Carbon monoxide remains a deadly threat every winter, especially in northern climes where people of limited means try to keep warm by using unvented kerosene heaters or similar heating elements. How does hemoglobin, designed to carry oxygen, get deceived into carrying a payload of carbon monoxide instead? And are there any therapeutic benefits to moderate amounts of carbon monoxide (CO)? How much is a threat to life, and how much is a level that delivers benefits?
First, a description of the oxygen and carbon monoxide molecules. Found as O2, the two oxygen molecules are chemically bound to each other, with each one carrying two electrons in the first level and six in the second level. The most common O2 isotope has 16 total electrons. It is typically pictured as a barbell but is actually more like a widely-spread Vee. The carbon monoxide molecule, CO, looks very similar, shaped like a barbell with one oxygen molecule and one carbon molecule. The barbell has a negative charge on the carbon end, a result of the greater electron density. The carbon atom has just six electrons, two in the lower level and four in the upper level.
The hemoglobin molecule is a protein made of four chains of amino acid; each one contains the iron-containing heme which is supposed to bind with a molecule of oxygen (O2). A single red blood cell, containing 250 million hemoglobins, can theoretically carry a full payload of one billion oxygen molecules. The bond between the heme and the O2 is easily broken, to allow the O2 to be released promptly to low-oxygen tissues. However, carbon monoxide (CO) not only binds at the same sites but does so more tightly, exhibiting a COVALENT bond (Cohen B. 2005).
It is said that hemoglobin has a 200x greater affinity for CO over O2 (Health Central.com, 2005-2008); incidentally, hemoglobin (Heme Fe, made of one atom of iron and ) will also bind with other noxious gases that have small molecules with structures similar to O2, most commonly NO and H2S (EdInformatics.com, 1999). The greater affinity is due to CO binding with the hemoglobin to form a new molecule, carboxyhemoglobin (COHb), which in turn displaces oxygen and leads to tissue hypoxia.
The symptoms of carbon monoxide poisoning are nonspecific and include headache, dizziness, and confusion. One needs to examine a blood sample for the presence of carboxyhemoglobin (COHb). In the case of voluntary exposure to cigarette smoke, ie smoking tobacco, the COHb will be paired with equivalent CO in exhalate, (COex) and thiocyanate (SCN) in body fluids. (Scherer G. 2006). “Cigarette smokers increase their carboxyhemoglobin level by an average of 5% per pack smoked per day, and otherwise healthy smokers tolerate carboxyhemoglobin levels of 10% without having symptoms. Overt signs of toxic effects usually appear at carboxyhemoglobin levels of 15 -20%, and a level of 25% is an index of severe poisoning, which may lead to sudden loss of consciousness” (Piantadosi C. 2002).
“Carbon monoxide poisoning is an example of anemic hypoxia where the arterial oxygen tension remains near normal until substantial blood concentrations of carboxyhemoglobin are reached. Thus, there are no signs of respiratory distress, such as dyspnea. Instead, in response to a slowly developing hypoxia, the body initiates widespread peripheral vasodilation. In order to compensate for the increased volume of the vascular space, there must be an increased cardiac output. The cardiac output cannot increase indefinitely, and eventually the victim may faint” (Dartmouth.edu, undated).
A peculiarity of CO poisoning is that the symptoms seldom match the levels found by objective blood analysis. The levels of CO bound to blood hemoglobin and the levels of CO bound to internal tissues can differ widely, depending on activity level and number of hours elapsed since exposure.
Concentrations as low as 667 ppm can cause up to 50% of the body's hemoglobin to be converted to carboxy-haemoglobin (HbCO). In the U.S., OSHA limits long-term workplace exposure levels to 50 ppm. At 200 ppm, victims may suffer a light headache within 2-3 hours. At 400 ppm, victims usually feel a frontal headache within 1-2 hours, becoming widespread in 3 hours. At 800 ppm, victims suffer dizziness, nausea, convulsions within 45 minutes, insensible in 2 hours (CarbonMonoxideKills.com 2007).
So in conclusion, not only does the oxygen in the CO molecule have a covalent bond with the nitrogen, making it harder for the body’s cells to wrestle the oxygen away, the CO molecule has a covalent bond with the hemoglobin, making it harder for the hemoglobin to dump this toxic payload and get an O2 molecule. The CO remains bound to the hemoglobin often for the life of the red blood cell, unless medical attention is rendered.
Treatment varies from simply airing out a house and moving the patient to fresh air, to application of facemask hooked up to an oxygen tank, to hyperbaric oxygen therapy if treatment begins within 6-12 hours of exposure (Piantadosi C. 2002). Ironically, carbon monoxide has been tested as a treatment for ventilator-induced lung injury, for its anti-inflammatory effect on lung tissue. The best treatment for CO poisoning is still prevention because no oxygen treatment can fully reverse the cell death from hypoxia or anoxia.
CarbonMonoxideKills.com, Carbon Monoxide Kills, 2007.
Cohen, Barbara Janson, Memmler’s The Human Body in Health and Disease, Lippincott Williams & Wilkins, 2005.
Dartmouth.edu, Oxygen Transport, “A Woman With A Headache” Addendum, http://www.dartmouth.edu/~rpsmith/Oxygen_Transport.html, 1996.
Dolinay, T.et al, Inhaled Carbon Monoxide Confers Antiinflammatory Effects against Ventilator-induced Lung Injury, American Journal of Respiratory and Critical Care Medicine, Sept. 2004.
EdInformatics.com, Why is Carbon Monoxide so Dangerous?, The Interactive Library, http://www.edinformatics.com/interactive_molecules/carbon_monoxide.htm, 1999.
HealthCentral.com, Hemoglobin Derivatives, http://www.healthcentral.com/ency/408/003371.html, 2005-2008.
Organic Chemistry at Penn State, Carbon Monoxide, http://courses.chem.psu.edu/chem210/mol-gallery/co/co.html, 1997-2008.
Piantadosi, M.D., Claude A., (2002), Carbon Monoxide Poisoning, Duke University Medical Center, medical-journals.com, 347:1054-1055.
Scherer G., (2006), Carboxyhemoglobin and thiocyanate as biomarkers of exposure to carbon monoxide and hydrogen cyanide in tobacco smoke, Experimental and Toxicologic Pathology, 58:101-124.
University of Victoria online library, Molecular Orbital Diagram for CO including s,p mixing, http://web.uvic.ca/~djberg/chem222/Handout3.pdf, undated.