Update on heavy metals toxicity (Proceedings) - Veterinary Healthcare
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Update on heavy metals toxicity (Proceedings)


CVC IN KANSAS CITY PROCEEDINGS


Lead (Pb)

Sources

Lead-based paints, lead-based gasoline, solder, combustion residues, caulking compounds, improperly glazed pottery, batteries, buck-shots, sewage sludge, some canned commercial dog foods, electronic wastes, etc.

Canned foods dogs and cats - 2.6 (1.0-5.6) and 3.0 (0.9-7.0) respectively

Hankin, L. et al., 1975

Toxicokinetics

Exposure – Primarily by ingestion
Rapid and variable absorbed – 2-10% (mature) 30-40% (young/immature) animals
Unabsorbed lead (immature); Widely distributed - bone and teeth; soft tissues, kidneys, brain (grey matter and various nuclei) and blood: T1/2 in bones (10-30 years); soft tissues (40 days); blood (28-36 days) soft tissues.
Tightly bound (95%) to red blood cells (RBC) – membrane and hemoglobin
Excretion–Urine (20-30% of absorbed Pb – Dogs), bile >> feces, sweat, sloughed skin cells and hair).

Affects many organ systems.

The gastrointestinal, nervous, and heme synthesis are the most commonly affected

Clinical signs – common to all species

Gastrointestinal – abdominal pain, constipation, vomiting, anorexia, hypertension, oligurea, and weight loss.
Encephalopathy – seizures, blindness, depression (days post exposure), anemia, protein-urea. Dog/cats – Vomiting anorexia, constipation, anemia, basophilic stippling, nucleated RBC in peripheral blood (reticulocytosis), increased zinc proto-porphyrin.

Pathophysiology

Complexes with SH and other functional groups of enzymes, structural proteins, transport systems, and receptors.
Binds to delta-aminolevulenic acid dehydratase >> depress activity; Inhibits essential enzymes (delta-aminolevulinic acid dehydratase, ferrochelatase and coproporphyrinogen oxidase) in heme synthesis (presence of substrates – urine, plasma and blood are supportive of diagnosis) >> anemia. Zinc replaces ferrous iron at its binding sites within the porphyrin ring thereby forming zinc protoporphyrin. (diagnostic test for lead exposure/intoxication. Increased RBC fragility, normo-cyclic/normo-chromic erythrocytes. Increased cytoplasmic calcium leading to cell death. Inhibits energy metabolism in the brain capillaries – microvascular, accumulation >> encephalopathy
Renal - Intranuclear bodies and swelling

Diagnosis

Increased blood lead levels > 0.35ppm with appropriate clinical signs.(do not used blood lead alone diagnostically).
Confirm – Whole blood lead level (kidney and liver lead – supportive)
     0.35ppm in addition to appropriate clinical signs – Diagnostic
     0.20ppm - Excessive exposure
     10ppm - liver and kidney (wet weight) Diagnostic
Elevated nucleated RBC in peripheral circulation
               15 nucleated /10,000 RBC suggestive
               40 nucleated/10,000 RBC – diagnostic
Urinalysis – increased heme synthesis intermediates (Pb is inhibitory to Enzymes: aminolevulinic acid dehydratase, ferrochelatase and coproporphyrinogen oxidase)
Radiographic lesions – increased growth plate opacity, soft tissue lead deposits

Treatment

Cathartics – move unabsorbed lead from GI tract
Surgical intervention

Chelation: Dimercaprol (BAL): 6mg/kg deep IM for 3-5 days (do not exceed five days – nephrotoxicity). Crosses blood brain barrier and will chelate brain lead.
Meso-2,3-dimercapto-succinic acid "succimer" Dogs – 10 mg/kg,3x daily for 10 days PO.
Calcium disodium EDTA – 27 mg/kg, 4 daily for 5 days – slow IV or SQ
Drawbacks – does not cross blood brain barrier, nephrotoxic, induces hypocalcemia
D-Penicillamine – 8 mg/kg 4x daily (toxic response – anorexia, listlessness, vomiting).
Evaluate response to treatment and retreat if necessary.


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