A 34-year-old industry worker experiences rapid-onset shortness of breath, dizziness, palpitations, and flushed skin after accidental exposure to chemical fumes. Examination by an occupational physician shows that the patient is tachypneic and has a reddish discoloration of the skin without cyanosis. The patient is immediately instructed to inhale amyl nitrite from the safety kit. The success of this antidote is dependent upon its ability to convert hemoglobin into a form with increased affinity for which of the following substances?

Question

A 34-year-old industry worker experiences rapid-onset shortness of breath, dizziness, palpitations, and flushed skin after accidental exposure to chemical fumes.  Examination by an occupational physician shows that the patient is tachypneic and has a reddish discoloration of the skin without cyanosis.  The patient is immediately instructed to inhale amyl nitrite from the safety kit.  The success of this antidote is dependent upon its ability to convert hemoglobin into a form with increased affinity for which of the following substances?

Quizplus · Accepted Answer

11ec160b_36e1_0386_9249_bb573615ee34_MD0001_00 The toxicity of cyanide is dependent upon its ability to bind ferric iron (Fe³⁺) with high affinity, inhibiting cytochrome c oxidase in the mitochondria. This electron transport chain enzyme is essential for oxidative phosphorylation; inhibition results in severe lactic acidosis and death as a result of cells switching to anaerobic metabolism. Cyanide poisoning presents with reddish skin discoloration, tachypnea, headache, and tachycardia, often accompanied by nausea/vomiting, confusion, and weakness. Symptoms develop rapidly and can quickly progress to seizures and cardiovascular collapse. Laboratory studies indicate severe lactic acidosis in conjunction with a narrowing of the venous-arterial PO₂ gradient, resulting from the inability of tissue to extract arterial oxygen. Administration of inhaled amyl nitrite oxidizes ferrous iron (Fe²⁺) present in hemoglobin to ferric iron (Fe³⁺), generating methemoglobin. Methemoglobin is incapable of carrying oxygen but has a high affinity for cyanide; it binds and sequesters cyanide in the blood, freeing it from cytochrome oxidase and limiting its toxic effects. Hydroxycobalamin, a vitamin B₁₂ precursor, and sodium thiosulfate are also antidotes for cyanide poisoning. Their interactions with cyanide generate relatively nontoxic metabolites that are easily excreted in the urine. (Choices A and B) The presence of 2,3-biphosphoglycerate causes a right shift in the oxygen-hemoglobin dissociation curve, decreasing hemoglobin's affinity for oxygen and increasing its affinity for carbon dioxide. (Choice C) Hemoglobin has a much higher affinity for carbon monoxide than it does for oxygen. This is the basis for carbon monoxide poisoning, which is treated with high-flow oxygen. (Choice E) The affinity of hemoglobin for iron is not affected by nitrite administration, although nitrites do oxidize the heme iron to its Fe³⁺ state. (Choice F) Lead poisoning causes defective heme synthesis. If lead is acutely ingested, chelation therapy with dimercaprol or edetate disodium calcium (CaNa₂EDTA) should be initiated. Educational objective: Nitrites are oxidizing agents that are effective in treating cyanide poisoning due to their ability to induce methemoglobinemia. Methemoglobin contains ferric (Fe³⁺) rather than ferrous iron (Fe²⁺). Cyanide binds to ferric iron more avidly than to mitochondrial cytochrome enzymes, diminishing cyanide's toxic effect.

A 34-Year-Old Industry Worker Experiences Rapid-Onset Shortness of Breath, Dizziness