24 – Copper Flashcards
*Where is copper stored in the body?
- LIVER
*What can copper poisoning arise from?
- EXCESSIVE DIETARY INTAKE
o Rations meant for cattle or horses
o Mixing errors - OVER SUPPLEMENTATION
- Deficiency in biliary excretion
- Metabolic defect in copper metabolism
- Previous liver damage
- Chewing on treated lumbar
*What is the mechanism of copper poisoning?
- OXIDATIVE DAMAGE
*Copper toxicity: species sensitivity
- SHEEP»_space;> goats > cattle > monogastrics
Why are sheep more sensitive to copper?
- Higher affinity for copper in liver
- Limited ability to upregulate metal binding proteins
- Limited ability to store Cu-binding protein complexes
- Impaired ability to excrete copper in bile
Acute copper toxicosis: clinical features
- Relatively rare
o Following ingestion of high copper materials or massive overdose (ex. footbaths) - SEVERE GASTROENTERITIS AND MUCOSAL EROSISONS
- Colic signs
- If oral exposure: blue/green colour of feces
- Management: fluids, gastroprotectants
Chronic copper toxicosis: clinical features
- MOST common type
- HEMOLYTIC CRISIS
- TRIGGERED BY A STRESSFUL EVENT (Cu related from lysosomes in liver)
o Transport, lactation, pregnancy, exercise, disease, starvation, shearing - First signs: depression, anorexia
- Rumen stasis
- Brown and/or yellow MM, jaundice, hemoglobinuria
- Weakness, lethargy, recumbency
- Death within 1-2 days
What is the pathophysiology of chronic copper poisoning in small ruminants?
- Cu stored in lysosomes in liver
- Excessive Cu: apoptosis of hepatocytes is GREATER than the ability of liver to clear debris
- Release of free Cu ions
- High Cu in blood = OXIDATIVE DAMAGE TO RBCs
o Oxidative damage hemolytic anemia
o Cellular debris further perpetuates liver damage AND accumulates in kidneys and causes damage - Intravascular hemolysis: splenomegaly
Copper poisoning: management for clinically affected/at risk animals
- MetHb: methylene blue
- Sodium thiosulfate
- D-penicillamine
- Vit C
- Off-label treatments: consult FARAD for withdrawal times
Copper poisoning: management for herd
- Put on concentrate feed
- Compounding pharmacies and chemical companies
*Copper poisoning: find the source of excessive copper
- Test everything that goes in the sheep’s mouth
- Even sheep or goat labelled supplements can contain excess copper
- Recent treatment
*What are the gross pathology lesions of chronic copper poisoning?
- Jaundice
- Spelomegaly: dark
- Hepatomegaly: often deep orange
- Dark kidneys
- Urine: dark red/brown
- *almost pathognomic lesions in ruminants
What are the histological lesions with chronic copper poisoning?
- Acute hepatic necrosis
- Tubular degeneration and necrosis
Copper poisoning: diagnosis live animal
- Blood Cu is NOT helpful: liver is primary storage site (elevated serum copper is often transient and not indicative of overall Cu burden)
- Clin path: elevated liver enzymes
- Jaundice
Copper poisoning: diagnosis dead animal
- PM lesions
- Submit liver and kidney to toxicology lab
*Copper poisoning: prevention
- FEED RATIO OF Cu:Mo
o 2:1 normal
o >6:1 to 10:1 risk of toxicity
o *very high ratio can lead to toxicity in a few weeks of feeding
Companion animals: Cu toxicity
- *Differential for chronic hepatitis
- Excess Cu accumulation
- Lots of breeds at risk
o Bedlington terriers
o West highland white terrier
o Doberman pinscher
o Lab - Copper storage disease: Bedlington terriers
- Dietary factors: high Cu in commercial and alternative diets
Companion animals: Cu toxicity clinical features
- Period of no symptoms as Cu accumulates
- Period of CHRONIC ACTIVE HEPATITIS
- Non-specific signs: weight loss, anorexia, lethargy, vomiting
- Progresses to liver failure: ascites, hepatic encephalopathy
Companion animals: Cu toxicity clinical pathology
- Increased liver enzyme activity
o Non specific - Later: increased GGT, indicators of liver failure
- Renal involvement: proteinuria, low USG, glucosuria
*Copper hepatopathy in dog: diagnosis
- LIVER BIOPSY
o **Copper concentration and histology grade - Abdominal ultrasound and radiographs NOT overly sensitive or specific
*Copper hepatopathy in dog: management
- Goals: decrease Cu absorption and increase Cu excretion
- Low copper diet
- Oral chelation therapy: D-penicillamine
- Zinc supplementation
- Hepatoprotectants
- Monitor liver enzymes q6 months
Companion animals: Cu toxicity prognosis
- Better with early treatment
- Negative prognostic indicators
o Cirrhosis/bridging fibrosis
o Ascites
o Hyperbilirubinemia
o Icterus
o Neutrophilia
o Enlarged portal lymph nodes
