Carbon Monoxide Poisoning

Toxicology

• It is the scientific study of the adverse effects of chemical substances or situations on living organisms and encompasses a wide range of topics.
• Exposure routes commonly include inhalation, dermal contact, and ingestion.
• The essential thing on dose response relationship, (wherein the dose makes the poison) that's fundamental in toxicology, and the mechanisms of toxicity.
• Poison: any substance causing harmful effects upon exposure, with dose being a key factor in toxicity (fundamental law of toxicology).
• There are 4 disciplines:
  • Mechanistic: studies cellular and biochemical effects of toxins, aids in therapy design and exposure tests.
  • Descriptive: uses animal experiments to predict harm levels in humans (risk assessment); regulatory toxicologists interpret data to establish safety standards
  • Forensic: focuses on medicolegal consequences of toxin exposure and methods used in legal evidence, such as cause of death.
  • Clinical: examines interrelationships between toxin exposure and diseases, with emphasis on diagnostic testing and therapeutic intervention.
• Systems correlate dose with harmful responses, often using lethal outcomes as a measure (e.g., a single acute oral dose and its lethality in a 70 kg person).
• Most toxins cause harmful effects at lower doses than death (e.g., liver damage); assessed through responses like elevated serum ALT or GGT.
• The liver is the organ commonly affected.

Cumulative Frequency Histogram

• A tool to evaluate various toxic responses across doses, showing how the population reacts differently to the same dose
• Intentional Poisoning: 50% of poisoning cases (suicide attempts).
• Accidental Exposure: 30% of cases, most common in children but also in adults due to drug overdoses
• Occupational Exposure: occurs in industrial and agricultural settings.
• TD50 (Toxic Dose 50): The dose predicted to cause toxic response in 50% of the population and shows signs and symptoms.
• LD50 (Lethal Dose 50): The dose predicted to cause death in 50% of the population and mortality.
• ED50 (Effective Dose 50): The dose predicted to have therapeutic effects in 50% of the population.
• Therapeutic Index: Ratio of TD50 to ED50; a large index indicates a drug with few toxic side effects within its therapeutic range
• Toxins require entry into circulation, primarily through the gastrointestinal tract.
• Toxins are absorbed by passive diffusion across cell membranes (hydrophobic/water-based substances are absorbed easily compared to non-hydrophobic or liquid soluble substances.)
• Ionized substances cannot diffuse passively but may be absorbed based on pH (substances must appear as weak acids in the stomach, weak bases in the intestine)
• Other factors influencing absorption: dissolution rate, gastrointestinal motility, and interaction with other substances
• Non-absorbed toxins may cause local effects (e.g., diarrhea, bleeding, malabsorption) but not systemic effect.

Acute and Chronic Toxicity

• Acute: Results from short-term, high-dose exposure causing immediate toxic effects
• Chronic: caused by repeated, lower-dose exposure over time, potentially leading to toxic accumulation or delayed effects.
• Screening Tests: Simple, qualitative methods with high sensitivity but low specificity, used to detect specific substances or toxin classes
• Confirmatory Testing: A more specific, second method confirms the presence of toxins
• Immunoassays: For screening drugs, often detecting drug classes or specific drugs (e.g., THC)
• Thin-layer Chromatography: Simple and inexpensive method for detecting organic compounds
• Gas Chromatography (GC): Widely used for qualitative and quantitative analysis of volatile substances, often combined with mass spectrometry for identification

Alcohol

• Causes CNS depression leading to disorientation, confusion, euphoria, unconsciousness, and potentially death.
• Depresses the CNS by altering membrane properties; recovery from CNS effects is generally quick after cessation.
• Metabolized to aldehydes and acids, distinct toxicities from each type of alcohol, especially through biotransformation.
• Excessive ethanol consumption leads to major social, economic, and health issues, costing over $100 billion annually.
• Contributes to about 20% of hospital admissions and is a leading cause of premature death (about 80,000 deaths annually in the U.S.)
• Consumption during pregnancy can cause fetal alcohol syndrome or effects, impacting motor and mental development.
• 80 mg/dL limit for driving in most states and is associated with impaired judgment and motor skills
• Chronic alcohol use (50g/day for 10 years) damages liver, leading to fatty liver, alcoholic hepatitis, and cirrhosis.
• Acetaldehyde: Formed during ethanol metabolism, reacts with proteins and is a key factor in ethanol's pathologic effects.

Methanol/Wood Spirit/Methyl Alcohol

• Occurs in solvents and homemade alcohol
• Leads to acidosis and optic neuropathy-only alcohol that can potentially lead to blindness
• Converted into Formaldehyde and Formic Acid
• Isopropanol/Rubbing Alcohol: effects similar to ethanol but acetone has longer half life, prolonging symptoms
• Metabolized to Acetone
• Ethylene Glycol/Antifreeze: antifreeze and hydraulic fluids, ingested due to sweet taste
• Causes metabolic , kidney damage from calcium oxalate crystal formation
• Specimen Types for Alcohols: Serum, plasma, and whole blood are used; should be sealed to prevent ethanol evaporation.
• Methods for Alcohols:
  • Osmometry: Serum osmolarity.
  • Gas Chromatography: reference method
  • Enzymatic: Method Uses alcohol dehydrogenase (ADH) to oxidize ethanol to acetaldehyde, monitored by reduction of NAD to NADH
• Method Sensitivity: enzymatic methods relatively specific for ethanol but may produce low results for methanol or isopropanol intoxication.
• Chain of Custody: Proper documentation and handling critical for legal ethanol testing, especially DUI

Carbon Monoxide

• Properties: colorless, odorless, tasteless and rapidly absorbed into blood.
• Sources: incomplete combustion of carbon-containing, gasoline engines, improperly ventilated furnaces, and fires.
• CO binds to Hgb, forming carboxyhemoglobin (COHb) 200-225 times more strongly to hemoglobin than oxygen.
• Has effects: amount in air can lead to 50% carboxyhemoglobinemia, reducing the oxygen-carrying capacity of blood.
• CO shifts dissociation curve leftward, reducing oxygen delivery to tissues (hypoxia), affecting high-oxygen-demand organs.
• Decreased oxygen delivery to tissues (significant harm, particularly brain and heart.

Symptoms of Carboxyhemoglobinemia

• COHb (0-5%) = Typical in nonsmokers
• COHb (5-15%) Range of values seen in smokers
• COHb (10%) = Shortness of breath with vigorous exercise
• COHb (20%) = Shortness of breath with moderate exercise
• COHb (30%) = Severe headaches, fatigue, impairment of judgment
• COHb (40-50%) = Confusion, fainting on exertion
• COHb (60-70%) = Unconsciousness, respiratory failure, death with continuous exposure
• COHb (80%) Immediately fatal
• Treatment: 100% oxygen therapy and severe cases require hyperbaric oxygen therapy.
• Half-life of COHb: 60-90 minutes on 100% oxygen with normal respiratory function.
• COHb Diagnostic: cherry-red appearance.
• Spot test= add NaOH to whole blood. Persistence of a pink solution suggests COHb levels ≥20%
• Gas Chromatography (GC) reference method, mass spectrometry can measure COHb levels.
• Spectrophotometry Measures absorbance at multiple wavelengths to calculate the concentration of COHb and other hemoglobin forms. Common in automated systems

Caustic Agents

• Found in products and occupational
• Aspiration causes pulmonary edema and shock, potentially leading to death.
• Ingestion causes lesions in the esophagus and gastrointestinal tract, leading to perforations
• Metabolic Effects= Causes of metabolic acidosis or alkalosis.
• Treatment: Dilution
• Cyanide exists as gas, solid, or in solution. Found in processes and in insecticides, rodenticides, and burning plastics.
• Can occur via inhalation, ingestion, or transdermal absorption and often associated with smoke inhalation.
• Binds to heme iron and disrupts oxidative phosphorylation, resulting in increased oxygen tension. Due to lack of oxygen utilization.
• Low-level exposure: headaches, dizziness, and respiratory depression, high doses can lead to seizures, coma, and death
• Mediated by conversion to which is nontoxic when exposure exceeds clearance. and
• Toxic effects Mercury
• Eliminating sources for symptoms

Pesticides

• Designed to kill or harm unwanted organisms
• Chemicals harmful to humans
• Substances used in agriculture, vector, control, combat urban pests
• Significant health risks
• Exposure through ingestion, inhalation, and occupational

Routes of Exposure

• Inhalation
• Dermal absorption
• Insecticides: The most common type
• Herbicides: weeds
• Organophosphates: The most abundant insecticides

Analysis of Toxic Agents

• Two-Tiered Approach
  • Simple, rapid, and inexpensive
  • Accurate results
• Common Analytical Procedures
  • Chromogenic reactions, immunoassays, etc
• Stimulants for mental
  • increased physical capacity
  • Restlessness
  • Irritability
• Screen for amphetamines

MDMA

• Derivative of amphetamines, causing hallucinations
• Can increase sensitivity
• Causes liver toxicity
• Can prevent reexposure
• Positive test for amphetamines
• THC Lipophilic slow elimination

Cannabinoids

• Euphoria and impaired memory
• Can accumulate in the tissue
• Tests can be performed on dried flower stems
• Barbiturates

Vitamin A

• Necessary for vision differentiation
• Epithelial cells
• Causes night blindness
• Source form animal products

Vitamin D

• Essential from skeleton formation
• Mineral homeostasis
• Muslim women are at risk for vit D deficiency
• Major form for ergocalciferol
• Treatment for high intakes
• Rare in deficiency from adults
• Named from coagulation
• Rare in infants

Vitamin K

• Antibiotics reduce synthesis
• Supplementation reduces hemorrhage function
• B12 causes neurologic disorderer

Copper

• Essential for blood clotting
• Selenium high has potential side effects
• Low absorption through intestine disease
• Causes low immune system
• Brain function

Iron

• Transported by transferrin
• Can be used a therapeutic phlebotomy

Mangesium Toxicity

• Nausea
• vomiting
• Headache
• May resemble parkinson disease

Explore the dangerous effects of carbon monoxide (CO) poisoning and its impact on oxygen delivery in the body. Understand the mechanisms, consequences, and treatments associated with CO exposure. Learn about carboxyhemoglobinemia and its effects.