Hipokalsemi, Reprodüktif Sisteme Etkisi ve Klinik Yönetimi
Özet
Hipokalsemi (süt humması), yüksek verimli sütçü sığırlarda postpartum dönemde aniden artan kalsiyum ihtiyacına bağlı olarak şekillenen, akut ve potansiyel olarak ölümcül bir metabolizma hastalığıdır. Vücutta kas kontraksiyonları, sinir iletimi, enzim aktivasyonları ve bağışıklık fonksiyonları gibi birçok kritik fizyolojik süreçte görev alan kalsiyumun kan plazmasındaki düzeyi dar sınırlar arasında paratiroid hormonu (PTH) ve vitamin D aracılığıyla hassas bir şekilde regüle edilir. Ancak doğumla birlikte kolostrum ve süt üretimi için kalsiyum havuzundan aşırı tüketim yapılması, adaptasyon mekanizmalarının yetersiz kalması durumunda klinik veya subklinik hipokalsemiye yol açar. İleri yaş, rasyondaki yüksek katyon oranına bağlı metabolik alkalozis, hipomagnezemi ve yüksek fosfor seviyeleri kalsiyum hemostazisini olumsuz etkileyen başlıca faktörlerdir. Hipokalsemi, düz ve iskelet kaslarının kontraksiyon gücünü azaltarak myometriyum tonusunu düşürür; bu durum güç doğum, prolapsus uteri ve retensiyo sekundinarum riskini doğrudan artırır. Ayrıca nötrofil fonksiyonlarını ve hücresel bağışıklığı baskılayarak uterus involüsyonunun gecikmesine ve şiddetli uterus enfeksiyonlarına zemin hazırlar. Ovaryum aktivitelerinin yeniden başlamasını geciktiren ve fertilite parametrelerini olumsuz etkileyen bu hastalık ciddi ekonomik kayıplara neden olur. Korunmada ise gebeliğin son haftalarında rasyona anyonik tuzlar ilave edilmesi veya kalsiyum düzeyinin düşük tutulması kritik stratejilerdir.
Hypocalcemia (milk fever) is an acute and potentially fatal metabolic disease in high-producing dairy cows, triggered by the sudden increase in calcium demand during the postpartum period. The plasma level of calcium, which plays a critical role in various physiological processes such as muscle contractions, nerve conduction, enzyme activation, and immune functions, is precisely regulated within narrow limits by parathyroid hormone (PTH) and vitamin D. However, excessive depletion from the calcium pool for colostrum and milk production at calving leads to clinical or subclinical hypocalcemia if adaptation mechanisms fail. Advanced age, metabolic alkalosis due to high dietary cation-anion difference, hypomagnesemia, and high phosphorus levels are the primary factors negatively impacting calcium homeostasis. Hypocalcemia reduces the contraction strength of smooth and skeletal muscles, lowering myometrial tone, which directly increases the risks of dystocia, uterine prolapse, and retained fetal membranes. Furthermore, by suppressing neutrophil functions and cellular immunity, it delays uterine involution and predisposes cows to severe uterine infections. This disease, which also delays the resumption of ovarian activity and compromises fertility parameters, causes significant economic losses. For prevention, adding anionic salts to prepartum diets or restricting dietary calcium levels during late pregnancy represent critical strategies.
Referanslar
Başoğlu A, Sevinç M. Evcil hayvanlarda metabolik ve endokrin hastalıklar. Konya: Pozitif Matbaacılık; 2004.
Dabak M. Kalsiyum ve fosfor metabolizması bozukluklarının etiyopatogenezi. Türkiye Klinik Veteriner Bilimleri Dergisi, Sığırların Metabolizma Hastalıkları Özel Sayısı, 2011;2: 102-109.
Kalaycıoğlu L, Serpek B, Nizamlıoğlu M, et al. Biyokimya, (Üçüncü Baskı). Ankara: Nobel Yayın Dağıtım Ltd; 2006.
Yıldız R, Ülkü E. Çiftlik hayvanlarında kalsiyum, fosfor, magnezyum ve sodyum bozuklukları. Şen İ, editör. Çiftlik Hayvanlarında Sıvı ve Elektrolit Tedavisi. 1. Baskı. Ankara: Türkiye Klinikleri; 2021. p.53-59.
Noyan A. Yaşamda ve Hekimlikte Fizyoloji. 14. Baskı. Ankara: Meteksan Anonim Şirketi; 2004.
Wilkens MR, Nelson CD, Hernandez LL, et al. Symposium review: Transition cow calcium homeostasis—Health effects of hypocalcemia and strategies for prevention. Journal of dairy science. 2020;103(3):2909-2927. doi:10.3168/jds.2019-17268.
Seifi HA, Kia S. Subclinical hypocalcemia in dairy cows: Pathophysiology, consequences and monitoring. Iranian Journal of Veterinary Science and Technology. 2017;9(2): 1-15. doi:10.22067/veterinary.v9i2.69198.
Goff JP. The monitoring, prevention, and treatment of milk fever and subclinical hypocalcemia in dairy cows. The veterinary journal. 2008;176(1):50-57. doi:10.1016/j.tvjl.2007.12.020.
Goff JP. Calcium and magnesium disorders. Veterinary Clinics: Food Animal Practice. 2014;30(2): 359-381. doi:10.1016/j.cvfa.2014.04.003.
Murray RD, Horsfield JE, McCormick WD, et al. Historical and current perspectives on the treatment, control and pathogenesis of milk fever in dairy cattle. Veterinary Record. 2008;163(19): 561-565. doi:10.1136/vr.163.19.561.
DeGaris P, Lean I. Milk fever in dairy cows: a review of pathophysiology and control principles. The veterinary journal 2008;176(1): 58–69. doi:10.1016/j.tvjl.2007.12.029.
Martinez N, Risco CA, Lima FS, et al. Evaluation of peripartal calcium status, energetic profile, and neutrophil function in dairy cows at low or high risk of developing uterine disease. Journal of Dairy Science. 2012;95(12): 7158–7172. doi:10.3168/jds.2012-5812.
Martín-Tereso J, Martens H. Calcium and magnesium physiology and nutrition in relation to the prevention of milk fever and tetany (dietary management of macrominerals in preventing disease). Veterinary Clinics: Food Animal Practice. 2014;30(3): 643-670. doi:10.1016/j.cvfa.2014.07.007.
Oetzel GR. Non-infectious diseases: Milk fever. Encyclopedia of Dairy Sciences. Fuquay JW, Fox PF, McSweeney PLH. 2011.
Fikadu W, Tegegne D, Abdela N, et al. Milk fever and its economic consequences in dairy cows: a review. Global Veterinaria, 2016;16(5): 441-452. doi:10.5829/idosi.gv.2016.16.05.103137.
Serrenho RC, DeVries TJ, Duffield TF, et al. Graduate Student Literature Review: What do we know about the effects of clinical and subclinical hypocalcemia on health and performance of dairy cows?. Journal of Dairy Science. 2021;104(5): 6304-6326. doi:10.3168/jds.2020-19371.
Caixeta LS, Ospina PA, Capel MB, et al. Association between subclinical hypocalcemia in the first 3 days of lactation and reproductive performance of dairy cows. Theriogenology. 2017;94: 1-7. doi:10.1016/j.theriogenology.2017.01.039.
McArt JAA, Neves RC. Association of transient, persistent, or delayed subclinical hypocalcemia with early lactation disease, removal, and milk yield in Holstein cows. Journal of dairy science. 2020;103(1): 690-701. doi:10.3168/jds.2019-17191.
Caixeta LS, Omontese BO. Monitoring and improving the metabolic health of dairy cows during the transition period. Animals, 2021;11(2): 352. doi:10.3390/ani11020352.
Venjakob PL, Pieper L, Heuwieser W, et al. Association of postpartum hypocalcemia with early-lactation milk yield, reproductive performance, and culling in dairy cows. Journal of dairy science. 2018;101(10): 9396-9405. doi:10.3168/jds.2017-14202.
Venjakob PL, Borchardt S, Heuwieser W. Hypocalcemia—Cow-level prevalence and preventive strategies in German dairy herds. Journal of dairy science. 2017;100(11): 9258-9266. doi:10.3168/jds.2016-12494.
Goff JP, Horst RL, Jardon PW, et al. Field trials of an oral calcium propionate paste as an aid to prevent milk fever in periparturient dairy cows. Journal of Dairy Science. 1996;79(3): 378-383. doi:10.3168/jds.S0022-0302(96)76375-0.
Chapinal N, Carson M, Duffield TF, et al. The association of serum metabolites with clinical disease during the transition period. Journal of dairy science. 2011;94(10): 4897-4903. doi:10.3168/jds.2010-4075.
Reinhardt TA, Lippolis JD, McCluskey BJ, et al. Prevalence of subclinical hypocalcemia in dairy herds. The Veterinary Journal. 2011;188(1): 122-124. doi:10.1016/j.tvjl.2010.03.025.
Rodríguez EM, Arís A, Bach A. Associations between subclinical hypocalcemia and postparturient diseases in dairy cows. Journal of Dairy Science. 2017;100(9): 7427-7434. doi:10.3168/jds.2016-12210.
Jeong JK, Kang HG, Kim IH. Associations between serum calcium concentration and postpartum health and reproductive performance in dairy cows. Animal reproduction science. 2018;196: 184-192. doi:10.1016/j.anireprosci.2018.08.006.
Çitil M. Süt hummasının klinik ve subklinik tanısı. Türkiye Klinik Veteriner Bilimleri Dergisi, Sığırların Metabolizma Hastalıkları Özel Sayısı. 2011;2: 110-117.
Venjakob PL, Staufenbiel R, Heuwieser W, et al. Serum calcium dynamics within the first 3 days in milk and the associated risk of acute puerperal metritis. Journal of dairy science, 2019;102(12):11428-11438. doi:10.3168/jds.2019-16721.
Baştan A, Gürbulak K. Metabolik Bozukluklar. Çiftlik Hayvanlarında Doğum ve Jinekoloji. Malatya: Medipres; 2012. p. 373-408.
Oetzel GR, Goff JP. Milk fever (parturient paresis) in cows, ewes, and doe goats. Current Veterinary Therapy: Food Animal Practice, 5th ed. (David E. Anderson, Michael Rings eds.), Saunders, Philadelphia; 2008. p. 130–134.
Sweeney BM, Martens EM, Felippe MJ, et al. Impacts and evaluation of subclinical hypocalcemia in dairy cattle. Feed Dealers Seminars. 2014; 1-8.
Kimura KAYOKO, Reinhardt TA, Goff JP. Parturition and hypocalcemia blunts calcium signals in immune cells of dairy cattle. Journal of dairy science. 2006;89(7): 2588-2595. doi:10.3168/jds.S0022-0302(06)72335-9.
Oetzel GR. Monitoring and testing dairy herds for metabolic disease. Veterinary Clinics: Food Animal Practice. 2004;20(3): 651-674. doi:10.1016/j.cvfa.2004.06.006.
Xiao X, Xu C, Shu S, et al. Critical thresholds of ion concentration in plasma for hypocalcemia prediction in dairy cows using receiver operating characteristic (ROC) analysis. Indian Journal of Animal Research. 2019;53(11): 1526-1529. doi:10.18805/ijar.v0iOF.8476.
Neves RC, Leno BM, Stokol T, et al. Risk factors associated with postpartum subclinical hypocalcemia in dairy cows. Journal of Dairy Science. 2017;100(5): 3796-3804. doi:10.3168/jds.2016-11970.
Huntjens MF, Aalseth EP. Caring for transition cows. Hoards Dairyman Books. Illustrated, 2005; 17-21.
Tadesse E, Belete L. An Overview on milk fever in dairy cattle in and around West Shoa. World Journal of Biology and Medical Science. 2015;2: 115-125.
Ok M. Süt hummasının tedavisi ve tedavide başarısızlığın nedenleri. Türkiye Klinik Veteriner Bilimleri Dergisi, Sığırların Metabolizma Hastalıkları Özel Sayısı. 2011;2(2): 118-122.
Hernández-Castellano LE, Hernandez LL, Bruckmaier RM. Endocrine pathways to regulate calcium homeostasis around parturition and the prevention of hypocalcemia in periparturient dairy cows. Animal. 2020;14(2): 330-338. doi:10.1017/S1751731119001605.
Oetzel GR. Improving reproductive performance in dairy cattle via milk fever prevention. In American Association of Bovine Practitioners Conference Proceedings. 1995; 52-59.
Priyantha MAR. Overview of pathogenesis, control and management of milk fever in cattle in Sri Lanka. Corpus Journal of Dairy and Veterinary Science. 2021;2: 1021.
Mulligan F, O'Grady L, Rice D, et al. Production diseases of the transition cow: Milk fever and subclinical hypocalcaemia. Irish Veterinary Journal. 2006;59(12): 697-702. doi:10.1016/j.tvjl.2007.12.018.
Chamberlin WG, Middleton JR, Spain JN, et al. Subclinical hypocalcemia, plasma biochemical parameters, lipid metabolism, postpartum disease, and fertility in postparturient dairy cows. Journal of dairy science. 2013;96(11): 7001-7013. doi:10.3168/jds.2013-6901.
Tsiamadis V, Siachos N, Panousis N, et al. Association of post-partum serum Ca patterns with reproduction in Holstein cows. Theriogenology, 2022;184: 73-81. doi:10.1016/j.theriogenology.2022.03.002.
Esposito G, Irons PC, Webb EC, et al. Interactions between negative energy balance, metabolic diseases, uterine health and immune response in transition dairy cows. Animal reproduction science. 2014;144(3-4): 60-71. doi:10.1016/j.anireprosci.2013.11.007.
Goff JP. Invited review: Mineral absorption mechanisms, mineral interactions that affect acid–base and antioxidant status, and diet considerations to improve mineral status. Journal of Dairy Science. 2018;101.4: 2763-2813. doi:10.3168/jds.2017-13112.
Horst RL, Jorgensen NA. Elevated plasma cortisol during induced and spontaneous hypocalcemia in ruminants. Journal of dairy science, 1982;65(12): 2332-2337. doi:10.3168/jds.S0022-0302(82)82505-8.
Pascottini OB, LeBlanc SJ. Modulation of immune function in the bovine uterus peripartum. Theriogenology. 2020;150: 193-200. doi:10.1016/j.theriogenology.2020.01.042.
LeBlanc SJ. Relationships between metabolism and neutrophil function in dairy cows in the peripartum period. Animal. 2020;14(S1): 44-54. doi:10.1017/S1751731119003227.
Gallo EM, Canté-Barrett K, Crabtree GR. Lymphocyte calcium signaling from membrane to nucleus. Nature immunology. 2006;7(1): 25-32. doi:10.1038/ni1295.
Ducusin RJT, Uzuka Y, Satoh E, et al. Effects of extracellular Ca2+ on phagocytosis and intracellular Ca2+ concentrations in polymorphonuclear leukocytes of postpartum dairy cows. Research in Veterinary Science. 2003;75(1): 27-32. doi:10.1016/s0034-5288(03)00038-9.
Musal B, Köker A. Güç Doğum. Çiftlik Hayvanlarında Doğum ve Jinekoloji. Malatya: Medipres; 2012, 225-293.
Alaçam E. Evcil Hayvanlarda Doğum ve İnfertilite 8. Baskı. Medisan Yayınevi, Ankara, 2015.
Gürbulak K, Bademkıran S. Puerperal Dönem Sorunları. Çiftlik Hayvanlarında Doğum ve Jinekoloji. Malatya: Medipres; 2012. p. 345-371.
Kimura M, Masuda T, Yamada K, et al. Novel diphenylalkyl piperazine derivatives with dual calcium antagonistic and antioxidative activities. Bioorganic & medicinal chemistry letters. 2002;12(15): 1947-1950. doi:10.1016/S0960-894X(02)00322-0.
Melendez P, Donovan GA, Risco CA, et al. Plasma mineral and energy metabolite concentrations in dairy cows fed an anionic prepartum diet that did or did not have retained fetal membranes after parturition. American Journal of Veterinary Research, 2004;65(8): 1071-1076. doi:10.2460/ajvr.2004.65.1071.
Gunnink JW. Prepartum leucotytic activity and retained placenta. Veterinary Quarterly. 1984;6: 52-54. doi:10.1080/01652176.1984.9693910.
Bostedt H, Huber C. Long term analysis of blood samples from cows with postparturient paresis and data on their fertility. Vlaams-Diergen-eeskundig Tijdschrift. 1986;55: 121–134.
Kamgarpour R, Daniel RCW, Fenwick DC, et al. Post partum subclinical hypocalcaemia and effects on ovarian function and uterine involution in a dairy herd. The Veterinary Journal. 1999;158(1): 59-67. doi:10.1053/tvjl.1999.0348.
Heppelmann M, Krach K, Krueger L, et al. The effect of metritis and subclinical hypocalcemia on uterine involution in dairy cows evaluated by sonomicrometry. Journal of Reproduction and Development. 2015;61(6): 565–569. doi:10.1262/jrd.2015-015.
Whiteford LC, Sheldon IM. Association between clinical hypocalcaemia and postpartum endometritis. Veterinary Record. 2005;157(7): 202-203. doi:10.1136/vr.157.7.202.
Öcal H, Kalkan C. Puerperal Dönem Fizyolojisi. Çiftlik Hayvanlarında Doğum ve Jinekoloji. Malatya: Medipres; 2012. p. 313-343.
Sheldon IM, Williams EJ, Miller AN, et al. Uterine diseases in cattle after parturition. Veterinary Journal. 2008;176: 115–121. doi:10.1016/j.tvjl.2007.12.031.
Brodzki P, Brodzki A, Kurek Ł, et al. Effect of uterine inflammatory status as well as calcium and magnesium concentrations on the uterine involution process in dairy cows. Annals of Animal Science. 2016;16(3): 759-768. doi:10.1515/aoas-2015-0098.
Kasimanickam R, Duffield TF, Foster RA, et al. Endometrial cytology and ultrasonography for the detection of subclinical endometritis in postpartum dairy cows. Theriogenology. 2004;62(1-2): 9-23. doi:10.1016/j.theriogenology.2003.03.001.
Risco CA, Drost M, Thatcher WW, et al. Effects of calving-related disorders on prostaglandin, calcium, ovarian activity and uterine involution in postrartum dairy cows. Theriogenology. 1994;42(1): 183-203. doi:10.1016/0093-691x(94)90675-9.
Danet-Desnoyers G, Meyer MD, Gross TS, et al. Regulation of endometrial prostaglandin synthesis during early pregnancy in cattle: effects of phospholipases and calcium in vitro. Prostaglandins. 1995;50(5-6): 313-330. doi:10.1016/0090-6980(95)00131-x.
Burns PD, Hayes SH, Silvia WJ. Cellular mechanisms by which oxytocin mediates uterine prostaglandin F2α synthesis in bovine endometrium: role of calcium. Domestic Animal Endocrinology. 1998;15(6): 477-487. doi:10.1016/s0739-7240(98)00036-8.
Ribeiro ES, Lima FS, Greco LF, et al. Prevalence of periparturient diseases and effects on fertility of seasonally calving grazing dairy cows supplemented with concentrates. Journal of dairy science. 2013;96(9): 5682-5697. doi:10.3168/jds.2012-6335.
Sheldon IM, Dobson H. Postpartum uterine health in cattle. Animal reproduction science. 2004;82: 295-306. doi:10.1016/j.anireprosci.2004.04.006.
Williams EJ, Fischer DP, Pfeiffer DU, et al. Clinical evaluation of postpartum vaginal mucus reflects uterine bacterial infection and the immune response in cattle. Theriogenology. 2005;63(1): 102-117. doi:10.1016/j.theriogenology.2004.03.017.
Hammon D, Evjen IM, Dhiman TR, et al. Neutrophil function and energy status in Holstein cows with uterine health disorders. Veterinary immunology and immunopathology. 2006;113(1-2): 21-29. doi:10.1016/j.vetimm.2006.03.022.
Lundqvist-Gustafsson H, Gustafsson M, Dahlgren C. Dynamic Ca2+ changes in neutrophil phagosomes A source for intracellular Ca2+ during phagolysosome formation?. Cell calcium. 2000;27(6): 353-362. doi:10.1054/ceca.2000.0130.
Clemens RA, Lowell CA. Store‐operated calcium signaling in neutrophils. Journal of leukocyte biology. 2015;98(4): 497-502. doi:10.1189/jlb.2MR1114-573R.
Beagley JC, Whitman KJ, Baptiste KE, et al. Physiology and treatment of retained fetal membranes in cattle. Journal of veterinary internal medicine. 2010;24(2) 261-268. doi:10.1111/j.1939-1676.2010.0473.x.
Martinez NLDP, Sinedino RS, Bisinotto ES, et al. Effect of induced subclinical hypocalcemia on physiological responses and neutrophil function in dairy cows. Journal of Dairy Science. 2014;97:874–887. doi:10.3168/jds.2013-7408.
Leroy JLMR, Opsomer G, Van Soom A, et al. Reduced fertility in High‐yielding dairy cows: Are the oocyte and embryo in danger? Part I the importance of negative energy balance and altered corpus luteum function to the reduction of oocyte and embryo quality in High‐yielding dairy cows. Reproduction in domestic animals. 2008;43(5): 612-622. doi:10.1111/j.1439-0531.2007.00960.x.
Jonsson NN, Daniel RCW. Effects of hypocalcaemia on blood flow to the ovaries of the sheep. Journal of Veterinary Medicine Series A. 1997;44(1‐10): 281-287. doi:10.1111/j.1439-0442.1997.tb01112.x.
Gild C, Alpert N, Van Straten M. The influence of subclinical hypocalcemia on production and reproduction parameters in Israeli dairy herds. Israel Journal of Veterinary Medicine. 2015;70(1): 16-21.
Borsberry S, Dobson H. Periparturient diseases and their effect on reproductive performance in five dairy herds. The Veterinary Record, 1989;124(9): 217-219. doi:10.1136/vr.124.9.217.
Sedo SU, Rosa D, Mattioli G, et al. Associations of subclinical hypocalcemia with fertility in a herd of grazing dairy cows. Journal of dairy science. 2018;101(11): 10469-10477. doi:10.3168/jds.2017-14242.
Chapinal N, Carson ME, LeBlanc SJ, et al. The association of serum metabolites in the transition period with milk production and early-lactation reproductive performance. Journal of Dairy science. 2012;95(3): 1301-1309. doi:10.3168/jds.2011-4724.
McNally JC, Crowe MA, Roche JF, et al. Effects of physiological and/or disease status on the response of postpartum dairy cows to synchronization of estrus using an intravaginal progesterone device. Theriogenology. 2014;82(9): 1263-1272. doi:10.1016/j.theriogenology.2014.08.006.
Neves RC, Leno BM, Curler MD, et al. Association of immediate postpartum plasma calcium concentration with early-lactation clinical diseases, culling, reproduction, and milk production in Holstein cows. Journal of dairy science. 2018;101(1): 547-555. doi:10.3168/jds.2017-13313.
Martinez N, Sinedino LDP, Bisinotto RS, et al. Effects of oral calcium supplementation on mineral and acid-base status, energy metabolites, and health of postpartum dairy cows. Journal of Dairy Science. 2016;99(10): 8397-8416. doi:10.3168/jds.2015-10527.
