JPC SYSTEMIC PATHOLOGY
URINARY SYSTEM
January 2018
U-T10

SIGNALMENT (JPC# 1965664):  A sheep.

HISTORY:  This tissue is from a sheep that died during a hemolytic crisis.  Levels of copper in the liver were 1,183 ppm wet weight (normal=70-188 ppm wet weight).

MICROSCOPIC DESCRIPTION:  Kidney:  Multifocally, numerous cortical and medullary tubular lumina and less commonly Bowman’s space are ectatic and contain a bright red, hyaline to granular material (hemoglobin casts) or less often a pale eosinophilic homogenous to proteinaceous fluid that is often admixed with erythrocytes.  Multifocally, tubular epithelial cells demonstrate one or more of the following changes: are attenuated, contain pale vacuolated cytoplasm and swollen nuclei (degeneration), contain hypereosinophilic cytoplasm and pyknotic nuclei (necrosis), or contain numerous eosinophilic intracytoplasmic granules (hyaline droplets).  Multifocally medullary tubular lumina contain variably sized aggregates of deeply basophilic granular material (mineral). Rarely there are interstitial aggregates of few lymphocytes and plasma cells.  Multifocally the capsular surface is mildly undulant.

MORPHOLOGIC DIAGNOSIS: Kidney: Tubular degeneration and necrosis, acute, diffuse, severe, with protein and hemoglobin casts, hyaline droplet formation, and mineralization, breed not specified, ovine.

ETIOLOGY:  Chronic copper toxicity

ETIOLOGIC DIAGNOSIS:  Hemoglobinuria-associated acute tubular injury (previously hemoglobinuric nephrosis) secondary to chronic copper toxicity

50b: SINGALMENT (JPC # 2292838):  A dog.

HISTORY:  Tissue from a dog that had several coins composed of zinc (pennies) in its stomach at necropsy.

MORPHOLOGIC DESCRIPTION:  Kidney:  Multifocally, numerous cortical and medullary tubules are ectatic, lined by attenuated epithelium and contain a bright red, hyaline to granular material (hemoglobin casts) or less often a pale eosinophilic homogenous material (protein).  Multifocally, tubular epithelial cells are necrotic with hypereosinophilic cytoplasm and pyknotic nuclei or degenerative with pale vacuolated cytoplasm and swollen nuclei or contain variably sized light brown intracytoplasmic globules (hemosiderin).  Within more severely affected tubules, there is variable disruption of basement membranes (tubulorrhexis).  The interstitium is expanded and partially effaced by fibrin, hemorrhage, and edema and admixed with scattered aggregates of few lymphocytes and plasma cells.  Multifocally within Bowman’s space there is attachment of visceral to parietal epithelium (synechiae). 

MORPHOLOGIC DIAGNOSIS:  Kidney:  Tubular degeneration and necrosis, acute, diffuse, severe, with hemoglobin casts, tubulorrhexis, and glomerular synechia, breed not specified, canine.

ETIOLOGY:  Zinc toxicity

ETIOLOGIC DIAGNOSIS: Hemoglobinuria-associated acute tubular injury (previously hemoglobinuric nephrosis) secondary to zinc toxicity

GENERAL DISCUSSION: 

Copper:

  1. Primary metabolic defect in hepatic copper metabolism
  2. Altered hepatic biliary excretion
  3. Dietary excess

Zinc:

PATHOGENESIS:

Copper:

Zinc:

TYPICAL CLINICAL FINDINGS: 

Zinc:

TYPICAL GROSS FINDINGS: 

Copper:

Zinc:

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

Copper:

Zinc:

ADDITIONAL DIAGNOSTIC TESTS: 

DIFFERENTIAL DIAGNOSIS: 

Histologically, red pigment in kidneys (copper & zinc):

COMPARATIVE PATHOLOGY: 

Copper:

  1. Primary accumulation disease due to a metabolic defect that impairs biliary copper excretion; accumulation is centrilobular and concentrations greater than 2,000 ppm
  1. Secondary to hepatic inflammation that alters the biliary excretion; accumulation is primarily periportal and less than 2,000 ppm
  2. Dietary excess

Zinc:

REFERENCES: 

  1. Barthold SW, Griffery SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016:315.
  2. Bozynski CC, Evans TJ, Kim DY, et al. Copper with hemolysis and hemoglobinuric nephrosis in three adult Boer goats. J Vet Diagn Invest. 2009; 21(3):395-400.
  3. Brockus CW. Erythrocytes. In: Latimer KS, ed. Duncan and Prasse’s Veterinary Laboratory Medicine: Clinical Pathology. 5th ed. Ames IA: Wiley-Blackwell; 2011:20, 34-35.
  4. Brown DL, Van Wettere AJ, Cullen JM. Hepatobiliary system and exocrine pancreas. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:440,457.
  5. Cianciolo RE, Mohr FC: Urinary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2, 6th ed. St. Louis, MO: Elsevier; 2016:422-423,429-430.
  6. Cullen JM, Stalker MJ. Liver and biliary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2, 6th ed. St. Louis, MO: Elsevier; 2016:342-343.
  7. Evans TJ, Hanks BC, Kim DY, Ramirez CJ. Copper toxicosis in New Zealand White rabbits (Oryctolagus cuniculus). Vet Pathol. 2013; 50(6):1135-8.
  8. Fox JG. Other systemic diseases. In: Fox JG, Marini RP, eds. Biology and Diseases of the Ferret. 3rd ed. Ames, IA: John Wiley & Sons, Inc; 2014:435-436.
  9. George LW. Copper toxicosis.  In: Smith BP, ed.  Large Animal Internal Medicine. 5th ed. St. Louis, MO, Elsevier Mosby, 2015:1064-1066.
  10. Gurnee CM, Drobatz KJ. Zinc intoxication in dogs: 19 cases (1991-2003). J Am Vet Med Assoc. 2007; 230(8):1174-9.
  11. Haywood S, Simpson DM, Ross G, Beynon RJ. The greater susceptibility of North Ronaldsay sheep compared with Cambridge sheep to copper-induced oxidative stress, mitochondrial damage and hepatic stellate cell activation. J Comp Pathol. 2005;133(2-3):114-27.
  12. Haywood S, Vaillant C. Overexpression of copper transporter CTR1 in the brain barrier of North Ronaldsay sheep: Implications for the study of neurodegenerative disease. J Comp Path. 2014;150 (2-3): 216-224.
  13. Jubb KVF, Stent AW. Pancreas. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2, 6th ed. St. Louis, MO: Elsevier; 2016:356-357.
  14. LaDouceur EEB, Wynne J, Garner MM, Nyaoke A, Keel MK. Lesions in copper toxicosis in captive marine invertebrates with comparisons to normal histology. Vet Pathol. 2016;53(3):648-658.
  15. Mullaney T, Rumbeiha W, Smedley R. Copper-Associated Hepatitis in Labrador Retrievers.  Vet Pathol. 2009;46(3):484-90.
  16. Schmidt RE, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: Wiley Blackwell; 2015:73,88,140.
  17. Valli VEO, Kiupel M, Bienzle D: Hematopoietic system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:125-126.

 


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