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Diagnosis and management of negative energy balance and associated production diseases in bovines.


Presently, in India, the main focus is towards cross breeding practices to produce high yielding dairy animals in order to meet the demand of milk and milk products. Such high yielding animals are usually in a delicate balance between the input and output and many a times these animals maintain the output in terms of production even at the cost of body reserves and internal metabolites leading to development of number of production diseases viz., ketosis, fat cow syndrome, milk fever, downer's cow syndrome, hypomagnesemic tetany, post parturient haemoglobinuria etc. Peak incidence of metabolic diseases is observed during the transition period which extends from 3 weeks prior to parturition through 3 weeks after parturition. However, the effects of these diseases on dairy cow health and productivity extend far into the following lactation (Mulligan and Doherty, 2008). Fetal dry weight increases markedly during last trimester of pregnancy increasing the demand for energy, protein, calcium and other nutrients to fulfill the requirement. High producing dairy animals especially crossbred cows need to mobilize body reserves to be able to sustain their milk production and thereby enter a state of negative energy balance, losing high amounts of body condition.

During the transition period, the immunologic status is also compromised. Though, clinical effects become obvious in few animals, subclinical disturbances develop in larger proportion of animals. In general, subclinical disease incidence is more important than clinical disease because clinical signs are not evident to recognize the disease and animal continue to produce at a markedly reduced rate resulting into significant economic losses.

While traditionally regarded as encompassing the significant metabolic disorders of dairy cows (hypocalcaemia, hypomagnesaemia and ketosis), the term 'production disease' has been broadened to include conditions such as retained placenta, displacement of the abomasum and laminitis. Production diseases constitute a major proportion of the common health problems encountered on dairy farms and because they predispose cows to infectious diseases, infertility, production losses and lameness; they compromise the health and welfare of dairy cows and reduce farmer profitability. The most economically important production diseases of high yielding dairy animals which occur as a result of negative energy balance are ketosis and fat cow syndrome.

Monitoring nutritional status of cattle in a herd

Regular monitoring of the nutritional status of the cattle in a herd and modifying the feeding management accordingly can be very helpful in prevention of production diseases. Recently, it has been shown that nutritional management in early dry period, i.e., after cessation of milking, is important for maintaining the health and productivity of cows in transition (Dann et al., 2006). There is significant decrease in dry matter intake (DMI) by over 30 per cent in the last 3 weeks of gestation, limiting the availability of energy sources during the time of increased energy demand (Hayirli et al., 2002). This demand for glucose, fatty acids and amino acids further increases 2.5 times within 4 days post partum, mainly due to milk production. Estimation of body condition score, subcutaneous fat thickness and Compton metabolic profile test are important tools for monitoring nutritional status of the herd.

Body condition score (BCS)

There is a general recognition that BCS provides a gross but reasonably accurate measure of a cow's energy reserves, although its use is limited in very thin and very fat cows. The purpose of BCS is to achieve a balance between economic feeding, good production and good welfare. It is particularly useful as an aid to dry cow and pre calving management. Cows that calve thinner than this produce less milk, are less likely to get pregnant, and more likely to present themselves in an animal welfare-risk category. Cows that calve in greater BCS will have a reduced dry matter intake (DMI), will produce less milk, and are more likely to succumb to periparturient metabolic disorders like fat cow syndrome. Further research is required to elucidate the effect of BCS state and BCS change on animal health and welfare, as well as DMI, and the possibility of transgenerational epigenetic changes and associated effects on future production, health and reproduction.

Subcutaneous fat thickness

Dairy cows have the ability to use body energy

reserves which predisposes them to many metabolic cascades. Negative energy balance (NEB) during transition period leads to a homeorhetic response in which involvement of adipose tissue by increased lipolysis and muscle tissue by protein mobilization are predominant (Lucy et al., 1991), with adipose tissue representing the most important energy storage quantitatively. Therefore, assessment of adipose tissue to access energy balance of dairy cows is more promising approach as the amount of mobilized body fat approximates the energy demand lacking for milk production and maintenance (Waltner et al., 1993). Subcutaneous fat thickness can be estimated using real time ultrasound. Excessive adipose mass or a high rate of adipose mobilization or both have been associated with peri-partum disease risk in dairy animals. An increased risk of subclinical ketosis was observed when back fat thickness (BFT) was greater than 12mm.

For practical purposes if the average BFT in a herd is 12 to 14mm 2 to 3 weeks before calving, cows should be evaluated for feed intake and diet should be evaluated for energy density (Scroder and Staufenbeil, 2006).

Compton Metabolic Profile Test (CMPT)

Metabolic profile is defined as a series of specific analytic tests run in combination and used as a herd based, rather than individual based, diagnostic aid. It is an effective tool for assessing feeding management and periparturient diseases of dairy animals (Kida, 2002). The original intent of CMPT was to monitor metabolic health of the herd, help diagnose metabolic problems and production diseases. Recently, the shift to increasing herd size and recognition of significant health, production and economic consequences of periparturient diseases has lead to revised metabolic profile application in monitoring transition dairy animal health and disease risk. Besides, estimating different parameters in blood, one should also record data related to prevalence of clinical diseases, milk production and feed record of the herd. Evaluation of individual animals for body condition score, management and feeding practices adopted in the herd and analysis of feed and fodder are also critical. Appropriate sampling strategies are required for correct analysis of results. Blood samples are collected from 3 predefined groups of dairy animals like close up dry (>10 days following dry off and not < 30 days prior to calving), far off dry (Between 3 and 21 days prior to calving) and recently calved animals (3 to 30 days in milk). With the random selection process, selected dry animals may be at any point relative to expected calving. As a result of tremendous individual variation, cow should not be sampled within 3 days before or following calving. The original CMPT test measured 13 different analytes that included PCV, Hb, glucose, blood UN, total proteins, albumin, Ca, inorganic phosphorus, Mg, potassium, sodium, copper and iron. Normal range for these parameters for dairy cattle is given in table 1 and 2.

Recently some more parameters have been included in this list. Non-esterified fatty acid (NEFA) is one of the most important parameter helpful in assessment of energy balance and diagnosis of ketosis. Excessively high NEFA concentration because of negative energy balance either prepartum or early postpartum are predictive of increased risk of ketosis, left displacement of abomasums and most other periparturient diseases. [beta]-hydroxy butyrate (BHB) is another parameter useful in assessing energy status.

Urea nitrogen, creatinine, total proteins, albumin and creatine kinase level depends upon the protein balance. The GGT, AST and SDH, Total bilirubin, NEFA and cholesterol levels are helpful in evaluation of liver function. Macro and microminerals and vitamin levels in blood indicate their dietary availability. Macrominerals Ca, P, K, Mg, Na, Cl and S are of extreme interest as to their status relative to their role in milk fever, alert downer's cow and weak cow syndrome. Deficiencies in micro-minerals, such as copper, manganese, zinc and selenium, as well as fat-soluble vitamins may lead to a compromised immune system. A trace element screen as well as selenium and vitamin E, can be added to the CMPT, as needed. Specific acute phase proteins like ceruloplasmin and haptoglobin are routinely determined as a part of metabolic profiling (Van Saun 2005).

Monitoring of reticular temperature

Recently, a temperature sensing bolus that can be orally administered was tested for early detection of metabolic and periparturient diseases like metritis, mastitis, lameness, and pneumonia in dairy cows. This is based on the assumption that these diseases are associated with increase in reticular temperature. Researchers found that it can serve a useful tool in the early detection of mastitis and pneumonia in dairy cows, though it is not effective in diagnosis of other diseases like lameness and metritis (Adams et al., 2013).


Ketosis is seen in high producing cows. Signs of the disease can be seen before calving, but they occur most commonly during the first 10 to 60 days after calving. Subclinical ketosis (SCK) is more important because it causes heavy economic losses due to reduced milk production. Subclinical ketosis is defined as an excess of circulating ketone bodies without clinical signs of ketosis (Anderson, 1988). Besides significant decline in milk production, increased risk for early lactation removal, displaced abomasum, metritis and impaired fertility are other effects evident in subclinical ketosis. In India, incidence of ketosis has been recorded by various researchers varying from 4.22 to 50 per cent and highest incidence recorded during first 30 days of calving. Financial losses are from decreased milk, decreased body weight, cost of treatment, disposal of cows that have recurring cases and possibly death. In addition, ketosis increases the risk of developing other metabolic diseases such as displaced abomasum, retained placenta, mastitis and other metabolic problems.

Etiology and pathogenesis

Ruminants are most susceptible with regard to carbohydrate (CHO) metabolism and supply of glucose is essential for tissue metabolism. In ruminants, very little dietary CHO is absorbed as hexose sugar and dietary carbohydrates are fermented in rumen as short chain fatty acids principally acetic acid, butyric acid and propionic acid. Consequently, glucose need in ruminants is met by gluconeogenesis for which propionate and amino acids act as major precursors. During the last weeks of pregnancy, nutrient demands by the fetus are at their greatest, yet dry matter intake (DMI) may be decreased by 10 to 30 per cent compared with intake during the early dry period. High circulating estrogen is believed to be one major factor that contributes to decreased DMI around calving. If the amount of suitable carbohydrate in the diet is not enough to meet the glucose needs of the cow in full milk, the liver starts to manufacture glucose from other basic compounds in the body, usually from fat reserves. Negative energy balance results in a high ratio of growth hormone to insulin in blood of cows, which promotes mobilization of long chain fatty acids from adipose tissue (body fat). Fatty acids released from adipose tissue circulate as non-esterified fatty acids (NEFA), which are a major source of energy to the cow during this period. The release of NEFA from body fat overwhelms the capacity of the liver to use the fatty acids as fuel. They are instead converted to ketone bodies such as acetone, aceto-acetic acid, and ?-hydroxybutyrate (BHB).

Clinical signs

The most common complaint at presentation includes a sharp drop in milk production, a generally depressed attitude and a partial or complete anorexia. Animal has a woody appearance due to apparent wasting and loss of cutaneous elasticity due to disappearance of subcutaneous fat. A characteristic odor of ketones is present in breath and milk. In some cases there are nervous signs (Nervous ketosis) which include false chewing movements, frothing and salivating profusely, pressing forward in the stanchion, walking in an unusual "goose-stepping" manner, licking themselves continuously.


Diagnosis is based on history of recent calving, drastic decrease in milk production, type of feeding and clinical signs. For diagnosing sub-clinical ketosis, NEFA and BHB concentrations are most specific. Recent studies on Pre-partum NEFA and BHB cut points for predicting post-partum health

problem with highest sensitivity and specificity ranged from 0.3 to 0.5 mEq/ L and >0.8 mmol/ L, respectively. Likewise, post-partum NEFA and BHB cut points for predicting major metabolic health problems range from 0.70 to 1.0 mEq/ L and 1.2 to 1.4 mmol/ L, respectively. (LeBlanc et al., 2005; Ospina et al., 2010; Chapinal et al., 2011; Roberts et al., 2012). Post-partum BHB concentration of <1.4 mmol/L in plasma is gold standard for diagnosing SCK.

Clinical pathology

It includes hyperketonemia, ketonuria, ketolactia, hypoglycemia, and high blood concentration of non-esterified fatty acid (NEFA). Clinical cases are associated with plasma glucose concentration less than 35 mg/dl and NEFA concentration greater than 1000 mEq/ L. NEFA is a very good parameter to monitor body condition losses (Stengarde et al., 2008).

Cases of clinical ketosis are usually associated with total ketone body concentration greater than 30mg/dl. The BHB concentration alone is usually greater than 25mg/dl. Hand held meters for regular measurement of blood ?-hydroxybutyrate (BHB) and glucose concentrations can serve as a useful tool for controlling incidence of ketosis in dairy cows maintained in large herds (Voyvoda and Erdogan 2010).

Urine ketone body concentrations are usually two to four times higher than blood concentrations, whereas, milk ketone body concentrations are usually 40 to 50 per cent of blood concentrations. Rothera test is the simple and cheap qualitative test for detection of ketone bodies.


Intravenous administration of 500 ml of 50 per cent glucose or dextrose solution has been a standard treatment. Fructose and sorbitol have been used as alternatives to glucose therapy. Glucocorticoid therapy is also effective. Insulin in conjunction with glucocorticoid therapy may be more effective than glucocorticoid alone. Propylene glycol and salts of propionic acid have been used as glucose precursor @ 250-400g administered twice daily as an oral drench. Propylene glycol@ 125 ml + 12 g of niacin daily for 5-7 days used as a preventive or as a "follow up" after initial use of dextrose or glucocorticoids or both. Vit.[B.sub.12] and Cobalt are recommended to promote propionate production and Nicotinic acid 12 g daily to promote gluconeogenesis (Ruegsegger and Schultz 1986).

Fat cow syndrome (Fatty liver syndrome)

It occurs most commonly within first 2 weeks after parturition, usually in association with periparturient diseases. In cattle, it is seen most commonly in late pregnancy when nutrient intake is decreased in cattle, particularly in animals having good body condition. Mild cases of fatty liver are associated with reduced fertility and severe cases with increased culling, disease and death.

Etiology and pathogenesis

The intra-hepatic fat that accumulates in bovine fatty liver is primarily triglyceride. Cattle do not synthesize fatty acid precursors of triglyceride in the liver, thus fatty acid that accumulate as triglyceride in bovine fatty liver must be extrahepatic in origin. Fatty acids are stored as triglycerides in adipose tissue until mobilized. When they are mobilized in response to energy demand, adipose triglycerides are converted to non-esterified fatty acids (NEFA) and glycerol. They can be extracted from the blood and used as energy source by various tissues including the mammary gland, liver, spleen and muscle. In the liver, these fatty acids can undergo partial or complete oxidation or alternatively reesterification to triglycerides. Fatty acids esterified as triglycerides remain in the liver until they can be oxidized or secreted from the liver. Secretion of triglycerides from the liver is process requiring repackaging of the triglycerides into serum lipoprotein particles (Bobe et al., 2007). Lipoprotein synthesis and secretion is naturally a slow process in bovine liver and it may be further reduced in cows developing fatty liver. Fatty liver development can occur rapidly and within 48 hours under conditions of extreme adipose tissue mobilization. Some factors like obesity, insulin resistance and inflammation reduce the ability of the cow to adapt to negative energy balance. As cow approach calving, the sensitivity of tissue to insulin is normally reduced. Obesity further suppresses insulin sensitivity. Cytokines produced in response to inflammation can further impair insulin sensitivity increasing the risk of fatty liver.

Infiltration of hepatocytes with fat leads to reduced hepatic function, reduced immune function and clearance of endotoxin from the blood may be impaired because of reduced hepatic blood flow associated with fatty liver.

Clinical signs

Most consistent signs are depression, extreme anorexia, and ketonuria. It may also be associated with vague central nervous system signs including star gazing, somnolence, coma and recumbency and death.


Clinical ketonuria within one week of calving accompanied by depression or other peripartum diseases with death loss or both should be considered presumptive evidence of fatty liver. Although liver biopsy is most diagnostic approach for fatty liver, now a days real time ultrasonography of liver is gaining more popularity among researchers due to its non invasiveness and accuracy (Scroder and Staufenbeil, 2006).

Clinical pathology

The activities of aspartate amino transferase (AST) and ornithine carbamyl transferase (OCT) are probably the most sensitive predictors of bovine fatty liver. Serum AST activity greater than100U/L is consistent with fatty liver (Murondoti et al., 2004). Serum NEFA concentrations are best used as a herd screening tool to predict the risk of fatty liver. Acute phase reactant proteins particularly haptoglobin, calcitonin gene related peptide (CGRP), C-reactive protein and serum amyloid-A are the main disturbed blood variables that determine development of fatty liver. These acute phase proteins can also be used as predictors of fatty liver in cows (Katoh 2002).


Administration of dextrose solution i/v accompanied by insulin is practical and effective treatment in mild cases (Hayirli 2006). The use of orally administered glucogenic agents such as propylene glycol and sodium propionate may be effective and more practical than i/v glucose therapy but care should be taken not to suppress appetite. Propylene glycol prevents lipolysis, while choline facilitates the export of fatty acids from the liver as very-low-density-lipoproteins. Simulta-neous administration of rumen-protected choline has been reported to be very effective in preventing fatty cow syndrome. Choline probably enhances hepatic VLDL secretion while propylene glycol reduces fatty acid mobilization from adipose tissue (Grummer 2008).

Antioxidants such as vitamin E and selenium may be useful in therapy because of possible role of oxidative stress and lipoperoxidation in pathogenesis of fatty liver. A slurry of complete feed administered with a large bore stomach tube has been a useful treatment in extreme cases.

Prevention of production diseases

Prevention of ketosis is directed towards maximizing energy intake and providing adequate glucose precursors. Ration should be well balanced for all nutrients. Avoid excessive fattening before calving. Avoid abrupt changes in the feeding program at calving time. Increase concentrate intake moderately in the late dry period but as rapidly after calving as possible and maintain intake. Provide adequate amounts (one-third of the dry matter) of good quality roughage. Avoid feeding large amounts of silage to heavy producers. Herd body condition scoring can be a useful tool to avoid problems with fatty liver. The use of ultrasound measurement of change in subcutaneous fat thickness can be a useful tool to assess rate of adipose tissue mobilization. Improving dry matter intake during last 2 to 3 week before and the first 2 to 3 week after calving should be the top priority. Specific feed additives that might be of benefit in prevention of ketosis/ fatty liver include monensin and rumen protected choline. A new rumen protected form of choline appears to have promise in the management of fatty liver when fed to cows in late gestation and early lactation (Cook et al., 2007; Mulligan and Doharty 2008). Glucagon administration has also been claimed to be effective in prevention of fatty liver and ketosis in dairy cows (Hippen, 2002). Care must be taken to provide the prepartum dairy animals with a stress free environment. Successfully tested preventives are oral drenches of propylene glycol in the periparturient period or injections of glucocorticoids, glucagon, or low dosages of slow-release insulin in the first day after calving. Metabolic profile test may be used for herd monitoring. Milk fever can be prevented by restricted Ca feeding to less than 0.5% of the diet during dry period. Phosphorus intake must be less than 0.35 per cent of the diet during late pregnancy. Calcium deficient diet fed for at least 10 days before calving greatly reduces the risk of milk fever.


Adams, A.E., Olea-Popelka, F.J. and Roman-Muniz, I.N. (2013) Using temperature-sensing reticular boluses to aid in detection of production diseases in dairy cows. J. Dairy Sci. 96: 1549-55.

Andersson, L. (1988) Subclinical ketosis in dairy cows. Vet. Clinics North Am. Food Anim. Pract. 4: 233-51.

Bobe, G. Young, J. W., Beitz, D. C. (2007) Invited review: Pathophysiology, etiology, prevention and treatment of fatty liver in dairy cows. J. Diary Sci. 87: 3105-24.

Chapinal, N., Carson, M., Duffield, T.F., Capel, M., Godden, S., Overton, M., Santos, J.E. and LeBlanc, S.J. (2011) The association of serum metabolites with clinical disease during the transition period. J. Dairy Sci. 94: 4897-4903.

Cook, R. F., Rio, N Silva-Del, Caraviello, D. Z., Bertics, S.J., Ramos, M.H. and Grummer, R.R. (2007) Supplemental choline for prevention and alleviation of fatty liver in dairy cattle. J. Diary Sci. 90: 2413-18.

Dann, H.M., Litherland, N.B., Underwood, J.P., Bionaz, M., D'Angelo, A., McFadden, J.W. and Drackley, J.K. (2006) Diets during far-off and close-up dry periods affect periparturient metabolism and lactation in multiparous cows. J. Dairy Sci. 89: 3563-77.

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Ospina, P.A., Nydam, D.V., Stokol, T. and Overton, T.R. (2010) Associations of elevated nonesterified fatty acids and beta-hydroxybutyrate concentrations with early lactation reproductive performance and milk production in transition dairy cattle in the northeastern United States. J. Dairy Sci. 93: 1596-1603.

Roberts, T., Chapinal, N., Leblanc, S.J., Kelton, D.F., Dubuc, J. and Duffield, T.F. (2012) Metabolic parameters in transition cows as indicators for early-lactation culling risk. J. Dairy Sci. 95: 3057-63.

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Scroder, U.J. and Staufenbeil, R. (2006) Invited review: methods to determine body fat reserves in the dairy cows with special regard to ultrasonographic measurement of back fat thickness. J. Dairy Sci. 89:1-14.

Stengarde, L., Traven, M., Emanuelson, U., Holtenius, K., Hultgren, J. and Niskanen, R. (2008) Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis. Acta Veterinaria Scandinavica 50: 31.

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Voyvoda, H. and Erdogan, H. (2010) Use of a handheld meter for detecting subclinical ketosis in dairy cows. Res. Vet. Sci. 89: 344-51.

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S.N.S. Randhawa (1), Rakesh Ranjan (2), Randhir Singh (3), Naimi Chand (3)

College of Veterinary Science Guru Angad Dev Veterinary and Animal Sciences University (GADVASU) Ludhiana--141004 (Punjab)

(1.) Director of Research-cum-Dean (Postgraduate studies) and Corresponding author. E-mail:

(2.) Department of Teaching Veterinary Clinical Complex

(3.) Department of Veterinary Medicine

Table 1: Normal range of various blood
parameters over the periparturient period for
healthy, mature dairy cows

Analyte                     Close up dry     Fresh

Albumin (g/dl)                3.3-3.7       3.2-3.6
AST(IU/L)                    46.5-82.6     61.1-103
BHB(mg/dl)                    1.25-4.2      1.7-8.9
Cholesterol(mg/dl)             65-114       63-253
Glucose(mg/dl)                 51-74         42-68
NEFA(mEq/L)                  0.03-0.46     0.01-0.52
Total proteins(g/dl)          6.9-8.5       7.3-8.9
NEFA to Cholesterol ratio     0.03-0.2     0.03-0.4

Table 2: Fresh dairy animal mineral
concentrations in healthy population and
concentrations that are of concern for
potential disease risk

Analyte                           Adequate range   Concern levels

Calcium(mg/dl)                      8.7 to 11            <8
Phosphorus(mg/dl)                     4.5-8             <3.5
Magnesium(mg/dl)                      2-3.5             <1.5
Sodium(mEq/L)                        137-148            <137
Potassium(mEq/L)                     3.8-5.2         <3 or >5.5
Copper(ug/ml)                        0.6-1.5           <0.45
Zinc(ug/ml)                          0.8-1.4            <0.5
Selenium, serum(ng/ml)                70-100            <35
Selenium, whole blood(ng/ml)         120-250            <50
Serum vitamin A(ng/ml)               225-500            <150
Serum vitamin E(ug/ml)                 3-10              <3
Vitamin E to cholesterol ratio        2.5-6             <1.5
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Title Annotation:Research Article
Author:Randhawa, S.N.S.; Ranjan, Rakesh; Singh, Randhir; Chand, Naimi
Publication:Intas Polivet
Article Type:Report
Geographic Code:9INDI
Date:Jul 1, 2014
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