Ketosis

 

SYNONYM 

ACETONEMIA

DEFINITION

Ketosis is a metabolic disease of high yielding animals, characterized by hypoglycemia, ketonemia & ketonuria

                                OR

Ketosis means accumulation of abnormal amount of ketone-bodies in the tissues & tissue fluids

ETIOLOGY

☆ DIETARY FACTORS:

a)   ➡️  Under nutrition/starvation or feeding of low carbohydrate diet

b)  ➡️   Feeding of excess amount of protein rich diet

c)   ➡️   Excess feeding of silage

d)  ➡️ Deficiency of cobalt & phosphorus

☆ ANIMAL FACTORS-

a)      ➡️ High milk yield

b)     ➡️ Loss of exercise

c)      ➡️ Hepatic insufficiency

☆ HORMONAL FACTORS-

a)      ➡️ Adreno-cortical insufficiency

b)     ➡️ Hypothyroidism

c)      ➡️ Insulin insufficiency

☆ ENVIRONMENTAL FACTORS- expose to cold climate

☆ DISEASES RESPONSIBLE FOR LOSS OF APPETITE-

a)     ➡️ Systemic disease- metritis, mastitis, pneumonia, TRP, abomasal displacement

b)     ➡️ Infectious disease- surra, theileriosis

Ketone formation:

Ketones arise from 2 major sources 1. butyrate in the rumen and 2.mobilization of fat

.

A high proportion of butyrate is produced by rumen fermentation and converted to BHB in the rumen epithelium and absorbed as such form.

Free fatty acids are produced by the mobilization of fat and transported to the liver and oxidized, which produce acetyl-CoA and NADH.

Acetyl-CoA is oxidized via the tricarboxylic acid (TCA) cycle and metabolized to acetoacetyl-CoA.

Complete oxidation of acetyl-CoA through the TCA cycle which depends on supply of oxaloacetate and from the precursor of propionate.

If propionate and oxaloacetate are deficient so oxidation of acetyl-CoA through TCA cycle is limited and acetyl-CoA is metabolized to acetoacetyl CoA and produce the acetoacetate and BHB.

Here acetoacetate and BHB both are utilize as an energy source and they are normally present in serum or plasma in bovine.

Acetoacetate is convert to acetone which is volatile and so it was exhaled in the breath.

Sometimes acetone cross ruminal epithelium and ruminal flora metabolize acetone and convert into isopropanol which absorbed in rumen and increase plasma concentration.


CLASSIFICATION

1. Primary ketosis/production ketosis/estate acetonemia

➡️ Is occurs in high yielding animals, having well to excellent body condition & fed good quality rations, but are in negative energy  balance

➡️ Heavy body condition & high dietary protein may lead to excessive mobilization of fat

2. Secondary ketosis

➡️ Caused by various systemic or infectious diseases, which results in decreased food intake

➡️ Commonly due to abomasal displacement, traumatic reticulitis, mastitis or other diseases common to the post-parturient period

➡️ In this type, animal takes inadequate feed due to loss of appetite even though sufficient feed is offered

3. Alimentary ketosis

➡️ This form due to excessive amount of butyrate in silage

➡️ Also due to decreased food intake resulting from poor palatability of high butyrate silage

➡️ Silage made from succulent material may be more highly ketogenic than other types of ensilage

4. Starvation

➡️ It occurs in cattle that are in poor body conditions & fed poor-quality feed stuffs

➡️ It is due to deficiency of propionate in the diet & a limited capacity of gluconeogenesis from body reserves

➡️ Ketosis due to specific nutritional deficiency-

Specific dietary deficiency of cobalt & also phosphorus may lead to high incidence of ketosis

EPIDEMIOLOGY

Species: cows & buffaloes are affected

Breeds: buffaloes and crossbred cows are more susceptible than indigenous cows

Sex: primary ketosis is actually a disease of females

Age: common in 6-9 year old animals

Number of lactation: disease incidence is higher during the 3rd to 5th  lactation

Physiological status: is a disease of  lactating cows & buffaloes

Stage of lactation: commonly occurs b/w 10 days to 2 months of calving

Milk yield: high yielding animals are susceptible than low yielding animals

Season: incidence is higher during calving season (winter, September-December)

Feeding system: more common in housed or stall fed animals

Predisposing factors: cold stress

Economic importance: loss of milk production (25-100%), about 30-40% cases are complicated b concurrent diseases like metritis, TRP, abomasal diseases, surra, theileria & sometimes death of animal

CLINICAL SIGNS

➡️ Ketosis can be grouped as clinical & sub-clinical ketosis, based on presence or absence of signs

Clinical ketosis: It mainly occurs in two forms

1. Digestive/wasting form

2. Nervous form

 1. Digestive/wasting form

➡️ Most common form ( about 90% cases )

➡️ Selective appetite: Refusal of concentrate first, then ensilage but may continue to eat hay

➡️ Marked drop in milk yield (25-100%)

➡️ Emaciation/woody appearance, due to rapid loss of body weight

➡️ Moderate depression, hanghog appearance & disinclination to move

➡️ Loss of skin elasticity, due to disappearance of sub-cut fat

➡️ Dull skin & rough body coat

➡️ Faeces- firm, dry & covered with mucus

➡️ Ruminal motility- reduced & weak

➡️ Sweetish smell to breath, milk & urine

➡️ Body temperature, pulse & respiration- normal

➡️ If not treated, animal may die

➡️ Can spontaneously recover within a month but milk yield not re-gained

2. Nervous form

➡️ Less common (about 10%)

➡️ Begins quiet suddenly

➡️ Walking in circles

➡️ Straddling or crossing of legs

➡️ Head pushing

➡️ Aimless wandering

➡️ Vigorous licking of skin & inanimate objects

➡️ Depraved appetite

➡️ Chewing movements with profuse salivation

➡️ Animal bellowing on pinching

➡️ Nervous signs like hyperaesthesia, tremor, convulsions may occurs  in short episodes which last for 1 or 2 hours at an interval of about 8-12 hours

SUB-CLINICAL/SPONTANEOUS KETOSIS

➡️ It occurs in high yielding cattle, due to excessive production of aceto-acetic acid in mammary glands

➡️ Many cows that are in negative energy balance in early pregnancy will have ketonuria without showing clinical signs, but have decreased milk yield & reduction in fertility

DIAGNOSIS

1. History

           ➡️ Recent calving

           ➡️ High milk yield ( 2-8 weeks post-partum)

           ➡️ Underfeeding of carbohydrates

           ➡️ Excess feeding of protein rich concentrates

           ➡️ Exposure to cold climate

2. CLINICAL PATHOLOGY

i. Biochemistry:

➡️ BLOOD GLUCOSE- Decreased to 20-40mg/dl (normal: 50-60-mg/dl)

➡️ BLOOD KETONES- increased to 20-100mg/dl (normal: <10mg/dl)

➡️ KETONE BODIES IN URINE- increased upto 80-130mg/dl (normal: little or <10mg/dl)

➡️ MILK KETONE LEVEL- increased upto 10-40mg/dl (normal: not excreted, but may be upto 3mg/dl)

ii. Haematology:

➡️ DLC- indicate neutopenia (10%), lymphocytosis (60-80%) & eosinophlia (15-40%)

iii. Milk examination:

➡️ Milk samples are positive for ketone bodies

iv. Urinanalysis:

➡️ Urine samples are positive for  ketone bodies

Rothera's  test

➡️ 5 ml of urine + Saturated ammonium sulfate + Add small crystal of sodium nitroprusside mixed well

➡️ Add amoonia slowly slowly at the one side of test tube.

Positive : Purpule ring at the junction of two fluid.

3. Clinical findings

➡️ Selective appetite 

➡️ Drop in milk production
➡️ Emaciation
➡️ Sweetish smell from breath

Differential diagnosis

Wasting form

✔️ Abomasal displacement

✔️ Traumatic reticulitis

✔️ Cystitis & pyelonephritis

✔️ Diabetes mellitus

Nervous form

✔️ Rabies

✔️ Hypomagnesemia

✔️ Bovine spongiform encephalopathy

TREATMENT

Principle of the treatment of ketosis-

➡️ To relieve the need for glucose formation, from tissues &  allow ketone body (KBs) utilization to continue normally

1. REPLACEMENT THERAPY-

Glucose (dextrose):

➡️ Glucose 20% @ 0.5g/kg IV ,for 2-3 days (relieve need for glucose & allow to utilize KBs)

                               or

➡️ Glucose 500gm orally as drench, following pre-medication with 30gm sodium bicarbonate solution orally

➡️ Advantages- Simple and safe treatment

➡️ Orally glucose reaches directly to abomasums due to closure of reticular groove

           slow & transient absorption of glucose

           stimulate insulin release through gut-acting hormones

Glucose precursors:

➡️ Sodium propionate @ 80g PO, for 3-6 days

                             or

➡️ Propylene glycol @ 225g PO, b.i.d. , for 2 days, followed by 110g daily for 2 days

                             or

➡️ Propylene glycol @ 200-700g daily, or salts of propionic acid, can be administered in feed

➡️ Advantages- absorbed directly from rumen

                          Avoid repeated injections

2. HORMONAL THERAPY-

i. Gluco-corticoids-

Dexamethasone @ 0.04mg/kg IV daily, for 2-3 days

Role of corticosteroids:

➡️ Decreases tissue uptake of glucose

➡️ Promotes gluconeogenesis

➡️ Reduce milk production for 3 days

ii. Role of insulin:

➡️ Suppresses mobilization of fat

➡️ promote glucose uptake by tissues

➡️ stimulate hepatic gluconeogenesis

iii. Anabolic steroids:

➡️ Durabolin/trenbolone acetate @ 60-120 mg single dose

role of anabolic steroids;

➡️ stimulate appetite

➡️ Decrease ketone body & FFA concentration

➡️ Increases concentration of citrate in liver which helps in uptake of acetyl CoA

3. MISCELLANEOUS THERAPY-

➡️ Niacin @ 8gm orally daily, for 5-6 days (niacin is antilipolytic)

➡️  Cobalt sulphate @ 100mg/kg or Vit. B12  @ 1-2mg/kg IM/IV (Vit. B12 converts propionate to glucose

4. SUPPORTIVE THERAPY-

➡️ Injection Liver extract with B-complex @ 5-10 ml IM, on alternate days

➡️ Add mineral mixture comprising phosphorus and cobalt

CONTROL

➡️ Avoid either starvation or overfeeding at calving, so animal should neither thin nor over fat

➡️ Provide balanced ration to dairy animals as per feeding standards

Give extra allowance of concentrate ration (protein 16%) @ 1.5kg/day during advance pregnancy

After calving give concentrate ration (1kg concentrate for every 2.5-3 kg of milk produce)

➡️ Provide ration which increases propionate production & decreases acetate production, eg. Finely ground roughage, cooked grain

➡️ Provide ration containing adequate amount of phosphorus, cobalt & iodine

➡️ Avoid sudden changes in type of feed so as to prevent indigestion

➡️ Give adequate exercise to lactating animals, t promote utilization of ketone bodies

➡️ Protect lactating animals from cold stress

➡️ Select cows/buffaloes having good feed capacity & appetite

➡️ Give glucose precursors (propylene glycol) @ 200-400 ml daily, from 5 days before to 10 days after calving

  





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