Phosphorus deficiency is usually primary and is characterized by pica, poor growth, infertility and, in the later stages, osteodystrophy. Hypophosphatemia in dairy cattle is also associated with increased fragility of red blood cells and postparturient hemoglobinuria.
Etiology Usually a primary deficiency in diet; may be conditioned by vitamin D deficiency.
Epidemiology Primary phosphorus deficiency occurs worldwide. Soils and crops commonly deficient in phosphorus. Primary deficiency may occur in lactating dairy cattle in early lactation. Occurs under range conditions in beef cattle and sheep. In pigs not supplemented with sufficient phosphorus.
Signs Young animals grow slowly; develop rickets. Adults develop osteomalacia, unthriftiness, weight loss, reduced feed consumption, reluctance to move, leggy appearance, fractures, impaired fertility. Recumbency in high-producing cows on marginally phosphorus-deficient diet.
Clinical pathology Serum phosphorus. Phosphorus content of diet.
Necropsy findings Rickets and osteomalacia; lack of mineralization of bones.
Diagnostic confirmation Histology of bone lesions; bone ash analyses.
Differential diagnosis Those diseases resembling rickets and osteomalacia.
Treatment Phosphates parenterally and orally and vitamin D.
Control Supplement diets with adequate phosphorus, calcium, and vitamin D.
Phosphorus deficiency is usually primary under field conditions but may be exacerbated by a deficiency of vitamin D and possibly by an excess of calcium.
In contrast to calcium deficiency, a dietary deficiency of phosphorus is widespread under natural conditions.1 It has a distinct geographical distribution depending largely upon the phosphorus content of the parent rock from which the soils of the area are derived, but also upon the influence of other factors, such as excessive calcium, aluminum, or iron, which reduce the availability of phosphorus to plants. Large areas of grazing land in many countries are of little value for livestock production without phosphorus supplementation. In New Zealand, for example, where fertilization of pasture with superphosphate has been practiced for many years, phosphorus deficiency may still occur in dairy herds because of inadequate maintenance of application over several years.2 There is evidence also that the quality of the superphosphate declined over a period of several years. Soil reserves of phosphorus may also be low because of high phosphate retention soils. Animals in affected areas mature slowly and are inefficient breeders and additional losses due to botulism and defects and injuries of bones may occur. Apart from areas in which frank phosphorus deficiency is seen, it is probable that in many other areas a mild degree of deficiency is a limiting factor in the production of meat, milk, and wool.
Heavy leaching by rain and constant removal by cropping contribute to phosphorus deficiency in the soil and the low phosphorus levels of the plant cover may be further diminished by drought conditions. Pastures deficient in phosphorus are classically also deficient in protein.
The literature on phosphorus nutrition of grazing cattle has been reviewed.3 The degree of naturally occurring phosphorus deficiency in grazing cattle, the lack of uniformity in response to phosphorus supplementation and the suggested phosphorus requirements have resulted in considerable confusion in the United States and worldwide. Much of the confusion arises because animals have the ability to draw on skeletal phosphorus reserves when dietary phosphorus levels are inadequate. The mechanisms which control skeletal phosphorus withdrawal, the conditions which trigger withdrawal and the rate and extent of withdrawal without affecting animal performance are not well understood.
The earliest report of naturally occurring phosphorus deficiency in grazing cattle was at Armoedsvlakte in the Northern Cape of South Africa. The disease was called aphosphorosis and animals with the disease demonstrated a depraved appetite characterized by the desire to eat wood, bones, rocks, and other such materials. In severe deficiencies, cattle often died from botulism from eating bones from old carcasses contaminated with Clostridium botulinum. In advanced states of aphosphorosis, animals developed a stiffness in the forelegs resulting in a characteristic lameness referred to as ‘styfsiekte’ in South Africa, ‘creeps’ in Texas and ‘pegleg’ in Australia.3
A primary dietary deficiency of phosphorus in dairy cattle within the first several weeks of lactation can result in postparturient hemoglobinuria. In high-producing dairy cows, small restrictions in dietary phosphorus intake compared with National Research Council recommendations can result in acute recumbency in early lactation.4
Under range conditions, milking cows are most commonly affected, but under intensive conditions, it is the dry and young stock receiving little supplementation which will be affected. The incidence of the disease varies: it is most common in animals at pasture during drought seasons but can also be a serious problem in housed cattle fed on hay only.
A survey of the mineral status of bones of cattle at abattoirs in western New South Wales, Australia, found evidence of osteodystrophy based on ash density.5 They represented cattle attempting to grow in a poor season, often female and in poor body fat condition and light in body weight and mostly from red soils known to be deficient in phosphorus.
The dietary requirements of phosphorus are given in Table 30.10. Cattle constantly grazing pasture in the southern hemisphere appear to require somewhat less phosphorus in their diet (0.20% is probably adequate) than do higher-producing, partly housed livestock. The dietary requirements of phosphorus recommended by the National Research Council for beef cows weighing 450 kg may exceed the basic requirements.6 Over a period of several gestations a daily allowance of 12 g of phosphorus/day/animal was adequate for beef cows.6,7 Cattle given a phosphorus-deficient diet did not develop detectable signs of phosphorus deficiency until they had been on a severely deficient diet for 6 months.
Table 30.10 Approximate levels of phosphorus in soil and pasture (quoted as phosphate radical) at which phosphorus deficiency occurs in cattle
| Levels at which deficiency does not occur | Levels at which deficiency does occur | |
|---|---|---|
| Soil | 0.005% | 0.002% |
| Pasture | 0.3% | 0.2% – osteophagia |
| <0.01% – rickets and osteomalacia | ||
| Daily intake (cattle) | 40–50 g | 25 g |
All figures are on a dry matter (DM) basis and soil phosphate is citrate-soluble.
Sheep and horses at pasture are much less susceptible to the osteodystrophy of phosphorus deficiency than are cattle and their failure to thrive on phosphorus-deficient pasture is probably due in part to the low protein content of the pasture. In fact, there has been no clear demonstration of a naturally occurring phosphorus deficiency in sheep, nor is there any record of infertility in sheep caused by phosphorus deficiency.
There is some limited evidence that the serum inorganic phosphorus levels in Thoroughbred racehorses may be related to certain feeding regimens and to racing performance.8 Horses fed cubed or pelleted dietary supplement have serum inorganic phosphate concentrations consistently below an accepted mean of 1.032 mmol/L.8 It is suggested that a rapid rate of passage of the ingesta may affect absorption of phosphorus. Other observations indicate that some of the best track performers had significantly lower inorganic serum phosphorus concentrations compared with some of the worst performers.
A primary deficiency can occur in pigs kept in confinement and not provided with sufficient dietary phosphorus. Lactating sows are more commonly affected than growing pigs. In some situations, in the cereal grains, the phytate levels are so high and phytase levels so low, rickets and osteomalacia are common in the pig population.9
This is of minor importance compared with the primary condition. A deficiency of vitamin D is not necessary for the development of osteodystrophy, although with suboptimal phosphate intakes deficiency of this vitamin becomes critical. Excessive intake of calcium does not result in secondary phosphorus deficiency, although it may cause a reduction in weight gains, due probably to interference with digestion and may contribute to the development of phosphorus deficiency when the intake is marginal. The presence of phytic acid in plant tissues, which renders phosphate unavailable to carnivora, is a major consideration in pigs but of only minor importance in herbivora, except that increasing intakes of calcium may reduce the availability of phytate phosphorus even for ruminants. Rock phosphates containing large amounts of iron and aluminum have been shown to be of no value to sheep as a source of phosphorus. A high intake of magnesium, such as that likely to occur when magnesite is fed to prevent lactation tetany, may cause hypophosphatemia if the phosphorus intake of dairy cows is already low.
Hypophosphatemia has been induced in pigs by experimental supplementation of their diets with aluminum hydroxide.10 After 3 weeks, severe hypophosphatemia, intense hypercalcemia, decreased growth rate, and a lower concentration of 2,3-diphosphoglycerate in the erythrocytes developed.10
From 80 to 85% of the phosphorus of the body is located in the skeleton where it occurs as hydroxyapatite in a 1.0:1.7 ratio with calcium. These two minerals provide bone strength necessary for normal activities, such as grazing.3 Bone phosphorus also functions as an important phosphorus reservoir for resorption when body requirements temporarily exceed dietary intake. From 17 to 42% of bone could be resorbed in cattle and sheep in times of phosphorus deficiency.
Phosphorus is also essential for a broad range of enzymatic reactions, especially those concerned with energy metabolism and transfer. Phosphorus is also essential for the transfer of genetic information and is a vital component of various buffering systems. Phospholipids are necessary for maintenance of cell wall structure and integrity and as a integral components of myelin.
Rumen microbes have a phosphorus requirement apart from the animal’s requirement which must be met for optimum rumen microbial activity to occur.
Phosphorus is essential for the laying down of adequately mineralized bones and teeth and a deficiency will result in their abnormal development. Inorganic phosphate, which may be ingested as such, or liberated from esters during digestion or in intermediary metabolism, is utilized in the formation of proteins and tissue enzymes and is withdrawn from the plasma inorganic phosphate for this purpose.
Experimentally, female beef cattle fed diets containing <6 g of phosphorus/day developed an insidious and subtle complex syndrome characterized by weight loss, rough hair coat, abnormal stance, and lameness.6 Spontaneous fractures occurred in the vertebrae, pelvis, and ribs. Some affected bones were severely demineralized and the cortical surfaces were porous, chalky white, soft, and fragile. The osteoid tissue was not properly mineralized.
Experimental acute depletion of phosphorus in cattle results in a marked decline in serum inorganic phosphorus and affected animals display an avid appetite for old bones.11 The signs include:
Prolonged phosphorus deficiency was associated with increased plasma concentrations of total calcium and 1,25-dihydroxyvitamin D and reduced plasma concentrations of parathyroid hormone.
The pathophysiological effects of low dietary phosphorus in pigs have been examined.9 Determination of the serum concentrations of parathyroid hormone, 1,25-(OH)2 D and osteocalcin were monitored in Romanian Landrace pigs originating from herds with dietary P deficiency. Serum P concentrations were negatively correlated with those of 1,25-(OH)2 D. In lactating animals and sucklings, the linear relationships were not present. Serum P concentrations positively correlated with those of PTH and 1,25-(OH)2 D concentrations were negatively correlated. The serum concentrations of 1,25-(OH)2 D and osteocalcin were positively correlated. Milk P concentrations ranging from 3.10 to 7.49 mmol/L were correlated positively with urinary P concentrations ranging from 0.26 to 11.37 mmol/L. In conclusion, similar to other species, P homeostasis is achieved in pigs by feedback mechanisms between P, PTH, and 1,25-(OH)2 D and osteocalcin production is induced by 1,25-(OH)2 D
Inorganic phosphate also plays an important role in the intermediary metabolism of carbohydrate and of creatine in the chemical reactions occurring in muscle contraction. This may be of importance in those cows that are recumbent after calving and have hypophosphatemia. The loss of phosphorus in the phospholipids of milk due to the onset of profuse lactation may be the crucial factor in the development of postparturient hemoglobinuria. An increased susceptibility to bloat has been postulated as an effect of phosphorus deficiency.
Primary phosphorus deficiency is common only in cattle. Young animals grow slowly and develop rickets. In adults there is an initial subclinical stage followed by osteomalacia. In cattle of all ages a reduction in voluntary intake of feed is a first effect of phosphorus deficiency and is the basis of most of the general systemic signs. Retarded growth, low milk yield, and reduced fertility are the earliest signs of phosphorus deficiency. For example, in severe phosphorus deficiency in range beef cattle, the calving percentage has been known to drop from 70 to 20%. Although it is claimed that relative infertility occurs in dairy heifers on daily intakes of less than 40 g of phosphate, the infertility being accompanied by anestrus, subestrus, and irregular estrus and delayed sexual maturity this has not been borne out by other experimental work, which indicates that fertility is independent of the calcium or phosphorus content or the calcium:phosphorus ratio of the diet in cattle. The effects of malnutrition on fertility are likely to be general and the infertility may often be related to lack of total energy intake rather than to specific deficiency. The development and wear of teeth are not greatly affected, in contrast with the severe dental abnormalities that occur in a nutritional deficiency of calcium. However, malocclusion may result from poor mineralization and resulting weakness of the mandible.
In the experimental production of phosphorus deficiency in beef cows, several months on a deficient diet are necessary before clinical signs develop.7 The clinical signs included general unthriftiness, marked body weight loss, reduced feed consumption, reluctance to move, abnormal stance, bone fractures, and finally impaired reproduction. The detectable signs of phosphorus deficiency developed in the following sequence:
• Loss of body weight and condition
• Decreased whole blood phosphorus associated with increased whole blood calcium concentration
• Abnormal stance, locomotion and recumbency.6
In a severely deficient area, a characteristic conformation develops and introduced cattle revert to the district type in the next generation. The animals have a leggy appearance with a narrow chest and small girth, the pelvis is small, and the bones are fine and break easily. The chest is slab-sided due to weakness of the ribs and the hair coat is rough and staring and lacking in pigment. In areas of severe deficiency, the mortality rate may be high due to starvation, especially during periods of drought when deficiencies of phosphorus, protein and vitamin A are exaggerated. Osteophagia is common and may be accompanied by a high incidence of botulism. Cows in late pregnancy often become recumbent and, although they continue to eat, are unable to rise. Such animals present a real problem in drought seasons because many animals in the area may be affected at the same time. Parenteral injections of phosphorus salts are ineffective and the only treatment that may be of benefit is to terminate the pregnancy by the administration of corticosteroids or by cesarean section.
Acute recumbency in high-producing dairy cows on a marginally phosphorus-deficient diet may become recumbent in early lactation.4 Affected animals are recumbent and cannot stand. They may be bright and alert and their vital signs are within normal range.
Although sheep and horses in phosphorus-deficient areas do not develop clinically apparent osteodystrophy they are often of poor stature and unthrifty and may develop perverted appetites. An association between low blood phosphorus and infertility in mares has been suggested but the evidence is not conclusive. The principal sign in affected sows is posterior paralysis.
Blood levels of phosphorus are not a good indicator of the phosphorus status of an animal because they can remain at normal levels for long periods after cattle have been exposed to a serious deficiency of the element. Serum inorganic phosphorus levels are affected by such factors as age of animal, milk yield, stage of pregnancy, season of year, breed, feeding patterns, and dietary phosphorus. The times of sampling in a herd must be standardized to reduce the effect of diurnal variation in serum concentrations of inorganic phosphorus. Attention is drawn to the need to use standard methods of collection because of the effect that technique can have on phosphorus levels in blood. In cattle, the recommended procedure is to collect blood from the coccygeal vein and preserve it in buffered trichloroacetic acid. Hair does not reflect the status either. However, a marked hypophosphatemia is a good indicator of a severe phosphorus deficiency. The mild-to-moderate deficiencies, which are the most common ones, are usually accompanied by normal blood levels of phosphorus. Generally, clinical signs occur when blood levels have fallen from the normal of 4–5 mg/dL (1.3–1.7 mmol/L) to 1.5–3.5 mg/dL (0.5–1.2 mmol/L) and a response to phosphate supplementation in body weight gain can be anticipated in cattle that have blood inorganic phosphorus levels of less than 4 mg/dL (1.3 mmol/L). Levels may fall as low as 1 mg/dL (0.3 mmol/L) or less in severe clinical cases. Serum levels of calcium are usually unaffected.
Estimation of the mineral content in pasture and drinking water is a valuable aid in diagnosis, but has major difficulty in representing what the animal has actually been taking in. A technique has been devised for determining phosphorus intake of sheep by estimating the phosphorus content of feces. A pool of three pellets from each of 30 sheep is used as a sampling technique.
Determination of total bone ash concentrations and bone calcium and phosphorus concentrations from sample of rib can provide useful diagnostic information and comparison to normal values.12
There is usually a marked deterioration in the radiopacity of the bones. However, the bone content of phosphorus is still considered the most accurate indication of phosphorus status.
The necropsy findings are those of the specific diseases, rickets and osteomalacia.
A diagnosis of phosphorus deficiency depends upon evidence that the diet is lacking in phosphorus and that the lesions and signs are typical of those caused by phosphorus deficiency and can be arrested or reverted by the administration of phosphorus. Differentiation from those diseases that may resemble rickets and osteomalacia is dealt with under those headings.
The preparations and doses recommended under control can be satisfactorily used for the treatment of affected animals. In cases where the need for phosphorus is urgent, as in postparturient hemoglobinuria and in cases of parturient paresis complicated by hypophosphatemia, the intravenous administration of sodium acid phosphate (30 g in 300 mL distilled water) is recommended.
Phosphorus (P) deficiencies in grazing livestock can be prevented by direct treatment of the animal through supplementing the diet or the water-supply, or indirectly by approximate fertilizer treatment of the soils. Hand-fed animals are supplemented with P in their diets.
The phosphorus requirements for cattle in various stages of the production cycle have varied widely worldwide.3 Accurate P requirements must be established for all classes of cattle grazing under various conditions before producers can determine whether diets are adequate in P to meet animal needs or whether P supplements must be provided to optimize production.3 Apparent P requirements vary for a variety of reasons: differences among breeds of cattle, P availability in the feed, whether animals are pen fed or free grazing, possible interactions between nutrients, and the effects of disease and parasitism.
There is widespread belief among producers and consultants that reproductive performance in dairy cows can be improved by feeding phosphorus above recommended levels.4 The current NRC recommendations for early lactation (90 days in milk) diets are 0.36% P (DM basis) for cows milking 45 kg/d and 0.35% P for cows milking 35 kg/d. The NRC recommends up to 0.42% for the highest producing cows during the first few weeks of lactation.
Several studies indicate that dietary P at 0.38 to 0.40% is sufficient for high producing dairy cows.13,14 This concentration of P can be obtained with no supplementation or minimum supplementation of P, depending on feed ingredients. Dietary P at 0.31% can support high milk production but cannot sustain comparable high yield when cows proceed into late lactation. Cows conserve P when fed diets low in P by reducing P excretion in feces and urine. They may experience some negative balance in the first few weeks of lactation due to mobilization of P from bone, but this mobilized P can be restored in later lactation.
However, there has been a lack of information about the minimum intake level of P on which dairy cows can maintain health and milk production. In essence, the current requirements developed in various countries are mainly based on studies with non-lactating sheep and goats.
In the European Union and the USA, phosphorus (P) losses from dairy manure to the environment are becoming a more severe pollution problem.15,16 Ideally, P is recycled into the soil/plant/animal system from which only the P incorporated into the animal system escapes. In a sustainable dairy farming system, the amount of P expelled in the form of manure must be limited to that amount which crops need for maximum growth. However, due to high livestock intensities, overapplication of P from manure occurs, leading to P accumulation in the soil and finally leaching, thus causing eutrophication of lakes. Reducing P intake by dairy cows and thus also that excreted in the manure will contribute to reducing environmental pollution.
In Delaware County of New York, more P enters dairy farms than is exported in milk, meat, or crops sold, thus resulting in a net annual accumulation of P on the farm ranging from 19 to 41 kg/cow.17 Purchased feed is the single largest source of imported P on dairy farms, accounting for 65–85% of the 28–51 kg imported annually per cow for typical commercial dairy herds in New York. Similar amounts have been reported for dairy farms in the Netherlands.18
Dairy farms in the states of New York, Pennsylvania, Delaware, Maryland, and Virginia, fed P to lactating cows averaging 34% above the NRC recommendations.19 In 84% of the survey farms, ration formulation was provided by professionals rather than producers themselves. Most producers were feeding more P than cows needed because it was recommended by these consultants. Surveys in the USA show that dairy diets are formulated to contain approximately 0.45–0.50% P (DM basis), an amount that is about 20% in excess.16 This oversupplementation of P is costing the US dairy industry about US$100 million (in 1999). Most lactating dairy cow diets could have their P content reduced by 20%.16 This would result in a 25–30% reduction in P content of manure and a similar reduction in the amount of land required to accommodate the manure. Phosphorus is the most expensive nutrient in typical mineral-vitamin formulations for dairy cattle. Feeding a diet containing 0.45% P versus one containing 0.55% would save about $0.05/cow daily; for a 100 cows over 1 year, would save about $1825.00
Three factors which lead to excessive feeding of P include the notion that increasing P intake would improve reproduction, the absence of lactation trials showing the absolute minimum of P required to support milk production and the aggressive marketing of P supplements.16
Simulation models of the long-term effects of changes in feeding, cropping, and other production strategies on P loading and the economics of 100-cow and 800-cow dairy farms in south-eastern New York found that the most easily implemented change was to reduce the supplemented mineral P fed to that required to meet the current NRC recommended amounts, which would provide an annual increase in farm profit of about $22.00 per cow.20 Dairy farms in some areas can maintain a long-term P balance by: feeding P according to the NRC requirements; a cropping strategy and land base use supplies all of the forage needed; all animals are fed a high forage diet; replacement heifers are produced on the farm.
The effects of feeding low amounts of phosphorus to high yielding dairy cows has been examined.21 Lactating dairy cows were fed diets containing 67, 80, and 100%, respectively, of the phosphorus requirements recommended by the Dutch Committee on Mineral Nutrition for a period of 21 months. Nearly 5 months after the beginning of the feeding trial, the milk yield and milk lactose content of the 67% group decreased significantly. After 2 years, on the 80% diet, postparturient hemoglobinuria occurred in one high producing cow. It was concluded that rations for high yielding dairy cows should not contain phosphorus content lower than 3.0 g/kg DM. The P supply with the 80% ration was considered to be just sufficient.
The supplementation of dietary P above levels recommended by the NRC (0.38% considered adequate or 0.48% excessive) did not improve duration or intensity of estrus in dairy cows under Wisconsin conditions.4 Large lactation studies have shown that feeding P in excess of 0.37% of diet DM, which corresponds closely to the NRC P requirements, did not affect milk production, milk composition, or animal health.22 Digestion studies and P retention data also support the NRC recommendations.23 Biochemical markers of bone turnover in the dairy cow during lactation and the dry period are being used to measure bone formation and resorption during a complete lactation in dairy cattle.24
Based on calculation of P losses and the true absorption coefficient using data on saliva production, saliva-P content, and the efficiency of P absorption under conditions in the Netherlands, the P requirement recommended for dairy cows: P requirement (g/d per 600 kg cow) = 19+ 1.43 × kg milk. The recommendation is up to 22% lower than the current recommendation for high yielding dairy cows used in the UK.15
The overfeeding of P has important environmental implications. Phosphorus excretion increases linearly as P intake is increased above the requirement. Once P requirements are met, all of the excess dietary P is excreted in the feces. This excess P accumulates in the environment, primarily by the recycling of manure to land as fertilizer for crop production. The surface runoff of this excess P promotes the eutrophication of surface waters. (Eutrophication is the accidental or deliberate promotion of excessive growth of one kind of organism to the disadvantage of other organisms in the ecosystem.) Therefore, close monitoring of P inputs in the livestock industry is important to reduce the risk of eutrophication of lakes and streams. Reducing dietary intake closer to requirement will require frequent and accurate feed analysis, quantification of dry matter intake and ration management to ensure that formulated diets are mixed and delivered to the cows properly. Phosphorus reduction will be achieved by precision of feeding of dairy cattle.17 Portable and rapid tests are now available to determine the level of P in dairy cattle manure.25 These hand-held tools can yield real-time measurements of dissolved P and total P in manure.
As part of the US Environmental Protection Agency’s concentrated animal feeding operation (CAFO) final rule, all CAFOs will be required to develop and implement a nutrient management plan.26 The emphasis on better management of nutrients appropriately targets a critical environmental issue associated with animal production. The concentration of animals in livestock feeding operations, often separate from feed grain production, requires importing of substantial qualities of feed nutrients. Due to inefficiencies of nutrient utilization in livestock production, quantities of nitrogen and phosphorus in manure greater than can be utilized in local crop production often result. In a survey of 994 dairy farms in Pennsylvania, only 20% of the farms reported manure nutrient testing, compared with over 90% which did soil testing.27 Farm advisors and their services can be of vital importance in assisting producers make conscientious management decisions for enhanced nutrient utilization. Ration balancing involved the services of feed and mineral representatives on 85% of the farms, independent consultants on 12% and veterinarians only on 5% of farms. Nutrient management strategies and efforts must address the specific needs of farms with different animal densities and nutrient balances in order to be effective and applicable on the majority of farms.
Under field conditions, the difficulty usually encountered is that of providing phosphorus supplements to large groups of cattle grazing under extensive range conditions. The new recommendations for dairy cattle in 2001, are to provide phosphorus at 0.36–0.4% of dry matter intake.28 These are lower than the previous recommendation of 0.5% of dry matter intake.
Bone meal, dicalcium phosphate, disodium phosphate, and sodium pyrophosphate may be provided in supplementary feed or by allowing free access to their mixtures with salt or more complicated mineral mixtures. The availability of the phosphorus in feed supplements varies and this needs to be taken into consideration when compounding rations. The relative biological values for young pigs in terms of phosphorus are: dicalcium phosphate or rock phosphate 83%, steamed bone meal 56%, and colloidal clay or soft phosphate 34%. It is suggested that in deficient areas adult dry cattle and calves up to 150 kg BW should receive 225 g bone meal/week, growing stock over 150 kg BW 350 g/week, and lactating cows 1 kg weekly, but experience in particular areas may indicate the need for varying these amounts. The top-dressing of pasture with superphosphate is an adequate method of correcting the deficiency and has the advantage of increasing the bulk and protein yield of the pasture, but is often impractical under the conditions in which the disease occurs.
The addition of phosphate to drinking water is a much more satisfactory method provided the chemical can be added by an automatic dispenser to water piped into troughs. Adding chemicals to fixed tanks introduces errors in concentration, excessive stimulation of algal growth, and precipitation in hard waters. Monosodium dihydrogen phosphate (monosodium orthophosphate) is the favorite additive and is usually added at the rate of 10–20 g/20 L of water. Superphosphate may be used instead but is not suitable for dispensers, must be added in larger quantities (50 g/20 L) and may contain excess fluorine. A reasonably effective and practical method favored by Australian dairy farmers is the provision of a supplement referred to as ‘super juice’. Plain superphosphate at a rate of 2.5 kg in 40 L of water is mixed and stirred vigorously in a barrel. When it has settled for a day the ‘super juice’ is ready for use and is administered by skimming off the supernatant and sprinkling 100–200 mL on the feed of each cow.
The literature on the phosphorus nutrition of grazing beef cattle in the USA and other parts of the world has been reviewed.3 There has been a notable lack of research into the P requirements of grazing beef cattle of various age groups, under varying soil and forage conditions which has created considerable confusion and disagreement about the P requirements. The effects of P fertilizer on forage P levels and seasonal changes in P concentration are well understood, but the availability of P in different forage species, at different stages of maturity and grown under different management schemes and environmental conditions is not well understood.
The details of the phosphorus requirements for beef cattle of various age groups are available in the National Research Council. (2000) Nutrient Requirements of Beef Cattle, 7th revised ed., updated 2000.29
The phosphorus requirement of finishing feedlot calves is <0.16% of diet dry matter (DM) or 14.2 g/d.30 Typical grain-based feedlot cattle diets do not require supplementation of inorganic mineral P to meet P requirements. Plasma P, performance and bone characteristics indicate that P requirements are less than the predicted requirements and should be modified. Supplementation of mineral P in finishing diets is an unnecessary economic and environmental cost for beef feedlot producers and should discontinue.
The estimated dietary requirements for phosphorus for maximum growth and feed efficiency of pigs at 3–5, 5–10, 10–20, 20–50, 50–80, and 80–120 kg, as a percentage of diet (90% DM) are 0.70, 0.65, 0.60, 0.50, 0.45, and 0.40%, respectively.31 The form in which phosphorus exists in natural feedstuffs influences the efficiency of its utilization. In cereal grains, grain by-products, and oilseed meals, about 60–75% of the phosphorus is organically bound in the form of phytate which is poorly available to the pig. The biological availability of P in cereal grains is variable ranging from less than 15% in corn to approximately 50% in wheat which has naturally occurring phytase enzyme. The phosphorus in inorganic phosphorus supplements also varies in bioavailability. The P in ammonia, calcium, and sodium phosphates is highly available.31
The use of phosphate supplements in the diet is not without hazards. Phosphoric acid is directly toxic and should not be used and monosodium phosphate is unpalatable to many animals; the depression of appetite that results may discount the improved feed utilization it provides. Superphosphate used as fertilizer can cause toxicosis in ruminants.32 Clinical signs in sheep include teeth grinding, diarrhea, nervous system depression, apparent blindness, stiffness, and ataxia and high fatality rate.32
Valk H, Beyen AC. Proposal for the assessment of phosphorus requirements of dairy cows. Livestock Prod Sci. 2003;79:267-272.
Karn JF. Phosphorus nutrition of grazing cattle: a review. Anim Feed Sci Technol. 2001;89:133-153.
Satter L. What goes in must come out — phosphorus balance on dairy farms. Proc Ann Conv Am Assoc Bov Pract. 2002;35:125-130.
National Research Council. Minerals. Nutrient requirements of beef cattle, 7th revised ed. 2000. Washington, DC: National Academy of Sciences. Ch. 5. Updated 2000
National Research Council. Minerals. Nutrient requirements of dairy cattle, 7th revised ed. 2001. Washington, DC: National Academy of Sciences. Ch. 7
National Research Council. Minerals. Nutrient requirements of swine, 10th revised ed. 1998. Washington, DC: National Academy of Sciences. Ch. 4
Underwood EJ, Suttle NF. Phosphorus. The mineral nutrition of livestock, 3rd ed. 1999. Wallingford, Oxon: CAB International.
1 Underwood EJ, Suttle NF. Phosphorus. The mineral nutrition of livestock, 3rd ed. 1999. Wallingford, Oxon: CAB International.
2 Brooks HV, et al. N Z Vet J. 1984;32:174.
3 Karn JF. Anim Feed Sci Technol. 2001;89:133.
4 Lopez H, et al. Theriogenol. 2004;61:437.
5 Holst PJ, et al. Aust J Agric Res. 2002;53:947.
6 Shupe JL, et al. Am J Vet Res. 1988;49:1629.
7 Call JW, et al. Am J Vet Res. 1986;47:475.
8 Denny JEFM. J South Afr Vet Assoc. 1987;58:85.
9 Riond JL, et al. Vet J. 2001;161:165.
10 Haglin L, et al. Acta Vet Scand. 1988;29:91.
11 Blair-West JR, et al. Am J Physiol. 1992;263:R656.
12 Beighle DE, et al. Am J Vet Res. 1994;55:85.
13 Wu Z, et al. J Dairy Sci. 2000;83:1028.
14 Wu Z, Satter LD. J Dairy Sci. 2000;83:1052.
15 Valk H, Beyen AC. Livestock Prod Sci. 2003;79:267.
16 Satter L. Proc Ann Conf Am Assoc Bov Pract. 2002;35:125.
17 Cerosaletti PE, et al. J Dairy Sci. 2004:2314.
18 Valk H, et al. J Dairy Sci. 2002;85:2642.
19 Dou Z, et al. J Dairy Sci. 2003;86:3787.
20 Rotz CA, et al. J Dairy Sci. 2002;85:3142.
21 Valk H, et al. Vet Rec. 1999;145:673.
22 Lopez H, et al. J Dairy Sci. 2004;87:139.
23 Weiss WP, Wyatt DJ. J Dairy Sci. 2004;87:2158.
24 Holtenius K, Ekelund A. Res Vet Sci. 2005;78:17.
25 Lugo-Ospina A, et al. Environ Pollut. 2005;135:155.
26 Koelsch R. J Environ Qual. 2005;34:149.
27 Dou Z, et al. J Dairy Sci. 2001;84:966.
28 National Research Council. Minerals. Nutrient requirements of dairy cattle, 7th revised ed. 2001. Washington, DC: National Academy of Sciences. Ch. 7.
29 National Research Council. Minerals. Nutrient requirements of beef cattle, 7th revised ed. 2000. Washington, DC: National Academy of Sciences. Ch. 5.
30 Erickson GE, et al. J Anim Sci. 2002;80:1690.
31 National Research Council. Minerals. Nutrient requirements of swine, 10th revised ed. 1998. Washington, DC: National Academy of Sciences. Ch. 4
Vitamin D deficiency is usually caused by insufficient solar irradiation of animals or their feed and is manifested by poor appetite and growth and in advanced cases by osteodystrophy.
Etiology Lack of ultraviolet solar irradiation and/or deficiency of preformed vitamin D in diet.
Epidemiology Uncommon because diets are supplemented. Occurs in animals in countries with relative lack of UV irradiation especially in winter months; animals raised indoors for long periods. May occur in young grazing animals in winter months. May be antivitamin D factor.
Signs Reduced productivity; poor weight gain; reduced reproductive performance. Rickets in young; osteomalacia in adults.
Clinical pathology Serum calcium and phosphorus. Plasma vitamin D.
Necropsy findings Lack of mineralization of bone.
Diagnostic confirmation Histology of bone lesions.
Differential diagnosis list See Rickets and osteomalacia.
Treatment Administer vitamin D parenterally and oral calcium and phosphates.
Control Supplement diets with vitamin D. Injections of vitamin D when oral supplementation not possible.
A lack of ultraviolet solar irradiation of the skin, coupled with a deficiency of preformed vitamin D complex in the diet, leads to a deficiency of vitamin D in tissues.
Although the effects of clinically apparent vitamin D deficiency have been largely eliminated by improved nutrition, the subclinical effects have received little attention. For example, retarded growth in young sheep in New Zealand and southern Australia during winter months has been recognized for many years as responding to vitamin D administration.
However, general realization of the importance of this subclinical vitamin D deficiency in limiting productivity of livestock has come only in recent years. This is partly due to the complexity of the relations between calcium, phosphorus, and the vitamin and their common association with protein and other deficiencies in the diet. Much work remains to be done before these individual dietary essentials can be assessed in their correct economic perspective.
The lack of ultraviolet irradiation becomes important as distance from the equator increases and the sun’s rays are filtered and refracted by an increasing depth of the earth’s atmosphere. Cloudy, overcast skies, smoke-laden atmospheres, and winter months exacerbate the lack of irradiation. The effects of poor irradiation are felt first by animals with dark skin (particularly pigs and some breeds of cattle) or heavy coats (particularly sheep), by rapidly growing animals and by those that are housed indoors for long periods. The concentration of plasma vitamin D3 recorded in grazing sheep varies widely throughout the year. During the winter months in the UK, the levels in sheep fall below what is considered optimal, while in the summer months the levels are more than adequate.1 There is a marked difference in vitamin D status between sheep with a long fleece and those that have been recently shorn, especially in periods of maximum sunlight. The higher blood levels of vitamin D in the latter group are probably due to their greater exposure to sunlight. Pigs reared under intensive farming conditions and animals being prepared for shows are small but important susceptible groups.
The importance of dietary sources of preformed vitamin D must not be underestimated. Irradiated plant sterols with anti-rachitic potency occur in the dead leaves of growing plants. Variation in the vitamin D content of hay can occur with different methods of curing. Exposure to irradiation by sunlight for long periods causes a marked increase in anti-rachitic potency of the cut fodder, whereas modern hay-making technique with its emphasis on rapid curing tends to keep vitamin D levels at a minimum. Grass ensilage also contains very little vitamin D.
Based on a survey of the concentrations of vitamin D in the serum of horses in the UK, the levels may be low.2 In the absence of a dietary supplement containing vitamin D, the concentration of 25-OH D2 and 25-OH D3 are, respectively, a reflection of the absorption of vitamin D2 from the diet and of biosynthesis of vitamin D3.
Information on the vitamin D requirements of housed dairy cattle is incomplete and contradictory. It appears, however, that in some instances natural feedstuffs provide less than adequate amounts of the vitamin for optimum reproductive performance in high-producing cows.3
The grazing of animals, especially in winter time, on lush green feed including cereal crops, leads to a high incidence of rickets in the young. An antivitamin D factor is suspected because calcium, phosphorus and vitamin D intakes are usually normal, but the condition can be prevented by the administration of calciferol. Carotene, which is present in large quantities in this type of feed, has been shown to have antivitamin D potency but the existence of a further rachitogenic substance seems probable. The rachitogenic potency of this green feed varies widely according to the stage of growth and virtually disappears when flowering commences. Experimental overdosing with vitamin A causes a marked retardation of bone growth in calves. Such overdosing can occur when diets are supplemented with the vitamin and may produce clinical effects.4
The importance of vitamin D to animals is now well-recognized and supplementation of the diet where necessary is usually performed by the livestock owner. Occasional outbreaks of vitamin D deficiency are experienced in intensive systems where animals are housed and in areas where specific local problems are encountered, e.g. rickets in sheep on green cereal pasture in New Zealand.
Vitamin D is a complex of substances with anti-rachitogenic activity. The important components are as follows:
• Vitamin D3 (cholecalciferol) is produced from its precursor 7-dehydrocholesterol in mammalian skin and by natural irradiation with ultraviolet light
• Vitamin D2 is present in sun-cured hay and is produced by ultraviolet irradiation of plant sterols. Calciferol or viosterol is produced commercially by the irradiation of yeast. Ergosterol is the provitamin
• Vitamin D4 and D5 occur naturally in the oils of some fish.
Vitamin D produced in the skin or ingested with the diet and absorbed by the small intestine is transported to the liver. In the liver, 25-hydroxycholecalciferol is produced, which is then transported to the kidney where at least two additional derivatives are formed by 1-α-hydroxylase.5 One is 1,25-dihydroxycholecalciferol (DHCC) and the other is 24,25-DHCC. Under conditions of calcium need or calcium deprivation the form predominantly produced by the kidney is 1,25-DHCC. At present, it seems likely that 1,25-DHCC is the metabolic form of vitamin D most active in eliciting intestinal calcium transport and absorption and is at least the closest known metabolite to the form of vitamin D functioning in bone mineralization. The metabolite also functions in regulating the absorption and metabolism of the phosphate ion and especially its loss from the kidney. A deficiency of the metabolite may occur in animals with renal disease, resulting in decreased absorption of calcium and phosphorus, decreased mineralization of bone, and excessive losses of the minerals through the kidney. A deficiency of vitamin D per se is governed in its importance by the calcium and phosphorus status of the animal.
Because of the necessity for the conversion of vitamin D to the active metabolites, there is a lag period of 2–4 days following the administration of the vitamin parenterally before a significant effect on calcium and phosphorus absorption can occur. The use of synthetic analogs of the active metabolites such as 1-α-hydroxycholecalciferol (an analog of 1,25-DHCC) can increase the plasma concentration of calcium and phosphorus within 12 h following administration6 and has been recommended for the control of parturient paresis in cattle.
Maternal vitamin D status is important in determining neonatal plasma calcium concentration. There is a significant correlation between maternal and neonatal calf plasma concentrations of 25-OH D2, 25-OH D3, 24,25-(OH)2 D2, 24,25-(OH)2 D3 and 25,26-(OH)2 D3. This indicates that the vitamin D metabolite status of the neonate is primarily dependent on the 25-OH D status of the dam.7 The maternal serum concentrations of calcium, phosphorus, and magnesium do not determine concentrations of these minerals found in the newborn calf. The ability of the placenta to maintain elevated plasma calcium or phosphorus in the fetus is partially dependent on maternal 1,25-(OH)2 D status. Parenteral cholecalciferol treatment of sows before parturition is an effective method of supplementing neonatal piglets with cholecalciferol via the sow’s milk and its metabolite via placenta transport.6
When the calcium:phosphorus ratio is wider than the optimum (1:1 to 2:1), vitamin D requirements for good calcium and phosphorus retention and bone mineralization are increased. A minor degree of vitamin D deficiency in an environment supplying an imbalance of calcium and phosphorus might well lead to disease, whereas the same degree of vitamin deficiency with a normal calcium and phosphorus intake could go unsuspected. For example, in growing pigs, vitamin D supplementation is not essential provided calcium and phosphorus intakes are rigidly controlled, but under practical circumstances, this may not be possible.
The minor functions of the vitamin include maintenance of efficiency of food utilization and a calorigenic action, the metabolic rate being depressed when the vitamin is deficient. These actions are probably the basis for the reduced growth rate and productivity in vitamin D deficiency. Some evidence suggests that vitamin D may have a role in the immune system.8 Local production of 1,25-(OH)2 D by monocytes may be important in the immune function, particularly in the parturient dairy cow.
The most important effect of lack of vitamin D in farm animals is reduced productivity. A decrease in appetite and efficiency of food utilization cause poor weight gains in growing stock and poor productivity in adults. Reproductive efficiency is also reduced and the overall effect on the animal economy may be severe.
In the late stages lameness, which is most noticeable in the forelegs, is accompanied in young animals by bending of the long bones and enlargement of the joints. This latter stage of clinical rickets may occur simultaneously with cases of osteomalacia in adults. An adequate intake of vitamin D appears to be necessary for the maintenance of fertility in cattle, particularly if the phosphorus intake is low. In one study in dairy cattle, the first ovulation after parturition was advanced significantly in vitamin D-supplemented cows.3
A pronounced hypophosphatemia occurs in the early stages and is followed some months later by a fall in serum calcium. Plasma alkaline phosphatase levels are usually elevated. The blood picture quickly returns to normal with treatment, often several months before the animal is clinically normal. Typical figures for beef cattle kept indoors are serum calcium 8.7 mg/dL (10.8 normal), 2.2 mmol/L (2.7 normal); serum inorganic phosphate 4.3 mg/dL (6.3 normal), 1.1 mmol/L (1.6 normal); and alkaline phosphatase 5.7 units (2.75 normal).
The normal ranges of plasma concentrations of vitamin D and its metabolites in the farm animal species are now available9 and can be used to monitor the response of the administration of vitamin D parenterally or orally in sheep.10,11 The serum concentrations of vitamin D in the horse have been determined.2
The pathological changes in young animals are those of rickets, while in older animals there is an osteomalacia. In all ages, a variable amount of osteodystrophia fibrosa may develop and distinction of the origin of these osteodystrophies based on only gross and microscopic examination is impractical. A review of management factors and a nutritional analysis of the feed is essential. The samples for confirmation of the diagnosis at necropsy are as per calcium deficiency.
It is usual to administer vitamin D in the dose rates set out under control. Affected animals should also receive adequate calcium and phosphorus in the diet.
The administration of supplementary vitamin D to animals by adding it to the diet or by injection is necessary only when exposure to sunlight or the provision of a natural ration containing adequate amounts of vitamin D is impractical.
A total daily intake of 7–12 IU/kg BW is optimal. Sun-dried hay is a good source, but green fodders are generally deficient in vitamin D. Fish liver oils are high in vitamin D, but are subject to deterioration on storage, particularly with regard to vitamin A. They have the added disadvantage of losing their vitamin A and D content in premixed feed, of destroying vitamin E in these feeds when they become rancid and of seriously reducing the butterfat content of milk. Stable water-soluble vitamin A and D preparations do not suffer from these disadvantages. Irradiated dry yeast is probably a simpler and cheaper method of supplying vitamin D in mixed grain feeds.
Stable water-soluble preparations of vitamin D are now available and are commonly added to the rations of animals being fed concentrate rations. The classes of livestock that usually need dietary supplementation include:
• Calves raised indoors on milk replacers
• Pigs raised indoors on grain rations
• Beef cattle receiving poor quality roughage during the winter months
• Cattle raised indoors for prolonged periods and not receiving sun-cured forage containing adequate levels of vitamin D. These include calves raised as herd replacements, yearling cattle fed concentrate rations, bulls in artificial insemination centers and purebred bulls maintained indoors on farms
• Feedlot lambs fed grain rations during the winter months or under totally covered confinement
• Young growing horses raised indoors or outdoors on rations that may not contain adequate concentrations of calcium and phosphorus. This may be a problem in rapidly growing, well-muscled horses receiving a high level of grain.
Because there is limited storage of vitamin D in the body, compared to the storage of vitamin A, it is recommended that daily dietary supplementation be provided when possible for optimum effect.
In situations where dietary supplementation is not possible, the use of single IM injections of vitamin D2 (calciferol) in oil will protect ruminants for 3–6 months. A dose of 11 000 units/kg BW is recommended and should maintain an adequate vitamin D status for 3–6 months.
In mature non-pregnant sheep weighing about 50 kg, a single IM injection of 6000 IU/kg body weight produced concentrations of 25-hydroxyvitamin D3 at adequate levels for 3 months.11 The parenteral administration of vitamin D3 results in both higher tissue and plasma levels of vitamin D3 than does oral administration and IV administration produces higher plasma levels than does the IM injection.12 The timing of the injection should be selected so that the vitamin D status of the ewe is adequate at the time of lambing.11 The vitamin D3 status of lambs can be increased by the parenteral administration of the vitamin to the pregnant ewe.13 Dosing pregnant ewes with 300 000 IU of vitamin D3 in a rapidly available form, approximately 2 months before lambing, provides a safe means of increasing the vitamin D status of the ewe and the newborn lambs by preventing seasonally low concentrations of 25-hydroxyvitamin D3.14 In adult sheep there is a wide margin of safety between the recommended requirement and the toxic oral dose, which provides ample scope for safe supplementation if such is desirable.10 In adult sheep given 20 times the recommended requirements for 16 weeks there was no evidence of pathological calcification.10 Oral dosing with 30–45 units/kg BW is adequate, provided treatment can be given daily. Massive oral doses can also be used to give long-term effects, e.g. a single dose of 2 million units is an effective preventive for 2 months in lambs. Excessive doses may cause toxicity, with signs of drowsiness, muscle weakness, fragility of bones, and calcification in the walls of blood vessels. The latter finding has been recorded in cattle receiving 10 million units/d and in unthrifty lambs receiving a single dose of 1 million units, although larger doses are tolerated by healthy lambs.
Dobson RC, Ward G. Vitamin D physiology and its import ance to dairy cattle: a review. J Dairy Sci. 1974;57:985.
Horst RL, Reinhardt TA. Vitamin D metabolism in ruminants and its relevance to the periparturient cow. J Dairy Sci. 1983;66:661-678.
Wasserman RH. Metabolism, function and clinical aspects of vitamin D. Cornell Vet. 1975;65:3.
1 Smith BSW, Wright H. Vet Rec. 1984;115:537.
2 Smith BSW, Wright H. Vet Rec. 1984;115:579.
3 Ward G, et al. J Dairy Sci. 1971;54:204.
4 Grey RM, et al. Pathol Vet. 1965;2:446.
5 Engstrom GW, et al. J Dairy Sci. 1987;70:2266.
6 Goff JP. J Nutr. 1984;114:163.
7 Goff JP, et al. J Nutr. 1982;112:1387.
8 Reinhardt TA, Hustmyer FG. J Dairy Sci. 1987;70:952.
9 Horst RL, et al. Anal Biochem. 1981;116:189.
10 Smith BSW, et al. Res Vet Sci. 1985;38:317.
11 Smith BSW, Wright H. Res Vet Sci. 1985;39:59.
12 Hidiroglou M, et al. Can J Anim Sci. 1984;64:697.
Vitamin D toxicity has occurred in cattle,1 horses2, and pigs3 following the parenteral or oral administration of excessive quantities of the vitamin.
In cattle, large parenteral doses of vitamin D3 15–17 million IU, results in prolonged hypercalcemia, hyperphosphatemia and large increases in plasma concentrations of vitamin D3 and its metabolites.1 Clinical signs of toxicity occur within 2–3 weeks and include marked anorexia, loss of body weight, dyspnea, tachycardia, loud heart sounds, weakness, recumbency, torticollis, fever and a high case fatality rate.1 Pregnant cows 1 month before parturition are more susceptible than non-pregnant cows.
Hypercalcemia and hypervitaminosis D in 17-day-old lambs being fed a milk replacer has been described.4 The vitamin D content of the milk replacer was not excessive; there was no explanation for the abnormalities in the lamb which recovered when the milk replacer was changed. Serum concentrations of calcium were high at 23.61 mg/dL and 23.09, respectively in two lambs.
Accidental vitamin D3 toxicity has occurred in horses fed a grain diet that supplied 12 000–13 000 IU/kg BW of vitamin D3 daily for 30 days,2 equivalent to about 1 million IU vitamin D3/kg of feed. Clinical findings included anorexia, stiffness, loss of body weight, polyuria, and polydipsia. There was also evidence of hyposthenuria, aciduria, soft-tissue mineralization, and fractures of the ribs.2 Calcification of the endocardium and the walls of large blood vessels are characteristic.
Severe toxicity in pigs occurs at a daily oral dose of 50 000–70 000 IU/kg BW. Signs include a sudden onset of anorexia, vomiting, diarrhea, dyspnea, apathy, aphonia, emaciation, and death.2 Clinical signs are commonly observed within 2 days after consumption of the feed containing excessive vitamin D. At necropsy, hemorrhagic gastritis and mild interstitial pneumonia are commonly present.3 Arteriosclerosis with calcification of the heart base vessels may also be visible macroscopically in poisoned cattle. Osteoporosis with multiple fractures has been observed in subacute to chronic hypervitaminosis D in pigs. Histologically, there is widespread soft tissue mineralization, with a predilection for the lung and gastric mucosa, as well as elastin-rich tissue, such as blood vessels. Changes in bone vary with the duration of exposure to toxic levels of the vitamin.
Assay of the various metabolites of vitamin D in tissues is difficult. The diagnosis is therefore usually confirmed by correlating microscopic changes with a history of exposure to toxic levels of vitamin D.
Rickets is a disease of young, growing animals characterized by defective calcification of growing bone. The essential lesion is a failure of provisional calcification with persistence of hypertrophic cartilage and enlargement of the epiphyses of long bones and the costochondral junctions (so-called ‘rachitic rosary’). The poorly mineralized bones are subject to pressure distortions.
Etiology Deficiencies of any or combination of calcium, phosphorus, and vitamin D.
Epidemiology Young growing animals. No longer common. In calves on phosphorus-deficient diets (range or housed). In grazing lambs due to lack of solar irradiation. Rare in foals and pigs.
Signs Stiff gait and lameness, enlargement of ends of long bones, curvature of long bones, prolonged periods of recumbency. Delayed dentition.
Clinical pathology Elevated alkaline phosphatase; low serum calcium and phosphorus. Lack of density of bone radiographically.
Necropsy findings Abnormal bones and teeth. Bone shafts are soft, epiphyses enlarged. Ratio of bone ash to organic matter is decreased.
Diagnostic confirmation Histology of bone, especially epiphyses.
Treatment Vitamin D injections, calcium and phosphate orally.
Control Supplement deficient diets with calcium, phosphorus, and vitamin D.
Rickets is caused by an absolute or relative deficiency of any or a combination of calcium, phosphorus, or vitamin D in young, growing animals. The effects of the deficiency are also exacerbated by a rapid growth rate.
An inherited form of rickets has been described in pigs. It is indistinguishable from rickets caused by nutritional inadequacy.
Clinical rickets is not as important economically as the subclinical stages of the various dietary deficiencies that produce it. The provision of diets adequate and properly balanced with respect to calcium, phosphorus and sufficient exposure to sunlight, are mandatory in good livestock production. Rickets is no longer a common disease because these requirements are widely recognized, but the incidence can be high in extreme environments, including purely exploitative range grazing, intensive feeding in fattening units and heavy dependence on lush grazing, especially in winter months.
Rickets is a disease of young, rapidly growing animals and occurs naturally under the following conditions.
Primary phosphorus deficiency in phosphorus-deficient range areas and vitamin D deficiency in calves housed for long periods are the common circumstances. Vitamin D deficiency is the most common form of rickets in cattle raised indoors for prolonged periods in Europe and North America. Grazing animals may also develop vitamin D deficiency rickets at latitudes where solar irradiation during winter is insufficient to promote adequate dermal photobiosynthesis of vitamin D3 from 7-dihydrocholesterol. Rickets has occurred in yearling steers in New Zealand wintered on swede (Brassica napus) crop deficient in phosphorus.1
In young, rapidly growing cattle raised intensively indoors a combined deficiency of calcium, phosphorus and vitamin D can result in leg weakness characterized by stiffness, reluctance to move, and retarded growth. In some cases, rupture of the Achilles tendon and spontaneous fracture occur.2 The Achilles tendon may rupture at the insertion of, or proximal to, the calcaneus.
Lambs are less susceptible to primary phosphorus deficiency than cattle, but rickets does occur under the same conditions. Green cereal grazing and, to a lesser extent, pasturing on lush rye-grass during winter months may cause a high incidence of rickets in lambs; this is considered to be a secondary vitamin D deficiency. An outbreak of vitamin D deficiency rickets involving 50% of lambs aged 6–12 months grazing new grass and rape occurred during the early winter months in Scotland.3 In the South Island of New Zealand, where winter levels of solar irradiation are low, rickets occurs in hoggets grazing green oats, or other green crops, which have been shown to contain high levels of rachitogenic carotenes.1 A vitamin D responsive rickets has occurred in twin lambs 3–4 weeks of age.4
Dietary deficiencies of calcium, phosphorus, and vitamin D result in defective mineralization of the osteoid and cartilaginous matrix of developing bone. There is persistence and continued growth of hypertrophic epiphyseal cartilage, increasing the width of the epiphyseal plate. Poorly calcified spicules of diaphyseal bone and epiphyseal cartilage yield to normal stresses, resulting in bowing of long bones and broadening of the epiphyses with apparent enlargement of the joints. Rapidly growing animals on an otherwise good diet will be first affected because of their higher requirement of the specific nutrients.
The subclinical effects of the particular deficiency disease will be apparent in the group of animals affected and have been described in the earlier general section. Clinical rickets is characterized by:
• Enlargement of the limb joints, especially in the forelegs
• Enlargement of the costochondral junctions
• Long bones show abnormal curvature, usually forward and outward at the carpus in sheep and cattle
Outbreaks affecting 50% of a group of lambs have been described.3 Arching of the back and contraction, often to the point of virtual collapse, of the pelvis occur and there is an increased tendency for bones to fracture.
Eruption of the teeth is delayed and irregular, and the teeth are poorly calcified with pitting, grooving, and pigmentation. They are often badly aligned and wear rapidly and unevenly. These dental abnormalities, together with thickening and softness of the jaw bones, may make it impossible for severely affected calves and lambs to close their mouths. As a consequence, the tongue protrudes and there is drooling of saliva and difficulty in feeding. In less severely affected animals, dental malocclusion may be a significant occurrence. Severe deformity of the chest may result in dyspnea and chronic ruminal tympany. In the final stages, the animal shows hypersensitivity, tetany, recumbency and eventually dies of inanition.
The plasma alkaline phosphatase is commonly elevated, but serum calcium and phosphorus levels depend upon the causative factor. If phosphorus or vitamin D deficiencies are the cause, the serum phosphorus level will usually be below the normal lower limit of 3 mg/dL. The serum concentrations of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2are markedly decreased in vitamin D-deficient rickets compared with the normal values of >5 ng/mL.3 Serum vitamin D concentrations as low as 0.4 ng/mL have been reported in lambs with vitamin D responsive rickets.4 Serum calcium levels will be low only in the final stages. In leg weakness of young, rapidly growing cattle, the serum concentration of 25-hydroxyvitamin D may be non-detectable and the serum levels of calcium and inorganic phosphorus may be low.2
Radiographic examination of bones and joints is one of the most valuable aids in the detection of rickets. Rachitic bones have a characteristic lack of density compared with normal bones. The ends of long bones have a ‘woolly’ or ‘moth-eaten’ appearance and have a concave or flat, instead of the normal convex, contour. Surgical removal of a small piece of costochondral junction for histological examination has been used extensively in experimental work and should be applicable in field diagnosis.
Apart from general poorness of condition, the necropsy findings are restricted to abnormal bones and teeth. The bone shafts are softer and larger in diameter, due in part to the subperiosteal deposition of osteoid tissue. The joints are enlarged and on cutting, the epiphyseal cartilage can be seen to be thicker than usual. Histological examination of the epiphysis is desirable for final diagnosis. In sheep, the best results are obtained from an examination of the distal cartilages of the metacarpal and metatarsal bones.
A valuable diagnostic aid is the ratio of ash to organic matter in the bones. Normally the ratio is three parts of ash to two of organic matter but in rachitic bone this may be depressed to 1:2, or 1:3 in extreme cases. A reduction below 45% of the bone weight as ash also suggests osteodystrophy. Because of the difficulty encountered in repeating the results of bone ash determinations, a standardized method has been devised in which the ash content of green bone is determined, using either the metacarpus or metatarsus and the ash content related to the age of the animal, as expressed by the length of the bone. Although normal standards are available only for pigs, the method suggests itself as being highly suitable for all species.
• Toxicology – long bone (ASSAY (ash)); 500 g feed (ASSAY (Ca) (P) (Vit D))
• Histology – formalin-fixed long bone (including growth plate) (LM).
Rickets occurs in young, rapidly growing animals and is characterized by stiffness of the gait and enlargement of the distal physes of the long bones, particularly noticeable on the metacarpus and metatarsus as circumscribed painful swellings. A history of a dietary deficiency of any of calcium, phosphorus, or vitamin D will support the clinical diagnosis. Radiographic evidence of widened and irregular physes suggests rickets. Copper deficiency in young cattle under 1 year of age can also result in clinical, radiographic and pathological findings similar to rickets. Clinically, there is an arched back, severe stiffness of gait, reluctance to move, and loss of weight. There are marked swellings of the distal aspects of metacarpus and metatarsus and radiographically there is a widened zone of cartilage and lipping of the medial and lateral areas of the physeal plate. Copper concentration in plasma and liver are low and there is usually dietary evidence of copper deficiency.
Epiphysitis occurs in rapidly growing yearling cattle raised and fed intensively under confinement. There is severe lameness, swelling of the distal physes and radiographic and pathological evidence of a necrotizing epiphysitis. The etiology is uncertain but thought to be related to the type of housing.
Congenital and acquired abnormalities of the bony skeletal system are frequent in newborn and rapidly growing foals. Rickets occurs, but only occasionally. ‘Epiphysitis’ in young foals resembles rickets and is characterized by enlargements and abnormalities of the distal physes of the radius, tibia, third metacarpal and metatarsal bones and the proximal extremity of the proximal phalanx. There may or may not be deviation of the limbs caused by uneven growth rates in various growth plates. The suggested causes include improper nutrition, faulty conformation and hoof growth, muscle imbalance, overweight and compression of the growth plate. Recovery may occur spontaneously or require surgical correction.
Rickets in pigs is uncommon and the diagnosis may be difficult. The disease is usually suspected in young, rapidly growing pigs in which there is stiffness in the gait, walking on tiptoes, enlargements of the distal ends of long bones, and dietary evidence of a marginal deficiency of calcium or phosphorus. The radiographic and pathological findings may suggest a rickets-like lesion.
Mycoplasmal synovitis and arthritis clinically resemble rickets of pigs. There is a sudden onset of stiffness of gait, habitual recumbency, a decrease in feed consumption, and enlargements of the distal aspects of the long bones which may or may not be painful, spontaneous recovery usually occurs in 10–14 days. The locomotor problems in young, growing pigs raised in confinement and with limited exercise must be considered in the differential diagnosis. In performance testing stations, up to 20% of boars may be affected with leg weakness.
Rickets in lambs must be differentiated from chlamydial and erysipelas arthritis, which are readily diagnosed at necropsy.
Recommendations for the treatment of the individual dietary deficiencies (calcium, phosphorus and vitamin D) are presented under their respective headings. Lesser deformities recover with suitable treatment but gross deformities usually persist. A general improvement in appetite and condition occurs quickly and is accompanied by a return to normal blood levels of phosphorus and alkaline phosphatase. The treatment of rickets in lambs with vitamin A, vitamin D3, calcium borogluconate solution containing magnesium and phosphorus parenterally and supplementation of the diet with bone meal and protein resulted in a dramatic response.3 Recumbent animals were walking within a few days.
Osteomalacia is a disease of mature animals affecting bones in which endochondral ossification has been completed. The characteristic lesion is osteoporosis and the formation of excessive uncalcified matrix. Lameness and pathological fractures are the common clinical findings.
Etiology Absolute or relative deficiency of any one or combination of calcium, phosphorus, and vitamin D in adult animals.
Epidemiology Primarily in cattle and sheep on phosphorus-deficient diets. In feedlot animals due to excessive phosphorus without complementary calcium and vitamin D.
Signs Reduced productivity, licking and chewing inanimate objects, stiff gait, moderate non-specific lameness, shifting from leg to leg, crackling sounds while walking, arched back, lying down for long periods. ‘Milk lameness’ in high-producing dairy cows on deficient diet.
Clinical pathology Increased alkaline phosphatase, decreased serum phosphorus levels. Decreased density of long bones radiographically.
Necropsy findings Decreased density of bones, erosions of articular cartilages.
Diagnostic confirmation Histology of bones.
Treatment As for calcium, phosphorus, and vitamin D deficiency.
In general, the etiology and occurrence of osteomalacia are the same as for rickets except that the predisposing cause is not the increased requirement of growth but the drain of lactation and pregnancy.
Osteomalacia occurs in mature animals under the same conditions and in the same areas as rickets in young animals, but is recorded less commonly. Its main occurrence is in cattle in areas seriously deficient in phosphorus. It is also recorded in sheep, again in association with hypophosphatemia. In pastured animals, osteomalacia is most common in cattle, and sheep raised in the same area are less severely affected. In feedlot animals, excessive phosphorus intake without complementary calcium and vitamin D is likely as a cause, especially if the animals are kept indoors. It also occurs in sows that have recently weaned their pigs after a long lactation period (6–8 weeks) while on a diet deficient usually in calcium. A marginal deficiency of both phosphorus and vitamin D will exaggerate the condition. Intensively-fed yearling cattle with inadequate mineral supplementation may be affected with spontaneous fractures of the vertebral bodies, pelvic bones and long bones, leading to recumbency.1 Simply handling the animals through a chute for routine activities such as tuberculin testing may precipitate the fractures
Increased resorption of bone mineral to supply the needs of pregnancy, lactation and endogenous metabolism leads to osteoporosis, and weakness and deformity of the bones. Large amounts of uncalcified osteoid are deposited about the diaphyses. Pathological fractures are commonly precipitated by sudden exercise or handling of the animal during transportation.
In the early stages, the signs are those of phosphorus deficiency, including lowered productivity and fertility and loss of condition. Licking and chewing of inanimate objects begins at this stage and may bring their attendant ills of oral, pharyngeal, and esophageal obstruction, traumatic reticuloperitonitis, lead poisoning, and botulism.
The signs specific to osteomalacia are those of a painful condition of the bones and joints and include a stiff gait, moderate lameness often shifting from leg to leg, crackling sounds while walking, and an arched back. The hindlegs are most severely affected and the hocks may be rotated inwards. The animals are disinclined to move, lie down for long periods and are unwilling to get up. The colloquial names ‘pegleg’, ‘creeps’, ‘stiffs’, ‘cripples’, and ‘bog-lame’ describe the syndrome aptly. The names ‘milkleg’ and ‘milk-lameness’ are commonly applied to the condition when it occurs in heavily milking cows. Fractures of bones and separation of tendon attachments occur frequently, often without apparent precipitating stress. In extreme cases, deformities of bones occur and when the pelvis is affected dystocia may result. Finally, weakness leads to permanent recumbency and death from starvation.
Affected sows are usually found recumbent and unable to rise from lateral recumbency or from the dog-sitting position. The shaft of one femur or the neck of the femur is commonly fractured. The fracture usually occurs within a few days following weaning of the pigs. The placing of the sow with other adult pigs usually results in some fighting and increased exercise, which commonly precipitates the pathological fractures.
In general, the findings are the same as those for rickets, including increased serum alkaline phosphatase and decreased serum phosphorus levels. Radiographic examination of long bones shows decreased density of bone shadow.
It can be difficult to discern any gross changes as the epiphyses are seldom enlarged and the altered character of cancellous bone may not be macroscopically visible. Cortical bone may be somewhat thinned and erosions of the articular cartilages have been recorded in cattle suffering from primary phosphorus deficiency. The parathyroid glands may be enlarged. Histologically, abnormal osteoid covers trabeculae and a degree of fibrous tissue proliferation is often evident. Analysis reveals the bones to be lighter than normal with a low ratio of ash to organic matter.
The occurrence of non-specific lameness with pathological fractures in mature animals should arouse suspicion of osteomalacia. There may be additional evidence of subnormal productivity and reproductive performance and dietary evidence of a recent deficiency of calcium, phosphorus, or vitamin D.
A similar osteoporotic disease of cattle in Japan has been ascribed to a dietary deficiency of magnesium. The cattle are on high-concentrate, low-roughage diets, have high serum calcium and alkaline phosphatase levels, but a low serum magnesium level. The osteoporosis is observable at slaughter and clinical signs observed are those of intercurrent disease, especially ketosis, milk fever, and hypomagnesemia. Reproductive and renal disorders occur concurrently.
In cattle it must be differentiated from chronic fluorosis in mature animals, but the typical mottling and pitting of the teeth and the enlargements on the shafts of the long bones are characteristic. In some areas, e.g. northern Australia, where the water supply is obtained from deep sub-artesian wells, the two diseases may occur concurrently. Analysis of water supplies and foodstuffs for fluorine may be necessary in doubtful cases.
In sows, osteomalacia with or without pathological fractures must be differentiated from spinal cord compression due to a vertebral body abscess and chronic arthritis due to erysipelas.
Osteodystrophia fibrosa is similar in its pathogenesis to osteomalacia, but differs in that soft, cellular, fibrous tissue is laid down as a result of the weakness of the bones instead of the specialized uncalcified osteoid tissue of osteomalacia. It occurs in horses, goats, and pigs.
A secondary calcium deficiency due to excessive phosphorus feeding is the common cause in horses and probably also in pigs. The disease can be readily produced in horses on diets with a ratio of calcium:phosphorus of 1:2.9 or greater, irrespective of the total calcium intake. Calcium:phosphorus ratios of 1:0.9 to 1:1.4 have been shown to be preventive and curative. With a very low calcium intake of 2–3 g/d and a calcium: phosphorus ratio of 1:13 the disease may occur within 5 months. With a normal calcium intake of 26 g/d and a calcium:phosphorus ratio of 1:5, obvious signs appear in about 1 year, but shifting lameness may appear as early as 3 months. The disease is reproducible in pigs on similar diets to those described above and also on diets low in both calcium and phosphorus. The optimum calcium:phosphorus ratio is 1.2:1 and the intake for pigs should be within the range of 0.6–1.2% of the diet.
Osteodystrophia fibrosa is principally a disease of horses and other Equidae and to a lesser extent of pigs. It has also occurred in goats. Among horses, those engaged in heavy city work and in racing are more likely to be affected because of the tendency to maintain these animals on unbalanced diets. The major occurrence is in horses fed a diet high in phosphorus and low in calcium. Such diets include cereal hays combined with heavy grain or bran feeding. Legume hays, because of their high calcium content, are preventive.
The disease may reach endemic proportions in army horses moved into new territories, whereas local horses, more used to the diet, suffer little. Although horses may be affected at any age after weaning it is the 2–7-year age group that suffer most, probably because they are the group most likely to be exposed to the rations that predispose to the disease.
A novel occurrence has been recorded of an endemic form of the disease affecting large numbers of horses at pasture. The dietary intake of calcium and phosphorus and their proportions, were normal. The occurrence was thought to be due to the continuous ingestion of oxalate in specific grasses: Cenchrus ciliaris, Panicum maximum var. trichoglume, Setaria anceps, Brachiaria mutica and Pennisetum clandestinum.
Defective mineralization of bones follows the imbalance of calcium and phosphorus in the diet and a fibrous dysplasia occurs. This may be in response to the weakness of the bones or it may be more precisely a response to hyperparathyroidism stimulated by the excessive intake of phosphorus. The weakness of the bones predisposes to fractures and separation of muscular and tendinous attachments. Articular erosions occur commonly and displacement of the bone marrow may cause the development of anemia.
As in most osteodystrophies, the major losses are probably in the early stages before clinical signs appear or on diets where the aberration is marginal. In horses, a shifting lameness is characteristic of this stage of the disease and arching of the back may sometimes occur. The horse is lame, but only mildly so and in many cases, no physical deformity can be found by which the seat of lameness can be localized. Such horses often creak badly in the joints when they walk. These signs probably result from relaxation of tendon and ligaments and appear in different limbs at different times. Articular erosions may contribute to the lameness. In more advanced cases severe injuries, including fracture and visible sprains of tendons, may occur but these are not specific to osteodystrophia fibrosa, although their incidence is higher in affected than in normal horses. Fracture of the lumbar vertebrae while racing has been known to occur in affected horses.
The more classical picture of the disease has largely disappeared because cases are seldom permitted to progress to this advanced stage. Local swelling of the lower and alveolar margins of the mandible is followed by soft, symmetrical enlargement of the facial bones, which may become swollen so that they interfere with respiration.1 Initially these bony swellings are firm and pyramidal and commence just above and anterior to the facial crests. The lesions are bilaterally symmetrical. Flattening of the ribs may be apparent and fractures and detachment of ligaments occur if the horse is worked. There may be obvious swelling of joints and curvature of long bones. Severe emaciation and anemia occur in the final stages.
In pigs, the lesions and signs are similar to those in the horse and in severe cases, pigs may be unable to rise and walk, show gross distortion of limbs and enlargement of joints and the face. In less severe cases, there is lameness, reluctance to rise, pain on standing and bending of the limb bones, but normal facial bones and joints. With suitable treatment, the lameness disappears, but affected pigs may never attain their full size. The relationship of this disease to atrophic rhinitis is discussed under the latter heading.
An outbreak of the disease has been recorded in goats receiving a diet of wheat straw (60%) and 40% barley for 89 months.2 The ratio of calcium to phosphorus in the diet was 1:1.8. Affected goats were 9–10 months of age with a history of stunted growth, lameness, diarrhea, and tongue protrusion. Clinically there was symmetrical enlargement of the face and jaws, tongue protrusion, prominent eyeballs, and tremor. The enlarged bones were firm and painful on palpation. The hindlimbs were bent outwards symmetrically from the tarsal joints.
There are no significant changes in blood chemistry in horses affected with severe osteodystrophia fibrosa. However, the serum calcium level will tend to be lower than normal, the serum inorganic phosphorus higher than normal, and the alkaline phosphatase activity higher than normal. The levels of diagnostic alkaline phosphatase have not been determined. Affected horses may be unable to return their serum calcium levels to normal following the infusion of a calcium salt. Radiographic examination reveals increased translucency of bones.
The entire skeleton is abnormal in this severe form of metabolic bone disease, but the change is most notable in the mandibular, maxillary, and nasal bones, which may appear thickened and distorted. The fleshy tissue that replaces normal cancellous bone in these sites is also present in the metaphyses of the long bones. Microscopically, there is proliferation of fibrous tissue and markedly increased osteoclast activity along thinned and abnormally oriented bony trabeculae. The parathyroid glands are enlarged. It must be remembered that osteodystrophia fibrosa is a lesion, not a disease. The pathway to this lesion usually involves a dietary imbalance in calcium and phosphorus, but the kidneys should also be examined to rule out the possibility of renal secondary hyperparathyroidism.
• Toxicology – bone (ASSAY (ash)); 500 g feed (ASSAY (Ca) (P) (Vit D))
• Histology – formalin-fixed bone, parathyroid gland, kidney (LM).
In the early stages, the diagnosis may be difficult because of the common occurrence of traumatic injuries to horses’ legs. A high incidence of lameness in a group of horses warrants examination of the ration and determination of their calcium and phosphorus status. An identical clinical picture has been described in a mare with an adenoma of the parathyroid gland. Inherited multiple exostosis has been described in the horse.
In pigs, osteodystrophia can be the result of hypovitaminosis A and experimentally as a result of manganese deficiency.
A ration adequately balanced with regard to calcium and phosphorus (calcium:phosphorus should be in the vicinity of 1:1 and not wider than 1:1.4) is preventive in horses and affected animals can only be treated by correcting the existing imbalance. Even severe lesions may disappear in time with proper treatment. Cereal hay may be supplemented with alfalfa or clover hay, or finely ground limestone (30 g daily) should be fed. Dicalcium phosphate or bone meal are not as efficient because of their additional content of phosphorus.
This is a disease of lambs of unknown etiology. There is a characteristic lateral curvature of the long bones of the front legs, but the lesions differ from those of rickets. It has been observed only on unimproved range pasture in New Zealand. The cause is unknown, although phosphorus deficiency has been suggested.
Improvement of the pasture by top-dressing with superphosphate and sowing-improved grasses is usually followed by disappearance of the disease. Only sucking lambs are affected and cases occur only in the spring at a time when rickets does not occur. Up to 40% of a group of lambs may be affected without breed differences in incidence. A similar syndrome has been produced by the feeding of wild parsnip (Trachemene glaucifolia) and, experimentally, by the feeding of a diet low in both calcium and phosphorus.
The disease has also been reported from South Africa where it occurs primarily in ram lambs and develops from as early as 3 months up to 1 year of age.1 There is gradual bending of the forelimbs with hooves turned inwards and the carpal joints turned outwards. Animals of the South African Mutton Merino breed had significantly higher plasma phosphorus concentrations than those of the Merino and Dohne Merino breeds. The plasma calcium:phosphorus ratio was lower in affected lambs and their ewes and this converse ratio is thought to result in an induced plasma ionized calcium deficiency leading to improper calcification of bone.
Some tenderness of the feet and lateral curvature at the knees may be seen as early as 2–3 weeks of age and marked deformity is present at 6–8 weeks with maximum severity at weaning. The forelimbs are more commonly affected than the hindlimbs. Medial curvature occurs in rare cases. The sides of the feet become badly worn and the lateral aspects of the lower parts of the limbs may be injured and be accompanied by lameness. The lambs grow well at first, but by the time of weaning, affected lambs are in poor condition because of their inability to move about and feed properly. A rather similar syndrome has been observed in young Saanen bucks, but the condition showed a tendency to recover spontaneously.
At necropsy, in spite of the curvature of the limbs, there is no undue porosis and although the epiphyseal cartilages are thickened, they are supported by dense bone. There may be excessive synovial fluid in the joints and, in the later stages, there are articular erosions. Increased deposition of osteoid is not observed.
Supplementation of the diet with phosphorus or improvement of the pasture seems to reduce the incidence of the disease. Dosing with vitamin D or providing mineral mixtures containing all trace elements is ineffective.2
Degenerative arthropathy occurs in cattle of all breeds, but reaches its highest incidence as a sporadic disease of young beef bulls. The disease has been identified as hip dysplasia because of the pre-existing shallow contour of the acetabulum. It is considered to be inherited as a recessive characteristic and exacerbated by rapid weight gain in young animals. The occurrence of the condition in these animals is usually associated with rearing on nurse cows, housing for long periods, provision of a ration high in cereal grains and byproducts (i.e. a high phosphorus:calcium ratio), and possibly with an inherited straight conformation of the hindlegs. Although the disease occurs in all beef breeds, there is a strong familial tendency which appears to be directly related to the rate of body weight gain and the straightness of the hindleg. If the potential for rapid weight gain is being realized in animals being force fed, the rate of occurrence appears to be dependent on their breeding and animals in the same herd that are allowed to run at pasture under natural conditions are either not affected or are affected at a much later age. Thus, animals in a susceptible herd may show signs as early as 6 months of age if they are heavily hand-fed and raised on dairy cow foster mothers. In the same herd, signs do not appear until 1–2 years of age if supplementary feeding is not introduced until weaning and not until 4 years if there is no significant additional feeding.
Clinically there is a gradual onset of lameness in one or both hindlegs. The disease progresses with the lameness becoming more severe over a period of 6–12 months. In some animals, there is a marked sudden change for the worse, usually related to violent muscular movements, as in breeding or fighting. In severely affected animals, the affected limb is virtually useless and, on movement, distinct crepitus can often be felt and heard over the affected joints. This can be accomplished by rocking the animal from side to side or having it walk while holding the hands over the hip joints.
An additional method of examination is to place the hand in the rectum close to the hip joint, while the animal is moved. Passive movement of the limb may also elicit crepitus, or louder clinking or clicking sounds. The hip joints are always most severely affected, but in advanced cases, there may be moderate involvement of the stifles and minimal lesions in other joints. Affected animals lie down most of the time and are reluctant to rise and to walk. The joints are not swollen, but in advanced cases, local atrophy of muscles may be so marked that the joints appear to be enlarged. There is a recorded occurrence in which the lesions were confined mainly to the front fetlocks.
Radiographic examination may provide confirmatory or diagnostic evidence.
At necropsy, the most obvious finding is extensive erosion of the articular surfaces, often penetrating to the cancellous bone and disappearance of the normal contours of the head of the femur or the epiphyses in the stifle joint. The synovial cavity is distended, with an increased volume of brownish, turbid fluid; the joint capsule is much thickened and often contains calcified plaques. Multiple, small exostoses are present on the periarticular surfaces. When the stifle is involved the cartilaginous menisci, particularly the medial one, are very much reduced in size and may be completely absent. In cattle with severe degenerative changes in the coxofemoral joint, an acetabular osseous bulla may be present at the cranial margin of the obturator foramen.1
Adequate calcium, phosphorus, and vitamin D intake and a correct calcium: phosphorus ratio in the ration should be insured. Supplementation of the ration with copper at the rate of 15 mg/kg has also been recommended for the control of a similar disease.
Degenerative joint disease of cattle is recorded on an enzootic scale in Chile and is thought to be due to gross nutritional deficiency. The hip and tarsal joints are the only ones affected and clinical signs appear when animals are 8–12 months old. There is gross lameness and progressive emaciation. An inherited osteoarthritis is described under that heading. Sporadic cases of degenerative arthropathy, with similar signs and lesions, occur in heavy-producing, aged dairy cows and are thought to be caused by long-continued negative calcium balance. Rare cases also occur in aged beef cows but are thought to be associated with an inherited predisposition. In both instances the lesions are commonly restricted to the stifle joints.
Diseases associated with deficiencies of fat-soluble vitamins
A deficiency of vitamin A may be caused by an insufficient supply of the vitamin in the ration or its defective absorption from the alimentary canal. In young animals, the manifestations of the deficiency are mainly those of compression of the brain and spinal cord. In adult animals, the syndrome is characterized by night blindness, corneal keratinization, pityriasis, defects in the hooves, loss of weight and infertility. Congenital defects are common in the offspring of deficient dams. Vitamin A may also provide a protective effect against various infectious diseases and enhance many facets of the immune system.
Etiology Dietary deficiency of vitamin A or its precursors.
Epidemiology Primary vitamin A deficiency in animals fed diet deficient in vitamin A or its precursors. Common in cattle grazing dry pastures for long periods. Occurs when diet of hand-fed animals is not supplemented with vitamin A.
Signs Cattle: Night blindness. Loss of body weight. Convulsions followed by recovery. Episodes of syncope. Permanent blindness with dilated pupils and optic disc edema. Pigs: Convulsions, hindleg paralysis, congenital defects.
Clinical pathology Low levels plasma vitamin A.
Necropsy findings Squamous metaplasia of interlobular ducts of parotid gland. Compression of optic nerve tracts and spinal nerve roots. Degeneration of testes.
Diagnostic confirmation Low levels of plasma vitamin A and squamous metaplasia of interlobular ducts of parotid glands.
Differential diagnosis list Cattle
Treatment Vitamin A injections.
Control Feed diets with adequate carotene. Supplement diet with vitamin A. Parenteral injections of vitamin A at strategic times.
Vitamin A deficiency may be primary disease, due to an absolute deficiency of vitamin A or its precursor carotene in the diet, or a secondary disease in which the dietary supply of the vitamin or its precursor is adequate, but their digestion, absorption, or metabolism is interfered with to produce a deficiency at the tissue level.
Primary vitamin A deficiency is of major economic importance in groups of young growing animals on pasture or fed diets deficient in the vitamin or its precursors.1 In the UK, primary vitamin A deficiency occurs in housed cattle fed a ration containing little or no green forage.2 Animals at pasture receive adequate supplies of the vitamin, except during prolonged droughts, but animals confined indoors and fed prepared diets may be deficient if not adequately supplemented. For example, a diet of dried sugar beet pulp, concentrates and poor quality hay can result in hypovitaminosis-A in confined beef cattle.
Primary vitamin A deficiency occurs in beef cattle and sheep on dry range pasture during periods of drought. Clinical vitamin A deficiency does not always occur under these conditions because hepatic storage is usually good and the period of deprivation not sufficiently long for these stores to reach a critically low level.3 Young sheep grazing natural, drought-stricken pasture can suffer serious depletion of reserves of the vitamin in 5–8 months, but normal growth is maintained for 1 year at which time clinical signs develop. Adult sheep may be on a deficient diet for 18 months before hepatic stores are depleted and the disease becomes evident. Cattle may subsist on naturally deficient diets for 5–18 months before clinical signs appear. However, during the annual dry season (October–June), herds of cattle, sheep and goats in the Sahelian region of West Africa are managed on dry grasses and shrubby ligneous plants, which fail to provide maintenance levels of crude protein and vitamin A. These substandard conditions result in vitamin A deficiency characterized by night blindness, xerophthalmia, retarded growth rates, reproductive failures, and increased mortality.4 The pastoral herders associate the cure of night blindness with the consumption of green vegetation and will purposefully herd livestock into green vegetation areas when available. Certain ethnic groups of pastoral herders depend on ruminant milk as their principal source of vitamin A and night blindness in lactating and pregnant women as well as in young children appears after the onset of night blindness in their cattle and sheep during the latter half of the dry season. Therefore, increasing vitamin A levels in the milk of cows may alleviate the clinical signs of vitamin A deficiency in herder families.
Primary vitamin A deficiency is still relatively common in beef cattle that depend on pasture and roughage for the major portion of their diet. Beef calves coming off dry summer pastures at 6–8 months of age are commonly marginally deficient.
A maternal deficiency of vitamin A can result in herd outbreaks of congenital hypovitaminosis-A in calves.5 In one such occurrence, out of 240 heifers fed a vitamin A-deficient ration, 89 calves were born dead, 47 were born alive but blind and weak and died within 1–3 days after birth. Blindness with dilated pupils, nystagmus, weakness, and incoordination were characteristic. In another occurrence in the UK, 25% of the calves born from maternally vitamin A deficient heifer dams had ocular abnormalities.2
The status of the dam is reflected in that of the fetus only in certain circumstances, in that carotene, as it occurs in green feed, does not pass the placental barrier and a high intake of green pasture before parturition does not increase the hepatic stores of vitamin A in newborn calves, lambs, or kids and only to a limited extent in pigs. However, vitamin A in the ester form, as it occurs in fish oils, will pass the placental barrier in cows. Feeding of these oils, or the parenteral administration of a vitamin A injectable preparation before parturition, will cause an increase in stores of the vitamin in fetal livers. Antepartum feeding of carotene and the alcohol form of the vitamin does, however, cause an increase in the vitamin A content of the colostrum. Young animals depend on the dam’s colostrum for their early requirements of the vitamin which is always highest in colostrum and returns to normal levels within a few days of parturition. Pigs weaned very early at 2–4 weeks may require special supplementation. Pregnant beef cows wintered on poor quality roughage commonly need supplementation with vitamin A throughout the winter months to insure normal development of the fetus and an adequate supply of the vitamin in the colostrum at parturition.
The addition of vitamin A supplements to diets may not always be sufficient to prevent deficiency. Carotene and vitamin A are readily oxidized, particularly in the presence of unsaturated fatty acids. Oily preparations are thus less satisfactory than dry or aqueous preparations, particularly if the feed is to be stored for any length of time. Pelleting of feed may also cause a serious loss up to 32% of the vitamin A in the original feedstuff.
Heat, light, and mineral mixes are known to increase the rate of destruction of vitamin A supplements in commercial rations. In one study, 47–92% of the vitamin A in several mineral supplements was destroyed after 1 week of exposure to the trace minerals, high relative humidity, sunlight and warm temperatures.6
The disease still occurs in feedlot cattle in some parts of North America when feedlot cattle are fed rations low in carotene or vitamin A over a period of several months.7 The onset of clinical signs in growing feedlot cattle is typically seen 6–12 months after feeding a diet deficient in carotene or vitamin A. Small farm feedlots may feed their cattle a cereal grain such as barley and barley straw with no vitamin supplementation8 or inadequate supplementation.9 Grains, with exception of yellow corn, contain negligible amounts of carotene and cereal hay is often a poor source. Any hay cut late, leached by rain, bleached by sun, or stored for long periods loses much of its carotene content. The carotene content of yellow corn also deteriorates markedly with long storage. Moreover, under conditions not yet completely understood, the conversion by ruminants of carotene present in feeds such as silage may be much less complete than was formerly thought.
In feedlot cattle, the disease is most common in steers fed the same ration as heifers which may remain clinically normal.6,7 It is suggested that sexual dimorphism may be due to the production of vitamin A by the corpus luteum of heifers.7
Young pigs on a deficient diet may show signs after several months, but as in other animals, the length of time required before signs appear is governed to a large extent by the status before depletion commences. As a general rule it can be anticipated that signs will appear in pigs fed deficient rations for 4–5 months, variations from these periods probably being due to variations in the vitamin A status of the animal when the deficient diet is introduced. Congenital defects occur in litters from deficient sows, but the incidence is higher in gilts with the first litter than in older sows. It is presumed that the hepatic stores of vitamin A in older sows are not depleted as readily as in young pigs. Feeding white maize bran without supplementation can result in congenital defects in litters and paralysis in adult pigs.10
Secondary vitamin A deficiency may occur in cases of chronic disease of the liver or intestines because much of the conversion of carotene to vitamin A occurs in the intestinal epithelium and the liver is the main site of storage of the vitamin. Highly chlorinated naphthalenes interfere with the conversion of carotene to vitamin A and animals poisoned with these substances have a very low vitamin A status. The intake of inorganic phosphorus also affects vitamin A storage, low phosphate diets facilitating storage of the vitamin. This may have a sparing effect on vitamin A requirements during drought periods when phosphorus intake is low and an exacerbating effect in stall-fed cattle on a good grain diet. However, phosphorus deficiency may lower the efficiency of carotene conversion. Vitamins C and E help to prevent loss of vitamin A in feedstuffs and during digestion. Additional factors which may increase the requirement of vitamin A include high environmental temperatures, a high nitrate content of the feed, which reduces the conversion of carotene to vitamin A and rapid rate of gain. Both a low vitamin A status of the animal and high levels of carotene intake may decrease the biopotency of ingested carotene.
The continued ingestion of mineral oil, which may occur when the oil is used as a preventive against bloat in cattle, may cause a depression of plasma carotene and vitamin A esters and the carotene levels in buffer fat. Deleterious effects on the cattle are unlikely under the conditions in which it is ordinarily used because of the short period for which the oil is administered and the high intake of vitamin A and carotene.
Vitamin A is essential for the regeneration of the visual purple necessary for dim-light vision, for normal bone growth and for maintenance of normal epithelial tissues. Deprivation of the vitamin produces effects largely attributable to disturbance of these functions. The same tissues are affected in all species. However, there is a difference in tissue and organ response in the different species and particular clinical signs may occur at different stages of development of the disease. The major pathophysiological effects of vitamin A deficiency are as follows.
Ability to see in dim light is reduced because of interference with regeneration of visual purple.
An increase in CSF pressure is one of the first abnormalities to occur in hypovitaminosis-A in calves. It is a more sensitive indicator than ocular changes and, in the calf, it occurs when the vitamin A intake is about twice that needed to prevent night blindness. The increase in CSF pressure is due to impaired absorption of the CSF due to reduced tissue permeability of the arachnoid villi and thickening of the connective tissue matrix of the cerebral dura mater. The increased CSF pressure is responsible for the syncope and convulsions, which occur in calves in the early stages of vitamin A deficiency. The syncope and convulsions may occur spontaneously or be precipitated by excitement and exercise. It is suggested that the CSF pressure is increased in calves with subclinical deficiency and that exercise further increases the CSF pressure to convulsive levels.
Vitamin A is necessary to maintain normal position and activity of osteoblasts and osteoclasts. When deficiency occurs there is no retardation of endochondral bone growth, but there is incoordination of bone growth in that shaping, especially the finer molding of bones, does not proceed normally. In most locations this has little effect but may cause serious damage to the nervous system. Overcrowding of the cranial cavity occurs with resulting distortion and herniations of the brain and an increase in CSF pressure up to four to six times normal. The characteristic nervous signs of vitamin A deficiency, including papilledema, incoordination and syncope, follow. Compression, twisting and lengthening of cranial nerves and herniations of the cerebellum into the foramen magnum, causing weakness and ataxia and of the spinal cord into intervertebral foraminae results in damage to nerve roots and localizing signs referable to individual peripheral nerves. Facial paralysis and blindness due to constriction of the optic nerve, are typical examples of this latter phenomenon. The effect of excess vitamin A on bone development by its interference with vitamin D has been discussed elsewhere. Dwarfism in a group of pigs in a swine herd was suspected to be due to vitamin toxicosis.11
Vitamin A deficiency leads to atrophy of all epithelial cells, but the important effects are limited to those types of epithelial tissue with a secretory as well as a covering function. The secretory cells are without power to divide and develop from undifferentiated basal epithelium. In vitamin A deficiency these secretory cells are gradually replaced by the stratified, keratinizing epithelial cells common to non-secretory epithelial tissues. This replacement of secretory epithelium by keratinized epithelium occurs chiefly in the salivary glands, the urogenital tract (including placenta but not ovaries or renal tubules) and the paraocular glands and teeth (disappearance of odontoblasts from the enamel organ). The secretion of thyroxine is markedly reduced. The mucosa of the stomach is not markedly affected. These changes in epithelium lead to the clinical signs of placental degeneration, xerophthalmia and corneal changes.
Experimental vitamin A deficiency in lambs results in changes in the epithelium of the small intestine characterized by vesicular microvillar degeneration and disruption of the capillary endothelium.12 Diarrhea did not occur.
Vitamin A is essential for organ formation during growth of the fetus. Multiple congenital defects occur in pigs and rats and congenital hydrocephalus in rabbits on maternal diets deficient in vitamin A. In pigs, administration of the vitamin to depleted sows before the 17th day of gestation prevented the development of eye lesions but administration on the 18th day failed to do so. A maternal deficiency of vitamin A in cattle can result in congenital hypovitaminosis-A in the calves, characterized by blindness with dilated pupils, nystagmus, weakness, and incoordination. Constriction of the optic canal with thickening of the dura mater results in ischemic necrosis of the optic nerve and optic disc edema resulting in blindness. Retinal dysplasia also occurs. Thickening of the occipital and sphenoid bones and doming of the frontal and parietal bones with compression of the brain also occur. Dilated lateral ventricles may be present and associated with increased CSF pressure.
The effects of vitamin A and β-carotene on host defense mechanisms have been uncertain and controversial for many years.13 Some workers claim that the incidence and severity of bacterial, viral, rickettsial and parasitic infections are higher in vitamin A-deficient animals.13 It is possible that vitamin A and β-carotene afford protection against infections by influencing both specific and non-specific host defense mechanisms. The protective effect of vitamin A may be mediated by enhanced polymorphonuclear neutrophil function but this effect is also influenced by the physiological status of the animal such as lactation status in dairy cattle.14 Experimentally, a severe vitamin A deficiency in lambs is associated with alterations in immune function, but the exact mechanism is unknown.15
In general, similar syndromes occur in all species, but because of species differences in tissue and organ response, some variations are observed. The major clinical findings are set out below.
Inability to see in dim light (twilight or moonlit night) is the earliest sign in all species, except in the pig in which it is not evident until plasma vitamin A levels are very low. This is an important diagnostic sign.
True xerophthalmia, with thickening and clouding of the cornea, occurs only in the calf. In other species a thin, serous mucoid discharge from the eyes occurs, followed by corneal keratinization, clouding and sometimes ulceration, and photophobia.
A rough, dry coat with a shaggy appearance and splitting of the bristle tips in pigs is characteristic, but excessive keratinization, such as occurs in cattle poisoned with chlorinated naphthalenes, does not occur under natural conditions of vitamin A deficiency. Heavy deposits of bran-like scales on the skin are seen in affected cattle. Dry, scaly hooves with multiple, vertical cracks are another manifestation of skin changes and are particularly noticeable in horses. A seborrheic dermatitis may also be observed in deficient pigs but is not specific to vitamin A deficiency.
Under natural conditions, a simple deficiency of vitamin A is unlikely to occur and the emaciation commonly attributed to vitamin A deficiency may be largely due to multiple deficiencies of protein and energy. Although inappetence, weakness, stunted growth and emaciation occur under experimental conditions of severe deficiency, in field outbreaks severe clinical signs of vitamin A deficiency are often seen in animals in good condition. Experimentally, sheep maintain their body weight under extreme deficiency conditions and with very low plasma vitamin A levels.
Loss of reproductive function is one of the major causes of loss in vitamin A deficiency. Both the male and female are affected. In the male, libido is retained but degeneration of the germinative epithelium of the seminiferous tubules causes reduction in the number of motile, normal spermatozoa produced. In young rams, the testicles may be visibly smaller than normal. In the female, conception is usually not interfered with, but placental degeneration leads to abortion and the birth of dead or weak young. Placental retention is common.
Signs related to damage of the nervous system include:
• Paralysis of skeletal muscles due to damage of peripheral nerve roots
These defects occur at any age but most commonly in young, growing animals and they have been observed in all species except horses.
The paralytic form is manifested by abnormalities of gait due to weakness and incoordination. The hindlegs are usually affected first and the forelimbs later. In pigs, there may be stiffness of the legs, initially with a stilted gait or flaccidity, knuckling of the fetlocks and sagging of the hindquarters. Complete limb paralysis occurs terminally.
Encephalopathy, associated with an increase in CSF pressure, is manifested by convulsions, which are common in beef calves at 6–8 months, usually following removal from a dry summer pasture at weaning time. Spontaneously, or following exercise or handling, affected calves will collapse (syncope) and during lateral recumbency a clonic-tonic convulsion will occur, lasting for 10–30 s. Death may occur during the convulsion or the animal will survive the convulsion and lie quietly for several minutes, as if paralyzed, before another convulsion may occur. Affected calves are usually not blind and the menace reflex may be slightly impaired or hyperactive. Some calves are hyperesthetic to touch and sound. During the convulsion there is usually ventroflexion of the head and neck, sometimes opisthotonos and, commonly, tetanic closure of the eyelids and retraction of the eyeballs. Outbreaks of this form of hypovitaminosis-A in calves have occurred and the case fatality rate may reach 25%.9 The prognosis is usually excellent; treatment will effect a cure in 48 h but convulsions may continue for up to 48 h following treatment.
Seizures and acute death attributable to hypovitaminosis-A and hypovitaminosis-D have occurred in feeder pigs fed ground red wheat and whole milk and housed in a barn with no exposure to sunlight.16 Lethargy, inappetence, diarrhea, and vomiting and progression to convulsions were characteristic.
The ocular form of hypovitaminosis-A occurs usually in yearling cattle (12–18 months old) and up to 2–3 years of age. These animals have usually been on marginally deficient rations for several months. Night blindness may or may not have been noticed by the owner. The cattle have usually been fed and housed for long periods in familiar surroundings and the clinical signs of night blindness may have been subtle and not noticeable. The first sign of the ocular form of the disease is blindness in both eyes during daylight. Both pupils are widely dilated and fixed and will not respond to light. Optic disc edema may be prominent and there may be some loss of the usual brilliant color of the tapetum. Varying degrees of peripapillary retinal detachment, papillary and peripapillary retinal hemorrhages, and disruption of the retinal pigment epithelium may also be present.6 The menace reflex is usually totally absent, but the palpebral and corneal reflexes are present. The animal is aware of its surroundings and usually eats and drinks, unless placed in unfamiliar surroundings. The CSF pressure is increased in these animals, but not as high as in the calves described earlier. Convulsions may occur in these cattle if forced to walk, or if loaded onto a vehicle for transportation. The prognosis for the ocular form with blindness is unfavorable and treatment is ineffective because of the degeneration of the optic nerves. Exophthalmos and excessive lacrimation are present in some cases.
These have been observed in piglets and calves. In calves, the defects are limited to congenital blindness due to optic nerve constriction and encephalopathy. In piglets, complete absence of the eyes (anophthalmos), or small eyes (microphthalmos), incomplete closure of the fetal optic fissure, degenerative changes in the lens and retina, and an abnormal proliferation of mesenchymal tissue in front of and behind the lens are some of the defects encountered. Ocular abnormalities in newborn calves from maternally vitamin A deficient heifers included corneal dermoid, microphthalmos, aphakia (absence of lens) and in some cases, both eyes covered by haired skin.2
Other congenital defects attributed to vitamin A deficiency in pigs include cleft palate and harelip, accessory ears, malformed hindlegs, subcutaneous cysts, abnormally situated kidneys, cardiac defects, diaphragmatic hernia, aplasia of the genitalia, internal hydrocephalus, herniations of the spinal cord, and generalized edema. Affected pigs may be stillborn, or weak and unable to stand, or may be quite active. Weak pigs lie on their sides, make slow paddling movements with their legs, and squawk plaintively.
Increased susceptibility to infection is often stated to result from vitamin A deficiency.9,13 The efficacy of colostrum as a preventive against diarrhea in calves was originally attributed to its vitamin A content, but the high antibody content of colostrum is most important.
Edema of the limbs and brisket have been associated with vitamin A deficiency in feedlot cattle, especially steers.17 The pathogenesis is not understood. The edema can be extensive, include all four limbs, ventral body wall and extending to the scrotum. Heifers were unaffected.
Vitamin A levels in the plasma are used extensively in diagnostic and experimental work. Plasma levels of 20 μg/dL are the minimal concentration for vitamin A adequacy.18 Papilledema is an early sign of vitamin A deficiency which develops before nyctalopia and at plasma levels below 18 μg/dL. Normal serum vitamin A concentrations in cattle range from 25 to 60 μg/dL. In pigs, levels of 11.0 μg/dL have been recorded in clinical cases, with normal levels being 23–29 μg/dL.16 In experimental vitamin A deficiency in lambs, serum levels declined to 6.8 μg/dL (normal lambs at 45.1 μg/dL).12
The clinical signs may correlate with the serum concentrations of vitamin A.8 In one outbreak, feedlot cattle with serum concentrations between 8.89 and 18.05 μg/dL had only lost body weight, those between 4.87 and 8.88 μg/dL had varying degrees of ataxia and blindness and those below 4.88 μg/dL had convulsions and optic nerve constriction.8 Clinical signs can be expected when the levels fall to 5 μg/dL.9 For complete safety, optimum levels should be 25 μg/dL or above.
Some information on the plasma retinol values in stabled Thoroughbred horses is available. The mean plasma level of retinol in 71 horses 2–3 years of age was 16.5 μg/dL. The serum retinol levels in racing Trotters in Finland are lower than during the summer months, which is a reflection of the quality of the diets.19
Plasma carotene levels vary largely with the diet. In cattle, levels of 150 μg/dL are optimum and, in the absence of supplementary vitamin A in the ration, clinical signs appear when the levels fall to 9 μg/dL. In sheep, carotene is present in the blood in only very small amounts even when animals are on green pasture.
A direct relationship between plasma and hepatic levels of vitamin A need not exist since plasma levels do not commence to fall until the hepatic stores are depleted. A temporary precipitate fall occurs at parturition and in acute infections in most animals. The secretion of large amounts of carotene and vitamin A in the colostrum of cows during the last 3 weeks of pregnancy may greatly reduce the level of vitamin A in the plasma.
Hepatic levels of vitamin A and carotene can be estimated in the living animal from a biopsy specimen. Biopsy techniques have been shown to be safe and relatively easy, provided a proper instrument is used. Hepatic levels of vitamin A and carotene should be of the order of 60 and 4.0 μg/g of liver, respectively. These levels are commonly as high as 200–800 μg/g. Critical levels at which signs are likely to appear are 2 and 0.5 μg/g for vitamin A and carotene, respectively.
CSF pressure is also used as a sensitive indicator of low vitamin A status. In calves, normal pressures of less than 100 mm of saline rise after depletion to more than 200 mm. In pigs, normal pressures of 80–145 mm rise to above 200 mm in vitamin A deficiency. An increase in pressure is observed at a blood level of about 7 μg vitamin A/dL plasma in this species. In sheep, normal pressures of 55–65 mm rise to 70–150 mm when depletion occurs. In the experimentally induced disease in cattle, there is a marked increase in the number of cornified epithelial cells in a conjunctival smear and distinctive bleaching of the tapetum lucidum as viewed by an ophthalmoscope. These features may have value as diagnostic aids in naturally occurring cases.
Gross changes are rarely observed at necropsy. Careful dissection may reveal a decrease in the size of the cranial vault and of the vertebrae. Compression and injury of the cranial and spinal nerve roots, especially the optic nerve, may be visible. In outbreaks in which night blindness is the primary clinical sign, atrophy of the photoreceptor layer of the retina is evident histologically, but there are no gross lesions.
Congenital ocular abnormalities in newborn calves from vitamin A deficient heifer dams included aphakia, absence of a uveal tract and aqueous humour, microphalmos, bony outgrowths of the occipital bone, compression of the cerebellum and cardiac abnormalities similar to the tetralogy of Fallot.2
Squamous metaplasia of the interlobular ducts of the parotid salivary gland is strongly suggestive of vitamin A deficiency in pigs, calves, and lambs, but the change is transient and may have disappeared 2–4 weeks after the intake of vitamin A is increased. This microscopic change is most marked and occurs first, at the oral end of the main parotid duct. Abnormal epithelial cell differentiation may also be observed histologically in a variety of other sites such as the tracheal, esophageal, and ruminal mucosae, preputial lining, pancreatic ducts, and urinary epithelium. Hypovitaminosis-A has also been associated with an increased incidence of pituitary cysts in cattle. Secondary bacterial infections, including pneumonia and otitis media, are also common, due at least in part to the decreased barrier function of the lining epithelia.
The abnormalities that occur in congenitally affected pigs have already been described.
• Toxicology – 50 g liver, 500 g feed ASSAY (Vit A)
• Histology – formalin-fixed parotid salivary gland (including duct), rumen, pituitary, pancreas, brain (including optic nerves), cervical spinal cord (including nerve roots); Bouin’s-fixed eye (LM).
When the characteristic clinical findings of vitamin A deficiency are observed, a deficiency of the vitamin should be suspected if green feed or vitamin A supplements are not being provided. The detection of papilledema and testing for night blindness are the easiest methods of diagnosing early vitamin A deficiency in ruminants. Incoordination, paralysis, and convulsions are the early signs in pigs. Increase in CSF pressure is the earliest measurable change in both pigs and calves. Laboratory confirmation depends upon estimations of vitamin A in plasma and liver, the latter being most satisfactory. Unless the disease has been in existence for a considerable time, response to treatment is rapid. For confirmation at necropsy, histological examination of parotid salivary gland and assay of vitamin A in the liver, are suggested.
The salient features of the differential diagnosis of diseases of the nervous system of cattle are summarized in Table 32.3.
Convulsive form of vitamin A deficiency in cattle must be differentiated from:
• Polioencephalomalacia: characterized by sudden onset of blindness, head-pressing, and tonic-clonic convulsions, usually in grain-fed animals but also in pastured animals ingesting an excess of sulfate in water and grass
• Hypomagnesemic tetany: primarily in lactating dairy cattle on pasture during cool windy weather; characterized by hyperesthesia, champing tonic-clonic convulsions, normal eyesight and tachycardia, and loud heart sounds
• Lead poisoning: in all age groups, but most commonly in pastured calves in the spring; characterized by blindness, tonic-clonic convulsions, champing of the jaw, head-pressing, and rapid death
• Rabies: in all age groups; characterized by bizarre mental behavior, gradually progressive ascending paralysis with ataxia leading to recumbency, drooling saliva, inability to swallow, normal eyesight, and death in 4–7 days.
Ocular form of vitamin A deficiency in cattle must be differentiated from those diseases of cattle characterized by central or peripheral blindness:
Bilateral ophthalmitis due to ocular disease.
Loss of body condition in cattle, failure to grow and poor reproductive efficiency are general clinical findings not limited to vitamin A deficiency.
Convulsive form of vitamin A deficiency in pigs must be differentiated from:
Paralytic form of vitamin A deficiency in pigs must be differentiated from:
Congenital defects similar to those caused by vitamin A deficiency may be caused by deficiencies of other essential nutrients, by inheritance or by viral infections in early pregnancy in all species. Maternal vitamin A deficiency is the most common cause of congenital defects in piglets. Final diagnosis depends upon the necropsy findings, analysis of feed and serum vitamin A of the dams.
Animals with curable vitamin A deficiency should be treated immediately with vitamin A at a dose rate equivalent to 10–20 times the daily maintenance requirement. As a rule, 440 IU/kg BW is the dose used. Parenteral injection of an aqueous rather than an oily solution is preferred. The response to treatment in severe cases is often rapid and complete, but the disease may be irreversible in chronic cases. Calves with the convulsive form due to increased CSF pressure will usually return to normal in 48 h following treatment. Cattle with the ocular form of the deficiency and that are blind will not respond to treatment and should be slaughtered for salvage.
Daily heavy dosing (about 100 times normal) of calves causes reduced growth rate, lameness, ataxia, paresis, exostoses on the planter aspect of the third phalanx of the fourth digit of all feet, and disappearance of the epiphyseal cartilage. Persistent heavy dosing in calves causes lameness, retarded horn growth and depressed CSF pressure. At necropsy, exostoses are present on the proximal metacarpal bones and the frontal bones are thin. Very high levels fed to young pigs may cause sudden death through massive internal hemorrhage and excessive doses during early pregnancy are reputed to result in fetal anomalies. However, feeding vitamin A for prolonged periods at exceptionally high levels is unlikely to produce severe embryotoxic or teratogenic effects in pigs.
The minimum daily requirement in all species is 40 IU of vitamin A/kg BW, which is a guideline for maintenance requirements. In the formulation of practical diets for all species, the daily allowances of vitamin A are commonly increased by 50–100% of the daily minimum requirements. During pregnancy, lactation, or rapid growth the allowances are usually increased by 50–75% of the requirements. The supplementation of diets to groups of animals is governed also by their previous intake of the vitamin and its probable level in the diet being fed. The rate of supplementation can vary from 0 to 110 IU/kg BW/d (1 IU of vitamin A is equivalent in activity to 0.3 μg of retinol; 5–8 μg β-carotene has the same activity as 1 μg of retinol).
Nutrient studies have indicated that pre-ruminant Holstein calves being fed milk replacer should receive 11 000 IU of vitamin A/kg DM for optimum growth and to maintain adequate liver vitamin A stores.20
The amounts of the vitamin to be added to the ration of each species to meet the requirements for all purposes should be obtained from published recommended nutrient requirements of domestic animals. Some examples of daily allowances of vitamin A for farm animals are set out in Table 30.11.
Table 30.11 Daily dietary allowances of vitamin A
| Animal | Vitamin A (IU/kg BW daily) | |
|---|---|---|
| Cattle | ||
| Growing calves | 40 | |
| Weaned beef calves at 6–8 months | 40 | |
| Calves 6 months to yearlings | 40 | |
| Maintenance and pregnancy | 70–80 | |
| Maintenance and lactation | 80 | |
| Feedlot cattle on high energy ration | 80 | |
| Sheep | ||
| Growth and early pregnancy and fattening lambs | 30–40 | |
| Late pregnancy and lactation | 70–80 | |
| Pigs | ||
| Growing pigs | 40–50 | |
| Pregnant gilts and sows | 40–50 | |
| Lactating gilts and sows | 70–80 | |
| Horses | ||
| Working horse | 20–30 | |
| Growing horse | 40 | |
| Pregnant mare | 50 | |
| Lactating mare | 50 | |
The method of supplementation will vary depending on the class of livestock and the ease with which the vitamin can be given. In pigs, the vitamin is incorporated directly into the complete ration, usually through the protein supplement. In feedlot and dairy cattle receiving complete feeds, the addition of vitamin A to the diet is simple. In beef cattle, which may be fed primarily on carotene-deficient roughage during pregnancy, it may not be possible to supplement the diet on a daily basis. However, it may be possible to provide a concentrated dietary source of vitamin A on a regular basis by feeding a protein supplement once weekly. The protein supplement will contain 10–15 times the daily allowance, which permits hepatic storage of the vitamin.
An alternative method to dietary supplementation is the IM injection of vitamin A at intervals of 50–60 days at the rate of 3000–6000 IU/kg BW. Under most conditions, hepatic storage is good and optimum plasma and hepatic levels of vitamin A are maintained for up to 50–60 days. In pregnant beef cattle the last injection should not be more than 40–50 days before parturition to insure adequate levels of vitamin A in the colostrum. Ideally, the last injection should be given 30 days before parturition but this may not be practical under some management conditions. However, the most economical method of supplementing vitamin A is, in most cases, through the feed and when possible should be used.
The use of injectable mixtures of vitamins A, D, and E is not always justifiable. The injection of a mixture of vitamins A, D, and E of feeder cattle in northern Australia prior to transport did not, contrary to anecdotal evidence, reduce weight loss associated with transportation.21 Cattle in Queensland and north-western Australia have very high concentrations of hepatic vitamin A and in fact, drought-stricken cattle in the terminal stages of malnutrition have also had high liver concentration. The indiscriminate use of vitamin A preparations in cattle is a public health concern because some bovine livers may contain high levels of vitamin A which are potentially teratogenic for pregnant women.22
The oral administration of a single bolus of vitamin A at a dose of 2.8 mg/kg BW to debilitated Sahelian cattle during the dry season was effective in raising the milk levels of vitamin A and was as effective as adding 10 g of the powder to the drinking water.4 Both the powder and bolus products provided high levels of vitamin A in milk within 3 days of treatment and according to herder testimonials, night-blind people consuming milk from cattle previously treated with either oral vitamin A preparation were no longer affected with night blindness.
1 Davies IH. Cattle Pract. 2000;8:139.
2 Mason CS, et al. Vet Rec. 2003;153:213.
3 Molokwu ECI. Br Vet J. 1978;134:493.
4 Remillard RL, et al. Prev Vet Med. 1990;9:173.
5 van der Lugt JJ, Prozesky L. Am J Vet Res. 1989;56:99.
6 Divers TJ, et al. J Am Vet Med Assoc. 1986;189:1579.
7 Paulsen ME, et al. J Am Vet Med Assoc. 1989;194:933.
8 Booth A, et al. J Am Vet Med Assoc. 1987;190:1305.
9 Sustronck B, et al. Vlaams Diergen Tijdschrift. 1993;62:95.
10 Salum MR, Njavike SM. Bull Anim Health Prod Africa. 1993;41:163.
11 Doige CE, Schoonderwoerd M. J Am Vet Med Assoc. 1988;193:691.
12 Holland RE, et al. Dig Dis Sci. 1993;38:333.
13 Chew BP. J Dairy Sci. 1987;70:2732.
14 Tjoelker LW, et al. J Dairy Sci. 1988;71:3112. 3120
15 Bruns NJ, Webb KEJr. J Anim Sci. 1990;68:454.
16 Lakritz J, et al. J Am Vet Med Assoc. 1993;202:1276.
17 Brenner J, et al. Israel J Vet Med. 1998;53:78.
18 Chew BP, et al. J Dairy Sci. 1984;67:1316.
19 Maepaa PH, et al. Equine Vet J. 1987;19:237.
20 Swanson KS, et al. J Dairy Sci. 2000;83:2027.
A primary deficiency of vitamin K is unlikely under natural conditions in domestic animals because of the high content of substances with vitamin K activity in most plants and the substantial synthesis of these substances by microbial activity in the alimentary canal. Sporadic cases may occur when impairment of the flow of bile reduces the digestion and absorption of this fat-soluble vitamin. Experimentally produced vitamin K deficiency in piglets is manifested by hypersensitivity, anemia, anorexia, weakness, and a marked increase in prothrombin time. The minimum daily requirement for newborn pigs is 5 μg/kg BW and the minimum curative injection dose is four times larger.
A hemorrhagic disease of recently weaned pigs from 6 to 15 weeks of age is considered to be associated with vitamin K deficiency.1 Affected pigs fail to grow, become pale, develop large subcutaneous hematomas and exhibit lameness and epistaxis.1 Excessive and fatal hemorrhage following routine castration may occur in pigs from 30 to 40 days of age, but not at 15–20 days of age.2 Subcutaneous massive hemorrhage is more common in pigs at 40–70 days of age. Prothrombin time and activated partial thromboplastin time are prolonged along with decreased levels of vitamin K-dependent factors II, VII, IX, and X.2 At necropsy, hemorrhages are extensive in the muscles of the hindlimbs, forelimbs, and axillary and mandibular region.
Vitamin K, or vitamin K2, given at a dose of 3 mg/kg BW IM as a single dose will restore the blood coagulation defects to normal.3 Vitamin K3 added to the feed at a rate of 25 mg/kg for 4 days was also effective. The cause of the vitamin K deficiency was considered to be related to the use of antibacterial drugs in the feed but this has not been substantiated.
The most important therapeutic use of vitamin K in domestic animals is in sweet clover poisoning where toxic quantities of coumarin severely depress the prothrombin levels of the blood and interfere with its clotting mechanism. Industrial poisons used in rodent control which contain anticoagulants of the coumarin type, e.g. warfarin, cause fatal hypothrombinemia; vitamin K is an effective antidote. For warfarin-induced anticoagulation in the horse, the administration of 300–500 mg of vitamin K1 SC every 4–6 h until the prothrombin time returns to baseline values is recommended.4
Diseases associated with deficiencies of water-soluble vitamins
Water-soluble vitamins, including vitamin C and the B complex, are of minor importance in ruminants (except for vitamin B12) because of their synthesis in the alimentary tract of these animals.
The dairy cow’s requirements for the B-complex vitamins were established in the 1940–1950s. At that time, vitamin requirements were defined as the smallest dietary amount necessary to prevent clinical signs of deficiency.1 It was demonstrated that even when fed a vitamin-free diet, the synthesis of B-complex vitamins by the rumen microflora was sufficient to avoid deficiencies. Consequently, it was concluded that a dietary supply of B-complex vitamins was unnecessary in ruminants. However, there is now evidence that in high-producing dairy cows the requirements for biotin, nicotinic acid, folic acid, and vitamin B12 are increased under certain circumstances and the amounts supplied by the diet and by ruminal synthesis are not always adequate to maximize health and productivity of dairy cows.1
Niacin requirements per feed unit are higher with high-energy feeds. Niacin increases the number of ruminal protozoa and in cows with clinical or subclinical ketosis, repeated doses of niacin lead to a rapid decrease of non-esterified fatty acids. Dietary supplementation of niacin at 6 mg/d, have improved milk production.
Biotin supplementation of 20 mg/head per day in early lactation can result in improved hoof horn health. After 5 months of biotin supplementation, there is an improvement in the quality and resistance of cow heel and sole horns but 10 months of supplementation is required before an improvement in quality of coronary horn is observed.
Folic acid is essential for cell division and growth for protein synthesis. Supplementation of folic acid may increase milk production but there is insufficient data available to make a recommendation.
Vitamin B12 requirements are usually met by ruminal microflora synthesis if the dietary supply cobalt is adequate. High concentrate diets can modify bacterial synthesis of the vitamin and metabolic utilization of propionate increases the demand for Vitamin B12.
Thiamin, nicotinic acid, riboflavin, pantothenic acid, pyridoxine, biotin, and folic acid are all synthesized by microbial activity. Nicotinic acid and vitamin C are synthesized by other means. The young calf or lamb, in the period before ruminal activity begins, is likely to receive inadequate supplies of these vitamins and deficiency states can be produced experimentally. In the pre-ruminant stage, colostrum and milk are good sources of the water-soluble vitamins, ewes’ milk being much richer than cows’ milk. The production of signs of deficiency of the B vitamins in horses by the feeding of deficient diets has raised some doubts as to the availability of the B vitamins synthesized in the large intestine in this species.
Vitamin C is synthesized by all species and is not an important dietary essential in any of the domestic animals. Synthesis occurs in tissues and, although blood levels fall after birth, in the newborn calf they begin to rise again at about 3 weeks of age. However, a dermatosis of young calves has been associated with low levels of ascorbic acid in their plasma and responds to a single injection of 3 g of ascorbic acid. A heavy dandruff, followed by a waxy crust, alopecia and dermatitis commences on the ears and spreads over the cheeks, down the crest of the neck and over the shoulders. Some deaths have been recorded, but spontaneous recovery is more usual.
There is some interest in the administration of high doses of ascorbic acid orally to horses to counteract the effects of stress and minimize the effects of infections. A single oral dose of 20 g of ascorbic acid does not result in any increase in plasma concentrations. However, daily administration of either 4.5 g or 20 g results in significant increases in plasma concentrations.2
The disease caused by deficiency of thiamin in tissues is characterized chiefly by nervous signs.
Thiamin deficiency may be primary, due to deficiency of the vitamin in the diet, or secondary, because of destruction of the vitamin in the diet by thiaminase. A primary deficiency is unlikely under natural conditions because most plants, especially seeds, yeast, and milk contain adequate amounts.
Thiamin is normally synthesized in adequate quantities in the rumen of cattle and sheep on a well-balanced roughage diet. The degree of synthesis is governed to some extent by the composition of the ration, a sufficiency of readily fermentable carbohydrate causing an increase of synthesis of most vitamins of the B complex and a high intake in the diet reducing synthesis. The etiology of polioencephalomalacia has been discussed in detail under that heading. Microbial synthesis of thiamin also occurs in the alimentary tract of monogastric animals and in young calves and lambs, but not in sufficient quantities to avoid the necessity for a dietary supply, so that deficiency states can be readily induced in these animals with experimental diets. Thiamin is relatively unstable and easily destroyed by cooking.
The coccidiostat amprolium is a thiamin antagonist and others are produced by certain plants, bacteria, fungi, and fish.
One of the best examples of secondary thiamin deficiency is inclusion of excess raw fish in the diet of carnivores, resulting in destruction of thiamin because of the high content of thiaminase in the fish.
Two major occurrences of secondary thiamin deficiency are recorded. In horses, the ingestion of excessive quantities of bracken fern (Pteridium aquilinum) and horsetail (Equisetum arvense) causes nervous signs because of the high concentration of thiaminase in these plants. The disease has been induced in a pig fed bracken rhizomes and the possibility exists of it occurring under natural conditions. It has also been reported in horses fed large quantities of turnips (Beta vulgaris) without adequate grain. The second important occurrence of thiamin deficiency is in the etiology of polioencephalomalacia and is discussed under that heading.
A thiaminase-induced subclinical thiamin deficiency causing suboptimal growth rate of weaner lambs has been described.1 Higher levels of thiaminase activity were present in the feces and rumen contents of lambs with poor growth rate compared with normal lambs. Bacillus thiaminolyticus was isolated from the feces and ruminal fluids of affected lambs and supplementation of thiaminase-excreting lambs with IM injections of thiamine hydrochloride was associated with significantly improved growth rate.1
Thiamin deficiency occurs in sheep being subjected to live export from Australia to the Middle East.2 Sheep that died or were clinically ill and euthanized had significantly lower hepatic and ruminal thiaminase concentrations than clinically healthy control sheep. A high proportion had thiamin concentrations comparable with those found in sheep that die with polioencephalomalacia. The evidence indicates that the thiamin deficiency is a primary one associated with deprivation of feed during transportation to the pre-embarkation feedlots. The low feed intake and failure of the ruminal microbes to adapt, thrive and synthesize a net surplus of thiamin during alterations in the ruminal environment are considered to be major contributing factors.
The only known function of thiamin is its activity as a cocarboxylase in the metabolism of fats, carbohydrates and proteins and a deficiency of the vitamin leads to the accumulation of endogenous pyruvates. Although the brain is known to depend largely on carbohydrate as a source of energy, there is no obvious relationship between a deficiency of thiamin and the development of the nervous signs which characterize it. Polioencephalomalacia has been produced experimentally in pre-ruminant lambs on a thiamin-free diet. There are other prodromal indications of deficiency disease. For example, there is a decrease in erythrocyte precursors and in erythrocyte transketolase. Additional clinical signs also in the circulatory and alimentary systems, but their pathogenesis cannot be clearly related to the known functions of thiamin. Subclinical thiamin deficiency due to thiaminases in the alimentary tract is associated with low erythrocyte transketolase activities and elevated thiamin pyrophosphate effects, which may explain the poor growth rate.1
Incoordination and falling and bradycardia due to cardiac irregularity, are the cardinal clinical signs of bracken fern poisoning in the horse. These signs disappear after the parenteral administration of thiamin. Similar clinical effects occur with horsetail. Swaying from side to side occurs first, followed by pronounced incoordination, including crossing of the forelegs and wide action in the hindlegs. When standing, the legs are placed well apart and crouching and arching of the back are evident. Muscle tremor develops and eventually the horse is unable to rise. Clonic convulsions and opisthotonos are the terminal stage. Appetite is good until late in the disease when somnolence prevents eating. Temperatures are normal and the heart rate slow until the terminal period when both rise to above normal levels. Some evidence has also been presented relating the occurrence of hemiplegia of the vocal cords in horses with a below normal thiamin status. Neither plant is palatable to horses and poisoning rarely occurs at pasture. The greatest danger is when the immature plants are cut and preserved in meadow hay.
These syndromes have not been observed to occur naturally but are produced readily on experimental rations.
In pigs, inappetence, emaciation, leg weakness and a fall in body temperature, respiratory rate, and heart rate occur. The electrocardiogram is abnormal and congestive heart failure follows. Death occurs in 5 weeks on a severely deficient diet. In calves, weakness, incoordination, convulsions, and retraction of the head occur and in some cases anorexia, severe scouring and dehydration.
Lambs 1–3 days old placed on a thiamin-deficient diet show signs after 3 weeks. Somnolence, anorexia, and loss of condition occur first, followed by tetanic convulsions.
Horses fed amprolium (400–800 mg/kg BW daily) developed clinical signs of thiamin deficiency after 37–58 days. Bradycardia with dropped heart beats, ataxia, muscle fasciculation and periodic hypothermia of hooves, ears, and muzzle were the common signs, with blindness, diarrhea, and loss of body weight occurring inconstantly.
Blood pyruvic acid levels in horses are raised from normal levels of 2–3 μg/dL to 6–8 μg/dL. Blood thiamin levels are reduced from normal levels of 8–10 μg/dL to 2.5–3.0 μg/dL. Electrocardiograms show evidence of myocardial insufficiency. In pigs, blood pyruvate levels are elevated and there is a fall in blood transketolase activity. These changes occur very early in the disease. In sheep subjected to export, liver and rumen thiamin concentrations and erythrocyte transketolase activities, were all below levels found in clinically normal sheep.2
No macroscopic lesions occur in thiamin deficiency other than non-specific congestive heart failure in horses. The myocardial lesions are those of interstitial edema and lesions are also present in the liver and intestine.
In the experimental syndrome in pigs, there are no degenerative lesions in the nervous system, but there is multiple focal necrosis of the atrial myocardium accompanied by macroscopic flabbiness and dilatation without hypertrophy of the heart.
Diagnosis of secondary thiamin deficiency in horses must be based on the signs of paralysis and known access to bracken fern or horsetail. A similar syndrome may occur with poisoning by:
It is accompanied by hepatic necrosis and fibrosis. The encephalomyelitides are usually accompanied by signs of cerebral involvement, by fever and failure to respond to thiamin therapy.
In clinical cases the injection of a solution of the vitamin produces dramatic results (5 mg/kg BW given every 3 h). The initial dose is usually given IV followed by IM injections for 2–4 days. An oral source of thiamin should be given daily for 10 days and any dietary abnormalities corrected.
Although riboflavin is essential for cellular oxidative processes in all animals, the occurrence of deficiency under natural conditions is rare in domestic animals because actively growing green plants and animal protein are good sources and some synthesis by alimentary tract microflora occurs in all species. Synthesis by microbial activity is sufficient for the needs of ruminants but a dietary source is required in these animals in the pre-ruminant stage. Milk is a very good source. Daily requirements for pigs are 60–80 μg/kg BW and 2–3 g/tonne of feed provides adequate supplementation. The trend towards confinement feeding of pigs has increased the danger of naturally occurring cases in that species.
On experimental diets the following syndromes have been observed:
• Pigs: slow growth, frequent scouring, rough skin, and matting of the hair coat with heavy, sebaceous exudate are characteristic. There is a peculiar crippling of the legs with inability to walk and marked ocular lesions, including conjunctivitis, swollen eyelids, and cataract. The incidence of stillbirths may be high
• Calves: anorexia, poor growth, scours, excessive salivation and lacrimation, and alopecia occur. Areas of hyperemia develop at the oral commissures, on the edges of the lips, and around the navel. There are no ocular lesions.
Nicotinic acid or niacin is essential for normal carbohydrate metabolism. Because of the high content in most natural animal feeds, deficiency states are rare in ordinary circumstances, except in pigs fed rations high in corn. Corn has both a low niacin content and a low content of tryptophan, a niacin precursor. A low protein intake exacerbates the effects of the deficiency, but a high protein intake is not fully protective.
In ruminants, synthesis within the animal provides an adequate source. Even in young calves, signs of deficiency do not occur and because rumen microfloral activity is not yet of any magnitude, extra-ruminal synthesis appears probable.
The oral supplementation of niacin in the diet of periparturient dairy cows may result in an increase in serum inorganic phosphorus and a decrease in serum potassium, calcium, and sodium concentrations. Niacin has been used to study the effects of artificially induced ketonemia and hypoglycemia in cattle.
The daily requirements of niacin for mature pigs are 0.1–0.4 mg/kg BW, but growing pigs appear to require rather more (0.6–1 mg/kg BW) for optimum growth.
Experimentally induced nicotinic acid deficiency in pigs is characterized by inappetence, severe diarrhea, a dirty yellow skin with a severe scabby dermatitis and alopecia. Posterior paralysis also occurs. At necropsy, hemorrhages in the gastric and duodenal walls, congestion and swelling of the small intestinal mucosa, and ulcers in the large intestine are characteristic and closely resemble those of necrotic enteritis caused by infection with Salmonella spp.
Histologically, there is severe mucoid degeneration followed by local necrosis in the wall of the cecum and colon. Experimental production of the disease in pigs by the administration of an antimetabolite to nicotinamide causes ataxia or quadriplegia, accompanied by distinctive lesions in the gray matter of the cervical and lumbar enlargements of the ventral horn of the spinal cord. The lesions are malacic and occur in the intermediate zone of the gray matter. The identical lesions and clinical picture have been observed in naturally occurring disease.
The oral therapeutic dose rate of nicotinic acid in pigs is 100–200 mg; 10–20 g/tonne of feed supplies sufficient nicotinic acid for pigs of all ages. Niacin is low in price and should always be added to pig rations based on corn.
A deficiency of pyridoxine in the diet is not known to occur under natural conditions. Experimental deficiency in pigs is characterized by periodic epileptiform convulsions and at necropsy by generalized hemosiderosis with a microcytic anemia, hyperplasia of the bone marrow, and fatty infiltration of the liver. The daily requirement of pyridoxine in the pig is of the order of 100 μg/kg BW or 1 mg/kg of solid food, although higher levels have been recommended on occasions. Certain strains of chickens have a high requirement for pyridoxine and the same may be true of pigs.
Experimentally induced deficiency in calves is characterized by anorexia, poor growth, apathy, dull coat and alopecia. Severe, fatal epileptiform seizures occur in some animals. Anemia with poikilocytosis is characteristic of this deficiency in cows and calves.
Pantothenic acid is a dietary essential in all species other than ruminants, which synthesize it in the rumen. Deficiency under natural conditions has been recorded mainly in pigs on rations based on corn.
In pigs, a decrease in weight gain due to anorexia and inefficient food utilization occurs first. Dermatitis develops with a dark brown exudate collecting about the eyes and there is a patchy alopecia. Diarrhea and incoordination with a spastic, goose-stepping gait are characteristic. At necropsy, a severe, sometimes ulcerative, colitis is observed constantly, together with degeneration of myelin.
Calcium pantothenate (500 μg/kg BW/d) is effective in treatment and prevention. As a feed additive, 10–12 g/tonne is adequate.
Experimentally induced pantothenic acid deficiency in calves is manifested by rough hair coat, dermatitis under the lower jaw, excessive nasal mucus, anorexia and reduced growth rate, and is eventually fatal. At necropsy, there is usually a secondary pneumonia, demyelination in the spinal cord and peripheral nerves and softening and congestion of the cerebrum.
Biotin or vitamin H, has several important biochemical functions. It is a cofactor in several enzyme systems involved in carboxylation and transcarboxylation reactions and consequently has a significant effect on carbohydrate metabolism, fatty acid synthesis, amino acid deamination, purine synthesis, and nucleic acid metabolism. Biotin is found in almost all plant and animal materials and, being required in very small quantities, is unlikely to be deficient in diets under natural conditions, especially as microbial synthesis occurs in the alimentary tract.
Biotin is now considered a significant factor in lameness of cattle.1 Biotin is important for the differentiation of epidermal cells which are required for normal production of keratin and hoof horn tissue. Biotin also acts as a co-factor in carboxylase enzymes and is an important factor in both gluconeogenesis and fatty acid synthesis. Significant differences in the fatty acid profile of horn tissue of cattle with claw lesions have been observed. Biotin supplementation reduces clinical white line disease, reduces horn lesions, and improves horn quality by strengthening the intercellular cementing material between keratinocytes.2 Improved hoof integrity in intensively managed dairy cows has occurred following biotin supplementation.3 However, a long period of supplementation is required before the effect of the vitamin on hoof health care is expressed. In addition, there may be improved milk production, milk composition, and cow fertility with biotin supplementation.
Biotin is synthesized in the rumen and absolute biotin deficiency has not been recognized. However, ruminal synthesis of biotin may be compromised by acidic conditions in the rumen, which may increase the need for supplementation of biotin in the diet of high-producing dairy cows. In the dairy cow in the periparturient period and early lactation, the levels of biotin may decrease. A decrease in plasma biotin levels of dairy cows at 25 days in milk (DIM), returning to constant levels from 100 DIM until the end of lactation.3 Feeding supplemental biotin at 20 g/d during the last 16 days post partum and at 30 g/d from calving through to 70 days post partum elevated concentrations of plasma and milk compared with cows unsupplemented with biotin.4 Supplemental biotin also elevated plasma glucose and lowered non-esterified fatty acids, which indicates that supplemental biotin is involved in hepatic gluconeogenesis. The triacylglycerol concentration in liver tended to decrease at a faster rate within 2 days after parturition.
The supplementation of Holstein cows in the Atherton Tablelands in Australia, with biotin at 20 mg/head per day resulted in improved locomotion scores compared to unsupplemented cows.5 In the wet summer period, the number of lame cows observed by the farmer, were significantly fewer during the rainy period for the biotin-supplemented herds and required fewer antibiotic treatments than unsupplemented herds. Most hoof lesions were most commonly observed in the outer claws of the hind limb.
In a randomized control field trial on five commercial dairy farms in Gloucestershire, south-west UK, the effect of parity and duration of supplementation with oral biotin at 20 mg/d on white line disease was studied over a period of 18 months.6 The incidence of white line disease increased with increasing parity independent of biotin supplementation from two cases per 100 cow years in primiparous cows to 15.5 cases per 100 cow years in all multiparous cows, but up to 47.7 cases per 100 cow years for cows in parities =5. Supplementation with biotin reduced white line disease lameness by 45% in multiparous cows down to 8.5 cases per 100 cow years, whereas the effect of biotin supplementation in primiparous cows was not significant. A supplementation of length of at least 6 months was required to reduce the risk of white line lameness in multiparous cows. The overall incidence rate of lameness (per 100 cows per year) was 68.9 with a range of 31.6 to 111.5 per farm.5,7 The incidence rates of the four most frequently reported causes of lameness were sole ulcer, 13.8; white line separation, 12.7; digital dermatitis, 12.0; and interdigital necrobacillosis, 7.1 per 100 cows per year. The incidence of lameness was highly variable between farms. However, when the data from all farms were pooled, the risk of lameness caused by white line separation in cattle supplemented with biotin was approximately 50%. Approximately 130 days of biotin supplementation is required before a significant difference in white line lesion lameness occurs.
A controlled 14-month field trial evaluated the effect of biotin supplementation on hoof lesions, milk production and reproductive performance of dairy cows housed in the same free-stall facility with the same environment, base diet, and management.8 Supplemented cows received 20 mg/d by computer feeder. The feet of a select number of cows were trimmed three times at 6-month intervals and hoof health was evaluated. At the final hoof trimming, the incidence of sole hemorrhages was significantly higher in the control group (50%) compared with the supplemented group at 24%. No cases of lameness occurred. Milk production and fat yield increased in all parities and fertility was improved in first calf heifers.
It is possible that biotin improves the quality of claw horn, which encourages the replacement of defective horn, improves healing and makes it less likely for sole lesions to develop from laminitis in its early stages. The administration of biotin at 40 mg per day for 50 days to dairy cows with uncomplicated sole ulcers, resulted in significant improvement in histological horn quality of the newly formed epidermis covering the sole ulcer.9 Biotin supplementation at 20 mg/d did not affect the tensile strength of the white line.10
Vertical fissures, or sandcracks, are vertical cracks of the hoof that may extend across the coronary band and continue to the bearing surface of the dorsal wall of the claw.11 Sandcracks are common in beef cattle in western Canada. One survey, 37.5% of beef cows were affected with one or more cracks. Supplementary dietary biotin at 10 mg/head per day significantly increased serum levels of biotin and increased claw hardness compared with unsupplemented cows. After 18 months, 15% of the biotin supplemented cows had vertical fissures compared with 35% in the unsupplemented cows.
The principal source of biotin for the pig is the feed it receives and feeds vary greatly in their biotin content and in the biological availability of that biotin. Diets based on cereals with a low available biotin content may provide insufficient dietary biotin for the maintenance of hoof horn integrity in pigs. The biotin content in basal diets fed to pigs has varied from 29 to 15 μg/kg available biotin and supplementation of these diets has resulted in improvements in litter size. Continuous feeding of sulfonamides or antibiotics may induce a deficiency. An antivitamin to biotin (avidin) occurs in egg white and biotin deficiency can be produced experimentally by feeding large quantities of uncooked egg white.12
In pigs, experimental biotin deficiency is manifested by alopecia, dermatitis, and painful cracking of the soles and the walls of the hooves.13,14
Naturally occurring outbreaks of lameness in gilts and sows associated with lesions of the soles and the walls of the hooves, which responded to biotin supplementation, have now been well-described.13,14 The severe lameness and long course of convalescence have been responsible for a high rate of culling in breeding animals. In gilts fed a basal diet with a low level of biotin (32 μg available biotin/kg) from 25 kg live weight to 170 days of age, there were no significant differences in the number of lesions and claws affected compared with gilts fed a biotin-supplemented diet (350 μg available biotin/kg).15 However, between 170 days of age and the first weaning, the incidence of hoof lesions increased markedly. Over the next four litters, the incidence of lesions increased with the age of the sow. The predominant lesions in the foot were cracks, which occurred mainly in two associated regions: the heel/toe junction and the heel and the sidewall and adjacent white-line region of the toe.15 Supplementation of the diet of breeding sows with biotin at an early stage of development makes a significant contribution to the maintenance of horn integrity.
Affected animals become progressively lame after being on a biotin-deficient ration for several months. Arching of the back and a haunched stance with the hindlegs positioned forward occurs initially. This posture has been described as a ‘kangaroo’-sitting posture. The foot pads become softer and the hoof horn less resilient. The feet are painful and some sows will not stand for breeding. Deep fissures at the wall-sole junction may extend upwards beneath the wall horn and gaping cracks may separate the toe and heel volar surfaces. The foot pads initially show excessive wear, later longitudinal painful cracks develop. In well-developed cases, the foot pads appear enlarged, the cracks are obvious and covered by necrotic debris. The foot pads of the hindfeet are usually more severely affected that those of the forefeet and the lateral digit is more frequently affected. The dewclaws also are affected by cracks and the accumulation of necrotic tissue.
Skin lesions also develop in affected gilts and sows. There is gradual alopecia, particularly over the back, the base of the tail, and the hindquarters. The hairs are more bristly than normal and break easily. The alopecia is accompanied by a dryness of the skin.
As the lesions of the feet and skin develop there is a marked drop in the serum biotin concentrations, which is considered as a sensitive index of biotin deficiency.12 Adequate biotin status may be indicated by serum biotin levels (ng/L) >700; marginal, 600–700; inadequate, 400–600; and deficient below 400.12 Compression and hardness tests made on external hoof have also been used as an indirect measure of biotin adequacy in pigs.16 The tests indicate that significant improvements in the strength and hardness of pig hoof horn are produced by biotin. Supplementation of the diet with biotin does not affect either horn growth or wear rates.14 Biotin supplementation does affect the structure of the coronary epidermis; there is an increase in the density of the horn tubules in the stratum medium, the horny squames in the stratum medium are more tightly packed and the tubules are more clearly defined.17
Reproductive performance of sows is also influenced by their biotin status.18 Supplementation of the diet with biotin may increase litter size, increase the number of pigs weaned, decrease the mean interval in days from weaning to service and improve conception rate. Over a period of four parities, piglet production increased by 1.42 pigs/sow year.18
The daily requirements of biotin for pigs have not been well-defined, but certain amounts have been associated with an absence of lameness and improved reproductive performance. Basic diets for gilts contain 35–50 μg/kg and the addition of 350–500 μg/kg is recommended. This provides a daily intake of 4.0–5.0 mg/sow per day. The response to dietary supplementation may take several months; therefore, supplementation should begin at weaning. The details of biotin studies in pigs, including experimental deficiency, the absorption and synthesis of biotin, biotin availability in feedstuffs, and the biotin requirements of the growing pig are available.19
Supplementation of a basal diet, calculated to contain 56 μg/kg available biotin with daily allowances of biotin at 1160 μg/sow per day in pregnancy and 2320 μg/sow per day in lactation, produced significant improvements in litter size in second and fourth parity sows. It is suggested that the requirement is in excess of 175 μg available biotin per kg of diet.18 In a swine herd with a lameness problem, the supplementation of the sow’s ration during pregnancy and lactation with daily intakes of biotin of 400 and 800 μg/sow per day, respectively and the rations of the weaners and growers to 150 and 250 was effective.
The dietary supplementation of horses with 10–30 mg biotin/d for 6–9 months is considered to be effective as an aid in the treatment of weak horn hoof in horses.20 The hoof horn quality of more than two-thirds of the Lippizaner horses had moderate to severe changes: microcracks visible in the transition from the middle to the inner zone of the coronary horn; separation of the sole from the coronary horn in the region within the white zone. Biotin supplementation for 19 months improved horn quality.21 Continuous dietary supplementation with biotin at a daily dose of 20 mg is necessary to improve and maintain hoof horn quality in horses with less than optimum quality hoof.22
1 Hedges VJ, et al. Cattle Pract. 2002;10:157.
2 Mulling CK, et al. Anat Histol Embryol. 1999;28:103.
3 Midla LT, et al. Am J Vet Res. 1998;59:733.
4 Rosendo O, et al. J Dairy Sci. 2004;87:2535.
5 Fitzgerald T, et al. J Dairy Sci. 2000;83:338.
6 Potzsch CJ, et al. J Dairy Sci. 2003;86:2577.
7 Hedges J, et al. J Dairy Sci. 2001;84:1969.
8 Bergsten C, et al. J Dairy Sci. 2003;86:3953.
9 Lischer CHJ, et al. Vet J. 2002;163:51.
10 Collis VJ, et al. J Dairy Sci. 2004;87:2874.
11 Campbell JR, et al. Can Vet J. 2000;41:690.
12 Misir R, et al. Can Vet J. 1986;60:106.
13 Thomas KW, et al. Aust Vet J. 1990;67:215.
14 Johnston AM, Penny RHC. Vet Rec. 1989;125:130.
15 Simmins PH, Brooks PH. Vet Rec. 1988;122:431.
16 Webb NG, et al. Vet Rec. 1984;114:185.
17 Kempson SA, et al. Vet Rec. 1989;124:37.
18 Simmins PH, Brooks PH. Vet Rec. 1983;112:415.
19 Kopinski JS, et al. Br J Nutr. 1989;62:751. 761, 767, 773, 781
20 Comben N, et al. Vet Rec. 1984;115:642.
Folic acid (pteroylglutamic acid) is necessary for nucleic acid metabolism and its deficiency in humans leads to the development of pernicious anemia. A dietary source is necessary to all species and an adequate intake is provided by pasture. Although naturally occurring deficiencies have not been diagnosed positively in domestic animals, folic acid has numerous and complex interrelationships with other nutrients and the possibility of a deficiency playing a part in inferior animal performance should not be overlooked. The vitamin has a particular interest for equine nutritionists. Permanently stabled horses and some horses in training may require additional folic acid, preferably on a daily basis by the oral route.1 Folic acid deficiency can be induced in fetal foals and adult horses by administration of folate orally coincident with administration of inhibition of folate metabolism (pyrimethamine trimethoprim, sulfonamides).2,3 Folic acid at a dose of 1 mg/kg BW orally daily for 2 weeks was used successfully for the treatment of acquired alopecia in a 3-week-old Charolais calf, but spontaneous recovery without treatment was a possibility.4
Choline is a dietary essential for pigs and young calves. Calves fed on a synthetic choline-deficient diet from the second day of life develop an acute syndrome in about 7 days. There is marked weakness and inability to get up, labored or rapid breathing, and anorexia. Recovery follows treatment with choline. Older calves are not affected. On some rations, the addition of choline increases daily gain in feedlot steers, particularly during the early part of the feeding period.
Supplementation of 20 g/day of rumen protected choline to dairy cows 14 days before parturition increased milk production during the first month of lactation and the concentration of choline in milk, but did not affect fat or protein concentration in the milk, or plasma levels of glucose, β-hydroxybutyrate, cholesterol and non-esterified fatty acids (NEFA).1 The NEFA concentrations at the time of parturition were lower in treated animals than in controls, indicating improved lipid metabolism. Choline also increased α-tocopherol plasma concentrations.
In pigs, ataxia, fatty degeneration of the liver and a high mortality rate occur. Enlarged and tender hocks have been observed in feeder pigs. For pigs, 1 kg/tonne of food is considered to supply sufficient choline.2
Congenital splayleg of piglets has been attributed to choline deficiency but adding choline to the ration of the sows does not always prevent the condition.
Vitamin B12deficiency is unlikely to occur under natural conditions other than because of a primary dietary deficiency of cobalt, which is an important disease in many countries of the world.
Although microbial synthesis of the vitamin occurs in the rumen in the presence of adequate cobalt and in the intestines of other herbivores such as the horse, it is probably a dietary essential in the pig and young calf. Animal protein is a good source. A deficiency syndrome has been produced in young calves on a synthetic ration. Signs include anorexia, cessation of growth, loss of condition, and muscular weakness. The daily requirement under these conditions is 20–40 μg of vitamin B12. Sows vary in their ability to absorb the vitamin and those with poor absorption ability, or on deficient diets, show poor reproductive performance. For pigs, 10–50 mg/tonne of feed is considered to be adequate.1
The vitamin is used empirically in racing dogs and horses to alleviate parasitic and dietetic anemias in these animals at a dose rate of 2 μg/kg BW. Cyanocobalamin zinc tannate provides effective tissue levels of vitamin B12 for 2–4 weeks after one injection and normal and abnormal blood levels have been established for all species. It is also used as a feed additive for fattening pigs, usually in the form of fish or meat meal or as ‘animal protein factor’. It is essential as a supplement if the diet contains no animal protein and maximum results from the feeding of antibiotics to pigs are obtained only if the intake of vitamin B12 is adequate.