呼吸功能障碍性毒物 Respiratory dysfunction toxicant Department of Forenxic Toxicology Shizhong Bian

氰化物中毒 Cyanide Poisoning

Cyanide  rapid acting toxin (used for suicide)  combined with sugar as cyanogenic glycoside  localized in vacuoles in leaves and seeds  enzymes that separate CN from sugar are in the cytosol  wilting or crushing plant releases CN

Cyanide  more than 1000 plant species  variety of CN glycosides – don’t learn names or structures: cherriesprunasin and amygdalin sorghumdhurrin flaxlinamarin white cloverlotaustralin arrowgrasstriglochinin

Potential CN glycoside toxicity  concentration in plant, N in soil  species of plant; breed crop for less CN  stage of growth (young plants)  hormone herbicides  dry weather followed by rain  low sunlight – glycosides may accumulate over night so highest toxicity in morning

Potential CN glycoside toxicity  damage to plant – trampling, frosting  amount eaten, rate of ingestion  size and type of animal – ruminants most susceptible (enzymes more active at neutral pH, microbes release CN)  food ingested with it

Detoxification of cyanide  endogenous thiosulfate  catalyzed by rhodanese  thiocyanate forms (thiocyanates from chronic low level exposure produce goiter in adult or fetus)  excreted in urine

Other sources of cyanide  electroplating or cleaning metals  soil sterilant  rodenticides

Cyanide  CN combines with cytochrome oxidase system  ties up ferric iron so can no longer transport oxygen into cells  histotoxic anoxia  bright red blood with lots of oxygen

Mechanism of toxicity Mechanism of toxicity Cyanide ions bind to the iron atom of the enzyme cytochrome c oxidase (also known as aa3) in the fourth complex in the mitochondrial membrane in the mitochondria of cells. This deactivates the enzyme, and the final transport of electrons from cytochrome c oxidase to oxygen cannot be completed. As a result, the electron transport chain is disrupted, meaning that the cell can no longer aerobically produce ATP for energy. Cyanide ions bind to the iron atom of the enzyme cytochrome c oxidase (also known as aa3) in the fourth complex in the mitochondrial membrane in the mitochondria of cells. This deactivates the enzyme, and the final transport of electrons from cytochrome c oxidase to oxygen cannot be completed. As a result, the electron transport chain is disrupted, meaning that the cell can no longer aerobically produce ATP for energy. enzymecytochrome c oxidase mitochondriacytochrome c oxidaseelectron transport chainATP enzymecytochrome c oxidase mitochondriacytochrome c oxidaseelectron transport chainATP

Mechanism of toxicity Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.aerobic respirationcentral nervous systemheartaerobic respirationcentral nervous systemheart binds to sulfhydryl groups and sulphur, disrupts sulfhydryl or sulphur -containing enzymes. binds to sulfhydryl groups and sulphur, disrupts sulfhydryl or sulphur -containing enzymes.

Clinical signs  found dead (15 min)  excited, generalized muscle tremors  rapid breathing, dyspnea  increased salivation and lachrymation  involuntary urination and defecation

Clinical signs  down, gasping for breath  clonic convulsions  dilated pupils  mucous membranes bright pink  blood very bright red  Rarely time to treat

Necropsy of acute case  bright red blood  blood slow to clot or does not clot  hemorrhage from terminal struggling  bitter almond odor to ingesta

Diagnosis  history of exposure, clinical signs  confirm by testing blood, rumen content, liver, muscle for CN  test forage for CN  freeze sample, submit frozen  preserve in 1-3% mercuric chloride if can’t freeze

Picric acid test

It is the second drug that comes to mind when one talks about homicidal poisoning is cyanide. Cyanide has been discussed in detail in another section of the book and this discussion will not be repeated. It is the second drug that comes to mind when one talks about homicidal poisoning is cyanide. Cyanide has been discussed in detail in another section of the book and this discussion will not be repeated.

Carbon monoxide

Carbon Monoxide CO Colorless The SILENT KILLER Colorless The SILENT KILLER Odorless Odorless Tasteless Tasteless Slightly lighter than air (drop in a fire!) Slightly lighter than air (drop in a fire!) Product of incomplete combustion Product of incomplete combustion –1. Time –2. Temperature –3. Turbulence (oxygen)

Carbon monoxide Carbon monoxide Odorless and colorless. Non-irritating. Found in car exhausts. It is cumulative - repeated small doses can build up over time. It kills by preventing the blood from carrying oxygen. Symptoms: Initially, dizziness and headaches when exerting yourself, then when at rest too. A higher dose affects coordination and makes the heart throb. Then comes collapse and death. Often the victim is unaware and just drifts slowly to sleep. Carbon monoxide Odorless and colorless. Non-irritating. Found in car exhausts. It is cumulative - repeated small doses can build up over time. It kills by preventing the blood from carrying oxygen. Symptoms: Initially, dizziness and headaches when exerting yourself, then when at rest too. A higher dose affects coordination and makes the heart throb. Then comes collapse and death. Often the victim is unaware and just drifts slowly to sleep.

 Post-mortem appearance: Pinky skin. Cherry-red blood. Blood is fluid and doesn't want to clot. Lungs congested and the upper air passages contain a frothy fliud. Carbon monoxide remains in the blood for up to six months after death.

COHB Carboxyhemoglobin Carboxyhemoglobin Oxygen carried by hemoglobin on red blood cell (rbc) Oxygen carried by hemoglobin on red blood cell (rbc) Hemoglobin likes CO better than it likes oxygen Hemoglobin likes CO better than it likes oxygen Tissues (brain) don ’ t get enough oxygen Tissues (brain) don ’ t get enough oxygen

Chloroform

Chloroform Heavy colorless liquid. Nice smell. Used as anaesthetic, and to render a victim unconsious. However, it's not easy to cholorform a sleeping victim without waking them, and it can take up to 15 minutes to knock the victim out. Victim often convulses as the drug takes effect. Skin blisters on face, where choloroform is in contact with the skin. Prolonged inhalation leads to death by heart failure, and ingestion by heart and liver failure. Chloroform Heavy colorless liquid. Nice smell. Used as anaesthetic, and to render a victim unconsious. However, it's not easy to cholorform a sleeping victim without waking them, and it can take up to 15 minutes to knock the victim out. Victim often convulses as the drug takes effect. Skin blisters on face, where choloroform is in contact with the skin. Prolonged inhalation leads to death by heart failure, and ingestion by heart and liver failure.

Chloral Hydrate is related. It is usually ingested and, in small doses, can knock someone out very quickly if, for example, placed in their drink. Larger doses cause death by heart and lung failure Chloral Hydrate is related. It is usually ingested and, in small doses, can knock someone out very quickly if, for example, placed in their drink. Larger doses cause death by heart and lung failure