What binds to the hemoglobin (Hb) in red blood cells instead of oxygen in methemoglobinemia?

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Last updated: April 8, 2025 • View editorial policy

From the Research

In methemoglobin, the iron in hemoglobin is oxidized from its normal ferrous (Fe²⁺) state to the ferric (Fe³⁺) state, which prevents oxygen from binding to the red blood cell, and instead, water molecules bind to the ferric iron. This alteration in the hemoglobin molecule renders it unable to carry oxygen effectively, leading to a condition called methemoglobinemia. When methemoglobin levels rise above normal (typically >1% of total hemoglobin), tissues may not receive adequate oxygen, resulting in cyanosis and other symptoms. Methemoglobinemia can be caused by exposure to certain medications or chemicals like nitrates, local anesthetics, and dapsone, or it can be congenital due to enzyme deficiencies, as discussed in a recent study 1.

Pathophysiology and Causes

The pathophysiology of methemoglobinemia involves the oxidation of the iron ion in the heme molecule, which can occur due to various factors, including exposure to oxidizing agents, such as local anesthetics and quinolones, or due to congenital enzyme deficiencies, such as cytochrome b5 reductase deficiency 1, 2. The clinical presentation of methemoglobinemia includes symptoms such as headache, dizziness, nausea, and cyanosis, which can be complicated by severe metabolic disorders leading to death 1.

Diagnosis and Treatment

Diagnosis of methemoglobinemia can be complex, but CO-oximetry is superior to standard pulse oximetry in detecting methemoglobinemia, as noted in a study published in 2020 3. Treatment is mainly based on identifying the etiology and restoring the heme molecule to its physiological state, with methylene blue being the main antidote in cases of elevated methemoglobin levels, although precautions must be taken in its use, especially in patients with G6PD deficiency 1, 2.

Key Points

  • Methemoglobinemia is a condition characterized by the presence of ferric form of hemoglobin in the blood, which cannot bind to oxygen effectively.
  • The condition can be caused by exposure to oxidizing agents, congenital enzyme deficiencies, or other factors.
  • Diagnosis is complex, but CO-oximetry is a useful tool.
  • Treatment involves identifying the etiology and restoring the heme molecule to its physiological state, with methylene blue being a common antidote.

References

Research

[Methemoglobinemia].

La Revue de medecine interne, 2024

Research

Methemoglobinemia.

Journal of education & teaching in emergency medicine, 2022

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