrupt muscle energy.
• Malignant hyperthermia and high fevers: These may be contributors.
• Hereditary myopathies
  • Hereditary myopathies, such as McArdle syndrome and muscular dystrophy, can precipitate myoglobinuria.
  • The differential diagnosis for myoglobinuria must include metabolic myopathies. This diverse and complex list of disorders is long, with new additions each year.
  • In general, patients with myopathies report exercise intolerance, muscle pain, and cramps rather than weakness. Patients with some types of muscular dystrophy or inflammatory myositis (eg, dermatomyositis, polymyositis) may present with progressive weakness.
• Metabolic disorders
  • Patients with defects of carbohydrate metabolism (eg, myophosphorylase, phosphofructokinase, phosphohexoisomerase deficiency) have symptoms of easy fatigability or cramping induced by dynamic isometric exercise, such as heavy lifting, or prolonged exercise, such as swimming or running. Acute muscle breakdown can lead to myoglobinuria. These patients typically present after participating in high-intensity exercise, such as weight lifting.
  • Defects in lipid metabolism include carnitine deficiency, beta-oxidation enzyme deficiency, or disorders of fatty acid transport. Prolonged fasting or prolonged activity induces muscle pain and myoglobinuria. Fever, sepsis, and exposure to cold can also induce muscle fatigue in this set of disorders. These patients typically develop symptoms after prolonged low-intensity exercise, such as walking.
  • Patients with mitochondrial disorders (beta-oxidation disorders) usually present with static and progressive muscular weakness. Failure to thrive, floppy-baby syndrome, and generalized muscle weakness are present in most of these children. Patients usually present with chronic muscle cramping and weakness rather than episodic muscle cramping and weakness. Patients with some types of muscular dystrophy or inflammatory myositis may present with progressive weakness.
• Heat exhaustion and cold exposure: These conditions induce abnormal muscle metabolism by means of various mechanisms, including poor perfusion and decreased oxygenation, acidosis, rhabdomyolysis, or glucose and/or glycogen depletion. Reye syndrome may also be included in this group. Patients with recurrent exercise-induced myoglobinuria may have defective carnitine palmitoyltransferase activity.⁶

• Search for CME/CE on This Topic »

• Glycogen-Storage Disease Type V (Pediatrics: Genetics and Metabolic Disease)
• Glycogen-Storage Disease Type VII (Pediatrics: Genetics and Metabolic Disease)
• Electrical Injuries (Emergency Medicine)
• Carnitine Deficiency (Pediatrics: Genetics and Metabolic Disease)

• FDA Safety Changes: Sarafem, Mavik, Cordarone

• Heatstroke During Endurance Exercise: Is There Evidence for Excessive Endothermy?
• Effects of Simvastatin 40 mg Daily on Muscle and Liver Adverse Effects in a 5-Year Randomized Placebo-Controlled Trial in 20,536 High-Risk People
• Ecstasy in the Emergency Department: MDMA Ingestion