Methemoglobinemia
Basics
Description
Description
- Methemoglobin is a form of hemoglobin containing iron in the oxidized, or ferric (Fe3+), rather than ferrous (Fe2+) state
- Methemoglobin (MetHb):
- Decreases total oxygen-carrying capacity (causing a functional anemia)
- Shifts the hemoglobin–oxygen dissociation curve to the left (impairing O2 release to tissues)
- Is present physiologically and maintained at a level of 1–2% by nicotinamide adenine dinucleotide (NADH)-methemoglobin (cytochrome B5) reductase in red blood cells (RBCs)
- Methemoglobinemia refers to the presence of a supra-physiologic level of methemoglobin (i.e., more than 1–2% of total body hemoglobin); it may be hereditary or acquired
- Symptoms due to methemoglobin:
- Typically occur at a MetHb levels >20%
- Are more serious with coexisting anemia
- Are more severe than those caused by an equivalent degree of anemia
- Reflect both the rate of formation and absolute amount of MetHb
- Hereditary methemoglobinemia is due to
- NADH-methemoglobin (cytochrome B5) reductase deficiency (homozygous or heterozygous)
- Heterozygous hemoglobin M and other abnormal hemoglobins
- Acquired methemoglobinemia results from oxidant stress on RBCs via the following mechanisms:
- Direct oxidation by a methemoglobin-inducing agent (e.g., nitrites)
- Oxidation by N-hydroxylamine producing metabolites
- The formation of methemoglobinemia may be delayed relative to initial substance exposure
- Many methemoglobin-inducing agents also cause Heinz body hemolytic anemia (HA):
- Caused by oxidant injury of RBC proteins
- Glucose-6-phosphate dehydrogenase (G6PD)–deficient patients have higher risk
- Patients with methemoglobinemia should be worked up for HA
- Methemoglobinemia may serve as a marker for genetic abnormalities:
- Heterozygous NADH-methemoglobin (cytochrome B5) reductase deficiency
Etiology
Etiology
- Cyanide (CN) antidote kit:
- Amyl and sodium nitrate induce methemoglobinemia
- CN will complex preferentially with methemoglobin producing cyanomethemoglobin; that complex is subsequently metabolized by rhodanese to thiocyanate which is cleared renally
- Nitrates/nitrites:
- Nitrites (NO2)
- Nitrates (NO3) (e.g., nitroglycerine, via metabolic conversion to nitrites)
- Nitric oxide (NO)
- Dyes:
- Aniline dyes
- Methylene blue (excessive)
- Antiparasitic drugs (high potential for MetHb formation):
- Dapsone
- Primaquine
- Chloroquine
- Local anesthetics (high potential for MetHb formation):
- Benzocaine
- Lidocaine
- Prilocaine
- Analgesics:
- Phenazopyridine (Pyridium)
- Phenacetin
- Antibiotics:
- Nitrofurantoin
- Sulfones
- Sulfonamides
- Others:
- Metoclopramide
- Naphthalene (mothballs)
- Paraquat (herbicide)
- Arsine gas (AsH3)
- Chlorates (ClO4)
- Phenols (e.g., dinitrophenol, hydroquinone)
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Citation
Schaider, Jeffrey J., et al., editors. "Methemoglobinemia." 5-Minute Emergency Consult, 6th ed., Lippincott Williams & Wilkins, 2020. Emergency Central, emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307055/all/Methemoglobinemia.
Methemoglobinemia. In: Schaider JJJ, Barkin RMR, Hayden SRS, et al, eds. 5-Minute Emergency Consult. Lippincott Williams & Wilkins; 2020. https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307055/all/Methemoglobinemia. Accessed December 7, 2024.
Methemoglobinemia. (2020). In Schaider, J. J., Barkin, R. M., Hayden, S. R., Wolfe, R. E., Barkin, A. Z., Shayne, P., & Rosen, P. (Eds.), 5-Minute Emergency Consult (6th ed.). Lippincott Williams & Wilkins. https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307055/all/Methemoglobinemia
Methemoglobinemia [Internet]. In: Schaider JJJ, Barkin RMR, Hayden SRS, Wolfe RER, Barkin AZA, Shayne PP, Rosen PP, editors. 5-Minute Emergency Consult. Lippincott Williams & Wilkins; 2020. [cited 2024 December 07]. Available from: https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307055/all/Methemoglobinemia.
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