Post on 15-Jan-2017
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