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Derangements of Tonicity and Implications for Veterinary Patients

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Derangements of Tonicity and Implications for Veterinary Patients DERANGEMENTS OF TONICITY AND IMPLICATIONS FOR VETERINARY PATIENTS by JENNIFER M. REINHART B.S., University of Michigan, 2004 D.V.M., University of Illinois, 2010 A THESIS submitted in partial fulfillment of the requirements for the degree MASTER OF SCIENCE Department of Clinical Sciences College of Veterinary Medicine KANSAS STATE UNIVERSITY Manhattan, Kansas 2014 Approved by: Major Professor Thomas Schermerhorn Abstract Tonicity is property of a solution that is defined as the total effective (impermeable) osmole concentration that drives fluid movement across a semipermeable membrane via osmosis. Tonicity is related to but distinct from solution osmolality, which is a summation of all solute concentrations, regardless of the solute membrane permeability. In the mammalian body, tonicity is tightly regulated at both a cellular and systemic level; tonic derangements cause rapid change in cell and tissue volume leading to significant dysfunction. Input from the central nervous, circulatory, endocrine, gastrointestinal, and urinary systems are integral to osmoregulation, so many diseases in veterinary medicine are associated with tonicity disorders. However, because the homeostatic mechanisms that control tonicity overlap with those regulating electrolyte and acid-base balance as well as hydration and vascular volume, tonic consequences of disease can be difficult to isolate. Understanding of disease-associated changes in tonicity is further complicated by the fact that the tonic contributions of many solutes that accumulate in disease are unknown. Additionally, direct assessment of tonicity is difficult because tonicity is not just a physiochemical property, but it implies a physiologic effect. Thus, simple summation of osmole concentrations is an inadequate measurement of tonicity. The following report includes three studies investigating various aspects of tonicity as it applies to veterinary patients. Chapter 2 reports a study that examines the tonic effects of ketoacids and lactate using two different in vitro red blood cell assays. Results demonstrated that the ketoacids, beta-hydroxybutyrate and acetoacetate, behave as ineffective osmoles while the tonic behavior of lactate is variable, implying a more complex cellular handling of this anion. Two additional studies examine whether the mean corpuscular volume difference (dMCV) is a novel clinical marker for hypertonicity in dogs. Results of separate retrospective (Chapter 3) and prospective (Chapter 4) studies provide evidence that dMCV is a useful clinical marker for hypertonicity in dogs. Table of Contents List of Figures ................................................................................................................................. v List of Tables ................................................................................................................................ vii Acknowledgements ...................................................................................................................... viii Chapter 1 - Physiology and Pathophysiology of Tonicity .............................................................. 1 Osmolality and Tonicity ............................................................................................................. 1 Components of Extracellular Tonicity ........................................................................................ 1 Electrolytes ............................................................................................................................. 2 Nonionic Osmolytes ................................................................................................................ 3 Osmolytes of Unknown Tonic Effect ..................................................................................... 3 Tonic Stress and Mechanisms of Cellular Osmoregulation ........................................................ 5 Extracellular Fluid Tonicity and Mechanisms of Systemic Osmoregulation ............................. 6 Osmoregulatory Sensors: Osmoreceptors ............................................................................... 7 Osmoregulatory Effectors: ADH, Thirst, and Salt Appetite ................................................... 8 Osmoregulatory and Vascular Control Integration ................................................................. 9 Hypotonicity in Clinical Disease .............................................................................................. 10 Hypotonic Diseases with Solute Loss ................................................................................... 10 Hypotonic Diseases with Water Gain ................................................................................... 11 Treatment of Hypotonicity .................................................................................................... 12 Hypertonicity in Clinical Disease ............................................................................................. 13 Hypertonic Diseases with Water Loss .................................................................................. 13 Hypertonic Diseases with Solute Gain ................................................................................. 14 Hypertonicity in Human Medicine ....................................................................................... 16 Treatment of Hypertonicity ................................................................................................... 17 Clinical Measurement of Osmolality and Tonicity ................................................................... 18 Chapter 2 - Tonic Effects of Ketones and Lactate Assessed Using Two Canine Red Blood Cell Assays .................................................................................................................................... 23 Abstract ..................................................................................................................................... 23 Introduction ............................................................................................................................... 23 iii Materials and Methods .............................................................................................................. 25 Modified Osmotic Fragility Assay ........................................................................................ 25 Canine dRBC Assay ............................................................................................................. 27 Results ....................................................................................................................................... 29 Modified Osmotic Fragility Assay ........................................................................................ 29 Canine dRBC Assay ............................................................................................................. 31 Osmoles of Known Tonic Effect ...................................................................................... 31 Osmoles of Unknown Tonic Effect (BHB, AA, and lactate) ........................................... 31 Discussion ................................................................................................................................. 32 Chapter 3 - In Vitro Increase of Mean Corpuscular Volume Difference (dMCV) as a Marker for Serum Hypertonicity in Dogs ................................................................................................ 36 Abstract ..................................................................................................................................... 36 Introduction ............................................................................................................................... 36 Materials and Methods .............................................................................................................. 38 Cases ..................................................................................................................................... 38 Clinical Pathology ................................................................................................................. 39 Calculations ........................................................................................................................... 39 Data Analysis ........................................................................................................................ 40 Results ....................................................................................................................................... 40 Discussion ................................................................................................................................. 44 Chapter 4 - Mean Corpuscular Volume Difference (dMCV) as a Marker for Serum Hypertonicity During Water Deprivation in Dogs ........................................................................................ 47 Abstract ..................................................................................................................................... 47 Introduction ............................................................................................................................... 47 Materials and Methods .............................................................................................................. 49 Results ......................................................................................................................................
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