Saturday, March 27, 2021

Carbon Monoxide Poisoning Case File

Posted By: Medical Group - 3/27/2021 Post Author : Medical Group Post Date : Saturday, March 27, 2021 Post Time : 3/27/2021
Carbon Monoxide Poisoning Case File
Eugene C.Toy, MD, William E. Seifert, Jr., PHD, Henry W. Strobel, PHD, Konrad P. Harms, MD

An elderly couple is taken by ambulance to the emergency department after their son noticed that they were both acting “strangely.” The couple had been in good health prior to the weekend. Their son usually visits or calls them daily, but because of a terrible blizzard was not able to make it to their house. They had been snowed in at their house until the snowplows cleared the roads. They had plenty of food and were kept warm by a furnace and blankets. When the son was able to see them for the first time in 2 days, he noticed that they both were complaining of bad headaches, confusion, fatigue, and some nausea. On arrival to the emergency department, both patients were afebrile with normal vital signs and O2 saturation of 99 percent on 2 L of O2 by nasal cannula. Their lips appeared to be very red. Both patients were slightly confused but otherwise oriented. The physical examinations were within normal limits. Carboxyhemoglobin levels were drawn and were elevated.

◆ What is the most likely cause of these patients’ symptoms?

◆ What is the biochemical rationale for 100 percent O2 being the treatment of choice?


Summary: Two elderly patients, with no medical problems present with acute mental status change, fatigue, red lips, and nausea after being snowed in their home during a blizzard with warmth provided by a furnace. The carboxyhemoglobin level is elevated.

◆ Most likely cause: Carbon monoxide poisoning (increase carboxyhemoglobin level).

◆ Rationale for treatment: Administration of 100 percent O2 displaces CO from hemoglobin.

Carbon monoxide, a molecule with one carbon and one O2 atom, binds very avidly to hemoglobin. It is a colorless and odorless gas and may arise from internal combustion engines, fossil-fueled home appliances (heaters, furnaces, stoves), and incomplete combustion of almost all natural and synthetic materials. Because it does not give warning signs, CO is considered a significant hazard. The patient generally has confusion and symptoms of O2 deprivation, but not the symptoms of dyspnea, since the hemoglobin is saturated. The lips are a distinct red color as a result of the hemoglobin being “oxygenated.” However, because CO binds so avidly to the hemoglobin, no transfer of O2 occurs in the peripheral tissue. Carbon monoxide also disrupts the O2-dependent steps of the electron transport chain, leading to unavailability of ATP. Treatment is thus 100 percent O2 to displace the CO from the hemoglobin, and in severe cases, hyperbaric therapy to increase the amount of O2 available to “drive out” the CO.

1. Understand the process by which CO causes symptoms.
2. Know how CO disrupts O2 transport and uncouples the ETC.


Oxidase: An enzyme requiring molecular O2 as a substrate to produce water as a reduced product. In the case of cytochrome oxidase, water is the only product of oxygen reduction. With some other oxidases (called mixed function oxidases), one atom of molecular oxygen is converted to water, whereas the other atom of oxygen may be a hydroxylated product. 
Methemoglobin: Hemoglobin in which the iron atom has been oxidized to the ferric (+3) state and is therefore incapable of binding O2
Carboxyhemoglobin: Hemoglobin that has bound CO is called carboxyhemoglobin. Carbon monoxide binds to hemoglobin with 200 times the affinity of O2.


Carbon monoxide poisoning has two primary effects: interference with Otransport to tissues and interference with the interaction of O2 with cytochromes, especially the cytochromes in the electron transport chain.

The transport of O2 from the lungs to peripheral tissues and central organs is mediated by hemoglobin, a four subunit (2α- and 2β-globin chains) protein. Hemoglobin has four active sites enabling it to bind four molecules of O2 per molecule in the lungs for transport by the red blood cell to distant tissues, where O2 is released for direct use or for binding to other proteins such as muscle myoglobin. Although the globin portion of myoglobin is similar to hemoglobin, it acts as a monomer with only one O2-binding site. The four O2-binding sites of hemoglobin exhibit positive cooperativity in binding O2. The binding of the first molecule of O2 occurs with a modest affinity but causes a conformational change that enhances hemoglobin’s binding affinity for a second molecule of O2. Likewise, the binding of the second enhances the binding affinity for the third and the third, for the fourth molecule of O2.

Carbon monoxide competes with O2 for the four hemoglobin-binding sites, but CO binds 220 times more avidly to hemoglobin than O2. Moreover, CO shows the same positive cooperativity that O2 does. These features combine in favor of CO binding. Atmospheric air is 21 percent O2, whereas the usual CO concentration is 0.1 parts per million (ppm). In heavy traffic, the CO concentration may be 115 ppm. A nearly tenfold increase, up to 1000 ppm (0.1 percent) carbon monoxide, results in a 50 percent carboxyhemoglobinemia. Although the reduction in O2-transport capacity is proportional to the proportion of carboxyhemoglobin [COHb], the amount of O2 available to tissues for use is further reduced by the inhibitory effect of COHb on the dissociation of oxyhemoglobin. Although the average person may show no symptoms at 10 percent of hemoglobin in the form of COHb, any complication such as anemia that reduces O2 transport capacity may exhibit symptoms at a lower percentage of carboxyhemoglobin. At 10 to 20 percent COHb, headache and dilation of cutaneous blood vessels may appear, whereas at 20 to 30 percent, headaches may become stronger. At 30 to 40 percent carboxyhemoglobin, serious headache, dizziness, disorientation, nausea, and vomiting occur. At levels exceeding 40 percent, patients usually collapse and have worsening of other symptoms. These symptoms reflect failure of O2 transport as well as direct inhibition of O2-binding cytochromes such as cytochrome oxidase or myoglobin.

In the electron transport chain (see Figure 16-1 in Case 16) only complex IV (cytochrome oxidase) interacts directly with O2. As with hemoglobin, CO has a higher affinity for cytochrome oxidase than O2. Thus CO binds tightly to cytochrome oxidase and inhibits the transfer to O2. In tightly coupled mitochondria the binding of CO to cytochrome oxidase also results in the inhibition of the phosphorylation of adenosine diphosphate (ADP), reducing the production of adenosine triphosphate (ATP). This becomes more profound as additional molecules of cytochrome oxidase are bound by CO. Similarly, myoglobin also binds CO more avidly than O2, and the transfer of O2 to enzymes requiring O2 is inhibited.

The binding of CO to hemoglobin is fully dissociable, and dissociation requires ventilation. After removal from exposure to CO, administration of O2 reverses CO binding to hemoglobin. Utilization of 100 percent O2 accelerates the washout of CO. Use of hyperbaric chambers with pressures up to 2 atmospheres speeds up the CO washout process even more. Addition of 5 to 7 percent CO2 to the O2 is sometimes used as a prompt to ventilatory exchange. One disadvantage of the addition of CO2 is the serious acidosis that results when the respiratory acidosis produced by CO2 inhalation is added to the metabolic acidosis produced by O2 deprivation in the tissues because of CO poisoning.

An elderly couple living in the suburbs of Hanover, New Hampshire, was snowbound for several days in their home during a blizzard. During periods of electrical outage they relied on an unvented gas heater to warm one room in their home where they stayed throughout the blizzard. As soon as the roads cleared, their granddaughter came to check on them and found them disoriented, complaining of headache, fatigue, and nausea and breathing and walking hesitantly and with a stumbling gait.

[17.1] Laboratory data show a remarkably increased carboxyhemoglobin level in the blood. The best explanation for this finding is that CO has which of the following effects?
A. It increases the hydrogen ion concentration causing oxyhemoglobin to precipitate
B. It changes the valence state of iron in hemoglobin
C. It competitively displaces O2 from oxyhemoglobin
D. It converts myoglobin to carboxyhemoglobin at a rapid rate
E. It prevents transfer of O2 across the alveolar membranes

[17.2] Which of the following treatment strategies is the most effective remediation for CO poisoning?
A. Removal from CO source
B. Removal from CO source and administration of 100 percent O2
C. Administration of 5 to 7 percent CO2 to stimulate respiration followed by 100 percent O2
D. Administration of 5 to 7 percent CO2 to stimulate respiration
E. Removal from CO source and administration of 5 to 7 percent CO2 to stimulate respiration

[17.3] In addition to forming carboxyhemoglobin, the toxic effects of CO include inhibition of which of the following enzymes involved in oxidation-reduction reactions?
A. NADPH dehydrogenase
B. Coenzyme Q reductase
C. Cytochrome c reductase
D. Succinate dehydrogenase
E. Cytochrome oxidase

[17.1] C. Carbon monoxide binds to hemoglobin with 220 times the affinity of O2. Thus CO displaces O2 from oxyhemoglobin to form carboxyhemoglobin. Carbon monoxide has no appreciable effect on pH such as CO2 may have. It does not change the valence state of iron or interfere with O2 transport across membranes. CO binding does not change myoglobin to hemoglobin.

[17.2] B. Removal from the CO is always the first step. Increasing the Oconcentration serves to displace the CO to hemoglobin and cytochrome oxidase. Adding CO2 may stimulate respiration rate, but it also causes an additional pH perturbation.

[17.3] E. Carbon monoxide binds to cytochrome oxidase but not to the other enzymes listed.

❖ Carbon monoxide poisoning interferes with O2 transport to tissues and the interaction of O2 with cytochromes, especially the cytochromes in the electron transport chain (ETC).

❖ The four O2 binding sites of hemoglobin exhibit positive cooperativity in binding O2, leading to the sigmoid shape of hemoglobin dissociation curve.

❖ The binding of the first molecule of O2 occurs with a modest affinity but causes a conformational change that enhances hemoglobin’s binding affinity for a second molecule of O2, and so on.

❖ Carbon monoxide binds 220 times more avidly to hemoglobin than O2.


Devlin TM, ed. Textbook of Biochemistry with Clinical Correlations, 5th ed. New York: Wiley-Liss, 2002:577–82. 

Goodman AG, Gilman LS, eds. The Pharmacological Basis of Therapeutics, 10th ed. New York: McGraw-Hill, 2001.


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