Tuesday, 30 April 2013

Ketosis and Pregnancy Toxaemia



Hi :) In this post we’ll take a look at the epidemiology, pathogenesis, treatment and prevention of ketosis and pregnancy toxaemia.

Ketosis       

Ruminants rely on gluconeogenesis in order to produce glucose and use it as a source of energy. When these animals are in late pregnancy and lactation they need larger amounts of energy than normal and this may drain glucose supplies. When the ruminant body requires extra energy, it mobilises fat and this causes the release of NEFAs (Non Esterified Fatty Acids) into the circulation. NEFAs can be toxic when they reach a certain concentration in the blood and so the body converts them into ketone bodies. The tissues that are able to use ketone bodies for energy do so and this spares blood glucose for those tissues that have an absolute requirement for glucose.

However, the use of ketone bodies is saturable and when saturation occurs, pathological ketosis happens. This is characterised by hypoglycaemia, ketonaemia and ketonuria.

Epidemiology

Ketosis is most common in dairy cows and there is a higher risk of developing this disease during the first 6 weeks of lactation. Other risk factors include:
§  60 days post calving
§  Increased age
§  Increased milk production
§  Low energy, high protein diets
§  Obesity at calving.
In addition, ketosis usually develops secondary to another disease. There is also low heritability and ketosis can be sub-clinical or clinical.

Pathogenesis

As explained earlier, ruminants rely on gluconeogenesis in order to maintain glucose homeostasis and during late pregnancy and lactation these animals are often in a negative energy balance. Because of this NEFAs are mobilised from adipose tissues and this is stimulated by low glucose and insulin and high amounts of lipolytic hormones.

The NEFAs can either enter the ketogenic pathway where they are oxidised in the liver to become ketone bodies, or the esterification pathway where they are converted to triglycerides in the liver. If the NEFAs enter the ketogenic pathway, the cow is predisposed to ketogenesis. Low glucose availability favours ketogenesis. Ketosis occurs when the uptake of ketones by tissues is saturated and the level of ketone in the blood is elevated.

There are three types of ketosis: alimentary ketosis, primary under feeding and secondary under feeding ketosis.

Alimentary Ketosis

 This condition is associated with the feeding of poor quality silage that have high levels of preformed butyrate. Butyrate is a precursor for ketones and so high levels of butyrate predispose the animal to developing alimentary ketosis. In addition, these poor quality feeds often have poor palatability and this may contribute to the development of underfeeding ketosis.

Primary Underfeeding 
 
This occurs when poor quality feed is given to cattle in poor body condition. These feeds have poor quality roughage, low protein and insufficient concentrates. This means that there is limited gluconeogenesis occurring from the feed. As a result, more adipose tissue must be mobilised which means that, ultimately, more NEFAs are converted to ketones and this predisposes the animal to developing ketosis.

Secondary Ketosis

 Secondary ketosis results in a decreased food intake secondary to an underlying disease (such as abomasal displacement, toxaemia, metritis, mastitis, acidosis etc.) As a result of reduced feed intake, less propionate (a volatile fatty acid) is produced in the gut which means that there is a lower rate of glucose synthesis. Thus, more adipose tissue has to be mobilised which means that more NEFAs are converted to ketones. This predisposes the animal to developing ketosis.

Treatment

Treatments aim to restore blood glucose levels and correct the clinical signs of ketosis. There are two main methods of treatment: replacement therapy and hormonal/supportive therapy.

Replacement Therapy

This form of treatment administers propionate precursors (e.g. propylene glycol) as a drench or in feed. These are converted to pyruvate and oxaloacetate after being absorbed through the wall of the rumen. Intravenous glucose therapy can also be used if the animal is looking particularly bad.

Hormonal / Supportive Therapy

Corticosteroids are commonly used in this form of treatment as they cause a decrease in the use of glucose by peripheral tissues and increased Acetyl CoA utilisation. Some people may use anabolic steroids which stimulate appetite and decrease the level of ketones in the blood. B Group vitamins may also be given as Niacin increases blood glucose and decreases the ketone concentration of the blood. Digestive tract stimulants may also help a poor appetite.

Prevention

In order to avoid ketosis, one should avoid poor quality silages that may contain large amounts of butyrate particularly in the 60days after calving. The body condition score should also be managed carefully as scores over 3.5 greatly increase the risk of ketosis (this is because there is more fat to mobilise). The cow should also receive adequate amounts of forage, vitamins and minerals in their diet. Animals at risk of developing ketosis should also be identified early to start preventative measures. The use of monensin, an ionophore can also reduce the risk of ketosis.

Pregnancy Toxaemia

Like ketosis, pregnancy toxaemia is also a disorder of energy and protein metabolism. It affects sheep, cattle and goats and similar to ketosis and causes hepatic lipidosis (fatty liver). It is more common in animals that have twins and triplets.

Epidemiology

Pregnancy Toxaemia is most prevalent in very late gestation (the four weeks preceding parturition) where there is a declining plane of nutrition. The presence of multiple foetuses also increases the risk of developing this disorder as well as younger growing animals. Stress also increases the risk.

Pathogenesis

In late pregnancy the foetus, placenta and uterus have an increased demand for glucose and amino acids. It is often difficult for the animal to meet these requirements especially if it is on a poor quality forage. This problem is compounded by the fact that the loss of nutrients to the foetus is irreversible.

With sheep in late gestation, the requirements for glucose by the foetus each day exceeds the glucose available in the blood by four times. Thus there is a need for substantial amounts of gluconeogenesis. In addition, the mother has decreased insulin sensitivity late in lactation and this reduces the use of glucose by peripheral tissues and increases the lipid and ketone metabolism. This results in fatty acids being mobilised from body stores and transported to the liver to form triacylglycerol’s (TAGs). The excess TAG results in hepatic lipidosis (fatty liver) and pregnancy toxaemia.  

The TAGs are may be oxidised via the TCA cycle. If they aren’t oxidised they are converted to ketone bodies which are acidic, this may lead to metabolic acidosis.

Pregnancy toxaemia is associated with hypoglycaemia, increased levels of NEFAs in the blood plasma, hyperketonaemia, and ketonuria. It may also lead to an enlarged, fat infiltrated liver and the kidney, heart and adrenal glands may show signs of fat infiltration.

Treatment

The treatment of pregnancy toxaemia involves providing gluconeogenic precursors such as glycerol. Any electrolyte imbalance or dehydration should also be corrected and the foetus should be removed. This can be done via a caesarean or by inducing parturition. Corticosteroids may also be administered as this will increase the amount of endogenous gluconeogenic precursors present as well as the amino acids for gluconeogenesis. It also has the effect of inducing pregnancy. Better quality feed should also be provided to the herd.

Prevention

In order to prevent pregnancy toxaemia it is important to provide the animal with dry matter that has sufficient energy, protein, mineral and vitamin content to meet or slightly exceed the nutrient requirements. Additional supplements should also be given to animals with multiple pregnancies and those that have low body condition scores.

Parasites should also be controlled and a healthy body condition should be maintained. Stressful events, such as bad weather, should also be avoided when possible. Ionophores may be helpful and trace and macro- elements should be provided.

That’s all for this post, see you next time :)

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