Hyperketonemia

Question 1

please explain the difference between type 1 and type 2 ketosis

Answer 1

type 1: occurs in late lactation, a primary ketosis due to lack of feed intake to meet energy requirements

type 2: occurs in early lactation, secondary ketosis due to fat infiltration of the liver, liver sucks at gluconeogenesis (glucose demand is high)

Question 2

what is the NEW definition of hyperketonemia?

Answer 2

BHBA> or equal to 1.2mmol/L

Question 3

difference between primary hyperketonemia and secondary hyperketonemia

Answer 3

primary: due to not having enough glucose to meet metabolic demands of milk production –> usually happens in early lactation

secondary: results from other conditions causing anorexia

Question 4

why were the terms “subclinical ketosis” and “clinical ketosis” changed?

Answer 4

because cows with low BHBA could be clinical and cows with a high BHBA could be subclinical, it depends on the cow, so it doesn’t make sense to separate them based on the ketone level doesn’t make sense. The new way is just to say that a cow has hyperketonemia if it’s blood BHBA level is greater than 1.2mmol/L

Question 5

why do we not want our cows to be fat when they calve?

Answer 5

the more fat the cow is, the more fat she has to mobilize when she reaches that negative energy balance period (peak lactation), which means more inflammatory mediators being released, which decreases the cow’s DMI, making her ketosis worse!

Question 6

please explain the general pathophysiology of hyperketonemia as commonly seen in dairy cows, starting with hypoglycemia

Answer 6

hypoglycemia leads to a decrease in insulin. Since the mammary tissue does not require insulin for uptake of glucose, it sucks up all the glucose for milk production and leaves very little for peripheral tissue. Because blood glucose is so low, glucagon increases. The body tries to get energy from fat, so there is an increase in lipolysis in adipose tissue. This leads to beta oxidation (breakdown of fat into energy) and gluconeogenesis in the liver

Question 7

what effect does glucagon have on hormone sensitive lipase (in regards to pathophysiology)

Answer 7

increased glucagon (in response to low blood glucose levels), stimulates hormone sensitive lipase (HSL) release, which causes a big increase in albumin bound FFA (free fatty acids) and NEFA (non esterifed fatty acids)

Question 8

what is the role of prolactin in the pathophys of ketosis?

Answer 8

prolactin is released at the start of lactation and activates HSL, which prevents lipogenesis (fat production) and esterification, which causes an increase in NEFA in the blood. this makes sense because you need fat to make milk!

Question 9

what process does increased NEFAs in the blood support?

Answer 9

colostrum and milk production

Question 10

explain in regards to the TCA cycle how hyperketonemia occurs

Answer 10

beta oxidation of free fatty acids causes the co-enzymes for ATP synthesis to build up. the end product is acetyl coA, which usually enters the TCA cycle to make energy. When there is too much acetyl coA, it creates a funnelling effect where it is diverted into other reactions including ketone body formation

Question 11

explain the pathophys behind “fatty liver” that happens in cows with hyperketonemia

Answer 11

the cow is in a negative energy balance, so she needs to get energy from fat stores. FFAs and NEFAs undergo beta oxidation to form acetyl co A, which can then enter the TCA cycle to help generate energy (and can also help gluconeogenesis). The system becomes overwhelmed and acetyl co A is diverted into other pathways such as ketone body formation. This entire process is like a funneling effect, where everything gets backed up. This means there are a lot of FFAs and NEFAs “waiting in line”. These can get re-esterified to triglycerides. These triglycerides are either exported from the liver, or they accumulate as fat droplets in the liver cells creating “fatty liver”. These fat droplets cna impair liver function.

Question 12

true or false: the production of ketones is an abnormal physiologic response to negative energy balance

Answer 12

false! it is a NORMAL process; it only becomes a problem when cows produce too many ketones

Question 13

the liver extracts NEFAs from the blood and can do 2 things:

Answer 13

• esterification and stored in the liver as TGs
• oxidazed into acetyl coA

Question 14

acetyl coA can do 2 things:

Answer 14

• oxidaized completely to CO2
• incomplete oxidation to ketones

Question 15

excessive storage of NEFAs into TGs in the liver can….

Answer 15

impair liver function

Question 16

true or false: oxidation of NEFAs suppresses feed intake

Answer 16

true

Question 17

why do cows normally do lipolysis right before they give birth?

Answer 17

before birth, lipolysis happens to provide NEFAs as an alternate fuel source to the liver and other tissues too. Glucose levels in the blood is maintained this way until calving when DMI decreases. NEFAs are needed in the blood to increase the fat concentration of colostrum and milk (meeting calf demands)

Question 18

list some general reasons why you should care about hyperketonemia

Answer 18

• the cows we’ve selected for make more milk so they lose more BCS after calving which increases the risk of ketosis
• cows that get ketosis are at risk for DAs, metritis, etc
• early culling, decreased milk production
• increased calving to conception intervals

Question 19

What are some clinical signs of hyperketonemia?

Answer 19

FIRST SIGN: decrease in DMI (but remember this is also normal before birth)

• cows will refuse grain, then forage, then hay (sick cows like high fiber stuff)
• decrease milk production
• dry firm feces
• lethargy
• rapid/severe loss of BCS

Question 20

please explain what nervous ketosis is

Answer 20

super severe ketosis where the cow will literally kill you; pica, abnormal licking/chewing, ataxia or gait abnormalities, excessive salivation, blindness?

Question 21

what is the gold standard for ketone detection post partum in the dairy cow? What is one “problem” or issue you might face when doing this?

Answer 21

a lab BHBA test that is run on serum–>looking for a level greater than or equal to 1.2mmol/L

problem: BHBA levels can vary throughout the day, tend to be high right after feeding and low at night/early morning

Question 22

What are 4 other ways to detect ketones (besides gold standard method)?

Answer 22

• some can smell ketones
• urine acetoacetate
• milk BHBA –>strips require refigeration
• Precision Xtra (whole blood BHBA) this is the most sensitive and specific

Question 23

when doing a Precision Xtra test, where should you sample from (and where should you NOT sample from)?

Answer 23

sample from the tail vein and not the milk vein–>mammary tissue uses BHBAs and so blood from the milk vein will have a falsely low

Question 24

when should you test for sub clinical ketosis?

Answer 24

first 5 days in milk

Question 25

describe why dextrose is used to treat ketosis. Is it a good option? why or why not?

Answer 25

since theyre low in glucose, just give them a bunch of sugar! but this isn’t a great method because:
- it causes a spike in BG and then it returns to normal in 2 hours
- renal excretion of the excess glucose can waste electrolytes leading to hypophosphatemia

Question 26

when should you use dextrose to treat ketosis?

Answer 26

ONLY in extreme cases like w/ nervous ketosis, and only give 250mLs of 50% dextrose, and ALWAYS follow up with oral propylene glycol

Question 27

why are glucocorticoids used to treat ketosis? is this a good treatment option? why or why not?

Answer 27

glucocorticoids promote hyperglycemia and hyperlipidemia, it increases appetite, decreases milk yield

short term effects are okay, but long term they may have negative impacts on the animals metabolic state and can make it worse if it happens again. therefore you should NOT use glucocorticoids!

Question 28

why is insulin used as a treatment for ketosis? is it a good option? why or why not?

Answer 28

insulin promotes fat synthesis and decreases fat catabolism and favors the use of ketone bodies

it can be helpful, but never use it alone since it promotes hypoglycemia. there’s also not a lot of evidence for its use. therefore DO NOT use this

Question 29

why is B12 used to treat ketosis? is this a good treatment? why or why not?

Answer 29

B12 supports the activity of enzymes in the TCA cycle which icnreases efficinecy of the cycle and increases gluconeogenesis

theres not a ton of research on it but it doesn’t hurt to give it so it can be helpful! it’s water soluble so any extra can be excreted

Question 30

why is oral propylene glycol used to treat ketosis? is it a good treatment? why or why not?

Answer 30

it is converted to proprionate in the rumen which stimulates insulin release and gluconeogenesis, AND it can be absorbed directly entering the TCA cycle to help more Act CoA to be oxidized

this is the treatment you want to use!!!

Question 31

why do you give prolylene glycol orally

Answer 31

to stimulate the insulin release

Question 32

dose for giving propylene glycol?

Answer 32

300grams or mLs Q24 for 5 days

Question 33

what are some risk factors for getting hyperketonemia?

Answer 33

• breed (jersey and holstein more at risk)
• parity (primiparous more common vs multiparous less common)
• any limitation of DMI (overcrowding, stress, etc)
• age of first calving (have baby later, get ketosis worse)
• previous ketosis event
• increased pre calving NEFAs

Question 34

what is the best way to manage hyperkeonemia, especially subclinically?

Answer 34

• cow side BHBA testing
• test all fresh cows 2x between 3-9 DIM
• treat cows with propylene glycol if test shows more than 1.2mmol/L

Question 35

what are the best ways to PREVENT ketosis?

Answer 35

• manage cow body condition
• making sure cows get re-bred on time so they dont get fat esp in late lactation when they tend to put on weight
• use transition diets that are balanced to meet energy demands with the smallest DMI

Question 36

what is the reocmmended BCS for cows at calving?

Answer 36

heifers: 3.25
mature cow: 3

Question 37

what is monensin and how does it work?

Answer 37

it is a feed additive that shifts the bacterial population in the rumen to increase proprionate levels, which increases glucose levels, giving more energy to the cow and decreasing odds of ketosis. it is also a coccidiostat

Question 38

what are the effects of monensin? name at least 3

Answer 38

• decreases DA, ketosis, mastitis
• decreases DMI (increases efficiency)
• increases milk and efficinecy

Question 39

when should you use BHBA vs NEFA tests to monitor for ketosis?

Answer 39

BHBA: quick, cheap, should be used as the primary monitoring tool

NEFA: if you think there’s herd issues in transition cows and they don’t have high BHBA, you should use this

Question 40

How many cows should you test to monitor for ketosis in the herd?

Answer 40

7-12 animals from each group