RN 414
Date:
81902106
Update on Dairy Herd Nutrition Troubleshooting (Oetzel; pg 117-120)
Etiology and Nutritional Prevention of Metabolic Disorders (NRC; pg 188-189)
PART I — BACKGROUND
1. What is Ketosis?
Ketosis is a metabolic disorder of lactating dairy cows that occurs shortly after calving and is characterized by
abnormally elevated concentrations of ketone bodies acetoacetic acid, acetone and beta-hydroxibutyrate (BHB) in
body tissues and fluids. The condition is associated with negative energy balance in the last few days before
calving and in the first few weeks of lactation, a reduction of glucose in the blood and an increased fat
mobilization resulting in elevated ketones bodies. Under normal condition, the concentration of glucose in the
blood is 50 mg/dl or higher and BHB is low and usually less than 10 mg/dl. In sub-clinical ketosis, blood glucose
ranges between 20 and 40 mg/dl but blood concentration of BHB is greater than 10 mg/dl. In clinical cases, blood
glucose is typically 28 mg/dl or less, BHB is greater than 26 mg/dl and blood acetone concentration can rise
above 15 mg/dl (Fleming, 2002).
Figure 1: Change in plasma glucose (left panel A),
insulin (left panel B), serum NEFA (right panel A)
and serum BHB (right panel B) in dairy cows fed a
control diet (open squares) or the same diet
supplemented with propylene glycol (solid circles)
(Chibisa et al., 2007).
2. Fat mobilization and utilization by the liver….
(Modified from Goff and Horst, 1997)
During early lactation, the amount of energy
that is required for maintenance of body tissues
and milk production exceeds the amount of energy
the cow can obtain from dietary sources. As a
result, the cow must utilize body fat as a source of
energy. The triglycerides stored in adipose tissues
are released in the blood as non-esterified fatty
acid (NEFA). The NEFA are taken-up by the liver,
however there is a limit to the amount of fatty
acids that can be completely oxidized to H2O and
CO2 by the tricarboxylic acid cycle (TCA). There
is also a limit on the packaging of fatty acids into very
low density lipoprotein (VLDL) for export from the liver. When these limits are reached, the fatty acids are
esterified and the resulting triglycerides accumulate within the hepatocytes (liver cells), impairing their function.
The incomplete oxidation of the fatty acids results in the formation of acetoacetate and BHB in the liver. These
ketone bodies are easily exported from the liver and serve as an important source of fuel for many body tissues (in
particular the brain) during periods of negative energy balance. An elevated level of ketone bodies in the blood,
milk, and urine is diagnostic of ketosis and usually becomes clinically evident from 10 days to 3 weeks after
calving. Although numerous researchers have offered hypotheses to explain why the liver has a limited capacity
for the oxidation of fatty acids, the limiting step(s) in biochemical pathways that limits efficient oxidation of fatty
acids remains unclear. On the practical side, however, we know that the liver of an over-conditioned cow has a
more limited ability to oxidize fatty acids than the liver of a cow with a “normal” body condition score (BCS = ±
3.50). As a consequence, cows with high BCS at calving (BCS>4.00) have a greater risk of liver dysfunction after
calving.
3. High glucose demand and glucogenesis in the liver…
Also, in early lactation, the demand for glucose synthesis (glucogenesis) by the liver increases considerably to
provide the building blocks needed for the synthesis of lactose (milk sugar) in the mammary gland. Under normal
1
RN 414
81902106
circumstances the propionate produced during ruminal fermentation is absorbed in the blood and taken up by the
liver to synthesize glucose. It is typical for the concentration of glucose in the blood of early lactating cows to
drop significantly because the glucose synthesis in the liver can hardly keep-up with the high demand for glucose
by the mammary gland. Low blood glucose (and low insulin) is a signal that the cow needs an alternative source
of energy and thus it favors the mobilization of lipids from adipose tissues. When excess mobilization of adipose
tissues results in fat accumulation in the liver, glucogenesis by the liver becomes impaired, resulting in a
worsening of the hypoglycemia (low blood glucose). A vicious circle gets established as a reduced blood glucose
leads to low insulin which leads to further mobilization of adipose tissue, which leads to fatty liver which leads to
lower output of glucose by the liver, and so on.
4. Importance of dry matter intake… (Bertics et al., 1992)
Research has demonstrated the importance of feed intake at calving on the etiology of the fatty liver-ketosis
syndrome. In the average cow, DMI decreases precipitously by 30% on d 1 or 2 before calving and does not
recover until 1 to 2 d after calving. Triglyceride and lipid accumulation in the liver is a much earlier phenomenon
than previously assumed. Liver biopsies taken several weeks before calving, at calving, and 4 wk into lactation
showed that liver triglycerides were increased 3-fold by the day of calving. By 4 wk into lactation, the liver
triglycerides were 4-fold higher than before calving. The importance of avoiding the drop in DMI at calving on
the risk of fatty liver-ketosis syndrome was illustrated by an experiment in which DMI was not allowed to drop
around the time of calving by forcing feed into the rumen through a rumen fistula. Cows whose intake was
maintained “artificially” normal showed significantly lower accumulation of triglycerides in the liver.
5. Importance of transition cow management and “transition cow diet” …
Any factor, such as milk fever, that exacerbates reduction in feed intake at calving increases the energy deficit
of the cow and the risk of fatty liver and ketosis (Marquardt et al., 1977). Other factors limiting the amount of
energy the cow can derive from the diet shortly after calving include a limited ability of the rumen wall to absorb
volatile fatty acids (VFAs) when the rumen is poorly transitioned from the high NDF low NFC diet of the far-off
dry cow to the much lower NDF, much higher NFC diet of the early lactating cow. In a fully adapted rumen, a
ration with higher energy density can be fed without causing rumen acidosis. Unfortunately, rumen acidosis is
common and reduces feed intake in early lactation. Diet composition should be carefully monitored such that
rumen fermentation yield highest amounts of propionic acid without undesirable drop in rumen pH (i.e., used high
NFC diets and dietary buffers). The quality of the silages cannot be over-emphasized. Poor quality silage with
high concentration of poorly digestible NDF yielding limited energy, and poorly preserved silage with a high
level of butyric acid (which is converted to beta-hydroxybutyrate as it crosses the rumen wall and enters the
blood) are examples of feeding conditions that may exacerbate the risk of sub-clinical ketosis.
6. Citations:
Bertics, S. J., R. R. Grummer, C. Cadorniga-Valino, D. W. LaCount, and E. E. Stoddard. 1992. Effect of prepartum dry
matter intake on liver triglyceride concentration and early postpartum lactation. J. Dairy Sci. 75:1914.
Chibisa, G. E., G. N. Gozho, A. G. Van Kessel, A. A. Olkoski, and T. Mutsvangwa. Effect of peripartum propylene glycol
supplementation on nitrogen metabolism, body composition, and gene expression for the major protein degradation
pathways in skeletal muscle in dairy cows. J. Dairy Sci. 91: 2512-3527.
Fleming, S. 2002. Metabolic Endocrine and Metabolic Diseases, ch 39: Pg 1242-1247 in: Large Animal Internal Medicine 3rd
Edition, Smith, B. P. (Ed). Mosby St. Louis MO.
Goff, J. P. and L Horst. 1997. Physiological Changes at Parturition and Their Relationship to Metabolic Disorders. J. Dairy
Sci. 80:1260-1268.
Marquardt, J. P., R. L. Horst, and N. A. Jorgensen. 1977. Effect of parity on dry matter intake at parturition in dairy cattle. J.
Dairy Sci. 60:929.
PART II — Test your knowledge: multiple choices
1. The three ketone bodies produced by the liver include:
a) Acetone, oxaloacetate, and Non-esterified fatty acid
b) Beta-hydroxy butyrate, Non-esterified fatty acid and actetoacetate
c) Beta-hydroxy butryrate, acetone and acetoacetate
d) Acetone, beta-hydroxy butyrate, and oxaloacetate
Explanation:
2
RN 414
81902106
2. According to Oetzel, what is the “alarm proportion rate” for cows tested for NEFA immediately
prepartum?
a) 0%
b) 6%
c) 10%
d) 15%
Explanation:
3. Clinical ketosis involves blood level of BHBA
a) 1) >5.5 mg/dl
b) 2) >14.4 mg/dl
c) 3) >26 mg/dl
d) 4) >50 mg/dl
Explanation:
4. Blood glucose in a dairy cow free from ketosis is approximately
a) 100 mg/dl
b) 50 mg/dl
c) 25 mg/dl
d) 12 mg/dl
Explanation:
5. Which of the following cows are the “eligible” for BHBA testing?
a) Lactating cows, about 5 to 150 days in milk
b) Lactating cows, about 5 to 50 days in milk
c) Pre-fresh cows, ideally 5 to 14 days from calving
d) Lactating cows at any stage of lactation
Explanation:
6. The BHBA test (to test for subclinical ketosis) is usually performed on which of the following type of
sample?
a) Urine samples.
b) Fecal samples
c) Liver tissue samples
d) Serum samples
Explanation:
3
RN 414
81902106
7. When BHBA is above 14.4 mg/dl, cows are at greater risk of
a) Displaced abomasum
b) Clincal ketosis
c) Decreased milk production
d) All of the above
Explanation:
8. Beta-hydroxy butyrate (BHB) may come from
a) Consumption of poorly preserved silage
b) Conversion of butryric acid produced in the rumen by the rumen wall
c) Incomplete oxidation of fatty acid by the liver
d) All of the above
Explanation:
9. NEFA and BHBA levels will be ___________ in late lactation cows compared with early lactation
cows.
a) greater
b) lower
c) similar
Explanation:
10. Which test(s) vary in concentration with time relative to feeding?
a) NEFA
b) BHBA
c) Choices a) and b)
d) Urea Nitrogen
e) All of the above
Explanation:
PART III: CLASS ACTIVITY: Discuss
your understanding of the ketosis with team members and use the
space below to draw the main factors contributing to the disorder and their relationships with one
another. Use arrows and pluses (+) or minuses (-) to illustrate positive or negative relationships.
Make sure you include Triglycerides (TG), non-esterified Fatty acids (NEFA), beta-hydroxybutrate
(BHB), Glucose (G), propionic acid (Pr.), butyric acid (Bu.) and insulin (In).
RUMEN
DMI
4
RN 414
81902106
ADIPOSE TISSUES
PANCREAS
LIVER
UDDER
5