“Rules of Thumb” regarding chemical poisons (there are only a few useful ones):

    1. Anatomic lesions may be minimal. If lesions are present, will be mostly degeneration & necrosis NOT cellular inflammation.

    ; Systemic poisons usually affect organs where they are absorbed, metabolized, or excreted (i.e. gut, liver, kidney, brain, heart, lung)

    2. Diagnose via clinical lab findings

    ; Routine workup –can indicate which organs are damaged and how much (ex. basophilic stippling of RBCs, oxalate crystals in urine)

    ; If toxin is suspected –detect & measure toxin in bld, urine, feces, hair to help determine degree of intoxication

    3. Treatment –evaluate elimination of toxin, monitor improvement in organ function

     Mechanism Manifests as… Note

     I. Hypoxia

     ； Pulmonary edema; hemorrhage; hyaline Premature babies given >40% OA. 70-100% O: produces O free radicals & ？ O2222Incubator/resuscitator syndromes membrane; proliferation of Type II bronchopulmonary dysplasia & mediators of acute inflammation

    pneumocytes ； ARDS ； fibrosis retrolental fibroplasias ( *lesion is the same as seen in radiating

     pneumonitis b/c it’s also due to damage

     via free radicals *？ doses of CO, SO, NO, NO, Cl, 2222 NH, O all cause similar but more 33 chronic pulmonary lesions ； COPD B. CO: CO forms carboxyhemoglobin by Cherry red cyanosis (hypoxia but bld COHb = red compound 2+Auto exhaust & poor combustion outcompeting O and binding to Fe of remains red) *but pressure points of the body will not 2 heme; COHb can’t carry O be filled w/ bld ；will NOT be cherry 2 red ； can determine body’s position @ C. CN: death by looking at diff in color Plant seeds, silver polish, combustion Cyanide (CN) blocks Cytochrome saturated blood; body cells *both venous & arterial bld are bright Bright red O23+ products in burning buildings, pesticides oxidase Fe； Ocan’t be removed are hypoxic. red; has different mechanism than CO; 2 from the RBC CN gas smells like almonds D. CO, cyanides, HS (sewer gas): 2 Acute generalized hypoxia & death Survivors have brain damaged due to without anatomic lesions hypoxia E. Vasorestrictive Agents: Ergot alkaloid drugs used to tx migraine Local Hypoxia

    O from mucosa Acids: char mucosa (appears dark) Acids: withdraw HII. Local Necrosis 2

     Alkalis: penetrate tissue deeply Alkalis: liquefy tissue ； hemorrhage, A. Corrosives ulcerations, perforations Strong acids & alkalis

     III. Nervous Overstimulation

     Antidote: atropine blocks Ach *use with Inhibit Achesterase ； Ach is ， ？ stimulation of autonomic (esp. A. Organic Phosphates pralidoxime degraded parasympathetic & myoneuronal Insecticides junctions)

     Reduced hatching of eggs due to DDT B. Chlorinated Hydrocarbons

    Stimulates spinal reflexes, NSL C. Strychnine

     Phenycylidine (angel dust/PCP), LSD, D. Hallucinogens

    cocaine

     Mechanism Manifests as… Note

     IV. Cellular Degeneration & Necrosis

    Arsenic (As): rat poison, insecticides, Acute: CNS depression, GI hemorrhage at Distant Sites

    contaminated drinking HO *chronic As poisoning common in 2

    China & India where water wells are A. Heavy Metals: As, Hg(inorganic & Chronic: hyperkeratosis,

    contaminated by As hyperpigmentation of the skin ； organic), Cd, Pb

    *hair & finger nails are good to look at squamous cell carcinoma & peripheral for proof of heavy metal poisoning neuropathy

    Mercury Inorganic Hg: disinfectants, drugs Nephrosis, colitis, neurosis inorganic Hg NOT dangerous unless it’s

    “Mad hatters disease” (inorganic Hg) inhaled b/c it’s not absorbed thru skin

    Organic Hg: fungicides; ingestion of Lesions: nerve cell necrosis w/ brain Colon & kidney eliminate Hg ； they are

    fungicide tx’d grains; ingestion of atrophy of visual cortex Hg is methylated by marine bacteria ； affected

    animals that have eaten fungicide tx’d *fetuses are more susceptible; are born taken up by sea creatures ； eaten by

    grains w/ cerebral & cerebellar hypoplasia humans (bioaccumulation)

    Cadmium Cd: industrial pollution Neuropathy, nephropathy, cancer Lead Pb: paint, putty, HO from lead pipes, Signs: (1) burtonian gingival line (blue L burtonian gingival LINE 2

     improper glaze on ceramics, illicit color in gums) –adults (2) lead lines in E ERYTHROCYT. basophilic stippling/ ENCEPHALOPAHTY *problem in low SES populations (pipes whiskey, solder, pesticides, dust/dirt growing metaphyses of long bones, (3) A Anemia & paint) from renovations, leaching of external basophilic stippling of RBC’s, (4) D DROP wrist, foot Occupational/ environmental exposure – house paint peripheral neuropathy –adults (5) miners, plumbers, foundry or battery porphyrins & ALA in urine, (6) Pb in bld, Acutely poisoned children: injured urine, & hair workers cerebral capillaries ； cerebral edema, possible hemorrhage, and laminar Lesions: necrosis in prox. convoluted necrosis in severe cases tubule epithelium; acid fast intranuclear inclusions; anemia (b/c of interference w/ Subclinical intoxication sequela: heme synthesis) ？ fine motor control ； mental

    retardation

    EtOH –most common toxicant of adults B. Non Metals Acute: gastritis, fatty ; in liver, edema of brain, pancreatitis

    (5-10% of Americans)

     Chronic: fatty ; in liver, kidney, & heart; gastric ulcers; encephalopathies; *recognize hemorrhagic diathesis by cardiomyopathy; ？ resistance ； pneumonia; hepatic injury ； cirrhosis ； portal HTN contusions (bruises) and tendency to ； ascites , esophageal varices ； hematemesis, liver failure ； vitamin deficiencies ； bleed hemorrhagic diathesis; fetal alcohol syndrome; ？ cancer in mouth, esophagus, &

    stomach; ？ atherosclerosis; may be cerebral or testicular atrophy 2+ Ethylene Glycol: antifreeze, plants Liver metabolizes to Caoxalate ；acidosis; oxalate crystals block renal &

    sometimes cerebral vessels ； uremia & convulsions

    Adverse Drug Reactions (ADR) Cancer chemo drugs ； myelosuppression, immunosuppression, carcinogenesis; some

     kidney, liver, lung lesions

    *blood dyscrasias are common in serious Halothane, acetaminophen ； liver cell necrosis

    ADRs Aspirin ； gastritis & hemorrhage

    Phenacetin + Aspirin ； renal papillary necrosis

    Diethylstilbestrol (DES) ； reproduct. problems if exposed in utero ； clear cell

    carcinoma of vagina

Special Subjects:

    1. Drug addiction: LSD, cocaine, heroin, PCP

    ; Skin abscesses when ; Endocarditis ; Foreign body pneumonia ; Myocardial arrhythmia &

    injected subcutaneously ; Hypersensitivity angiitis ; Viral hepatitis infarction

    ; Phlebitis ; Pulmonary edema (acute ; AIDS ; Cardiomyopathy

    ; Ceullulitis overdose

2. Tobacco smoking:

    ; Cancer of lung, mouth, larynx, esophagus, pancreas, bladder, kidney

    ; COPD

    ; Coronary & cerebral vascular disease

    ; ？ infant mortality when fetus is exposed in utero

Warfare & Terrorist Toxicants:

    1. Nerve Agents: Soman (GD), Sarin (GB), Tuban (GA), VX, & VF

    ; Organophosphates

    ; Colorless, odorless, tasteless

    ; Inhibit Achesterase ； hyperactivation of cholinergic pathway ； convulsions, tremor, hypersecretion, & respiratory failure

    ; Antidote: atropine w/ pralidoxime; anticonvulsants can also be used

    *pretreatment w/ pyridostigmine enhances antidote’s effects

2. Vessicants: Sulfur Mustard (HD) & Lewisite (L) General: ; Cause blisters on skin, mucous membranes, eyes & lungs (if inhaled) 12-24 hrs after exposure ; 2,000,000 poisonings in US/ year ; Mustards & VX are persistent in the environment for many days ; 6-10,000 deaths due to poisoning/ year ; Few deaths generally *50% of these deaths are due to suicide ; Injuries require hospitalization (L – several weeks; HD – 1-4 months) ; Accidental poisoning = most common in children, age 2-5 y.o. 3. Pulmonary Toxicants: Phosgene (CG), Diphosgene (DP) & Chlorine ; Iatrogenic poisonings can occur in adverse ; Induce death due to pulmonary edema drug reactions ; Do NOT persist in the environment ; Almost any substance can be a poison ; May penetrate protective equipment Ex. if a marathon runner just drinks water ; Cyanides are less toxic but are difficult to handle w/o replacing electrolytes he loses while sweating, the water can be 4. Botulinum Toxin:

     fatal! ; Most potent toxin on the planet

    ; Only bacterial toxin formed outside of the organism

    ; Is usually an intoxicant NOT an infection *exception: infants and rare GI infections

    ; Toxins A-G interfere w/ Ach release ； paralysis

    ; 12-72 hrs after exposure:

     -symmetric descending flaccid paralysis w/ bulbar palsies

     -4 D’s: diplopia, dysarthria, dysphonia, dysphagia

     -afebrile

     -clear sensorium

     -paralysis of neck and eventually the respiratory muscles

    ; Tx: antitoxin & respiratory support until new axons innervate the muscle *new toxoid is available