2. Definition
• It is a metabolic disease
occurring most commonly in
adult cows, within 12-72
hours of parturition.
•It is characterized by
hypocalcemia, general
muscular weakness, paresis,
circulatory collapse,
depression of consciousness
and recumbence.
3. Normal Blood Calcium Concentration= 9-10
mg/100ml
Extracellular Ca Pool ~11 g
Serum Ca pool ~ 3.5 g
4. Extracellular Ca Pool ~11 g
Serum Ca pool ~ 3.5 g
Urine Ca
0.2 - 6 g *
Endogenous
Fecal Loss
5-8 g Ca
5. Extracellular Ca Pool ~11 g
Serum Ca pool ~ 3.5 g
Urine Ca
0.2 - 6 g *
Lactation- 20-30 g Ca
Colostrum –2.3 g Ca/ L
Milk – 1.1 g Ca / L
Endogenous
Fecal Loss
5-8 g Ca
6. Extracellular Ca Pool ~11 g
Serum Ca pool ~ 3.5 g
Bone
~ 8 Kg Ca
Bone
Fluid
~ 9 -
15 g
Ca *
Osteoclast
recruitment &
activation
Urine Ca
0.2 - 6 g *
Lactation- 20-30 g Ca
Colostrum –2.3 g Ca/ L
Milk – 1.1 g Ca / L
PTH
Endogenous
Fecal Loss
5-8 g Ca
7. Parathyroid Hormone
Extracellular Ca Pool ~11 g
Serum Ca pool ~ 3.5 g
Bone
~ 8 Kg Ca
Bone
Fluid
~ 9 -
15 g
Ca *
Osteoclast
recruitment &
activation
Urine Ca
0.2 - 6 g *
Lactation- 20-30 g Ca
Colostrum –2.3 g Ca/ L
Milk – 1.1 g Ca / L
PTH
Endogenous
Fecal Loss
5-8 g Ca
10. Parathyroid Hormone
Extracellular Ca Pool ~11 g
Serum Ca pool ~ 3.5 g
Bone
~ 8 Kg Ca
Bone
Fluid
~ 9 -
15 g
Ca *
Osteoclast
recruitment &
activation
Urine Ca
0.2 - 6 g *
Diet Ca = 45- 150 g**
Passive Ca
Transport
Lactation- 20-30 g Ca
Colostrum –2.3 g Ca/ L
Milk – 1.1 g Ca / L
PTH
Endogenous
Fecal Loss
5-8 g Ca
11.
12. Calcium level
Normal level: 9-10 mg %
Milk fever: 2-6 mg %
Alteration in calcium homeostasis by :
• Excessive loss of calcium in the colostrums
• impairment of absorption of calcium :
• deficiency of Vitamin D.1,25 dihydroxycholecaciferol is the
activated from of Vitamin D3.
• acts on the gut cells and helps in the absorption of ca++ from the
intestine and resorption of ca++ from bone
• less acidic pH in gut.
EtioPathogenesis
13. •Failure to mobilize skeletal calcium
•Parathormone (P.T.H) insufficiency.
•Excessive calcitonin level
•Effect of estrogen
•“Milk fever syndrome”: milk fever is associated
with:
hypocalcaemia
hypophosphtaemia
and hypomagnesaemia
14. Other risk factors
Day period nutrition: Nutrition during dry period plays an important role in
causing milk fever such as:
1) Increase Ca feeding during the dry period increase
the incidence of milk fever so feeding pre-partum
diets containing a low concentration of calcium
prevent milk fever by activating PTH increasing Ca
transport ’ mechanisms in the intestine and bone
prior to parturition and adapt the animal before
lactation to drain of Ca.
15. 2) Pre-partum diet high in phosphorus also increases the incidence of milk fever.
3) Dietary anion cation balance (DACB): Diets high in cation (like Na, K) associated
with increased incidence of the disease.
4) Acidosis and diarrhea reduce calcium absorption.
(2) Increase the age of cow (more commons at 5-10 years old).
(3) High producing dairy cattle (more common at the third to seventh parities and
lactating period but does not occur in heifers).
(4) Winter season when animal are fed on poor quality roughage or fed on diets high
in cation (Na+, K+) as barseem than anion (C1‘ and S’ ).
16. Other theories
(1) Parathyroid dysfunction.
(2) Anaerobic microorganism in the udder.
(3) General anemia.
(4) De-arrangement of the adrenal gland.
17.
18. Pathophysiology
1. Hypocalcemia may be termed as deficiency disease.
2. If the deficiency of calcium in feed is not main causes of
the disease and there are other causal factors, the disease is
termed as metabolic disease.
3. Normally there is Ca pool in blood, which is maintained
with PTH by absorption of Ca from the small intestine
resorption of Ca from bone then mineralized in bone or
excreted in gut, urine and milk so that excessive drainage of
Ca in milk just after parturition causes hypocalcemia.
19. 4. The normal ratio of Ca:ph level in the blood is
2.3:1.If this ratio is upset, hypo or
hypercalcemia may take place.
5. When milk fever is associated with hypocalcemia,
hypophosphatemia and hypomagnesemia, it is known
as milk fever syndrome or milk fever complex that
treated by Ca, Mg and ph therapy.
20. • 6. Ca is very important to maintain the tonicity and excitability of
muscle and helps in the transmission of nerve impulse.
A. Ca increases the muscle tone while Mg decreases the muscle
tone. They are antagonistic to each other.
Ca helps to maintain neuromuscular tone.
The release of unbound Ca ion into
the sarcolemma of the muscle fiber
triggers the contractile protein action
of myosin, which produce the
contraction of the myofibers.
21. The normal ratio of Ca to Mg in blood is
6:1.
In hypermagnesemia the ratio decreased
from 6:1 to 2:1 stimulating the release of
acetylcholine so that the patient becomes
paretic and necrosis supervenes.
B. Hypocalcemia inhibits the release of
insulin but the hyperglycemia is not common
in milk fever.
22. 7. The onset of lactation at the time of parturition results in
a sudden loss of Ca in colostrum.
Colostrum has more Ca than milk (8 times) and blood (12-13
times).
Also, milk fever is associated with higher milk production
due to reduction of intestinal vitamin D3 receptors and a
higher than normal production of parathyroid hormone
related protein by the mammary gland which increases Ca
transport from blood to milk.
8. During the dry period calcium demand is low, therefore
intestinal absorption and bone resorption of calcium is
relativity inactivate.
23. 9. Some degree of hypocalcemia occurs in all cows at the
onset of lactation, and this stimulates calcium absorption
from the intestine and increase bone resorption.
10. Stimulation of 1, 25 dihydroxy-vitamin D (1, 25 {OH2} D)
need 24 hours for stimulation and parathyroid hormone (PTH)
need 48 hours for stimulation. If these adaptions to increase
calcium demand are prolonged, clinical
hypocalcemia may develop.
24. •Pathogenesis
(1) Milk fever is a hypocalcemic mineral deficiency.
When cow grows older it assimilate less calcium from feeds.
Cow secretes about 12 times of blood calcium through
colostrum.
All the calcium salts in milk have to come from the blood
stream.
As such, blood calcium must be replaced about 12 times a day
so if there is any wrong with the mechanism of maintaining
calcium homeostasis, the symptoms of hypocalcemia will start
appearing.
25. (2) Hypocalcemia affects muscular contraction in several different
ways:
A. Calcium has a member stabilizing effect on peripheral nerves,
hyperesthesia and mild tetany seen in early stages of
parturient paresis due to a lack of nerve cell membrane
stabilization.
B. Ca is required for release of acetylcoline at the neuromuscular
junction. Inability to release acetylcholine, caused by
hypocalcemia, causes paralysis by blocking the transmission of
nerve impulse fibers.
C. Calcium is also directly required by muscle cells for contraction
to occur by hindering calcium dependent action.
D. Lack of smooth muscle tone results in gastrointestinal stasis
and ruminal stasis. Decrease contractility of cardiac muscle and
lowered stroke volume.
E. Death occurs due to respiratory failure.
26. Epidemiology
• Cattle
• In high producing adult lactating dairy cattle
• 5-10 year age group.
• Jerseys are most susceptible
• Stress :distant transport , forced exercised, etc predisposes the condition
• Drugs
• estrus
• Sheep and goats
• 6 weeks before to 10 weeks after lambing.
27. Clinical signs and symptoms
• Cattle
• Stage I
• Stage II/ sternal recumbency
• Stage III/ lateral recumbency
• Sheep and goats
• loss of anal reflex, constipation,
tachycardia
• hyposensitivity, ruminal stasis and
tympany,
• salivation and tachypnea.
28. Forms of milk fever
Typical milk
fever
usually within a few
days after parturition
respond well to
treatment.
Refractory or
atypical milk
fever
remain alert, eat,
and Milk but cannot
regain her feet.
become a creeping
downer cow with
flexed pasterns and
posterior paralysis.
Rupture of the large
muscle or group of
muscles in one or
both hind legs.
Tremors or sub-
acute
Cows are easily
excited with muscle
twitching and
tremors occurring.
29. Diagnosis
Clinical signs and symptoms
Hypocalcemia and response to treatment with calcium borogluconate.
by biochemical examination of blood.
Total serum calcium levels
• reduced to below 8 mg/dL usually to below 5 mg
ionized calcium level in blood of cows
• Normal levels of 4.3-5.1 mg/dL serum
• light hypocalcemia 4.2-3.2 mg/dL
• moderate 3.2-2.0 mg/dL
• severe hypocalcemia <2.0 mg/dL
30. Diagnosis
Hypophosphatemia
• Normal level: 4-6 mg/dl
• Serum inorganic phosphorous Level decreased to 1.5-3 mg/dl
Variable serum magnesium level
• Normal level: 2-3 mg/dl
• Only in some complicated cases level moderately increased above 3mg/dl
increases in the serum muscle enzymes
• creatine phosphokinase(CPK) and
• aspartate aminotransferase (ASl) or SGOT.
Hemogram
• eosinopenia, a neutrophilia, lymphopenia.
32. Line of Treatment:
General management and clinical procedure
•Treatment
•first stage of the disease, before the cow is
recumbent, is the ideal situation.
•Cows found in lateral recumbency (third stage) should
be placed in sternal recumbency which reduce the
chances of aspiration if the cow regurgitate.
•Avoidance of this complication necessitates the
placement of rubber or other mats under the cow
33. Treatment
Replacement Therapy
• Calcium borogluconate:
• milk fever can be treated successfully with 8-10 g of calcium
(calcium borogluconate is 8.3% calcium) in cow.
• solutions available vary from 18 to 40% calcium borogluconate.
• 800-1000 mL of a 25% solution: an initial dose a large cow (540-590 kg)
• 400-500 mL: small cow (320-360 kg)
• standard rate of administration :
• rapid intravenous administration of the calculated dose of calcium
borogluconate (often supplemented with phosphorus, magnesium,
and glucose) over a period of 15 min.
34. Treatment
Dietary anion –cation balance diet
• Recent concept of treatment and prevention of disease.
• Results are more reassuring and currently appears to be the best way to prevent.
• increased incidence of milk fever with
• Prepartum diets high in cations such as sodium and potassium
• Most forage such as legumes and grasses are high in potassium and are alkaline.
Metabolic alkalosis predisposes cows to milk fever.
• incidence of the disease decrease with
• diets high in anions, especially chloride and sulfur.
• The addition of anions to the diet of dairy cows prior to parturition effectively
reduced the incidence of milk fever by inducing a metabolic acidosis which facilitates
bone resorption of calcium.(Radostits et al.,2000)
• The DCAD is expressed using the equation. (Radostits et al., 2000)
DCAD in mEq/kg DM = (Na +K) - (CI + S)
35. Treatment
Dietary anion –cation balance diet
• Rations having negative DCAD (i.e. anions >cations) compel the body to produce positively charged
ions (H+) to neutralize the effects of Cl, SO4
- etc.
• Thus an acidosis ensues and general compensatory mechanisms are triggered on to annul alteration
in blood pH.
• Bone tissue serves as an important reserve of carbonate (CO3
-) which buffers and corrects acidosis.
• In the process, bone Ca is mobilized and active absorption of Ca from the gut is enhanced. This goes
on as long as the animal is on the anionic diets.
Major
effect
• Thus a higher blood Ca level is maintained which is immensely helpful to the cow in the
periparturient period in meeting a sudden increase in demand for Ca.
• Directly acidifying diet enhances the passive absorption of the Ca from intestine but negative DCAD
diet increases the active absorption of Ca through 1,25-(OH)2vitD3 .
Advange
36. Preventive measures
• Limiting Ca intake
• less than 80-100g/day;
• Limiting P consumption
• less than 45g/day;
• Holding Ca:P ratio
• less than 2:1 without exceeding P limits.
• These methods directly stimulate the intestinal Ca absorption or mobilize bone Ca prior to
parturition or do both to avoid hypocalcemia when intestinal Ca demand is suddenly
increased after the calving.
• More recently Goff et al., (1992), have studied the effects of recombinant bovine
interleukin- 1(IL-1) has been shown to be homologues to osteoclast-activating factor
and is capable of stimulating increased osteoclastic bone resorption.
• Administration of Vit D3
• Besides dietary and hormonal treatments, good housing is also very important for the
prevention.
37. Summary
• The basis principal to prevent milk fever is to maintain a high plasma Ca level at the time of
parturition to overcome the sudden high demand for Ca.
• hormonal therapy and dietary manipulations are successful in this regard.
• The dietary manipulation may be the best and easiest way to prevent milk fever in field
condition.
• The supplementation of anionic diet salts brings about a mild acidosis thus increasing the
rapid absorption of Ca through intestine and bone resorption.
• Thus the extracellular level of Ca increases which helps in coping with the demand of Ca
particularly in the early lactation.
• Among the anionic salts, MgSo4 (magnesium sulfate) may be used commonly.
• A useful tool is to measure the urine pH i.e. pH 5.5-6.5 to monitor anion cation balance in
diet.