Table of Contents
Definition of Methemoglobinemia and Causes
A blood oxygenation disorder in which methemoglobin, a structure of hemoglobin molecules that prevents iron from binding with oxygen, accumulates in the blood. The result is diminished or insufficient oxygen delivery to the body’s cells.
Methemoglobin represents excessive iron molecule structures that are in a ferric state, in which they are unable to bind with oxygen. Normal iron molecules in the hemoglobin are ferrous.
Methemoglobin forms naturally in the blood as a process of oxidation (cellular metabolism), though an enzyme system that converts ferric iron to ferrous iron continuously restores methemoglobin to hemoglobin. Methemoglobin is normally present in the blood in minute quantities, accounting for less than 1 percent of the total hemoglobin forms. Levels above 10 percent begin to cause symptoms, and levels above 70 percent are fatal.
A potential cause of methemoglobinemia is the illicit use of “nitrite poppers,” inhaled isobutyl nitrite, butyl nitrite, and amyl nitrate products that are popular among some recreational drug users.
Methemoglobinemia most commonly results from toxic exposure to oxidizing chemicals or drugs. Dozens of industrial chemicals can cause methemoglobinemia, as can numerous medications in the nitrate, chlorate, and sulfonamide families of drugs, as well as topical anesthetics such as benzocaine and lidocaine.
Exposure is usually chronic. Other causes of methemoglobinemia include hemoglobin disorders that allow excessive methemoglobin formulation and abnormalities in the blood enzyme system that normally removes methemoglobin from the blood.
Symptoms and Diagnostic Path
Symptoms of methemoglobinemia may mimic those of ANEMIA, such as fatigue and shortness of breath (DYSPNEA) especially with exertion or exercise, though important differences are present to help distinguish methemoglobinemia from other hemoglobin disorders. The most significant is a characteristic CYANOSIS that gives the SKIN a bluish brown color and does not improve with the administration of OXYGEN THERAPY. Blood tests that analyze hemoglobin composition determine the amount of methemoglobinemia in the blood; levels higher than 1 or 2 percent confirm the diagnosis though most people who show symptoms have much higher levels.
Treatment Options and Outlook
Most often, removing exposure to the causative substance allows the blood to recover on its own, usually within 72 hours. The doctor may choose to hospitalize the person until hemoglobin levels return to normal, to make sure the person receives adequate oxygenation. When symptoms are severe or persist, treatment may include methylene blue, a chemical that converts the hemoglobin’s iron from ferric to ferrous.
The typical therapeutic approach is to administer an intravenous injection of methylene blue to rapidly convert enough methemoglobin to hemoglobin to relieve symptoms, then switch to oral methylene blue until hemoglobin returns to normal. Rarely, a person who is having severe symptoms may require hyperbaric treatment, in which oxygen under pressure can enter the body through the skin to deliver oxygen to the tissues. Hyperbaric therapy may also be appropriate for people who cannot take methylene blue.
Recovery is generally complete when the cause is toxic exposure. Genetic disorders of the hemoglobin or the enzyme mechanisms that regulate the balance between methemoglobin and hemoglobin may result in chronic methemoglobinemia and consequently the need for ongoing treatment (such as oral methylene blue) to prevent toxic accumulations.
Risk Factors and Preventive Measures
The most common cause of methemoglobinemia is toxic exposure to substances that cause oxidation, which overwhelms the body’s normal mechanisms for managing cell metabolism. Avoiding chemicals, including drugs, that may cause methemoglobinemia is not simple, as they number in the dozens and include such commonly used medications as nitrates (cardiovascular) and topical anesthetics.
People who have genetic disorders that interfere with hemoglobin production and function have increased risk for methemoglobinemia and should make every effort to avoid known causative agents.
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