17 Laboratory Diagnostic Toxicology
Principles of Toxicologic Diagnosis
To assist with clinical observations and help determine organ systems affected, Tables 17-1 through 17-6 show probable toxicoses associated with different organ systems and clinical signs (e.g., seizures, hepatic failure, vomiting); however, very few toxicoses have pathognomonic signs. While many signs of poisoning (e.g., vomiting, seizures) are also caused by infectious, metabolic, and endocrine diseases, knowledge of high-risk toxicology differentials is the first step in working through the diagnostic process. A thorough history and physical examination should be completed to determine potential exposure to toxicants. Telephone instructions should include having the owners collect any potential baits, vomitus, or other suspect materials for possible chemical analysis.
TOXICANT | COMMON SOURCES | ADDITIONAL SIGNS |
---|---|---|
Excitation | ||
Aminopyridine | Bird control baits. | Tremors, ataxia, may be hyperexcitable. |
Caffeine, other methylxanthine alkaloids | Chocolate, coffee, tea; stimulant or anti-drowsiness pills sold OTC. | Excitement, exaggerated reflexes, hyperreflexia; cardiac arrhythmia, hyperpnea, vomiting. Alkaloids detectable in GI contents, blood, or urine. |
Cyanide | Cyanogenic plants (apple, peach, cherry seeds); fumigants; rodenticides (rarely); industrial chemicals. | Excitement, agitation, seizures progressing to ataxia, weakness, and collapse; also salivation, hyperpnea, pink mucous membranes. Very rapid course. Test stomach contents, blood for cyanide, or liver and muscle from dead animals. |
Lead | Paint (pre-1970) or specialty paints, lead objects (drapery weights, fishing sinkers). | Intermittent vomiting and behavioral changes; tremors, ataxia, seizures, altered vision, anorexia. |
Metaldehyde | Snail and slug baits; solid fuels sold OTC. | Continuous tremors, occasional seizures; incoordination and cerebellar ataxia; nystagmus, salivation also prominent. |
Pyrethrins, pyrethroids | Active ingredients in insecticides for pets and homes. | Tremors, hyperexcitability, excitement, occasional seizures; sometimes alternate with depression. |
Strychnine | Mole and gopher baits, usually less than 0.05% for below-ground use. | Acute onset of hyperesthesia, hyperreflexia progressing to tetanic seizures exacerbated by external stimuli; rapid shallow respirations, tachycardia. |
Tremorgenic mycotoxins | Penitrem A on moldy walnuts, other nut products; less commonly, spoiled dairy products. | Tremors, ataxia, and hypermetria are characteristic and may be continuous; exacerbated by exercise or stress. Test stomach contents or suspect materials for penitrem A or other tremorgens. Available laboratory testing is limited. |
Zinc phosphide | Used as alternative to anticoagulants; sold OTC in some states. Bait has mild garlic or acetylene odor. | Excitement, stimulation, and seizures; may include tremors and “running fits.” Alternative sign may be depression. Vomiting, colic often accompany the neurologic signs. |
Depression or coma | ||
Alcohols | Beverages, disinfectants, brewery residues. | Depression, disorientation early, followed by coma, respiratory depression, acidosis, cardiac arrest. Alcohol residues appear in blood and urine. |
Barbiturates | Access to tablets or capsules; occasionally in meat from animals euthanatized with barbiturates. | Depression, loss of reflexes, hypothermia, hypotension, coma, respiratory failure. Barbiturates in blood or urine of living animals; liver or kidney of dead animals. |
Bromethalin | Relatively new rodenticide, often used as an alternative to anticoagulant rodenticides. | Signs may include posterior ataxia and weakness, sometimes vomiting resulting from cerebral edema. Available laboratory testing is limited. |
Citrus oils | Citrus extracts used in insecticides and repellents (e.g., d-limonene). Most hazardous to cats. | Depression, ataxia, coma, and pronounced hypothermia. Citrus extracts are conjugated in the liver and excreted in urine. Few laboratories offer routine testing for these products. |
Carbon monoxide | See Table 17-5. | See Table 17-5. |
Ethylene glycol | Automobile radiator antifreeze solutions. Also used to prevent freezing in water pipes of vacant houses or mobile homes. | Profound depression early is due to alcohol-like inebriation; later signs of depression are due to severe metabolic acidosis. |
Hydrocarbons (aliphatic and aromatic) | Petroleum distillates and pine oil compounds; most available in paint thinners, mineral spirits, cleaning solutions; exposed by spilling on skin, footpads, or by inhalation of fumes. | Generally there is initial depression and ataxia similar to ethanol intoxication. High dosage leads to vomiting, possible liver and/or kidney damage, severe depression, coma, respiratory depression, and death. |
Signs of parasympathetic stimulation | ||
Blue-green algae | Blue-green algae (Anabaena spp. and Microcystis spp.) are most prevalent in lakes and farm ponds during late summer. | In addition to sudden death (neuromuscular paralysis) and hepatotoxicity, blue-green algae may inhibit cholinesterase, causing signs of salivation, vomiting, tremors, and dyspnea. Cholinesterase inhibitor resting requires whole blood sample. Water samples for blue-green algae should be submitted fresh and fixed (addition of 1 part formalin/9 parts water). |
Ivermectin, milbemycin, moxidectin | Anthelmintics, ectoparasite control, both small animal and large animal (higher concentration products). | Ataxia, hyperesthesia, salivation, vomiting, bradycardia, recumbence. See MDR1 gene general description in text. |
Opioids | Prescription or recreational drugs. | Miosis, salivation, arrhythmia, vomiting, defecation, urination. Urine samples may test positive. |
Organophosphate and carbamate insecticides | Home and garden pest control; limited use for small animal ectoparasite control. | Salivation, lacrimation, miosis vomiting, diarrhea, bradycardia, dyspnea, urination, ataxia and muscle weakness. Whole blood sample for confirmation of cholinesterase inhibition. |
Nicotine | Tobacco products, specialty insecticides (e.g., nicotine sulfate). Also used occasionally in capture guns. | Initial signs are due to early depolarization (tremors, excitement, lacrimation, vomiting), followed by paresis, ataxia, and complete collapse with death from respiratory paralysis. Nicotine alkaloid is readily detected in stomach contents, blood, or urine. |
Signs of parasympatholytic agents | ||
Amphetamines | Prescription or recreational drugs, including methamphetamine. | Mydriasis, tachycardia, but lack other predominant effects of anticholinergics. |
Atropine | Plant, Atropa belladonna, may be grown as ornamental in gardens. | Causes dry mucous membranes, mydriasis, tachypnea, tachycardia, hyperthermia, disorientation, visual dysfunction, GI stasis. Readily detected in blood and/or urine. |
Ephedra/ma huang | Herbal product for weight loss, decongestant, recreational. | Mydriasis, tremors, seizures, hyperthermia, salivation, death. |
Scopolamine | Hyoscyamus niger and Datura spp. are common plant sources. Also available as pharmaceutical. | Signs and effects are similar to those with atropine (above). |
SSRIs (selective serotonin reuptake inhibitors) | Prescription drugs. Veterinary use for urine spraying, lick granuloma, separation anxiety. | Mydriasis, autonomic instability, tremors, seizures, bradycardia, vomiting, diarrhea, colic. |
Ataxia, incoordination, weakness, or paralysis | ||
Aminoglycoside antibiotics | Kanamycin, neomycin, streptomycin, gentamicin. | Effects are due to post-synaptic receptor blockade of neuromuscular junctions, results in paresis, paralysis, and death from respiratory failure. Testing of blood and/or urine may establish exposure. |
Botulism | Clostridium botulinum growth in decaying organic matter, especially with high protein content. | Lower motor neuron paralysis results in muscle weakness, difficult deglutition, progressive paresis and paralysis, mydriasis, dysphagia. Suspect material from stomach contents may be cultured or injected in mice as a bioassay, followed by protection tests with antitoxin. |
Cholinesterase inhibitors | See Signs of parasympathetic stimulation. | Test for confirmation of cholinesterase inhibitors as described above for organophosphate and carbamate insecticides in Signs of parasympathetic stimulation. |
Ivermectin, milbemycin | See Signs of parasympathetic stimulation. | |
Mycotoxins, tremorgenic | Moldy refrigerator foods (e.g., cream cheese, walnuts, peanuts, high-protein products). | Vomiting, diarrhea, agitation, tremors, hyperthermia, tachycardia, pigmenturia from rhabdomyolysis. |
Modification of behavior | ||
Atropine/scopolamine | See Signs of parasympatholytic agents. | Behavioral effects of disorientation and possible loss of vision appear secondary to overdose of atropine. Diagnosis of atropine overdose is described in Signs of parasympatholytic agents. |
Ethanol | See Depression or coma. | See Signs of depression or coma. |
Lead | See Excitation. | Lead exposure may cause changes in mental abilities, lost recognition of familiar persons, belligerence, and hysteria. |
Lysergic acid diethylamide (LSD) | Sources are some plant forms (morning glory seeds, ergotized grains) or illicit street drugs. | May be profound behavioral changes ranging from excitement and hallucinations to deep depression. Analysis of vomitus or stools may help to establish exposure. |
Marijuana | Illicit street drugs, prepared from leaves or seeds of Cannabis sativa. Sometimes prepared in foods such as brownies. | Behavioral changes may include depression, excitement, hallucinations with barking at unknown stimuli; nystagmus, vomiting, and diarrhea. Diagnosis by recognition of suspect material and/or testing of blood or urine for cannabis alkaloids. |
GI, Gastrointestinal; OTC, over-the-counter.
TOXICANT | COMMON SOURCES | COMMENTS |
---|---|---|
Direct irritants | Very nonspecific. Expect acute onset, potential oropharyngeal lesions, gagging, colic, emesis and/or diarrhea (possibly hemorrhagic); bloat or flatulence. | |
Acids, alkalis, aldehydes | Batteries, cleaners and bleaches, disinfectants. | Salivation, dysphagia, acute glossopharyngeal swelling, cough, nasal discharge. Laboratory testing of suspect materials may establish source, but animal testing for these substances is usually not practical or helpful. |
Petroleum distillates | Solvents, paint thinners, furniture cleaners, gasoline, kerosene. | Coughing, vomiting, choking. Possible sequel is aspiration pneumonia and central nervous system depression. Agents are difficult to detect in blood or tissues by laboratory tests. |
Volatile oils | Turpentine, gum spirits, pine oil, eucalyptus oil, pennyroyal oil, lemon oil. | Acute gastroenteritis with vomiting and possibly diarrhea. Systemic effects can include seizures, delirium, depression, and coma. |
Gastroenteritis, hemorrhagic | Aflatoxin, aspirin, NSAIDs. | Aflatoxin is also hepatotoxic; Aspirin and NSAIDs may include gastric ulcers, platelet dysfunction, and/or renal damage. |
Gastroenteritis, hyperemic/necrotic | ||
Amanita phalloides (death cap, death angel) | Wild, toxic mushroom. Most prominent in eastern or western seacoast regions. | Acute clinical signs are hemorrhagic gastroenteritis with vomiting and bloody diarrhea, hepatosis after a latent period of 12–24 hours. Available laboratory testing is limited. |
Arsenic, antimony, bismuth | Older insecticides or herbicides, including ant baits; old paint pigment. Most uses of arsenic are restricted or canceled. Antimony may be present in caustic pastes. | Acute vomiting, followed by moderate to severe diarrhea changing from watery to necrotizing and hemorrhagic within 24–48 hours. Hypotension, shock and renal tubular damage are additional effects. Analysis of urine or gastrointestinal contents can help to establish exposure. Liver and kidney concentrations from postmortem specimens can be helpful. |
Iron | Accidental access to dietary iron supplements. | Acute gastroenteritis, shock, vascular collapse and death, liver damage 1–2 days later. Test for liver function, assay total serum iron and total iron-binding capacity. |
Staphylococcus toxins | Spoiled foods, especially egg and high-protein products left at room temperature. | Severe vomiting and diarrhea may develop after short latent period (<3 hr). Cultures may identify the potential bacterium but alone are not confirmatory. |
Gastroenteritis, nonhemorrhagic | ||
Digitalis glycosides | Accidental access to prescription medicines; plant sources including foxglove, oleander. | Cardiac signs may be preceded or accompanied by colic and vomiting. |
Lead | See Table 17-1. | Vomiting is intermittent. |
TOXICANT | COMMON SOURCES | COMMENTS |
---|---|---|
Acetaminophen | Over-the-counter pain killer and anti-inflammatory drug. | Initial signs of vomiting, cyanosis, and facial edema are followed by icterus, depression, and mild methemoglobinemia. |
Amanita phalloides | Wild mushroom, most common in East or West coast areas. | Acute vomiting is followed in 1–2 days by liver failure. |
Blue-green algae | Algal forms, commonly concentrated by low water and prevailing winds. | Acute gastroenteritis, vomiting, and hemorrhagic diarrhea. Water fixed in formalin 1 : 10 can be examined for presence of blue-green algae. Frozen samples are used for toxic activity by mouse bioassay. |
Iron | Dietary supplement pills. | See Table 17-2. |
Petroleum distillates | Solvent in paints, paint thinners, paint strippers; fuels including gasoline, kerosene. | Liver damage may accompany initial signs of neurologic dysfunction. |
Sago palm | Toxic plant outdoors in tropical climates, indoors as potted plant. | Icterus, severe liver damage, secondary signs from liver failure. Often fatal if left untreated. |
TOXICANT | COMMON SOURCES | COMMENTS |
---|---|---|
Albuterol | Inhalers, decongestant. | Arrhythmias, tachycardia. |
Alpha2-adrenergic agents | Xylazine (often iatrogenic), detomidine, romifidine for veterinary use. | Arrhythmias, bradycardia, hypotension, AV block, vomiting, occasional apnea. Hyperglycemia is common. |
Amphetamines, methamphetamine | Prescription of recreational drugs. | Tachycardia. Accompanied by seizures, tachypnea, mydriasis. |
Azalea | Ornamental shrub. | Arrhythmias, often preceded by vomiting and gastroenteritis. |
Baclofen | Human prescription drug. Skeletal muscle relaxant. | Arrhythmias, bradycardia in severe overdose. Other signs are vomiting, ataxia, salivation, hypothermia. |
Calcium channel blockers | Human and veterinary cardiovascular prescription. | Bradycardia, arrhythmia, hypotension, vomiting, weakness. |
Cardioactive glycosides | Digoxin and related prescription drugs; foxglove, oleander, Bufo spp. toads. | Vomiting, colic, diarrhea, followed by weakness, bradycardia, and arrhythmia. |
Cholecalciferol | Vitamin supplements, rodenticides. High dosages cause signs in 12–36 hr. | Hypercalcemia, azotemia, bradycardia, arrhythmias, dystrophic calcification. |
Cocaine | Illegal street drug. | Tachycardia and arrhythmias. Test plasma or urine. |
Ionophores | Poultry coccidiostats; ruminant feed supplements. Dangerous to dogs. | Trembling, weakness, stiffness, recumbency, cardiovascular insufficiency. Analysis of stomach contents; cardiac muscle biopsy for diagnosis. |
Pimobendan | Veterinary prescription for congestive heart failure—usually accidental overdose. | Large overdose causes arrhythmias, hypotension, tachycardia, vomiting, diarrhea. |
Yew bushes | Ornamental evergreen shrubs with strap-like, two-ranked, dark-green leaves. | Sudden death several hours after ingestion; nervousness, trembling, bradycardia and arrhythmia. Test for yew alkaloids in stomach. |
AV, Atrioventricular.
TOXICANT | COMMON SOURCES | COMMENTS |
---|---|---|
Anemia, hemolytic | ||
Methionine | Urinary acidifier (given to dogs to decrease brown spots in lawn). | Heinz body anemia, also methemoglobinemia in cats; abdominal pain, agitation, hyperactivity. CBC, chemistry panel for low BUN, hypoglycemia. |
Mothballs, naphtha | Home care product; exposure possible by oral or inhalation routes. | Heinz body anemia. Confirm with hematology examination. |
Onions, garlic | Accidental access to large amounts in prepared foods or by direct ingestion. | Acute signs are typical of hemolytic crisis. |
Phenothiazine anthelmintics | Older, little-used anthelmintics. | Acute hemolytic crisis may occur. Phenothiazine in urine becomes oxidized to a red color. Phenothiazine can be detected in blood or urine, but routine testing is not offered by many laboratories. |
Propylene glycol | Component of many consumer products. Alternative antifreeze. | Heinz body anemia (cats). Also depression, weakness, hypotension, acidosis. |
Zinc | Zinc metal objects, galvanized food or water containers, zinc ointments, pennies minted after 1983. | Vomiting and diarrhea in combination with pale mucous membranes and icterus. |
Methemoglobin | ||
Acetaminophen | OTC analgesic and anti-inflammatory. See Table 17-3. | Hepatotoxicosis is prominent. Blood may display dark-brown color due to methemoglobinemia. |
Aniline dyes | Shoe polish, inks, paints. More prominent in older products. | See Nitrites, below. |
Chlorates | Soil/contact herbicide or soil sterilant. Used where prolonged suppression of plant growth is desired. Accidental ingestion of granules may occur. | See Nitrites, below. |
Nitrites | Lawn fertilizers, explosives, meat-curing agents, contaminated well water. | Methemoglobinemia, cyanosis, weakness, depression, hyperpnea. See Acetaminophen in text for analysis of methemoglobin. |
Carboxyhemoglobin | ||
Carbon monoxide | Poorly vented heaters, automobile exhaust. | Depression, weakness, somnolence, coma, and death. Mucous membranes are bright pink and blood is cherry-red to pink. |
Aplastic anemia and thrombocytopenia | ||
Benzene | Gasoline and industrial or commercial products as a solvent. Small animals could be at risk by inhalation exposure. | Causes initial central nervous system signs of tremors, ataxia. Cardiac fibrillation may occur at high acute exposures. Prolonged exposures usually cause pancytopenia. Serum iron is increased and fetal hemoglobin may be increased. Anemia is macrocytic with relatively few reticulocytes that are generally immature. |
Estrogens | Used to correct mismating, treat prostatic hyperplasia, induce abortion, or reduce urinary incontinence. | Lethargy, weakness, pale mucous membranes, petechial hemorrhages, hematuria, melena. Pancytopenia, reduced reticulocyte count. |
Coagulopathy | ||
Anticoagulant rodenticides | OTC baits for rodent control in homes and business. | Dermal and mucosal petechiae and ecchymoses, hemoptysis, epistaxis, melena, pale mucous membranes, weakness, dyspnea, subcutaneous hematoma, muffled heart and lung sounds, depression, and death. |
BUN, Blood urea nitrogen; CBC, complete blood count; OTC, over-the-counter.
TOXICANTS | COMMON SOURCES | COMMENTS |
---|---|---|
Aminoglycoside antibiotics | Primarily kanamycin, neomycin, and gentamicin. | Usually occurs with extended treatment. Initial findings are polydipsia/polyuria followed by vomiting and azotemia. |
Ethylene glycol | Automobile radiator antifreeze fluids. | Initial signs are in central nervous system with ataxia and depression, followed by metabolic acidosis, oxalate nephrosis, and azotemia. |
Fungal toxins | Ochratoxin or citrinin in refrigerated table foods (cream cheese, nuts). | Signs are polydipsia, polyuria from renal tubular nephrosis. |
Grapes/raisins | Accidental access to large amounts by dogs. | Anorexia, lethargy, vomiting and diarrhea. Confirm with renal function tests and hypercalcemia/hyperphosphatemia. |
Halogenated hydrocarbons | Solvents in commercial products, paints, cleaning agents. | Initial signs may include inebriation, incoordination, and depression followed in 1–3 days by toxic tubular nephrosis. Clinical laboratory findings reflect acute tubular injury. |
Metals | Many metals and metalloids are potent tubular toxicants. | Effects and signs are typical of tubular nephrosis. Samples for analysis of metals should include blood, urine, kidney, and liver. |
Nonsteroidal anti-inflammatory agents | Ibuprofen, naproxen, usually accidental or owner administered. | Renal damage and clinical laboratory findings are similar to those for the aminoglycoside antibiotics. See Table 17-1. |
Plants (non-oxalate) | Easter lily (Lilium spp.), daylily (Hemerocallis spp.). | Cats appear most at risk to these plants. The lilies have a potent tubular toxicant. Suspect animals should be tested for renal function. No toxicant analyses currently available. |
Vitamin D3 | Vitamin supplements and vitamin D3 (cholecalciferol)-based rodenticides. | Signs after latent period of 18–24 hr; progress over 1–3 days to polyuria, polydipsia, renal pain on palpation. |
Clinical Laboratory Tests
After clinical data are obtained from history and physical examination, laboratory testing is used to identify and characterize pathophysiologic effects typical of specific toxicants (e.g., basophilic stippling and nucleated red blood cells [RBCs] without reticulocytosis suggest lead toxicosis; high serum osmolality, hypocalcemia, and an increased anion gap are consistent with ethylene glycol [EG] toxicosis). Table 17-7 summarizes clinical laboratory tests that may be altered by specific toxicoses. Several clinical laboratory parameters may be altered by some toxicants, although others may cause no significant changes.
LABORATORY PARAMETER | TOXICANT(S) | EFFECT ON VALUES |
---|---|---|
Alanine aminotransferase | Acetaminophen, aflatoxin, benzimidazole anthelmintics, halogenated hydrocarbons (e.g., halothane, chloroform) hydrocarbon solvents, iron, melaleuca oil, mushrooms (Amanita spp.), phosphides, sago palm, xylitol, zinc | Moderate to massive increase depending on dosage and toxicant. |
Ammonia | Ammonium-based fertilizers | Increased. |
Toxic liver injury | Increase associated with signs of hepatic encephalopathy. | |
Anemia, nonregenerative | Cadmium, lead, zinc | Varies in severity; lead usually mild anemia, zinc often is clinically important. |
Cancer chemotherapy (e.g., 5-fluorouracil ointments for skin cancer) | Dosage dependent: 5-fluorouracil patients may die acutely before anemia develops. | |
Phenylbutazone | ||
Chloramphenicol | More likely in cats than dogs. | |
Estrogen therapy | Usually only at high dosage over extended time period. Ferrets may be unusually sensitive. | |
Anemia, regenerative | Acetaminophen, aspirin, copper, methionine, mothballs (naphtha), onions/garlic, phenols, propylene glycol | Heinz bodies indicate oxidant injury from toxicants listed. |
Azotemia | Calcium supplements | Also decreased GFR, nephrolithiasis. |
Methionine | Also elevated serum ammonia and lipase. | |
Mothballs | Also hyperbilirubinemia and acidosis. | |
NSAIDs, veterinary | Also anemia, oliguria, hypoalbuminemia. | |
Paintballs | Also lactic acidosis and hypovolemia. | |
Paraquat | Also oliguria. | |
Sago palm | Also hypoalbuminemia and hypoglycemia. | |
Salt | Also acidosis and hypernatremia. | |
Zinc | Increased urinary hemoglobin and bilirubin. | |
Basophilic stippling | Lead | Accompanied by nucleated red cells. Mild anemia of low clinical significance. |
Bile acids | Acetaminophen, aflatoxins, corticosteroids, diethylcarbamazine, 5-fluorouracil, sago palm, thiacetarsamide (Caparsolate) | Early onset of mild to moderate increase, often preceding other parameters of liver injury. |
Bilirubin | Acetaminophen, aflatoxins, thiacetarsamide (Caparsolate) | Increased. |
Blood pH | ||
Acidosis | Alcohols, aspirin, bread dough, cholecalciferol, essential oils, ethylene glycol, grapes/raisins, hops, iron, metaldehyde, methionine, oxalates, paintballs, phenol/pine oils, phosphides, propylene glycol | Acidosis, usually resulting from metabolic disturbance or less commonly from acidic nature of the toxicant. |
Alkalosis | Calcium supplements, diuretics, foreign bodies, phenols/pine oil, | |
Calcium, serum | Calcipotriene, cholecalciferol rodenticide, diuretics, grapes/raisins, hops, xylitol | Increased. |
Ethylene glycol, fluorides, hydrofluoric acid, oxalates, phosphate enemas, rhubarb, soaps | Decreased. | |
Casts, renal | Aminoglycoside antibiotics, arsenic (cats), cadmium, lilies (most species), nonsteroidal anti-inflammatory drugs | Renal epithelial damage as sequel to renal tubule toxicosis. |
Chloride, serum | Ammonium chloride | Mechanisms of elevation include loss of concentrating ability, laboratory interference. |
Amphotericin | ||
Bromides | Watch for potential laboratory error. | |
Lithium | ||
Cholinesterase in RBCs | Blue-green algae, hydrofluoric acid, ivermectin, organophosphate/carbamate insecticides, phosphides | |
Coagulation factors | Anticoagulants for human cardiovascular disease (“blood thinners”); coumarin-based rodenticides (e.g., warfarin, brodifacoum, bromadiolone) | Prolonged PT and aPTT associated with loss of factors II, VII, IX, X. |
Creatine kinase | Ionophores (e.g., monensin, lasalocid, salinomycin) | Increased. |
Crystalluria | Oxalate-containing plants (e.g., rhubarb, oxalis) | Oxalate crystals in urine sediment. |
Ethylene glycol metabolites | Oxalate crystals appear in urine, also from impression smears of kidney at necropsy. | |
Melamine/cyanuric acid in contaminated commercial foods. | Outbreak reported in 2007. Usually accompanied by advancing signs of renal failure. | |
Gamma-glutamyl transpeptidase | Barbiturates, glucocorticoids | Moderate increase. |
Glucose | Albuterol, alcohols/aldehydes, alpha2-adrenergic agonists (detomidine, dexmedetomidine, xylazine), amitraz insecticide, calcium channel blockers, ephedra/ma huang, iron, pyrethrins/pyrethroids, scorpion envenomation, sodium monofluoroacetate (compound 1080) | Increased. Causes of hyperglycemia are varied, primarily related to blocking of TCA cycle or sympathetic stimulation of glucose release. |
Hemoglobinuria | Acetaminophen, brown recluse spider venom, chlorate herbicides, copper, crotalid snake (pit viper) venom, mothballs, onions/garlic, propylene glycol (cats), Zinc (metallic) | Elevated, mild to severe. Often a result of strong RBC oxidant and hemolytic properties of the toxicant. |
Icterus, serum | Acetaminophen, aflatoxin, benzodiazepines, blue-green algae, club drugs, mothballs, mushrooms, phosphides, sago palm, veterinary NSAIDs, xylitol, zinc | Also reflected at lower concentrations as hyperbilirubinemia in clinical laboratory profile. |
Leukocyte count | Benzene | Neutropenia with likely left shift. |
Chloramphenicol | Chemical neutropenia and/or pancytopenia is generally due to inhibition or destruction of stem cells after prolonged use. | |
Estrogens (dog) | ||
Phenylbutazone | ||
Magnesium, serum | Gentamicin | Decreased, secondary to nephrosis or hypercalcemia. |
Vitamin D–induced hypercalcemia | ||
Methemoglobin | Acetaminophen, benzocaine, chlorate herbicides, copper, meat curing salts (nitrites), methionine, nitrites, onions/garlic, phenols, smoke inhalation | MetHb increased more than 40% causes clinical signs. MetHb may be metabolized rapidly or change after collection; contact laboratory for instructions on preservation and shipping. |
Osmolarity | Aspirin, ethanol, ethylene glycol, phosphate enema | Hyperosmolarity and high osmolar gap. |
Porphyrinuria | Hexachlorobenzene, lead | Moderate increase from inhibition of porphyrin synthesis pathway. |
Pancytopenia | Benzene derivatives, cancer chemotherapy, chloramphenicol, 5-fluorouracil, thallium | |
Phosphate, serum | Cestrum diurnum (night blooming jessamine), cholecalciferol rodenticides | Increased due to vitamin D effect. |
Xylitol | Xylitol is reported to cause either hyperphosphatemia or hypophosphatemia. | |
Phosphate, serum | Albuterol | Decreased. |
Potassium, serum | Angiotensin-converting enzyme inhibitors, calcium channel blockers, digitalis glycosides, diuretics, grapes/raisins, matches/fireworks, NSAIDs | Increased. |
Potassium, serum | Albuterol | Decreased. Albuterol also may cause decreased serum phosphate and serum magnesium, elevated lactate, and secondary hyperglycemia resulting from sympathetic stimulation. |
Sodium, serum | Aspirin, chocolate/caffeine, dehydration, excess salt intake, grapes/raisins, paintballs | Increased. |
Thrombocyte count | Aflatoxin, cephalosporins, crotalid (pit viper) snakes, estrogens, 5-fluorouracil, IFE therapy, NSAIDs, phenols, sago palm, xylitol, zinc | Decreased. |
aPTT, activated partial thromboplastin time; GFR, glomerular filtration rate; IFE, intravenous fat emulsion; MetHb, methemoglobin; NSAIDs, nonsteroidal anti-inflammatory drugs; PT, prothrombin time; RBC, red blood cell; TCA, tricarboxylic acid.
A major use of the toxicology laboratory is to determine the presence and possibly the amount of a specific toxicant. Two levels of toxicant testing are suggested by various authorities. The first is clinical evaluation (as in the previous paragraph). These include blood gases, electrolytes, glucose, blood urea nitrogen (BUN), creatinine, hepatic function tests, anion gap, osmolality, and renal function. The second level is specific drug or toxicant assays.6 After clinical laboratory evaluation, clinicians may utilize some form of “screening” test for rapid turnaround to suggest potential toxicant groups. Depending on results of screening procedures, a specific confirmatory instrumental or immunologic procedure may be chosen to support the initial diagnosis. These are often most important when there is potential product liability or a need for forensic evidence (as in suspected malicious poisoning). Quantification of a positive test may be important for interpretation of some toxicoses, but not for others. For example, any amount of strychnine in stomach contents is considered diagnostic of a toxicosis while other toxicant diagnoses depend on quantitation (e.g., lead) above a threshold to establish toxicosis. Quantification of toxicants is greatly influenced by passage of time and the half-life of that specific toxicant. Thus if specific confirmatory tests are anticipated, early collection of vomitus, feces, blood, and urine may be the key to a good chemical laboratory confirmation.