Heavy metal toxicoses in pet birds: Watch for combination of gastrointestinal and nervous systems signs
Surgery may be necessary if the lead particles cannot be removed with other methods.
Heavy metal toxicoses are commonly reported in companion and free-ranging avian species. Most often toxicosis occurs from ingestion lead from various sources including fishing and curtain weights, batteries, standard solder, lead pellets, lead-based paints, hardware cloth and other galvanized wire, foil from wine and champagne bottles, linoleum, Venetian blinds (plastic), glazed ceramics, plaster, seeds coated with lead arsenate, costume jewelry, mirror backing, leaded gas fumes and some bird toys. Once the lead is ingested, it is degraded in the stomach (often remaining in the ventriculus) then slowly released into the gastrointestinal tract and absorbed into the bloodstream. The lead absorbed from the digestive tract is then sequestered in soft tissues and bone, and excreted by the kidneys over a period of weeks to months.
The toxic effects of lead are numerous due to its ability to disrupt many biochemical processes within the body.
In general, lead toxicosis affects the development of the nervous system by impairing cell-to-cell connections resulting in alterations in neuronal circuitry and cellular migration. Lead also greatly affects calcium homeostasis and uptake by calcium membrane channels and substitutes for calcium in calcium-sodium ATP pumps. Lead also blocks the entry of calcium into the nerve terminals, inhibits calcium uptake in brain mitochondria, and interferes with calcium receptors that are coupled with second-messenger functions [e.g. calmodulin, protein kinase C (cell division and proliferation, cell-cell communication and organization of the cytoskeleton)]. Lead-induced Schwann cell degeneration may also lead to segmental demyelination and axonal degeneration resulting in a peripheral neuropathy.
Photo 1: Lateral radiographic view of a 5-year-old umbrella cockatoo showing heavy metal metallic densities within the lumen of the ventriculus. Also note the marked distension of the proventriculus, ventriculus and small intestines.
Lead intoxication may cause an anemia (microcytic hypochromic) as a result of decreased life span of the red blood cells and disruption of heme synthesis. The exact biochemical process is not known; however, the effects are usually accompanied by inhibition of sodium-potassium dependent ATPases.
A nephropathy associated with lead toxicosis is a common occurrence. The biochemical processes involved in lead toxicity include a decrease in energy-dependent transport functions including aminoaciduria, glucosuria and ion transport. These changes are possibly related to leads effect on mitochondrial respiration and phosphorylation.
Lead toxicity can directly or indirectly alter many aspects of bone cell formation. The accumulation of lead in bone occurs under many of the same mechanisms involved in regulating calcium influx and efflux, including parathyroid hormone, calcitonin and vitamin D. Lead is also reported to compete with calcium for absorption from the gastrointestinal tract.
In general, acute lead toxicosis is more common in companion avian species while chronic lead toxicosis is seen more often in free-ranging avian species, especially waterfowl. Interestingly, chickens are reported to be more resistant to lead toxicosis than waterfowl.
Clinical signs of lead toxicosis can vary depending upon the amount of lead ingested. However, any bird with a combination of gastrointestinal and nervous systems signs should have heavy metal toxicosis high on the list of differential diagnoses. Once the lead enters the circulatory system clinical signs may be pansystemic. Anorexia, weight loss, emaciation, regurgitation, vomiting, diarrhea, increased gastrointestinal transit time, depression, ataxia and weakness, seizures, blindness, hematuria, hemoglobinuria, polyuria and polydipsia, and death are all signs associated with lead toxicosis.
Diagnosis of lead toxicosis is based upon a combination of clinical signs, hematology, biochemical analysis, radiology, toxicologic analysis and, in some cases, post-mortem evaluation. A hypochromic regenerative anemia arising from the premature destruction and decreased production of red-blood cells may be noted. Red-blood cells may also contain cytoplasmic vacuoles and basophilic stippling (hemoglobin precipitation) although they may not be easily observed. Biochemical parameters that might be altered in cases of lead intoxication include elevations in LDH and AST activity, total protein, uric acid and CK activity. Blood and tissue lead analysis are useful diagnostic tools; however, ante-mortem measurement of tissue levels is not routinely performed in live birds. Whole-blood samples should be submitted in heparinized tubes since the majority of lead is found in the RBCs. Radiographs may be useful if metallic densities are noted in the gastrointestinal tract (Photo 1). However, the absence of identifiable metal densities in the GI tract with appropriate clinical signs does not rule out lead intoxication.
If blood lead levels are greater than 20 microgram/dl (0.2 ppm) and documented clinical signs are consistent with lead toxicosis, then lead poisoning is a very likely diagnosis. Blood levels greater than 50 microgram/dl in most species are considered to be diagnostic, although, clinical signs have been correlated with blood lead levels as low as 15 microgram/dl (0.15 ppm). As mentioned previously, chickens appear to be more resistant to lead toxicosis than other species and may appear normal even with blood lead levels as high as 800 microgram/dl (8.0 ppm). Tissue (fresh frozen kidney, liver, brain and bone) levels 3 to 6 ppm or higher are considered significant. Elevated protoporphyrin levels (PP) or decreased aminolevulinic acid dehydrogenase (ALAD) activity may be detected in some, but not all, birds and may not correlate well with clinical signs.
Pathologic lesions associated with lead intoxication include demyelination of peripheral nerves, focal areas of vascular damage in the cerebellum, vascular necrosis, multifocal myocardial degeneration, renal nephrosis (with degeneration and necrosis of tubular epithelial cells), hemosiderosis in the spleen and other organs, arrested mitotic activity in the proventricular epithelial cells and testicular degeneration.
Therapeutic goals for managing heavy metal intoxication should concentrate on stabilizing the patient's condition, removing the source of intoxication from the GI tract, removing lead from the tissues of the patient and prevention of further exposure to the toxicant. Supportive care includes administration of fluid (Lactated ringer's solution IV or subcutaneously with dextrose), corticosteroids (the use of corticosteroids is controversial) to relieve cerebral edema, control of seizures with diazepam (0.5 to 1.0 mg/kg q 8-12 hours as needed), iron replacement therapy in severe cases of anemia and chelation with calcium ethylenediaminetetraacetate (CaEDTA) (Calcium Disodium Versonate, Riker Laboratories, Northridge, CA, USA) (30-35 mg/kg q 12 hours for 5-10 days), D-Penicillamine (Cuprimine, Merck, Rahway, NJ, USA) (55 mg/kg PO q 12 hours for one to two weeks) or dimercaptosuccinic acid (DMSA) (25-35 mg/kg q 12 hours). Although acute necrotizing nephrosis associated with administration of CaEDTA has not been documented in avian species, chelation therapy with CaEDTA is most commonly limited to five days with a rest period of five to seven days between additional treatments. Clinical signs associated with CaEDTA toxicosis include polydipsia, polyuria, proteinuria and hematuria. Nephrotoxicity was not observed in a study that compared two heavy metal chelators in a group of cockatiels receiving chelation therapy (40 mg/kg q 12h for 21 days) for lead or in two studies in which falcons receiving undiluted CaEDTA at a does of 50 mg/kg IM q 12h for 2-23 consecutive days or 100 mg/kg IM q 12h for 5-25 consecutive days depending upon the falcons blood lead concentration. It has been suggested that D-Penicillamine may increase the absorption of lead from the GI tract despite the thought that it is a better chelating agent than CaEDTA. Combining CaEDTA and D-Penicillamine for several days until the symptoms dissipate followed by a three-to six-week treatment period with D-Penicillamine alone has been suggested as the best regimen for lead toxicity. Endoscopy, bulk diets, binding agents and even flushing of the GI tract with the patient under general anesthesia may assist in the removal of lead from the gastrointestinal tract. Surgery may be necessary if the lead particles cannot be removed with other methods.
Zinc toxicosis, also know as "new wire disease", is also reported in avian species and should always be included in the same differential list with lead if heavy metal intoxication is suspected. Sources of zinc are numerous and include galvanized mesh and metal clips, hardware cloth, staples, galvanized nails or wire, galvanized feed and water containers, fertilizers, some paints, zinc pyrithione shampoos, zinc oxide, zinc undecylenate (Desenex cream) and pennies (post 1982). Depending upon the type, some galvanized coatings may contain 99.9 percent zinc while others may contain 98 percent zinc and 1 percent lead.It should be noted that fumes from welding galvanized materials may also contain zinc, lead or iron.
Clinical signs of zinc toxicosis are similar to those seen with lead and include polyuria, polydipsia, weight loss, diarrhea, weakness, vomiting, anemia, cyanosis and hypoglycemia. Systemic effects are associated with damage to the kidneys, gastrointestinal tract and pancreas.
The diagnosis of zinc toxicosis requires a complete clinical history, physical examination, radiology and demonstration of elevated blood (serum) or tissue (pancreas) zinc levels. Radiographs may demonstrate metallic densities within the gastrointestinal tract; however, toxicosis may be present without identifiable metallic densities within the esophagus, crop, stomach or lower gastrointestinal tract. Samples used for blood zinc analysis should be collected in glass or all-plastic syringes and tubes. Rubber stoppers on serum tubes and the grommets on some plastic may artifactually elevate the zinc levels in the collected sample. Serum tubes with royal blue stoppers are free of zinc and are the most appropriate for collecting samples for analysis. Blood zinc levels greater than 200 microgram/dl (2.0 ppm) are diagnostic for zinc toxicosis. Tissue levels greater than 1,000 microgram/g are also suggestive of zinc toxicosis.
Treatment of zinc toxicosis is similar to that used for lead toxicosis. Zinc is not stored in the bone and therefore, equilibrates and chelates faster than lead. The incidence of "new wire disease" may be decreased by scrubbing galvanized wire with vinegar.
Dr. Jones is associate professor of avian and zoological medicine at the University of Tennessee's College of Veterinary Medicine. He is a diplomate of the American Board of Veterinary Practitioners — Avian Specialty. Dr. Jones' clinical interests include raptor medicine, orthopedic and soft-tissue surgery, avian nutrition and avian infectious diseases. He is also a master falconer with 15 years experience.