Week 9 Flashcards
Organic Arsenic
Sources: (1) overdose, (2) prolonged use, or (3) recommended concentrations in debilitated, dehydrated or sick animals
Use: Feed additive to improve weigh gain and feed efficiency. To control enteric infections in swine & poultry
• Arsanilic acid is mainly used in swine. Roxarsone is mainly used in poultry. Both can be used in other animals.
Properties: phenylarsonic acid (benzenearsonic acid) derivatives – Arsenic is in the pentavalent oxidation state
Toxicity: Organic pentavalent arsenicals are less toxic than inorganic arsenic
• Arsanilic acid- 500 ppm for 7‐10 days causes toxicosis in swine
o Recommended concentration as a growth promoter in swine and poultry is 50‐100 ppm
o Recommended concentration to control swine dysentery is 250‐400 for 5‐6 days
• Roxarsone-250 ppm for 7‐10 days causes toxicosis in swine
o The recommended concentration as a growth promoter in poultry is 25‐50 ppm, and in swine is 25‐37.5 ppm
o The recommended concentration to control swine dysentery is 200 ppm for 5‐6 days
• Toxicity is enhanced by dehydration, water deprivation, and renal insufficiency
TK: Small amount is absorbed from the GI tract Distributed throughout the body Excreted unchanged in urine and other routes
MOA: Unknown- Peripheral nerve demyelination and axonal damage very similar to vitamins B deficiency
CS- Peripheral neural toxicity ( local motor signs) in Swine w/ Arsanilic acid, and Poultry w/ Rozarsone
• Arsanilic acid
o Swine–acute toxicosis-3‐5 days - incoordination, ataxia, then partial paralysis but still have good appetite (No GI irritation)
♣ Blindness may develop
♣ May be erythema and sensitivity to sunlight
♣ In chronic toxicosis, gradual onset of blindness and partial paralysis but pigs still eat and drink
o Poultry- Anorexia, depression, coma, and death
• Roxarsone
o Swine–Sudden onset (minutes), marked hyperexcitability, tremors, collapse, coma, and may be death, but no blindness
o Poultry – Incoordination and ataxia
Swine Lesions
• Possible erythema in light‐skin pigs
• May be muscle atrophy in chronic cases
• Microscopically, peripheral nerve and optic nerve degeneration, demyelination , and gliosis
Diagnosis: History of exposure to organic arsenicals, clinical signs, no gross lesions, microscopic peripheral nerve demyelination, and chem analysis
• Chemical analysis: Specimens are suspected feed, liver, and kidney
Treatment: no antidote. Withdrawal or organic arsenicals. Supportive therapy- water, fluids, vitamins, antibiotics to prevent bacterial infection
• Recovery may take 2-4 weeks
Ddx:
• Arsanilic acid toxicosis in swine- (1) Subacute selenium toxicosis (paralysis without blindness in swine only – will discuss later) (2) Organic mercury (seizure- uncommon- wont discuss) (3) Vitamin B complex deficiency (4) Infectious diseases
• Roxarsone in swine- (1) Many Pesticides (cause CNS stimulation) (2) Water deprivation/sodium ion toxicosis
ACUTE Copper Toxicosis
Source: Not common now that pennies are now not made out of it – ingestion of high concentrations (Cooper Sulfate- used in water)
CS: Rapid onset of severe GI signs including vomiting, colic , hemorrhagic diarrhea, dehydration and shock, due to the direct corrosive action
Treatment: supportive/symptomatic
CHRONIC Copper Toxicosis in Sheep
Source: (1) Ingestion of Copper - Feed additive, soils & plants (ie clover) contaminated by mining, soils fertilized with poultry litter or swine manure. (2) Molybdenum deficiency. Normal copper/molybdenum ratio is 6:1 (3) Unavailability of sulfate
Properties:
• Normally, molybdate (MoO42‐) binds to copper (Cu2+) in tissues at a ratio 4:3, to form copper molybdate (CuMoO4) that is readily excreted in urine
• Rumen sulfates and sulfites are reduced to sulfides that binds copper, reducing its absorption
• Accumulation of copper in the liver is due to imbalances between copper, molybdenum, and sulfate
Toxicity:
• Normal feed and forage copper levels (10-20 ppm) cause copper accumulation when molybdenum is deficient (less than 1‐2 ppm), or sulfate is unavailable
• Accumulation requires about 2‐10 weeks exposure in sheep
• Liver damage may cause copper accumulation by hepatocytes (secondary copper toxicosis)
o Stress may cause sudden loss of copper from the liver to the blood Copper toxicosis
TK:
• Copper is absorbed from the intestine then carried by serum and erythrocytes to different tissues
o Adequate Sulfate and Molybdate decrease absorption. Zinc also decreases toxicity.
• The liver (sink organ) removes most of copper from the blood
• Copper is bound to the hepatic lysosomes, mitochondria, and nucleus liver damage
• Copper is mainly excreted in bile
MOA: Copper accumulation in the liver causes liver degeneration and necrosis
• Release of copper from the liver and excess copper in blood causes oxidation of erythrocyte membranes increasing their fragility resulting in a hemolytic crisis
•
Copper also oxidizes hemoglobin to methemoglobin (can not carry oxygen)
CS: Sudden onset of weakness, anorexia, pale mucous membranes, icterus, hemoglobinuria, fever, dyspnea, and shock. Due to hemolysis!
Lesions: Icterus, hemolysis, and methemoglobinemia
• The liver is enlarged, yellow, and friable
• The kidneys are enlarged, hemorrhagic, bluishdark, and friable (gunmetal kidneys)
• The spleen is enlarged and dark brown to black (blackberry jam spleen) Port wine urine
Diagnosis: History, sudden hemoglobinuria, jaundice, and signs of shock and respiratory insufficiency, hemolysis, & lab
• Elevated serum or whole blood Cu (> 1.5 ppm), Elevated liver and kidney Cu (> 150 ppm, and 15 ppm respectively)
• Elevated liver enzymes (AST, LDH) seen 3‐6 weeks before a hemolytic crisis
Treatment & Prevention: Give Molybdate to prevent (many different ways). D-penicillamine (Chelating agent-$$$). Zinc to reduce accumulation.
• Ammonium tetrathiomolybate (1.7‐3.4 mg/day IV or SC for 3 treatments EOD)
• Molybdenized copper phosphate sprayed on pastures at the rate of 4 ounces/acre
o Sheep rations should contain Cu/Mo at 6:1 ratio
o Addition of molybdate to sheep rations at 2‐4 ppm for prevention
o Ammonium molybdate (50 mg) and thiosulfate (0.3‐1.0 g) orally per day prevents copper toxicosis in individual sheep
• Supplemental zinc (250 ppm) reduces hepatic copper accumulation
• D‐penicillamine (50 mg/kg orally for up to 6 days) –chelating agent- Expensive
•
DDx:
• Hemolytic agents- Zinc, naphthalene, phenolics, DMSO, guaifenesin
• Poisonous plants- Onion, gossypol (cottonseed), red maple (Acer rubrum- in horses), mustard
• Certain snake venoms
• Infectious diseases- Leptospirosis, babesiosis, anaplasmosis, bacillary hemoglobinuria
Chronic Copper Toxicosis in DOGs
• Heredity Mainly seen in Bedlington terrier due to an autosomal recessive disorder at 2‐6 years of age
o Other breeds including West Highland White terriers, Skye terriers and Doberman pinscher are also susceptible
MOA: Excess free copper causes chronic active hepatitis and liver necrosis due to lipid peroxidation of mitochondrial membranes
• Hemolytic crisis due to sudden release of copper is much less likely in dogs
Treatment- D‐penicillamine and symptomatic
Molybdenum Toxicosis
Source: Excess Molybdenum (less common) & Copper deficiency (more common)
• Excess molybdenum can be from Soil rich in molybdenum, or contaminated with molybdenum (Florida, California, Oregon, Nevada), Plants*, Industrial contamination (brick plants, steel mills) and Molybdenum‐containing fertilizers
Properties: essential trace elements- a component of xanthine oxidase, which converts the purine xanthine to uric acid
• Elevated molybdenum interferes with copper absorption & Excess molybdenum causes copper deficiency
Toxicity: Cattle are most susceptible, but it has been seen in sheep. Horses and Pigs are resistant.
• High levels of dietary sulfate increases toxicity
• Dietary copper decreases toxicity
• The maximum tolerable dietary level is 5‐10 ppm
TK: Absorbed from the GI tract. Widely distributed. Excreted in milk in toxic levels (source for humans and nursing animals).
MOA: Copper Deficiency
• Copper is involved in hematopoeisis, CT metabolism, myelin formation in newborn animals, pigmentation, and bone formation
• Copper is a component in essential enzymes such as cytochrome oxidase and aromatic amino acid‐metabolizing enzymes (tyrosinase, dopamine hydroxylase, MAO)
• Copper‐containing proteins (cupreins) in most aerobic cells have superoxide dismutase activity
• Direct Irritation
CS: – Severe diarrhea (greenish, with fluids and gas bubbles) after 8‐10 days following exposure
• Rough hair coat and depigmentation (achromotrichia) of hair especially around the eyes (“spectacled” appearance)
• Loss of weight, microcytic anemia, osteoporosis and exostosis, lameness, and pica
• Decreased libido in bulls and infertility in cows
Diagnosis: History, clinical signs, lesions, and laboratory diagnosis
• Elevated molybdenum in the Whole blood (> 0.1 ppm) and in the liver (> 5 ppm) – need to know specimens
• Decreased copper in the blood (
