Myoglobinuria - Causes, Diagnosis, and Treatment

Introduction:

Myoglobin is a protein containing iron in the skeletal (muscles attached to the bones) and cardiac muscles (muscles of the heart). Due to the presence of iron, myoglobin helps carry oxygen to the body's muscles. In addition, the affinity for oxygen is more in myoglobin than in hemoglobin.

Thus it can receive oxygen from hemoglobin and transfer it from the blood to the body's muscles. Myoglobinuria means the presence of myoglobin in the urine. Myoglobin is present in the muscle cells or myocytes. Damage to the muscle cells causes myoglobin to leak out into the urine. This damage to the muscle cells is known as rhabdomyolysis.

What Is the Pathophysiology of Myoglobinuria?

The iron-containing protein or myoglobin is removed from the muscle cells because of muscle cell damage and changes in the penetrability of the cell membrane of the skeletal muscles. Typically the sodium-potassium ATPase pump (a pump that maintains an average electrolyte balance in the body) keeps a low sodium concentration within the body's cells.

A sodium-calcium channel then pumps extra sodium into the cells in exchange for releasing calcium from the cells. However, the destruction of the myocytes interferes with these mechanisms, leading to increased calcium within the cells. This high cellular calcium further breaks down the outer covering of the cells, releasing cellular contents such as myoglobin, etc., into the blood circulation. This released myoglobin is taken up by the kidneys and passed out in the urine, causing myoglobinuria.

What Are the Causes of Myoglobinuria?

Different causes of myoglobinuria are:

• Trauma - This is one of the most common causes of myoglobinuria. Individuals with crush injuries, such as getting buried under, after earthquakes, etc., have rhabdomyolysis leading to myoglobinuria. Electric shock can also cause muscle damage leading to myoglobinuria.

• Exertion or Strain - Most athletes undergo exertion myoglobinuria but are occasionally symptomatic unless they do not undergo proper training, inadequate fluid intake, dehydration, and heat exposure. Injury to the muscles from repeated blows releases myoglobin in the urine. Athletes have a higher concentration of myoglobin in their muscle cells and are thus prone to various symptoms, even with a little muscle injury.

• Viral Myositis - Viral infections from different viruses may cause myoglobinuria. Viral myositis causes rhabdomyolysis in children. The influenza virus is the most common virus causing rhabdomyolysis.

• Electrolyte Imbalances - Muscle metabolism disorders might be associated with myoglobinuria. Males are affected more than females. The symptoms are aggravated by exercise and heat injuries. Myoglobinuria has also been found to be related to the exhaustion of potassium.

• Toxins, Drugs, and Food - Snake bites and other poisons might cause muscle injury and myoglobinuria. Certain drugs, such as AZT (Azidothymidine) (a drug used to treat AIDS-acquired immunodeficiency syndrome), Lovastatin (a drug used to treat high cholesterol), and Statins (a group of medications that lower the levels of bad cholesterol in blood), can make individuals susceptible to rhabdomyolysis. Substances like alcohol, cocaine, Amphetamines, Phencyclidine, ecstasy, etc., may cause myoglobinuria. Ingesting ethylene glycol, isopropyl alcohol, quail, and Phencyclidine might lead to myoglobinuria in specific individuals.

• Infection - Muscular destruction causes gas gangrene, tetanus, and Legionnaire disease or shigellosis, which leads to myoglobinuria. Coxsackie infection is one of the common causes of a mild form of myoglobinuria.

• Endocrine Dysfunction - Endocrine dysfunction means disorders related to hormones. Conditions such as diabetic ketoacidosis (accumulation of blood acids called ketones), myxedema (an uncommon complication of hypothyroidism), and nonketotic hyperosmolar comas can damage the muscles.

• High Fever - Elevated body temperature.

• Hereditary Myopathies - Myopathies are disorders causing muscle weakness. Conditions such as McArdle syndrome and muscular dystrophy can cause myoglobinuria.

• Metabolic Disorders - Defective carbohydrate metabolism causes muscle damage induced by specific exercises. This muscular breakdown leads to myoglobinuria. In addition, low lipid or fat metabolism can also lead to myoglobinuria.

• Heat Exhaustion - Certain conditions, such as poor blood supply to the cells and decreased oxygen in the cells, acidosis, etc., due to heat exhaustion can lead to myoglobinuria.

How Is Myoglobinuria Diagnosed?

Various tests help in diagnosing myoglobinuria. They are:

• Medical History - To determine if the individual is taking any medication related to rhabdomyolysis.

• Urine Dipstick Test - A dipstick is a plastic stick with chemical strips. This stick is placed in urine. The different strips change color in the presence of certain substances in the urine. In patients with myoglobinuria, the dipstick test is positive.

• Urinalysis - It is the microscopic analysis of urine. It does not show the presence of red blood cells under a microscope. However, a high level of creatine in the urine test justifies muscle breakdown and myoglobinuria.

• Immunohistochemistry - A test used to check the presence of antigens in tissues.

• Spectrophotometry - A test that uses light to measure the reflection and transmission of light by solids, liquids, and gasses.

• Radioimmunoassay - A test that measures the presence of any biological substance.

• Renal function tests - This test measures how the kidneys are functioning.

• Urine Toxicology Screen - This test measures the amount of drug taken.

• ESR (Erythrocyte Sedimentation Rate) - A test is done to find inflammatory muscular disorders such as dermatomyositis and polymyositis.

How Is Myoglobinuria Treated?

The most important treatment goal is to prevent the progression of acute kidney injury.

• Intravenous normal saline administration to remove myoglobin accumulated in the kidneys.

• The management of electrolyte imbalances, especially hyperkalemia or increased potassium in the blood.

• Alkalization of urine with the help of intravenous administration of sodium bicarbonate. This prevents the formation of uric acid crystals.

• Hemodialysis - This technique is a last resort for individuals not responding to normal saline. It removes the toxins from the kidneys and treats electrolyte imbalances.

• Dialysis - Early treatment of rhabdomyolysis with dialysis might improve kidney injury outcomes.

What Are the Complications of Myoglobinuria?

• Acute Kidney Injury (AKI) - It is the most common complication of myoglobinuria. Certain studies suggest that around fifty percent of rhabdomyolysis cases can progress to acute kidney injury.

• Electrolyte Imbalance - The electrolyte imbalance, such as hyperkalemia or increased potassium concentration in the blood.

How Is the Prognosis of Myoglobinuria?

The prognosis of myoglobinuria is good in most cases, though it can progress to acute kidney injury in a few individuals. However, the kidney damage is minimal as well as reversible.

Conclusion:

Myoglobinuria is the presence of myoglobin, an iron-containing protein in the blood. It is usually caused by the breakdown of muscles leading to the release of myoglobin in the urine. If untreated, it can progress to acute kidney injury. Prompt treatment with the help of saline, diuretics, etc., can help to prevent mortality and morbidity. Athletes should be educated about rhabdomyolysis. The importance of proper hydration should be advised to avoid renal damage. Early intervention and education lead to a good outcome.