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Zinc is an essential trace metal that plays an important role in many biologic processes. It is ubiquitous in nature and exists in many forms. The ingestion of some forms leads to creation of toxic zinc salts in the acidic gastric environment. Zinc toxicity has been documented in humans as well as in a wide range of large, small, exotic, and wild animals. It is seen commonly in pet dogs, possibly because of a higher degree of dietary indiscretion and greater levels of exposure to zinc-containing substances. Common sources of zinc include batteries, automotive parts, paints, zinc-oxide creams, herbal supplements, zippers, board-game pieces, screws and nuts on pet carriers, and the coating on galvanized metals such as pipes and cookware. One of the most well known sources of zinc that causes toxicity following ingestion is the USA Lincoln penny. Some pennies minted during 1983, and all pennies minted since, are 97.5% zinc by weight (~2,440 mg of elemental zinc per coin).
Pathogenesis
The low pH in the stomach causes the formation of soluble zinc salts. These are absorbed from the duodenum and rapidly distributed to the liver, kidneys, prostate, muscles, bones, and pancreas. Zinc salts have direct irritant and corrosive effects on tissue, interfere with the metabolism of other ions such as copper, calcium, and iron, and inhibit erythrocyte production and function. The mechanisms by which zinc exerts these toxic effects are not completely understood. The median lethal dose (LD50) of zinc salts in cases of acute toxicity has been reported to be ~100 mg/kg. Also, diets containing high levels of zinc (>2,000 ppm) have been reported to cause chronic zinc toxicosis in large animals.
Clinical Signs and Lesions
Clinical signs vary based on the duration and degree of exposure. Signs progress from anorexia and vomiting to more advanced symptoms such as diarrhea, lethargy, icterus, shock, intravascular hemolysis, hemoglobinuria, cardiac arrhythmias, and seizures. Large animals often show decreases in weight gain and milk production, and lameness has been reported in foals secondary to epiphyseal swelling.
Major histopathologic findings include hepatocellular centrolobular necrosis with hemosiderosis and vacuolar degeneration, renal tubular necrosis with hemoglobin casts, and pancreatic duct necrosis with fibrosis of the interlobular fat.
Diagnosis
Radiodense material is easily seen on radiographs of the GI tract in animals with zinc-containing foreign bodies. Changes in the CBC, chemistry profile, urinalysis, and coagulation profile reflect the degree of toxicity to various organ systems. The hemogram typically reveals a regenerative hemolytic anemia characterized by changes in erythrocyte morphology (eg, spherocytosis and Heinz body formation). It has been suggested that zinc's interference with enzymes such as glutathione reductase leads to erythrocyte fragility due to oxidative damage. The leukogram often shows a neutrophilic leukocytosis secondary to stress, pancreatitis, and a regenerative bone marrow. Serum chemistry changes that are seen secondary to hepatic damage include elevations in bilirubin, the trans-aminases, and alkaline phosphatase.
As zinc accumulates in the pancreas, increases in amylase and lipase can be seen following pancreatitis and pancreatic necrosis. Glomerular damage and renal tubular epithelial necrosis result in elevations in BUN, creatinine, amylase, and urine protein. Hemoglobinuria can be differentiated from hematuria during urinalysis; the urine color will not clear after centrifugation in the presence of hemoglobinuria. Prolongation of prothrombin time and activated partial thromboplastin time can result from toxic effects on the synthesis or function of coagulation factors.
The hematologic and clinical findings in animals with zinc toxicosis are similar to the changes in animals with immune-mediated hemolytic anemia (IMHA). Misdiagnosis of a primary autoimmune disorder can lead to the inappropriate use of immunosuppressive drugs. Zinc toxicosis can cause the direct antiglobulin test (direct Coombs' test) to be positive in the absence of a primary auto-immune disorder. The direct Coombs' test is therefore not reliable when differentiating between zinc intoxication and IMHA.
Definitive diagnosis of zinc poisoning is achieved by measuring zinc levels in blood or other tissue. In dogs and cats, the normal serum zinc level is 0.7–2 μg/mL. Serum samples can be submitted in green-top heparinized tubes or in royal blue-top trace element tubes. Methods for quantifying zinc levels from saliva and hair have not been validated in domestic animals, and measuring zinc in urine is unreliable because elimination of zinc through the kidneys is variable.
Differential diagnoses should include any infectious, toxic, immune-mediated, neoplastic, genetic, or other medical disorder characterized by clinical signs and laboratory test results similar to those seen in cases of zinc toxicity. These include IMHA, hypophosphatemia, splenic torsion, babesiosis, ehrlichiosis, heartworm disease, leptospirosis, hemobartonellosis, feline leukemia infection, hemangiosarcoma, lymphosarcoma, phosphofructokinase or pyruvate-kinase deficiency, and toxicity from acetaminophen, naphthalene, paradichlorobenzene, Allium, lead, or copper.
Treatment and Prevention
After stabilizing the animal with fluids, oxygen, and blood products as necessary, removal of the source of zinc as early as possible is paramount. This often requires surgery or endoscopy. Inducing emesis to remove chronic gastric zinc foreign bodies is typically not rewarding because zinc objects often adhere to the gastric mucosa.
Diuresis with a balanced crystalloid solution is indicated to promote renal excretion of zinc and prevent hemoglobinuric nephrosis.
There is debate regarding the necessity of chelation therapy in cases of zinc toxicosis. Animals often recover from zinc intoxication following only supportive care and removal of the source. Chelation therapy can enhance elimination of zinc and thus accelerate recovery, but there is some concern that chelation treatment may actually increase zinc absorption from the intestines. Chelation can be achieved through the use of specific compounds. Calcium disodium ethylenediaminetetraacetate (Ca-EDTA) chelates zinc when given at 100 mg/kg/day IV or SC for 3 days (diluted and divided into 4 doses), but may exacerbate zinc-induced nephrotoxicity. Although they have been used to treat animals with zinc toxicity, d-penicillamine and dimercaprol (British antilewisite) have not been specifically validated for this purpose. Reported doses are 110 mg/kg/day for 7–14 days for d-penicillamine, and 3–6 mg/kg tid for 3–5 days for dimercaprol. Chelation therapy with any of these agents should be performed only after careful consideration and monitored with serial serum zinc levels to help determine the appropriate duration of treatment.
If diagnosed early and treated appropriately, the outcome is usually favorable for animals with zinc toxicosis. Eliminating sources of zinc from the environment is essential in preventing recurrence.
Last full review/revision March 2012 by Raymond Cahill-Morasco, MS, DVM
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