Iron, Copper, and Molybdenum Toxicosis

Question 1

What are the usual sources of iron toxiciosis?

Answer 1

Accidental ingestion of human oral supplements

Overdosage in pet or piglets

Question 2

What are the three forms that iron is present in?

Which is the most irritating and astringent?

Answer 2

Elemental
Divalent (ferrous)
Trivalent (ferric) —> most irritating and astringent

Question 3

T/F: toxicity of oral iron preparations is more toxic than parenteral preparations

Answer 3

False

Parenteral is more toxic than oral

Question 4

Greater than 5000ppm iron in diet can lead to ________ in piglets because it interferes with phosphate absorption

Answer 4

Rickets

Question 5

How is iron absorbed ??

Answer 5

Ferrous iron absorbed in small intestine using energy-dependent carrier

Ferrous iron is oxidized to ferric iron once absorbed

Question 6

Ferric iron binds to ___________ in plasma and is distributed throughout the body

Answer 6

Transferrin

70% to hemoglobin
10% to myoglobin
Rest to enzymes or stored in liver/spleen/bones

Question 7

What is the MOA of iron toxicosis ?

Answer 7

Primary on GI tract: GI tract, liver, and CV leading to shock and death

GI: direct corrosion of the GI mucosa, vomiting, diarrhea, and shock

Liver: accumulation causing mitochondrial damage, acidosis and shock

CV: free radical lipid peroxidation and damage to membranes, increased vascular permeability, hemorrhage, vasodilation, CV collapse, and shock

Question 8

Injectable iron can cause what type of reaction causing an acute rapid death?

Answer 8

Anaphylactic reaction -histamine release

Question 9

What are the 4 stages of acute iron toxicosis?

Answer 9

1. Nausea, vomiting, diarrhea, GI hemorrhage
2. Apparent recovery
3. Vomiting, diarrhea, GI hemorrhage, metabolic acidosis, coagulation disorders, hepatic failure, CV collapse
4. GI obstruction

Question 10

What lesion is associated with parenteral preparations of iron?

Answer 10

Yellowish-brown discoloration at injection site and near lymph node

Question 11

What lesions are seen with oral preparations of iron?

Answer 11

GI ulcer and hemorrhagic enteritis

Congestion of liver, kidney, liver necrosis, icterus, and hemoglobinuria

Question 12

How do you treat iron toxicosis?

Answer 12

GI decontamination:

• emesis, or gastric lavage before onset of clinical signs
• activated charcoal is NOT effective
• milk of magnesia to precipitate iron

Supportive therapy

• IV fluids, dehydration, acidosis, and hypovolemic shock
• GI protectants like sucralfate

Chelation therapy
-only indicated in severe toxicosis with deferoxamine

Question 13

What is more common, acute or chronic copper toxicosis?

Answer 13

Chronic

Question 14

Vomiting, colic, hemorrhagic diarrhea, dehydration, and shock are signs of acute/chronic copper toxiciosis?

Answer 14

Acute

—> direct corrosive action of copper on GI

Question 15

What are the sources of chronic copper toxiciosis?

Answer 15

Excess copper

• feed additives
• natural in soil/plants
• contaminated by mining
• fertilized with poultry litter/swine manure

Molybdenum deficiency
-normal ratio is 6:1 copper/molybdenum

Unavailability of sulfate

Question 16

What normally binds copper in tissues and forms a compound that is readily excreted in the urine?

Answer 16

Molybdenum

Binds to copper at 4:3 ratio —> copper molybdate (CuMoO4)

Question 17

What is reduced in the rumen that binds copper to reduce its absorption?

Answer 17

Sulfites are reduced to sulfides

Question 18

T/F: Normal feed and forage copper levels can cause toxicity when molybdenum or sulfate is unavailable

Answer 18

True

Question 19

How long does it take for copper accumulation to occur in sheep?

Answer 19

2-10weeks exposure

Question 20

What is the MOA of copper toxicosis?

Answer 20

Copper accumulates in liver causing liver degeneration and necrosis

Release of copper from the liver and excess in blood —> oxidation of erythrocytes membranes —> hemolytic crisis

Oxidation of hemoglobin to methemoglobinemia

Question 21

What are the clinical signs of chronic copper toxicity?

Answer 21

Sudden onset of weakness, anorexia, pale mucous membranes, icterus, hemoglobinuria, fever, dyspnea, and shock

Question 22

What lesions do you see in chronic copper toxicosis?

Answer 22

Icterus, hemolysis, and methemoglobinemia

Liver is enlarged, yellow, and friable

Kidney is enlarged, hemorrhagic, bluish-dark, and friable (gunmetal )

Spleen is enlarged, dark brown to black (blackberry jam)

Question 23

What is the DDX for copper toxicity?

Answer 23

Hemolytic agents- zinc, naphthalene, DMSO, Guaifenesin

Poisonous plants- onion, gossypol, red maple

Snake venoms

Infectious diseases - lepto, babesisosis, anaplasmosis, bacillary hemoglobinuria

Question 24

What is the treatment of copper toxicosis?

Answer 24

Ammonium tetrathiomolybate

D-penicillamine

Question 25

How can copper toxicosis be prevented?

Answer 25

Molybdenized copper phosphate sprayed on pastures Sheep rations should contain Cu/Mo at 6:1 ratio Addition of molybdate to sheep ratios at 2-4ppm for prevention Ammonium molybdate and thiosulfate orally per day prevents copper toxicosis in individual sheep Supplemental since reduces hepatic copper accumulation

Question 26

What are sources of molybdenum toxicosis?

Answer 26

``` Excess molybdenum -soil rich in molybdenum -plant accumulation -industrial contamination -fertilizers Copper deficiency ```

Question 27

What is the normal function of molybdenum ?

Answer 27

Component of xanthine oxidase, which converts the purine xanthine to uric acid Elevated molybdenum interferes with copper absorption Excess molybdenum causes copper deficiency

Question 28

What animals are the most susceptible animals to molybdenum toxicosis?

Answer 28

Cattle

Question 29

What species are resistant to molybdenum toxicosis?

Answer 29

Horses and pigs

Question 30

High dietary levels of __________ increases molybdenum toxicosis, while high dietary levels of ________ will decrease toxicosis?

Answer 30

Sulfate; copper

Question 31

Where is molybdenum excreted?

Answer 31

Milk

Question 32

What is the MOA of molybdenum toxicosis?

Answer 32

Copper deficiency —> lack of hematopoeisis, CT metabolism, myelin formation, pigmentation, and bone formation —> lack of cytochrome oxidase and aromatic amino acid-metabolizing enzymes

Question 33

What are clinical signs associated with molybdenum toxicosis?

Answer 33

Severe diarrhea Rough hair coat and depigmentation Loss of weight, anemia, osteoporosis, exostosis, lameness, pica Decreased libido in bulls and infertility in cows

Question 34

How do you treat molybdenum toxicosis?

Answer 34

Copper glycinate SC | Copper sulfate added to diet