GHENT UNIVERSITY FACULTY OF VETERINARY MEDICINE Academic year 2013 - 2014 THE SATIN SYNDROME IN GUINEA PIGS Nephropathy, hyperparathyroidism and bone disease of satin cavies by Eva Stoffels-Adamowicz Promoter: Prof. Dr. Katleen Hermans Research project as part of the Master's Dissertation Universiteit Gent, its employees and/or students, give no warranty that the information provided in this thesis is accurate or exhaustive, nor that the content of this thesis will not constitute or result in any infringement of third-party rights. Universiteit Gent, its employees and/or students do not accept any liability or responsibility for any use which may be made of the content or information given in the thesis, nor for any reliance which may be placed on any advice or information provided in this thesis. TABLE OF CONTENTS SUMMARY .............................................................................................................................................. 1 SAMENVATTING .................................................................................................................................... 2 1. INTRODUCTION ................................................................................................................................. 4 1.1. THE SATIN FACTOR IN GUINEA PIGS: ORIGIN AND CONSEQUENCES .............................. 4 1.2. THE SATIN SYNDROME ............................................................................................................. 6 1.3. THE SCOPE OF THIS WORK ..................................................................................................... 6 2. REVIEW OF PAST RESEARCH ......................................................................................................... 8 2.1. STUDIES OF SATIN DISEASE ................................................................................................... 8 2.1.1. First clinical examinations, medical imaging and blood tests ............................................... 8 2.1.2. Fibrous osteodystrophy ...................................................................................................... 10 2.2. DIFFERENTIAL DIAGNOSES ................................................................................................... 11 2.2.1. Vitamin C deficiency (scurvy) ............................................................................................. 11 2.2.2. Osteomalacia (vitamin D deficiency) .................................................................................. 12 2.2.3. Metastatic calcification ........................................................................................................ 13 2.2.4. Primary (idiopatic) osteoarthritis ......................................................................................... 13 2.2.5. Osteoporosis ....................................................................................................................... 13 2.2.6. Neoplasia ............................................................................................................................ 14 2.2.7. Paget disease of bone ........................................................................................................ 15 2.2.8. Other conditions .................................................................................................................. 15 3. THE SATIN SYNDROME: CLINICAL PRESENTATION AND EPIDEMIOLOGY ............................. 17 3.1. INTRODUCTION ........................................................................................................................ 17 3.2. MATERIALS AND METHODS ................................................................................................... 17 3.2.1. Husbandry and diet ............................................................................................................. 17 3.2.2. Weight, lifespan and lameness scores ............................................................................... 18 3.2.3. Acquired dental disease ..................................................................................................... 18 3.2.4. Statistical analyses ............................................................................................................. 19 3.3. RESULTS ................................................................................................................................... 19 3.3.1. Vitality of satin guinea pigs ................................................................................................. 19 3.3.2. Lameness prevalence and scores ...................................................................................... 19 3.3.3. Acquired dental disease ..................................................................................................... 21 3.3.3.1. Clinical manifestation .................................................................................................. 21 3.3.3.2. ADD in satin guinea pigs ............................................................................................. 21 3.4. DISCUSSION ............................................................................................................................. 22 3.4.1. Acquired dental disease ..................................................................................................... 22 3.4.2. General discussion and concluding remarks ...................................................................... 23 4. CALCIUM HOMEOSTASIS ............................................................................................................... 25 4.1. INORGANIC IONS IN THE ORGANISM ................................................................................... 25 4.2. REGULATION OF CALCIUM AND PHOSPHATE LEVELS ...................................................... 26 4.2.1. Solubility in physiological fluids ........................................................................................... 26 4.2.2. Intermezzo: tissue calcification inhibitors ........................................................................... 28 4.3. THE RENAL-BONE AXIS .......................................................................................................... 29 4.3.1.The parathyroid gland and hormone.................................................................................... 30 4.3.2. Calcitonin ............................................................................................................................ 32 4.3.3. The biochemistry of vitamin D ............................................................................................ 32 4.3.4. The intestine ....................................................................................................................... 34 4.3.5. The bone ............................................................................................................................. 35 4.4. THE KIDNEY .............................................................................................................................. 36 4.4.1. Anatomy .............................................................................................................................. 36 4.4.2. Glomerular filtration ............................................................................................................ 36 4.4.3 Proximal tubule .................................................................................................................... 38 4.4.4. Loop of Henle...................................................................................................................... 39 4.4.5. Distal tubule ........................................................................................................................ 40 4.4.6. Renin-angiotensin-aldosterone system .............................................................................. 40 4.4.7. Acid-base regulation ........................................................................................................... 41 4.5 CALCIUM, SODIUM AND PROTEIN INTERACTIONS .............................................................. 42 4.5.1 Modeling tubular ion flows ................................................................................................... 42 4.5.2. Calcium-sodium interaction ................................................................................................ 45 4.5.3. Calcium-protein interaction ................................................................................................. 47 4.5.4. Conclusion .......................................................................................................................... 49 5. RENAL OSTEODYSTROPHY........................................................................................................... 50 5.1. CKD IN ANIMAL MODELS ........................................................................................................ 50 5.2. BONE REMODELING ................................................................................................................ 52 5.2.1. Bone matrix and cells ......................................................................................................... 52 5.2.2. Bone remodeling ................................................................................................................. 54 5.2.3. Bone morphology ................................................................................................................ 55 5.3.