ETIOPATHOGENESIS, THERAPY, PREVENTION AND CONTROL OF MILK FEVER IN DAIRY CATTLE

• Radhika Vaidya• M5444 • MVSc 1ST Year• Division of Veterinary

Medicine• IVRI

Introduction A disease of cattle, sheep, and goats

occurring around the time of parturition and caused by hypocalcemia and characterized by weakness, recumbency, and ultimately shock and death

“Fever” is a misnomer, as body temperature during the disease is usually below normal

Milk fever has been associated with 3 fold increase in risk of dystocia, uterine prolapse, retained fetal membranes, metritis, abomasal displacement and a nearly 9 fold increase in clinical ketosis and mastitis (Kelton et al., 1998)

3% cases

• occur few days before calving

6% cases

• occur just few hours before or at time of parturition

87% cases

• occur within 24 hours after calving

4% cases

• occur 48 hours after calving

Radositis et al., 2007

Predisposing factors

1. Breed Jersey and to lesser extent, Swedish Red

and White and Norwegian Red breeds have a higher incidence of milk fever as opposed to Holstein cows

Goff et al. (1995) have suggested that intestine of Jersey cows possesses 15% fewer receptors for 1,25 (OH)2D3 than intestine of Holstein cows

2. Age The risk of a cow developing milk fever

increases with age

It is rare for milk fever to occur at first calving and relatively uncommon at second

Incidence increases dramatically in third and greater lactations

Growing bones have large numbers of osteoclasts present, which can respond to parathyroid hormone more readily than the bones of mature cows

Osteoblasts are the only type of bone cell to express the 1,25- (OH)zD receptor protein and the decrease in the numbers of osteoblasts with increasing age could delay the ability of bone to contribute calcium to the plasma calcium pool

Horst et al. (1990) demonstrated that intestinal receptors for 1,25 (OH)2D3 decline as age advances

Johnson et al. (1995) showed that the C 24-hydroxylase, an enyme that inactivates 1,25 (OH)2D3, increases dramatically in the older cow

3. Nutrition In Vitamin D deficiency, reduction in

production of 1,25 (OH)2D3, resulting increase the risk for milk fever

Normal plasma 20 - 50ng/ml <5ng/ ml are indicating of Vitamin D

deficiency

Dietary phosphorus Prepartum diets high in phosphorus (>80

g P/d) also increases the incidence of milk fever and the severity of hypocalcemia

Increased serum P Inhibitory to renal

enzymes producing di hydroxy vit D

Reduced intestinal Ca absorption

Dietary cation anion balance Metabolic alkalosis predisposes cows to

milk fever and sub-clinical hypocalcaemia In-vitro studies suggest the conformation of

the PTH receptor is altered during metabolic alkalosis rendering tissues less sensitive to PTH

Metabolic alkalosis is largely the result of a diet that supplies more cations (K, Na, Ca, and Mg) than anions (chloride (Cl), sulfate (SO4), and phosphate (PO4) to the blood

Low blood magnesium can reduce PTH secretion from the parathyroid glands and also can alter responsiveness of tissues to PTH

High dietary potassium reduces ruminal magnesium absorption in addition to causing metabolic alkalosis

4. Parity

later parity cows produce more colostrum and milk making demand for Calcium greater

History of milk fever seems to be a large determinant of whether or not a cow develops hypocalcemia and milk fever at subsequent parturitions

Ruminal dysfunction, acidosis and diarrhoea decreases calcium absorption from intestine, whereas high content of oxalate, silicate and phytates in diet reduces bioavailability of calcium

Pathogenesis

On the day of parturition, dairy cows commonly produce ten liter or more colostrum containing 23 g or more of Calcium that is six times as much as extra cellular pool contains

Blood plasma 8.5-10.4 mg/dl Colostrum 2.3g Ca/ kg Milk 1.2g Ca/kg

A depression of the levels of ionized calcium in tissue fluids is the basic biochemical defect in milk fever

PTH

Increase renal reabsorption of Ca

Continued PTH secretion

Ca reabsortion from bone

Negative effect on the adaptation process to maintain calcium levels:

• PTH works poorly on kidney and bone when blood ph is high (forage high in K)

• Oestrogens also inhibit calcium mobilization (oestrogen levels rise at parturition)

Vitamin D

•passive diffusionVitamin D

independent absorption

•active transportVitamin D dependent absorption

The activity of renal enzyme responsible for converting 25- OH Vit D to the steroid hormone 1,25-dihydroxy Vit D (1,25 (OH)2D) is regulated by PTH

excessive loss

of Ca in

colostrum

s

impairment

of absorption of Ca from intest

ine

mobilization of Ca from

storage in

skeleton not

sufficiently

rapid

Milk feve

r

Milk fever and subclinical hypocalcemia cause secretion of cortisol which impairs the immune system of the fresh cow (Wang et al., 1991)

This provides a strong basis for the suggested association between milk fever and endometritis and mastitis

Milk fever cows also exhibit a greater decline in feed intake after calving than non-milk fever cows exacerbating the negative energy balance commonly observed in early lactation

In addition, hypocalcemia prevents secretion of insulin, preventing tissue uptake of glucose which would exacerbate lipid mobilization at calving, increasing the risk of ketosis

Stage I Stage II/ sternal recumbencyStage III/ lateral recumbency

Clinical findings

Diagnosis History of parturition High milk yield Typical clinical signs viz. sternal or lateral

recumbency with subnormal body temperature

Clinical response to calcium therapy is adequate for confirmation of diagnosis of milk fever

Serum calcium level

Normal dairy cattle 8 -10 mg/dl

At calving 8 mg/ dl Milk fever 6.5,

5.5 and 4.5 mg/dl

Treatment Treatment during first stage of the

disease, before cow is recumbent, is the ideal situation

Calcium borogluconate (25%) @ 400-800 ml or 1 gm/45 kg body weight IV is standard treatment

As calcium is cardiotoxic, the calcium containing solutions should be administered slowly (10-20min) while cardiac auscultation is performed

Atropine sulphate can be used to overcome cardiac arrhythmia

Magnesium sulphate 10% solution is administered @100-400ml IV to antagonize cardio-excitatory effects of calcium

Subcutaneous Calcium treatment

Absorption of calcium from subcutaneous administration requires adequate peripheral perfusion

Ineffective in cows that are severely hypocalcemic or dehydrated

irritating and can cause tissue necrosis administration should be limited to no

more than 75 ml of a 23% calcium gluconate solution (about 1.5g elemental calcium) per site

Response to Calcium  therapy

Belching Muscle tremor – flanks→ whole body Pulse rate   decreases and amplitude

improves Heart sound intensity is increased  Sweating of muzzle Defecation – firm stool with mucous

Relapse of Milk Fever About 25% cases of milk fever that

responded to initial IV calcium therapy show relapse within 12-48 hours

These cows may be treated with intramuscular injection of Vit D3 and intravenous infusion of preparations containing calcium, phosphorous and magnesium

Calcium levulinate therapy with IM route has superior bioavailability and is less irritant (Kulkarni et al., 2007) hence can be used for maintaining blood calcium level following IV calcium therapy

Oral Calcium supplementation

Calcium propionate in propylene glycol gel or powdered calcium propionate (0.5 kg dissolved in 8–16 L water administered as a drench) is effective

Also supplies the gluconeogenic precursor propionate

Prevention of Milk fever

Reduction in Ca content of diet

Low Ca diet < 20g/day last 2 wk before parturition

Use of dietary straw and calcium-binding agents such as zeolite, zinc oxide

Ca:P ratio 1.3:3

DCAD in mEq/kg DM = (Na +K) - (CI + S) +200 to +300 mEq/kg

This method is more effective and more practical than lowering prepartum calcium in diet

Feeding of anionic supplements primarily chloride and sulphates reduce incidence of milk fever by increasing calcium absorption

reducing the potassium content of diet Corn silage Alfafa hay

Oral Ca supplement At least two doses

one at calving and a second dose the next day

Vitamin D A single dose of Vit D3 @ 10 million unit

i.e. 1 million units/ 45 kg body weight IM one week before calving has been reported to be effective

Goff et al. (1992) have studied the effects of recombinant bovine interleukin- 1(IL-1) has been shown to be homologus to osteoclast-activating factor and is capable of stimulating increased osteoclastic bone resorption

Milk fever and subclinical hypocalcemia could be prevented with PTH infusions or injections or implants