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Introduction to Metals Flashcards

1
Q

What functions do metals serve in biology?

A
  • Easily donate and accept electrons
  • Form water soluble cations through electron loss
  • Perform essential biological functions
    • Electron transfer
    • Redox reactions
    • Electrochemistry and signaling (Ex: Na, Ca, K)
    • Structural (Ex: Ca in bone)
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2
Q

What are the toxicity mechanisms of metals?

A
  • Oxidative damage (Zn)
  • Altered electrophysiology and osmotic states (Na)
  • Competition with normal elements for absorption (Mo/Cu)
  • Incorporation into proteins in place of normal constituents (Pb/Ca)
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3
Q

What metals are of the highest concern for veterinarians?

A
  • Lead
  • Copper
  • Zinc
  • Sodium
  • Iron
  • Arsenic
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4
Q

What is a metal?

A
  • A chemical element whose atoms readily lose electrons to form cations, and form metallic bonds between other metal atoms and ionic bonds with nonmetal atoms
  • Exist as elements or compounds
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5
Q

`What is a heavy metal?

A
  • Poorly defined subset of elements tat exhibit metallic properties
  • Relatively toxic (Pb, Sn, Hg, Tl, Au, Pt, Ba)
  • Considered meaningless by IUPAC
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6
Q

What are the toxicological properties of heavy metals?

A
  • Cumulative in biological systems
  • Can change valence
  • Complex with organic molecules
  • Persistent in the environment
  • Can be strong oxidants
  • Bind to essential molecules
  • Many metal to metal interactions
  • Clinical toxic effects vary widely
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7
Q

What are the oxidation states of heavy metals?

A
  • Multiple states
  • This lead to the formation of different compounds having different toxicological properties
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8
Q

What elements form covalent bonds with heavy metals?

A
  • Sulfur, oxygen, and nitrogen
  • Can be basis for toxicity
    *
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9
Q

What animals are commonly affected by lead poisoning?

A
  • Cattle
  • Dogs
  • Cats, Pet birds, zoo animals
  • Sporadically hoses and sheep
  • Pigs are resistant
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10
Q

What are the major effects of lead?

A
  • Nervous system is the primary target
  • Mild irritant to GI mucosa
  • Anemia due to interference with RBC maturation
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11
Q

What are the sources for lead?

A
  • Lead carbonate used to be a common component of paint
    • Strictly controlled since the 1970’s
    • Old buildings/ stored paint remain important sources
  • Lead-acid Batteries
  • Industrial/mining pollution
  • Lead shot, bullets
  • Lead weights
  • lead sinkers
  • lead toys
  • Motor oil form leaded gas engines
  • Old grease
  • Old linoleum
  • Pollution
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12
Q

What are the important kinetic factors of lead?

A
  • More surface area = more absorption
    • Lead/acid battery plates
    • GIT mucosal surface area
  • Acidic environment = more absorption
    • low pH leads to ionization
  • More time = more absorption
    • lead particles may be trapped in the reticulum
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13
Q

What is the half-life of lead in various tissues?

A
  • Blood - a few days
  • Liver/kidney - weeks
  • Brain - months
  • Bone - >1000 days (practically a lifetime burden)
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14
Q

What is the common signalment for lead poisoning?

A
  • Seasonal incidence - spring, early summer
  • Age - often younger animals (pups, calves)
  • Locations:
    • Dogs - older homes, low income areas, work places
  • Cattle - casual management, old buildings, junk piles
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15
Q

What are the Toxicokinetics of lead

A
  • Ingested lead typically requires solubilizing
    • Acidic environment of stomach vs. lead in soft tissue
    • Poorly absorbed - ~2% from GI tract
    • Dust inhalation - fine particles < 0.5 um
  • Tissue binding - first to erythrocytes
    • 90% binds to RBC, some to albumin
  • Crosses blood-brain barrier and placenta - embryo toxicity
  • Incorporation into bone:
    • storage site, detoxification mechanism
    • Lead line - in radiographs, in gums
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16
Q

How is lead eliminated from the body?

A
  • Fecal
  • Urinary
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17
Q

What are the acute toxicity amounts of lead?

(Calves, cattle, dog, horse, ducks geese)

A
  • Calves - 40-600 mg/kg
  • Cattle - 600-800 mg/kg
  • Dog - 191-1000 mg/kg
  • Horse - 500-750 mg/kg
  • Ducks - 18 pellets of #6 shot
  • Geese - 25 pellets of #6 shot
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18
Q

What are the chronic toxicity amounts of lead?

(Calves, cattle, dog, horse, ducks geese)

A
  • Calves - none (would be adults)
  • Cattle 1-7 mg/kg
  • Dog 1.8-2.6 mg/kg
  • Horse 2.4-7 mg/kg
  • Ducks 2 mg/kg
  • Geese - unknown
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19
Q

What is the MOA of lead?

A
  • Binding to sulfhydryl groups
    • Heme synthesis ⇓
    • Altered GABA transmission
  • Competition with divalent cations Ca++ ions
    • Displace Ca++ from binding proteins
    • Altered nerve and muscle transmission
  • Inhibition of membrane associated enzymes
    • Calmodulin, Na./K pumps
  • Altered vit D metabolism
    • Impaired Ca++ absorption & Zn related enzymes
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20
Q

What is the clinical presentation of lead toxicosis?

A
  • Clinical onset usually delayed several days
    • Time for absorption, binding to active sites
  • Depends on form of lead
    • Organic: rapidly absorbed and distributed
    • Metallic: slower absorption & onset
      • Carbon, nitrate, oxide salts > acetate & chloride salts
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21
Q

What are the clinical signs of lead toxicosis in most species?

A
  • Onset = several days after exposure
  • Signs quite variable: slow vs explosive
  • GI + Neurologic combo
    • Complete anorexia
    • CNS depression / Convulsion
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22
Q

What are the clinical signs of lead toxicity in Dogs?

A
  • GI: vomiting, anorexia, tender abdomen, diarrhea/constipation
    • usually appear first
  • CNS: lethargy, hysteria, convulsions, ataxia, blindness, mydriasis
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23
Q

What clinical pathology is found in dogs with lead toxicosis?

A
  • Increased nucleated RBC’s and basophilic stippling without severe anemia
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24
Q

What are the differential diagnosis for lead toxicosis in dogs?

A
  • Canine distemper
  • Parasites
  • Methylxanthines
  • Tremorgenic mycotoxins
  • NSAIDs (GI)
  • Salt toxicosis
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25
What are the clinical signs of lead toxicosis in cats?
* Less common due to eating habits * Lethargy * Anorexia * Vomiting * Weight loss * Excessive salivation * Neurologic signs can be minimal
26
What are the clinical pathology findings in cats with lead toxicosis?
* Inconsistent nucleated RBC's and basophilic stippling * Elevated AST, ALP
27
What are the differential diagnosis for cats with lead toxicosis?
* Organophosphates * Bromethalin * methylxanthines * Hepatic encephalopathy
28
What are the clinical signs of lead toxicosis?
* GI: anorexia, rumen stasis, gaunt, salivation * CNS: blindness, muscle twitching, head bobbing, depression, bruxism, circling, convulsions * Acute convulsive death in calves
29
What are the differential diagnosis for cattle with lead toxicosis?
* Water deprivation * Polio * Organophosphates * nervous coccidiosis * Rabies
30
What are the clinical signs of Birds with lead toxicosis?
* Depressed * Weak * Anorectic * weight loss * esophageal paralysis * regurgitation * diarrhea * Wing droop
31
What are the clinical signs of lead toxicosis in horses?
* Recurrent laryngeal nerve paralysis results in “roaring” * Ataxia, incoordination * Foals - metaphyseal sclerosis
32
What is the gross pathology of lead toxicosis in cattle?
* Lead objects in rumen or stomach * Rumen protozoa dead or inactive * Laminar cortical necrosis (DDx from PEM) * Inconsistent acidophilic intra-nuclear inclusions in renal tubules * Porphyrinuria
33
How is Lead toxicosis diagnosed?
* History, clinical signs * Lead in **whole blood** * \>0.35 ppm (0.25 avian) * Normal = \< 0.05 ppm * Lead in Kidney or Liver * \>8 ppm * Normal = \<0.5 ppm * Radiography- Lead objects in gut * **Peripheral blood smear (dogs)** * nucleated RBC's, basophilic stippling * **Ca-EDTA mobilization test** * Urinalysis: increased delta aminolaevulinic acid (ALA), Lead concentration
34
What is the treatment for lead toxicosis? (Broad sense)
* Remove animal from source * Stop further absorption * Increase excretion-chelators * Supportive care
35
How can further absorption of Lead be stopped?
* Decontaminate GI tract * cathartics, enema according to species * Endoscopy or gastrotomy to remove objects * Oral MgSO4 in cattle (laxative and formation of insoluble PbSO4 * **Charcoal NOT effective for metals**
36
What Chelators are used for lead toxicosis treatment
* CaEDTA - IV/SQ * standard for cattle - FDA restricts use * D penicillamine - PO in SA * Succimer * DMSA (dimercaptosiccinic acid) Chemet, Bock (PO in SA) * Approved (dogs) 20mg/kg TID for 5 days then BID for 2 weeks * Effective in cattle, dosage and expense preclude
37
What is the supportive care for lead toxicosis?
* Fluids, thiamine * Control seizures: valium, pentobarbital+/- * Mannitol, dexamethasone for cerebral edema * Antioxidants (Vit C, E): N-acetylcysteine * Good nursing care
38
What are the public health concerns with lead?
* Children in household exposed to the same lead source as pets * Food safety: * long residue time in bone * transfer to milk in early lactation * Residues can vary from weeks to months * Contact state veterinarian recommended
39
What is Arsenic (As)?
* Metalloid * Elementa, organic, and inorganic * Trivalent (+3) comes as organic and inorganic * Pentavalent (+5) comes as organic and inorganic
40
What are the sources of Arsenic?
* Mining sites and smelters * Insecticides and herbicides * Wood preservative * Medicinal (heartworm therapy) * feed supplements
41
What are the sources for inorganic Arsenic?
* Old pesticides - Lead arsenate, herbicides * Terro ant poison * Ashes of Chromated Copper Arsenate (CCA) lumber * common source for cattle
42
What are the Toxicokinetics of Arsenic?
* Absorption of different forms is variable * major toxicity factor * Distribution: * Accumulation initially in liver and then slowly distributed to other tissues (ie spleen, liver, lung) later accumulates to keratinized tissue * Crosses placenta and is embryotoxic * Crosses blood-brain barrier * Hair and keratinized tissue - eliminated in the feces and urine
43
What are the toxic mechanisms of inorganic Arsenic?
* Binds with sulfhydryl enzymes * Blocks cellular respiration * Acts on tissues with high respiration * Gut epithelium, capillaries * Phosphate competition - uncouples oxidativephosphorylation * Toxicity: trivalent is 5-10x more toxic than pentavalent * **Arsenite (+3) \> Arsenate (+5) \> organic As** * **Arsenite-** inhibits ATP synthesis * sulfhydryl inhibition (enzymes) * a-lipoic acid - TCA cycle * Arsenate- resembles Pi in structure and reactivity, replaces phosphate
44
What Arsenic was used in Heartworm therapy and what are the effects?
* Thiacetarsamide - Caparsolate * Vomiting * Liver and kidney damage * Ivermectin, melarsomine (melaminylthioarsenate) and **Diroban (melarsomine HCL**) commonly used now
45
What are the GIT clinical signs of inorganic Arsenic toxicosis?
* Vomiting * Intense abdominal pain * Diarrhea (+/- blood) * Fluid loss * Maybe acute death (hours) * Marked dehydration * Weakness, staggering gait
46
What lesions are common with inorganic arsenic toxicosis?
* GI hemorrhage, edema, fluid filled * Sloughing, mucosa * Renal tubular degeneration
47
How is inorganic arsenic toxicosis diagnosed?
* Arsenic analysis of kidney, liver \>8ppm * Suspect material * Urine contains As if kidneys are functioning * Accumulates in hair for chronic exposure * Blood is NOT a good diagnostic source
48
What are the treatment options for inorganic arsenic toxicosis?
* Most attempts are futile * Rehydration * BAL (dimercaprol) is classic antidote, best _before_ signs * Thiotic acid 50mg/kg q8hr * Succimer (DMSA)
49
What is Iron (Fe)?
* Common in human dietary supplements and vitamin/mineral tablets * Ingestion of concentrated Fe sources can be toxic to children and pets * Injections can be toxic
50
What are the levels of toxicity of Iron?
* Non toxic \<20 mg/kg * Mild-Moderate 20-60 mg/kg * Serious \>60 mg/kg * Life threatening \>200 mg/kg
51
What are the 4 stages of clinical effects of Iron toxicosis
1. 0-6hr: Corrosive effects 1. nausea, vomiting, diarrhea, GI hemorrhage 2. 6-12hr: Apparent remission 3. 12-24 hr (in severely poisoned dogs) 1. Severe lethargy 2. Reocurrance of GI signs 3. Metabolic acidosis 4. Liver necrosis 5. Coagulopathy 6. Cardiovascular collapse, shock 4. Several weeks later: 1. scarring and stricture of GI tract
52
How is Iron toxicosis diagnosed?
* History, Clinical signs * Abdominal radiograph * mass of pills in stomach * Serum Fe: * normal 80-249 ug/dL * 300-500 ug/dL monitor * \>500 chelation therapy * If serum Fe\>TIBC = poison likely * (Total iron binding capacity)
53
What is the treatment for iron toxicosis?
* Emetic in alert animal, gastric lavage or gastrotomy * NOT CHARCOAL * Fluids, electrolytes, A/B balance * GI protectants * Chelation therapy: * Deferoxamine (Desferol) * Initial IV infusion - 15 mg/kg/hr * IM 40 mg/kg q 4-8hr * Continue until serum Fe is below 350 ug/dL
54
What is Mercury (Hg)?
* Toxicosis is infrequent and sporadic * in last 30 years are associated with Hg fungicide treated seed * Unusual metal because it is a liquid at normal temperatures * **Hg vapor poses a substantial hazard** * 3 different forms in the environment * Elemental Hg, Hg0- metallic or vapor * Inorganic mercury, Hg Salts HgCl2 * Organomercurial compounds, * alkyl forms = ethyl, methyl, propyl, dimethyl, etc, and aryl forms of Hg such as phenylmercuric acetate * Hg accumulates as alkyl, methyl, and ethyl mercury
55
What are the sources for Mercury?
* Batteries * Some pharmaceuticals - * calomel - antiseptic salve, in laboratory electrodes and as a fungicide * Industrial effluents, sewage sludge * Ocean waters - marine fish, shell fish, mackerel, shark, swordfish, tilefish, tuna * Thermometers, barometers fluorescent tube
56
What are the toxic levels of Mercury?
* Elemental Hg is low in toxicity orally * Hg salts: 1mg/kg/day is toxic to cats in 15 days * Hg salts: large animals 8-12 mg/kg * Methyl (alkyl) mercury 0.2 - 0.5 mg/kg * Phenyl (aryl) mercury - Swine 1 mg/kg * Highly toxic on a chronic basis
57
What are the clinical effects of inorganic mercury?
* Gi and renal tubular necrosis
58
What are the clinical effects of organic mercury?
* **Crosses BBB and Placenta** * Neurologic fibrinoid degeneration of arterioles * neuronal necrosis ⇢ blindness, staggering, incoordination, recumbency, death
59
How is mercury absorbed?
* Elemental Hg poor GIT absorption * Vapors are absorbed and dangerous * Salts and organ mercurial are absorbed in the GIT
60
How is Mercury excreted?
* Kidney ⇢ urine * Fecal * Lungs
61
What are the mechanisms of toxicity of Mercury?
* Primary targets are the kidneys and CNS * Bind to sulfhydryl groups * Inhibit enzymes and protein synthesis * Inhibit mitochondrial function by binding to alpha lipoic acid and thioctic acid * Sulfur containing organic acid cofactor involved in aerobic metabolism * Pyruvate dehydrogenase complex (PDC)
62
How is Mercury toxicosis diagnosed?
* Whole blood \> 1ppm * Liver * Kidney * Hair * Urine * Feeds
63
How is Mercury toxicosis treated?
* Acute exposure: * Egg white, activated charcoal, sodium thiosulfate (0-1 g/kg) * Saline cathartic or sorbitol * Oral penicillamine (1-50mg/kg) orally * DMSA * Chronic organic exposure: selenium and Vit E
64
What risk does mercury pose to public health?
* Bioaccumulation & bio magnification in the food chain * sediments ⇢ fish ⇢ mammals * Mercury residues in kidney & muscle tissue * highest concern in fish - (0.7 - 1.5 ppm)
65
What is Thallium (Tl)?
* Discovered in 1861 Sir William Crooks * Elementary Tl is Non-toxic * **Monovalent and trivalent salts are very toxic** * Thallous - +1 oxidation state * Thallic - +3 oxidation state * Heavy metal - very toxic and highly cumulative
66
Sources of thallium?
* World production is 12 tons/yr * Semiconductors, photocells, optic glass, thermometers * Tl201 radioactive tracer used in heart scintigraphy to detect myocardial ischemia * Rodenticides
67
What is the MOA of Thallium?
* Blocks energy utilization by Na-K-ATPase channel * blocks active transport of K across the cell membrane * Similarities in charge between K+ and Tl * Tl has a 10x greater affinity than K+ in neuronal, cardiac, and skeletal muscle cells * Half-life of 30 days * Blocks energy production from glucose * ADP to ATP by pyruvate kinase - K requiring enzyme * Tl binds with 50x affinity compared to K+ * Damages riboflavin, forming an insoluble complex and intracellular sequestration of vit B6 * Binds to SH groups and interferes with formation of disulphide bonds in keratin, structural damage to hair and nails (depilatory) * Causes activation or inhibition of other enzymes * ALA synthetase, B12 metabolism
68
What are the clinical effects of thallium toxicosis?
* Multisystemic disease * GI necrosis - sever hemorrhagic gastritis, congested oral mucosa * Neurologic - trembling, motor paralysis, mental retardation * Alopecia and skin sloughing from 7 days to 2-3 weeks after ingestion, renal and liver injury * Blindness
69
How is Thallium toxicosis diagnosed?
* Urine thallium (any concentration is significant) * Kidney * liver, feces
70
What is the treatment for Thallium toxicosis?
* Radiogardase - prussian blue insoluble capsules * ineffective once clinical signs are apparent * Dithizon - chelator for Thallium
71
What is Fluoride?
* Reactive, water soluble non-metal * Common in nature, variable in distribution
72
What are the sources for fluoride?
* Mining deposits * Rock phosphates (feeds) * Water from deep wells/geothermal water * Industrial pollution (particles may settle on pastures) * Production of industrial processing of aluminum ores or phosphate fertilizers * fertilizers and calcium phosphate minerals must be defluorinated * Pesticides
73
What are the \_\_\_\_\_\_\_
* Affects mineralized tissue * teeth bone * Deposits in hydroxyapatite crystal of bone and distorts normal Haversian system remodeling * Dental fluorosis is dystrophic formation of dentin and enamel in erupting teeth only (marker for time of exposure)
74
What are the clinical effects of fluoride toxicosis?
* Chronic exposure: * Progressive debilitating disease * Cattle, horses, wild herbivores * Osteofluorosis: * Bone formation on outside of long bones (exostoses) * produces lameness * Dental fluorosis: * Softening of tooth enamel, early wear
75
What are the kinetics of fluoride?
* Rapidly absorbed * Excreted through urine * some through milk * ~50% absorbed dose sequesters in bone * Mostly in developing/remodeling bone * Developing teeth - erupted teeth unaffected
76
What is the clinical picture of Fluoride toxicosis?
* Large, acute exposure: * GI irritation and kidney damage * Moderate/Chronic exposure: * more common * affects bones and developing teeth * Osteogenesis is interrupted/altered * Prominent effects seen in long bones, mandibles and rib surfaces * Articular surfaces are NOT affected * Spurring around joints produce pain and lameness * Abnormal postures, stiffness, disinclination to move, weight loss
77
How is Fluoride Toxicosis diagnosed?
* History, clinical signs, lesions * Feed, mineral, and water analyses * Biopsies of coccygeal vertebrae or ribs * Urine fluoride may be helpful within 1-3 weeks of exposure * kidney and liver can be tested postmortem
78
What are the clinical signs of fluoride toxicosis?
* Lameness * weight loss * elongated hooves * lapping water
79
What are the common lesions seen with fluoride toxicosis?
* Dental fluorosis in erupting teeth * Exostosis of limbs, ribs, mandible * Fl analysis: * Urine (15-20 ppm) - recent * bone (\>3000 ppm) - prolonged exposure
80
What is the treatment for Fluoride toxicosis?
* No specific treatment * poor prognosis * Pain management and soft feed may allow salvage following extended recovery periods * Avoid exposure * Aluminum or Ca-carbonate at 1% of diet will reduce fluoride absorption

Toxicology (25 decks)

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