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Grace Schulz 4748148

Periparturient
Hypocalcaemia in
Dairy Cows

Figure 1: The most popular dairy breed in the world, the Holstein breed1

Name: Grace Schulz


Student number: 4748148
Word count: 2,415
Statement of originality: I declare that the following assignment is my own work and all
material previously published or written by another person and used in this assignment has
been appropriately acknowledged and referenced. Additionally, this assignment has not
been previously submitted for any other courses at the University of Queensland or at any
other higher education institution.

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Grace Schulz 4748148

Part A
Introduction
Periparturient hypocalcaemia (hypocalcaemia) also known as periparturient paresis or milk
fever, is a common metabolic disorder which occurs due to calcium deficiency in high
producing adult dairy cows.2 Normally, dairy cows have calcium levels ranging between 8.5-
10 mg/dL, however in their early lactations post-calving they use between 20 and 30g of
calcium in the production of colostrum and milk.2,3 This sudden surge in the need for
calcium is usually balanced through an increase in the absorption of calcium from bone
reserves and the rumen or intestines.4 However, these stores are limited and therefore once
the blood calcium levels are under a certain threshold the parathyroid glands release
parathyroid hormones (PTH).4 This hormone causes more mobilisation of calcium from the
cows’ bones and allows for calcium homeostasis to be regulated.4 Hypocalcaemia usually
occurs as a result of either, a limited response to the PTHs or a deficiency of the PTH’s. 4

There are two forms of hypocalcaemia: clinical and subclinical. Subclinical hypocalcaemia
occurs when the cows blood calcium level is between 8-5.5mg/dL and the cow does not
display any symptoms of the disease.5,6 This occurs in around 47% of dairy cows undergoing
their second or higher lactation experience subclinical hypocalcaemia and in around 25%
first-calf heifers.7,8 Clinical hypocalcaemia, on the other hand, refers to cases where the
cow’s calcium levels have dropped below 5mg/dL and physical signs of the disease are
exhibited, this occurs in around 5% of dairy cows yearly.7,9

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Signalment
Around 52% of dairy cows are affected by hypocalcaemia yearly.5,7 However, it mainly
effects high producing dairy cows with 75% of cases occurring within the first 24 hours after
calving and a further 12% occur between 24 and 48 hours after.5

Jersey cows are the most susceptible breed and are 2.25 times more likely to develop
hypocalcaemia than Holstein cows.9 This is due to the Jersey’s colostrum having a higher
amount of calcium, them producing more milk per kilogram of bodyweight and having less
vitamin D receptors than less prone breeds such as Holstein.5 Additionally, age plays a large
role in the prevalence of hypocalcaemia in dairy cows as the risk of developing it increases
by around 9% each lactation cycle.4 This is due to older cows being unable to mobilise
calcium from their bones easier than younger cows.4

A study published by the Australian Journal of Experimental Agriculture also found that the
Body Condition Score (BCS) of a cow could predispose it to hypocalcaemia.10 If the cow has a
BCS of under 4.2 (on an 8-point scale) they were more likely to have subclinical
hypocalcaemia whereas if they had a score over 5.8 clinical hypocalcaemia was more
common.10

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Historical findings (Observational habits and things like that)


In clinical hypocalcaemia the afflicted cow will show physical symptoms of the disease since,
to become clinical, the cows calcium levels have become so low (>1.4mmol/L or >5.5mg/dL)
that it physically effects them.7,10 This makes it easier for the animal’s owner or career to
recognise that something is wrong with their animal and report the symptoms they observe
to a veterinarian. Clinical hypocalcaemia occurs in three stages, all of which are defined by
different symptoms and increase with severity from 1-3.5

The first stage of clinical hypocalcaemia is characterised by symptoms such as excitability,


weight shifting and more, as listed in Table 1, which make the cow seem restless.5 Cows
remain in this phase for less than an hour and are ambulatory.3 Together, these fleeting and
subtle symptoms result in stage one of clinical hypocalcaemia usually going by unnoticed by
owners and careers.3,5

Stage two is distinguished by sternal recumbency since the cow can no longer support its
weight and thus, becomes a ‘downer cow’- a cow that cannot stand up.5 Other symptoms
which occur in this stage are shown in Table 1.5 Furthermore, stage two takes place over a
longer period of time than stage one, between one and 12 hours, and includes more
obvious symptoms which increases the chance of the owner seeking veterinary attention for
their animal.5

In the final stage of clinical hypocalcaemia the symptoms from stage two become more
severe and the cow begins to lose consciousness, as indicated in Table 1.5 The most
prominent distinction between these two stages is the type of recumbency which the cow
enters. In this final phase the cow becomes laterally recumbent as a result of its calcium
deficiency (0.25-0.85 mmol/L) which means that it is no longer able to hold itself in the
sternal position.5 Without treatment cows who have progressed to this stage of clinical
hypocalcaemia are unable to survive longer than a few hours.5

A recumbent cow is very concerning to veterinary professionals and those in the cattle
industry since, if it occurs over a prolonged time, it can cause lasting muscle and nerve
damage and result in the cow becoming crippled or permanently downed.3 Therefore,

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recumbency would likely be the first thing reported to the veterinarian since it is a very
obvious symptom which expresses the urgency of the situation.

Table 1: Clinical findings, amount of time spent in stages and positioning of the cow in each
of the three stages of clinical hypocalcaemia5
Clinical findings Amount of time in Position of cow
(Symptoms) stage
Stage l Excitability, <1 hour Standing
nervousness,
hypersensitivity,
weakness, anorexia,
weight shifting and the
shuffling of hind feet
Stage ll Flaccid paralysis 1 to 12 hours Sternal recumbency
(results in sternal (‘Downer cow’)
recumbency),
depression, head
turned or extended ‘S’
curve to neck, fine
muscle tremors, cold
extremities, mild bloat
and constipation
Stage lll Stage two symptoms No more than 2-3 Lateral recumbency
become more hours without
pronounced, loss of treatment
consciousness to point
of coma and severe
bloating

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Physical examination findings


Clinical cases of hypocalcaemia presented different vital signs and physical findings
depending on which of the three stages they were in. Table 2 compares the anomalies and
physical examination findings found in each of the stages to ‘normal’ findings for cows. It
shows the stage one has the least anomalies with only a slight increase in temperature
(>39.5℃) and a mildly accelerated heartbeat usually being found.5

Cows in stage two of clinical hypocalcaemia usually display the most anomalies in their vital
signs with the animal’s heartbeat becoming harder to find but reaching above 100bpm
instead of the normal range of 48-84bpm.5 In addition, they are usually hypothermic and
can have any of the other possible findings listed in Table 2. In the last phase of clinical
hypocalcaemia, the cows heartbeat commonly exceeds 120bpm as they experience severe
tachycardia which makes it near impossible to hear their heart beat.5

In cows with subclinical hypocalcaemia there would be no anomalies in their physical


examinations since, as mentioned previously, they do not present physical signs of the
disease.

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Table 2: Total blood calcium and physical examination findings during the three stages of
clinical hypocalcaemia2,3,5,7,11
Total blood Calcium Physical examination findings and anomalies
(""#$/&)
Normal >2.1 (>8.5mg/dL) Heartbeat: 48-84bpm
Temperature: 38.5℃ (<37.8℃ or >39.5℃ indicates
hypothermia or hyperthermia)
Subclinical 1.4-2.0 (5.5-8mg/dL) Same as normal
Hypocalcaemia
Stage I <1.40 (<5.5mg/dL) Mild tachycardia,
Slight hyperthermia,
Bellowing
Stage II 0.85-1.40 Tachycardia - Heartbeat above 100bpm,
Hypothermia (35.6-37.8),
Loss of anal reflex,
Gastrointestinal atony (stomach cannot contract
properly)- leads to anorexia,
Dilated pupils,
Light unresponsive pupils,
Dry muzzle
Stage III 0.25-0.85 Severe tachycardia (Almost inaudible heartbeat),
Heartbeat above 120bmp

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Diagnostic tests and procedures


To confirm the diagnosis of hypocalcaemia in dairy cows, blood samples are taken and
analysed to determine whether the calcium levels of the cow are below 8mg/dL or 2mmol/L
which would indicate at least subclinical hypocalcaemia (Table 2). Currently there are two
blood tests options; the first tests for blood calcium level and the other tests for blood
ionized calcium.2

Option one more commonly used since it is cheaper, more accessible and overall simpler.
However, it is less accurate than option two since it tests for overall the blood calcium level
which includes calcium which is attached to proteins or protein complexes.5 This calcium is
considered ‘inactive’ because it cannot be used for neuromuscular function.5,7

Option two assesses the blood ionized calcium concentration and only tests for the amount
of metabolically ‘active’ calcium.7 This excludes the ‘inactive’ calcium mentioned above and
therefore gives a more accurate and reliable result.5 However, this option has more complex
steps such as the; ‘anaerobic collection of whole blood samples in heparinised syringes,
refrigeration of samples and rapid analysis after sample collection’.5

Nonetheless, the blood ionized calcium concentration is typically similar to the total blood
calcium level when the metabolism of protein and the balance of the acid-base remain
undisturbed, which usually occurs when an animal is hypocalcaemic.5,7 Therefore, either
method can be used to diagnose hypocalcaemia reliably.

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Treatment
The treatment of hypocalcaemia is dependent on the severity of the cow’s calcium
deficiency as shown in Table 2.

Therefore, in stage one it is suggested that the cow receives calcium either orally or
subcutaneously in a way that it can be gradually absorbed over an extended period of time,
usually several hours.3,5 Subcutaneous injections should be restricted to 1-1.5g calcium per
injection site and occur around the neck or shoulder area. However, the absorption of
calcium may be compromised if the animal is dehydrated due to the restricted blood flow.2,5
Oral dosing is usually given as calcium chloride which causes some of the calcium to be
passively absorbed through the intestine and gut. Calcium chloride can also generate
uncompensated metabolic acidosis which improves the calcium homeostatic mechanisms of
the cow.5 Oral treatments are difficult to administer since the veterinarian needs to be
careful to avoid damaging the pharyngal region or the cow inhaling the fluid and entering its
airway.2 Both these methods require little patient care as the career only needs to check-up
on the patient to ensure that the disease is not progressing further after the treatment is
applied. Further the only consideration after treatment is that the recovering cow should be
only partially milked after the treatment.3

Stage two and three requires immediate treatment with calcium salts (generally calcium
borogluconate) via an Intravenous solution (IV) or subcutaneous injections to prevent
prolonged recumbency.2 An IV is the most rapid way increase the calcium levels in a cow
with hypocalcaemia and should be administered at a rate of 1g/min.2 This treatment
method causes an immediate improvement in the cardiac functions and within two hours
neuromuscular functions return to 75% of cows and they are able to stand up.2,3 However,
IV’s can cause the blood calcium levels to exceed the upper threshold amount which results
in calcitonin being released to prevent hypercalcemia from occurring.5 This leads to
between 25- 40% of cases relapsing within 12-48 hours following the treatment. Yet, the
addition of calcium gluconate subcutaneously at the time of the IV treatment allows for the
slower release of calcium over time which could reduce relapses to between 5-10%.5 There
is more patient care needed for the cows treated with an IV since a large proportion of them

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tend to relapse and may need further treatment.2 Therefore, it would be logical to keep the
afflicted cow or cows separate from their herd in order to keep a closer eye on their health.

It is important for all treatments that the calcium is gradually absorbed into the blood
stream as hypocalcaemic cows having a greater risk of cardio arrest and hypocalcaemic
relapse while being infused with calcium.2,5 Similarly, no solutions containing glucose
should be injected subcutaneously as they can cause abscesses to form, sloughing at the
injection site and tissue necrosis in the cow.5

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Prognosis
Subclinical hypocalcaemia occurs prior to clinical hypocalcaemia when the blood calcium
levels are between 8mg/dL and 5.5mg/dL as displayed in Table 2.5 It has no clinical
symptoms but affects almost 50% of dairy cows post-calving. While subclinical
hypocalcaemia does not result in death, unless it becomes clinical, it is viewed as a ‘gateway
disease’.5,11 This is because it can lead to the cow being more susceptible to metabolic
disorders and other health problems, a few of which are listed below: 2,4,12
• Reduced milk productivity and quality
• Reduced fertility
• Increased risk of abosmasal displacement
• Reduced feed intake resulting in weight loss
• Increased risk of mastitis
• Impaired immune cell response
• Increased risk of ketosis (causes weight loss)
• Increased risk of uterine prolapse

Clinical hypocalcaemia on the other hand, occurs in around 5% of cows per year post-calving
and in 8% of these cases results in death and a further 12% were prematurely culled as a
result of their diagnosis.5 Similarly to subclinical hypocalcaemia, the clinical form also
increases the cows risk of developing secondary diseases like those listed above.5

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Grace Schulz 4748148

Prevention
There are many methods used by farmer to help prevent hypocalcaemia from occurring
post-calving, two of the most common methods are explained below.

One of these techniques is feeding the cows a calcium deficient diet pre-calving in order to
trigger the PTH earlier as the blood calcium concentration will decrease slightly.5 This will
cause the cows to draw calcium from its bones through osteoclastic bone reabsorption
which means that calcium homeostasis is already active by the post-birth stage.2 This low
calcium diet must contain considerably less calcium than what the National Research
Council (NRC) suggest in order to stimulate the PTH (around 0.15% of what is usually given).4
It is important however, that the cow is put on a high calcium diet after calving.4

Another process is through the acidification of the diet since a proper acid-base balance in
their diet is important to decrease the risk of hypocalcaemia. If the cow is fed a diet with
more cation than anions, the electrical charge of the blood can be too positive.4 This can be
evened out by adding more anions to increase the number of '! ions which lowers the pH
of the cows blood.5 Figure 3 shows the concentration of the suggested ions which should be
included in the dairy cow’s diet in order to best prevent hypocalcaemia from occurring.2
Additionally, urine tests are cheap and easy ways for farmers to test whether the
concentrations of these ions are working to reduce the pH of the cow or if they need to be
changed slightly from the generalised concentrations (Table 3).4

Table 3: Ideal concentrations of ions in diet to reduce prevalence of hypocalcaemia4


Type of ion Concentration
Sodium (()! ) 1.2g/kg
Calcium (*)"! ) 8.5-10g/kg
Magnesium (+,"! ) 3.5-4.0g/kg
Phosphorous (-#$ ) 4g/kg
Sulphur (. "$ ) <4g/kg
Potassium (/ ! ) 10g/kg
Chlorine (*$ $ ) 5g/kg

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Grace Schulz 4748148

Part B
Part 1
Table 4: Critical appraisal of two research studies done on hypocalcaemia in dairy cows 8,11
Author(s) Study design Patient or Intervention Comparison (if Outcome Conclusion(s) by Rate the strength of evidence and
& Population (or Exposure) applicable) variable(s) authors explain the rating
publicatio
n date
P.L. Cross-sectional 1388 cows, 12 from 43.5% of farms 50 out of the 115 The prevalence of Cows who had given birth Average- data collected by veterinarian,
Venjakob study each of the 115 had a control farms had a control hypocalcaemia and more than once were far samples were randomised if >12 were
(2016) commercial German strategy strategy- 40 used oral whether the different more likely to experience provided, detailed overview procedure and
dairy farms in 8 calcium products and preventative hypocalcaemia than cows methods used, selection of herds may have
different states, 112 10 used anionic salts strategies help reduce which had only given birth been biased – herd enrolment may have
had dominantly in the close-up diet it in commercial once, there was a negative been due to their history with the disease,
Holstein Friesians, German dairy herds association between small sample size from each herd, common
one had mainly Jersey calcium and magnesium herd dynamics and proportions were not
and two kept represented in the study, finding would be
Simmental cattle, applicable to commercial dairy operations
sampled cows had but not to smaller herds
calved within 48
hours
N. Martinez Clinical trials Ten nonpregnant, Half the cows Normocalcemic cows Physiological The solution used to induce Moderately strong- small study size,
et al. (2014) (Randomized nonlactating Holstein were received continuous responses and hypocalcaemia was randomized allocation of groups,
controlled cows average age of normocalemia IV with NaCl (0.9%) function of immune successful, subclinical standardized conditions, no conflict of
trials) 4.4 years old and 2.4 (control) and half while subclinical cells in dairy cows hypocalcaemia has interest mentioned
lactations were induced induced cows with induced negative effects on the
with subclinical received a continuous subclinical energy metabolism, dry
hypocalcaemia IV of complex salt hypocalcaemia matter intake and function
solution of innate immune cells and
increases the cow’s
vulnerability to peripartum
diseases

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Part 2
The majority (75%) of the references used in this literature review were peer reviewed
articles all of which had been published within the last 16 years. Additionally, seven of the
sources were research studies, three of which were cross-sectional studies (~43%), two
were surveys (~29%) and two were randomized clinical trials (~29%). The variety in the
types of studies available on hypocalcaemia in dairy cows allowed for a large range of expert
literature to be used in this review, thus ensuring that it is as accurate and informative as
possible. It was suggested in a few of the studies used that there could be bias in the results
since with the cross-sectional studies the farms chose whether they would like to take part
in it or not. This meant that there was a chance that farmers who had previous problems
with hypocalcaemia were more likely to agree to take part, thus creating bias. However,
despite this all of the studies used in this review corroborated each other’s results and
findings which suggests that the range of references used were strong.

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Reference List
1. Gray E. Holstein Cattle Breed https://petkeen.com/holstein-cattle-breed/. 2022.
2022.

2. Goff JP. The monitoring, prevention, and treatment of milk fever and subclinical
hypocalcemia in dairy cows. The Veterinary Journal 2008;176:50-57.

3. Allen AJ. Parturient Paresis in Cows. https://www.msdvetmanual.com/metabolic-


disorders/disorders-of-calcium-metabolism/parturient-paresis-in-cows. 2015. 2022.

4. DeGaris PJ, Lean IJ. Milk fever in dairy cows: A review of pathophysiology and control
principles. The Veterinary Journal 2008;176:58-69.

5. Oetzel GR. Diseases of Dairy Animals | Non-Infectious Diseases: Milk Fever. In:
Fuquay JW, editor. Encyclopedia of Dairy Sciences (Second Edition). Academic Press, San
Diego, 2011:239-245.

6. da Silva DC, Fernandes BD, Dos Santos Lima JM et al. Prevalence of subclinical
hypocalcemia in dairy cows in the Sousa city micro-region, Paraíba state. Trop Anim Health
Prod 2019;51:221-227.

7. Fiore F, Cocco R, Musina D, Spissu N. On-farm use of a water hardness test kit to
assess total blood calcium level in dairy cattle. Journal of Dairy Research 2020;87:56-59.

8. Martinez N, Sinedino LDP, Bisinotto RS et al. Effect of induced subclinical


hypocalcemia on physiological responses and neutrophil function in dairy cows. Journal of
Dairy Science 2014;97:874-887.

9. Lean IJ, DeGaris PJ, McNeil DM, Block E. Hypocalcemia in dairy cows: meta-analysis
and dietary cation anion difference theory revisited. J Dairy Sci 2006;89:669-684.

10. Stockdale CR. Effects of body condition and diet in late gestation on the subsequent
health and performance of dairy cows. Australian Journal of Experimental Agriculture
2007;47:495-501.

11. Venjakob PL, Borchardt S, Heuwieser W. Hypocalcemia-Cow-level prevalence and


preventive strategies in German dairy herds. J Dairy Sci 2017;100:9258-9266.

12. Reinhardt TA, Lippolis JD, McCluskey BJ, Goff JP, Horst RL. Prevalence of subclinical
hypocalcemia in dairy herds. The Veterinary Journal 2011;188:122-124.

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