Cardio Fluorosis

1st compartment

Blood Half-life = days to weeks

3rd compartment

Bone Half-life = years

1st compartment

Blood Half-life = days to weeks

2nd compartment

Soft tissues Half-life = weeks to months

Bile

Urine

Sweat hair nails

^ GI tract

Feces figure 3.1 Ingested lead distributes in a three-compartment model. Ingested lead is distributed in a three-compartment model in which the heavy metal is initially distributed to a central circulatory compartment; then to a highly perfused visceral organ compartment; and finally to the least perfused third compartment composed of bone, teeth, nails, and hair.

Absorption Distribution Excretion

Absorption Distribution Excretion

Bagassosis

FIGURE 3.2 Ingested lead distributes in a five-compartment model. Ingested lead is distributed in a five-compartment model in which the heavy metal is initially distributed to a central circulatory compartment; then to a highly perfused visceral organ compartment; and finally to the least perfused third compartment composed of bone and soft tissues, subdivided into labile and stable subcompartments.

FIGURE 3.2 Ingested lead distributes in a five-compartment model. Ingested lead is distributed in a five-compartment model in which the heavy metal is initially distributed to a central circulatory compartment; then to a highly perfused visceral organ compartment; and finally to the least perfused third compartment composed of bone and soft tissues, subdivided into labile and stable subcompartments.

Laboratory Assessment of the Poisoned Patient types of Lab tests

Chromatographic Assays

Monitoring: Requires precision. Example: gen-tamicin levels.

Screening: Requires sensitivity (Is a toxin present?). Example: employee urine drug tests. Diagnostic: Requires specificity (What is the toxin?). Example: forensic toxicology (tox) test.

Testing Methods (and Degree of Sensitivity and Specificity, + to +++)

Chemical Spot Tests (+)

Mechanism: Identify the chemical reactivity, usually by a color change, between a drug and its specific reagent.

Indications: Quick detection of single substances.

Example: Urine ferric chloride test for aspirin.

Spectrophotometry Tests (+)

Mechanism: Convert target drugs into identifiable light-absorbing compounds. Indications: Co-oximetry (for carbon monoxide, cyanide, and hydrogen sulfide poisoning) and colorimetry.

Example: Carboxyhemoglobin (COHb) levels.

Immunoassays (++)

Mechanism: Wide application; use drug-specific antibodies to identify toxic antigens, often using fluorescent polarization. Indications: Employee urine drug testing; affords rapid turn-around.

Thin-layer chromatography: Drugs are spotted and coated onto plates, then recoated with silica gels for identification by unique properties. High-pressure liquid chromatography: Drugs are separated as liquids under high pressure within tightly packed columns for identification by unique properties.

Gas chromatography: Drugs are extracted as gases at specific temperatures for identification by unique properties.

Gas chromatography/mass spectrometry GC/

MS): Highest sensitivity/specificity; effluent gases from initial gas chromatography are then ionized and separated by mass spectrometry. Example: opioid and amphetamine confirmation tests.

Blood/Serum Levels

Order for Diagnosis (Overdose Levels)

Acetaminophen (>150 mcg/mL) Carbon monoxide (>15% COHb levels) Ethanol (>0.08-0.10%) Ethylene glycol (>25 mg/dL) Iron (>500 mcg/dL) Methanol (>25 mg/dL)

Methemoglobin (MetHb) (>20-30% MetHb levels)

Salicylate (>60 mg/dL) Theophylline (>90-100 mcg/mL)

Order for Treatment

Therapeutic monitoring for all diagnostics, except ethanol Digoxin (>4 ng/mL) Heavy metals: arsenic, lead, mercury • Lithium (>4 mEq/L)

Organophosphates: Acetylcholinesterase (AchE) levels

Phenobarbital (>100 mcg/ml)

Routine Serum toxicology toxins routinely Detected

Alcohols Analgesics Antihistamines Antidepressants Barbiturates and sedatives Benzodiazepines Cardiovascular drugs Opioids and neuroleptics

Miscellaneous: theophylline, caffeine, nicotine, sulfonylureas, strychnine

Characteristics of toxins Not Routinely Detected and Mechanisms of Nondetection

Too polar (highly water soluble): Antibiotics, diuretics, ethylene glycol, isoniazid, lithium, metals.

Too nonpolar: Digoxin, steroids.

Too volatile: Anesthetics (nitrous oxide), hydrocarbons.

Too nonvolatile: Plant alkaloids. Too low: Very potent drugs taken in small doses with resulting low serum concentrations — fen-tanyl, sufentanil, alfentanil, colchicine, lysergic acid diethylamide (LSD).

Too toxic: Anions — bromide, cyanide, fluoride, nitrites.

Too new: All new drugs whose unique phys-iochemical signatures have yet to be fully determined.

Radiographic Evaluation

Visualizing Toxins

Unknown Radiopaque Toxins

Radiopacity = high physical density + high atomic number.

Radiopaque medications will contain elemental constituents of atomic number greater than 15: most heavy metals, barium, bismuth, calcium, chlorine, iron, lead, potassium. CHIPS = anticipate radiopacity with: Chloral hydrate, heavy metals (As, Cd, Cr, Fe, Hg, Pb, Th, Tl), iron, phenothiazines, sustained-release, and enteric-coated tablets (ECTs).

Known radiopaque toxins

Iron: Ferrous gluconate/sulfate. • Heavy metals: As, Bi, Cd, Cr, Fe, Hg, Pb, Tl. Toxins in radiopaque packets and containers:

Illicit packers and stuffers. Mothballs: Para-dichlorobenzene (densely radiopaque) > naphthalene > camphor (radiolucent).

Halogenated hydrocarbons: More chlorine groups contribute to radiopacity — carbon tetrachloride (CCl4), chloral hydrate, chloroform, halothane.

Radiopacity Crack Cocaine

FIGURE 3.3 Bismuth subsalicylate (Pepto-Bismal®) abuse. Abdominal radiograph that demonstrates ascending right colon and transverse colon radi-opaque substances in a patient with chronic bismuth subsalicylate abuse. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

FIGURE 3.3 Bismuth subsalicylate (Pepto-Bismal®) abuse. Abdominal radiograph that demonstrates ascending right colon and transverse colon radi-opaque substances in a patient with chronic bismuth subsalicylate abuse. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

Decreased Bone Density

Toxin-Induced Skeletal Changes

Increased Bone Density

Transverse metaphyseal bands on long bones:

Lead (arsenic) lines (see Figure 3.4). Fluorosis (children and adults): Otosclerosis, osteophytosis, ligament calcifications. Pediatric hypervitaminosis A: Subperiosteal new bone and cortical hyperostosis. Pediatric hypervitaminosis D: Generalized otosclerosis.

Corticosteroids: Diffuse osteoporosis and focal osteonecrosis (avascular necrosis, especially of the femoral heads) (see Figure 3.5). Adult hypervitaminosis D: Diffuse osteoporosis. Focal, lytic osteomyelitis: Intravenous drug users (IVDUs) with septic emboli to sternum and ster-noclavicular joints.

Distal acro-osteolysis: Vinyl chloride monomer exposure.

Lead Poisoning Treatment

FIGURE 3.4 Metaphyseal "Lead Lines." Frontal long bone radiograph of the legs of a 3.5-year-old girl with a chronic history of ingesting lead paint chips. Note the thickened, transverse, radiodense metaphyseal "lead (or arsenic) lines" and the widening of the metaphyses. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

Figure 3.5 Steroid-induced osteonecrosis. Coronal magnetic resonance (MRI) of the left hip in a patient on chronic corticosteroid therapy that demonstrates the characteristic "double line" sign of steroid-induced osteonecrosis with inner and outer hyperintense rim lines. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

FIGURE 3.4 Metaphyseal "Lead Lines." Frontal long bone radiograph of the legs of a 3.5-year-old girl with a chronic history of ingesting lead paint chips. Note the thickened, transverse, radiodense metaphyseal "lead (or arsenic) lines" and the widening of the metaphyses. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

Chest X-Rays: Lungs Airspace Filling

Diffuse filling: Acute respiratory distress syndrome — noncardiogenic pulmonary edema = aspirin, opioids, cocaine (see Figure 3.6). Diffuse filling: Cardiogenic pulmonary edema-alcoholic and cobalt cardiomyopathy, barbiturate overdoses, cocaine cardiomyopathy. Diffuse filling: Cholinergic bronchorrhea = organophosphate and carbamate pesticides, inhalants, low solubility gases (nitrogen dioxide, phosgene).

Focal filling: Aspiration, especially hydrocarbons.

Figure 3.5 Steroid-induced osteonecrosis. Coronal magnetic resonance (MRI) of the left hip in a patient on chronic corticosteroid therapy that demonstrates the characteristic "double line" sign of steroid-induced osteonecrosis with inner and outer hyperintense rim lines. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

Heroin Lung Intoxication And Steroid

FIGURE 3.6 Non-Cardiogenic Pulmonary Edema: Heroin Overdose. Frontal chest radiograph that demonstrates normal size and configuration of the cardiomediastinal silhouette with diffuse bilateral non-cardiogenic pulmonary edema following heroin overdose. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

FIGURE 3.6 Non-Cardiogenic Pulmonary Edema: Heroin Overdose. Frontal chest radiograph that demonstrates normal size and configuration of the cardiomediastinal silhouette with diffuse bilateral non-cardiogenic pulmonary edema following heroin overdose. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

Interstitial Patterns

Reticulonodular pattern: Hypersensitivity pneumonitis (sulfa drugs — nitrofurantoin) and allergic alveolitis (farmer's lung, bagassosis). Interstitial fibrosis: Cytotoxic chemothera-peutics (busulfan, bleomycin, methotrexate, cyclophosphamide).

Phospholipidosis: Amiodarone; injected particles in IVDUs from adulterated cocaine and heroin powders — talcosis from adulterated cocaine and heroin powders. Pneumoconioses: Asbestos, beryllium, coal, silica.

Chest X-Rays: Pleura, Mediastinum, Heart

Pleural effusions: Drug-induced lupus syndromes = hydralazine and procainamide; iso-niazid, methyldopa, chlorpropamide. Pneumomediastinum: Caustic-induced esophageal perforation, ipecac- or alcohol-induced Mallory-Weiss syndrome. Pleural plaques: Asbestosis. Hilar lymphadenopathy: Phenytoin, anthrax. Cardiomegaly: Alcoholic and cobalt cardio-myopathy, cardiotoxic chemotherapeutics = adriamycin.

Aortic dissection: Cocaine.

Abdominal X-Rays

Pneumoperitoneum: Secondary to gastrointestinal perforation = caustics (acids, alkalis, iron), cocaine, ipecac, lavage tube. Mechanical obstruction: Secondary to gastric outlet bezoars, or small bowel obstruction = enteric-coated tablets, concretions, body packers and stuffers (see Figure 3.9). Ileus: Secondary to decreased gastrointestinal motility = anticholinergics, antihistamines, tri-cyclic antidepressants (TCAs), opioids, ischemic bowel (cocaine, oral contraceptives), hypokale-mia, hypomagnesemia.

Intramural gas: Secondary to intestinal vaso-spasm, thrombosis, infarction = cocaine, ergots, oral contraceptives, clostridium derfringens toxin-induced pneumotosis intestinalis (pigbel).

Fluorosis Ray Kub

FIGURE 3.7 Pneumomediastinum: crack-cocaine inhalation. Frontal chest radiograph that demonstrates abnormal scattered radiolucencies in the mediastinum and base of neck consistent with pneumomediasti-num and cervical subcutaneous emphysema following crack-cocaine inhalation. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

FIGURE 3.7 Pneumomediastinum: crack-cocaine inhalation. Frontal chest radiograph that demonstrates abnormal scattered radiolucencies in the mediastinum and base of neck consistent with pneumomediasti-num and cervical subcutaneous emphysema following crack-cocaine inhalation. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

FIGURE 3.8 Cocaine-induced acute aortic dissection. Sagittal, oblique, T-1 weighted magnetic resonance image (MRI) of the chest demonstrating an intimal flap that divides the lumen of the descending aorta into a false lumen and a true lumen with blood flow, consistent with acute thoracic aortic dissection Type B in an intravenous crack-cocaine abuser. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

FIGURE 3.8 Cocaine-induced acute aortic dissection. Sagittal, oblique, T-1 weighted magnetic resonance image (MRI) of the chest demonstrating an intimal flap that divides the lumen of the descending aorta into a false lumen and a true lumen with blood flow, consistent with acute thoracic aortic dissection Type B in an intravenous crack-cocaine abuser. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

Radiodense foreign bodies = bismuth subsalicy-late, calcium carbonate, clay (pica), iron and other heavy metals, especially lead.

Body Stuffer

Figure 3.9 Body stuffer: heroin. Axial abdominal oral and intravenous contrast-enhanced computerized tomogram (CT) at the level of the renal veins that demonstrated a rectangular container of heroin in a jejunal loop. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

Figure 3.9 Body stuffer: heroin. Axial abdominal oral and intravenous contrast-enhanced computerized tomogram (CT) at the level of the renal veins that demonstrated a rectangular container of heroin in a jejunal loop. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

FIGURE 3.11 Cocaine-induced intestinal ischemia. Abdominal radiograph (KUB) demonstrating gas in the main portal vein and its intrahepatic primary and secondary branches with diffuse dilation and pneumotosis intestinalis of the small bowel and colon in a chronic cocaine abuser with acute mesenteric ischemia and multiple small bowel infarctions. Chronic ergot alkaloid ingestion may also be associated with acute mesenteric ischemia and small bowel infarction. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

Mechanical Ileus Kub

FIGURE 3.10 Opioid bowel: colonic ileus in a methadone abuser. Abdominal radiograph (KUB) that demonstrates air distension of the small bowel and transverse colon consistent with chronic constipation and colonic ileus in a methadone abuser. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

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