Ketosis is a common disease of adult cattle. It typically occurs in dairy cows in early lactation and is most consistently characterized by partial anorexia and depression. Rarely, it occurs in cattle in late gestation, at which time it resembles pregnancy toxemia of ewes. In addition to inappetence, signs of nervous dysfunction, including pica, abnormal licking, incoordination and abnormal gait, bellowing, and aggression are occasionally seen. The condition is worldwide in distribution, but is most common where dairy cows are bred and managed for high production.
Etiology and Pathogenesis
The pathogenesis of bovine ketosis is incompletely understood, but it requires the combination of intense adipose mobilization and a high glucose demand. Both of these conditions are present in early lactation, at which time negative energy balance leads to adipose mobilization and milk synthesis creates a high glucose demand. Adipose mobilization is accompanied by high blood serum concentrations of nonesterified fatty acids (NEFA). During periods of intense gluconeogenesis, a large portion of serum NEFA is directed to ketone body synthesis in the liver. Thus, the clinicopathologic characterization of ketosis includes high serum concentrations of NEFA and ketone bodies and low concentrations of glucose. In contrast to many other species, cattle with hyperketonemia do not have concurrent acidemia. The serum ketone bodies are acetone, acetoacetate, and β-hydroxybutyrate (BHB).
There is speculation that the pathogenesis of ketosis cases occurring in the immediate postpartum period is slightly different than that of cases occurring closer to the time of peak milk production. Ketosis at this time is sometimes described as type II ketosis. Cases of ketosis in very early lactation are usually associated with fatty liver. Both fatty liver and ketosis are probably part of a spectrum of conditions associated with intense fat mobilization in cattle. Ketosis cases occurring closer to peak milk production, which usually occurs at 4–6 wk postpartum, may be more closely associated with underfed cattle experiencing a metabolic shortage of gluconeogenic precursors than with excessive fat mobilization. Ketosis at this time is sometimes described as type I ketosis.
The exact pathogenesis of the clinical signs is not known. They do not appear to be associated directly with serum concentrations of either glucose or ketone bodies. There is speculation that they may be due to metabolites of the ketone bodies.
All dairy cows in early lactation (first 6 wk) are at risk of ketosis. The overall prevalence in cattle in the first 60 days of lactation is estimated at 7–14%, but prevalence in individual herds varies substantially and may exceed 14%. The peak prevalence of ketosis occurs in the first 2 wk of lactation. Lactational incidence rates vary dramatically between herds and may approach 100%. Ketosis occurs in all parities (although it appears to be less common in primiparous animals) and does not appear to have a genetic predisposition, other than being associated with dairy breeds. Cows with excessive adipose stores (body condition score ≥3.75 out of 5.0) at calving are at increased risk of ketosis, compared with those with lower body condition scores. Lactating cows with subclinical ketosis (see Ketosis in Cattle: Subclinical Ketosis) are at increased risk of developing clinical ketosis, compared with cows with lower serum BHB concentrations.
In cows maintained in confinement stalls, reduced feed intake is usually the first sign of ketosis. If rations are offered in components, cows with ketosis often refuse grain before forage. In group-fed herds, reduced milk production, lethargy, and an “empty” appearing abdomen are usually the signs of ketosis noticed first. On physical examination, cows are afebrile and may be slightly dehydrated. Rumen motility is variable, being hyperactive in some cases and hypoactive in others. In many cases there are no other physical abnormalities. CNS disturbances are noted in a minority of cases. These include abnormal licking and chewing, with cows sometimes chewing incessantly on pipes and other objects in their surroundings. Incoordination and gait abnormalities occasionally are seen, as are aggression and bellowing. These signs occur in a clear minority of cases, but because the disease is so common, finding animals with these signs is not unusual.
The clinical diagnosis of ketosis is based on presence of risk factors (early lactation), clinical signs, and ketone bodies in urine or milk. When a diagnosis of ketosis is made, a thorough physical examination should be performed because frequently ketosis occurs concurrently with other peripartum diseases. Especially common concurrent diseases include displaced abomasum, retained fetal membranes, and metritis. Rabies and other CNS diseases are important differential diagnoses.
Cow-side tests for the presence of ketone bodies in urine or milk are critical for diagnosis. The majority of commercially available test kits are based on the presence of acetoacetate or acetone in milk or urine. Dipstick tests are convenient, but those designed to detect acetoacetate or acetone in urine are not suitable for milk testing. All of these tests are read by observation for a particular color change. Care should be taken to allow the appropriate time for color development as specified by the test manufacturer. Handheld instruments designed to monitor ketone bodies in the blood of human diabetic patients are available. These instruments quantitatively measure the concentration of BHB in blood, urine, or milk and may be used for the clinical diagnosis of ketosis.
In a given animal, urine ketone body concentrations are always higher than milk ketone body concentrations. Trace to mildly positive results for the presence of ketone bodies in urine do not signify clinical ketosis. Without clinical signs, such as partial anorexia, these results indicate subclinical ketosis. Milk tests for acetone and acetoacetate are more specific than urine tests. Positive milk tests for acetoacetate and/or acetone usually indicate clinical ketosis. BHB concentrations in milk may be measured by a dipstick method that is available in some countries, or by the electronic device mentioned above. The BHB concentration in milk is always higher than the acetoacetate or acetone concentration, making these tests more sensitive than those based on the latter ketone bodies.
Treatment is aimed at re-establishing normoglycemia and reducing serum ketone body concentrations. Bolus IV administration of 500 mL of 50% dextrose solution is a common therapy. This solution is very hyperosmotic and, if administered perivascularly, results in severe tissue swelling and irritation, so care should be taken to assure that it is given IV. Bolus glucose therapy generally results in rapid recovery, especially in cases occurring near peak lactation (type I ketosis). However, the effect frequently is transient and relapses are common. Administration of glucocorticoids including dexamethasone or isoflupredone acetate at 5–20 mg/dose, IM, generally results in a more sustained response. Glucose and glucocorticoid therapy may be repeated daily as necessary. Propylene glycol (250–400 g/dose, PO, [~8–14 oz]) acts as a glucose precursor and may be effective as ketosis therapy, especially in mild cases or in combination with other therapies. This dose may be administered twice per day. Overdosing propylene glycol leads to CNS depression.
Ketosis cases occurring within the first 1–2 wk after calving (type II ketosis) frequently are more refractory to therapy than those cases occurring nearer to peak lactation. In these cases, a long-acting insulin preparation given IM at 150–200 IU/day may be beneficial. Insulin suppresses both adipose mobilization and ketogenesis, but should be given in combination with glucose or a glucocorticoid to prevent hypoglycemia. Use of insulin in this manner is an extra-label, unapproved use. Other therapies that may be of benefit in refractory ketosis cases are continuous IV glucose infusion and tube feeding. (Also see Hepatic Lipidosis: Fatty Liver Disease of Cattle.)
Prevention and Control
Prevention of ketosis is via nutritional management. Body condition should be managed in late lactation, when cows frequently become too fat. The dry period is generally too late to reduce body condition score. Reducing body condition in the dry period may even be counterproductive, resulting in excessive adipose mobilization prepartum. A critical area in ketosis prevention is maintaining and promoting feed intake. Cows tend to reduce feed consumption in the last 3 wk of gestation. Nutritional management should be aimed at minimizing this reduction. Controversy exists over the optimal dietary characteristics during this period. It is likely that optimal energy and fiber concentrations in rations for cows in the last 3 wk of gestation vary from farm to farm. Feed intake should be monitored and rations adjusted to maximize dry matter and energy consumption in late gestation. After calving, diets should promote rapid and sustained increases in feed and energy consumption. Rations should be relatively high in nonfiber carbohydrate concentration, but contain enough fiber to maintain rumen health and feed intake. Neutral-detergent fiber concentrations should usually be in the range of 28–30% with nonfiber carbohydrate concentrations in the range of 38–41%. Dietary particle size will influence the optimal proportions of carbohydrate fractions. Some feed additives, including niacin, calcium propionate, sodium propionate, propylene glycol, and rumen-protected choline, may be beneficial in preventing and managing ketosis. To be effective, these supplements should be fed in the last 2–3 wk of gestation, as well as during the period of ketosis susceptibility. In some countries, monensin sodium is approved for use in preventing subclinical ketosis and its associated diseases. Where approved, it is recommended at the rate of 200–300 mg/head/day.
Last full review/revision July 2011 by Thomas H. Herdt, DVM, MS, DACVN, DACVIM