1. Three Children with Electrolyte Problems by Larry Greenbaum, MD, PhD Pediatric Nephrology by Larry Greenbaum, MD, PhD Pediatric Nephrology

2. Patient One u Two year old with failure to thrive u Polyuria and polydipsia u Blood pressure of 160/90 147 1.8 106 32 8 0.4

3. Patient Two u One week old brought to the hospital for lethargy, poor feeding and dehydration 124 7.7 90 12 30 1.5 (Bun and creatinine normalized after hydration)

4. Patient Three u Four month old with fever and dehydration u Failure to thrive and decreased tone 120 2.6 59 41 18 0.6

5. Do you enjoy renal physiology? Yes No 10% 90% 95% 5%

6. Distal tubule

7. Na + K+K+ K+K+ K+K+ H+H+ K+K+ K+K+ K+K+ H+H+ - - - -

8. Adrenal Gland Kidney Aldosterone Renin ATII Volume Depletion Regulation of Aldosterone

9. Three Possible Problems u Excess aldosterone effect l Hypertension l Hypokalemia and metabolic alkalosis u Absence of aldosterone effect l Hypotension l Hyperkalemia, metabolic acidosis and hyponatremia u Physiologic aldosterone overproduction l Volume depletion l Hypokalemia and metabolic alkalosis

10. Excess Aldosterone Effect Adrenal Gland Kidney Aldosterone Adrenal adenoma

11. Na + K+K+ K+K+ K+K+ H+H+ K+K+ K+K+ K+K+ H+H+ - - - -

12. Absence of Aldosterone Effect Adrenal Gland Kidney Renin ATII Volume Depletion 21-Hydroxylase deficiency (CAH)

13. 17  -Hydroxypreg. 17  -hydroxyprog. 11-deoxycortisol Cortisol Pregnenolone Progesterone DOC Corticosterone 18-Hydroxycorticosterone Aldosterone DHEA Androstendione Testosterone GlucocorticoidsMineralocorticoidsAndrogens

14. Na + K+K+ K+K+ K+K+ H+H+ K+K+ K+K+ K+K+ H+H+

15. Physiologic Aldosterone Overproduction Adrenal Gland Kidney Aldosterone Renin ATII Volume Depletion Loop Diuretic

16. Distal tubule

17. Na + K+K+ K+K+ K+K+ H+H+ K+K+ K+K+ K+K+ H+H+ - - - -

18. Patient One u Two year old with failure to thrive u Polyuria and polydipsia u Blood pressure of 160/90 147 1.8 106 32 8 0.4

19. Case One Diagnosis u Excess aldosterone effect u Absence of aldosterone effect u Physiologic aldosterone overproduction Voting 85% 10% 5%

20. Na + K+K+ K+K+ K+K+ H+H+ K+K+ K+K+ K+K+ H+H+ - - - -

21. Liddle Syndrome u Severe hypertension u Hypokalemia and metabolic alkalosis u Polyuria, polydipsia and muscle weakness u Low aldosterone and renin levels u Autosomal dominant u Blood pressure does not improve with Aldactone but does improve with triamterene or amiloride

22. Na + K+K+ K+K+ K+K+ H+H+ K+K+ K+K+ K+K+ H+H+ - - - - A A A A TT TT

23. Patient Two u One week old brought to the hospital for lethargy, poor feeding and dehydration 124 7.7 90 12 30 1.5 (Bun and creatinine normalized after hydration)

24. Case Two Diagnosis u Excess aldosterone effect u Absence of aldosterone effect u Physiologic aldosterone overproduction Voting 5% 90% 5%

25. Na + K+K+ K+K+ K+K+ H+H+ K+K+ K+K+ K+K+ H+H+

26. Pseudohypoaldosteronism Type I u Dehydration and failure to thrive as neonates u Hyponatremia, hyperkalemia and metabolic acidosis u Elevated plasma renin and aldosterone u Aldosterone resistance in kidney, sweat and salivary glands, colonic mucosa u Autosomal recessive u Treatment with NaCl and Kayexalate

27. Patient Three u Four month old with fever and dehydration u Failure to thrive and decreased tone 120 2.2 59 41 18 0.6

28. Case Three Diagnosis u Excess aldosterone effect u Absence of aldosterone effect u Physiologic aldosterone overproduction Voting 0 100%

29. Na + K+K+ K+K+ K+K+ H+H+ K+K+ K+K+ K+K+ H+H+ - - - -

30. Distal tubule

31. Bartter Syndrome u Hypokalemia and metabolic alkalosis u Failure to thrive and muscle weakness u Polyuria and polydipsia (polyhydramnios and premature delivery) u Autosomal recessive

32. Differential of Excess Aldosterone Effect High Aldosterone Low Renin u Primary aldosteronism u Glucocorticoid- remediable aldosteronism Low Aldosterone Low Renin u Congenital adrenal hyperplasia u Liddle syndrome u Apparent mineralocorticoid excess u Licorice High Aldosterone High Renin u Renovascular disease u Renin-secreting tumor u Malignant hypertension u Birth control pills

33. Na K Aldosterone Cortisol 11  HSD Cortisone K 11  -Hydroxysteroid Dehydrogenase

34. Differential of Absence of Aldosterone Effect Aldosterone deficiency u Adrenal insufficiency u CAH u Aldosterone synthetase Aldosterone resistance u Pseudo- hypoaldosteronism u Obstructive uropathy u Pyelonephritis u Sickle cell disease u Chronic renal failure

35. Differential of Physiologic Aldosterone Overproduction Urine Chloride <10 u Loss of gastric fluids u Chloride-losing diarrhea u Sweat (CF) u Dietary chloride deficiency u Remote diuretics Urine Chloride >20 u Current diuretics u Bartter syndrome u Gitelman syndrome

36. The End