PRINCIPLES OF TOXICOLOGY

98 HEMATOTOXICITY: CHEMICALLY INDUCED TOXICITY OF THE BLOOD
the carbon monoxide and oxygen tensions (percentages), respectively, in air. In humans, M is reported
to be anywhere from 210 to 245, demonstrating that carbon monoxide binds to hemoglobin approximately
200 times more avidly than oxygen. To illustrate this further, consider the concentration of
carbon monoxide that is required to decrease hemoglobin oxygenation by 50 percent. First, the
concentrations of carboxyhemoglobin and oxyhemoglobin are equal so that the left side of the equation
becomes one, that is, 50 percent of the blood exists as HbCO and 50 percent exists as HbO 2 . The
equation then simplifies to
[PCO] = [PO2]
M
Since the normal oxygen concentration in air is 21 percent, solving the Haldane equation yields a
carbon monoxide concentration in air of 0.1 percent or approximately 1000 ppm. When equilibrium
is achieved, an individual inhaling 1000 ppm of CO will develop 50 percent carboxyhemoglobin and
a serious hypoxic situation. Compounding this hypoxia is the increased binding affinity of oxygen
caused by carbon monoxide inhibiting the release of oxygen to tissue. The ability of carbon monoxide
to decrease oxygen’s binding to hemoglobin and to increase oxygen’s affinity for hemoglobin is called
the Haldane effect.
Low level background carboxyhemoglobin concentrations of 1.0% or less normally exist in the
blood as a result of porphyrin metabolism. Cigarette smoking increases carboxyhemoglobin concentrations
to as much as 5–10 percent in heavy smokers—two packs per day, for example. If exposure
to carbon monoxide from exogenous sources increases carboxyhemoglobin concentrations to around
20 percent, subjective complaints may be reported. As shown in Table 4.4, the adverse effects of carbon
monoxide are concentration dependant.
Significant hypoxia caused by carboxyhemoglobin has been reported to produce brain injury
resulting in a Parkinson’s disease-like condition, cognitive impairment, and serious neurobehavioral
changes. Some of these neurological sequelae may not be apparent for a number of days or even weeks
following exposure. The more severe neurological effects generally occur in only a few individuals
under circumstances of life-threatening hypoxia. Fortunately, most individuals with mild to moderate
carbon monoxide poisoning experience complete recovery. Recovery is aided by the use of 100%
oxygen or hyperbaric oxygen treatment along with supportive measures.
Assessment of carbon monoxide poisoning is typically performed in the emergency room. However,
significant time may lapse between the exposure, emergency room arrival and the determination
of carboxyhemoglobin. The time between loss of consciousness or serious clinical effects and drawing
TABLE 4.4 Carboxyhemoglobin and Effects
Carboxyhemoglobin (%
Hemoglobin Saturation
with Carbon Monoxide) Effect
0.3–0.7 Background concentrations due to endogenous production of carbon monoxide
1–5 Increase in blood flow via compensating mechanisms such as increased heart rate or
increased contractility (these concentrations are typically observed in cigarette
smokers)
2–9 A reduction in exercise tolerance and an increase in the visual threshold for light
awareness
16–20 Headache; abnormal visual responses
20–30 A throbbing headache accompanied by nausea, vomiting, and a decrease in finemotor
movement
30–40 Severe headaches, nausea, vomiting, and weakness
50+ Coma and convulsions
67–70 Lethal if not aggressively treated