Effects of Carbon Monoxide and Cyanide Poisoning on Human Health

Carbon Monoxide Poisoning

Etiology: In carbon monoxide poisoning, heamoglobin binds to CO. Heamoglobin binds to carbon monoxide with an affinity 240 times greater than oxygen [5]. This association result in formation of carboxyheamoglobin [2]. It causes the leftward shift of oxygen-heamoglobin dissociation curve of oxyheamoglobin [3]. The binding of CO forms stabilization in heamoglobin. This stabilized form is known as R state. It increases affinity for oxygen in other sites of heamoglobin. It reduces the release of oxygen [4]. Carbon monoxide shows greater affinity to myoglobin compared to heamoglobin and cause myocardial infarction and hypotension. Both of these finally result in cellular hypoxia [3].

Similarly carbon monoxide binds to ferrous ion of Cytochrome oxidase of mitochondria and stop oxidative phosphorylation. It causes decrease in Adenosine triphosphate production or the energy production of body [10]. The shuffling of electrons continues to take place between components of electron transport chain and form superoxides, which can cause cell, damage [4].

Pathophysiology: Carbon monoxide enters into the body mainly through inhalation. It enters the lungs and diffuses to alveolar membranes and then into heamoglobin of blood [6]. Studies shows that inhalation of carbon monoxide causes more toxicity when compared to transfusion of similar concentration of carbon monoxide exposed RBC. In case of non smokers the carboxyheamoglobin levels greater than 2% and for smokers a level greater than 10% is enough to produce symptoms [4]. The carboxyheamoglobin level in blood of poisoned patient is directly correlated with clinical manifestation [3].

The presence of excess carbon monoxide can activate platelets by displacing NO from heamproteins in platelet. These NO react with super oxides and form peroxynitrate and inhibit function of mitochondria [4]. Thus carbon monoxide poisoning increase the activation of platelets [11]. These activated platelets stimulate neutrophils in blood to release myeloperoxidase (MPO). The release of MPO results in inflammatory effects by activating more neutrophils [12]. It again causes the formation of Xanthine oxidase which generates reactive oxygen species (ROS). Thus both MPO and ROS catalyze lipid peroxidation and increase the myelin content in body. This myelin increases the lymphocyte responses and activates microglia of brain [4]. Finally all these process leads to neurological and cardiac injuries [12].

Carbon monoxide poisoning causes inactivation of Calcium ATPase in plasma membrane and cause large influx of calcium ions, which results in brain injury. The intracellular lipases and proteases are activated by decrease in ATP production, which causes the depolarization of mitochondrial membranes and can cause death of the person [4]. Carbon monoxide exposure can increase carbon monoxide production in body [13]. The brain systolic heam levels are increased by CO exposure [4]. It induces activation of heamoxygenases, which is dependent on heam content of body [13]. Then the heamoxygenase enzyme form CO from tissues and increase the effects of poisoning.

Toxico Kinetics: According to World Health Organization, a long term exposure greater than 6ppm of carbon monoxide is toxic to human beings [4]. The half life of carbon monoxide is 320 minutes in a standard room with 21% of oxygen. While in 1000% of oxygen the half life reduces to less than 90 minutes. In hyperbaric oxygen condition of 3 ATM the half life of CO again reduces to 23 minutes so hyperbaric oxygen therapy is used for reducing the effects of carbon monoxide poisoning [2].

Clinical Manifestations: The signs and symptoms vary with concentration and duration of exposure. Low concentration of toxicant causes both cardiovascular and neurobehavioral effects. Acute and lengthy exposure leads to coma and death, the starting of chronic poisoning can be mistaken as flu depression, food poisoning [3]. The common clinical manifestations are headache, nausea, weakness, lethargy. Lethargy can lead to misdiagnosis of chronic fatigue syndrome [14]. Acute CO poisoning also show symptoms like tachycardia, hypertension, central nervous symptoms, abdominal pain, dizziness, paresis, convulsions, unconsciousness, myocardial ischemia, arterial fibrillation, pulmonary edema, erythrocytosis, hyperglycemia, muscle necrosis, acute renal failure, parkinsonism. Young adults express peripheral neuropathy also Psychiatric effects like irritability, depression and neuropsychological defects like impairment to attention, short term memories are also expressed [14, 15]. Body organs like kidney, liver, pancreas are rarely affected. Muscle necrosis is caused by the increase in creatine phosphokinase. Chronic exposures in pregnant ladies cause growth retardation, fetal distress, death of fetus [3].

Diagnosis and Treatment: The diagnosis of carbon monoxide poisoning should be based on clinical triad, which assesses consistent symptoms, history of recent exposure, increased carboxyheamoglobin levels. Of these carboxy heamoglobin levels act as confirmation for the suspect [4]. But recent studies shows that normal levels of carboxy heamoglobin can’t be taken as absence of carbon monoxide poisoning [4]. Pulse CO oximetry measurement is also used for diagnosis fetus, but the differentiation between wavelength of carboxy heamoglobin and oxyheamoglobin is difficult. Carbon monoxide breath analyzer is a simple screening test that can be used, but smoking and alcohol use of patients confound the result [3].

There are no available antidotes for the poisoning. 100% normobaric oxygen therapy and hyper baric oxygen therapy are used and found effective. Both methods remove the carbon monoxide from heamoglobin by increasing partial pressure of oxygen, which in turn increase the dissociation rate [16]. Normobaric oxygen therapy decreases the half life into 74 minutes while HBOT decreases the half life into 20 minutes. HBOT shows a reversal effect on inflammation and dysfunction of mitochondria [4]. It is highly effective against neuro cognitive dysfunction. It is recommended for serious cases of acute poisonings [17].

Other than these, some other methods are used. Application of high concentration of oxygen with carbon dioxide is used as CO poisoning cause decrease in carbon dioxide level in body. So this method increases ventilation from carbon dioxide. Similarly normocapnic hyperpnea, extracorporeal membrane oxygenation, photo dynamic blood illuminations are used as optional methods. The study of Roderique and collegues claims that hydroxycobalamine and ascorbic acid can be used to convert CO into carbon dioxide. Cyclo dextrin encapsulated porphyrin complex are also found helpful by Kitagshi and colleagues [4].

The survivors have to compromise with quality of life with low cognitive performance, depression, stress [18]. In case of intentional poisoning they are referred to psychiatric counseling. Follow up of the patient is recommended within 4-8 weeks after exposure. Special care should be given to depression, neurocognitive impairments and myocardial infarction [2].

Prevention Measures: To find out CO poisoning CO detectors are installed in home. It should be on same level as fuel burning appliance. The alarm should be kept in a place, which is heard from all rooms. It minimizes the risk of exposure during sleep [5]. Public health campaigns should be done to make awareness on people about incidents on home and workplaces. The visible example of the campaign is shown by U.S through their “invisible killer campaign”. The use of catalytic converters reduces the exposure from automobiles [4]. Public education should be provided by gas industry also. Physicians, engineers, gas industries should be well aware of the issue. Proper ventilation should be done in houses [3]. The person should be removed from the exposure immediately to prevent complications [2].

Cyanide Poisoning

Etiology: Cyanide is readily available and widely used chemical. It is well known for its toxic effects. Exposure to cyanide can be occurred through contaminated air, water, food, soil [8]. Exposure through inhalation depends on respiratory condition of individuals. Oral exposure results in continued absorption of toxicant [10].

Pathophysiology: Inhalation of cyanide gas is having more toxicant effects than ingestion. Cyanide diffuses into blood after exposure [7]. After absorption CN maintain equilibrium between cyanide anion and undissociated form of HCN. HCN form can easily cross cell membrane compare to other forms.HCN also inhibit enzymes like succinic dehydrogenase, mutase, and cytochrome oxidase of electron transport chain. Cyanide binds with ferric ion of cytochrome a3 in electron transport chain of mitochondria and inhibits oxidative phosphorylation and thereby aerobic respiration. Thus anaerobic metabolism increases and it results in academia and hyper lactemia. Potassium cyanide and sodium cyanide change to hydrogen cyanide in stomach acidic conditions [10]. Cyanide is a hepato toxic and neuro toxic chemical [6].

Toxic Kinetics: The concentration of 40 mol/L is enough to express signs and symptoms of the poisoning. The body contains a special detoxification mechanism for cyanide. The enzyme named rhodanese help in this. It is found particularly in liver and muscle. Rhodanese convert cyanide to thiocyanate. Thiocyanate is soluble in water, so it is excreted through urine. Thiosulfate acts as a sulfur donor in this mechanism [7].

Clinical Manifestations: In exposures through inhalations symptoms are expressed within seconds. But in oral ingestion of poison it will take hours to express the symptoms. Symptoms vary with concentration of poison in body. The lethal dose of cyanide is 50 mg, an exposure greater than 50 mg cause death of individuals in 5-15 minutes. It will take at least 1-4 hours, if we are consuming small quantities of cyanide [19]. The low dose symptoms are headache, vomiting, dizziness, mild confusion; abdominal pain and high dose symptoms are hyperventilation, tachycardia, bradycardia, respiratory arrest, hypotension, dyspnea, seizures, coma and can cause death [10]. Increased lactate levels in blood and high concentration of oxygen levels in venous can cause sepsis, myocardial infarction, liver failure [10]. For patients in coma 2 clinical features are important. They are absence of cyanosis and bradycardia. Cyanide inhibits oxidative phosphorylation and thereby oxygen transport. So a fully oxygenated heamoglobin will be present and cyanosis is absent in them [19].

Diagnosis and Treatment: The toxic effect of poisoning is directly related to quantity of cyanide in body. The diagnostic methods include quantification of cyanide in blood, urine, saliva. But analysis of blood is taken as reliable. The reliability of oral swab depends on the quantity of cyanide in saliva at the time of swab collection. Whereas in case of urine, smoking increase cyanide concentration in urine and due to filtration of kidney the actual content of cyanide is not available. The diagnosis can be toxidrome, which is symptom based analysis of exposure. It helps to avoid delay in treatment by waiting laboratory confirmation [10].

The treatment methods are administration of 100% oxygen and decontamination methods like using activated charcoal, gastric lavage. The effective treatment is providing antidote intravenously or intraosseous. It should be done without delay. Intravenous administration requires skill. Treatment for cyanide poisoning can be divided into 3. First one is methamoglobin generators and nitric oxide donors. It includes sodium nitrite, amyl nitrite, and dimethyl aminophenol. They create hypotension and methemoglobinemia [10]. Use of sodium nitrite can cause cerebral haemorrhage [20]. The second group is sulfur donors. It includes sodium sulfate and glutathione [10]. Sodium thiosulfate is a category C drug for pregnant women. It create protection for fetus by creating a gradient towards mother [6]. The third group is directly binding agents, like hydroxycobalamine, cobalt ethylene diamine tetra- acetate [10]. Hydroxycobalamine is an expensive antidote. It should be given intravenous within 10-15 minutes of exposure [21]. Hydroxycobalamine convert cyanide into cyanocobalamine or vitamin B12 and it is excreted through urine. But it can cause kidney injury [6]. Cobalt EDTA creates a cobaltocyanide and reduces toxic effects [22]. In case of intentional poisonings they should be referred to psychiatric counseling [7].

Prevention Measures: As breathing cause high toxic effects avoid situations that lead to inhalation of the toxicants, especially in labs. Leave the area of exposure as soon as possible. Remove the clothing and discard the exposed clothes. Wash the exposed body parts with soap and water. Avoid touching contaminated areas, clothes, jewelry. Avoid mouth to mouth resuscitation as it cause risk to the person who provide CPR [8]. Provide education to public and workers about such possibilities [7].