1. Meghan Ellis Calcium and Phosphorus Metabolism in Reptiles

2. Clinical Importance More than 3.9 million US households with 1+ reptile pets Ca and P derangements are common in pet reptiles Preventable with proper husbandry Treatable with early intervention

3. Calcium Importance Cell signaling Neural transmission Muscle function Blood coagulation Enzymatic co-factor Membrane and cytoskeletal functions Bone mineralization

4. Calcium Regulation

5. Parathyroid Gland

6. PTH Regulation Decreased serum ionized calcium  increased synthesis and secretion of PTH from chief cells Increased serum ionized calcium  negative feedback loop Increased phosphorus  decreased serum Ca  stimulation of PTH  increased renal excretion of phosphorus

7. Metabolic Functions of PTH Activate osteoclasts  mobilizes calcium from bone Increase renal tubular reabsorption of calcium Increases conversion of vitamin D to active dihydroxy form in kidneys Augments GI calcium absorption

8. Metabolic Functions of Calcitonin Promotes absorption of calcium by skeletal system Inhibits resorption of bone by osteoclasts

9. Calcitonin Regulation Increased serum ionized calcium  increased synthesis and secretion of calcitonin by C cells of thyroid gland Decreased serum ionized calcium  negative feedback loop

10. Thyroid Gland

11. Phosphorus Importance Bone mineralization Phospholipid in cellular membranes Cellular respiration Component of DNA and RNA Post-transcriptional modification of proteins

12. Phosphorus Regulation

13. Vitamin D3 Stimulates calcium and phosphorus absorption by intestinal mucosa Maintains calcium and phosphorus balance for optimal bone mineralization

14. Calcium Clinical Pathology Normal total serum calcium: 8-11mg/dL in most reptiles Normal ionized calcium in Green Iguana: 1.47 +/- 0.104 mmol/L

15. Hypocalcemia (<8.0 mg/dL) Dietary deficiency Excessive dietary phosphorus Secondary nutritional hyperparathyroidism Vitamin D3 deficiency (dietary or lack of UV light) Hypoablbuminemia Hypoparathyroidism

16. Hypercalcemia (>20mg/dL) Excessive dietary calcium and vitamin D3 Primary hyperparathyroidism Pseudohyperparathyroidism Osteolytic bone disease Vitellogenesis (physiologic)

17. Phosphorus Clinical Pathology Normal serum phosphorus: 1-5mg/dL

18. Hypophosphatemia Starvation Nutritional deficiency

19. Hyperphosphatemia (>5mg/dL) Excessive dietary phosphorus Hypervitamintosis D3 Renal disease Severe tissue trauma Osteolytic bone disease Sample handling error

20. Nutritional Secondary Hyperparathyroidism Cause: diet low in calcium or vitamin D3, diet high in phosphorus, lack of exposure to UV-B light Pathogenesis: Low serum Ca  PTH secretion  increased bone resorption, increased renal absorption of Ca and increased excretion of PO4, stimulation of 1,25-dihydroxycholecalciferol which increases GI absorption of Ca  increase serum calcium and decrease serum PO4

21. NSHP Effects Hypocalcemia  neural hyperexcitability  twitching digits, hyperreflexia, ataxia, disorientation, cloacal prolapse Increased osteoclastic osteolysis  demineralization of bone  fractures of long bones and spine, thickening and swelling of long bones and mandibles, “rubber jaw”

22. NSHP Effects continued Effects on reproduction: decreased calcification of egg shells  weak rubbery eggs Clinical Pathology: low normal serum calcium; increased PTH

23. NSHP

24. NSHP Treatment Correct hypocalcemia Rehydrate Correct Husbandry

25. Renal Secondary Hyperparathyroidism Cause: chronic renal disease- degenerative nephroses due to inadequate husbandry, poor nutrition, NSHP Pathogenesis:failure of kidneys to excrete excess phosphorus  decreased serum Ca due to Ca X P rule  PTH secretion Hyperphosphatemia  renal tubular cells cannot hydroxylate 25-hydroxycholecalciferol to active vitamin D3  increased PTH secretion Decreased vitamin D3  no GI absorption of Ca

26. RSHP Effects Crispy critters: Ca x P >9  mineralization of kidneys; >12 mineralization of other soft tissues especially GI and cardiorespiratory systems Ischemic necrosis of tail, vomiting, passing poorly digested food, congestion of peripheral blood vessels especially obvious in sclera All the signs of hypocalcemia

27. RSHP

28. RSHP Clinical Pathology Hyperphosphatemia Low or low normal serum calcium Dehydration Nonregenerative anemia Inverted Ca:P ratio (should be 1.2-2:1) Increased PTH Iohexol clearance study for GFR estimate

29. Other Methods Renal biopsy Ultrasound Radiograph

30. RSHP Treatment Usually present in end-stage renal failure Reduce dietary protein Correct hyperphosphatemia Correct hypocalcemia Correct and prevent dehydration Supplement vitamin B complex Omega-6: Omega-3 = 3:1 Correct husbandry

31. The End

32. References Robbins and Cotran Pathologic Basis of Disease 7 th ed Nelson and Couto Small Animal Internal Medicine 3 rd ed Mader Reptile Medicine and Surgery Hernandez-Divers, Stephen et al “Renal evaluation in healthy green iguanas (Iguana iguana): assessment of plasma biochemistry, glomerular filtration rate, and endoscopic biopsy.” Journal of Zoo and Wildlife Medicine June 2005; 36(2):155-168