1. DIABETES INSIPIDUS Richard Sachson MD

2. Anatomy of the neurohypophysis Anatomy of the neurohypophysis

3. Magnetic resonance imaging of posterior pituitary gland Magnetic resonance imaging of posterior pituitary gland

4. Chemical structure of vasopressin Chemical structure of vasopressin

5. The gene that encodes AVP-NP is located on the short arm of chromosome 20 Vasopressin Is Encoded in a Gene That Also Encodes Neurophysin II, an AVP- Binding Protein Signal Peptide AVP NeurophysinGlycopeptide (Copeptin) Exon 1 Exon 2 Exon 3 Its three exons encode a signal peptide, the vasopressin molecule, its neurophysin binding protein, and a terminal glycoprotein. The precursor is processed to yield equimolar quantities of vasopressin and NP II.

6. How Vasopressin Works

7. Physiologic regulation of vasopressin Physiologic regulation of vasopressin

8. Plasma osmolality and plasma vasopressin concentration Plasma osmolality and plasma vasopressin concentration

10. Urine osmolality and plasma vasopressin concentration Urine osmolality and plasma vasopressin concentration

11. Water deprivation test in normal person Water deprivation test in normal person

12. Water deprivation test in diabetes insipidus Water deprivation test in diabetes insipidus

13. Urine osmolality during water deprivation Urine osmolality during water deprivation

14. Plasma arginine vasopressin vs. serum osmolality concentration Plasma arginine vasopressin vs. serum osmolality concentration

15. Thirst, plasma arginine vasopressin, and plasma osmolality in dipsogenic DI Thirst, plasma arginine vasopressin, and plasma osmolality in dipsogenic DI

16. Relationship of plasma and urinary AVP to plasma osmolality ©Copyright Science Press Internet Services

17. Differential Diagnosis of Hypotonic Polyuria ©Copyright Science Press Internet Services

18. Causes of nephrogenic diabetes insipidus Causes of nephrogenic diabetes insipidus

19. Agents that alter the response of the collecting duct to vasopressin Agents that alter the response of the collecting duct to vasopressin

20. Inherited Nephrogenic Diabetes Insipidus Is (Mostly) X-Linked 90% of patients are males with X-linked recessive form of the disease Less than 10% of familial nephrogenic DI has been transmitted as autosomal recessive or autosomal dominant trait Reviewed for your reading pleasure in Ann Rev Physiol 63:607 (2001)

21. Clinical Features Of X-linked Nephrogenic Diabetes Insipidus Untreated nephrogenic DI results in repeated episodes of dehydration in early infancy Early recognition and therapy (abundant water intake, low sodium diet, hydrochlorothiazide) may allow normal mental development and (maybe) normal growth

22. Most V2 Receptor Mutations Are in Transmembrane Domains of the Protein Morello and Bichet 2001; Ann Rev Physiol 63:607 V2 Receptor is a G-protein coupled receptor with seven transmembrane domains

23. Genetic mutations in the aquaporin 2 gene Genetic mutations in the aquaporin 2 gene

24. The Rarest Form Of Inherited Nephrogenic Diabetes Insipidus Is Due to Mutations In A Water Channel Gene AQP2 is encoded by a gene on chromosome 12 Most mutations are recessive, but some transmit a dominant phenotype

25. Causes of central diabetes insipidus Causes of central diabetes insipidus

26. Genetic mutations in neurogenic diabetes insipidus Genetic mutations in neurogenic diabetes insipidus

27. Genetic mutations in the vasopressin 2 receptor gene Genetic mutations in the vasopressin 2 receptor gene

28. Agents that alter vasopressin release Agents that alter vasopressin release

29. Treatment of diabetes insipidus Treatment of diabetes insipidus

30. Diabetes insipidus in pregnancy associated with abnormally high circulating vasopressinase activity J. A. Durr, J. G. Hoggard, J. M. Hunt, and R. W. Schrier NEJM 1987 316:1070

31. Aggravation of subclinical diabetes insipidus during pregnancy Y Iwasaki, Y Oiso, K Kondo, S Takagi, K Takatsuki, H Hasegawa, K Ishikawa, Y Fujimura, S Kazeto, and A Tomita Aggravation of subclinical diabetes insipidus during pregnancy Y Iwasaki, Y Oiso, K Kondo, S Takagi, K Takatsuki, H Hasegawa, K Ishikawa, Y Fujimura, S Kazeto, and A Tomita NEJM 1991 324:522

32. TERMINATION OF DEHYDRATION TEST 5% Loss of body wt 5% Loss of body wt Posm >295-300 Posm >295-300 Na >150 Na >150 Uosm >600 Uosm >600 SG >1.020 SG >1.020

33. PT JL TIMEVOLuSGuOSMNapOSMWT 7 PM 8700100516313828382.5 9200100516313828282.2 10200103830213881.7 1160101344013881.2 1250101138713781.2 1 AM 30 2:30150101137813927881.3