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Bessie the cow

4 years old, 30 days fresh (after calving), making 90 lbs of milk, Body condition score 2.5
One day she is suddenly
Off feed Decreased milk production Hard feces Elevated ketones in blood, milk, or urine

Physical Exam
Temperature 102 F Pulse 60, Respiration rate 40 bpm RUMBA
Rumen 1 contraction every 3 minutes Uterus normal involution for 30 days fresh Mammary gland palpates normal, CMT normal all 4 quarters Bronchial Tree (lungs) Auscult normal Abomasum no pings on either side of abdomen

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Extra diagnostics
Ketostick on urine moderate to large
How do you get a urine sample from a cow?

Some of you may have smelled acetone on her breath

Diagnosis: Spontaneous Ketosis

is a state of elevated ketone bodies in the body

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Treament
500 cc of 50% dextrose IV
250 g of glucose (about 1/40th of her dairy calorie requirement) Goal increase insulin release, decrease lipid mobilization Rumen inert compound, converted to glucose in liver IV glucose gives immediate response, propylene glycol provides support for next few hours

16 ounces of propylene glycol, repeat tomorrow

Treatment
Dexamethasone or Isoflupredone (PREDEF 2X)
Increase gluconeogenesis from amino acids

Rumen drench with 1 lb of AAS in 5 gallons H20

Alfalfa meal, Ca propionate, KCl, yeast Provide rumen substrates for VFA production over 12 + hours

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Outcome
Over next 3 days her milk production returned to 80 lbs / day and dry matter intake increased to 40 lbs / day

What does Bessie have in common with

An unregulated diabetic dog? The Atkins diet? Body builders prepping for an event? A sheep with pregnancy toxemia? An alcoholic?

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Ketosis

Normal State
Most animals eat meals
Initially after eating store nutrients Later after eating release stored nutrients Examples
After eating store glycogen and make fat Later after eating release glycogen and fat

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Fasts or Starvation
Lack of food leads to depletion of glucose and glycogen (hours-days) Remaining fuel sources fat and muscle
Adipose releases Free Fatty acids (FFA), aka Non-esterified Fatty acids (NEFA)
Completely oxidized in liver Partially oxidized to AcetoAcetate

But I thought Bessie was eating?

Most early lactation females are in negative energy balance
Calories for maintenance + milk > calories from intake Compensation is to milk off her back or to burn fat to compensate for daily energy deficit Most cows handle this, some (10-30%) become subclinically or clinically ketotic
Weight loss while eating alot

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Ketone bodies
Acetoacetate -OH butyrate Acetone:

Result of incomplete oxidation of fatty acids in mitochondria Enzymatic conversion of acetoacetate in cytosol From butyrate (rumen microbes) From silages slow and spontaneous conversion of acetoacetate to acetone

Ketone bodies
Exported by liver for use by other tissues
Muscle heart Brain

Seems to be a pretty reasonable strategy to provide fuel for essential tissues when glucose is limited

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Clinical Presentations of Ketosis

Starvation Spontaneous Ketosis and Secondary Ketosis in dairy cows Diabetic Ketoacidosis
Type 1 diabetes Alcoholic

Diet induced
Atkins type diet High butyrate silages

Secondary Ketosis
Cow had a case of
Metritis Mastitis Displaced abomasum

Now she is ketotic Pregnancy toxemia in sheep Hepatic lipidosis in cats and cows

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Ketoacidosis in diabetic pets

Many unregulated diabetics may have elevated ketones A small subset can present with Ketoacidosis
Severe uncompensated condition Prognosis poor Requires immediate attention and intense therapy

Back to Krebs
Early 50s Ketone bodies were not normal intermediates of fatty oxidation, but were formed by special reactions Krebs hypothesized under pathologic ketosis, there is a relative deficiency of Oxaloacetic Acid (OAA) that prevents AcCoA entry into the Krebs cycle Excess AcCoA was converted to ketone bodies

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Glucose metabolism

http://www.techedlab.com/temp/keto-metabolism.gif

Burning fat and ketone bodies

http://www.techedlab.com/temp/keto-metabolism.gif

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Ketosis

Exported from liver to body

Diet induced ketosis

Rumen microbes produce VFAs
Butyrate produced by rumen bugs converted to -OH butyrate Butyrate can also be present in ensiled feeds like corn silage

Ketogenic diets
Low carb higher fat Atkins Create relative hypoglycemia in body, increase utilization of body fat, will increase ketones in body

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Check on some bodybuilding sites

Role of ketogenic and glucogenic amino acids

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Summary
Most animals have the ability to make ketone bodies
A mechanism to convert fat to an intermediate compound that can be exported from the liver to other tissues Normal ruminants are relatively ketotic to monogastrics
10% of energy supply in normal ruminant

Disease condition when ketone supply exceeds the bodys capacity to utilize Support animals with glucose

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