JPC SYSTEMIC PATHOLOGY
Signalment (JPC# 2548860): 5-year-old male American Eider duck (Someteria mollisima dresseri)
HISTORY: This duck was depressed. A radiograph revealed a penny in the ventriculus. The duck was treated with itraconazole, fluids, enrofloxacin, and calcium versonate. There was no improvement over the next 10 days. The penny was surgically removed, but the duck died 24 hours later.
HISTOPATHOLOGIC DESCRIPTION: Pancreas and small intestine: Diffusely affecting 70% of the pancreatic tissue is marked acinar cell atrophy and loss. Atrophied acinar cells are characterized by shrunken, angular cytoplasm, decreased intensity of zymogen granule staining and loss of zymogen granules. Surrounding, widely separating, compressing and distorting remaining islands of acini are broad bands of loose fibrous connective tissue and a marked increase in ductal epithelium. Ductal cells are individualized or formed into variably-sized ducts (tubular complexes) and have round to oval, often crowded, vesiculate nuclei. The small intestinal serosa and peripancreatic and peri-intestinal adipose tissue is mildly to moderately expanded by heterophils, lymphocytes, and macrophages admixed with hemorrhage, fibrin and scattered 1x 3 um bacilli. Multifocally, there is atrophy of peripancreatic adipose tissue.
- Pancreas, exocrine: Acinar atrophy and loss, diffuse, marked, with extensive fibrosis and ductal cell proliferation, American Eider duck (Someteria mollisima dresseri), avian.
- Small intestine and adipose tissue: Serositis, fibrinous and heterophilic, diffuse, subacute, moderate, with bacilli.
ETIOLOGIC DIAGNOSIS: Pancreatic zinc toxicosis
CAUSE: Zinc intoxication
CONDITION SYNONYM: New wire disease
- The pancreas is the main organ for zinc excretion/homeostasis
- The pancreas accumulates zinc absorbed from the diet and secretes it as a component of exocrine pancreatic secretions, which is mediated by metallothionein
- Zinc is an essential trace mineral and a component of ~200 metaloenzymes
- Fourth most commonly used metal; therefore there are numerous sources of exposure: pennies minted after 1982, shot pellets, nuts, bolts, galvanized cage wire mesh, topical creams containing zinc oxide/zinc salts, or inhalation (smelter fumes); other sources include pesticides and herbicides
- Natural toxicosis is described in birds, cats, dogs, sheep, calves, horses, piglets receiving total parenteral nutrition, and humans
- Experimentally produced in cats, sheep, chickens, ducklings, rats, and ferrets
- Pathogenesis of pancreatic lesions is not understood
- Toxicosis occurs through complex combination of inhibition of selenium, copper, iron or calcium absorption and/or metabolism
- Ingestion (or inhalation) > Zn released in low pH of stomach > absorption in small intestine > bound to plasma albumin and macroglobulins > extracted by the liver and returned to bloodstream > concentrates in exocrine pancreas, hepatocytes, spleen, and renal tubular epithelium
- Piglets: Acinar cells are targeted and undergo necrosis > atrophy > interstitial fibrosis
- Ducklings: Acinar cells also targeted and undergo apoptosis
- Sheep and cattle: Ductal epithelium is initial target and undergoes necrosis; acinar degeneration, necrosis, and interstitial fibrosis centers on damaged ducts
- Hypothesized pathogenesis for Zn-induced hemolysis: Inhibition of glutathione reductase and enzymes of hexose-monophosphate-shunt pathway > increased RBC susceptibility to oxidative damage > marked RBC fragility and decreased lifespan > extra- and/or intravascular hemolysis > spherocytosis and Heinz body anemia > regenerative anemia
TYPICAL CLINICAL FINDINGS:
- Nonspecific: Vomiting, lethargy, inappetence, weight loss, weakness
- Pigmenturia (mostly hemoglobinuria), polyuria, polydipsia
- Mild elevations in AST, ALP, amylase, phosphorus, and uric acid
- Mild decreases in calcium (Zn competes with calcium for intestinal absorption), glucose and total protein
- Heinz body hemolytic anemia
TYPICAL GROSS FINDINGS:
- Acute phase: Pale and enlarged with edematous interlobular connective tissue that separates and widens lobules
- Chronic phase: Shrunken with fibrosis replacing the edema
- GI: ulcers brittle, discolored koilin layer in ventriculus
- Liver: Shrunken with dark sunken areas of necrosis and collapse; transitioning to later phase of disease appearing as postnecrotic scarring
- Ileus mild to severe typhlitis
- Pericardial mineralization
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Pancreatic acini:
- Acute: Microvesicular degeneration and necrosis of acinar cells characterized by loss of zymogen granules, decreased basophilia, cytoplasmic vacuolization, cellular atrophy, and necrosis of individual acinar cells
- Chronic: atrophy, loss and fibrosis of acinar cells
- Tubular complexes separated by abundant fibrous connective tissue (duct-like structures with low cuboidal or flattened cells which lack zymogen granules and surround a large lumen; they are thought to be a response to pancreatic injury)
- Inflammation generally minimal or absent; islets are spared
- Liver: Centrilobular hepatocyte vacuolation and necrosis
- Kidney: Renal tubular necrosis
- Ventriculus: Necrotizing ventriculitis
ADDITIONAL DIAGNOSTIC TESTS:
- Radiographic evidence of metallic objects within GI tract
- High tissue or serum Zn concentrations
- Obtain samples with all-plastic syringes and store in glass vials with a royal blue stoppers (rubber contains Zn and can invalidate analyses)
- Pancreatic lesions in mammals:
- Duct obstruction by calculi or parasites: causes interstitial edema and ischemic damage to acinar cells; may resemble lesions of Zn toxicosis, particularly in ruminants, because lesions center on damaged pancreatic ducts; however, Zn toxicity lesions progress more slowly and have less uniform distribution than in duct obstruction
- Direct damage to acinar cells: Zinc; Cassia occidentalis; T-2 toxin (trichothecene mycotoxin affecting pigs), deoxynivalenol (vomitoxin) produced by Fusarium Fungal plant pathogen; drugs (sulfonamides, potassium bromide-phenobarbital combinations); ischemia due to a variety of causes
- Corticosteroids: Induction of P450 enzyme pathway within pancreatic exocrine tissue and oxidative damage
- Disturbed cytoplasmic enzyme trafficking in acinar cells: acute pancreatic necrosis
- Pancreatic necrosis in avian species:
- Hydropericardium syndrome (group I avian adenovirus): Intranuclear inclusion bodies; inflammatory cells should be present
- Highly pathogenic avian influenza: Heterophils and macrophages should be present
- West Nile Virus: American crows, necrosis in multiple organs
- Domestic mammals: Generally show GI distress, anemia, and hypoproteinemia
- Often present with vomiting, diarrhea, anorexia, icterus, and severe Heinz body hemolytic anemia with hemoglobinuria and hematuria
- May also develop acute renal failure with hyperphosphatemia and granular casts
- Gross lesions: Splenomegaly and diffusely red kidneys
- One study reported prolonged partial thromboplastin time (PTT) due to inhibition of factors VIII, IX, XI, and XII (intrinsic pathway) (prothrombin time [PT, extrinsic pathway] was not prolonged)
- Ruminants: May develop necrotizing abomasitis and duodenitis with congestion and edema, and grossly green discoloration; ductular elements of the pancreas most vulnerable to damage
- Pigs: May develop bone and joint lesions resembling osteochondrosis; acinar tissue most vulnerable to damage
- Foals: Susceptible to chronic zinc toxicosis (possibly inhalation route of exposure); develop severe generalized osteochondrosis
- Rats, chickens (experimental): Direct injection into testes produces testicular tumors
- Bildfell RJ, et al. A review of episodes of zinc phosphide toxicosis in wild geese (Branta ) in Oregon (2004–2011). J Vet Diagn Invest. 2013; 25(1): 162–167.
- Blundell R, Adam F. Haemolytic anaemia and acute pancreatitis associated with zinc toxicosis in a dog. Vet Rec. 2013; 172(1): 17.
- Garland T. Zinc. In: Gupta RC, ed. Veterinary Toxicology: Basic and Clinical Principles. New York, NY: Academic Press; 2007: 470-472.
- Gurnee CM, Drobatz KJ. Zinc intoxication in dogs: 19 cases (1991-2003). J Am Vet Med Assoc. 2007; 230:1174-1179.
- Jubb KV, Stent AW. Pancreas. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier Ltd; 2016:354-357.
- Sebastian MM. Role of pathology in diagnosis. In: Gupta RC, ed. Veterinary Toxicology: Basic and Clinical Principles. New York, NY: Academic Press; 2007:1112.