LARGE ANIMAL | METABOLIC DISEASE ONLINE EDITION

Milk fever – an overview fever or periparturient hypocalcaemia, is a metabolic disease of dairy cows that occurs around the time of calving. During the dry period, requirements are relatively low; but at calving there is a sudden increase in calcium requirement as begins. If this demand is not met quickly enough, the concentration of calcium in the blood drops below a critical threshold, resulting in either clinical or subclinical milk fever. Jenny Bellini BVSc MRCVS A cow can lose 23g of calcium 10 in 10 litres of in Jenny qualified from the one milking; yet, typically, only has 12g of free calcium 9.0 University of Bristol in 2014 8 available to her. This huge and started working soon 8.0 after for Friars Moor Livestock demand for calcium must be Health – a member practice met from elsewhere to prevent of XLVets*. Jenny works milk fever developing. The 6 primarily in dairy practice, average incidence of clinical with particular interests in milk fever in the UK dairy herd 4.8 nutrition, heifer rearing and is four to nine per cent, while 4 block-calving systems. the incidence of subclinical milk fever is estimated to be between 25 to 50 per cent. Times more likely 3.0 *XLVets is a community 2 2.6 The average cost of a case of of independently-owned, 2.0 progressive veterinary milk fever is approximately 1.7 practices that work together to £200 (Husband, 2005). achieve the highest standards 0 of veterinary care. As plasma calcium is required LDA 30d) for neuromuscular function, Mastitis Ketosis www.xlvets.co.uk Metritis Dystocia Retained milk fever is characterised placenta by decreased feed intake, Culling (1- decreased heart rate, Figure 1. The incidence of other conditions associated with milk inhibition of urination and fever (Source: EBVC, 2011). defaecation, rumen and intestinal stasis and reduced rectal temperature. If it is left untreated, cows progress to lateral recumbency, and eventually coma and death.

Reduced feed intake leads to greater fat mobilisation, and one study (Reinhardt et al, 2011) has shown cows with low blood calcium levels post calving (<2mmol/L) have higher concentrations of non- esterified fatty acids (NEFAs). 0.75 As muscle contraction is hours* inhibited, the teat sphincter relaxes; which leads to an increased risk of mastitis. Hypocalcaemia post calving also directly impairs immune *Suggested Personal & Professional cell response to an activating Development (PPD) stimulus, therefore making these cows more susceptible to disease. As shown in Figure 1, the METABOLIC DISEASE incidence of mastitis and Figure 2. A cow with milk fever and metritis. ketosis in cows recovering from

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ONLINE EDITION METABOLIC DISEASE | LARGE ANIMAL

Mechanisms involved in calcium metabolism

Low calcium High calcium

+ Parathyroid - hormone +

1-a-hydroxylase

Kidney

Activated 1,25(OH) D Inactive 25-OH-D3 2 3

Bone Gut

Steps enchanced by induction of mild metabolic acidosis

Figure 3. The mechanisms involved in calcium metabolism in the Figure 4. Milk fever is a disease that can largely be prevented and cow (Husband J, 2005). controlled through careful transition cow feeding. milk fever is eight and nine within minutes. Although the first month of lactation. 1,25 that there are fewer intestinal times greater, respectively. The amount of calcium available (OH)2 D3 also increases renal receptors for 1,25 (OH)2 D3 in incidences of dystocia, retained for recovery from the urine is tubular reabsorption of calcium these breeds. foetal membranes, displaced small, this process may still and stimulates active transport abomasum and uterine be sufficient to compensate of dietary calcium across the The risk of milk fever also prolapse are all greater in cows for small decreases in plasma intestinal wall. increases with age, rising by nine with milk fever (Figure 2). calcium. However, in many per cent per lactation. (DeGaris cases this mechanism alone These mechanisms take et al, 2009). There are several During the dry period, is insufficient and continued between 24 and 48 hours reasons for this – there is usually calcium requirements for PTH secretion stimulates to correct the negative an increasing milk yield and, skeletal development and calcium resorption from bone. calcium balance and both are therefore, demand for calcium maintenance are low – at less The bones are the source of 95 magnesium dependant. The with increasing age. Older cows than 30g/day. At calving, the per cent of the cow’s calcium, nadir in blood calcium occurs are also less able to mobilise demand for calcium is much which is available to the cow at 12 to 24 hours post calving. calcium from the bone, and increased – 2.3g Ca/L of in two forms. Normal blood calcium for an have reduced active transport colostrum produced and 1.2g adult cow is 2.1-2.8mmol/L, of calcium from the intestines Ca/L milk produced. Calcium There is a soluble, readily with clinical or subclinical owing to reduced production quantity in milk increases as available pool of calcium in the milk fever occurring below this of the steroid hormone, 1, 25 butterfats increase. The cow fluid surrounding bone cells. (Merck Veterinary Manual). (OH2)D3 and reduced receptors does not have enough calcium PTH acts on bone lining cells on target tissues. in her bloodstream to meet to transfer this soluble calcium Certain breeds are more these increased demands, into the extracellular pool. susceptible to milk fever, Prevention of milk fever and so it must be replaced by There is approximately 6-10g of including Jerseys, Channel Milk fever is a disease that the activation of homeostatic calcium available here, which Islands and Swedish red and can largely be prevented and mechanisms to increase its can be increased by 6-8g in whites. It is thought this is a controlled through careful intestinal absorption, reduce cows under metabolic acidosis. consequence of the increased transition cow feeding (Figure renal excretion and increase loss of calcium in their milk 4). Some of the key principles resorption from the bone PTH also activates the renal with increasing butterfat, and are discussed overleaf. (Figure 3). enzyme responsible for producing the vitamin D

Low blood calcium causes the metabolite, 1,25 (OH)2 D3. This “A cow can lose 23g of calcium in 10 parathyroid glands to secrete stimulates osteoclastic bone (PTH). resorption activity to mobilise litres of colostrum in one milking; yet, This hormone increases renal more calcium from the skeleton typically, only has 12g of free calcium re-absorption of calcium – cows typically lose nine to 13 from glomerular filtrate per cent of skeletal calcium in available to her”

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7.0 DCAB Feed component (mEq/kg Comments DM) 6.0 Grass silage (2003 +390 Extremely variable (up to +1,000), season to date) 5.0 higher with legumes Grass silage +391 4.0 (2002 season) Maize silage +194 Less variable than grass silage 3.0 Whole crop silage +158 Consistently low DCAB 2.0 Straw +139

Milk fever incidence (%) 1.0 Barley +25 0.0 Brewer's grains -220 Can be useful to 'dilute' high -40 -20 0 20 40 60 80 100 120 DCAB silages DCAD (meq/100 g DM) Fodder beet +300

Figure 5. The linear relationship between DCAB and milk fever Kale +806 incidence (DeGaris PJ and Lean IJ, 2009). Maize gluten +137 Molasses Dietary cation anion two cations in the DCAB +681 balance (DCAB) equation, sodium and Potatoes +343 The transition diet can be potassium must be kept at Rape extract -201 manipulated to push the cow low levels to achieve a low into mild metabolic acidosis, DCAB. Potassium in UK diets Wheat -6 which has been shown to is usually the most difficult to Sugar beet pulp -123 reduce the risk of clinical control. Grass, grass silage Soya extract +203 milk fever. Reducing the and hay can all be very high DCAB reduces the risk of milk in potassium, while maize, Wheat feed +177 fever – the two have a linear whole crop silages and straw Data supplied by Thomson & Joseph, Norwich. relationship (Figure 5). are usually low in potassium.

DCAB (meq/kg DM) = It is crucial to have all forages Figure 6. The DCAB of common feedstuffs (Husband J, 2005). (sodium + potassium) - fed to dry cows analysed (chlorine + sulphur) for their mineral content, diet and the cow too much. of PTH in response to Feeding a dry cow diet higher because there can be great If high levels of anionic salts hypocalcaemia and increases in anionic salts, chloride and variation (Figure 6). As a rule, are fed, palatability is reduced the tissue sensitivity to PTH. sulphur, reduces the DCAB, potassium must be kept <1% and, therefore, so is dry Magnesium is primarily making the cow acidotic DM. Potassium in grass can matter intake (DMI). absorbed from the rumen and and the blood and urine pH be reduced by having dry cow cows need a constant supply decrease. These acidotic paddocks with no manure Urine pH is a good indicator of it in the diet. As the rumen conditions increase the tissues’ spread on them and using of whether the dry cow diet is pH increases above 6.5 – responsiveness to PTH as the just N fertiliser at moderate acidified enough or too much. and on higher forage diets, receptors for PTH on bone to heavy applications. Target urine pH is 6.2-6.8. If conditions common to dry and cells function Potassium levels in grass are average urine pH is 5-5.5, the cows – magnesium solubility better, as well as increasing the highest in spring and autumn, diet is too acidic and DMI will declines sharply. when the grass growth is production of 1,25 (OH)2D3 be suppressed. Urine pH can and, therefore, increasing greatest, and the potassium be checked 48 hours after High potassium active transport of calcium antagonises magnesium, dietary changes and should, concentrations may across the intestine. Cows in which causes seasonal ideally, be measured after one also reduce magnesium metabolic acidosis are thus peaks in staggers to three weeks. absorption in the rumen. more able to mobilise more or hypomagnesaemia. Recommended levels of calcium and meet the increasing Magnesium magnesium are 0.4% DM. requirements without suffering 2. Adding anionic salts to Magnesium – although Increasing dietary magnesium from milk fever. achieve a low DCAB not included in the DCAB from 0.3% DM to 0.4% DM It can be difficult to achieve equation – is important can reduce milk fever by A low DCAB dry cow diet can a low enough DCAB just by for the prevention of milk approximately 62 per cent be achieved by two means. manipulating forages and fever. It increases the supply (Lean et al, 2006). concentrates fed. Anionic 1. Manipulating the diet to salts can be added to the diet achieve a low DCAB to reduce the DCAB further. By manipulating the diet, it Typical choices are magnesium “Treatment of milk fever should raise the may be possible to achieve or ammonium chloride. Care blood calcium levels for long enough until a DCAB of <50-100 without must be taken when adding adding anionic salts. The anionic salts not to acidify the the homeostatic mechanisms are functional”

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Calcium References Calcium requirements for a dry cow are around 30g/day. DeGaris PJ and Lean IJ (2009). Calcium-restricting dry cow Milk fever in dairy cows: A review diets – where calcium in the of pathophysiology and control diet is less than 20g/day for principles The Veterinary Journal, three weeks pre-calving and 176: 58- 69. the cow is in true negative calcium balance – work to Goff JP (2008). The monitoring, reduce the risk of milk fever at prevention, and treatment parturition. The mechanisms of milk fever and subclinical to increase calcium hypocalcaemia in dairy cows. The production once lactation Veterinary Journal 176: 50-57. starts are already activated and the cow can meet Horst RL et al (1997). Strategies increasing calcium demand for Preventing Milk Fever in Dairy once she calves. However it is Cattle. J Dairy Sci, 80: 1269-1280. not usually possible to get the calcium supply in the diet this Husband J (2005). Strategies for low, with most ranging from the control of milk fever. In Practice, 27: 88-92. 50g-100g calcium per day. Figure 7. A recumbent cow following treatment for milk fever.

Calcium binders, such as Lean IJ et al (2006). Hypocalcaemia zeolite, can be added to diets calcium per 100kg bodyweight flow to the periphery in Dairy Cows: Meta-analysis and to achieve these low dietary to correct hypocalcaemia. is compromised. Dietary Cation Anion Difference calcium levels. These products Intravenous (IV) calcium Theory Revisited. Journal of Dairy bind calcium in the intestines should be administered Oral calcium Science, 89(2): 669-684. and it is passed out in faeces. slowly, at 1g/minute to avoid Large amounts of soluble They often have to be fed in cardiac complications and calcium can be given orally. Merck Veterinary Manual. https:// large quantities of 0.5kg-3kg arrhythmias. Increases in This forces calcium across www.msdvetmanual.com per day for at least two weeks. blood calcium following the intestinal tract by passive They can bind phosphorus as IV administration last diffusion between intestinal Reinhardt TA et al (2011). well, so extra phosphorus may approximately four hours. epithelial cells. Oral solutions Prevalence of subclinical sometimes be required. contain approximately 50g of hypocalcaemia in dairy herds. The Subcutaneous calcium; and many of these Veterinary Journal, 188: 122-124. The basics! calcium salts products are available for Ensure all dry cows have Absorption of calcium from administration at calving and access to fresh food and preparations administered by again 24 hours later. clean water. Dry cows need this route is variable as blood 80cm of feed trough space per individual. Making sure that food troughs are cleaned out and fresh food PPD Questions is presented daily will ensure palatability is maximised. 1. What is the normal blood calcium range for a dairy cow? Current recommendations are to provide at least 10cm 2. How much calcium is required a) per litre of milk of drinking space per cow and produced and b) per litre of colostrum produced? ensuring there are enough water troughs for 10 per cent of the group to drink at once 3. Which hormones are released when blood calcium levels (AHDB Dairy, 2018). are too low?

Treatment of milk fever 4. What is the recommended level of potassium in a dry Treatment of milk fever should cow diet to prevent milk fever? raise the blood calcium levels for long enough until the homeostatic mechanisms are 5. When urine pHs are used to monitor acidification of the

functional (Figure 7). diet, what is the target range?

6.2-6.8. 5.

<1% DM <1% Intravenous calcium 4.

3 2

PTH and 1,25 (OH 1,25 and PTH 3. borogluconate D )

1.2g and 2.3g respectively 2.3g and 1.2g w 2.

Each 400ml of 40% /w 2.1-2.8mmol/L

solution provides 12g calcium 1.

– cows need approximately 2g Answers

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