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Methemoglobinemia: Symptoms, Causes, Diagnosis And Treatment
When there are elevated levels of methemoglobin in the blood, the condition is known as methemoglobinemia [1] . This blood disorder can be acquired or congenital. Hemoglobin is the protein in red blood cells that carry and distribute oxygen to the body [2] . Methemoglobin is a form of hemoglobin. When this disorder exists, hemoglobin can successfully carry oxygen but it cannot release it effectively to body tissues. Read on to know more about this disorder, what causes the acquired and congenital types, its symptoms, diagnosis, treatment options and preventive steps.
What Is Methemoglobinemia?
This blood disorder causes a very little amount of oxygen to be delivered to the body's cells [3] . Under normal conditions, after successfully carrying the oxygen through the bloodstream, hemoglobin would release that oxygen to the cells. But in the case of methemoglobinemia, methemoglobin (a specific form of hemoglobin) carries oxygen through the blood but fails to release it to the cells [4] .
When the body produces too much methemoglobin, it can replace the normal hemoglobin. This can cause reduced levels of oxygen reaching the cells.
Symptoms Of Methemoglobinemia
The major symptoms are as follows [5] :
- Chocolate-brown coloured blood
- Cyanosis (bluish colour of the skin), occurs especially on the lips and fingers [6]
The occurrence of cyanosis has led to this disorder being referred to as 'baby blue syndrome'.
When the level of methemoglobin increases, the symptoms get severe. It can include the following [7] :
- Shortness of breath
- Nausea
- Headache
- Rapid heart rate
- Fatigue and lethargy
- Loss of consciousness
- Confusion
Causes Of Methemoglobinemia
The main two causes of methemoglobinemia are as follows:
- Inherited or congenital - when it is passed down through families [8] . Usually, the parents do not have the condition but carry the gene that results in the condition.
- Acquired - due to exposure to certain medicines or chemicals such as nitrobenzene, antibiotics like chloroquine, anaesthetics like benzocaine and certain foods such as carrots, spinach or beets [9] .
Inherited methemoglobinemia can be of the following types:
1. Type 1: It is also known as erythrocyte reductase deficiency [10] . It happens when RBCs lack the enzyme called cytochrome b5 reductase [11] .
2. Type 2: It is also known as generalized reductase deficiency [12] . It happens when the enzyme called cytochrome b5 reductase does not work in the body.
3. Hemoglobin M disease: This happens when the hemoglobin protein is defective [13] .
Diagnosis Of Methemoglobinemia
Blood tests are done to diagnose the condition. The blood tests are meant to check the level of functional hemoglobin in the blood.
Another method used by the doctor is pulse oximetry [14] . This is used to check the oxygen level of the blood, followed by a blood test that checks the concentration of gases in the blood (arterial blood gas analysis) [15] .
Treatment Of Methemoglobinemia
People with congenital methemoglobinemia, who do not show any symptoms, might not need any treatment as such. Also, mild cases of acquired methemoglobinemia does not require any treatment too. In such cases, the only treatment approach suggested would be avoiding the substance that caused the problem. In severe cases, doctors may prescribe ascorbic acid to reduce the level of methemoglobin in the blood [16] .
Methylene blue is a popular medicine in the treatment of methemoglobinemia. However, it might be unsafe for certain people and the doctor will be the best person to decide if the medicine is safe for consumption or not [17] . In extreme cases, the patient might require a blood transfusion or exchange transfusion. In some cases, if a requirement arises, oxygen therapy [18] is also provided.
Possible Complications Of Methemoglobinemia
Methylene blue is used for the treatment of severe forms of this condition. Use of this can be unsafe for people who have or have the risk of developing a disease known as G6PD deficiency [19] . Severe cases of methemoglobinemia can cause seizures, shock and even death.
Prevention Of Methemoglobinemia
The inherited form of this condition cannot be prevented. People who have a family history of this kind of blood disorder should get genetic counselling from their healthcare practitioner before they begin to plan the start of a family.
The acquired form of this condition can be prevented by avoiding causative factors such as benzocaine. This is usually present in most of the topical sprays that we use and are considered quite harmful. Children who are below the age of 6 months should not be given foods containing nitrates such as beets, carrots and spinach.
- [1] Rehman H. U. (2001). Methemoglobinemia.The Western journal of medicine,175(3), 193–196.
- [2] Stadler, A. M., Digel, I., Artmann, G. M., Embs, J. P., Zaccai, G., & Büldt, G. (2008). Hemoglobin dynamics in red blood cells: correlation to body temperature.Biophysical journal,95(11), 5449–5461.
- [3] Trivedi, D. J., Joshiraj, B., Bidkar, V., & Rao, R. (2017). Methemoglobinemia: Living with Dormant Devil.Indian journal of clinical biochemistry : IJCB,32(2), 248–250.
- [4] Pittman, R. N. (2011, April). Regulation of tissue oxygenation. InColloquium series on integrated systems physiology: from molecule to function(Vol. 3, No. 3, pp. 1-100). Morgan & Claypool Life Sciences.
- [5] Pereira, R. O., & Costa, J. (2008). Methemoglobinemia: from diagnosis to treatment.Revista brasileira de anestesiologia,58(6), 651-664.
- [6] Lundsgaard, C., Van Slyke, D. O. N. A. L. D., & Abbott, M. E. (1923). Cyanosis.Canadian Medical Association Journal,13(8), 601.
- [7] Wright, R. O., Lewander, W. J., & Woolf, A. D. (1999). Methemoglobinemia: etiology, pharmacology, and clinical management.Annals of emergency medicine,34(5), 646-656.
- [8] Scott, E. M. (1960). The relation of diaphorase of human erythrocytes to inheritance of methemoglobinemia.The Journal of clinical investigation,39(7), 1176-1179.
- [9] Ash-Bernal, R., Wise, R., & Wright, S. M. (2004). Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals.Medicine,83(5), 265-273.
- [10] Shirabe, K., Yubisui, T., Borgese, N., Tang, C. Y., Hultquist, D. E., & Takeshita, M. (1992). Enzymatic instability of NADH-cytochrome b5 reductase as a cause of hereditary methemoglobinemia type I (red cell type).Journal of Biological Chemistry,267(28), 20416-20421.
- [11] Spatz, L., & Strittmatter, P. (1973). A form of reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase containing both the catalytic site and an additional hydrophobic membrane-binding segment.Journal of Biological Chemistry,248(3), 793-799.
- [12] Vieira, L. M., Kaplan, J. C., Kahn, A., & Leroux, A. (1995). Four new mutations in the NADH-cytochrome b5 reductase gene from patients with recessive congenital methemoglobinemia type II.Blood,85(8), 2254-2262.
- [13] GERALD, P. S. (1958). The electrophoretic and spectroscopic characterization of Hgb M.Blood,13(10), 936-949.
- [14] Tremper, K. K. (1989). Pulse oximetry.Chest,95(4), 713-715.
- [15] Sood, P., Paul, G., & Puri, S. (2010). Interpretation of arterial blood gas.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine,14(2), 57–64.
- [16] Turner, M. D., Karlis, V., & Glickman, R. S. (2007). The recognition, physiology, and treatment of medication-induced methemoglobinemia: a case report.Anesthesia progress,54(3), 115–117.
- [17] Su, Y. F., Lu, L. H., Hsu, T. H., Chang, S. L., & Lin, R. T. (2012). Successful treatment of methemoglobinemia in an elderly couple with severe cyanosis: two case reports.Journal of medical case reports,6, 290.
- [18] Tibbles, P. M., & Edelsberg, J. S. (1996). Hyperbaric-oxygen therapy.New England Journal of Medicine,334(25), 1642-1648.
- [19] Beutler, E. (1994). G6PD deficiency.Blood,84(11), 3613-3636.
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