PRINCIPLES OF TOXICOLOGY - Biology East Borneo

98 HEMATOTOXICITY: CHEMICALLY INDUCED TOXICITY OF THE BLOODthe carbon monoxide and oxygen tensions (percentages), respectively, in air. In humans, M is reportedto be anywhere from 210 to 245, demonstrating that carbon monoxide binds to hemoglobin approximately200 times more avidly than oxygen. To illustrate this further, consider the concentration ofcarbon monoxide that is required to decrease hemoglobin oxygenation by 50 percent. First, theconcentrations of carboxyhemoglobin and oxyhemoglobin are equal so that the left side of the equationbecomes one, that is, 50 percent of the blood exists as HbCO and 50 percent exists as HbO 2. Theequation then simplifies to[P CO ] = [P O 2]MSince the normal oxygen concentration in air is 21 percent, solving the Haldane equation yields acarbon monoxide concentration in air of 0.1 percent or approximately 1000 ppm. When equilibriumis achieved, an individual inhaling 1000 ppm of CO will develop 50 percent carboxyhemoglobin anda serious hypoxic situation. Compounding this hypoxia is the increased binding affinity of oxygencaused by carbon monoxide inhibiting the release of oxygen to tissue. The ability of carbon monoxideto decrease oxygen’s binding to hemoglobin and to increase oxygen’s affinity for hemoglobin is calledthe Haldane effect.Low level background carboxyhemoglobin concentrations of 1.0% or less normally exist in theblood as a result of porphyrin metabolism. Cigarette smoking increases carboxyhemoglobin concentrationsto as much as 5–10 percent in heavy smokers—two packs per day, for example. If exposureto carbon monoxide from exogenous sources increases carboxyhemoglobin concentrations to around20 percent, subjective complaints may be reported. As shown in Table 4.4, the adverse effects of carbonmonoxide are concentration dependant.Significant hypoxia caused by carboxyhemoglobin has been reported to produce brain injuryresulting in a Parkinson’s disease-like condition, cognitive impairment, and serious neurobehavioralchanges. Some of these neurological sequelae may not be apparent for a number of days or even weeksfollowing exposure. The more severe neurological effects generally occur in only a few individualsunder circumstances of life-threatening hypoxia. Fortunately, most individuals with mild to moderatecarbon 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 determinationof carboxyhemoglobin. The time between loss of consciousness or serious clinical effects and drawingTABLE 4.4 Carboxyhemoglobin and EffectsCarboxyhemoglobin (%Hemoglobin Saturationwith Carbon Monoxide)Effect0.3–0.7 Background concentrations due to endogenous production of carbon monoxide1–5 Increase in blood flow via compensating mechanisms such as increased heart rate orincreased contractility (these concentrations are typically observed in cigarettesmokers)2–9 A reduction in exercise tolerance and an increase in the visual threshold for lightawareness16–20 Headache; abnormal visual responses20–30 A throbbing headache accompanied by nausea, vomiting, and a decrease in finemotormovement30–40 Severe headaches, nausea, vomiting, and weakness50+ Coma and convulsions67–70 Lethal if not aggressively treated