Methemoglobinemia
Methemoglobinemia is a blood disorder characterized by an abnormal increase in methemoglobin levels, a form of hemoglobin that contains ferric iron and is inefficient at carrying oxygen. This condition can manifest in both inherited and acquired forms, with the acquired version being more common. Symptoms can vary depending on the severity, starting from a bluish tint to the skin (cyanosis) at lower levels of methemoglobin to severe complications such as fainting and even coma at higher concentrations. Common causes of acquired methemoglobinemia include exposure to certain medications, chemicals, and toxins, with specific examples being nitrates, anesthetics, and some dyes.
While a small amount of methemoglobin is normal, levels above 1% can lead to oxygen deprivation in tissues. Treatment options may include supplemental oxygen, methylene blue injections, or blood transfusions, depending on the severity of the condition. Inherited forms of the disorder, though rare, can arise from genetic mutations affecting hemoglobin or enzymes related to its production. Understanding methemoglobinemia is crucial, especially since the symptoms can escalate quickly and may require prompt medical attention.
Methemoglobinemia
Methemoglobinemia (met-hee-muh-glow-buh-NEE-mee-uh), sometimes called MetHb, is a blood disorder that affects normal functioning of erythrocytes, or red blood cells (RBCs), in the bloodstream. More specifically, methemoglobinemia changes hemoglobin—the protein in RBCs that binds to oxygen molecules and delivers them to cells and tissues throughout the body—into methemoglobin, which is not an efficient oxygen carrier. A few forms of methemoglobinemia, including both inherited and acquired versions, exist, although the acquired form is more common. One of the most common physical symptoms of methemoglobinemia is a grayish or bluish coloring of the skin known as cyanosis. Exposure to toxins, including certain chemicals and medications, is the most common cause of acquired methemoglobinemia.
Background
Two types of iron exist—ferrous and ferric. Under normal circumstances, heme, a component of the protein hemoglobin found in RBCs, contains iron in its ferrous form. Ferrous iron easily binds to oxygen. As a result, hemoglobin is able to pick up oxygen in the lungs and deliver it to cells and tissues throughout the body. Interference with the normal production of hemoglobin can produce methemoglobin. Methemoglobin contains iron in its ferric form. Ferric iron is a poor oxygen carrier. A small amount of methemoglobin in the blood is normal, but when methemoglobin levels rise to more than 1 percent of the hemoglobin in RBCs, methemoglobinemia results. As methemoglobin levels increase, cells and tissues receive less and less of the oxygen they need to function.
Symptoms of methemoglobinemia become more severe as methemoglobin in the body increases. At levels ranging from 1 to 3 percent, people generally show no symptoms. People may notice a light bluish or grayish tinge to their skin when levels are between 3 and 15 percent. At levels between 15 and 20 percent, cyanosis occurs, and skin takes on a noticeable blue or purple hue due to a lack of oxygen in cells and tissues. At methemoglobin levels between 25 and 50 percent, people begin to feel light-headed and may experience fainting episodes. Many develop a headache and may experience shortness of breath, chest pain, or confusion. Levels between 50 and 70 percent can cause irregular heartbeats, seizures, hallucinations, loss of consciousness, and coma. Levels above 70 percent are fatal. Blood drawn from patients with methemoglobinemia often appears chocolate brown in color rather than bright red.
Treatments for methemoglobinemia vary. Physicians often treat patients whose levels are below 20 percent by having them breathe oxygen to help saturate normal hemoglobin so it can deliver necessary oxygen to tissues and cells. Patients with higher levels of methemoglobin often receive an injection of a substance called methylene blue, which can assist in converting methemoglobin back into hemoglobin. Other treatment options include transfusions of RBCs or hyperbaric oxygen therapy, which involves breathing 100 percent oxygen in a special chamber.
Overview
Several forms of methemoglobinemia exist. The acquired form of the disorder is common and typically results from exposure to certain medications or chemicals. Inherited forms of the disorder, those passed down from parents to their children, are rare. One form must be passed down from both parents; the other form may be passed down from just one parent.
For a child to be born with the first form of inherited methemoglobinemia, both parents must pass on the recessive gene that causes the disorder. The gene causes a problem with an enzyme called cytochrome b5 reductase. This form of the disorder is further divided into two types. With Type 1, the problem is limited to a lack of the enzyme in RBCs only. People with Type 1 often have bluish skin, but they can usually tolerate the disorder and their prognosis is good. Type 2 is more serious. In patients with Type 2, the enzyme does not function at all. Type 2 affects not only RBCs, but also some white blood cells (WBCs) and body tissues. Children born with Type 2 may have developmental delays or mental deficiencies and may experience seizures. The prognosis for children born with Type 2 is poor. Type 2 often proves fatal within the first few years of life.
The second form of inherited methemoglobinemia is sometimes called hemoglobin M disease. For a child to be born with hemoglobin M disease, only one parent must pass on the gene that causes the disorder. This form does not result from a problem with an enzyme but from a problem with the hemoglobin itself. While some people who have hemoglobin M disease may notice a bluish tint to their skin, many do not experience any symptoms at all.
The acquired form of methemoglobinemia is far more prevalent than the inherited forms and usually results from exposure to a specific chemical or compound. For example, in 1945, a physician from Iowa named Hunter Comly documented two cases of so-called "blue baby syndrome." Both infants presented with bluish skin, and it was determined that both had consumed formula mixed with water from wells that tested high in nitrates. (Wells can become contaminated with nitrates from fertilizers, sewage disposal systems, livestock facilities, and landfills.) When a person consumes nitrates, the body converts them into nitrites, which are capable of changing the ferrous iron in hemoglobin into ferric iron. As a result, methemoglobin forms. Rising levels of methemoglobin limit RBCs' ability to carry oxygen, making it harder for them to deliver oxygen to cells and tissues in the body. It is important to note that the nitrates that people consume as part of a normal diet—in vegetables such as beets, broccoli, carrots, and spinach or in meat and fish preservatives—are usually not enough to cause methemoglobinemia. Concentrated forms, such as carrot juice, however, can lead to the development of methemoglobinemia.
Causes of acquired methemoglobinemia beyond water and food sources include certain medications, dyes, and chemicals. For example, silver nitrate used to treat skin burns and nitroglycerin used to treat heart conditions can lead to the development of methemoglobinemia. Anesthetics, such as lidocaine and benzocaine, and antibiotics, such as dapsone and sulfonamides, can cause the disorder. Aniline dye is a known cause of methemoglobinemia. Methylene blue, while often used as a treatment for methemoglobinemia, can actually cause the disorder as well. In addition, methemoglobinemia may be caused by substances found in mothballs, gun cleaners, plant fungicides, exhaust fumes, and smoke.
People with acquired methemoglobinemia may develop bluish skin and experience fatigue, headache, and shortness of breath. They usually recover after treatment, and often no treatment is necessary. However, people should identify whatever caused the problem in the first place and avoid contact with that substance in the future.
Bibliography
Denshaw-Burke, Mary. "Methemoglobinemia." Medscape, 4 Jan. 2016, emedicine.medscape.com/article/204178-overview. Accessed 19 June 2017.
"Glucose-6-Phosphate Dehydrogenase Deficiency." New York Times, 28 Mar. 2013, www.nytimes.com/health/guides/disease/methemoglobinemia/overview.html. Accessed 19 June 2017.
"Methemoglobinemia." Civetta, Taylor and Kirby's Critical Care. 4th ed., edited by Andrea Gabrielli et al., Lippincott Williams & Wilkins, 2009, pp. 1002–4.
"Methemoglobinemia." MedlinePlus, medlineplus.gov/ency/article/000562.htm. Accessed 19 June 2017.
"Methemoglobinemia, Beta-Globin Type." Genetics Home Reference, US National Library of Medicine, 13 June 2017, ghr.nlm.nih.gov/condition/methemoglobinemia-beta-globin-type. Accessed 19 June 2017.
"Methemoglobinemia Due to Deficiency of Methemoglobin Reductase." Online Mendelian Inheritance in Man, www.omim.org/entry/250800. Accessed 19 June 2017.
Rehman, Habib Ur. "Methemoglobinemia." Western Journal of Medicine, vol. 175, no. 3, Sept. 2001, pp. 193–6, www.ncbi.nlm.nih.gov/pmc/articles/PMC1071541/. Accessed 19 June 2017.
Shindler, Daniel. "Methemoglobinemia." Water Encyclopedia, vol. 2, edited by Jay H. Lehr and Jack Keeley, Wiley, 2005, pp. 219–23.
Stöppler, Melissa Conrad. "Acquired Methemoglobinemia." MedicineNet.com, 9 Dec. 2014, www.medicinenet.com/script/main/art.asp?articlekey=155409. Accessed 19 June 2017.