Ketosis in cattle
Symptoms, main factors and 3 preventive strategies to prevent ketosis in cattle, a transition period metabolic disorder
Ketosis in dairy cows relates to the formation of ketone bodies (i.e. acetone, acetoacetate and beta-hydroxybutyrate, BHB) and is a measure of the liver’s capacity to convert circulating non-esterified fatty acids (NEFA) into glucose via the gluconeogenesis process.
Ketosis is a transition period metabolic disorder, with the risk zone lasting from one week before calving and up to 30 days post-calving. Ketosis is marked by elevated levels of ketone bodies measured in blood or milk, indicating that the metabolic processes in the liver are overwhelmed, leading to cell stress and liver damage, thus reducing liver function.
Beta-hydroxybutyrate is the predominant ketone body produced by the liver, with most cow-side monitoring techniques focused on this metabolite. Clinical ketosis is defined as having a BHB blood level of ≥3.0 mmol/l (31.2 mg/d), and generally affects up to 15% of cows, whereas sub-clinical ketosis begins at ≥1.2 mmol/l (12.4 mg/dl), and shows a prevalence of over 40% of cows in contemporary commercial herds.
The level of ketone bodies present in blood or milk are also correlated to increased risk for a number of metabolic disorders, including metritis, mastitis, left-displaced abomasum, all of which contribute to lower milk production and poor reproductive performance.
Moreover, clinical ketosis preludes fatty liver syndrome, whereby circulating lipids that are not metabolized are deposited within the liver, resulting in further reduction in metabolic capacity and increasing risk of subsequent metabolic disorders. A number of management and nutrition steps can be taken to reduce the occurrence and impact of sub-clinical and clinical ketosis in cattle. Preventative management focuses on body condition score (BCS) pre-calving and enhancing dry matter intake (DMI) post-calving.
Risk zones for ketosis development
Pre-calving
Ketosis is essentially the result of the inability of the liver to keep up with the glucose demand during early lactation. However, the risk of developing ketosis begins during the close-up period, generally one week before calving. At this time, DMI generally decreases sharply, limiting nutrient intake.
Restricted nutrient intake coincides with when foetus development demands are at their highest, placing an additional strain on available glucose. This leads to a state known as negative energy balance (NEB), whereby energy demand exceeds available supply.
A NEB state induces the cow to mobilise body reserves to compensate for the lack of nutrient intake, predisposing the cow to an inflammatory catabolic condition. During the pre-calving period, ketosis risk level can be monitored by circulating BHB or NEFA levels in blood. Prior to calving, the immune response also decreases, leaving the cow more susceptible to pathogens and other metabolic disorders.
Post-calving
In the initial weeks after calving, the nutrient demand to support milk production increases rapidly as does the risk of developing ketosis. Milk production is driven by glucose supply, which in turn is dependent on metabolism in the liver. To further facilitate glucose sparing for milk production, insulin production is depressed in combination with increased insulin resistance in some tissues (Ospina et al., 2013).
Although post-calving, cows are fed highly palatable, nutrient dense rations, the DMI is typically insufficient to match the demands for milk production. Moreover, rumen microflora must adapt to the new diet, during which time, rumen fermentation and feed digestion is impeded.
This disbalance in rumen function leaves the cows more vulnerable to sub-acute rumen acidosis (SARA). The severity and duration of this NEB period will impact the degree to which body reserves are mobilized, and the extent the liver is inundated with NEFA. The catabolic breakdown of tissues further contributes to the pro-inflammatory state the cow is in post-calving, at a time when her immune system is at its lowest (Esposito et al., 2014).
This NEB risk zone persists until appetite returns, DMI increases and glucose levels normalize. Monitoring NEFA levels in blood or BHB levels in blood or milk in the fresh period can give an assessment of ketosis risk and severity, as well as an indication of probability of developing other secondary metabolic disorders.
Monitoring ketosis prevalence is a valuable management tool due to the close association with development of other metabolic disorders. Pre-calving BCS remains the most tell-tale signal for the risk of developing ketosis, however, there are other monitoring tools indicative of potential problems.
Other factors managers should monitor are:
- Rapid loss of BCS post-calving
- Post-calving DMI
- Milk fat-protein ratio
- Early lactation culling rates
- Poor conception rates
- Abnormal high average herd DIM. (days in milk)
Factors contributing to ketosis development
Body condition
The leading cause for the predisposition of ketosis development is excess body condition prior to calving. During periods of NEB, tissue mobilization is predominantly from fat reserves; however, muscle tissues are also mobilized. The proportion of fat or muscle tissues mobilized depends on the BCS of the cow, with those having higher BCS mobilizing more body fat, more rapidly (NRC 2001). For this reason, cows slightly below the ideal body score are at less risk of developing ketosis than those with higher body scores.
Cows should enter the dry period close to the ideal calving BCS, to avoid stunting the development of the calf in utero, or risking dystocia at calving. Cows or heifers entering the far-off dry period, or 60 days before calving, with BCS of 4 or more are indicative of management issues earlier in the production cycle. For cows, high BCS at dry-off is indicative of breeding issues, which may be linked to metabolic disorders during the prior transition phase.
When breeding is delayed, the cow tends to stay longer within a group being fed an energy dense diet, at a time when DMI can now exceed milk production. Similarly, the BCS of heifers after breeding needs to be closely monitored, to ensure steady lean growth without accumulation of excess body fat.
The ideal BCS for a Holstein at calving has been revised downward, with 3,5 now being considered as the target BCS. For a cow calving at 650kg, one unit of BCS is represents 84 kg of body tissues, or the equivalence of 564 kg of 4% energy corrected milk (NRC 2001). To reduce the risk of developing ketosis, or other metabolic disorders, producers should work to limit BCS loss to no more than 0.5 to 0.75 units during the first 60 to 80 days post-calving. This is primarily focused on promoting higher DMI pre- and post-calving.
Low feed intake
In the week prior to calving, there is a generally a sharp drop in DMI that induces fat mobilization and a corresponding rise in circulating NEFA to support the energy needs of the unborn neonate. Tissue mobilization is an anabolic event, meaning inflammatory response is heightened at a period when the cow’s immune response is already suppressed (Ortega and Fernández-Real, 2013). Averting low DMI through diet management is key to sub-clinical ketosis and subsequent metabolic disease prevention.
Post-calving, cows that have marked lower intake than cohorts in a group are at a much higher risk of developing ketosis than those that are more aggressive eaters. Low DMI further compounds the effects of the NEB in early lactation, increasing the strain on the body reserves. Moreover, cows with low DMI tend to be more selective, thus increasing the risk of developing SARA. Various management steps can be taken to encourage greater DMI in early lactation to ease the metabolic stress on the liver and reduce the risk of sub-clinical or clinical ketosis.
Metabolic diseases associated with ketosis
Displaced Abomasum
The growth of the fetus during the last phase of the pregnancy tends to limit rumen volume, which may also contribute to declining intake leading up to calving. After calving, the rumen can resume its normal volume, however, it is during this period that the cow is susceptible to a condition called left-displaced abomasum, where the abomasum can literally twist in the body cavity, blocking the flow of nutrients.
Intake of a high proportion of small particles post-calving does not contribute adequately to rumen fill and fiber stratification, thus increasing the risk of left-displaced abomasum. Cows in the sub-clinical ketosis risk range (BHB level 1.2 mmol to 3 mmol) have an eight times higher risk of developing left-displaced abomasum than those below the threshold level (Suthar et al., 2013). Encouraging greater DMI post-calving greatly reduces the risk of developing left-displaced abomasum.
Lameness
Lameness related to sub-clinical ketosis is often not apparent until later in the lactation. However, the initial catalyst begins with the associated metabolic disorders during the transition period. Cows having clinical lameness at 70 DIM are 25% less likely to conceive than non-lame cows (Bicalho et al 2007). When sub-clinical ketosis disrupts eating behavior, leading to increased tissue mobilization and/or SARA conditions, the epithelial layer in the small intestine can be damaged, resulting in a condition known as “leaky-gut” syndrome.
Leaky-gut syndrome implies a breakdown between the tight junctions that act as a protective barrier between cells in the small intestine. As the permeability of the small intestine is increased, small particulates, pathogenic bacteria and inflammatory proteins enter the cows’ circulatory system. Histamines in particular has been linked to inflammation in the claw, leading to weakened claw structure and bacterial infiltration.
Furthermore, excess loss of BCS has also been linked to reductions in the fat pad of the digital cushion in the claws. This reduces the cushioning capacity of the soft tissue beneath the claw, leaving the cow more susceptible to floor abrasion and development of sole ulcers and white line disease (Bicalho et al., 2009). Cows in the sub-clinical ketosis risk range (BHB level 1.2 mmol to 3 mmol) have a 5 times higher risk of developing lameness than those below the threshold level (Suthar et al., 2013).
Metritis
Metritis is an inflammation of the uterus that can be caused by a variety of factors such as dystocia, hypocalcemia, ketosis, bacterial contamination during calving, or poor uterine contraction/cleaning post-calving.
Suppression of the cow’s immune system at calving increases the likelihood of developing metritis, such as when challenged by sub-clinical ketosis. Cows in the sub-clinical ketosis risk range (BHB level 1.2 mmol to 3 mmol) have a 2 times higher risk of developing metritis than those below the threshold level (Suthar et al., 2013).
Low milk yield
Milk yield is driven by lactose production, which is directly connected to liver function and glucose levels. Restricted glucose production in early lactation hinders the maturation of the milk secretion cells. Even below sub-clinical ketosis cut-off points (BHB >1.2mmol), milk production potential is compromised.
The impact of ketosis on milk production depends on the severity. Conservative estimates from research suggest losses can range from 1 to 3 kg, which can exceed 350 kg lost production over the lactation (Ospina et al., 2010).
Poor fertility
A voluntary waiting period of 60 days prior to first service is generally adequate, however, if suffering from sub-clinical or clinical ketosis, the associated NEB period will delay ovulation or result in poor conception.
Determining the exact impact of sub-clinical or clinical ketosis on fertility is difficult due to the prevalence and compounding effects of other metabolic diseases. In the case of sub-clinical ketosis, conception rates are suggested to be increased by 0.8 (Rutherford et al., 2016), with an average of 103 DIM at conception (McArt et al., 2012).
Diagnosing Ketosis
Pre-calving symptoms
Metabolic tests indicate circulating NEFA levels above 0.30 mEq/L, or BHB levels of 0.6 to 0.8 mmol/L (≥ 6.25mg/dL) pre-calving put the cows at significantly higher risk of developing metritis, retained placenta, displaced abomasum, in addition to developing clinical ketosis (Ospina et al., 2013). At the herd level, 2 in 12 cows, or >15% testing high for NEFA or BHB pre-calving indicates a significant risk of post-partum metabolic disease development and an alarm level for management intervention.
Post-calving symptoms
As with pre-calving, circulating NEFA or BHB levels can be used to assess the relative risk of developing a host of metabolic diseases, including clinical ketosis. Although correlated, circulating NEFA is a better indicator of metabolic disorder risk than BHB, in blood or milk.
Cut-off values for NEFA risk of samples collected within the first 14 days are 0.6 to 0.7 mEq/L. Currently, there are no cow-side NEFA analysis methods and laboratory analysis generally takes a couple of days. For these reasons, routine monitoring of NEFA at the herd level may be more practical for most producers.
Cow-side test for BHB levels, either from blood of milk, are available and are more appropriate for immediate spot-checking at-risk cows in early lactation. Empirical cut-off levels of BHB are ≥1.2 mmol/l (12.4 mg/dl) for sub-clinical ketosis and ≥3.0 mmol/l (31.2 mg/d) for clinical ketosis. It is important to note that individual outcomes depend on the individual and liver damage can occur below these threshold limits.
To properly assess the risk factors on individuals, ketosis testing should be performed at least twice between 3 and 14 days in milk (Ospina et al., 2013). Alternatively, monitoring at the herd level, whereby 1 in 12 cows in early lactation testing above the 1.2 mmol/L cut-off, is indicative that ketosis is prevalent in the herd (Oetzel, 2004).
Visual signals
Whereas routine testing at the herd level or systematic measuring of individual cows is the most accurate way of assessing ketosis prevalence at the farm level, there are a number of visual clues that indicate an underlying ketosis challenge.
Rapid loss of BCS following calving is generally a strong indication of ketosis. Ideally, a cow will only lose 0.5 to 0,75 of a BCS, or roughly 40-65 kg of body weight. New technologies using 3D cameras are available to help monitor BCS, but most managers must rely on visual assessment of the fresh group. Low DMI relies on visual assessment of the cow’s rumen fill when viewed from behind.
A cow that has a decent appetite will have a slight rumen bulge on the left-hand side. A cow that has been inadequately eating for more than a day will have a relatively straight belly line. Cows with poor intake can also be observed as the ones tending to be slow to come to feed or needing to be pushed up at milking time.
How to prevent ketosis in cattle
Producers can take several steps to prevent ketosis in cattle, namely:
- Encourage greater dry matter intake
- Apply prophylactic treatment
- Use feed additives in diet
Encouraging greater DMI
Encouraging greater DMI is the single most effective preventative measure against ketosis. Greater DMI enables similar energy intake, at a lower energy density, which allows the necessary effective fiber levels to maintain rumen function and metabolic processes. In comparison, increasing energy density is usually at the expense of effective fiber in exchange for higher soluble carbohydrates or fats content, leading to greater risk of rumen upset and SARA conditions, which generally results in further reductions in DMI. The importance of DMI for a smoother transition period does not begin at calving, but is already a priority in the close-up period.
Prophylactic treatment
Continual monitoring and early response to sub-clinical ketosis make prophylactic propylene glycol treatment a successful strategy to reduce the instances of clinical ketosis. The concept is to provide a “shock” amount of easily metabolizable glycerol that will increase circulating insulin levels sufficiently to reduce the mobilization of body fat and ease the metabolic pressure on the liver.
Treatments are continued daily until the sub-clinical ketosis has been resolved. However, the relatively large risk zone for developing sub-clinical ketosis make such practices of repeated treatment very labor intensive. Alternatively, propylene glycol treatment is often applied at the first sign of clinical ketosis. At this stage, damage to the liver has already been incurred and the risk of developing secondary metabolic disorders significantly increased.
If clinical ketosis does occur, glucose or glucose-derivatives can be given intravenously. Most cows will respond to intravenous treatment, however, damage to the liver has likely already occurred and lactation performance will have been compromised.
Feed additives
Feed additives that encourage greater DMI will help to reduce the instances of sub-clinical ketosis. Yeast supplements are commonly fed in dairy rations for their general effect of enhancing rumen buffering capacity and improving the degradation of feeds. This action stabilizes the rumen pH and microbiota, which in turn encourages greater mobility of the cow and more time spent at the feed bunk.
Greater digestion of feedstuffs increases the flow of volatile fatty acids available for glucose production. Managers that pursue energy dense, high starch diets to encourage greater propionic acid production and thereby glucose levels, may use ionophores, where allowed, to mitigate lactic acid production, however, such diets also tend to reduce rumination and DMI. Increasing energy density by using feed fat should also be discouraged as this increases the metabolic burden on the liver, increasing the likelihood of developing ketosis and fatty liver syndrome.
To alleviate excess fat deposition in the liver, choline and methionine can be fed to help mobilize accumulated fat out of the liver where it can then be excreted into the milk. Use of plant secondary metabolites, or phytogenic feed additives, such as Digestarom® Dairy, are a more natural way of encouraging greater intake by stimulating rumination and chewing duration, both of which increase absorption of rumen volatile fatty acids as well as buffering the rumen against SARA conditions.
Feed bunk management
In many instances, bunk space is limiting, feed is not easily accessible, or there are sorting issues that disrupt the nutrient intake balance. Feed bunk management as a preventative measure is important as cows are social animals and prefer to do activities as a group. Bunk management of dry cows is often neglected as they are not considered to be productive animals, however, they too need adequate bunk space in order to ease social stress and maintain regular eating patterns.
This is more so in the close-up group where the “belly-touch” rule should be applied. This means that sufficient bunk space should be available so that all cows can eat at once, without their sides rubbing. This reduces social stress in the group and helps maintain DMI levels.
Feed freshness can also be a factor, with feed refusals from the high production group sometimes being diluted with forage, then fed the following day to the dry cows. Such practices result in inconsistent nutrient supply and the risk of mycotoxin growth, both of which can influence eating patterns and risk of metabolic disorders.
Post-calving, it is critical that cows have ample access to fresh feed to encourage DMI. This includes plenty of bunk space as well as regular delivery of fresh feed. Having adequate space in the fresh pen enables those that are not feeling fit a chance to move away from the more dominant animals without compromising feeding patterns.
Regular feeding and feed push-up also encourages regular feeding patterns by keeping the feed attractive to the cows and reduces the risk of sorting. Without regular feeding and feed push-up, these vulnerable cows are at a higher risk of inadequate intake and nutrition, prolonging the NEB period and increasing the vulnerability to metabolic disorders such a sub-clinical or clinical ketosis.
In addition to space allotment, sorting is a common problem with feed bunk management and can occur at any stage of production. While cows determine the extent of sorting, it is the TMR wagon operator who determines how easily the cows are capable of sorting the TMR. In relation to ketosis, most early lactation diets are formulated for minimal effective fiber content in order to maximize nutrient density. However, cows are also more prone to sorting which can lead to SARA conditions that further decrease DMI and increase the risk of sub- or clinical ketosis development.
Most sorting is against long fibers. Cows are apt at sorting against wet silage that is “balled”, larger particles from corn stalks and cobs, or pelleted feed. Problems relating to sorting can generally be corrected with proper feed preparation techniques. An effective way to monitor TMR preparation and sorting is by following the recommendations as outlined in the Penn State Particle Separator guidelines. Performing regular TMR audits ensures greater consistency among workers preparing the diets as well as reducing day to day variation in cow intake.
Social stress
The negative impact of overcrowding at the feed-bunk and lying areas cannot be over emphasized. In the weeks following calving, cows suffer generally from some degree of inflammation, which depresses their desire to eat. These cows are more prone to be the last to the feed bunk and more easily displaced by the fitter, more dominant cows. As a consequence, their feeding patterns become erratic and can result in goring or “slug feeding”, which increases the risk of SARA and sub-clinical ketosis.
Most managers have fresh cows separated from the lactating herd for the first 21 to 30 days. This allows extra attention and management intervention to minimize the risk of metabolic disorders. Separating subsequent lactation groups based on primiparous and multiparous cows help to manage the nutritional needs of the cows more efficiently.
This is a good practice to mitigate stress as the multiparous cows are larger and more dominant in the hierarchy, which can lead to primiparous cows being left more vulnerable to bullying and susceptible to a prolonged NEB period. When space allows, separation at parity should begin at calving as primiparous cows are more susceptible to metabolic disorders and at a higher risk of early culling.
Lameness
Lameness during the dry period can have a lasting effect into the fresh period as lameness affects cow comfort. Even mild lameness can increase laying time and disrupt eating patterns. This has a direct effect on daily DMI and energy consumption, increasing the pressure on body fat reserves in early lactation inducing sub-clinical or clinical ketosis.
Lameness in early lactation can have a prolonged effect on the NEB and BCS of the cow. Care should be taken to ensure claws are trimmed and checked to minimise the risk of poor mobility during the transition phase.
Hypocalcemia
Generally, hypocalcemia, or milk fever, occurs directly after calving, with 25% of primiparous and up to 50% multiparous cows suffering from subclinical conditions (Reinhardt et al., 2011). Lower circulating calcium levels can affect muscle contraction, including rumen mobility.
If rumen mobility is compromised, absorption of volatile fatty acids from fermentation of feedstuffs is reduced, limiting the potential for glucose formation. Low circulating glucose affects insulin levels, leading to increased fat mobilization and heightening the risk of developing ketosis or fatty liver syndrome.
References
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