51 Methemoglobinemia and Other Dyshemoglobinemias Flashcards
Baseline level of methemoglobin
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.
Cyanosis is seen when total methemoglobin exceeds
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.
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
Methemoglobinemia
A term used for modified hemoglobins (eg, methemoglobin, carboxyhemoglobin, nitrosohemoglobin, and sulfhemoglobin) that are associated with normal amino acid sequence of hemoglobin tetramers
Dyshemoglobinemia
The most common cause of acquired methemoglobinemia
- Exposure to nitrites or nitrates found in certain foods (e.g., cured meat) and
- Drugs (e.g., sulfonamides)
Agents causing clinically significant methemoglobinemia
- Sulfonamides, especially dapsone
- Lidocaine, Benzocaine
- Other aniline derivatives
- Nitrites
Bold= most common
TRUE OR FALSE
Chemicals that induce methemoglobinemia may also cause hemolysis, leading to a combination of effects
TRUE
Chemicals that induce methemoglobinemia may also cause hemolysis, leading to a combination of effects
Binds to hemoglobin and prevents spontaneous and oxidant-induced methemoglobin formation
Antioxidant protein 2 (AOP2)
Infants are more susceptible to acquired toxic methemoglobinemia after prototypical ingestion of well water containing nitrites because of low levels of an enzyme:
Cytochrome b5 reductase
Converts methemoglobin to hemoglobin in the newborn period
Presentation of methemoglobinemia in infants
Diarrhea, acidosis, and methemoglobinemia
Methemoglobinemia can occur in acidotic infants with diarrhea, possibly related to soy formula feeding
Chronic methemoglobinemia is usually asymptomatic, but at levels greater than _____ %, mild erythrocytosis is often present.
20%
Treatment and also a cause of methemoglobinemia
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
Enzyme deficiency that leads to methemoglobinemia, and if restricted to erythrocytes, cyanosis is the only phenotype
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.
Cytochrome b5 reductase deficiency is present in all cells (not restricted to erythrocytes) and leads to intellectual disability, developmental defects, and early death
Type II cytochrome b5 reductase
deficiency
Cytochrome b5 reductase deficiency treatment that lowers the methemoglobin level but is of cosmetic benefit only (reduces cyanosis)
Ascorbic acid (200–600 mg/d orally, divided into four doses)
The globins are mutated changing amino acid in hemoglobin tetramers
Resultant cyanosis from methemoglobinemia is inherited as a dominant disorder
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
TRUE OR FALSE
No effective treatment for methemoglobinemia due to hemoglobin M is known.
TRUE
No effective treatment for methemoglobinemia due to hemoglobin M is known.
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
Sulfhemoglobin
0.5 g/dL sulfhemoglobin
Sulfhemoglobinemia is usually well tolerated and does not affect overall health.
Is the most potent initiator of cyanosis, causing a greenish pigment that does not transport oxygen
Sulfhemoglobin
Causes of sulfhemoglobinemia
- Ingestion of various drugs, particularly sulfonamides, phenacetin, acetanilide, and phenazopyridine
- Chronic constipation or purging
- Intestinal Morganella morganii infection
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
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
Sources of acute CO intoxication
- Home appliances
- Weather-related disasters
- Boating activities
Common symptoms of mild to moderate CO poisoning
Irritability, headache, nausea, lethargy, and sometimes a flulike condition
Acute and severe CO poisoning can result in:
Cerebral edema, pulmonary edema, and cardiac arrhythmias that may be deadly, and significant residual neurologic deficits may remain in survivors
Chronic CO intoxication is commonly caused by _________________ , leading to an average percent COHb of 4%, with a usual range of 3–8%
Cigarette smoking
Treatment for CO poisoning
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)
A soluble gas, is continuously synthesized in endothelial cells by isoforms of the NO synthase enzyme
Causes vasodilation
Nitric oxide (NO)
