L2. Introduction to Heavy Metals Flashcards
Metals in Biology
Easily donate and accept electrons
Form water soluble cations through electron loss
- Perform essential biological functions
- Electron transfer
- Redox reactions
- Electrochemistry and signaling
- Structural
Toxicity Mechanisms
Oxidative Damage: zinc
Altered electrophysiology and osmotic states: Na
Competition with “normal” elements for absorption: Mo/Cu
Incorporation into protiens in place of normal constituents: Pb/Ca
Metals of Most Veterinary Concern
lead
copper
zinc
sodium
iron
arsenic
Meatals - What are they?
A metal is 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
What is a Heavy Metal?
Poorly defined subset of elements that exhibit metallic properties
Relatively toxic (Pb, Sn, Hg, Ti, Au, Pt, Ba)
Considered meaningless by IUPAC
Toxilogical Properties
Cumulative in biological systems
Can change valence
Complex with organic molecules
Persistent in the environment
Can be strong oxidant
Bind to essential molecules
Many metal to metal interactions
Clinical toxic effects vary widely
General Considerations
In order to understand the basis fo heavy metal toxicity be familiar with their chemical properties and reactivity
Oxidation states
Bonding
Oxidation States
Heavy metals have multiple oxidation states
Common oxidation states of Se: -2, 0, +4, +6
This leads to the formation of different compounds having different toxicological properties
Bonding
Many heavy metals have coordinate covalent bonds
Sulfur, Oxygen, and Nitrogen bind to heavy metals through this type of bond
Can be basis for toxicity
Example: Heavy metals can bind to S atom on proteins and inactivate the enzymes
Lead
Killing people and animals for 4000+ years
Lead:
The king of toxic metals
Long use in human history
Maleable and low melting point
Forms many compounds (oxides, halides, sulfides, proteinates)
No offensive odor or taste
Highly cumulative in biological systems
Pb in Veterinary Medicine
The most common cause of Heavy metal intoxication
Poisoning most frequent in:
Cattle
Dogs
Cats, pet birds, zoo animals
Sporadically horse, sheep
Pigs resistant
Pb In Veterinary Medicine:
Example
Budgies in the zoo were poisoned by and old door in the exhibit that contained lead based paint
Curators set up the exhibit to look like an old mining set up in australia
Lead:
Major Effects
nervous system in the primary target
Mildly irritant to the GI mucosa
Anemia due to interference iwht RBC maturation
Lead (Pb):
Major Public Health Concern
Persistent in the environment
Increase Pb = Decreased IQ
No safe exposure level in people
Lead (Pb):
Significant in Animals
very commonly diagnosed in KSVDL in cattle, also often seen in dogs and pet birds
High risk to birds of prey, water fowl
Lead (Pb):
Source
- Lead carbonate used to be a common component of paint
- strictly controlled since the 1970s
- Old buildings/stored paint remain important sourses
- Lead-acid batteries:
- dumb sites, scrap cars
- Industrial/mining pollution
- Lead shot, Fishing weights, toys, ect.
Lead (Pb):
Important Kinetic Factors
- More surface area = more absorption
- lead/acid battery plates
- GIT mucosal surface area
- Acidic environments = more absorption
- Low pH leads ot ionization
- More time = more absorption
- lead particles may be trapped in the reticulum
- Relative tissue half lives
- blood → a few days
- liver/kidney → weeks
- Brain → months
- Bone → 1000 days
Lead (pB):
Sources for small animals
Pb based paint, chips, solder
Lead weights, sinkers, toys
Pb batteries
Motor oil form leaded gas engines
Old grease
Old linoleum
Pollution
Lead (Pb):
Signalment
- Seasonal incidence, spring, early summer
- Age:
- often younger animals
- Location:
- Dogs:
- older homes, lower income areas, work places
- Cities grew west ward from a river, east part of town has Pb, newer part does not
- Cattle:
- casual management, old buildings, junk piles, old machinery, unattended batteries
- Dogs:
- Species:
- dogs, cattle most frequently
Lead (Pb):
Toxicokinetics
Poorly absorbed …. 2% form GI tract
Dust Inhalation … Fine particles <0.5um
Lead shot/bullets in tissue …. 90% binds to RBC, some to albumin
- Ingested lead typically requires solubilizing
- acid environment of stomach vs, lead in soft tissue
- Tissue binding - first to erythrocytes
- Crosses blood-brain barrier and plancenta
- embryo toxicity
- Incorporation into bone:
- storage sites, detoxification mechanism
- Lead line: in radiographs, in gums
- Elimination:
- fecal
- urinary
Lead (Pb):
Mechanism of Action
- Binding to sulfydryl 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 and Zn related enzymes
Lead (Pb):
Clinical Presentation
Clinical onset usually delayed several days.
Time for absorption, binding to active sites
Depends on form of Pb
Organic: rapidly absorbed and distributed
Metallic: Slower absorption and onset
Carbonate, nitrate, oxide salts > acetate and Chloride salts
Lead (Pb):
Clinical Signs
Most Species
Onset = several days after exposure
Signs quite variable: slow vs, explosive
Gastrointestinal and Neurologic combo
Complete anorexia
CNS depression or convulsion
Species differences are important
Lead (Pb):
Clinical Signs
Dogs
GI: vomiting, anorexia, tender abdomen, Diarrhea/constipation
CNS: lethargy, hysteria, convulsions, ataxia, blindness, mydraisis
Clin Path → Increased nucleated RBCs and basophilic stippling without severe anemia
Lead (Pb):
Dogs
DDx:
Canine distemper, parasites
Methylxanthines, thremorgenic mycotoxins
NSAIDs
Salt Toxicolsis
Lead (Pb):
Cats
Clinical Signs
Less common due to eating habits
Lethargy, anorexia, vomiting, weight loss, excessive salivation
Neurological signs can be minimal
Inconsistent nucleated RBCs and basophilic stippling
Elevated AST, ALP
Lead (Pb):
Cats
DDx
OP’s, bromethalin, methylxanthines
Hepatic Encephalopathy
Lead (Pb):
Cattle
Clinical Signs
More common in calves
- GI:
- anorexia, rummen stasis, gaunt, salivation
- CNS:
- blindness, muscle twitching, head bobbing, depression, bruxism, circling, convulsions
- Acute convulsive death in calves
Lead (Pb):
Cattle:
DDx
Water deprivation, polio, OPs, nervous coccidiosis, Rabies
Lead (Pb):
Birds - pets, waterfowl
Clinical signs
Depressed, weak, anorectic, weight loss, esophageal paralysis, regurgitation, diarrhea,
wing droop
Lead (Pb):
Horses
Clinical Signs
Recurrent laryngeal nerve paralysis results in “roaring”
Ataxia, incoordination
Foals: metaphyseal sclerosis
Lead (Pb):
Pathology in cattle
Few Significant gross lesions
Pb objects in rumen or stomach
Rumen protozoa dead or inactive
Laminar Cortical necrosiss (DDx from PPM)
Inconsistent acidophilic intra-nuclear inclusions in renals tubules
Porphyrinuria
Lead (Pb):
Diagnosis
History Clinical Signs
Pb in WHOLE BLOOD
>0.35ppm (0.25ppm avian)
Normal = <0.05ppm
Pb in kidney or liver
Radiography - Pb objects in gut
Peripheral blood smear in dogs
Ca-EDTA mobilization test
Urinalysis: increased delta aminolevulinic acid, Pb concentration
Submit whole blood in a Purple Top Tube
Lead (Pb):
Therapy
*Remove animal from source*
- Stop further absorption
- decontaminate GI tract
- cathartics, enema according to species
- Endoscopy or gastrotomy to remove objects
- Oral MgSA4 in cattle-laxative anf formation of insoluble PbSO4
- Charcoal not effecitve for metals
- decontaminate GI tract
Lead (Pb):
Chelation
Treatment - increase excretion - chelators
CaEDTA-IV, SQ
D Penicillamine - Oral in SA
Succimer - approved in dogs 10mg/kg TID for 5 days then BID for 2 wks
Effective in cattle, but dosage and expensie preclude
Lead (Pb):
Treatment
Supportive
- Fluids, thiamine
- Control Seizures:
- valium
- Pnetobarbital +/-
- Mannitol, dexamethasone for cerebral edema
- Antioxidants
- Vit-C
- Vit-E
- N-acetylcysteine
- Good Nursing care
Lead (Pb):
Public Health
Children in household exposed to the same Pb source as pets - pets can be sentinals
- Food Safety:
- long residue time in bone
- Transfer to milk in early lactation
- Residues can vary from weeks to months
- Contact state veterinarian recommended
Prevention: owner/producer education
