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(Milk Fever) in Dairy Cows Jesse Paul Goff Iowa State University

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(Milk Fever) in Dairy Cows Jesse Paul Goff Iowa State University Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1986 Prevention of parturient paresis (milk fever) in dairy cows Jesse Paul Goff Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Animal Sciences Commons, and the Veterinary Medicine Commons Recommended Citation Goff, Jesse Paul, "Prevention of parturient paresis (milk fever) in dairy cows " (1986). Retrospective Theses and Dissertations. 8001. https://lib.dr.iastate.edu/rtd/8001 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. INFORMATION TO USERS This reproduction was made from a copy of a manuscript sent to us for publication and microfilming. While the most advanced technology has been used to pho­ tograph and reproduce this manuscript, the quality of the reproduction is heavily dependent upon the quality of the material submitted. Pages in any manuscript may have indistinct print. In all cases the best available copy has been filmed. The following explanation of techniques Is provided to help clarlly notations which may appear on this reproduction. 1. Manuscripts may not always be complete. When it Is not possible to obtain missing pages, a note appears to indicate this. 2. When copyrighted materials are removed from the manuscript, a note ap- pesirs to indicate this. 3. Oversize materials (maps, drawings, and charts) are photographed by sec­ tioning the original, beginning at the upper left hand comer and continu­ ing from left to right in equal sections with small overlaps. Each oversize page is also filmed as one exposure and is available, for an additional charge, as a standard 35mm slide or in black and white paper format.* 4. Most photographs reproduce acceptably on positive microfilm or micro­ fiche but lack clarity on xerographic copies made from the microfilm. For an additional charge, all photographs are available in black and white standard 35mm slide format.* *For more information about black and white slides or enlarged paper reproductions, please contact the Dissertations Customer Services Department. "UoÎMersily Mîcroafaiis M .=. Internoional 8615048 Goff, Jesse Paul PREVENTION OF PARTURIENT PARESIS (MILK FEVER) IN DAIRY COWS Iowa State University PH.D. 1986 University Microfilms Intern&tion&l 300 N. Zeeb Road, Ann Arbor, Ml 48106 Prevention of parturient paresis (milk fever) in dairy cows by Jesse Paul Goff A Dissertation Submitted to the Graduate Faculty in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY Departments: Veterinary Physiology and Pharmacology Animal Science Co-majors: Veterinary Physiology Nutritional Physiology Approved ! Members of the Committee: Signature was redacted for privacy. Signature was redacted for privacy. In Charge of Major Work Signature was redacted for privacy. Signature was redacted for privacy. Signature was redacted for privacy. For the Major I^^artment Signature was redacted for privacy. For the Graduate College Iowa State University Ames, Iowa 1986 ii TABLE OF CONTENTS Page GENERAL INTRODUCTION 1 Dissertation Format 2 LITERATURE REVIEW 3 Calcium Homeostasis 3 Intracellular calcium concentration 3 Parathyroid glands 5 PTH biosynthesis 7 Peripheral metabolism of PTH 10 PTH Secretion 14 Factors Affecting PTH Secretion 16 Calcium 16 Magnesium 18 Sodium and potassium 18 Phosphate 19 Factors that act through cAMP 20 Miscellaneous factors 22 Physiologic Actions of PTH 23 Effects on the kidney 23 Phosphate excretion 23 Calcium excretion 24 Magnesium excretion 26 Excretion of other substances 26 Renal production of 1,25-dihydroxyvitamin D 26 Formation and resorption of bone 27 Cancellous bone remodeling 29 Cortical bone remodeling 32 Hormonal control of bone resorption 33 iii Page SECTION I. BONE RESORPTION, RENAL FUNCTION, AND MINERAL STATUS IN COWS TREATED WITH 1,25-DIHYDROXYCHOLECALCIFEROL AND ITS 24-FLUORO ANALOGUES 36 INTRODUCTION 37 MATERIALS AND METHODS 40 Vitamin D Compounds 40 Animals 40 Diet 40 Design 40 Protocol 41 Physiologic Parameters Monitored 41 Analysis 42 RESULTS 43 DISCUSSION 46 LITERATURE CITED 57 SECTION II. USE OF 24-F-l,25-DTHYDROXY- VITAMIN Da TO PREVENT PARTURIENT PARESIS (MILK FEVER) IN DAIRY COWS 62 INTRODUCTION 63 MATERIALS AND METHODS 65 RESULTS 67 DISCUSSION 69 LITERATURE CITED 77 iv Page SECTION III. EFFECT OF SYNTHETIC BOVINE PARA­ THYROID HORMONE IN DAIRY COWS: PREVENTION OF PARTURIENT PARESIS (MILK FEVER) 80 INTRODUCTION 81 MATERIALS AND METHODS 83 Pregnant Cow Experiment 83 Periparturlent Cow Experiment 84 Parameters Monitored 86 RESULTS 88 Pregnant Cow Experiment 88 Periparturlent Cow Experiment 90 DISCUSSION 93 LITERATURE CITED 109 SU>1MARY AND DISCUSSION 114 LITERATURE CITED 115 ACKNOWLEDGMENTS 127 1 GENERAL INTRODUCTION Calcium homeostasis is a complex endocrinological process involv­ ing phosphorus, magnesium, parathyroid hormone, calcitonin, and the vitamin D metabolites. This homeostatic mechanism is capable of maintaining normal blood calcium concentrations under most conditions. However, there are certain pathological conditions in which the homeo­ static mechanism is insufficient. One such state is exhibited in the periparturient dairy cow - parturient paresis fmilk fever). The outstanding clinical features of this syndrome are severe hypocalcemia and recumbency. Left untreated, the cow becomes comatose and would die. The incidence of parturient paresis is greatly reduced by feeding cows a low calcium diet the 2 weeks before parturition (Goings e_t £l., 1974). Green e£ al. (1981) found that low calcium diets act to increase blood concentrations of immunoreactive parathyroid hormone and 1,25-dihydroxyvitamin D. By stimulating production of these homeo­ static hormones prior to parturition, the calcium demands associated with the onset of lactation could be adequately met. However, using low calcium diets (< 20 g calcium/day) to prevent parturient paresis has not been universally feasible. Therefore, other methods for preventing parturient paresis have been sought. Since endogenously-produced parathyroid hormone and 1,25-dihy- droxyvitamin D are capable of preventing parturient paresis, perhaps by exogenously supplying the cow with these hormones prior to parturition 2 the physiologic and clinical benefits of a low calcium diet can be achieved. In these experiments, the ability of vitamin D metabolites and parathyroid hormone to prevent parturient paresis were assessed. Dissertation Format This dissertation is presented in the alternate thesis format, which includes three manuscripts. The paper in Section I is coauthored by R. L. Horst, E. T. Littledike, A. Boris, and M. R. Uskokovic, and has been accepted for publication in the Journal of Nutrition. The papers in Sections II and III are coauthored by R. L. Horst and E. T. Littledike. Both are being submitted to the Journal of Dairy Science for publication. A review of the literature precedes the first manuscript. It is primarily concerned with parathyroid hormone. At the end of each section, a separate Literature Cited section has been included to facilitate publication. A general Summary and Discussion follows the final manuscript. The doctoral candidate, Jesse Paul Goff, was the principal Investigator in each of these studies. 3 LITERATURE REVIEW Calcium Homeostasis Intracellular calcium concentration Free calcium ion concentration within the cytosol of cells is -7 -8 estimated to be between 10 and 10 M (Kretsinger, 1979). Under normal conditions, extracellular fluid calcium ion concentration is about 1.2 mM. This means that the extracellular free calcium ion concentration Is 10,000 to 100,000 times the Intracellular free calcium concentration. Internal calcium ion concentration is pre­ cisely controlled since even minor changes can have wide-ranging physiologic, and even pathologic, effects (Carafoli and Pennlston, 1985). Calcium ions act as a second messenger, relaying electrical and chemical messages that arrive at the cell surface to the biochemi­ cal machinery within the cell. Before the implications of changes in Intracellular calcium concentration can be understood, it is necessary to first discuss how very low calcium ion concentrations within the cell can be so precisely maintained against a tremendous concentration gradient. Extracellular calcium ions continually leak into the cytosolic compartment of the cell through calcium channels located within the plasma membrane. There are three mechanisms available for removal of calcium ions from the cytosolic compartment of the cell. Initially, the free calcium ions can become bound to proteins within the cytosol. There are a great number of proteins that are special­ ized for binding calcium within the cytosol; some of them, e.g., calmodulin, are important as physiologic messengers in addition to 4 their role in regulating calcium ion concentration (Rasmussen, 1980). The capacity of this mechanism for removal of cytosolic calcium is very low. The second mechanism is capable of moving many calcium ions out of the cytosol. Within the cell membrane there is a protein structuré that allows sodium ions outside the cell to be exchanged for calcium ions inside the cell. Three sodium ions are brought into the cell for every
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