Methemoglobinemia

Descriptive text is not available for this imageBASICS

DESCRIPTION

  • Methemoglobin (MetHb) is a form of dysfunctional hemoglobin that has been oxidized from the ferrous (Fe2+) to the ferric state (Fe3+).
  • An accumulation of MetHb will hinder the ability to carry and deliver oxygen to tissues.

EPIDEMIOLOGY

  • Exposure to oxidizing chemicals or toxins is the most common cause of methemoglobinemia.
  • In infants <6 months of age, acute diarrheal illness is a common cause.
  • Congenital methemoglobinemia is rare, and true incidence and prevalence are unknown.

ETIOLOGY

  • Toxic methemoglobinemia
    • Exogenous
      • Medications: dapsone, antimalarials, topical anesthetics, nitric oxide, nitroglycerin, sulfonamides
      • Chemicals: aniline, aniline dyes, antifreeze, benzenes, hydrogen peroxide, nitrates/nitrites, chlorates/chromates
  • Enteritis-associated methemoglobinemia
    • Mechanism is not fully understood but is hypothesized to be caused by increased enteric nitrite production and immature cytochrome b5 MetHb reductase (Cyb5R) enzyme function in infants.
  • Congenital methemoglobinemia
    • Cyb5R deficiency is an autosomal recessive mutation in the CYB5R3 gene, leading to chronic cyanosis.
    • Hemoglobin M disease is caused by genetic variants in the globin gene, producing heme that is resistant to reduction.

PATHOPHYSIOLOGY

  • MetHb makes up about 1% of total hemoglobin and is formed via auto-oxidation, reactions with free radicals, and exposure to exogenous chemicals.
  • Ferric heme of MetHb cannot bind oxygen and causes normal ferrous heme to bind more tightly to oxygen, leading to a functional anemia.
  • In normal RBC metabolism, MetHb is reduced by the enzyme Cyb5R.
  • Increase in MetHb production or decrease in its reduction will disrupt the equilibrium, leading to clinically significant methemoglobinemia.
  • Reduced nicotinamide adenine dinucleotide phosphate (NADPH) MetHb reductase is a normally inactive enzymatic pathway that can be activated by therapeutics like methylene blue (MB).

COMMONLY ASSOCIATED CONDITIONS

  • Heinz body hemolytic anemia
    • Oxidant stress on the globin protein may cause hemolysis and subsequent formation of MetHb.
  • Sulfhemoglobinemia
    • Oxidant stress on the hemoglobin porphyrin ring may cause sulfhemoglobinemia, clinically similar to methemoglobinemia but does not respond to MB therapy.

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