Metabolic Disorders

Ketosis

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.

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

Ketosis in beef cows

Whereas ketosis in early lactation mainly affects high-yielding dairy cows, ketosis or pregnancy toxaemia in late pregnancy mainly affects beef cows. Cows of all ages can be affected, but overfat animals and those carrying twins are most at risk. Beef cows often get overfat on good summer pastures. If the same cows do not have access to high quality forage during the winter months, when they are in late pregnancy, they will succumb to ketosis due to a low energy intake. Affected cows are usually 7-9 months pregnant, and the initial clinical signs are the same as for ketosis in early lactation. However, many cows become recumbent fairly quickly and most die three to fourteen days later. Cows affected close to parturition often die during parturition

Methods of Control and Prevention

As at least 60% of the diet fed to dairy cows in organic farming should consist of fresh or conserved roughage, this should be of excellent quality during early lactation to meet the energy and protein requirements. This is especially important on organic farms where cows are high yielding. The high level of roughage in the diet of organically managed cows has the advantage of promoting good rumen digestion Cows should not be too fat at calving. A condition score of 2.5-3.0 would be optimal, and anything higher would be considered too fat.

Concentrates fed during lactation should be introduced in small amounts, approximately two weeks before calving, to allow adjustments of the rumen microflora. Dietary changes during early lactation should be made gradually.

Roughage high in butyric acid should be avoided in early lactation. Forage quality should be checked every year. In cobalt deficient areas, measures should be taken to ensure adequate cobalt intake .A sufficient supply of high quality forage is essential for beef cows in late pregnancy. Pregnancy scanning of the beef herd may identify twin-bearing cows with greater needs.

Metabolic profiles in groups of dry cows and cows in early lactation can help veterinarians predict whether a certain diet will predispose the cows to ketosis during late pregnancy or early lactation. Milk tests are also being developed to test for ketosis. The heritability for ketosis is relatively high, and this trait should be used to advantage in organic farms

Housing also seems to have an effect on the level of ketosis in the herd. Research from Norway indicates that a significantly higher proportion of herds with tie stalls experienced ketosis compared to those with free stall herds (relative risk = 1.59) (. The reason for this is not known.

Methods of Treatment

There are three main aims of treatment:

1. To restore blood glucose levels as quickly as possible;
2. To replenish oxaloacetate, an essentail intermediate in the tricarboxylic acid cycle (TCA), so that fatty acids are completely oxidised and the production of ketone bodies reduced;
3. To increase the availability of dietary glucogenic precursors, notably propionic acid.

Intravenous glucose therapy with 500 ml 40% glucose will give a transient rise in blood glucose levels that will only last 2 hours. It should be accompanied by oral administration of a glucose precursor, preferably propylene glycol. Administer propylene glycol twice daily for three to four days. Cobalt salts are frequently added to propylene glycol.

In conventional farming, glucocorticoid drugs are the most commonly administered therapy, used either alone, or in combination with glucose therapy, or followed by oral administration of glucose precursors. Whether these drugs should be used in organic cows depends on the severity of the condition and should be discussed with the veterinary surgeon. Homeopathy has been recommended as a substiute to glucocorticoid therapy in ketosis.

It is important that the cow's appetite is returned to normal as soon as possible after treatment, so access to high quality fodder is important.

Most cows with ketosis (pregnancy toxaemia) in late pregnancy are so severely affected that medical treatments invariably fail to succeed. Immediate removal of the calf by caesarean section may save the cow. This should be followed by the treatments mentioned above

Good Practice based on Current Knowledge

Prevention:

• Feed at least 60% of the diet as fresh or conserved roughage.
• Feed high quality roughage during early lactation.
• Use cows suitable to the organic system, i.e. do not breed for high yields.
• Ensure cows are not too fat at calving (condition score 2.5-3.5).
• Introduce concentrates in small amounts approximately two weeks before calving.
• Avoid major dietary changes during early lactation.
• Avoid roughage high in butyric acid in early lactation.
• Use regular condition scoring throughout the lactation. Look out for sudden changes in trends.
• Ensure that all cows have good access to feed, i.e. enough feeding space for the lower ranking cows.
• Ensure adequate cobalt intakes.
• Check forage quality every year.
• Beef cows should receive adequate levels of high quality forage to prevent ketosis (pregnancy toxaemia) in late pregnancy.
• Take metabolic profiles in groups of dry cows and cows in early lactation to check whether the diet is adequate.

Treatment:

• Treat cases with intravenous glucose followed by an oral glucose precursor for several days.
• Severe cases should be treated with glucocorticoid drugs on veterinary advice.
• Homeopathy has been recommended for the treatment of clinical ketosis.
• In the case of ketosis (pregnancy toxaemia) in late pregnancy, the veterinarian may have to carry out a caesarean section to save the cow.

Ketosis In Cattle

(Acetonemia, Ketonemia)

Ketosis is a metabolic disease of lactating dairy cows characterized by weight loss, pica, inappetance, decreased milk production, and neurologic abnormalities that usually occur during the first 6 wk of lactation. Ketosis occurs worldwide whenever dairy cows are selected and fed for high milk production. It affects both primiparous and multiparous cows. Incidence is highest during the third and fourth weeks of lactation in closely confined stabled dairy cows that are improperly fed and conditioned during the dry period and early lactation. Ketosis can occur whenever a cow goes off feed for any reason. Significant predisposing and concomitant conditions are retained fetal membranes, metritis, mastitis, displaced abomasa, fatty livers, environmental stresses, faulty nutrition, and mismanagement. The overall incidence in a herd is determined by the inherited capability of the herd to produce large quantities of milk and by the presence of predisposing conditions. If these conditions are not present, incidence of ketosis is very low; if they are present and seriously compromising the general health of the herd, most of the cows in the herd may develop clinical ketosis. After a cow develops the condition once, she is more likely to be affected during succeeding lactations. Etiology and Pathogenesis: Ketosis is basically the result of a negative energy balance in the 6 wk after parturition. The cow is unable to eat or assimilate enough nutrients to meet her energy needs for maintenance and milk production during this period. Therefore, blood glucose levels drop and hypoglycemia results. In an effort to correct this condition, body fat and limited protein stores are mobilized in the form of triglycerides and amino acids for gluconeogenesis. Ketone bodies (acetoacetic acid, acetone, and β-hydroxybutyric) are produced during the mobilization process. This occurs to a limited degree in practically all high-producing cows in early lactation, and only a subclinical ketosis develops if the herd is properly fed and conditioned and free of predisposing factors. However, if this is not the case, clinical ketosis develops when the production and absorption of ketone bodies exceeds their use as an energy source. This results in increased blood ketones, free or nonesterified fatty acids, and decreased blood glucose. Ketone bodies are produced primarily in the liver but also in smaller quantities in the mammary gland and rumen wall.

Clinical Findings:

Onset of signs is usually gradual, and close observation is required to determine their presence. Initial signs include a slight decrease in feed intake, drop in milk production, lethargy, and firm mucus-covered stools. As the disease progresses, a marked weight loss occurs that may approach several hundred pounds in a few days. Pica is often seen in which affected cows refuse grain and seek coarse materials such as coarse hay, straw, ground, and even tree twigs. As the disease progresses, depression deepens, movement is limited, and cows stand with a humpbacked posture. There may be an acetone odor to the breath, urine, or milk. Although most cows exhibit the lethargic wasting signs, some show frenzy and aggression. They may compulsively lick metal stanchions, mangers, or their own bodies. Head or nose pressing may occur along with chewing and bellowing. Walking may be abnormal with staggering, circling, and falling. Some cows seriously injure themselves during these activities, and death may result. If ketosis is untreated, milk production decreases to an insignificant amount that does not require much energy to produce. Because energy requirements for body maintenance are relatively small compared with those for high milk production, intake of carbohydrate precursors (as described in the Krebs cycle) may gradually reach demand, and a slow recovery occurs. However, for the cow to make a complete recovery and to reach her full potential for milk production, the predisposing conditions must also be successfully treated.

Lesions:

Although few cows die of primary ketosis that is not complicated with predisposing factors, ketosis does produce some pathology. The carcass is thin and malnourished with little body fat, indicative of starvation. The liver, kidneys, and heart are likely to show fatty infiltration. The liver is most seriously affected and is often pale yellow and may be soft and friable; in severe and prolonged cases, it may be necrotic. The adrenals are often enlarged, flabby, and infiltrated with fat. Regressive changes in the pituitary gland, acute involution of the pancreas, and fattened epithelial cells in the thyroid gland have also been reported.

Diagnosis:

It is extremely important to obtain a complete history when ketosis is suspected. Special attention should be given to length of dry period, nutrition during the dry period, parturition date, nutrition since parturition, and daily milk production records, if available. Rapid loss of body weight, depression, decreased appetite, pica, drop in milk production, bizarre behavior, and a near normal temperature should alert the diagnostician to suspect ketosis. Oftentimes, an observant caretaker may have detected an abnormal odor from the cow"s breath, urine, or milk. All cows suspected of having ketosis should receive a thorough physical examination along with Rothera"s test for ketone bodies. Rothera"s test for ketones is usually conducted on urine but because ketones are so highly concentrated in urine (up to 1200 mg/dL), vary widely due to urine concentration, and are normally present in early lactation high-producing cows, a positive urine test is usually not considered to be diagnostic of clinical ketosis. Because ketone levels in milk are much lower (usually not exceeding 50 mg/dL in clinical cases) and less variable, a positive Rothera"s test of milk is considered to be a much more accurate diagnosis of clinical ketosis. Blood glucose levels are also helpful in arriving at a diagnosis. Normal levels of 40-60 mg/dL drop to below 25 mg/dL in clinical ketosis. Differential diagnoses should include but not be limited to hypocalcemia, retained fetal membranes, metritis, indigestion, abomasal displacement, traumatic reticulitis, poisoning, pyelonephritis, listeriosis, and rabies.

Treatment:

Routine treatment is IV administration of 500 mL of 50% glucose and IM administration of the glucocorticoid of choice. Propylene glycol (225 g, b.i.d. for 2 days, followed by 100 g daily for 2 days) or other glucose precursors are also administered PO in many cases. Glucose administration results in an increase in blood glucose and prompt improvement in clinical signs and milk production. However, the recovery is usually transitory, and both clinical signs and milk production soon return to pretreatment levels unless glucose treatment is repeated in 24-48 hr. After glucocorticoid therapy, blood glucose levels return to normal in 8-10 hr and behavior improves markedly within 24 hr. Milk production may temporarily decrease after glucocorticoid administration but increases rapidly after several days. The response to propylene glycol is slow and is often used as supportive treatment after administration of glucocorticoids and glucose. To effect a rapid and lasting recovery, any predisposing conditions must also be eliminated, and proper nursing and nutrition provided.

Prevention:

Cows should be properly conditioned during late lactation and the dry period. They should be fed so that body score at calving will be 3.5 on a 5-point scale. About 2 wk before parturition, cows should be started on a small amount of the concentrate ration they will receive during early lactation. The amount of concentrate should be gradually increased so that at parturition, the cow will be consuming 1 lb per 150 lb body wt daily. Because feed intake is normally limited voluntarily just before and immediately after parturition, it is extremely important not to overfeed during this period, which may throw the cow off feed completely. There is a fine line between overfeeding and underfeeding at this time, and extreme care must be exercised. Maximum energy and dry-matter intake should be encouraged shortly after parturition by supplying highly palatable and nutritious rations containing 16-18% crude protein and 19-21% fiber. The ration should contain adequate amounts of essential vitamins and minerals. In problem herds, it is usually helpful to limit silage and increase long hay in the ration. Various feed additives such as propylene glycol, sodium propionate, yeasts, niacin, choline, etc have been recommended and fed with varying results. It is extremely important to prevent, identify, treat, and control or eliminate predisposing conditions, such as retained fetal membranes, metritis, mastitis, displaced abomasa, fatty livers, nutritional errors, and environmental stresses.