An elderly couple was brought by ambulance to the emergency department after their daughter noticed that they were both acting “strangely.” The couple had been in good health prior to the weekend. Their daughter had gone out to spend the week-end with her friends.
The couple 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. On reaching home after two days, their daughter 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?
The elderly couple is most probably suffering from CO poisoning. The cause might be the accidental exposure to CO by the burning of the furnace in the closed room. The symptoms, of headache, confusion, fatigue, nausea and red lips are suggestive of CO poisoning. Since the level of carboxy hemoglobin is also high, so the diagnosis is confirmed that the couple is suffering from CO poisoning.
Carbon monoxide (CO) poisoning, one of the most common fatal poisonings, occurs by inhalation. Carbon monoxide is a colorless, odorless gas produced by the combustion of carbon-containing materials. Poisoning may occur as a result of suicidal or accidental exposure to automobile exhaust, smoke inhalation in a fire, or accidental exposure to an improperly vented gas heater or other appliance. Inhaling tobacco smoke results in CO in the blood but not enough to cause poisoning.
Mechanisms of CO toxicity are not completely understood. They appear to involve the following
1) Carbon monoxide avidly binds to hemoglobin, with an affinity approximately 250 times that of oxygen. This results in displacement of O2 from Hb resulting in reduced oxygen-carrying capacity and altered delivery of oxygen to cells.
2) Binding of CO to hemoglobin causes an increased binding of oxygen molecules at the 3 other oxygen-binding sites, resulting in a leftward shift in the oxyhemoglobin dissociation curve and decreasing the availability of oxygen to the already hypoxic tissues.
3) Inhibition of mitochondrial electron transport chain
4) Possibly direct toxic effects on brain tissue
CO binds to cardiac myoglobin with an even greater affinity than to hemoglobin; the resulting myocardial depression and hypotension exacerbates the tissue hypoxia. Toxicity primarily results from cellular hypoxia caused by impedance of oxygen delivery.
The transfer of O2 to enzymes requiring O2 is also inhibited. Several different sites within the body get affected but its most profound impact is on the organs (eg, brain, heart) with the highest oxygen requirement. Following severe intoxication, patients display central nervous system (CNS) pathology, including white matter demyelination.
Inhibition of Electron Transport Chain
CO toxicity causes impaired oxygen delivery and utilization at the cellular level. CO disrupts the O2-dependent step of the electron transport chain, leading to unavailability of ATP. In the electron transport chain, 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 binding of O2 This results in inhibition of electron transport chain with the resultant inhibition of phosphorylation of adenosine diphosphate (ADP), to form adenosine triphosphate (ATP). This becomes more profound as additional molecules of cytochrome oxidase are bound by CO.
Clinical symptoms- Symptoms tend to correlate well with the patient’s peak blood carboxy hemoglobin levels. Many symptoms are nonspecific.
- Headache and nausea can begin when levels are 10 to 20%.
- Levels > 20% commonly cause vague dizziness, generalized weakness, difficulty concentrating, and impaired judgment.
- Levels > 30% commonly cause dyspnea during exertion, chest pain (in patients with coronary artery disease), and confusion.
- Higher levels can cause syncope and seizures,
- Hypotension, coma, respiratory failure, and death may occur, usually when levels are > 60%.
Management- The binding of CO to hemoglobin is fully dissociable, and dissociation requires ventilation. Patients should be removed from the source of CO and stabilized as necessary. They are given 100% O2 and treated supportively.
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.Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!