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2013 PASA Conference                                            2/7/2013




                         Copper deficiencies
                         and excesses
                         SUSAN SCHOENIAN AND JEFF SEMLER
                         UNIVERSITY OF MARYLAND EXTENSION




                        Copper (Cu)
                        Why we think it’s an important topic.

                       • Sheep are very susceptible
                         to copper toxicity.
                       • Sheep and goats differ
                         significantly in their copper
                         requirements and
                         tolerance for excess
                         copper in their diet.
                       • Raising sheep and goats
                         together presents some
                         challenges from the
                         standpoint of copper
                         nutrition.




Susan Schoenian and Jeff Semler                                       1
2013 PASA Conference                                                             2/7/2013




                        Copper (Cu)
                        Why we think it’s an important topic.

                        • “Copper” is being
                          recommended (again)
                          as an anthelmintic.
                        • Some books and
                          people are
                          recommending that
                          copper be added to
                          sheep diets.
                        • Copper nutrition is
                          complex because of
                          its interaction with
                          other minerals.




                       Importance of copper (Cu)
                        Copper is a trace mineral that is a dietary essential.
                        Hemoglobin formation
                        Involvement in enzyme systems
                        Nerve function
                        Cardiovascular integrity
                        Bone structure
                        Connective tissue formation
                        Fertility and reproduction
                        Immune function
                        Protection against superoxide radicals
                        Pigmentation and hair texture




Susan Schoenian and Jeff Semler                                                        2
2013 PASA Conference                                                                                         2/7/2013




                       Copper basics: plants
                        • Fresh grasses are poor sources
                          of copper.
                        • Acidic soils increase Cu and
                          lower Mo in forages.
                        • Mo is higher in alkaline or high
                          organic matter soils.
                        • Copper absorption in plants is
                          limited by alkaline pH or higher
                          organic matter.
                        • Liming can increase Mo in
                          forage and disturb the Cu:Mo
                          ratio (Cu:Mo ratios of at least
                          are considered safe and will
                          avoid copper deficiency).
                        • Copper-containing fertilizer can
                          increase copper levels in plants
                          (e.g. poultry/pig manure).
                                                             Soil ingestion can increase intake of copper.




                       Copper status of forages




Susan Schoenian and Jeff Semler                                                                                    3
2013 PASA Conference                                             2/7/2013




                       Copper basics: animal
                        • Copper is absorbed from the
                          small intestines.

                        • Absorbed copper in excess of
                          requirements in stored in the liver
                          (a small amount is removed by
                          the kidneys).

                        • When net copper absorption is
                          insufficient to meet metabolic
                          requirements, liver stores are
                          mobilized.

                        • If the concentration of copper in
                          the liver exceeds a certain critical
                          value, there may be a sudden
                          release of massive amounts of
                          copper into the bloodstream, with
                          potentially deadly consequences.




                       Copper absorption
                        • More important than its
                          concentration in feed.
                        • Affected by species,
                          breed, genetics, and age.
                        • Young ruminants absorb
                          Cu more efficiently.
                          • 70-75% (up to 90%) absorption
                            in young ruminant vs. > 10% in
                            mature ruminants.
                          • Copper crosses placenta, but
                            only a small amount is
                            secreted in the milk.
                        • Ionophores increase efficiency
                          of copper absorption.




Susan Schoenian and Jeff Semler                                        4
2013 PASA Conference                                                                                                2/7/2013




                       Copper absorption is affected by
                       other minerals in the diet
                                                                     • Molybdenum (Mo) and
                                                                       sulfur (S) form insoluble
                                                                       complexes with Cu and
                                                                       prevent its absorption.
                                                                     • Cu absorption is
                                                                       decreased when there is
                                                                       excess zinc (Zn) and iron
                                                                       (Fe) in the diet.
                                                                     • Cu absorption can also
                                                                       be affected by cadmium
                                                                       and vitamin C.




                       Copper requirements
                                       SHEEP                                          GOATS
                       Cu requirement            Reference           Cu requirement           Reference
                       5 mg/kg                   NRC, 1975           8-10 mg/kg               1991, 2000
                       1 - 8.6 mg/kg             ARC, 1980           10-23 mg/kg              1992
                       7-11 mg/kg                NRC, 1985           10-23 mg/kg              1997
                       4.3 – 28.4 mg/kg          1999
                                                                     15 mg/kg*
                                                                     lactating goat           NRC, 2007
                        Equations which use different absorption
                        coefficients of copper and variable levels   20 mg/kg*                *Adjustments
                        of absorption antagonists and metabolic      mature goats and bucks   should be made
                          interactions are used to calculate the                              for the level of Mo
                                                                     25 mg/kg*                and S in the diet.
                        copper requirements for different classes
                                                                     growing goats
                                  of sheep (NRC, 2007).

                       Maximum tolerable level: 15 mg/kg             A maximum tolerable level has not
                       when diets contain normal Mo (1-2             been established for goats. Cattle
                       mg/kg and S (0.15-0.25 percent).              level is 40 mg/kg.




Susan Schoenian and Jeff Semler                                                                                           5
2013 PASA Conference                                                                   2/7/2013




                     Copper excesses and deficiencies
                                                        GOATS

                       SHEEP
                                   +                     • More likely to experience
                                                           copper deficiency.
                        • More likely to experience      • Goats have a higher
                          copper toxicity.                 requirement and
                        • Sheep are the species            tolerance for excess
                          most susceptible to              copper as compared to
                          copper toxicity.                 sheep.
                        • There is a narrow
                          margin between
                          requirements and
                                                                     (-)
                          toxic levels.




                       Two forms of copper toxicity
                       ACUTE                            CHRONIC
                        • Caused by ingestion of         • High levels of copper are
                          high copper feeds, salts,        ingested over time, but
                          pesticides, poultry litter,      at levels below the
                          or other high copper             acutely toxic level.
                          substances.                    • Usually occurs when
                        • Can occur at intakes of          there is a high
                          20-100 mg/kg (or ppm).           Cu:Mo ratio.
                                                         • Stress is usually
                                                           the trigger.




Susan Schoenian and Jeff Semler                                                              6
2013 PASA Conference                                                                                         2/7/2013




                       Two phases of copper toxicity

                        PRE-HAEMOLYTIC                       HAEMOLYTIC
                        • When copper                         • When copper is
                          accumulates in liver                  released from the
                          to exceed 1000 mg                     liver and blood
                          Cu/kg DM                              copper values rise.
                        • Lasts from weeks to                 • Lasts from hours
                          more than a year.                     to days.


                                                 STRESS




                       Diagnosis of copper toxicity
                        1.   Clinical signs
                        2.   Laboratory tests
                        3.   Necropsy
                        4.   Determine
                             mineral
                             concentrations of
                             the diet and
                             other potential
                             sources of
                             excess copper.
                                                          Texel sheep are more susceptible to Cu toxicity.




Susan Schoenian and Jeff Semler                                                                                    7
2013 PASA Conference                                                                       2/7/2013




                       Diagnosis of copper toxicity
                       Clinical signs
                        •   Weakness
                        •   Panting
                        •   Dullness
                        •   Pale mucous
                            membranes
                        •   Yellow discoloration
                            (jaundice) of mucous   Images from Colorado State University
                            membranes
                        •   Dark brown or red-
                            colored urine
                        •   Abortion
                        •   Death




                       Diagnosis of copper toxicity
                       Laboratory tests

                         • Liver copper
                         • Kidney copper
                         • Blood level
                             • Serum
                             • Plasma
                         • Liver enzymes




Susan Schoenian and Jeff Semler                                                                  8
2013 PASA Conference                                                                                  2/7/2013




                       Diagnosis of copper toxicity
                       Necropsy
                                                   Images from Colorado State University




                                  Icterus (jaundice)                     “gun, metal, blue” kidneys




                       Diagnosis of copper toxicity
                       Determine mineral concentrations in diet



                        1.   Copper
                        2.   Molybdenum
                        3.   Sulfur
                        4.   Iron




Susan Schoenian and Jeff Semler                                                                             9
2013 PASA Conference                                                                  2/7/2013




                       Common sources of excess copper
                        • Errors in feed formulation
                          and mixing
                        • Consumption of feedstuffs
                          formulated for other animals.
                        • Consumption of non-traditional
                          feedstuffs that are high in
                          copper.
                        • Grazing on pastures fertilized
                          with pig or poultry manure.
                        • Grazing forages deficient in
                          molybdenum.
                        • Use of copper-containing
                          anthelmintics.
                        • Use of copper-containing
                          footbaths.
                        • Copper supplements.




                       Treatment of Cu toxicity
                                                           • Usually unrewarding
                                                             for severely-affected
                                                             animals.
                                                           • Administer both
                                                             molybdenum and
                                                             sulfate as a drench or
                                                             add to feed.
                                                             • Ammonium molybdate
                                                             • Sodium sulfate
                                                           • Reduce or eliminate
                                                             extraneous sources of
                                                             copper.




Susan Schoenian and Jeff Semler                                                            10
2013 PASA Conference                                       2/7/2013




                     Copper deficiency
                     Common causes
                        1. Primary
                            • Low intake of copper
                               • Fresh forages have less
                                 Cu than cured hays.
                               • Grasses has less Cu
                                 than legumes
                               • Liming reduces Cu
                                 uptake by plants.

                        2. Secondary
                            • High concentrations of
                              Mo, S, Fe, Cn, Se, and
                              ascorbic acid (vitamin C).
                            • Alkaline soils




                       Diagnosis of copper deficiency

                       1. Clinical signs
                       2. Lab tests
                       3. Necropsy
                       4. Determine mineral
                          concentrations of
                          the diet.
                       5. Clinical response
                          to copper
                          supplementation.




Susan Schoenian and Jeff Semler                                 11
2013 PASA Conference                                    2/7/2013




                       Diagnosis of copper deficiency
                       Clinical signs
                         • Anemia
                         • Reduced growth rate
                         • Connective tissue
                           disorders
                         • Generalized osteoporosis
                         • Increased susceptibility
                           to all diseases.
                         • Neonatal or congenital
                           ataxia (swayback)
                         • De-pigmentation of skin,
                           hair, or wool.
                         • Loss of crimp, steely or
                           stringy wool




                       Treatment of copper deficiency

                        • Injectable copper
                          (can cause tissue damage)
                        • Oral copper
                          (short-acting)
                        • Copper oxide
                          particles
                        • Mineral supplement
                        • Copper-containing
                          fertilizers.




Susan Schoenian and Jeff Semler                              12
2013 PASA Conference                                    2/7/2013




                       Copper as an anthelmintic

                        1. Copper mineral
                           supplement

                        2. Copper sulfate
                           (Cu2SO4)

                        3. Copper oxide wire
                           particles (COWP).




                       Copper sulfate (Cu2SO4)
                         • Historical dewormer used
                           in the early 1900’s before
                           synthetic dewormers
                           became available.

                         • Was often combined with
                           lead arsenic or nicotine
                           sulfate to broaden its
                           efficacy.

                         • Due to the widespread
                           development of drug-
                           resistant worms, copper
                           sulfate is being re-
                           evaluated as a dewormer.




Susan Schoenian and Jeff Semler                              13
2013 PASA Conference                                            2/7/2013




                        Copper sulfate (Cu2SO4)
                       • Usually administered as a 1-1.5
                         percent solution in water.
                       • How copper sulfate compares to
                         a synthetic dewormer depends
                         upon the degree of resistance to
                         the synthetic dewormer.
                       • Recent research has shown that
                         copper sulfate can be effective
                         at reducing fecal egg counts
                         without causing copper toxicity.
                         • When/if used, copper sulfate
                           should only be administered to
                           clinically-parasitized animals.
                         • Copper toxicity is always risk if
                           copper sulfate is not administered
                           properly, especially to sheep!




                        Copper oxide
                          • Slow dissolving form of
                            copper.

                          • Not absorbed as well as
                            copper sulfate.

                          • Sold as a supplement to
                            treat or prevent copper
                            deficiency in cattle.

                          • Cattle doses need to be
                            re-sized for sheep and
                            goats.




Susan Schoenian and Jeff Semler                                      14
2013 PASA Conference                                      2/7/2013




                       Copper oxide wire particles
                         • Recent research has
                           shown COWPs to be as
                           effective as most
                           anthelmintics in reducing
                           fecal egg counts.
                         • However, COWPs are
                           only effective against the
                           barber pole worm.
                         • COWPs seem to be more
                           effective on young stock.
                         • Their exact mode of
                           action is not known.




                       Copper oxide wire particles
                        • Experts disagree as
                          to whether to
                          recommend COWPs
                          as an anthelmintic
                          for sheep.
                          • Most research has been
                            done with hair sheep and
                            goats.
                          • There hasn’t been any
                            copper toxicity in research
                            studies.




Susan Schoenian and Jeff Semler                                15
2013 PASA Conference                                                                   2/7/2013




                       Copper oxide wire particles (COWPs)
                       Recommendations
                        • No problem using COWPs in
                          goats.
                        • Do not use in sheep unless
                          you have total anthelmintic
                          failure or you are a certified
                          organic producer.
                          • Check with inspector to see if
                            COWPs would be allowed as a
                            dewormer.
                        • Only administer COWPs to
                          clinically-parasitized animals
                          (FAMACHA© 3-5).
                        • Since copper accumulates in
                          the liver over time, limit the
                          use of COWPs to lambs that
                          will be going to slaughter.




                       Raising sheep and goats together
                       Copper presents a dilemma.

                                                             • Feeding sheep mineral
                                                               (low copper) to sheep
                                                               and goats increases
                                                               the risk of copper
                                                               deficiency in goats.

                                                             • Feeding goat mineral
                                                               (higher copper) to
                                                               sheep and goats
                                                               increases the risk of
                                                               copper toxicity in
                                                               sheep.




Susan Schoenian and Jeff Semler                                                             16
2013 PASA Conference                                               2/7/2013




                       Raising sheep and goats together
                       Copper poses a problem.

                        • Feed them
                          separately.
                        • House them
                          separately at night
                        • Put mineral feeder
                          for goats where
                          sheep can’t get it.
                        • Give goats copper
                          supplements, e.g.
                          boluses.




                        Questions? Thank you for your attention.




Susan Schoenian and Jeff Semler                                         17

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Copper

  • 1. 2013 PASA Conference 2/7/2013 Copper deficiencies and excesses SUSAN SCHOENIAN AND JEFF SEMLER UNIVERSITY OF MARYLAND EXTENSION Copper (Cu) Why we think it’s an important topic. • Sheep are very susceptible to copper toxicity. • Sheep and goats differ significantly in their copper requirements and tolerance for excess copper in their diet. • Raising sheep and goats together presents some challenges from the standpoint of copper nutrition. Susan Schoenian and Jeff Semler 1
  • 2. 2013 PASA Conference 2/7/2013 Copper (Cu) Why we think it’s an important topic. • “Copper” is being recommended (again) as an anthelmintic. • Some books and people are recommending that copper be added to sheep diets. • Copper nutrition is complex because of its interaction with other minerals. Importance of copper (Cu) Copper is a trace mineral that is a dietary essential. Hemoglobin formation Involvement in enzyme systems Nerve function Cardiovascular integrity Bone structure Connective tissue formation Fertility and reproduction Immune function Protection against superoxide radicals Pigmentation and hair texture Susan Schoenian and Jeff Semler 2
  • 3. 2013 PASA Conference 2/7/2013 Copper basics: plants • Fresh grasses are poor sources of copper. • Acidic soils increase Cu and lower Mo in forages. • Mo is higher in alkaline or high organic matter soils. • Copper absorption in plants is limited by alkaline pH or higher organic matter. • Liming can increase Mo in forage and disturb the Cu:Mo ratio (Cu:Mo ratios of at least are considered safe and will avoid copper deficiency). • Copper-containing fertilizer can increase copper levels in plants (e.g. poultry/pig manure). Soil ingestion can increase intake of copper. Copper status of forages Susan Schoenian and Jeff Semler 3
  • 4. 2013 PASA Conference 2/7/2013 Copper basics: animal • Copper is absorbed from the small intestines. • Absorbed copper in excess of requirements in stored in the liver (a small amount is removed by the kidneys). • When net copper absorption is insufficient to meet metabolic requirements, liver stores are mobilized. • If the concentration of copper in the liver exceeds a certain critical value, there may be a sudden release of massive amounts of copper into the bloodstream, with potentially deadly consequences. Copper absorption • More important than its concentration in feed. • Affected by species, breed, genetics, and age. • Young ruminants absorb Cu more efficiently. • 70-75% (up to 90%) absorption in young ruminant vs. > 10% in mature ruminants. • Copper crosses placenta, but only a small amount is secreted in the milk. • Ionophores increase efficiency of copper absorption. Susan Schoenian and Jeff Semler 4
  • 5. 2013 PASA Conference 2/7/2013 Copper absorption is affected by other minerals in the diet • Molybdenum (Mo) and sulfur (S) form insoluble complexes with Cu and prevent its absorption. • Cu absorption is decreased when there is excess zinc (Zn) and iron (Fe) in the diet. • Cu absorption can also be affected by cadmium and vitamin C. Copper requirements SHEEP GOATS Cu requirement Reference Cu requirement Reference 5 mg/kg NRC, 1975 8-10 mg/kg 1991, 2000 1 - 8.6 mg/kg ARC, 1980 10-23 mg/kg 1992 7-11 mg/kg NRC, 1985 10-23 mg/kg 1997 4.3 – 28.4 mg/kg 1999 15 mg/kg* lactating goat NRC, 2007 Equations which use different absorption coefficients of copper and variable levels 20 mg/kg* *Adjustments of absorption antagonists and metabolic mature goats and bucks should be made interactions are used to calculate the for the level of Mo 25 mg/kg* and S in the diet. copper requirements for different classes growing goats of sheep (NRC, 2007). Maximum tolerable level: 15 mg/kg A maximum tolerable level has not when diets contain normal Mo (1-2 been established for goats. Cattle mg/kg and S (0.15-0.25 percent). level is 40 mg/kg. Susan Schoenian and Jeff Semler 5
  • 6. 2013 PASA Conference 2/7/2013 Copper excesses and deficiencies GOATS SHEEP + • More likely to experience copper deficiency. • More likely to experience • Goats have a higher copper toxicity. requirement and • Sheep are the species tolerance for excess most susceptible to copper as compared to copper toxicity. sheep. • There is a narrow margin between requirements and (-) toxic levels. Two forms of copper toxicity ACUTE CHRONIC • Caused by ingestion of • High levels of copper are high copper feeds, salts, ingested over time, but pesticides, poultry litter, at levels below the or other high copper acutely toxic level. substances. • Usually occurs when • Can occur at intakes of there is a high 20-100 mg/kg (or ppm). Cu:Mo ratio. • Stress is usually the trigger. Susan Schoenian and Jeff Semler 6
  • 7. 2013 PASA Conference 2/7/2013 Two phases of copper toxicity PRE-HAEMOLYTIC HAEMOLYTIC • When copper • When copper is accumulates in liver released from the to exceed 1000 mg liver and blood Cu/kg DM copper values rise. • Lasts from weeks to • Lasts from hours more than a year. to days. STRESS Diagnosis of copper toxicity 1. Clinical signs 2. Laboratory tests 3. Necropsy 4. Determine mineral concentrations of the diet and other potential sources of excess copper. Texel sheep are more susceptible to Cu toxicity. Susan Schoenian and Jeff Semler 7
  • 8. 2013 PASA Conference 2/7/2013 Diagnosis of copper toxicity Clinical signs • Weakness • Panting • Dullness • Pale mucous membranes • Yellow discoloration (jaundice) of mucous Images from Colorado State University membranes • Dark brown or red- colored urine • Abortion • Death Diagnosis of copper toxicity Laboratory tests • Liver copper • Kidney copper • Blood level • Serum • Plasma • Liver enzymes Susan Schoenian and Jeff Semler 8
  • 9. 2013 PASA Conference 2/7/2013 Diagnosis of copper toxicity Necropsy Images from Colorado State University Icterus (jaundice) “gun, metal, blue” kidneys Diagnosis of copper toxicity Determine mineral concentrations in diet 1. Copper 2. Molybdenum 3. Sulfur 4. Iron Susan Schoenian and Jeff Semler 9
  • 10. 2013 PASA Conference 2/7/2013 Common sources of excess copper • Errors in feed formulation and mixing • Consumption of feedstuffs formulated for other animals. • Consumption of non-traditional feedstuffs that are high in copper. • Grazing on pastures fertilized with pig or poultry manure. • Grazing forages deficient in molybdenum. • Use of copper-containing anthelmintics. • Use of copper-containing footbaths. • Copper supplements. Treatment of Cu toxicity • Usually unrewarding for severely-affected animals. • Administer both molybdenum and sulfate as a drench or add to feed. • Ammonium molybdate • Sodium sulfate • Reduce or eliminate extraneous sources of copper. Susan Schoenian and Jeff Semler 10
  • 11. 2013 PASA Conference 2/7/2013 Copper deficiency Common causes 1. Primary • Low intake of copper • Fresh forages have less Cu than cured hays. • Grasses has less Cu than legumes • Liming reduces Cu uptake by plants. 2. Secondary • High concentrations of Mo, S, Fe, Cn, Se, and ascorbic acid (vitamin C). • Alkaline soils Diagnosis of copper deficiency 1. Clinical signs 2. Lab tests 3. Necropsy 4. Determine mineral concentrations of the diet. 5. Clinical response to copper supplementation. Susan Schoenian and Jeff Semler 11
  • 12. 2013 PASA Conference 2/7/2013 Diagnosis of copper deficiency Clinical signs • Anemia • Reduced growth rate • Connective tissue disorders • Generalized osteoporosis • Increased susceptibility to all diseases. • Neonatal or congenital ataxia (swayback) • De-pigmentation of skin, hair, or wool. • Loss of crimp, steely or stringy wool Treatment of copper deficiency • Injectable copper (can cause tissue damage) • Oral copper (short-acting) • Copper oxide particles • Mineral supplement • Copper-containing fertilizers. Susan Schoenian and Jeff Semler 12
  • 13. 2013 PASA Conference 2/7/2013 Copper as an anthelmintic 1. Copper mineral supplement 2. Copper sulfate (Cu2SO4) 3. Copper oxide wire particles (COWP). Copper sulfate (Cu2SO4) • Historical dewormer used in the early 1900’s before synthetic dewormers became available. • Was often combined with lead arsenic or nicotine sulfate to broaden its efficacy. • Due to the widespread development of drug- resistant worms, copper sulfate is being re- evaluated as a dewormer. Susan Schoenian and Jeff Semler 13
  • 14. 2013 PASA Conference 2/7/2013 Copper sulfate (Cu2SO4) • Usually administered as a 1-1.5 percent solution in water. • How copper sulfate compares to a synthetic dewormer depends upon the degree of resistance to the synthetic dewormer. • Recent research has shown that copper sulfate can be effective at reducing fecal egg counts without causing copper toxicity. • When/if used, copper sulfate should only be administered to clinically-parasitized animals. • Copper toxicity is always risk if copper sulfate is not administered properly, especially to sheep! Copper oxide • Slow dissolving form of copper. • Not absorbed as well as copper sulfate. • Sold as a supplement to treat or prevent copper deficiency in cattle. • Cattle doses need to be re-sized for sheep and goats. Susan Schoenian and Jeff Semler 14
  • 15. 2013 PASA Conference 2/7/2013 Copper oxide wire particles • Recent research has shown COWPs to be as effective as most anthelmintics in reducing fecal egg counts. • However, COWPs are only effective against the barber pole worm. • COWPs seem to be more effective on young stock. • Their exact mode of action is not known. Copper oxide wire particles • Experts disagree as to whether to recommend COWPs as an anthelmintic for sheep. • Most research has been done with hair sheep and goats. • There hasn’t been any copper toxicity in research studies. Susan Schoenian and Jeff Semler 15
  • 16. 2013 PASA Conference 2/7/2013 Copper oxide wire particles (COWPs) Recommendations • No problem using COWPs in goats. • Do not use in sheep unless you have total anthelmintic failure or you are a certified organic producer. • Check with inspector to see if COWPs would be allowed as a dewormer. • Only administer COWPs to clinically-parasitized animals (FAMACHA© 3-5). • Since copper accumulates in the liver over time, limit the use of COWPs to lambs that will be going to slaughter. Raising sheep and goats together Copper presents a dilemma. • Feeding sheep mineral (low copper) to sheep and goats increases the risk of copper deficiency in goats. • Feeding goat mineral (higher copper) to sheep and goats increases the risk of copper toxicity in sheep. Susan Schoenian and Jeff Semler 16
  • 17. 2013 PASA Conference 2/7/2013 Raising sheep and goats together Copper poses a problem. • Feed them separately. • House them separately at night • Put mineral feeder for goats where sheep can’t get it. • Give goats copper supplements, e.g. boluses. Questions? Thank you for your attention. Susan Schoenian and Jeff Semler 17