Ketosis and Hepatic Lipidosis in Dairy Cows

Ketosis and Hepatic Lipidosis

• Ketones are produced through the incomplete hepatic oxidation of free fatty acids.
• Ketosis occurs when cows derive energy from stored fat molecules instead of glucose.
• Ketosis is considered a prevalent metabolic disease in U.S. dairy herds.
• Subclinical ketosis affects 80-90% of fresh dairy cows.
• The risk of ketosis increases with lactation number.

Impact of Ketosis

• Animals with clinical or subclinical ketosis have a 3-9X higher risk for displaced abomasum (DA).
• There is a 3X higher risk for culling within the first 30 days in milk (DIM) post-calving.
• Milk production decreases by 3-7%
• Cows are 1.7X less likely to conceive at 1st breeding.
• Herd effects include increased DA incidence and heightened culling rates within the first 60 DIM.

Ketosis Categories

• Type I: Spontaneous underfeeding or low dry matter intake, which is more common in component-fed herds. TMR use allows for feeding greater amounts of energy with a reduced risk of acidosis.
• Type II: Over-conditioned transition cows, also known as fat-cow syndrome.
• Type III: Caused by butyric acid silage formed in very wet (>70% moisture) grass-silage. Consuming >50 grams of butyrate per day results in ketosis. Alfalfa haylage is the most associated forage. It is not associated with corn or sorghum silage.

Dairy Cows and Glucose

• Dairy cows absorb very little glucose from their diet.
• They depend on liver gluconeogenesis.
• Glucose is necessary for lactose production in the mammary gland, brain function, erythrocytes, and muscle function
• Gluconeogenesis precursors include propionate (a volatile fatty acid from rumen fermentation), amino acids, and L-lactate.
• Grains have more starch compared to forages, and starch promotes propionate production.
• Excess starch is associated with rumen acidosis.
• Acidosis can be prevented by limiting grain (starch).

Clinical Type I Ketosis

• Peak period is 3-6 weeks post-calving.
• Cows are usually thin, with a sudden decrease in milk production and may display nonspecific symptoms like constipation and anorexia.
• Ketones are elevated in milk, urine, and blood, and acetonemia breath may be present.
• Signs of nervous ketosis include chewing on inanimate objects and aggressiveness.
• Mortality is low
• Treatments include propylene glycol at 10 oz. PO daily for 5 days, or GAH with 500 ml IV 50% dextrose one time without 20 mg dexamethasone.
• Treatment response is excellent, with glucose precursors being effective.

Type I Chain of Events:

• Low dry matter intake of food that does not contain the appropriate amount of glucose precursors (starch).
• Gluconeogenesis is impeded.
• Lipolysis of body fat occurs as an alternate energy source.
• Incomplete oxidation of fat leads to elevated ketones.
• Elevated ketones suppress appetite, causing more lipolysis

Type I Prevention:

• Concentrate on POST-calving nutrition and management.
• Provide a properly formulated diet.
• Assess anything that impacts feed intake.
• Ensure adequate bunk space (at least 30"/cow) and fresh feed access for at least 20 hours per day.
• Minimize time away from the pen and minimize overcrowding to improve cow comfort. Subordinate animals have difficulty eating when they want.
• Minimize pens containing both first-lactation and older cows, as younger animals do not compete well for food and space.
• Maximize cow comfort and focus on stall design/maintenance and heat abatement.

Clinical Type II Ketosis

• Peak period is 1-15 days post calving.
• Cows are usually fat or have lost a lot of weight quickly with low milk starting lactation.
• Anorexia and slightly elevated ketones for many days
• Difficulty overcoming other diseases (metritis, mastitis, etc.)
• There may be Hepatic encephalopathy
• High mortality.
• Treatments include continuous glucose drip, daily IV dextrose bolus, stimulation to eat, and dexamethasone.
• Treatment response is poor due to hepatic pathology.

Type II Chain of Events

• Extreme NEB pre-calving (low DMI/improper diet).
• Lipolysis occurs faster than the liver can repackage into lipoproteins.
• The liver becomes infiltrated with fat.
• Liver function is compromised
• Cannot perform gluconeogenesis
• This causes further lipolysis, i.e. “I need energy!"
• Liver infiltrated with more fat
• Liver compromised: Immunity impaired

Type II Prevention

• Nutritional management must be concentrated on PRE-calving
• Give an appropriate diet formulation with energy density (NeL) & protein.
• Maintain Ration balanced for correct expected DIM at 24 lbs/day
• Bunk space should have at least 30"/cow.
• Provide adequate availability of water.
• Do not overcrowd pen, <85% capacity is best, certainly never >100%.
• Monitor proper body condition at calving.
• Monensin: 115-410 mg/head/day
• Manage pen movement

Overcrowding

• Maximum projected production may not change.
• Very low projections disappeared.

Pen Movement Strategies

• Pen moves are stressful to the group.
• Antagonistic behavior is highest on the day of movement. 80% of interactions were physical and two days later, 40% physical and 60% postural.
• Subordinate animals (heifers) take the brunt of antagonism, resulting in lower DMI and greater health risk.
• Group stability is re-established within 2 days.
• Reduce the number of pen moves.
• Move groups of animals, not individuals, and move at night.

Maternity Pen Moves

• Moving from close-up pen to maternity pen and the length of time spent in maternity pen can be detrimental.
• 60 day post calving culling rates and displaced abomasum rates are 2X greater for cows/heifers that spend 3 or more days in the maternity/calving pen.
• This can exacerbate type II ketosis.
• Goals are to move cows less than 2 days prior to calving into the maternity pen. Herds with 24-hour human labor should move cows into maternity pen when 2nd stage labor starts and/or neonatal feet are present.

Ketosis Diagnosis

• Urine strips can be used at the chute side:
  • "Small" = positive
  • Measures acetoacetate
  • Sensitivity = 80%
  • Specificity = 95%
  • ~$1/per
• Milk strips can be used at the chute size
  • Measures acetoacetate
  • Sensitivity = 83%
  • Specificity = 82%
  • ~$1.25/per

Subclinical Ketosis

• Defined as excessive levels of ketones w/o clinical signs
• A gold standard is serum with B hydroxybutyrate (BHBA)
• SCK = >14.4 mg/dL

Chute-Side Blood Ketone Meter

• Abbott Precision Xtra™ meter costs $75-$90; strips cost $4.50-$6.00/per
• Sensitivity: 91%
• Specificity: 94%

Diagnosing Type I SCK

• Do so with a sample size of 12-15 animals
• Who: 5-50 DIM (not cows reported as ill, lame, etc.)
• Timing: not important in ad libitum TMR herds but for others, conduct 4-5 hours post-feeding
• Sample serum
• Do a sample site from jugular or tail (mammary vein = lower values)
• A positive test result is more than 10% w/ BHBA ≥14.4 mg/dL, indicating a SCK herd issue

Diagnosing Type II SKC

• Use a sample size of 12-15 animals
• Who: 2-14 days before the expected calving date
• Timing: same time at each evaluation; prior to morning feeding
• Perform a serum sample (using a serum separator tube may return abnormal values)
• Sample site: jugular or tail (mammary vein = lower values)
• A positive test result is more than 10% with NEFA >0.3 mEq/L
• NEFA is a measure of negative energy balance

Ketosis Treatment

• Propylene glycol 10 oz. once a day X 5 days PO as a drench can be done, however, this is not effective in severe Type II when gluconeogenesis is not occurring
  • increases supply of propionate
  • reduces insulin sensitivity
  • can be rumen toxic: do not increase dose or duration
  • Results in zero milk and meat withdrawal
• Vitamin B12 can be used with dosages of 1-2 ml/100lbs. bw, once
  • Catosal® (butaphosphan & cyanocobalamin: B12) converts propionate to succiny-CoA (TCA cycle)
  • Results in zero milk and meat withdrawal
• 50% Dextrose is controversial if not a drip or if not administered in small doses several times a day
  • 500 ml IV
  • Has Immediate action but short lived
  • Results in zero milk and meat withdrawal
• Dexamethasone or Isoflupredone can be used
  • The overdose of Predef® may have effects similar to K downer cow issues
  • 20 mg IV once
  • Decrease glucose update in tissues (fat and mammary)
  • Inhibits gluconeogenesis suppression by insulin
  • Is immunosuppressive
  • Some suggest not using with Dextrose (hyperglycemic)
  • Some suggest not using in cows first 14 DIM
  • Has 3 day meat and 1 day milk withdrawal

Summarized Differences Between Type I and II Ketosis

• Type 1: risk during 3-6 weeks post calving and Type II: risk during 5-15 days post calving
• Type 1: Very high Serum BHBA and Type II: High Serum BHBA
• Type 1: High Serum NEFA and Type II: High Serum NEFA
• Type 1: Low Serum Glucose and Type II: High Serum Glucose
• Type 1: Dependent Insulin status and Type II: Resistant Insulin status
• Type 1: Usually thin Body Condition and Type II: Usually fat or has lost significant weight Body Condition
• Type 1: Ketones NEFA fate and Type II: Hepatic triglycerides
• Type 1: Adequate Gluconeogenesis and Type II: Very low
• Type 1: None Hepatic pathology and Type II: Lipidosis
• Type 1: BHBA Dx test and Type II: NEFA
• Type 1: Post calving nutritional management Intervention and Type II: Pre-calving nutritional management