Carbon monoxide, with the chemical formula CO, is a colorless , odorless and tasteless, yet highly toxic gas. Its molecules consist of one carbon atom covalently bonded to one oxygen atom. There are two covalent bonds and a coordinate covalent bond between the oxygen and carbon atoms.
Carbon monoxide is produced from the partial oxidation of carbon-containing compounds, notably in internal-combustion engines. Carbon monoxide forms in preference to the more usual carbon dioxide when there is a reduced availability of oxygen present during the combustion process.
Carbon monoxide is a significantly toxic gas and has no odor or color. It is the most common type of fatal poisoning in many countries.
Exposures can lead to significant toxicity of the central nervous system and heart. Following poisoning, long-term sequelae often occurs. Carbon monoxide can also have severe effects on the fetus of a pregnant woman.
Symptoms of mild poisoning include headaches and dizziness at concentrations less than 100 ppm. Concentrations as low as 667 ppm can cause up to 50% of the body’s haemoglobin to be converted to carboxy-haemoglobin (HbCO).
Carboxy-haemoglobin is quite stable but this change is reversible. Carboxy-haemoglobin is ineffective for delivering oxygen, resulting in some body parts not receiving oxygen needed. As a result, exposures of this level can be life-threatening. In the United States, OSHA limits long-term workplace exposure levels to 50 ppm.
The mechanisms by which carbon monoxide produces toxic effects are not yet fully understood, but haemoglobin, myoglobin, and mitochondrial cytochrome oxidase are thought to be compromised. Treatment largely consists of administering 100% oxygen or hyperbaric oxygen therapy, although the optimum treatment remains controversial. Domestic carbon monoxide poisoning can be prevented by the use of household carbon monoxide detectors.
Physiopathology
The precise mechanisms by which toxic effects are induced by CO are not fully understood. Known mechanisms include carbon monoxide binding to hemoglobin reducing oxygen transportation, binding to myoglobin decreasing its oxygen storage capacity, and binding to mitochondrial cytochrome oxidase inhibiting cellular respiration.
Hemoglobin
Carbon monoxide has a significant affinity to the iron sites in hemoglobin, the principal oxygen-carrying compound in blood. The affinity between hemoglobin and carbon monoxide is about 230 times stronger than the affinity between hemoglobin and oxygen.
CO binds to hemoglobin, producing carboxyhemoglobin (COHb); the traditional belief is that carbon monoxide toxicity arises from the formation of carboxyhemoglobin, which decreases the oxygen-carrying capacity of the blood. This inhibits the transport, delivery, and utilization of oxygen.
Because hemoglobin is a tetramer with four oxygen binding sites, binding of CO at one of these sites also increases the oxygen affinity of the remaining 3 sites, which interferes with normal release of oxygen. This causes hemoglobin to retain oxygen that would otherwise be delivered to the tissue.
Levels of oxygen available for tissue use are decreased. This situation is described as CO shifting the oxygen dissociation curve to the left. Blood oxygen content is actually increased in the case of carbon monoxide poisoning; because all the oxygen is in the blood, none is being given to the tissues, and this causes tissue hypoxic injury. However, despite CO affecting oxygen availability, other mechanisms may contribute to the crucial effects of CO poisoning.
A sufficient exposure to carbon monoxide can reduce the amount of oxygen taken up by the brain to the point that the victim becomes unconscious, and can suffer brain damage or even death from hypoxia. The brain regulates breathing based upon carbon dioxide levels in the blood, rather than oxygen levels, so a victim can succumb to hypoxia without ever noticing anything up to the point of collapse. Hallmark pathological change following CO poisoning is bilateral necrosis of the pallidum.
Hemoglobin acquires a bright red color when converted to carboxyhemoglobin, so a casualty of CO poisoning is described in textbooks as looking pink-cheeked and healthy. However, this "classic" cherry-red appearance is not always seen in living patients. Care should be taken not to overlook the diagnosis even if this color is not present.
Myoglobin
Carbon monoxide also has a high affinity for myoglobin. CO bound to myoglobin may impair cardiac output and result in cerebral ischemia. A delayed return of symptoms has been reported and appears to result following a recurrence of increased carboxyhemoglobin levels; this effect may be due to late release of CO from myoglobin, which subsequently binds to hemoglobin.
Cytochrome oxidase
A second mechanism involves co-effects on the mitochondrial respiratory enzyme chain that is responsible for effective tissue utilization of oxygen. CO does not bind to cytochrome oxidase with the same affinity as oxygen, so it likely requires significant intracellular hypoxia before binding. This binding interferes with aerobic metabolism and efficient adenosine triphosphate (ATP) synthesis. Cells respond by switching to anaerobic metabolism, causing anoxia, lactic acidosis, and eventual cell death.
Other mechanisms
Another mechanism that is thought to have a significant influence on delayed effects involves formed blood cells and chemical mediators, which cause brain lipid peroxidation. CO causes endothelial cell and platelet release of nitric oxide, and the formation of oxygen free radicals including peroxynitrite.
In the brain, this causes further mitochondrial dysfunction, capillary leakage, leukocyte sequestration, and apoptosis. The end result is lipid peroxidation (degradation of unsaturated fatty acids), which causes delayed reversible demyelinization of white matter in the central nervous system, and can lead to edema and focal areas of necrosis within the brain.
This brain damage occurs mainly during the recovery period and results in cognitive defects (especially affecting memory and learning) and movement disorders. The movement disorders are related to a predilection of CO to damage the basal ganglia. These delayed neurological effects may develop over days following the initial acute poisoning.
Pregnancy
Carbon monoxide poisoning can have significant fetal effects. CO causes fetal tissue hypoxia by decreasing the release of maternal oxygen to the fetus, and by carbon monoxide crossing the placenta and combining with fetal hemoglobin, which has a 10 to 15% higher affinity for CO than adult hemoglobin.
Elimination of carbon monoxide is also slower in the fetus, leading to an accumulation of CO. The level of fetal morbidity and mortality in acute carbon monoxide poisoning is significant, so despite maternal wellbeing, severe fetal poisoning can still occur. Due to these effects, pregnant patients are treated with normal or hyperbaric oxygen for longer periods of time than non-pregnant patients.