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Hypocalcemia
In Diary Cattle
Stefanie A Newhouse
Senior Seminar
Dr. Tera Montgomery
By
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Table of Contents
TABLE OF CONTENTS ......................................................................................................................................................................2
ABSTRACT .........................................................................................................................................................................................3
INTRODUCTION ...............................................................................................................................................................................4
MEDICAL IMPACTOF HYPOCALCEMIA ................................................................................................................................................4
ECONOMIC IMPACTOF HYPOCALCEMIA..............................................................................................................................................5
PHYSIOLOGICAL EFFECTS OF HYPOCALCEMIA ..........................................................................................................................6
NEUTROPHIL FUNCTION....................................................................................................................................................................7
BONE RESORPTION MARKERS............................................................................................................................................................8
CALCIUMSIGNALING IN IMMUNE CELLS.............................................................................................................................................9
CAUSES OF HYPOCALCEMIA..........................................................................................................................................................9
DCAD THEORY ...............................................................................................................................................................................10
HYPOPARATHYROIDISM...................................................................................................................................................................11
PREVENTION OF HYPOCALCEMIA..............................................................................................................................................12
EFFECTS ON BEHAVIOR....................................................................................................................................................................12
DIETARY POTASSIUM (K) .................................................................................................................................................................13
TREATMENT OF HYPOCALCEMIA ...............................................................................................................................................14
SECONDARY HEALTH EFFECTS ..........................................................................................................................................................15
CONCLUSION ..................................................................................................................................................................................15
FUTURE RESEARCH..........................................................................................................................................................................15
REFERENCES....................................................................................................................................................................................17
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HYPOCALCEMIA IN DAIRY CATTLE
Abstract
Subclinical andclinical hypocalcemiaduringthe transitionperiodindairycattle hasdetrimental effects
on animal health,welfare,andproduction. Anarrayof causesfor decreasedcalciumlevelsinhigh-
productiondairycattle have beendiscoveredoverthe lastfew decades.These causescaninclude the
level of calciuminthe pre-partumdiet,Dietary Cation-AnionDifference (DCAD) dietlevel beingfed,and
tissue sensitivityto parathyroidhormone (PTH) levels.Anotherimportantareaof interestfor
researchershasbeenthe physiological effectsof hypocalcemiaonthe immune cells,neutrophil
function,andbone resorptionmarkers. Alongwithdietarychanges,behaviorhasbeenstudiedasa
possible waytopreventhypocalcemia. Behavioral traitshave beenstudied,butfew correlationshave
beenmade betweenacow’sbehaviorandthe developmentof hypocalcemia,especiallysubclinical
hypocalcemia.Several treatmentoptionsforchronicclinical hypocalcemiahave beenimplementedto
on-farmuse, includingoral calciumsupplementsandintravenousinfusionsof calcium.Overall,there isa
greaterunderstandingof hypocalcemiaindairycattle.However,there isstill future researchthatneeds
to be conductedinorder topreventanddetectmore hypocalcemiacasesindairycattle before ithasa
negative effectonthe productionforthe farmer.
Key words: dairycow,hypocalcemia,neutrophilfunction,bone resorptionmarkers,immunecells,
behavior,parathyroidism
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Introduction
Milkproductionindairycattle has continuedtoincrease steadily overthe pastseveral decades.Since
calciumisthe mainmineral componentof milk,the cow’sneedforreadilyavailable calciumatthe
beginningof herlactationhasalsocontinuedtoincrease.However,if the demandbythe mammary
glandfor calciumisnot met,the cow becomeshypocalcemic. Hypocalcemiaisadisorderthatdevelops
whena cow isunable tomaintainadequate blood-calciumconcentrations. Eachyear,approximately5-
10% of dairycattle developclinicalhypocalcemia,andanadditional 25-50% of dairycattle are affected
by subclinical hypocalcemia.
Anymammal can develophypocalcemiaduringthe transitionperiod.However,dairycattle have been
bredto produce such a large amountof milkthattheyare particularlysusceptible tobecoming
hypocalcemic.Whenthe cow’sbodyhassucha large needforcalcium, anincrease incalcium
mobilizationfromthe bone occurs.The mobilizationof calciumfrombone happensbecause dietary
calciumisnot sufficienttosupportthe demandsof lactation.Hypocalcemiahasbeenlinkedto
significantnegative effectsonmilkyieldandreproduction.Additionally,hypocalcemiacanlead toa
varietyof secondaryhealthproblemsordisorders suchasmetritis, retainedplacenta, mastitis,ora
displacedabomasum.Thisarray of issues,stemmingfromhypocalcemia, cancostdairyproducersover
250 milliondollarseachyearinthe UnitedStatesalone.
MedicalImpact of Hypocalcemia
Hypocalcemiais definedas the deficiencyof calciuminthe bloodstream.Thisdisordercanbe clinical in
whichthe animal isphysicallydisplayingsignssuchasmuscle weaknessandadecrease inbody
temperature, orsubclinical where the animalisnotshowinganyreadilyobservable symptoms. Some of
the initial signsof clinical hypocalcemiacanbe excitability,hypersensitivity,andrestlessness.Once the
calciumconcentrationsgetsolowthat tetanybeginstosetin,the cow may experience tachycardiaor
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HYPOCALCEMIA IN DAIRY CATTLE
mildhyperthermia.Asthe cow’shealthcontinuestodecline,muscleswill weakentothe point atwhich
the cow will be sternallythenlaterallyrecumbent. The cow will appeartobe tremblingatfirst,butthen
she will become a“downer”cowonce she has reachedthe stage of recombency. Some of the more
severe caseswill exhibitsymptomssuchasconstipation,mildtoseverebloating,weakpulses,poor
pupillarylightresponse,flaccidparalysis,comaorevendeath (Bovine PostparturientParesis).
Most cows that sufferfromhypocalcemiawillbe diagnosedbasedontheirsymptomstheyexhibit.Since
the illnessissorapidinnature, a laboratorytestisnot a feasible diagnostictool if the animal isshowing
clinical symptomsalready.However,if acow has subclinical hypocalcemia,diagnosisismuchmore
difficult.Subclinical hypocalcemiccowsare diagnosedafterbloodisdrawnanda laboratorytestreveals
lowserumcalciumlevels (BovinePostparturientParesis).
Economic Impact of Hypocalcemia
It iseasyto understandthe negative effectclinical hypocalcemiccowshave onthe profitabilityof the
farm.First of all,a clinical hypocalcemiccow wouldmostlikelyneedtobe treatedbya veterinarian
usingan intravenousinfusionof calcium.Alongwiththe costof the veterinarytreatment,studieshave
shownclinical hypocalcemiacausesadecrease in milkproduction,aswell asahighersusceptibilityto
othersecondaryhealthconditions,which include:metritis,displacedabomasum, retainedplacenta, and
mastitis.Additionally,withmanyof the secondaryhealthproblems,more expensesfromthe producer
will be involvedforthe treatmentof thatanimal.Clearly,aclinical hypocalcemiccow canbe verycostly
for a producer.
Similartoclinical hypocalcemiccows, studieshave shownthat subclinical hypocalcemiccowshave a
higherinstance of secondaryhealthproblems,decreasedmilkproductionandadecreasedchance of
beingbredback.Since subclinical hypocalcemiaaffectsapproximatelyhalf of the cowsondairyfarmsin
the UnitedStates,mostof themgoundiagnosedanduntreated.Thus,the issuesthatarise and decrease
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productionresultinthe lossof over250 milliondollarseachyearinthe UnitedStatesdue to
hypocalcemia.
Hypocalcemiahasa huge economicimpactonthe dairy industryinthe UnitedStatesandaroundthe
world.Inrecentdecades,the studyof hypocalcemiahascontinuedtogrow inorderto try and
understandthe disorderbettertoreduce the amountof moneylostto thisdisorder.A lotof knowledge
relatingtothe causes,prevention,andtreatmentof hypocalcemiahave beendiscoveredandcontinue
to be discoveredbyscientists.
Physiological Effects of Hypocalcemia
Whena dairy cowexperienceshypocalcemicconditions,theyneedtocompensate forthe decreased
bloodcalciumbecause calciumisa veryimportantpartof regulatingawhole hostof bodilyfunctions,
includingsmoothmuscle contraction,intracellularactivity, andetc.Calciumabsorptionbythe intestine
will typicallyincrease.However,the primarymode forthe bodytorestore homeostaticcalciumlevelsis
throughcalciumresorptionfromthe bone.
The primaryhormone that isresponsible
for the mobilizationof calciumfromthe
bonesat the onsetof lactationin
mammalsisparathyroidhormone
related-protein(PTHrP),whichis
synthesizedwithinthe mammarygland
and isonlydetectable inthe circulatory
systemduringlactationandtimesof
metastaticbone cancers.
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HYPOCALCEMIA IN DAIRY CATTLE
PTHrP issimilartoparathyroidhormone (PTH) andit hasbeenextensivelystudiedinthe humanand
rodentmodels.However,little researchhasbeendone relatingtoitsfunctionindairycattle.Serotonin,
5-hydroxytryptamine (5-HT) regulatesthe inductionof PTHrP.The molecularmechanismsgoverningthis
actionare still unknown.Manipulationof 5-HTnear the end of a pregnancyperiodmaybe a critical
factor inpreventingthe onsetof hypocalcemiaduringearlylactation.5-HTisa homeostaticregulatorof
the mammary gland.5-HT isproducedina two-steppathwayfromthe aminoacidL-tryptophanusing
the rate-limitingenzyme tryptophanhydroxylase 1(TPH1).AfterL-tryptophanisconvertedinto5-
hydroxy-L-tryptophan,itundergoesdecarboxylationtoform5-HT.
Preventinghypocalcemiacouldgreatlybenefitthe dairyindustry.Cowsthatremainhealthythroughthe
transitionperiodare more likelytoproduce anadequate amountof milk,aswell asanothercalf,and
bothof these factorsare critical inmaintainingthe economicviabilityof the dairyfarmsandthe
sustainabilityof the humanfoodproductionsystem.
Neutrophil Function
Martinezconducteda studythat waspublishedinthe Journal of DairyScience in2013 aboutthe effects
of the neutrophil functioninhypocalcemicdairycattle.The study,conductedatthe Universityof Florida
DairyUnit in Gainsville, Florida,directlycomparedthe neutrophil functionof normcalcemicandinduced
subclinical hypocalcemiaintennon-pregnant,non-lactatingHolsteincows (Martinez).
Amongthe most importantdatacollected,theydiscoveredthat the neutrophilfunctionwassuppressed
incows withsubclinical hypocalcemia.Cowsthathadinducedsubclinical hypocalcemiahadareduced
percentage of neutrophilswithphagocyticactivity.Additionally,subclinical hypocalcemiccowshada
reductioninthe percentage of neutrophilswithoxidativeburstactivity.Finally,phagocytosisand
oxidative burstdeclinedat72 hoursafterthe beginningof the infusioninsubclinical hypocalcemiccows,
where asthose valuesbothincreasedinnormcalcemiccows (Martinez).
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The main outcome of thisstudyrevealedthe dropincalciuminthe bloodthatoccurs during
hypocalcemianegativelyeffectsthe neutrophilsandmakesthe cow lesslikelytofightagainst
pathogenicbacteria.The depressionof bacterial killingiscausedfromthe neutrophil suppressionof
phagocytosis.Thispointalsosupportsthe factthathypocalcemiccowshave an increasedinstance of
secondaryhealthissues. Extracautionshouldbe takenforthese cowsinorderto preventsecondary
bacterial infections.
Bone Resorption Markers
A studyconductedbyLiesegang,publishedinthe Journal of DairyScience in1998, exploredthe bone
resorptionmarkersinhypocalcemicdairycattle.The study,conductedatthe Universityof Zurichin
Switzerland,investigatedwhetherhydroxyproline,deoxypyridinoline,orthe carboxyterminal
telopeptide of type Icollagencouldbe usedasmarkerstoprovide evidence of bone resorptionduring
hypocalcemiaindairycows (Liesegang).
Amongthe most importantdatathat was collected,cowsshowingsymptomsof hypocalcemiahad
increasedurinaryhydroxyprolineconcentrationsfromparturitiontoday14. Deoxypyridinoline
concentrationsinthe urine were increasedafterparturitionuntil day9and carboxyterminal
telopeptidesof type Icollagenpeakedatday5. However,these valueswere the same betweencows
withhypocalcemicsymptomsandcowswithout (Liesegang).
The main conclusionresearchersmade wasthatassaysfor urinarydeoxypyridinoline andserum
carboxyterminal telopeptideof type Icollagendeterminationsare useful toolstofollow the course of
degradationof bone collagenindairycattle duringhypocalcemia. Furtherresearchcoulddevelopon-
farm teststo determinelevelsof these bone resorptionmarkersinordertodeterminethe severityof a
hypocalcemiccow.
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HYPOCALCEMIA IN DAIRY CATTLE
CalciumSignaling in Immune Cells
A studypublishedinthe Journal of DairyScience in2005 by Kimuraoutlinedthe influencesof
hypocalcemiaonimmune cellsindairycows. The study,conductedatthe National Animal Disease
CenterinAmes,Iowa,testedif the increaseddemandforcalciuminperiparturientcowsadversely
affectsintracellularcalciumstoresof immune cells (Kimura).
Amongthe importantdata theycollected, researcherswere able toconclude thatintracellularcalcium
storesdecreasedinperipheral bloodmononuclearcells(PBMC) before parturitionanddevelopmentof
hypocalcemia. Thisisthe cause of a bluntedintracellularcalciumreleaseresponse toanimmune
activationsignal.The studysuggeststhatsystemiccalciumstressprecedesmeasurable hypocalcemia,
especiallyincowsthatwill developclinical hypocalcemia.PBMCintracellularcalciumstoresare amore
sensitivemeasure of calciumstressesintransitioncows (Kimura).
The conclusionresearchersdevelopedwiththe datafromthisstudyshowsa depletionof intracellular
calciumstoresstarts several dayspriortocalvinginhypocalcemiccows.Furtherresearchshouldbe
done inthisarea to develop asimple testforon-farmuse thatmeasuresPBMC.PBMCis responsible for
the flux of calciumthat wouldordinarilyactivatethe cellsandpreventthe cow fromexperiencing
immunosuppression (Kimura).
Causes of Hypocalcemia
The physiological effectsof hypocalcemiaare verycomplicated anditisdifficulttostudyjustone part of
the calciumhomeostaticregulatorysystem.Since the entire processissocomplex,the causesof
hypocalcemiaare hardto pinpoint.Historically,highlevelsof dietarycalcium have beenbelievedtobe
the major cause of hypocalcemiaindairycattle.Scientistshave begunexploringotherfactorsthatcould
contribute toa cow’srisk of developinghypocalcemia. A majorareaof nutrition relatedtothe cause of
hypocalcemiaisthe DietaryCation-AnionDifference (DCAD)Theory. Hypoparathyroidism,anothercause
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of hypocalcemia, hasrecentlybeenlinkedtohypocalcemiabecause itaffectsthe body’stissue
sensitivitytoparathyroidhormone.Overall,understandingsome of the majorcausesof thisdisorderis
an importantpart of understandinghypocalcemiaindairycattle.
DCAD Theory
The DietaryCation-AnionDifference Theory(DCAD) hasbecome atopicindairyscience thatis being
studiedmore andmore nowadays.DCADisbasicallyanequationof the cations (potassiumandsodium)
and the anions (chlorine andsulfur) inthe dietof adairycow ina relationshipsuchas ( 𝑁𝑎 + 𝐾) − (𝐶𝑙 +
𝑆). DCAD isresponsibleforinfluencingthe animal’sacid-basehomeostasis,calciumstatusaround
calving,andmineral elementutilization.Previousstudieshave showndecreasingthe DCADimproves
calciumhomeostasisatthe onsetof lactation.Additionally,the riskof developinghypocalcemiais
greatestincowsin a state of metabolicalkalosis,whichisinducedfromfeedingahigh-DCADdiet.
A studyconductedin2005 byLean was publishedinthe Journal of DairyScience,revisitedprevious
workrelatedtothe DCADTheory.The study,conductedat the Bovine ResearchAustralasiainAustralia,
aimedtoexamine whichformof the DCADequationprovidedthe bestestimateof hypocalcemiarisk
and to clarifyrolesof calcium,magnesium, andphosphorusconcentrationsof twopre-partumdietsin
the pathogenesisof hypocalcemia (Lean).
Amongthe most importantdatathe researchersfound,hypocalcemiariskwashighest withpre-partum
dietaryconcentrations of 1.35%calcium.Additionally,increasingpre-partumdietarymagnesium
concentrationshadthe largesteffectondecreasingincidence inhypocalcemia.Finally,increasing
dietaryphosphorusconcentrationspre-partumincreasedthe riskof hypocalcemia (Lean).
The main suggestionresearchersmade toproducerswasthe datastronglysupportsthe needto
evaluate macromineral nutritionapartfromDCAD of the diet. It iscritical for producerstoassessand
control the levelsof dietarymacromineralsincludedinthisstudyof the pre-partumdietinorderto
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HYPOCALCEMIA IN DAIRY CATTLE
preventthe instancesof hypocalcemiainthe herd. The diettakingDCADlevelsintoaccountinthisstudy
isso far the bestmodel currentlyavailable forpredictinghypocalcemia incidence indairycattle (Lean).
Hypoparathyroidism
A studypublishedinthe Journal of DairyScience in2013 conductedby Goff aimedtolookat the effect
of high-DCADdietsfedtopre-partumcowstosee if itreducestissue sensitivitytothe parathyroid
hormone (PTH),inducingapseudohypoparathyroid state thatdiminishescalciumhomeostatic
responses.The study,conductedatthe UnitedStatesDepartmentof Agriculture –Agricultural Research
Service inAmes,Iowa,directlycomparedcowsfedlow-DCADandhigh-DCADdietstoinduce a
compensatedmetabolicalkalosisandacidosisstate,respectively,followedbysyntheticPTHinjections (J.
P. Goff).
Amongthe most importantdatatheycollected,theynoticedcowsfedthe high-DCADdiethadplasma
calciumconcentrationsthatincreasedata much lowerrate.Additionally,the cowsthatwere fedthe
high-DCADdietproducedsignificantlyless1,25-dihydroxyvitaminDinresponse tothe PTH injections
than the cowsthat were fedthe low-
DCAD diet.Finally,the cowsthatwere
fedthe high-DCADdiethad
numericallylowerserum
concentrationsof the bone resorption
markercarboxyterminal telopeptide of
type 1 collagenthanthe cowsfedthe
low-DCADdiet.However,the numbers
were notstatisticallydifferent (J.P.
Goff).
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Researchersinthisstudymade one mainsuggestiontodairyproducerstotry anddecrease instancesof
hypocalcemiaintheircattle.Itisimportantthatcowsthat are nearingparturition,especially
multiparouscows,are consuminglow-DCADdiets.Low-DCADdietscanincrease the intestinal
absorptionof calcium, aswell asenhance the release of calciumfrombones.AccordingtoGoff,
“because cowsfedlow-DCADdietsdoexcretemore calciumintheirurine,ithasbeensuggestedthat
renal reabsorptionof thispotentialpool of calcium(5-7g of Ca/d) couldprovide the calciumneededto
preventthe developmentof hypocalcemiaandmilkfever.”
Prevention of Hypocalcemia
Preventingclinical andsubclinical hypocalcemiacasesinadairyherdis the keyto reducingthe
productionlossesfromthe effectedcows. Bypreventingthe hypocalcemicissuesfromoccurring,the
cow’schancesof havingsecondaryhealthissuesare eliminatedaswell.Several wayshypocalcemiais
beingpreventedisthroughthe studyof a cow’sbehavioraroundthe transitionperiodandthroughthe
manipulationof the potassiumlevelsinthe cow’sdiet.
Effectson Behavior
A 2011 study,publishedinthe Journal of DairyScience byJawor,aimedtodescribe the associationsof
subclinical hypocalcemiawithmilkyield,feeding,drinkingandrestingbehaviorduringthe periodaround
calving.Thisinformationcouldhelpproducerspredictwhencowsare beingaffectedbysubclinical
hypocalcemiabasedontheirbehaviors.The study,conductedatthe Universityof BritishColumbia’s
DairyEducationand ResearchCentre,directlycomparedthese behaviorsinHolsteindairycowswhich
had subclinical hypocalcemiawith control cows (Jawor).
Amongthe importantdata theycollected,cowswithsubclinical hypocalcemiaproducedanaverage of
5.7 kg/dmore milkduringweeks2,3, and 4 of lactationcomparedto control cows.Also,hypocalcemic
cowsthat were intheirthirdlactationsustainedgreatermilkyieldsthroughout280 DIM. Additionally,
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HYPOCALCEMIA IN DAIRY CATTLE
dry matterintake was,onaverage,1.7 kg/dgreaterduringthe weeks -2and -1 and fewervisitstothe
waterand feedbinsoccurredinthe firstfew weeksaftercalvingamongcowswithsubclinical
hypocalcemia.Finally,the cowswithsubclinical hypocalcemiaonaverage stoodfor2.6 h longerduring
the 24-hour periodbefore calvingand2.7 h lessstandingduringd+1 (Jawor).
The researchersmade twomainsuggestionstodairyproducersrelatingtohypocalcemiccows’behavior.
First,dairycattle withsubclinical hypocalcemiaduringthe 24-hperiodpostpartumdidnotexhibitany
majorchangesin productionorbehaviorthatwouldtypicallybe associatedwithpoorhealth.Forthis
reason,cowsneedtobe closelymonitoredduringthistime periodincase symptomsdoappear.
Secondly,the resultsrelatedtothe amountof tripsto the feedandwaterbinspost-partumdisplayed
the importance of ensuringcowshave adequate accesstofeedinganddrinkingareasduringthe period
followingcalving. Thisisnecessaryinorderto allow the cowsto meettheirnutrientrequirements.
Therefore,itisimportanttomanage the pensof freshcowscloselytoensure a low stockingdensity.
DietaryPotassium (K)
A studyconductedbyR. L. Horst in 1997, publishedinthe Journal of DairyScience, lookedatstrategies
for preventinghypocalcemiaindairycattle.The study,conductedatthe National AnimalDiseaseCenter
inAmes,Iowa,studiedwaystominimizethe effectsof dietarypotassiumonhypocalcemiaincidences
(Horst).
Amongthe most importantdatacollected,Horstfounddirectevidence thatcowsfedadietlow in
potassiumandsodiumhave lessmilkfeverthanthose ondietshighinKor Na. Second,overfertilization
of alfalfawithKresultsinplantswithhighconcentrationsof Kthat are detrimental tothe healthof the
periparturientdairycow.Finally,since manydairyproducerspurchase aportionof theirfeedstuffs,soil
K concentrationscontinue tobuildovertime asmostof the K broughtontothe farmin purchasedfeed
remainsonthe farm (Horst).
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Researchersmade one mainsuggestionwiththisstudyrelatingtodietaryK.Itis importanttofeedlow
levelsof dietaryKindairycattle rationsbecause Kplaysa significantrole inpredisposingcowsto
hypocalcemia.The researchersalsoshowedthe importance of the acid-base balanceof the dieton
calciummetabolism.Finally,Horstsuggested,“future researchshouldfocusoneffective methodsfor
managingdietaryK,resultingindecreasedreliance onanionicsalts.”
Treatment of Hypocalcemia
The amount of researchbeingdone related tothe treatmentof clinical andsubclinical hypocalcemiahas
beenslowlydecreasingoverthe yearsbecause of the factthat causesand prevention forhypocalcemia
are becomingthe focus. The specifictype of treatmentforhypocalcemiadependsonthe severityof the
disorder.A standingcowwouldbe treateddifferentlythanacow whichisunable tostandup on her
own(Oetzel).
Cowsthat are experiencingsubclinical hypocalcemiaorare displayingclinical signsof hypocalcemia and
are still able tostandon theirownare in the verymildstagesof the disorder.Atthispoint,cowscan be
treatedwithoral calciumsupplementation.Withinahalf hourafterthe supplementation,the cowis
able to absorban effectiveamountof calciumintoherbloodstream. The calciumconcentrationsinthe
cow’sbloodwill remainelevatedfromthe supplementationfor4-6hours afterward (Oetzel).
In more severe hypocalcemiacases,whenthe cow isunable tostand,a fastertreatmentisrequired.The
mostrapid treatmentfortreatingseverelyhypocalcemiccowsiswithintravenouscalciuminfusions.
Withthistreatment,calciumlevelsinthe bloodare restoredalmostimmediately.The downfalltothis
type of treatmentisthat bloodcalciumconcentrationsare raisedtoextremelyandpotentially
dangerouslevels.Therefore,if acowis experiencingseverehypocalcemia,aveterinarianshouldbe
involvedinthe treatment.
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HYPOCALCEMIA IN DAIRY CATTLE
SecondaryHealth Effects
A wide arrayof issuescanstemfromsubclinical andclinical hypocalcemiaindairycattle.Firstof all,
studieshave shownmetabolicdisordersimpairimmunefunctionwhichpredisposesthe cow touterine
infectionsandmastitisfollowingparturitionandatthe beginningof theirlactation.Additional
researcherhaslinkedthe instancesof ketosiswithsubclinical hypocalcemia.Finally,retainedplacenta
and endometritishashighersusceptibilityratesincowsthathave had hypocalcemiaatthe beginningof
theirlactation.If a cow developshypocalcemia,aproducershouldtake extracare to insure the riskof
any of the secondaryissuesisreduced.A veterinariancanhelpdetermine the besttreatmentand
aftercare fora hypocalcemiccow (J.P.Goff).
Conclusion
Subclinical andclinical hypocalcemiaare majorhealthproblemsinamajorityof dairycattle and oftengo
untreated.Cowswithsubclinical hypocalcemiatypicallydonotshow signsorsymptomsuntil the
problemissevere.A cow’sbehaviorshouldbe closelymonitoredbefore andafterparturition,and
propermanagementstrategiesshouldbe enforcedondairyfarms.Takingthese simple stepsasa
producercouldendup saving themthousandsof dollarseveryyearfromthe earlydetectionof
hypocalcemiainthe cows. Byfocusingthe effortsonthe preventionof hypocalcemia,throughfocusing
on majorfactors contributingtohypocalcemia,suchaspseudohypoparathyoidism,the instancescanbe
greatlydecreased.Inall,thiswouldbe beneficialtodairycowsand producersworldwide.
Future Research
The study of clinical andsubclinical hypocalcemiahasbeenincreasingoverthe lastfew decades.Thisis
due to the large economicimpactthat the disorderhason dairyindustry.However,studiesare moving
away fromthe treatmentof hypocalcemiaandshiftingtowardfocusingonthe causesandpreventionof
the disorder. A lotof researchshould continued tobe done focusing onthe developmentof on-farm
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detectionsforhypocalcemiaandpreventionstoaidthe producerand minimize productionlossesinthe
yearsto come.Overall,hypocalcemiaisavery importantdisordertostudy inthe dairyindustrytohelp
make the industrymore productive asa whole.
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HYPOCALCEMIA IN DAIRY CATTLE
References
Bovine Postparturient Paresis. 2015. VetCentric. online.1 February 2015.<http://www.vetmedclinic.com/?p=279>.
Goff, J. P. "Diet-induced pseudohypoparathyroidism:A hypocamcemia and milk fever risk factor." Journal of Dairy
Science 97 (2014): 1520-1528.In print. 1 February 2015.<http://dx.doi.org/10.3168/jds.2013-7467>.
Goff, Jesse P. Impact of Milk Fever and Hypocalcemia on Reproductive Performance of the Dairy Cow. 26 January
2011.Iowa State University.online.1 February 2015. <http://www.extension.org/pages/26036/impact-
of-milk-fever-and-hypocalcemia-on-reproductive-performance-of-the-dairy-cow#.VQ8L7454pqI>.
Horst, R. L. "Strategies for Preventing Milk Fever in Diary Cattle." Journal of Dairy Science 80 (1997):1269-1280.In
print. 1 February 2015.
Jawor, P. E. "Associations of subclinical hypocalcemia atcalvingwith milk yield,and feeding, drinking,and standing
behaviors around partrition in Holstein cows." Journal of Dairy Science 95.3 (2011): 1240-1248.in print.1
February 2015.<http://dx.doi.org/10.3169/jds.2011-4586>.
Kimura,K. "Parturition and Hypocalcemia Blunts CalciumSignalsin ImmuneCells of Diary Cattle." Journal of Dairy
Science 89.7 (2006): 2588-2598.in print.1 February 2015.
<http://www.sciencedirect.com/science/article/pii/S0022030206723359>.
Lean, I. J. "Hypocalcemia in Diary Cows: Meta-analysisand Dietary Cation Anion Differnce Theory Revisited."
Journal of Dairy Science 89.2 (2006): 669-684.in print. 1 February 2015.
<http://www.sciencedirect.com/science/article/pii/S0022030206721300>.
Liesegang, A. "Comparison of BoneResorption Markers DuringHypocalcemia in Dairy Cattle." Journal of Dairy
Science 81.10 (1998): 2614-2622.in print.1 February 2015.
<http://www.sciencedirect.com/science/article/pii/S0022030298758199>.
Martinez, N. "Effects of induced subclinical hypocalcemiaon physiological responses and neutrophil function in
dary cows." Journal of Dairy Science 97 (2014):874-887.In print.1 February 2015.
<http://dx.doi.org/10.3168/jds.2013-7408>.
Oetzel, Garrett R. "MinimizingHypocalcemia DuringEarly Lactation." Tri-State Dairy Nutrition Conference (2013):
23-34. in print.1 February 2015.
<http://tristatedairy.osu.edu/Proceedings%202013/Garrett%20Oetzel.pdf>.

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Hypocalcemia in Dairy Cattle

  • 1. Hypocalcemia In Diary Cattle Stefanie A Newhouse Senior Seminar Dr. Tera Montgomery By
  • 2. 2 NEWHOUSE Table of Contents TABLE OF CONTENTS ......................................................................................................................................................................2 ABSTRACT .........................................................................................................................................................................................3 INTRODUCTION ...............................................................................................................................................................................4 MEDICAL IMPACTOF HYPOCALCEMIA ................................................................................................................................................4 ECONOMIC IMPACTOF HYPOCALCEMIA..............................................................................................................................................5 PHYSIOLOGICAL EFFECTS OF HYPOCALCEMIA ..........................................................................................................................6 NEUTROPHIL FUNCTION....................................................................................................................................................................7 BONE RESORPTION MARKERS............................................................................................................................................................8 CALCIUMSIGNALING IN IMMUNE CELLS.............................................................................................................................................9 CAUSES OF HYPOCALCEMIA..........................................................................................................................................................9 DCAD THEORY ...............................................................................................................................................................................10 HYPOPARATHYROIDISM...................................................................................................................................................................11 PREVENTION OF HYPOCALCEMIA..............................................................................................................................................12 EFFECTS ON BEHAVIOR....................................................................................................................................................................12 DIETARY POTASSIUM (K) .................................................................................................................................................................13 TREATMENT OF HYPOCALCEMIA ...............................................................................................................................................14 SECONDARY HEALTH EFFECTS ..........................................................................................................................................................15 CONCLUSION ..................................................................................................................................................................................15 FUTURE RESEARCH..........................................................................................................................................................................15 REFERENCES....................................................................................................................................................................................17
  • 3. 3 HYPOCALCEMIA IN DAIRY CATTLE Abstract Subclinical andclinical hypocalcemiaduringthe transitionperiodindairycattle hasdetrimental effects on animal health,welfare,andproduction. Anarrayof causesfor decreasedcalciumlevelsinhigh- productiondairycattle have beendiscoveredoverthe lastfew decades.These causescaninclude the level of calciuminthe pre-partumdiet,Dietary Cation-AnionDifference (DCAD) dietlevel beingfed,and tissue sensitivityto parathyroidhormone (PTH) levels.Anotherimportantareaof interestfor researchershasbeenthe physiological effectsof hypocalcemiaonthe immune cells,neutrophil function,andbone resorptionmarkers. Alongwithdietarychanges,behaviorhasbeenstudiedasa possible waytopreventhypocalcemia. Behavioral traitshave beenstudied,butfew correlationshave beenmade betweenacow’sbehaviorandthe developmentof hypocalcemia,especiallysubclinical hypocalcemia.Several treatmentoptionsforchronicclinical hypocalcemiahave beenimplementedto on-farmuse, includingoral calciumsupplementsandintravenousinfusionsof calcium.Overall,there isa greaterunderstandingof hypocalcemiaindairycattle.However,there isstill future researchthatneeds to be conductedinorder topreventanddetectmore hypocalcemiacasesindairycattle before ithasa negative effectonthe productionforthe farmer. Key words: dairycow,hypocalcemia,neutrophilfunction,bone resorptionmarkers,immunecells, behavior,parathyroidism
  • 4. 4 NEWHOUSE Introduction Milkproductionindairycattle has continuedtoincrease steadily overthe pastseveral decades.Since calciumisthe mainmineral componentof milk,the cow’sneedforreadilyavailable calciumatthe beginningof herlactationhasalsocontinuedtoincrease.However,if the demandbythe mammary glandfor calciumisnot met,the cow becomeshypocalcemic. Hypocalcemiaisadisorderthatdevelops whena cow isunable tomaintainadequate blood-calciumconcentrations. Eachyear,approximately5- 10% of dairycattle developclinicalhypocalcemia,andanadditional 25-50% of dairycattle are affected by subclinical hypocalcemia. Anymammal can develophypocalcemiaduringthe transitionperiod.However,dairycattle have been bredto produce such a large amountof milkthattheyare particularlysusceptible tobecoming hypocalcemic.Whenthe cow’sbodyhassucha large needforcalcium, anincrease incalcium mobilizationfromthe bone occurs.The mobilizationof calciumfrombone happensbecause dietary calciumisnot sufficienttosupportthe demandsof lactation.Hypocalcemiahasbeenlinkedto significantnegative effectsonmilkyieldandreproduction.Additionally,hypocalcemiacanlead toa varietyof secondaryhealthproblemsordisorders suchasmetritis, retainedplacenta, mastitis,ora displacedabomasum.Thisarray of issues,stemmingfromhypocalcemia, cancostdairyproducersover 250 milliondollarseachyearinthe UnitedStatesalone. MedicalImpact of Hypocalcemia Hypocalcemiais definedas the deficiencyof calciuminthe bloodstream.Thisdisordercanbe clinical in whichthe animal isphysicallydisplayingsignssuchasmuscle weaknessandadecrease inbody temperature, orsubclinical where the animalisnotshowinganyreadilyobservable symptoms. Some of the initial signsof clinical hypocalcemiacanbe excitability,hypersensitivity,andrestlessness.Once the calciumconcentrationsgetsolowthat tetanybeginstosetin,the cow may experience tachycardiaor
  • 5. 5 HYPOCALCEMIA IN DAIRY CATTLE mildhyperthermia.Asthe cow’shealthcontinuestodecline,muscleswill weakentothe point atwhich the cow will be sternallythenlaterallyrecumbent. The cow will appeartobe tremblingatfirst,butthen she will become a“downer”cowonce she has reachedthe stage of recombency. Some of the more severe caseswill exhibitsymptomssuchasconstipation,mildtoseverebloating,weakpulses,poor pupillarylightresponse,flaccidparalysis,comaorevendeath (Bovine PostparturientParesis). Most cows that sufferfromhypocalcemiawillbe diagnosedbasedontheirsymptomstheyexhibit.Since the illnessissorapidinnature, a laboratorytestisnot a feasible diagnostictool if the animal isshowing clinical symptomsalready.However,if acow has subclinical hypocalcemia,diagnosisismuchmore difficult.Subclinical hypocalcemiccowsare diagnosedafterbloodisdrawnanda laboratorytestreveals lowserumcalciumlevels (BovinePostparturientParesis). Economic Impact of Hypocalcemia It iseasyto understandthe negative effectclinical hypocalcemiccowshave onthe profitabilityof the farm.First of all,a clinical hypocalcemiccow wouldmostlikelyneedtobe treatedbya veterinarian usingan intravenousinfusionof calcium.Alongwiththe costof the veterinarytreatment,studieshave shownclinical hypocalcemiacausesadecrease in milkproduction,aswell asahighersusceptibilityto othersecondaryhealthconditions,which include:metritis,displacedabomasum, retainedplacenta, and mastitis.Additionally,withmanyof the secondaryhealthproblems,more expensesfromthe producer will be involvedforthe treatmentof thatanimal.Clearly,aclinical hypocalcemiccow canbe verycostly for a producer. Similartoclinical hypocalcemiccows, studieshave shownthat subclinical hypocalcemiccowshave a higherinstance of secondaryhealthproblems,decreasedmilkproductionandadecreasedchance of beingbredback.Since subclinical hypocalcemiaaffectsapproximatelyhalf of the cowsondairyfarmsin the UnitedStates,mostof themgoundiagnosedanduntreated.Thus,the issuesthatarise and decrease
  • 6. 6 NEWHOUSE productionresultinthe lossof over250 milliondollarseachyearinthe UnitedStatesdue to hypocalcemia. Hypocalcemiahasa huge economicimpactonthe dairy industryinthe UnitedStatesandaroundthe world.Inrecentdecades,the studyof hypocalcemiahascontinuedtogrow inorderto try and understandthe disorderbettertoreduce the amountof moneylostto thisdisorder.A lotof knowledge relatingtothe causes,prevention,andtreatmentof hypocalcemiahave beendiscoveredandcontinue to be discoveredbyscientists. Physiological Effects of Hypocalcemia Whena dairy cowexperienceshypocalcemicconditions,theyneedtocompensate forthe decreased bloodcalciumbecause calciumisa veryimportantpartof regulatingawhole hostof bodilyfunctions, includingsmoothmuscle contraction,intracellularactivity, andetc.Calciumabsorptionbythe intestine will typicallyincrease.However,the primarymode forthe bodytorestore homeostaticcalciumlevelsis throughcalciumresorptionfromthe bone. The primaryhormone that isresponsible for the mobilizationof calciumfromthe bonesat the onsetof lactationin mammalsisparathyroidhormone related-protein(PTHrP),whichis synthesizedwithinthe mammarygland and isonlydetectable inthe circulatory systemduringlactationandtimesof metastaticbone cancers.
  • 7. 7 HYPOCALCEMIA IN DAIRY CATTLE PTHrP issimilartoparathyroidhormone (PTH) andit hasbeenextensivelystudiedinthe humanand rodentmodels.However,little researchhasbeendone relatingtoitsfunctionindairycattle.Serotonin, 5-hydroxytryptamine (5-HT) regulatesthe inductionof PTHrP.The molecularmechanismsgoverningthis actionare still unknown.Manipulationof 5-HTnear the end of a pregnancyperiodmaybe a critical factor inpreventingthe onsetof hypocalcemiaduringearlylactation.5-HTisa homeostaticregulatorof the mammary gland.5-HT isproducedina two-steppathwayfromthe aminoacidL-tryptophanusing the rate-limitingenzyme tryptophanhydroxylase 1(TPH1).AfterL-tryptophanisconvertedinto5- hydroxy-L-tryptophan,itundergoesdecarboxylationtoform5-HT. Preventinghypocalcemiacouldgreatlybenefitthe dairyindustry.Cowsthatremainhealthythroughthe transitionperiodare more likelytoproduce anadequate amountof milk,aswell asanothercalf,and bothof these factorsare critical inmaintainingthe economicviabilityof the dairyfarmsandthe sustainabilityof the humanfoodproductionsystem. Neutrophil Function Martinezconducteda studythat waspublishedinthe Journal of DairyScience in2013 aboutthe effects of the neutrophil functioninhypocalcemicdairycattle.The study,conductedatthe Universityof Florida DairyUnit in Gainsville, Florida,directlycomparedthe neutrophil functionof normcalcemicandinduced subclinical hypocalcemiaintennon-pregnant,non-lactatingHolsteincows (Martinez). Amongthe most importantdatacollected,theydiscoveredthat the neutrophilfunctionwassuppressed incows withsubclinical hypocalcemia.Cowsthathadinducedsubclinical hypocalcemiahadareduced percentage of neutrophilswithphagocyticactivity.Additionally,subclinical hypocalcemiccowshada reductioninthe percentage of neutrophilswithoxidativeburstactivity.Finally,phagocytosisand oxidative burstdeclinedat72 hoursafterthe beginningof the infusioninsubclinical hypocalcemiccows, where asthose valuesbothincreasedinnormcalcemiccows (Martinez).
  • 8. 8 NEWHOUSE The main outcome of thisstudyrevealedthe dropincalciuminthe bloodthatoccurs during hypocalcemianegativelyeffectsthe neutrophilsandmakesthe cow lesslikelytofightagainst pathogenicbacteria.The depressionof bacterial killingiscausedfromthe neutrophil suppressionof phagocytosis.Thispointalsosupportsthe factthathypocalcemiccowshave an increasedinstance of secondaryhealthissues. Extracautionshouldbe takenforthese cowsinorderto preventsecondary bacterial infections. Bone Resorption Markers A studyconductedbyLiesegang,publishedinthe Journal of DairyScience in1998, exploredthe bone resorptionmarkersinhypocalcemicdairycattle.The study,conductedatthe Universityof Zurichin Switzerland,investigatedwhetherhydroxyproline,deoxypyridinoline,orthe carboxyterminal telopeptide of type Icollagencouldbe usedasmarkerstoprovide evidence of bone resorptionduring hypocalcemiaindairycows (Liesegang). Amongthe most importantdatathat was collected,cowsshowingsymptomsof hypocalcemiahad increasedurinaryhydroxyprolineconcentrationsfromparturitiontoday14. Deoxypyridinoline concentrationsinthe urine were increasedafterparturitionuntil day9and carboxyterminal telopeptidesof type Icollagenpeakedatday5. However,these valueswere the same betweencows withhypocalcemicsymptomsandcowswithout (Liesegang). The main conclusionresearchersmade wasthatassaysfor urinarydeoxypyridinoline andserum carboxyterminal telopeptideof type Icollagendeterminationsare useful toolstofollow the course of degradationof bone collagenindairycattle duringhypocalcemia. Furtherresearchcoulddevelopon- farm teststo determinelevelsof these bone resorptionmarkersinordertodeterminethe severityof a hypocalcemiccow.
  • 9. 9 HYPOCALCEMIA IN DAIRY CATTLE CalciumSignaling in Immune Cells A studypublishedinthe Journal of DairyScience in2005 by Kimuraoutlinedthe influencesof hypocalcemiaonimmune cellsindairycows. The study,conductedatthe National Animal Disease CenterinAmes,Iowa,testedif the increaseddemandforcalciuminperiparturientcowsadversely affectsintracellularcalciumstoresof immune cells (Kimura). Amongthe importantdata theycollected, researcherswere able toconclude thatintracellularcalcium storesdecreasedinperipheral bloodmononuclearcells(PBMC) before parturitionanddevelopmentof hypocalcemia. Thisisthe cause of a bluntedintracellularcalciumreleaseresponse toanimmune activationsignal.The studysuggeststhatsystemiccalciumstressprecedesmeasurable hypocalcemia, especiallyincowsthatwill developclinical hypocalcemia.PBMCintracellularcalciumstoresare amore sensitivemeasure of calciumstressesintransitioncows (Kimura). The conclusionresearchersdevelopedwiththe datafromthisstudyshowsa depletionof intracellular calciumstoresstarts several dayspriortocalvinginhypocalcemiccows.Furtherresearchshouldbe done inthisarea to develop asimple testforon-farmuse thatmeasuresPBMC.PBMCis responsible for the flux of calciumthat wouldordinarilyactivatethe cellsandpreventthe cow fromexperiencing immunosuppression (Kimura). Causes of Hypocalcemia The physiological effectsof hypocalcemiaare verycomplicated anditisdifficulttostudyjustone part of the calciumhomeostaticregulatorysystem.Since the entire processissocomplex,the causesof hypocalcemiaare hardto pinpoint.Historically,highlevelsof dietarycalcium have beenbelievedtobe the major cause of hypocalcemiaindairycattle.Scientistshave begunexploringotherfactorsthatcould contribute toa cow’srisk of developinghypocalcemia. A majorareaof nutrition relatedtothe cause of hypocalcemiaisthe DietaryCation-AnionDifference (DCAD)Theory. Hypoparathyroidism,anothercause
  • 10. 10 NEWHOUSE of hypocalcemia, hasrecentlybeenlinkedtohypocalcemiabecause itaffectsthe body’stissue sensitivitytoparathyroidhormone.Overall,understandingsome of the majorcausesof thisdisorderis an importantpart of understandinghypocalcemiaindairycattle. DCAD Theory The DietaryCation-AnionDifference Theory(DCAD) hasbecome atopicindairyscience thatis being studiedmore andmore nowadays.DCADisbasicallyanequationof the cations (potassiumandsodium) and the anions (chlorine andsulfur) inthe dietof adairycow ina relationshipsuchas ( 𝑁𝑎 + 𝐾) − (𝐶𝑙 + 𝑆). DCAD isresponsibleforinfluencingthe animal’sacid-basehomeostasis,calciumstatusaround calving,andmineral elementutilization.Previousstudieshave showndecreasingthe DCADimproves calciumhomeostasisatthe onsetof lactation.Additionally,the riskof developinghypocalcemiais greatestincowsin a state of metabolicalkalosis,whichisinducedfromfeedingahigh-DCADdiet. A studyconductedin2005 byLean was publishedinthe Journal of DairyScience,revisitedprevious workrelatedtothe DCADTheory.The study,conductedat the Bovine ResearchAustralasiainAustralia, aimedtoexamine whichformof the DCADequationprovidedthe bestestimateof hypocalcemiarisk and to clarifyrolesof calcium,magnesium, andphosphorusconcentrationsof twopre-partumdietsin the pathogenesisof hypocalcemia (Lean). Amongthe most importantdatathe researchersfound,hypocalcemiariskwashighest withpre-partum dietaryconcentrations of 1.35%calcium.Additionally,increasingpre-partumdietarymagnesium concentrationshadthe largesteffectondecreasingincidence inhypocalcemia.Finally,increasing dietaryphosphorusconcentrationspre-partumincreasedthe riskof hypocalcemia (Lean). The main suggestionresearchersmade toproducerswasthe datastronglysupportsthe needto evaluate macromineral nutritionapartfromDCAD of the diet. It iscritical for producerstoassessand control the levelsof dietarymacromineralsincludedinthisstudyof the pre-partumdietinorderto
  • 11. 11 HYPOCALCEMIA IN DAIRY CATTLE preventthe instancesof hypocalcemiainthe herd. The diettakingDCADlevelsintoaccountinthisstudy isso far the bestmodel currentlyavailable forpredictinghypocalcemia incidence indairycattle (Lean). Hypoparathyroidism A studypublishedinthe Journal of DairyScience in2013 conductedby Goff aimedtolookat the effect of high-DCADdietsfedtopre-partumcowstosee if itreducestissue sensitivitytothe parathyroid hormone (PTH),inducingapseudohypoparathyroid state thatdiminishescalciumhomeostatic responses.The study,conductedatthe UnitedStatesDepartmentof Agriculture –Agricultural Research Service inAmes,Iowa,directlycomparedcowsfedlow-DCADandhigh-DCADdietstoinduce a compensatedmetabolicalkalosisandacidosisstate,respectively,followedbysyntheticPTHinjections (J. P. Goff). Amongthe most importantdatatheycollected,theynoticedcowsfedthe high-DCADdiethadplasma calciumconcentrationsthatincreasedata much lowerrate.Additionally,the cowsthatwere fedthe high-DCADdietproducedsignificantlyless1,25-dihydroxyvitaminDinresponse tothe PTH injections than the cowsthat were fedthe low- DCAD diet.Finally,the cowsthatwere fedthe high-DCADdiethad numericallylowerserum concentrationsof the bone resorption markercarboxyterminal telopeptide of type 1 collagenthanthe cowsfedthe low-DCADdiet.However,the numbers were notstatisticallydifferent (J.P. Goff).
  • 12. 12 NEWHOUSE Researchersinthisstudymade one mainsuggestiontodairyproducerstotry anddecrease instancesof hypocalcemiaintheircattle.Itisimportantthatcowsthat are nearingparturition,especially multiparouscows,are consuminglow-DCADdiets.Low-DCADdietscanincrease the intestinal absorptionof calcium, aswell asenhance the release of calciumfrombones.AccordingtoGoff, “because cowsfedlow-DCADdietsdoexcretemore calciumintheirurine,ithasbeensuggestedthat renal reabsorptionof thispotentialpool of calcium(5-7g of Ca/d) couldprovide the calciumneededto preventthe developmentof hypocalcemiaandmilkfever.” Prevention of Hypocalcemia Preventingclinical andsubclinical hypocalcemiacasesinadairyherdis the keyto reducingthe productionlossesfromthe effectedcows. Bypreventingthe hypocalcemicissuesfromoccurring,the cow’schancesof havingsecondaryhealthissuesare eliminatedaswell.Several wayshypocalcemiais beingpreventedisthroughthe studyof a cow’sbehavioraroundthe transitionperiodandthroughthe manipulationof the potassiumlevelsinthe cow’sdiet. Effectson Behavior A 2011 study,publishedinthe Journal of DairyScience byJawor,aimedtodescribe the associationsof subclinical hypocalcemiawithmilkyield,feeding,drinkingandrestingbehaviorduringthe periodaround calving.Thisinformationcouldhelpproducerspredictwhencowsare beingaffectedbysubclinical hypocalcemiabasedontheirbehaviors.The study,conductedatthe Universityof BritishColumbia’s DairyEducationand ResearchCentre,directlycomparedthese behaviorsinHolsteindairycowswhich had subclinical hypocalcemiawith control cows (Jawor). Amongthe importantdata theycollected,cowswithsubclinical hypocalcemiaproducedanaverage of 5.7 kg/dmore milkduringweeks2,3, and 4 of lactationcomparedto control cows.Also,hypocalcemic cowsthat were intheirthirdlactationsustainedgreatermilkyieldsthroughout280 DIM. Additionally,
  • 13. 13 HYPOCALCEMIA IN DAIRY CATTLE dry matterintake was,onaverage,1.7 kg/dgreaterduringthe weeks -2and -1 and fewervisitstothe waterand feedbinsoccurredinthe firstfew weeksaftercalvingamongcowswithsubclinical hypocalcemia.Finally,the cowswithsubclinical hypocalcemiaonaverage stoodfor2.6 h longerduring the 24-hour periodbefore calvingand2.7 h lessstandingduringd+1 (Jawor). The researchersmade twomainsuggestionstodairyproducersrelatingtohypocalcemiccows’behavior. First,dairycattle withsubclinical hypocalcemiaduringthe 24-hperiodpostpartumdidnotexhibitany majorchangesin productionorbehaviorthatwouldtypicallybe associatedwithpoorhealth.Forthis reason,cowsneedtobe closelymonitoredduringthistime periodincase symptomsdoappear. Secondly,the resultsrelatedtothe amountof tripsto the feedandwaterbinspost-partumdisplayed the importance of ensuringcowshave adequate accesstofeedinganddrinkingareasduringthe period followingcalving. Thisisnecessaryinorderto allow the cowsto meettheirnutrientrequirements. Therefore,itisimportanttomanage the pensof freshcowscloselytoensure a low stockingdensity. DietaryPotassium (K) A studyconductedbyR. L. Horst in 1997, publishedinthe Journal of DairyScience, lookedatstrategies for preventinghypocalcemiaindairycattle.The study,conductedatthe National AnimalDiseaseCenter inAmes,Iowa,studiedwaystominimizethe effectsof dietarypotassiumonhypocalcemiaincidences (Horst). Amongthe most importantdatacollected,Horstfounddirectevidence thatcowsfedadietlow in potassiumandsodiumhave lessmilkfeverthanthose ondietshighinKor Na. Second,overfertilization of alfalfawithKresultsinplantswithhighconcentrationsof Kthat are detrimental tothe healthof the periparturientdairycow.Finally,since manydairyproducerspurchase aportionof theirfeedstuffs,soil K concentrationscontinue tobuildovertime asmostof the K broughtontothe farmin purchasedfeed remainsonthe farm (Horst).
  • 14. 14 NEWHOUSE Researchersmade one mainsuggestionwiththisstudyrelatingtodietaryK.Itis importanttofeedlow levelsof dietaryKindairycattle rationsbecause Kplaysa significantrole inpredisposingcowsto hypocalcemia.The researchersalsoshowedthe importance of the acid-base balanceof the dieton calciummetabolism.Finally,Horstsuggested,“future researchshouldfocusoneffective methodsfor managingdietaryK,resultingindecreasedreliance onanionicsalts.” Treatment of Hypocalcemia The amount of researchbeingdone related tothe treatmentof clinical andsubclinical hypocalcemiahas beenslowlydecreasingoverthe yearsbecause of the factthat causesand prevention forhypocalcemia are becomingthe focus. The specifictype of treatmentforhypocalcemiadependsonthe severityof the disorder.A standingcowwouldbe treateddifferentlythanacow whichisunable tostandup on her own(Oetzel). Cowsthat are experiencingsubclinical hypocalcemiaorare displayingclinical signsof hypocalcemia and are still able tostandon theirownare in the verymildstagesof the disorder.Atthispoint,cowscan be treatedwithoral calciumsupplementation.Withinahalf hourafterthe supplementation,the cowis able to absorban effectiveamountof calciumintoherbloodstream. The calciumconcentrationsinthe cow’sbloodwill remainelevatedfromthe supplementationfor4-6hours afterward (Oetzel). In more severe hypocalcemiacases,whenthe cow isunable tostand,a fastertreatmentisrequired.The mostrapid treatmentfortreatingseverelyhypocalcemiccowsiswithintravenouscalciuminfusions. Withthistreatment,calciumlevelsinthe bloodare restoredalmostimmediately.The downfalltothis type of treatmentisthat bloodcalciumconcentrationsare raisedtoextremelyandpotentially dangerouslevels.Therefore,if acowis experiencingseverehypocalcemia,aveterinarianshouldbe involvedinthe treatment.
  • 15. 15 HYPOCALCEMIA IN DAIRY CATTLE SecondaryHealth Effects A wide arrayof issuescanstemfromsubclinical andclinical hypocalcemiaindairycattle.Firstof all, studieshave shownmetabolicdisordersimpairimmunefunctionwhichpredisposesthe cow touterine infectionsandmastitisfollowingparturitionandatthe beginningof theirlactation.Additional researcherhaslinkedthe instancesof ketosiswithsubclinical hypocalcemia.Finally,retainedplacenta and endometritishashighersusceptibilityratesincowsthathave had hypocalcemiaatthe beginningof theirlactation.If a cow developshypocalcemia,aproducershouldtake extracare to insure the riskof any of the secondaryissuesisreduced.A veterinariancanhelpdetermine the besttreatmentand aftercare fora hypocalcemiccow (J.P.Goff). Conclusion Subclinical andclinical hypocalcemiaare majorhealthproblemsinamajorityof dairycattle and oftengo untreated.Cowswithsubclinical hypocalcemiatypicallydonotshow signsorsymptomsuntil the problemissevere.A cow’sbehaviorshouldbe closelymonitoredbefore andafterparturition,and propermanagementstrategiesshouldbe enforcedondairyfarms.Takingthese simple stepsasa producercouldendup saving themthousandsof dollarseveryyearfromthe earlydetectionof hypocalcemiainthe cows. Byfocusingthe effortsonthe preventionof hypocalcemia,throughfocusing on majorfactors contributingtohypocalcemia,suchaspseudohypoparathyoidism,the instancescanbe greatlydecreased.Inall,thiswouldbe beneficialtodairycowsand producersworldwide. Future Research The study of clinical andsubclinical hypocalcemiahasbeenincreasingoverthe lastfew decades.Thisis due to the large economicimpactthat the disorderhason dairyindustry.However,studiesare moving away fromthe treatmentof hypocalcemiaandshiftingtowardfocusingonthe causesandpreventionof the disorder. A lotof researchshould continued tobe done focusing onthe developmentof on-farm
  • 16. 16 NEWHOUSE detectionsforhypocalcemiaandpreventionstoaidthe producerand minimize productionlossesinthe yearsto come.Overall,hypocalcemiaisavery importantdisordertostudy inthe dairyindustrytohelp make the industrymore productive asa whole.
  • 17. 17 HYPOCALCEMIA IN DAIRY CATTLE References Bovine Postparturient Paresis. 2015. VetCentric. online.1 February 2015.<http://www.vetmedclinic.com/?p=279>. Goff, J. P. "Diet-induced pseudohypoparathyroidism:A hypocamcemia and milk fever risk factor." Journal of Dairy Science 97 (2014): 1520-1528.In print. 1 February 2015.<http://dx.doi.org/10.3168/jds.2013-7467>. Goff, Jesse P. Impact of Milk Fever and Hypocalcemia on Reproductive Performance of the Dairy Cow. 26 January 2011.Iowa State University.online.1 February 2015. <http://www.extension.org/pages/26036/impact- of-milk-fever-and-hypocalcemia-on-reproductive-performance-of-the-dairy-cow#.VQ8L7454pqI>. Horst, R. L. "Strategies for Preventing Milk Fever in Diary Cattle." Journal of Dairy Science 80 (1997):1269-1280.In print. 1 February 2015. Jawor, P. E. "Associations of subclinical hypocalcemia atcalvingwith milk yield,and feeding, drinking,and standing behaviors around partrition in Holstein cows." Journal of Dairy Science 95.3 (2011): 1240-1248.in print.1 February 2015.<http://dx.doi.org/10.3169/jds.2011-4586>. Kimura,K. "Parturition and Hypocalcemia Blunts CalciumSignalsin ImmuneCells of Diary Cattle." Journal of Dairy Science 89.7 (2006): 2588-2598.in print.1 February 2015. <http://www.sciencedirect.com/science/article/pii/S0022030206723359>. Lean, I. J. "Hypocalcemia in Diary Cows: Meta-analysisand Dietary Cation Anion Differnce Theory Revisited." Journal of Dairy Science 89.2 (2006): 669-684.in print. 1 February 2015. <http://www.sciencedirect.com/science/article/pii/S0022030206721300>. Liesegang, A. "Comparison of BoneResorption Markers DuringHypocalcemia in Dairy Cattle." Journal of Dairy Science 81.10 (1998): 2614-2622.in print.1 February 2015. <http://www.sciencedirect.com/science/article/pii/S0022030298758199>. Martinez, N. "Effects of induced subclinical hypocalcemiaon physiological responses and neutrophil function in dary cows." Journal of Dairy Science 97 (2014):874-887.In print.1 February 2015. <http://dx.doi.org/10.3168/jds.2013-7408>. Oetzel, Garrett R. "MinimizingHypocalcemia DuringEarly Lactation." Tri-State Dairy Nutrition Conference (2013): 23-34. in print.1 February 2015. <http://tristatedairy.osu.edu/Proceedings%202013/Garrett%20Oetzel.pdf>.