1. Sodium, Potassium and H 2 0 Disorders Maria E. Ferris, MD, MPH

2. Case Presentation 14 y.o male  chronic illnesses is admitted for knee surgery & 12 hr. post  Sz (GTC) Labs: Na 128, K 4.5, Cl 98, CO 2 20, Ca 9, Mg 2, glucose 130 & U.Na 35 a) CHF, b)  total body Na, c) dilutional  Natremia, d) Renal Na wasting e) third spacing of fluid

3. Answer C) Dilutional Hyponatremia Must investigate the IVF that were hung during surgery (D5W)

4. Question Maintenance daily Na requirements for a 50 Kg, 12 y.o. boy? a) 150 mEq, b) 100 mEq, c) 63 mEq, d) 50 mEq and e) 45 mEq

5. Answer c) 63 mEq/ day

6. Na Transport along the nephron ANPNa Channels3%Late Distal Tubule & CCT AldosteroneNaCl symport4 %Distal Tubule Aldosterone1 Na-1K-2Cl symport 25 %Loop of Henle Angiotensin II, Epinephrine, Norepinephrine & Dopamine Na-H exchange, NA co-transport w/ a.a. & org. solutes, Na/H/Cl/anion exchange 67 %Proximal Tubule HormonesMechanism of Na Reabsorption Filtered load reabsorbed Segment

7. ADH & ANP Passive8-17%Late Distal Tubule & CCT None 0 %Distal Tubule NoneDescending Thin Limb 15 %L.of Henle NonePassive67 %Prox. Tubule HormonesMechanism of H 2 O Reabsorption Filtered load reabsorbed Segment H 2 O Transport along the nephron

8. Na and Cl Reabsorption In the Proximal Tubule, 17,000 mEq of the 25,200 mEq (67%) of NaCl filtered per day is absorbed by para-cellular and trans-cellular pathways. Auto regulation of the GFR, glomerular-tubular balance, load dependency by the L.of H. & the DT, maintain a constant fraction of the filtered Na load to the beginning of the collecting duct.

9. Hyponatremia In.95 of the cases it is due to impairment of H 2 O excretion Factors that affect this excretion are: –Fluid intake –Ability to deliver NaCl to diluting segment and its reabsorption –ADH suppression

10. Hyponatremia In renal dysfunction, a 1-2 fold change in SCr will  volume excretion of free H 2 O by 4-fold This in great part due to  delivery

11. Case Presentation 6y.o c/o VP shunt malfunction, afebrile and lethargic BUN 3, SCr 0.5, NA 125,Cl 90, Urine Osmolality 300, UNa 60. Best next step? a) Demeclocycline b) diuretics, c) IV Normal Saline, d) Immediate VP shunt removal e) fluid restriction

12. Answer e) fluid restriction

13. Case Presentation 4 y.o. with severe DH due to NV, (-) PMHx Labs: Na 125, Serum Osm 315. Findings are most likely due to an increase in: a) Cl, b) SCr c) glucose, d) P & e) K

14. Answer c) Glucose

15. Hypernatremia

16. Case Presentation 2 Wk old, + PNC, nl delivery w/ GTC Sz Wt. 2.5 Kg (200 gm < birth wt) male, BP 70/40,P:140, R:50 Glu: 120, BUN 50, NA 170, CO 2 12, Ca 9 & Mg 1.5. The Sz is likely due to a)  Ca, b)  glycemia, c)  Mg, d) intracraneal hge. e) meningitis

17. Answer d) Intracraneal hemorrhage due to hypernatremia

18. Case Presentation 2 y.o. with Cong. heart Dz  1 day Hx of resp. distress & LE’s edema BUN 40, SCr 1.5, NA 125, K 4, Cl 95, CO 2 20. Most appropriate next test? a) Serum Osmolality b) Urine FENa, c) Urine pH, d) Urine S.G, e) venous pH

19. Answer B) FENa

20. Potassium Disorders

21. K + Homeostasis Diet:100 mEq/d Int. Abs: 90 mEq/d ECF: 65mEq/dTissue Stores Plasma K, Aldo & ADH Insulin, Epi & Aldosterone Feces: 10 mEq/d Urine 90 mEq/d

22. K + Homeostasis K + is one of the most abundant cations in the body and a major determinant of the resting membrane potential, which is crucial for cell growth/division & excitability of nerve muscle. Homeostasis is maintained by hormones & the kidneys, which adjust K excretion to match PO intake. K excretion is determined by the rate of K secretion by the distal tubule & CCD

23. 3Na + 2K + ATPase Transcellular K+ Distribution K + cell = 140-160 mEq/L K + e = 4-5 mEq/L

24. Relationship Between [K + ] serum and Total Body Potassium in 70 kg Adult Serum [K + ] mEq/L Total Body Potassium Normal-150 mEq+150 mEq 2 3 4 5 6

25. Potassium Distribution ECF ICF 3920 mEq 80 mEq 98% 2%

26. Potassium Content in Fruits and Vegetables Amount of Potassium MilligramsmEq Potato with skin 844 mg20 3 Oz. Dried Fruit796 mg20 10 Dried Prunes 626 mg16 1 Banana 451 mg11 Tomato254 mg6.5 1 Kiwi252 mg 6.5 8 Oz. Glass of 250 mg6.5 Orange Juice 1Grapefruit 158 mg4

27. Renal Tubular Potassium Handling Filtered load 600-700 mEq per day K+ Reabsorption 60-70% K+ Reabsorption 20-30% K+ Secretion Urinary Excretion 90mEq/day

28. Urinary Potassium Excretion Normal kidneys have the capacity to excrete 500- 600 mEq per day (average K + excretion 40-100 mEq/day). The key site of renal potassium excretion regulation occurs at the cortical collecting duct.

29. Cortical Collecting Duct - Principle Cells Na + K+K+ 3Na + 2K + AldosteroneR-Aldo Cl - Peritubular capillary Tubular lumen ATPase Na +

30. Cortical Collecting Duct ATPase Tubular lumen Peritubular Capillary Principle Cell Intercalated Cell K+ H+ OH- + CO 2 HCO 3 - T Cl - H2OH2O H+ 3Na + 2K + Cl- K+ Na+ ATPase 3Na + 2K + R-Aldo NH 3 H + + NH 4 + Na+ Aldosterone

31. Mechanisms Leading to Hyperkalemia Impaired entry into cells Increased release from cells Decreased urinary excretion

32. 3Na + 2K + ATPase K+K+  H +  Glucose  Insulin Digoxin β-blockers Cell injury Hyperkalemia – Redistribution: ICF  ECF

33. Factors that Impair Urinary K+ Excretion Collecting duct lumen relatively more electropositive  Flow and sodium delivery to the CCD  Aldosterone production or activity

34. Effect of Amiloride Predict changes in the following: Relative lumen charge Renal K+ excretion Serum potassium Renal H+ excretion Arterial pH Aldosterone Tubular lumen

35. Hyperkalemia: Decreased Renal Excretion Volume depletion  decreased flow in CCD Decreased renin-AII-aldo production –NSAIDS   renin –ACEI   AII –Heparin   aldosterone production –Spironolactone   aldosterone activity Inhibition of CCD Na+ channel –Amiloride, triamterene, trimethoprim, pentamidine

36. ECG Changes of Hyperkalemia Serum K+ (mEq/L)ECG 9 Sinoventricular V-fib 8 Atrial standstill Intraventricular block 7 Tall T wave. Depressed ST segment 6 Tall T wave. Shortened QT interval

37. ECG Changes due to Hyperkalemia

38. Treatment of Hyperkalemia TherapyMechanism of Action CalciumStabilization of Membrane Potential InsulinIncreased K+ entry into Cells Beta-2 Agonists Bicarbonate(if pH a <7.2 in setting of acidosis) DialysisPotassium removal Cation Exchange Resin (sodium polystyrene = Kayexalate)

39. Differential Diagnosis of Hypokalemia Increased entry into cells Inadequate intake or GI losses Urinary losses

40. 3Na + 2K + ATPase K+K+ Hypokalemia: Redistribution: ECF  ICF  Insulin β-2 agonists Alkalosis Barium poisoning Hypokalemic periodic paralysis

41. Factors that Enhance Urinary K+ Excretion Lumen of CCD more electronegative Enhanced flow and sodium delivery to the CCD Increased aldosterone

42. Thiazide Diuretics Loop diuretics Na+ K+ 2Cl-- BloodLumen Loop diuretics Na+ Cl- Thiazide diuretics Sites of Action of Diuretics Lumen Blood (Defect = Bartter’s) (Defect = Gitelman’s)

43. Interpretation of Urinary K + in the Setting of Hypokalemia GI Losses or priorRenal K Loss or Diuretic TherapyCurrent Diuretic Use 24 o Urine K 30 mEq FeK 10 %

44. Serum [HCO3-] U pH U [Cl - ] 35 30 25 20 7.0 5.5 4.0 50 30 10 Generation PhaseLate Maintenance Phase Volume Depletion Metabolic Alkalosis in Vomiting Early Maintenance Phase

45. Effect of Gastric Loss of HCl, Na+/H 2 O (Volume) Predict changes in the following: 1. Relative lumen charge 2. Renal K+ excretion 3. Serum potassium 4. Renal H+ excretion 5. Arterial pH HCO 3 -

46. Urine Na+ and Cl- in the Differential Diagnosis of Metabolic Alkalosis and Hypokalemia Urine Electrolytes Na+Cl- Condition (meq/L) Vomiting Alkaline urine>15<15 Acidic urine<15<15 Diuretic Drug active>15>15 Remote use<15<15 Hyperaldosteronism>15>15

47. K + disequilibrium Acid-base disturbances –Acute metabolic acidosis =  K –Chronic metabolic acidosis =  K –Metabolic alkalosis =  K Exercise (+  -blockers =  K) Cell lysis (trauma, burns, tumor-lysis, G-I bleed) Plasma osmolality  (  by 10 mOsm/Kg =  K) Changes in tubular fluid flow

48. Case Presentation 10 month old with CHF on 2 mg/Kg lasix b.i.d. His most likely serum labs? a) pH 7.2, K 3.0, b) pH 7.2, K 3.5, c) 7.2, K 4.5, d) pH 7.5 K 3.0, e) pH 7.5, K4.5

49. Answer d) Metabolic alkalosis with hypokalemia

50. Case Presentation After gaining 150 yards and 28 carries a football player becomes disoriented, gross hematuria & LOC T:106.7,P160,R30,100/60, BUN54, CK  Next day oliguria develops despite CR and fluid support. Most likely Dx? a) Heat stroke, b) HUS, c)Hgic. shock & encephalopathy, d)Reye Sx. e) viral Sx

51. Answer a) Heat stroke and Rhabdomyolysis

52. Chloride disorders

53. Answer a) Urinary Cl

54. Case presentation 6 Week old baby c/o emesis p. each feed X 2 wks. ‘always hungry’, emaciated, dry mucosas, ? RUQ abdominal mass. Labs? a) Hypochloremic metabolic acidosis, b) Hypochloremic metabolic alkalosis, c) Resp. alkalosis, d) Respiratory acidosis & metabolic compensation, e) nl. electrolytes

55. Answer b) Hypochloremic metabolic alkalosis likely 2o. To pyloric stenosis