Volume 22 • Issue 03 • 2018
Protein breakdown for gluconeogenesis from amino acids plays an important role in energy metabolism in cows , and it has recently been suggested that cows with an insufficiency of this pathway , or rather an imbalance between lipolysis and proteolysis , may be at an increased risk of ketosis .
Pathogenesis of type I ketosis The clinical manifestations are caused by :
• hypoglycaemia the brain needs glucose for normal functioning ,
• hyperketonaemia it is speculated that the isopropyl alcohol formed from ß hydroxybutyrate is toxic and may cause the nervous symptoms seen ,
• suboptimal liver function - detoxification function of liver affected ,
• distension of liver-abdominal pain ,
• acidosis there is usually a mild metabolic acidosis ( ketone bodies are acids ) - Compare with pregnancy toxaemia in sheep where there may be a more severe acidosis .
The key underlying factor leading to type I ketosis is a deficiency in glucose due to a severe negative energy balance ( NEB ). The loss of glucose through milk production is not hormonally regulated , and will thus carry on despite causing harm to the health of the cow . Glucose in the ruminant has three main sources .
Firstly it can be absorbed directly from the small intestine in the form of sugars or starches , and secondly it can be metabolised from propionic acid , one of the most common volatile fatty acids produced in the rumen through microbial fermentation . In the third place it can be synthesised from acetyl-CoA , a metabolite of two other volatile fatty acids ( butyric and acetic acid ) or of fat break-down . Acetyl-CoA is an important fuel in ruminants , and apart from being a glucose precursor , it can be metabolised further into ketone bodies ( acetone , aceto-acetate and betahydroxy butyric acid ) that can also act as fuel in many tissues . The brain however requires glucose as energy source and cannot function on ketone bodies .
Ketone bodies enter the Krebbs cycle , a carbon cycle that utilises Acetyl-CoA and other substrates for glucose production , in the liver as well as many other tissues in the body to form glucose for energy production . This is the most important mechanism of energy production in the udder of lactating dairy cows , and is a unique property of ruminants . A very severe depletion of glucose stores , however , leads to a deficiency of 4-carbon substrate ( oxaloacetate ) needed to combine with Acetyl-CoA in order to enter the Krebbs cycle . This leads to failure of the Krebbs cycle to utilise all the available Acetyl-CoA , the excess being metabolised into excessive levels of ketone bodies .
GLUCOSE
NEGATIVE ENERGY BALANCE
BST PROLACTIN
LOW INSULIN
GLUCOSE SUBSTRATE
NEFA
Hormone sensitive lipase
GLYCEROL
LIVER CELL
+ + +
FAT STORES
NEFA
GLUCOSE
ACETYL CoA
KETONE PRODUCTION
MITOCHONDRIUM
Diagram illustrating how a negative energy balance ( NEB ) leads to Type I Ketosis
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