Methemoglobinemia is when there is an elevated level of methemoglobin in the blood. Methemoglobin is a derivative of hemoglobin that gives red blood cells their color and binds oxygen for transport throughout the body. Because methemoglobin cannot bind oxygen, methemoglobinemia results in a systemic undersupply of oxygen, including bluish skin discoloration, fatigue, and dizziness.
What is methemoglobinemia?
Methemoglobinemia occurs when the proportion of methemoglobin in the total hemoglobin content of the blood exceeds its physiologic value. An exact threshold value is not defined for this. In a healthy person, the proportion of methemoglobin is about 3%. First clinical symptoms occur from about 10%, serious tissue hypoxia from 30% (especially in the brain). From 40% methemoglobin content, there is danger to life. Hemoglobin (Hb) is a protein consisting of 4 subunits. Embedded in each subunit is an iron atom of oxidation state II, which can bind and release oxygen molecules. When the divalent iron atom is oxidized to a trivalent iron atom, methemoglobin (MetHb) is formed. Not only can methemoglobin itself not bind oxygen, but it also affects the hemoglobin in its vicinity so that the latter only binds oxygen but no longer releases it. Therefore, methemoglobinemia jeopardizes the oxygen supply of the entire organism.
Causes
Basically, congenital methemoglobinemia is distinguished from acquired methemoglobinemia. The congenital variant is due to genetic defects in hemoglobin or in enzymes that prevent oxidation of hemoglobin, but it is very rare. Much more frequently, methemoglobinemia results from intoxication. Many different substances are possible triggers: in clinical practice, methemoglobinemia occurs most frequently after administration of certain drugs, including dapsone and amide-type local anesthetics. Aromatic compounds in dyes (e.g., aniline) and nitrite compounds are also known triggers. Nitrite poisoning occurs, for example, through pickling salt, unrefrigerated spinach dishes, or the preparation of baby food with water containing nitrates. Frequent cases of methemoglobinemia in infants (so-called infant cystitis) in the 1950s and 1960s led to the introduction of nitrate limits in drinking water in Germany.
Symptoms, complaints, and signs
The symptoms of this disease and their severity depend, on the one hand, on the age of the patient. On the other hand, underlying cardiac or vascular diseases also influence the severity of symptoms. If the methaemoglobin level in the blood remains below three percent, those affected usually have no symptoms at all. When the level exceeds three percent, the first signs of oxygen deficiency appear. These can be headaches, a slight dizziness or shortness of breath. In addition, the skin becomes paler and takes on a grayish color. If the concentration of MetHB rises above ten percent, the skin and mucous membranes turn bluish (cyanosis) and the arterial blood is significantly undersupplied with oxygen (hypoxemia). At a level of about 30-50 percent MetHB in the blood, severe respiratory disorders must be expected, and vascular functions are also impaired. The blood turns dark and takes on a chocolate-like color. Dizziness intensifies, brief unconsciousness and a pronounced feeling of weakness may occur. If the concentration increases to over 50 percent, the brain can no longer be supplied with sufficient oxygen and neurological disorders become apparent. The patient falls into deep unconsciousness, the heart reacts with rhythm disturbances. Death is highly likely to occur above 70 percent MetHB in the blood.
Diagnosis and course
The first sign of methemoglobinemia is cyanosis, which is a bluish to grayish discoloration of the skin. This is particularly noticeable on the lips and mucous membranes. The methemoglobin itself has a brown color; therefore, blood freshly drawn under methemoglobinemia looks chocolate brown. Other symptoms include dizziness, fatigue, impaired consciousness, shortness of breath, and an accelerated heartbeat (tachycardia). The diagnosis of methemoglobinemia is confirmed by a spectroscopic blood test.In addition, there is a simple bedside test in which a drop of normal blood and a drop of patient blood are dripped side by side onto a filter paper and compared one minute later. In methemoglobinemia, the patient’s blood retains its characteristic brown color. A pulse oximetry measurement of oxygen saturation can be misleading:
This still indicates high oxygen saturation even in severe methemoglobinemia. Untreated methemoglobinemia can be fatal if the oxygen deficiency is so severe and prolonged that tissue dies. The brain and kidneys are particularly sensitive.
Complications
As a result of methemoglobinemia, the patient primarily experiences a severely decreased supply of oxygen. This undersupply has a very negative effect on the patient’s overall health and can significantly reduce quality of life. In most cases, the internal organs are also damaged by this undersupply. Those affected also suffer from headaches and fatigue, and in severe cases, methemoglobinemia can also cause respiratory distress. Furthermore, the brain is also damaged by the lack of supply. As the disease progresses, loss of consciousness occurs, possibly leading to injury if a fall occurs. The affected person suffers from a disturbance of consciousness and a blue discoloration of the skin. The ability of the affected person to cope with stress is significantly reduced by methemoglobinemia, so that even the performance of ordinary activities or occupations may be limited. As a rule, methemoglobinemia can be treated relatively easily and quickly, so that in most cases there are no complications or subsequent damage. Complications usually occur when there is no treatment and the deficiency persists for a long period of time. Therefore, life expectancy is also not usually reduced by methemoglobinemia.
When should you see a doctor?
If the affected person suffers from diffuse symptoms that cause a general feeling of malaise or sickness, a physician should be consulted. In case of a gradual increase of symptoms over several months, a medical clarification of the cause is needed. A discoloration of the skin, blue lips or shortness of breath are signs of an existing irregularity that must be investigated and treated. If headaches, dizziness or fatigue occur repeatedly, a visit to the doctor is advisable. A decrease in performance, fatigue or rapid fatigue when performing everyday tasks indicate a health impairment. A doctor should be consulted so that a comprehensive examination can take place. If a disturbance of consciousness develops, there is cause for concern. If there is a loss of consciousness, an emergency physician must be alerted. If left untreated, methemoglobinemia can lead to premature death of the affected person. Therefore, timely medical checks should be performed in case of disturbances of the heart rhythm, an elevated pulse, as well as a feeling of a lack of oxygen in the organism. In case of sleep disturbances, general dysfunction or a loss of well-being, a physician is needed.
Treatment and therapy
The prognosis of methemoglobinemia is usually good. Mild intoxications regress on their own, provided the toxic substance is not further supplied. The basis of this regression is the fact that erythrocytes are constantly being broken down and regenerated in the human body (about two million per second), and the poisoned erythrocytes are replaced along the way. In serious cases of poisoning, therapy consists of oxygen administration and an intravenous supply of solutions with redox dyes such as methylene blue or toluidine blue. In very severe cases, blood transfusion may also be necessary. Another antidote is ascorbic acid (vitamin C). Daily vitamin C administration is the drug of choice for hereditary methemoglobinemias; these are not curable, but can only be alleviated.
Outlook and prognosis
The prognosis of methemoglobinemia is usually favorable. Not all patients require medical management. In some cases, spontaneous recovery occurs, so no further action is needed. If the disease is due to the administration of medications, a change in the prescribed preparations may already contribute to the recovery of methemoglobinemia.However, if a genetic disease is present, the affected person will need drug treatment during the course of his or her life so that an improvement in his or her situation is possible. The therapy helps to optimize the level of methemoglobin in the blood and to meet the needs of the organism. The patient must expect to take part in long-term therapy, otherwise within a few weeks or months there will be a recurrence of symptoms. Without recourse to medical care, the quality of life of the affected person is limited in the case of genetic disease over the entire lifespan. In these cases, the prognosis is worsened due to the discomfort. In acute phases or severe courses of the disease, ultimately only a blood transfusion can lead to relief of the symptoms. Again, it is possible that this measure will have to be resorted to several times in the course of life, as it is only a temporary improvement in health.
Prevention
Methemoglobinemia can be prevented essentially by avoiding exposure to toxic triggers. Infants who are particularly susceptible to methemoglobinemia should not consume foods with high nitrite content.
Follow-up
Follow-up care for methemoglobinemia is similar to preventive measures. Thus, it primarily involves treatment of the causative disease. To minimize the risk in children, parents should be careful not to restrict breathing by mechanical means. Generally, follow-up is based on whether the condition is congenital and resulted from poisoning. Adults over the age of 35 are advised to attend regular check-ups. Through these tests, changes and abnormalities can be noticed early so that prompt therapy can be initiated.
What you can do yourself
In the case of methemoglobinemia, it is usually sufficient to avoid the triggering substance. Patients who regularly take medications should switch to a different drug or reduce the dose in consultation with their physician. If the typical symptoms occur as a result of excessive intake of pickling salt or spinach dishes, a visit to the doctor is also indicated. Those affected should also change their diet and, if symptoms persist, talk to a nutritionist. The individual symptoms must be treated individually. For headaches and fatigue, sleep and gentle sedatives and painkillers from natural medicine can help. Dizziness and confusion can usually be alleviated by exercise in the fresh air. Depending on the intensity of the symptoms, bed rest and sparing are also indicated. If complications occur, methemoglobinemia must be hospitalized in any case. Before treating methemoglobinemia, adequate nutrition and drinking plenty of fluids are important. Otherwise, circulatory shock and symptoms such as fever may occur. After the therapy, the patient should initially rest in bed and take it easy. The doctor in charge can give further advice on how best to overcome the discomfort.
