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Mechanism

By Monica Adams,2014-05-09 20:59
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Mechanism

“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

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