Ketosis (Acetonaemia) in Cattle

Ketosis in Cattle

The Condition

Ketosis, or acetonaemia, is a metabolic disorder. Hypoglycaemia is the major factor involved in the onset and development of clinical signs of ketosis. There is a gradual loss of body condition over several days or even weeks. There is also a moderate decline in milk yield over two to four days before the onset of obvious clinical signs. The disease is most commonly seen in high-yielding dairy cows in early lactation. Secondary ketosis as a result of another disease can be seen at any stage of lactation. Beef cows can also suffer from ketosis during pregnancy.

Introduction

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.

Ketosis in dairy cows

The clinical signs include a refusal to eat grain and concentrate feeds and a more sudden drop in milk output. There is a sweet smell of acetone in the breath and milk. Some cows may exhibit nervous signs, which include excessive salivation, abnormal chewing movements, licking of walls, gates or metal bars, malcoordination with apparent blindness and a degree of aggression. The nervous signs often only last for a few hours. The affected cows have fatty infiltration and degeneration of the liver. To satisfy the requirements of milk production, the cow can draw on two sources of nutrients, food intake and body reserves. During early lactation, the energy intake is insufficient to meet the energy output in milk and the animal is in a negative energy balance.

In conventional farming, this is considered to be a normal metabolic situation in high-yielding dairy cows. These cows will have slightly raised blood ketone levels and may even excrete ketones in urine and milk. Cows in early lactation are therefore in a vulnerable situation, and any stress that causes a reduction in feed intake may lead to the onset of clinical ketosis. A reduction in the production of propionic acid, the main precursor of glucose in ruminants, will result in hypoglycaemia. Hypoglycaemia leads to a mobilization of free fatty acids and glycerol from the fat stores. However, the liver cannot deal with the acetyl-CoA, which results from the oxidization of these fatty acids, because of a lack of energy. The excess acetyl-CoA is converted into the ketone bodies, acetoacetate and b -hydroxybutyrate and, to a small extent, acetone. Tissues other than the liver can use ketone bodies, but if their production exceeds the rate at which they are used by muscle and other tissues, they accumulate, and ketosis is the result. Ketone bodies are excreted in milk and urine.

The reduction of propionic acid production is usually the result of underfeeding or a reduced feed intake caused by inappetance. The inappetance may be caused by a deterioration of forage quality, sudden changes in diet or excessive fatness at calving. Other risk factors are parity, ketosis in the previous lactation, 305-day milk yield in the previous lactation and the average milk protein percentage in the previous lactation. Butyrate is a precursor of acetyl-CoA and is therefore ketogenic. In the UK, the butyric acid content of silage is of considerable importance in the aetiology of the disease, because wet conditions predispose to butyric fermentation of the silage. Silage intake containing high levels of butyric acid is also less palatable to cattle.

Secondary ketosis

Secondary ketosis is common and is the result of diseases causing a reduction in appetite in early lactation, such as displaced abomasum, mastitis, metritis, etc. In areas of cobalt deficiency, ketosis is commonly diagnosed in grazing cattle. Cobalt is required for rumen microbial synthesis of vitamin B12 and is also essential for adequate utilization of propionic acid.

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.

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. 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.

Epidemiology:

All dairy cows in early lactation (first 6 wk) are at risk of ketosis. The incidence in lactation is estimated at 5-16%, but incidence in individual herds varies substantially. Ketosis occurs in all parities (although it appears to be less commin 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 hyperketonemia (subclinical ketosis—serum BHB concentrations >12 mg/dL) are at increased risk of developing clinical ketosis, compared with cows with lower serum BHB concentrations.

Clinical Findings:

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.

Diagnosis:

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.

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. A dipstick designed to detect BHB in milk, available in Japan and Europe, is more sensitive than milk tests for acetone and acetoacetate and may be useful for monitoring incidence of subclinical ketosis.

Treatment

Treatment is aimed at reestablishing 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. 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 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.

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.