Methemoglobin

The structure of the enzyme that converts methemoglobin to hemoglobin^[1]

Methemoglobin (British: methaemoglobin) (pronounced "met-hemoglobin") is a hemoglobin in the form of metalloprotein, in which the iron in the heme group is in the Fe³⁺ (ferric) state, not the Fe²⁺ (ferrous) of normal hemoglobin. Sometimes, it is also referred to as ferrihemoglobin.^[2] Methemoglobin cannot bind oxygen, which means it cannot carry oxygen to tissues. It is bluish chocolate-brown in color. In human blood a trace amount of methemoglobin is normally produced spontaneously, but when present in excess the blood becomes abnormally dark bluish brown. The NADH-dependent enzyme methemoglobin reductase (a type of diaphorase) is responsible for converting methemoglobin back to hemoglobin.

Normally one to two percent of a person's hemoglobin is methemoglobin; a higher percentage than this can be genetic or caused by exposure to various chemicals and depending on the level can cause health problems known as methemoglobinemia. A higher level of methemoglobin will tend to cause a pulse oximeter to read closer to 85% regardless of the true level of oxygen saturation.

Etymology[]

The word methemoglobin derives from the Ancient Greek prefix μετα- (meta-: behind, later, subsequent) and the word hemoglobin:

methemoglobin = meta-hemoglobin.

Other hypothetic similar sounding attributions like methane-, methyl-, or metal- hemoglobin make no sense. While being highly flammable and explosive, methane is a non-toxic gas and does not combine with hemoglobin. In no way, is methemoglobin related to methane poisoning, which in fact simply does not exist.

The name hemoglobin is derived itself from the words heme and globin, reflecting the fact that each subunit of hemoglobin is a globular protein with an embedded heme group. Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces. The most common type of hemoglobin in mammals contains four such subunits.

Common causes of elevated methemoglobin[]

• Reduced cellular defense mechanisms
  • Children younger than 4 months exposed to various environmental agents
  • Pregnant women are considered vulnerable to exposure of high levels of nitrates in drinking water^[3]
  • Cytochrome b5 reductase deficiency
  • G6PD deficiency
  • Pyruvate kinase deficiency
• Various pharmaceutical compounds
  • Local anesthetic agents, especially prilocaine and benzocaine.^[4]
  • Amyl nitrite, chloroquine, dapsone, nitrates, nitrites, nitroglycerin, nitroprusside, phenacetin, phenazopyridine, primaquine, quinones and sulfonamides
• Environmental agents
  • Aromatic amines (e.g. p-nitroaniline, patient case)
  • Arsine
  • Chlorobenzene
  • Chromates
  • Nitrates/nitrites^[5]
• Inherited disorders
  • Some family members of the Fugate family in Kentucky, due to a recessive gene, had blue skin from an excess of methemoglobin.^[6]
• In cats
  • Ingestion of paracetamol (i.e. acetaminophen, tylenol)^[7]

Therapeutic uses[]

Amyl nitrite is administered to treat cyanide poisoning. It works by converting hemoglobin to methemoglobin, which allows for the binding of cyanide (CN^–) anions by ferric (Fe³⁺) cations and the formation of . The immediate goal of forming this cyanide adduct is to prevent the binding of free cyanide to the cytochrome a₃ group in cytochrome c oxidase.^[8]

Methemoglobin saturation[]

Methemoglobin is expressed as a concentration or a percentage. Percentage of methemoglobin is calculated by dividing the concentration of methemoglobin by the concentration of total hemoglobin. Percentage of methemoglobin is likely a better indicator of illness severity than overall concentration, as underlying medical conditions play an important role. For example, a methemoglobin concentration of 1.5 g/dL may represent a percentage of 10% in an otherwise healthy patient with a baseline hemoglobin of 15 mg/dL, whereas the presence of the same concentration of 1.5 g/dL of methemoglobin in an anemic patient with a baseline hemoglobin of 8 g/dL would represent a percentage of 18.75%. The former patient will be left with a functional hemoglobin concentration of 13.5 g/dL and potentially remain asymptomatic while the latter patient with a functional hemoglobin concentration 6.5 g/dL may be severely symptomatic with a methemoglobin of less than 20%.^[9]

• 1-2% Normal
• Less than 10% metHb - No symptoms
• 10-20% metHb - Skin discoloration only (most notably on mucous membranes)
• 20-30% metHb - Anxiety, headache, dyspnea on exertion
• 30-50% metHb - Fatigue, confusion, dizziness, tachypnea, palpitations
• 50-70% metHb - Coma, seizures, arrhythmias, acidosis
• Greater than 70% metHb - High risk of death^[5]

This may be further compounded by the "functional hemoglobin's" decreased ability to release oxygen in the presence of methemoglobin. Anemia, congestive heart failure, chronic obstructive pulmonary disease, and essentially any pathology that impairs the ability to deliver oxygen may worsen the symptoms of methemoglobinemia.^[9]

Blood stains[]

Increased levels of methemoglobin are found in blood stains. Upon exiting the body, bloodstains transit from bright red to dark brown, which is attributed to oxidation of oxy-hemoglobin (HbO₂) to methemoglobin (met-Hb) and hemichrome (HC).^[10]

See also[]

• Blue baby syndrome
• Carboxyhemoglobin
• Methemoglobinemia

References[]

External links[]

• Methemoglobin at the US National Library of Medicine Medical Subject Headings (MeSH)
• MetHb Formation
• The Blue people of Troublesome Creek