12. ketosis

list the circulating ketone bodies

• beta-hydroxybutyrate (BHBA)

• acetoacetate

• acetone

ketosis definition

• increased levels of circulating ketone bodies

• more specifically, hyperketonemia

  • blood BHBA concentration ≥ 1.2 mmol/L

what are the 4 types of clinical ketosis?

1. primary ketosis — most common; affects high-producing cattle in early lactation

2. secondary ketosis — also affects high-producing cattle in early lactation, but is secondary to another disease process that affects appetite more than milk production (ex. LDA, metritis)

3. undernutritional ketosis — rare; occurs in extreme cases of poor nutrition and advanced cachexia

4. pregnancy toxemia — pre-partum primary ketosis; uncommon in dairy cattle; associated with twin pregnancies

when does ketosis occur? under what conditions does it occur?

occurs during early lactation when 2 conditions are met:

1. energy demands (from milk production) exceed dietary intake → negative energy balance (NEB)

2. negative energy balance is sufficient to cause excessive mobilization of adipose tissue relative to carbohydrate (glucose) supply

   • ruminant absorb low amounts of glucose from GI tract

   • carbohydrates are fermented to volatile fatty acids (VFAs) → VFAs account for most of cow’s energy

pathophysiology of ketosis

1. high drive to milk

2. not eating enough carbohydrates to meet energy demands

3. body tries to use fat to make energy

4. fatty acids are partially oxidized to acetyl-CoA, but need oxaloacetate to enter TCA cycle

5. oxaloacetate is in low supply due to impaired gluconeogenesis

   • gluconeogenic precursors for oxaloacetate are propionate, lactate, and pyruvate

   • cow prioritizes using these precursors for milk production (lactose) instead of glucose

6. acetyl-CoA canot enter TCA cycle → instead directed toward ketone body formation

what happens to the liver when excess adipose tissue is mobilized?

• lipolysis may exceed hepatic capacity for oxidation

  • mobilized fatty acids, specifically non-esterified fatty acids (NEFAs) are re-esterified → stored in liver as triacylglycerol (TAG)

  • mild increase in TAG is tolerated, but larger amounts disturb liver function

• hepatic lipidosis impairs gluconeogenesis

consequences of ketosis

• reduced milk yield

• increased risk for displaced abomasum

• increased risk for metritis

• impairs fertility

• increased risk for early lactation herd removal

• can be costly & frustrating to treat

clinical signs of hyperketonemia

• decreased milk yield

• diminished appetite

  • difficult to observe with group feeding

• better appetite for hay than silage or grain

• dull mentation

• dry manure

• excessive weight loss

• reduced rumen motility

• sweet-scented breath (acetone)

clinical signs of nervous ketosis

encephalopathic form of ketosis

• aggression

• pica (constantly licking or chewing inanimate objects)

• leaning into stall, head pressing

• circling, ataxia, hyperesthesia

• transient blindness

what are the cowside hyperketonemia testing options?

• blood

  • excellent accuracy

  • must keep meter & strips warm — enzymatic reactions are temp sensitive

• urine

  • more likely to produce false negatives

• milk

  • ok sensitivity & specificity (better than urine, less than blood)

which ketone body is measured by blood testing? what is the cutoff value for ketosis?

• BHBA

• ≥ 1.2 mmol/L

which ketone body is measured by urine ketone strips?

acetoacetate

which ketone body is measured in milk?

BHBA

• milk BHBA moderately associated with blood BHBA

what is the current recommendation for treatment of mild to moderate ketosis?

300 mL propylene glycol (or equivalent glucose precursor) orally once daily x 3d

what is the current recommendation for treatment of severe ketosis?

250 mL 50% dextrose IV (once) followed by oral glucose precursor x 3d

what are glucose precursor options?

• propylene glycol

  • 300 mL orally once daily

• glycerin

  • same or slightly higher dose than glycol

• calcium propionate

  • 1 pound in 5 gallons of water

how are other types of ketosis treated?

• secondary ketosis

  • treat the underlying condition (metritis, mastitis, displaced abomasum) + treat ketosis

• under-nutritional ketosis

  • poor prognosis for recovery — prevent it from happening!

• pregnancy toxemia

  • treat the ketosis

  • ± terminate pregnancy depending on value of calves vs. cow

what is a risk factor for chronic ketosis?

• cows that are over-conditioned (BCS ≥ 4.0) at time of calving are high risk for chronic ketosis

  • lower feed intakes

  • high adipose sensitivity

  • insulin resistance

• easily develop underlying fatty liver

what are herd-level strategies for preventing ketosis?

• no overcrowding in transition period (competition for resources increases stress)

  • must allow 30” bunk space per cow

  • must have adequate resting space

• avoid obesity before caving (goal BCS at calving = 3.5)

  • avoid prolonged dry period ( > 3 months)

• dietary management

  • controlled-energy, high-roughage diet throughout transition period (± 21d of calving)

• cow comfort

  • minimize pen moves

• house first-lactation heifers separate from multiparous cows → reduces stress

ketogenic silage

overly wet haylage at harvest → excess growth of clostridial organisms → clostridia sp. ferment carbohydrates to butyric acid instead of lactic acid → butyric acid is converted into BHBA, directly causing ketosis

what are individual-level strategies for ketosis prevention?

feed additives

• niacin (vitamin B3)

  • higher blood glucose & lower BHBA than control animals

• rumen-protected choline (B-complex vitamin)

  • may improve transport of lipids in the blood to reduce risk of fatty liver

• ionophores (monensin)

  • shifts ruminal fermentation patterns to favor propionate over acetate