Tissue asphyxiants

Tissue asphyxiants are a class of chemicals that disrupt the utilization of oxygen at the cellular level in the body. These tissue asphyxiants specifically target cells where oxygen is used to produce energy. Oxygen enters the arteries through the lungs, then binds with hemoglobin of erythrocyte (RBC) to form a temporary compound called oxyhemoglobin. Tissue asphyxiants interfere with this process, leading to a disruption in ATP production. This disruption can lead to hypoxia. This can cause organ damage, neurological problems, and even death.

Mechanism of action

Main article: Cellular respiration

Through cellular respiration, cells convert nutrients, particularly glucose, into energy in the form of ATP. This process happens in several stages. The mitochondria produces the most energy. At the final stage, the high-energy electrons flow through the electron transport chain, and the energy they release is used to produce ATP.

In the electron transport system, electrons flow through a series of protein complexes within the inner mitochondrial membrane. As protons are pumped across the membrane, a proton gradient is created. This process is known as oxidative phosphorylation. Oxygen acts as the final electron acceptor in the ETC.

Tissue asphyxiants are chemicals that disrupt this normal mitochondrial function and interfere with cellular respiration.

Common tissue asphyxiants

Main article: Carbon monoxide poisoning

Carbon Monoxide (CO)

Carbon monoxide is a colorless and odorless gas. Carbon monoxide is dangerous because it can bind to hemoglobin, the molecule in RBC. It binds to hemoglobin with 250 times the affinity of oxygen and form a compound called carboxyhemoglobin. This binding prevents oxygen from being transported to tissues and causes a condition called cellular hypoxia. Carbon monoxide also interferes with cellular respiration by binding to cytochrome c oxidase, further worsening the lack of oxygen at the cellular level. Exposure to carbon monoxide can cause various symptoms. Early symptoms often resemble the flu, including headache, dizziness, weakness, and confusion. Symptoms can worsen including chest pain, shortness of breath, and impaired judgment. In severe cases, individuals may develop cherry-red skin, a classic but rare sign of carbon monoxide poisoning.

Cyanide (CN-)

Cyanide, a very poisonous compound, is found in various industrial processes like metal plating, mining, and the production of chemicals such as hydrogen cyanide and sodium cyanide. Cyanide is toxic because it blocks the enzyme cytochrome c oxidase, which is needed in the mitochondria’s electron transport chain. When cyanide blocks this enzyme, electrons cannot be transferred to oxygen. So, ATP cannot be produced. Without ATP, cells cannot function properly, causes rapid energy failure and cell death. Cyanide poisoning can occur rapidly, with symptoms often being severe. Early signs include a bitter almond smell on the breath (detectable by some due to a genetic trait), rapid breathing, and a feeling of suffocation. Victims may experience seizures, loss of consciousness, and coma. Cyanide poisoning can be deadly within minutes.

Hydrogen Sulfide (H₂S)

Hydrogen sulfide is a toxic gas. It is produced naturally by the decay of organic matter. It is also a byproduct of various industrial activities. Hydrogen sulfide has a similar effect to cyanide. It blocks the cytochrome c oxidase enzyme in the electron transport chain. This disrupts the cellular respiration process - ATP production and cellular hypoxia. Initial symptoms of exposure include eye and respiratory irritation, coughing, and shortness of breath. With continued exposure, individuals may experience dizziness, nausea, and rapid collapse. High concentrations of ${\ce {H2S}}$ can cause sudden unconsciousness and death due to respiratory failure.

Sodium Azide (NaN₃)

Sodium azide is a chemical compound used in laboratories as a biocide to prevent microbial contamination. Sodium azide affects mitochondrial function by inhibiting the cytochrome c oxidase enzyme, similar to the effects of cyanide and hydrogen sulfide. This inhibition disrupts the electron transport chain and the production of ATP and causes cellular energy failure. Sodium azide can also cause vasodilation, which may lead to hypotension. Symptoms of sodium azide exposure vary depending on the route and amount of exposure. Initially, a person may experience headaches, dizziness, nausea, and vomiting. As the poisoning progresses, symptoms may include low blood pressure, trouble breathing, seizures, and loss of consciousness. In severe cases, sodium azide can be fatal due to its impact on cellular energy production and cardiovascular function.

Diagnosis

Medical testing

Diagnosing exposure to tissue asphyxiants requires a comprehensive clinical evaluation. The evaluation is combined with targeted laboratory tests. These tests confirm the presence and extent of exposure. When a patient has nonspecific symptoms, medical professionals will perform tests. These symptoms may include headache, dizziness, confusion, or respiratory distress. The patient may have a known history of exposure to potential toxins. The tests help establish the cause of the patient's symptoms.

• Carbon Monoxide (CO) poisoning: In cases of suspected carbon monoxide poisoning, the primary diagnostic tool is the measurement of carboxyhemoglobin levels in the blood. Carbon monoxide binds to hemoglobin with much greater affinity than oxygen. This can significantly reduce the oxygen-carrying capacity of the blood, even at low levels of exposure. Normal carboxyhemoglobin levels in non-smokers are typically below 5%. Smokers may naturally have levels between 5% and 10%. Levels above 20% in non-smokers are a strong indicator of significant CO exposure, requiring immediate intervention. Clinical symptoms such as headaches, nausea, dizziness, and in severe cases, cherry-red skin coloration, further support the diagnosis. Blood gas analysis may also reveal a reduced partial pressure of oxygen, providing additional evidence of impaired oxygen transport.
• Cyanide poisoning: Diagnosing cyanide poisoning is difficult. This is because the symptoms come on quickly and are severe. Doctors often use a combination of signs and tests to diagnose it. The signs include a bitter almond smell on the breath (but not everyone can smell this), trouble breathing quickly, seizures, and loss of consciousness. Doctors can also test the blood to measure cyanide levels. But this test may only be available in special labs, which can delay the diagnosis. So, treatment often starts based on the doctor's suspicion alone. In cyanide poisoning, the blood also has high levels of lactate. This is because the cells switch to a type of metabolism that doesn't use oxygen.
• Hydrogen Sulfide (H₂S) poisoning: The diagnosis of hydrogen sulfide poisoning is usually based on clinical symptoms, exposure history and the presence of a rotten egg smell, which is a hallmark of this toxic gas. Blood tests can measure sulfhemoglobin levels, a compound formed when hydrogen sulfide binds to hemoglobin. But like cyanide testing, this may not be available in all settings. Patients exposed to high levels of H₂S may rapidly develop symptoms such as respiratory irritation, dizziness, unconsciousness and in severe cases, respiratory failure. Pulse oximetry and arterial blood gas analysis may show signs of hypoxia despite normal oxygen saturation levels. This is indicative of impaired oxygen utilization at the cellular level.
• Sodium Azide exposure: Diagnosing sodium azide exposure requires both clinical assessment and laboratory testing. Symptoms like severe low blood pressure, headaches, dizziness, and difficulty breathing, along with a history of potential exposure (e.g., from lab accidents or faulty airbag systems), can lead to further investigation. Toxicology tests can detect sodium azide or its byproducts in the blood or urine, which confirms exposure. Blood tests may also show metabolic acidosis, a common sign of poisoning that indicates the body's shift to anaerobic metabolism due to impaired mitochondrial function.

Toxicology

Toxicological testing is important in confirming exposure to substances that can deprive tissues of oxygen. This is especially true when the diagnosis is not clear from the patient's symptoms alone.

• Carbon Monoxide testing: Carboxyhemoglobin levels are the best way to diagnose carbon monoxide poisoning. This test is easily available in most emergency rooms. It provides quick results that help guide the treatment. In more severe cases, co-oximetry may also be needed. Co-oximetry can differentiate between different forms of hemoglobin. This gives a more detailed understanding of the extent of the poisoning.

• Cyanide toxicology: Blood cyanide concentration is a definitive test for cyanide poisoning. However, this test is often only available at specialized facilities. For rapid assessment, other indicators can be used. These indicators include elevated blood lactate levels or significant metabolic acidosis. These indicators can prompt immediate treatment even before cyanide levels are confirmed. Some emergency settings may also use rapid cyanide detection kits, although these kits are less common.

• Hydrogen Sulfide detection: Sulfhemoglobin levels can be measured to confirm hydrogen sulfide exposure. However, this test is not commonly available in emergency settings. When direct testing is not possible, the diagnosis may be supported by other lab findings. These findings include unexplained hypoxia or metabolic acidosis. They must be combined with a known exposure history and characteristic symptoms.

• Sodium Azide toxicology: Detecting sodium azide or its byproducts in biological samples, such as blood or urine, is crucial to confirm exposure. This test is often done in specialized labs, and the results may take time. So, doctors must use their clinical judgment and patient history to start treatment quickly. Like other asphyxiants, a key diagnostic sign is blood gas analysis showing metabolic acidosis.

Treatment

When someone is exposed to tissue asphyxiants, quick and effective treatment is very important. This is to reduce damage and improve the outcome. The treatment plan usually includes:

1. Immediately removing the person from the source of exposure.

1. Giving specific antidotes if they are available.
2. Providing supportive care to manage the symptoms and stabilize the patient.

The key is to act fast and provide the necessary medical care to minimize the harm caused by the exposure.

Immediate action

• Removal from exposure: The first and most important step is to remove the affected person from the contaminated environment. This is crucial to prevent further absorption of the toxin. For example, in carbon monoxide poisoning, the person should be moved to an area with fresh air as soon as possible. Similarly, in industrial settings with chemicals like cyanide or hydrogen sulfide, workers should be evacuated to safety right away.

• Administering oxygen: After removing the person from the exposure, giving 100% oxygen is the priority. Oxygen helps replace the asphyxiant from hemoglobin, like in carbon monoxide poisoning. It also supports cellular respiration by increasing the oxygen in the blood. If the patient is unconscious or has severe symptoms, oxygen should be given through a mask or endotracheal tube. This ensures the airway is clear and the oxygenation is maximized.

Specific antidotes

• Hydroxocobalamin for Cyanide poisoning: Hydroxocobalamin is a specific antidote for cyanide poisoning. It works by binding to cyanide ions. This forms cyanocobalamin, a non-toxic compound. This non-toxic compound can be safely excreted in the urine. Hydroxocobalamin is often administered intravenously. It is considered the first-line treatment for cyanide poisoning. This is due to its effectiveness and relative safety. In some cases, sodium thiosulfate may also be administered. It is administered alongside hydroxocobalamin. This can further enhance the detoxification process.

• Hyperbaric Oxygen Therapy for Carbon Monoxide poisoning: Hyperbaric oxygen therapy (HBOT) is a specialized treatment. It is used for severe cases of carbon monoxide poisoning. The patient is placed in a pressurized chamber. They breathe 100% oxygen at higher-than-normal atmospheric pressures. This treatment increases the amount of oxygen dissolved in the blood. It helps to displace carbon monoxide from hemoglobin more rapidly. This restores oxygen delivery to tissues. HBOT can also help reduce the risk of long-term neurological damage. This damage is associated with carbon monoxide exposure.

Supportive care

Intravenous fluids are often given to patients. The fluids help maintain blood pressure and hydration. This is especially important if the patient has low blood pressure or is in shock. The fluids support the circulatory system. They ensure that the organs receive enough blood flow.

The patient may not be able to breathe well on their own due to respiratory failure or severe poisoning. In these cases, the patient may need mechanical ventilation. This means using a ventilator to help the patient breathe or to do the breathing for them. The ventilator ensures that oxygen gets to the lungs and that carbon dioxide is removed from the body.

Continuous monitoring is very important for patients who are exposed to substances that can cause tissue asphyxiation. This includes:

• Monitoring vital signs like heart rate, blood pressure, and oxygen levels
• Doing regular blood tests to check the toxin levels and the patient's metabolic state
• Looking for any signs of organ problems

In cases of severe poisoning, the patient may need intensive care to manage complications. These complications can include seizures, metabolic acidosis, or organ failure.

References

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