Occurrence

The disease occurs most commonly within the first 2 or 3 days after calving in high-producing dairy cows immediately following milk fever. Cattle may also become persistently recumbent for many reasons other than complications of milk fever such as peracute coliform mastitis and carbohydrate engorgement.

Downer cows can be divided generally into non-ambulatory cows with non-progressive neurological findings and non-ambulatory with progressive neurological findings indicative of the presence of lesions in the nervous system as the cause of the recumbency.²

A survey of bovine veterinarians in the USA in 1998 collected data on non-ambulatory dairy and beef cows with non-progressive neurological findings, and non-ambulatory with progressive neurological findings.² Of the population studied, 0.25% developed a non-ambulatory non-progressive neurological disorder for a case rate of 066 animals/10⁶ cow years or 10⁶ cows/year. Of these, 74.3% failed to recover. In non-ambulatory dairy cows with non-progressive neurological findings, 85% of cases fit into three categories: injury/trauma, septicemia/toxemia, or non-responsive milk fevers. Of the total, 3.3% remain undiagnosed. In non-ambulatory beef cows with non-progressive neurological findings, trauma/injury, septicemia, and other neurological cases accounted for 78% of cases. Of the population studied, 0.12% of cows developed non-ambulatory non-progressive neurological findings syndrome for a case rate of 2476/10⁶cows. Of the total, 73% failed to recover. Of the beef cows, 0.0053% remain undiagnosed, which implies that 4.3% of all beef cows with non-ambulatory non-progressive CNS findings were unknown and undiagnosed and 96% were diagnosed.

Of the total number of non-ambulatory progressive CNS cases reported for dairy cattle, the percentage was 0.027% for a case rate of 554/10⁶. Of these, 17.7% were unknown or undiagnosed indicating that 82% of progressive CNS dairy cattle cases were diagnosed. The progressive CNS cases of unknown cause represented 0.0047% of the study’s cattle population, or a rate of 94 cases/10⁶ dairy cows. Seventy-one of the cases failed to recover for a mortality of 375 cases per million dairy cows in the study.

The profile of a progressive CNS dairy cow case found that other known CNS diseases, septicemia/toxemia, unknown CNS diseases, and non-responsive milk fever to be the most frequently reported cases.

Of the total number of non-ambulatory progressive CNS cases reported in beef cattle, the percentage was 0.018%. Of these, 9.0% were of unknown etiology indicating that 91% of progressive CNS beef cow cases were diagnosed by veterinarians. The unknown progressive CNS case rate was 32 cases/10⁶ beef cattle. The total deaths in progressive CNS cases accounted for a mortality rate of 282/10⁶.

The profile of progressive CNS beef cow cases found that four categories accounted for 83.4% of the total causes: injury/trauma, known infectious agent, septicemia, toxemia, and known CNS disease.

Incidence

The incidence as a complication of milk fever is high because many affected animals are high producers and of high economic value. Accurate data on the incidence are not available because of variations in the nomenclature used and the accuracy of diagnoses. For example, some observations report that all cases are caused by nerve injury.³ Cases included in this classification are classified by others as maternal obstetric paralysis, obturator paralysis, or hypophosphatemia. Because it is a syndrome lacking in clinical definition and includes all those ‘other cases’ which cannot be otherwise classified, the incidence varies depending on the clinical acuity of the individual veterinarian, and on various environmental factors in different areas. However, the incidence seems to be increasing, particularly in intensive dairy farming areas, although this impression could arise from the increased necessity to effect a cure in valuable animals.

A mail survey of 723 dairy herds in Minnesota found a downer cow incidence of 21.4/1000 cow years at risk.³ The overall outcome was that 33% recovered, 23% were slaughtered and 44% died. The owners perceived that downer cows were high producers (48%) or average producers (46%), with only 6% being low producers. Approximately 58% occurred within 1 day of parturition and 37% occurred during the first 100 days of lactation. The incidence was highest (39%) during the three coldest months: December, January, and February. In New Zealand, the prevalence ranges from 3 to 5% of all dairy cows at calving time.⁴

In a clinical and laboratory survey of 433 periparturient recumbent cows in New Zealand, 39% recovered, 30% died, and 32% were destroyed.⁴ The case-fatality rate was 11% higher in pre-calving recumbent cows than post-calving cows.

An audit of 21 slaughter plants in the USA in 1993 found 1.1% of arriving dairy cows were non-ambulatory, and in 1999, 1.5%.⁵ In 1993, 1.0% of beef cows arriving at slaughter plants were non-ambulatory and in 1999, 0.7%.⁵

Risk factors

Summary

Downer cow syndrome is a complication of the recumbency associated with milk fever. A delay of 4 h or more in that treatment of cows with milk fever may result in ischemic necrosis of the muscles of the pelvic limbs. Traumatic injury to leg muscles at the time of parturition or when the cow is unsteady and falls during the first stage of milk fever will also result in the inability of the cow to stand following treatment of milk fever.

Prolonged recumbency before treatment

A long delay in the treatment of milk fever can result in pressure damage and the subsequent inability to stand after treatment for the primary disease. Prolonged recumbency results in pressure damage, which occurs secondarily and is a factor common to all cases.³

Regardless of the cause, the prolonged recumbency results in varying degrees of ischemic necrosis of major muscles of the hindlimbs, particularly the semitendinous muscle and muscles caudal to the stifle. Prolonged compression of the muscle leads to tissue anoxia, cell damage and inflammation which causes swelling; the swelling causes a further increase in pressure which limits tissue perfusion and leads to a detrimental cascade of events. The thick fascial boundaries of the semitendinous muscle prevent expansion which results in pressure-induced compartmental syndrome. Sciatic nerve damage due to pressure also occurs and may contribute to downer cow syndrome. Experimental external compression of the pelvic limb of the goat, to simulate limb compression in recumbent cows, resulted in a marked reduction in nerve condition velocity of the peroneal nerve which was associated with clinically evident limb dysfunction. Damage to the peroneal nerve will result in hyperflexion of the fetlock if and when the cow is able to stand.

Traumatic injury to limb muscles and nerves immediately prior to parturition or at the time of parturition can also result in prolonged recumbency and subsequent pressure damage.¹

Experimental sternal recumbency

Experimentally induced sternal recumbency with one hindlimb positioned under the body to simulate prolonged recumbency will result in a swollen rigid limb within 6–9 h.¹² Following injury to the muscle cells, the serum levels of CPK are markedly elevated at about 12 h after the onset of recumbency. Proteinuria and in some severe cases myoglobinuria occur between 12 and 36 h after the onset of prolonged recumbency, due to the release of myoglobin from damaged muscles. In cows which make efforts to stand but cannot do so, continued struggling results in rupture of muscle fibers and hemorrhage which increases the severity.

Acute focal myocarditis may occur in about 10% of cases resulting in tachycardia, arrhythmia, and the unfavorable response to IV calcium salts observed in some cases. The cause of the myocardial lesion is unknown but repeated administration of calcium salts has been suggested.¹ Downer cows with a poor prognosis also have greatly enhanced adrenocortical function.¹⁰

The prolonged recumbency can result in additional complications such as acute mastitis, decubitus ulcers, and traumatic injuries of the limbs.

The pathogenesis of the non-alert downer cow is not understood.¹³ Most have had an initial episode of milk fever but do not respond satisfactorily. Within 1 or 2 days, affected cows have a preference for lateral recumbency and exhibit expiratory moaning and groaning. They represent about 2% of all cases of milk fever.

Experimental prolonged hypocalcemia

Experimental prolonged hypocalcemia may provide some clues about the pathogenesis of downer cow syndrome as a complication of milk fever. The prolonged infusion of ethylenediamine tetra-acetic acid (EDTA) in sheep over 18 h at a rate to induce hypocalcemia and maintain recumbency results in prolonged periods of recumbency, ranging from 36 to 64 h before the animals are able to stand.¹⁴ There are also decreases in plasma sodium, plasma potassium, and erythrocyte potassium and prolonged increases in packed cell volumes, which suggests that fluid replacement therapy may be indicated in cattle with prolonged recumbency associated with hypocalcemia.¹⁵ A 4-h IV infusion of EDTA in high erythrocyte potassium and low erythrocyte potassium dairy cows causes decreases in plasma inorganic phosphorus and plasma potassium which are still below normal 24 h later.¹⁶ The AST, CPK, and PCVs and WBC counts are also elevated 24 h later. Plasma magnesium and erythrocyte sodium and potassium were decreased but this was delayed. The increase in PCV was most pronounced in the low erythrocyte potassium cows, which may provide some clues about the pathogenesis of downer cow syndrome. Some cows may have a more precipitate increase in PCVs due to loss of plasma volume and an inability to mobilize calcium. As a basis for studying the effects of hypertonic solutions to correct these abnormalities in downer animals, a 200 mL solution of 10 g of sodium chloride and 0.5 g of potassium chloride can be given IV to sheep safely over a period of 4–8 min.¹⁷

Clinical examination of the downer cow

Clinical examination of the downer cow can be very difficult and challenging depending on the environmental circumstances and the physical size of the animal. Many different metabolic, nutritional, musculoskeletal, toxic, neurological, neoplastic, inflammatory, and infectious diseases can cause recumbency in cattle.^18-20 It is very important to obtain an adequate history of the case on the first visit to the animal. Key aspects of the history include age of the animal, duration of recumbency, any previous clinical abnormalities before the recumbent stage such neurological in the case of bovine spongiform encephalopathy, or spinal cord lymphomatosis, any previous treatments with particular attention to mineralocorticoids which may cause hypokalemia, the anatomical location of any parenteral injections, time since recent parturition, diet and accidental access to new feeds, sudden unaccustomed exercise, and an assessment of the management provided.

The environment and the ground surface surrounding the recumbent animal may provide clues about the possibility that the animal slipped, fell, and was injured.

A systematic physical examination of all accessible body systems is necessary. The animal should be examined visually from a distance for evidence of abnormalities of the carriage of the head and neck, the position of the limbs, observe any attempts of the animal to stand or creep along the ground surface.

The details of the clinical examination are presented in Chapter 1. The standard close clinical examination is necessary to determine body temperature, heart rate and pulse, respiratory rate, and the state of the major body systems such as the respiratory tract, cardiovascular system, central nervous system for mental state, and gastrointestinal tract, mammary gland, reproductive tract, any of which may indicate the presence of abnormalities associated with shock which results in recumbency.

In the recently calved cow, particular emphasis must be given to adequate examination of the udder for mastitis, the uterus for metritis, and the gastrointestinal tract for diseases associated with toxemia and dehydration and shock (acute diffuse peritonitis, carbohydrate engorgement), which results in recumbency. A urine sample must always be obtained and tested for ketones, and the presence of myoglobinuria. A vaginal examination of the uterus should always be done along with a rectal examination.

Careful systematic examination of the musculoskeletal system includes palpating the muscles, bones, joints, and feet of each limb, including passive flexion and extension of each limb is necessary. The coxofemoral joints are examined for evidence of dislocation. The vertebral column is examined for evidence of painful sites or displacement of vertebrae. It is important to examine both sides of the animal which means rolling the cow over from side to side; often the animal may have to be rolled over more than once to repeat a particular examination.

A neurological examination includes examination of the withdrawal reflexes and sensation of all four limbs, reflex arcs of the spinal cord, careful examination of lumbar and sacral areas including sensation and tone in the tail, and examination of the cranial nerves.

The examination can be extended by lifting the downer cow with appropriate lifters and observing if the animal extends its limbs and attempts to bear weight. While the animal is being assisted to stand, additional examinations of other parts of the body can be made.

Fluid and electrolyte therapy

Many treatments including the injections of magnesium salts, phosphates, corticosteroids, stimulant tonics, and vitamin E and selenium have been used without consistent success. The use of parenteral solutions containing potassium, calcium, magnesium, and phosphorus has been recommended¹⁰ but there is no scientific evidence that these electrolytes, in addition to what was probably given to the cow already, are indicated or are of any beneficial value. Large quantities of fluid and multiple electrolyte therapy by the oral or parenteral route is indicated for cows which may not be drinking normal quantities of water. Multiple electrolytes can be added to the drinking water if the cow is drinking normally.

Bedding and clinical care

The most important aspect of treatment is to provide the most comfortable bedding possible and to roll the cow from side to side several times daily to minimize the extent of ischemic necrosis and para-analgesia which results from prolonged recumbency. With conscientious care and the provision of good bedding, palatable feed and liberal quantities of water, most cows will attempt to stand with some difficulty and assistance within 24 h, and will stand unassisted and normally 1 or 2 days later. A sand or dirt pack is the ideal ground surface which facilitates standing when downer cows attempt to stand.¹² If affected cows are left on a slippery ground surface, they will not make an effort to stand and will become progressively worse. Cows should be milked normally and the udder kept clean by washing with germicide soap before milking, and post-milking teat dips applied.

Assisted lifting to aid standing

The clinician and farmer are commonly faced with the questions of whether or not to lift a recumbent cow which has not attempted to stand within a few hours after treatment for milk fever. The guiding principle should be the behavior of the cow. If the cow makes an effort to stand on her own or by some coaxing such as a gentle nudge in the ribs, she should be assisted to stand by insuring a good non-slip ground surface, deep bedding, and lifting up on the tailhead when she attempts to stand. The cow should be rolled from side to side every few hours and encouraged to stand a few times daily. With good clinical care, most cows with the uncomplicated form of downer cow syndrome secondary to milk fever will stand in 12–24 h.

Lifting devices

Several different kinds of cow-lifting devices have been used to assist downer cows to stand. Hip lifters, which fit and tighten over the tuber coxae, and body slings like harnesses are designed to fit around the abdomen and thorax of the animal. These devices can assist a downer cow to stand if she makes some effort on her own and it appears that ‘if she were given some help she could stand’. For those cows which make some effort to stand, the hip lifters or slings can be applied and the animal lifted to the standing position. If the animal bears weight on all four legs, she should be allowed to stand with the aid of the devices for 20–30 min and then lowered down. This procedure should be repeated several times daily. In most cases, such downer cows will stand on their own within a few days. While the cow is in the standing position, she can be milked and other clinical examinations can be carried out.

The hip lifters can result in traumatic injuries to the tissues surrounding the tuber coxae if not used judiciously. Animals which make no effort to stand and bear weight on their own must not be left suspended in the lifter for more than a few minutes but lowered immediately. If the hip lifters are not applied carefully, the animal may slip out of the device while she is being lifted, which commonly results in tissue injury around the tuber coxae; fractures of the coxae have even occurred. These injuries are often unnoticed clinically, contribute to persistent recumbency and the true extent of the lesions are evident at necropsy. Lifting devices must be used carefully by experienced personnel.

Body slings which fit around the abdomen and thorax of the animal appear to be the ideal ‘animal lifter’ because they distribute the weight over several sites in contrast to the hip lifters, which concentrate the weight over the tuber coxae. However, the body slings are cumbersome to apply to a recumbent animal, and require more time and experienced personnel to insure proper application. When the slings are applied properly, they do appear to allow the lifted animal to stand comfortably for 30 min or more and promote recovery.

Lifting cows which make no effort to stand on their own is usually unsuccessful. When lifted, they usually do not bear any significant weight.

A water flotation tank has been designed for the management of downer cows.²³ A prototype consists of a metal tub with inside dimensions of 92 in long, 43 in wide, and 51 in deep. The system is affordable, portable, durable, effective, and simple to use. The downer cow is pulled into the tub on a mat and the ends of the tub closed to make a water-tight container with an open top like a bath tub. With the cow’s head held up by a halter, the tub is filled with water at 100–102°F as quickly as possible. Cows in lateral recumbency will roll into sternal recumbency when 12–24 in of water are in the container and will usually attempt to stand when the tub is one-half to two-thirds full. Cows are allowed to stand in the water for 6–8 h. If the water temperature falls below 95°F, more hot water is added. When the decision is made to remove the cow, the water is drained and the end of the tub opened, which allows the cow to walk out preferably onto a ground or grass surface. A success rate of 46% has been reported.²³ However, the success rate could be higher if the selection of cases for flotation are more rigorous. Cows with ruptured tendons, fractures, luxated coxofemoral joints, septic polyarthritis, and other physical injuries of the musculoskeletal system are not good candidates for flotation. The most suitable case for flotation would appear to be the downer cow as a sequel to milk fever.

Handling, transportation, and disposition of non-ambulatory cattle

There has been considerable controversy and disparity among veterinarians and livestock producers about the handling, transportation, and disposition of non-ambulatory cattle.²⁴ Economics has a major influence on decision making in these cases. There has been no common understanding of whether or not they are fit for transportation and which ones are fit for slaughter for salvage. When the owner and veterinarian are faced with a downer cow which is valuable, and the cause of the recumbency is uncertain, the tendency is to either attempt to provide treatment for several days and assess the progress, or consider slaughter for salvage. In the case of valuable breeding animals which are recumbent as a complication of milk fever, or a disease such as acute carbohydrate engorgement, peracute mastitis, supportive, and specific therapy are commonly selected. In the case of downer cattle of commercial value, slaughter for salvage has been a common option. Cattle producers would like to obtain as much financial return as possible by slaughter for salvage. Cattle affected with complications of milk fever (ischemic necrosis of the pelvic limbs), traumatic injuries of the musculoskeletal system and other diseases not associated with toxemia or septicemia were commonly submitted to slaughter for salvage. Transportation of these compromised animals has always been an animal welfare issue because of the difficulty of loading them humanely because of their size. The mere act of lifting, pulling, dragging, and by other means of forcefully loading an animal weighing 500–800 kg onto a truck cannot be done without considerable pain and discomfort to the animal. However, beginning in the 1990s worldwide, concern emerged from the public about the handling and disposition of non-ambulatory animals particularly downer cows regardless of the cause of their recumbency. Government animal health regulatory agencies, livestock associations, and veterinary associations began drafting regulations on the care and handling of non-ambulatory recumbent animals like the downer cow.²⁴

The downer cow syndrome is an animal welfare issue and the veterinarian should be proactive about the problem. Society is concerned about how downer animals are cared for and handled and the methods used for their disposition.²⁵ If recovery does not occur within a few days the prognosis is uncertain and the owner and veterinarian must decide whether to continue providing clinical care to the downer cow or if the animal should be euthanized. In the USA in 1990–1992, 117 301 recumbent cattle were slaughtered at federally inspected abattoirs. Many consumers believe that meat derived from any non-ambulatory animal is unwholesome.

Magnesium homeostasis

There is no feedback regulatory mechanism to control concentrations of magnesium in the body of ruminants. As a consequence, magnesium concentrations in blood and extracellular fluid are essentially determined by the balance between dietary intake of magnesium, loss in feces and milk, and the modulating effect of magnesium homeostasis by the kidney.¹

Factors influencing absorption of magnesium

In the adult ruminant, magnesium absorption occurs in the forestomach with little absorption in the abomasum and small intestine. Some absorption occurs in the large intestine, particularly in sheep,² however it cannot compensate for malabsorption in the forestomach.

Magnesium in pastures and tetany hazard

The dietary intake of magnesium in grazing animals is directly related to the magnesium concentration in pastures but other elements in pastures also influence magnesium absorption by the ruminant as detailed earlier.

Winter hypomagnesemia

The occurrence of hypomagnesemia is not restricted to cattle grazing lush pastures and it also occurs in the winter periods. In housed lactating dairy cattle being fed conserved feeds, hypomagnesemia probably has the same genesis as that in grazing cattle being associated with a high lactational drain of magnesium in combination with the feeding of conserved feeds prepared from pastures with marginal magnesium concentrations. It also occurs in cattle outwintered on poor quality feed.

Hypomagnesemia and hypocalcemia

In some outbreaks of hypomagnesemic tetany, there is also hypocalcemia and, although it is of less severe degree than in parturient paresis, there is increasing evidence that the actual onset of clinical tetany may be associated with a rapid fall in serum calcium levels superimposed on a pre-existing hypomagnesemia. This is particularly true for wheat pasture poisoning but can also apply to outbreaks with different predisposing factors.

Chronic hypomagnesemia can have a profound effect on calcium homeostasis. Hypomagnesemia reduces the production and secretion of parathyroid hormone, reduces hydroxylation of vitamin D in the liver, and also causes target organ insensitivity to the physiological effects of parathyroid hormone and 1,25-dihydroxyvitamin D₃.^6,10,11 Chronic subclinical hypomagnesemia can increase susceptibility to milk fever and can predispose to episodes of milk fever and downer cows in lactating dairy cows during the period of peak lactation.

Summary of etiology

In summary, it appears that a number of factors are capable of causing hypomagnesemia in ruminants and that under particular circumstances one or other of them may be of major importance.

In lactation tetany of cows and ewes turned on to lush pasture in the spring, a primary dietary deficiency of magnesium or the presence of high relative concentrations of potassium and nitrogen in the diet reduces the absorption of magnesium and possibly calcium.

In wheat (cereal) pasture poisoning, the ingestion of abnormally large amounts of potassium and low levels of calcium in the diet leads to hypomagnesemia and also hypocalcemia.

Hypomagnesemic tetany in cattle wintered at pasture and exposed to inclement weather is associated with low magnesium intake and inadequate caloric intake, and possibly to the resultant hyperactivity of the thyroid gland.

Although the above suggestions as to the most important etiological factors in each set of circumstances in which lactation tetany occurs may be valid, undoubtedly combinations of these and other factors have etiological significance in individual outbreaks of the disease. The worst combination of causative factors, and the most common circumstances in which the disease occurs, is inadequate energy intake with a low dietary content of magnesium (grass pasture) in recently calved cows during a spell of cold, wet, and especially windy weather.

One other important factor is the variation between individual animals in susceptibility to hypomagnesemia and to the clinical disease. These variations are quite marked in cattle and in intensively managed, high-producing herds it is probably worthwhile to identify susceptible animals and give them special treatment.¹²

Occurrence and risk factors for lactation tetany

Lactation tetany in dairy and beef cattle turned out to graze on lush, grass dominant pasture after winter housing is common in northern Europe, the UK, and the northern parts of North America. Grass tetany also occurs in Australia and New Zealand, where the cows are not housed in winter but have access to a phenomenal flush of pasture growth in the spring.¹³ This also commonly occurs in beef cattle in all countries.

With housed cattle, or cattle fed conserved feed during the winter, most cases occur during the first 2 weeks after the cattle are turned out to spring pasture. Pasture which has been heavily topdressed with fertilizers rich in nitrogen and potash is potentially the most dangerous. The disease may also occur on this type of pasture even when the cattle have wintered on pasture in temperate regions. In regions where there is an autumn flush of pasture, a high incidence of hypomagnesemic tetany may occur in the autumn or early winter.

Cattle in the first 2 months of lactation and 4–7 years of age are most susceptible, which probably reflects an increased risk due to a higher loss of magnesium in milk. Friesian cows have lower magnesium concentrations than Jerseys grazed under the same conditions.¹⁴

In the northern parts of the USA, outbreaks commonly occur during periods of low barometric pressure when the ambient temperature ranges between 7°C (45°F) and 15.5°C (60°F) and soil temperatures are below 7°C (45°F). Outbreaks may be precipitated by inclement weather. In beef cattle there is commonly a history of poor nutrition and falling body condition in the past few weeks due to diminishing hay supplies.

Occurrence and risk factors for wheat (cereal) pasture poisoning

Wheat pasture poisoning is a misnomer as it can occur with grazing of any small-grain cereal pasture. It has been recorded in many countries but is most prevalent where young cereal crops are utilized for ‘winter grazing’. The southwestern USA has experienced heavy losses of cattle caused by this disease. This pasture can induce hypomagnesemia in pregnant and lactating cattle and sheep. The risk is with young rapidly growing pasture, either in the spring, or in the autumn and winter with pastures planted in late summer. The pasture is usually dangerous for only a few weeks but heavy losses may occur in all classes of sheep and cattle. Bos taurus breeds are more susceptible to the development of hypomagnesemia than Bos indicus.¹⁵

Occurrence and risk factors for winter hypomagnesemia

Hypomagnesemic tetany in cattle wintered in the open causes some losses in the UK, New Zealand, southern Australia, and the east-central states and Pacific slope of the USA. It occurs in cattle grazed on pasture in the winter with minimal supplemental hay and in cattle grazed on aftermath crops and corn stover. The disease occurs in regions with temperate climates, and risk is increased by exposure to bad weather, which is exacerbated by absence of trees or other shelter in fields and by failure to supply supplementary feed during these cold spells. The disease does not seem to occur in cattle kept outside in prolonged winters where environmental temperature is consistently very low and there is adequate feed. Hypomagnesemia, commonly presenting as chronic hypomagnesemia and sudden death, has been recognized as occurring in housed cattle in the winter in Europe for many years and recently has also been reported in the USA.

Morbidity and mortality

In all of these forms of the disease, the morbidity rate is highly variable, reaching as high as 12% in individual herds, and up to 2% in particular areas. The incidence varies from year to year depending largely on climatic conditions and management practices, and the disease is often limited in its occurrence to particular farms and even to individual fields.

Although an effective treatment is available, the case-fatality rate is high because of the short course. Since animals die before they are observed to be ill, there are not accurate figures on case fatality, but it is probably of the order of 30% in dairy cattle and considerably higher in beef cattle.

There have been few epidemiological studies specifically addressing the importance of the syndrome. In Finland, a lactational incidence rate varying between 0.1% and 0.3% is recorded, with an increase in parity to at least six for lactation tetany occurring on pasture but not for indoor tetany.¹⁵ No association with other diseases was found other than for milk fever. In Northern Ireland, approximately 10% of dairy cows and 30% of beef cows have subnormal or deficient blood magnesium concentrations during the grazing season and hypomagnesemia is considered the cause of 20% of the ‘sudden death’ mortality in beef cattle.^16,17 Surveys of beef cattle owners of the relative importance of different diseases invariably rate hypomagnesemia high in importance.

Pasture risk factors

In most areas of the world, there is a strong association between risk for hypomagnesemia and systems of pasture improvement and pasture fertilization to increase forage yield. There are a number of influences on the concentration of magnesium and other elements in pasture.

Animal and management risk factors

Animal movement

Epinephrine release will result in a precipitous fall in serum magnesium and this may explain the common observation that clinical cases are often precipitated by excitement or movement of the herd.

Hypomagnesemia in sheep

Hypomagnesemia occurs in sheep, particularly in Australia and the United Kingdom. The disease is not common but appears to be increasingly associated with pasture improvement practices, and can cause heavy losses in individual flocks. It is more common in ewes bred for milk and lamb production. In outbreaks, ewes with twins are more liable to develop clinical disease than those with singles and the main occurrence is in ewes 1–4 weeks after lambing with cases up to 8 weeks after lambing.

Disease is often precipitated by a management procedure involving movement and temporary food deprivation and cases will occur within the first 24 h following this and for a few days afterwards. As in cattle, disease occurs when ewes are placed on lush grass pastures but it is especially common where ewes in early lactation are placed on young cereal pastures. Losses usually cease when the flock is moved onto rough, unimproved pasture.

Cases also occur in sheep which are exposed to inclement weather when on low nutritive intake. Simultaneous hypomagnesemia and ketosis can occur in ewes after lambing if they are exposed to low feed availability. These cases do not respond well to treatment. Hypomagnesemia in ewes is predisposed by prior pregnancy toxemia in the flock.

Acute lactation tetany

The animal may be grazing at the time and suddenly cease to graze, adopt a posture of unusual alertness and appear uncomfortable; twitching of the muscles and ears is also evident. There is severe hyperesthesia and slight disturbances precipitate attacks of continuous bellowing, frenzied galloping, and occasionally aggression. The gait becomes staggering and the animal falls with obvious tetany of the limbs, which is rapidly followed by clonic convulsions lasting for about a minute. During the convulsive episodes there is:

Between episodes, the animal lies quietly but a sudden noise or touch may precipitate another attack.

The temperature rises to 40–40.5°C (104–105°F) after severe muscle exertion; the pulse and respiratory rates are also high. The absolute intensity of the heart sounds is increased so that they can be heard some distance away from the cow. Death usually occurs within 5–1 h and the mortality rate is high because many die before treatment can be provided. The response to treatment is generally good if the animal is treated early.

Subacute lactation tetany

In this form of the disease, the onset is more gradual. Over a period of 3–4 days, there is slight inappetence, wildness of the facial expression and exaggerated limb movements. The cow often resists being driven and throws her head about as though expecting a blow. Spasmodic urination and frequent defecation are characteristic. The appetite and milk yield are diminished and ruminal movements decrease. Muscle tremor and mild tetany of the hindlegs and tail with an unsteady, straddling gait may be accompanied by retraction of the head and trismus. Sudden movement, noise, the application of restraint or insertion of a needle may precipitate a violent convulsion.

Animals with this form of the disease may recover spontaneously within a few days or progress to a stage of recumbency with a similar but rather milder syndrome than in the acute form. Treatment is usually effective but there is a marked tendency to relapse.

Chronic hypomagnesemia

Many animals in affected herds have low serum magnesium levels but do not show clinical signs. There may be sudden death.²² A few animals do evidence a rather vague syndrome including dullness, unthriftiness and indifferent appetite and may subsequently develop one of the more obvious syndromes. In lactating cows, this may be the development of paresis and a milk fever-like syndrome that is poorly responsive to calcium treatment. Depressed milk production has also been attributed to chronic hypomagnesemia in dairy herds in New Zealand.²³ The chronic type may also occur in animals which recover from the subacute form of the disease.

Parturient paresis with hypomagnesemia

This syndrome is described under parturient paresis and consists of paresis and circulatory collapse in an adult cow which has calved within the preceding 48 h but in which dullness and flaccidity are replaced by hyperesthesia and tetany.

Serum magnesium concentrations

Normal serum magnesium concentrations are 1.7–3 mg/dL (0.70–1.23 mmol/L). These levels in cattle are often reduced in seasonal subclinical hypomagnesemia to between 1 and 2 mg/dL (0.41 and 0.82 mmol/L) but risk for tetany is not present until the level falls to below 1.2 mg/dL (0.49 mmol/L).

The average level at which signs occur is about 0.5 mg/dL (0.21 mmol/L) and in sheep it is suggested that clinical tetany does not occur until the serum magnesium level is below 0.5 mg/dL (0.21 mmol/L).

Serum magnesium in some animals may fall to as low as 0.4 mg/dL (0.16 mmol/L) without clinical illness. This may be due to individual animal variation in the degree of ionization of the serum magnesium and in the difference between serum and CSF concentrations. It is also possible that a transitory elevation of serum concentrations occurs after violent muscular exercise.

Total serum calcium levels are often reduced to 5–8 mg/dL (1.25–2.00 mmol/L) and this may have an important bearing on the development of clinical signs. Serum inorganic phosphate levels may or may not be low.

In wheat pasture poisoning of cattle there is hypocalcemia, hypomagnesemia, and hyperkalemia. In acute tetany, serum potassium levels are usually dangerously high and may contribute to the high death rate.

CSF magnesium concentrations

Magnesium concentrations in CSF can be used as a diagnostic procedure but CSF is not easily or safely collected in tetany cases. Fluid collected up to 12 h after death can be used diagnostically.

Levels in CSF of 1.25 mg/dL (0.51 mmol/L) magnesium were found in tetanic cows with hypomagnesemia (serum magnesium levels of 0.54 ± 0.41 mg/dL; 0.22 ± 0.17 mmol/L). In clinically normal cows with hypomagnesemia comparable levels in CSF were 1.84 mg/dL (0.74 mmol/L) and in serum 0.4 mg/dL (0.16 mmol/L). In normal animals CSF levels are the same as in plasma, i.e. 2.0 mg/dL (0.82 mmol/L) and up. The magnesium content of ventricular CSF may be quite different to that of lumbar CSF. It is also more responsive to changes in magnesium levels of the blood and is preferred for diagnosis at necropsy.²⁵

Urine magnesium concentrations

The occurrence of low urine magnesium levels is good presumptive evidence of hypomagnesemia.²⁶

Herd diagnosis

The kidney is the major organ of homeostasis and it has been argued that analysis of urine magnesium status is a more accurate method of assessing herd magnesium status than serum magnesium concentrations.²⁷ The magnesium status of a herd, and the need to supplement the diet to prevent lactation tetany, can be established from:

Laboratory charges for urinary magnesium fractional clearance ratios are expensive. The determination of the creatinine-corrected urinary magnesium concentration from 10 cows in a herd has been found to be a more sensitive indicator of magnesium status of the herd than estimates from serum, and a better predictor of response to supplementation. Values of less than 1.0 mmol/L indicate that a positive response to supplementation is likely.²⁷ Urine magnesium concentrations below 1.0 mg/dL (0.4 mmol/L) indicate a danger for tetany.

Provision for further cases

The predisposing factors that lead to a case of hypomagnesemia apply to the herd as a whole and it is probable that further clinical cases will occur before the effects of corrective strategies are in effect. In extensive range situations, it is advisable to instruct the owner on how to treat cases as a delay in treatment can markedly increase the rate of treatment failures. SC treatment is within the realm of most, but successful therapy is also recorded by the rectal infusion of 30 g of magnesium chloride in a 100 mL solution; serum concentrations of magnesium return to normal levels within 10 min of administration.²⁹

Feeding of magnesium supplements

The preventive measure which is now universally adopted is the feeding of magnesium supplements to cows during the danger period. The feeding of magnesite (containing not less than 87% magnesium oxide), or other sources of magnesium oxide, prevents the seasonal fall in serum magnesium levels. Daily administration by drenching, or in the feed, of at least 60 g of magnesium oxide per day is recommended to prevent the disease. This is not always completely effective and in some circumstances large doses may be necessary. Daily feeding of 120 g is safe and effective but 180 g daily may cause diarrhea. The dose for sheep is 7 g daily or 14 g every second day. Magnesium phosphate (53 g/d) is also a safe and effective way of insuring a good intake of magnesium. The protection afforded develops within several days of commencing administration and terminates abruptly after administration ceases.

Heavy magnesium ‘bullets’

The use of heavy ‘bullets’ of magnesium to prevent hypomagnesemia has been effective in laboratory trials and they are available commercially in some countries. The objective is to place a heavy ‘bullet’ of magnesium in the reticulum from which site it constantly liberates small amounts of magnesium – about 1 g/d. This objective is achieved and the occurrence of the clinical disease is usually greatly reduced but not eliminated. In dangerous situations, it is customary to administer up to four bullets at a time. As with all bullets, there is a proportion lost by regurgitation and by passage through the gut. A special sheep-sized ‘bullet’ is used in ewes with similar results.

Top dressing of pasture

This, together with magnesium-rich fertilizers, raises the level of magnesium in the pasture and decreases the susceptibility of cattle to hypomagnesemia. For top dressing, calcined magnesite (1125 kg/ha) or magnesic limestone (5600 kg/ha) are satisfactory, the former resulting in a greater increase in pasture magnesium.

Other magnesium-containing fertilizers can be used depending on cost. The duration of the improved magnesium status varies with the type of soil: greatest on light sandy loams on which a dressing of 560 kg/ha of calcined magnesium can provide protection for 3 years. On heavy soils protection for only 1 year is to be expected. To avoid unnecessary expense, it may be possible to top dress one field with the magnesium fertilizer and keep this field in reserve for spring grazing. Fertilization with magnesium is expensive and the response of pastures varies markedly with the soil type. It is advisable to seek agronomic advice.

Foliar dusting and spraying

The magnesium content of pastures can be raised much more quickly by spraying with a 2% solution of magnesium sulfate at fortnightly intervals or by application of very finely ground magnesium oxide to the pasture (30 kg/ha) before grazing commences. The technique is referred to as ‘foliar dusting or spraying’ and has the advantage over feed supplementation that the intake is standard. It is very effective in cattle in maintaining serum magnesium levels and preventing the occurrence of the clinical disease.

Dusting is with 20–50 kg MgO/ha can provide protection for up to 3 weeks but the duration is adversely influenced by wind and rain. A MgO-bentonite-water slurry sprayed onto pastures (26 kg MgO and 2.6 kg bentonite/ha) is effective in providing protection in high rainfall periods.

Provision in drinking water

The problem with water medication is that the water intake of the group to be treated is not known but may be minimal on rapidly growing pastures. However, water medication may provide a delivery system for magnesium on management systems such as extensive range pastures where other methods may have limited success. Water sources other than the medicated supply need to be fenced off or otherwise restricted. The addition of magnesium sulfate (500 g/100 L) or magnesium chloride hexahydrate (420 g/100 L) to the water supply during the risk period for hypomagnesemia has proved effective.

Management of pasture fields

The economics of daily farming make it necessary to produce maximum pasture growth, and the development of tetany-prone pastures is unavoidable in many circumstances. In some areas it may be possible to reduce the danger of such pastures by encouraging the development of legumes. In other areas the period of legume growth does not coincide with the period of maximum risk for grass tetany.

Restricting the amount of potash added to pastures, especially in the period immediately preceding the risk period for tetany, or using potash fertilizers in the autumn or late spring after the period of risk, can reduce risk of the disease. The grazing of low-risk animals on high-risk pastures is another strategy. Insuring that ample salt is available during the danger period to counteract the high intake of potassium can also reduce risk of the disease.

Plant geneticists are developing cultivars of cool-season grasses with high magnesium content that could be used for grazing during the tetany season. Lactating sheep grazing a high magnesium cultivar of perennial rye grass (Lolium perenne cv Radmore) in the spring have shown higher blood magnesium concentrations than sheep grazing control cultivar³¹ and cultivars of tall fescue (Festuca arundinacea) with high Mg and Ca concentrations and low tetany potential are also available.³²

Provision of shelter

In areas where winter pasturing is practiced, the observation that serum magnesium levels fall during the winter and in association with inclement weather suggests that cattle and sheep should be provided with shelter at such times. If complete housing is impractical, it may be advisable to erect open access shelters in those fields that have no tree cover or protection from prevailing winds. Fields in which lactating cows are kept should receive special attention in this regard. Unfortunately, the disease is most common on highly improved farms, where most natural shelter has been removed and it is desired to keep the cows on the highly improved pasture to maintain milk production or fatten calves rapidly.

Time of calving

In areas where the incidence of the disease is high, it may be advisable to avoid having the cows calve during the cold winter months when seasonal hypomagnesemia is most likely to develop. Unfortunately it is often important to have cows calve in late winter to take advantage of the flush of spring growth when the cows are at the peak of their lactation.

Feeding on hay and unimproved pasture

Because of the probable importance of lush, improved, grass pasture in producing the disease, the provision of some grain, hay or rough grazing may reduce its incidence. It is most important that the periods of fasting, such as occur when cattle or sheep are yarded or moved or during bad weather, should be avoided, especially in lactating animals and when seasonal hypomagnesemia is likely to be present.

Magnesium homeostasis in the calf

Milk has low concentrations of magnesium. A milk diet provides adequate magnesium for the requirements of a growing calf up to a body weight of approximately 50 kg, but if milk is the sole diet, the intake of magnesium will be inadequate for requirements once his body weight is reached.¹ The deficit will perpetuate if the other feeds that are fed are also low in magnesium.

In the young calf, magnesium is absorbed in the intestine; however, the efficiency of magnesium absorption decreases markedly up to about 3 months of age, when maximum susceptibility to the disease occurs. The efficiency of absorption is decreased by a reduction in transit time in the intestine caused by diarrhea.

In contrast to adult cattle, young calves can mobilize body stores of magnesium, which are principally located in the skeleton. Approximately 40% of the magnesium stored in the skeleton can be mobilized, which will protect against a short-term deficit.¹

Hypomagnesemic tetany in calves is often complicated in field cases by the coexistence of other diseases, especially enzootic muscular dystrophy.

Occurrence

The disease is not common. Cases may occur sporadically or a number of deaths may occur on the one farm within a short period of time.

Risk factors

The disease can occur under a number of different circumstances.

Most commonly, hypomagnesemic tetany occurs in calves 2–4 months of age or older which are fed solely on a diet of whole milk, and calves receiving the greatest quantity of milk and growing most rapidly are more likely to be affected because of their greater need for magnesium for incorporation into developing soft tissues. It is most likely to occur in calves being fattened for veal. Those cases which occur on milk replacer appear to be related to chronic scours and low magnesium content of the replacer. This problem is less common than it once was because most modern commercial milk replacers have added adequate magnesium.

A significant loss of magnesium in the feces also occurs in calves allowed to chew fibrous material such as bedding; the chewing stimulates profuse salivation and creates greater loss of endogenous magnesium. Peat and wood shavings are bedding materials known to have this effect.

Cases have also been reported in calves fed milk-replacer diets or milk, concentrates, and hay, and in calves running at pasture with their dams. Deaths due to hypomagnesemic tetany have also occurred in 3–4-month-old calves whose hay and silage rations were low in magnesium content.²

Hypomagnesemia also occurs in young cattle, about 6 months of age, which are being fattened intensively indoors for the baby beef market. The phosphorus content of their diet is high and a lack of vitamin D is probable. The situation is exacerbated by a shortage of roughage. The hypomagnesemia is accompanied by a hypocalcemia.

Experimental reproduction

A condition closely resembling the field syndrome has been produced experimentally by feeding an artificial diet with a very low content of magnesium; a high calcium content and biochemical hypomagnesemia is readily produced in calves with a diet based on skim milk and barley straw.³ Hypomagnesemia has also been produced experimentally in very young foals by feeding a diet with a very low magnesium content. The clinical signs are similar to those in calves, and the calcification found in the walls of vessels of calves also occurs in foals.

Glucose metabolism in ruminants

The maintenance of adequate concentrations of glucose in the blood is critical to the regulation of energy metabolism. The ruminant absorbs very little dietary carbohydrate as hexose sugar because dietary carbohydrates are fermented in the rumen to short chain fatty acids, principally acetate (70%), propionate (20%) and butyrate (10%). Consequently, glucose needs in ruminants must largely be met by gluconeogenesis. Propionate and amino acids are the major precursors for gluconeogenesis with glycerol and lactate of lesser importance.¹

Propionate is produced in the rumen from starch, fiber, and proteins. It enters the portal circulation and is efficiently removed by the liver, which is the primary glucose-producing organ. Propionate is the most important glucose precursor; an increased availability can spare the hepatic utilization of other glucose precursors,² and production of propionate is favored by a high grain inclusion in the diet.³

Energy balance

In high-producing dairy cows there is often a negative energy balance in the first few weeks of lactation. The highest dry matter intake does not occur until 8–10 weeks after calving but peak milk production is at 4–6 weeks and energy intake may not keep up with demand. In response to a negative energy balance and low serum concentrations of glucose and insulin, cows will mobilize adipose tissue with consequent increases in serum concentrations of non-esterified fatty acids (NEFA) and subsequently BHBA. The hepatic mitochondrial metabolism of fatty acids promotes both gluconeogenesis and ketogenesis. Cows partition nutrients during pregnancy and lactation and are in a lipolytic stage in early lactation and at risk for ketosis during this period.

Hepatic insufficiency in ketosis

Hepatic insufficiency has been shown to occur in bovine ketosis but it does not occur in all cases.^3,4 It has been suggested that ketosis can be divided into two types.^3,5 In Type I, or ‘spontaneous’ ketosis, it is proposed that the gluconeogenic pathways are maximally stimulated and ketosis occurs when the demand for glucose outstrips the capacity of the liver for gluconeogenesis because of an insufficient supply of glucose precursors. Rapid entry of non-esterified fatty acids (NEFA) into hepatic mitochondria occurs and results in high rates of ketogenesis and high blood ketones. There is little conversion of NEFA to triglycerides resulting in little fat accumulation in the liver. In Type II ketosis, manifest with fatty liver, gluconeogenic pathways are not maximally stimulated and consequently mitochondrial uptake of NEFA is not as active and NEFA become esterified in the cytosol, forming triglyceride. The capacity of cattle to transport triglyceride from the liver is low, resulting in accumulation and fatty liver.³ The occurrence of a fatty liver can further suppress hepatic gluconeogenic capacity. Hepatic insufficiency may occur more commonly in those cows predisposed to ketosis by overfeeding in the dry period.⁵

Ketone formation

Ketones arise from two major sources: butyrate in the rumen and mobilization of fat. A large proportion of butyrate produced by rumen fermentation of the diet is converted to β-hydroxybutyrate (BHBA) in the rumen epithelium and is absorbed as such. Free fatty acids produced from the mobilization of fat are transported to the liver and oxidized to produce acetyl-CoA and NADH.

Acetyl-CoA may be oxidized via the TCA cycle or metabolized to acetoacetyl-CoA. Its oxidation via the TCA cycle depends upon adequate supply of oxaloacetate from the precursor propionate. If propionate, and consequently oxaloacetate, is deficient, oxidation of acetyl-CoA via the TCA cycle is limited and it is metabolized to acetoacetyl CoA and subsequently to acetoacetate and BHBA.¹

The ketones BHBA and acetoacetate can be utilized as an energy source. They are normally present in blood and their concentration is a result of the balance between production in the liver and utilization by the peripheral tissues.

Role of insulin and glucagon

The regulation of energy metabolism in ruminants is primarily governed by insulin and glucagon. Insulin acts as a glucoregulatory hormone stimulating glucose use by tissues and decreasing hepatic gluconeogenesis. Blood insulin concentrations decrease with decreasing blood concentrations of glucose and propionic acid. Insulin also acts as a liporegulatory hormone stimulating lipogenesis and inhibiting lipolysis. Glucagon is the primary counter-regulatory hormone to insulin. Their counteracting effects play a central role in the homeostatic control of glucose. A low insulin: glucagon ratio stimulates lipolysis in adipose tissue and ketogenesis in the liver. Cows in early lactation have low insulin: glucagon ratios because of low blood insulin and are in a catabolic state.⁵ Elevated ketones may stimulate insulin production and may act as a negative feedback.^5,6 Regulation is also indirectly governed by somatotropin, which is the most important determinant of milk yield in cattle and is also lipolytic. Factors that decrease the energy supply to ruminants, that increase the demand for glucose, or that increase the utilization of body fat as an energy source are likely to increase ketone production and ketonemia. There is however considerable cow-to-cow variation in risk for clinical ketosis.

Individual cow variation

The rate of occurrence of negative energy status, and therefore the frequency of clinical cases, has undoubtedly increased sharply in the recent past because of the steep increase in the lactation potential of the modern dairy cow. Because of the mammary gland’s metabolic precedence in the partitioning of nutrients, especially glucose, milk production continues at a high rate, causing an energy drain. In many individual cows, the need for energy is beyond their capacity for dry matter intake but there is between-cow variation in risk under similar nutritional stress.^1-35 Clinical ketosis has been produced in recently calved dairy cows by reducing the daily feed intake by 15–20% ad libitum and supplementing it with 1,3-butanediol, a ketogenic substrate. The biochemical characteristics of ketosis including depletion of hepatic glycogen and major increases in hepatic stores of triglycerides and ketone bodies were produced but ketosis was only produced in those cows that had a predisposition to the disease.^7,8

Types of bovine ketosis

There are many theories on the cause, biochemical and hormonal pathogenesis of ketosis, and the importance of predisposing factors. Reviews of these studies are cited at the end of this disease section. In general, it can be stated that clinical ketosis occurs in ruminants when they are subjected to demands on their resources of glucose and glycogen that cannot be met by their digestive and metabolic activity.

Lean¹ has presented a classification of the disease based on its natural presentation in intensively and extensively managed dairy herds, and one that accounts for the early lactational demand for glucose, a limited supply of propionate precursors and preformed ketones or mobilized lipids in the pathogenesis. Such a classification includes the following geneses of ketosis, which will be discussed in turn:

Occurrence

Ketosis is a disease of dairy cattle and is prevalent in most countries where intensive farming is practiced. It occurs mainly in animals housed during the winter and spring months and is rare in cows that calve on pasture. In housed or free-stalled cattle it occurs year around. The occurrence of the disease is very much dependent upon management and nutrition and varies between herds. As might be expected, lactational incidence rates vary between herds and a recent review of eleven epidemiological studies showed a lactation incidence rate for ketosis that varied from 0.2–10.0%.¹⁴

Rates of subclinical ketosis are influenced by the cut-point of plasma BHBA used for definition but are much higher, especially in undernourished herds, and can approach 40%.^2,15-19

Animal and management risk factors

There are conflicting reports on the significance of risk factors for ketosis and subclinical ketosis which probably reflect that the disease can be a cause or effect of interacting factors. The disease occurs in the immediate postparturient period with 90% of cases occurring in the first 60 days of lactation.^15-20 Regardless of specific etiology, it occurs most commonly during the first month of lactation, less commonly in the second month, and only occasionally in late pregnancy. In different studies, the median time to onset following calving has varied from 10 to 28 days,^20,21 with some recent studies showing a peak prevalence of subclinical ketosis in the first 2 weeks post-calving.^2,15 A prolonged previous inter-calving interval increases risk.²

Economic significance

Clinical and subclinical ketosis are major causes of loss to the dairy farmer.^2,19,39 In rare instances the disease is irreversible and the affected animal dies but the main economic loss is due to the loss of production while the disease is present, the possible failure to return to full production after recovery and the increased occurrence of periparturient disease.^1,2 Both clinical and subclinical ketosis are accompanied by decreased milk yields and lower milk protein and milk lactose^1,2,16,35,40 and increased risk for delayed estrus and lower first service conception rates, increased inter-calving intervals^10,41 and increased risk of cystic ovarian disease, metritis and mastitis and increased involuntary culling.^11,35,42 A year 2001 report has estimated the loss from a single case of subclinical ketosis at US$145.¹⁹

Subclinical ketosis

Many cows that are in negative energy balance in early pregnancy will have ketonuria without showing clinical signs, but will have diminished productivity including depression of milk yield and a reduction in fertility. Clinical diagnosis is not effective and in one study,²² diagnosis by routine urine testing at 5–12 days post partum was considerably more efficient (15.6% detected) than diagnosis by the herdsman (4.35% detected). In a British study of 219 herds the annual mean rate of reported clinical ketosis was 0.5 per 100 adult cows but the rate of subclinical ketosis, as defined by high blood concentrations of BHBA and non-esterified fatty acids, was substantially higher.^47,48

Potential milk production is reduced by 1–9%.^17,20 Surveys of large populations show a declining prevalence of ketosis-positive cows after a peak in the period immediately after calving, and a positive relationship between hyperketonemia and high milk yield.^15,49 Infertility may appear as an ovarian abnormality, delayed onset of estrus or as endometritis resulting in an increase in calving to conception interval and reduced conception rate at first insemination.

Glucose

Blood glucose levels are reduced from the normal of approximately 50 mg/dL to 20–40 mg/dL. Ketosis secondary to other diseases is usually accompanied by blood glucose levels above 40 mg/dL and often above normal. Conversion factors are shown in Table 29.7.

Table 29.7 To convert from the SI unit to the conventional unit divide by the conversion factor. To convert from the conventional unit to the SI unit multiply by the conversion factor

Blood ketones

Most commonly, plasma or serum β-hydroxybutyrate (BHBA) measured in SI units is used for analysis of ketonemia. BHBA is the predominant circulating ketone body. Plasma concentrations of BHBA significantly correlate with plasma concentrations of acetoacetate but acetoacetate is unstable in samples whereas BHBA is relatively stable.² Normal cows have plasma BHBA concentrations less than 1000 μmol/L, cows with sub-clinical ketosis have concentrations greater than 1400 μmol/L, and cows with clinical ketosis have concentrations often in excess of 2500 μmol/L. Plasma BHBA shows some diurnal variation in cows fed twice daily with peak concentrations occurring approximately 4 h after feeding and higher concentrations in the morning than in the afternoon. This is not seen in cows fed a total mixed ration ad libitum.^50,51

Plasma BHBA is not a cost effective or convenient analysis for routine analysis and cow side monitoring and the content of acetoacetate or BHBA in urine and milk are used for these purposes. Concentrations of BHBA and acetoacetate in urine and milk are less than those in blood and the correlation coefficients for blood and milk BHBA and blood and milk acetoacetate are 0.66 and 0.62, respectively.⁵²

Milk and urine cowside tests

Cowside tests have the advantage of being inexpensive, giving immediate results, and they can be used as frequently as necessary. A minor source of error is that the concentration of ketone bodies in these fluids will depend not only on the ketone level of the blood but also on the amount of urine excreted or on the milk yield. Milk is less variable, easier to collect and may give fewer false negatives with subclinical ketosis.

Milk and urine ketone levels have been traditionally detected by the reaction of acetone and acetoacetate with sodium nitroprusside and can be interpreted in a semi-quantitative manner based on the intensity of the reaction. Several products are available commercially as test powders or strips are commonly accompanied by a color chart that allows a classification in grades such as negative, trace, small, moderate, large, based on the intensity of the color of the reaction.

Conventional wisdom is that milk powder tests are not sensitive for detection of subclinical ketosis (report too many false negatives) and urine tests are not sufficiently specific (report too many false positives).⁵³

Replacement therapy

Hormonal therapy

Energy supplements

Propylene glycol is used for the prevention of clinical and subclinical ketosis. Traditionally, propylene glycol has been drenched to cattle in early lactation at doses varying from 350 to 1000 mL daily for 10 days after calving. There is a linear effect of dose on plasma glucose.⁶⁸ Propylene glycol can also added to feed and is frequently present in commercial feed product but a bolus dose of propylene glycol is more effective in raising blood glucose than incorporation in feed.² A dose of 1 L per day given as an oral drench for 9 days prior to parturition has also been shown efficacious.⁶⁹ At doses above 500 mL administered by drench or present in feed some cows may develop rapid and shallow respiration, ataxia, salivation, and somnolence.

Glycerol can be substituted for propylene glycol at equivalent dose rates. A preliminary report of a small experimental study with larger doses of glycerol showed that glycerol given orally at a dose of 1, 2, or 3 L elevated blood glucose concentrations to 16, 20, and 25% of pre-treatment values at 0.5 h after treatment and that these concentrations remained elevated for 8 h. Staggering, depression and diuresis were observed in some cows given the 2 or 3 L dose but this could be prevented by administering the glycerol in a large (37 L) volume of water. It concluded that a dose of 1 L was effective in increasing milk production and reducing urinary letones.⁷⁰ Glycerol, fed as a constant component in the transition dairy cow diet is not effective, and possibly may be ketogenic when fed continually.⁷¹ Glycerol should only be used as drench in hypoglycemic cows and not fed as a component of the diet.

General control