Hematology
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Lead Toxicosis

This is a blood smear from an opossum that was emaciated when rescued. The CBC analysis revealed low normal PCV, moderate to marked polychromasia, occasional nucleated RBCs (metarubricytosis) and basophilic stippling (figure 1). The CBC findings are suspicious for lead toxicosis in this case.
This is a blood smear from an opossum that was emaciated when rescued. The CBC analysis revealed low normal PCV, moderate to marked polychromasia, occasional nucleated RBCs (metarubricytosis) and basophilic stippling (figure 1). The CBC findings are suspicious for lead toxicosis in this case.
December 2, 2022

Lead toxicosis is a well-recognized cause of morbidity and mortality in wildlife, humans, and domestic animals. It is the most common form of heavy metal toxicity, and is now thought to be the most frequent poisoning caused by a contaminant in many animal species worldwide.1  Common sources of lead exposure in wildlife species include ammunition, fishing sinkers, coins, contaminated sediment, as well as ingestion of affected animals (i.e. secondary poisoning).  

Lead is capable of causing lesions and dysfunction in a wide variety of organs including cardiovascular, neurological, hematopoietic, gastrointestinal, reproductive, and immunological organs. Although the mechanism of lead-induced toxicity is not completely understood, the main targets of lead are enzymes involved in heme synthesis as well as thiol-containing antioxidants and enzymes (e.g. superoxide dismutase, catalase glutathione peroxidase, glucose 6-phosphate dehydrogenase, glutathione).2  Low levels of lead in blood and tissue are sufficient to inhibit the activity of these enzymes, causing various effects including impaired heme synthesis and generation of reactive oxygen species (ROS). Additionally, lead inhibits and mimics the action of calcium, thus disrupting calcium-dependent pathways.  

One of the characteristic hematology findings of lead toxicosis is basophilic stippling. Basophilic stippling represents aggregation of ribosomes and polyribosomes within the RBC. In samples stained with Romanowsky stains (e.g. Wright-Giemsa stain), affected RBCs contain fine punctate basophilic structures that are uniformly distributed within the cytoplasm. 

Immature RBCs contain larger amounts of RNA, which makes them stain basophilic with Romanowsky stains. As they mature, they progressively break down and eliminate RNA; 5’ nucleotidase, an important enzyme in RNA breakdown, is inhibited by lead, resulting in aggregation and accumulation of RNA within the affected RBCs. Additionally, due to the inhibition of heme synthesis, nonregenerative anemia is another common finding in lead toxicosis3

While gross lesions can be nonspecific or absent, there are characteristic histologic changes that can be associated with lead toxicosis. These include epithelial cell degeneration in the renal proximal convoluted tubules (Figure 2) and intranuclear inclusions that stain positively with Acid Fast (Figure 3). 

Figure 2
Figure 3

Generally, kidney and liver concentrations of lead above 36mg/kg on a dry weight basis are considered diagnostic for lead toxicosis in animals4

In this present case, there was a borderline anemia with low normal PCV and RBC density. Although there was evidence of prominent RBC regeneration (i.e. moderate to marked polychromasia and occasional nucleated RBCs), together with the presence of frequent basophilic stippling and borderline anemia, the findings are highly suspicious for lead toxicosis. As basophilic stippling can be challenging to identify, a thorough review of the RBC morphology by an experienced pathologist is helpful in cases with suspected lead toxicosis.

References  

  1. Samour J. Toxicology. In Avian Medicine. 2nd edition. Mosby Elsevier; 2008: 269-281. 
  1. Nemsadze K et al. Mechanisms of lead-induced poisoning. Georgian Med News. Jul-Aug 2009; (172-173):92-6 
  1. Brooks MB et al. In Schalm’s Veterinary Hematology, 7th Edition. Wiley Blackwell; 2022.
  2. Puls, R. (1994) Mineral Levels in Animal Health. Diagnostic Data. 2nd Edition, Sherpa International, Clearbrook, 82.

Figure legends 

Figure 1. Blood smear, Opossum. Wright-Giemsa. 1000x. Diffuse basophilic stippling and a polychromatic metarubricyte (lower left). 

Figure 2. Kidney, African Penguin. H&E.400x.  Multifocally, the tubular epithelial cells exhibit degeneration, necrosis and occasional epithelial cells slough into the tubular lumen (arrows).

Figure 3. Kidney, African Penguin. Ziehl-Neelsen. 400x. Proximal convoluted tubules contain occasional intranuclear inclusions that stain positively with Acid Fast (arrows). 

Hematology
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Lead Toxicosis

Lead toxicosis is a well-recognized cause of morbidity and mortality in wildlife. Learn what lead toxicosis looks like in an opossum blood smear sample sent to Moichor.

December 2, 2022
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