呼吸功能障碍性毒物呼吸功能障碍性毒物Respiratory dysfunction toRespiratory dysfunction to

xicantxicant

Department of Forenxic ToxicDepartment of Forenxic Toxicologyology

Shizhong Bian Shizhong Bian

氰化物中毒氰化物中毒

Cyanide PoisoningCyanide Poisoning

CyanideCyanide

rapid acting toxin (used for suicide)rapid acting toxin (used for suicide)combined with sugar as cyanogenic glycombined with sugar as cyanogenic gly

cosidecosidelocalized in vacuoles in leaves and seedlocalized in vacuoles in leaves and seed

ssenzymes that separate CN from sugar aenzymes that separate CN from sugar a

re in the cytosolre in the cytosolwilting or crushing plant releases CNwilting or crushing plant releases CN

CyanideCyanide

more than 1000 plant speciesmore than 1000 plant speciesvariety of CN glycosides – don’t learn nvariety of CN glycosides – don’t learn n

ames or structures:ames or structures:cherriescherries prunasin and amygdaprunasin and amygda

linlinsorghumsorghum dhurrindhurrinflaxflax linamarinlinamarinwhite cloverwhite clover lotaustralinlotaustralinarrowgrassarrowgrass triglochinintriglochinin

Potential CN glycoside Potential CN glycoside toxicitytoxicityconcentration in plant, N in soilconcentration in plant, N in soilspecies of plant; breed crop for less CNspecies of plant; breed crop for less CNstage of growth (young plants)stage of growth (young plants)hormone herbicideshormone herbicidesdry weather followed by raindry weather followed by rainlow sunlight – glycosides may low sunlight – glycosides may

accumulate over night so highest accumulate over night so highest toxicity in morningtoxicity in morning

Potential CN glycoside Potential CN glycoside toxicitytoxicitydamage to plant – trampling, frostingdamage to plant – trampling, frostingamount eaten, rate of ingestionamount eaten, rate of ingestionsize and type of animal – ruminants size and type of animal – ruminants

most susceptible (enzymes more most susceptible (enzymes more active at neutral pH, microbes active at neutral pH, microbes release CN)release CN)

food ingested with itfood ingested with it

Detoxification of cyanideDetoxification of cyanide

endogenous thiosulfateendogenous thiosulfatecatalyzed by rhodanesecatalyzed by rhodanesethiocyanate formsthiocyanate forms

(thiocyanates from chronic low level exp(thiocyanates from chronic low level exposure produce goiter in adult or fetus)osure produce goiter in adult or fetus)

excreted in urineexcreted in urine

Other sources of cyanideOther sources of cyanide

electroplating or cleaning metalselectroplating or cleaning metalssoil sterilantsoil sterilantrodenticidesrodenticides

CyanideCyanide

CN combines with cytochrome oxidase sCN combines with cytochrome oxidase systemystem

ties up ferric iron so can no longer transties up ferric iron so can no longer transport oxygen into cellsport oxygen into cells

histotoxic anoxiahistotoxic anoxiabright red blood with lots of oxygenbright red blood with lots of oxygen

• Mechanism of toxicityMechanism of toxicity• Cyanide ions bind to the iron atom of thCyanide ions bind to the iron atom of th

e e enzymeenzyme cytochrome c oxidase (also kn cytochrome c oxidase (also known as aa3) in the fourth complex in the own as aa3) in the fourth complex in the mitochondrial membrane in the mitochmitochondrial membrane in the mitochondria of cells. This deactivates the enzyondria of cells. This deactivates the enzyme, and the final transport of electrons fme, and the final transport of electrons from cytochrome c oxidase to oxygen carom cytochrome c oxidase to oxygen cannot be completed. As a result, the electnnot be completed. As a result, the electron transport chain is disrupted, meaninron transport chain is disrupted, meaning that the cell can no longer aerobically g that the cell can no longer aerobically produce ATP for energy.produce ATP for energy.

Mechanism of toxicityMechanism of toxicity

• Tissues that mainly depend on aerobic rTissues that mainly depend on aerobic respiration, such as the central nervous sespiration, such as the central nervous system and the heart, are particularly affystem and the heart, are particularly affected.ected.

• binds to sulfhydryl groups and binds to sulfhydryl groups and sulphur sulphur , disru, disrupts sulfhydryl or pts sulfhydryl or sulphursulphur-containing enzyme-containing enzymes.s.

Clinical signsClinical signs

found dead (15 min)found dead (15 min)excited, generalized muscle tremorsexcited, generalized muscle tremorsrapid breathing, dyspnearapid breathing, dyspneaincreased salivation and lachrymationincreased salivation and lachrymationinvoluntary urination and defecationinvoluntary urination and defecation

Clinical signsClinical signs

down, gasping for breathdown, gasping for breathclonic convulsionsclonic convulsionsdilated pupilsdilated pupilsmucous membranes bright pinkmucous membranes bright pinkblood very bright redblood very bright redRarely time to treatRarely time to treat

Necropsy of acute caseNecropsy of acute case

bright red bloodbright red bloodblood slow to clot or does not clotblood slow to clot or does not clothemorrhage from terminal strugglinghemorrhage from terminal strugglingbitter almond odor to ingestabitter almond odor to ingesta

DiagnosisDiagnosis

history of exposure, clinical signshistory of exposure, clinical signsconfirm by testing blood, rumen confirm by testing blood, rumen

content, liver, muscle for CNcontent, liver, muscle for CNtest forage for CNtest forage for CNfreeze sample, submit frozenfreeze sample, submit frozenpreserve in 1-3% mercuric chloride if preserve in 1-3% mercuric chloride if

can’t freezecan’t freeze

Picric acid test

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

Carbon monoxideCarbon monoxide

Carbon Monoxide COCarbon Monoxide CO

• Colorless The SILENT KILLERColorless The SILENT KILLER• OdorlessOdorless• TastelessTasteless• Slightly lighter than air (drop in a fire!)Slightly lighter than air (drop in a fire!)• Product of incomplete combustionProduct of incomplete combustion

– 1. Time1. Time– 2. Temperature2. Temperature– 3. Turbulence (oxygen)3. Turbulence (oxygen)

Carbon monoxideCarbon monoxide

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

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

COHBCOHB

• CarboxyhemoglobinCarboxyhemoglobin• Oxygen carried by hemoglobin on red blOxygen carried by hemoglobin on red bl

ood cell (rbc)ood cell (rbc)• Hemoglobin likes CO better than it likes Hemoglobin likes CO better than it likes

oxygen oxygen • Tissues (brain) don’t get enough oxygeTissues (brain) don’t get enough oxyge

nn

ChloroformChloroform

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

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