A 48-year-old woman comes to the emergency department with headache, dizziness, and nausea for the past several hours. She has no fever, nasal congestion, or cough but reports that her husband has also been complaining of headache. The patient has been burning wood in the fireplace to warm her house after losing electricity during a snowstorm. Her temperature is 37 C (98.6 F), blood pressure is 135/70 mm Hg, and pulse is 94/min and regular. Physical examination is unremarkable. The substance responsible for this patient's condition most likely impairs hemoglobin function through which of the following mechanisms?
This patient most likely has carbon monoxide (CO) poisoning, a condition that presents with nonspecific findings ranging from headache and dizziness to convulsions and respiratory arrest depending on concentration and exposure. CO is a colorless, odorless, tasteless gas that is a byproduct of incomplete hydrocarbon combustion. CO poisoning is most often caused by smoke inhalation from a fire or the burning of fuel sources such as wood, coal, or natural gas in poorly ventilated environments.
CO toxicity occurs because of CO's ability to competitively bind iron present in heme proteins. The gas binds to heme iron with a much higher affinity than oxygen, forming carboxyhemoglobin. Even if only 1 of the 4 heme sites is affected, the remaining 3 heme groups have increased oxygen affinity (leftward shift of the oxygen dissociation curve), impeding oxygen delivery to tissues. CO is also capable of binding cardiac myoglobin with high affinity, disrupting the heart's ability to use oxygen and thereby decreasing cardiac output. At a cellular level, CO binds to cytochrome oxidase, inhibiting aerobic metabolism and exacerbating tissue hypoxia.
Treatment for CO poisoning is administration of high-flow or hyperbaric oxygen therapy as this hastens the dissociation of CO from carboxyhemoglobin.
(Choice A) The partial pressure of oxygen (pO2) is a measure of dissolved oxygen in the plasma, the amount of which does not change in CO poisoning.
(Choice C) NADH methemoglobin reductase reduces ferric iron (Fe3+) to ferrous iron (Fe2+), regenerating hemoglobin from methemoglobin. Enzyme deficiency results in congenital methemoglobinemia.
(Choice D) Globin chain denaturation occurs in G6PD-deficient red blood cells when oxidant stressors cause sulfhydryl group cross-linking.
(Choice E) CO reversibly binds hemoglobin at its heme moieties.
(Choice F) Heme consists of an iron bound to protoporphyrin IX. CO binds to iron in metalloproteins but does not cause oxidation of the porphyrin component.
Educational objective:
Carbon monoxide binds heme iron in hemoglobin with an affinity much greater than oxygen, generating carboxyhemoglobin. Remaining binding sites on carboxyhemoglobin have an increased affinity for oxygen that causes the oxygen dissociation curve to shift to the left, impeding oxygen delivery to tissues.