51 Methemoglobinemia and Other Dyshemoglobinemias

Question 1

Baseline level of methemoglobin

Answer 1

Less than 1%

Increased methemoglobin from a baseline of less than 1% occurs due to oxidation of ferro to ferric iron of hemoglobin due to environmental agents or due to underlying germline mutations causing diminished reduction of methemoglobin to hemoglobin.

Question 2

Cyanosis is seen when total methemoglobin exceeds

Answer 2

15 g/L

1.5–2.0 g/dL methemoglobin

Thus, at 10% of methemoglobin, those with hemoglobin concentrations above 150 g/L would have cyanosis, whereas those with hemoglobin below 150 g/L would not.

Question 3

A patient with cyanosis whose arterial blood is brown with a SpO2 that is found to be normal on blood gas examination is likely to have

Answer 3

Methemoglobinemia

Question 4

A term used for modified hemoglobins (eg, methemoglobin, carboxyhemoglobin, nitrosohemoglobin, and sulfhemoglobin) that are associated with normal amino acid sequence of hemoglobin tetramers

Answer 4

Dyshemoglobinemia

Question 5

The most common cause of acquired methemoglobinemia

Answer 5

• Exposure to nitrites or nitrates found in certain foods (e.g., cured meat) and
• Drugs (e.g., sulfonamides)

Question 6

Agents causing clinically significant methemoglobinemia

Answer 6

• Sulfonamides, especially dapsone
• Lidocaine, Benzocaine
• Other aniline derivatives
• Nitrites

Bold= most common

Question 7

TRUE OR FALSE

Chemicals that induce methemoglobinemia may also cause hemolysis, leading to a combination of effects

Answer 7

TRUE

Chemicals that induce methemoglobinemia may also cause hemolysis, leading to a combination of effects

Question 8

Binds to hemoglobin and prevents spontaneous and oxidant-induced methemoglobin formation

Answer 8

Antioxidant protein 2 (AOP2)

Question 9

Infants are more susceptible to acquired toxic methemoglobinemia after prototypical ingestion of well water containing nitrites because of low levels of an enzyme:

Answer 9

Cytochrome b5 reductase

Converts methemoglobin to hemoglobin in the newborn period

Question 10

Presentation of methemoglobinemia in infants

Answer 10

Diarrhea, acidosis, and methemoglobinemia

Methemoglobinemia can occur in acidotic infants with diarrhea, possibly related to soy formula feeding

Question 11

Chronic methemoglobinemia is usually asymptomatic, but at levels greater than _____ %, mild erythrocytosis is often present.

Answer 11

20%

Question 12

Treatment and also a cause of methemoglobinemia

Answer 12

Intravenous methylene blue (given at 1–2 mg/kg over 5 minutes)

• Excessive amounts of methylene blue or its use in patients with glucose-6-phosphate dehydrogenase deficiency can cause acute hemolysis. (AA sa G6PD)
• Ascorbic acid (300–600 mg orally) can also be beneficial
• Blood transfusion may be helpful in patients in shock
• Cimetidine may decrease the methemoglobinemia produced by dapsone

Question 13

Enzyme deficiency that leads to methemoglobinemia, and if restricted to erythrocytes, cyanosis is the only phenotype

Answer 13

Cytochrome b5 reductase deficiency- Homozygosity or compound heterozygosity

Type I cytochrome b5 reductase deficiency

Heterozygosity for cytochrome b5 reductase deficiency is usually not clinically significant but may predispose to toxic methemoglobinemia.

Question 14

Cytochrome b5 reductase deficiency is present in all cells (not restricted to erythrocytes) and leads to intellectual disability, developmental defects, and early death

Answer 14

Type II cytochrome b5 reductase
deficiency

Question 15

Cytochrome b5 reductase deficiency treatment that lowers the methemoglobin level but is of cosmetic benefit only (reduces cyanosis)

Answer 15

Ascorbic acid (200–600 mg/d orally, divided into four doses)

Question 16

The globins are mutated changing amino acid in hemoglobin tetramers

Resultant cyanosis from methemoglobinemia is inherited as a dominant disorder

Answer 16

M hemoglobins

• Cyanosis may be evident at birth in hemoglobin M disease with the α-chain mutant
• β-chain variant, this will evolve over 6 to 9 weeks after birth as γ-globin chains (fetal hemoglobin) are replaced by β chains
• Four Hb M variants are named after the geographic locations where they were first described: Boston, Saskatoon, Iwate, and Hyde Park

Question 17

TRUE OR FALSE

No effective treatment for methemoglobinemia due to hemoglobin M is known.

Answer 17

TRUE

No effective treatment for methemoglobinemia due to hemoglobin M is known.

Question 18

Produced by addition of hydrogen sulfide to hemoglobin

Cyanosis is present, and occasionally mild hemolysis occurs.

Unlike methemoglobin and carboxyhemoglobin, cannot be converted back to normal hemoglobin

Answer 18

Sulfhemoglobin

0.5 g/dL sulfhemoglobin

Sulfhemoglobinemia is usually well tolerated and does not affect overall health.

Question 19

Is the most potent initiator of cyanosis, causing a greenish pigment that does not transport oxygen

Answer 19

Sulfhemoglobin

Question 20

Causes of sulfhemoglobinemia

Answer 20

• Ingestion of various drugs, particularly sulfonamides, phenacetin, acetanilide, and phenazopyridine
• Chronic constipation or purging
• Intestinal Morganella morganii infection

Question 21

Toxic, odorless, colorless, and tasteless gas that binds with high affinity to Hb, generating COHb

One of the most common causes of morbidity as a result of poisoning in the United States

Answer 21

Carbon monoxide (CO)

Normal adult level of COHb is less than 1.5%

Higher index of suspicion should attend the simultaneous presentation of multiple patients from the same family or housing complex

Question 22

Sources of acute CO intoxication

Answer 22

• Home appliances
• Weather-related disasters
• Boating activities

Question 23

Common symptoms of mild to moderate CO poisoning

Answer 23

Irritability, headache, nausea, lethargy, and sometimes a flulike condition

Question 24

Acute and severe CO poisoning can result in:

Answer 24

Cerebral edema, pulmonary edema, and cardiac arrhythmias that may be deadly, and significant residual neurologic deficits may remain in survivors

Question 25

Chronic CO intoxication is commonly caused by _________________ , leading to an average percent COHb of 4%, with a usual range of 3–8%

Answer 25

Cigarette smoking

Question 26

Treatment for CO poisoning

Answer 26

Prompt removal of patients from the source of CO (for mild to moderate cases of CO poisoning) followed by administering 100% supplemental oxygen via a tight-fitting mask (in severe cases of CO poisoning)

Question 27

A soluble gas, is continuously synthesized in endothelial cells by isoforms of the NO synthase enzyme

Causes vasodilation

Answer 27

Nitric oxide (NO)