Etiopathogenesis, therapy, prevention and control of milk fever in dairy cattle

1. ETIOPATHOGENESIS,
THERAPY, PREVENTION AND
CONTROL OF MILK FEVER IN
DAIRY CATTLE
• Radhika Vaidya
• M5444
• MVSc 1ST Year
• Division of Veterinary
Medicine
• IVRI

2. 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

3.  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)

4. 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

5. Predisposing factors

6. 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

7. 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

8.  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

9. 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

10. 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

11. 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

12.  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

13. 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

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

15. Pathogenesis

16.  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

18. 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)

19. Vitamin D
• passive diffusion
Vitamin D
independent
absorption
• active transport
Vitamin 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

20. excessive loss
of Ca in
colostrums
impairment of
absorption of Ca
from intestine
mobilization of
Ca from storage
in skeleton not
sufficiently rapid
Milk fever

21.  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

22.  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

23. Stage I
Stage II/ sternal
recumbency
Stage III/ lateral
recumbency
Clinical findings

25. 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

26. 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

27. 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

28.  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

29. 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

30. 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

31. 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

32.  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

33. 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

34. Prevention of Milk fever

35. 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

36. 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

37. Oral Ca supplement
 At least two doses
one at calving and a
second dose the next
day

38. 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

39.  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