Medicine Lecture 5th Stage 92-10-2017 Dr.Osamah Muwafk
KETOSIS:
It is a condition characterized by abnormally elevated concentrations of
ketone bodies in the body tissues and fluids, it is classified as clinical or
subclinical on the basis of levels of ketone bodies in the blood, urine and
milk and presence or absence of clinical signs.
Glucose metabolism in ruminants:
1- The maintenance of adequate concentrations of glucose in the blood is
critical to the regulation of energy metabolism .
2- The ruminant absorbs very little dietary carbohydrate as hexose sugar
because dietary carbohydrates are fermented in the rumen to short
chain fatty acids, principally acetate (70%), propionate (20%) and
butyrate (10 %).
3- Consequently, glucose needs in ruminants must largely be met by
gluconeogenesis.
4- Propionate and amino acids are the major precursors for
gluconeogenesis with glycerol and lactate of lesser importance.
5- Propionate is produced in the rumen from starch, fiber, and proteins.
6- It enters the portal circulation and is efficiently removed by the liver,
which is the primary glucose producing organ.
7- Propionate is the most important glucose precursor; an increased
availability can spare the hepatic utilization of other glucose
precursors.
8- The majority of amino acids are glycogenic and are also important
precursors for gluconeogenesis.
9- Dietary protein is the most important quantitative source but the labile
pool of body protein is also an important source.
10- They contribute to energy synthesis and milk lactose synthesis as
well as milk protein synthesis.
11- Dietary acetate is transported to peripheral tissues and to the
mammary gland and metabolized to long chain fatty acids for storage
as lipids or secretion as milk fat.
Medicine Lecture 5th Stage 92-10-2017 Dr.Osamah Muwafk
Etiology:
1- In high-producing dairy cows there is often a negative energy balance
in the first few weeks of lactation.
2- In response to a negative energy balance and low serum
concentrations of glucose and insulin, cows will mobilize adipose
tissue with consequent increases in serum concentrations of non-
esterified fatty acids (NEFA) and subsequently BHBA.
3- The hepatic mitochondrial metabolism of fatty acids promotes both
gluconeogenesis and Ketogenesis.
4- Ketones arise from two major sources: butyrate in the rumen and
mobilization of fat.
5- A large proportion of butyrate produced by rumen fermentation of the
diet is converted to 13-hydroxybutyrate (BHBA) in the rumen
epithelium and is absorbed as such.
6- Free fatty acids produced from the mobilization of fat are transported
to the liver and oxidized to produce acetyl-CoA and NADH.
7- Acetyl-CoA may be oxidized via the TCA cycle or metabolized to
acetoacetyl CoA.
8- Its oxidation via the TCA cycle depends upon adequate supply of
oxaloacetate from the precursor propionate.
9- If propionate, and consequently oxaloacetate, is deficient, oxidation of
acetyl-CoA via the TCA cycle is limited and it is metabolized to
acetoacetyl CoA and subsequently to acetoacetate and BHBA.
10- The ketones BHBA and acetoacetate can be utilized as an energy
source.
11-
They are normally present in blood and their concentration is a
result of the balance between production in the liver and utilization by
the peripheral tissues.
12-
A low insulin: glucagon ratio stimulates lipolysis in adipose
tissue and Ketogenesis in the liver.
13-
Cows in early lactation have low insulin: glucagon ratios
because of low blood insulin and are in a catabolic state.
Medicine Lecture 5th Stage 92-10-2017 Dr.Osamah Muwafk
Types of bovine ketosis:
Primary ketosis (production ketosis):
1- It is of most herds, the so called estate acetonemia.
2- It occurs in cows in good to excessive body condition that have high
lactation potential and are being fed good-quality rations but that are
in a negative energy balance.
3- There is a tendency for the disease to recur in individual animals.
4- A proportion of cases appear as clinical ketosis but a much greater
proportion occur as cases of subclinical ketosis in which there are
increased levels of circulating ketone bodies but no overt clinical
signs.
Secondary ketosis:
1- This occurs where other disease results in a decreased food intake.
The cause of the reduction in food intake is commonly the result of
abomasal displacement, traumatic reticulitis, metritis, mastitis, or
other diseases' common to the postparturient period.
Alimentary ketosis:
1- This form is due to excessive amounts of butyrate in silage and
possibly also due to decreased food intake resulting from poor
palatability of high butyrate Silage, This type of ketosis is commonly
subclinical but it may predispose to the development of production or
primary ketosis.
Starvation ketosis:
1- This occurs in cattle that are in poor body condition and that are fed
poor-quality feedstuffs. There is a deficiency of propionate and protein
from the diet and a limited capacity of gluconeogenesis from body
reserves. Affected cattle recover with correct feeding.
Medicine Lecture 5th Stage 92-10-2017 Dr.Osamah Muwafk
Ketosis due to specific nutritional deficiency:
1- Specific dietary deficiencies of cobalt and possibly phosphorus may
also lead to a high incidence of ketosis. This may be due in part to a
reduction in the intake of total digestible nutrients (TDN), but in
cobalt deficiency, the essential defect is a failure to metabolize
propionic acid into the tricarboxylic acid (TCA) cycle.
Epidemiology:
1- It is prevalent in most countries where intensive farming is practiced.
2- Occur in animals housed during the winter and spring months and is
rare in cows that calve on pasture.
3- The disease occurs in
4- It occurs most commonly during the first month of lactation, less
commonly in the second month, and only occasionally in late
pregnancy.
5- The disease occurrence increases from a low prevalence at the first
calving to a peak at the fourth.
6- There is a greater risk for the development of ketosis in cows that
have an extended long dry period, that develop milk fever, retained
placenta, lameness or hypomagnesemia.
7- Cows with twins are also at risk for ketosis in the terminal stages of
pregnancy.
Economic significance:
1- Clinical and subclinical ketosis are major causes of loss to the dairy
farmer.
2- Main economic loss is due to the loss of production while the disease
is present, the possible failure to return to full production after
recovery and the increased occurrence of periparturient disease.
3- decreased milk yields and lower milk protein and milk lactose.
4- increased risk for delayed estrus and lower first service conception
rates, increased inter-calving intervals.
5- increased risk of cystic ovarian disease, metritis and mastitis and
increased involuntary culling.
Medicine Lecture 5th Stage 92-10-2017 Dr.Osamah Muwafk
Pathogenesis:
1- The principal metabolic disturbances observed, hypoglycemia and
ketonemia.
2- Acetoacetic acid is known to be toxic and probably contributes to the
terminal coma in diabetes mellitus in man.
3- Production of isopropyl alcohol, a breakdown product of Acetoacetic
acid in the rumen are thought to be responsible to the nervous signs
which occur in some cases of bovine ketosis, although the requirement
of nervous tissue for glucose to maintain normal function may also be a
factor in these cases.
4- Changes in ruminal flora after a long period of anorexia may also cause
continued impairment of digestion.
5- Fatty degeneration of the liver in protracted cases may prolong the
recovery period.
Clinical Findings:
A- The wasting form
1- It is the most common.
2- It is manifest with a gradual but moderate decrease in appetite and
milk yield over 2-4 days.
3- cow first refuses to eat grain, then ensilage but may continue to eat
hay.
4- Body weight is lost rapidly.
5- 'woody' appearance due to the apparent wasting and loss of
cutaneous elasticity due ' presumably to disappearance of
subcutaneous fat.
6- The feces are firm and dry but serious constipation does not occur.
7- The cow is moderately depressed.
8- hangdog appearance and disinclination to move and to eat may
suggest the presence of mild abdominal pain.
9- The temperature and the pulse and respiratory rates are normal
10-
the ruminal movements may be decreased in amplitude and
number
Medicine Lecture 5th Stage 92-10-2017 Dr.Osamah Muwafk
11-
A characteristic odor of ketones is detectable on the breath and
often in the milk.
12-
Very few affected animals die, but without treatment the milk
yield falls.
13-
Spontaneous recovery usually occurs over about a month.
B- The nervous form:
1- Signs are usually bizarre and begin quite suddenly.
2- syndrome is suggestive of delirium rather than of frenzy.
3- Walking in circles.
4- Straddling or crossing of the legs.
5- Head pushing or leaning into the stanchion.
6- Apparent blindness.
7- Aimless movements and wandering.
8- Vigorous licking of the skin and inanimate objects.
9- Depraved appetite.
10- Chewing movements with salivation.
11- Hyperesthesia may be evident, the animal bellowing on being
pinched or stroked.
12- Moderate tremor and tetany may be present and there is usually an
incoordinate gait.
13- The nervous signs usually occur in short episodes which last for 1 or
2 h.
14- may recur at intervals of about 8-12 h.
15- Affected cows may injure themselves during the nervous episodes.
C- Sub clinical ketosis:
1- Many cows that are in negative energy balance in early pregnancy
will have ketonuria without showing clinical signs,
2- Diminished productivity including depression of milk yield and a
reduction in fertility.
3- Potential milk production is reduced by 1_9%.
4- Infertility as an ovarian abnormality.
5- Delayed onset of estrus, endometritis resulting in an increase in
calving to conception interval.
6- reduced conception rate at first insemination.
Medicine Lecture 5th Stage 92-10-2017 Dr.Osamah Muwafk
Clinical Pathology:
1- Hypoglycemia, ketonemia and ketonuria are characteristic of the
disease.
2- Blood glucose levels are reduced from the normal of approximately
50 mg/dL to 20-40 mg/dL.
3- Normal cows have plasma BHBA concentrations less than 1000
μmol/L, cows with subclinical ketosis have concentrations greater
than 1400 μmol/L, and cows with clinical ketosis have concentrations
often in excess of 2500 μmol/L.
4- Detection levels of ketone in Milk and urine (cowside tests).
5- Milk fat concentration tends to increase and milk protein
concentration tends to decrease during postpartum negative energy
balance .
Differential diagnosis:
A- Wasting form:
1- Abomasal displacement.
2- Traumatic reticulitis.
3- Primary indigestion.
4- Cystitis and pyelonephritis.
5- Diabetes mellitus.
B- Nervous form:
1- Rabies.
2- Hypomagnesemia.
3- Bovine spongiform encephalopathy.
Treatment:
1- Replacement therapy
a- Glucose (dextrose) The IV injection of 500 mL of a 50% solution
of glucose.
b- Propylene glycol and glycerin/glycerol 225 g twice daily for 2
days, followed by 110 g daily for 2 days to cattle.
2- Hormonal therapy:
a- Glucocorticoids:
Medicine Lecture 5th Stage 92-10-2017 Dr.Osamah Muwafk
Hyperglycemia occurs within 24 h of administration and appears to
result from a repartitioning of glucose in the body.
3- Insulin facilitates cellular uptake of glucose, suppresses fatty acid
metabolism and stimulates hepatic gluconeogenesis.
4- Vitamin B12 and cobalt are indicated in regions where cobalt
deficiency is a risk factor for ketosis.
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