Chapter 19: Methemoglobinemia and Other Dyshemoglobinemias

DEFINITION

• Cyanosis is most frequently caused by low arterial oxygen saturation because of cardiac or pulmonary disease, but rarely, it may be caused by increased concentrations of methemoglobin or sulfhemoglobin, or by abnormal hemoglobins with low oxygen affinity.

METHEMOGLOBINEMIA

Toxic Methemoglobinemia

• Drugs or chemicals may cause methemoglobinemia either by oxidizing hemoglobin directly or by enhancing its oxidization by molecular oxygen.

• Table 19–1 lists common agents that cause methemoglobinemia.

• Infants are more susceptible because of low levels of NADH diaphorase (cytochrome b5 reductase) in the newborn period. A syndrome of diarrhea, acidosis, and methemoglobinuria of yet unexplained etiology occurs in infancy.

• Severe acute methemoglobinemia impairs oxygen delivery, and levels exceeding 50 percent can be fatal.

• Chronic methemoglobinemia is usually asymptomatic, but at levels greater than 20 percent, mild erythrocytosis is often present.

• Treatment with intravenous methylene blue (given at 1 to 2 mg/kg over 5 minutes) is rapidly effective. Excessive amounts of methylene blue, or its use in G-6-PD–deficient patients, can cause acute hemolysis.

Cytochrome b₅ Reductase Deficiency

• Cytochrome b₅ reductase deficiency (also known as NADH diaphorase) catalyzes the reduction of cytochrome b₅, which, in turn, reduces methemoglobin to hemoglobin.

• Hereditary cytochrome b₅ reductase deficiency results in an accumulation of methemoglobin and is inherited as a recessive disorder.

• If restricted to erythrocytes, cyanosis is the only phenotype (type I cytochrome b₅ reductase deficiency). This is seen sporadically in all racial groups but is reported to be endemic in certain native Siberian ethnic groups, Navajo Indians, and Athabascan natives of Alaska.

• In some patients, cells other than erythrocytes may be involved, and a less common hereditary syndrome of cyanosis with mental retardation and other neurologic defects may occur (type II cytochrome b₅ reductase deficiency).

• Methemoglobin levels vary between 8 and 40 percent, and the cytochrome b₅ reductase level is less than 20 percent of normal.

• Treatment with ascorbic acid (200 to 600 mg/d orally, divided into four doses) lowers the methemoglobin level.

• Infants have transiently low levels of cytochrome b₅ reductase and are more likely to develop acute toxic methemoglobinemia.

Cytochrome b₅ Deficiency

• Rarely, cytochrome b₅ itself is deficient, causing the same clinical picture as type II cytochrome b₅ reductase deficiency.

Hemoglobins M

• Some amino acid substitutions in hemoglobin lead to enhanced formation and inability to reduce methemoglobin. These abnormal proteins are termed hemoglobins M and ...