1 Definition, Importance of Ketosis, Etiology of Ketosis
Transcript
I welcome all the practicing Vets for this class on Ketosis.
As you all know, Ketosis is an important production disease, which more commonly occurs in the immediate postpartum period. It is a recent trend in selecting the dairy cows genetically for higher milk yield results in Ketosis.
So, Ketosis has adverse effects or it can have a direct and indirect effect on the economy of the animal. Directly it affects the milk yield and also the production of the animal and in turn, it also affects the health of the animal. So, the cattle are exposed to or are predisposed to the other metabolic disorders in the periparturient period and indirectly or the latent effect of this Ketosis especially the sub-clinical Ketosis is, that it will make the animal succumb to cystic ovaries, there will be an increase in the calving to the first service, increase in the interval between calving to the first service and increase in the interval between calving to the last service. And all the other reproductive failures will occur because of subclinical ketosis.
Now we are going to see about Ketosis in five classes.
Lesson-1; will deal with the Definition and the Importance of Ketosis and its Etiology,
Lesson-2; the second class is about the Etiology and also the Epidemiology of both the Ovine and Bovine Ketosis,
Lesson-3; third class is about the Pathophysiology of Bovine or Ovine Ketosis, and
Lesson-4; fourth class is regarding the Clinical Signs, Clinical Pathology, the Diagnosis and Differential Diagnosis of both Bovine and Ovine Ketosis and
Lesson-5; fifth class we are going to deal with the Treatment Management and Control of the Bovine and Ovine Ketosis.
Let’s start with the topic. So, in first class, we will see about:
The Definition of Ketosis: Ketosis is defined as a multifactorial disorder of energy balance, it is a basic metabolic disturbance resulting from negative energy balance during early lactation reduction in blood glucose and also the liver glucose level, and an increased fat mobilization that results in elevated Ketone body concentration. It is characterized by abnormally elevated concentrations of Ketone bodies and Hypoglycemia. So, Ketone bodies include acetoacetic acid, beta-hydroxybutyrate, and acetone.
Next, we’ll see something about the Importance of Ketosis: why ketosis is so important as a production disease. See nowadays in modern agriculture practice animals are selected for the increase in milk yield. Genetically animals are selected for increased milk yield, so this increase in milk yield exceeds the capacity of the animal to ingest sufficient feed to meet the requirements for energy, especially during lactation. So, the net result is the negative energy balance, this results in the negative to offset the negative energy balance, mobilization of the fat and protein occurs, this results to the that is, it is transported as triglyceride and amino acids to the liver, where it undergoes the gluconeogenesis and ketogenesis for the production of energy. Always in the lactating animal, there will be a certain degree of Ketosis. Cows’ pregnancy undergoes a partition of nutrients during pregnancy and lactation and is always in a lipolytic stage in early lactation and or at a higher risk for Ketosis during this early lactation period, that is immediately after postpartum.
When does ketosis become a disease condition? It is when the absorption and the production of Ketone bodies exceed their use by the ruminants as an energy source, that results in an elevated blood Ketone, which is free or non-esterified fatty acids.
So, coming to Etiology, that is Etiology of Bovine Ketosis, before going deep into the Etiology of Bovine Ketosis, understanding why the Ketone bodies are formed and how the Ketone bodies are formed are essential. This understanding of the glucose metabolism, energy metabolism in the case of animals, the role of insulin and glucagon, ketone body formation, and how this ketone body formation is going to affect the Hepatic insufficiency or it leading to the Hepatic insufficiency in cattle is more important.
So how glucose metabolism is more important in the case of cattle. So, maintenance of adequate concentration of glucose in the plasma is always essential for the regulation of the energy metabolism. In the case of ruminants, they will absorb very little hexose sugar as carbohydrates, the remaining carbohydrates are fermented in the rumen into short-chain fatty volatile fatty acids like acetate, propionate, and butyrate. In this acetate and butyrate are ketogenic and the propionate is glycogenic.
Propionate and amino acids are the important precursors for gluconeogenesis, whereas the glycerol and lactate are less important for gluconeogenesis. So, the propionate that is formed is its most important glucose precursor and it is produced in the rumen from starch fiber and proteins. So, this enters the portal circulation and reaches the liver and it is efficiently removed by the liver. And the production of the propionate is increased, or it is favored by the inclusion of the starch in the diet.
The amino acids: coming to amino acids the importance of amino acids is it is gluconeogenic or it’s a glucogenic factor and it is an important precursor for gluconeogenesis you all know dietary protein is an important source or it is the most important quantitative source for the amino acids and the second source is the Labile pool of body protein, that is particularly of the skeletal muscles, is also an important source. This contributes to energy synthesis, milk protein synthesis, and milk lactone synthesis.
So, coming to energy metabolism; see all high producing dairy cows will always be in a negative energy balance, especially during the first few weeks of lactation. This is because the high dry matter intake does not occur until 8 -10 weeks after calving, but the animal will go for peak lactation within 4-6 weeks. Hence the energy intake does not keep up with the production, so the net result is the animal will go to a negative energy balance and there will be low serum glucose and low serum insulin will be there. So, this will lead to the or will make the cow mobilize the adipose tissues in the form of, that is present the form of triglycerides, with a subsequent increase in the non-esterified fatty acids. So, this subsequent increase in the serum concentration of leads to the mobilization of the fat as free fatty acids and non-estrogen fatty acids to the liver will increase the serum concentration of the ketone bodies like beta-hydroxybutyrate, acetoacetate, and acetone. So the Hepatic mitochondrial metabolism of fatty acids promotes both glyconeogenesis and also ketogenesis.
How Ketone bodies are formed?
So there are two main sources for the Ketone bodies production in the ruminants.
- One is Butyrate in the Rumen: this is mainly produced by the rumen fermentation of the diet, where it is converted into beta-hydroxybutyrate in the ruminal epithelium and is absorbed as such.
- whereas the second one is the Mobilization of the fat: where mobilized fat will be transported to the liver and will be oxidized to acetyl CoA and nicotinamide adenosine dinucleotide plus hydrogen ion (NADH). so, what happens to the acetyl-CoA that is formed it has to be oxidized via the TCA cycle, so for this oxidation auxiliary state is required supply of oxaloacetate is required for which the precursor propionate is required as I told the carbohydrates are converted into short-chain fatty acids like acetate, butyrate, and propionate. The propionate plays a major role, or the importance of the propionate lies over here, where it is important for the supply of oxaloacetate. Once this oxaloacetate is propionate is decreased, in turn, the auxiliary state is going to be decreased, so this will affect the TCA cycle, that is acetyl-CoA oxidation in the TCA cycle. So, the next is what happens is this acetyl CoA will be metabolized to acetyl-CoA where again it will be converted into acetoacetate and beta-hydroxybutyrate thereby leading to Ketone body formation. And in the case of cattle any animal that is in recent calving or the immediate postpartum period, some degree of hepatic insufficiency or some degree of fatty liver is more common. So, uptake of fatty acids by the liver leads to the fatty liver, which will lead to hepatic insufficiency. See as I told you any animal that is in the immediate postpartum period will have a certain degree of negative energy balance, okay so the degree of the negative energy balance usually depends upon the level of milk yield high production or it is a medium producing animal. So, this depends upon the production level or how much milk yield is there in each animal. So, what happens is there will be an uptake of fatty acid by the liver which leads to the formation of fatty liver. There will be a certain degree of hepatic insufficiency, so this hepatic insufficiency occurs in cows that are pre-disposed to ketosis, by over-feeding, especially during the dry period.
So based on the hepatic insufficiency presence of hepatic insufficiency ketosis can be divided into:
Type 1
Type 2 and
Type 3.
So in the case of Type 1 ketosis what they say is it is spontaneous ketosis. Here what happens is gluconeogenesis pathways are maximally stimulated, so what happens is whenever there is a negative energy balance or this negative energy balance is offset by the mobilization of the fat, ketosis occurs when the demand for the glucose increases or outstrips the capacity of the liver to go for gluconeogenesis due to insufficient glucose precursor. So as I told you there will be a decrease or there will be a deficiency of propionate leading to the deficiency of the oxaloacetate, so the acetyl-CoA oxidation via the TCA cycle will be impacted, this will lead to the mobilization so there will be a decrease in the energy level, there will be a rapid entry of NEFA into the hepatic mitochondria resulting in a higher rate of the ketogenesis. So there will be high plasma or serum ketone concentration will be there, see whatever the NEFA that is remaining that is a free fatty acid so the non-esterified fatty acids will be again converted into triglyceride and it will be stored in the liver or it will be converted as fatty liver.
So, in Type 1 ketosis, there will be a little conversion of the NEFAs to triglycerides hence little fat accumulation in the liver.
Whereas in the case of Type 2 Ketosis: it is also called a fatty liver, the gluconeogenic pathway. You have to understand the difference between Type 1 and Type 2:
In the case of Type 1, gluconeogenic pathways are maximally stimulated, so what happens is whatever the NEFA and the free fatty acids, that are mobilized to the liver will be resynthesized as triglycerides and it will be used for the ketone body production, whatever the remaining NEFA and this thing will be stored as the fat in the liver crossing the fatty liver, but the degree of fat deposition differs in Type 1 and Type 2 whereas the Type 2 is truly called as a fatty liver.
In this Type 2 Ketosis, gluconeogenic pathways are not maximally stimulated, so the NEFA obtained by the cytosol is not active, NEFA becomes esterified in the cytosol forming triglyceride. So, the capacity of the cattle to transport triglyceride from the liver is low, this will result in the accumulation of the triglyceride in the liver causing fatty liver. So, the animal will go for fatty liver, this fatty liver will further depress the gluconeogenesis and excess butyrate the already present glucose decrease in the gluconeogenesis.
Type 3 Ketosis: here this is because the animals are due to feeding the animal with a high butyrate-producing diet, especially maize.
Coming to the Role of insulin and glucose: see insulin and glucagon, these two hormones are more important to regulate the energy metabolism in ruminants. Both the hormone has got a counteracting effect. The counteracting effects play a major role in maintaining the homeostatic control of glucose metabolism. Low insulin glucagon ratio will stimulate it will be there in the immediate postpartum period or lactating animals this will stimulate the lipolysis from the adipose tissues and result in the ketogenesis in the liver.
Cows in early lactation will have low insulin and low glucagon ratio.
There will be an elevated ketone body or the presence of the elevated ketone body will stimulate insulin production and it will have a negative feedback effect, and regulation is also indirectly governed by the hormone Somatotrophin. Somatotrophin is again lipolytic and it is also an important determinant of milk yield in ruminants.
So the Importance of Ketosis is mainly due to the presence of the subclinical ketosis it not only causes affects the production of the animal and also the reproduction, but it will not allow the animal to respond to the underlying disease or respond to the treatment given to the primary diseases, thereby decreasing the production of the animal.
So Subclinical Ketosis: In this subclinical ketosis, there will be an elevated concentration of blood ketones without clinical disease and this is more common than the clinical ketosis, it causes a significant economic loss to the farmer and it is common in high producing dairy cows, especially during 2-7 weeks postpartum period and small, see what happens is the animal will be in subclinical ketosis, so any minor nutritional insult diffusion deficiency or any metabolic insult is going to be there this will lead to the development of the Clinical Ketosis.
We have seen the Definition of Ketosis, and also the Importance of Ketosis in ruminants and followed by the Etiology, and in that Etiology how the ketone bodies are produced and why the ketone bodies are produced, and how it is going to affect the health of the animal by going for the Sub-clinical ketosis and Clinical ketosis, and
Next class, I will talk about the remaining Etiology and Pathophysiology.
Thank you!
