Methemoglobinemia

Basics

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

  • 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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