The precise mechanisms by which the effects of<unk><unk>  are induced upon bodily systems are complex and not yet fully understood. Known mechanisms include<unk><unk>  binding to hemoglobin, myoglobin and mitochondrial cytochrome c oxidase and restricting oxygen supply, and<unk><unk>  causing brain lipid peroxidation. Hemoglobin<unk><unk>  has a higher diffusion coefficient compared to oxygen, and the main enzyme in the human body that produces<unk><unk>  is heme oxygenase, which is located in nearly all cells and platelets. Most endogenously produced CO is stored bound to hemoglobin as<unk> yhemoglobin. The simplistic understanding for the mechanism of<unk><unk>  toxicity is based on excess<unk> yhemoglobin decreasing the oxygen-delivery capacity of the blood to tissues throughout the body. In humans, the affinity between hemoglobin and<unk><unk>  is approximately 240 times stronger than the affinity between hemoglobin and oxygen. However, certain mutations such as the Hb-Kirklareli mutation has a relative 80,000 times greater affinity for<unk><unk>  than oxygen resulting in systemic<unk> yhemoglobin reaching a sustained level of 16% COHb. Hemoglobin is a tetramer with four prosthetic heme groups to serve as oxygen binding sites. The average red blood cell contains 250 million hemoglobin molecules, therefore 1 billion heme sites capable of binding gas. The binding of<unk><unk>  at any one of these sites increases the oxygen affinity of the remaining three sites, which causes the hemoglobin molecule to retain oxygen that would otherwise be delivered to the tissue; therefore<unk><unk>  binding at any site may be as dangerous as<unk><unk>  binding to all sites. Delivery of oxygen is largely driven by the Bohr effect and Haldane effect. To provide a simplified synopsis of the molecular mechanism of systemic gas exchange in layman's terms, upon inhalation of air it was widely thought oxygen binding to any of the heme sites triggers a conformational change in the globin/protein unit of hemoglobin which then enables the binding of additional oxygen to each of the other vacant heme sites. Upon arrival to the cell/tissues, oxygen release into the tissue is driven by "acidification" of the local pH (meaning a relatively higher concentration of 'acidic' protons/hydrogen ions) caused by an increase in the biotransformation of<unk>  dioxide waste into<unk> ic acid via<unk> ic anhydrase. In other words, oxygenated arterial blood arrives at cells in the "hemoglobin R-state" which has deprotonated/unionized amino acid residues (regarding nitrogen/amines) due to the less-acidic arterial pH environment (arterial blood averages pH 7.407 whereas venous blood is slightly more acidic at pH 7.371). The "T-state" of hemoglobin is deoxygenated in venous blood partially due to protonation/ionization caused by the acidic environment hence causing a conformation unsuited for oxygen-binding (in other words, oxygen is 'ejected' upon arrival to the cell because acid "attacks" the amines of hemoglobin causing ionization/protonation of the amine residues resulting in a conformation change unsuited for retaining oxygen). Furthermore, the mechanism for formation of carbaminohemoglobin generates additional 'acidic' hydrogen ions that may further stabilize the protonated/ionized deoxygenated hemoglobin. Upon return of venous blood into the lung and subsequent exhalation of<unk>  dioxide, the blood is "de-acidified" (see also: hyperventilation) allowing for the deprotonation/unionization of hemoglobin to then re-enable oxygen-binding as part of the transition to arterial blood (note this process is complex due to involvement of chemoreceptors and other physiological functionalities).<unk><unk>  is not 'ejected' due to acid, therefore<unk>  disturbs this physiological process hence the venous blood of poisoning patients is bright red akin to arterial blood since the<unk> yl/carbon<unk>  is retained. Hemoglobin is dark in deoxygenated venous blood, but it has a bright red color when carrying blood in oxygenated arterial blood and when converted into<unk> yhemoglobin in both arterial and venous blood, so poisoned cadavers and even commercial meats treated with<unk><unk>  acquire an unnatural lively reddish hue. At toxic concentrations,<unk><unk>  as<unk> yhemoglobin significantly interferes with respiration and gas exchange by simultaneously inhibiting acquisition and delivery of oxygen to cells and preventing formation of carbaminohemoglobin which accounts for approximately 30% of<unk>  dioxide exportation. Therefore a patient suffering from<unk>  may experience severe hypoxia and acidosis (potentially both respiratory acidosis and metabolic acidosis) in addition to the toxicities of excess<unk><unk>  inhibiting numerous hemoproteins, metallic and non-metallic targets which affect cellular machinery. Myoglobin<unk><unk>  also binds to the hemeprotein myoglobin. It has a high affinity for myoglobin, about 60 times greater than that of oxygen.<unk><unk>  bound to myoglobin may impair its ability to utilize oxygen. This causes reduced cardiac output and hypotension, which may result in brain ischemia. A delayed return of symptoms have been reported. This results following a recurrence of increased<unk> yhemoglobin levels; this effect may be due to a late release of<unk><unk>  from myoglobin, which subsequently binds to hemoglobin. Cytochrome oxidase Another mechanism involves effects on the mitochondrial respiratory enzyme chain that is responsible for effective tissue utilization of oxygen.<unk><unk>  binds to cytochrome oxidase with less affinity than oxygen, so it is possible that it requires significant intracellular hypoxia before binding. This binding interferes with aerobic metabolism and efficient adenosine triphosphate synthesis. Cells respond by switching to anaerobic metabolism, causing anoxia, lactic acidosis, and eventual cell death. The rate of dissociation between<unk><unk>  and cytochrome oxidase is slow, causing a relatively prolonged impairment of oxidative metabolism. Central nervous system effects The mechanism that is thought to have a significant influence on delayed effects involves formed blood cells and chemical mediators, which cause brain lipid peroxidation (degradation of unsaturated fatty acids).<unk><unk>  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 result of these effects is lipid peroxidation, which causes delayed reversible demyelination of white matter in the central nervous system known as Grinker myelinopathy, which can lead to edema and necrosis within the brain. This brain damage occurs mainly during the recovery period. This may result in cognitive defects, especially affecting memory and learning, and movement disorders. These disorders are typically related to damage to the cerebral white matter and basal ganglia. Hallmark pathological changes following poisoning are bilateral necrosis of the white matter, globus pallidus, cerebellum, hippocampus and the cerebral cortex. Pregnancy<unk>  in pregnant women may cause severe adverse fetal effects. Poisoning causes fetal tissue hypoxia by decreasing the release of maternal oxygen to the fetus.<unk><unk>  also crosses the placenta and combines with fetal hemoglobin, causing more direct fetal tissue hypoxia. Additionally, fetal hemoglobin has a 10 to 15% higher affinity for<unk><unk>  than adult hemoglobin, causing more severe poisoning in the fetus than in the adult. Elimination of<unk><unk>  is slower in the fetus, leading to an accumulation of the toxic chemical. The level of fetal morbidity and mortality in acute<unk>  is significant, so despite mild maternal poisoning or following maternal recovery, severe fetal poisoning or death may still occur.
Carbon monoxide poisoning
Cyanide poisoning
Nitrogen dioxide poisoning
Upper respiratory tract infection
Chlorine gas poisoning
Alcoholic ketoacidosis
Salicylate poisoning
Theobromine poisoning