Primary copper deficiency

The diseases caused by a primary deficiency of copper in ruminants are enzootic ataxia of sheep in Australia, New Zealand, and the USA, licking sickness, or liksucht of cattle in Holland and falling disease of cattle in Australia.

Copper deficiency occurs naturally in grazing livestock in many parts of the world. It has long been recognized as an endemic disease in the Salado’s river basin in Buenos Aires Province, Argentina, affecting over 50% of the cattle population.³ Some 81% of this wide area of 56 000 km² is devoted to breeding over 6.5 million head of beef cattle. The copper content in the grass is inadequate for most of the year and is most critical in autumn.⁴

A concurrent deficiency of both copper and cobalt occurs in Australia (coast disease) and Florida in the USA (salt sickness) and is characterized by the appearance of clinical signs of both deficiencies in all species of ruminants. The disease is controlled by supplementation of the diet with copper and cobalt.

In the USA, copper deficiency is not restricted to a single geographic region.⁵ In a survey of 2007 beef cows and heifers from 256 herds, 1.7% were deficient and 38% were marginally deficient. In herds, 36% were marginally deficient and 0.8%, deficient. Approximately 50% of the producers reported use of copper supplements, but a significant portion of cattle from those herds were classified as marginally deficient or deficient.

A survey in Saskatchewan, Canada, found that 67% of slaughter cattle had liver levels lower than 10 mg copper/kg on a wet weight (WW). A survey of the copper status of the fetuses and livers from adult animals found that 20% of steers, 54% of pregnant cows, 52% of heifers, and 77% of non-pregnant cows had liver levels <25 mg/kg DM. The concentrations of copper in the liver of the fetuses were directly proportional to the liver copper concentrations in the dams. Liver copper levels of fetuses from dams with liver copper >25 mg/kg DM were higher than those in fetuses from dams with liver copper levels <25 mg/kg DM. During gestation, the level of copper progressively increased in the fetal liver and decreased in the maternal liver. The concentration of copper in fetal livers increased with increasing fetal age and at term, the newborn calf has high levels of liver copper to meet postnatal requirements because cows’ milk is a poor source of copper. The magnitude of copper deficiency in some areas is extensive and emphasizes the importance of adequate copper nutrition in pregnant cattle in order to maintain adequate fetal levels of copper.

Copper deficiency has been diagnosed in Canada in a herd of captive musk-oxen, which had originated in the Northwest Territories.⁶

Copper deficiency may also cause anemia in sucking pigs and reduced growth rate and cardiac disease in growing pigs. Adult horses are unaffected, but abnormalities of the limbs and joints of foals reared in copper-deficient areas do occur. Osteochondrosis is associated with a copper deficiency in young, farmed red deer and wapiti X red deer hybrids in New Zealand.⁷

Secondary copper deficiency

The diseases caused by secondary copper deficiency, mostly due to high dietary intakes of molybdenum and sulfate, are listed in Table 30.2. They include syndromes characterized by diarrhea or by unthriftiness. ‘Yellow calf’, a disease of nursing calves occurs on Hawaii’s rangeland where copper content of forages ranges from 2.6 to 11.8 mg/kg and the molybdenum from <1 to 39 mg/kg. Swayback of lambs in the UK has been classed as a secondary copper deficiency, but no conditioning factor has been determined. While swayback is a naturally occurring disease caused by a primary deficiency of copper, identical lesions occur experimentally by feeding molybdenum and sulfate to the ewes. There is some evidence that heavy lime dressing of a pasture may predispose to swayback. A wasting disease similar to peat scours and preventable by the administration of copper and unthriftiness (‘pine’) of calves, occur in the UK, but in both instances the copper and molybdenum intakes are normal. Molybdenum appears to be the conditioning agent in enzootic ataxia in the USA. A dietary excess of molybdenum is known to be the conditioning factor in the diarrheic diseases, peat scours in New Zealand, California, and Canada and ‘teart’ in Britain.

High concentrations of molybdenum in forage (21–44 mg/kg DM) have been identified in several reclaimed mining areas in British Columbia but cattle have grazed these areas for 12-week periods yearly for 3 years without developing secondary copper deficiency.⁸ One-half of the animals received a copper supplement and there were no differences in weight gain, liver molybdenum, serum copper, and molybdenum and milk copper and molybdenum between the two groups. The results indicated that the upper tolerable dietary concentrations of 5–10 mg molybdenum described by the National Research Council and the minimum safe copper to molybdenum ratio of 2:1 are not universal.⁸

Moose sickness is a disease of moose (Alces alces L.) in Sweden.⁹ The disease has also been known as ‘Alvsborg disease’ and ‘wasting disease’. About 4–5% of the moose population is affected annually. The appearance of the disease coincided with intensified liming of wetlands, lakes, and forests during the 1980s, undertaken to counteract the deleterious effects of acid rain. The increase in pH caused by the liming affected the availability of nutrients in the soil, reducing copper availability and increasing molybdenum.

Copper deficiency may be a factor contributing to the population decline of moose in North-western Minnesota.¹⁰ In moose found dead, the copper concentrations based on criteria set for cattle, were deficient in 39.5% of livers, marginally deficient in 29.5% and adequate in 31%.¹⁰ The lower concentrations of copper in moose from bog and forest areas compared with the agricultural and prairie areas of North-western Minnesota coincide with a lower calf-to-cow ratio in the north-west forest area compared with the northwestern prairies.

Age susceptibility

Young animals are more susceptible to primary copper deficiency than adults. Calves on dams fed deficient diets may show signs at 2–3 months of age. As a rule, the signs are severe in calves and yearlings, less severe in 2-year-olds and of minor degree in adults. Enzootic ataxia is primarily a disease of sucking lambs whose dams receive insufficient dietary copper. Ewes with a normal copper status take some time to lose their hepatic reserves of copper after transfer to copper-deficient pastures and do not produce affected lambs for the first 6 months. The occurrence of the disease in sucklings and its failure to appear after weaning, point to the importance of fetal stores of copper and the inadequacy of milk as a source of copper. Milk is always a poor source of copper and when it is the sole source of nourishment the intake of copper will be low. Milk from normal ewes contains 20–60 μg/dL (3.1–9.4 μmol/L) copper, but under conditions of severe copper deficiency this may be reduced to 1–2 μg/dL (0.16–0.31 μmol/L).

Breed and species susceptibility

There are marked genetic differences in copper metabolism between breeds of sheep. The Welsh Mountain ewe can absorb copper 50% more efficiently than the Scottish blackface,¹¹ and the Texel cross blackface 145% more efficiently than pure blackface lambs.¹¹ The susceptibility to, or protection from, the effects of copper deficiency and also copper poisoning, is influenced from birth by genetic effects. These affect copper status of the lamb at birth, through the maternal environment controlled by the dam’s genes and through the effect of the lamb’s own genes. Later in life, the animal’s own genes become the predominant influence determining its copper status on any given nutritional regimen. These genetic differences have physiological consequences reflected in differences in the incidence of swayback, both between and within breeds and in effects on growth and possibly on reproduction. The differences observed are due to genetic differences in the efficiency of absorption of dietary copper.

The genetic effects determining the copper status of the lamb are already present in utero and the effects are not controlled by the lamb’s own genotype but by that of its dam. The maternal effect is still present at weaning at 9 weeks of age, but disappears after weaning when the genetic differences are due to the sheep’s own genotype.

The existence of genes determining plasma copper has been shown by the successful continued selection for high and low concentrations in closed lines of a single breed type. Ram selection is made on the basis of plasma copper concentrations at 18 and 24 weeks of age. The proportion of the normal variation in plasma copper that is heritable is 0.3. The high-line female sheep retain more copper in the liver than the low-line females, caused by a positive correlation between the concentration of copper in plasma and the efficiency of absorption.

The genetic variation in the copper metabolism of sheep has important physiological consequences. Breeds show wide variation in their susceptibility to swayback; the incidence of swayback may vary from 0 to 40% between breeds within one flock and the incidence according to breed type is closely related to the differences in the concentration of copper in the liver than in blood. When these high and low female lines are placed on improved and limed pasture, which can induce a severe copper deficiency, soon after birth there are indications of swayback, general dullness, lack of vigor and mortality in the lambs. By 6 weeks of age, the mortality rate is higher in the lambs from the low copper line than in those from the high copper line. In addition, at 6 weeks of age, lambs from the low line are 2 kg lighter than those in the high line.

There are significant differences in the copper requirements and tolerance between goats and sheep.¹² The dietary copper requirements of goats are uncertain but may be higher than in sheep. Dietary levels of copper which could cause copper toxicity in sheep, do not cause toxicity in goats. Some limited data on growth performance indicates a stimulatory effect of 100–300 pap copper in the diet of Nubian goats. Extra copper accumulated in liver and to a lesser extent in other tissues and was excreted through the biliary system and into the feces.

Certain breeds of cattle, e.g. the Simmental and Charolais, may have higher copper requirements than other breeds, e.g. Angus and these differences may be related to differences in copper absorption in the gastrointestinal tract. Angus heifers have a lower minimal copper requirement than Simmental.¹³ Based on liver copper, the control diets containing 4.4 mg or 6.4 mg of copper/kg DM did not meet the copper requirement of either breed during gestation and lactation or growth, Addition of 7 mg of copper/kg DM to the control diets met the copper requirements of both breeds.

Fetal liver copper

During gestation, the copper concentration increases progressively in the ovine and bovine fetal liver and decreases in the maternal liver. The developing bovine fetus obtains its copper by placental transfer and at birth, the liver concentration of copper is high and declines postnatally to adult levels within the first few months. Placental transfer is less efficient in sheep and lambs are commonly born with low liver reserves, making the neonatal lambs susceptible to copper deficiency. In copper-deficient cattle, the accumulation of liver copper in the fetus continues independent of the dam’s liver copper until the fetus is about 180 days, then a gradual decline in fetal liver copper occurs. The liver copper concentration in fetuses from dams on a copper-adequate diet continues to increase and not decline at 180 days of gestation. All of this indicates an increase in copper requirements by the dam during pregnancy; during the last month of pregnancy, the daily requirement for copper in cattle increases to approximately 70% above the maintenance requirements, which means that the dietary allowance of 10 mg/kg DM needs to be increased up to 25 mg/kg DM during pregnancy. The concentrations of copper, iron, manganese, and zinc are consistently lower than normal in the livers of aborted fetuses, indicating a non-specific change in trace element status which is probably an effect of abortion and not a cause.

Colostrum is rich in copper, allowing the newborn with its preferential ability to absorb copper to increase hepatic stores. Later, the copper content of milk declines rapidly so that it is usually insufficient to meet the requirements of the sucking neonate for copper. The young milk-fed animal is able to absorb about 80% of its copper intake, but the efficiency of absorption declines with age as the rumen becomes functional, when only 2–10% of available copper is absorbed.

Pasture composition

The absorption (or availability) of copper is influenced by the type of diet, the presence of other substances in the diet such as molybdenum, sulfur, and iron, the interaction between the type of diet and the chemical composition of the diet and the genetic constitution of the animals. Copper is well-absorbed from diets low in fiber, such as cereals and Brassicas, but poorly absorbed from fresh forage. Conservation of grass as hay or silage generally improves its availability. This explains why copper deficiency is a problem of the grazing animal and seen only rarely in housed ruminants receiving diets that are commonly adequate in copper.

Molybdenum and sulfur

Only small increases in the molybdenum and sulfur concentration of grass will cause major reductions in the availability of copper. This is especially notable in ruminants grazing improved pastures in which the molybdenum and sulfur concentrations were increased. The copper content of feedstuffs should be expressed in terms of available copper concentration, using appropriate equations, which permits a more accurate prediction of clinical disease and can be used for more effective control strategies.

The effect of changes in molybdenum and sulfur concentrations in grass on the availability of copper is changed by conservation. At a given concentration of sulfur, the antagonistic effect of molybdenum is proportionately less in hay than in fresh grass. At a low concentration of molybdenum, the effect of sulfur is more marked in silage than in fresh grass. The use of formaldehyde as a silage additive may weaken the copper sulfur antagonism and yield material of high availability. Thus, fields of herbage high in molybdenum should be used for conservation when possible and sulfuric acid should not be used as an additive for silage unless accompanied by a copper salt because it significantly raises the sulfur concentration of the silage.

Copper in diet

For general purposes, pasture containing <3 mg/kg DM of copper will result in signs of deficiency in grazing ruminants. Levels of 3–5 mg/kg DM can be considered as dangerous and levels >5 mg/kg DM (preferably 7–12) are safe unless complicating factors cause secondary copper deficiency. The complexity of minimum copper requirements, affected as they are by numerous conditioning factors, necessitates examination under each particular set of circumstances. For example, plant molybdenum levels are related directly to the pH reaction of the soil. Grasses grown on strongly acidic molybdenum-rich soils are characterized by low molybdenum values (<3 mg/kg DM), whereas those associated with alkaline molybdenum-poor soils may contain up to 17 mg/kg DM. Thus, it seems likely that conditioned copper deficiency can be related to regionally enhanced levels of plant available rather than soil molybdenum. Heavily limed pastures are often associated with a less than normal copper intake and a low copper status of sheep grazing them. Secondary copper deficiency is also recorded in pigs whose drinking water contains very large amounts of sulfate.

Dietary iron

A dietary intake of iron can interfere with copper metabolism.¹⁴ Dietary levels of iron in the range of 500–1500 mg/kg DM, within the range of their fluctuation in silage and forage and higher levels, are a risk of inducing copper deficiency in ruminants, especially when the copper intake is marginal. Ruminants obtain iron from ingested soil and mineral supplements and, in areas where hypocuprosis is likely to occur, the risk can be minimized by avoiding the use of mineral supplements of high iron content, minimizing the use of bare winter pasture and avoiding the excessive contamination of silage with soil during harvesting.

Molybdenum-induced secondary copper deficiency in cattle occurred when motor oil containing molybdenum bisulfide was spilled on a pasture located on the side of a railway bed near the farm.

Stored feeds

Livestock that are housed have a slightly different dietary intake to those on pasture. Concentrates and proprietary feeds usually contain adequate copper. Pasture is less likely to contain sufficient copper, especially in early spring when the grass growth is lush and silage and haylage may be deficient. Hay is more mature and usually contains more of all minerals, so that animals housed for the winter are protected against copper deficiency for a few weeks after they come out onto pasture in the spring. Young, growing animals will be first affected. These comments should not be interpreted to mean that housed or feedlot animals cannot be affected by hypocuprosis; they can if the locally produced feed is copper-deficient, or more likely has a high concentration of molybdenum. Both are likely to be prevented, or less severe, if there is some supplementary feeding.

Soil characteristics

Copper deficiency

In general, there are two types of soil on which copper-deficient plants are produced. Sandy soils, poor in organic matter and heavily weathered, such as on the coastal plains of Australia and in marine and river silts, are likely to be deficient in copper as well as other trace elements, especially cobalt.

The second important group of soils is ‘peat’ or muck soils reclaimed from swamps and are soils more commonly associated with copper deficiency in the USA, New Zealand, and Europe. Such soils may have an absolute deficiency of copper, but more commonly, the deficiency is relative in that the copper is not available and the plants growing on the soils do not contain adequate amounts of the element.

The cause of the lack of availability of the copper is uncertain, but is probably the formation of insoluble organic copper complexes. An additional factor is the production of secondary copper deficiency on these soils due to their high content of molybdenum. A summary of the relevant levels of copper in soils and plants is given in Table 30.3.

Table 30.3 Copper levels of soils and plants in primary and secondary copper deficiency

Chromosomal abnormalities

The association between copper deficiency and DNA damage in cattle has been examined.^3,15 The Comet assay is a sensitive, reliable and rapid method for the detection of DNA double- and single-strand breaks and alkali-labile sites detection.¹⁶ In naturally-occurring copper deficiency in Aberdeen Angus cattle in Argentina, cytogenetic analysis of peripheral lymphocyte cultures showed a significant increase in the frequency of abnormal metaphases in moderate to severe copper deficient groups. Thus, copper deficiency in cattle is associated with an increase in the frequency of chromosomal aberrations (clastogenic effect) as well as in DNA migration.

Wool

The straightness and stringiness of this wool is due to inadequate keratinization, probably due to imperfect oxidation of free thiol groups. Provision of copper to such sheep is followed by oxidation of these free thiol groups and a return to normal keratinization within a few hours.

Body weight

In the later stages of copper deficiency, the impairment of tissue oxidation causes interference with intermediary metabolism and loss of condition or failure to grow.

Diarrhea

The pathogenesis of copper deficiency in causing diarrhea is uncertain and there is little evidence that a naturally-occurring primary copper deficiency will cause diarrhea. There are no histological changes in gut mucosa, although villous atrophy is recorded in severe, experimentally produced cases. Diarrhea is usually only a major clinical finding in secondary copper deficiency associated with molybdenosis.

Anemia

The known importance of copper in the formation of hemoglobin accounts for the anemia in copper deficiency. The presence of hemosiderin deposits in tissues of copper-deficient animals suggests that copper is necessary for the reutilization of iron liberated from the normal breakdown of hemoglobin. There is no evidence of excessive hemolysis in copper-deficiency states. Anemia may occur in the later stages of primary copper deficiency, but is not remarkable in the secondary form unless there is a marginal copper deficiency, as occurs in peat scours in New Zealand. The unusual relationship in New Zealand between copper deficiency and postparturient hemoglobinuria is unexplained. Heinz body anemia in lambs with deficiencies of copper or selenium and moved from improved pasture to rape (Brassica napus) has been reported.

Bone

The osteoporosis that occurs in some natural cases of copper deficiency is caused by the depression of osteoblastic activity.¹¹ In experimentally induced primary copper deficiency, the skeleton is osteoporotic and there is a significant increase in osteoblastic activity. There is a marked overgrowth of epiphyseal cartilage, especially at costochondral junctions and in metatarsal bones. This is accompanied by beading of the ribs and enlargement of the long bones. There is also an impairment of collagen formation. When the copper deficiency is secondary to dietary excesses of molybdenum and sulfate, the skeletal lesions are quite different and characterized by widening of the growth plate and metaphysis and active osteoblastic activity.

Copper deficiency in foals causes severe degenerative disease of cartilage, characterized by breaking of articular and growth plate cartilage through the zone of hypertrophic cells, resulting in osteochondrosis of the articular-epiphyseal complex (A–E complex).¹¹ The incidence and severity of osteochondrosis in foals can be decreased by supplementation of the diets of mares during the last 3–6 months of pregnancy and the first 3 months of lactation. Foals from non-supplemented mares have separation of the thickened cartilage from the subchondral bone. Clinical, radiographic, and biochemical differences occur between copper-deficient and copper-supplemented foals and there may be a relationship between low copper intakes in rapidly growing horses, inferior collagen quality, biomechanically weak cartilage, and osteochondritis.¹⁷

Copper is essential for metalloenzyme lysyl oxidase, which produces aldehydic groups on hydroxylysine residues as a prerequisite for eventual cross-link formation in collagen and elastin. Similar lesions in foals have been attributed to zinc toxicity from exposure of affected animals to pasture polluted by smelters. Experimentally, the addition of varying amounts of zinc to the diet of foals containing adequate copper will result in zinc-induced copper deficiency, but there are no effects with zinc intakes up to 580 ppm and it is suggested that 2000 ppm or higher are necessary to affect copper absorption in horses.¹⁸ Similar lesions of osteochondrosis have occurred in young farmed red deer and wapiti X red deer hybrids in New Zealand.⁷

Connective tissue

Copper is a component of the enzyme lysyl oxidase, secreted by the cells involved in the synthesis of the elastin component of connective tissues and has important functions in maintaining the integrity of tissues such as capillary beds, ligaments, and tendons.

Heart

The myocardial degeneration of falling disease may be a terminal manifestation of anemic anoxia, or be due to interference with tissue oxidation. In this disease, it is thought that the stress of calving and lactation contribute to the development of heart block and ventricular fibrillation when there has already been considerable decrease in cardiac reserve. Experimentally induced copper deficiency in piglets causes a marked reduction in growth and hematocrit and cardiac pathology and electrical disturbances.

Blood vessels

Experimentally produced copper deficiency has also caused sudden death due to rupture of the heart and great vessels in a high proportion of pigs fed a copper-deficient diet. The basic defect is degeneration of the internal elastic laminae. There is no record of a similar, naturally occurring disease. A similar relationship appears to have been established between serum copper levels and fatal rupture of the uterine artery at parturition in aged mares.

Pancreas

Lesions of the pancreas may be present in normal cattle with a low blood copper status. The lesions consist of an increase in dry matter content and a reduction in the concentrations of protein and copper in wet tissue. The cytochrome oxidase activity and protein:RNA ratio are also reduced. There are defects in acinar basement membranes, splitting, and disorganization of acini, cellular atrophy and dissociation and stromal proliferation.

Nervous tissue

Copper deficiency halts the formation of myelin and causes demyelination in lambs, probably by a specific relationship between copper and myelin sheaths. Defective myelination can commence as early as the midpoint of the fetus’s uterine life. The focus of lesions in the white matter shifts from the cerebrum in lambs affected at birth (congenital swayback) to the spinal cord in delayed cases, which may reflect respective peaks of myelin development at those sites at 90 days’ gestation and 20 days after birth. The postnatal development of delayed swayback has been confirmed through its control by copper supplementation after birth. In experimental animals, it has been shown that copper deficiency does interfere with the synthesis of phospholipids. While anoxia is a cause of demyelination, an anemic anoxia is likely to occur in highly deficient ewes and anemic ewes produce a higher proportion of lambs with enzootic ataxia, there is often no anemia in ewes producing lambs with the more common subacute form of the disease. Severely deficient ewes have lambs affected at birth and in which myelin formation is likely to have been prevented. The lambs of ewes less severely deficient have normal myelination at birth and develop demyelination in postnatal life.

Reproductive performance

There is no evidence that copper deficiency causes reproductive failure in dairy cows. Copper glycinate given to dairy cattle does not affect the average interval in days between calving and first observed heat, services per conception, or first service conception rate compared with untreated cows in the same population. Experimentally, the addition of molybdenum to the diet of heifers delayed the onset of puberty, decreased the conception rate and caused anovulation and anestrus in cattle without accompanying changes in copper status or in live weight gain. Thus, the presence of molybdenum rather than low copper status may affect reproductive performance of cattle. Geochemical data indicate that approximately 10% of the cultivated area of England and Wales has soils that may result in forage molybdenum concentrations similar to those used in the above experimental diet. It appears inadvisable to ascribe poor reproductive performance to subclinical hypocuprosis on the evidence of blood copper analysis alone. Other factors, such as management and energy and protein intake, should be examined.

Immune system

Copper is an essential trace mineral with an important role in the immune response but the precise mechanism is not well understood. In experimental secondary copper deficiency in cattle induced by molybdenum at 30 ppm and sulfate at 225 ppm, the intracellular copper content of peripheral blood lymphocytes, neutrophils, and monocyte-derived macrophages was reduced between 40% and 70%.¹⁹ In copper deficient animals, the serum ceruloplasmin activity decreased to 50% of control values. Both the copper-zinc-superoxide dismutase and the cytochrome c oxidase activities are significantly reduced in leukocytes. Thus, copper deficiency alters the activity of several enzymes, which mediate antioxidant defenses and ATP formation. These effects may impair cell immune function, affecting the bactericidal capacity and making the animals more susceptible to infection.

Copper deficiency results in decreased humoral and cell-mediated immunity, as well as decreased non-specific immunity regulated by phagocytic cells, such as macrophages and neutrophils.^20,21 The decreased resistance to infection in sheep is amenable to treatment with copper and genetic selection. In lambs genetically selected for low and high concentrations of plasma copper, the mortality from birth to 24 weeks of age in the high line was half that in the low line. Most of the losses were due to a variety of microbial infections. Experimental viral and bacterial infections of cattle can cause a rapid, though transient, increase in serum ceruloplasmin and plasma copper in copper-replete animals, suggesting a major protective role for copper in infectious diseases. These changes in copper metabolism evolve from an interleukin-1 mediated increase in hepatic synthesis and release of ceruloplasmin, an acute phase protein. Copper concentrations in organs involved in immune regulations such as liver, spleen, thymus, and lung are substantially reduced by copper deficiency, suggesting that copper-deficient animals are at greater risk for infection than copper-adequate animals. However, experimental low copper diets with or without supplemental molybdenum does not alter the specific immunity of stressed cattle.²²

The severity of copper depletion needed for immune dysfunction is less than required to induce clinical signs of copper deficiency and endogenous copper may contribute to the regulation of both non-immune and immune inflammatory responses. Low molecular weight complexes may have an anti-inflammatory effect in animal models of inflammation and it is postulated that the elevation of plasma copper-containing components during inflammatory disease represents a physiological response.

In experimental coliform mastitis in dairy cattle, copper in the diet at 20 ppm reduced the clinical response but not duration of the mastitis compared with animals receiving 6.5 ppm beginning 60 days prepartum through 42 days of lactation.²³ Liver copper in the supplemented group was 162 and 33 ppm at calving and 256 and 45 ppm at 42 days post partum, respectively.

Copper deficiency in heifers in Northern India was associated with significant reduction in the candidacidal activity of neutrophils compared with copper supplemented animals.²⁴

Sequence of clinical signs development

In experimental copper deficiency in calves, beginning at 6 weeks of age, subclinical and clinical abnormalities appear after the following intervals: hypocupremia at 15 weeks, growth retardation from 15 to 18 weeks, rough hair coat at 17 weeks, diarrhea at 20 weeks and leg abnormalities at 23 weeks. These signs correlate well with the onset of hypocupremia and are indicative of a severe deficiency. Even with these signs of deficiency, the histological abnormalities may be only minor in degree.

In experimental primary copper deficiency in calves, beginning at 12 weeks of age, clinical signs of the deficiency may not become apparent for about 6 months. Musculoskeletal abnormalities include a stilted gait, a ‘knock-kneed’ appearance of the forelimbs, overextension of the flexors, splaying of the hooves and swellings around the metacarpophalangeal and carpometacarpal joints. Changes in hair pigmentation occur after about 5 months and diarrhea between 5 and 7 months. The diarrhea ceased 12 h after oral administration of a small amount (10 mg) of copper.

Copper absorption

On the basis of a response to copper injections and no response to copper administered orally to sheep on a high molybdenum intake, it is suggested that interference occurs with the absorption of copper from the gut.

It is proposed that thiomolybdates form in the rumen from the reaction of dietary molybdenum compounds with sulfides produced from the reduction of dietary sulfur compounds by rumen bacteria. The thiomolybdates reduce the absorption of dietary copper from the intestine and also inhibit a number of copper-containing enzymes, including ceruloplasmin, cytochrome oxidase, superoxide dismutase and tyrosine oxidase.

Copper utilization

Sulfate and molybdate can interfere with mobilization of copper from the liver, inhibition of copper intake by the tissues, inhibition of copper transport both into and out of the liver and inhibition of the synthesis of copper-storage complexes and ceruloplasmin.

The clinical signs of hypocuprosis (such as steely wool) can occur in sheep on diets containing high levels of molybdenum and sulfate, even though blood copper levels are high. This suggests that under these circumstances copper is not utilizable in tissues and the blood copper rises in response to the physiological needs of the tissues for the element. In pigs, a copper– molybdenum complex can exist in animals and that in this form the copper is unavailable. This would interfere with hepatic metabolism of copper and the formation of copper-protein complexes such as ceruloplasmin.

Hepatic storage

The copper status of the liver depends on whether the animals are receiving adequate dietary copper. With adequate dietary levels, the liver copper levels are less in the presence of molybdate and sulfate. If the animals are receiving a copper-deficient diet such that copper is being removed from the liver, then the molybdate plus sulfate animals retain more copper in their liver than copper-deficient animals not receiving sulfate plus molybdate. This supports the hypothesis that molybdate and sulfate together impair the movement of copper into or out of the liver, possibly by affecting copper transport. Sulfate alone exerts an effect. An increase in intake reduces hepatic storage of both copper and molybdenum.

Phases of copper deficiency

The development of a deficiency can be divided into four phases:

During the depletion phase, there is loss of copper from any storage site, such as liver, but the plasma concentrations of copper may remain constant. With continued dietary deficiency, the concentrations of copper in the blood decline during the phase of marginal deficiency. However, it may be some time before the concentrations or activities of copper-containing enzymes in the tissues begin to decline and it is not until this happens that the phase of dysfunction is reached. There may be a further lag before the changes in cellular function are manifested as clinical signs of disease.

Summary

The overall effect of these interactions is as follows. Molybdate reacts with sulfides to produce thiomolybdates in the rumen. The subsequent formation of copper-thiomolybdate complexes isolates the copper from being biologically available.¹ The thiomolybdates reduce the effectiveness of enzymes containing copper and there are some significant interactions between copper, zinc, and iron.

Subclinical hypocuprosis

No clinical signs occur, blood copper levels are marginal or below 57 mg/dL (9.0 mmol/L) and there is a variable response in productivity after supplementation with copper. Some surveys in copper-deficient areas found that about 50% of beef herds and 10% of dairy herds within the same area have low blood levels of blood copper associated with low copper intake from natural forages. The deficiency is likely to be suspected only if production is monitored and found to be suboptimal.

A perplexing feature of subclinical hypocuprosis is the wide variation in improved growth rate obtained when cattle of the same low copper status are given supplementary copper under field conditions.

General syndrome

Falling disease

The characteristic behavior in falling disease is for cows in apparently good health to throw up their heads, bellow, and fall. Death is instantaneous in most cases, but some fall and struggle feebly on their sides for a few minutes with intermittent bellowing and running movement attempts to rise. Rare cases show signs for up to 24 h or more. These animals periodically lower their heads and pivot on the front legs. Sudden death usually occurs during one of these episodes.

Peat scours (‘teart’)

Persistent diarrhea with the passage of watery, yellow-green to black feces with an inoffensive odor occurs soon after the cattle go on to affected pasture, in some cases within 8–10 days. The feces are released without effort, often without lifting the tail. Severe debilitation is common, although the appetite remains good. The hair coat is rough and depigmentation is manifested by reddening or gray flecking, especially around the eyes, in black cattle. The degree of abnormality varies a great deal from season to season and year to year and spontaneous recovery is common. Affected animals usually recover in a few days following treatment with copper.

Unthriftiness (pine) of calves

The earliest signs are a stiffness of gait and unthriftiness. The epiphyses of the distal ends of the metacarpus and metatarsus may be enlarged and resemble the epiphysitis of rapidly growing calves deficient in calcium and phosphorus or vitamin D. The epiphyses are painful on palpation and some calves are severely lame. The pasterns are upright and the animals may appear to have contracted flexor tendons. The unthriftiness and emaciation are progressive and death may occur in 4–5 months. Grayness of the hair, especially around the eyes in black cattle, is apparent. Diarrhea may occur in a few cases.

General syndrome

Swayback and enzootic ataxia in lambs and goat kids

These diseases have much in common, but there are differences in epidemiology and some subtle clinical ones.

Swayback is the only authentic manifestation of a primary nutritional deficiency of copper in the UK. The incidence can vary greatly among breeds of sheep, reflecting the genetic differences in copper metabolism both between and within breeds of sheep. The disease occurs in several forms.

A congenital form, cerebrospinal swayback, occurs only when the copper deficiency is extreme. Affected lambs are born dead or weak and unable to stand and suck. Incoordination and erratic movements are more evident than in enzootic ataxia and the paralysis is spastic in type. Blindness also occurs occasionally. There is softening and cavitation of the cerebral white matter and this probably commences about day 120 of gestation.

Progressive (delayed) spinal swayback begins to develop some weeks after birth with lesions and clinical signs appearing at 3–6 weeks of age.

Postnatal acute fatal swayback may be a third form of the disease and appears to occur only in Wales. It resembles the more usual delayed form, but develops suddenly. There is a sudden onset of recumbency with death occurring 1–2 days later due to acute swelling of the cerebrum.

Enzootic ataxia affects only unweaned lambs. In severe outbreaks, the lambs may be affected at birth, but most cases occur in the 1–2-month age group. The severity of the paresis decreases with increasing age at onset. Lambs affected at birth or within the first month usually die within 3–4 days. The disease in older lambs may last for 3–4 weeks and survival is more likely, although surviving lambs always show some ataxia and atrophy of the hindquarters. The first sign to appear in enzootic ataxia is incoordination of the hindlimbs, appearing when the lambs are driven. Respiratory and cardiac rates are also greatly accelerated by exertion. As the disease progresses, the incoordination becomes more severe and may be apparent after walking only a few yards. There is excessive flexion of joints, knuckling over of the fetlocks, wobbling of the hindquarters and finally falling. The hindlegs are affected first and the lamb may be able to drag itself about in a sitting posture. When the forelegs eventually become involved recumbency persists and the lamb dies of inanition. There is no true paralysis, the lamb being able to kick vigorously even in the recumbent stage. The appetite remains unaffected.

Deer

Enzootic ataxia in red deer is remarkably different from the disease in lambs in that it develops in young adults well past weaning age, and in adults. The clinical signs include ataxia, swaying of the hindquarters, a dog-sitting posture and, eventually, inability to use the hindlimbs. Spinal cord demyelination and midbrain neuronal degeneration are characteristic. Osteochondrosis of young, farmed deer with copper deficiency is characterized by lameness, one or more swollen joints and an abnormal ‘bunny-hopping’ gait or ‘cow-hocked’ stance.⁷ Copper deficiency in red deer in Australia during a period of drought caused loss of weight in lactating hinds after calving and steely hair coats (the hair had a lustre resembling that of so-called steely wool of copper-deficient sheep). Both adult and yearling stags had normal hair coats but those of the yearling hinds were patchy, with large areas of harsh, light colored, steely hair.²¹ The high sulfur content of the diet and possible accidental iron ingestion from being fed on the ground may have resulted in secondary copper deficiency.

Pigs

Naturally occurring enzootic ataxia has occurred in growing pigs 4–6 months of age. Posterior paresis progresses to complete paralysis in 1–3 weeks. Dosing with copper salts had no effect on the clinical conditions, but hepatic copper levels were 3–14 mg/kg (0.05–0.22 mmol/kg). Copper deficiency in piglets 5–8 weeks of age has been reported and was characterized clinically by ataxia, posterior paresis, nystagmus, inability to stand, paddling movements of the limbs and death in 3–5 days. Demyelination of the spinal cord and degenerative lesions of the elastic fibers of the walls of the aorta and pulmonary arteries are present.

The inclusion of copper sulfate, at levels of 125–250 mg/kg of copper, in the diets of pigs 11–90 kg live weight and fed ad libitum, results in slight improvements in growth rate and feed efficiency, but has no significant effect on carcass characteristics. The supplemental copper causes a marked increase in liver copper concentration which poses a potential hazard and it is recommended that copper supplementation be limited to starter and grower diets fed to pigs weighing less than 50 kg live weight.

Horses

Adult horses are unaffected by copper deficiency, but there are unconfirmed reports of abnormalities of limbs of foals. Foals in copper-deficient areas may be unthrifty and slow-growing, with stiffness of the limbs and enlargement of the joints. Contraction of the flexor tendons causes the animal to stand on its toes. There is no ataxia or indication of involvement of the central nervous system. Signs may be present at birth or develop before weaning. Recovery occurs slowly after weaning and foals are unthrifty for up to 2 years.

Geophagia or soil eating in horses in Australia has been associated with larger concentrations of iron and copper in soil samples compared to paired control samp les, suggesting that these elements provide the stimulus for geophagia.²⁵

Phases

The development of a deficiency can be divided into four phases¹¹ (Fig. 30.1):

Fig. 30.1 The four phases of copper deficiency.

During the depletion phase, there is loss of copper from any storage site, such as liver, but the plasma concentrations of copper may remain constant. With continued dietary deficiency, the concentrations of copper in the blood will decline during the phase of marginal deficiency. However, it may be some time before the concentrations or activities of copper-containing enzymes in the tissues begin to decline and it is not until this happens that the phase of dysfunction is reached. There may be a further lag before the changes in cellular function are manifested as clinical signs of disease.

Interpretation of laboratory results

The three principles governing the interpretation of biochemical criteria of trace element status include:

From these principles, the concentrations of liver copper are insensitive indices of deficiency, but good indicators of excess. Plasma copper <57 μg/dL (9 μmol/L) is a good index of marginal deficiency, but values may have to fall to below 19 μg/dL (3 μmol/L) before there is a risk of dysfunction and loss of production in sheep and cattle. However, these are only guidelines. The range of values and the cut-off levels above which animals are normal, or below which they are deficient, have not been well-established. There is considerable biological variation dependent on the species, the breed of animal, the length of time over which the depletion has occurred and the presence of intercurrent disease.

Serum copper concentration in cattle is fairly specific for detection of low liver copper but only marginally sensitive when serum copper concentration of 0.45 μg/g is used as a test endpoint.²⁷ The value of serum copper concentration as a diagnostic indicator depends on the prevalence of copper deficiency in the particular area.

The interpretation of serum copper can change depending on what liver copper concentration is considered low.²⁸ With a liver copper <20 μg/g DM as indicative of copper deficiency, serum copper concentrations =9 mmol/L will be a good indicator of copper deficient status but concentrations >9 mmol/L will be a poor indicator of copper sufficient status. If 10 μg/g DM is used as liver copper cut-off, then serum concentrations >9 mmol/L are reliable as indicative of copper sufficient status but not on concentrations =9 mmol/L as indicative of copper deficiency.

Concentrations of copper in liver and blood may be of diagnostic value but should be interpreted with caution since clinical signs of copper deficiency may appear before there are significant changes in the levels of copper in the blood and liver. Conversely, the plasma levels of copper may be very low in animals that are otherwise normal and performing well. There is a tendency to overestimate the presence of copper deficiency because veterinarians use a diagnostic threshold for copper deficiency that is too high.^11,26 Among veterinary laboratories, there is a wide variation in the normal range currently used for equine serum copper values.

Very low levels of both blood and liver copper in a group of animals need not be associated with clinical abnormalities. In a study in the Netherlands, in a group of dairy heifers, the copper status was determined at regular intervals over an 18-month period.²⁹ One group was supplemented with copper sulfate and the other was not. The copper and molybdenum levels in the grass were within normal limits as accepted in the Netherlands; copper 7–15 mg/kg DM and molybdenum <5 mg/kg DM. The levels of copper in both the blood and liver were much below the reference ranges used in the Netherlands (6–15 μmol/L in blood and >30 mg/kg DM in liver). No clinical signs of copper deficiency occurred and there were no differences in growth rate and reproductive performance.

Cattle and sheep

In cattle and sheep, plasma copper levels between 19 μg/dL and 57 μg/dL (3.0 and 9.0 μmol/L) represent marginal deficiency and levels below 19 μg/dL (3 μmol/L) represent functional deficiency or hypocuprosis. The internationally recognized threshold to assess copper deficiency is 9.4 μmol/L. In both species a value for plasma or serum of 11.0 μmol/L can be associated with a liver concentration from 789 to 3786 μmol/kg DM (50–240 mg/kg). By contrast, a value of 9.3 μmol/L will usually be associated with liver copper values of 315–789 μmol (20–50 mg/kg DM), which are regarded as marginally inadequate. Plasma copper levels of 49.9 μg/dL (7.85 μmol/L) or less are indicative of low liver copper levels. Plasma copper levels above 90.2 μg/dL (14.2 μmol/L) are usually associated with liver levels above 38.1 mg/kg (0.6 mmol/kg) DM. Of the two estimations, that on liver is the most informative as levels in blood may remain normal for long periods after liver copper levels commence to fall and early signs of copper deficiency appear. Levels of copper in adult liver above 200 mg/kg DM (3.14 mmol/kg) in sheep and above 100 mg/kg DM (1.57 mmol/kg) in cattle are considered to be normal. Levels of less than 80 mg/kg DM (1.5 mmol/kg) in sheep and less than 30 mg/kg DM (0.5 mmol/kg) in cattle are classed as low. Liver copper levels in fetuses and neonates are usually much higher than in adults and normal foals have had levels of 219 mg/kg (3.4 mmol/kg DM) compared with a normal of 31 mg/kg (0.49 mmol/kg DM) in adults.

Horses

A threshold level of plasma copper of 16 μmol/L is used to distinguish between the normal and subnormal values.³¹ Liver copper from horses sampled at slaughter vary widely about a mean of 113.7 μmol/kg WW.³¹ The threshold of 52.5 μmol/kg WW of copper in liver is proposed to distinguish deficient from marginal liver copper status. Many healthy horses have serum values between 12 and 16 μmol/L.

The mean hepatic copper concentrations of horses fed diets containing 6.9–15.2 mg copper/kg DM were 17.1–21.0 μg/g DM (0.27–0.33 μmol/g DM) tissue. The plasma copper concentrations ranged from 3.58 to 4.45 μg/dL (22.8–28.3 μmol/L). There was no simple mathematical relationship between plasma and hepatic copper concentrations. The range of serum copper concentrations in Thoroughbred horses at grass was 63–196 μg/dL (9.91–30.85 mmol/L) and in stabled Thoroughbreds the range was 47–111 μg/dL (7.40–17.47 mmol/L).

Farmed red deer (Cervus elaphus)

The suggested reference ranges for serum and liver copper concentrations to categorize the copper status of deer are: serum concentrations (μmol/L): <5, deficient; 5–8 marginal and; >8, adequate; and liver copper concentrations (μmol/kg weight wet, WW): <60, deficient; 60–100, marginal and >100, adequate.³² Enzootic ataxia and osteochondrosis occur when liver copper concentrations are <60 μmol/kg fresh tissue and serum copper concentrations are below 3–4 μmol/L.³³ Growth responses to copper supplementation are equivocal when blood copper concentrations are <3–4 μmol/L, but are significant when mean blood copper concentrations are 0.9–4.0 μmol/L. No antler growth or body weight response to copper supplementation occurs when blood ceruloplasmin (ferroxidase) levels averaged 10–23 IU/L (equivalent to serum copper concentrations of 6–13 μmol/L) and liver concentrations averaged 98 μmol/kg fresh tissue. This suggests deficient, marginal and adequate ranges for serum copper concentrations should be <5, 5–8 and >8 μmol/L, respectively and those for liver copper concentrations should be <60, 60–100 and >100 μmol/kg, respectively.³³

Copper toxicity

The incidence of copper toxicity in dairy cattle in the UK has increased recently.³⁸ Apparent subclinical hepatopathy, with no clinical disease, due to excess copper intake in lactating dairy cattle has been described. On average, each cow received 963 mg copper daily from the mineral supplement alone. Calculation of the total dietary copper found that high producing cow had an estimated intake of 1325 mg copper daily, while each low producing cow received 1250 mg daily. The estimated copper requirements of the cows were 290 and 217 mg/cow per day, respectively. Thus oversupplementation of dairy cows with copper may be a significant problem in dairy herds without overt clinical signs of toxicity.

Oral dosing

Oral dosing with copper sulfate (5 g to cattle, 1.0 g to sheep, weekly) is adequate as prophylaxis and will prevent the occurrence of swayback in lambs if the ewes are dosed throughout pregnancy. Lambs can be protected after birth by dosing with 35 mg of copper sulfate every 2 weeks. However, regular oral dosing with copper sulfate is laborious and time-consuming and is no longer widely practiced.

Dietary supplementation

Sheep

A dose of 0.1 g/kg live weight (5 g) in sheep is safe and does not induce copper toxicity in the susceptible North Ronaldsay breed. The response in liver copper concentrations is dose-dependent. In sheep given doses ranging from 2.5 to 20 g per animal, the liver copper concentrations will peak 10 weeks after administration and will thereafter decline in a linear fashion over the next 40 weeks.

The administration of a single dose of 2 g cupric oxide needles orally to lambs between 3 and 5 weeks of age is an effective method for the prevention of induced hypocuprosis manifested as ill-thrift in lambs grazing pastures improved by liming and reseeding. The treatment maintained the lambs in normocupremia, provided adequate liver copper reserves, prevented clinical signs of hypocuprosis and produced a live weight gain advantage. The administration of the needles to ewes in the first half of pregnancy is also effective for the prevention of swayback in their lambs. The administration of cupric oxide needles to ewes at parturition is effective in preventing hypocupremia for up to 17 weeks in animals on pasture previously shown to cause a molybdenum-sulfur-induced copper deficiency. The treatment of the ewes at parturition also resulted in higher concentrations of copper in the milk in the initial weeks of lactation.

However, this increase in milk copper will not be effective in preventing hypocupremia and hypocuprosis in the lambs, which can be treated with cupric oxide needles at 6 weeks of age. Because some breeds of sheep may have a propensity to concentrate excess quantities of copper in the liver, it is important to adhere to the recommended dosage. Cupric oxide needles at a dose of 4 g per animal have also been used for the prevention of swayback in goats and to maintain liver copper levels for up to 5 months in farmed red deer grazing on a marginally copper-deficient pasture.

Copper oxide needles given to ewes in early pregnancy increases their liver copper status through gestation and early lactation and the copper status of their lambs from birth to 36 days old.⁴⁶ Serum copper concentration was not affected by treatment but a marked rise was observed in all lambs between birth and 10 weeks of age.

Cattle

A single dose of 20 g of copper oxide needles to hypocupremic suckler cows was sufficient to maintain adequate copper status for at least 5 months. The use of 20 g of copper oxide needles to young cattle weighing 190 kg effectively prevented growth retardation and severe hypocupremia, which occurred in an undosed control over a 70-day trial period. The currently recommended doses for beef cattle are 5 g for calves, 10 g for yearlings and 20 g for heavier or adult cattle, which will give protection for at least 6 months. A single oral dose of 20 g of copper oxide needles at the beginning of the grazing season is effective in increasing or maintaining stores of copper in the liver of grazing cows and calves consuming low-copper, high-molybdenum forage, and high-sulfate water supplies. The use of 50 g of needles in adult cows (55 kg BW) sustained higher levels of plasma concentrations than the SC injection of copper glycinate and 100, 200, or 300 g of needles given orally did not cause clinical effects.

Farmed red deer

The administration of 20 g boluses of copper-oxide wire particles to rising 2-year-old red deer stags did not significantly alter velvet antler weight, daily velvet antler growth rate, days from casting to removal, grade or value, or stag live weight gain.⁴⁷ Copper supplementation increased mean serum ceruloplasmin (ferroxidase) concentrations by approximately 10 IU/L. Mean liver copper concentrations in control deer was 99 μmol/kg and ranged from 194 to 386 μmol/kg in the treated groups.

Field trials on New Zealand deer farms using 5 g of copper oxide wire particles given to deer 4–7 months old found no effect on live weight gain despite evidence of hypocupremia in 38% of non-supplemented animals, which gained weight at similar rates to those which had adequate plasma copper levels.⁴⁸ This suggests that the extent of the hypocupremia was either not sufficiently severe, or not maintained for a long enough period to cause copper deficiency resulting in live weight gain. This indicates that deer farmers need to reassess the need for copper supplementation in young deer.

Dietary and environmental factors

A simple deficiency of iodine in the diet and drinking water may occur and is related to geographical circumstances. Areas where the soil iodine is not replenished by cyclical accessions of oceanic iodine include large continental land masses and coastal areas where prevailing winds are offshore. In such areas, iodine deficiency is most likely to occur where rainfall is heavy and soil iodine is continually depleted by leaching. Over a 3-year period, several calves were born with goiter in a dairy herd located 200 km from the sea on sandy soil.⁶ The calves were born from first-calf heifers which had not received any iodine supplementation.

Soil formations rich in calcium or lacking in humus are also likely to be relatively deficient in iodine. The ability of soil to retain iodine under conditions of heavy rainfall is directly related to their humus content, and limestone soils are, in general, low in organic matter. A high dietary intake of calcium also decreases intestinal absorption of iodine, and in some areas, heavy applications of lime to pasture are followed by the development of goiter in lambs. This factor may also be important in areas where drinking water is heavily mineralized.

There are several situations in which the relationship between iodine intake and the occurrence of goiter is not readily apparent. Goiter may occur on pasture containing adequate iodine; it is then usually ascribed to a secondary or conditioned iodine deficiency. A diet rich in plants of the Brassica spp., including cabbages and brussels sprouts, may cause simple goiter and hypothyroidism in rabbits, which is preventable by administered iodine. Severe iodine deficiency can occur when ewes are fed Brassica crops for long periods. Brassicas such as swedes, turnips, and kale have low iodine content and contain goitrogens, and may result in weak newborn lambs with enlarged thyroid glands.⁷ Goiter occurred in 85% of lambs examined at necropsy, born from ewes on the Brassica crop and not supplemented with iodine.

Diffuse hyperplastic goiter has occurred in calves in beef cows in Japan which were on pasture or being fed feed containing Rorippa indica, Hiern, genus Brassica, family Crucifera, ‘Inugarash’, which contains thiocyanate.⁸ The iodine content of the waters on affected farms was low at 0.361 μg/L and 0.811 μg/L and that of the pastures, 87 and 121 μg/kg, on two different farms.

Hypothyroidism has also been produced in rats by feeding rapeseed, and in mice by feeding rapeseed oil meal. Feeding large quantities of kale to pregnant ewes causes a high incidence of goiter and hypothyroidism, also preventable by administering iodine in the newborn lambs. The goitrogenic substance in these plants is probably a glucosinolate capable of producing thiocyanate in the rumen. The thiocyanate content, or potential content, varies between varieties of kale, being much less in rape-kale, which also does not show the two-fold increase in thiocyanate content other varieties show in autumn. Small young leaves contain up to five times as much thiocyanate as large, fully formed leaves. Some of these plants are excellent sources of feed, and in some areas, it is probably economical to continue feeding them, provided suitable measures are taken to prevent goiter in the newborn. Although kale also causes mild goiter in weaned lambs this does not appear to reduce their rate of gain.

A diet high in linseed meal (20% of ration) given to pregnant ewes may result in a high incidence of goitrous lambs, which is preventable with iodine or thyroxine. Under experimental conditions, groundnuts are goitrogenic for rats, the goitrogenic substance being a glycoside-arachidoside. The goitrogenic effect is inhibited by supplementation of the diet with small amounts of iodine. Soybean byproducts are also considered to be goitrogenic. Gross bacterial contamination of drinking water by sewage is a cause of goiter in humans in countries where hygiene is poor. There is a record of a severe outbreak of goitrous calves from cattle running on pasture heavily dressed with crude sewage. Prophylactic dosing of the cows with potassium iodide prevented further cases. Feeding sewage sludge is also linked to the occurrence of goiter.

Goiter in lambs may occur when permanent pasture is plowed and resown. This may be due to the sudden loss of decomposition and leaching of iodine-binding humus in soils of marginal iodine content. In subsequent years the disease may not appear. There may be some relation between this occurrence of goiter and the known variation in the iodine content of particular plant species, especially if new pasture species are sown when the pasture is plowed. The maximum iodine content of some plants is controlled by a strongly inherited factor and is independent of soil type or season. Thus, in the same pasture, perennial rye grass may contain 146 μg iodine per 100 g dry matter (DM) and Yorkshire for grass only 7 μg/100 g DM. Because goiter has occurred in lambs when the ewes are on a diet containing less than 30 μg iodine per 100 g DM, the importance of particular plant species becomes apparent. A high incidence of goiter associated with heavy mortality has been observed in the newborn lambs of ewes grazing on pasture dominated by white clover and by subterranean clover and perennial rye-grass.

Congenital goiter has been observed in foals born to mares on low iodine intake, but also to mares fed an excessive amount of iodine during pregnancy.

Sows

Feeding sows a diet supplemented with 2000 mg iron/kg DM of diet will satisfactorily prevent iron-deficiency anemia in the piglets. The piglets will ingest about 20 g of sows feces per day, which will contain sufficient iron and obviate the need for IM injection of iron-dextran. The piglets grow and thrive as well as those receiving the iron-dextran.

Veal calves

Milk replacers for veal calves may contain up to 40 mg/kg DM of iron for the first months, but commonly only 10–15 mg/kg DM for the finishing period. The best indicator of the onset of anemia in calves on vealer diets is loss of appetite, which is a more sensitive indicator than biochemical measurement.

Heifer calf herd replacements

The National Research Council recommends that milk replacers fed to herd replacements or dairy beef contain 100 mg/kg of DM, with an upper limit of 1000 mg/kg DM.¹⁷ The pre-ruminant calf can tolerate between 2000 and 5000 ppm DM iron in milk replacer.¹⁷

Infertility in ewes

Infertility in ewes and a dietary deficiency of zinc have not been officially linked, but a zinc-responsive infertility has been described in ewes. Again, attention is drawn to the need for response trials when soil and pasture levels of an element are marginal.

An experimental zinc deficiency in pregnant ewes results in a decrease in the birth weight of the lambs and a reduced concentration of zinc in the tissues of the lambs; these effects are due to the reduced feed intake characteristic of zinc deficiency.⁷ The zinc content of the diet did not significantly influence the ability of the ewes to become pregnant or maintain pregnancy. The combination of pregnancy and zinc deficiency in the ewe leads to highly efficient utilization of ingested zinc, and the developing fetus will accumulate about 35% of the total dietary intake of zinc of the ewe during the last trimester of pregnancy. The disease is correctable by the supplementary feeding of zinc.