Chapter 30 Diseases associated with nutritional deficiencies
INTRODUCTION 1691
DEFICIENCIES OF ENERGY AND PROTEIN 1697
DISEASES ASSOCIATED WITH DEFICIENCIES OF MINERAL NUTRIENTS 1698
DISEASES ASSOCIATED WITH DEFICIENCIES OF FAT-SOLUBLE VITAMINS 1771
DISEASES ASSOCIATED WITH DEFICIENCIES OF WATER-SOLUBLE VITAMINS 1778
The following criteria are suggested for the assessment of the importance of nutrition in the etiology of a disease state in a single animal or in a group of animals:
• Is there evidence from an examination of the diet that a deficiency of a specific nutrient or nutrients may be occurring?
• Is there evidence from an examination of the animals that a deficiency of the suspected essential nutrient or nutrients could cause the observed disease?
• Does supplementation of the diet with the essential nutrient or nutrients prevent or cure the condition?
The difficulties encountered in satisfying these criteria and making an accurate and reliable diagnosis of a nutritional deficiency have increased as investigations have progressed into the area of trace elements and vitamins. The amounts of such substances as selenium present in feedstuffs and body tissues are exceedingly small and their estimation difficult and expensive. Because of these difficulties it is becoming more acceptable to describe individual syndromes as responsive diseases, i.e. which satisfy only the third of the above criteria. The practice leaves much to be desired but has the advantage that applicable control measures are more readily available.
General evidence will include either evidence of deficiency in the diet, or abnormal absorption, utilization or requirement of the nutrient under consideration. Special evidence may be obtained by chemical or biological examination of the feed.
The diet for a considerable period prior to the occurrence of the disease must be considered because body stores of most dietary factors may delay the appearance of clinical signs. Specific deficiencies are likely to be associated with particular soil types, and in many instances soil and geological maps may predict the probable occurrence of a nutritional disease.1 Diseases of plants may also indicate specific soil deficiencies, e.g. ‘reclamation disease’ of oats indicates a copper deficiency in the soil. Domination of the pasture by particular plant species may also be important, e.g. subterranean clover selectively absorbs copper, legumes selectively absorb molybdenum, and Astragalus spp. are selector plants for selenium.
Farming practices may have a marked bearing on the presence or absence of specific nutrients in livestock feed. For example, heavy applications of nitrogen fertilizer can reduce the copper, cobalt, molybdenum, and manganese content of the pasture. On the other hand, many applications of lime reduce plant copper, cobalt, zinc, and manganese levels, but increase the molybdenum content. Effects such as these are sufficiently severe to suggest that animals grazing the pasture might suffer trace element deficiency. Modern hay-making methods, with their emphasis on the artificial drying of immature forage, tend to conserve vitamin A but may result in a gross deficiency of vitamin D. Soil and pasture improvement by exaggeration of the depletion of nutrients, particularly trace elements, from marginally deficient soil may give rise to overt deficiency disease. Thus, local knowledge of farming and feeding practices in a particular area is of primary importance in the diagnosis of nutritional deficiency states.
Even though a diet may contain adequate amounts of a particular nutrient, some other factor, by decreasing the absorption of the nutrient, may reduce the value of the dietary supply. For instance, excess phosphate reduces calcium absorption, excess calcium reduces the absorption of iodine, and absence of bile salts prevents proper absorption of the fat-soluble vitamins. Chronic enteritis reduces the absorption of most dietary essentials. The list of antagonisms that exist between elements grows all the time, most of them being interferences with absorption. For example, excess calcium in the diet interferes with the absorption of fluorine, lead, zinc, and cadmium, so that it may cause nutritional deficiencies of these elements, but it also reduces their toxic effects when they are present in the diet in excessive amounts.
This may also have an effect on the development of conditioned deficiency diseases. For example, molybdenum and sulfate reduce copper storage, vitamin E has a sparing effect on vitamin A, and thiamine reduces the dietary requirements of essential fatty acids.
Stimulation of the growth rate of animals by improved nutrition or other practices may increase their requirement of specific nutrients to the point where deficiency disease occurs. There seems to be little doubt that there is a genetic variation in mineral metabolism and it has even been suggested that it may be possible to breed sheep to ‘fit’ actual deficiency conditions, but the significance of the inherited component of an animal’s nutritional requirement is unknown and probably small. It should not be overlooked, however, when policies of upgrading livestock in deficient areas are initiated.
Evidence is usually available from experimental work to indicate the clinical signs and necropsy findings one can expect to be produced by each deficiency. Several modifying factors may confuse the issue. Deficiencies under natural circumstances are unlikely to be single and the clinical and necropsy findings will be complicated by those caused by deficiencies of other factors or by intercurrent infections. In addition, most of the syndromes are both variable and insidious in onset and the minimal nature of the necropsy lesions in many nutritional deficiency diseases adds further difficulty to the making of a diagnosis.
Special clinical and laboratory examinations of the animals are valuable aids to diagnosis in many instances. However, the ranges of blood or tissue concentrations of minerals and vitamins, or their biochemical markers, in normal animals and those values which indicate deficiency have not been well-established. In other words, the cut-off values above which animals are normal and below which they are abnormal or deficient have not been adequately determined in naturally occurring nutritional deficiencies. Experimentally induced nutritional deficiencies provide an indication of the changes that occur in the concentrations of a particular nutrient marker, but variations due to age, genotype, production cycle, length of time on the inadequate diet, previous body stores of the element and other stressors commonly complicate the results and render them difficult to interpret accurately and with repeatability.
In most cases, nutritional deficiencies affect a proportion of the herd or the flock at the same time and the clinicopathological examination should include both normal and clinically affected animals. Comparison of the laboratory results of normal and abnormal animals allows for more accurate and reliable interpretation and the making of a diagnosis.
The best test of the diagnosis in suspected nutritional deficiency is to observe the effects of specific nutrient additions to the ration. Confounding factors are frequently encountered. Spontaneous recoveries may occur and adequate controls are essential. Curative responses may be poor because of an inadequate dose rate, because of advanced tissue damage, or because the abnormality may have been only a predisposing factor or secondary to a complicating factor that is still present. Another common cause of confusion in therapeutic trials is the impurity of the preparations used, particularly when trace elements are involved. Finally, the preparations used may have intrinsic pharmacological activity and produce some amelioration of the disease without a deficiency having been present.
The feeds and feeding program have a major influence on reproductive performance, growth rate, and milk production and must be monitored regularly. The veterinarian must be aware of any changes in the feeding program that have occurred since the last farm visit or that are intended in the near future. On breeding farms, there are several different age groups of animals at different levels of growth and production. This requires close surveillance to avoid undernutrition or overnutrition. Scoring of the body condition of dairy cattle, beef cows, sheep, and pigs is becoming commonplace as an indicator of the adequacy of the diet. Veterinary clinical nutrition is now a veterinary medical specialty that should provide new and useful information for the practitioner working with a particular species or class of food animals. The American College of Veterinary Nutrition also provides consultants in veterinary nutrition who can be called on for advice in solving nutritional problems. An experienced and competent nutritionist should be consulted to assist with complex nutritional problems.
Advising farms about nutrition is a key activity for dairy cattle practitioners. Feed costs constitute approximately 60% of the total cost of producing milk, and even minor improvements in feeding efficiency can be profitable. Some dairy practitioners function as the nutritional specialists for the dairy farms they serve. They may collect feed samples for nutrient analysis, formulate rations, and advise the farmer regarding crop and harvesting conditions. These veterinarians often devote a considerable amount of their professional time to nutritional management.
It is common for farms to employ a professional nutritionist or to use a nutritionist employed by a feed company or local cooperative. These professional nutritionists generally formulate the rations and submit feed samples for nutrient analysis. On these herds, the veterinarian can have an important role in ensuring that the diet described on paper is adequately formulated and delivered to the cows. Routine scheduled activities such as measuring the dry matter of forages, hand mixing total mixed rations (TMR) for one cow and comparing it with the machine-mixed TMR (‘TMR test mix’), and scoring the feed bunk to assess feed sorting and dry matter intake are important procedures that help to ensure the successful delivery of a nutritional program. Assessing pasture conditions by periodic inspection of pasture is an important component of managing the nutritional program of herds that use management-intensive grazing. These quality control activities should be conducted routinely as part of the health and production management program.
There is probably no aspect of a dairy enterprise that has a wider impact than the feeding program. Dairy farm feeding programs have direct effects on production and growth and set the stage for future productive potentials. Many health problems on a dairy relate in some way to the feeding program. Feed costs on the average dairy account for more than 60% of total operating expenses in the USA. A significant part of the average dairy’s labor force devotes its time to planting, growing, harvesting, mixing, and feeding rations to a variety of animals. Investments in equipment used in feeding programs are an important part of the dairy’s debt load. Small changes in feeding programs may bring about large changes in productivity, health, income, feed costs, labor allocation, and debt load. The total savings from small changes can be substantial. Without considering improved production or health effects, one study has shown that routine nutritional consultation by veterinarians can save 14% of total feed costs on dairies.
For all these reasons, veterinarians who intend to serve their dairy clients on a herd basis must become actively involved in the herd’s feeding program. Dairy herds are commonly fed unbalanced, expensive rations. By serving as independent consultants, veterinarians can provide unbiased advice to their clients. Those veterinarians who wish to serve their clients at a herd level constantly find their attention focused on the feeding program. The next recumbent, hypocalcemic cow raises questions about dry cow feeding. The next anestrous, thin cow with smooth ovaries raises questions about early lactation energy levels in the ration and dry matter intake (DMI). The next time the herd average mature equivalent milk production falls by 500 lb, the problem generates the same sense of urgency as a cow with a prolapsed uterus. As a profession, dairy veterinary medicine must come to grips with the fact that it cannot truly serve client needs by practicing therapeutic medicine separately from nutritional consulting. Veterinarians must train themselves to deal with nutrition directly, consistently and knowledgeably.
In recent years, as herd size has increased, many dairies have come to rely on a team of advisors rather than only one or two. A nutritional consultant, local veterinarian, and outside consultant may all be providing advice to a dairy. In these circumstances, communication about the feeding program and resulting performance is critical. It is imperative that the veterinarian be knowledgeable about dairy nutrition and involved in ration formulation. The veterinarian needs to maintain their involvement as part of the advisory team.
Having decided to be involved in a dairy’s feeding program, the veterinarian and client should first agree on the level of nutrition service that is to be provided. The level varies from herd to herd, depending on the veterinarian’s expertise, the client’s ability and interest, and the role being played by other consultants to the farm. There are essentially four levels of service that might be provided:
At level 1, the veterinarian takes on the task of monitoring the dairy herd for indicators that there might be nutrition-related problems. Many areas need to be monitored: production, milk components, DMI, body scores, disease rates, growth rates, and feed costs. Based on these monitored areas, the veterinarian can call attention to problems as they arise, form and test hypotheses about likely causes, and interact with other farm service personnel as the problems are addressed.
At level 2, the veterinarian evaluates the nutritional adequacy of diets as they are fed to the cows. If problems of balance or economics are identified, they are referred to the appropriate person for reformulation. This level is difficult to sustain over time because, after a while, the person formulating the ration is likely to resent being ‘second-guessed’. It can work well if the ‘team approach’ is part of the procedure on the dairy.
At level 3, the veterinarian takes on the responsibility of formulating the ration. To operate responsibly at this level, veterinarians need several additional skills beyond those traditionally taught at veterinary colleges. The veterinarian must know how to use a computer to formulate a balanced, deliverable, cost-effective ration. The veterinarian should have experience in the daily mechanics of how feeds are handled and how cows are fed. It requires an intimate knowledge of the farm and its personnel. The veterinarian must maintain daily contact with the feed industry, so that feed prices and availability can be factored into the farm’s overall feeding program.
If not managed carefully, this level of service has several pitfalls. It lacks the on-farm follow-up, supervision of implementation, and monitoring of results that are included in level 4. There is a truism about feeding dairy cows that every cow has three rations: the one formulated, the one delivered, and the one actually eaten. The best feeding programs minimize the difference among these three rations. If the veterinarian’s role stops at formulation, then mistakes can occur in delivery and feed bunk management that can doom the program to failure. If the program fails, the veterinarian’s formulation is likely to be blamed.
Level 4 of nutritional service includes those aspects missing in level 3. The veterinarian plays an active role in implementing the feeding recommendations. Attention is paid to areas such as bunk management, cow comfort, feeding frequency and scheduling, quality control and consistency of feeding management. Working closely with the producer, plans for future forage production can be generated, including attention to factors such as timing the harvest for maximum feed value. The monitoring described in level 1 is sustained, and timely adjustments and feedback are provided to ensure that the rations are accomplishing the desired ends. In the long term, this is the level of service that is most desirable for both the veterinarian and the client. The producer benefits from the added supervision and support, and the veterinarian can assure the client that the program is carried out as designed. If the program is not working, it can be modified. Total program consulting can be accomplished with the veterinarian as a part of the team that would include the nutritionist, as well as by the veterinarian alone. With many larger herds, particularly, multiple outside consultants are used, and a team approach provides the owner with the best opportunity for expert advice. In many herds, the veterinarian is best suited to be the ‘team leader’.
Good nutrition provides the essential basis for optimum productivity in cattle breeding operations. Despite this, nutritional expertise has not been a traditional strength of many food-animal veterinarians.
Throughout the world, beef-breeding operations are generally range or pasture based. These operations are conducted in diverse environments, with great variation in nutritional management. Even within the USA, the area of pasture or rangeland required to maintain a cow-calf unit may vary from 3 acres or more in the south-west to 1 or 2 acres in more intensive regions. In parts of Australia, the corresponding area may be measured in square miles. However, in general, the area of land, or amount of pasture, necessary for production is related to local economic realities. This, in turn, is related to levels of managerial and resource inputs that can differ with regions, markets, and enterprise priorities. Notwithstanding such caveats, there are a number of principles of good nutritional management that may be universally applied to cattle breeding operations. Regardless of region, an important consideration is that of maintaining or improving production while reducing costs. In simple terms, financial return from a beef breeding operation is a function of number of calves, their weaning weight, and price. On the cost side of the ledger is the maintenance cost of the breeding females. This varies considerably, both within and between regions. Market price, in general, is usually unmanageable at the farm level. However, both the number of calves born and their weaning weights are strongly influenced by nutrition. For example, good nutritional management helps to ensure that as many females as possible are cycling at the start of the breeding season. This, in turn, helps to ensure that calves are born early with the result that they are older, and heavier, at weaning than later-born calves.
In general, nutrition is the most important limiting factor of beef breeding performance. For veterinarians, an understanding of the principles underlying the nutritional management of breeding females is necessary. Effective counseling and troubleshooting does not necessarily require a higher degree in nutrition, although it should include sufficient knowledge and wisdom to know when such expertise is needed. A starting point is to have a working knowledge of the different energy measuring systems (total digestible nutrients (TDN), metabolizable energy (ME) and net energy, NE) that are commonly used, their applications for different classes of animals, activities and feedstuffs, and to identify one with which the veterinarian can work best. The Nutrient Requirements of Beef Cattle from the National Research Council (NRC) in the USA is a useful document revised in 2000. This is packaged with a computer program that includes ration formulators as well as a library of feeds and feedstuffs. A number of computer programs are now available for least-cost-ration formulation in beef herds.
Feedlots frequently consult a qualified nutritionist to assist in the formulation of cost-effective diets. The veterinarian should communicate regularly with the nutritionist to be aware of the composition of the diets and any changes that are being planned. Because feed is the major portion of the cost per unit of body weight gain, it is imperative that the diet be the lowest-cost diet possible while providing nutrients that allow optimum growth and finishing. Most of the emphasis in feedlot nutrition has been on the development of cost-effective diets that support a maximum growth rate without any deleterious effects. Considerable information is available on the nutrient requirements for feedlot cattle and on the feeds and feeding systems used.
The precise specifications of the diets are the responsibility of the nutritionist, but the feedlot veterinarian frequently is in a position to evaluate the quality of the feed delivery system. This means checking to determine whether cattle are fed on time, whether the feed is mixed properly, and whether the feed intake is intermittent because of inclement weather or muddy ground surfaces. Any deviations should be communicated to the consulting nutrtionist.
Nutritional deficiency diseases are uncommon in feedlot cattle, because cattle usually receive a diet that contains the nutrients required for maintenance and promotion of rapid growth. Diets prepared according to the Nutrient Requirements of Beef Cattle should meet all the requirements under most conditions.
Specific nutrient deficiencies are extremely rare, because diets are prepared every few days or daily and it would be highly unusual for a feedlot to use a feedstuff deficient in a specific nutrient for a prolonged period. However, such a situation may occur in a small farm feedlot that prepares its own feedlot diet with little or no attention to the necessity for supplementation of homegrown feeds. Thus, there are only a few nutrition-related diseases that may affect a well-managed feedlot, but these diseases may cause large economic losses when they occur. They include the following:
Veterinarians involved in health management of swine-herds must be well informed about the nutrient requirements of the different age groups of pigs. Since feed constitutes 60–80% of the cost of producing a market pig, every effort must be made to increase the economic efficiency of feed use. Some surveys of well-managed pig farms in Alberta, Canada, found a 20% difference in feed costs, and it is estimated that in the industry the range in feed costs is likely to be near 50%. Reduction of the feed cost of the highest costing farm to that of the lowest costing farm would save that farm more than US$23 000 annually, which is equivalent to a cost reduction in production of $6.80/pig. The trend is to use complete feeds formulated by feed company nutritionists who are familiar with the nutrient composition of local feedstuffs. With complete diets, specific nutrient deficiencies are uncommon.
The major problem is the efficiency of utilization of the different feeds throughout the life cycle of the pig. The nutrient requirements of the pig at various phases of growth from birth to market weight and of breeding stock are well established. The remaining questions appear to be about the levels of feed that should be provided during the different phases of the growth of the pig in order to achieve optimum production and to yield the best carcass. Proper nutrition can greatly increase the efficiency of pig production, because feed represents such a large percentage of the cost involved. The following are some recommended practices for increasing efficiency of feed utilization with pigs:
• Provide well-balanced diets with adequate levels of amino acids, energy, vitamins, and minerals necessary to meet the particular demands of the pig at each stage of its life cycle. The diet depends on the demands, usually characterized as the growth rate or lean deposition. Feed intake is the supply function. Feed intake is limited by appetite, and thus other nutrients are matched to expected energy intake and subsequent growth
• Use least-cost formulation to the extent that it is feasible. The least-cost energy source in most of the pig-rearing areas is corn, and the most common protein source is soybean meal
• Restrict the level of a properly balanced diet for sows during gestation to avoid overfeeding. Sows that have lost excessive body weight in the previous lactation need supplemental feed during the dry period to avoid the thin-sow syndrome
• Ad-lib feeding for growing pigs is usually optimum, unless the genotype deposits excess fat during the latter stages of growth
• Market pigs as close to optimum slaughter weight as possible to maximize margin over feed costs
• Avoid feed wastage by using well-designed feeding systems and proper adjustment of those feeders
• Use pelleting of diets to increase digestibility, especially of small grains, and to decrease feed wastage. However, pelleting also predisposes pigs to gastroesophageal ulcers.
The feed efficiency of the pigs from weaning to market should be monitored regularly. It is often difficult to obtain accurate data on this item for specific groups of pigs, because the amount fed to each group may not be calculable when a common feeding system is in use. However, the total amount of feed used and the total weight of pigs marketed will give an estimate of feed efficiency.
The National Research Council (NRC) in the USA provides an important service in establishing the nutrient requirements of swine and other species. The 10th revised edition of the Nutrient Requirements of Swine was published in 1998. The 200-page edition incorporates the wealth of new research information that has emerged over the past 10 years since the 8th edition, and addresses new areas such as modelling nutrient requirements and reducing nutrient excretion.
Even though the nutrient requirements of pigs are well known, they do continue to change because of changes in growth and production characteristics of pigs. Pigs with high lean-growth rates require higher levels of amino acids to support their increased rate of body protein deposition. Similarly, high milk-producing sows nursing large litters have increased amino acid requirements.
In the 10th edition, a new approach is used to produce estimates of nutrient requirements that take into consideration not only the pig’s body weight, but also its accretion rate of lean (protein) tissue, gender, health status, and various environmental factors. To accurately estimate nutrient needs of gestating and lactating sows, there is a need to account for body weight, weight gain during gestation, weight loss during lactation, number of pigs in the litter, weight gain of the litter (a reflection of milk yield), and certain environmental factors.
A series of integrated mathematical equations was used to account for the many factors now known to influence nutrient requirements. These equations provide the framework for modeling the biological basis of predicting requirements. The NRC models predict the levels of nutrients (outputs) needed to achieve a certain level of production under a given set of environmental conditions (inputs).
Five principles were used to develop the models. The models: (1) were made for ease of use by people with varying levels of nutritional expertise and with limited information; (2) were developed for continued relevance for several years to come; (3) were intended to be structurally simple, so they could be understood readily by users; (4) were developed to be transparent so that all of the equations could be available to the user and (5) were firmly anchored to empirical data at the whole-animal level rather than being simply based on theoretical values. Three independent models were developed for growth, gestation, and lactation. The growth model estimates amino acid requirements of pigs from weaning to market weight, and the gestation and lactation models estimate energy and amino acid requirements of gestating and lactating sows.
Few revisions were made in the previously published mineral requirements. Based on recent findings, higher dietary requirements for sodium and chloride in the young pig were established. The manganese requirements were increased from 10 to 20 ppm for gestating and lactating sows.
Several changes were made in the feed composition tables. Nutrient composition of feeds was obtained from as many data bases as possible, including from the feed industry and from data sets outside the USA and Canada.
The information on water was expanded considerably, with more detailed information on the factors that influence water intake. There is additional new information on non-nutritive feed additives, such as antimicrobial agents, anthelmintics, microbial supplements, oligosaccharides, enzymes, acidifiers, flavors, odor control agents, antioxidant pellet binders, flow agents, high-mineral supplements, and carcass modifiers.
A new chapter on minimizing nutrient excretion is included in the 10th edition. It addresses environmental issues and the importance of reducing the excretion of nutrients, particularly nitrogen and phosphorus, which can potentially contribute to environmental pollution.
The influence of nutrition on the reproductive performance of ewes has been a matter of concern to sheep farmers and sheep production research workers throughout the world. It is clear that the relationship between nutritional provision and nutrient requirements for optimum reproductive performance is seldom ideal because of the wide range of environmental conditions and the seasonality of breeding that most sheep breeds exhibit. Prolonged periods of undernutrition during mid-pregnancy are partly the result of the decline in feed availability and quality over that stage of the reproductive cycle.
Prolonged duration of moderate to severe undernutrition of ewes bearing twins in mid-pregnancy can reduce placental development causing significant reductions in lamb birth weight with increased mortality. Considerable progress has been made in understanding the principles of nutrition of sheep and in defining their nutrient requirements for maintenance, pregnancy, and lactation.
The sensitivity of lamb birth weight, particularly in twins and triplets, to the ewe’s plane of nutrition during late pregnancy is well known. It has been established that mortality rates are high in lambs with birth weights below the breed norm, and that after birth the absolute growth rates are lower in surviving light lambs than in heavier lambs of the same breed. The plane of nutrition and the size of the placenta have been recognized as major determinants of the fetal growth rate. Fetal growth retardation in undernourished ewes has a placental component, and the factors that affect placental growth are relevant here.
The 21-week gestation can be divided into a number of periods to consider the effects of nutrition on reproduction within each period. In the first month of gestation, embryonic loss is the main sequel to inadequate nutrition. During this period, it is generally recommended that the BCS of the ewe be maintained at 2.5–3.5 (scale of 1 to 5) to minimize embryonic and early fetal losses. This is followed by a period of 2 months in which there is rapid growth of the placenta, but during which growth of the fetus in absolute terms is still small. Over this period, it is normal to advocate that losses in body weight should not exceed 5%. Finally, there is the phase from 90 days to parturition, in which gain in the mass of the fetus amounts to 85% of its birth weight; during this period, nutrient intake must be increased.
Placental development in the pregnant ewe begins about 30 days after conception, the number of placentomes associated with each fetus is fixed at this time, and the total weight of the placentomes increases until about 90 days of gestation, after which there is little change. The factors that influence the ultimate size of the placenta and its weight include hormonal and nutritional factors, prolonged environmental heating of pregnant ewes, parity of ewes, and possibly genotype, but the most important determinant is nutrition of the ewe. Moderately severe undernutrition during early pregnancy and midpregnancy significantly reduces placental weight at or near term and causes chronic intrauterine growth retardation.
The size of the placenta is a major determinant of fetal growth. In well-fed ewes, the fetal growth rate before 120 days of gestation is not correlated positively with placental weight, but fetal growth rate in the last 3 to 4 weeks of pregnancy is limited by the size of the placenta. Earlier placental influences on fetal growth are evident, however, when ewes are underfed. Placental weight and fetal growth rate are correlated positively during periods of maternal underfeeding, which starts before 90, at 95, or at 112 days of gestation. During the first 90 days of pregnancy, placental growth is reduced when ewes are moderately underfed. Low-weight fetuses in ewes with placenta weights near the bottom of the normal range are affected with chronic and progressive hypoxemia and hypoglycemia, which affect fetal metabolism. The consequences are fetal death during late pregnancy, fetal hypoxemia during parturition, premature birth, and a high perinatal mortality rate caused by hypoglycemia and hypothermia.
The extent to which ewes maintained on a fixed ration draw on their own body reserves in an attempt to meet the energy costs of pregnancy is determined by fetal weight. In well-fed ewes, fetal growth rate remains constant until at least 120 days of gestation and decreases thereafter. However, its absolute growth rate increases markedly during the last 8 weeks of gestation, when fetal growth is most rapid, exceeding 100 g/day near birth. The growth rate among fetuses is highly variable, which accounts for birth weights ranging from 2 kg to over 7 kg. When ewes that have been well fed are severely underfed at any stage during the last 40 to 50 days of pregnancy, the fetal growth rate decreases within 3 days, by 30% to 70%. This illustrates that the mobilization of maternal reserves is substantially less than fetal requirements and emphasizes the importance of ensuring a continuous supply of good-quality feed during late pregnancy. The larger the fetal burden, the more susceptible a ewe is to hypoglycemia during underfeeding.
Re-feeding after severe underfeeding can reverse the reduced growth rate of fetuses, but the response depends on the duration of the underfeeding. If the period of underfeeding is 16 days or less, the growth rate increases when ewes are re-fed, but there is no change when re-feeding occurs after 21 days of severe underfeeding. Moderate underfeeding of pregnant ewes for 85 days reduces the fetal growth rate irreversibly, and refeeding them in late pregnancy does not cause the fetal growth rate to increase but does prevent further decreases after 120 days.
The major consequences of prenatal growth retardation are on lamb survival. The neonatal mortality of lambs increases markedly in many environments as the birth weight falls below 3–3.5 kg. Compared with normal lambs, low-birth-weight animals have reduced insulation because of the smaller number of wool fibers, greater relative heat loss because of their larger surface area per unit of body weight, and a reduced capability to maintain heat production because of their lower fat and energy reserves. All these factors increase their susceptibility to environmental stress and reduce their ability to compete with normal-sized siblings. Underfeeding during pregnancy can also reduce available body lipids in lambs by about 47% and also decreases the lactose, lipid, and protein available in colostrum during the first 18 h by about 50%. Newborn lambs have to draw on body reserves of glycogen in order to maintain heat production during the first 18 h after birth, and thus depend heavily on colostrum intake and supplemental feeding to avoid hypoglycemia and hypothermia.
The effects of maternal nutrition on udder development and on the production and yield of colostrum and milk in ewes have also been examined. In the last 30 days before birth, there is a marked increase in the rate of mammary tissue growth in the ewe. In well-fed ewes with one or two lambs, large volumes of colostrum accumulate in the mammary glands during the last few days of pregnancy and copious milk secretion begins soon after birth, with averages of 1800 to 2800 mL of colostrum and milk being produced during the first 18 h. Udder growth rates are proportional to fetal growth rates in that the greatest increase in udder weight occurs in the last 30 days of gestation and the weight of udder tissue is 30–40% of the total weight of the litter. Colostrum production is proportional to udder weight, and re-feeding of ewes a few days before lambing fills the udder tissue present but does not increase udder tissue weight. In underfed ewes, prenatal colostrum accumulation is reduced markedly, lactogenesis is delayed, and the total production of colostrum and milk during the first 18 h averages about 1000 mL. Subsequently, in both types of ewe, milk production increases, reaching a peak about 1–2 weeks after birth. Underfeeding ewes beginning at 105 days of gestation can reduce the total yield of colostrum during the first 18 h after birth by decreasing mammary tissue growth. Thus, the prepartum accumulation of colostrum and its sub-sequent rates of secretion are reduced. Improving the ewe’s nutrition from 1 h after birth can increase the secretion rates of colostrum between 10 and 18 h.
The growth rate of lambs during the first few weeks of life is correlated positively with birth weight. Low planes of maternal nutrition during late pregnancy and early lactation are generally associated with low birth weights, milk yields, and postnatal growth rates, and high planes of nutrition with the opposite effects. A marked increase in the plane of maternal nutrition at birth can overcome the inhibitory effects on lactation and lamb growth rate of underfeeding in late pregnancy.
At breeding time, the aim is to achieve a body score of 3.0–3.5, which ensures maximum ovulation rate. For ewes with a BCS of 3.5 at breeding, it is desirable to allow them to lose no more than 5% of their body weight steadily, equivalent to approximately 0.5 to 1 unit of condition score during the second and third months of pregnancy. This mild degree of undernutrition enhances placental growth and establishes the basis for maximum fetal growth in the 4th and 5th months of pregnancy, the period during which the fetus achieves over 80% of its growth. During these final 2 months of pregnancy, there is a limit to the extent to which body fat reserves can be used, because excessive mobilization of depot fats as a consequence of inadequate dietary energy supply leads to pregnancy toxemia. In late gestation, the optimum BCS ranges from 2.5 to 3.0. In contrast, early lactation is a period in which body fat can be safely used to meet some of the high energy demands of lactation. During this period, a loss of BCS of 1.0 (equivalent to 5 kg fat for a 70 kg ewe at mating) is acceptable, and during lactation it ranges from 1.5 to 2.5. The replacement of the body fat that is used before the next breeding cycle is important in achieving a maximum ovulation rate and subsequently optimum reproductive performance.
Winter shearing of pregnant ewes during the final 10 weeks of pregnancy has been shown to cause a significant increase in lamb birth weight. Shearing pregnant sheep at 8 weeks before lambing leads to a chronic increase in energy requirements, which are met by oxidizing body fat depots without risks of clinical ketosis. Fetal growth is enhanced as a result of these metabolic adaptations.
The nutrient requirements for maintenance, breeding, pregnancy, and lactation of ewes have been catalogued, and optimum feeding strategies for the breeding ewe can be formulated. The evaluation of the ewes’ ration during late gestation by monitoring plasma concentrations of the ketone body 3-OH butyrate has been described with accurate guidelines, which have been used as the basis for flock nutritional advice during late gestation.
The achievement of optimum reproductive performance involves changing feeding strategies and adjusting the nutrient value of the diet as necessary throughout the reproductive cycle to meet the needs of the particular stage. The requirements for metabolizable energy begin to increase steadily above maintenance levels beginning at between 8 and 12 weeks of pregnancy and continuing into late pregnancy and lactation. During early lactation, when the energy requirements of prolific ewes exceed those required by the voluntary consumption of all but the highest-quality diets, the body fat reserves are used and then replenished toward the end of lactation, when milk yield declines, and in the period leading up to rebreeding.
In contrast to the ability of the ewe, particularly in early lactation, to use body reserves when the intake of energy fails to meet her needs, there is little scope for sustaining production by drawing on body protein. For example, lactating ewes can lose up to 7 kg of body fat during a 4-week period in early lactation, when energy intake is below requirements. For ewes on a low-protein intake, the maximum daily loss of protein was 26 g. Thus, it is important to meet the protein needs of the ewe at all times during pregnancy, but especially during late pregnancy, for fetal growth, udder development, and colostrum production. The estimates for protein are also based on the important principle of distinguishing between the needs of the rumen microflora for rumen-degradable protein and of the host animal for additional undegraded dietary protein when rumen-degradable protein fails to meet those requirements; this represents the minimum protein needs of the animal. In practice, the dietary allowances for late pregnancy and early lactation are higher than the sum of the rumen-degradable protein and undegradable protein.
The rapid growth of the fetus after 90 days of pregnancy requires an increased allowance of dietary energy, which can be met with concentrates if only hay is available. This is particularly true for ewes carrying twins or triplets. The daily dietary energy requirement of ewes of varying body weights and fetal number ranging from singletons to triplets has been described in conjunction with a monitoring program for dietary energy supply based on plasma concentration of the ketone body 3-OH butyrate. This system forms the basis of flock advisory visits made by veterinarians during late gestation in UK flocks. Correct nutrition during late gestation guarantees appropriate lamb birth weights despite litter size and sufficient accumulation of protective immunoglobulin in the udder.
. Subcommittee on Dairy Cattle Nutrition, Committee on Animal Nutrition, Board on Agriculture, National Research Council Subcommittee on Dairy Cattle Nutrition. Nutrient requirements of dairy cattle, 7th ed. 2000. Washington, DC: National Academy Press.
. Subcommittee on Beef Cattle Nutrition, Committee on Animal Nutrition, Board on Agriculture, National Research Council. Nutrient requirements of beef cattle, 7th revised ed. 2000. Washington, DC: National Academy Press.
. Subcommittee on Swine Nutrition, Committee on Animal Nutrition, Board on Agriculture, National Research Council. Nutrient requirements of swine, 10th revised ed. 1998. Washington, DC: National Academy Press.
. Subcommittee on Horse Nutrition, Committee on Animal Nutrition, Board on Agriculture, National Research Council. Nutrient requirements of horses, 5th revised ed. 1989. Washington, DC: National Academy Press.
. Subcommittee on Sheep Nutrition, Committee on Animal Nutrition, Board on Agriculture, National Research Council. Nutrient requirements of sheep, 6th revised ed. 1985. Washington, DC: National Academy Press.
DEFICIENCIES OF ENERGY AND PROTEIN
Insufficient quantity or quality of feed is a common nutritional deficiency and practical problem of feeding livestock.1,2 The term protein-energy malnutrition is used to describe a form of incomplete starvation in which energy and protein are present in the diet in suboptimal quantities. Protein and energy deficiencies usually occur concurrently in underfed livestock and often cannot be strictly separated.
A deficiency of energy is the most common nutrient deficiency limiting performance of farm animals. There may be inadequate amounts of feed available, or the feed may be of low quality. Supplies of feed may be inadequate because of overgrazing, drought, snow covering, or it may be too expensive to be fed to the animals. Available feed may be of such low quality and digestibility that animals cannot consume enough to meet energy requirements. In some cases, forage may contain a high concentration of water, which limits total energy intake.
The clinical findings of an energy deficiency depends on the age of the animal, whether or not it is pregnant or in lactation, the presence of concurrent deficiencies of other nutrients and environmental influences. In general, an insufficient supply of energy in young animals results in retarded growth and delay in the onset of puberty. In mature animals, there is a marked decline in milk production and a shortened lactation. A prolonged energy deficiency in pregnant beef heifers will result in a failure to produce adequate quantities of colostrum at parturition. In mature animals, there is also a marked loss of body weight, especially during high demands for energy as in late pregnancy and early lactation. There are prolonged periods of anestrus lasting up to several months, which has a marked effect on reproductive performance in the herd. Primigravid females are particularly susceptible to protein-energy malnutrition because of growth and maintenance requirements.1 A prolonged deficiency of energy during late gestation may result in undersized, weak neonates with a high mortality rate. A deficiency of energy during prolonged periods of cold weather, especially in pregnant beef cattle, and ewes being wintered on poor quality roughage, may result in abomasal impaction. Heat loss from the animal to the environment increases remarkably during cold weather, and when ambient temperatures are below the critical temperatures, the animal responds by increasing metabolic rate to maintain normal body core temperature. If sufficient feed is available when temperatures are below the lower critical temperature, ruminants will increase their voluntary feed intake to maintain body temperature. If sufficient feed is not available, the animal will mobilize energy stored as fat or muscle to maintain body temperature and thus lose body weight. In the case of ruminants and horses, if the feed is of poor quality, for example, poor quality roughage, the increased feed intake may result in impaction of the abomasum and forestomachs in cattle and of the large intestine in the horse.
Cold, windy, and wet weather will increase the needs for energy and the effects of a deficiency are exaggerated, often resulting in weakness, recumbency and death. A sudden dietary deficiency of energy in fat, pregnant beef cattle and ewes can result in starvation ketosis and pregnancy toxemia. Hyperlipemia occurs in fat, pregnant or lactating ponies that are on a falling plane of nutrition.
Protein-energy malnutrition occurs in neonatal calves fed inferior quality milk replacers that may contain insufficient energy or added non-milk proteins which may be indigestible by the newborn calf. A major portion of the body fat present at birth can be depleted in diarrheic calves deprived of milk and fed only fluids and electrolytes for 4–7 days. Feeding only fluids and electrolytes to normal, healthy newborn calves for 7 days can result in a significant loss of perirenal and bone marrow fat, and depletion of visible omental, mesenteric and subcutaneous fat stores.3 The amount of body fat present in a calf at birth is an important determinant of the length of time an apparently healthy calf can survive in the face of malnutrition. Calves born from dams on an adequate diet usually have sufficient body fat to provide energy for at least 7 days of severe malnutrition. The absence of perirenal fat in a calf at 2–4 days of age suggests inadequate reserves of fat at birth and chronic fetal malnutrition.3
Oetzel GR, Berger LL. Protein-energy malnutrition in domestic ruminants. Part 1. Predisposing factors and pathophysiology. Comp Cont Educ Pract Vet. 1985;7:S672-S679.
Oetzel GR, Berger LL. Protein-energy malnutrition in domestic ruminants. Part 2. Diagnosis, treatments and prevention. Comp Cont Educ Pract Vet. 1986;8:S16-S21.
A deficiency of protein commonly accompanies a deficiency of energy. However, the effects of the protein deficiency, at least in the early stages, are usually not as severe as those of energy. Insufficient protein intake in young animals results in reduced appetite, lowered feed intake, inferior growth rate, lack of muscle development, and a prolonged time to reach maturity. In mature animals, there is loss of weight and decreased milk production. In both young and mature animals, there is a drop in hemoglobin concentration, packed cell volume, total serum protein, and serum albumin. In the late stages, there is edema associated with the hypoproteinemia. Ruminants do not normally need a dietary supply of essential amino acids, in contrast to pigs which need a natural protein supplement in addition to the major portion of total protein supplied by the cereal grains. The amino acid composition of the dietary protein for ruminants is not critical because the ruminal flora synthesize the necessary amino acids from lower quality proteins and non-protein sources of nitrogen.
The clinical findings of an energy deficiency are similar to those of a protein deficiency and the clinical findings of both resemble many other specific nutrient deficiencies and subclinical disease. Protein-energy malnutrition in beef cattle occurs most commonly in late gestation and is characterized clinically by weakness, clinical recumbency, marked loss of body weight, a normal mental attitude, and a desire to eat.1,2 Cows with concurrent hypocalcemia will be anorexic. If the condition occurs at the time of parturition, there will be an obvious lack of colostrum. Calves of these cows may attempt to vigorously suck their dams, attempt to eat dry feed, drink surface water or urine and bellow continuously. Affected cows and their calves may die within 7–10 days.
Protein-energy malnutrition is less common in dairy cattle because they are usually fed to meet the requirements of maintenance and milk production. Dairy calves fed inferior quality milk replacers during periods of cold weather will lose weight, become inactive, lethargic, and may die within 2–4 weeks. Affected calves may maintain their appetites until just before death. Diarrhea may occur concurrently and be confused with acute undifferentiated diarrhea due to the enteropathogenic viruses or cryptosporidiosis. Affected calves recover quickly when fed cow’s whole milk.
Protein-energy malnutrition also occurs in sheep and, less commonly, in goats. Excessive dental attrition is a common cause in grazing sheep, which is exacerbated by the excessive ingestion of soil.
The diagnosis will depend on an estimation of the concentration of energy and protein in the feed, or a feed analysis, and comparing the results with the estimated nutrient requirements of the affected animals. In some cases, a sample of feed used several weeks earlier may no longer be available or the daily amount of feed intake may not be known. Marginal deficiencies of energy and protein may be detectable with the aid of a metabolic profile test. Specific treatment of livestock affected with protein-energy malnutrition is usually not undertaken because of the high cost and prolonged recovery period. Oral and parenteral fluid and electrolyte therapy can be given as indicated. The provision of high-quality feeds appropriate to the species is recommended.
The prevention of protein-energy malnutrition requires the provision of the nutrient requirements of the animals according to age, stage of pregnancy and production, the environmental temperature and the cost of the feeds. Body-condition scoring of cattle and sheep can be used as a guide to monitor body condition and nutritional status. Regular analysis of feed supplies will assist in the overall nutritional management program. The published nutrient requirements of domestic animals are only guidelines to estimated requirements since they were determined in experimental animals selected for uniform size and other characteristics. Under practical conditions, all of the common factors that affect requirements must be considered.
Oetzel GR, Berger LL. Protein-energy malnutrition in domestic ruminants. Part 1. Predisposing factors and pathophysiology. Comp Cont Educ Pract Vet. 1985;7:S672-S679.
Oetzel GR, Berger LL. Protein-energy malnutrition in domestic ruminants. Part 2. Diagnosis, treatments and prevention. Comp Cont Educ Pract Vet. 1986;8:S16-S21.
Diseases associated with 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. Improving trace element nutrition of grazing livestock, in a way that is cost effective and that meets consumer perceptions and preferences, is a continuing challenge.1
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 UK, 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.
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 flock 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 pre-clinical 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 a small percentage of 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.1 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 low 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 for prolonged periods.
In developing countries, the trace element problem is confounded by the common deficiencies of energy, protein, phosphorus, and water, which affect postnatal 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.
The physiological basis of trace element deficiency is complex.1 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 pathways by the body in the face of a deficiency
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 are summarized in Table 30.1.
Table 30.1 Principal pathological and metabolic defects in essential trace element deficiencies5
| Deficiency | Pathological consequence | Associated metabolic defect |
|---|---|---|
| Copper | Defective melanin production | Tyrosine/DOPA oxidation |
| Defective keratinization; hair, 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 | Tetrahydrofolate methyl transferase | |
| Anemia | ||
| Selenium | Myopathy; cardiac/skeletal | Peroxide/hydroperoxide destruction |
| Liver necrosis | Glutathione peroxidase | |
| Defective neutrophil function | OH; O2 generation | |
| Zinc | Anorexia, growth failure | ? |
| Parakeratosis | Polynucleotide synthesis, transcription, translation? | |
| Perinatal mortality | ||
| Thymic involution | ||
| Defective cell-mediated immunity | ||
| Iodine | Thyroid hyperplasia | Thyroid hormone synthesis |
| Reproductive failure | ||
| Hair, wool loss | ||
| Manganese | Skeletal/cartilage defects | Chondroitin sulfate synthesis |
| Reproductive failure | ? |
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 non-specific 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 importance, 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.
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 will generally be sigmoid in 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 respond 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 impaired. 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 element 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 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 of those markers for future diagnosis. The strategies for anticipating and preventing trace element deficiencies include regular analysis of the feed and soil, which 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.
Underwood EJ, Suttle NF. Cobalt. In The mineral nutrition of livestock, 3rd ed., Wallingford, Oxon: CAB International; 1999:251-282.
Lee J, Masters DG, White CL, Grace ND, Judson GJ. Current issues in trace element nutrition of grazing livestock in Australia and New Zealand. Aust J Agric Res. 1999;50:1341-1364.
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. Cobalt was first shown to be an essential nutrient for sheep and cattle as an outcome of Australian investigations in the 1930s of two naturally occurring diseases, ‘coast disease’ of sheep, and ‘wasting disease’ or enzootic marasmus, of cattle.1
Etiology Dietary deficiency of cobalt resulting in a deficiency of vitamin B12.
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.
Necropsy findings Emaciation, hemosiderosis of spleen.
Diagnostic confirmation Vitamin B12 and cobalt of liver.
Common causes of ill-thrift in ruminants:
Treatment Oral dosing with cobalt or parenteral injections of vitamin B12.
Control Dietary supplementation with cobalt. Cobalt-heavy pellets.
The disease is caused by a deficiency of cobalt in the diet which results in a deficiency of vitamin B12.
The literature on the diagnosis, treatment, control of cobalt deficiency in ruminants in New Zealand has been reviewed.2 The literature on the occurrence of cobalt deficiency, and the use of diagnostic tests in sheep, and their limitations and reference ranges for various age groups has also been reviewed.3
Cobalt deficiency occurs in Australia, New Zealand, the UK, North America, the Netherlands,4 and probably occurs in many other parts of the world.5 Where the deficiency is extreme, large tracts of land are unsuitable for the raising of ruminants, and in certain areas suboptimal growth and production may be limiting factors in the husbandry of sheep and cattle.
Historically, in severely cobalt deficient areas in New Zealand, ill-thrift was so marked that calves and lambs died. In those that survived, growth rates were markedly depressed and often zero over summer months compared with cobalt supplemented lambs.6 In New Zealand, cobalt deficiency is now mainly confined to lambs, because severely deficient areas, where the deficiency occurred in adult sheep and cattle, and in lambs, have had cobalt fertilizer applied for many decades.2 Cobalt responsive ill-thrift in lambs still occurs where cobalt fertilizer applications or vitamin B12 injections to lambs are haphazard. Live weight gains to supplementary vitamin B12injections of up to 180 g/d have been reported.6
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 B12status was found in 55% of herds sampled.7 However, the significance of the cobalt deficiency clinically is uncertain.8
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. Cobalt/vitamin B12 deficiency occur in grazing lambs in the Netherlands and chronic hepatitis or ovine white liver disease are manifestations of the deficiency.4 It has been described in beef cattle in the Netherlands.9
Although the disease occurs most commonly in ruminants at pasture in severely deficient areas, sporadic cases occur in 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.
A disease of moose called ‘moose sickness’ occurs in Eastern North America is related to a cobalt- and vitamin B12deficiency.10 Affected moose are geographically localized mainly to the regions of the Tobeatic and Cape Breton Highlands of Nova Scotia in Canada. There are low concentrations of cobalt and vitamin B12 in liver and increased concentrations of methylmalonic acid in the plasma. There are striking similarities between the North American moose sickness and the ‘mysterious’ moose disease in Sweden, which is caused by molybdenosis.10
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.
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.11 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.12
Primary cobalt deficiency occurs only on soils which are deficient in cobalt.
Such soils do not appear to have any geological similarity, varying from 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.
After the introduction of domestic livestock into New Zealand, it was realized that in some areas livestock did not thrive, or were affected with particular diseases not occurring in other areas. Large parts of New Zealand were subsequently discovered to be trace-element deficient (cobalt, selenium, and copper) and these deficiencies have been a significant part of the agricultural scene ever since.6 Livestock grazing pastures grown on such soils may be deficient in one or more of these trace elements.
In New Zealand, soil types are categorized as severe, moderate or marginal. In total, of the land considered suitable for farming, about 1 million hectares in the North Island and 918,000 hectares in the South Island have been defined as cobalt deficient.6
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.13 In the Netherlands, on farms with a history of ill-thrift caused by cobalt/vitamin B12 deficiency, the acetic acid-extractable soil cobalt content of the pastures was above the reference value for cobalt deficiency (≤0.30 mg Co/kg dried soil).4 These concentrations are below the minimum requirement for sheep (0.07 mg/kg DM). The high soil pH (6.5) and the good drainage conditions on the farm were probably primary factors responsible for the low soil cobalt availability.
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.
A specific hepatic dysfunction of sheep has been described in New Zealand, Australia, the UK,14 Norway,15 and in grazing lambs in the Netherlands.4 It has been called ‘white liver disease’ because of the grayish color of the liver. Clinically, it is manifested by photosensitization 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.16
Hepatic lipidosis has occurred in Omani goats in many parts of Oman for many years but the cause was unknown.17,18 It is now known that low levels of serum vitamin B12or low levels cobalt in the liver are associated with the liver lesion, and it can be experimentally reproduced using low levels of cobalt intake.19 Abattoir surveys of goat livers found that hepatic lipidosis was one of the most frequent cause of their condemnation.18 Because the goat is the predominant domesticated animal type raised for meat in the Sultanate of Oman, the condemnation of goat livers at slaughter represents a significant economic loss.18
Cobalt deficiency can be reproduced in sheep diet containing less than 70 μg/kg cobalt. Feeding a diet containing 4.5 μg/kg to lambs produced a severe vitamin B12 deficiency, characterized by subnormal plasma and liver concentrations of vitamin B12 and reduced growth rate, serous ocular discharge, alopecia, and emaciation, similar to naturally occurring outbreaks of cobalt deficiency in sheep.20 Fatty degeneration of the liver was associated with reduced concentrations of vitamin B12(14.5 pmol/g) at necropsy. Liver lesions included accumulation of lipid droplets and lipofuscin particles in hepatocyte, dissociation and necrosis of hepatocyte, and sparse infiltration by neutrophils, macrophages, and lymphocytes. Ultrastructural hepatocytic alterations included swelling, condensation and proliferation of mitochondria, hypertrophy of smooth endoplasmic reticulum, vesiculation and loss of arrays of rough endoplasmic reticulum, and accumulation of lipid droplets and lipofuscin granules in cytoplasm of hepatocytes. Co-factors are not a prerequisite to development of hepatic damage in cobalt-deficient sheep. Reduced activities of the vitamin B12dependent enzymes, methylmalonyl CoA mutase and methionine synthesis, and lipid peroxidation are likely pathogenetic importance in the development of the lesions.
Cobalt is unique as an essential trace element in 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 B12 (cyanocobalamin), and compared with other species the requirement for vitamin B12 is very much higher in ruminants. In sheep, the requirement is of the order of 11 μg/d, and probably 500 μg/d are 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 B12 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.
A key biochemical pathway for propionic acid from rumen fermentation involves adenosyl cobalamin, one of several cobalt-containing coenzymes of the vitamin B12 complex that is required for the conversion of methylmalonyl coenzyme A to succinyl coenzyme A, both intermediates in the utilization pathway of propionate. Lack of vitamin B12 results in accumulation of methylmalonic acid which can be measured in the serum. The clinical and pathological signs of cobalt deprivation are preceded by characteristic biochemical changes in tissues and fluids of the body. As soon as depletion begins, the concentration of cobalt and vitamin B12 fall in rumen fluid. Vitamin B12values in serum also show an early decline, because they measure vitamin which is in transit, which is largely a reflection of the adequacy of current rumen synthesis, Serum vitamin B12 declines before liver vitamin B12 which confirms that the liver does not serve as an active storage pool.
A prolonged moderate cobalt deficiency in beef cattle (83 μg/kg) for 43 weeks results in several changes in lipid metabolism in addition to impaired growth.21 There is severe accumulation of plasma homocysteine, and a marked increase of trace elements iron and nickel in the liver.22
The efficiency of cobalt in preventing staggers in sheep grazing pasture dominated by (Phalaris tuberosa) and possibly by canary grass (Phalaris minor) or rhompa grass, a hybrid Phalaris spp., is unexplained. A suggestion that a dietary deficiency of cobalt can lead to the development of polioencephalomalacia 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.15 Cobalt fertilization of deficient pastures results in an increase in vitamin B12 in lambs.16 Hepatic dysfunction occurs in affected sheep.23 Affected lambs generally have higher serum levels of copper than in cobalt/vitamin B12-supplemented lambs grazing the same pastures.24 Dosing affected lambs with copper oxide needles resulted in toxic levels of liver copper.25 It is suggested that the disease is a manifestation of B12 deficiency made worse by factors triggering early hepatic fatty change, resulting in more severe liver damage and loss of intracellular homeostasis, rendering the hepatocytes more vulnerable to other elements such as copper.26 The amount of fructan in the pasture may be an important factor in the pathogenesis of the lesion.11 One hypothesis suggests that the high level of fructan may initiate hepatic lipodystrophy, leading to hepatic insufficiency, growth reduction and ovine white liver disease.11 Vitamin B12 is therapeutic.27
The pathological changes in lambs grazing cobalt-deficient pastures are related to blood concentrations of vitamin B12, methylmalonic acid, and homocysteine, and lesions are confined mainly to the liver and brain.28 Acute and chronic hepatitis are characteristic and the liver lesions are associated with polymicrocavitation of the brain.
Hepatic encephalopathy associated with cobalt deficiency and white liver disease has been described in lambs.29 Symmetrical vacuolation and status spongiosus of the neuropil in the brain were characteristic and hyperammonemia secondary to the hepatic lesion is considered to be the cause of the brain lesions.
Caprine hepatic lipidosis has been induced experimentally using low intakes of low levels of dietary cobalt.19 Goats provided with a diet which contains the minimum daily requirement of cobalt as specified for sheep not only developed a syndrome characterized by reduced weight gains, dry scruffy hair goat and a decline in erythrocyte indices but also lesions consistent with hepatic lipidosis. Goats fed diets containing levels of cobalt less than 0.1 mg/kg DM could experience even greater clinical and pathological consequences.
In ‘Moose sickness’ there are low concentrations of cobalt and vitamin B12 in liver and increased concentrations of methylmalonic acid in plasma.10
No specific signs are 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 observed in 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 in decreased lambing percentage, increased percentage of stillbirths, and increased neonatal mortality.30 Lambs from deficient ewes are slower to start sucking, have reduced concentrations of serum colostral immunoglobulins, and have lower serum vitamin B12 and higher methylmalonic acid concentrations than lambs from cobalt-adequate dams.
‘Moose sickness’ in Nova Scotia is characterized by a loss of fear of man, weakness, and a staggering gait, apparent blindness, drooping of the ears, and emaciation and infestation by ticks.10 A decreased intake of food, increasing lethargy and collapse, accompanied by loss of use of one or more limbs, precedes death.
Changes in the concurrent serum concentrations of methylmalonic acid and vitamin B12 of ewes and their lambs on cobalt deficient pastures, and their response to cobalt supplementation can be evaluated and monitored.31 Those same changes can be evaluated during supplementation of lambs while suckling and after weaning on farms in the South Island of New Zealand considered to be cobalt-deficient.32 These measurements are commonly done along with recording live weight gains, and analysis of pasture for cobalt content at the sampling times for blood MMA and vitamin B12.
Growth responses to cobalt or vitamin B12 supplementation is anticipated when cobalt levels in herbage fall below 0.08–0.1 mg/K DM.31
Cobalt concentrations in the serum of normal sheep are of the order of 1–3 μg/dL (0.17–0.51 μmol/L), and in deficient animals these are reduced to 0.03–0.41 μmol/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 B12levels are used as a laboratory test of cobalt status in animals. Levels of 0.2–0.25 μg/L are indicative of cobalt deficiency. These rise rapidly to 0.5–1.0 μg/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. Serum vitamin B12 values greater than 0.2 μg/L are indicative of a normal vitamin B12 status in cattle. Deprivation of feed from sheep for 24 h 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.
Concurrent serum MMA and vitamin B12 concentrations.
Concurrent changes in serum MMA and vitamin B12concentrations in cobalt supplemented ewes and their lambs on cobalt-deficient farms were monitored. Serum concentrations of vitamin B12 fell below 250 pmol/L during early lactation, and as low as 100 pmol/L.31 MMA concentration was maintained below 2 μmol/L in serum from supplemented ewes but increased to mean concentrations ranging from 7 to 14 μmol/L at the nadir of serum vitamin B12 concentration during peak lactation.31 A significant live weight response to supplementation occurred in ewes, and the vitamin B12 concentration in the ewe’s milk and in the livers of their lambs more than doubled. Serum MMA concentration provides a more precise indication of responsiveness to vitamin B12 or cobalt supplementation than serum vitamin B12 concentrations in ewes and lambs. Neither very low serum vitamin B12 concentrations nor elevated MMA concentrations are necessarily indicative of responsiveness to supplementation in suckling lambs, but MMA gave an early indication of impending responsiveness. Supplementation of the ewe with a cobalt bullet appears to protect the growth performance of the lamb for 90 days and influence the subsequent serum vitamin B12 response in the lamb to vitamin B12supplementation.31
In New Zealand, the serum vitamin B12and MMA have been compared as indices of cobalt/vitamin B12deficiency in lambs on cobalt-deficient farms, around lambing, and supplemented with either cobalt bullets, or short- or long-acting vitamin B12 preparations.32 Serum MMA concentrations in excess of 9–14 μmol/L provide a more reliable diagnostic test for cobalt deficiency. However, there may be considerable variation between farms.
A critical evaluation of serum MMA and vitamin B12 concentrations for the assessment of cobalt deficiency in growing lambs in New Zealand indicates that the current reference ranges for vitamin B12 responsiveness are conservatively high and result in over-diagnosis of vitamin B12 deficiency in ill-thriftiness of sheep.33 It would be preferable if vitamin B12 weight gain response trials were compared with reference curves.34
Serum concentrations of MMA allow better differentiation of a responsive condition than vitamin B12 concentrations. Serum MMA concentrations >13 μmol/L indicate responsiveness to supplementation while concentrations of <7 μmol/L indicate unresponsiveness. In the range 7–13 μmol/L, variation in response was observed and predictability of response is less certain but supplementation is advisable.
Normal hepatic cobalt levels in lambs range between 0.03 and 0.1 μg/g WW.35 Levels below 0.02 μg/g WW (0.07 μg DM) are associated with clinical cobalt deficiency, and 0.015 μg/g WW (0.05 μg DM) is considered as a critical level. In lambs with clinical signs of ovine white liver disease, mean hepatic cobalt concentrations ranged from 0.013 to 0.024 μg/g WW. An average cobalt level below 0.025 μg/g WW in a sheep flock is considered marginal.35 In a survey of the cobalt and copper concentrations of lamb livers at slaughter in Norway, the average hepatic levels of cobalt varied from <0.003 to 0.22 μg/g WW, and of copper from 5 to 240 μg/g WW.35
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.33,36 The determination of MMA has the potential to distinguish between subclinically 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.37 It is recommended that 10 μmol/L be an upper limit of normality for plasma MMA in barley-fed animals, and 5 μmol/L be the upper limit for grass-fed animals.37 Measurement of serum MMA as diagnostic measures of cobalt status in cattle indicates that a level <2 μmol/L is normal, 2–4 μmol/L represents subclinical deficiency, and >4 μmol/L represents deficiency.38 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.16 Cobalt-adequate lambs have plasma MMA levels of less than 5 μmol/L, urinary MMA less than 120 μmol/L and urinary MMA/creatinine values of less than 0.022 μmol MMA/mmol of urinary creatinine. An unequivocal result for methylmalonic acid is a concentration of greater than 30 μg/mL for ten animals selected randomly from a flock. If the urine is kept for more than 24 h it should be acidified to avoid degradation of the methylmalonic acid. Commercial kits are now available for assay of vitamin B12 in ruminant blood.
The concentration of formiminoglutamic acid in urine is a reliable indicator of the cobalt status of lambs. Levels of 0.08–20 μmol/mL in the urine of affected lambs return to 0 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.
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 (<60 mg glucose/dL plasma) and have low serum alkaline phosphatase levels (<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.
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.20
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 in 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 vitamin B12 in the liver are of the order of 0.3 mg/kg, falling to 0.1 mg/kg in deficient lambs. In cattle, clinical signs occur with liver vitamin B12 levels of less than 0.10 mg/kg, and levels of more than 0.3 mg/kg of liver are necessary for optimum growth. 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 B12 levels reflect cobalt status, it is often useful to submit sera from surviving herdmates when attempting to confirm the diagnosis.
Cobalt deficiency must be differentiated from other causes of ‘ill-thrift’ or ‘enzootic marasmus’.
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 most common 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 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.
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.
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.39 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 live weight response to supplementation and the probability of obtaining a response.39 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.39 The results from published and unpublished cobalt/vitamin B12 weight response trials in young sheep grazing pasture in New Zealand have been reviewed.39 No significant weight gain responses occurred to vitamin B12 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 Fg/day BW gain) is not likely is 336 pmol/L for serum and 282 nmol/kg for liver.39 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 h after changes in dietary cobalt.
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/d 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 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 h. 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 flockmates 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 μg 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 (hydroxocobalamin) 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 hydroxocobalamin results in an immediate beneficial response and treatment is repeated 10 days later.14
Overdosing with cobalt compounds 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/d. 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.
The recommended level of cobalt in the diet for sheep and cattle has for many years been about 100 μg/kg DM. Based on the levels of homocysteine and methylmalonic acid together with the vitamin B12 and hepatic folate status as predictors of the magnitude of cobalt-vitamin B12status in assessing the cobalt requirements in cattle, the recommended levels of dietary cobalt to achieve maximum vitamin B12 levels are 250 μg/kg DM.40 If such levels are 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.41
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/ha cobalt sulfate annually or 1.2–1.5 kg/ha 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 deficiency in grazing ruminants. A regular cobalt input is required to build up reserves. This input requirement is about 350 g cobalt sulfate/ha 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.42
Supplementation of the diet with 0.1 mg cobalt/d for sheep and 0.3–1.0 mg/d 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.
The use of ‘heavy pellets’ containing 90% cobalt oxide is an alternative means of overcoming the difficulty of maintaining an adequate cobalt intake in a deficient area. The pellet is in 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 in very small but adequate amounts. Reports on their use in sheep and cattle indicate that they are effective. Administration 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, re-treatment 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 if 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.
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.
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 μg 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.43
The relationship in lambs between daily weight gains and vitamin B12 status in the serum and liver vitamin B12 concentrations is well defined. Lambs with serum vitamin B12concentrations >335 pmol/L and liver vitamin B12 concentrations <280 nmol/kg fresh tissue are cobalt deficient and will show a marked increase in growth rates when supplemented with cobalt or vitamin B12.
The subcutaneous injection of a soluble vitamin B12 in lambs was effective in increasing and maintaining the vitamin B12status for about 24 days.44 In cobalt deficient areas lambs should be given a 2 mg dose of vitamin B12at least bimonthly to reduce the risk of vitamin B12deficiency.45
A microencapsulated vitamin B12in lactide/glycolide copolymers is able to increase and maintain vitamin B12status of lambs for at least 210 days.46 The treatment of ewes grazing cobalt deficient pastures 4–5 weeks prior to mating should ensure an increase in the storage of vitamin B12 in the fetal liver and an increase in the vitamin B12 content of colostrum and milk. The growth rates of cobalt deficient lambs, 4–6 weeks of age, were markedly improved by injections of 3.0, 4.5, or 6.0 mg of microencapsulated vitamin B12and live weights were maintained for at least 260 days.47 An injection of 3 mg microencapsulated vitamin B12 given to lambs at tailing will prevent cobalt deficiency and increase and maintain live weight gains in a flock for up to 8 months.
The vitamin B12 status of ewes can be increased during gestation and lactation by three injections of a long-acting preparation of vitamin B12microencapsulated in an organic acid polymer given subcutaneously at 120 days prepartum (30 days after the ram had bred the ewes), 40 days prepartum, and 40 days post partum.48 Compared with controls, serum and liver vitamin B12 concentrations of the treated ewes were increased by 70% during gestation. Fetal liver vitamin B12 concentrations were increased 270%. Over the lactation, ewe serum and milk vitamin B12concentrations were increased at least 200% and 44%, respectively. The liver vitamin B12 stores of the newborn lambs from vitamin B12 treated ewes were depleted within 58 days. Ewes with a high vitamin B12 status will ensure an adequate supply of vitamin B12to their lambs for at least the first 30 days of life.
A long-acting injectable microencapsulated vitamin B12at a dose rate of 0.12–0.24 mg/kg BW will increase and maintain the vitamin B12in dairy calves for at least 110 days.2,49
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Lee J, McMasters DG, White CL, Grace ND, Judson GJ. Current issues in trace element nutrition of grazing livestock in Australia and New Zealand. Aust J Agric Res. 1999;50:1341-1364.
Vellema P. Cobalt/vitamin B12 deficiency in beef cattle: a short review. Tijdschr Diergeneeskd. 2000;125:190-192.
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