Veterinary Medicine ketosis

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<p>Chapter 17 ■ Metabolic and Endocrine Diseases1708</p><p>recently calved, bullocks, steers, dry cows,</p><p>and lambs. Risk factors include the following:</p><p>• Heavy feeding before shipment</p><p>• Deprivation of feed and water for more</p><p>than 24 hours during transit</p><p>• Unrestricted access to water</p><p>• Exercise immediately after unloading</p><p>There is an increased incidence of the disease</p><p>during hot weather. The cause is unknown,</p><p>although physical stress is an obvious factor.</p><p>Lambs show the following characteristics:</p><p>• Restlessness</p><p>• Staggering</p><p>• Partial paralysis of hindlegs</p><p>• Early assumption of lateral recumbency</p><p>Death may occur quickly, or after 2 to 3 days</p><p>of recumbency. There is mild hypocalcemia</p><p>(7 to 7.5 mg/dL; 1.75 to 1.87 mmol/L). The</p><p>recovery rate even with treatment is only fair.</p><p>Clinical signs may occur while the cattle</p><p>are still on the transportation vehicle or up</p><p>to 48 hours after unloading. In the early</p><p>stages, animals may exhibit excitement and</p><p>restlessness, trismus, and grinding of the</p><p>teeth. A staggering gait with paddling of the</p><p>hindlegs and recumbency occur, accompa-</p><p>nied by stasis of the alimentary tract and</p><p>complete anorexia. Animals that do not</p><p>recover gradually become comatose and die</p><p>in 3 to 4 days. There may be moderate hypo-</p><p>calcemia and hypophosphatemia in cattle. In</p><p>sheep of various ages, some are hypocalce-</p><p>mic and hypomagnesemic, some are hypo-</p><p>glycemic, and some have no detectable</p><p>biochemical abnormality. There are no</p><p>lesions at necropsy other than those related</p><p>to prolonged recumbency. Ischemic muscle</p><p>necrosis is the most obvious of these lesions.</p><p>The relationship of the disease to transport</p><p>or forced exercise is diagnostic.</p><p>Some cases respond to treatment with</p><p>combined calcium, magnesium, and glucose</p><p>injections. Repeated parenteral injections of</p><p>large volumes of electrolyte solutions are rec-</p><p>ommended. In lambs, the SC injection of a</p><p>solution of calcium and magnesium salts is</p><p>recommended, but the response is usually</p><p>only 50%, due probably because of an inter-</p><p>current myonecrosis.</p><p>If prolonged transport of cows or ewes in</p><p>advanced pregnancy is unavoidable, they</p><p>should be provided with adequate food,</p><p>water, and rest periods during the trip.</p><p>The incidence of this condition after trans-</p><p>portation appears to have been markedly</p><p>reduced with increased monitoring and</p><p>awareness of transportation-related morbid-</p><p>ity and mortality.</p><p>KETOSIS AND SUBCLINICAL</p><p>KETOSIS (HYPERKETONEMIA)</p><p>IN CATTLE</p><p>ETIOLOGY</p><p>Glucose Metabolism in Cattle</p><p>The maintenance of adequate concentrations</p><p>of glucose in the plasma is critical to the</p><p>regulation of energy metabolism. The rumi-</p><p>nant absorbs very little dietary carbohydrate</p><p>as hexose sugar because dietary carbohy-</p><p>drates are fermented in the rumen to short-</p><p>chain fatty acids, principally acetate (70%),</p><p>propionate (20%), and butyrate (10%). Con-</p><p>sequently, glucose needs in cattle must</p><p>largely be met by gluconeogenesis. Propio-</p><p>nate and amino acids are the major precur-</p><p>sors for gluconeogenesis, with glycerol and</p><p>lactate being of lesser importance.</p><p>Propionate is produced in the rumen</p><p>from starch, fiber, and proteins. It enters the</p><p>portal circulation and is efficiently removed</p><p>by the liver, which is the primary glucose-</p><p>producing organ. Propionate is the most</p><p>important glucose precursor; an increased</p><p>availability of propionate can spare the hepa-</p><p>tic utilization of other glucose precursors,</p><p>and production of propionate is favored</p><p>by a high grain inclusion in the diet. The</p><p>gluconeogenic effect of propionate should be</p><p>contrasted to acetate, which is transported to</p><p>peripheral tissues and to the mammary gland</p><p>and metabolized to long-chain fatty acids for</p><p>storage as lipids or secretion as milk fat.</p><p>Amino acids. The majority of amino</p><p>acids are glucogenic and are also important</p><p>precursors for gluconeogenesis. Dietary</p><p>protein is the most important quantitative</p><p>source, but the labile pool of body protein</p><p>(particularly skeletal muscle) is also an</p><p>important source; together they contribute</p><p>to energy synthesis , milk lactose synthesis,</p><p>and milk protein synthesis.</p><p>Energy Balance</p><p>In high-producing dairy cows there is always</p><p>a negative energy balance in the first few</p><p>weeks of lactation. The highest dry matter</p><p>intake does not occur until 8 to 10 weeks after</p><p>calving, but peak milk production is at 4 to</p><p>6 weeks, and energy intake may not keep up</p><p>with demand. In response to a negative</p><p>energy balance and low serum concentra-</p><p>tions of glucose (and consequently low serum</p><p>concentrations of insulin), cows will mobilize</p><p>adipose tissue, with consequent increases in</p><p>serum concentrations of nonesterified fatty</p><p>acids (NEFA) and subsequent increases in</p><p>serum concentrations of β-hydroxybutyrate</p><p>(BHB), acetoacetate, and acetone. The</p><p>hepatic mitochondrial metabolism of fatty</p><p>acids promotes both gluconeogenesis and</p><p>ketogenesis. Cows partition nutrients during</p><p>pregnancy and lactation and are in a lipolytic</p><p>stage in early lactation and at risk for ketosis</p><p>during this period.</p><p>Hepatic Insufficiency in Ketosis</p><p>Hepatic insufficiency has been shown to</p><p>occur in bovine ketosis, but it does not occur</p><p>in all cases. Ketosis is defined as an increased</p><p>plasma or serum concentration of ketoacids</p><p>and is divided into three types. In type I,</p><p>or “spontaneous” ketosis, the gluconeogenic</p><p>pathways are maximally stimulated, and</p><p>ketosis occurs when the demand for glucose</p><p>outstrips the capacity of the liver for gluco-</p><p>neogenesis because of an insufficient supply</p><p>of glucose precursors. Rapid entry of NEFAs</p><p>into hepatic mitochondria occurs and results</p><p>in high rates of ketogenesis and high plasma/</p><p>serum ketone concentration. There is little</p><p>conversion of NEFAs to triglycerides, result-</p><p>ing in little fat accumulation in the liver. In</p><p>type II ketosis, manifest with fatty liver,</p><p>gluconeogenic pathways are not maximally</p><p>stimulated, and consequently mitochondrial</p><p>uptake of NEFAs is not as active, and NEFAs</p><p>become esterified in the cytosol, forming tri-</p><p>glyceride. The capacity of cattle to transport</p><p>triglyceride from the liver is low, resulting in</p><p>accumulation and fatty liver. The occurrence</p><p>of a fatty liver can further suppress hepatic</p><p>gluconeogenic capacity. Hepatic insuffi-</p><p>ciency may occur more commonly in those</p><p>cows predisposed to ketosis by overfeeding</p><p>in the dry period. In type III ketosis, cattle</p><p>results in hypoglycemia, ketonemia (the</p><p>accumulation in blood of acetoacetate,</p><p>β-hydroxybutyrate [BHB] and their</p><p>decarboxylation products acetone and</p><p>isopropanol), and ketonuria.</p><p>Epidemiology Primary ketosis and subclinical</p><p>ketosis occurs predominantly in well-</p><p>conditioned cows with high lactation</p><p>potential, principally in the first month of</p><p>lactation, with a higher prevalence in cows</p><p>with a higher lactation number. Loss of</p><p>body condition in the dry period and</p><p>immediately postpartum. Secondary ketosis</p><p>occurs where other disease reduces feed</p><p>intake.</p><p>Clinical findings Cattle show wasting with</p><p>decrease in appetite, body condition, and</p><p>milk production. Some have short periods</p><p>of bizarre neurologic and behavioral</p><p>abnormality (nervous ketosis). Response to</p><p>treatment is good. Subclinical ketosis</p><p>(hyperketonemia) is detected by tests for</p><p>ketones, usually BHB in blood, plasma, or</p><p>serum, and acetoacetate in urine.</p><p>Clinical pathology Hypoglycemia, ketonemia,</p><p>ketonuria, or elevated ketones in milk.</p><p>Necropsy findings None specific. Varying</p><p>degrees of hepatic lipidosis.</p><p>Diagnostic confirmation Ketonemia,</p><p>ketonuria, or, less commonly, elevated</p><p>ketone concentration in milk.</p><p>Treatment Intravenous glucose, parenteral</p><p>corticosteroid, and oral glucose precursors</p><p>such as propylene glycol. The disease</p><p>responds readily to treatment in cattle with</p><p>mild hepatic lipidosis and is self-limiting.</p><p>Control Correction of energy imbalance. Herd</p><p>biochemical monitoring coupled with</p><p>condition scoring. Daily monensin</p><p>administration to late-gestation and</p><p>early-lactation dairy cows.</p><p>SYNOPSIS</p><p>Etiology A multifactorial disorder</p><p>of energy</p><p>metabolism. Negative energy balance</p><p>V</p><p>etB</p><p>ooks.ir</p><p>Metabolic Diseases of Ruminants 1709</p><p>are fed a diet (typically a high-maize ration)</p><p>that results in a higher ruminal production</p><p>of butyrate, which is directly metabolized by</p><p>ruminal epithelial cells to butyrate.</p><p>Ketone Formation</p><p>Ketones arise from two major sources: butyr-</p><p>ate in the rumen and mobilization of fat. A</p><p>large proportion of butyrate produced by</p><p>rumen fermentation of the diet is converted</p><p>to BHB in the rumen epithelium and is</p><p>absorbed as such. Free fatty acids produced</p><p>from the mobilization of fat are transported</p><p>to the liver and oxidized to produce acetyl-</p><p>CoA and NADH.</p><p>Acetyl-CoA may be oxidized via the tri-</p><p>carboxylic acid (TCA) cycle or metabolized</p><p>to acetoacetyl-CoA. Complete oxidation of</p><p>acetyl-CoA via the TCA cycle depends on</p><p>an adequate supply of oxaloacetate from</p><p>the precursor propionate. If propionate, and</p><p>consequently oxaloacetate, is deficient, oxi-</p><p>dation of acetyl-CoA via the TCA cycle is</p><p>limited, and acetyl-CoA is metabolized to</p><p>acetoacetyl CoA and subsequently to aceto-</p><p>acetate and BHB.</p><p>The ketones BHB and acetoacetate can be</p><p>utilized as energy sources. They are normally</p><p>present in the plasma/serum of cattle, and</p><p>their concentration is a result of the balance</p><p>between production in the liver and utiliza-</p><p>tion by the peripheral tissues. Acetoacetate</p><p>can spontaneously convert to acetone, which</p><p>is volatile and therefore exhaled in the breath;</p><p>diffusion of acetone across the rumen epithe-</p><p>lium into the rumen means that some</p><p>acetone is eructated. Ruminal flora (most</p><p>likely bacteria) can metabolize acetone to</p><p>isopropanol, which can then be absorbed to</p><p>increase plasma concentrations of isopropa-</p><p>nol, a 3-carbon alcohol.1</p><p>Role of Insulin and Glucagon</p><p>The regulation of energy metabolism in</p><p>ruminants is primarily governed by insulin</p><p>and glucagon. Insulin acts as a glucoregula-</p><p>tory hormone stimulating glucose use by</p><p>tissues and decreasing hepatic gluconeogen-</p><p>esis. Plasma insulin concentrations decrease</p><p>with decreasing plasma concentrations of</p><p>glucose and propionate. Insulin also acts as</p><p>a liporegulatory hormone stimulating lipo-</p><p>genesis and inhibiting lipolysis. Glucagon is</p><p>the primary counterregulatory hormone to</p><p>insulin. The counteracting effects of insulin</p><p>and glucagon therefore play a central role in</p><p>the homeostatic control of glucose. A low</p><p>insulin : glucagon ratio stimulates lipolysis</p><p>in adipose tissue and ketogenesis in the liver.</p><p>Cows in early lactation have low insulin : glu-</p><p>cagon ratios because of low plasma glucose</p><p>concentrations and are in a catabolic state.</p><p>Regulation is also indirectly governed by</p><p>somatotropin, which is the most important</p><p>determinant of milk yield in cattle and is also</p><p>lipolytic. Factors that decrease the energy</p><p>supply, increase the demand for glucose, or</p><p>increase the utilization of peripheral fat</p><p>reserves as an energy source are likely to</p><p>increase ketone production and ketonemia.</p><p>There is, however, considerable cow-to-cow</p><p>variation in the risk for developing clinical</p><p>ketosis.</p><p>ETIOLOGY OF BOVINE KETOSIS</p><p>It is not unreasonable to view clinical ketosis</p><p>as one end of a spectrum of a metabolic state</p><p>that is common in heavily producing cows</p><p>in the postcalving period. This is because</p><p>high-yielding cows in early lactation are in</p><p>negative energy balance and are subclinically</p><p>ketotic as a result.</p><p>Cattle are particularly vulnerable to</p><p>ketosis because, although very little carbohy-</p><p>drate is absorbed as such, a direct supply of</p><p>glucose is essential for tissue metabolism,</p><p>particularly the formation of lactose associ-</p><p>ated with milk production. The utilization of</p><p>volatile fatty acids for energy purposes is also</p><p>dependent on a supply of available glucose.</p><p>This vulnerability is further exacerbated in</p><p>the lactating dairy cow by the tremendous</p><p>rate of turnover of glucose.</p><p>In the period between calving and peak</p><p>lactation, the demand for glucose is increased</p><p>and cannot be completely restrained. Cows</p><p>will reduce milk production in response to</p><p>a reduction of energy intake, but this does</p><p>not follow automatically nor proportionately</p><p>in early lactation because hormonal stimuli</p><p>for milk production overcome the effects</p><p>of reduced food intake. Under these cir-</p><p>cumstances, lowered plasma glucose con-</p><p>centrations result in lowered plasma insulin</p><p>concentrations. Long-chain fatty acids are</p><p>released from fat stores under the influence</p><p>of both a low plasma insulin : glucagon ratio</p><p>and the influence of high somatotropin</p><p>concentration, and this leads to increased</p><p>ketogenesis.</p><p>Individual Cow Variation</p><p>The rate of occurrence of negative energy</p><p>status, and therefore the frequency of clinical</p><p>ketosis cases, has increased markedly over</p><p>the last 4 decades because of the increase in</p><p>the lactation potential of the modern dairy</p><p>cow. Because of the mammary gland’s meta-</p><p>bolic precedence in the partitioning of nutri-</p><p>ents, especially glucose, milk production</p><p>continues at a high rate, causing an energy</p><p>drain. In many individual cows, the need</p><p>for energy is beyond their capacity for</p><p>dry matter intake, but there is between-cow</p><p>variation in risk under similar nutritional</p><p>stress. Clinical ketosis is easily produced in</p><p>early-lactation dairy cows by reducing the</p><p>daily feed intake.2 Subclinical ketosis (hyper-</p><p>ketonemia) in early-lactation dairy cows is</p><p>associated with decreased dry matter intake</p><p>and feeding time during the week before</p><p>calving.6</p><p>Types of Bovine Ketosis</p><p>There are many theories on the cause and</p><p>biochemical and hormonal pathogenesis of</p><p>ketosis, in addition to the importance of pre-</p><p>disposing factors. Reviews of these studies</p><p>are cited at the end of this disease section. In</p><p>general, it can be stated that clinical ketosis</p><p>occurs in cattle when they are subjected to</p><p>demands on their resources of glucose and</p><p>glycogen that cannot be met by their diges-</p><p>tive and metabolic activity.</p><p>A common classification of the disease</p><p>based on its natural presentation in inten-</p><p>sively and extensively managed dairy herds,</p><p>and one that accounts for the early lactational</p><p>demand for glucose, a limited supply of pro-</p><p>pionate precursors, and preformed ketones</p><p>or mobilized lipids in the pathogenesis, has</p><p>been developed. Such a classification scheme</p><p>includes the following mechanisms for keto-</p><p>sis, which will be discussed in turn:</p><p>• Primary ketosis (production ketosis)</p><p>• Secondary ketosis</p><p>• Alimentary ketosis</p><p>• Starvation ketosis</p><p>• Ketosis resulting from a specific</p><p>nutritional deficiency</p><p>Primary Ketosis (Production Ketosis)</p><p>This is the ketosis of most herds, the so-</p><p>called estate acetonemia. Primary ketosis</p><p>occurs in cows in good to excessive body</p><p>condition that have high lactation potential</p><p>and are being fed good-quality rations but</p><p>that are in a negative energy balance. There</p><p>is a tendency for the disease to recur in indi-</p><p>vidual animals, which is probably a reflection</p><p>of variation between cows in digestive capac-</p><p>ity or metabolic efficiency. A proportion of</p><p>primary ketosis cases appear as clinical</p><p>ketosis, but a much greater proportion</p><p>occurs as cases of subclinical ketosis in</p><p>which there are increased concentrations of</p><p>circulating ketone bodies but no overt clini-</p><p>cal signs. Affected cattle recover with correct</p><p>feeding and ancillary treatment.</p><p>Secondary Ketosis</p><p>Secondary ketosis occurs where the presence</p><p>of other disease results in a decreased food</p><p>intake. The cause of the reduction in food</p><p>intake is commonly the result of abomasal</p><p>displacement, traumatic reticulitis, metritis,</p><p>mastitis, or other diseases common to the</p><p>postparturient period. A high incidence of</p><p>ketosis has also been observed in herds</p><p>affected with fluorosis. An unusual occur-</p><p>rence reported was an outbreak of acetone-</p><p>mia in a dairy herd fed on a ration</p><p>contaminated by a low level (9.5 ppm) of lin-</p><p>comycin, which caused ruminal microbial</p><p>dysfunction. The proportion of cases of</p><p>ketosis that are secondary and their diagno-</p><p>sis as</p><p>such are both matters of great interest</p><p>because a significant proportion of all cases</p><p>of ketosis in lactating dairy cattle are second-</p><p>ary to other disease.</p><p>Alimentary Ketosis</p><p>Alimentary ketosis (also called type III in</p><p>some classification systems) is a result of</p><p>V</p><p>etB</p><p>ooks.ir</p><p>Chapter 17 ■ Metabolic and Endocrine Diseases1710</p><p>excessive amounts of butyrate in silage and</p><p>possibly also a result of decreased food</p><p>intake resulting from the poor palatability of</p><p>high-butyrate silage. Silage made from suc-</p><p>culent material may be more highly keto-</p><p>genic than other types of ensilage because of</p><p>its higher content of preformed butyric acid.</p><p>Spoiled silage is also a cause, and toxic bio-</p><p>genic amines in silage, such as putrescine,</p><p>may also contribute. This type of ketosis is</p><p>commonly subclinical, but it may predispose</p><p>to the development of production or primary</p><p>ketosis.</p><p>Starvation Ketosis</p><p>Starvation ketosis occurs in cattle that are in</p><p>poor body condition and that are fed poor-</p><p>quality feedstuffs. There is a deficiency of</p><p>propionate and protein from the diet and a</p><p>limited capacity of gluconeogenesis from</p><p>body reserves. Affected cattle recover with</p><p>correct feeding.</p><p>Ketosis Resulting From Specific</p><p>Nutritional Deficiency</p><p>Specific dietary deficiencies of cobalt and</p><p>possibly phosphorus may also lead to a high</p><p>incidence of ketosis. This may be in part a</p><p>result of a reduction in the intake of total</p><p>digestible nutrients, but in cobalt deficiency,</p><p>the essential defect is a failure to metabolize</p><p>propionic acid in the TCA cycle. The problem</p><p>is restricted to the cobalt-deficient areas of</p><p>the world, although the occurrence of cobalt</p><p>deficiency in high-producing dairy cows in</p><p>nondeficient areas has been described.</p><p>There is a marked nadir in food intake</p><p>around calving, followed by a gradual</p><p>increase. This increase is quite variable</p><p>between cows, but in the great majority of</p><p>cases does not keep pace with milk yield. The</p><p>net result is that high-yielding dairy cows are</p><p>almost certain to be in negative energy</p><p>balance for the first 2 months of lactation.</p><p>EPIDEMIOLOGY</p><p>Occurrence</p><p>Ketosis is a very common disease of lactating</p><p>dairy cattle and is prevalent in most coun-</p><p>tries where intensive farming is practiced.</p><p>Ketosis occurs mainly in animals housed</p><p>during the winter and spring months and is</p><p>rare in cows that calve on pasture. In housed</p><p>or free-stalled cattle, ketosis occurs year</p><p>around. The occurrence of the disease is</p><p>very much dependent on management and</p><p>nutrition and varies between herds. As might</p><p>be expected, lactational incidence rates</p><p>vary between herds, and a review of 11 epi-</p><p>demiologic studies showed a lactation inci-</p><p>dence rate for ketosis that varied from 0.2%</p><p>to 10.0%.</p><p>The incidence of subclinical ketosis</p><p>(more correctly called hyperketonemia) is</p><p>influenced by the cut-point of plasma BHB</p><p>used for definition, but it is much higher</p><p>than the incidence of clinical ketosis, espe-</p><p>cially in undernourished herds, and can</p><p>approach 40%. Incidence can be challenging</p><p>and expensive to estimate because preva-</p><p>lence information is usually measured. In</p><p>general, the incidence of subclinical ketosis</p><p>is 1.8 times the prevalence.</p><p>Animal and Management</p><p>Risk Factors</p><p>There are conflicting reports on the signifi-</p><p>cance of risk factors for ketosis and subclini-</p><p>cal ketosis, which probably reflect that the</p><p>disease can be a cause or effect of a number</p><p>of interacting factors. The disease occurs in</p><p>the immediate postparturient period, with</p><p>90% of cases occurring in the first 60 days of</p><p>lactation. Regardless of the specific etiology,</p><p>ketosis occurs most commonly during the</p><p>first month of lactation, less commonly in</p><p>the second month, and only occasionally in</p><p>late pregnancy. In different studies, the</p><p>median time to onset following calving</p><p>has varied from 10 to 28 days, with some</p><p>recent studies showing a peak prevalence of</p><p>subclinical ketosis in the first 2 weeks post-</p><p>calving. A prolonged previous intercalving</p><p>interval increases risk.</p><p>Age. Cows of any age may be affected, but</p><p>the disease increases from a low prevalence</p><p>at the first calving to a peak at the fourth</p><p>calving, associated with the level of milk pro-</p><p>duction. Lactational incidence rates of clini-</p><p>cal ketosis of 1.5% and 9%, respectively, were</p><p>found in a study of 2415 primiparous and</p><p>4360 multiparous cows. Clinical ketosis can</p><p>also recur in the same lactation.</p><p>Herd differences in prevalence are very</p><p>evident in clinical practice and in the litera-</p><p>ture, with some herds having negligible</p><p>occurrence. Although apparent differences</p><p>in breed incidence are reported, evidence for</p><p>a heritable predisposition within breeds is</p><p>minimal. Feeding frequency has an effect,</p><p>with the prevalence of ketosis being much</p><p>lower in herds that feed a total mixed ration</p><p>(TMR) ad libitum compared with herds that</p><p>feed roughage and concentrate separately fed</p><p>twice a day (component fed).</p><p>Body-Condition Score. There are conflict-</p><p>ing reports on the relation between BCS at</p><p>calving and ketosis, but it is very likely that</p><p>studies that have found no relationship have</p><p>not had many fat cows in the herds exam-</p><p>ined. Fat body condition postpartum was</p><p>observed to be associated with a higher first-</p><p>test-day milk yield, milk-fat-to-protein ratio</p><p>of greater than 1.5, increased body-condition</p><p>loss, and a higher risk for ketosis. In another</p><p>study, cows with a BCS greater than 3.25 at</p><p>parturition and that lost 0.75 points in BCS</p><p>in the first 2 months of lactation developed</p><p>subclinical ketosis. Body-condition loss</p><p>during the dry period also increases risk for</p><p>ketosis in the following lactation.</p><p>Season. There is no clear association with</p><p>season. In some but not all summer grazing</p><p>areas, a higher risk is generally observed in</p><p>cattle during the winter housing period.</p><p>Higher prevalence has been observed in the</p><p>late summer and early winter in Scandina-</p><p>vian countries.</p><p>Other Interactions. There is a greater risk</p><p>for the development of ketosis in cows that</p><p>have an extended long dry period;3 those that</p><p>develop milk fever, retained placenta, lame-</p><p>ness, or hypomagnesemia; or those that have</p><p>high milk production and high first milking</p><p>colostrum volume.3 Cows with twins are also</p><p>at risk for ketosis in the terminal stages of</p><p>pregnancy. There is a bidirectional relation</p><p>between risk for displaced abomasum and</p><p>risk for ketosis, but in a field study of 1000</p><p>cows in 25 herds, cows that had a serum</p><p>BHB concentration greater than 1.4 mmol/L</p><p>in the first 2 weeks of lactation had odds of</p><p>4 : 1 that a displaced abomasum would be</p><p>diagnosed 1 to 3 weeks later. In another</p><p>study of 1010 cows, a serum BHB concentra-</p><p>tion of 1.5 mmol/L or greater in the first</p><p>2 weeks of lactation was found to be associ-</p><p>ated with a threefold increase in ketosis</p><p>or displaced abomasum. Interestingly, cows</p><p>with increased blood BHB concentration</p><p>immediately before surgical correction of</p><p>left-displaced abomasum have increased lon-</p><p>gevity within the herd, compared with cattle</p><p>with BHB concentrations within the refer-</p><p>ence interval.7,8</p><p>Economic Significance</p><p>Clinical and subclinical ketosis are major</p><p>causes of loss to the dairy farmer. In rare</p><p>instances the disease is irreversible and the</p><p>affected animal dies, but the main economic</p><p>loss results from the loss of production while</p><p>the disease is present, the possible failure</p><p>to return to full production after recovery,</p><p>and the increased occurrence of periparturi-</p><p>ent disease. Both clinical and subclinical</p><p>ketosis are accompanied by decreased milk</p><p>yields; lower milk protein and milk lactose;</p><p>increased risk for delayed estrus and lower</p><p>first-service conception rates; lower preg-</p><p>nancy rates; increased intercalving intervals;</p><p>increased risk of cystic ovarian disease,</p><p>metritis, and mastitis; and increased invol-</p><p>untary culling.4 The estimated economic</p><p>loss from a single case of subclinical ketosis</p><p>was US$117 in 2015, and the estimated</p><p>average total cost per case of subclinical</p><p>ketosis was $289 after considering the costs</p><p>of displaced abomasum and metritis attrib-</p><p>uted to hyperketonemia.5</p><p>PATHOGENESIS</p><p>Bovine Ketosis</p><p>The principal metabolic disturbances</p><p>observed, hypoglycemia and ketonemia, may</p><p>both exert an effect on the clinical syndrome.</p><p>However, in the experimental disease in</p><p>cattle, it is not always clear what determines</p><p>the development of the clinical signs in cases</p><p>that convert from subclinical to clinical</p><p>V</p><p>etB</p><p>ooks.ir</p><p>Metabolic Diseases of Ruminants 1711</p><p>ketosis. In many cases, the severity of the</p><p>clinical syndrome is proportional to the</p><p>degree of hypoglycemia, and this, together</p><p>with the rapid response to parenterally</p><p>administered glucose in cattle, suggests</p><p>hypoglycemia as the predominant factor.</p><p>This hypothesis is supported by the develop-</p><p>ment of prolonged hypoglycemia and a</p><p>similar clinical syndrome to that of ketosis,</p><p>after the experimental IV or SC injection of</p><p>insulin (2 U/kg BW).</p><p>However, in most field cases the severity</p><p>of the clinical syndrome is also roughly</p><p>proportional to the degree of ketonemia.</p><p>This is an understandable relationship</p><p>because ketone bodies are produced in larger</p><p>quantities as the deficiency of glucose</p><p>increases. However, the ketone bodies are</p><p>thought to exert an additional influence on</p><p>the clinical signs observed; for instance, ace-</p><p>toacetic acid is known to be toxic and prob-</p><p>ably contributes to the terminal coma in</p><p>diabetes mellitus in humans.</p><p>The nervous signs that occur in some</p><p>cases of bovine ketosis are thought to be</p><p>caused by the production of isopropanol, a</p><p>breakdown product of acetone in the</p><p>rumen,1 although the requirement of</p><p>nervous tissue for glucose to maintain</p><p>normal function may also be a factor in</p><p>these cases. A reasonable explanation for the</p><p>development of nervous ketosis is that a</p><p>rapid increase in plasma acetone concentra-</p><p>tion in an animal that has an active rumen</p><p>flora leads to a rapid increase in ruminal</p><p>acetone concentration. The acetone is</p><p>metabolized by rumen microflora to isopro-</p><p>panol, which is then absorbed into the</p><p>bloodstream, potentially leading to neuro-</p><p>logic abnormalities. This mechanism is con-</p><p>sistent with observations that nervous signs</p><p>of ketosis are more common in cattle with</p><p>severe ketosis that is rapidly induced.</p><p>Spontaneous ketosis in cattle is usually</p><p>readily reversible by treatment; incomplete</p><p>or temporary response is usually a result of</p><p>the existence of a primary disease, with</p><p>ketosis present only as a secondary develop-</p><p>ment, although fatty degeneration of the</p><p>liver in protracted cases may prolong the</p><p>recovery period. Changes in ruminal flora</p><p>after a long period of anorexia may also</p><p>cause continued impairment of digestion.</p><p>Immunosuppression has been demon-</p><p>strated with energy deficiency and ketosis.</p><p>The higher susceptibility of ketotic postpar-</p><p>tum cows to local and systemic infections</p><p>may be related to impairment of the respira-</p><p>tory burst of neutrophils that occurs with</p><p>elevated plasma concentrations of BHB.</p><p>CLINICAL FINDINGS</p><p>Two major clinical forms of bovine ketosis</p><p>are described—wasting and nervous—but</p><p>these are the two extremes of a range of</p><p>syndromes in which wasting and nervous</p><p>signs are present in varying degrees of</p><p>prominence.</p><p>The wasting form is the most common of</p><p>the two and is manifest with a gradual but</p><p>moderate decrease in appetite and milk yield</p><p>over 2 to 4 days. In component-fed herds, the</p><p>pattern of appetite loss is often very specific</p><p>in that the cow first refuses to eat grain, then</p><p>ensilage, but may continue to eat hay. The</p><p>appetite may also be depraved.</p><p>Body weight is lost rapidly, usually at a</p><p>greater rate than one would expect from the</p><p>decrease in appetite. Farmers usually describe</p><p>affected cows as having a “woody” appear-</p><p>ance because of the apparent wasting and</p><p>loss of cutaneous elasticity presumably</p><p>resulting from disappearance of subcutane-</p><p>ous fat. The feces are firm and dry, but serious</p><p>constipation does not occur. The cow is</p><p>moderately depressed and is quieter than</p><p>usual. The disinclination to move and to eat</p><p>may suggest the presence of mild abdominal</p><p>pain, but localized pain cannot be detected</p><p>via abdominal palpation.</p><p>The temperature and the pulse and respi-</p><p>ratory rates are normal, and although the</p><p>ruminal movements may be decreased in</p><p>amplitude and number, they are within the</p><p>normal range unless the course is of long</p><p>duration, in which case they may virtually</p><p>disappear. The characteristic sweet odor of</p><p>ketones is detectable on the breath and often</p><p>in the milk, but people vary in their ability</p><p>to detect ketones on the breath (specifically</p><p>the volatile ketone, acetone).</p><p>Very few affected animals die, but without</p><p>treatment the milk yield falls; although spon-</p><p>taneous recovery usually occurs over about a</p><p>month, as equilibrium between the drain of</p><p>lactation and food intake is established, the</p><p>milk yield is never fully regained. The fall in</p><p>milk yield in the wasting form may be as</p><p>much as 25%, and there is an accompanying</p><p>sharp drop in the solids-not-fat content of</p><p>the milk. In the wasting form, nervous signs</p><p>may occur in a few cases, but they rarely</p><p>comprise more than transient bouts of stag-</p><p>gering and partial blindness.</p><p>In the nervous form (nervous ketosis),</p><p>signs are usually bizarre and begin quite</p><p>suddenly. The syndrome is suggestive of</p><p>delirium rather than of frenzy, and the char-</p><p>acteristic signs include the following:</p><p>• Walking in circles</p><p>• Straddling or crossing of the legs</p><p>• Head pushing or leaning into the</p><p>stanchion</p><p>• Apparent blindness</p><p>• Aimless movements and wandering</p><p>• Vigorous licking of the skin and</p><p>inanimate objects (Fig. 17-6)</p><p>• Depraved appetite</p><p>• Chewing movements with salivation</p><p>Hyperesthesia may be evident, with the</p><p>animal bellowing on being pinched or</p><p>stroked. Moderate tremor and tetany may be</p><p>present, and there is usually an incoordinate</p><p>gait. The nervous signs usually occur in</p><p>short episodes that last for 1 or 2 hours and</p><p>may recur at intervals of about 8 to 12 hours.</p><p>Affected cows may injure themselves during</p><p>the nervous episodes. Surgical correction of</p><p>displaced abomasum in cows exhibiting</p><p>some signs consistent with nervous ketosis</p><p>should be delayed until their energy status</p><p>has been evaluated and treatment instituted,</p><p>if indicated.</p><p>Subclinical Ketosis (Hyperketonemia)</p><p>Subclinical ketosis is defined as an increase</p><p>in blood/plasma/serum BHB above the</p><p>normal reference range or ketonuria in a cow</p><p>without detectable clinical signs of disease.</p><p>Many cows that are in negative energy</p><p>balance in early pregnancy will have ketonu-</p><p>ria without showing clinical signs, but they</p><p>Fig. 17-6 Holstein–Friesian cow with nervous ketosis, manifest as excessive and sustained</p><p>licking behavior.</p><p>V</p><p>etB</p><p>ooks.ir</p><p>Chapter 17 ■ Metabolic and Endocrine Diseases1712</p><p>will have diminished productivity, including</p><p>depression of milk yield and a reduction in</p><p>fertility. Clinical diagnosis is not effective,</p><p>and in one study, diagnosis by routine urine</p><p>testing at 5 to 12 days postpartum was con-</p><p>siderably more efficient (15.6% detected)</p><p>than diagnosis by the herdsman (4.4%</p><p>detected). In a British study of 219 herds the</p><p>annual mean rate of reported clinical ketosis</p><p>was 0.5 per 100 adult cows, but the rate of</p><p>subclinical ketosis, as defined by increased</p><p>plasma concentrations of BHB and nonester-</p><p>ified fatty acids, was substantially higher.</p><p>There is debate about whether subclinical</p><p>ketosis is the correct term, with some support</p><p>for replacing the term with hyperketonemia.</p><p>Potential milk production in cows with</p><p>subclinical ketosis is reduced by 1% to 9%.</p><p>Surveys of large populations show a declin-</p><p>ing prevalence of ketosis-positive cows after</p><p>a peak in the period immediately after</p><p>calving and a positive relationship between</p><p>hyperketonemia and high milk yield. Infer-</p><p>tility may appear as an ovarian abnormality,</p><p>delayed onset of estrus, or endometritis</p><p>resulting in an increase in the calving-to-</p><p>conception interval</p><p>and reduced conception</p><p>rate at first insemination.4</p><p>CLINICAL PATHOLOGY</p><p>Hypoglycemia, ketonemia, and ketonuria are</p><p>characteristic of the disease.</p><p>Glucose</p><p>Plasma glucose concentrations are reduced</p><p>from the normal of approximately 50 to</p><p>65 mg/dL to 20 to 40 mg/dL. Ketosis second-</p><p>ary to other diseases is usually accompanied</p><p>by plasma glucose concentrations above</p><p>50 mg/dL, and many cattle have much</p><p>higher concentrations. Conversion factors</p><p>are shown in Table 17-7.</p><p>Ketones</p><p>Most commonly, plasma or serum β-</p><p>hydroxybutyrate (BHB) measured in SI</p><p>units (mmol/L) is used for analysis of keto-</p><p>nemia. BHB is the quantitatively highest</p><p>circulating ketone body in cattle. Plasma</p><p>concentrations of BHB significantly correlate</p><p>with plasma concentrations of acetoacetate,</p><p>but acetoacetate is unstable in blood samples,</p><p>whereas BHB is stable, particularly when</p><p>samples are refrigerated or frozen. Normal</p><p>cows have plasma BHB concentrations less</p><p>than 1.0 mmol/L; cows with subclinical</p><p>ketosis have blood or plasma/serum concen-</p><p>trations greater than 1.0, 1.2, or 1.4 mmol/L</p><p>(the cut-point varies depending on the study,</p><p>analytical method, and whether blood or</p><p>plasma is analyzed).9,10 Different cut-points</p><p>have been proposed for serum BHB concen-</p><p>tration in the first week postpartum</p><p>(1.0 mmol/L) and the second week postpar-</p><p>tum (1.4 mmol/L);11 this may be attributable</p><p>to blood BHB concentrations being highest</p><p>at 8 days in milk.12 In general, because the</p><p>cut-point for the diagnosis of subclinical</p><p>ketosis should be based on a detectable effect</p><p>on decreasing milk production or an</p><p>increased risk of adverse health events,10 a</p><p>consensus is developing around the use of</p><p>serum/plasma BHB concentration greater</p><p>than 1.0 mmol/L as the cut-point for sub-</p><p>clinical ketosis based on the association with</p><p>impaired reproductive performance11 and</p><p>increased risk of developing a displaced</p><p>abomasum, puerperal metritis, or clinical</p><p>ketosis.13</p><p>Cows with clinical ketosis usually have</p><p>serum/plasma BHB concentrations in excess</p><p>of 2.5 mmol/L, with values rarely reaching</p><p>10.0 mmol/L. Plasma BHB shows some</p><p>diurnal variation in cows fed twice daily,</p><p>with peak concentrations occurring approxi-</p><p>mately 4 hours after feeding and higher con-</p><p>centrations in the morning than in the</p><p>afternoon. This diurnal variation is not as</p><p>prominent in cows fed a total mixed ration</p><p>ad libitum.</p><p>Measurement of blood or plasma/serum</p><p>BHB concentration has recently become a</p><p>cost-effective and convenient method for</p><p>routine analysis and cow-side monitoring,</p><p>with the introduction of low-cost point-of-</p><p>care devices for measurement (US$2/test).</p><p>The concentration of acetoacetate or BHB</p><p>in urine and milk is also used for diagnos-</p><p>tic purposes.14 Concentrations of BHB and</p><p>acetoacetate in urine and milk are less than</p><p>those in plasma/serum, but the correlation</p><p>coefficients for plasma/serum and milk</p><p>BHB and plasma/serum and milk acetoac-</p><p>etate are 0.66 and 0.62, respectively. For</p><p>cow-side use, urine acetoacetate concentra-</p><p>tion using the nitroprusside test and blood</p><p>BHB concentration using a point-of-care</p><p>device are currently the preferred tests for</p><p>detecting subclinical or clinical ketosis in</p><p>cattle.</p><p>Milk and Urine Cow-Side Tests</p><p>Cow-side tests have the advantage of being</p><p>inexpensive and giving immediate results,</p><p>and they can be used as frequently as neces-</p><p>sary. A minor source of error is that the</p><p>concentration of ketone bodies in these</p><p>fluids will depend not only on the ketone</p><p>concentration of the plasma, but also on</p><p>the amount of urine excreted or on the</p><p>milk yield. Milk concentration of ketones is</p><p>less variable, easier to collect, and may give</p><p>fewer false negatives in cows with subclinical</p><p>ketosis.</p><p>Milk and urine ketone concentrations</p><p>have been traditionally detected by the</p><p>reaction of acetoacetate with sodium nitro-</p><p>prusside and can be interpreted in a semi-</p><p>quantitative manner based on the intensity</p><p>of the reaction. The nitroprusside reaction</p><p>detects both acetoacetate and acetone, but it</p><p>is much more sensitive to acetoacetate than</p><p>acetone; the latter is only detected when</p><p>acetone concentrations are greater than</p><p>600 mmol/L, which represents a supraphysi-</p><p>ologic concentration.15 As a consequence,</p><p>the nitroprusside test functions as a semi-</p><p>quantitative test of acetoacetate concentra-</p><p>tion and should be clinically regarded as a</p><p>test of acetoacetate and not acetone. Several</p><p>products are available commercially as strips</p><p>or test powders and are commonly accom-</p><p>panied by a color chart that allows a clas-</p><p>sification of acetoacetate concentration in</p><p>grades such as negative, trace (5 mg/dL;</p><p>0.5 mmol/L), small (15 mg/dL; 1.0 mmol/L),</p><p>moderate (40 mg/dL; 2.0 mmol/L), or large</p><p>(>80 mg/dL; 5 mmol/L), based on the inten-</p><p>sity of the color of the reaction.15 Milk</p><p>powder tests are not sufficiently sensitive for</p><p>detection of subclinical ketosis (report too</p><p>many false negatives), and urine tests are not</p><p>sufficiently specific (report too many false</p><p>positives).</p><p>Milk Testing. The sensitivity and specificity</p><p>of the nitroprusside powder test with milk in</p><p>various studies is reported as 28% to 90%</p><p>and 96% to 100%, respectively. Currently, a</p><p>milk strip test detecting the concentration</p><p>of BHB in milk is available and is graded</p><p>on the concentration of BHB. In different</p><p>studies, milk BHB has a reported sensitivity</p><p>and specificity of 58% to 96% and 69% to</p><p>99%, respectively. These variations are in</p><p>part a result of the use of different plasma</p><p>BHB reference values (1.2 and 1.4 mmol/L)</p><p>for designation of subclinical ketosis and</p><p>different statistical methods for analysis.</p><p>Somatic cell counts in milk greater than 1</p><p>million cells/mL will cause an elevation in</p><p>reading of both the BHBA strip test and the</p><p>nitroprusside tests.</p><p>Urine Testing. A nitroprusside tablet has a</p><p>reported sensitivity and specificity of 100%</p><p>and 59%, respectively, compared with serum</p><p>BHB concentrations above 1.4 mmol/L;</p><p>a nitroprusside strip test has a reported</p><p>Table 17-7 To convert from the SI unit to the conventional unit, divide by the</p><p>conversion factor; to convert from the conventional unit to the SI unit, multiply by the</p><p>conversion factor</p><p>Substrate Conventional unit Conversion factor SI unit</p><p>β-hydroxybutyrate mg/dL 0.0961 mmol/L</p><p>Acetoacetate mg/dL 0.0980 mmol/L</p><p>Acetone mg/dL 0.1722 mmol/L</p><p>V</p><p>etB</p><p>ooks.ir</p><p>Metabolic Diseases of Ruminants 1713</p><p>sensitivity and specificity of 78% and 96%,</p><p>respectively, with a urine cut-point corre-</p><p>sponding to “small” on the color chart or</p><p>49% and 99%, respectively, with a urine</p><p>cut-point corresponding to “moderate” on</p><p>the color chart. BHB test strips when used</p><p>with urine have a reported sensitivity and</p><p>specificity of 73% and 96%, respectively, at</p><p>a urine cut-point of 0.1 mmol/L BHB and</p><p>27% and 99%, respectively, at a urine cut-</p><p>point of 0.2 mmol/L BHB. Urinary ketone</p><p>concentrations are more closely related to</p><p>plasma ketone concentrations than are milk</p><p>BHB and acetoacetate concentrations.16,17</p><p>Moreover, urine acetoacetate concentration</p><p>appears superior to milk BHB concentration</p><p>in diagnosing ketosis.17</p><p>Milk-Fat-to-Protein Ratio. Milk-fat con-</p><p>centration tends to increase, and milk protein</p><p>concentration tends to decrease, during</p><p>postpartum negative energy balance. A fat-</p><p>to-protein ratio greater than 1.5 in first-day</p><p>test milk is indicative of a lack of energy</p><p>supply in the feed and of risk for ketosis and</p><p>provides a similar test sensitivity (Se = 0.63)</p><p>for detecting subclinical ketosis as does</p><p>milk BHB concentration (Se = 0.58).17 Milk</p><p>production in multiparous animals is also</p><p>separately associated with postpartum nega-</p><p>tive energy balance.18</p><p>Clinical Chemistry and Hematology.</p><p>White and differential cell counts are vari-</p><p>able and not of diagnostic value for ketosis.</p><p>There are usually elevations of liver enzyme</p><p>activity in plasma/serum, but liver function</p><p>tests are within the normal range. Liver</p><p>biopsy is the only accurate method to deter-</p><p>mine the degree</p><p>of liver damage.</p><p>Plasma concentrations of NEFAs and</p><p>total bilirubin are elevated in ketosis, with</p><p>mean NEFA concentrations increasing above</p><p>0.3 mmol/L from 3 days before parturition</p><p>to approximately 0.7 mmol/L from 0 to 9</p><p>days in milk, after which time plasma NEFA</p><p>concentration gradually decreases.12 The</p><p>increase in bilirubin is attributed, in part,</p><p>to hepatic dysfunction; however, bilirubin</p><p>is not a sufficiently sensitive indicator to</p><p>assess the extent of fat mobilization and liver</p><p>function in cows with ketosis. Plasma cho-</p><p>lesterol concentration is typically decreased</p><p>for the stage of lactation; the decrease in cho-</p><p>lesterol is a result of decreased hepatocyte</p><p>secretion of very-low-density lipoproteins</p><p>(VLDLs), which are cholesterol rich, or</p><p>increased mammary uptake of cholesterol</p><p>relative to cholesterol availability. After</p><p>secretion, VLDLs are processed in plasma to</p><p>intermediate-density lipoproteins by hydro-</p><p>lysis of triglycerides.19 Intermediate-density</p><p>lipoproteins are then metabolized in plasma</p><p>to cholesterol-rich low-density lipoproteins</p><p>that carry cholesterol to peripheral tissues,</p><p>including the mammary gland.19,20 A clini-</p><p>cally significant proportion of lactating dairy</p><p>cattle with ketosis have low plasma cortisol</p><p>concentrations;21 although the mechanism</p><p>has not been determined, it is possible that</p><p>decreased cholesterol availability negatively</p><p>affects cortisol synthesis.</p><p>Liver glycogen levels are low, and the</p><p>glucose tolerance curve may be normal. Vol-</p><p>atile fatty acid levels in the rumen are much</p><p>higher in ketotic than in normal cows, and</p><p>the ruminal concentrations of butyrate are</p><p>markedly increased relative to acetate and</p><p>propionate acids. There is a small but signifi-</p><p>cant drop in serum calcium concentrations</p><p>(down to about 9 mg/dL [2.25 mmol/L]),</p><p>probably as a result of decreased dry matter</p><p>intake in lactating dairy cattle relative to the</p><p>level of milk production.</p><p>Plasma and urine metabolic profiling</p><p>shows promise as a means of differentiating</p><p>cattle with clinical ketosis and subclinical</p><p>ketosis from healthy cattle at the same stage of</p><p>lactation. Twenty-five plasma metabolites22,23</p><p>and 11 urine proteins24 have been identified</p><p>to differ between these three groups. Differ-</p><p>ences include changes in plasma amino acid</p><p>concentrations that may reflect differences in</p><p>feed intake relative to milk production or</p><p>altered metabolic pathways and changes in</p><p>urine polypeptide concentrations that may</p><p>reflect decreased immune responsiveness.</p><p>NECROPSY FINDINGS</p><p>The disease is not usually fatal in cattle, but</p><p>fatty degeneration of the liver and secondary</p><p>changes in the anterior pituitary gland and</p><p>adrenal cortex may be present.</p><p>treatment for subclinical ketosis is usually</p><p>not applied on an individual basis, but nutri-</p><p>tion and management issues should be</p><p>investigated whenever a large proportion of</p><p>early-lactation cows are diagnosed with sub-</p><p>clinical ketosis.</p><p>The rational treatment in ketosis is to</p><p>relieve the need for glucose formation from</p><p>tissues and allow ketone-body utilization to</p><p>continue normally. Theoretically, the sim-</p><p>plest means of doing this is by the adminis-</p><p>tration of glucose replacement therapy. The</p><p>effect of the administration of glucose is</p><p>complex, but it allows the reversal of keto-</p><p>genesis and the establishment of normal</p><p>patterns of energy metabolism. Ideally, treat-</p><p>ment should be at an early stage of the</p><p>disease to minimize loss, and with subclini-</p><p>cal ketosis this requires biochemical testing.</p><p>Replacement Therapy</p><p>Glucose (Dextrose)</p><p>The IV injection of 500 mL of a 50% solution</p><p>of glucose results in transient hyperglycemia,</p><p>increased insulin and decreased glucagon</p><p>secretion, and reduced plasma concentration</p><p>of NEFAs. Glucose administration effects a</p><p>marked improvement in most cows, but</p><p>relapses occur commonly unless repeated</p><p>treatments are used. This is probably a result</p><p>of the transience of the hyperglycemia (3 to</p><p>4 hours) or insufficient dosing—the dose</p><p>required varies directly with the amount of</p><p>lactose being lost in the milk. Contrary to</p><p>widespread belief, very little of the admin-</p><p>istered glucose is lost to urinary excretion</p><p>(<10%).25,26 SC injections of hypertonic</p><p>glucose prolong the response, but they are</p><p>not recommended because they cause dis-</p><p>comfort, and large unsightly swellings, which</p><p>often become infected, may result. Intraperi-</p><p>toneal injections of 20% solution of dextrose</p><p>have also been used, but they are not recom-</p><p>mended because of the risk of infection.</p><p>Other Sugars</p><p>Other sugars, especially fructose, either</p><p>alone or as a mixture of glucose and fructose</p><p>(invert sugar), and xylitol, have been used in</p><p>an effort to prolong the response, but idio-</p><p>syncratic responses to some preparations, in</p><p>the form of polypnea, muscle tremor, weak-</p><p>ness, and collapse, can occur while the injec-</p><p>tion is being given.</p><p>Propylene Glycol and</p><p>Glycerine/Glycerol</p><p>To overcome the necessity for repeated injec-</p><p>tions, propylene glycol can be administered</p><p>as a drench. The traditional dose is 225 ml</p><p>twice daily for 2 days, followed by 110 ml</p><p>daily for 2 days to cattle, but higher volumes</p><p>are also used for larger cattle (a typical treat-</p><p>ment protocol in North America is 300 ml</p><p>PO daily for 5 days). Some of the adminis-</p><p>tered propylene glycol is metabolized to pro-</p><p>pionate in the rumen and absorbed, whereas</p><p>some of the propylene glycol is absorbed</p><p>DIFFERENTIAL DIAGNOSIS</p><p>Cattle</p><p>The clinical picture is usually too indefinite,</p><p>especially in cattle, to enable a diagnosis to</p><p>be made solely on clinical grounds. General</p><p>consideration of the history, with particular</p><p>reference to the time of calving, and the</p><p>feeding program, and biochemical</p><p>examination to detect the presence of</p><p>hypoglycemia, ketonemia, and ketonuria are</p><p>necessary to establish a diagnosis.</p><p>Wasting form:</p><p>• Abomasal displacement</p><p>• Traumatic reticulitis</p><p>• Primary indigestion</p><p>• Cystitis and pyelonephritis</p><p>Nervous form:</p><p>• Rabies</p><p>• Hypomagnesemia</p><p>• Bovine spongiform encephalopathy</p><p>TREATMENT</p><p>In cattle, a number of effective treatments are</p><p>available for ketosis, but in some affected</p><p>animals, the response is only transient; in</p><p>rare cases, the disease may persist and cause</p><p>death or necessitate slaughter of the animals.</p><p>Most of these cases are secondary, and failure</p><p>to respond satisfactorily to treatment is a</p><p>result of the primary disease. Specific</p><p>V</p><p>etB</p><p>ooks.ir</p><p>Chapter 17 ■ Metabolic and Endocrine Diseases1714</p><p>directly across ruminal epithelium and</p><p>metabolized by the liver. Propylene glycol</p><p>(200 to 700 g daily), or salts of propionate,</p><p>can be administered in the feed and give</p><p>good results. Administration in feed is pre-</p><p>ferred by some because this method avoids</p><p>dangers of aspiration with drenching;</p><p>however, cows not used to its inclusion in the</p><p>feed may show feed refusal. Studies also</p><p>suggest that drenching of propylene glycol</p><p>provides a more beneficial response than</p><p>including the same amount in a total mixed</p><p>ration; the bolus effect of propionate produc-</p><p>tion appears to be more beneficial than a</p><p>steady-state increase as a result of a bolus</p><p>increase in plasma insulin concentration. It</p><p>is recommended that for best results, dosing</p><p>with propylene glycol should be preceded by</p><p>an IV injection of glucose.</p><p>Parenteral infusions of glucose solutions</p><p>and the feeding of glycerol depress the fat</p><p>content of milk, and the net saving in energy</p><p>may favorably influence response to these</p><p>drugs. Glycerol and propylene glycol are not</p><p>as efficient as glucose because conversion</p><p>to glucose utilizes oxaloacetate. Propylene</p><p>glycol is absorbed directly from the rumen</p><p>and acts to reduce ketogenesis by increasing</p><p>mitochondrial citrate concentrations; its</p><p>metabolism to glucose occurs via conversion</p><p>to pyruvate, with subsequent production of</p><p>oxaloacetate via pyruvate carboxylase.</p><p>Other Glucose Precursors</p><p>Because of its glucogenic effect, sodium pro-</p><p>pionate is theoretically a suitable treatment,</p><p>but when administered in</p><p>110- to 225-g</p><p>doses daily, the response in cattle is often</p><p>very slow. Lactates are also highly gluco-</p><p>genic, but both calcium and sodium lactate</p><p>(1 kg initially, followed by 0.5 kg for 7 days)</p><p>and sodium acetate (110 to 500 g/d) have</p><p>given less satisfactory results than those</p><p>obtained with sodium propionate. Ammo-</p><p>nium lactate (200 g for 5 days) has, however,</p><p>been used extensively, with reported good</p><p>results. Lactose, in whey or in granular form</p><p>in the diet, can increase dry matter intake,</p><p>but it also increases ruminal butyrate con-</p><p>centration and plasma BHB concentrations.</p><p>Hormonal Therapy</p><p>Glucocorticoids. The efficiency of gluco-</p><p>corticoids in the treatment of bovine ketosis</p><p>has been demonstrated in both experimental</p><p>and field cases. The observation that a clini-</p><p>cally significant proportion of lactating dairy</p><p>cattle with ketosis have low plasma cortisol</p><p>concentrations21 provides support for gluco-</p><p>corticoid administration. Hyperglycemia</p><p>occurs within 24 hours of glucocorticoid</p><p>administration and appears to result from a</p><p>repartitioning of glucose in the body rather</p><p>than from gluconeogenesis.</p><p>Historically, many glucocorticoid prepa-</p><p>rations have been used successfully, but cur-</p><p>rent drugs are more potent, require lower</p><p>dosage, and have fewer side effects. A hyper-</p><p>glycemic state is produced for 4 to 6 days</p><p>in ketotic cows given 10 mg of dexametha-</p><p>sone 21-isonicotinate, and other prepara-</p><p>tions that have a shorter duration of action,</p><p>such as dexamethasone sodium phosphate</p><p>(40 mg) and flumethasone (5 mg), are also</p><p>used. Dexamethasone 21-isonicotinate (20</p><p>to 25 mg IM) decreases whole-body insulin</p><p>sensitivity and affects glucose and lipid</p><p>metabolism; it decreases liver fat content in</p><p>early-lactating dairy cows with surgically</p><p>corrected left-displaced abomasum.27 Label</p><p>regulations vary between countries; in gen-</p><p>eral, the recommendations of the manufac-</p><p>turer with regard to glucorticoid use and</p><p>dosage should be followed. Profound hypo-</p><p>kalemia with high case fatality is a potential</p><p>sequel to prolonged repeated therapy of</p><p>ketosis with isoflupredone acetate, which has</p><p>both glucocorticoid and mineralocorticoid</p><p>activity. For this reason, only one treatment</p><p>of isoflupredone acetate is recommended for</p><p>cows with ketosis. Response of cows with</p><p>primary ketosis to treatment with cortico-</p><p>steroids and IV glucose is superior to ther-</p><p>apy with corticosteroids or IV glucose alone,</p><p>with fewer relapses.</p><p>Insulin facilitates cellular uptake of</p><p>glucose, suppresses fatty acid metabolism,</p><p>and stimulates hepatic gluconeogenesis.</p><p>Insulin is administered in conjunction with</p><p>either glucose or a glucocorticoid and may</p><p>be of particular value in early-onset cases of</p><p>ketosis that are unresponsive to glucose or</p><p>corticosteroid therapy, but it is not com-</p><p>monly used. The dose of protamine zinc</p><p>insulin is 200 to 300 IU per animal (depend-</p><p>ing on body weight) administered SC every</p><p>24 to 48 hours as required. It should be rec-</p><p>ognized that endogenous insulin is released</p><p>in all lactating dairy cattle administered</p><p>500 mL of 50% dextrose, although to a lower</p><p>extent in ketotic cattle because they have a</p><p>lower peak plasma glucose concentration</p><p>following IV infusion of glucose or propio-</p><p>nate;28 consequently, IV dextrose administra-</p><p>tion should always be considered as a dual</p><p>treatment of glucose and insulin.</p><p>Anabolic steroids have also been used</p><p>for treatment of lactational ketosis and</p><p>ketosis in late pregnant cows that are overfat,</p><p>stressed, or have twin fetuses. Experimen-</p><p>tally, 60 mg and 120 mg of trenbolone acetate</p><p>are effective as single injections, but no</p><p>extensive field trials are recorded, and the</p><p>drug is banned for use in food animals in</p><p>most countries.</p><p>Miscellaneous Treatments. Vitamin B12</p><p>and cobalt are indicated in regions where</p><p>cobalt deficiency is a risk factor for ketosis.</p><p>Cobalt is sometimes administered to cattle</p><p>with ketosis in regions where cobalt defi-</p><p>ciency does not occur, but the therapeutic</p><p>value is not proven. Cyanocobalamin</p><p>(vitamin B12, 1 to 4 mg daily IV) in a com-</p><p>bined formulation with butaphosphan has</p><p>strong evidence supporting its role in</p><p>normalizing energy status in early-lactation</p><p>dairy cows when administered to dairy cattle</p><p>before or around parturition.29,30 Cyanoco-</p><p>balamin is essential for gluconeogenesis</p><p>from propionate, and a theoretical argument</p><p>can be made for the administration of cya-</p><p>nocobalamin for ketotic dairy cattle being</p><p>treated for ketosis. It is also thought that</p><p>high-producing dairy cows in early lactation</p><p>have a relative or actual deficiency of cyano-</p><p>cobalamin.30 Cysteamine (a biological pre-</p><p>cursor of coenzyme A) and also sodium</p><p>fumarate have been used to treat cases of the</p><p>disease. Reported results were initially good,</p><p>but the treatment has not been generally</p><p>adopted. The recommended dose rate of cys-</p><p>teamine is 750 mg IV for three doses at 1- to</p><p>3-day intervals.</p><p>Glucagon, although ketogenic, is strongly</p><p>gluconeogenic and glycogenolytic, and glu-</p><p>cagon concentrations are decreased in the</p><p>plasma of fat cows at calving and cows with</p><p>ketonemia. Glucagon could be of value in</p><p>prevention and therapy, but it would require</p><p>a prolonged delivery system because it has a</p><p>very short physiologic half-life and its effects</p><p>following a single injection are short-lived.</p><p>TREATMENT AND CONTROL</p><p>Treatment</p><p>Propylene glycol (300 to 500 mL daily for 5</p><p>days, PO) (R-1)</p><p>Dextrose (500 mL of 50% dextrose once, IV)</p><p>(R-1)</p><p>Dexamethasone, dexamethasone-21-</p><p>isonicotinate or flumethasone, IM (R-1)</p><p>Cyanocobalamin (vitamin B12, 1 to 4 mg IV,</p><p>daily for 2 to 6 treatments) (R-2)</p><p>Isoflupredone (20 mg, IM, multiple injections)</p><p>(R-3)</p><p>Insulin (lente formulation, 200 IU SC daily for</p><p>3 days) (R-3)</p><p>Control</p><p>Monensin (11 to 22 g/ton of total mixed</p><p>ration on a 100% dry matter basis; oral</p><p>administration of a controlled-release</p><p>capsule delivers 335 mg/day for 95 days)</p><p>(R-1)</p><p>Propylene glycol (300 to 500 mL daily, PO)</p><p>(R-1)</p><p>Rumen-protected choline (15g daily, PO, from</p><p>25 days precalving to 80 days postcalving)</p><p>(R-2)</p><p>Cyanocobalamin (vitamin B12, 1 to 4 mg IV,</p><p>daily for 2 to 6 treatments before or at</p><p>calving) (R-2)</p><p>Isoflupredone (20 mg, IM, once), with or</p><p>without insulin (100 U, SC) (R-3)</p><p>CONTROL</p><p>The control of clinical ketosis is integrally</p><p>related to the adequate nutrition of the cow</p><p>in the dry and lactating periods. This encom-</p><p>passes details such as the following:</p><p>V</p><p>etB</p><p>ooks.ir</p><p>Metabolic Diseases of Ruminants 1715</p><p>• Dry matter intake</p><p>• Fiber digestibility</p><p>• Particle size distribution</p><p>• Energy density</p><p>• Fat incorporation in early lactation</p><p>rations</p><p>• Protein content</p><p>• Feeding systems</p><p>• Rumen size</p><p>• Other factors better covered in texts on</p><p>nutrition</p><p>It is difficult to make general recommenda-</p><p>tions for the control of the ketosis because of</p><p>the many conditions under which it occurs,</p><p>its probable multiple etiology, and feeding</p><p>systems that vary from those that feed com-</p><p>ponents separately to those that feed total</p><p>mixed rations. Cows neither should have</p><p>been starved nor be overfat at calving.</p><p>Careful estimation of diets by reference to</p><p>feed value tables is recommended, and</p><p>detailed recommendations on diet and man-</p><p>agement are available, with the caveat that</p><p>planned rations can deviate from feed bunk</p><p>rations, and feed bunk dry matter and actual</p><p>dry matter intake may not be the same. Too</p><p>low a feeding frequency and the feeding of</p><p>concentrates separate from roughage rather</p><p>than as a total mixed ration can lead to an</p><p>increase in rates of ketosis.</p><p>In the United States, dry cows are typi-</p><p>cally divided into two groups: far-off and</p><p>close-up cows. Far off cows are generally fed</p><p>to National Research Council (NRC) dry-</p><p>cow feeding guidelines, and close-up cows</p><p>are given an acidogenic ration that decreases</p><p>the incidence of clinical milk fever (peri-</p><p>parturient hypocalcemia) starting 3 weeks</p><p>before the estimated calving date. Practical</p><p>recommendations based on British feeding</p><p>standards and units</p><p>are also available.</p><p>In high-producing cows being fed stored</p><p>feeds, poor-quality roughage commonly</p><p>leads to ketosis. Wet ensilage containing</p><p>much butyrate, and moldy or old and dusty</p><p>hay, are the main offenders. In concentrates,</p><p>it is the change of source that creates off-feed</p><p>effects and precipitates attacks of ketosis.</p><p>Cows that are housed should get some</p><p>exercise each day, and in herds where the</p><p>disease is a particular problem during the</p><p>stabling period, the cattle should be turned</p><p>out to pasture as soon as possible in the</p><p>spring.</p><p>The ration should contain adequate</p><p>amounts of cobalt, phosphorus, and iodine.</p><p>If there is a high incidence of ketosis in a</p><p>herd receiving large quantities of ensilage,</p><p>reduction of the amount fed for a trial period</p><p>is indicated.</p><p>Energy Supplements</p><p>Propylene glycol is used for the prevention</p><p>of clinical and subclinical ketosis. Tradition-</p><p>ally, propylene glycol has been drenched to</p><p>cattle in early lactation at doses varying from</p><p>350 to 1000 mL daily for 10 days after</p><p>calving. There is a linear effect of dose on</p><p>plasma glucose. Propylene glycol can also be</p><p>added to feed and is frequently present in</p><p>commercial feed products, but a bolus dose</p><p>of propylene glycol is more effective in</p><p>raising blood glucose than incorporation in</p><p>feed. A dose of 1 L per day given as an oral</p><p>drench for 9 days before parturition has also</p><p>been shown efficacious; however, it is impor-</p><p>tant to note that at doses above 500 mL</p><p>administered by drench or present in feed,</p><p>some cows may develop rapid and shallow</p><p>respiration, ataxia, salivation, and somno-</p><p>lence. For this reason, a maximum daily dose</p><p>of 500 mL as a drench should considered.</p><p>Glycerol can be substituted for propylene</p><p>glycol at equivalent dose rates, although</p><p>most studies indicate that glycerol is inferior</p><p>to propylene glycol. A preliminary report of</p><p>a small experimental study with larger doses</p><p>of glycerol showed that glycerol given orally</p><p>at a dose of 1 L, 2 L, or 3 L elevated blood</p><p>glucose concentrations to 16%, 20%, and</p><p>25%, respectively, of pretreatment values at</p><p>0.5 hours after treatment and that these con-</p><p>centrations remained elevated for 8 hours.</p><p>Staggering, depression, and diuresis were</p><p>observed in some cows given the 2-L or 3-L</p><p>dose, but this could be prevented by admin-</p><p>istering the glycerol in a large (37-L) volume</p><p>of water. It concluded that a dose of 1 L was</p><p>effective in increasing milk production and</p><p>reducing urinary ketones. Glycerol fed as a</p><p>constant component in the transition dairy</p><p>cow diet is not effective and possibly may be</p><p>ketogenic when fed continually. Glycerol</p><p>should only be used as drench in hypoglyce-</p><p>mic cows and not fed as a component of</p><p>the diet.</p><p>Propionic Acid and Its Salts</p><p>Propionic acid absorbed across the rumen</p><p>wall is transported to the liver, where it is</p><p>converted to glucose via gluconeogenesis to</p><p>result in an increase in serum blood glucose</p><p>levels. Older literature reports that 110 g/d</p><p>fed daily for 6 weeks, commencing at calving,</p><p>has given good results in reducing the inci-</p><p>dence of clinical bovine ketosis and improv-</p><p>ing production, but is not palatable and has</p><p>the risk of reducing feed intake. In controlled</p><p>trials, feeding energy supplements contain-</p><p>ing propionic acid and/or its salts for 3 weeks</p><p>prepartum and 3 weeks postpartum had a</p><p>beneficial effect on milk production, but a</p><p>variable effect on reducing subclinical ketosis.</p><p>Ionophores</p><p>Ionophores alter bacterial flora of the rumen,</p><p>leading to decreases in gram-positive bac-</p><p>teria, protozoa, and fungi and increases in</p><p>gram-negative bacteria. The net effect of these</p><p>changes in bacterial flora is increased pro-</p><p>pionate production and a decrease in acetate</p><p>and butyrate production providing increased</p><p>gluconeogenic precursors. Field trials with</p><p>monensin have consistently demonstrated a</p><p>reduction in serum or blood BHB, acetoac-</p><p>etate, and HEFA concentrations. In addition,</p><p>monensin increased serum or blood glucose,</p><p>urea, and cholesterol concentrations, and</p><p>decreased the prevalence of clinical ketosis,</p><p>clinical mastitis, and displaced abomasum</p><p>in dairy cattle.31-33 Monensin also decreases</p><p>methane production by cattle; methane</p><p>production by ruminants has been con-</p><p>sidered as contributing to global warming.</p><p>Although approved for administration to</p><p>lactating dairy cows in more than 20 coun-</p><p>tries, ionophores are not labeled for inclu-</p><p>sion in lactating-cow rations in a number of</p><p>countries.</p><p>Monensin is approved for continuous</p><p>administration (>14 days) to dairy cattle in</p><p>the United States at 185 to 660 (mg/head)/</p><p>day monensin to lactating cows or 115 to 410</p><p>(mg/head)/day monensin to dry cows. To</p><p>accomplish this, monensin is approved to be</p><p>fed at 11 to 22 g/ton of total mixed ration on</p><p>a 100% dry matter basis, at a daily per-cow</p><p>cost of about 2 to 4 cents. Monensin is also</p><p>approved for use in the United States as part</p><p>of a component feeding system at 11 to</p><p>400 g/ton (as is basis); this includes applica-</p><p>tion as a “top dress,” where a small amount</p><p>of feed is added to a ration.</p><p>In some countries, monensin can be</p><p>administered orally as a controlled-release</p><p>capsule to cattle 2 to 4 weeks before calving.</p><p>The capsule contains 32 g of monensin and</p><p>releases approximately 335 mg monensin a</p><p>day for 95 days. This product is effective and</p><p>practical for a variety of feeding systems, and</p><p>approximately 18% of dairy herds in Canada</p><p>are administering monensin by controlled-</p><p>release capsule.</p><p>Corticosteroids</p><p>Isoflupredone acetate (20 mg, IM, once)</p><p>was not effective in preventing subclinical</p><p>ketosis in early-lactation dairy cows, and it</p><p>actually increased the likelihood of subclini-</p><p>cal ketosis.34</p><p>Ancillary Agents</p><p>A commercially available injectable product</p><p>containing cyanocobalamin (vitamin B12, 1</p><p>to 4 mg daily IV) in a combined formulation</p><p>with butaphosphan is effective in normal-</p><p>izing energy status when administered to</p><p>dairy cattle 2 to 6 times before or around</p><p>parturition.29,30 The administration of cya-</p><p>nocobalamin and butaphosphan may be</p><p>most beneficial in cows at increased risk of</p><p>developing ketosis, such as older cows, over-</p><p>conditioned cows, or those experiencing</p><p>dystocia or metritis.29 Phosphorus may be</p><p>limiting in early lactation, based on low liver</p><p>phosphorus content in dairy cattle.35 It is not</p><p>clear whether additional phosphorus miti-</p><p>gates the reduction in hepatic phosphorus</p><p>content.</p><p>Rumen protected choline (15 g/day) fed</p><p>daily starting 25 days before calving and con-</p><p>tinuing to 80 days after calving decreased the</p><p>incidence of clinical ketosis and improved</p><p>the health of lactating dairy cows.36 Choline</p><p>V</p><p>etB</p><p>ooks.ir</p><p>Chapter 17 ■ Metabolic and Endocrine Diseases1716</p><p>is a precursor for phosphatidylcholine, which</p><p>is thought to be rate limiting in early lacta-</p><p>tion; phosphatidylcholine deficiency is asso-</p><p>ciated with impaired lipid metabolism.</p><p>Niacin is antilipolytic and induces</p><p>increases in blood glucose and insulin, but</p><p>there is conflicting evidence that niacin</p><p>given in the feed has a beneficial effect on</p><p>subclinical ketosis in cattle. It has been sug-</p><p>gested that niacin should be supplemented</p><p>from 2 weeks before parturition to 12 weeks</p><p>postpartum.</p><p>General Control</p><p>Herd Monitoring. There is currently no</p><p>consensus as to the optimal monitoring pro-</p><p>gram for ketosis and subclinical ketosis in</p><p>lactating dairy cattle, and consequently a</p><p>variety of monitoring programs have been</p><p>proposed. Challenges with developing opti-</p><p>mal monitoring programs are the herd</p><p>size (through the influence on the eligible</p><p>numbers of animals available to be tested),</p><p>ease of testing, cost of the test, and test sen-</p><p>sitivity and specificity. In addition, the goals</p><p>of the monitoring program need to be</p><p>defined; typically they are either to monitor</p><p>the adequacy of the diet relative to the level</p><p>of milk production (i.e., the magnitude of</p><p>negative energy balance in early lactation) or</p><p>to identify animals to receive a standard</p><p>treatment protocol,</p><p>such as daily oral propyl-</p><p>ene glycol drenching. The optimal time for</p><p>testing appears to be cows 3 to 9 days in milk</p><p>because cows that are hyperketonemic at this</p><p>stage of lactation are at highest risk for sub-</p><p>sequent negative production and health</p><p>effects, with the incidence and prevalence of</p><p>subclinical ketosis occurring on day 5 of lac-</p><p>tation.37 A recent modeling approach utiliz-</p><p>ing 13,000 cows from 833 dairy farms in</p><p>North America and Europe suggested that</p><p>testing cows twice weekly from 3 to 9 days in</p><p>milk was the most cost effective strategy</p><p>when the subclinical ketosis incidence was</p><p>between 15% and 50%; below an incidence</p><p>of 15% it was not economical to test, and</p><p>above 50% all cows should be treated without</p><p>testing.38 In addition, whenever the subclini-</p><p>cal ketosis incidence increased to above 15%,</p><p>a variety of testing and treatment protocols</p><p>are economically beneficial.38</p><p>The six most valuable and practical</p><p>indices for monitoring negative energy</p><p>balance are urine acetoacetate concentration,</p><p>blood BHB concentration, blood glucose</p><p>concentration, body-condition score, back-</p><p>fat thickness determined ultrasonographi-</p><p>cally, and milk-fat-to-protein ratio. The first</p><p>five indices can be obtained cow side and at</p><p>no cost or relatively low cost, although deter-</p><p>mining the blood BHB concentration costs</p><p>approximately 5 to 10 times that of the first</p><p>two tests and requires a blood sample. The</p><p>milk-fat-to-protein ratio is readily obtained</p><p>from individual monthly test data and is</p><p>more highly correlated with energy balance</p><p>than plasma BHB or glucose concentration.39</p><p>This should be coupled with body-condition</p><p>scoring or back-fat thickness to monitor the</p><p>efficacy of the nutritional program. Plasma</p><p>NEFA concentration is an excellent monitor-</p><p>ing test of negative energy balance, but it is</p><p>currently too expensive for routine herd</p><p>monitoring, and an easy-to-use cow-side test</p><p>is not available.</p><p>Urine testing using the nitroprusside test</p><p>for acetoacetate is the simplest of the cow-side</p><p>tests, and despite some reports that urine</p><p>samples are difficult to obtain from all cattle,</p><p>urine is easily obtained from more than 90%</p><p>of cattle using the following standardized</p><p>technique. First, stimulation of the perineum</p><p>to obtain a urine sample must be the first part</p><p>of the examination of the cow and ideally</p><p>should be performed without the cow being</p><p>aware that the veterinarian is present. Second,</p><p>never hold the tail while stimulating the</p><p>perineum because tail holding alerts the cow</p><p>to the presence of the veterinarian, and it is</p><p>not needed because cattle never urinate on</p><p>their tails when posturing to urinate. Third,</p><p>obtain urine samples in the normal environ-</p><p>ment of the animal; because cattle urinate on</p><p>average five times per day, urine samples are</p><p>easily obtained on recumbent cattle that are</p><p>gently encouraged to stand.</p><p>Blood BHB testing has become very</p><p>popular because of the availability of low-</p><p>cost point-of-care meters. Despite this, it</p><p>must be recognized that obtaining a blood</p><p>sample is more complicated than obtaining a</p><p>urine sample, and that the cost, although low,</p><p>is much higher than that for urine acetoac-</p><p>etate or blood glucose testing. Moreover,</p><p>serum BHB concentration is correlated with</p><p>energy balance in a similar manner to plasma</p><p>glucose concentration.40 Automated moni-</p><p>toring by in-line measurements of ketone</p><p>bodies in milk has been studied and may be</p><p>of particular value in large dairies. BHB is</p><p>proposed as the candidate because it is the</p><p>more robust in milk, and where cows are fed</p><p>a total mixed ration, it is not subject to sig-</p><p>nificant diurnal variation. Milk BHB concen-</p><p>tration can be measured in real-time with a</p><p>fluorometric method that requires no pre-</p><p>treatment of the milk.</p><p>Biochemical monitoring of herds for</p><p>subclinical ketosis and adequacy of peripar-</p><p>turient feeding can be conducted using blood</p><p>glucose estimations on a sample of cows in</p><p>their second week of lactation. Plasma glucose</p><p>concentrations below 45 mg/dL (2.4 mmol/L)</p><p>suggest subclinical ketosis. For individual</p><p>cows, blood glucose estimations should be</p><p>done at about 14 days after calving. This</p><p>method of monitoring is inexpensive using</p><p>widely available point-of-care devices.</p><p>FURTHER READING</p><p>Gordon JL, LeBlanc SJ, Duffield TF. Ketosis treatment in</p><p>lactating dairy cattle. Vet Clin North Am Food Anim</p><p>Pract. 2013;29:433-445.</p><p>Ingvartsen KL. Feeding- and management-related</p><p>diseases in the transition cow. Physiological</p><p>adaptations around calving and strategies to reduce</p><p>feeding-related diseases. Anim Feed Sci Technol.</p><p>2006;126:175-213.</p><p>McArt JAA, Nydam DV, Oetzel GR, Overton TR,</p><p>Ospina PA. Elevated non-esterified fatty acids and</p><p>β-hydroxybutyrate and their association with</p><p>transition dairy cow performance. Vet J.</p><p>2013;198:560-570.</p><p>Opsina PA, McArt JA, Overton TR, Stokol T, Nydam</p><p>DV. Using nonesterified fatty acids and</p><p>β-hydroxybutyrate concentrations during the</p><p>transition period for herd-level monitoring of</p><p>increased risk of disease and decreased reproductive</p><p>and milking performance. Vet Clin North Am Food</p><p>Anim Pract. 2013;29:387-412.</p><p>Zhang Z, Liu G, Wang H, Li X, Wang Z. Detection of</p><p>subclinical ketosis in dairy cows. Pakistan Vet J.</p><p>2012;32:156-160.</p><p>REFERENCES</p><p>1. Sato H. Anim Sci J. 2009;80:381.</p><p>2. Loor JJ, et al. Physiol Genomics. 2007;32:105.</p><p>3. Vanholder T, et al. J Dairy Sci. 2015;98:880.</p><p>4. Shin EK, et al. Theriogenology. 2015;84:252.</p><p>5. McArt JAA, et al. J Dairy Sci. 2015;98:2043.</p><p>6. Goldhawk C, et al. J Dairy Sci. 2009;92:4971.</p><p>7. Croushore WS, et al. J Am Vet Med Assoc.</p><p>2013;243:1329.</p><p>8. Reynen JL, et al. J Dairy Sci. 2015;98:3806.</p><p>9. Kessel S, et al. J Anim Sci. 2008;86:2903.</p><p>10. Borchardt S, et al. 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J Dairy Sci. 2002;85:3314.</p><p>FATTY LIVER IN CATTLE</p><p>(FAT-MOBILIZATION SYNDROME,</p><p>FAT-COW SYNDROME, HEPATIC</p><p>LIPIDOSIS, PREGNANCY</p><p>TOXEMIA IN CATTLE)</p><p>Fatty liver (hepatic lipidosis) is an important</p><p>metabolic disease of dairy cows in early lacta-</p><p>tion and is associated with decreased health</p><p>status and reproductive performance.</p><p>V</p><p>etB</p><p>ooks.ir</p>