Diseases caused by deficiencies of mineral nutrients An enormous ...

Diseases caused by deficiencies of mineral nutrients
An enormous literature exists on the subject of mineral nutrient deficiencies in animals and it is
not possible to review it all here. However, some general comments should be made. The era of
large-scale deficiencies affecting very large numbers of animals and comprising single elements
has now largely passed in developed countries. The diagnostic research work has been done and
the guidelines for preventive programs have been outlined and put into action in the field, so that
the major breakthroughs have already been made, and what remains is in many ways a tidying-up
operation after large-scale control campaigns. The loose edges needing to be refined include
correcting overzealous application of minerals, which can produce toxicoses, sorting out the
relative importance of the constituent elements in combined deficiencies, which are characterized
by incomplete response to provision of single elements, and devising means of detecting marginal
deficiencies.
At least 15 mineral elements are nutritionally essential for ruminants. The macrominerals are
calcium, phosphorous, potassium, sodium, chlorine, magnesium, and sulfur. The trace elements,
or microminerals, are copper, selenium, zinc, cobalt, iron, iodine, manganese, and molybdenum.
INCIDENCE AND ECONOMIC IMPORTANCE
Despite increasing experimental evidence that anomalies in trace element supply can influence
growth, reproductive performance or immunocompetence of livestock, few data exist from which
the incidence and economic significance of such problems can reliably be assessed. Most
published reports of the more readily recognized trace element-related diseases continue to
provide insufficient quantitative information to assess their incidence and true economic impact.
Despite these deficiencies in information, the FAO/WHO Animal Health yearbooks indicate that,
of the countries providing information on animal diseases, 80% report nutritional diseases of
moderate or high incidence, and trace element deficiencies or toxicities are involved in more than
half of those whose causes were identified. In the United Kingdom it has been estimated that,
despite the activities of its nutritional and veterinary advisory services and extensive policies of
ration supplementation, characteristic clinical signs of copper deficiency develop annually in
about 0.9% of the cattle population. In light of recently described evidence that copper deficiency
can predispose to increased mortality due to infectious diseases in lambs, the economic losses
from copper deficiency may be grossly underestimated.
DIAGNOSTIC METHODS AND STRATEGIES
In developed countries with highly developed animal industries, the emphasis is on disease
prevention rather than therapy, and elimination or economical control of trace element
deficiencies is a matter of education rather than research. However, because copper, cobalt,
selenium, and iodine deficiencies can affect reproductive performance, appetite, early postnatal
growth, and immunocompetence on a herd or Hock basis, increasing emphasis is being placed on
diagnostic methods that will identify a developing risk long before specific clinical manifestations
appear. In addition, it is not good enough to merely define the distribution of animal populations
with an abnormal trace element status indicated by blood or tissue analysis, or to detect a
deficiency of the trace element in the diet. The only feasible way of monitoring the preclinical
stages of trace element deficiency is the identification of a biochemical indicator which reflects
changes in the activity of the enzyme involved or the concentration in tissues of its substrate or
products. The demand is growing for techniques that will predict when the likely pathological
outcome of such anomalies justifies the introduction of protective measures. For example, recent

observations indicate that a high proportion of grazing cattle become hypocupremic if maintained
on forage, but fail to develop characteristic clinical signs of deficiency and, furthermore, only
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a small percentage cf these animals exhibit any physiological response to the administration of
copper. This illustrates the lack of understanding of the variables involved in the development of
clinical manifestations of copper deficiency and whether they are induced by a simple dietary
deficiency of copper or by specific copper antagonists present in the diet. A relatively new and
interesting area of development is the observation of genetic variation in dietary requirements for
copper among different breeds of sheep and that sheep can be selected for a high or tow
concentration of plasma copper, which in turn will have profound physiological consequences in
the low group. There is now evidence that heredity is involved in the utilization of trace elements
by animals. A small amount is necessary, but a larger amount may be toxic, and there is a need to
determine the optimal economic balance.
Thus, it is likely that trace element deficiencies are widespread, but their incidence and
importance are probably underestimated because subclinical forms of deficiency can occur and go
unnoticed or prolonged periods.
DEFICIENCIES IN DEVELOPING COUNTRIES
In developing countries, the trace element problem is confounded by the common deficiencies of
energy, protein, phosphorus and water, which affect post¬natal growth and reproductive
performance. Undernutrition is commonly accepted as the most important limitation to herbivore
livestock production in tropical countries. However, mineral deficiencies or imbalances in soils
and forages have long been held responsible for low production and reproduction problems among
grazing tropical cattle. Cattle grazing forages in areas severely deficient in phosphorus, cobalt, or
copper are even more limited by lack of these elements than either that of energy or protein.
PATHOPHYSIOLOGY OF TRACE ELEMENT DEFICIENCY
The physiological basis of trace element deficiency is complex. Some elements are involved in a
single enzyme, some in many more, and a lack of one element may affect one or more metabolic
processes. Furthermore, there are wide variations in how individual animals respond clinically to
lowered blood or tissue levels of a trace element. For example, two animals in a herd or flock with
the same copper levels in their blood may be in different bodily condition. The susceptibility to
clinical disease may be a function of the stage of physiological development at which they occur,
genetic differences within a species, and interrelationships with other trace elements. There is now
good evidence to show that the amounts of dietary copper adequate for some breeds of sheep were
deficient for others, and even toxic to others.
A dietary deficiency does not necessarily lead to clinical disease. Several factors predispose the
animal to clinical disease and they include:
•The age at which the deficiency occurs (for example fetal lambs are highly susceptible to
demyelination due to copper deficiency in late fetal life)
•Differences in genotype requirements
•Discontinuous demands for trace elements because of changes in environment
•The challenge of infections, diet, and production demands
•Individual variations in response to the deficiency, the use of alternative path ways by the body in
the face of a deficiency
•Size of the functional reserves.

The trace elements are involved as component parts of many tissues, and one or more enzyme
activities and their deficiency leads to a wide variety of pathological consequences and metabolic
defects. These arc summarized in Table 29.1.
Table 29.1 Principal pathological and metabolic defects in essential trace element deficiencies
(1)
Deficiency Pathological consequence Associated metabolic defect
Copper Defective melanin production
Tyrosine/DOPA oxidation
Defective keratinization; ha ir, wool -SH oxidation to S-S
Connective tissue defects
Lysyl oxidase
Ataxia, myelin aplasia
Cytochrome oxidase
Growth failure
?
Anemia
?
Uricemia
Urate oxidase
Cobalt Anorexia
Methyl malonyl CoA mutase
Impaired oxidation of propionate
Anemia
Tetrahydrofolate methyl transferase
Selenium Myopathy; cardiac/skeletal
Peroxide/hydroperoxide destruction Glutathione
Liver necrosis
peroxidase
Defective neutrophil function
OH; O2 generation
Zinc Anorexia, growth failure
?
Parakeratosis
Polynucleotide synthesis, transcription,
Perinatal mortality
Thymic involution
Defective cell-mediated immunity
translation?
Iodine Thyroid hyperplasia
Reproductive failure Hair,
wool loss
Thyroid hormone synthesis
Manganese
Skeletal/cartilage defects
Reproductive failure
Chondroitin sulfate synthesis?
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The soil-plant -animal interactions in relation to the incidence of trace element deficiencies
in livestock are being examined. The soil and its parent materials are the primary sources of trace
elements on which soil-plant-animal relationships are built. The natural ranges in concentration of
most trace elements in soils are wide and range from deficient soils to those which are potentially
toxic. The availability of trace elements to plants is controlled by their total concentration in the
soil and their chemical form. Certain species of plants take up more trace elements than do others.
The ingestion of soil can have a profound effect on trace element nutrition and metabolism.
Geochemical surveys can now assist in the identification of areas in which livestock are exposed
to excessive ingestion or deficiencies of trace elements.
The dose-response trial will continue to play a significant role in the delineation of trace
element deficiencies because it is often difficult to determine the role of individual trace elements.
A deficiency of one trace element may result in clinical disease, which may be indistinguishable
from a deficiency of more than one trace element. Many of the trace element deficiencies may

produce nonspecific as well as specific effects.
A dose-response trial can be defined as the application of a test and a control substance to a
group, or replicates, of individuals and the measurement of the response to the treatment. The
requirements for a reliable dose-response trial include a careful appraisal of the basis for
conducting the trial, a suitable form of the test substance for treatment, the careful selection of
animals for the test, a reliable biochemical method for monitoring the response to the trace
element, a measurable production response, an adequate system for measurement of the variable
that may influence the response, and a means of measuring the economic impact.
The ad hoc field observations made by veterinarians who make a diagnosis of a trace element
deficiency, followed by treatment or dietary changes, are subjective and usually lack controls but
are nevertheless of value in indicating the magnitude and variability of response that might be
expected in future experimental studies. Dose-response trials help to establish a link between a
trace element and certain clinical signs; they may identify factors which modify the response to a
trace element and, of paramount impotance, give an indication of the economic importance of
adequate supplementation of the element in the diet.
There are major problems in the diagnosis and anticipation of trace element deficiencies in
grazing livestock. Because of the interplay between the constituents of the diet and the
homeostatic mechanisms of the body, it is often impossible to predict from dietary composition
alone whether a particular nutritional regimen will result in clinical disease. The assessment of the
absorbable, rather than the total, concentration of elements in the diet is now considered to be
more important in understanding the nutritional basis for the deficiencies.
LABORATORY DIAGNOSIS OF MINERAL DEFICIENCIES
The diagnosis of mineral deficiencies, particularly trace element deficiencies, will depend heavily
on the interpretation of the biochemical criteria of the trace element status. This is because
deficiencies of any one or more of several trace elements can result in non-specific clinical
abnormalities, such as loss of weight. growth retardation, anorexia, and inferior reproductive
performance.
The interpretation of biochemical criteria of trace element status are governed by three
important principles: relationship with intake, time, and function.
1. Relationship between the tissue concentrations of a direct marker and the dietary intake
of the element willgenerally besigmoidin shape (a dose-response curve). The important point on
the curve is the intake at which the requirement of the animal is passed, which is the intake of the
nutrient needed to maintain normal physiological concentrations of the element and/or avoid
impairment of essential functions. For several markers of trace element status, the position on the
X-axis at which requirement is passed coincides with the end of the lower plateau of the response
in marker concentration. Under these conditions, the marker is an excellent index of sufficiency
and body reserves, but an insensitive index of a deficiency. If requirement is passed at the
beginning of the upper plateau, the marker is a poor index of sufficiency, but a good index of
deficiency. This principle allows direct markers to be divided into storage and non-storage types
corresponding to the former and latter positions on the x-axis.
2.Non-storage criteria can be divided into indicators of acute and chronic deficiency and two
types of relationships can be distinguished:a rapid,early decline in marker concentration followed
by a plateau, and a slow, linear rate of decline. Markers with a slow, linear response will be good
indices of a chronic deficiency, but unreliable indices of acute deficiency, because they cannot

espond quickly enough. Conversely, the marker with a rapid, early decline will be a good index
of acute deficiency, but an unreliable indicator for chronic deficiency if the low plateau is reached
before functions are unpaired. Those biochemical criteria that are based on metalloenzyme or
metalloprotein concentrations in erythrocytes are of the slow type because the marker is
incorporated into the erythrocyte before its release into the bloodstream, and thereafter its half-life
is determined by that of the erythrocyte that is 150 days or more. Metalloenzymes or
metalloproteins in the plasma with short half-lives provide markers of the rapid type.
3.A deficiency can be divided into four phases:depletion,deficiency(marginal), dysfunction and
clinical disease.
Depletion is a relative term describing the failure of the diet to maintain the trace element status
of the body, and it may continue for weeks or months without observable clinical effects when
substantial body reserves exist. When the net requirement for an essential element exceeds the net
flow of absorbed clement across the intestine then depletion occurs. The body processes may
respond by improving intestinal absorption or decreasing endogenous losses. During the depletion
phase there is a loss of trace element from any storage sites, such as the liver, during which time
the plasma concentrations of the trace element may remain constant. The liver is a common store
for copper, iron, and vitamins A and B12.
If the dietary deficiency persists, eventually there is a transition from a state of depletion to one
of deficiency, which is marked by biochemical indications that
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the homeostatic mechanisms are no longer maintaining a constant level of trace elements
necessary for normal physiological function. After variable periods of time, the concentrations or
activities of trace element-containing enzymes will begin to decline leading to the phase of
dysfunction. There may be a further lag period, the subclinical phase, before the changes in
cellular function are manifested as clinical disease. The biochemical criteria can be divided,
according to the phase during which they change, into indicators of marginal deficiency and
dysfunction. The rate of onset of clinical disease will depend on the intensity of the dietary
deficiency, the duration of the deficit and the size of the initial reserve. If reserves are non-existent,
as with zinc metabolism, the effects may be acute and the separate phases become superimposed.
The application of these principles to the interpretation of biochemical criteria of trace element
status are presented later in this chapter where applicable under each mineral nutrient.
The definitive etiological diagnosis of a trace element deficiency will depend on the response
in growth and health obtained following parenteral treatment or supplementation of the diet. The
concurrent measurement of biochemical markers will aid in the interpretation and validation ol
those markers for future diagnosis. The strategies for anticipating and preventing trace element
deficiencies include regular analysis of the feed and soil, winch are not highly reliable, and
monitoring samples from herds and flocks to prevent animals from entering the zone of marginal
trace element deficiencies which precedes the onset of functional deficiency. The decision to
intervene can be safely based on the conventional criteria of marginal trace element status.
REVIEW LITERATURE
Suttle, N. F. (1986) Problems in the diagnosis and anticipation of trace element deficiencies in
grazing livestock. Vet. Rec, 119, 148-152.
COBALT DEFICIENCY
Cobalt deficiency is a disease of ruminants ingesting a diet deficient in cobalt, which is required

for the synthesis of vitamin B12. The disease is characterized clinically by inappetence and loss of
body weight. Some effects on reproductive performance in sheep have been reported.
Synopsis
Etiology. Dietary deficiency of cobalt resulting in a deficiency of vitamin Bl2.
Epidemiology. Occurs primarily in cattle and sheep unsupplemented with cobalt worldwide
where soils are deficient in cobalt. Associated with ovine white liver disease.
Signs. Inappetence, gradual loss of body weight, pica, marked pallor of the mucous membranes.
Wool and milk production decreased. Decreased lambing percentage.
Clinical pathology. Cobalt, or vitamin B12. concentration of liver. Cobalt concentrations.
Methylmalonic acid in plasma and urine. Formiminoglutamic acid in urine. Anemia.
Lesions. Emaciation, hemosiderosis of spleen.
Diagnostic confirmation. Vitamin B12 and cobalt of liver.
Differential diagnosis list:
Common causes of ill-thrift in ruminants:
•Copper deficiency
•General nutritional deficiency (protein
and energy)
•Johne's disease
•Intestinal helminthiasis.
Treatment. Oral dosing with cobalt or parenteral injections of vitamin B12.
Control. Dietary supplementation with
cobalt. Cobalt-heavy pellets.
ETIOLOGY
The disease is caused by a deficiency of cobalt in the diet which results in a deficiency of vitamin
B12.
EPIDEMIOLOGY
Occurrence
Cobalt deficiency occurs in Australia, New Zealand, the United Kingdom and North America, and
probably occurs in mainy other parts of the world (1). Where the deficiency is extreme, large
tracts of land are unsuitable for the raising of ruminants, and in certain areas suboptima] growth
and production may be limiting factors in the husbandry of sheep and cattle. The concentration of
cobalt in the soil can vary widely as, for example, in Irish cattle farms where the soil cobalt
content varied between 0.2 and 18 mg/kg dry matter (DM), the forage had marginal to normal
cobalt content, and low or very low blood vitamin B12 status was found in 55% of herds sampled
(2). However, the significance of the cobalt deficiency clinically is uncertain (3).
Cattle and sheep are similarly affected and the signs are similar in both species. Cattle are
slightly less susceptible than sheep, and lambs and calves are more seriously affected than adults.
Frank deficiency is unlikely to occur in pigs, or in other omnivores or carnivores, because vitamin
B12 is present in meat and other animal tissues, but there are some reports of improved weight
gains following supplementation of the ration with cobalt. Horses appear to be unaffected.
Although the disease occurs most commonly in ruminants at pasture in severely deficient areas,
sporadic cases occurin marginal areas, especially after long periods of stable feeding. Bulls, rams,
and calves are the groups most commonly affected, although dairy cows kept under the same
conditions may develop a high incidence of ketosis.

Risk factors
Dietary and environmental factors
Pastures containing less than 0.07 and 0.04 mg/kg DM result in clinical disease in sheep and cattle,
respectively. The daily requirement for sheep at pasture is 0.08 mg/kg DM of cobalt; for growing
lambs the need is somewhat greater and at pasture levels of less than 0.10 mg/kg DM inefficient
rates of gain are likely. For growing cattle, an intake of 0.04 mg/kg DM in the feed is just below
requirement levels (4). Variations in the cobalt content of pasture occur with seasonal variations in
pasture growth and with drainage conditions. The increased incidence of the disease, which has
been observed in the spring, may be related to domination of the pasture by rapidly growing
grasses, which have a lower cobalt content than legumes. There is also a great deal of variation
between years in the severity of the losses encountered due to variations in the cobalt status of the
animals. Forage grown on well-drained soils has a greater cobalt content than that grown on
poorly drained soils of the same cobalt status. Plant growth is not visibly affected by a low cobalt
content of the soil, but the addition of excessive quantities may retard growth.
Cobalt is also protective against the liver damage in sheep exposed to annual ryegrass (5).
Primary cobalt deficiency occurs only on soils which are deficient in cobalt. Such soils do
not appear to have any geological similarity,varying from
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windblown shell sands to soils derived from pumice and granite. Japanese soils composed largely
of volcanic ash are seriously deficient. A survey in New Brunswick, Canada, revealed the average
value for grass samples was 0.028 mg/kg DM, and for legume samples, 0.088 mg/kg DM, which
justifies supplementation of ruminant diets with cobalt. The soils in New Brunswick are naturally
acidic and with the heavy annual rainfall of 120 cm the cobalt content of the soil is decreased by
leaching. Outbreaks of cobalt deficiency have occurred in cattle grazing on pastures on the
granite-derived northern tablelands of New South Wales in Australia, and in sheep grazing pasture
on soils derived from weathered rhyolite and ignimbrite, the former being inherently-low in cobalt.
Cobalt deficiency is now-occurring in areas where it has never before been diagnosed, and in
seasons of lush spring and summer pasture growth, cobalt deficiency should be suspected as a
cause of unthriftiness. Lambs grazing cobalt-deficient pastures of the Northern Netherlands are 6.7
times more likely to die if unsupplemented with cobalt than supplemented lambs (6).
Although soils containing less than 0.25 mg/kg cobalt are likely to produce pastures containing
insufficient cobalt, the relationship between levels of cobalt in soil and pasture is not always
constant. The factors governing the relationship have not been determined, although heavy liming
is known to reduce the availability of cobalt in the soil. Manganese appears to have a similar
action, but the agricultural significance of the relationship is unknown.
Ovine white liver disease
A specific hepatic dysfunction of sheep has been described in New Zealand, Australia, the United
Kingdom (7), and Norway (8). It has been called 'white liver disease' because of the grayish color
of the liver. Clinically, it is manifestedby pho-tosensitization when the disease is acute, and
anemia and emaciation when the disease is chronic. It seems likely that the disease is a toxic
hepatopathy against which adequate levels of dietary cobalt are protective (9).
PATHOGENESIS
Cobalt is unique as an essential trace element m ruminant nutrition because it is stored in the body
in limited amounts only and not in all tissues. In the adult ruminant, its only known function is in

the rumen and it must, therefore, be present continuously in the feed.
The effect of cobalt in the rumen is to participate in the production of vitamin Bl2
(cyanocobalamin), and compared to other species the requirement for vitamin B]2 is very much
higher in ruminants. In sheep, the requirement is of the order of 11ug/day, and probably 500
ug/day arc-produced in the rumen, most being lost in the process. Animals in the advanced stages
of cobalt deficiency are cured by the oral administration of cobalt or by the parenteral
administration of vitamin B12. On cobalt-deficient diets the appearance of signs is accompanied by
a fall of as much as 90% in the vitamin 13,, content of the feces, and on oral dosing with cobalt the
signs disappear and vitamin B12 levels in the feces return to normal. Parenteral administration of
cobalt is without appreciable clinical effect, although some cobalt does enter the alimentary tract
in the bile and leads to the formation of a small amount of cobalamin.
The essential defect in cobalt deficiency in ruminants is an inability to metabolize propionic acid,
which is accompanied by a failure of appetite and death from inanition. The efficiency of cobalt m
preventing staggers m sheep grazing pasture dominated by (Phalaris tuberosa) and possibly by
canary grass {Phalaris minor) or rhompa grass, a hybrid Phalaris spp., is also unexplained. A
suggestion that a dietary deficiency of cobalt can lead to the development of polio-ence
phalomalacia appears not to be valid.
The pathogenesis of ovine white liver disease is unclear. It is unknown if the disease is a simple
cobalt deficiency, or a hepatotoxic disease in cobalt/vitamin B12-deficient lambs. Marginal to
deficient cobalt-deficient grass is essential for the development of the disease (8). Cobalt
fertilization of deficient pastures results in an increase in vitamin BP in lambs (9). Hepatic
dysfunction occurs in affected sheep (10). Affected lambs generally have higher serum levels of
copper than in cobalt/vitamin B12-supplemented lambs grazing the same pastures (11). Dosing
affected lambs with copper oxide needles resulted in toxic levels of liver copper (12). It is
suggested that the disease is a manifestation of Bl2 deficiency made worse by factors triggering
early hepatic fatty change, resulting in more severe liver damage and loss of intracellular
homeo-stasis, rendering the hepatocytes more vulnerable to other elements such as copper (13).
The amount of fructan in the pasture may be an important factor in the pathogenesis of the lesion
(4). One hypothesis suggests that the high level of fructan may initiate hepatic lipodystrophy,
leading to hepatic insufficiency, growth reduction and ovine white liver disease (4). Vitamin B12 is
therapeutic (14).
CLINICAL FINDINGS
No specific signs arc characteristic of cobalt deficiency. A gradual decrease in appetite is the only
obvious clinical sign. It is accompanied by loss of body weight, emaciation and weakness, and
these are often observedin the presence of abundant green feed. Pica is likely to occur, especially
in cattle. There is marked pallor of the mucous membranes and affected animals are easily
fatigued. Growth, lactation, and wool production are severely retarded, and the wool may be
tender or broken. In sheep, severe lacrimation with profuse outpouring of fluid sufficient to mat
the wool of the face is one of the most important signs in advanced cases. Signs usually become
apparent when animals have been on affected areas for about 6 months and death occurs in 3-12
months after the first appearance of illness, although severe wasting may be precipitated by the
stress of parturition or abortion.
Cobalt deficiency in pregnant ewes can result m decreased lambing percentage, increased
percentage of stillbirths, and increased neonatal mortality (15). Lambs from deficient ewes are

slower to start sucking, have reduced concentrations of serum colostra] immunoglobulins, and
have lower serum vitamin BI2 and higher methylmalonic acid concentrations than lambs from
cobalt-adequate dams.
CLINICAL PATHOLOGY
Estimation of the cobalt or vitamin B12 content of the liver, as described under necropsy findings,
is the most valuable diagnostic test available. All tests suffer from the disadvantage that tissue
cobalt levels will reflect the cobalt intake for a considerable time prior to the estimation, and
animals suffering from acute cobalt deficiency may be observed to have normal tissue levels of
the clement. Estimations of the cobalt content of soils and pasture have limited value because of
the seasonal variations that occur.
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Cobalt concentrations
Cobalt concentrations in the plasma of normal sheep are of the order of 1-3 ug/dL (0.17-0.51
umol/L), and in deficient animals these are reduced to 0.03-0.41 umol/L. Clinical signs of cobalt
deficiency in sheep are associated with serum vitamin B12 levels of less than 0.20 mg/mL, and
serum vitamin B12 levels are used as a laboratory test of cobalt status in animals. Levels of
0.2-0.25 ug/L are indicative of cobalt deficiency. These rise rapidly to 0.5-1.0 ug/L on treatment.
The value of serum vitamin B12 assay as a diagnostic tool is in some doubt, but correctly
interpreted they appear to be worthwhile. Radioassay methods for measuring serum and liver
vitamin B12 in cattle and sheep have now replaced the microbiological assays. Serum vitamin B12
values greater than 0.2 ug/L are indicative of a normal vitamin Bl2 status in cattle. Deprivation of
feed from sheep for 24 hours results in a marked increase in serum vitamin B12. The serum
vitamin B12 levels of sheep at pasture are unreliable indicators of liver vitamin B12.
Methylmalonic acid
Because of some of the difficulties with the interpretation of serum vitamin B12 levels, other
biochemical tests, especially methylmalonic acid (MMA) in plasma and urine as diagnostic and
prognostic indicators and formiminoglutamic acid (FIGLU) tests are now used (16). The
determination of MMA has the potential to distinguish between subchmically and clinically
affected animals, which serum vitamin B12, cannot do. Methylmalonic acid is ordinarily
metabolized in ruminants by a vitamin B12 enzyme system. An elevated plasma concentration of
MMA is a comparatively early indicator of functional vitamin B12 deficiency (17). It is
recommended that 10 umol/L be an upper limit of normality for plasma MMA in barley-fed
animals, and 5 umol/L be the upper limit for grass-fed animals (17). A comparison of serum
vitamin Bl2 and serum MMA as diagnostic measures of cobalt status in cattle indicates that =2
umol/L is normal, 2-4 umol/L represents subclinical deficiency, and =4 umol/L reprcsents
deficiency (18). In a cobalt-deficient animal the methylmalonic content of urine is abnormally
high and this has some merit as a test for the presence of the deficiency (9). Cobalt-adequate
lambs have plasma MMA levels of less than 5 umol/L, urinary MMA less than 120 umol/L and
urinary MMA/creatinine values of less than 0.022 umol MMA/mmol of urinary creatinine. An
unequivocal result for methylmalonic acid is a concentration of greater than 30 ug/mL for ten
animals selected randomly from a flock. If the urine is kept for more than 24 hours it should be
acidified to avoid degradation of the methylmalonic acid. Commercial kits are now available for
assay of vitamin B12in ruminant blood.

Formiminoglutamic acid
The concentration of formiminoglutamic acid in urine is a reliable indicator of the cobalt status of
lambs. Levels of 0.08-20 umol/mL in the urine of affected lambs return to zero rapidly after
treatment. However, the concentration of formiminoglutamic acid increases in the urine of lambs
only in the later stages of cobalt deficiency when there is weight loss and ill-thrift. Animals with
subclinical cobalt deficiency do not produce urinary formiminoglutamic acid at levels that would
be useful diagnostically. Neither MMA nor formiminoglutamic acid is a normal constituent of
urine and their presence in urine, without the need for a quantitative measurement, is probably a
positive indication of cobalt deficiency.
Hematology
Affected animals are anemic, but their hemoglobin and erythrocyte levels are often within the
normal range because of an accompanying hemoconcentration. The anemia is normocytic and
normochromic. There is also a decrease in cellularity of the bone marrow in cobalt-deficient sheep.
It is not repaired by the administration of vitamin B12 or by the parenteral administration of cobalt.
Affected animals are also hypoglycemic (less than 60 mg glucose per dL of plasma) and have low
serum alkaline phosphatase levels (less than 20 U/L). The response to cobalt administration is
matched by a very rapid return to normal of these levels. Unfortunately, there are too many other
factors affecting their concentration for them to be of much value in diagnostic work.
NECROPSY FINDINGS
At necropsy, emaciation is extreme. The livers of sheep affected with white liver disease are pale
and fatty. In most cases of cobalt deficiency the spleen is dark due to the accumulation of
hemosiderin. The microscopic changes of ovine white liver disease include hepatocellular
dissociation and intracytoplasmic accumulations of lipid and ceroid-lipofuscin within hepatocytes.
The ultrastructural changes of experimentally-induced ovine white liver disease have also been
documented (19).
Biochemical assays reveal very high iron levels in the liver and spleen, and low cobalt levels in
the liver. In normal sheep, cobalt levels in the liver are usually above 0.20 mg/kg DM, but m
affected sheep are typically less than 0.05 mg/kg DM. Liver cobalt levels in cattle fed excessive
amounts of cobalt and thought to be affected by cobalt poisoning can be as high as 69 mg/kg DM.
Normal levels of the vitamin of cattle in New Zealand are 0.70-1.98 mg/kg of liver. After oral
dosing with cobalt, "the level of the element in the liver rises, but returns to the pretreatment level
in 10-30 days. Since serum B]2 levels reflect cobalt status, it is often useful to submit sera from
surviving herdmates when attempting to confirm the diagnosis.
Samples for confirmation of diagnosis
•Toxicology-50 gliver(ASSAY(Co)), 2 mL serum (ASSAY (B12)).
•Histology - formalin-fixed liver (LM).
DIFFERENTIAL DIAGNOSIS
Cobalt deficiency must be differentiated from other causes of ‘ill-thrift' or ‘enzootic marasmus'.
Ill-thrift
In young animals, in which this situation is most often encountered, nutritional deficiencies of
copper, selenium and vitamin D are possible causes of ill-thrift. Lack of total digestible nutrients
is the commonest cause of thin animals, but owners are usually aware of the shortage and do not
present their animals for diagnosis. However, it does happen, especially with urban people who
become farmers and are unaware of the actual

1486
needs of animals. So it is best to check the feed supply and also to check whether or not the
animals have any teeth. These circumstances are seen so commonly in today's era of hobby farms
that a new disease category 'hobby farm malnutrition' is warranted.
Internal parasitism
Careful necropsy or fecal examination will determine the degree of helminth infestation, but
cobalt-deficient animals are more susceptible to parasitism and the presence of a heavy parasite
load should not rule out the diagnosis of primary cobalt deficiency. It is also common for parasitic
disease and cobalt deficiency to occur together in the one animal. It is then necessary to make two
diagnoses and conduct two control programs. In sheep, special care is needed to differentiate the
disease from Johne's disease. The differential diagnosis of anemia has been discussed elsewhere
(pp. 416, 1295).
Dietary supplementation response
The most conclusive method of determining if animal production is being affected by the
deficiency of a trace mineral is to measure the response of a production parameter, such as weight
gain, milk production, wool production, or reproductive performance following supplementation
of animals with the element under consideration (20). However, if the degree of response can be
related to a tissue level of the element, or its metabolites, then tissue analyses can replace the need
for field trials, which require considerable expertise and resources and can take several months to
monitor the results and obtain a quantitative outcome.
Growth response curve to supplementation A new approach to defining mineral deficiencies is
based on constructing response curves for any specified level of serum vitamin B12 that can be
used to determine liveweight response to supplementation and the probability of obtaining a
response (20). The technique closely relates the tissue mineral or biochemical indicator with the
degree of production response to treatment. The advantages of this method over the traditional
method have been described (20). The results from published and unpublished cobalt/vitamin B12
weight response trials in young sheep grazing pasture in New Zealand have been reviewed (20).
No significant weight gain responses occurred to vitamin B,? or cobalt treatment in trials with
serum vitamin B12 levels above 500 pmol/L or liver vitamin B12
levels greater than 500 nmol/kg. The fitted response curve approached 0 g/day at 500 pmol/L for
serum vitamin B12 and 375 nmol/kg for liver vitamin B12. The minimum vitamin B12 at which an
economic response to treatment (=10 g/day BW gain) is not likely is 336 pmol/L for serum and
282 nmol/kg for liver (20). Variable responses to cobalt or vitamin B12 include age, breed, sex,
energy intake, concurrent disease, and length of pasture. Higher soil contamination on short
pastures may result in increased cobalt intake and reduced response to vitamin B12 or cobalt.
Serum vitamin B12 levels may also increase following prolonged yarding, and within 24-48 hours
after changes in dietary cobalt.
TREATMENT
Cobalt and vitamin B12
Affected animals respond satisfactorily to oral dosing with cobalt or the IM injection of vitamin
B12. Oral dosing with vitamin B12 is effective, but much larger doses are required. Oral dosing
with cobalt sulfate is usually at the rate of about 1 mg cobalt/day in sheep and can be given in
accumulated doses at the end of each week. Intervals of 2 weeks between dosing are inadequate
for the best possible response. On the other hand, the monthly dosing of lambs with oral doses of

300 mg of cobalt is sufficient greatly to reduce deaths and permit some growth at suboptimal
levels. The response to dosing is very quick, significant elevation of serum vitamin B12 levels
being evident within 24 hours. When large doses of cobalt are administered to some sheep, other
undosed sheep on the same pasture may find sufficient additional cobalt on the pasture from the
feces of their Hock-mates to meet their needs. No exact data are available on dose rates for cattle
but ten times the prophylactic rate should be effective. Vitamin B12 should be given in 100-300 ug
doses for lambs and sheep at weekly intervals. Vitamin B12,, therapy is not likely to be used
generally because of the high cost and the comparable effect of oral cobalt administration.
However, vitamin B12 (hydroxycobalainin) may be a suitable therapeutic agent. One injection of 1
mg provides protection to lambs for 14 weeks, and for weaners protection for up to 40 weeks.
Treatment of lambs with ovine white liver disease with hydroxycobalamin results in an immediate
beneficial response and treatment is repeated 10 days later (7).
Cobalt toxicity
Overdosing with cobalt compo inds is unlikely, but toxic signs of loss of weight, rough hair coat,
listlessness, anorexia, and muscular incoordination appear in calves at dose rates of about 40-45
mg of elemental cobalt per 50 kg BW per day. Sheep appear to be much more resistant to the toxic
effects of cobalt than are cattle. Pigs have tolerated up to 200 mg cobalt/kg of diet. At intakes of
400 and 600 mg/kg there is growth depression, anorexia, stiff legs, incoordination, and muscle
tremors. Supplementation of the diet with methionine, or with additional iron, manganese, and
zinc alleviates the toxic effects.
CONTROL
The recommended safe level of cobalt in the diet for sheep and cattle is 0.11 mg cobalt kg/DM
diet. If this is not available, supplementation of the diet with cobalt is necessary. Calves reared on
cobalt-deficient pastures require cobalt or vitamin B12, supplementation prior to weaning. Cobalt
deficiency in grazing animals can be prevented most easily by the top-dressing of affected pasture
with cobalt salts. The amount of top-dressing required will vary with the degree of deficiency.
Recommendations include 400-600 g/ hectare cobalt sulfate annually or 1.2-1.5 kg/hectare every 3
-4 years. The response to pasture treatment is slow, requiring some weeks to complete. Affected
animals should be treated orally or by injection of vitamin B12 to obtain a quick, interim response.
In New Zealand, the requirement for cobalt of ruminants grazing on the pumice soils of the
Central Plateau was established in the 1930s and top-dressing to increase the cobalt intake was
widely practiced for many years. An on-farm survey conducted in 1978-1979 indicated that cobalt
inputs could be halved because adequate reserves of soil cobalt had accumulated. However, the
economic downturn in agriculture resulted in less use of cobalt, and follow-up surveys indicated a
general overall decline in soil and pasture cobalt levels, which was pronounced in areas with a
poor history of cobalt top-dressing. There is now a need to increase the soil level of cobalt to
prevent cobalt
1487
deficiency in grazing ruminants. A regular cobalt input is required to build up reserves. This input
requirement is about 350 g cobalt sulfate/hectare for 7-10 years on the most deficient areas.
Individual farm to farm variation exists within an area and it is necessary to monitor their soil,
pasture, and animal cobalt status. To achieve a level of cobalt of 0.08 mg/kg DM in pasture (the
critical level for sheep) a soil cobalt level of 1.7 and 2.2 mg/kg DM is required for the
yellow-brown pumice soils and yellow-brown loams, respectively (21).

Supplementation of the diet with 0.1 mg cobalt/day for sheep and 0.3-1.0 mg/day for cattle is
required, and can be accomplished by inclusion of the cobalt in salt or a mineral mixture. Cobalt
can also be supplied to cattle in their drinking water supply.
Cobalt-heavy pellet
The use of'heavy pellets' containing 90% cobalt oxide is an alternative means of overcoming the
difficulty of maintaining .\n adequate cobalt intake in a deficient area. I he pellet is m the form of
a bolus (5 g for sheep, 20 g for cattle) which, when given by mouth, lodges in the reticulum and
gives off cobalt continuously m very small but adequate amounts. Reports on their use in sheep
and cattle indicate that they are effective. Adminisation of the pellets to lambs and calves less than
2 months old is likely to be ineffective because of failure to retain them in the undeveloped
reticulum. The problem of cobalt deficiency in sucking animals can be overcome in part if the
dams are treated because of the increased vitamin B12 content of their milk, but the daily intake of
the lambs will still be much below the minimal requirement. In about 5% of animals the pellets do
not lodge in the reticulum and approximately 20% are rejected during the year after administration.
If no response occurs, retreatment is advisable. A further possible cause of failure is where pellets
become coated with calcareous material, particularly if the drinking water is highly mineralized or
it pasture top-dressing is heavy. The effects of pellet coating can be overcome by simultaneous
dosing with an abrasive metal pellet. The cost is relatively high and, where top-dressing of
pastures is practiced, addition of cobalt to the fertilizer is the cheaper form of
administration.Pellets are preferred in extensive range-grazing where top-dressing is impracticable
and animals are seen only at infrequent intervals.
Controlled release glass boluses of cobalt
Boluses of controlled release glass containing cobalt are available for oral administration to cattle
and sheep. The boluses are retained in the forestomachs for up to several months and slowly
release cobalt.
Combine cobalt with administration of anthelmintics
Anthelmintics are convenient and efficient vehicles for supplementing the diet with selenium and
cobalt on a regular basis, because both the selenium and cobalt status of lambs decline as they
become dependent on forage, with its adherent nematode larvae, for their nutrients. As a result, the
periods of highest incidence of cobalt and selenium deficiency and helminthiasis coincide. In one
trial, there were lasting responses to selenium but transient, though significant, responses to the
cobalt in the form of increases in plasma vitamin B12, In some trials, the administration of a
monthly bolus of 250 mg cobalt was more effective than the cobalt in the anthelmintic. The
optimum level of cobalt supplementation of an anthelmintic ranges from 20 to 100 mg cobalt per
treatment. When the anthelmintic is given at 3-weekly intervals there may be a cumulative effect.
A comparison of giving 500 ug cyanocobalamin subcutaneously to one group of lambs, with 2.5
mg cobalt orally in an anthelmintic to another group, revealed that even the lowest dose of cobalt
in anthelmintics will be of some nutritional benefit (22).
REFERENCES
(1)McDonald, I. W. (1993) Aust.J. AXr. Res.,44, 347.
(2)Mcc.J. F. & Rogers. P. A. M. (1996) IrishVet.J., 49, 160.
(3)Mee.J. F. & Rogers, P. A. M. (1996) IrishVet.J., 49, 529.
(4)Uvlund, M. J. & Pestalozzi, M. (1990) AdaVet. Scand., 31, 373.
(5) Davits, S. C. ct al. (1993) Ami. Vet.J., 70, 1866.

(6)Vellema, P. ct al. (1997) Vet. Quart., 19,1.
(7)Dannatt, L. & Porter, T. A. (1996) Vet.Rec., 7.!9, 371.
(8)Uvlund. M.J. & Pestaloxzzi, M. (1990) Acta Vet. Scand., 31. 257.
(9) Uvlund, M.J. (1990) Ada Vet. Scand., 31, 267.
(10)Uvlund, M.J. (1990) Acta Vet. Scand., 31,277.
(11)Uvlund, M.J. (1990) Acta Vet. Scand., 31,297.
(12)Uvlund, M.J. (1990) Acta Vet. Scand., 31,287.
(13)Uvlund, M.J. (1990) Ada Vet. Scand., 31,309.
(14)Uvlund, M.J. (1990) Ada Vet. Scand., 31,369.
(15)Fisher, G. E. ik MacPherson, A. (1991)Res. Vet. Set., 50, 319.
(16)McGhie.T. K. (1991)J. Chmmatograph.Biomed. Appi, 566, 215.
(17)O'Harte, F. R M. ct al. (1989) Br.J. Nutr.,62, 729.
(18)Paterson.J. E. & MacPherson, A. (1990)Vet. Rec, 126, 329.
(19)Kennedy, S. et al. (1997) Vet. Hatlwl., 34,575.
(20)Clark, R. Ci. et al. (1989) NZ Vct.J., 37,7.
(21)Hawke, M. F. et al. (1994) Proc. NZGrassland Assoc, 56, 249.
(22)Suttle, N. F. et al. (1990) Vet. Rec, 126,192.
COPPER DEFICIENCY
Synopsis
Etiology. Primary copper deficiency due to inadequate levels in diet. Secondary copper deficiency
due to conditioning factors such as excess molybdenum and sulfur in diet. Epidemiology.
Primarily in young pastured ruminants in spring and summer. Primary deficiency occurs in sandy
soil and heavily weathered areas; secondary in peat or muck soil areas. Feed and water supplies
may contain molybdenum, sulfate and iron salts, which interfere with copper metabolism. May be
congenital in newborn lambs (swayback) if ewes deficient or delayed in nursing lambs (enzootic
ataxia). Some breeds of sheep highly susceptible.
Signs. Herd problem. Young growing ruminants on pasture. Unthriftiness, changes in hair color,
chronic diarrhea in molybdenosis (secondary deficiency), chronic lameness, neonatal ataxia,
anemia later stages of deficiency, and falling disease in adult cattle.
Clinical pathology. Low serum and hepatic copper. Ceruloplasmin. Anemia.
Lesions. Anemia, emaciation, hemosiderosis, osteodystrophy, demyelination in enzootic ataxia,
myocardiopathy.
Diagnostic confirmation. Low serum and hepatic copper and response to treatment.
1488
Differential diagnosis list
Copper deficiency must be differentiated from herd problems associated with the following
clinical findings:
•Unthriftiness due to intestinal parasitism (Chapter 26)
•Malnutrition due to energy-protein deficiency (p. 100)
•Lameness caused by osteodystrophy due to calcium, phosphorus and vitamin D imbalance (pp.
561, 1533)
•Anemia due to pediculosis (p. 1398)
•Neonatal ataxia in lambs (congenital swayback and enzootic ataxia) from border disease (p.
1238); cerebellar hypoplasia (daft lamb disease) (p. 1740); hypothermia (pp. 52, 129); meningitis

(p. 538)
•Sudden death due to other causes(p. 75).
Treatment. Copper sulfate orally; copper glycinate parenterally.
Control. Provide source of copper by oral dosing or dietary supplementation in feed or on pasture.
Parenteral administration of copper at strategic times. Copper oxide needles orally for prolonged
effectiveness. Controlled-release boluses. Genetic selection. Removal of sulfates from water
supply.
ETIOLOGY
Copper deficiency may be primary, when the intake in the diet is inadequate, or secondary
(conditioned) when the dietary intake is sufficient but the utilization of the copper by tissues is
impeded.
Primary copper deficiency
The amount of copper m the diet may be inadequate when the forage is grown on deficient soils or
on soils in which the copper is unavailable.
Secondary copper deficiency
In secondary copper deficiency, the amount of copper in the diet is adequate, but conditioning
dietary factors interfere with the utilization of the copper. Such secondary copper deficiencies are
summarized in Table 29.2. The administration of copper is preventive and curative. The
conditioning factor is known only in some instances, but a dietary excess of molybdenum is one of
the most common. A high molybdenum intake can induce copper deficiency even when the
copper content of the pasture is quite high, and a higher copper intake can overcome the effect of
the molybdenum. Conversely, supplementation of the diet with molybdenum can be used to
counteract the copper intake when its content in the diet is dangerously high. There are species
differences in response to high copper and molybdenum intake; sheep are much more susceptible
to copper poisoning, cattle to excess molybdenum.
Zinc, iron, lead, and calcium carbonate are also conditioning factors, and in New Zealand the
administration of selenium to sheep on copper-deficient pastures increases copper absorption and
improves the growth rate of lambs. The use of zinc sulfate for the control official eczema may
cause a depression of plasma copper levels, which can be alleviated by the injection of copper
glycinate.
Dietary inorganic sulfate in combination with molybdenum has a profound effect on the
uptake of copper by ruminants. Sheep consuming a complete diet, low in sulfur and molybdenum
and with a modest I 2-20 mg copper/kg dry matter (DM), may die from copper toxicity, while
others grazing pasture of similar copper content but high in molybdenum and sulfur can give birth
to lambs affected with the copper deficiency disease sway-back (1). An increase of sulfate
concentration m a sheep diet from 0.1 to 0.4% can potentiate a molybdenum content as low as 2
mg/kg (0.02 mmol/kg) to reduce copper absorption to below normal levels. Additional sulfate in
the diet also has a depressing effect on the absorption of selenium so that areas of a country with
marginal copper and selenium levels in the soil may produce deficiency syndromes in animals if
sulfate is added; this is likely to happen when heavy dressings of superphosphate are applied. Such
combined deficiencies are becoming more common. The possibility of interaction between copper
and selenium must also be considered because of the reported failure of animals to respond to
treatment unless both elements are provided.
EPIDEMIOLOGY

Occurrence
Copper deficiency is endemic worldwide and causes diseases of economic importance that may be
severe enough to render large areas of otherwise fertile land unsuitable for grazing by ruminants
of all ages, but primarily young, growing ruminants. Based on serum copper surveys of cattle
herds in Britain, copper deficiency constitutes a serious problem requiring vigilance. It is
estimated that characteristic clinical signs of copper deficiency develop annually in about 0.9% of
the cattle population in the United Kingdom. In some surveys, the lowest levels of serum copper
were in heifers being reared as heifer replacements. Although heavy mortalities occur m affected
areas, the major loss is due to failure ot animals to thrive. Enzootic ataxia may affect up to 90% of
a lamb flock in badly affected areas and most of these lambs die of inanition. In falling disease, up
to 40% of cattle in affected herds may die.
Geographical distribution
Primary copper deficiency
The diseases caused by ciency of copper in a primary deficiency of copper in ruminants are
enzootic ataxia of sheep in Australia, New Zealand and the United States, licking sickness, or
liksucht of cattle in Holland, and falling disease of cattle in Australia.
Table 29.2 Secondary copper deficiency status
Disease Country Species affected Copper level in Probable
liver
conditionin
g factor
Swayback Britain,united states Sheep
Low
Unkonw
Renguerra Peru
Sheep
Low
Unkonw
Teart
Britain
Sheep and cattle Unkonw Molybdenu
Scouring disease Holland
Cattle
Unkonw m
Peat scours New zealand
Cattle
Low
Unkonw
Peat scours Britain
Cattle
Unkonw,low Molybdenu
level in blood m
Peat scours Canada
Cattle
Unkonw Unkonw
Salt sick
Pine (unthrifty)
United states(florida)
Scotland
Cattle
Cattle
Unkonw
Low
Moiybdenu
m
Unkown
Unkonw
1489
A concurrent deficiency of both copper and cobalt occurs in Australia (coast disease) and
Florida in the United States (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 pigs, copper deficiency may 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 (2).

Secondary copper deficiency
The diseases caused by secondary copper deficiency, mostly due to high dietary intakes of
molybdenum and sulfate, arc-listed in Table 29.2. They include syndromes characterized by
diarrhea or by unthriftiness. Yellow calf, a disease of nursing calves occurs on Hawaii's
range-land where copper content of forages ranges from 2.6 to 11.8 mg/kg and the molybdenum
from less than 1 to 39 mg/kg. Swayback of lambs in the United Kingdom 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 United Kingdom, but in both instances the copper and molybdenum intakes are normal.
Molybdenum appears to be the conditioning agent in enzootic ataxia in the United States. 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.
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 less than 25 mg/kg DM (3). The concentrations of
copper in the liver of the fetuses were directly proportional to the liver copper concentrations in
the darns (3). Liver copper levels of fetuses from dams with liver copper greater than 25 mg/kg
DM were higher than those in fetuses from dams with liver copper levels lower than 25 mg/kg
DM. During gesta¬tion, 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 new¬born 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.
Seasonal incidence
Both primary and secondary copper deficiency occur most commonly in spring and summer
coinciding with the lowest levels of copper in the pasture.
Large monthly variations occur in the serum levels of copper in both beet and dairy cattle and
are commonly correlated with the rainfall; the higher the rainfall the lower the copper level.
The incidence of secondary copper deficiency may be highest at other times, depending upon
the concentration of the conditioning factor in the forage. For example, the molybdenum content
may be highest in the autumn when rains stimulate a heavy growth of legumes.
Risk factors
Several factors influence the plasma and tissue concentrations of copper, particularly in ruminants,
including:
•Age of animal
•Demands of pregnancy and lactation
•Stage of growth
•Copper sources available to the animals
•Mineral composition of feed

•Season of the year
•Soil characteristics and its mineral composition
•Breed of animal
•Concentration of minerals, such as sulfur and molybdenum, which can interfere with the
availability of copper (4, 5).
Animal factors
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 ug/dL (3.1-9.4 umol/L) copper, but under conditions of severe copper
deficiency this may be reduced to 1 2 (0.16-0.31 umol/L).
Breed 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 (6), and the
Texel cross blackface 145% more efficiently than pure blackface lambs (6). 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 m 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 con-
1490
trolled 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. I he 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 (7).
The genetic variation in the copper metabolism of sheep has important physiological
consequences. Breeds show wide variation in their susceptibility to sway-back; the incidence of

swayback may vary from 0 to 40% between breeds within one Hock, 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 sway-back, general
dullness, lack of vigor and mortality m 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.
Certain breeds of cattle, e.g. the Simmental and Charolais, may haw: higher copper
requirements than other breeds, e.g. Angus, and these differences may be related to differences in
copper absorption in the gastrointestinal tract (8, 9).
Fetal liver copper
During gestation, the copper concentration increases progressively in the ovine and bovine fetal
liver and decreases in the maternal liver (10). The developing bovine fetus obtains its copper by
placenta] transfer and at birth the liver concentration of copper is high and declines postnatally
to adult levels within the first few months (3). Placental transfer is less efficient in sheep, and
lambs are commonly born with low liver reserves, making the neonatal lambs susceptible to
copper deficiency (10). 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
mainte¬nance requirements, which means that the dietary allowance of 10 mg/kg DM needs to be
increased up to 25 mg/kg DM during pregnancy (10). 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 (11).
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.
Dietary factors
Pasture composition
The absorption (or availability) of copper is influenced by the type of diet, the pres¬ence 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 (6).
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 (6). 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 m 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 (6). 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 less than 3 mg/kg DM of copper will result in signs of
deficiency m grazing ruminants. Levels of 3-5 mg/kg DM can be considered as dangerous, and
levels greater than 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 p}l reaction of
the soil. Grasses grown on strongly acidic molybdenum-rich soils are characterized by low
molybdenum values (less than 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 limedpastures are often
1491
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 (12). 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 (13).
Stored feeds
Livestock that are housed are in a different position 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. lay 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, it 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 are 'peat' or muck soils reclaimed from swamps, and
are soils more commonly associated with copper deficiency in the United States, 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 29.3.
Molybdenum excess
Pastures containing less than 3 mg/kg DM of molybdenum are considered to be safe, but disease
may. occur at 3-10 mg/kg DM if the copper intake is low. Pastures containing more than 10 mg/kg
DM of molybdenum are dangerous unless the diet is supplemented with copper. Excess
molybdenum may occur in soils up to levels of 10 and even 100 mg/kg. Perhaps more dangerous
is the risk that overzealous application of molybdenum to pasture to increase bacterial nitrogen
fixation may have similar effects, which are likely to be long-lasting.
In the United Kingdom appreciable land is underlain by marine black shales rich in
molybdenum, resulting in a high content of molybdenum in the soil and pastures, and in a
secondary copper deficiency that, potentially, limits livestock performance. Secondary
(conditioned) copper deficiency is now recognized in cattle in many parts of Canada. Large areas
of west-central Manitoba are underlain by molybdeniferous shale bedrocks and the soils contain
up to 20 mg/kg of molybdenum. However, in the same geographical location, hypocupremia may
be associated with a primary deficiency of copper in the forage, or a secondary copper deficiency
clue to molybdenum in the forages.
PATHOCLNES1S
Effects on tissues
Copper is necessary in tissue oxidation by either supplementing cytochrome oxidase systems or
entering into their formation. Ceruloplasmin is the copper-containing enzyme through which
copper exerts its physiological function. The pathogenesis of most of the lesions of copper
deficiency has been explained in terms of faulty tissue oxidation because of failure of these
enzyme systems. This role is
Table 29.3 Copper levels of soils and plants in primary and secondary copper deficiency

Condition Area
Normal
Primary copper
deficiencyWes
Secondary copper
deficiency
-
West Australia
New Zealand
New Zealand
HollandSand
New Zealand
Britain
Britain
Britain
Ireland
Holland
Canada
Soil type Soil copper
mg/kg
-
various
Sand
Peat
Sand
Peat
Peat
Limestone
Stiff clay
Shale deposits,
peat marine alluvial soils
sand
Burned-over peat
18-22
1-2
0.1-0.6
-
-
5
-
-
-
-
20-60
Plant
copper
(mg/kg dry
matter)
11
3-5
3
3
5
10-25
1492
exemplified in the early stages of copper deficiency by the changes in the wool of sheep.
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 diar-rhea. There are no histologica]
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 relation¬ship in New Zealand between copper deficiency and postparturient
hemoglobinuria is unexplained. Heinz body ane-mia in lambs with deficiencies of copper or

selenium and moved from improved pasture to rape (Brassicaa napus) has been reported.
Bone
The osteoporosis that occurs in some natural cases of copper deficiency is caused by the
depression of osteoblastic activity (14).
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) (5). 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 (4). 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 (16), 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 (5), 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 tanned red deer and wapiti X red deer hybrids in New Zealand (2).
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 myocardia] 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 (19).
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. I here 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
1493
development at those sites at 90 days of gestation and 20 days after birth. The postnatal
development of delayed sway-back 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 to 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 liveweight gain. Thus, the presence
of molybdenum rather than low copper status may affect reproductive performance of cattle.
Geo-chemical data indicate that approximately 10% of the cultivated area of England and Wales
have 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 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. 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 (20).
These changes in copper metabolism evolve from an interleukin-1 mediated increase in hepatic
synthesis and release of ceruloplasmin, an acute phase protein (20). 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. Experimental copper depletion and repletion did not
affect neutrophil or lymphocyte function in growing beef cattle heifers (21).
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.
Sequence of clinical signs development
In experimental copper deficiency in calves, beginning at 6 weeks of age, sub-clinical 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 etacarpophalangeal and
carpometacarpal joints. Changes in hair pigmentation occur after about 5 months, and diarrhea
between 5 and 7 months. The diarrhea ceased 12 hours after oral administration of a small amount
(10 mg) of copper.
Copper-molybdenum-sulfate relationship
The interaction between copper, molybdenum, and sulfur in ruminant nutrition is unique in its
effects on health and production. Copper, molybdenum, and sulfur from organic or inorganic
sources can combine in the rumen to form an unabsorbable triple complex, copper
tetrathiomolybdate, and deplete the host tissues of copper (1).
Secondary or conditioned copper deficiency occurs when the dietary intake of copper is
adequate, but absorption and utilization of the copper are inadequate because of the
presence of interfering substances in the diet (1). Molybdenum and sulfate alone orin
combination can affect copper metabolism and the mechanisms by which this occurs are now
being clarified. This effect also operates in the fetus and interferes with copper storage in the fetal
liver. Besides the relationship with molybdenum, an interaction between the absorption of copper
and selenium has been demonstrated, the administration of selenium to sheep on copper-deficient
pastures causing an improvement in copper absorption.
The toxicity of any level of dietary molybdenum is affected by the ratio of the dietary
molybdenum to dietary copper. The critical copper:molybdenum ratio in animal feeds is 2, and
feeds or pasture with a lower ratio may result in conditioned copper deficiency. In some regions of

Canada, the copper: molybdenum ratio will vary from 0.1 to 52.7 (5). Higher critical ratios closer
to 4.1-5.1 have been recommended for safety (5). The influence of dietary molybdenum on copper
metabolismin ponies has been examined experimentally.
The copper status of growing calves can also be affected to a similar degree by the inclusion of
appropriate levels of sup-
1494
plementary iron or molybdenum in the diet. Following such inclusion, the liver and plasma
concentrations of copper will decline within 12-16 weeks to levels indicating severe copper
deficiency. The clinical signs of copper deficiency, as indicated by reduced growth rate and
changes in the hair texture and color, are evident after 16-20 weeks only in animals supplemented
with molybdenum. The reduced growth rate was accompanied by a decreased feed intake and
reduced efficiency of feed utilization.
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 from 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. Tins 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 existin 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 increasein intake reduces hepatic
storage of both copper and molybdenum.
Phases of copper deficiency
The development of a deficiency can be divided into tour phases:
1.Depletion

2.Deficiency (marginal)
3.Dysfunction
4.Disease.
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
thiomolybdatesin 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.
CLINICAL FINDINGS
The general effects of copper deficiency are the same in sheep and cattle, but in addition to these
general syndromes there are specific syndromes more or less restricted to species and to areas.
What follows is a general description of the disease caused by copper deficiency, in turn followed
by the specific syndromes of enzootic ataxia, swayback, falling disease, peat scours, teart, and
unthriftiness (pine).
Cattle
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
supoptimal.
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
Primary copper deficiency
Primary copper deficiency causes unthriftiness. loss of milk production, and anemia in adult cattle.
The coat color is affected, red and black cattle changing to a bleached, rusty red. and the coat itself
becomes rough and staring. In severely deficient states, which are now uncommon, calves grow
poorly, and there is an increased tendency for bones to fracture, particularly the limb bones and
the scapula. Ataxia may occur after exercise, with a sudden loss of control of the hindlimbs and
the annual tailing or assuming a sitting posture. Normal control returns after rest. Itching and
hair-licking are also recorded as manifestations of copper deficiency in cattle. Although diarrhea
may occur, persistent diarrhea is not characteristic of primary copper deficiency and its occurrence
should arouse suspicion of molybdenosis or helminthiasis. In some affected areas, calves develop

stiffness and enlargement of the joints and contraction of the flexor tendons causing the affected
animals to stand on their toes. These signs may be present at birth or occur before weaning.
Paresis and incoordination are not evident.
An increased occurrence of postparturient hemoglobinuria is also recorded,
1495
but only in New Zealand, and may be unrelated to copper deficiency.
Secondary copper deficiency
This syndrome includes the signs of primary copper deficiency, except that anemia occurs less
commonly, probably due to the relatively better copper status in the secondary state, anemia being
largely a terminal sign in primary copper deficiency. For example, anemia occurs in peat scours of
cattle in New Zealand, but in this instance the copper intake is marginal. In addition to the other
signs, however, there is a general tendency for diarrhea to occur, particularly in cattle. Because
diarrhea is not a major sign in naturally occurring primary copper deficiency it is possible that it is
due to the conditioning factor, which reduces the availability of copper. For example, the severity
of the diarrhea is roughly proportional to the level of intake of molybdenum.
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 hours 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 arc 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.
Sheep
General syndrome
Primary copper deficiency
Abnormalities of the wool are the first observed signs, and may be the only sign in areas of
marginal copper deficiency. Fine wool becomes limp, glossy and loses its crimp, developing a
straight, steely appearance. Black wool shows depigmentation to gray or white, often in bands

coinciding with the seasonal occurrence of copper deficiency. The straight, steely defect may
occur in similar bands, and the staple may break easily. There appear to be some differences
between breeds in susceptibility to copper deficiency. Merino sheep appearing to have a higher
copper requirement than mutton sheep. The fleece abnormalities of Merino sheep in Australia
have not been observed in Romney Marsh sheep in copper-deficient areas in New Zealand, but
this may be due in part to the difficulty of detecting abnormality in wool that is normally rather
straight and steely. Anemia, scouring, unthriftiness, and infertility may occur in conditions of
extreme deficiency, but in sheep the characteristic findings are in the lamb, the disease enzootic
ataxia being the major manifestation. Retardation of growth, diarrhea, delay to marketing, and
increased mortality are common clinical findings in lambs genetically selected for low plasma
copper and placed on improved and limed upland pastures. Osteoporosis, with increased tendency
of the long bones to fracture, has also been recorded under conditions of copper deficiency
insufficient to cause enzootic ataxia.
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 United Kingdom. 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 un-weaned lambs. In severe outbreaks the lambs may be
affected at birth, but most cases occur in the 1-2-month age group. The seventy 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
1496

kick vigorously even in the recumbent stage.the appetite remains unaffected.
Enzootic ataxia due to copper deficiency has been reported in young goat kids. The disease is
similar in most respects to the disease in lambs. Kids may be affected at birth, or the clinical signs
may be delayed until the animals are several weeks of age. Cerebellar hypoplasia is a frequent
finding in goats.
Other species
Deer
Enzootic ataxia in red deer is remarkably different from the disease in lambs in that it develops
in young adults well past wearning 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 (2). 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-deficent
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 (22). 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 were present.
The inclusion of copper sulfate, at levels of 125-250 mg/kg of copper, in the diets of pigs 11-90 kg
liveweight and fed ad libitum, results in slight improvements in growth rate and feed efficiency,
but has no significant effect on carcass characteristics (23). 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 liveweight.
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.
CLINICAL PATHOLOGY
The laboratory evaluation of the copper status of form animals is complex because the
biochemical values are often difficult to interpret and to correlate with the clinical state of the

animal. Interpretation of the copper status of an individual animal is more difficult than of a herd.
The guidelines for the laboratory diagnosis of primary and secondary copper deficiency in cattle
and sheep are summarized in Table 29.4.
HERD DIHAGNOSIS The diagnosis of copper deficiency in a herd of animals is based on a
combination of collection and interpretation of the history, clinical examination of the affected
animals, laboratory tests on serum and liver samples, and examination of the environment
including analysis of the feed and water supplies, and perhaps soil analysis (24).
It is necessary to be especially careful when collecting specimens for copper analysis to avoid
contamination by needles, copper distilled water, vial caps, cans for liver specimens, and other
possible sources of copper. An additional problem is the possible effect of intercurrent disease on
plasma levels of copper.
TREATMENT RESPONSE TRIAL A comparison of health and production variables in a group
of animals treated with copper, and a similar group not treated with copper, is also desirable.
Variables include calf growth rates, calf mortality, and reproductive performance.
COPPER STATUS OF HERD In order to assess the copper status of herd, a standard practice is
to take blood samples at random from at least 10% of clinically affected animals and from 10% of
normal animals. however, this may be inapprot
Table 29.4 Copper levels in body tissues and fluids in primary and secondary copper deficiency
Species and tissue Normal level Primary copper Secondary copper
deficiency
deficiency
Cattle
1.26±31
Less than 0.5 and as Less than 0.5 and as
Blood plasma More than 100 low as 0.1-0.2 low as 0.2-0.3
(fig/mL) (convert to (usually 200) Less than 20 and as Less than 10
SI units by
0.05-0.20
low as 4
5.5
multiplying
6.6-10.40.7-1.3More 0.01-0.02
0.4-0.7
by 15.7 which gives than 200 (usually 1.8-3.4
15-19
nmol/L). Adult liver 350+)
0.1-0.2
(mg/kg dry matter)
(convert to SI units by
multiplying by 0.0157
which gives mmol/kg)
Milk (mg/L) Hair
(mg/kg)
Sheep
Blood plasma (ug/mL)
Adult liver (mg/kg dry
matter)
20
1497
priate when there may be a wide variation in the serum copper concentration within a herd. In
some cases, a 10% sample may be too large and in other cases too small. The minimal sample size
for random samples from a finite population of a normal continuously distributed variable has
been calculated as follows:
[n = Nt2cv2/[(N-1)E2 t2cv2 ]]

Where n = minimal sample size; N= herd size; = Student t value; cv = coefficient of variation; and
E = allowable error. Initial testing can be used to estimate variability of serum copper
concentration within a herd, and a minimal sample size may be calculated. Each class of animal
according to age groups, diet, and production status should also be sampled. Follow-up samples
should be taken from the same animals following therapy or the institution of control measures.
Laboratory diagnosis
Historically, the laboratory diagnosis of copper deficiency in cattle and sheep centered on the
determination of serum or plasma copper and liver copper. However, it is now known that serum
copper levels alone are not reliable as indicators of copper status, and liver samples collected
either by liver biopsy or at slaughter should be used to accurately assess copper status in cattle (25,
26). Clinically normal animals may have marginal levels of serum copper, or unthrifty animals
may have marginal or deficient serum levels of copper. Furthermore, when either the normal
animals with the marginal levels of copper or the unthrifty animals with the marginal or deficient
levels are treated with copper there may or may not be an improvement in weight gain as might be
expected in the former, or improvement in clinical condition in the latter.
Phases
The development of a deficiency can be divided into four phases:
1.Depletion
2.Deficiency (marginal)
3.Dysfunction
4.Disease.
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:
•The relationships between the concentration of the marker and the intake of the element
•The time the animal is on an adequate diet
•Disturbances of tissue function.
From these principles, the concentrations of liver copper are insensitive indices of deficiency,
but good indicators of excess. Plasma copper less than 57µg/dL (9 µmol/L) is a good index of
marginal deficiency, but values may have to fall to below 19µg/dL.(3µmol/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.
Concentrations of copperin 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 (27). Among veterinary laboratories, there is a wide
variation in the normal range currently used for equine serum copper values (28).
Plasma and hepatic copper levels
Cattle and sheep
In cattle and sheep, plasma copper levels between 19µ g/dL and 57 µg/dL (3.0 and 9.0 µmol/L)
represent marginal deficiency, and levels below 19µg/dL (3 µmol/L) represent functional
deficiency or hypocuprosis. The internationally recognized threshold to assess copper deficiency
is 9.4µ mol/L (27). 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
9.3µ mol/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 copperin 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 to a normal of 31 mg/kg
(0.49 mmol/kg DM) in adults.
Milk and hair copper
The levels of copper in milk and hair are also lower in deficient than in normal cattle and
estimation of the copper content of hair is now acceptable as a diagnostic aid. It has the advantage
of providing an integrated progressive record of nutritional intake. The levels of copper in bovine
hair are more markedly depressed when extra molybdenum is fed.
Ceruloplasmin
The difficulty of interpreting plasma levels of copper led to the estimation of plasma levels of
copper-protein complexes, especially ceruloplasmin. Ceruloplasmin
1498
contains greater than 95% of the circulating copper in normal animals. There is a highly
significant correlation between plasma copper levels and plasma ceruloplasmin activity, which is a
less complicated and more rapid procedure than plasma copper. The regression analyses indicate a
strongly positive correlation coefficient of ceruloplasmin with serum of cattle and sheep of 0.83
and 0.92,respectively. The correlation between serum ceruloplasmin activity and hepatic copper
concentrations in cattle was only 0.35, indicating an unreliable relationship. Normal plasma
ceruloplasmin levels in sheep are in the region of 45-100 mg/L. Normal levels of serum
ceruloplasmin activity in cattle range from 120 to 200 mg/L. The mean copper and ceruloplasmin
levels are higher in plasma than serum; the percentage of copper associated with ceruloplasmin is
lessin serum (55%) thanin plasma (66%). Normal plasma ceruloplasmin levelsin sheep range from
4.5 to 10 mg/dL. In experimental primary copper deficiencyin calves, rapid decreases occurin

plasma ceruloplasmin activity at least 80 days before overt clinical signs of deficiency.
Erythrocyte dismutase
The measurement of the activity of erythrocyte superoxide dismutase (ESOD), a
copper-containing enzyme, is now being evaluated as a procedure for the diagnosis of copper
deficiency. The activity of this enzyme decreases more slowly than plasma or liver copper in
copper-deficient animals and may be more closely correated with the presence of imminence of
hypocuprosis. In marginal deficiency, the ESOD value ranges from 2 to 5 U/mg hemoglobin, and
in functional deficiency the value is below 2 (29).
Hepatic copper
Because the liver is a storage compartment for copper, the concentrations of liver copper indicate
the state of depletion rather than deficiency. There is no particular threshold value for liver copper
below which the performance and health of livestock are likely to be impaired. A broad range of
values may, for example, coincide with the marginally deficient state, e.g. 5.1-20.3 mg (0.08-0.32
mmol) copper/kg liver DM. The concentration of hepatic copper in sheep is uniform, and a single
biopsy sample should be representative of the whole liver. The technique of liver biopsy for
assessing the copper status of sheep has been evaluated. Frequency of biopsy does not affect
copper concentration, the variability between successive samples is small, and the biopsy
procedure does not reduce body weight or rate of gain. Copper concentrations in the kidney cortex
may be of more diagnostic value because concentrations are normally within a narrow range of
12.7-19.0 mg/kg DM (0.2-0.3 mmol/kg DM). Thus, concentrations below 12.7 mg/kg DM (0.2
mmol/kg DM) in the kidney may be a more reliable indicator of dysfunction than liver copper
concentration.
Horses
A threshold level of plasma copper of 16 umol/L is used to distinguish between the normal and
subnormal values (30). Liver copper from horses sampled at slaughter vary widely about a mean
of 113.7n.mol/kg WW (30). The threshold of 52.5 umol/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 umol/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 umol/g DM) tissue. The plasma copper concentrations
ranged from 3.58 to 4.45 ug/dL (22.8-28.3 umol/L). There was no simple mathematical
relationship between plasma and hepatic copper concentrtions. The range of serum copper
concentrations in Thoroughbred horses at grass was 63-196 ug/dL (9.91-30.85 mmol/L), and in
stabled Thoroughbreds the range was 47-111 ug/dL (7.40-17.47 mmol/L).
Hematology
Anemia may occur in advanced cases of primary copper deficiency, hemoglobin levels being
depressed to 50- 80 g/L and erythrocytes to 2-4 X 10 12 /L. A high proportion of cows in problem
herds may have a Heinz-body anemia without evidence of hemoglobinuria, and the severity of the
anemia will be related to the hypocupremia.
NECROPSY FINDINGS
The characteristic gross findings in copper deficiency of ruminants are those of anemia and
emaciation. Hair and wool abnormalities may be present as already described. Extensive deposits
of hemosiderin can cause darkening of the liver, spleen and kidney in most cases of primary
copper deficiency, and in the secondary form if the copper status is sufficiently low. In lambs

there may be severe osteoporosis and long bone fractures. Osteoporosis is less evident in cattle,
but can be confirmed radiographically and histologically. In naturally occurring secondary copper
deficiency in cattle, associated with high dietary molybdenum and sulfate, there is widening of the
growth plates due to abnormal mineralization of the primary spongiosia, resulting in a grossly
rachitic appearance to the bones.
The most significant finding in enzootic ataxia is the degeneration of axons and myelin within
the cerebellar and motor tracts in the spinal cord, a change only evident at the microscopic level.
Chromatolysis of neurons in a variety of locations within the central nervous system is usually
detectable. In a few extreme cases, and in most cases of sway-back, the myelin loss also involves
the cerebrum, where there is destruction and cavitation of the white matter. There is marked
internal hydrocephalus in such cases and the convolutions of the cerebrum are almost obliterated.
Acute cerebral edema with marked brain swelling and cerebellar herniation, reminiscent of
polioencephalomalacia, may also accompany the more typical myelopathy and multifocal cerebral
leukomalacia in lambs with hypocuprosis.
In falling disease, the heart is flabby and pale. There is generalized venous congestion and the
blood may appear watery. The liver and spleen are enlarged and dark. Histological examination
reveals atrophy of the cardiac muscle fibers and considerable cardiac fibrosis. Deposits of
hemosiderin are present in the liver, spleen and kidney.
Necropsy findings associated with copper deficiency in non-ruminant species are not
well-documented. Degenerative changes with subsequent rupture of the aorta have been
experimentally induced in swine, but this has not been described as a naturally occurring disease.
A myelopathy with white matter changes similar to those of enzootic ataxia has also been reported
in 4-5-month-old copper-deficient pigs. Musculoskeletal changes
1499
similar to those described for calves have also been reported in foals with hypocuprosis.
Necropsy examinations should include assay of copper in viscera .The levels of copper in liver
are usually low (see Table 29.4), and in secondary copper deficiency there may be a high level of
copper in the kidney, and high levels of molybdenum in the liver, kidney, and spleen. Copper
levels in body tissues and Hinds in primarm and secondary copper deficiency are listed in Table
29.4.
Samples for confirmation of diagnosis
•Toxicology - 50 g liver, kidney(ASSAY (Cu) (Mo)).
•Histology - formalin-fixed samples of:long bone (including growth plate),skin, liver, spleen.
Enzootk ataxia/
swaybaik: halt of midsagittally-sectioned brain, lumbar and cervical spinal cord. Falling disease:
heart (several sections), bone marrow, spleen(LM).
DIFFERENTIAL DIAGNOSIS
The clinical findings which are common in young, growing ruminants, include a herd problem of
unthriftiness and progressive loss of weight, changes in hair coat color or texture of wool, chronic
lameness, neonatal ataxia in lambs and kids, and terminal anemia. In adult cattle on pasture with
excess molybdenum, chronic diarrhea is charactic. A combination of serum and liver copper, and
serum molybdenum, are major diagnostic aids in distinguishing between copper deficiency and
the other diseases.
Several disease complexes that are herd or flock problems in cattle and sheep may resemble

oth primary and secondary copper deficiency. The emphasis is on many animals being affected at
about the same time, with a chronic debilitating disease complex, under the same dietary and
seasonal circumstances.
Cattle
Unthriftiness and progressive weight loss may be due to protein-energy malnutrition and
examination of the diet will reveal the cause.
Changes in hair coat color in young growing cattle is caused only by copper deficiency.
Chronic lameness in young growing cattle may be caused by a calcium, phosphorus and
vitamin D imbalance,which is determined by examination of the diet and radiography of the long
bones. The radiographic changes in cattle with secondary copper deficiency consist of widened
irregular epiphyseal plates with increased bone density in the metaphysis and metaphyseal lipping.
These findings are similar to those described for rickets and secondary nutritional
hyperparathyroidism in cattle.
Chronic diarrhea in young cattle may be due to intestinal parasitism and fecal examination
and response to therapy are diagnostic. Diarrhea in a group of adult cattle on pasture known to be
high in molybdenum is probably due to secondary copper deficiency and response to therapy is
diagnostic.
Winter dysentery of cattle, salmonellosis, coccidiosis and mucosal disease are acute diseases
characterized by diarrhea but are accompanied by other signs and clinicopathological findings
which facilitate their identification. Many poisons, particularly arsenic, lead and salt, cause
diarrhea in ruminants but there are usually additional diagnostic signs and evidence of access to
the poison. Assay of feed and tissues helps to confirm a diagnosis of poisoning.
A diagnosis of peat scours is usually made if there is an immediate response to oral dosing
with a copper salt.
Falling disease occurs only in adult cattle and must be differentiated from other causes of
sudden death. Poisoning by the gidgee tree (Acacia georginaa) produces a similar syndrome in
cattle.
Sheep and goats
Unthriftiness and abnormal wool or hair as a flock or herd problem are characteristic of copper
deficiency in sheep and goats, which must be differentiated from protein-energy malnutrition,
intestinal parasitism, cobalt deficiency, and external parasites.
Lameness in a group of lambs several weeks of age must be differentiated from nutritional
osteodystrophy due to a calcium, phosphorus and vitamin D deficiency or imbalance, stiff lamb
disease due to enzootic muscular dystrophy.
Neonatal ataxia caused by congenital swayback and enzootic ataxia in newborn lambs and kids
due to maternal copper deficiency must be differentiated from border disease of newborn lambs,
characterized by an outbreak of newborn lambs with hairy fleece and tremors, cerebellar
hypoplasia (daft lamb disease), and hypothermia.
TREATMENT
The treatment of copper deficiency is relatively simple, but it advanced lesions are already present
in the nervous system or myocardium complete recovery will not occur. Oral dosing with 4 g of
copper sulfate for calves from 2 to 6 months of age and 8-10 g for mature cattle given weekly for
3-5 weeks is recommended tor the treatment of primary or secondary copper deficiency.
Parenteral injections of copper glycinate may also be used and the dosages are given under control.

The diet of affected animals should also be supplemented with copper. Copper sulfate may be
added to the mineral-salt mix at a level of 3-5% of the total mixture. A commonly recommended
mixture for cattle is 50% calcium-phosphorus mineral supplement. 45% cobalt-iodized salt, and
3-5% copper sul-tate. This mixture is offered free of choice or can be added to a complete diet at
the rate of 1% of the total diet.
CONTROL
Dietary requirements
The minimum dietary requirement for copper for cattle is 10 mg copper/kg DM and 5 mg/kg DM
for sheep.
The requirement necessary to prevent subclinical or clinical copper deficiency will depend on
the presence of interfering substances such as molybdenum, sulfur and iron in the diet and
possibly the genotype of the animal. Copper sulfate is considered a better supplement than copper
oxide needles or injectable copper for cattle consuming diets containing excess molybdenum or
molybdenum plus sulfur. Although there is a marked difference between breeds of sheep in their
susceptibility to hypocuprosis, this would not seem to have an immediate practical application.
The estimated copper requirement in the diet of mature ponies is 3.5 mg/kg DM.
Copper can he supplied by several different methods as outlined below. The dose rates given
are those recommended for the control of primary copper deficiency, and these may have to be
increased or treatment given more frequently in some instances of secondary copper deficiency. In
these circumstances it is often necessary to determine the most satisfactory dosing strategy by a
field trial.
Copper sulfate
Oral closing
Oral dosing with copper sulfate (5 g tocattle, 1.0 g to sheep, weekly) is adequate
1500
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
The copper sulfate may be mixed with other minerals into a mineral premix, which is then
incorporated into the concentrate part of the ration. The final concentration of copper is usually
adjusted to provide an overall intake of at least 10 ppm of copper in the DM of the final ration. If
the forage components of the ration contain much less than 10 ppm, the concentrate part of the
ration may need to contain much larger concentrations of copper. Where a secondary copper
deficiency is due to molybdenum in the forage, up to 1200 mg copper (approximately 5 g of
hydrated copper sulfate) is added to the concentrate daily. When sheep are grazing toxic lupin
stubble, the signs of lupinosis may be exacerbated by the supplementation of only 10 mg
copper/kg DM as copper sulfate, and therefore the supply of copper in the absence of suitable
amounts of molybdenum and sulfur should be kept to a minimum (31).
If animals are not receiving concenrates containing copper, an alternative is to provide free
access to a mineral mixture or salt-lick containing 0.25-0.5% of copper sulfate for sheep and 2%
for cattle, which will supply sufficient copper provided an adequate intake of the mixture is
assured. The mineral mixture usually contains iodized salt, cobalt, calcium, phosphorus, and other

trace minerals.
In some deficient areas, an effective method of administering copper is by the annual
top-dressing of pasture with 10 kg/hectare copper sulfate, although the amount required mayvary
widely with the soil type and the rainfall. Top-dressing may cause copper poisoning if livestock
are turned onto pasture while the copper salt is still adherent to the leaves. Treated pasture should
be left unstocked for 3 weeks or until the first heavy rain. It is also possible that chronic copper
poisoning may result if the copper status of the soil increases sufficiently over a number of years.
Addition of copper salts to drinking water is usually impractical because the solution corrodes
metal piping, and maintenance of the correct concentration of copper in large bodies of water is
difficult. However, if the need is great, some way around these difficulties can usually be found
and a system has been devised for automatic supplementation for short periods via the drinking
water, and has been effective in controlling copper deficiency in cattle. Copper pellets which
provide 2-3 mg copper/L of water have been recommended for cattle. Calves can tolerate copper
in milk replacers at a concentration of 50 ppm but there is no advantage in providing more than 10
ppm.
There is no evidence that copper or molybdenum supplementation of the diets of pregnant ewes
and lambs at 10 mg/kg DM had any effect on selenium status.
Removal of sulfates
The removal of sulfates from drinking water by water purification, using a process of reverse
osmosis, may have a positive effect on the copper status of beef cows. Cows drinking desulfated
water had an increased availability of copper compared to those drinking water containing a large
concentration of sulfates.
Parenteral injections of copper
To overcome the difficulty of frequent individual dosing or top-dressing of parture, periodic
parenteral injection of copper compounds that release copper gradually has given good results.
They can be given at strategic times depending on the circumstances. They also have the
advantage of avoiding fixation of copper by molybdenum in the alimentary tract. Injectable
preparations of copper are now the method of choice for the prevention of swayback in lambs. The
following have been evaluated under field conditions:
•Copper calcium ethylenediamine tetra-acetate (copper calcium
edetate)
•Copper methionate
•Copper heptonate
•Copper glycinate
•Copper oxyquinoline sulfonate.
The criteria used to judge these injections are minimal damage at the site of injections,
satisfactory liver storage (90-100%) of the administered dose, and a safe margin between
therapeutic and toxic doses. The dose of copper in any of the compounds for cattle is 400 mg and
for sheep 150 mg. Copper heptonate at the rate of 25 mg of copper in 2 mL of preparation given
by IM injection to ewes in mid-pregnancy was successful in preventing swayback in lambs.
Copper calcium edetate has the advantage of giving maximum copper storage very quickly - 1
week after injection - and blood levels are elevated within a few hours. Because of the rapidity of
the absorption, toxic effects can be encountered unless proper dose levels are observed. As well as
deaths from serious overdosing, some deaths occur in groups of sheep for unexplained reasons. It

is suggested that stress be minimized and simultaneous other therapy be avoided.
A marked local reaction occurs at the site of injection so that SC injection is preferable in
animals to be used for meat, although to avoid an unsightly blemish, breeding animals should
receive an IM injection. The injections are a small risk for precipitating blackleg in cattle on farms
where this disease occurs. For sheep, a single injection of 45 mg of copper as copper glycinate in
midpregnancy is sufficient to prevent swayback in the lambs.
The SC injection of copper calcium edetate or copper oxyquinoline sulfonate into sheep
results in a rapid increase in the concentration of copper in whole blood, serum, and urine within
the first 24 hours. Following the injection of copper methionate, the concentration of. copper in
blood and serum rises steadily over a period of 10 days, and there is no detectable increase in
urinary copper. After the injection of any of the three compounds, there is a steady increase in
serum ceruloplasmin activity over a period of 10-20 days, followed by a slow fall to preinjection
activity by 40 days. The lower toxicity of copper injected as methionate compared with that as
copper calcium edetate or copper oxyquinoline sulfonate is due to the slower absorption and
transport of the copper to the liver and kidney. Death has occurred in sheep following the
parenteral administration of diethylamine oxyquinoline sulfonate at recommended doses. Affected
sheep manifested signs of hepatic encephalopathy, and at necropsy there was acute, severe,
generalized, cen-
1501
trilobular hepatocellular necrosis. The use of copper disodium edetate at recommended doses in
calves has also resulted in deaths associated with liver necrosis and clinical signs of hepatic
encephalopathy.
Injectable copper glycinate is an excellent source of supplementary copper for increasing the
concentration of copper in the serum of copper-deficient cattle and maintaining grazing cattle in
an adequate copper status. One dose of copper glycinate will maintain adequate copper levels for
about 60-90 days. The recommended dose in beef herds is 120 mg of copper for adult cattle and
60 mg of copper for calves. A supplemental source of copper is required for the calf during the
pasture season because milk is a poor source of copper, particularly from copper-deficient cows,
and calves do not have the opportunity to increase or maintain body stores of copper while grazing.
When the dam is severely hypocupremic in the spring, the calf is also severely hypocupremic or
copper-deficient. Insufficient copper is secreted into the milk of copper-treated cows. Therefore,
where the dam has not received an adequate copper intake during pregnancy, direct treatment of
the calf will be required in early life. The copper reserves of newborn calves are increased in fetal
liver at the expense of copper stores in the dam's liver, which are dependent on the availability ot
dietary or supplemental copper to the dam. Calves usually have sufficient liver copper at birth and
do not need an injection of 50 mg until they are 6 weeks old. Because of the higher requirements
for copper during the last trimester of pregnancy (demands of the fetal liver), a program of copper
supplementation should involve the use of copper supplements, throughout the year as required.
One dose of copper glycinate is sufficient when cattle are grazing forage that contains no more
than 3 mg/kg DM of molybdenum and 3 g/kg DM of sulfur. With higher levels of molybdenum
and sulfur, repeated injections of copper glycinate are recommended. The injectable copper may
be supplemented by the use of copper sulfate in a mineral supplement at a level of 1%. The
inclusion of copper sulfate in the mineral supplement may be adequate for cows, but the calves
may not consume an adequate amount of mineral and injectable copper. The level of

supplementation required to prevent a drop in serum copper over the pasture season will depend
upon the concentration of dietary molybdenum and sulfur and their effect upon the coefficient of
absorption of copper.
Injectable copper complex compounds have been evaluated as supplementary copper for
grazing beef cattle under Canadian conditions. Copper edetate at 100 mg of copper, copper
glycinate at 120 mg, and copper methionate at 120 mg were used and were equally effective in
improving copper status of copper-deficient cattle and maintaining them in an adequate copper
status for 90 days (32). The copper methionate was least acceptable because of the incidence and
severity of reactions at the site of injection.
Controlled-release glass
Death due to poisoning is one of the dangers of parenteral administration because it is difficult to
control the rate at which the supplement releases the copper, especially if the controlling
mechanism is chemical binding. Methods used to control the release include the development of
soluble controlled-release glass for oral administration to sheep and cattle. The copper is slowly
released, absorbed, and stored in the liver. Initial field evaluations indicate that the boluses may
not contain sufficient copper to maintain normal levels of copper for a sufficient length of time
compared to the use of copper oxide needles.
Boluses of a soluble copper-containing controlled-release glass have been devel¬oped and
evaluated. The boluses are based on a phosphate-type glass into which appropriate quantities of
trace elements are incorporated. The boluses lodge in the rumen and release copper at a slow rate.
They can provide additional supplies of copper to ruminants at an almost uniform rate for many
months. One commercial product contains selenium and cobalt, and in one experiment increased
ceraloplasmin activity for at least 1 year. In one field study, the admin¬istration of two
commercial soluble glass boluses containing copper and selenium, the selenium levels were
increased from marginal to adequate, but adequate copper levels were not maintained.
Copper oxide needles
Copper oxide needles or wire particles (fragments of oxidized copper wire up to 8 mm in length
and 0.5 mm in diameter) are used for oral dosing and one of the most effective and safest methods
for the control of copper deficiency in ruminants. Its major advantages are prolonged effectiveness
and low cost. A single treatment can be effective for an entire summer or winter season. The
needles are retained in the forcstomachs and aboma-sum for up to 100 days or more and the
copper is slowly released, absorbed, and stored in the liver. A dose of 0.1g/kg live weight (5g) 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 cop¬per concentrations will peak 10 weeks after administration and
will thereafter decline in a linear fashion over the next 40 weeks. A single dose of 20g of copper
oxide needles to hypocupremic suclder 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 hypocuprcrma, 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. 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 reseed-ing. The
treatment maintained the lambs in norrnocupremia, provided adequate liver copper reserves,
prevented clinical signs of hypocuprosis, and produced a liveweight gain advantage. The
administration of the needles to ewes in the first half of pregnancy is also effective for the
1502
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 treat-ment of the
ewes at parturition also resulted in higher concentrations of cop- per 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 propen-sity 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 powder
Copper oxide powder administered in the form of experimental, sustained-release rumen boluses
significantly increased blood and liver copper concentrations in growing sheep, in out-wintered
stickler cows during late pregnancy and early lactation, and m growing cattle at grass in the
summer periods over periods of at least 170 and 123 days, respectively (33).
Genetic selection
It is now possible to manipulate trace element metabolism by genetic selection in farm animals.
Within a period of 5 years, selection of sheep based on plasma concentration of copper resulted in
two divergent sets of progeny, one with a high level of copper status, the other with a low level,
which resulted in clinical manifestations of copper deficiency in the low level and protection in
the high level.
General guidelines
Several rules of thumb are important and useful.
•A dietary intake of copper equivalent to l0mg/kg DM will prevent the
occurrence of primary copper deficiency in both sheep and cattle •Diets containing less than 5
mg/kg DM will cause hypocuprosis
•Diets with copper: molybdenum ratios of less than 5:1 are conducive to conditioned (secondary)
hypocuprosis
•The newborn calf is protected against neonatal hypocuprosis by donations from the dam, but
newborn lambs assume the same copper status as the ewe •Cattle are more susceptible to copper
deficiency than are sheep.
REVIEWUTERATUE Gooneratne, S. R., Buckley, W. T. & Christensen, D. A. (1989) Review of
copper
deficiency and metabolism in ruminants. Can.J.Anim.Sci.,69,819-5. Smart, M. E., Cymbaluk, N. .

f& Christensen,
D. A. (1992) A review of copper status of cattle in Canada ami recommendations for
supplementation. Can. Vet.J, 33, 163-170. Suttle, N. F. (1986) Problems in the diagnosis and
anticipation of trace element deficiencies in grazing livestock. Vet.Rec, It9, 148-152.
Suttle, N. F. (1986) Copper deficiency in ruminants, recent developments. Vet. Rec, 119, 519-522.
Suttle, N. F. (1987) The nutritional requirement for copper in animals and man. In: Copper in
Animals and Mem. Volume I. Eds HoweU,
M. & Gawthorne, J. M. Boca Raton, FL:
CRC Press, pp. 21-43. Suttle, N. F. (1991) The interactions between copper, molybdenum, and
sulphur in ruminant nutrition. Ann. Rcir. Nutr., 1 /, 121-140.
Suttle, N. F. (1994) Meeting the copper requirements of ruminants: In: Recent Advances in
Animal Nutrition. Eds Garnsworthy, P. C. & Cole, D.J. A.
Nottingham: Nottingham Univ. Press, pp. 173-187. Wikse, S. E., Herd, IX, Field, R. & Holland, P.
(1992) Diagnosis of copper deficiency m cattle./ Am. Vet. Med. Assoc, 200, 1625-1629.
REFERENCES
(1)Suttle, N. F. (1992) Ann. Rev. Nutr., II, 121.
(2)Thompson, K. G. el al. (1994) NZ Vei.J., 42, 137.
(3)Gooneratne, S. R. & Christensen, D. A. (1989) Can. J. Anim. Sci., 69, 141.
(4)Knight, D. A. et al. (1990) Equine Vet.J., 22, 426.
(5)Smart, M. E. et al. (1992) Can. Vet.}., 33, 163.
(6)Suttle, N. F. (1986) Vet. Rec. 119, 519.
(7)WooliamsJ. A. et al. (1985) Anim. Prod., 41, 219.
(8)WardJ. D. et al. (1995) /. Anim. Sci., 13, 571.
(9)Gooneratne, S. R. et al. (1994) Can). Anim. Sci., 14, 315.
(10)Gooneratne. S. R. et al. (1989) Can.}. Anim. Sci., 69, 819.
(11)Graham, T. W. et al. (1994)J. Vet. Diagn. Invest., 6, 77.
(12)SchonewilleJ. T. et al. (1995) Vet. Quart.. 11, 14.
(13)Sas, B. (1989) Vet. Hum. Toxuol., 31. 29.
(14)Suttle, N. F. (1987) In: Copper in Animals and Man Volume I. Eds HowellJ. M. & Gawthorne,
J. M. Boca Raton, FL: CRC Press, pp. 21 43.
(15)Bridges, C. H. & Moffitt, P. G. (1990) Am.]. Vet. Res., 51, 275.
(16)Flurtig, M. et al. (1991) Proc. Amu Cow. Am. Assoc. Equine Pract., 36, 637.
(17)Hurtig, M. ct al. (1993) Equine Vet.J., Suppl., 16, 66.
(18)Hoyt, Z. K. et al. (1995)7. Equine. Vet. Sci., 15, 357.
(19)Wildman, R. E. C. et al. (1996) Biol. Trace Element. Res., 55, 55.
(20)Stabel.J. R. et al. (1993)/ Anim. Sci., 11, 1247.
(21)Arthington.J. D. ct al. (1995) /. Anim. Sci., 13, 2079.
(22)Fyffe.J.J. (1996) Aust. Vet.J., 13, 188.
(23)BowlandJ. V. (1990) % News & Info., 11, 163.
(24)Wikse, S. E. et al. (1992) /. Am. Vet. Med. Assoc, 200, 1625.
(25)Vermunt, J. J. ik West, D. M. (1994) NZ Vet.J., 42, 194.
(26)Clark, R. G. & Ellison, R. S. (1993) NZ Vet.J., 41, 98.
(27)Suttle, N. F. (1993) Vet. Rec, 133, 123.
(28)Mee.J. F. & McLaughlm, J. (1995) Vet. Rec, 136. 275.

(29)Suttle, N. F. (1986) Vet. Rec, 119, 148.
(30)Suttle, N. F. et al. (1996) Equine Vet.J..2H, 497.
(31)White. C. F. et al. (1994) Ausl.J. Agr.Res., 45, 279.
(32)Boila, R. J. et al. (1984) Can.}. Arum. Sci.,64. 365.
(33)Parkins, J. J. et al. (1994) Br. Vet.J., 150,547.
IODINE DEFICIENCY
Synopsis
Etiology. Primary dietary deficiency ofiodine or secondary toconditioning factors such as calcium,
Brassica plants, or bacterial pollution of water. Epidemiology. In all species, most common in
continental land masses. Neonatal animals. Diets of dams deficient in iodine or containing
conditioning factors such as certain plants.
Signs. Goiter as palpable enlargement of thyroid gland. Neonatal mortality due to stillbirths, weak
neonates may not be able to suck and die in few days, alopecia at birth, myxedema. Clinical
pathology. Blood iodine levels.
Lesions. Thyroid enlargement, alopecia, myxedema. Diagnostic confirmation. Goiter and iodine
deficiency.
Differential diagnosis list:
•Weak calf syndrome
•Abortion
1503
•Congenital defects (Chapter 34).
Treatment. Not usually undertaken.
Control. Insure dietatry intake of iodine in pregnant animals
ETIOLOGY
Iodine deficiency may be due to deficient iodine intake or secondarily conditioned by a high
intake of calcium, diets consisting largely of Brasska spp., or gross bacteial pollution of feedstuffs
or drinking water. A continued intake of a low level of cyanogenetic glycosides, e.g. in white
clover, is commonly associated with a high incidence of goitrous offspring. Lmamann, a glycoside
in linseed meal, is the agent producing goiter in newborn lambs born from ewes fed the meal
during pregnancy. A continued intake of the grass Cynodon aethiopicus with low iodine and high
cyanogenetic glucoside contents may cause goiter in lambs. Rapeseed and rapeseed meal are also
goitrogenic.
EPIDEMIOlOGY
Occurrence
Goiter caused by iodine deficiency occurs in all of the continental land masses. It is not ot major
economic importance because of the ease of recognition and correction, but if neglected may
cause heavy mortalities in newborn animals. The most common cause of iodine deficiency in
farm animals is the failure to provide iodine in the diet. The sporadic occurrence of the disease
in marginal areas attracts most attention. An epi-demiological survey in Germany found up to
10% of cattle and sheep farms, and 15% of swine herds were affected with iodine deficiency,
which were both primary and secondary due to the presence of nitrates, thiocyanates or
glucosinolates in the diet (1).
The importance of subclinical iodine deficiency as a cause of neonatal mortality could be much
greater than clinical disease. For example, in southern Australia ewes supplemented with iodine

y the single injection of iodine in oil, have had less mortality in the lambs, have grown larger
lambs, or performed the same as controls.
Young animals are more likely to bear goitrous offspring than older ones and this may account
for the apparent breed susceptibility of Dorset Horn sheep, which mate at an earlier age than other
breeds.
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. 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 arc, 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.
Risk factors
Dietary and environmental factors
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. Hypothyroidism has also
been produced in rats by feeding rape-seed, and in mice by feeding rapeseed oil meal, heeding
large quantities of kale to pregnant ewes causes a high incidence of goiter and hypothyroidism,
also pre¬ventable by administering iodine in the newborn lambs. The goitrogenic substance in
these plants is probably a glu-cosinolate capable of producing thiocyanate in the rumen. The
thio-cyanate 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
glyco-side-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 7µg/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 new¬born lambs of ewes grazing on pasture dominated by
white clover and by subterranean clover and perennial ryegrass.
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.
1504
PATHOGENESIS
Iodine deficiency results in a decreased production of thyroxine and stimulation of the secretion of
thyrotropic hormone by the pituitary gland. This commonly results in hypcrplasia of thyroid tissue
and a considerable enlargement of the gland. Most cases of goiter of the newborn are of this type.
The primary deficiency of thyroxine is responsible for the severe weakness and hair abnormality
of the affected animals. Although the defect is described as hairlessness, it is truly hypoplasia of
the hairs, with many very slender hairs present and a concurrent absence and diminution in size of
hair follicles. A hyperplastic goiter is highly vascular and the gland can be felt to pulsate with the
arterial pulse and a loud murmur may be audible over the gland. Colloid goiter is less common in
animals and probably represents an involutional stage after primary hyperplasia.
Other factors, particularly the ingestion of low levels of cyanide, exert their effects by inhibiting
the metabolic activity of the thyroid epithelium and restricting the uptake of iodine. Thiocyanates
and sulfocyanates are formed during the process of detoxication of cyanide in the liver and these
substances have a pronounced depressing effect on iodine uptake by the thyroid. Some pasture and
fodder plants, including white clover, rape and kale, are known to have a moderate content of
cyanogenetic glucosides. These goitro-genic substances may appear in the milk and provide a
toxic hazard to both animals and man. The inherited form in cattle is due to the increased activity
of an enzyme that deiodinatesiodotyrosines so rapidly that the formation of thyroxine is inhibited.
Iodine is an essential element for normal fetal brain and physical development in sheep. A
severe iodine deficiency in pregnant ewes causes reduction in fetal brain and body weight from 70
days of gestation to parturition. The effects are mediated by a combination of maternal and fetal
hypothyroidism, the effect of maternal hypothyroidism being earlier than the onset of fetal thyroid
secretion (2). There is also evidence of fetal hypothyroidisms, and absence of wool growth and
delayed skeletal maturation near parturition.
CLINICAL FINDINGS
Although loss of condition, decreased milk production, and weakness might be anticipated these
signs are not usually observed in adults. Loss of libido in the bull, failure to express estrus in the
cow, and a high incidence of aborted, stillborn or weak calves have been suggested as

manifestations of hypothyroidism m cattle, whereas prolonged gestation is reported in mares, ewes,
and sows.
A high incidence of stillbirths and weak, newborn animals is the most common manifestation
of iodine deficiency. Partial or complete alopecia and palpable enlargement of the thyroid gland
are other signs that occur with varying frequency in the different species. Affected foals have a
normal hair coat and little thyroid enlargement, but are very weak at birth. In most cases they are
unable to stand without support and many are too weak to suck. Excessive flexion of the lower
forelegs and extension of lower parts of the hindlegs has also been observed in affected foals.
Defective ossification has also been reported, the manifestation is collapse of the central and third
tarsal bones leading to lameness and deformity of the hock. Enlargement of the thyroid also occurs
commonly in adult horses in affected areas, Thoroughbreds and light horses being more
susceptible than draft animals.
In cattle, the incidence of thyroid enlargement in adults is much lower than in horses and the
cardinal manifestations are gross enlargement of the thyroid gland and weakness in newborn
calves. If they are assisted to suck for a few days, recovery is usual, but if they are born on the
range during inclement weather many will die. In some instances, the thyroid gland is sufficiently
large to cause obstruction to respiration. Partial alopecia is a rare accompaniment.
In pigs, the characteristic findings are birth of hairless, stillborn or weak piglets often with
myxedema of the skin of the neck. The hairlessness is most marked on the limbs. Most affected
piglets die within a few hours of birth. Thyroid enlargement may be present but is never
sufficiently great to cause visible swelling in the live pig. Survivors arc-lethargic, do not grow
well, have a waddling gait and leg weaknesses due to weakness of ligaments and joints.
Adult sheep in iodine-deficient areas may show a high incidence of thyroid enlargement but are
clinically normal in other respects. Newborn lambs manifest weakness, extensive alopecia and
palpble, if not visible, enlargement of the thyroid glands. Goats present a similar clinical picture,
except that all abnormalities are more severe than in lambs. Goat kids are goitrous and alopecic.
The degree of alopecia varies from complete absence of hair, through very fine hair, to hair that is
almost normal.
Animals surviving the initial danger period after birth may recover, except for partial
persistence of the goiter. The glands may pulsate with the normal arterial pulse and may extend
down a greater part of the neck and cause some local edema. Auscultation and palpation of the
jugular furrow may reveal the presence of a murmur and thrill, the 'thyroid thrill', due to the
increased arterial blood supply of the glands.
Experimental hypothyroidism produced in horses by surgical excision of the gland results in a
syndrome of poor growth, cold sensitivity, long, dull hair coat, docility, lethargy, edema of
hindlimbs and a coarse, thick appearance of the face. The rectal temperature is depressed and
blood cholesterol levels are high. Administration of thyroprotein reverses the syndrome.
CLINICAL PATHOLOGY
Estimations of iodine levels in the blood and milk are reliable indicators of the thyroxine status of
the animal. Organic or protein-bound iodine is estimated in serum or plasma and used as an index
of circulating thyroid hormone, provided access to exogenous iodine in the diet, or as treatment, is
adequately controlled. There may be between-breed differences in blood iodine levels but levels of
2.4-14 µg of protein-bound iodine per 100 mL of plasma appear to be in the normal range. In ewes,
an iodine concentration in milk of below 8 µg/L indicates a state of iodine deficiency.

Levels of thyroxine in the blood have not been much used to measure thyroid gland sufficiency
in animals. Work in ewes has shown that normal lambs at birth have twice the serum thyroxine
levels of their dams, but goitrous lambs have levels less than those of their dams. However, low
mean thyroxine levels (50 nmol/L is normal) are not a definitive indication of iodine deficiency
because of the variety of factors affecting thyroxine levels. These levels fall rapidly soon after
birth and approximate the dam's levels at 5-6 weeks of age.
Bloodcholesterollevelshavebeen
1505
used as an indicator of thyroid function in humans but are not used in the investigation of goiter in
animals.
In determining the iodine status of an area, iodine levels in soil and pasture should be obtained
but the relationship between these levels, and between them and the status of the grazing animal,
may be complicated by conditioning factors.
NECROPSY FINDINGS
Macroscopic thyroid enlargement, alopecia and myxedema may be evident. The weights of
thyroid glands have diagnostic value. In full-term normal calves the average fresh weight is 6.5g,
in lambs 2g is average. The iodine content of the thyroid will also give some indication of the
iodine status of the animal. At birth a level of 0.03% of iodine on a wet weight basis (0.1% on dry
weight) can be considered to be the critical level in cattle and sheep. On histological examination,
hyperplasia of the glandular epithelium may be seen. The hair follicles will be found to be
hypoplastic. Delayed osseous maturation, manifested by absence of centers of ossification, is also
apparent in goitrous newborn lambs.
Samples for confirmation of diagnosis
•Toxicology - 1 thyroid gland (ASSAY(Iodine))
•Histology - skin, thyroid (LM).
DIFFERENTIAL DIAGNOSIS
Iodine deficiency is easily diagnosed if goiter is present but the occurrence of stillbirths without
obvious goiter may be confusing. Abortion due to infectious agents in cattle and sheep must be
considered in these circumstances. In stillbirths due to iodine deficiency, gestation is usually
prolonged beyond the normal period, although this may be difficult to determine in animals bred
at pasture. Inherited defects of thyroid hormone synthesis are listed under the heading of inherited
diseases. Hyperplastic goiter without gland enlargement has been observed in newborn foals in
which rupture of the common digital extensor tendons, forelimb contracture, and mandibular
prognathism also occur. The cause of the combination of defects in unknown.
TREATMENT
Treatment of neonates with obvious clinical evidence of iodine deficiency is usually not
undertaken because of the high case fatality rate. When outbreaks of iodine deficiency occur in
neonates, the emphasis is usually on providing additional iodine to the pregnant dams. The
recommendations for control can be adapted to the treatment of affected animals.
CONTROL
The recommended dietary intake of iodine for cattle is 0.8-1.0 mg/kg DM of feed for lactating and
pregnant cows, and 0.1-0.3 mg/kg DM of feed for non-pregnant cows and calves.
Iodine can be provided in salt or a mineral mixture. The loss of iodine from salt blocks may be
appreciable and an iodine preparation that is stable but contains sufficient available iodine is

equired. Potassium iodate satisfies these requirements and should be provided as 200 mg of
potassium iodate per kg of salt. Potassium iodide alone is unsuitable, but when mixed with
calcium stearate (8% of the stearate in potassium iodide) it is suitable for addition to salt - 200
mg/kg of salt.
Individual dosing of pregnant ewes, on two occasions during the 4th and 5th months of
pregnancy, with 280 mg potassium iodide or 370 mg potassium iodate has been found to be
effective in the prevention of goiter in lambs when the ewes are on a heavy diet of kale. For
individual animals, weekly application of tincture of iodine (4 mL cattle, 2 mL pig and sheep) to
the inside of the flank is also an effective preventive. The iodine can also be administered as an
injection in poppy seed oil (containing 40% bound iodine): 1 mL given IM 7-9 weeks before
lambing is sufficient to prevent severe goiter and neonatal mortality in the lambs. Control of goiter
can be achieved for up to 2 years. The gestation period is also reduced to normal. A similar
injection 3-5 weeks before lambing is less efficient.
A device to release iodine slowly into the forestomachs, while still retaining its position there,
has given good results in preventing congenital goiter in lambs when fed to ewes during late
pregnancy.
REFERENCES
(1)Korber, R. al. (1985) Mh Vet. Med., 40,220.
(2)Hetzel, B. S. & Mano, M. T. (1989) J. Nutr.,119, 145.
IRON DEFICIENCY
Synopsis
Etiology. Dietary deficiency of iron
Epidemiology. Young animals on milk diet; most commonly nursing piglets which have not
received supplemental iron. Housed nursing lambs. Occurs in veal calves fed milk with limited
quantities of iron. Continued blood loss due to hemorrhage (lice, blood sucking helminths).
Subclinical iron deficiency occurs in calves and foals of doubtful significance. May be more
susceptible to infectious diseases.
Signs. Pale white skin of well grown nursing piglets, dyspnea, pallor of mucosae, sudden death
may occur. Stillbirths if sows iron deficient. Secondary infectious diseases.
Clinical pathology. Subnormal levels of hemoglobin of serum iron, microcytic hypochromic
anemia.
Lesions. Pallor, thin watery blood, anasarca, dilated heart, enlarged liver.
Diagnostic confirmation. Low serum hemoglobin and serum iron with microcytic hypochromic
anemia. Response to iron therapy.
Differential diagnosis. Other causes of anemia (p. 414).
Treatment. Parenteral and oral iron salts.
Control. Insure adequate iron intake. Parenteral iron dextran to nursing piglets and lambs.
ETIOLOGY
Iron deficiency is usually primary and most likely to occur in newborn animals whose sole source
of iron is the milk of the dam, milk being a poor source of iron. Deposits of iron in the liver of the
newborn are insufficient to maintain normal hemopoiesis for more than 2-3 weeks, and are
particularly low in piglets.
EPIDEMIOLOGY
Iron-deficiency states are not common in farm animals except in the very young confined to a

milk diet.
Iron deficiency anemia occurs in nursing piglets for three reasons:
1.They do not have access to soil, which is a main source of iron for young farm animals
2.They grow rapidly and their absolute requirements for iron are high
3.Milk is a poor source of iron.
The administration of iron dextran to the piglets at a few days of age is preventive and is a
routine health management strategy in modern swine production. If they do not receive
supplemental iron dextran, clinical
1506
disease occurs usually when the piglets are 3-6 weeks old. The losses that occur include those due
to mortality, which may be high in untreated pigs and to failure to thrive. Under modern swine
production systems piglets do not have access to sufficient dietary iron until they are weaned to a
dry diet containing supplemental iron. Thus, the need for parenteral iron dextran at a few days of
age.
Iron deficiency anemia occurs in nursing lambs that are housed and do not have access to
soil, do not consume much feed other than their dam's milk for the first 7-10 days of life, and grow
at 0.4 kg per day (1). The parenteral administration of iron dextran at 24 hours of age prevents the
anemia (1).
Continued blood loss by hemorrhage in any animal may result in subclinical anemia and iron
deficiency. Cattle heavily infested with sucking lice may develop serious and even fatal anemia.
The chronic form is characterized by a non-regenerative anemia with subnormal levels of serum
iron, and treatment with iron is necessary for an optimal response. Horses carrying heavy burdens
of bloodsucking strongylid worms often have subnormal hemoglobin levels and respond to
treatment with iron. On occasions veal calves, and possibly young lambs and kids, may also suffer
from an iron deficiency.
Good quality veal is traditionally pale in color and is produced by feeding calves an all-liquid
milk replacer diet with a low concentration of available iron (2, 3). The pallor of veal is due
largely to low concentrations of myoglobin and other iron-containing compounds in muscle. Milk
replacers containing only 10 mg iron/kg DM results in marked anemia and reduced growth
performance (3). Feeding milk replacers with 50 mg iron/kg DM is considered, physiologically,
the optimum amount of iron for veal calves but may be too high for acceptable carcass yield in
some countries (3). A severe iron defi¬ciency with reduced growth rate in veal calves may be
associated with a higher incidence of infectious disease because of an unpaired immune system (4).
The objective in veal calf management is to walk the narrow line between the maximum
production of white meat and a degree of anemia insufficient to interfere with maximum
production.
Subclinical iron-deficiency anemia also occurs in newborn calves and kids but there is debate
as to wheteher the condition has practical significance. In newborn calves affected with a
nor-mochromic, normocytic, and poikilo-cytic anemia the levels of serum iron are not
significantly different from normal calves (5). It has been proposed that severe poikilocytosis in
calves is associated with abnormalities of hemoglobin com¬position and protein 4.2 in the
erythro-cyte membrane, and iron deficiency is the cause of moderate poikilocytosis in calves (6).
Clinicopathological anemia, without clinical signs, is most likely to occur when calves are born
with low hemoglobin and hematocrit levels, a relatively common occurrence in twins. It is

possible that suboptimal growth may occur during the period of physiological anemia in early
postnatal life. There is some evidence for this in calves in which hemoglobin levels of 11 g/dL at
birth fall to about 8 g/dL between the 30th and 70th days and only begin to rise when the calves
start to eat roughage. The daily intake of iron from milk is 2-4mg in calves, and their daily
requirement during the first 4 months of life is of the order of 50 mg, so that iron supplementation
of the diet is advisable if the calves are fed entirely on milk. Even when hay and gram are fed to
calves and lambs in addition to milk, there is a marked growth response to the administration of
iron-dextran preparations at the rate of 5.5 mg/kg BW. The dietary iron requirement for
fast-growing lambs is between 40 and 70 mg/kg BW, and growth rate is suboptimal on diets of
less than 25 mg/kg BW.
Low serum iron concentration and low serum ferritin have been observed in hospitalized
young foals (7). Hemoglobin concentrations and packed cell volume decrease in foals from values
at birth, which are similar to those for adult horses, to mean values during the first weeks and
months of life below those reported in adults. Serum iron concentration, total iron-binding
capacity, and packed cell volume decreased during the foal's first 24 hours of life (8). Based on the
studies of foals from birth to 1 year of age, the potential for iron deficiency developing under 5
weeks of age is possible because 65% of foals had minimum ferritin concentrations =45 ng/mL,
and 81% of foals had these minimum values recorded between 2 and 4 weeks.
Competition horses are frequently given iron supplementation to treat anemia and to
improve performance despite the fact that neither application has any scientific basis (7). In
contrast, iron overload and toxicity have occurred in competition horses (9, 10). Some studies
have shown high total plasma iron in British 3-day event team horses prior to transport (77µM)
compared to normal levels of 24 µM. Immediately after travelling for 3 days on the road, the
plasma levels had declined to 29 µM (11). The iron-binding antioxidant activity, an indicator of
transfernn saturation, had also declined, suggesting greater saturation of available transfernn in the
plasma or a decreased capacity to sequester iron. The saturation of mechanisms to sequester iron,
such as may occur with excessive supplementation, may predispose the horses to iron-catalyzed
oxidant injury (11). The total iron intake exceeded the normal recommendation of between 550
and 600 mg/day. Anemia (or a low packed cell volume) is not synonymous with iron deficiency
but is frequently associated with disease processes. Poor performance in an iron-deficient animal
is more likely due to a reduction in the activity of metabolically active iron-containing enzymes
rather than a reduction in oxygen transport. In addition, iron deficiency is unlikely to occur in
healthy horses.
Calcium carbonate added to the diet of weaned and finishing pigs may cause a conditioned
iron deficiency and a moderate anemia but this effect is not apparent in mature pigs. Manganese
may exert a similar antagonistic effect.
PATHOGENESIS
More than half the iron in the animal body is found as a constituent of hemoglobin. A relatively
small amount is found in myoglobin and in certain enzymes which play a part in oxygen
utilization.
Piglets at birth have hemoglobin levels of about 90-110g/L. A physiological fall to 40-50 g/dL
occurs in all pigs, the lowest levels occurring at about the 8th--10th day of life. Levels of iron in
the liver at birtli are unusually low in this species and cannot be increased appreciably by

supplementary feeding of the sow during pregnancy. The IM injection of iron-dextran preparations
to sows during late pregnancy docs elevate the hemoglobin levels of the piglets during the first
1507
few weeks of life but not sufficiently to prevent anemia in them. Piglets with access to iron show a
gradual return to normal hemoglobin levels starting at about the 10th day of life, but in pigs denied
this access the hemoglobin levels continue to fall.
One of the important factors in the high incidence of anemia in piglets is the rapidity with
which they grow in early postnatal life. Piglets normally reach four to five times their birth weight
at the end of 3 weeks, and eight times their birth weight at the end of 8 weeks. The daily
requirement of iron during the first few weeks of life is of the order of 15 mg. The average intake
in the milk from the sow is about 1 mg/day and the concentration in sow's milk cannot be elevated
by feeding additional iron during pregnancy or lactation. Apart from the specific effect on
hemoglobin levels, iron-deficient piglets consume less creep feed, and after the first 3 weeks of
life make considerably slower weight gains than supplemented piglets. Although specific
pathogen-free pigs show a less marked response to the administration of iron than pigs reared in
the normal manner, it is obvious that they need supplementary iron to prevent the development of
anemia. Iron-deficient piglets appear to be more susceptible to diarrhea at about 2 weeks of age
than are piglets that have received iron. A marked impairment of gastric secretion of acid and
chloride and atrophic gastritis occurs in iron-deprived piglets. Villous atrophy of the small
intestine and changes in the gastrointestinal flora also occur in iron-deficient piglets which may
contribute to the increased susceptibility to diarrhea.
Severe iron deficiency in veal calves is characterized by impaired growth and reduced feed
intake and utilization. The growth rate is reduced only when hemoglobin concentrations fall below
70g/L (12). The reduced growth rate may be due to reduction in the half-life of growth hormone.
CLINICAL FINDINGS
The highest incidence of iron deficiency anemia in piglets occurs at about 3 weeks of age, but it
can occur up to 10 weeks of age.
Affected pigs may be well grown and in good condition, but the growth rate of anemic pigs is
significantly lower than that of normal pigs and feed intake is reduced. A mild diarrhea may occur
but the feces are usually normal in color. Dyspnea, lethargy, and a marked increase in amplitude
of the apex beat of the heart can be felt after exercise. The skin and mucosae are pale and may
appear yellow in white pigs. Edema of the head and forequarters, giving the animal a fat,
puffed-up appearance may be present. A lean, white hairy look is probably more common. Death
usually occurs suddenly, or affected animals may survive in a thin, unthrifty condition. A high
incidence of infectious diseases, especially enteric infection with Escherichia coli, is associated
with the anemia, and streptococcal pericarditis is a well-recognized complication. Under
experimental conditions, similar signs occur in calves and there is, in addition, an apparent
atrophy of the lingual papillae. A high incidence of stillbirths is recorded in the litters of sows
suffering from iron-deficiency anemia.
CLINICAL PATHOLOGY
In normal piglets there is a postnatal fall of hemoglobin levels to about 8g/L and sometimes to as
low as 4-5g/L during the first 10 days of life. In iron-deficient pigs there is a secondary fall to
20-40g/L during the 3rd week. The hemoglobin level at which clinical signs appear in pigs is
about 40g/L (13). Erythrocyte counts also fall from a normal of 5-8 × 10 12 /L down to 3-4 ×10 12 /L

and may be a better index of iron status than hemoglobin levels. Iron-deficiency anemia in piglets
is a microcytic hypochromic anemia. In chronic blood loss anemia in cattle infested with sucking
lice, there is a non-regenerative anemia and a decrease in serum iron levels. Serum levels of iron
considered to be normal in sheep and cattle are 100-200 µg/dL (17.9-35.8 (µmol/L). In newborn
calves, the levels are 170 µg/dL (30.4µmol/L) at birth and 67µg/dL (12.0µmol/L) at 50 days of age.
Serum ferntin concentration is an index for monitoring prelatent iron deficiency of calves (14).
The borderline of iron-deficiency anemia of veal calves at 16-20 weeks of age has been defined
as a hemoglobin concentration of 9g/L and a saturation of total iron binding capacity of 10% (15).
NECROPSY FINDINGS
The carcass is characterized by pallor, watery blood, and moderate anasarca. The heart is always
dilated, sometimes extremely so. The cardiac dimensions in severely anemic neonatal pigs
indicate that dilatation and hypertrophy occur consistently. The liver in all cases is enlarged, and
has a mottled tan-yellow appearance. Histological examination of the bone marrow reveals
maturation asynchrony of the erythroid line and a lack of hemosiderin stores. Other microscopic
changes described include periacinar hepatocellular changes typical of hypoxia and decreased
numbers of parietal cells in the gastric mucosa.
Samples for confirmation of diagnosis
•Toxicology - 50 g liver (ASSAY (Fe))(Note that serum ferritin from surviving littermates is a
better indicator ofiron status)
•Histology - liver, heart, bone marrow,stomach (LM).
DIFFERENTIAL DIAGNOSIS
Confirmation of the diagnosis will depend upon hemoglobin determinations and curative and
preventive trials with administered iron. The possibility that anemia in piglets may be caused by
copper deficiency should not be overlooked especially if the response to administered iron is poor.
Isoimmunization hemolytic anemia can be differentiated by the presence of jaundice and
hemoglobinuria, and the disease occurs in much younger pigs. Eperythrozoonosis occurs in pigs
of all ages and the protozoan parasites can be detected in the erythrocytes.
TREATMENT
The recommendations for the prevention of the disease are set out below and can be followed
when treating clinically affected animals. Horses with poor racing performance often have
suboptimal blood levels of hemoglobin and a blood loss anemia due to parasitism, and respond
well to treatment with iron. Treatment is usually parentcral and consists of organic iron
preparations such as iron-dextran, iron-sorbitol-citric acid complex, iron saccharate or gluconate.
These must be given exactly as prescribed by the manufacturer as some are quite irritant, causing
large sloughs when injected IM. The dose rate is 0.5-1 g elemental iron in one injection per week.
When given IV, or even IM, some horses show idiosyncratic reactions and literally drop dead.
Vitamin B12 (cyanocobalamin) is often used in the same injection at a dose rate of 5000 µg
1508
per week in a single dose. Other additives, especially folic acid and choline, are also used but with
little justification. Oral treatment with iron sulfate or gluconate at a dose rate of 2-4 g daily for 2
weeks is as effective and much cheaper, but lacks the style of the parenteral injection. It has the
disadvantage of being unpalatable and is best dispensed in liquid form to be mixed with molasses
and poured onto dry feed.
CONTROL

Preventive measures must be directed at the neonatal piglets because treatment of the sows before
or after farrowing is generally ineffective, although some results are obtained if the iron
preparations are fed at least 2 weeks before farrowing. Ferric choline citrate appears to have some
special merit in this field. Allowing the nursing piglets access to pasture or dirt yards, or
periodically placing sods in indoor pens, offer adequate protection. Where indoor housing on
impervious floors is necessary, iron should be provided at the rate of 15 mg/day until weaning
either by oral dosing with iron salts of a commercial grade or by the IM injection of organic iron
preparations. These methods are satisfactory, but the results are not usually as good as when
piglets are raised outdoors. However, indoor housing is practiced in many areas to avoid exposure
to parasitic infestation and some bacterial diseases, especially erysipelas. If sods are put into pens
care must be taken to insure that these diseases are not introduced.
Dietary supplementation
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 20g 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 2 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 (13). The preruminant calf
can tolerate between 2000 and 5000 ppm DM iron in milk replacer (13).
Oral dosing
Daily dosing with 4 mL of 1.8% solution of ferrous sulfate is adequate. Iron pyrophosphatc may
also be used (300 mg/day for 7 days). To overcome the necessity for daily dosing, several other
methods of administering iron have been recommended. A single oral treatment with iron-dextran
or iron-galactan has been recommended, provided an excellent creep feed is available, but the
method seems unnecessarily expensive. With this oral treatment it is essential that the iron be
given within 12 hours of birth because absorption has to occur through the perforate neonatal
intestinal mucosa; later administration is not followed by absorption. Reduced iron (British
Veterinary Codex) can be administered in large doses because it does not cause irritation of the
alimentary mucosa. A single dose of 0.5-1g once weekly is sufficient to prevent anemia.
Alternatively, the painting of a solution of ferrous sulfate on the sow's udder has been
recommended (450g ferrous sulfate, 75g copper sulfate, 450g sugar, 2L water - applied daily) but
has the disadvantage of being sticky and of accumulating litter. Pigs raised on steel gratings can
derive enough iron from them to avoid the need for other supplementation. Excessive oral dosing
with soluble iron salts may cause enteritis, diarrhea, and some deaths in pigs. High intakes of
ferric hydroxide cause diarrhea, loss of weight, and low milk production in cattle. The presence of
diarrhea in a herd prevents absorption of orally administered iron, and treatment by injection is
recommended in this circumstance.

Intramuscular injection of iron preparations
Suitable preparations must be used and are usually injected IM in piglets on one-occasion only,
between the 3rd and 7th day of life. Iron-extran, fumarate, and glutamate are most commonly used.
A dose of 200 mg of a rapidly absorbed and readily utihzablc form of iron within the first few
days of life will result in greater body weights at 4 weeks of age than piglets given only 100 mg
(16). Multiple injections give better hemoglobin levels but have not been shown to improve
weight gain and, thus, a second injection at 2-3 weeks of age may not be economical. A total dose
of 200 mg is usually recommended as being required to avoid clinically manifest iron-deficiency
anemia, but in order to avoid any chance of a subclinical deficiency the feed should contain
additional iron at the level of 240 mg/kg. A new preparation (Heptomcr) contains 200mg/mL of
iron, permitting a full dose in one injection. Contrasting information is that one injection of 100
mg of iron is adequate for baby pigs. Acute poisoning and rapid death occurs in piglets given
iron-dextran compounds parenterally if the piglets were born from sows which were deficient in
vitamin E and selenium during gestation. This is discussed under iron-dextran poisoning. In
normal piglets the iron-dextran com¬pounds are safe and are usually not toxic even on repeated
injection. These preparations are ideal for treatment because of the rapid response they elicit and
the absence of permanent discoloration of tissues after their use if given during the first month of
life. A combination of sodium selenite and iron-dextran has been given to piglets at 3 days of age
and is superior to treatment with iron alone when the piglets are deficient in selenium.
Iron deficiency anemia in housed lambs is preventable by the IM injection of 300 mg iron
dextran at 24 hours of age (1). At 12 and 24 days after treatment, the liematological values in the
treated group were significantly different than the unsupplemented group, and at weaning the
treated lambs were 1.0 kg heavier than untreated lambs (1).
Comparable doses of parenteral iron-dextran compounds have been used for the treatment of
iron-deficiency or iron-loss anemias in other species, but accurate doses have not been established
and the use of these preparations in cattle and horses is expensive. In addition, iron-dextran
preparations given IM to horses may cause death within a few minutes after administration. The
most inexpensive method of supplying iron is to use ferrous sulfate orally at a dose of 2-4 g daily
for 2 weeks to adult cattle and horses with iron-deficiency anemia.
Iron injection of beef calves in the first week alter birth will result in an
1509
increase in packed cell volume (PVC), hemoglobin (Hb), mean corpuscular volume (MCV), and
mean corpuscular hemoglobin (MCH) which persists for 12 weeks. However, weight gains during
the first 18 weeks of life were not affected.
REFERENCES
(1)Green, L. E. et al. (1997) Vet. Rec, 140,219.
(2)Limit, F. & BlumJ. W. (1994)J. Vet.Med, A. 41, 237.
(3)Limit, F. & Blum.J. W. (1994)/ Vet.Med., A. 41, 333.
(4)Gygax, M. ct al. (1993) /. Vet. Med. A.,40. 345.
(5)McGillivray, S. R. el al. (1985) Can.].Comp. Med.. 49, 286.
(6)Okabe.J. et al. (1996) J. Vet. Med. Sci., 58,629.
(7)Smith, J. E. et al. (1986)/ Am. Vet. Med.Assoc, 188, 285.
(8)Harvey, J. W. et al. (1987) Am.). Vet.Res., 48, 1348.
(9)Edens, 1. M. et al. (1993) Equine Vet.J..25, 81

(10)LavoieJ. P. & Teuscher, E. (1993) EquineVet. J.. 25, 552.
(11)Mills, V. C. & Marlin, D.J. (1996) Vet.Ret., 139. 215.
(12)Ceppi, A. et al. (1994) Ann. Nutr. Metal,.,38, 281.
(13)Jenkins, K.J. & Hidiroglou, M. (1988) J.Dairy Sci., 70, 2349.
(14)Mivata, Y. et al. (1984) J. Dairy Set. 61,1256.
(15)Wekhnun, D.DeB, et al. (1988) Vet.Ret.. 123, 505.
(16)Daykm, M. M. et al. (1982) Vet. Rec, 110. 535.
SODIUM CHLORIDE DEFICIENCY
A dietary deficiency of sodium is most likely to occur:
•During lactation, as a consequence of losses of the element in the milk, in rapidly growing young
animals fed on low-sodium, cereal-based diets
•Under very hot environmental conditions where large losses of water and sodium occur in the
sweat and where the grass forage and the seeds may be low in sodium
•In animals engaged in heavy or intense physical work and in animals grazing pastures on sandy
soils heavily fertilized with potash, which depresses forage sodium levels (1).
Naturally occurring salt deficiency causing illness in grazing animals is uncommon except
under certain circumstances. The most commonly cited occurrences are on alpine pastures and
heavily fertilized pasture leys. Pasture should contain at least 0.15g/100g dry matter (DM) and
clinical signs are evident after about 1 month on pasture containing 0.1 g/100g DM. Under
experimental conditions, lactating cows give less milk until the chloride deficiency is
compensated. After a period of up to 12 months there is considerable deterioration in the animal's
health and anorexia, a haggard appearance, lusterless eyes, rough coat and a rapid decline in body
weight occur. high-producing animals are most severely affected and some may collapse and die.
The oral administration of sodium chloride is both preventive and rapidly curative. Experimental
sodium depletion in horses for up to 27 days has no deleterious effect on general health.
In dairy cattle on a sodium-deficient diet there is polyuria, polydipsia, salt hunger, pica,
including licking dirt . and each other's coats, drinking urine, loss of appetite and weight, and a fall
in milk production (2). Urination is frequent and the urine has a lower than normal specific gravity
and the urine concentrations of sodium and chloride are decreased and the potassium increased.
The salivary concentration of sodium is markedly decreased, the potassium is increased and the
salivary sodium:potassium ratio is decreased. The concentration of serum sodium and chloride are
also decreased, but the measurement of urinary or salivary sodium concentration is a more
sensitive index of sodium intake than plasma sodium concentration (2). Of these, it is urinary
sodium which is depressed first and is therefore the preferred indicator in cattle (3) and horses (4).
The polyuria associated with severe sodium depletion may be an antidiuretic hormone
insensitivity due to lack of an effective countercurrent mechanism and hyperaldosteronism (2).
Experimental restriction of chloride in the diet of dairy cows in early lactation results in a
depraved appetite, lethargy, reduced feed intake, reduced milk production, scant feces, gradual
emaciation, and severe hypochloremia and secondary hypokalemic metabolic alkalosis (5).
Lethargy, weakness, and unsteadiness occur after about 6 weeks on the chloride-deficient diet (6).
Bradycardia is also common. The concentration of chloride in cerebrospinal fluid is usually
maintained near normal while the scrum concentrations decline (7). The experimental induction of
a severe, total body chloride deficit by the provision of a low-chloride diet and the daily removal
of abomasal contents results in similar clinical findings to those described above and lesions of

nephrocalcinosis (8).
The diagnosis of salt deficiency is dependent on the clinical findings, analysis of the feed and
water supplies, serum levels of sodium and chlorine, and determination of the levels of sodium in
the saliva, urine and feces of deficient animals (9). The concentration of sodium in saliva is a
sensitive indicator of sodium deficiency. In cattle receiving an adequate supply of sodium and
chlorine, the sodium levels in saliva vary from 140 to 150 mmol/L, in deficient cattle the levels
may be as low as 70-100 mmol/L (9). The levels of sodium in the urine are low, with a reciprocal
rise in potassium (4). The serum sodium levels are less reliable, but licking begins when the level
falls to 137 mmol/L and signs are intense at 135 mmol/L.
Experimentally induced sodium deficiency in young pigs causes anorexia, reduced water
intake and reduced weight gains (10).
The provision of salt in the diet at a level of 0.5% is considered to be fully adequate for all farm
animal species. Under practical conditions, salt mixes usually contain added iodine and cobalt. In
some situations the salt mixes are provided on an ad libitum basis rather than adding them to the
diet. However, voluntary consumption is not entirely reliable. The daily amount consumed by
animals having unrestricted access to salt can be highly variable and often wasteful. Two factors
influencing voluntary salt intake include the physical form of the salt and the salt content of the
water and feed supplies. Some cattle consume much more loose than block salt, though the lower
intakes of block salt may be adequate. Also, animals dependent on high saline water for drinking
consume significantly less salt than when drinking non-saline water. Voluntary salt consumption is
generally high in cows on low-sodium pastures, which are low inherently or as a result of heavy
potash fertilization. Lactating gilts may require 0.7% salt in their diets (11) and energy efficiency
in feedlot cattle may be improved by feeding high
1510
levels (5% of diet) of salt in the diet of finishing steers (12).
REVIEW LITERATURE
Aitkcn, F. C. (1976) Sodium and potassium in nutrition of mammals. Commw. Bur. Anim.
Nutr. Techn. Commun., 26. Michel], A. R. (1985) Sodium in health and disease: a comparative
review with emphasis on herbivores. Vet. Rec, 116, 653 657.
REFERENCES
(1)Underwood, E.J. (1981) The Mineral Nutrition of Livestock, 2nd edn. Farnham Royal,
Commonwealth AgriculturaI3ureaux.
(2)Whitloik, R. H. etal. (1975) Cornell Vet..65, 512.
(3)Launer, P. & Storm, R. (1979) Mh. Vet.Med., 34, 364.
(4) Meyer, H. & Ahlswede, L. (1979) Zentralbl. Veterinarmed., 26A, 212.
(5)Fettman, M. J. et al. (1984)/. Dairy So.,61, 2321.
(6)Fettman, M.J. etal. (1984)J. Am. Vet.Med. Assoc, 185, 167.
(7)Fettman, M.J. et al. (1984) Am. J. Vet.Res., 45, 403.
(8)Blackmon, D. M. et al. (1984) Am.J. Vet.Res., 45, 1638.
(9)Murphy, G. M. & Gartner. R. J. W.(1974) Aust. Vet.J., 50, 280.
(10) Yusken.J. W. & Reber, E. F. (1957)
(11)Trans. 111. Acad. Sci., 50, 118. (1 1) Friend. D. W. & Wolynetz, M. S. (1981)
(12)Can. J.Anim. So., 61, 429. (12) Croom, W. J. et al. (1982) Can.). Anim. Sci., 62, 217.
MAGNESIUM DEFICIENCY

A nutritional deficiency of magnesium plays a role in causing lactation tetany in cows and
hypomagnesemic tetany of calves, and these diseases are dealt with in Chapter 28 on metabolic
diseases. In both diseases, there are complicating factors that may affect the absorption and
metabolism of the clement.
Magnesium is an essential constituent of rations for recently weaned pigs (1). Experimentally
induced deficiency causes weakness of the pasterns, particularly in the forelegs, causing backward
bowing of the legs, sickled hocks, approximation of the knees and hocks, arching of the back,
hyperirritability, muscle tremor, reluctance to stand, continual shifting of weight from limb to limb,
and eventually tetany and death. A reduction in growth rate, feed consumption and conversion,
and levels of magnesium in the serum also occur. The requirement of magnesium for pigs weaned
at 3-9 weeks of age is 400-500 mg/kg of the total ration.
REFERENCE
(1) Mayo, R. H. et al. (1959) J. Anim. Sci., 18, 264.
ZINC DEFICIENCY (PARAKERATOSIS)
Synopsis
Etiology. Dietary deficiency of zinc and factors which interfere with zinc
utilization.
Epidemiology. Growing pigs, cattle and sheep. Excess of calcium favors disease in pigs.
Signs.
Pigs: Loss of body weight gain.
Symmetrical, crusty skin lesions (parakeratosis) over dorsum and ears, tail;become thick and
fissured. No pruritus.
Ruminants: Alopecia, over muzzle, ears,tail-head, hindlegs, flank and neck. Stiff gait and
swelling over coronets. Loss of wool and thickened skin is sheep.Infertility in rams.Poor growth in
goats and skin lesions.
Clinical pathology. Serum zinc levels lower than normal.
Lesions. Parakeratosis.
Diagnostic confirmation. Histology of skin lesions and serum zinc levels.
Differential diagnosis list:
•Sarcoptic mange in cattle and pigs
•Exudative epidermitis in piglets.
Treatment. Add zinc to diet.
Control. Supplement zinc in diet.
ETIOLOGY
Swine
A zinc deficiency in young, growing swine can cause parakeratosis, but it is not due to a simple
zinc deficiency. The availability of zinc in the diet is adversely affected by the presence of phytic
acid, a constituent of plant protein sources such as soybean meal (1). Much of the zinc in plant
protein is in the bound form and unavailable to the monogastric animal such as the pig (2). The
use of meat meal or meat scraps in the diet will prevent the disease because of the high availability
of the zinc. Another unique feature of the etiology of parakeratosis in swine is that an excess of
dietary calcium (0.5-1.5%) can favor the development of the disease, and the addition of zinc to
such diets at levels much higher (0.02% zinc carbonate or 100 mg/kg zinc) than those normally
required by growing swine prevents the occurrence of the disease. The level of copper in the diet

may also be of some significance, increasing copper levels decreasing the requirement for zinc. A
concurrent enteric infection with diarrhea exacerbates the damage done by a zinc deficiency in
pigs.
Ruminants
A primary zinc deficiency due to low dietary zinc in ruminants is rare but does occur (3). Many
factors influence the availability of zinc from soils, including the degree of compaction of the soil,
and the nitrogen and phosphorus concentration. The risk of zinc deficiency increases when soil pH
rises above 6.5 and as fertilization with nitrogen and phosphorus increases. Some legumes contain
less zinc than grasses grown on the same soil, and zinc concentration decreases with aging of the
plant. Several factors may deleteriously affect the availability of zinc to ruminants and cause a
secondary zinc-deficiency. These include the consumption of immature grass, which affects
digestibility, the feeding of late-cut hay, which may be poorly digestible, and the presence of
excessive dietary sulfur. The contamination of silage with soil at harvesting can also affect the
digestibility of zinc (3).
EPIDEMIOLOGY
Swine
Parakeratosis in swine was first recorded in North America in rapidly growing pigs, particularly
those fed on diets containing growth promoters. The disease occurs most commonly during the
period of rapid growth, after weaning and between 7 and 10 weeks of age. From 20-80% of pigs in
affected herds may have lesions, and the main economic loss is due to a decrease in growth rate.
In general, the incidence is greater in pigs fed in dry lot on self-feeders of dry feed than in pigs
with access to some pasture, which is preventive and curative.
A low level of dietary zinc intake during pregnancy and lactation of gilts can result in skin
lesions, stressful parturition and an increased incidence of intrapartum mortality of piglets and
deleterious effects on neonatal growth (4).
It has been suggested that parakeratosis occurs because very rapidly growing pigs outstrip their
biosynthesis of essential fatty acids, and when the diet is high in calcium the digestibility of fat in
the diet is reduced at the same time. The net effect in rapidly growing pigs could
1511
be a relative deficiency of essential fatty acids.
Ruminants
There are naturally occurring cases in cattle, sheep, and goats. The disease is well-recognized in
Europe, especially in calves. It is common in some families of cattle and an inherited increased
dietary requirement for zinc is suspected. The inherited disease occurs in Friesian and Black pied
cattle and is known as lethal trait A46 (5). Signs of deficiency appear at 4-8 weeks of age. The
main defect is an almost complete inability to absorb zinc from the intestine; zinc administration is
curative.
The disease in cattle has been produced experimentally on diets low in zinc, and naturally
occurring cases have responded to supplementation of the diet with zinc (3). Calves remain
healthy on experimental diets containing 40 mg/kg zinc, but parakeratosis has occurred in cattle
grazing pastures with a zinc content of 20-80 mg/kg (normal 93 mg/kg) and a calcium content of
0.6%. There is also an apparently improved response in cattle to zinc administration if copper is
given simultaneously. Parakeratosis has also been produced experimentally in goats and sheep.
Outbreaks of the disease have occurred in Sudanese Desert ewes and their lambs fed on a

zinc-deficient diet of Rhodes grass containing less than 10 mg/kg of zinc. The disease has also
been diagnosed in mature sheep and goats and the cause of the deficiency could not be
determined. A marginal zinc deficiency, characterized by subnormal growth and fertility and low
concentration of zinc in serum, but without other clinical signs, can occur in sheep grazing
pastures containing less than 10 mg/kg zinc (6).
PATHOGENESIS
The pathogenesis of zinc deficiency is not well-understood. Zinc is a component of the enzyme
carbonic anhydrase, which is located in the red blood cells and parietal cells of the stomach, and is
related to the transport of respiratory carbon dioxide and the secretion of hydrochloric acid by the
gastric mucosa. Zinc is also associated with RNA function and related to insulin, glucagon, and
other hormones. It also has a role in keratinization, calcification, wound healing, and somatic and
sexual development. Because it has a critical role in nucleic acid and protein metabolism a
deficiency may adversely affect the cell-mediated immune system.
A zinc deficiency results in a decreased feed intake in all species (6) and is probably the reason
for the depression of growth rate in growing animals and body weight in mature animals. Failure
of keratimzation resulting in parakeratosis, loss and failure of growth of wool and hair, and lesions
of the coronary bands probably reflect the importance of zinc in protein synthesis. There are
lesions of the arteriolar walls of the dermis. The bones of zinc-deficient ruminants reveal
abnormal mineralization and reduction of zinc concentration in bones. Retarded tcsticular
development occurs in ram lambs, and complete cessation of spermatogenesis suggests
impairment of protein synthesis.
CLINICAL FINDINGS
Pigs
A reduced rate and efficiency of body weight gain is characteristic. Circumscribed areas of
erythema appear in the skm on the ventral abdomen and inside the thigh. These areas develop into
papules 3-5 mm in diameter, which are soon covered with scales followed by thick crusts. These
crusts arc most visible in areas about the limb joints, ears and tail, and are distributed
symmetrically in all cases. The crusts develop fissures and cracks, become quite thick (5-7 mm)
and easily detached from the skin. They are crumbly and not flaky or scaly. No greasiness is
present except in the depths of fissures. Little scratching or rubbing occurs. Diarrhea of moderate
degree is common. Secondary subcutaneous abscesses occur frequently, but in uncomplicated
cases the skin lesions disappear spontaneously in 10-45 days if the ration is corrected.
Ruminants
In the naturally occurring disease in cattle, in severe cases, parakeratosis and alopecia may affect
about 40% of the skin area. The lesions are most marked on the muzzle, vulva, anus, tail-head,
ears, backs of the hindlegs, kneefolds, flank, and neck. Most animals are below average body
condition and are stunted in growth. After treatment with zinc, improvement is apparent in 1 week
and complete in 3 weeks. Experimentally produced cases exhibit the following signs:
•Poor growth
•A stiff gait
•Swelling of the coronets, hocks, and knees
•Soft swelling containing fluid on the anterior aspect of the hind fetlocks
•Alopecia
•Wrinkling of the skin of the legs, scrotum and on the neck and head, especially around the

nostrils
•Hemorrhages around the teeth
•Ulcers on the dental pad.
The experimental disease in cattle is manifested by parakeratotic skin, mainly on the hindlimbs
and udder, and similar lesions on teats, which tend to become eroded during milking. The fetlocks
and pasterns are covered with scabby scales. There is exudation first with matting of hair, then
drying and cracking. The skin becomes thickened and inelastic. Histologically, there is
parakeratosis. Clinical signs develop about 2 weeks after calves and lambs go onto a deficient diet
so that there is no evidence of storage of zinc in tissues in these animals. In goats, hair growth,
testicular size, and spermatogenesis are reduced, and growth rate is less than normal. Return to a
normal diet does not necessarily reverse these-signs and the case fatality rate is high. There is a
marked delay in wound healing.
Sheep
The natural disease in sheep is characterized by loss of wool and the development of thick,
wrinkled skin. Wool-eating also occurs in sheep and may be one of the earliest signs noticed in
lambs after being on a zinc-deficient diet for 4 weeks. Induced cases in lambs have exhibited
reduced growth rate, salivation, swollen hocks, wrinkled skin, and open skin lesions around the
hoof and eyes. The experimental disease in goats is similar to that in lambs.
One of the most striking effects of zinc deficiency in ram lambs is impaired testicular growth
and complete cessation of spermatogenesis. Diets containing 2.44 mg/kg dry matter (DM) caused
poor growth, impaired testicular growth, cessation of spermatogenesis, and other signs of zinc
deficiency within 20-24 weeks. A diet containing 17.4 mg/kg DM of zinc is adequate for growth,
but a content of 32.4 mg/kg DM is necessary for normal testicular development and
spermatogenesis. On severely deficient experimental diets, other clinical signs in young rams are:
1512
•Drooling copious amounts of saliva when ruminating
•Parakeratosis around eyes, on nose,feet and scrotum
•Shedding of the hooves
•dystrophy and shedding of wool,which showed severe staining
•development of a pungent odor.
In naturally occurring cases in rams the animals stood with their backs arched and feet close
together.
A marginal zinc deficiency in ewes may be characterized by only a reduction in feed intake and
a slightly reduced body weight, and no other external signs of disease. This is important because,
in grazing ruminants, the lack of external signs indicates that zinc deficiency could easily pass
undetected.
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 (6). The zinc content of the diet did not
significantly influence the ability of the ewes to become pregnant or maintain pregnancy. The

combination of i 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.
Goats
Experimentally induced zinc deficiency in goats results in poor growth, low food intake, testicular
hypoplasia, rough dull coat with loss of hair, and the accumularion of hard, dry, keratinized skin
on the hindlimb scrotum, head and neck. Onthe lower limbs the scabs fissure, crack, and produce
some exudate. In naturally occurring cases in pygmy goats there was extensive alopecia, a
kyphotic stance, extensive areas of parakeratosis, abnormal hoof growth and flaky, painful
coronary bands. A zinc-responsive alopecia and hyperkeratosis in Angora goats has been described.
Affected animals had recurrent pruritus, hyperemia, exfoliation, fleece loss over the hindquarters,
face and ears, and a decline in reproductive performance.
Immediately before parturition in cows there is a precipitate fall in plasma zinc concentration,
which returns to normal slowly after calving. The depression of zinc levels is greater in cows that
experience dystocia. This has led to the hypothesis that dystocia in beef heifers may be caused in
some circumstances by a nutritional deficiency of zinc and that preparturient supplementation of
the diet with zinc may reduce the occurrence of difficult births. This phenomenon does not appear
to occur in sheep. The level of serum zinc increased in cattle during the season of facial eczema
when sporidesmin intoxication causes depiction of liver zinc (7).
CLINICAL PATHOLOGY
Skin scraping
Laboratory examination of skin scrapings yields negative results, but skin biopsy will confirm the
diagnosis of parakeratosis.
Zinc in serum and hair
Serum zinc levels may have good diagnostic value. Normal levels are 80- 120 µg/dL
(12.2-18.2µmol/L) in sheep and cattle. Calves and lambs on deficient diets may have levels as low
as 18µg/dL (3.0 µmol/L). Normal serum zinc levels in sheep are above 78 µg/dL (12 µmol/L), and
values below 39 µg/dL (6 µmol/L) or less arc considered as evidence ot deficiency (6). There is a
general relationship between the zinc content of the hair and the level of zinc in the diet, but the
analysis of hair is not considered to be a sufficiently accurate indicator of an animal's zinc status.
In experimental disease in piglets there is a reduction in serum levels of zinc, calcium and alkaline
phosphatase, and it is suggested that the disease could be detected by measuring the serum
alkaline phosphate and serum zinc levels. Levels of zinc in the blood are very labile and simple
estimations of it alone arc-likely to be misleading. For example, other intercurrent diseases
commonly depress serum calcium and copper levels.In addition, zinc levels in plasma fall
precipitately at parturition in cows; they are also depressed by hyperthermal stress. After 1 week
on a highly deficient diet serum zinc levels fall to about 50% of normal, or pretreatment levels.
NECROPSY FINDINGS
Necropsy examinations are not usually performed, but histological examination of skin biopsy
sections reveals a marked increase in thickness of all the elements of the epidermis. Tissue levels
of zinc differ between deficient and normal animals but the differences are statistical rather than
diagnostic.
DIFFERENTIAL DIAGNOSIS

Sarcoptic mange may resemble parakeratosis, but is accompanied by much itching and rubbing.
The parasites may be found in skin scrapings. Treatment with appropriate parasiticides relieves the
condition.
Exudative epidermitis is quite similar in appearance, but occurs chiefly in unweaned pigs. The
lesions have a greasy character that is quite different from the dry, crumbly lesions of
parakeratosis. The mortality rate is higher.
TREATMENT
In outbreaks of parakeratosis in swine, zinc should be added to diet immediately at the rate of 50
mg/kg DM (200 mg of zinc sulfate or carbonate per kg of feed). The calcium level of the diet
should be maintained at between 0.65 and 0.75%. The injection of zinc at a rate of 2-4 mg/kg BW
daily for 10 days is also effective. Zinc oxide suspended in olive oil and given IM at a dose of 200
mg of zinc for adult sheep and 50 mg of zinc for lambs will result in a clinical cure within 2
months. The oral administration of zinc at the rate of 250 mg zinc sulfate daily for 4 weeks
resulted in a clinical cure of zinc deficiency in goats in 12-14 weeks.
CONTROL
Swine
The calcium content of diets for growing pigs should be restricted to 0.5-0.6%. However, rations
containing as little as 0.5% calcium and with normal zinc content (30 mg/kg DM) may produce
the disease. Supplementation with zinc (to 50 mg/kg DM) as sulfate or carbonate has been found
to be highly effective as a preventive and there appears to be a wide
1513
margin of safety in its use, diets containing 1000mg/kg DM added zinc having no apparent toxic
effect. The standard recommendation is to add 200 g of zinc carbonate or sulfate to each tonne of
feed. Weight gains in affected groups arc appreciably increased by the addition of zinc to the diet.
The addition of oils containing unsaturated fatty acids is also an effective preventive. Access to
green pasture, reduction in food intake, and the deletion of growth stimulants from rations will
lessen the incidence of the disease but arc not usually practicable.
Ruminants
For cattle, the feeding of zinc sulfate (2-4 g daily) is recommended as an emergency measure
followed by the application of a zinc-containing fertilizer. As an alternative to dietary
supplementation for ruminants, an intraruminal pellet has been demonstrated in sheep. It was
effective for 7 weeks only and would not be satisfactory for long-term use. The creation of
subcutaneous depots of zinc by the injection of zinc oxide or zinc metal dust has been
demonstrated. The zinc dust offered a greater delayed effect.
REVIEW LITERATURE
Lamand, M. (1984) Zinc deficiency in
ruminants. Irish Vet.)., 38, 40-47. Luccke, R. W. (1984) Domestic animals in theelucidation of
zinc's role in nutrition. Fed.
Proc, 43, 2823-2828.
REFERENCES
(1)Luecke, R. W. (1984) Fed. Proc, 43, 2823.
(2)Forbes. R. M. (1984) Fed. Proc, 43, 2835.
(3)Lamand, M. (1984) Irish Vel.J., 38, 40.
(4)Kalinowski.J. & Chavez, E. R. (1986) Can. J.Anim. Sci., 66,201, 217.

(5)Machen, M. el al. (1996)/. Vet. Diagn. Invest., 2, 219.
(6)Underwood, E.J. (1981) The Mineral Nutrition of Livestock, 2nd edn. Farnham Royal,
Commonwealth Agricultural Bureaux.
(7)Dewes, H. F. & Lowe, M. D. (1987) NZ Vet.J., 35, 16.
MANGANESE DEFICIENCY
A dietary deficiency of manganese may cause infertility and skeletal deformities both congenitally
and after birth.
ETIOLOGY
A primary deficiency occurs endemically in some areas because of a geological defiency in the
local rock formations (1). Apart from a primary dietary deficiency of manganese, the existence of
factors depressing the availability of ingested manganese is suspected. An excess of calcium
and/or phosphorus in the diet is known to increase the requirements of manganese in the diet of
calves (5), and is considered to reduce the availability of dietary manganese to cattle
generally.Congential chondrodystrophy in calves has been associated with a manganese deficiency
(2), and an outbreak of congenital skeletal defects in Holstein calves due to manganese deficiency
has been reported (3).
EPIDEMIOLOGY
Soils containing less than 3 mg/kg of manganese are unlikely to be able to support normal fertility
in cattle. In areas where manganese-responsive infertility occurs, soils on farms with infertility
problems have contained less than 3 mg/kg of manganese, whereas soils on neighboring farms
with no infertility problems have had levels of more than 9 mg/kg. A secondary soil deficiency is
thought to occur and one of the factors suspected of reducing the availability of manganese in the
soil to plants is high alkalinity. Thus, heavy liming is associated with manganese-responsive
infertility. There are three main soil types on which the disease occurs:
•Soils low in manganese have low out put even when pH is less than 5.5
•Sandy soils where availability starts to fall
•Heavy soils where availability starts to fall at pH of 7.0.
Many other factors are suggested as reducing the availability of soil manganese but the
evidence is not conclusive. For example, heavy liming of soils to neutralize sulfur dioxide
emissions from a neighboring smelter is thought to have reduced the manganese intake of grazing
animals.
Herbage on low manganese soils, or on marginal soils where availability is decreased (possibly
even soils with normal manganese content), is low in manganese. A number of figures are given
for critical levels. It is suggested that pasture containing less than 80 mg/kg of manganese is
incapable of supporting normal bovine fertility, and that herbage containing less than 50 mg/kg is
often associated with infertility and anestrus. The Agricultural Research Council feels that,
although definite figures are not available, levels of 40 mg/kg dry matter (DM) in the diet should
be adequate. Other authors state that rations containing less than 20 mg/kg DM may cause
anestrus and reduction in conception rates in cows and the production of poor quality semen by
bulls. Most pasture contains 50-100 mg/kg DM. Skeletal deformities in calves occur when the
deficiency is much greater than the above for example, a diet containing more than 200 mg/kg
DM is considered to be sufficient to prevent them.
Rations fed to pigs usually contain more than 20 mg/kg DM of manganese, and deficiency is
unlikely unless there is interference with manganese metabolism by other substances.

There are important variations in the manganese content of seeds, an important matter in
poultry nutrition (1). Maize and barley have the lowest content. Wheat or oats have three to five
times as much, and bran and pollard are the richest natural sources with 10-20 times the content of
maize or wheat. Cows' milk is exceptionally low in manganese.
PATHOGENESIS
Manganese plays an active role in bone matrix formation, and in the synthesis of chondroitin
sulfate, responsible for maintaining the rigidity of connective tissue. In manganese deficiency
these are affected deleteriously and skeletal abnormalities result. Only 1% of manganese is
absorbed from the diet and the liver removes most of it, leaving very low blood levels of the
element (2).
CLINICAL FINDINGS
In cattle, the common syndromes are infertility, calves with congenital limb deformities and calves
with manifest poor growth, dry coat, and loss of coat color. The deformities include knuckling
over at the fetlocks, enlarged joints and, possibly, twisting of the legs. The bones of affected lambs
are shorter and weaker than normal and there are signs of joint pain, hopping gait, and reluctance
to move.
A severe congenital chondrodystrophy in Charolais calves occurred on one farm (2). The limbs
were shortened and the joints enlarged. The pregnant cows were fed on apple pulp and corn silage
both of which were low in manganese.
1514
An outbreak of congenital skeletal malformations in Holstein calves was characterized
clinically by small birth weights (average 15 kg). Abnormalities included joint laxity, doming of
the foreheads, superior brachynathia, and a dwarflike appearance due to the short long bones. The
features of the head were similar to those of the wildebeest. The majority of affected calves were
dyspneic at birth, and snorting and grunting respratory sounds were common. Affected calves
failed to thrive and most were culled due to poor performance.
A manganese-responsive infertility has been described in ewes and is well known in cattle. In
cattle it is manifested by slowness to exhibit estrus, and failure to conceive, often accompanied by
subnormal size of one or both ovaries. Subestrus and weak estrus have also been observed.
Functional infertility' was once thought to occur in cattle on diets with calcium to phosphorus
ratios outside the range of 1:2 to 2:1. This was not upheld on investigation but may have been
correct if high calcium to phosphorus intakesdirectly reduced manganese (or copper or iodine)
availability in diets marginally deficient in one or other of these elements.
In pigs,experimental diets low in manganese cause reduction in skeletal growth, muscle
weakness, obesity, irregular, diminished or absent estrus, agalactia, and resorption of fetuses or the
birth of stillborn pigs. Leg weakness, bowing of the front legs, and shortening of bones also occur.
CLINICAL PATHOLOGY
Thebloodofnormalcattlecontains18-19 µg/dL (3.3-3.5 µmol/L) of manganese, although
considerably lower levels are sometimes quoted.The livers of normalcattlecontain12 mg/kg(0.21
mmol/kg) of manganese anddownto 8mg/kg(0.15 mmol/kg)innewborn calves, which also have a
lower content in hair.Themanganesecontentofhairvaries with intake.The normal level is
about12mg/kg(0.21 mmol/kg)and infertility is observed in association with levelsoflessthan8
mg/kg(0.15 mmol/kg). In normal cows,the manganese content of hair falls during pregnancy from
normal levels of 12 mg/kg (0.21 mmol/kg)in the first month of pregnancy to 4.5 mg/kg (0.08

mmol/kg) at calving.Allof these figures require much more critical evaluation than they have had,
before they can be used as diagnostic tests.
Although tissue manganese levels in normal animals have been described as being between 2
and 4 mg/kg (0.04 and 0.07 mmol/kg), in most tissue (1) there appears to be more variation
between tissues than this. However, tissue levels of manganese do not appear to be depressed in
deficient animals, except for ovaries in which levels of 0.6 mg/kg (0.01 mmol/kg) and 0.85 mg/kg
(0.02 mmol/kg) are recorded in contrast to a normal level of 2 mg/kg (0.04 mmol/kg).
There is then no simple, single diagnostic test permitting detection of manganese deficiency in
animals. Reproductive functions, male and female, are most sensitive to manganese deficiency
and are affected before possible biochemical criteria, e.g. blood and bone alkaline phosphatase,
and liver arginase levels, are significantly changed. The only certain way of detecting moderate
deficiency states is by measuring response to supplementation. Clinical findings in response to
treatment which may provide contributory evidence of manganese deficiency are set out below.
NECROPSY FINDINGS
In congenital chondrodystrophy in calves, the limbs are shortened and all the joints are enlarged.
Histologically, there is poor cartilage maturation with excessive amounts of rarefied cartilage
matrix. There are degenerative changes in the chondrocytes and severe reduction in the
mucopolysaccharide content of all body hyaline cartilage (2, 3).
TREATMENT AND CONTROL
Young cattle have shown a general response in fertility to 2 g MnSO4 daily, but the general
recommendation is daily supplementation with 4 g manganese sulfate providing 980 mg elemental
manganese. This level of feeding is estimated to raise the dietary intake by 75 mg/kg DM
(estimated on a daily intake of 12 kg DM by a 450 kg cow). In some herds a full response was
obtained only after doubling this rate of feeding. Although the feeding of 15 g of manganese
sulfate daily is reported to cause no signs of toxicity, manganese is known to interfere with the
utilization of cobalt and zinc in ruminants. Very large levels of intake to calves can reduce growth
rate and hemoglobin levels. The recommended procedure is to feed the supplement for 9 weeks
commencing 3 weeks before the first service.
Excessive supplementation, up to 5000 mg/kg, of the diet with manganese for periods of up to 3
months appeared to cause only a reduction in appetite and weight gain.
For pigs, the recommended dietary intakes are 24-57 mg manganese per 45 kg BW. Expressed
as a proportion of food intake the recommended dietary level is 40 mg/kg DM in feed.
REFERENCES
(1)Underwood, E.J. (1981) The Mineral Nutrition of Livestock, 2nd edn. Famhain Royal,
Commonwealth Agricultural Bureaux.
(2)Valero, G. et al. (1990) NZ Vet.]., 38, 161.
(3)Stalcy, G. P. et al. (1994)/ South African Vet. Assoc., 65, 73.
POTASSIUM DEFICIENCY
Naturally occurring dietary deficiency of potassium is thought to be rare. However, calves fed on
roughage grown on soils deficient in potassium, or in which the availability of potassium is
reduced, may develop a clinical syndrome of poor growth, anemia, and diarrhea. Supplementation
of the diet with potassium salts appears to be curative. A similar syndrome has been produced
experimentally in pigs (1) that manifested poor appetite, emaciation, rough coat, incoordination,
and marked cardiac impairment as indicated by electrocardiographs examination. The optimum

level of potassium in the diet of young, growing pigs is about 0.26%, and in ruminants 0.5% (i.e.
65 mg/kg BW) (2). Electrocardiographic changes have also been observed in cattle on
potassium-deficient diets and these are probably related to the degeneration of Purkinje fibers of
the myocardium which occurs on such diets. Similar changes have been recorded on diets
deficient in magnesium or vitamin E.
An intake of potassium above requirement is more likely to occur than a deficiency and,
although very large doses of potassium are toxic, ruminants are capable of metabolizing intakes
likely to be encountered under natural conditions (3). It seems probable, however, that potassium
interferes with the absorption of magnesium and heavy applications of potash fertilizers to grass
pastures may contribute to the development
1515
of the hypomagnesemia of lactation tetany.
Hypokalemia in cattle may occur secondary to anorexia, diarrhea, upper gastrointestinal
obstruction, right-side displacement and torsion of the abomasum, and impaction of the abomasum.
In most cases, the hypokalemia is not severe enough to cause weakness and recumbency.
Hypokalemia resulting in severe weakness and recumbency has occurred in dairy cattle treated
with isoflupredone acetate for ketosis (4). Serum potassium levels were below 2.3 mEq/L. Cows
ranged in age from 2 to 7 years, all had a history of moderate to severe ketosis and had calved
within the previous 30 days. Most had been treated with insulin, glucose IV, and propylene glycol
orally. Affected cows were recumbent, profoundly weak, appeared flaccid, and lay in sternal or
lateral recumbency. They were unable to support the weight of their heads off the ground and they
were commonly held in their flanks. Anorexia was common. Cardiac arrhythmias were detectable
on auscultation, and atrial fibrillation was confirmed on elcctrocardiography. Treatment included
IV and oral administration of potassium chloride and fluid therapy, but the response was
ineffective. Most affected cattle died or were euthanized. At necropsy,muscle necrosis was present
in the pelvic limbs, and histological examination of non-weight bearing muscle revealed
multifocal myonecrosis with macrophage infiltration and myofiber vacuolation, which is
characteristic of hypokalemic myopathy in man and dogs. It is important to note that myopathy
was also present in muscles not subject to ischemia or recumbency.
Potassium excretion by the kidneys is via secretion by the distal tubular cells. Aldosterone or
other steroids with mineralocorticoid activity enhance distal tubular secretion of potassium by
increasing permeability of the tubular luminal membranes to potassium and increasing losses of
potassium in the urine. Glucocorticoids are often used to treat ketosis; the most commonly used
are dexamethasone and isoflupredone acetate. Dexamethasone has little mineralocorticoid activity
compared to prednisone and prednisolone, which are related chemically to isoflupredone. It is
recommended for the treatment of ketosis in dairy cattle at a single dose of 10-20 mg IM, and
repeated if necessary, 12-24 hours later. Field observatons indicate that repeated doses of
isoflupredone acetate decreases plasma concentrations of potassium by 70-80%, which suggests a
strong mineralocorticoid activity. It is recommended that isoflupredone be used judiciously and
animals be monitored for plasma potassium and any evidence of weakness and recumbency.
Treatment with oral potassium choride may be required, but may be ineffective.
REFERENCES
(1)CoxJ. L. et al. (1966)J. Anim. Sci., 25, 203.
(2)Telle, P. P. et al. (1964)J Aium. Sci., 23, 59.

(3)Ward, G. M. (1966) J. Dairy Sri., 49, 268.
(4)Sielman, E. S. et al. (1997) J. Am. Vet. Med. Assoc., 210, 240.
SELENIUM AND/OR VITAMIN E DEFICIENCIES
Several diseases of farm animals are caused by, or associated with, a deficiency of either selenium
or vitamin E alone or in combination, usually in association with predisposing factors such as
dietary polyunsaturated fatty acids, unaccustomed exercise, and rapid growth in young animals.
These are summarized in Table 29.5. All of these diseases are described under one heading
because both selenium and vitamin E are important in the etiology, treatment and control of the
major diseases caused by their deficiencies.
They are also known as selenium-vitamin E-responsive diseases because, with some exceptions,
they can be prevented by adequate supplementation of the diet with both nutrients.
The term 'selenium-responsive disease' has created some confusion relative to the
selenium-deficiency diseases. In some regions of the world, particularly New Zealand, and in parts
of Australia and North America, diseases such as ill-thrift in sheep and cattle, and poor
reproductive performance respond beneficially to selenium administration. While these usually
occur in selenium-deficient regions, they may not be due solely to selenium deficiency. Thus,
there are some reasonably well-defined selenium deficiency diseases, and some ill-defined
'selenium-responsive' diseases.
Synopsis
Etiology. Dietary deficiencies of selenium and vitamin E, and conditioning factors like dietary
polyunsaturated fatty acids.
Epidemiology
•Enzootic muscular dystrophy occurs in young growing calves, lambs, goat kids,and foals born
to dams in selenium-deficient areas and unsupplemented.Occurs worldwide and common in
Australasia, United Kingdom, Great Plains of North America where soils are deficient in selenium.
Vitamin E deficiency in animals fed poor quality forage and diets high in polyunsaturated fatty
acids. Outbreaks of muscular dystrophy precipitated by exercise.
•Mulberry heart disease in finishing pigs.
•Selenium-responsive diseases occur in Australasia and are not obvious clinically but respond to
selenium supplementation. Selenium and vitamin E deficiency may be involved in reproductive
performance, retained placenta in cattle, resistance to infectious disease like bovine mastitis.
Controversial.
Signs. Muscular dystrophy characterized by groups of animals with stiffness, weakness,
Table 29.5 Diseases considered to be caused by or associated with a deficiency of either selenium
or vitamin E or both (including 'selenium-responsive' diseases)
Cattle Horse Swine
Nutritional
(enzootic)
muscular
dystrophy
Retained fetal
Nutritional
muscular
dystrophy
Mulberry heart
disease Hepatosis
dietetica
Exudative
diathesis Iron
hypersensitivity
Sheep
Nutritional (enzootic) muscular
dystrorrropf
Reproductive inefficiency
Bone marrow abnormalities
'selenium responsive'

membranes
Resistance to
mastitis
Nutritional
muscular
dystrophy
Anemia
1516
recumbency, severe in myocardial form.Mulberry heart disease characterized by outbreaks of
sudden death in finishing pigs.
Clinical pathology. Increased plasma levels of creatine kinase. Low serum levels of selenium and
vitamin E. Glutathione peroxidase activity.
Lesions. Bilaterally symmetrical pale skeletal muscle, pale streaks in myocardial muscle. Hyaline
degeneration of affected muscle.
Diagnostic confirmation. Low selenium and vitamin E in diet and tissues, increased creatine
kinase and muscle degeneration.
Differential diagnosis list:
Acute muscular dystrophy in calves and yearlings:
•Haemophilus somnus septicemia (p. 895)
•Pneumonia (p. 443).
Subacute enzootic muscular dystrophy:
•Musculoskeletal diseases-plyarthritis, traumatic or infectious myopathies (blackleg),
osteodystrophy, and fractures of long bones (Chapter 13)
•Diseases of the nervous system-spinal cord compression (p. 543), Haemophilus somnus
meningoencephalitis (pp. 528, 895), and myelitis (p. 546), organophosphatic insecticide poisoning
(p. 1615)
•Diseases of the digestive tract-arbohydrate engorgement resulting in lactic acidosis, shock,
dehydration, and weakness (p. 284).
•Muscular dystrophy in lambs and kids-zootic ataxia and swayback (p. 1495)
•Muscular dystrophy in foals-raumatic injury to the musculoskeletal system and polyarthritis
(Chapter 13); meningitis (pp. 538, 708); traumatic injury to the spinal cord.
Treatment. Vitamin E and selenium parenterally.
Control. Selenium and vitamin E supplementation of diet, strategic oral and/or parenteral vitamin
E and selenium to pregnant dams or young animals on pasture.
ETIOLOGY
The selenium- and vitamin E-responsive or deficiency diseases of farm animals are caused by
diets deficient in selenium and/or vitamin E, with or without the presence of conditioning factors
such as an excessive quantity of polyunsaturated fatty acids in the diet. Almost all of the diseases
that occur naturally have been reproduced experimentally using diets deficient in selenium and/or
vitamin E. Conversely, the lesions can usually be prevented with selenium and vitamin E
supplementation. In certain instances, as for example in hand-fed dairy calves, the incorporation of
excessive quantities of polyunsaturated fatty acids was a major factor in the experimental disease
and this led to the conclusion that certain myopathic agents were necessary to produce the lesion,
which is no longer tenable. The presence of polyunsaturated fatty acids in the diet may cause a
conditioned vitamin E deficiency because the vitamin acts as an antioxidant. In the case of
naturally occurring muscular dystrophy in calves, lambs and foals on pasture, the myopathic agent,

if any, is unknown and selenium is protective. However, selenium is not protective against the
muscular dystrophy associated with the feeding of cod liver oil to calves.
Selenium is an essential nutrient for animals, and diseases due to selenium inadequacy in
livestock are of worldwide distribution (1). Selenium is a biochemical component of the enzyme
glutathione peroxidase (GSH-PX). The activity of the enzyme in erythrocytes is positively related
to the blood concentration of selenium in cattle, sheep, horses and swine, and is a useful aid for
the diagnosis of selenium deficiency and to determine the selenium status of the tissues of these
animals. The enzyme from the erythrocytes of both cattle and sheep contains 4 g atoms of
selenium per mol of enzyme (1). Selenium is also a component of thyroid gland hormones.
Plasma GSH-PX protects cellular membranes and lipid-containing organelles from
peroxidative damage by inhibition and destruction of endogenous peroxides, acting in conjunction
with vitamin E to maintain integrity of these membranes (1). Hydrogen peroxide and lipid
peroxides are capable of causing irreversible denaturation of essential cellular proteins, which
leads to degeneration and necrosis. GSH-PX catalyzes the breakdown of hydrogen peroxide and
certain organic hydroperoxides produced by glutathione during the process of redox cycling. This
dependence of GSH-PX activity on the presence of selenium offers an explanation for the
interrelationship of selenium, vitamin E, and sulfur-containing amino acids in animals. The
sulfur-containing amino acids maybe precursors of glutathione, which in turn acts as a substrate
for GSH-PX and maintains sulfhydryl groups in the cell. Selenium is also a component of several
other proteins such as selenoprotein of muscle, selenoflagellin, Se-transport proteins, and the
bacterial enzymes, formate dehydrogenase and glycine reductase. Selenium also facilitates
significant changes in the metabolism of many drugs and xenobiotics. For example, selenium
functions to counteract the toxicity of several metals such as arsenic, cadmium, mercury, copper,
silver, and lead.
Vitamin E is an antioxidant that prevents oxidative damage to sensitive membrane lipids by
decreasing hydroperoxide formation (1). The vitamin has a central role in protection of cellular
membranes from lipoperoxidation, especially membranes rich in unsaturated lipids, such as
mitochondria, endoplasmic reticulum, and plasma membranes.
An important interrelationship exists between selenium, vitamin E, and the sulfur-containing
amino acids in preventing some of the nutritional diseases caused by their deficiency. If vitamin E
prevents fatty acid hydroperoxide formation, and the sulfur amino acids (as precursors of GSH-PX)
and selenium are involved in peroxide destruction, these nutrients would produce a similar
biochemical result, that is, lowering of the concentration of peroxides or peroxide-induced
products in the tissues (1). Protection against oxidative damage to susceptible non-membrane
proteins by dietary selenium, but not by vitamin E, might explain why some nutritional diseases
respond to selenium but not to vitamin E. On the other hand, certain tissues or subcellular
components may not be adequately protected from oxidant damage because they are inherently
low in GSH-PX even with adequate dietary selenium. Damage to such tissues would be expected
to be aggravated by diets high in unsaturated fatty acids and to respond adequately to vitamin E
but not to selenium. The variations in GSH-PX activity between certain tissues, such as liver, heart,
skeletal and myocardial muscles, would explain the variations in the severity of lesions between
species.

There are both selenium-dependent GSH-PX and non-selenium-dependent GSH-PX activities
in the tissues and blood. The non-selenium-dependent enzyme does not contain selenium and does
not react with hydrogen peroxide but shows activity toward organic
1517
hydroperoxide substrates. The spleen, cardiac muscle, erythrocytes, brain, thymus, adipose tissue,
and striated muscles of calves contain only the selenium-dependent enzyme. The liver, lungs,
adrenal glands, testes, and kidney contain both enzymes. Hepatic tissue contains the highest level
of non-selenium-dependent enzyme.
EPIDEMIOLOGY
Enzootic nutritional muscular dystrophy (NMD)
Occurrence
This muscular dystrophy occurs in all farm animal species, but most commonly in young, rapidly
growing calves, lambs, goat kids, and foals born from dams that have been fed for long
periods,usually during the winter months, on diets low in selenium and vitamin E (2). It is an
important cause of mortality in goat kids from birth to about 3 months of age(3). Goat kids may
require more selenium than lambs or calves, which may explain the higher incidence of the
disease in kids.The disease in kids may also be associated with low α-tocopherol levels and
normal selenium status (4).
NMD in horses occurs most commonly in foals to about 7 months of age (5). In reported cases,
the concentration of selenium in the blood of the mares was subnormal, the concentrations of
selenium and vitamin E in the feedstuffs were subnormal, the level of unsaturated fatty acids in
the feed was high and vitamin E and selenium supplementation prevented the disease. The disease
is not well-recognized in adult horses, but sporadic cases of dystrophic myodegeneration are
recorded in horses from 5 to 10 years of age (5). Some baseline data for selenium and vitamin E
concentration in horses from breeding farms is available (6).
The disease also occurs in grain-fed yearling cattle. Stressors such as being turned outdoors
after winter housing, walking long distances, the jostling and movement associated with
vaccination and dehorning procedures and the like are often precipitating factors. The disease has
occurred in steers and bulls 12-18 months of age under feedlot conditions. There may even be
laboratory evidence of subclinical myopathy in normal animals in a group from which an index
case occurred. Outbreaks of severe and fatal NMD have occurred in heifers at the time of
parturition which were previously on a diet deficient in both selenium and vitamin E. The disease
may also occur sporadically in adult horses that are deficient in selenium.
There are two major syndromes:
•An acute form - myocardial dystrophy, which occurs most commonly in young calves and lambs,
and occasionally foals
•A subacute form - skeletal muscular dystrophy, which occurs in older calves and yearling cattle.
The two forms are not mutually exclusive.
Geographical distribution
NMD occurs in most countries of the world but is common in the United Kingdom, the United
States, Scandinavia, Europe, Canada, Australia, and New Zealand. In North America, it is
common in the northeast and northwest and uncommon on the relatively high selenium soils of the
Great Plains, where selenium toxicity has occurred. It is one of most common deficiency diseases
of farm livestock in the United States (7). Soils, and therefore the pastures they earn vary widely

in their selenium content, depending largely on their geological origin. In general, soils derived
from rocks of recent origin, e.g. the granitic and pumice sands of New Zealand, are notably
deficient in selenium. Soils derived from igneous rocks are likely to be low in selenium.
Sedimentary rocks, which are the principal parent material of agricultural soils, are richer in
selenium. Forage crops, cereal grains and corn grown in these areas are usually low in selenium
content (below 0.1 mg/kg dry matter (DM)), compared to the concentration in crops (above 0.1
mg/kg DM) grown in areas where the available soil selenium is much higher and usually adequate.
The disease occurs in pigs, usually in association with other more serious diseases, such as
mulberry heart disease and hepatosis dietetica.
Selenium in soil and animals
In the United States, the States of the Pacific northwest and of the northeastern and southeastern
seaboard are generally low in selenium (2). In Canada, western prairie grains generally contain
relatively high levels of selenium, whereas in the eastern provinces, soils and feedstuffs usually
have low selenium concentrations. Most soils in the Atlantic provinces of Canada are acidic and,
consequently, the forages are deficient in selenium. Most forage samples contain less than 0.10
mg/kg DM of selenium, and enzootic nutritional muscular dystrophy is common throughout the
region.
Surveys in the United Kingdom found that the selenium status may be low in sheep and cattle
fed locally produced feedstuffs without any mineral supplementation. In some surveys, up to 50%
of farms are low in selenium, which places a large number of animals at risk. There are also
differences in the selenium concentrations of different feeds grown in the same area. For example,
in some areas 75% of cattle fed primarily corn silage, or 50% of the cattle fed sedge hay, might be
receiving diets inadequate in selenium.
There may be wide variations in the serum selenium concentrations and glutathione peroxidase
activities in cattle grazing forages of various selenium concentrations within the same
geographical area. The selenium status of beef cows can vary between geographical areas within a
region of a country, which is likely due to variations in selenium concentration of the soil and
plants in these areas (8). Beef herds from areas with adequate soil levels of selenium, herds
provided with supplemental feed on pasture, and herds in which pregnancy diagnosis was done,
had higher average herd blood selenium values than other herds (8).
Several factors influence the availability of soil selenium to plants.
•Soil pH - alkalinity encourages selenium absorption by plants and the presence of a high level of
sulfur,which competes for absorption sites with selenium in both plants and animals,are two
factors reducing availability
•Variation between plants in their ability to absorb selenium; ‘selector' and ‘converter'plants are
listed under the heading of selenium poisoning;legumes take up much less selenium than do
grasses
•Seasonal conditions also influence the selenium content of pasture, the content being lowest in
the spring and when rainfall is heavy. Blood selenium in dairy cows in the United States were
lower during the summer and fall than during the winter and spring (9).
1518
In this way a marginally deficient soil may produce a grossly deficient pasture if it is heavily
fertilized with superphosphate, thus increasing its sulfate content, if the rainfall is heavy and the
sward is lush and dominated by clover as it is likely to be in the spring months.

Environmental sulfur from various anthropogenic activities has been suspected to be a
significant factor in contributing to several health problems in livestock (10). Livestock producers
near natural sour gas desulfurization plants have reported that sulfur emissions are responsible for
an increased occurrence of nutritional muscular dystrophy, weak calves, and retarded growth.
Experimentally, a moderate increase in dietary sulfur does not impair selenium and copper status,
or cause related disease in cattle (10).
Vitamin E
Vitamin E deficiency occurs most commonly when animals are fed inferior quality hay or straw or
root crops. Cereal grains, green pasture, and well-cured fresh hay contain adequate amounts of the
vitamin.
α-Tocopherol levels are high in green grasses and clovers, but there are wide variations in the
concentrations from one area to another. The serum tocopherol levels are higher in calves born
from cows fed grass silage than in those born from cows fed the same grass as hay. Many factors
influence the tocopherol content of pasture and hence the animals' intake. The level of tocopherol
in pasture declines by up to 90% as it matures. Levels as low as 0.7 mg/kg DM have been reported
in dry summer pastures grazed by sheep. The α-tocopherol content of rye-grass and clover pasture
ranges from 22 to 350 and 90 to 210 mg/kg DM, respectively. After harvesting and storage, the
tocopherol content of pasture and other crops may fall further, sometimes to zero. Preservation of
grain with propionic acid does not prevent the decline. Thus, the dietary intake of α-tocopherol by
cattle and sheep may be expected to vary widely and lead to wide variations in tissue levels. The
plasma vitamin E status of horses is highest from May to August in Canada when fresh grass is
being grazed and lowest when the horses are being fed harvested or stored feed during the same
period (11). Plasma vitamin E levels in dairy cows in the United States were higher during the
summer and fall than during the winter and spring (9).
Outbreaks of NMD may occur in yearling cattle fed on high-moisture grain treated with
propionic acid as a method of inexpensive storage and protection from fungal growth. There is a
marked drop in the vitamin E content of acid-treated grain, and an increase in the levels of
peroxides of fat, which is consistent with a loss of naturally occurring antioxidants such as the
tocopherols (secondary vitamin E deficiency). In these situations, the levels of selenium in the
feed were below 0.05 mg/kg DM, which is inadequate and emphasizes the interdependence of
selenium and vitamin E. The tocopherol content of moist grain (barley and maize) stored for 6
months, with or without propionic acid, falls to extremely low levels compared to conventionally
stored grain in which the tocopherol levels usually persist over the same length of time.
Selenium-deficient barley treated with sodium hydroxide to deplete it of vitamin E can be used to
induce NMD when fed to yearling cattle. The disease may occur in sucking lambs with low
plasma α-tocopherol levels and an adequate selenium status, which indicates that the sparing
effect of each nutrient may not occur over the broad spectrum of clinical deficiencies.
Polyunsaturated fatty acids (PUFAs) in diet
Diets rich in PUFA such as cod liver oil,other fish oils, fishmeal used as a protein
concentrate, lard, linseed oil, soybean and corn oils have been implicated in the production of
NMD, particularly in calves fed milk replacers containing these ingredients. The disease can be
reproduced experimentally in young ruminant cattle 6-9 months of age, by feeding a diet low in
vitamin E and selenium, and adding a linolenic acid. There are widespread
lesions of myodegeneration of skeletal and myocardial muscles (12). Fresh spring grass containing

a sufficient concentration of linolenic acid to equal the amount necessary to produce NMD in
calves may explain the occurrence of the naturally occurring disease in the spring months. The
oxidation during rancidification of the oils causes destruction of the vitamin ,thus increasing the
dietary requirements (a conditioned vitamin E deficiency), and the presence of myopathic agents
in the oils may also contribute to the occurrence of the disease. A secondary vitamin E deficiency
occurs when NMD develops on rations containing vitamin E in amounts ordinarily considered to
be adequate, but the disease is prevented by further supplementation with the vitamin. The lack of
specificity of vitamin E in the prevention of muscular dystrophy in some circumstances is
indicated by its failure, and by the efficiency of selenium, as a preventive agent in lambs on lush
legume pasture.
Other myopathic agents in diet
Not all of the myopathic agents that maybe important in the development of NMD in farm animals
have been identified. Unsaturated fatty acids in fish and vegetable oils may be myopathic agents in
some outbreaks of NMD of calves and lambs. Lupinosis-associated myopathy in sheep is a
substantial skeletal muscle myopathy encountered in weaner sheep grazing lupin stubbles infected
with the fungus Phomopsis spp. (13). Affected sheep have a stiff gait, walk reluctantly, stand with
their back humped and their feet under the body.and have difficulty getting to their feet.
Unaccustomed exercise
Historically, NMD occurred most commonly in rapidly growing, well-nourished beef calves 2-4
months of age, shortly following unaccustomed exercise. This was commonplace in countries
where calves were born and raised indoors until about 6-8 weeks of age when they were turned
out onto new pasture in the spring of the year. This has been a standard practice in small beef
herds in the United Kingdom, Europe, and North America. A similar situation applies for ewes
that lambed indoors and the lambs were let out to pasture from 1 to 3 weeks of age. Thus,
unaccustomed activity in calves and lambs running and frolicking following their turnout onto
pasture is an important risk factor but is not necessarily a prerequisite for the disease. In lambs, the
vigorous exertion associated with running and sucking may account for the peracute form of
myocardial dystrophy in young lambs on deficient pastures and from deficient ewes. In older
lambs up to 3 months of age, outbreaks of acute NMD and stifflamb disease may be associated
with the driving of flocks long distances. A similar
1519
situation applies for calves that are moved long distances from calving grounds and early spring
pastures to lush summer pastures. The wandering and bellowing that occurs in beef calves weaned
at 6-8 months of age may precipitate outbreaks of subacute NMD. Degenerative myopathy of
yearling cattle (feedlot cattle, housed yearling bulls and heifer replacements) is now being
recognized with increased frequency (14). The disease resembles subacute NMD of calves, and in
the United Kingdom is often seen when yearlings are turned outdoors in the spring of the year
after being housed during the winter and fed a poor quality hay or straw or propionic acid-treated
grain. Unaccustomed exercise is a common precipitating factor. However, the disease has
occurred in housed yearling bulls with no history of stress or unaccustomed exercise but whose
diet was deficient in selenium and vitamin E.
In horses subjected to exercise there is an increase in erythrocyte malondialdehyde, a product of
peroxidation, but selenium supplementation has no beneficial effect. There is inconclusive
evidence that a selenium-vitamin E deficiency causes NMD in adult horses. There is no evidence

that paralytic myoglobinuria and the 'tying-up' syndrome are due to a deficiency of selenium and
vitamin E.
Congenital nutritional muscular dystrophy
Congenital NMD is rare in farm animals. Isolated cases have been reported but not
well-documented. Similarly, NMD can occur in calves and lambs only a few days of age but
rarely. Selenium readily crosses the bovine placenta and fetal selenium is always higher than the
maternal status (15). There is no evidence that the weak-calf syndrome is associated with selenium
deficiency (16). Long-term parenteral supplementation with neither selenium alone nor in
combination with vitamin E had any effect on the incidence of the weak-calf syndrome.
In pigs, NMD has been produced experimentally on vitamin E - and selenium-deficient rations
but is usually only a part of the more serious complex of mulberry heart disease and hepatosis
dietetica.
Vitamin E-Selenium Deficiency (VESD) syndrome
Mulberry heart disease, hepatosis dietetica, exudative diathesis and nutritional myopathy,
also known as the VESD syndrome (vitamin E and selenium deficiency), occurs naturally in
rapidly growing pigs, usually during the postweaning period (3 weeks to 4 months), particularly
during the finishing period. It is usually associated with diets deficient in both selenium and
vitamin E and those that may contain a high concentration of unsaturated fatty acids. Such diets
include those containing mixtures of soybean, high-moisture corn, and the cereal grains grown on
soils with low levels of selenium. The feeding of a basal ration of cull peas, low in selenium and
vitamin E, to growing pigs can cause the typical syndrome, and low tissue levels of selenium are
present in pigs with spontaneously occurring hepatosis dietetica. However, there are reports of
naturally occurring cases of mulberry' heart disease of swine in Scandinavia in which the tissue
levels of selenium and vitamin E are within normal ranges compared to normal pigs (17). In
Ireland, in spite of supplementation of pig rations with vitamin E and selenium at levels higher
than that necessary to prevent experimental disease, spontaneous mulberry heart disease may still
occur (18). Affected pigs have lower tissue vitamin E levels than control pigs, which suggests an
alteration in а-tocopherol metabolism unrelated to dietary selenium and PUFA contents.
Natural occurrence of the disease complex in swine is not uncommonly associated with diets
containing 50% coconut meal, fish-liver oil emulsion, fish scraps with a high content of
unsaturated fatty acids, or flaxseed, which produces yellow and brown discoloration of fat
preventable by the incorporation of adequate amounts of а-tocopherol or a suitable antioxidant.
The quality of the dietary fat does not necessarily influence blood vitamin E levels, but the
presence of oxidized fat reduces the resistance of the red blood cells against peroxidation. The
higher requirement for vitamin E by pigs fed oxidized fat may be due to the low vitamin E content
in such fat.
Mulberry heart disease
This is the most common form of selenium and vitamin E deficiency of swine. It occurs most
commonly in rapidly growing feeder pigs (60-90 kg) in excellent condition being fed on a
high-energy diet low in vitamin E and selenium. The diets most commonly incriminated are
soybean, corn, and barley. The а-tocopherol content of corn is usually low and it is virtually
absent from solvent-extracted soybean meal. Both are low in selenium. The use of high-moisture
corn may further exacerbate the tocopherol deficiency. The level of PUFAs in the diet was thought
to be an important etiological factor but this is now not considered to be a necessary prerequisite.

Outbreaks of the disease may occur in which 25% of susceptible pigs are affected, and the case
mortality rate is about 90%. The disease has occurred in young piglets and in adult sows.
Hepatosis dietetica
Hepatosis dietetica appears to be less common than mulberry heart disease but the
epidemiological characteristics are similar. It affects young growing pigs up to 3-4 months of age.
NMD in swine usually occurs in cases of mulberry heart disease and hepatosis dietetica but it has
occurred alone in gilts (11-12 months of age) 48 hours after farrowing. The gilts had been fed on a
diet of barley and lupin seed which contained only 0.03 mg/kg of selenium.
Selenium-responsive unthriftiness
In New Zealand, a variety of diseases have been known as selenium-responsive diseases (19),
because they respond beneficially to the strategic administration of selenium. These include
ill-thrift in lambs and calves on pasture, ewe infertility, and diarrhea in older calves and
lactating ewes. The pathogenesis of these selenium-responsive diseases is not known but it would
appear that the selenium deficiency is only marginal. Most investigations into selenium-responsive
diseases have occurred in selenium-deficient areas in which diseases such as NMD of calves and
lambs occur (19). The evidence that selenium deficiency in breeding ewes can result in a decline
in reproductive performance has not been substantiated experimentally. Reproductive performance
was not affected in ewes on a selenium-depleted diet. A recent report indicated that
selenium-responsive infertility in ewes may be present when the whole blood levels of selenium
are below 10 ng/mL (12.7 nmol/L) (19).
Selenium-responsive unthriftiness in sheep has received considerable attention in New Zealand
where the response to selenium administration
1520
has been most dramatic compared to Australia where the syndrome has also been recognized but
where the response is much smaller. The oral administration of selenium to lambs in these areas
results in greater body weight gains from weaning to 1 year of age compared to lambs not
receiving selenium supplementation (19). The mean fleece weight of selenium-treated lambs is
also greater.
The diagnosis of selenium-responsive unthriftiness depends on analyses of the soil, pasture and
animal tissues for selenium, and response trials to selenium supplementation. A deficiency state
might be encountered when the selenium content of the soil is below 0.45 mg/kg, the pasture
content below 0.02 mg/kg DM, the liver content below 21ug/kg (0.27 µmol/kg) (WW) and wool
concentrations below 50-60µg/kg (0.63-0.76 µmol/kg). For the blood in selenium-responsive
unthriftiness of sheep the following criteria are suggested (19):
•Mean blood selenium
•Selenium status (ug/dL)
Deficient = 1.0
•Doubtful 1.1-1.9
•Normal~2.0.
The GSH-PX activity is a good index of the selenium status of sheep with a
selenium-responsive disease. If measured on a regular basis, it can provide an indication of the
selenium status of grazing sheep in individual flocks. Single measurements of GSH-PX activity
may fail to detect recent changes in grazing area, differences in pasture species and pasture
composition, and alterations in the physiological state of the animals.

Subclinical selenium insufficiency
Subclinical insufficiencies of selenium in grazing ruminants are widespread over large areas of
southern Australia (20). The plasma concentrations of affected sheep flocks are low, there are no
obvious clinical signs of insufficiency in the ewes, and there are significant responses in wool
production and fiber diameter to selenium supplementation. The incidence of estrus and fertility is
not affected by selenium supplementation (21). Liveweights at birth, in mid-lactation and at
weaning were increased in lambs born to selenium-supplemented and crossbred ewes, and in
lambs born as singletons (22).
Clean fleece weight at 10 months of age was increased by 9.5% and fiber diameter by 0.3um in
lambs born to ewes that had received supplementary selenium. Differences in fleece weight and
liveweight were not detected at 22 months, suggesting that subclinical selenium insufficiency in
early life did not permanently impair productivity if selenium status subsequently increased.
Selenium is a component of type-I iodothyronine deiodinase, which catalyzes the extrathyroidal
conversion of thyroxine (T4) to the more active triiodothyronine (T3). Sheep grazing pastures low
in selenium frequently have higher circulating T4 and lower circulating T3 concentrations than
sheep receiving selenium supplementations.
When ewes grazing pastures low in selenium were supplemented thiocyanate (to cause iodine
insufficiency), iodide and selenium, there was no evidence of clinical deficiencies (23). Growth
rates of lambs were not affected by thiocyanate of their dams during midpregnancy, but plasma T3
and T4 concentrations were depressed in ewes receiving thiocyanate. The iodide supplementation
increased thyroid hormone concentrations in ewes, but depressed plasma T3 concentrations in
lambs. Supplementation of sheep grazing pastures low in selenium with both selenium and thyroid
hormones improved wool characteristics, liveweight gain, and blood selenium, but there was no
evidence of an interaction between the selenium and the hormones (24). Thus it seems unlikely
that the decline in the quantity of T3 produced, or of T4 utilized for T3 production, in
selenium-deficient sheep is responsible for the observed differences in the productivity of
selenium-deficient and supplemented sheep. The thyroids have a major role in regulating
thermogenesis, and lambs born to ewes supplemented with iodide tend to have higher rectal
temperatures during cold stress (25). The thermoregulatory ability of the perinatal lamb is not
adversely affected by subclinical selenium deficiency.
Reproductive performance
The published information on the effects of vitamin E and selenium deficiency or of dietary
supplementation with one or the other or both on reproductive performance in farm animals are
conflicting and controversial. Reproductive performance is complex and dependent on the
interaction of many factors. Reproductive inefficiency is likewise complex, and it is difficult to
isolate one factor like a deficiency of vitamin E or selenium as a cause of reproductive
inefficiency. Conversely, it is difficult to prove that supplementation with these nutrients will
insure optimum reproductive performance.
Sheep
The evidence about the effect of selenium and vitamin E deficiency on reproductive performance
in sheep is conflicting. Observations in the 1960s concluded that selenium deficiency caused
embryonic deaths 20-30 days after fertilization in ewes. But supplementation of ewes, low or
marginal in selenium status, with selenium did not improve reproductive performance.
Experimental studies using selenium-deficient diets in ewes have been unable to find any adverse

effect of selenium depletion on ewe conception rates, embryonic mortality or numbers of lambs
born. The parenteral administration of selenium to pregnant ewes between 15 and 35 days after
mating resulted in a reduced embryonic survival rate and is not recommended during the first
month of pregnancy (26).
Cattle
The importance of selenium and vitamin E for the maintenance of optimum reproductive
performance is not clear. The IM injection of dairy cattle with selenium and vitamin E 3 weeks
prepartum did not have any effect on average days to first estrus or first service, average days to
conception, services per conception, or number of uterine infusions required. The prepartum IM
injection of vitamin E and selenium 3 weeks prepartum increased the percentage of cows pregnant
to first service, reduced the number of services per conception, decreased the incidence of retained
placenta, and reduced the interval from calving to conception (27). In a randomized field trial in a
large dairy herd in the United States, oral supplementation of pregnant first-calf dairy heifers with
selenium using a commercially available sustained-release intraruminal selenium bolus, increased
blood selenium concentrations in treated animals at 30 days after treatment until after calving (28).
However, based on data analyzed midlactation and late lactation, there were no differences
between
1521
treated and control groups in somatic cell count, days not pregnant, total milk production, or times
bred. The use of an intra-ruminal pellet of selenium at two different levels in dairy herds in New
Zealand was evaluated in yearling heifers (29). The recommended dose was effective in elevating
whole blood GSH-FX activity and selenium concentrations to over 10 times those of control
animals. Milk production was increased and there was a trend to decreased somatic cell counts.
There were no differences in calving-first-service or calving-conception intervals, or in the
percentage of animals pregnant to first or all services. In other observations, following the
treatment of dairy cows with oral selenium pellets there was an improvement in first service
conception rate and significantly higher blood levels of GSH-PX. The inconsistent results
obtained following the use of selenium and vitamin E in pregnant cows may be related to the
selenium status of the animals; in some herds the blood levels are marginal and in others the levels
are within the normal range.
Retained fetal placenta
A high incidence (more than 10%) of retained fetal membranes has been associated with marginal
levels of plasma selenium compared with herds without a problem. In some cases, the incidence
could be reduced to below 10% by the injection of pregnant cattle with selenium and vitamin E
about 3 weeks prepartum, while in other studies similar prepartum injections neither reduced the
incidence nor improved reproductive performance. A single injection of selenium 3 weeks
prepartum can reduce the number of days postpartum required for the uterus to reach minimum
size and to reduce the incidence of metritis and cystic ovaries during the early postpartum period.
The parenteral administration of a single injection of 3000 mg vitamin E prepartum to dairy cows
of all ages decreased the incidence of retained placenta and metritis to 6.4% and 3.9%,
respectively, in the treated group, compared to 12.5% and 8.8%, in the control group (30). The
injection, 20 days prepartum, of 50 mg of selenium and 680 IU of vitamin E reduced the incidence
of retained fetal membranes in one series, but did not in another series. The plasma selenium
concentration at parturition ranged from 0.02 to 0.05 ppm in control cows in winch there was an

incidence of 51% retained membranes, and from 0.08 to 0.1 ppm in treated cows in which the
incidence was reduced to 9%. A dietary level of 0.1 mg/kg DM selenium is recommended to
minimize the incidence of the problem. The complex nature of the etiology of retained fetal
membranes also requires a well-designed experimental trial to account for all of the possible
factors involved.
Resistance to infectious disease
Many studies have examined the role of selenium and vitamin E resistance to infectious disease
(31). Most of the evidence is based on in vitro studies of the effects of deficiencies of selenium or
vitamin E or supplementation with the nutrients on leukocyte responses to mitogens, or on the
antibody responses of animals to a variety of pathogens. The status of selenium and vitamin E in
an animal can alter; antibody response, phagocytes function, lymphocyte response, and resistance
to infectious disease (31). In general, a deficiency of selenium results in immunosuppression, and
supplementation with low doses of selenium augments immunological functions. A deficiency of
selenium has been shown to inhibit:
• Resistance to microbial and viral infections
• Neutrophil function
• Antibody production
• Proliferation of T and B lymphocytes in response to mitogens
•Cytodestruction of T lymphocytes and natural killer lymphocytes (32).
Vitamin E and selenium have interactive effects on lymphocyte responses to experimental
antigens (33).
Neutrophil function
Selenium deficiency can affect the function of polymorphonuclear neutrophils (PMNs), which are
associated with physiological changes in GSH-PX levels. In calves on an experimental
selenium-deficient diet, the oxygen consumption and the activities of GSH-PX are lower than
normal in neutrophils. The feeding of 80-120 mg of selenium/kg of mineral mixture provided ad
libitum is an effective method of increasing blood selenium in a group of cattle and optimizing the
humoral antibody response experimentally. It is suggested that blood selenium levels over 100
(Jg/L are necessary to maintain optimum immunocompetence in growing beef cattle (34). In
selenium-deficient goats, the production of leukotriene B4, a product of neutrophil arachidonic
acid lipoxygenation and a potent chemotactic and chemokinetic stimulus for neutrophils, is
decreased, resulting in dysfunction of the neutrophils. A deficiency of selenium in pregnant sows
impairs neutrophil function, and vitamin E deficiency impairs function of both neutrophils and
lymphocytes, which may result in increased susceptibility of their piglets to infectious diseases
(35). It is suggested that selenium supplementation be maintained at 0.3 mg/kg of the diet.
Immune response
The effects of selenium deficiency and supplementation on the immune response of cattle to
experimental infection with the infectious bovine rhinotracheitis virus, and sheep to
parainfluenza-3 virus indicate that a deficiency can affect the humoral response and
supplementation enhances the response. Pigs fed a vitamin E and selenium-deficient diet develop
an impaired cell-mediated immunity as measured by lymphocyte response to mitogenic
stimulations. Supplementation of the diets of young swine with selenium at levels above those
required for normal growth has increased the humoral response, but not in sows. The wide
variations in antibody responses that occur in these experiments indicate that there is a complex

elationship between the selenium status of the host, humoral immune responses, and protective
immunity. The concept of using selenium supplementation to enhance antibody responses in sheep
to vaccines is probably unfounded.
Vitamin E can stimulate the immune defense mechanisms in laboratory animals and cattle,
experimentally (36). In most cases, the immunostimulatory effects of additional vitamin E are
associated with supplementation in excess of levels required for normal growth. The parenteral
administration to calves of 1400 mg of vitamin E weekly increases their serum vitamin E
concentrations and lymphocyte stimulation indices. Similarly in growing pigs, a serum vitamin E
concentration above 3 mg/L was necessary to achieve a significant response of the lymphocytes to
stimulation with mitogens.
1522
General resistance
These changes may render selenium-deficient animals more susceptible to infectious disease, but
there is no available evidence to indicate that naturally occurring selenium and vitamin E
deficiencies are associated with an increase in the incidence or severity of infectious diseases.
Neutrophils from selenium-deficient animals lose some ability to phagocytose certain organisms,
but how relevant this observation is in naturally occurring infections is unclear. Field studies of
the incidence and occurrence of pneumonia in housed calves found that selenium status was not a
risk factor.
Neonatal morbidity and mortality
Based on some preliminary observations of the selenium content of hair samples of young calves,
higher selenium levels in newborn calves may have some protective effect against morbidity due
to neonatal disease. Similarly, neonatal piglets with high blood levels of GSH-PX activity may be
more resistant to infectious diseases or other causes of neonatal mortality. Administration of
vitamin E and selenium to dairy cows in late pregnancy resulted in the production of increased
quantities of colostrum and the calves have increased quantities of GSH-PX at birth and 28 days
of age, but the improved selenium status did not provide any improvement in passive immunity or
growth (37). Supplementing selenium to beef cows grazing selenium-deficient pastures with a salt
mineral mix containing 120 mg selenium/kg of mix increased the selenium status of the cows and
increased the serum IgG concentration, or enhanced transfer of IgG from serum to colostrum and
increased the selenium status of the calves (38). The parenteral administration of 0.1 mg Se and 1
mg ot vitamin E/kg BW at midgestation did not affect the production of systemic or colostrai
antibodies. Supplementation of dairy cows at dry-off with selenium at 3 mg/d as selenite via an
intrarurninal bolus resulted in sufficient transfer of selenium to meet a target concentration of
more than 2.2 p.g of selenium/g of liver DM in newborn calves (39).
Mastitis in dairy cattle
There is some evidence that a dietary deficiency of vitamin E may be associated with an
increased incidence of mastitis in dairy cattle (40). An increased incidence of mastitis during the
early stages of lactation coincides with the lowest plasma concentration of vitamin E.
Supplementation of the diet of dairy cows beginning 4 weeks before and continuing for up to 8
weeks after parturition with vitamin E at 3000 IU/cow/d combined with an injection of 5000 IU, 1
week before parturition, prevented the suppression of blood neutrophil and macrophage function
during the early postpartum period compared to controls (40). The vitamin E prevented the
suppression of blood neutrophils during the postpartum period (41). Cows in both the treated and

control groups were fed diets containing selenium at 0.3 ppm of total dry matter. When selenium
status in dairy cows is marginal, plasma concentrations of a-tocopherol should be at least 3 µg/mL
(42). Cows receiving a dietary supplement of about 1000 IU/d of vitamin E had 30% less clinical
mastitis than did cows receiving a supplement of 100 lU/d of vitamin E (42). The reduction was
88% when cows were fed 4000 IU/d of vitamin E during the last 14 days of the dry period (42).
The selenium status of dairy cows may also have an effect on the prevalence of mastitis and
mammary gland health (43, 44). Dairy herds with low somatic cell counts had significantly higher
mean blood GSH-PX and higher whole blood concentrations of selenium than in herds with high
somatic cell counts (44). The prevalence of infection due to Streptococcus agalactiac and
Staphylococcus aureus was higher in herds with the high somatic cell counts compared to those
with the low somatic cell counts. This suggests that phagocytic function in the mammary gland
may be decreased by a marginal selenium deficiency. In a survey of cattle in herds in Switzerland,
those with chronic mastitis had lower serum levels of selenium than healthy control herds (45).
Experimental coliform mastitis in cattle is much more severe in selenium-deficient animals than
selenium-adequate animals (46). The severity was in part due to the increased concentrations of
eicosanoids.
Milk neutrophils from cows fed a selenium-deficient diet have significantly reduced capacity to
kill ingested Escherichia coli and Staph. aureus, compared to cells from cows fed a
selenium-supplemented diet (47). However, other experimental results are not as convincing.
Blood abnormalities
In young cattle from areas where NMD is endemic, and particularly at the end of winter housing,
the erythrocytes have an increased susceptibility to hemolysis following exposure to hypotonic
saline. During clinical and subclinical white muscle disease in calves, there is a significant
increase in both the osmotic and the peroxidative hemolysis of the erythrocytes. This defect is
thought to be the result of alterations in the integrity of cell membranes of which tocopherols are
an essential component. Abnormalities of the bone marrow associated with vitamin E deficiency
in sheep have been described, and abnormal hematological responses have been described in
young growing pigs on an experimental selenium and vitamin E deficient diet. Vitamin E
deficiency in sheep results in increased hemolytic susceptibility of erythrocytes, which may
provide a basis for a single functional test for vitamin E deficiency in sheep (48).
Anemia characterized by a decreased packed cell volume, decreased hemoglobin concentration,
and Heinz body formation has been observed in cattle grazing on grass grown on peaty muck soils
in the Florida everglades. Selenium supplementation corrected the anemia, prevented Heinz body
formation, increased the body weight of cows and calves, and elevated blood selenium.
Equine degenerative myeloencephalopathy
Equine degenerative myeloencephalopathy, which may have an inherited basis (49), has been
associated with a vitamin E deficiency. The vitamin E status is low in some affected horses and
supplementation with the vitamin was associated with a marked reduction in the incidence of the
disease. However, scrum vitamin E and blood GSH-PX activities determined in horses with
histologically confirmed diagnosis of the disease compared to age-matched controls failed to
reveal any differences, and the findings did not support a possible role for vitamin E deficiency as
a cause (50). Foals sired by a stallion with degenerative myeloencephalopathy and with
neurological deficits consistent with the disease during their first year of life had lower plasma
levels of a-tocopherol when the levels were determined serially beginning at 6

1523
weeks to 10 months of age than age-matched controls (51). Absorption tests with vitamin E
revealed that the lower a-tocopherol levels were not due to an absorption defect (51). The protocol
for the oral vitamin E absorption test has been reported (52).
Equine motor neuron disease
This a neurodegenerative disease of the somatic lower motor neurons resulting in a syndrome of
diffuse neuromuscular disease in the adult horse (53). Case-control studies found the mean plasma
vitamin E concentrations in affected horses were lower than that of control horses. Adult horses
are affected with the risk peaking at 16 years of age. In addition to the role of vitamin E depletion,
other individual and farm-level factors, contribute to the risk of developing the disease.
Generalized steatitis
Steatitis in farm animals and other species may be associated with vitamin E and/or selenium
deficiency. Most cases in horses have involved nursing or recently weaned foals. Generalized
steatitis in the foal has been described as either generalized cachexia due to steatitis alone, or as a
primary myopathy or myositis with steatitis of secondary importance. The terms used have
included steatitis, generalized steatitis, fat necrosis, yellow fat disease, polymyositis, and muscular
dystrophy. The relationships between steatitis and vitamin E and selenium deficiency in the horse
are not clear and there may be none. Many more clinical cases must be examined in detail before a
cause-effect relationship can be considered.
PATHOGENESIS
Dietary selenium, sulfur-containing amino acids and vitamin E act synergistically to protect
tissues from oxidative damage (1). GSH-PX, which is selenium-dependent, functions by
detoxifying lipid peroxides and reducing them to nontoxic hydroxy fatty acids. Vitamin E prevents
fatty acid hydroperoxide formation. High levels of PUFAs in the diet increase the requirements for
vitamin E and, with an inadequate level of selenium in the diet, tissue oxidation occurs, resulting
in degeneration and necrosis of cells. Vitamin E protects cellular membranes from
lipoperoxidation, especially membranes rich in unsaturated lipids, such as mitochondric,
endoplasmic reticulum, and plasma membranes. Thus dietary PUFA are not a prerequisite for the
disease. Diets low in selenium and/or vitamin E do not provide sufficient protection against the
'physiological' lipoperoxidation that occurs normally at the cellular level.
The relative importance of selenium, vitamin E and sulfur-containing amino acids in providing
protection in each of the known diseases caused by their deficiency is not clearly understood.
Selenium has a sparing effect on vitamin E and is an efficient prophylactic against muscular
dystrophy of calves and lambs at pasture, but does not prevent muscular dystrophyin calves fed on
a diet containing cod liver oil. The current understanding of the biochemical function of selenium
and its relation to vitamin E and the mechanisms of action of selenium and vitamin E in protection
of biological membranes has been reviewed (54).
Nutritional muscular dystrophy
A simplified integrated concept of the pathogenesis of the NMD would be as follows. Diets
deficient in selenium and/or vitamin E permit widespread tissue lipoperoxidation leading to
hyalineh degeneration and calcification of muscle fibers. One of the earliest changes in
experimental selenium deficiency in lambs is the abnormal retention of calcium in muscle fibers
undergoing dystrophy, and selenium supplementation prevents the retention of calcium.
Unaccustomed exercise can accelerate the oxidative process and precipitate clinical disease.

Muscle degeneration allows the release of enzymes, such as lactate dehydrogenase, aldolase and
creatine phosphokinase, the last of which is of paramount importance in diagnosis. Degeneration
of skeletal muscle is rapidly and successively followed by invasion of phagocytes and
regeneration. In myocardial muscle, replacement fibrosis is the rule.
In calves, lambs, and foals the major muscles involved are skeletal, myocardial, and
diaphragmatic. The myocardial and diaphragmatic forms of the disease occur most commonly in
young calves, lambs and foals, resulting in acute heart failure, respiratory distress and rapid death,
often in spite of treatment. The skeletal form of the disease occurs more commonly in older calves,
yearling cattle and older foals, and results in weakness and recumbency, is usually less severe and
responds to treatment. The biceps femoris muscle is particularly susceptible in calves, and muscle
biopsy is a reliable diagnostic aid.
In foals with NMD there is a higher proportion of type IIC fibers and a lower proportion of type
I and IIA fibers than in healthy foals. The type IIC fibers are found in fetal muscle and are
undifferentiated and still under development. During the recovery period, fibers of types IIA and
IIB increase and the proportion of type IIC fibers decreases. A normal fiber type composition is
present in most surviving foals 1-2 months after the onset of the disease.
Acute NMD results in the liberation of myoglobin into the blood, which results in
myoglobinuria. This is more common in horses, older calves and yearling cattle, than in young
calves whose muscles have a lower concentration of myoglobin. Hence, the tendency to
myoglobinuria will vary depending on the species and age of animal involved.
Subclinical selenium insufficiency
Selenium deficiency affects thyroid hormone metabolism and may explain the cause of ill-thrift.
The conversion of the iodine-containing hormone, thyroxine (T4) to the more potent
triiodothyronine (T3) is impaired in animals with low selenium status and
iodothyroninedeiodinase is a selenoprotein which mediates this conversion (54).
VESD syndrome and others
The pathogenesis of mulberry heart disease, hepatosis dietetica, exudative diathesis, and muscular
dystrophy of swine is not yet clear. Vitamin E and selenium are necessary to prevent widespread
degeneration and necrosis of tissues, especially liver, heart, skeletal muscle, and blood vessels.
Selenium and vitamin E deficiency in swine results in massive hepatic necrosis (hepatosis
dietetica), degenerative myopathy of cardiac and skeletal muscles, edema, microangiopathy, and
yellowish discoloration of adipose tissue. Myocardial and hepatic calcium concentrations are
increased in pigs with mulberry heart disease (55). In addition, there may be esophagogastnc
ulceration, but it is uncertain whether or not this lesion is caused by a selenium and/or vitamin E
deficiency. Anemia has also occurred and has been attributed to a block in bone marrow
maturation, resulting in inadequate erythropoiesis, hemolysis
1524
or both. However, there is no firm evidence that anemia is a feature of selenium and vitamin E
deficiency in swine. The entire spectrum of lesions has been reproduced experimentally in swine
with natural or purified diets deficient in selenium and vitamin E, or in which an antagonist was
added to inactivate vitamin E or selenium. However, in some studies, the selenium content of
tissues of pigs that died from mulberry heart disease was similar to that of control pigs without the
disease.
The extensive tissue destruction in pigs may account for the sudden death nature of the complex

(mulberry heart disease and hepatosis dietetica) and the muscle stiffness that occurs in some
feeder pigs and sows of farrowing time with muscular dystrophy. The tissue degeneration is
associated with marked increases in serum enzymes related to the tissue involved. An indirect
correlation between vitamin E intake and peroxide hemolysis in pigs on a deficient diet sugests
that lipoperoxidation is the ultimate biochemical defect in swine and that vitamin E and selenium
are protective.
CLINICAL FINDINGS
Acute enzootic muscular dystrophy
Affected animals may collapse and die suddenly after exercise without any other premonitory
signs. The excitement associated with the hand-feeding of dairy calves may precipitate peracute
death. In calves under dose observation, a sudden onset of dullness and severe respiratory distress,
accompanied by a frothy or blood-stained nasal discharge, may be observed in some cases.
Affected calves, lambs, and foals are usually in lateral recumbency and may be unable to assume
sternal recumbency even when assisted. When picked up and assisted to stand, they feel and
appear limp. However, their neurological reflexes are normal. Their eyesight and mental attitude
are normal and they are usually thirsty and can swallow unless the tongue is affected. The heart
rate is usually increased up to 150-200/min and often with arrhythmia, the respiratory rate is
increased up to 60-72/min and loud breath sounds are audible over the entire lung fields. The
temperature is usually normal or slightly elevated. Affected animals commonly die 6-12 hours
after the onset of signs in spite of therapy. Outbreaks of the disease occur in calves and lambs in
which up to 15% of susceptible animals may develop the acuteform, and the case fatality
approaches100%.
Subacute enzootic muscular dystrophy
This is the most common form in rapidly growing calves, 'white muscle disease', and in young
lambs, 'stiff-Iamb disease'.Affected animals may be found in sternal recumbency and unable to
stand but some make an attempt to stand. If they are standing, the obvious signs are stiffness,
trembling of the limbs, weakness and, in most cases, an inability to stand for more than a few
minutes. The gait in calves is accompanied by rotating movements of the hocks, and in lambs a
stiff, goose-stepping gait. Muscle tremor is evident if the animal is forced to stand for more than a
few minutes. On palpation the dorsolumbar, gluteal, and shoulder muscle masses may be
symmetrically enlarged and firmer than normal (although this may be difficult to detect). Most
affected animals retain their appetite and will suck if held up to the dam or eat if hand-fed. Major
involvement of the diaphragm and intercostal muscles causes dyspnea with labored and
abdominal-type respiration. The temperature is usually in the normal range but there may be a
transient fever (41℃, 105℃) due to the effects of myoglobmemia and pain. The heart rate may be
elevated, but there are usually no rhythmic irregularities. Following treatment, affected animals
usually respond in a few days, and within 3-5 days they are able to stand and walk unassisted.
In some cases, the upper borders of the scapulae protrude above the vertebral column and are
widely separated from the thorax. This has been called the 'flying scapula' and has occurred in
outbreaks in heifers from 18 to 24 months of age within a few days after being turned out in the
spring following loose-housing throughout the winter (56, 57). The abnormality is due to bilateral
rupture of the serratus ventralis muscles (58) and has been reported in a red deer (59).
Occasionally, the toes are spread and there is relaxation of carpal and metacarpal joints or
knuckling at the fetlocks and standing on tip-toe, inability to raise the head, difficulty in

swallowing, inability to use the tongue, and relaxation of abdominal muscles. Choking may occur
when the animal attempt to drink. In 'paralytic myoglobinuria' of yearling cattle, there is usually a
history of recent turning out on pasture following winter housing. Clinical signs occur within 1
week and consist of stiffness, recumbency, myoglobinuria, hyperpnea, and dyspnea. Severe cases
may die within a few days and some are found dead without premonitory signs. In rare cases,
lethargy, anorexia, diarrhea, and weakness are the first clinical abnormalities recognized, followed
by recumbency and myoglobinuria.
Subcapsular liver rupture in lambs has been associated with vitamin E deficiency in lambs
usually under 4 weeks of age (60). Affected lambs collapse suddenly, become limp, and die within
a few minutes or several hours after the onset of weakness.
In foals, muscular dystrophy occurs most commonly during the first few months of life and is
common in the first week. The usual clinical findings are failure to suck, recumbency, difficulty in
rising, and unsteadiness and trembling when forced to stand. The temperature is usually normal
but commonly there is polypnea and tachycardia.
In adult horses with muscular dystrophy, a stiff gait, myoglobinuria, depression, inability to
eat, holding the head down low, and edema of the head and neck are common. The horse may be
presented initially with clinical signs of colic.
In pigs, muscular dystrophy is not commonly recognized clinically because it is part of the
more serious disease complex of mulberry heart disease and hepatosis dietetica. However, in
outbreaks of this complex, sucking piglets, feeder pigs, and sows after farrowing may exhibit an
uncoordinated, staggering gait suggestive of muscular dystrophy.
Subclinical nutritional muscular dystrophy occurs in apparently normal animals in herds at
the time clinical cases are present. The serum levels of creatine phosphokinase levels may be
elevated in susceptible animals for several days before the onset of clinical signs; following
treatment with vitamin E and selenium the level of serum enzymes returns to normal. Grossly
abnormal electrocardiograms occur in some animals and may be detectable before clinical signs
are evident.
Mulberry heart disease
In mulberry heart disease, affected animals are commonly found dead without premonitory
1525
signs. More than one pig may be found dead. When seen alive, animals show severe dyspnea,
cyanosis and recumbency, and forced walking can cause immediate death. In some outbreaks,
about 25% of pigs will show a slight inappetence and inactivity, these are probably in the
subclinical stages of the disease.The stress of movement, inclement weather or transportation will
precipitate further acute deaths. The temperature is usually normal, the heart rate rapid,and
irregularities maybe detectable. The feces are usually normal.
Hepatosis dietetica
In hepatosis dietetica, most pigs are found dead. In occasional cases, before death there will be
dyspnea, severe depression, vomiting, staggering, diarrhea and a state of collapse. Some pigs are
icteric. Outbreaks also occur similar to the pattern in mulberry heart disease. Muscular dystrophy
is almost a consistent necropsy finding in both mulberry heart disease and hepatosis dietetica but
is usually not recognized clinically because of the seriousness of the two latter diseases. Clinical
muscular dystrophy has been described in gilts at 11 months of age. About 48 hours after
farrowing, there was muscular weakness, muscular tremors, and shaking. This was followed by

collapse, dyspnea, and cyanosis. There were no liver or heart lesions. In experimental selenium
and vitamin E deficiency in young growing pigs, a subtle stiffness occurs along with a significant
increase in the creatinine phosphatase (CPK) and serum glutamicoxaloacetic transaminase (SGOT)
values.
CLINICAL PATHOLOGY
Myopathy
Plasma creatine kinase (CK)
This is the most commonly used laboratory aid in the diagnosis of NMD. The enzyme is highly
specific for cardiac and skeletal muscle and is released into the blood following unaccustomed
exercise and myodegeneration. In cattle and sheep, its half-life is 2-4 hours and plasma levels
characteristically decline quickly unless there is continued myodegeneration, but remain a good
guide to the previous occurrence of muscle damage for a period of about 3 days. The normal
plasma levels of CK (IU/L) are: sheep 52 +/- 10; cattle 26 +/- 5; horses 58 +/-6; and pigs 226 +/-
43. In cattle and sheep with NMD, the CK levels will be increased usually above 1000 IU/L,
commonly increased to 5000-10000 IU/L and not uncommonly even higher. Following turnout of
housed cattle onto pasture the CK levels will increase up to 5000 IU/L within a few days. The CK
levels will usually return to normal levels within a few days following successful treatment.
Persistent high levels suggest that muscle degeneration is still progressive or has occurred within
the last 2 days. Measurement of plasma CK activity could be used to monitor recovery of animals
treated for nutritional myopathy (61).
Aspartate aminotransferase
Aspartate aminotransferase (AST) activity is also an indicator of muscle damage, but is not as
reliable as the CK because increased AST levels may also indicate liver damage. The AST activity
remains elevated for 3-10 days because of a much longer half-life than CK. In acute cases, levels
of 300-900 IU/L in calves and 2000-3000 IU/L in lambs have been observed. In normal animals of
these species, serum levels are usually less than 100 IU/L.
The magnitude of the increase in AST and CK is directly proportional to the extent of muscle
damage. Both are elevated initially; an elevated AST and declining CK would suggest that muscle
degeneration is no longer active. The levels of both enzymes will be increased slightly in animals
that have just been turned out and subjected to unaccustomed exercise, horses in training, and in
animals with ischemic necrosis of muscle due to recumbency caused by diseases other than
muscular dystrophy. However, in acute muscular dystrophy, the levels are usually markedly
elevated.
Selenium status
Although information on the critical levels of selenium in soil and plants is accumulating
gradually, the estimations are difficult and expensive. Most field diagnoses are made on the basis
of clinicopathological findings, the response to treatment and control procedures using selenium.
The existence of NMD is accepted as presumptive evidence of selenium deficiency, which can
now be confirmed by analyses of GHS-PX and the concentrations of selenium in soil, feed
samples, and animal tissues. Tentative critical levels of the element are as follows:
•Forages and grains - A content of 0.1 mg/kg DM is considered adequate
•Soil - Soils containing less than 0.5 mg/kg are likely to yield crops inadequate in selenium
concentration (2)
•Animal tissues, blood, and milk -

The concentration of selenium in various tissues are reliable indicators of the selenium status of
the animal.There is a positive correlation between the selenium content of feed and the selenium
content of the tissues and blood of animals ingesting that feed and the values fluctuate with the
dietary intake of the element (2).
Kidney cortex and liver
Normal liver selenium concentrations range from 1.2 to 2.0 µg/g DM, regardless of species or age
(62). Levels of 3.5-5.3 mg/g (67-101 nmol/g) DM in the kidney cortex and 0.90-1.75 µg/g (11-22
nmol/g) DM in the liver of cattle are indicative of adequate selenium. Levels of 0.6-1.4 µg/g (8-18
nmol/g) in the kidney cortex and 0.07-0.60 µg/g (0.9-8 nmol/g) in the liver represent a deficient
state.
The selenium content of bovine fetal liver samples collected at an abattoir contained
0.77(µg/mL WW. and 0.13 µg/mL WW, from dairy breeds and beef breeds of cattle, respectively
(63). Mean liver selenium levels from aborted bovine fetuses with myocardial lesions were
5.5 .µmol/kg, 6.5 µmol/kg in fetuses without myocardial lesions and 7.5 µmol/kg in fetuses from
the abattoir, which suggests that selenium deficiency may be the cause of abortion (64).
Blood and milk
Blood and milk levels of selenium are used as indicators of selenium status in cattle and the effect
of dietary supplementation (65). Serum selenium values increase gradually with age from starting
ranges for neonates of 50-80 ng/L for calves and sheep, and 70-90 for foals and pigs (62).
Expected or normal values for adults are in the ranges of 70-100 for cattle, 120-150 for sheep,
130-160 for horses, and 180-220 for swine.
Dams of affected calves have had levels of 1.7ng/ml (2.2 nmol/L) (blood) and 4.9 ng/mL(6.2
nmol/L) (milk); their
1526
calves have blood levels of 5 8 ng/mL (6.3-10.1 nmol/L). Normal selenium-supplemented cows
have 19-48 ng/mL (24.1-60.8 nmol/L) in blood and 10-20 ng/mL (12.7-25.3 nmol/L) in milk, and
their calves have blood levels of 33-61 ng/mL (41.8-77.2 nmol/L). Mean selenium concentrations
in the blood of normal mares have been 26-27 ng/mL (32.9-34.2 nmol/L). In Thoroughbred horses,
selenium concentrations in serum range from 39.5 to 118.5mg/mL (50-150 µmol/L) and there arc
significant differences between various stables of horses.
Bulk tank milk
The bulk tank milk selenium levels are closely related to the mean herd blood and milk levels and
have the potential to be a low-cost, non-invasive means of evaluating herd selenium levels in order
to determine selenium deficiency in the dairy herd (66).
Glutathione peroxidase
There is a direct relationship between the GSH-PX activity of the blood and the selenium levels of
the blood and tissues of cattle, sheep, horses, and pigs (1). The normal selenium status of cattle is
represented by whole blood selenium concentration of 100 ng/mL (126.6 nmol/L) and blood
GSH-PX activity of approximately 30 mU/mg hemoglobin (67). There is a high positive
relationship (r = 0.87-0.958) between blood GSH-PX activity and blood selenium concentrations
in cattle (67). Blood selenium levels less than 50 ng/mL are considered as selenium-deficient,
while levels between 50 and 100 ng/mL (126.6 nmol/L) are marginal, and greater than 100 ng/mL
are adequate (1). Comparable whole blood levels of GSH-PX are deficient if less than 30 mU/mg
hemoglobin, marginal if 30-60 mU/mg, and adequate if greater than 60 mU/mg hemoglobin (1).

There is some evidence of variation in GSH-PX activities between breeds of sheep; levels may
also decrease with increasing age. Low levels in some breeds of sheep may also be a reflection of
adaptation to low selenium intake because of low levels of selenium in the soil and forages.
The GSH-PX activity is a sensitive indicator of the level of dietary selenium intake and the
response to the oral or parenteral administration of selenium (1, 2). Because selenium is
incorporated into erythrocyte GSH-PX only during erythropoiesis, an increase in enzyme activity
of the blood will not occur for 4-6 weeks following administration of selenium (1). Plasma
GSH-PX will rise more quickly and will continue to increase curvihnearly with increasing dietary
selenium levels because it is not dependent on incorporation of the selenium into the erythrocytes.
The liver and selenium concentration and scrum GSH-PX activity may respond to changes in
dietary selenium more rapidly than either whole blood selenium or erythrocyte GSH-PX activity.
The response in GSH-PX activity may depend upon the selenium status of the animals at the time
when selenium is administered. Larger increases in the enzyme activity occur in
selenium-deficient animals. The GSH-PX activity in foals reflects the amount of selenium given to
the mare during pregnancy.
The sandwich ELISA is a simplified method for the estimation of GSH-PX activity and
selenium concentration in bovine blood, and can be used for rapid screening of the selenium status
of a large number of cattle (68).
The GSH-PX activity can be determined rapidly using a spot test which is semiquantitative and
can place a group of samples from the same herd or flock into one of three blood selenium
categories: deficient, low marginal, and marginal adequate (69). A commercial testing kit known
as the Ransel Kit is now available (70). Because of the instability of GSH-PX plasma, GSH-PX
activity in sheep, cattle, and pigs should be measured in fresh plasma or stored at -20℃ (-4 ℉ ) .
For absolute measurements, it is suggested that swine plasma GSH-PX activity be measured
immediately after separation from the blood cells, or be assayed within 24 hours under specified
laboratory conditions (71).
Vitamin E status
Vitamin E occurs in nature as a mixture of tocopherols in varying proportions. They vary widely
in their biological activity so that chemical determination of total tocopherols is of much less
value than biological assay. Tocopherol levels in blood and liver provide good information on the
vitamin E status of the animal. However, because of the difficulty of the laboratory assays of
tocopherols, they are not commonly done and insufficient reliable data available. Analysis of liver
from clinically normal animals on pasture reveal a mean a-tocopherol level of 20 mg/kg WW for
cattle and 6 mg/kg WW for sheep. The corresponding ranges were 6.0-53 WW mg/kg for cattle
and 1.8-17 mg/kg WW in sheep. The critical level below which signs of deficiency may be
expected are 5 mg/kg WW for cattle and 2 mg/kg WW for sheep. Tocopherol levels in the serum
of less than 2 mg/L in cattle and sheep are considered to be critical levels below which deficiency
diseases may occur. However, if the diet contains adequate quantities of selenium, but not an
excessive quantity of PUFAs, animals may thrive on low levels of serum tocopherols. In growing
pigs, the serum vitamin E levels are between 2 and 3 mg/L (72). In summary, there are insufficient
reliable data available on the vitamin E status on animals with NMD to be of diagnostic value.
The mean plasma vitamin E levels in clinically normal horses of various ages and breeds were
2.8 µg/mL (73). The optimal method for storing equine blood prior to a-tocopherol analysis is in
an upright position in the refrigerator for up to 72 hours (74). If a longer period is needed, the

serum or plasma should be separated, blanketed with nitrogen gas, and frozen in the smallest
possible vial; the a-tocopherol in these samples will be stable at 16 for at least 3 months.
A summary of the GSH-PX activity, tocopherol and selenium levels in blood and body tissues
of animals deficient in selenium appears m Table 29.6. Normal values are also tabulated for
comparison (75). Both the abnormal and normal .values should be considered as guidelines for
diagnosis because of the wide variations in levels between groups of animals. The level of dietary
selenium may fluctuate considerably, which may account for variations in GSH-PX.
Swine
An increase in the activity of several plasma enzymes occurs in selenium and vitamin E
deficiencies of swine. The measurement of AST, CPK, lactic acid dehydrogenase and isucitrate
dehydrogenase can be used to detect the onset of degeneration of skeletal and myocardial muscles
and liver. However, these are not commonly used for diagnostic purposes because of the acuteness
of the illness.
The determination of the levels of selenium in feed supplies,tissues,and
1527
Table 29.6 Glutathione peroxidase (GSH-PX) activity and selenium levels in blood and body
tissues of animals deficient in selenium
species
Catter
sheep
pigs
Clinical state or
degree of deficienc
Normal or adequte
marginal
deficient
normal or adequte
marginal
deficient
adequte
deficient
Erythrocyte gsh-px
activity µmol/min at
37. ℃ /g hemoglobin
19.0-36.0
10.0-19.0
0.2-10.0
60-180
8-30
2-7
100-200

400-1500 nmol/L. These values must be interpreted along with the concentration of PUFAs in the
diet.
There is a close relationship between blood vitamin E and resistance of erythrocytes against
lipid peroxidation. The supplementation of the diet of pigs with vitamin E will increase both the
serum levels of vitamin E and the resistance of the erythrocytes to lipid peroxidation (72).
NECROPSY FINDINGS
The microscopic appearance of the muscle lesions is quite constant, but the distribution of affected
muscles varies widely in different animals. Affected groups of skeletal muscle are bilaterally
symmetrical and contain localized white or graying areas of degeneration. These areas may be in
streaks, involving a large group of muscle fibers that run through the center of the apparently
normal muscle or as a peripheral boundary around a core of normal muscle. In the diaphragm, the
distribution of damaged bundles gives the tissue a radially striated appearance. The affected
muscle is friable and edematous and may be mineralized. Secondary pneumonia often occurs in
cases where the muscles of the throat and chest are affected. In cases with myocardial involvement,
white areas of degeneration are visible, particularly under the endocardium of the left ventricle in
calves and of both ventricles in lambs. The lesions may extend to involve the inter-ventricular
septum and papillary muscles and have a gritty character consistent with mineralization.
Pulmonary congestion and edema is common.
Histologically, the muscle lesions are non-inflammatory.Hyaline degeneration is followed by
coagulation necrosis and variable degrees of mineralization.
A generalized steatitis has been described in newborn foals less than 2 months of age. The
microscopic appearance of this yellow-brown fat consists of necrotic fat infiltrated by neutrophils,
macrophages, and giant cells. Supplemental vitamin E is believed to protect against this condition.
In mulberry heart disease the carcass is in good condition. All body cavities contain excessive
amounts of fluid and shreds of fibrin. In the peritoneal cavity, the fibrin is often in the form of a
lacy net covering all the viscera. The liver is enlarged, mottled, and has a characteristic nutmeg
appearance on the cut surface. The lungs are edematous and excessive fluid in the pleural cavities
is accompanied by collapse of the ventral lung field. The pericardia! sac is filled with gelatinous
fluid interlaced with bands of fibrin. Beneath the epicardium and endocardium are multiple
hemorrhages of various sizes. Usually, this hemorrhage is more severe on the right side of the
heart. Histologically, the characteristic lesion is widespread myocardial congestion, hemorrhage,
and myofiber degeneration. Multiple fibrinous microthrombi are within the myocardial capillaries
and, occasionally, degenerative changes are visible in walls of small arterioles in many organs,
including the heart. Malacia of cerebral white matter, or more rarely the molecular layer of the
cerebellum, may occur and is attributable to microvascular damage. It should be stressed that, in
some cases, the disease course is so rapid that morphologic changes are not discernible in the
myocardial cells. Since it can be extremely difficult to distinguish mulberry heart disease from
Strep, suis septicemia histologically, it is prudent to also attempt bacteriologic culture when
attempting to confirm the diagnosis.
In hepatosis dietetica the liver is swollen and has a mottled to mosaic-like appearance throughout
its lobes. Typically, the disease course is so rapid that jaundice does not develop. Histologically,
there is a distinct lobular distribution of hemorrhage, degeneration, and necrosis. In NMD of
swine the lesions are often only visible at the microscopic level and consist of areas of bilaterally
distributed areas of muscular degeneration. The changes include hyalinization, loss of striations,

and fragmentation of myofibers. A mild degree of NMD may accompany some cases of hepatosis
dietetica.
Samples for confirmation of diagnosis
•Toxicology - 50 g liver (ASSAY (Se) (Vit E))
•Histology-formalin-fixedskeletal muscle (multiple sites), heart (both left
1528
and right ventricular walls), brain (including cerebral hemisphere) (LM) Bacteriology (for
mulberry heart disease only)-heart, liver, swab from pericardia sac (CULT).
DIFFERENTIAL DIAGNOSIS
Nutritional muscular dystrophy
NMD is most common in young rapidly growing animals fed a selenium-vitamin E deficient
ration or whose dams were on a deficient, unsupplemented ration throughout the winter months.
Characteristically, the disease is sudden in onset, and several animals are affected initially or
within a few days, particularly following unaccustomed exercise. In the acute form, generalized
weakness and a state of collapse are common. In the subacute form, the major clinical findings are
stiffness in walking, long periods of recumbency or total recumbency, inability to stand, a normal
mental attitude and appetite, and no abnormal neurological findings to account for the recumbency.
The CP levels are markedly elevated.
Calves and yearlings
Acute enzootic muscular dystrophy in calves with myocardial involvement must be
differentiated from other diseases causing generalized weakness, toxemia and shock. These
include:
•Septicemias-Haemophilus septicemia resulting in weakness, recumbency, and fever
•Pneumonia-Pneumonic pasteurellosis causing dyspnea, toxemia, fever, and weakness,. .
Subacute enzootic muscular dystrophy in which skeletal muscle lesions predominate must be
differentiated from other diseases of young calves and yearlings characterized clinically by paresis
and paralysis. The subacute form is more common in yearlings and young cattle, and is
characterized by recumbency with other body systems being relatively within normal ranges. The
other diseases include:
•Musculoskeletal diseases - Polyarthritis, traumatic or infectious myopathies (blackleg),
osteodystrophy and fractures of long bones
•Diseases of the nervous system-Spinal cord compression, Haemophilus meningoencephalitis
and myelitis, organophosphatic insecticide poisoning
•Diseases of the digestive tract-Carbohydrate engorgement resulting in lactic acidosis, shock,
dehydration, and weakness.
Lambs and kids
In lambs with 'stiff-lamb' disease there is stiffness and a stilted gait, affected animals prefer
recumbency, they are bright and alert, and will suck the ewe if assisted. The serum levels of CPK
and SGOT are also markedly elevated. Differentiation may be necessary from enzootic ataxia and
sway-back, but in these two diseases stiffness is not characteristic but rather weakness and paresis.
Foals
In foals, NMD must be differentiated from acute diseases of the musculoskeletal and nervous
system causing abnormal gait, weakness and recumbency. They include:
•Traumatic injury to the musculoskeletal system

•Polyarthritis . .
•Meningitis
•Traumatic injury to the spinal cord.
Mulberry heart disease
Mulberry heart disease must be differentiated from other common causes of sudden death in pigs
in which the diagnosis is made at necropsy and include:
•Acute septicemias due to salmonellosis, erysipelas, pasteurellosis, and anthrax
•Porcine stress syndrome
•Gut edema
•Intestinal volvulus, heat exhaustion, suffocation during transportation.
TREATMENT
Because of the overlapping functions of selenium and vitamin E, and because it is not always
possible to know the relative etiological importance of one nutrient or the other in causing some of
the acute conditions already described, it is recommended that a combined mixture of selenium
and α-tocopherol be used in treatment. α-Tocopherol is the most potent form of the tocopherols
and is available in a number of pharmaceutical forms, which also vary in their biological activity.
It has become necessary to express the unitage of vitamin E in terms of international units of
biological activity. (1 IU:1 mg synthetic racemic α-tocopherol acetate. Natural D-α-tocopherol
acetate 1 mg: 1 IU and natural D-α-tocopherol mg:0.92 IU).
Nutritional muscular dystrophy
For treatment of NMD in calves, lambs, and foals a mixture containing 3 mg
selenium (as sodium or potassium selenite) and 150IU/mL of DL-α-tocopherol acetate, given IM
at 2 mL/45 kg BW is recommended. One treatment is usually sufficient. Animals with severe
myocardial involvement will usually not respond to treatment, and the case mortality rate is about
90%. However, all incontact animals in the herd (calves, lambs, and foals) should be treated
prophylactically with the same dose of selenium and vitamin E. They should be handled carefully
during treatment to avoid precipitating acute muscular dystrophy. Animals with subacute skeletal
muscular dystrophy will usually begin to improve by 3 days following treatment and may be able
to stand and walk unassisted within a week.
Mulberry heart disease
In outbreaks of mulberry heart disease, hepatosis dietetica, and related selenium and vitamin E
deficiency diseases in pigs, all clinically affected pigs and all pigs at risk should be treated
individually with a combination of selenium and vitamin E parenterally.
CONTROL
The control and prevention of the major diseases caused by selenium and vitamin E deficiencies
can generally be accomplished by the provision of both nutrients to susceptible animals fed on
deficient rations. The following points are relevant and applicable to most situations:
•Provide selenium and vitamin E
•Maternal transfer to newborn
•Selenium potentially toxic
•Selenium in milk supplies
•Dietary requirement of selenium
•High sulfate diets
•Gluthathione peroxidase activity

•Different methods of supplementation.
Provide selenium and vitamin E
While selenium alone is protective against a greater spectrum of diseases than is vitamin E, there
are situations in which vitamin E is more protective. Both selenium and vitamin E should be
provided when the diets are deficient in both nutrients, but this may not apply in every situation.
NMD can occur in ruminants with vitamin E deficiency and an adequate selenium status (76).
Most of the emphasis has been on selenium supplementation at the
1529
expense of vitamin E, which is more expensive and less stable. Most injectable vitamin E and
selenium preparations are adequate in selenium but insufficient in vitamin E.
Maternal transfer to newborn
Diseases caused by selenium deficiency are preventable by the administration of selenium to the
dam during pregnancy or directly to the young growing animal. Selenium is transported across the
placenta and provides protection for the neonate. Oral supplementation of beef cattle with
selenium will provide sufficient to maintain blood levels in the dam and for adequate transfer to
the fetus, ; which can sequester selenium when the levels are low in the dam. The colostrum of
selenium-supplemented cattle also contains an adequate amount of selenium to prevent severe
selenium-deficiency diseases (39). However, by 7 days after parturition, the levels in milk may be
inadequate to maintain adequate serum levels in calves. The strategic administration of selenium
and vitamin E before the expected occurrence of the disease is also a reliable method of
preventing the disease.
Selenium potentially toxic
Selenium is toxic, and any treatment and control program using it must be carefully monitored.
Selenium injected into or fed to animals concentrates in liver, skeletal muscle, kidney and other
tissues, and withdrawal periods before slaughter must be allowed. There is some concern that
selenium may be a carcinogen for man. The only tissues that appear likely to consistently
accumulate more than 3-4 mg/kg of selenium are the kidney and liver, and these are very unlikely
to constitute more than a very small part of the human diet. There have been no reports of
untoward effects of selenium on human health when it has been used at nutritional levels in
food-producing animals. The incorporation of selenium into commercially prepared feeds for
some classes of cattle and swine has been approved in some countries.
Selenium in milk supplies
The use of selenium in the diet of lactating dairy cows has caused concern about possible
adulteration of milk supplies. However, the addition of selenium to the diets of lactating dairy
cows at levels that are protective against the deficiency diseases does not result in levels in the
milk that are hazardous for human consumption. The feeding of excessive quantities of selenium
to dairy cattle would cause toxicity before levels became toxic for man.
Dietary requirement of selenium
The dietary requirement of selenium for both ruminants and non-ruminants is 0.1 mg/kg DM of
the element in the diet. There may be nutritionally important differences in the selenium status
between the same feeds grown in different regions and between different feeds within a region.
Even within a region featuring high selenium concentrations, some feeds may contain levels of
selenium below the 0.1 mg/kg minimum requirement for livestock. Thus a selenium analysis of
feeds appears necessary in order to supplement livestock appropriately. Some geographical areas

are known to be deficient in selenium and the feeds grown in these areas must be supplemented
with selenium and vitamin E on a continuous basis.
High sulfate diets
Avoidance of high sulfate diets is desirable, but provision of adequate selenium overcomes the
sulfate effect.
Glutathione peroxidase activity
Whole blood GSH-PX activity is a reliable and useful index for monitoring the selenium status of
cattle and sheep, perhaps not as reliable in pigs, and not a good indicator in the horse.
Different methods of supplementation
The prevention of the major diseases caused by selenium and vitamin E deficiencies can be
achieved by different methods, including:
•Dietary supplementation in the feed or water supplies
•Individual parenteral injections
•Oral administration
•Pasture top-dressing.
The method used will depend on the circumstances of the farm, ease of administration, cost, the
labor available, severity of the deficiency that exists, and whether or not the animals are being
dosed regularly for other diseases such as parasitism. The subcutaneous injection of barium
selenate, the administration of an intraruminal pellet, and the addition of selenium to the water
supply were compared in cattle; each method was effective for periods ranging from 4 to 12
months.
Dietary supplementation
The inclusion of selenium and vitamin E in the feed supplies or salt and mineral mixes has been
generally successful in preventing the major diseases caused by deficiencies of these two nutrients.
Muscular dystrophy
Under most conditions, NMD of calves and lambs can be prevented by providing selenium and
vitamin E in the diets of the cow or ewe during pregnancy at 0.1 mg/kg DM of actual selenium,
and (a-tocopherol at 1 g/d/cow and 75 mg/d/ewe. If possible, the supplementation should be
continued during lactation to provide a continuous source of selenium to the calves and lambs.
Under some conditions the level of 0.1 mg/kg DM may be inadequate. In some circumstances the
optimal selenium concentration in the feed is considerably higher than 0.1 mg/kg DM, and levels
up to 1.0 mg/kg DM in the feed result in increases in GSH-PX activity which may be beneficial;
however, the cost-effectiveness has not been determined. Pregnant ewes being fed on alfalfa hay
may require selenium at a level of up to 0.2 mg/kg DM to prevent white muscle disease in their
lambs. Young growing cattle, particularly beef cattle likely to receive hay and straw deficient in
selenium and those which are fed high-moisture grain, should receive a supplement of selenium at
the rate of 0.1 mg/kg DM and a-tocophero] at 150 mg/d/head. If selenium-supplemented
concentrates are used as part of a feeding program for dairy cows, it is not necessary to provide
additional selenium by parenteral injection.
Lambs are born with a low serum level of vitamin E but the concentration increases rapidly
after the ingestion of colostrum (77). Supplementation of pregnant ewes with a-tocopherol, either
as a single IM dose (500 mg 2 weeks before lambing) or orally (150 mg daily during 3-4 weeks
before lambing) results in a
1530

marked increase in the levels of the vitamin in the serum and colostrum. The vitamin E
concentration in colostrum was 5-11 times higher than in milk 1 week after lambing.
Vitamin E supplementation of the feed of weaner sheep by oral drench or feed additive is
effective in increasing plasma α-tocopherol concentrations. This is the most practical method for
housed sheep and prevents subclinica] myopathy (78). The IM oily injection was slow to increase
plasma levels of tocopherols and did not prevent myopathy in grazing experiments. Vitamin E
supplements have no beneficial effects on wool quality or quantity in grazing sheep, and unless
certain flocks are susceptible to vitamin E deficiency myopathy it is not recommended.
Salt-mineral mixture
NMD can be prevented in unweaned beef calves and lambs by the inclusion of selenium (14.8
mg/kg) and vitamin E (2700 IU/kg) in the mineral supplement provided ad libitum to the pregnant
cows and ewes on a selenium-deficient ration during the latter two-thirds of gestation and for the
first month of lactation. Under most conditions this will provide selenium at 0.1 mg/kg DM in the
diet.
The provision of sodium selenite in a salt-mineral mixture to provide 90 mg of selenium/kg
salt-mineral mixture on a year-round basis, even under range conditions, increased GSH-PX
activity levels into normal ranges in beef cows for 3 months when fed to extremely deficient
animals. Calves of these cows had increased weaning weights and decreased incidence of
infectious diseases, but the trial was uncontrolled. The provision of 30 mg selenium/kg
salt-mineral mixture was insufficient to raise the GSH-PX activity levels to normal ranges. Peak
blood selenium levels were achieved in wearied beef calves supplemented with 80 and 160 mg
selenium/kg in free-choice salt-mineral mixtures for a period of 108 days. In some jurisdictions, it
may be necessary for the veterinarian to prescribe a supplement containing higher levels than
those permitted by legislation. A level of 25 mg/kg selenium of a salt-mineral mixture provided ad
libitum for sheep will result in sufficient levels of selenium in the dam's blood and milk to prevent
selenium deficiency diseases. Each ewe must consume from 8 to 12 g of the salt-mineral mixture
per day.
Daily cattle
The legal commercial selenium supplementation of complete rations for dairy cattle in the United
States has recently been increased from 0.1 to 0.3 mg/kg DM of complete feed (79). At this rate, a
lactating cow consuming 20 kg of DM/d would consume about 6 mg supplemental selenium in
addition to that naturally present in the feedstuffs. Current recommendations indicate that
selenium intake for lactating and gestating dairy cattle should range from 5 to 7 mg/d for adequate
concentrations in serum or plasma which would range from 70 to 100 ng of selenium/ml., serum
(80). Such supplementation should result in improved selenium status of the newborn, improved
concentration of selenium in colostrum, and improved health of the calves. The effects of
selenium supplementation in dairy cattle on reproductive performance is equivocal. Some studies
over a period of two lactations revealed no effect on reproductive performance (79), while others
report an improvement in dairy cattle in a district considered to be marginally deficient in
selenium. Intakes of inorganic selenium as sodium selenite in amounts of 50 mg/d for 90 days or
100 mg/d for 28 days by adult dairy cows (10-30 times the nutritional requirement) did not cause
any health problems (81). The toxic dose for cattle ranges from 0.25 to 0.5 mg/kg BW.
Milk replacers for dairy calves should contain a suitable antioxidant and be supplemented with
300 IU/kg DM of a-tocopherol acetate at the rate of 0.1 mg/kg DM of the milk replacer.

Swine
In growing swine, both selenium and vitamin E at 30 IU/kg DM of feed are necessary for the
prevention of the diseases caused by diets deficient in vitamin E and selenium. Supplementation
of the diet of the sow will result in an adequate transfer to the piglets. Satisfactory protection of
the diseases of swine caused by vitamin E selenium deficiency depends on the correct balance
between selenium, α-tocopherol, PUFAs in the diet, and the presence of a suitable antioxidant to
conserve the a-tocopherol.
Selenium dose
The generally recommended dose of selenium is 0.1 mg/kg BW SC. The GSH-PX activity will
increase to peak levels at about 30 days following the administration of the selenium. The SC
administration of selenium at 0.10 or 0.15 mg/kg BW, as sodium selenate, will increase and
maintain the blood selenium and GSH-PX activity in dairy cattle for up to 6 months following
injection. A single SC or oral dose of 5 mg of selenium at strategic intervals to prevent or treat
selenium deficiency in weaned lambs will increase the selenium residues in the meat, but not at
levels considered hazardous to the public.
Individual injections
Injections of selenium and vitamin E have been used successfully for prevention, particularly in
circumstances where the diet cannot be easily supplemented. Following IM injections of sodium
selenite into calves, lambs and piglets, the selenium concentration of the tissues, particularly the
liver, increases and then declines to reach preinjection levels in 23 days in calves, and 14 days in
lambs and piglets. Adequate sources of vitamin E also must be provided. Injectable preparations
of selenium and vitamin E are usually adequate in selenium and deficient in vitamin E and it may
not be possible to correct a marginal deficiency of vitamin E in pregnant beef cattle, for example,
by IM injection of a selenium and vitamin E preparation which contains an inadequate
concentration of vitamin E (82). The current label dose of injectable selenium, 0.055 mg
selenium/kg BW, which is therapeutically adequate for NMD, is not sufficient for long-term
selenium supplementation of cattle on a selenium-deficient diet (83). Copper and selenium
supplementation by parenteral administration can be combined when both deficiencies are present
(84).
Subcutaneous injection
A slow-release preparation of barium selenate for SC injection is now available for use in cattle
and sheep (69). A SC injection of 1 mg selenium/kg BW to ewes 3 weeks before breeding
elevated the selenium level in milk during lactation, and increased the selenium concentration and
GSH-PX in the blood of the lambs during the period when they are at
1531
greatest risk from selenium-deficiency diseases (85). At a dose of 1 mg selenium/kg BW to
pregnant ewes, the GSH-PX activity is increased and maintained at adequate levels for up to 5
months. There is adequate transfer of selenium to the lambs, providing protetion for up to 12
weeks of age, which covers the period when lambs are at greatest risk. A dose of 1.2 mg
selenium/kg BW provided adequate selenium status for as long as two consecutive lambing
seasons. Barium selenate at 1 mg selenium/kg BW SC provides protection in young sheep for at
least 3 months and is not associated with risk of selenium toxicity or unacceptable residues of
selenium in tissues other than the site of injection (69). A dose of 1 mg selenium/kg BW (barium
selenate) to cattle SC increased the GSH-PX activity within 4 weeks and was maintained at high

levels for up to 5 months.
The SC injection of barium selenate of pregnant sows at 0.5-1.0 mg selenium/kg BW resulted in
a significant difference in GSH-PX activity in the piglets from treated sows compared to untreated
controls. The SC injection of barium selenate .it 2.5 mg selenium/kg BW into pigs weighing 20 kg
also maintained blood levels of selenium and GSH-PX activity during the most rapid growing
period. The relative safety of barium selenate is due to its slow rate of release from the site of
injection. By comparison, when selenium is administered as a soluble salt, such as sodium
selenate, acute toxicity may occur at doses of 0.45 mg selenium/kg BW. Treatment with barium
selenate increases the concentration of selenium in blood, liver and muscle, and persists for at
least 4 months. One disadvantage of barium selenate is that a large residue persists at the site of
injection for long periods. The use of sodium selenate also increases tissue and blood
concentrations of selenium, but they begin to decline by 23 days. The bovine liver rapidly
removes approximately 40% of injected selenium salts (soluble) from the systemic plasma, binds
it to a plasma component, and within 1 hour of injection releases it back into circulation.
NMD in the neonate
If the risk of NMD is high in the first few weeks of life for any of the species, selenium can be
given to the dam; if it is later, at say 2-3 months of age, it is administered to the lamb or calf. The
recommended dose rates of repeated injections at monthly intervals are: 1 mg of selenium to
lambs, 5 mg to ewes, 10 mg to calves, and 30 mg to adult cattle. The injections are administered
about 1 month before the anticipated danger period. In calves on a selenium-deficient pasture a
dose of 0.1 selenium mg/kg BW every 2 months or 0.2 selenium mg/kg BW every 4 months may
be necessary. Comparable dose rates of the various compounds in use are: 1 mg selenium is
equivalent to 2.2 mg anhydrous sodium selenate, 2.4 mg anhydrous sodium selenate, or 4.7 mg
hydrated sodium selenate. These doses may be repeated without danger at monthly intervals. A
mixture of selenium and vitamin E can also be used as a preventive at half the dose recommended
under the heading of treatment above. It can be administered to the young or to the dam and
repeated at 2-4 week intervals.
The prevention of NMD and lupinosis-associated myopathy in weaner sheep at 6-12 months of
age in Western Australia can be achieved by the SC injection of selenomethionine (0.1 mg
selenium/kg BW) and α-tocopherol acetate (2000 iU per sheep) (13). The SC treatment was highly
effective in preventing lupinosis-associated myopathy, and also produced the highest vitamin E
concentrations in plasma and liver. The supplemental vitamin E was more efficacious than
supplemental selenium. An oral dose of vitamin E was the least effective method of increasing
concentrations in liver.
Weak-calf syndrome
The parenteral injection of selenium and iodine to pregnant cattle in Ireland did not significantly
reduce the incidence of the weak-calf syndrome, which is often attributed to a selenium deficiency
(16).
Swine
The injection of selenium 0.06 mg/kg BW into piglets under 1 week of age, repeated at weaning
time and into the sow 3 weeks before farrowing will be effective. The minimum lethal dose of
selenium for piglets is 0.9 mg/kg BW, which provides a reasonably wide range of safety. A high
concentration of selenium in the diet of pregnant sows in the last half of gestation has been
associated with hemorrhagic lesions on the claws of newborn piglets (86).

Horses
Little information is available on the need of horses for selenium but the optimum intake is 6
mg/week or 2.4ug/kg BW daily. The oral supplementation of 1 mg selenium/d increases blood
selenium concentrations above levels associated with myodegeneration in horses and foals. To
insure nutritional adequacy, and to have an adequate safety margin, adult Standardbred horses
should receive 600-1800 mg DL-a-tocopherol daily in their feed. The parenteral administration of
vitamin E and selenium to mares in late pregnancy, and to their foals beginning at birth, will
increase blood selenium to adequate levels. In selenium-deficient areas or when mares are fed
selenium-deficient hay, the prepartum injections of selenium and vitamin E are indicated followed
by intermittent injection of the foals, or supplementation of the diet with selenium at 0.1 mg/kg
DM.
Intra-ruminal selenium pellets
Sheep
Intra-ruminal selenium pellets, similar to those used in cobalt deficiency, have produced
satisfactory blood levels of selenium for up to 4 years in ewes at pasture (69). A satisfactory pellet
is composed of 0.5 g elemental selenium and finely divided metallic iron. The technique is
efficient, but not completely, due to wide variations between animals in the absorption rate of the
selenium. The average delivery of selenium is 1 mg/d and there is no danger of toxicity. In sheep
grazing selenium-deficient pastures, the ruminal pellets increase the selenium status and weight
gains compared to controls. About 15% of treated sheep reject the pellets within 12 months and in
varying degrees the pellets acquire deposits of calcium phosphate. Sheep fed pellets recovered
from sheep have low selenium levels, which suggests a low release of selenium from pellets that
have been in the rumen of other sheep for several months. The peak levels of selenium occur 3
months after administration; there is a rapid decline in activity between 5 and 13 months.
Sustained-released boluses containing sodium selenate, cobalt sulfate, potassium iodide,
manganese sulfate, zinc oxide and sulfate, and vitamins A, D and
1532
E have also been formulated to provide long-term maintenance of selenium (87).
Cattle
A selenium pellet containing 10% selenium and 90% iron grit is available for cattle and will
maintain plasma selenium and GSH-PX activity above the critical level for up to 2 years (88).
When given to beef cows in the last 3 months of pregnancy, the selenium levels in milk are higher
than in controls, and the selenium status of the calves was sufficient to prevent NMD. The use of
these pellets at two, three and four times the recommended dose in growing cattle weighing
300-350 kg did not cause toxicosis, and the selenium levels in the tissues at slaughter were not a
risk for humans (89).
Use of the intra-ruminal selenium pellets in dairy cattle in New Zealand resulted in improved
growth and milk production in herds where the selenium status was below the adequate range, but
there was no effect on udder health and reproductive performance (29).
A sustained-release intra-reticular bolus is an osmotic pump designed to release 3 mg selenium
into the reticulorumen (88). It is intended to provide selenium supplementation for 120 days in
grown heifers and pregnant beef cattle.
Oral selenium and anthelmintics
Oral dosing using sodium selenate is sometimes combined with the administration of

anthelmintics and vaccinations. The dose should approximate 0.044 mg/kg BW. A routine
program in a severely deficient area comprises three doses of 5 mg of selenium (11 mg sodium
selenate) each to ewes, one before mating, one at mid-pregnancy, and one 3 weeks before lambing,
and four doses to the lambs. The first dose to lambs (of 1 mg) is given at docking and the others (2
mg each) at weaning and then at 3-month intervals. A 100-day controlled release anthelmintic
capsule containing 13.9 mg of selenium will protect lambs from selenium deficiency for at least
180 days (90).
Both selenium and cobalt can be incorporated into an anthelmintic program. The levels of
GSH-PX activity may be monitored on a regular basis following the drenching with selenium and
provide a good indication of selenium availability and selenium status of grazing sheep.
Selenium toxicity and residues
Selenium intoxication can occur follow ng the administration of toxic amounts of a selenium salt.
The use of selenium selenate instead of sodium selenate and giving a dose of five times the
intended dose resulted in a high mortality within several hours after administration (91). Animals
deficient in selenium are more susceptible to selenium toxicosis than those that are
selenium-adequate. The pharmacokineaics of selenium toxicity in sheep given selenium selenate
parenterally has been examined. When oral preparations of selenium and monensin are given
concurrently as part of a routine dietary management practice, there is greater risk of selenium
intoxication than if the selenium is given alone (92). Administration of monensin sodium at a
constant, safe dosage enhanced the toxicity of selenium as demonstrated by increased severity of
the signs of intoxication, fatalities, tissue selenium concentrations and intensified gross,
histopathological, and biochemical changes (93). There is some concern about selenium
supplementation of beef cattle being a potential source of contamination for nearby aquatic
systems, but there is no evidence that this has occurred (94).
Pasture top-dressing
The application of sodium selenate as a top-dressing to pasture is now practiced and permitted in
some countries (95). Top-dressing at the approved rate of 10 g selenium/hectare is effective for 12
months and has a toxicity margin of safety of about 20 times. Sodium selenate is now used in
preference to sodium selenate because only about one-fifth is required to raise the pasture level of
selenium to the same concentrations provided by sodium selenate. Top-dressing severely deficient
pumice soils in New Zealand prevented deficiency for at least 12 months, sheep were protected
against white muscle in lambs, and reproduction performance and weight gains were improved. It
is recommended that sodium selenate be applied annually to all selenium-deficient soils at the rate
of 10 g selenium/hectare added to the superphosphate fertilizer, or as prills of sodium selenate
alone. Top-dressing is an economical alternative to individual animal dosing, particularly in
severely deficient areas with a high stocking rate. At the approved rate no adverse effects are
anticipated in human or animal health or on the environment.
REVIEW LITERATURE
Gerloff, B.J. (1992) Effect of selenium
supplementation on dairy cattle. J. Anim. Sci., 70, 3934-3940.
Macphereon, A. (1994) Selenium, vitamin E and biological oxidation. In: Recent Advances in
Animal Nutrition. Eds. Garnsworthy, P. C. & Cole, D.J. A. Nottingham: Nottingham Press,
pp.3-30.

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(2)National Academy of Science (1983) Selenium in Nutrition. Washington, DC: National
Research Council.
(3)Rammcll, C. G. et al. (1989) NZ Vei.J., 37, 4.
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DIETARY DEFICIENCY OF PHOSPHORUS. CALCIUM AND VITAMIN D AND
IMBALANCE OF THE CALCIUM:PHOSPHORUS RATIO
A dietary deficiency or disturbancein the metabolism of calcium, phosphorus or vitamin D,
including imbalance of the calcium:phosphorus ratio, is the principal cause of the
osteodystrophies. The interrelation of these various factors is often very difficult to define and
because the end result in all these deficiencies is so similar the precise etiologicasl agent is often
difficult determine in any given circumstance.
In an attempt to simplify this situation the diseases in this section have been dealt with in the
following order:
•Calcium deficiency (hypocalcicosis)
•Primary-an absolute deficiency in the diet
•Secondary-when the deficiency is conditioned by some other factor, principally an excess intake
of phosphorus
•Phosphorus deficiency (hypophosphatosis)
•Primary-an absolute deficiency in the diet
•Secondary-when the deficiency is conditioned by some other factor; although in general terms an
excessive intake of calcium could be such a factor, specific instances of this situation are lacking
•Vitamin D deficiency(hypovitaminosis-D)
•Primary-an absolute deficiency intake of the vitamin
•Secondary-when the deficiency is conditioned by other factors of which excess carotene intake is
the best known.
In different countries with varying climates, soil types, and methods of husbandly, these
individual deficiencies are of varying importance. For instance in South Africa, northern Australia,
and North America the most common of the above deficiencies is that of phosphorus; vitamin D
deficiency is uncommon. In Great Britain, Europe, and parts of North America, a deficiency of
vitamin D can also be of major importance. Animals are housed indoors for much of the year, they
are exposed to little ultraviolet irradiation, and their forage may contain little vitamin D. Under
such conditions the absolute and relative amounts of calcium and phosphorus in the diet need to be
greater than in other areas if vitamin D deficiency is to be avoided. In New Zealand, where much
lush pasture and cereal grazing is used for feed,the vitamin D status is
1534

educed not only by poor solar irradiation of the animal and plant sterols, but in addition an
anti-vitamin D factor is present in the diet possibly in the form of carotene.
Now that the gross errors of managment with respect to calcium and phosphorus and vitamin D
are largely avoided, more interest is devoted to the marginal errors; in these, diagnosis is not
nearly so easy and the deficiency can be evident only at particular times of the year. The conduct
of a response trial in which part of the herd is treated is difficult unless they are hand-fed daily;
there are no suitable reticular retention pellets or long-term injections of calcium or phosphorus
because the daily requirement is so high. Two methods suggest themselves:
1.Analysis of ash content of samples of spongy bone from the tuber coxae
2.The metabolic profile method.
The latter program may have some value as a monitoring and diagnostic weapon in the fields of
metabolic disease, nutritional deficiency, and nutritional excesses.
ABSORPTION AND METABOLISM OF CALCIUM AND PHOSPHORUS
In ruminants, dietary calcium is absorbed by the small intestine according to body needs. Whereas
young animals with high growth requirements absorb and retain calcium in direct relation to
intake over a wide range of intakes, adult male animals, irrespective of intake, absorb only enough
calcium to replace that lost by excretion into urine and intestine, retaining none of it. Calcium
absorption is increased in adult animals during periods of high demand, such as pregnancy and
lactation, or after a period of calcium deficiency, but a substantial loss of body stores of calcium
appears to be necessary before this increase occurs. The dietary factors influencing the efficiency
of absorption of calcium include the nature of the diet, the absolute and relative amounts of
calcium and phosphorus present in the diet and the presence of interfering substances. Calcium of
milk is virtually all available for absorption, but calcium of forage-containing diets has an
availability of only about 50%. The addition of grain to an all-forage diet markedly improves the
availability of the calcium.
Phosphorus is absorbed by young animals from both milk and forage-containing diets with a
high availability (80-100%), but the availability is much lower (50-60%) in adult animals. Horses
fed diets containing adequate amounts of calcium and phosphorus absorb 50-65% of the calcium,
and slightly less than 50% of the phosphorus present in a variety of feedstuffs. In grains, 50-65%
of the phosphorus is in the phytate form which is utilizable by ruminants, but not as efficiently by
non-ruminants like the horse and pig. An average availability of 70% has been assumed for
phosphorus in early weaning diets for young pigs, and a value of 50% in practical cereal-based
feeds as supplied to growing pigs, sows, and boars.
The metabolism of calcium and phosphorus is influenced by the parathyroid hormone calcitonin
and vitamin D. Parathyroid hormone is secreted in response to hypocalcemia and stimulates the
conversion of 25-dihydroxycholecalciferol to 1,25-dihydroxycholecalciferol (1,25-DHCC).
Parathyroid hormone and 1,25-DHCC together stimulate bone resorption, and 1,25-DHCC alone
stimulates intestinal absorption of calcium. Calcium enters the blood from bone and intestine, and
when the serum calcium level increases above normal, parathyroid hormone is inhibited and
calcitonin secretion stimulated. The increased calcitonin concentration blocks bone resorption and
the decreased parathroid hormone concentration depresses calcium absorption.
CALCIUM DEFICIENCY
Calcium deficiency may be primary or secondary, but in both cases the end result is an
osteodystrophy, the specific disease depending largely on the species and age of the animals

affected.
Synopsis
Etiology. Primary dietary deficiency of calcium uncommon. Secondary calcium deficiency due to
marginal calcium intake and high phosphorus intake.
Epidemiology. Sporadic. Not common if diets adequate.
Signs. Poor growth and dentition. Tetany may occur in lactating ewes. Inappetence, stiffness,
fracture of long bones. Specific diseases include: rickets, osteomalacia, and osteodystrophia
fibrosa.
Clinical pathology. Serum calcium and phosphorus. Radiography.
Lesions. Osteoporosis; low ash content of bone.
Diagnostic confirmation. Histology of bone and bone ash analyses.
Differential diagnosis list. See differential diagnosis of each specific disease.
Treatment. Calcium salts parenterally and orally.
Control. Adequate calcium and phosphorus levels in diet.
ETIOLOGY
A primary deficiency due to a lack of calcium in the diet is uncommon, although a secondary
deficiency due to a marginal calcium intake aggravated by a high phosphorus intake is not
uncommon. In ponies, such a diet depresses intestinal absorption and retention of calcium in the
body, and the resorption of calcium from bones is increased. The effects of reduced calcium intake
and parathyroidectomy are understandably additive in pigs, but parathyroid insufficiency seems an
unlikely natural phenomenon.
EPIDEMIOLOGY
Calcium deficiency is a sporadic disease occurring in particular groups of animals rather than in
geographically limited areas. Although death does not usually occur there may be considerable
loss of function and disabling lesions of bones or joints.
Horses in training, cattle being fitted for shows, and valuable stud sheep are often fed artificial
diets containing cereal or grass hays which contain little calcium, and grains which have a high
content of phosphorus. The secondary calcium deficiency that occurs in these circumstances is
often accompanied by a vitamin D deficiency because of the tendency to keep animals confined
indoors. Pigs are often fed heavy concentrate rations with insufficient calcium supplement. Dairy
cattle may occasionally be fed similarly unbalanced diets, the effects of which are exaggerated by
high milk production.
There are no well-established records of calcium deficiency in grazing sheep or cattle, but there
are records of low calcium intake in feedlots accompanied by clinical osteodystrophy. There is
also a well-recognized field occurrence of calcium deficiency in young sheep in southeast
Australia. Outbreaks can affect many sheep and are usually seen in winter and spring, following
exercise or temporary starvation. In most outbreaks the charac-
1535
teristic osteoporosis results from a long-term deprivation of food due to poor pasture growth.
Occasional outbreaks occur on green oats used for grazing. The calcium intake in some cases is as
low as 3-5 g /week in contrast to the requirement of 3-5 g/day.
High protein intake and rapid growth have been suggested as contributory factors in the
development of skeletal problems in young horses. However, a concentration of dietary protein of
20%, which is significantly above the NRC recommended level of 14% , is neither helpful nor

harmful to growing horses. The high protein intake did not affect the rate of growth, height, and
circumference of cannon bones compared with horses receiving the lower 14% diet. The high
protein diet did not result in hypercalciuria and did not affect calcium absorption or calcium
retention.
In females there is likely to be a cycle of changes in calcium balance, a negative balance
occurring in late pregnancy and early lactation, and a positive balance in late lactation and early
pregnancy and when lactation has ceased. The negative balance in late pregnancy is in spite of a
naturally occurring increased absorption of calcium from the intestine at that time, at least in ewes.
PATHOGENESIS
The main physiological functions of calcium are the formation of bone and milk, participation in
the clotting of blood, and the maintenance of neuromuscular excitability. In the development of
osteodystrophies, dental defects, and tetany the role of calcium is well understood but the relation
between deficiency of the element and lack of appetite, poor growth, loss of condition, infertility,
and reduced milk flow is not readily apparent. The disinclination of the animals to move about and
graze, and poor dental development may contribute to these effects.
Experimentally, feeding young lambs a diet low in calcium and phosphorus for 12 weeks results
in soft and pliable ribs with thickening of the costochondral junctions, reduction in feed intake by
about 34%, significant changes in plasma calcium and phosphorus concentrations, and changes in
dry matter digestibility (1). Feeding repletion diets results in complete remineralization of rib
bones, but only partial remineralization of the metatarsal bones.
Nutritional factors other than calcium, phosphorus, and vitamin D may be
important in the production of ostcodystrophies, which also occur in copper deficiency, fluorosis,
and chronic lead poisoning. Vitamin A is also essential for the development of bones, particularly
those of the cranium.
CLINICAL FINDINGS
The clinical findings, apart from the specific syndromes described later, are less marked in adults
than in young animals, in which there is decreased rate or cessation of growth and dental
maldevelopment. The latter is characterized by deformity of the gums, poor development of the
incisors, failure of permanent teeth to erupt for periods of up to 27 months, and abnormal wear of
the permanent teeth due to defective development of dentine and enamel, occurring principally in
sheep.
A calcium deficiency may occur in lactating ewes and sucking lambs whose metabolic
requirements for calcium are higher than in dry and pregnant sheep. There is a profound fall in
serum calcium. Tetany and hyperirritability do not usually accompany hypocalcemia in these
circumstances, probably because it develops slowly. However, exercise and fasting often
precipitate tetanic seizures and parturient paresis in such sheep. This is typical of the disease as it
occurs in young sheep in southeast Australia. Attention is drawn to the presence of the disease by
the occurrence of tetany, convulsions, and paresis but the important signs are ill-thrift and failure
to respond to anthelmintics. Serum calcium levels will be as low as 5.6 mg/dL (1.4mmol/L). There
is lameness, but fractures are not common even though the bones are soft. A simple method for
assessing this softness is compression of the frontal bones of the skull with the thumbs. In affected
sheep the bones can be felt to fluctuate.
Pigs fed on heavy concentrate rations may develop a hypocalcemic tetany, which responds to
treatment with calcium salts. Tetany may also occur in young growing cattle in the same

circumstances.
Inappetence, stiffness, tendency of bones to fracture, disinclination to stand, difficult parturition,
reduced milk flow, loss of condition, and reduced fertility are all non-specific signs recorded in
adults.
SPECIFIC SYNDROMES
Primary calcium deficiency
No specific syndromes are recorded.
Secondary calcium deficiency
Rickets, osteomalacia, osteodystrophia fibrosa of the horse and pig, and degenerative arthropathy
of cattle arc the common syndromes in which secondary calcium deficiency is one of the specific
causative factors. In sheep, rickets is seldom recognized, but there are marked dental abnormalities.
Rickets has been produced experimentally in lambs by feeding a diet low in calcium.
CLINICAL PATHOLOGY
Because of the effect of the other factors listed above on body constituents, examination of
specimens from living animals may give little indication of the primary cause of the disturbance.
For example, hypocalcemia need not indicate a low dietary intake of calcium. Data on serum
calcium and phosphorus, and plasma phosphatase levels, radiographical examination of bones, and
balance studies of calcium and phosphorus retention are all of value in determining the presence
of osteodystrophic disease, but determination of the initial causative factor will still depend on
analysis of feedstuffs and comparison with known standard requirements. The levels of serum
calcium may be within the normal range in most cases (2). However, in spite of evidence to the
contrary it seems that calcium deficiency is followed, at least in sheep, by a marked fall in serum
calcium levels to as low as 3.5 mg/dL (0.87 mmol/L). In an uncomplicated nutritional deficiency
of calcium in sheep, there is only a slight reduction in the radiopacity of bone, in contrast to sheep
with a low phosphorus and vitamin D status which show marked osteoporosis. The response to
dietary supplementation with calcium is also of diagnostic value.
NECROPSY FINDINGS
True primary calcium deficiency is extremely rare but when it does occur, severe osteoporosis and
parathyroid gland hypertrophy are the significant findings. The cortical bone is thinned and the
metaphyseal trabeculae appear reduced in size and number. The ash content of the bone is low
because the bone is resorbed before it is properly mineralized.
1536
Calcium deficiency secondary to other nutritional factors is common and typically induces the
form of osteodystrophy known as osteodystrophia fibrosa (sec subsequent description). In most
instances, the confirmation of a diagnosis of hypocalcinosis at necropsy inclucies an analysis of
the diet for calcium, phosphorus, and vitamin D content.
Samples for confirmation of diagnosis
•Toxicologylong bone (ASSAY (ash)); feed (ASSAY (Ca) (P) (Vit D))
•Histology formalin-fixed section of long bone (including metaphysis), parathyroid (LM).
DIFFERENTIAL DIAGNOSIS
A diagnosis of calcium deficiency depends upon proof that the diet is, either absolutely or
relatively, insufficient in calcium, that the lesions and signs observed are characteristic, and that
the provision of calcium in the diet alleviates the condition. The diseases that may be confused
with calcium deficiency are described under the diagnosis of each of the specific disease entities

described below.
The close similarity between the dental defects in severe calcium deficiency of sheep and those
occurring in chronic fluorosis may necessitate quantitative estimates of fluorine in the teeth or
bone to determine the cause.
TREATMENT
The response to treatment is rapid, and the preparations and doses recommended below are
effective as treatment. Parenteral injections of calcium salts arc-advisable when tetany is present.
When animals have been exposed to dietary depletion of calcium and phosphorus over a period of
time, it is necessary to supplement the diet with calcium and phosphorus during dietary mineral
repletion (1).
CONTROL
The provision of adequate calcium in the diet, the reduction of phosphorus intake where it is
excessive, and the provision of adequate vitamin D are the essentials of both treatment and
prevention. Some examples of estimated minimum daily requirements for calcium, phosphorus
and vitamin D are set out in Table 29.7. These are estimated minimum requirements and may need
to be increased by a safety factor of 10% to allow for variation in individual animal requirements,
the biological availability of nutrients in the feedstuffs, and the effect which total amount of. feed
intake has on absolute intake of minerals. For example, the use of a complete swine ration on a
restricted basis may require that the concentration of both calcium and phosphorus be increased in
order for that ration to deliver the actual total quantity of calcium and phosphorus necessary to
meet a particular requirement for growth, pregnancy or lactation. The information in Table 29.7 is
presented merely as a guideTable 29.7 Some examples of estimated daily requirements of calcium,
phosphorus and vitamin D
Species, kg body weight
and function
Calcium Phosphorus Vitamin D

DAIRY CATTLE
Growing heifers (large breeds)
159
300
400
Growing heifers (small breeds)
100
200
300
Growing bulls (large breeds)
300
400
500
Maintenance of mature lactating cows
400
500
600
Maintenance and pregnancy
400
500
600
Milk production
BEEF CATTLE
Dry mature pregnant cows
Cows nursing calves
Bulls, growth and maintenance
Growing heifers (200 kg live-weight
gaining 0.8 kg/day)
Growing steers (200 kg live-weight
gaining 0.8 kg/day)
SWINE
Growing swine (10-100 kg live-weight)
Breeding swine (gilts, sows, boars)
SHEEP
(g/animal)
15
24
26
9
15
19
27
30
30
17
20
22
23
29
34
Add 2-3 g
calcium and
1.7-2.4 g
phosphortfs to the
maintenance
requirements for
each kg of milk
produced
(% of ration)
0.16
0.30
0.26
0.33
0.36
0.65
0.75
300 iu/kg dry matter intake
12
18
20
7
11
14
20
23
23
13
15
17
18
22
26
300 iu/kg dry matter intake
0.160
0.25
0.20
0.26
0.28
0.50 200 iu/kg ration
0.50 275 /kg ration

Ewes
Maintenance
Pregnant(early)
Pregnant(late)
Lactating
Rams(40-120kg live-weight)
Lambs
Early weaned(10-30kg live-weight)
Finishing(30-55kg live-weight)
HORSES
Mature horses (400-600 kg live-weight)
Mares (400-600 kg live-weight)
Last 90 days pregnancy
Peak of lactation
Growing horses (400kg mature weight)
3 months old
6 months old
12 months old
Growing horses (500kg mature weight)
3 months old
6 months old
12 months old
0.30
0.27
0.24
0.52
0.35
0.40
0.30
0.30
0.38
0.50
0.68
0.68
0.45
0.69
0.82
0.43
0.28 250-300 iu/kg dry
matter intake
0.25 200 iu/kg dry matter
intake
0.23 200 iu/kg dry matter
intake
0.37 150 iu/kg dry matter
intake
0.19
0.27
0.20
0.20 6-8 iu/kg body weight
0.30
0.40
0.43
0.48
0.30
0.44
0.51
0.28
1537
line. When investigating a nutritional problem of formulating rations, it is recommended that the
most recently available publications on the nutrient requirements of domestic animals be consulted.
Ground limestone is most commonly used to supplement the calcium in the ration, but should
be prepared from calcite and not from dolomite. Variations in availability of the calcium in this
product occur with variations in particle size, a finely ground preparation being superior in this
respect. Bone meal and dicalcium phosphate are more expensive and the additional phosphorus
may be a disadvantage if the calcium: phosphorus ratio is very wide. Alfalfa, clover, and molasses
are also good sources of calcium but vary in their content. The optimum calcium:phosphorus ratio
is within the range of 2:1 to 1:1. In cattle, absorption of both elements is better at the 2:1 ratio. For
optimum protection against the development of urolithiasis in sheep a ratio of 2 2.5 calcium to 1
phosphorus is recommended.
The dustiness of powdered limestone can be overcome by dampening the feed or adding the
powder mixed in molasses. Addition to salt or a mineral mixture is subject to the usual
disadvantage that not all animals partake of it readily when it is provided free-choice, but this
method of supplementation is often necessary in pastured animals. High-producing dairy cows
should receive the mineral mixture in their ration as well as having access to it in boxes or in
blocks.

REFERENCES
(1)Temouth J H & Scvilla, C. C. (1990) ,Aust J Agnic. Res., 41, 413.
(2)Heaney, D. P. et al (1985) Can.J. Anim. Sci., 65, 163.
PHOSPHORUS DEFICIENCY
Phosphorus deficiency is usually primary and is characterized by pica, poor growth, infertility and,
in the later stages, osteo-dystrophy. Hypophosphatemia m dairy cattle is also associated with
increased fragility of red blood cells and postparturient hemoglobinuria.
Synopsis
Etiology. Usually a primary deficiency in diet; may be conditioned by vitamin D deficiency.
Epidemiology. Primary phosphorus deficiency occurs worldwide. Soils and crops commonly
deficient in phosphorus.Primary deficiency may occur in lactating dairy cattle in early lactation.
Occurs under range conditions in beef cattle and sheep.In swine not supplemented with sufficient
phosphorus.
Signs. Young animals grow slowly; develop rickets. Adults develop osteomalacia,unthriftiness,
weight loss, reduced feed consumption, reluctance to move, leggy appearance, fractures, impaired
fertility.Recumbency in high-producing cows on marginally phosphorus-deficient diet.
Clinical pathology. Serum phosphorus.Phosphorus content of diet.
Lesions. Rickets and osteomalacia; lack of mineralization of bones.
Diagnostic confirmation. Histology of bone lesions; bone ash analyses.
Differential diagnosis. Those diseases resembling rickets and osteomalacia.
Treatment. Phosphates parenterally and orally and vitamin D.
Control. Supplement diets with adequate phosphorus, calcium and vitamin D.
ETIOLOGY
Phosphorus deficiency is usually primary under field conditions but may be exacerbated by a
deficiency of vitamin D and possibly by an excess of calcium.
EPIDEMIOLOGY
Geographical occurrence
In contrast to calcium deficiency, a dietary deficiency of phosphorus is widespread under natural
conditions. It has a distinct geographical distribution depending largely upon the phosphorus
content of the parent rock from which the soils of the area are derived, but also upon the influence
of other factors, such as excessive calcium, aluminum or iron, which reduce the availability of
phosphorus to plants. Large areas of grazing land in many countries are of little value for livestock
production without phosphorus supplementation. In New Zealand, for example, where fertilization
of pasture with superphosphate has been practiced for many years, phosphorus deficiency may
still occur in dairy herds because of inadequate maintenance of application over several years (1).
There is evidence also that the quality of the superphosphate declined over a period of several
years. Soil reserves of phosphorus may also be low because of high phosphate retention soils.
Animals in affected areas mature slowly and are inefficient breeders, and additional losses due to
botulism and defects and injuries of bones may occur. Apart from areas in which frank
phospho¬rus deficiency is seen, it is probable that in many other areas a mild degree of deficiency
is a limiting factor in the production of meat, milk, and wool.
Heavy leaching by rain and constant removal by cropping contribute to phosphorus deficiency
in the soil, and the low-phosphorus levels of the plant cover may be further diminished by drought
conditions. Pastures deficient in phosphorus are classically also deficient in protein.

Cattle
A primary dietary deficiency of phosphorus in dairy cattle within the first several weeks of
lactation can result in postparturient hemoglobinuria (2).In high-producing dairy cows, small
restrictions in dietary phosphorus intake compared with National Research Council
recommendations can result in acute recumbency in early lactation (3).
Under range conditions milking cows are most commonly affected, but under intensive
conditions it is the dry and young stock receiving little supplementation which suffer. The
incidence of the disease varies: it is most common in animals at pasture during drought seasons
but can also be a serious problem in housed cattle feel on hay only. The dietary requirements of
phosphorus are given in Table 29.8. Cattle constantly grazing pasture in the southern hemisphere
appear to require somewhat less phosphorus in their diet (0.20% is probably adequate) than do
higher-producing, partly housed livestock. The dietary requirements of phosphorus recommended
by the National Research Council for beef cows weighing 450 kg may exceed the basic
requirements (4). Over a period of several gestations a daily allowance of 12 g of
phosphorus/day/animal was adequate for beef cows (4,5). Cattle given a phosphorus-deficient diet
did not develop detectable signs of phosphorus deficiency until they had been on a severely
deficient diet for 6 months.
Sheep and horses
Sheep and horses at pasture are much less susceptible to the osteodystrophy of phos¬phorus
deficiency than are cattle and their failure to thrive on phosphorus-deficient
1538
Table 29.8 Approximate levels of phosphorus in soil and pasture (quoted as phosphate radical) at
which phosphorus deficiency occurs in cattle
Levels at which deficiency Levels at which
does not occur
deficiency does not occur
Soil
0.005%
0.002%
Pasture
0.3%
0.2%-osteophagia

Secondary phosphorus deficiency
This is of minor importance compared with the primary condition. A deficiency of vitamin D is
not necessary for the development of osteodystrophy, although with suboptimal phosphate intakes
deficiency of this vitamin becomes critical. Excessive intake of calcium does not result in
secondary phosphorus deficiency, although it may cause a reduction in weight gains, due probably
to interference with digestion, and may contribute to the development of phosphorus deficiency
when the intake is marginal. The presence of phytic acid in plant tissues, which renders phosphate
unavailable to carnivora, is a major consideration in pigs but of only minor importance in
herbivora, except that increasing intakes of calcium may reduce the availability of phytate
phosphorus even for ruminants. Rock phosphates containing large amounts of iron and aluminum
have been shown to be of no value to sheep as a source of phosphorus. A high intake of
magnesium, such as that likely to occur when magnesite is fed to prevent lactation tetany, may
cause hypophosphatemia if the phosphorus intake of dairy cows is already low.
Hypophosphatemia has been induced in pigs by experimental supplementation of their diets
with aluminum hydroxide (7). After 3 weeks severe hypophosphatemia, intense hypercalcemia,
decreased growth rate, and a lower concentration of 2,3-diphosphoglycerate in the crythrocytes
developed (7).
PATHOGENESIS
Phosphorus is essential for the laying down of adequately mineralized bones and teeth, and a
deficiency will result in their abnormal development. Inorganic phosphate, which may be ingested
as such, or liberated from esters during digestion or in intermediary metabolism, is utilized in the
formation of proteins and tissue enzymes and is withdrawn from the plasma inorganic phosphate
for this purpose.
Experimentally, female beef cattle fed diets containing =6 g of phosphorus/day developed an
insidious and subtle complex syndrome characterized by weight loss, rough hair coat, abnormal
stance, and lameness (4). Spontaneous fractures occurred in the vertebrae, pelvis, and ribs. Some
affected bones were severely demineralized, and the cortical surfaces were porous, chalky white,
soft, and fragile. The osteoid tissue was not properly mineralized.
Experimental acute depletion of phosphorus in cattle results in a marked decline in serum
inorganic phosphorus and affected animals display an avid appetite for old bones (8). The signs
include:
•Failure to gain weight and maintain body condition
•Reduced bone weight
•Osteopenia radiographicaily
•Evidence of reduced bone formation.
Prolonged phosphorus deficiency was associated with increased plasma concen¬trations of total
calcium and 1,25-dihy-droxyvitamin D and reduced plasma concentrations of parathyroid
hormone.
Inorganic phosphate also plays an important role in the intermediary metabolism of
carbohydrate and of creatine in the chemical reactions occurring in muscle contraction. This may
be of importance in those cows that are recumbent after calving and have hypophosphatemia. The
loss of phosphorus in the phospholipids of milk due to the onset of profuse lactation may be the
crucial factor in the development of postparturient hemoglobinuria. An increased susceptibility to

loat has been postulated as an effect of phosphorus deficiency.
CLINICAL FINDINGS
Primary phosphorus deficiency is common only in cattle. Young animals grow slowly and develop
rickets. In adults there is an initial subclinical stage followed by osteomalacia. In cattle of all ages
a reduction in voluntary intake of feed is a first effect of phosphorus deficiency and is the basis of
most of the general systemic signs. Retarded growth, low milk yield, and reduced fertility are the
earliest signs of phosphorus deficiency. For example, in severe phosphorus deficiency in range
beef cattle, the calving percentage has been known to drop from 70% to 20%. Although it is
claimed that relative infertility occurs in dairy heifers on daily intakes of less than 40 g of
phosphate, the infertility being accompanied by anestrus, subestrus and irregular estrus, and
delayed sexual maturity this has not been borne out by other experimental work, which indicates
that fertility is independent of the calcium or phosphorus content or the calcium:phosphorus ratio
of the diet in cattle. The effects of malnutrition on fertility are likely to be general and the
infertility may often be related to lack of total energy intake rather than to specific
deficiency.Thedevelopmentand wearof
1539
teeth are not greatly affected, in contrast with the severe dental abnormalities that occur in a
nutritional deficiency of calcium. However, malocclusion may result from poor mineralization and
resulting weakness of the mandible.
In the experimental production of phosphorus deficiency in beef cows, several months on a
deficient diet are necessary before clinical signs develop (5). The clinical signs included general
unthrifti-ness, marked body weight loss, reduced feed consumption, reluctance to move, abnormal
stance, bone fractures, and finally impaired reproduction. The detectable signs of phosphorus
deficiency developed in the following sequence:
•Loss of body weight and condition
•Decreased whole blood phosphorus associated with increased whole blood calcium concentration
•Allotriophagia
•Abnormal stance, locomotion, and recumbency (4).
In a severely deficient area a characteristic conformation develops and introduced cattle revert to
the district type in the next generation. The animals have a leggy appearance with a narrow chest
and small girth, the pelvis is small, and the bones are fine and break easily. The chest is slab-sided
due to weakness of the ribs, and the hair coat is rough and staring and lacking in pigment. In areas
of severe deficiency the mortality rate may be high due to starvation, especially during periods of
drought when deficiencies of phosphorus, protein, and vitamin A are exaggerated. Osteophagia is
common and may be accompanied by a high incidence of botulism. Cows in late pregnancy often
become recumbent and, although they continue to eat, are unable to rise. Such animals present a
real problem in drought seasons because many animals in the area may be affected at the same
time. Parentcral injections of phosphorus salts are ineffective and the only treatment that may be
of benefit is to terminate the pregnancy by the administration of corticosteroids or by cesarean
section.
Acute recumbency in high-producing dairy cows on a marginally phosphorus-deficient diet may
become recumbent in early lactation (3). Affected animals are recumbent and cannot stand. They
may be bright and alert, and their vital signs are within normal range.

Although sheep and horses in phosphorus-deficient areas do not develop clinically apparent
osteodystrophy they are often of poor stature and unthrifty, and may develop perverted appetites.
An association between low blood phosphorus and infertility in mares has been suggested but the
evidence is not conclusive. The principal sign in affected sows is posterior paralysis.
CLINICAL PATIIOLOGY
Serum phosphorus
Blood levels of phosphorus are not a good indicator of the phosphorus status of an animal because
they can remain at normal levels for long periods after cattle have been exposed to a serious
deficiency of the element. Serum inorganic phosphorus levels are affected by such factors as age
of animal, milk yield, stage of pregnancy, season of year, breed, feeding patterns, and dietary
phosphorus. The times of sampling in a herd must be standardized to reduce the effect of diurnal
variation in serum concentrations of inorganic phosphorus. Attention is drawn to the need to use
standard methods of collection because of the effect that technique can have on phos¬phorus
levels in blood. In cattle, the recommended procedure is to collect blood from the coccygeal vein
and preserve it in buffered trichloracetic acid. Hair does not reflect the status either. However, a
marked hypophosphatemia is a good indicator of a severe phosphorus deficiency. The
mild-to-moderate deficiencies, which are the most common ones, are usually accompanied by
normal blood levels of phosphorus. Generally, clinical signs occur when blood levels have fallen
from the normal of 4-5 mg/dL (1.3-1.7 mmol/L) to 1.5-3.5 mg/dL (0.5-1.2 mmol/L) and a
response to phosphate supplementation in body weight gain can be anticipated in cattle that have
blood inorgarlic phosphorus levels of less than 4 mg/dL (1.3 mmol/L). Levels may fall as low as 1
mg/dL (0.3 mmol/L) or less in severe clinical cases. Serum levels of calcium are usually
unaffected.
Phosphorus content of diet
Estimation of the mineral content in pasture and drinking water is a valuable aid in diagnosis, but
has major difficulty in representing what the animal has actually
been taking in. A technique has been I devised for determining phosphorus intake of sheep by
estimating the phosphorus content of feces. A pool of three pellets from each of 30 sheep is used
as a sampling technique.
Bone ash concentrations
Determination of total bone ash concentrations, and bone calcium and phosphorus concentrations
from sample of rib can provide useful diagnostic information and comparison to normal values (9).
There is usually a marked deterioration in the radiopacity of the bones. However, the bone
content of phosphorus is still considered the most accurate indication of phosphorus status.
NECROPSY FINDINGS
The necropsy findings are those of the specific diseases, rickets, and osteomala-
DIFFERENTIAL DIAGNOSIS
A diagnosis of phosphorus deficiency depends upon evidence that the diet is lacking in
phosphorus, and that the lesions and signs are typical of those caused by phosphorus deficiency
and can be arrested or reverted by the administration of phosphorus. Differentiation from those
diseases that may resemble rickets and osteomalacia is dealt with under those headings (pp. 1543
and 1545).
TREATMENT
The preparations and doses recom¬mended under control can be satisfactorily used for the

treatment of affected animals. In cases where the need for phosphorus is urgent, as in
postparturient hemoglobinuria and in cases of parturient paresis complicated by
hypophosphatemia, the intravenous administration of sodium acid phosphate (30 g in 300 mL
distilled water) is recommended.
CONTROL
Phosphorus supplements
Under field conditions the difficulty usually encountered is that of providing phosphorus
supplements to large groups of cattle running under extensive range conditions. The minimum
daily requirement of cattle for phosphorus (as phosphate) is 15 g, and 40-50 g is considered
optimal. The Agricultural Research Council recommendation of 22 g phosphorus/day for a 470 kg
cow producing about 7.5 kg milk/day is adequate (10).
1540
Dairy cattle producing 7500 kg milk annually should receive diets containing 0.42% phosphorus
(3).
Bone meal, dicalcium phosphate, disodiurh phosphate and sodium pyrophosphate may be
provided in supplementary feed or by allowing free access to their mixtures with salt or more
complicated mineral mixtures. The availability of the phosphorus in feed supplements varies and
this needs to be taken into consideration when compounding rations. The relative biological values
for young pigs in terms of phosphorus are: dicalcium phosphate or rock phosphate 83%, steamed
bone meal 56%, and colloidal clay or soft phosphate 34%. It is suggested that in deficient areas
adult dry cattle and calves up to 150 kg should receive 225 g bone meal per week, growing stock
over 150 kg BW 350 g per week and lactating cows 1 kg weekly, but experience in particular
areas may indicate the need for varying these amounts. The top-dressing of pasture with
superphosphate is an adequate method of correcting the deficiency and has the advantage of
increasing the bulk and protein yield of the pasture, but is often impractical under the conditions in
which the disease occurs.
The addition of phosphate to drinking water is a much more satisfactory method provided the
chemical can be added by an automatic dispenser to water piped into troughs. Adding chemicals to
fixed tanks introduces errors in concentration, excessive stimulation of algal growth, and
precipitation in hard waters. Monosodium dihydrogen phosphate (monosodium or thophosphate)
is the favorite additive and is usually added at the rate of 10 20 g/20 L of water. Superphosphate
may be used instead but is not suitable for dispensers, must be added in larger quantities (50 g/20
L) and may contain excess fluorine. A reasonably effective and practical method favored by
Australian dairy farmers is the provision of a supplement referred to as 'super juice'. Plain
superphosphate at a rate of 2.5 kg in 40 L of water is mixed and stirred vigorously in a barrel.
When it has settled for a day the 'super juice' is ready for use and is administered by skimming off
the supernatant and sprinkling 100 200 mL on the feed of each cow.
Toxicity of supplements
The use of phosphate supplements in the diet is not without hazards. Phosphoricacid is directly
toxic and should not be used, and monosodium phosphate is unpalatable to many animals; the
depression of appetite that results may discount the improved feed utilization it provides.
Superphosphate used as fertilizer can cause toxicosis in ruminants (11). Clinical signs in sheep
include teeth grinding, diarrhea, nervous system depression, apparent blindness, stiffness and
ataxia, and high fatality rate (11).

REFER ENCES
(1)Brooks, H. V. et al. (1984) NZ Vet.]., 32,174.
(2)Ogawa, E. et al. (1989) Am. J. Vet. Res.,50, 388.
(3)Gerloff, B.J. & Swenson, E. P. (1996) J.Am. Vet. Med. Assoc, 208, Tib.
(4)Shupe.J. L. et al. (1988) Am.J. Vet. Res.,49, 1629.
(5)Call, J. W. et al. (1986) Am.]. Vet. Res ,41, 475.
(6)Denny, J. E. F. M. (1987) J. South Afr. Vet.Assoc, 58, 85.
(7)Haglin, L. et al. (1988) Ada. Vet. Scund.,29, 91.
(8)Blair-Wcst.J. R. et al. (1992) Am.].PhyswL, 26.1, R656.
(9)Beighle, 1). E. et al. (1994) Am.]. Vet.Res., 55, 85.
(10)Fishwick, G. & Hemingway, R. G. (1989)Br. Vet.J, 145. 141.
(11)East, N. E. (1993) J. Am. Vet. Med. Assoc,20 J, 1176.
VITAMIN D DEFICIENCY
VitaminD deficiencys usually caused by insufficient solar irradiationof animals or their feed and
is manifested by poor appetiteand growth, and in advanced cases by osteodystrophy.
Synopsis
Etiology. Lack of ultravioletsolar irradiation and/or deficiency of preformed vitamin D in diet.
Epidemiology. Uncommon because diets are supplemente. Occurs in animals in countries with
relative lack of UV irradiation especially in winter months; animals raised indoors for long periods.
May occur in young grazinganimals in winter months. May be antivitamin D factor.
Signs. Reduced productivity; poor weight gain; reduced reproductive performance. Rickets in
young; osteomalacia in adults.
Clinical pathology. Serumcalcium and phosphorus. Plasma vitamin D.
Lesions. Lack of mineralization of bone.
Diagnostic confirmation. Histology of bone
lesions.
Differential diagnosis list. See Rickets and
osteomalacia.
Treatment. Administervitamin D parenterally and oral calcium and phosphates.
Control. Supplement diets with vitamin D.Injections of vitamin D when oral supplementation not
possible.
ETIOLOGY
A lack of ultraviolet solar irradiation of the skin, coupled with a deficiency of preformed vitamin
D complex in the diet, leads to a deficiency of vitamin D in tissues.
EPIDEMIOLOGY
Although the effects of clinically apparent vitamin D deficiency have been largely eliminated by
improved nutrition, the subclinical effects have received little attention. For example, retarded
growth in young sheep in New Zealand and southern Australia during winter months has been
recognized for many years as responding to vitamin D administration.
However, general realization of the importance of this subclinical vitamin D deficiency in
limiting productivity of livestock has come only in recent years. This is partly due to the
complexity of the relations between calcium, phosphorus and the vitamin, and their common
association with protein and other deficiencies in the diet. Much work remains to be done before

these individual dietary-essentials can be assessed in their correct economic perspective.
Ultraviolet irradiation
The lack of ultraviolet irradiation becomes important as distance from the equator increases and
the sun's rays are filtered and refracted by an increasing depth of the earth's atmosphere. Cloudy,
overcast skies, smoke-laden atmospheres, and winter months exacerbate the lack of irradiation.
The effects of poor irradiation are felt first by animals with dark skin (particularly swine and some
breeds of cattle) or heavy coats (particularly sheep), by rapidly growing animals, and by those that
are housed indoors for long periods. The concentration of plasma vitamin D3 recorded in grazing
sheep varies widely throughout the year. During the winter months in the United Kingdom the
levels
1541
in sheep fall below what is considered optimal, while in the summer months the levels are more
than adequate (1). There is a marked difference in vitamin D status between sheep with a long
fleece and those that have been recently shorn, especially in periods of maximum sunlight. The
higher blood levels of vitamin D in the latter group are probably due to their greater exposure to
sunlight. Pigs reared under intensive farming conditions and animals being prepared for shows are
small but important susceptible groups.
Dietary vitamin D
The importance of dietary sources of preformed vitamin D must not be underestimated. Irradiated
plant sterols with anti-rachitic potency occur in the dead leaves of growing plants. Variation in the
vitamin D content of hay can occur with different methods of curing. Exposure to irradiation by
sunlight for long periods causes a marked increase in anti-rachitic potency of the cut fodder,
whereas modern haymaking technique with its emphasis on rapid curing tends to keep vitamin D
levels at a minimum. Grass ensilage also contains very little vitamin D
Based on a survey of the concentrations of vitamin D in the serum of horses m the United
Kingdom, the levels may be low (2). In the absence of a dietary supplement containing vitamin D,
the concentration of 25-OH D2 and 25-OH D3 are, respectively, a reflection of the absorption of
vitamin D2 from the diet and of biosynthesis of vitamin D3
Information on the vitamin D requirements of housed dairy cattle is incomplete and
contradictor)'. It appears, however, that m some instances natural feedstuffs provide less than
adequate amounts of the vitamin for optimum reproductive performance in high-producing cows
(3).
Grazing animals
The grazing of animals, especially in winter time, on lush green feed including cereal crops, leads
to a high incidence of rickets in the young. An antivitamin D factor is suspected because calcium,
phos¬phorus, and vitamin D intakes are usually normal, but the condition can be prevented by the
administration of calciferol. Carotene, which is present in large quantities in this type of feed, has
been shown to have antivitamin D potency but the existence of a further rachitogenic substance
seems probable. The rachitogenic potency of this green feed varies widely according to the stage
of growth and virtually disappears when flowering commences. Experimental overdosing with
vitamin A causes a marked retardation of bone growth in calves. Such overdosing can occur when
diets are supplemented with the vitamin, and may produce clinical effects (4).
The importance of vitamin D to animals is now well-recognized and supplementation of the diet
where necessary is usually performed by the livestock owner. Occasional outbreaks of vitamin D

deficiency are experienced in intensive systems where animals are housed and in areas where
specific local problems are encountered, e.g. rickets in sheep on green cereal pasture in New
Zealand.
PATHOGENESIS
Vitamin D is a complex of substances with anti-rachitogenic activity. The important components
are as follows:
•Vitamin D3 (cholecalciferol) is produced from its precursor 7-dehydro-cholesterol in mammalian
skin and by natural irradiation with ultraviolet light
•Vitamin D2 is present in sun-cured hay and is produced by ultraviolet irradiation of plant sterols.
Calciferol or viosterol is produced commercially by theirradiation of yeast. Ergosterol is
the :provitamin
•Vitamin D4 and D5 occur naturally in the oils of some fish.
Vitamin D produced in the skin or ingested with the diet and absorbed by the small intestine is
transported to the liver. In the liver, 25-hydroxycholecalcif-erol is produced, which is then trans
ported to the kidney where at least two additional derivatives are formed by 1-Ct-hydroxylase (5).
One is 1,25-dihydroxycholecalciferol (DHCC), and the other is 24,25-DHCC. Under conditions of
calcium need or calcium deprivation the form predominantly produced by the kidney is
1,25-DHCC. At present it seems likely that 1,25-DHCC is the metabolic form of vitamin D most
active in eliciting intestinal calcium transport ; and absorption and is at least the closest known
metabolite to the form of vitamin D functioning in bone mineralization. The metabolite also
functions in regulat- ing the absorption and metabolism of the phosphate ion, and especially its
loss from the kidney. A deficiency of the metabolite may occur in animals with renal disease,
resulting in decreased absorption of calcium and phosphorus, decreased mineralization of bone,
and excessive losses of the minerals through the kidney. A deficiency of vitamin D per se is
governed in its importance by the calcium and phosphorus status of the animal.
Because of the necessity for the conversion of vitamin D to the active metabolites, there is a lag
period of 2- 4 days following the administration of the vitamin parenterally before a significant
effect on calcium and phosphorus absorption can occur. The use of synthetic-analogs of the active
metabolites such as 1-α-hydroxycholecalciferol (an analog of 1,25-DHCC) can increase the
plasma concentration of calcium and phosphorus within 12 hours following administration (6) and
has been recommended for the control of parturient paresis in cattle.
Maternal status
Maternal vitamin D status is important m determining neonatal plasma calcium concentration. I
here is a significant correlation between maternal and neonatal calf plasma concentrations of
25-OH D2, 25-OH D3, 24,25-(OH)2, D2, 24,25-(OH)2, D3 and 25,26-(OH)2 D3. This indicates
that the vitamin D metabolite status of the neonate is primarily dependent on the 25-OH D status
of the dam (7). The maternal serum concentrations of calcium, phosphorus, and magnesium do not
determine concentrations of these minerals found in the newborn calf. The ability of the placenta
to maintain elevated plasma calcium or phosphorus in the fetus is partially dependent on maternal
1,25-(OH)2, D status. Parenteral cholecalciferol treatment of sows before parturition is an
effective method of supplementing neonatal piglets with cholecalciferol via the sow's milk and its
metabolite via placenta transport (6).
Calcium:phosphorus ratio

When the calcium:phosphorus ratio is wider than the optimum (1:1 to 2:1), vitamin D
requirements for good calcium and phosphorus retention and bone mineralization are increased. A
minor degree of vitamin D deficiency in an environment supplying an imbalance of calcium and
phosphorus might well lead to
1542
disease, whereas the same degree of vitamin deficiency with a normal calcium and phosphorus
intake could go unsus¬pected. For example, in growing pigs, vitamin D supplementation is not
essential provided calcium and phosphorus intakes are rigidly controlled, but under practical
circumstances this may not be possible.
The minor functions of the vitamin include maintenance of efficiency of food utilization and a
calorigenic action, the metabolic rate being depressed when the vitamin is deficient. These actions
are probably the basis for the reduced growth rate and productivity in vitamin D deficiency. Some
evidence suggests that vitamin D may have a role in the immune system (8). Local production of
1,25-(OH)2 D by monocytes may be important in the immune function, particularly in the
parturient dairy cow.
CLINICAL FINDINGS
The most important effect of lack of vitamin D in farm animals is reduced productivity. A
decrease in appetite and efficiency of food utilization cause poor weight gains in growing stock
and poor productivity in adults. Reproductive efficiency is also reduced and the overall effect on
the animal economy may be severe.
In the late stages lameness, which is most noticeable in the forelegs, is accompanied in young
animals by bending of the long bones and enlargement of the joints. This latter stage of clinical
rickets may occur simultaneously with cases of osteomalacia in adults. An adequate intake of
vitaminD appears to be necessary for the maintenance of fertility in cattle, particularly if the
phosphorus intake is low. In one study in dairy cattle, the first ovulation after parturition was
advanced significantly in vitamin D supplemented cows (3).
CLINICAL PATHOLOGY
Serum calcium and phosphorus
A pronounced hypophosphatemia occurs m the early stages and is followed some months later by
a fall in serum calcium. Plasma alkaline phosphatase levels are usually elevated. The blood picture
quickly returns to normal with treatment, often several months before the animal is clinically
normal. Typical figures for beef cattle kept indoors are serum calcium 8.7 mg/dL (10.8 normal),
2.2 mmol/L (2.7 normal); serum inorganic phosphate 4.3 mg/dL (6.3 normal), 1.1 mmol/L (1.6
normal); and alkaline phosphatase 5.7 units (2.75 normal).
Plasma vitamin D
The normal ranges of plasma concentrations of vitamin D and its metabolites in the farm animal
species are now available (9) and can be used to monitor the response of the administration of
vitamin D parenterally or orally in sheep (10, 11). The serum concentrations of vitamin I) in the
horse have been determined (2).
NECROPSY FINDINGS
The pathological changes in young animals arc those of rickets, while in older animals there is an
osteomalacia. In all ages a variable amount of osteodystrophcia fibrosa may develop, and
distinction of the origin of these osteodystrophies based on only gross and microscopic
examination is impractical. A review of management factors and a nutritional analysis of the feed

is essential. The samples for confirmation of the diagnosis at necropsy are as per calcium
deficiency.
DIFFERENTIAL DIAGNOSIS
A diagnosis of vitamin D deficiency depends upon evidence of the probable occurrence of the
deficiency and response of the animal when vitamin D is provided. Differentiation from clinically
similar syndromes is discussed under the specific osteodystrophies.
TREATMENT
It is usual to administer vitamin D in the dose rates set out under control. Affected animals should
also receive adequate calcium and phosphorus in the diet.
CONTROL
Supplementation
The administration of supplementary vitamin D to animals by adding it to the diet or by injection
is necessary only when exposure to sunlight or the provision of a natural ration containing
adequate amounts of vitamin D is impractical.
A total daily intake of 7-12 IU/kg BW is optimal. Sun-dried hay is a good source, but green
fodders are generally deficient in vitamin D. Fish liver oils arc-high in vitamin D, but are subject
to deterioration on storage, particularly with regard to vitamin A. They have the added
disadvantage of losing their vitamin A and 1) content in premixed feed, of destroying vitamin E in
these feeds when they become rancid, and of seriously reducing the butterfat content of milk.
Stable water-soluble vitamin A and D preparations do not suffer from these disadvantages.
Irradiated dry yeast is probably a simpler and cheaper method of supplying vitamin D in mixed
grain feeds.
Stable water-soluble preparations of vitamin D are now available and are commonly added to
the rations of animals being fed concentrate rations. The classes of livestock that usually need
dietary supplementation include:
•Calves raised indoors on milk replacers
•Pigs raised indoors on grain rations
•Beef cattle receiving poor quality roughage during the winter months
•Cattle raised indoors for prolonged periods and not receiving sun-cured forage containing
adequate levels of vitamin D. These include calves raised as herd replacements, yearling cattle fed
concentrate rations, bulls in artificial insemination centers, and purebred bulls maintained indoors
on farms
•Feedlot lambs fed grain rations during the winter months or under totally covered confinement
•Young growing horses raised indoors or outdoors on rations that may not contain adequate
concentrations of calcium and phosphorus. This may be a problem in rapidly growing,
well-muscled horses receiving a high level of grain.
Because there is limited storage of vitaminD in the body, compared to the storage of vitamin A,
it is recommended that daily dietary supplementation be provided when possible for optimum
effect.
Injection
In situations where dietary supplementa¬tion is not possible, the use of single IM injections of
vitamin D2 (calciferol) in oil will protect ruminants for 3-6 months. A dose of 1 1 000 units/kg
BW is recommended and should maintain an adequate vitamin D status for 3-6 months.

In mature non-pregnant sheep weighing about 50 kg, a single IM injection of 6000 IU/kg body
weight produced concentrations of 25-hydroxyvitamin D3 at adequate levels for 3 months (11).
The parenteral administration of vitamin D,
1543
results in both higher tissue and plasma levels of vitamin D3 than does oral administration, and IV
administration produces higher plasma levels than does the IM injection (12). The timing of the
injection should be selected so that the vitamin D status of the ewe is adequate at the time of
lambing (11). The vitamin D3 status of lambs can be increased by the parenteral administration of
the vitamin to the pregnant ewe (13). Dosing pregnant ewes with 300000 IU of vitamin D3 in a
rapidly available form, approximately 2 months before lambing, provides a safe means of
increasing the vitamin D status of the ewe and the newborn lambs by preventing seasonally low
concentrations of 25-hydroxyvitamin D3 (14). In adult sheep there is a wide margin of safety
between the recommended requirement and the toxic oral dose, which provides ample scope for
safe supplementation if such is desirable (10). In adult sheep given 20 times the recommended
requirements for 16 weeks there was no evidence of pathological cification (10). Oral dosing with
30-45 units/kg BW is adequate, provided treatment can be given daily. Massive oral doses can
also be used to give long-term effects, e.g. a single dose of 2 million units is an effective
preventive for 2 months in lambs. Excessive doses may cause toxicity, with signs of drowsiness,
muscle weakness, fragility of bones, and calcification in the walls of blood vessels. The latter
finding has been recorded in cattle receiving 10 million units per day and in unthrifty lambs
receiving a single dose of 1 million units, although larger doses are tolerated by healthy lambs.
REVIEW LITERATURE
Dobson, R. C. & Ward, G. (1974) Vitamin Dphysiology and its importance to dairy cattle:a
review. J. Dairy Sci., 57, 985.
Horst, R. L. & Reinhardt, T. A. (1983) Vitamin D metabolism in ruminants and its relevance
to the periparturient cow.J. Dairy Sci., 66, 661-678.
Wasserman, R. H. (1975) Metabolism, function and clinical aspects of vitamin D. Cornell , 65, 3.
REFERENCES
(1)Smith, B. S. W. & Wright, H. (1984) Vet..Rec, 115.537.
(2)Smith, B. S. W. & Wright, H. (1984) Vet.Rec, 115. 579.
(3)Ward, G. et al. (1971)J. Dairy Sci., 54, 204.
(4)Grey, R. M. et al. (1965) Pathol. Vet., 2,446.
(5)Engstrom, G. W. et al. (1987) J. Dairy Sci.,70, 2266.
(6)Goff.J. P. (1984) J. Nutr., 114, 163.
(7)Goff,J. P. ct al. (1982)J Nutr., 112, 1387.
(8)Reinhardt, T. A. & Hustmyer, F. G.(1987) J. Dairy Sci., 70, 952.
(9)Horst, R. L. et al. (1981) Anal. Biochem.,116, 189.
(10)Smith, B. S. W. et al. (1985) Res. Vet. Sci.,38, 317.
(11)Smith, B, S. W. & Wright, H. (1985) Res.Vet. Sci., 39, 59.
(12)Hidiroglou, M. et al. (1984) Can.J. Anim.Sci., 64, 697.
(13)Hidiroglou, M. & Knipfel.J. E. (1984)Can.J. Comp. Med., 48, 78.
(14)Smith, B. S. W. et al. (1987) Vet. Rec,120, 199.
VITAMIN D TOXICITY
Vitamin D toxicity has occurred in cattle (1), horses (2), and swine (3) following the parenteral or

oral administration of excessive quantities of the vitamin.
n cattle, large parenteral doses of vitamin D, 15 17 million IU, results in prolonged
hypercalcemia, hyperphosphatemia, and large increases in plasma concentrations of vitamin D,
and its metabolites (1). Clinical signs of toxicity occur within 2-3 weeks and include marked
anorexia, loss of body weight, dyspnea, tachycardia, loud heart sounds, weakness, recumbency,
torticollis, fever, and a high case fatality rate (1). Pregnant cows 1 month before parturition are
more susceptible than non-pregnant cows.
Accidental vitamin D3 toxicity has occurred in horses fed a grain diet that supplied 12000-13
000 IU/kg BW of vitamin D3 daily for 30 days (2), equivalent to about 1 million IU vitamin D,/kg
of feed. Clinical findings included anorexia, stiffness, loss of body weight, polyuria, and
polydipsia. There was also evidence of hyposthenuria, aciduria, soft-tissue mineralization, and
fractures of the ribs (2). Calcification of the endocardium and the walls of large blood vessels are
characteristic.
Severe toxicity in pigs occurs at a daily oral dose of 50000-70000 IU/kg BW. Signs include a
sudden onset of anorexia, vomiting, diarrhea, dyspnea, apathy, aphonia, emaciation, and death (2).
Clinical signs arc commonly observed within 2 days after consumption of the feed containing
excessive vitamin D. At necropsy, hemorrhagic gastritis and mild interstitial pneumonia are
commonly present (3). Arteriosclerosis with calcification of the heart base vessels may also be
visible macroscopically in poisoned cattle. Osteoporosis with multiple fractures has been observed
in subacute to chronic hypervitaminosis D in swine. Histologically, there is widespread soft tissue
mineralization, with a predilection for the lung and gastric mucosa, as well as elastinrich tissue,
such as blood vessels. Changes in bone vary with the duration of exposure to toxic levels of the
vitamin.
Assay of the various metabolites of vitamin D in tissues is difficult. The diagnosis is therefore
usually confirmed by correlating microscopic changes with a history of exposure to toxic levels of
vitamin D.
Samples for confirmation of diagnosis
•Toxicology - 500 g of suspect feed(ASSAY (Vit D))
•Histolog -formalin-fixed lung,stomach/abomasum, proximal aorta,lung, bone (LM).
REFERENCES
(1)Littledike. E. T. & 1 horst, R. L. (1982)J.Dairy Sci., 65. 749.
(2)Harrington, D. D. & Page, E. H. (1983) J.Am. Vet. Med. Assoc, 182, 1358.
(3)Long, G. C. (1984) J. Am. Vet. Med. Assoc,184, 164.
RICKETS
Rickets is a disease of young, growing animals characterized by defective calcification of growing
bone. The essential lesion is a failure of provisional calcification with persistence of hypertrophic
cartilage, and enlargement of the epiphyses of long bones and the costochondral junctions
(so-called 'rachitic rosary'). The poorly mineralized bones are subject to pressure distortions.
Synopsis
Etiology. Deficiencies of any or combination of calcium, phosphorus, and vitamin D.
Epidemiology. Young growing animals. No longer common. In calves on phosphorus-deficient
diets (range or housed). In grazing lambs due to lack of solar irradiation. Rare in foals and pigs.
Signs. Stiff gait and lameness, enlargement of ends of long bones, curvature of long bones,
prolonged periods of recumbency. Delayed dentition.

Clinical pathology. Elevated alkaline phosphatase; low serum calcium and
1544
phosphorus. Lack of density of bone radiographically.
Lesions. Abnormal bones and teeth. Bone shafts are soft, epiphyses enlarged. Ratio of bone ash to
organic matter is decreased.
Diagnostic confirmation. Histology of bone, especially epiphyses.
Differential diagnosis list:
• Epiphysitis
• Congenital and acquired abnormalities
• Infectious synovitis.
Treatment. Vitamin D injections, calcium and phosphate orally.
Control. Supplement deficient diets with calcium, phosphorus, and vitamin D.
ETIOLOGY
Rickets is caused by an absolute or relative deficiency of any or a combination of calcium,
phosphorus or vitamin D in young, growing animals. The effects of the deficiency are also
exacerbated by a rapid growth rate.
An inherited form of rickets has been described in pigs. It is indistinguishable from rickets
caused by nutritional inadequacy.
EPIDEMIOLOGY
Clinical rickets is not as important economically as the subclinical stages of the various dietary
deficiencies that produce it. The provision of diets adequate and properly balanced with respect to
calcium, phosphorus, and sufficient exposure to sunlight, are mandatory in good livestock
production. Rickets is no longer a common disease because these requirements are widely
recognized, but the incidence can be high in extreme environments, including purely exploitative
range grazing, intensive feeding in fattening units, and heavy dependence On lush grazing,
especially in winter months.
Rickets is a disease of young, rapidly growing animals and occurs naturally under the following
conditions.
Calves
Primary phosphorus deficiency in phosphorus-deficient range areas, and vitamin D deficiency in
calves housed for long periods are the common circumstances. Vitamin D deficiency is the most
common form of rickets in cattle raised indoors for prolonged periods in Europe and North
America. Grazing animals may also develop vitamin D deficiency rickets at latitudes where solar
irradiation during winter is insufficient to promote adequate dermal photobiosynthesis of vitamin
D3 from 7-dihydrocholesterol. Rickets has occurred in yearling steers in New Zealand wintered on
swede (Brassica napus) crop deficient in phosphorus (1).
In young, rapidly growing cattle raised intensively indoors a combined deficiency of calcium,
phosphorus, and vitamin D can result in leg weakness characterized by stiffness, reluctance to
move, and retarded growth. In some cases, rupture of the Achilles tendon and spontaneous
fracture occur (2). The Achilles tendon may rupture at the insertion of, or proximal to, the
calcaneus.
Lambs
Lambs are less susceptible to primary phosphorus deficiency than cattle, but rickets does occur
under the same conditions. Green cereal grazing and, to a lesser extent, pasturing on lush rye-grass

during winter months may cause a high incidence of rickets in lambs; this is considered to be a
secondary vitamin D deficiency. An outbreak of vitamin D deficiency rickets involving 50% of
lambs aged 6-12 months grazing new grass and rape occurred during the early winter months in
Scotland (3). In the South Island of New Zealand, where winter levels of solar irradiation are low,
rickets occurs in hoggets grazing green oats, or other green crops, which have been shown to
contain high levels of rachitogenic carotenes (1).
Pigs
Rickets in young pigs occurs in intensive fattening units where the effects of diet containing
excessive phosphate (high cereal diets) are exacerbated by vitamin D and calcium deficiencies.
Foals
Rickets is uncommon in foals under natural conditions, although it has been produced
experimentally.
PATHOGENESIS
Dietary deficiencies of calcium, phosphorus, and vitamin D result in defective mineralization of
the osteoid and cartilaginous matrix of developing bone. There is persistence and continued
growth ot hypertroplnc epiphyseal cartilage, increasing the width of the epiphyseal plate. Poorly
calcified spicules of diaphyseal bone and epiphyseal cartilage yield to normal stresses, resulting in
bowing of long bones and broadening of the epiphyses with apparent enlargement of the joints.
Rapidly growing animals on an otherwise good diet will be first affected because of their higher
requirement of the specific nutrients.
CLINICAL FINDINGS
The subclinical effects of the particular deficiency disease will be apparent in the group of animals
affected and have been described in the earlier general section. Clinical rickets is characterized by:
• Stiffness in the gait
• Enlargement of the limb joints, especially in the forelegs
• Enlargement of the costochondral junctions
• Long bones show abnormal curvature, usually forward and outward at the carpus in sheep and
cattle
• Lameness and a tendency to lie down for long periods.
Outbreaks affecting 50% of a group of lambs have been described (3). Arching of the back and
contraction, often to the point of virtual collapse, of the pelvis occur and there is an increased
tendency for bones to fracture.
Eruption of the teeth is delayed and irregular, and the teeth are poorly calcified with pitting,
grooving, and pigmentation. They are often badly aligned, and wear rapidly and unevenly. These
dental abnormalities, together with thickening and softness of the jaw bones, may make it
impossible for severely affected calves and lambs to close their mouths. As a consequence the
tongue protrudes, and there is drooling of saliva and difficulty in feeding. In less severely affected
animals dental malocclusion may be a significant occurrence. Severe deformity of the chest may
result in dyspnea and chronic ruminal tympany. In the final stages, the animal shows
hypersensitivity, tetany, recumbency, and eventually dies of inanition.
CLINICAL PATHOLOGY
The plasma alkaline phosphatase is commonly elevated, but serum calcium and phosphorus levels
depend upon the causative factor. If phosphorus or vitamin D deficiencies are the cause, the serum
phosphorus level will usually be below

1545
the normal lower limit of 3 mg/dL. The serum concentrations of 25-hydroxyvitamin D3 and
25-hydroxyvitamin D2 are markedly decreased in vitamin D-deficient rickets compared with the
normal values of≈ 5 ng/mL (3). Serum calcium levels will be low only in the final stages. In leg
weakness of young, rapidly growing cattle, the serum concentration of 25-hydroxyvitamin D may
be nondetectable and the serum levels of calcium and inorganic phosphorus may be low (2).
Radiographic examination of bones and joints is one of the most valuable aids in the
detection of rickets. Rachitic bones have a characteristic lack of density compared to normal bones.
The ends of long bones have a 'woolly' or 'motheaten' appearance and have a concave or flat,
instead of the normal convex, contour. Surgical removal of a small piece of costochondral junction
for histological examination has been used extensively in experimental work and should be
applicable in field diagnosis.
NECROPSY FINDINGS
Apart from general poorness of condition, the necropsy findings are restricted to abnormal bones
and teeth.The bone shafts are softer and larger in diameter,due in part to the subperiosteal
deposition of osteoid tissue. The joints are enlarged, and on cutting, the epiphyseal cartilage can
be seen to be thicker than usual. Histological examination of the epiphysis is desirable for final
diagnosis. In sheep, the best results are obtained from an examination of the distal cartilages of the
metacarpal and metatarsal bones.
A valuable diagnostic aid is the ratio of ash to organic matter in the bones. Normally the ratio is
three parts of ash to two of organic matter but in rachitic bone this may be depressed to 1:2, or 1:3
in extreme cases. A reduction below 45% of the bone weight as ash also suggests osteodystrophy.
Because of the difficulty encountered in repeating the results of bone ash determinations, a
standardized method has been devised in which the ash content of green bone is determined, using
either the metacarpus or metatarsus, and the ash content related to the age of the animal, as
expressed by the length of the bone. Although normal standards are available only for pigs, the
method suggests itself as being highly suitable for all species.
Samples for confirmation of diagnosis
• Toxicology - long bone (ASSAY(ash)); 500 g feed (ASSAY (Ca) (P)(Vit D))
•Histology - formalin-fixed long bone (including growth plate) (LM).
DIFFERENTIAL DIAGNOSIS
Rickets occurs in young, rapidly growing animals and is characterized by stiffness of the gait and
enlargement of the distal physes of the long bones, particularly noticeable on the metacarpus and
metatarsus as circumscribed painful swellings. A history of a dietary deficiency of any of calcium,
phosphorus, or vitamin D will support the clinical diagnosis. Radiographic evidence of widened
and irregular physes suggests rickets. Copper deficiency in young cattle under 1 year of age can
also result in clinical, radiographic, and pathological findings similar to rickets. Clinically, there is
an arched back, severe stiffness of gait, reluctance to move, and loss of weight. There are marked
swellings of the distal aspects of metacarpus and metatarsus, and radiographically there is a
widened zone of cartilage and lipping of the medial and lateral areas of the physeal plate. Copper
concentration in plasma and liver are low and there is usually dietary evidence of copper
deficiency.
Epiphysitis occurs in rapidly growing yearling cattle raised and fed intensively under
confinement. There is severe lameness, swelling of the distal physes, and radiographic and

pathological evidence of a necrotizing epiphysitis. The etiology is uncertain but thought to be
related to the type of housing.
Congenital and acquired abnormalities of the bony skeletal system are frequent in newborn
and rapidly growing foals. Rickets occurs, but only occasionally. 'Epiphysitis' in young foals
resembles rickets and is characterized by enlargements and abnormalities of the distal physes of
the radius, tibia, third metacarpal and metatarsal bones, and the proximal extremity of the
proximal phalanx. There may or may not be deviation of the limbs caused by uneven growth rates
in various growth plates. The suggested causes include improper nutrition, faulty conformation
and hoof growth, muscle imbalance, overweight, and compression of the growth plate. Recovery
may occur spontaneously or require surgical correction.
Rickets in swine is uncommon and the diagnosis may be difficult. The disease is usually
suspected in young, rapidly growing swine in which there is stiffness in the gait, walking on
tiptoes, enlargements of the distal ends of long bones, and dietary evidence of a marginal
deficiency of calcium or phosphorus. The radiographic and pathological findings may suggest a
rickets-like lesion.
Mycoplasmaj synovitis and arthritis clinically resemble rickets of pigs. There is a sudden
onset of stiffness of gait, habitual recumbency, a decrease in feed consumption, and enlargements
of the distal aspects of the long bones which may or may not be painful, spontaneous recovery
usually occurs in 10-14 days. The locomotor problems in young, growing pigs raised in
confinement and with limited exercise must be considered in the differential diagnosis. In
performance testing stations, up to 20% of boars may be affected with leg weakness.
Rickets in lambs must be differentiated from chlamydial and erysipelas arthritis, which are
readily diagnosed at necropsy.
TREATMENT AND CONTROL
Recommendations for the treatment of the individual dietary deficiencies (calcium, phosphorus,
and vitamin D) are presented under their respective headings. Lesser deformities recover with
suitable treatment but gross deformities usually persist. A general improvement in appetite and
condition occurs quickly, and is accompanied by a return to normal blood levels of phosphorus
and alkaline phosphatase. The treatment of rickets in lambs with vitamin A, vitamin D3, calcium
borogluconate solution containing magnesium and phosphorus parenterally, and supplementation
of the diet with bone meal and protein resulted in a dramatic response (3) Recumbent animals
were walking within a few days.
REFERENCES
(1)Thompson, K. G. & Cook, T. G. (1987) NZ Vet.J., 35, 11.
(2)Sturen, M. (1985) Acta Vet. Scand., 26, 169.
(3)Bonniwell, M. A. et al. (1988) Vet. Rec,122, 386.
OSTEOMALACIA
Osteomalacia is a disease of mature animals affecting bones in which endochondral ossification
has been completed. The characteristic lesion is osteoporosis and the formation of excessive
uncalcified
1546
matrix. Lameness and pathological fractures are the common clinical findings.
Synopsis
Etiology. Absolute or relative deficiency of any one or combination of calcium, phosphorus, and

vitamin D in adult animals.
Epidemiology. Primarily in cattle and sheep on phosphorus-deficient diets. In feedlot animals due
to excessive phosphorus without complementary calcium and vitamin D.
Signs. Reduced productivity, licking and chewing inanimate objects, stiff gait, moderate non
specific lameness, shifting from leg to leg, crackling sounds while walking, arched back, lying
down for long periods. 'Milk lameness' in high-producing dairy cows on deficient diet
Clinical pathology. Increased alkaline phosphatase, decreased serum phosphorus levels.
Decreased density of long bones radiographically.
Lesions. Decreased density of bones, erosions of articular cartilages.
Diagnostic confirmation. Histology of bones.
Differential diagnosis list:
•Chronic fluorosis
•Polysynovitis and arthritis
•Spinal cord compression.
Treatment. As for calcium, phosphorus, and vitamin D deficiency.
Control. Adequate supplementation of diet.
ETIOLOGY
In general, the etiology and occurrence of osteomalacia are the same as for rickets except that the
predisposing cause is not the increased requirement of growth but the drain of lactation and
pregnancy.
EPIDEMIOLOGY
Osteomalacia occurs in mature animals under the same conditions and in the same areas as rickets
in young animals, but is recorded less commonly. Its main occurrence is in cattle in areas seriously
deficient in phosphorus. It is also recorded in sheep, again in association with hypophosphatemia.
In pastured animals, osteomalacia is most common in cattle, and sheep raised in the same area are
less severely affected. In feedlot animals, excessive phosphorus intake without complementary
calcium and vitamin D is likely as a cause, especially if the animals are kept indoors. It also occurs
in sows that have recently weaned their pigs after a long lactation period (6-8 weeks) while on a
diet deficient usually in calcium. A marginal deficiency of both phosphorus and vitamin D will
exaggerate the condition.
PATHOGENESIS
Increased resorption of bone mineral to supply the needs of pregnancy, lactation, and endogenous
metabolism leads to osteoporosis and weakness and deformity of the bones. Large amounts of
uncalcified osteoid are deposited about the diaphyses. Pathological fractures are commonly
precipitated by sudden exercise or handling of the animal during transportation.
CLINICAL FINDINGS
Ruminants
In the early stages, the signs are those of phosphorus deficiency, including lowered productivity
and fertility and loss of condition. Licking and chewing of inanimate objects begins at this stage
and may : bring their attendant ills of oral, pharyngeal and esophageal obstruction, traumatic
reticuloperitonitis, lead poisoning, and botulism.
The signs specific to osteomalacia are those of a painful condition of the bones and joints, and
include a stiff gait, moderate lameness often shifting from leg to leg, crackling sounds while

walking, and an arched back.The hindlegs are most severely affected and thehocks may be rotated
inwards.The animals are disinclined to move, he down for long periods,and are
unwilling togetup.The colloquial names 'pegleg' ,creeps' , 'stiffs', 'cripples' and 'bog-lame' describe
the. syndrome aptly.The names and 'milk-lameness' are commonly applied to the condition when
it occurs in heavily milking 'milkleg' cows. Fractures of bones and separation of tendon
attachments occur frequently, often without apparent precipitating stress. In extreme cases,
deformities of bones occur, and when the pelvis is affected dystocia may result. Finally, weakness
leadsto permanent ; recumbency and death from starvation.
Swine
Affected sows are usually found recumbent and unable to rise from lateral recumbency or from
the dog-sitting position. The shaft of one femur or the neck of the femur is commonly fractured.
The fracture usually occurs within a few days following weaning of the pigs. The placing of the
sow with other adult pigs usually results in some fighting and increased exercise, which
commonly precipitates the pathological fractures.
CLINICAL PATHOLOGY
In general, the findings are the same as those for rickets, including increased scrum alkaline
phosphatase and decreased serum phosphorus levels. Radiographic examination of long bones
shows decreased density of bone shadow.
NECROPSY FINDINGS
It can be difficult to discern any gross changes as the epiphyses are seldom enlarged and the
altered character of cancellous bone may not be macroscopically visible. Cortical bone may be
somewhat thinned and erosions of the articular cartilages have been recorded in cattle suffering
from primary phosphorus deficiency. The parathyroid glands maybe enlarged. Histologicially ,
abnormal ostoid covers trabeculae and a degree of fibrous tissue proliferation is often evident.
Analysis reveals the bones to be lighter than normal with a low ratio of ash to organic matter.
Samples for confirmation of diagnosis
•Toxicology – long bone (ASSAY (ash)); 500 g feed(ASSAY (Ca) (P) (Vit D))
•Histology - formalin-fixed bone, parathyroid(LM).
DIFFERENTIAL DIAGNOSIS
The occurrence of non-specific lameness with pathological fractures in mature animals should
arouse suspicion of osteomalacia. There may be additional evidence of subnormal productivity
and reproductive performance, and dietary evidence of a recent deficiency of calcium, phosphorus,
or vitamin D.
A similar osteoporotic disease of cattle in Japan has been ascribed to a dietary deficiency of
magnesium. The cattle are on high-concentrate , low-roughage diets, have high serum calcium
and alkaline phosphatase levels, but a low serum magnesium level. The osteoporosis is observable
at slaughter and clinical signs observed are those of intercurrent disease,
1547
especially ketosis, milk fever, and hypomagnesemia. Reproductive and renal disorders occur
concurrently.
In cattle it must be differentiated from chronic fluorosis in mature animals, but the typical
mottling and pitting of the teeth and the enlargements on the shafts of the long bones are
characteristic. In some areas, e.g. northern Australia, where the water supply is obtained from
deep subartesian wells, the two diseases may occur concurrently. Analysis of water supplies and

foodstuffs for fluorine may be necessary in doubtful cases.
In sows, osteomalacia with or without pathological fractures must be differentiated from spinal
cord compression due to a vertebral body abscess and chronic arthritis due to erysipelas.
TREATMENT AND CONTROL
Recommendations for the treatment and control of the specific nutritional deficiencies have been
described under their respective headings. Some weeks will elapse before improvement occurs
and deformities of the bones are likely to be permanent.
OSTEODYSTROPHIA FIBROSA
Osteodystrophia fibrosa is similar in its pathogenesis to osteomalacia, but differs in that soft,
cellular, fibrous tissue is laid down as a result of the weakness of the bones instead of the
specialized uncalcified osteoid tissue of osteomalacia. It occurs in horses, goats, and swine.
ETIOLOGY
A secondary calcium deficiency due to excessive phosphorus feeding is the common cause in
horses and probably also in pigs. The disease can be readily produced in horses on diets with a
ratio of calcium:phosphorus of 1 :2.9 or greater, irrespective of the totalcalcium intake.
Calcium :phosphoru ratios of 1:0.9 to 1:1.4 have been shown to be preventive and curative. With a
very low calcium intake of 2-3 g/day and a calcium: phosphorus ratio of 1: 13 the disease may
occur within 5 months. With a normal calcium intake of 26 g/day and a calcium: phosphorus ratio
of 1:5, obvious signs appear ; in about 1 year, but shifting lameness may appear as early as 3
months. The disease is reproducible in pigs on similar diets to those described above and also on
diets low in both calcium and phosphorus. The optimum calcium: phosphorus ratio is 1.2:1 and
the intake for pigs should be within the rangeof 0.6-1.2%of the diet.
EPIDEMIOLOGY
Osteodystrophia fibrosa is principally a disease of horses and other Equidae, and to a lesser extent
of pigs. It has also occurred in goats. Amongst horses, those engaged in heavy city work and in
racing are more likely to be affected because of the tendency to maintain these animals on
unbalanced diets. The major occurrence is in horses fed a diet high in phosphorus and low in
calcium. Such diets include cereal hays combined with heavy gram or bran feeding. Legume hays,
because of their high calcium content, are preventive.
The disease may reach endemic proportions in army horses moved into new territories, whereas
local horses, more used to the diet, suffer little. Although horses may be affected at any age after
weaning it is the 2-7-year age group that suffer most, probably because they are the group most
likely to be exposed to the rations that predispose to the disease.
A novel occurrence has been recorded of an endemic form of the disease affecting large
numbers of horses at pasture. The dietary intake of calcium and phosphorus, and their proportions,
were normal. The occurrence was thought to be due to the continuous ingestion of oxalate in
specific grasses: Cenchrus ciharis, Panicum maximum var. trichoglume, Setaria anceps,
Brachiaria mutica and Pennisetum clandestinum.
PATHOGENESIS
Defective mineralization of bones follows the imbalance of calcium and phosphorus in the diet,
and a fibrous dysplasia occurs. This may be in response to the weakness of the bones or it may be
more precisely a response to hyperparathyroidism stimulated by the excessive intake of
phosphorus. The weakness of the bones predisposes to fractures and separation of muscular and
tendinous attachments. Articular erosions occur commonly and displacement of the bone marrow

may cause the development of anemia.
CLINICAL FINDINGS
Horse
As in most osteodystrophies, the major losses are probably in the early stages before clinical signs
appear or on diets where the aberration is marginal. In horses, a shifting lameness is characteristic
of this stage of the disease and arching of the back may sometimes occur. The horse is lame, but
only mildly so, and in many cases no physical deformity can be found by which the seat of
lameness can be localized. Such horses often creak badly in the joints when they walk. These
signs probably result from relaxation of tendon and ligaments and appear in different limbs at
different times. Articular erosions may contribute to the lameness. In more advanced cases severe
injuries, including fracture and visible sprains of tendons, may occur but these are not specific to
osteodystrophia fibrosa, although their incidence is higher in affected than in normal horses.
Fracture of the lumbar vertebrae while racing has been known to occur in affected horses.
The more classical picture of the disease has largely disappeared because cases are seldom
permitted to progress to this advanced stage. Local swelling of the lower and alveolar margins of
the mandible is followed by soft, symmetrical enlargement of the facial bones, which may become
swollen so that they interfere with respiration (1). Initially these bony swellings are firm and
pyramidal and commence just above and anterior to the facial crests.The lesions are bilaterally
symmetrical. Flattening of the ribs may be apparent, and fractures and detachment of ligaments
occur if the horse is worked. There may be obvious swelling of joints and curvature of long bones.
Severe emaciation and anemia occur in the final stages.
Swine
In pigs, the lesions and signs are similar to those in the horse and in severe cases pigs may be
unable to rise and walk, show gross distortion of limbs, and enlargement of joints and the face. In
less severe cases there is lameness, reluctance to rise, pain on standing, and bending of the limb
bones, but normal facial bones and joints. With suitable treatment the lameness disappears, but
affected pigs may never attain their full size. The relationship of this disease to atrophic rhinitis is
discussed under the latter heading.
CLINICAL PATHOLOGY
There are no significant changes in blood chemistry in horses affected with severe osteodystrophia
fibrosa. However,the
1548
serum calcium level will tend to be lower than normal, the serum inorganic phosphorus higher
than normal, and the alkaline phosphatase activity higher than normal. The levels of diagnostic
alkaline phosphatase have not been determined. Affected horses may be unable to return their
serum calcium levels to normal following the infusion of a calcium salt. Radiographic
examination reveals increased translucency of bones.
NECROPSY FINDINGS
The entire skeleton is abnormal in this severe form of metabolic bone disease, but the change is
most notable in the mandibular, maxillary and nasal bones, which may appear thickened and
distorted. The fleshy tissue that replaces normal cancellous bone in these sites is also present in
the metaphyses of the long bones. Microscopically, there is proliferation of fibrous tissue and
markedly increased osteoclast activity along thinned and abnormally oriented bony trabeculae.
The parathyroid glands are enlarged. It must be remembered that osteodystrophia fibrosa is a

lesion, not a disease. The pathway to this lesion usually involves a dietary unbalance in calcium
and phosphorus, but the kidneys should also be examined to rule out the possibility of renal
secondary hyperparathyroidism.
Samples for confirmation of diagnosis
•Toxicology -bone(ASSAY(ash));500 g feed (ASSAY (ca) (P) (Vit D))
•Histologyformalin-fixed bone,parathyroid gland, kidney (LM).
DIFFERENTIAL DIAGNOSIS
In the early stages, the diagnosis may be difficult because of the common occurrence of traumatic
injuries to horses' legs. A high incidence of lameness in a group of horses warrants examination
of the ration and determination of their calcium and phosphorus status. An identical clinical
picture has been described in a mare with an adenoma of the parathyroid gland. Inherited
multiple exostosis has been described in the horse.
In pigs, osteodystrophia can be the result of hypovitaminosis A, and experimentally as a result of
manganese deficiency.
TREATMENT AND CONTROL
A ration adequately balanced with regard to calcium and phosphorus
(calcium:phosphorus should be in the vicinity of 1:1 and not wider than 1:1.4) is preventive in
horses and affected animals can only be treated by correcting the existing imbalance. Even severe
lesions may disappear in time with proper treatment. Cereal hay may be supplemented with alfalfa
or clover hay, or finely ground limestone (30 g daily) should be fed. Dicalcium phosphate or bone
meal are not as efficient because of their additional content of phosphorus.
REFERENCE
(1) Clarke, C.J. et al. (1996) Vet. Rec., 138, 568.'BOWIE' OR 'BENTLEG'
This is a disease of lambs of unknown etiology. There is a characteristic lateral curvature of the
long bones of the front legs, but the lesions differ from those of ricket. It has been observed only
on unimproved range pasture in New Zealand. The cause is unknown, although phosphorus
deficiency has been suggested.
Improvement of the pasture by top-dressing with superphosphate and sowing-improved grasses
is usually followed by disappearance of the disease.Only sucking lambs are affected and cases
occur only in the spring at a time when rickets does not occur. Up to 40% of a group of lambs may
be affected without breed differences in incidence. A similar syndrome has been produced by the
feeding of wild parsnip (Trachemene glautifolia) and, experimentally, by the feeding of a diet low
in both calcium and phosphorus.
The disease has also been reported from South Africa where it occurs primarily in ram lambs
and develops from as early as 3 months up to 1 year of age (1). There is gradual bending of the
forelimbs with hooves turned inwards and the carpal joints turned outwards. Animals of the South
African Mutton Merino breed had significantly higher plasma phosphorus concentrations than
those of the Merino and Dohne Merino breeds. The plasma calcium: phosphorus ratio was lower
in affected lambs and their ewes, and this converse ratio is thought to result in an induced plasma
ionized calcium deficiency leading to improper calcification of bone.
Some tenderness of the feet and lateral curvature at the knees may be seen as early as 2-3 weeks
of age and marked deformity is present at 6-8 weeks with maximum seventy at weaning. The
forelimbs are more commonly affected than the hindlimbs. Medial curvature occurs in rare cases.
The sides of the feet become badly worn, and the lateral aspects of the lower parts of the limbs

may be injured and be accompanied by lameness. The lambs grow well at first, but by the time of
weaning, affected lambs are in poor condition because of their inability to move about and feed
properly. A rather similar syndrome has been observed in young Saanen bucks, but the condition
showed more tendency to recover spontaneously.
At necropsy in spite of the curvature of the limbs there is no undue porosis, and although the
epiphyseal cartilages are thickened they are supported by dense bone. There may be excessive
synovial fluid in the joints and, in the later stages, there are articular erosions. Increased deposition
of osteoid is not observed.
Supplementation of the diet with phosphorus or improvement of the pasture seems to reduce the
incidence of the disease. Dosing with vitamin D or providing mineral mixtures containing all trace
elements is ineffective (2).
REFERENCES
(1)van Niekerk, F. E. c-t al. (1989)J South Ajr.Vet. hM. Assoc., 60, 36.
(2)Cunningham, I.J. (1957) NZ I'ei.J.. 5, 103.
DEGENERATIVE JOINT DISEASE
Degenerative arthropathy occurs in cattle of all breeds, but reaches its highest incidence as a
sporadic disease of young beef bulls. The disease has been identified as hip dysplasia because of
the pre-existing shallow contour of the acetabulum. It is considered to be inherited as a recessive
characteristic and exacerbated by rapid weight gain in young animals. The occurrence of the
condition in these animals is usually associated with rearing on nurse cows, housing for long
periods, provision of a ration high in cereal grains and byproducts (a high phosphorus:calcium
ratio), and possibly with an inherited straight conformation of the hindlegs. Although the disease
occurs in all beef breeds there is a strong familial tendency which appears to be directly related to
the rate of body weight gain and the straightness
1549
of the hindleg. If the potential for rapid weight gain is being realized in animals being force fed,
the rate of occurrence appears to be dependent on their breeding, and animals in the same herd that
are allowed to run at pasture under natural conditions are either not affected or are affected at a
much later age. Thus, animals in a susceptible herd may show signs as early as 6 months of age if
they are heavily hand-fed and raised on dairy cow foster mothers. In the same herd, signs do not
appear until 1-2 years of age if supplementary feeding is not introduced until weaning, and not
until 4 years if there is no significant additional feeding.
Clinically there is a gradual on set of lameness in one or both hindlegs. The disease progresses
with the lameness becoming more severe over a period of 6-12 months. In some animals there is a
marked sudden change for the worse, usually related to violent muscular movements, as in
breeding or fighting. In severely affected animals the affected limb is virtually useless and, on
movement, distinct crepitus can often be felt and heard over the affected joints. This can be
accomplished by rocking the animal from side to side or having it walk while holding the hands
over the hip joints.
An additional method of examination is to place the hand in the rectum close to the hip joint,
whilst the animal is moved. Passive movement of the limb may also elicit crepitus, or louder
clinking or clicking sounds. The hip joints are always most severely affected, but in advanced
cases there may be moderate involvement of the stifles and minimal lesions in other joints.
Affected animals lie down most of the time and are reluctant to rise and to walk. The joints are not

swollen, but in advanced cases local atrophy of muscles may be so marked that the joints appear to
be enlarged. There is a recorded occurrence in which the lesions were confined mainly to the front
fetlocks.
Radiographic examination may provide confirmatory or diagnostic evidence.
At necropsy the most obvious finding is extensive erosion of the articular surfaces, often
penetrating to the cancellous bone, and disappearance of the normal contours of the head of the
femur or the epiphyses in the stifle joint. The synovial cavity is distended, with an increased
volume of brownish, turbid fluid, the joint capsule is much thickened and often contains calcified
plaques. Multiple, small exostoses are present on the periarticular surfaces. When the stifle is
involved the cartilaginous menisci, particularly the medial one, are very much reduced in size and
may be completely absent. In cattle with severe degenerative changes in the coxofemoral joint, an
acetabular osseous bulla may be present at the cranial margin of the obturator foramen (1).
Adequate calcium, phosphorus and vitamin D intake, and a correct calcium:phosphorus ratio in
the ration should be insured. Supplementation of the ration with copper at the rate of 15 mg/kg has
also been recommended for the control of a similar disease.
Degenerative joint disease of cattle is recorded on an enzootic scale in Chile and is thought to
be due to gross nutritional deficiency. The hip and tarsal joints are the only ones affected and
clinical signs appear when animals are 8-12 months old. There is gross lameness and progressive
emaciation. An inherited osteoarthntis is described under that heading. Sporadic cases of
degenerative arthropathy, with similar signs and lesions, occur in heavy-producing, aged dairy
cows, and are thought to be caused by long-continued negative calcium balance. Rare cases also
occur in aged beef cows but are thought to be associated with an inherited predisposition. In both
instances the lesions are commonly restricted to the stifle joints.