Heavy metals pt 2

What organ systems are commonly affected by heavy metal toxicosis?

The GI tract, kidneys, liver, and nervous system.

What are common sources of arsenic exposure in animals?

• Contaminated soil or water

  • arsenicals in rocks, ground water

• commercial products

  • chromated copper arsenate (CCA)- treated lumber

    • most common source of exposure in LA

• inorganic arsenical pesticides

  • used in orchards: arsenic can remain in soil for decades

    • 0.46% arsenic trioxide, sodium arsenate

How well are inorganic arsenicals absorbed after ingestion?

they are almost completely absorbed from the GI tract

arsenic in large animals

• most reports in last 10 years are in cattle

• sources:

  • ashes from burned, treated wood

  • arsenic chromate treated lumber

  • old herbicides and pesticides

inorganic vs organic arsenic

• inorganic

  • trivalent form (Sodium arsenite)

  • pentavalent form (Sodium arsenate)

• organic

  • methylated arsenicals

    • inorganic biotransformation in organisms, can be in trivalent forms

Where can arsenic accumulate after absorption?

The liver, kidneys, GI tract, spleen, lungs, and hair.

What is the main route of arsenic elimination?

Urine. The lecture cites about 40-70% of the dose excreted within 48 hours.

How does arsenite interfere with enzyme function?

• It reacts with sulfhydryl groups in proteins, uncouples oxidative phosphorylation by replacing phosphate

  • increased reactive oxygen species = damage to DNA, RNA, proteins, cells

How does arsenate interfere with ATP production?

• impairs tissue respiration - oxygen and ATP energy depleted - tissues with high oxygen demand/metabolic rates most affected

  • direct damage to cells in liver, kidney, GI tract, nerves, blood vessels/capillaries

  • causes hemolysis

arsenic clinical findings: blood vessels

• damage to capillaries and loss of capillary integrity

  • blood vessels: vasodilation and rupturing of blood vessels

arsenic clinical findings: GI tract

• movement of fluids into GI mucosa causes swelling

• loss of GI mucosa = “bloody rice water” diarrhea: huge loss of fluids, hypovolemia and shock

arsenic clinical findings: kidney and liver

• damages capillaries and glomeruli in kidney

• damages hepatocytes, cirrhosis

arsenic: acute toxicity signs

• signs within minutes, death within hours, high mortality

  • intense abdominal pain, weakness, ataxia

  • salivation, hematemesis

  • diarrhea (rice water diarrhea)

  • hypovolemia, shock

  • collapse, death

    • GI signs predominate → nephrotoxicity

arsenic toxicity signs: subacute-chronic

• abdominal pain

• vomiting

• incoordination/staggering

• rapid, weak pulse

• diarrhea

• dehydration

• resp distress

• skin (edema, blister, bleeding)

arsenic: clinicopathologic findings

Azotemia, hematuria, increased liver enzymes, and increased hematocrit from fluid loss.

arsenic treatment

-DMSA

-BAL or dimercaprol

-sodium thiosulfate in LA

What histopathologic lesions are associated with arsenic toxicosis?

Renal tubular necrosis and hepatic necrosis.

Which samples can be tested for arsenic?

Vomitus, urine, liver, kidney, GI contents, or suspected source material.

What are important differential diagnoses for acute arsenic toxicosis?

Infectious gastroenteritis, caustic ingestion, and adverse effects of antineoplastic drugs.

What is the main supportive-care priority in severe arsenic toxicosis?

Restore circulating volume with fluids and monitor renal function. GI support and dialysis may be considered as indicated.

copper sources

• feed, pet food

  • too much or too little copper added

What normal functions depend on copper?

Collagen maintenance, immune response, enzyme function, iron transport, RBC production, and reproduction.

What signs suggest copper deficiency in cattle?

• Poor weight gain

• diarrhea

• infertility

• anemia

• faded coat color

• swollen joints

• decreased resistance to infectious disease

• broken bones

• Calves may develop hindlimb weakness

what is copper storage disease

• genetic copper retention and liver toxicity

  • labrador retrievers

• autosomal recessive trait due to mutation of genes ATP7A and ATP7B

  • ATP7A → in intestinal epithelial cells and important for hepatic copper mobilization to tissues

  • ATP7B → in hepatocytes and important for excreting excess liver copper in bile

bedlington terriers and copper toxicity

• they have an autosomal recessive trait due to lack of gene (COMMD1) coding for a liver protein involved in excretion of copper in bile

  • livers abnormally accumulate copper

    • hepatitis and progressive scarring and cirrhosis

What is a major route of copper excretion?

Biliary excretion.

what happens when the liver abnormally accumulates copper

hepatitis and progressive scarring and cirrhosis

Which species are emphasized for copper toxicosis?

Sheep and dogs. The lecture emphasizes dietary toxicosis in sheep and copper storage disease in dogs.

What happens when excess copper accumulates in a dog's liver?

It can cause chronic hepatitis, fibrosis, and eventually cirrhosis.

How does dietary molybdenum affect copper in sheep?

Molybdenum antagonizes copper. Higher molybdenum lowers copper availability, and low molybdenum can increase toxicity risk.

What copper-to-molybdenum ratios does the lecture give for sheep feed?

About 6:1 as a reference ratio, with increased toxicity concern above 10:1.

Why can feeding pig feed to sheep lead to copper toxicosis?

Pig feed can contain more copper than sheep can safely handle.

What lesions are associated with acute copper ingestion?

GI irritation and mucosal erosions, with blue-green discoloration.

What are the two phases of chronic copper toxicosis?

• accumulation (pre-hemolytic) phase

  • accumulates in liver if inadequate biliary excretion

• hemolytic phase

what occurs with hepatic necrosis from copper toxicity

• hepatic necrosis → copper released into bloodstream

  • direct cytotoxic effect to RBCs and/or hepatocytes

  • nephrotoxicity:

    • secondary to hemolytic event

    • direct toxicity by copper accumulation

copper tox in sheep

• subchronic to chronic

  • acute RBC hemolysis, acute hemolytic crisis

  • necropsy: dark, swollen gun-metal blue kidneys

  • hepatic necrosis, RBC IV hemolysis, extravascular hemolysis, icterus, hemoglobinuric nephrosis → renal fail

What are the hallmark signs of a copper-associated hemolytic crisis in sheep?

Sudden weakness, anorexia, hemoglobinuria, and icterus.

What classic necropsy finding suggests copper toxicosis in sheep?

Dark, swollen gunmetal-blue to black kidneys associated with hemoglobin accumulation and acute tubular injury.

copper tox clinical signs

• depression

• dehydration

• anorexia

• vomiting

• abdominal pain

• increased LDH, AST, ALT, increased bilirubin

• anemia

• hemoglobin

What signs may occur in canine copper-associated liver disease?

• icterus

• bilirubinemia (dark urine)

• hemoglobinuria

• anemia

• melena

• hepatic encephalopathy

Which sample is used to quantify hepatic copper in suspected canine copper storage disease?

A liver biopsy.

What samples help investigate suspected dietary copper toxicosis?

Liver and serum for copper assessment, plus feed for copper and molybdenum analysis.

Which chelators does the lecture list for copper toxicosis?

D-penicillamine and trientine. Treatment and monitoring may be prolonged.

What are normal functions of zinc?

Zinc supports enzyme activity, cell division and growth, immune function, and skin integrity.

What causes zinc-responsive dermatitis?

Inadequate dietary zinc or impaired absorption, which can be genetic.

What signs can zinc deficiency cause?

Dermatitis, alopecia, and increased susceptibility to skin infections.

What are common sources of zinc toxicosis in small animals?

Zinc-core pennies, zinc-containing ointments or sunblock, and galvanized hardware or wire.

Why are U.S. pennies minted after 1982 a zinc hazard?

They contain approximately 96.5% zinc. One or two can cause toxicosis, depending on the circumstances.

Which animals are at risk from chewing galvanized wire or hardware?

Birds, ferrets, and reptiles.

How can horses or livestock encounter excess environmental zinc?

By grazing on contaminated pasture near zinc smelters.

What orthopedic signs of zinc toxicosis are reported in young horses?

Periarticular enlargement around long bones and lameness associated with osteochondritis dissecans.

Where is zinc absorbed, and how is it primarily eliminated?

It is absorbed in the small intestine and eliminated mainly via bile and feces.

Which organs or tissues are commonly affected by zinc toxicosis?

The GI tract, RBCs, liver, kidneys, and pancreas.

How does zinc toxicosis cause anemia?

RBC enzyme inhibition or direct oxidative damage can cause intravascular hemolysis and Heinz body formation.

What are Heinz bodies?

RBC inclusions made of oxidatively denatured hemoglobin.

What GI signs can occur with zinc toxicosis?

Vomiting, diarrhea, anorexia, hematemesis, and melena.

What findings suggest intravascular hemolysis in zinc toxicosis?

Pale mucous membranes, anemia, tachycardia, hemoglobinemia, hemoglobinuria, and Heinz bodies.

How do hemoglobinuria and hematuria differ?

Hemoglobinuria is free hemoglobin in the urine. Hematuria is the presence of intact RBCs in the urine.

What kidney, liver, and pancreatic findings may occur with zinc toxicosis?

Azotemia with oliguria or anuria, elevated liver enzymes, and pancreatitis.

What histopathologic lesions can occur with zinc toxicosis?

Pancreatic lesions, renal nephrosis, and centrilobular hepatic injury or necrosis.

Which samples can help confirm zinc toxicosis?

Serum, liver, kidney, pancreas, and suspected ingested material can be tested for elevated zinc.

Why use a trace-element collection tube for a zinc assay?

Some routine tube stoppers contain zinc and can contaminate the sample, falsely elevating the result.

What is the priority when a zinc-containing foreign body is still in the GI tract?

Remove the object to stop ongoing exposure. Supportive care can include IV fluids and transfusion when indicated.

What does the lecture say about chelation for zinc toxicosis?

It lists calcium disodium EDTA and notes that the benefit of chelation is uncertain.

What are differential diagnoses for zinc toxicosis?

Infectious GI disease, immune-mediated hemolytic anemia, and other causes of hemolysis such as onion or garlic ingestion or rattlesnake envenomation.

Which heavy metal toxicosis classically causes bloody rice-water diarrhea and rapid hypovolemic shock?

Arsenic.