28. Ketosis and Urea Poisoning

Transcription

1 Module 4 Nutrition Management for Grazing Animals Learning objectives 28. Ketosis and Urea Poisoning On completion of this topic you should be able to: John Nolan Describe the management strategies available to sheep producers to minimise the risk of pregnancy toxaemia. Describe the mechanisms of ketosis and the production and nutrition conditions that predispose animals to risk of developing ketosis. Describe why urea toxicity can be fatal to ruminants and apply management strategies that minimise the risk of urea toxicity. Key terms and concepts Ketosis; Pregnancy toxaemia; Urea toxicity. Introduction to the topic Pregnancy toxaemia is a relatively common metabolic disorder in Australian sheep production systems. Unfortunately, this type of metabolic disorder is not limited to sheep production but also beef cattle, dairy cattle, pigs and poultry. This topic describes the metabolic processes that lead to the development of ketosis and pregnancy toxaemia and strategies available for the prevention and management. Due to Australia s reliance on low quality native pastures for its livestock production, urea is a widely used supplement. While urea can be a relatively cheap and effective supplement for ruminant animals, it can also be fatally toxic. The processes by which urea toxicity can occur in ruminants and recommendations for the use of urea that will minimise the risk of toxicity are described Ketosis Ketosis is a metabolic disease condition characterised by excessively high blood concentration of compounds called ketone bodies or ketones, i.e. acetoacetate, acetone and α hydroxybutyrate. In a normal animal, ketone bodies are produced in the liver in relatively low amounts and are carried around the body in the blood. Non hepatic tissues extract them and use them as a source of energy or building units for long chain fatty acid (LCFA) synthesis. Ketones are a significant energy source for skeletal and cardiac muscle in normal animals (Figure 28 1). Applied Animal Nutrition ANUT300/

2 Figure 28.1 Biochemical pathways involving ketone body synthesis and utilisation. Note that oxaloacetate is required to enable Acetyl CoA to be taken into the TCA cycle to be oxidised and release energy for ATP generation. When both glucose and ATP are required simultaneously in early lactation, the functionality of the TCA cycle may be compromised when oxaloacetate is removed from the TCA cycle to enable gluconeogenesis to occur. This can result in Acetyl CoA backing up and there is diversion of fatty acid degradation intermediates to form ketone bodies (UNE Animals Science Database). Source: Nolan (2006). Ketone body synthesis is therefore quite normal. There is no basis for the older view that low level ketosis is pathological. We now recognise that ketonaemia is merely a sign of increasing dependence on LCFA as an energy source, and there is no evidence that even a severe ketonaemia (a high concentration of ketones in blood) is itself toxic. Indeed it has been suggested that ketone formation is essentially protective that ketones act weakly to prevent the toxic effects of high concentrations of LCFA by limiting lipolysis. In fed ruminants, â hydroxybutyrate is formed from butyrate when the later is being used as a source of energy in the rumen wall. A mild form of alimentary ketosis may develop in cows given certain silages. Ketonaemia. Clinically high concentrations of ketones in the blood. Excessive production of ketones producing high concentrations of ketones in the blood is associated with the metabolic disorder referred to as ketosis. This condition may occur in dairy cows and fat cattle. In sheep there is a related condition called pregnancy toxaemia. The condition usually occurs when the animal s requirements are high and feed intake is restricted for some reason. Thus, ketosis and pregnancy toxaemia usually occur in the last few days before or soon after parturition. Beef cows that are fat, and therefore have restricted abdominal and gut capacity, and these have restricted feed intakes, are particularly susceptible (as are, in the case of pregnancy toxaemia, fat ewes that are carrying multiple foetuses). In dairy cattle, the condition is most likely to develop at about the time of peak lactation when energy and glucose requirements for milk sugar (lactose) synthesis reach their highest levels. When energy requirements are high and energy intake is low, animals attempt to meet the energy shortfall by mobilising body stores. Fat is mobilised first and is degraded to glycerol and LCFA and the LCFA are then degraded by the removal of 2 carbon units that give rise to acetyl CoA. Acetyl CoA can then condense with oxaloacetate (when the latter is available) to form citrate. Oxidation of citrate in the citric acid cycle generates ATP to be used as a source of energy in the tissues (Figure 28 1). However, when fat is the principal energy store being degraded for this purpose, impairments in metabolism can prevent its complete degradation. Metabolites are diverted towards 28-2 Applied Animal Nutrition ANUT300/500

3 ketone body synthesis in mitochondria of liver cells leading to ketone release from the liver and high ketone body concentrations in the blood and the smell of one of these ketones, acetone, on the breath. At the same time ketones are also detectable by analysis in the milk, and blood glucose concentrations are usually low. Animals lose their appetite. Initially they may be restless. Later they go down and may fall into a coma. Death can occur in days. In summary, the condition is still not well understood but the factors involved include the following: High energy demand and low feed intake lead to rapid mobilisation of body fat stores, and an increase in LCFA and acetate synthesis; The mammary gland takes up more than normal amounts of LCFA, acetate and β hydroxybutyrate from the blood, but at the same time releases acetoacetate into the blood; These conditions seem to evoke hypoglycaemia that is characteristic of spontaneous ketosis ; Glucose (mainly synthesised from propionate absorbed from the rumen) seems to be insufficient to spare the oxaloacetate needed to allow acetyl CoA to enter the citric acid cycle. Insulin/glucagon hormone interactions may also be involved. As a consequence, the acetyl CoA backs up and its concentration increases. This promotes synthesis of ketones in the liver and ketonaemia. In cows near peak lactation, acetone can at times be detected on their breath (the smell of nail polish remover). This does not necessarily indicate that they have clinical ketosis. Prevention involves managing animals so that they do not become too fat at the time of parturition. Once the condition has developed, feeding a more rapidly fermentable diet may help, as this promotes propionate production in the rumen at the expense of a lower production and absorption of acetate and butryate. Animals are sometimes treated by providing intravenous glucose Pregnancy toxaemia (twin lamb disease of fat sheep) The energy requirements of sheep increase to 1.5 times maintenance in the last weeks of pregnancy. If intake is restricted at this stage, body tissues must be mobilised to meet the ewe s energy requirements. At the same time, however, feed intake is somewhat restricted by the reduced alimentary capacity as a results of the presence of the rapidly growing foetus(es). The condition is most likely to occur in fat animals especially if carrying multiple foetuses. The metabolic problems are similar to those of ketosis in dairy cows, i.e. a conflict between glucose production and energy conservation in ATP. Ewes with this condition have reduced feed intake and become isolated from the main flock. They become weak and characteristically raise their heads and appear to star gaze. At this time the blood ketone concentrations are elevated and glucose concentrations are low. The condition is again still not well understood but is thought to be brought on by the needs of the foetuses(es) for glucose which is required, at the same time, for gluconeogenesis and for utilisation of acetyl CoA in the citric acid cycle. In fasting pregnant ewes, LCFA and ketones are of about equal importance as energy sources for skeletal muscle (and together are able to account for more than 80% of oxygen consumption). Acetoacetate is able to provide energy for the oxidative requirements of the gravid uterus. Utilisation appears to be proportional to concentration, and up to 25% of energy needs can be met in this way in fasted pregnant ewes, since only a small and variable proportion may be released as acetoacetate. Neither β hydroxybutyrate nor acetoacetate appear to be used by the sheep brain nor do elevated concentrations appear to interfere in any way with glucose utilisation by the sheep brain. Applied Animal Nutrition ANUT300/

4 Prevention and treatment Prevention is assisted by management of the nutrition of ewes during pregnancy to prevent them from becoming over fat. Near term, it is important to ensure that ewes are not subjected suddenly to periods without adequate amounts of good quality feed. The chances of successful treatment are greater for ketosis in cattle than for pregnancy toxaemia in sheep. And the prognosis worsens as the condition progresses. Treatment usually involves administration of glucose precursors, e.g. drenching with glycerol. Kronfeld, an expert from Cornell University recommends an i/v administration of a balanced electrolyte solution containing 40 I.U. protamine zinc insulin and 25 mg dexamethazone Urea toxicity Urea is a useful nitrogen (crude protein) supplement for ruminant animals. After ingestion it is split in rumen fluid, by the action of microbial urease enzyme, to carbon dioxide and ammonia. Urea is a normal constituent found in saliva, blood and urine. Upon entering the rumen, urea is rapidly converted to ammonia and carbon dioxide by the action of microbial urease. Most of the bacteria present in the rumen, and especially the fibre degrading species can use ammonia as a building unit when synthesising their proteins. When these bacteria leave the rumen, the proteins are digested, absorbed and made available in the host s body tissues for meat, milk or wool production. The amount of ammonia being assimilated by rumen bacteria depends on their growth conditions especially on the availability of fermentable energy substrates, but also minerals and other growth factors. When excess urea enters the rumen, the resulting unused ammonia is absorbed across the rumen wall and diffuses into the portal blood, i.e. the blood that carries absorbed nutrients from the gut to the liver. The ammonia, which is toxic to nerve cells and most other body cells, is detoxified by its conversion to urea which is then released harmlessly into the bloodstream. Most of the urea circulating in the blood is then excreted in urine. Urea (ammonia) is assimilated more quickly when conditions are ideal for microbial growth and thus urea can be supplied at higher dietary concentrations when growth conditions are ideal than when they are not. Also more microbial protein will be synthesised using the N supplied by the urea. Toxicity can occur if the rate of urea entry into the rumen greatly exceed its rate of assimilation by rumen microbes. Under such conditions, the amount of ammonia arriving at the liver can exceed the capacity of the liver to convert it back into non toxic urea. Some of the ammonia passes out of the liver into the peripheral bloodstream where it can travel to the brain and central nervous system. Ammonia is toxic to cells in the brain and central nervous system and can result in clinical effects such as muscle spasms, frothing at the mouth, inability of the animal to stand, and in severe cases death. In practical situations, animals given block supplements are at risk of excessive intakes by drinking urea containing water collected in depressions on the surface of uncovered blocks after rain. Animals eating diets that do not promote microbial growth in the rumen or that lead to higher than normal ph in the rumen are more susceptible, as ammonia absorption from the rumen increases as ph increases. Animals with impaired liver function, or unaccustomed to urea supplements are particularly susceptible to toxicity Applied Animal Nutrition ANUT300/500

5 Readings! The following readings are available on CD: 1. Bauchart Lipid absorption and transport in ruminants. Journal of Dairy Science. Vol 76 pp Gallagher Biochemical studies on ovine pregnancy toxaemia. Australian Journal of Agricultural Research. Vol 10 pp McClymont Volatile fatty acid metabolism of ruminants with particular reference to the lactating bovine mammary gland and the composition of milk fat. Australian Journal of Agricultural Research. Vol 2 pp Reid and Hinks Carbohydrate metabolism of sheep. Australian Journal of Agricultural Research. Vol 13 pp Smith et al Metabolic characteristics of induced ketosis in normal and obese dairy cows. Journal of Dairy Science. Vol 80 pp Activities Multi-Choice Questions Self Assessment Questions Useful Web Links Assignment Questions Available on WebCT Submit answers via WebCT 1. What is ketonaemia? 2. Which is the TCA cycle intermediate used as a glucose precursor and as a react and that enables Acetyl Co A to be oxidised? 3. What are the management strategies that can be used to reduce the likelihood of pregnancy toxaemia in ewes? Available on WebCT Choose ONE question from ONE of the topics as your assignment. Short answer questions appear on WebCT. Submit your answer via WebCT Summary Summary Slides are available on CD Applied Animal Nutrition ANUT300/

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