1. Volume Assessment 2010

3. Old Paradigm Na + = Volume H 2 O = Tonicity TBW ICFECF Blood

4. Signs & Symptoms: Volume Overload Left sided failure –DOE –Orthopnea 90% sensitivity corr c pcwp –PND Right-sided Failure –Abdominal pain –Early satiety –Nausea/vomiting Non-specific –Fatigue –Feeling cold –Altered mentation

5. Physical Exam For Volume Excess States Lung ascultation – rales (20% with inc pcwp) CVS – S3 JVP (70% sens/79% spec) –Rondot sign, abd-jugular reflux (inc sens/spec to 80%) / Valsalva maneuver (82% predictive) Edema (50%, less in young adults/children)

6. Don’t Forget Daily Weight I/O???

7. JVD

8. Laboratory Assessment BNP (29pmol/l or 100 pg/ml 96% neg predictive value) NT-proBNP (14.75 pmol/l or 125 pg/ml for 75 100% neg predictive value) Nohria et al AmJCard 2005;96:32G

9. BNP and PCWP J Card Fail 2001;7:21

10. BNP/proNT-BNP and CKD Vickery et al. Am J Kidney Dis 46:610

11. Bedside Tests CXR –Cardiogenic vs. –Non-cardiogenic

12. CVP CVP corr coef 0.16 with blood vol CVP corr 0.18 with stroke index Osman et al Crit Care Med 2007; 35:64

13. Swann vs. Clinician ESCAPE study Am Heart J 2001;141:528

14. PCWP and Volume Expansion Osman et al Crit Care Med 2007; 35:64

15. Bioimpedance BIG substudy of ESCAPE Am Heart J 2009;158: 217-223Am Heart J158

16. Where does sodium go? Heer M, Baisch F, Kropp J, Gerzer R, Drummer C: High dietary sodium chloride consumption may not induce body fluid retention in humans. Am J Physiol Renal Physiol 278:F585

17. Skin? Schafflhuber M, Volpi N, Dahlmann A, Hilgers KF, Maccari F,Dietsch P, Wagner H, Luft FC, Eckardt KU, Titze J: Mobilization of osmotically inactive Na+ by growth and by dietary salt restriction in rats. Am J Physiol Renal Physiol 292:F1490 Dry Weight

18. How can sodium be made osmotically inactive? Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C–dependent buffering mechanism Agnes Machnik1, Wolfgang Neuhofer2, Jonathan Jantsch1,3, Anke Dahlmann1, Tuomas Tammela4,Katharina Machura5, Joon-Keun Park6, Franz-Xaver Beck2, Dominik N Mu¨ller7, Wolfgang Derer8,Jennifer Goss1, Agata Ziomber1, Peter Dietsch9, Hubertus Wagner10, Nico van Rooijen11, Armin Kurtz5,Karl F Hilgers1, Kari Alitalo4, Kai-Uwe Eckardt1, Friedrich C Luft7,8, Dontscho Kerjaschki12 & Jens Titze1

19. 1. High salt diet leads to hypertonic sodium accumulation in skin via hyperplasia of lymphcapillaries.

20. 2. Activation of tonicity-responsive enhancer binding protein (TonEBP) in mononuclear phagocyte system (MPS) cells infiltrating the interstitium of the skin LS vs. HS

21. 3. TonEBP binds the promoter of the gene encoding vascular endothelial growth factor-C

22. 4. MPS depletion or VEGF-C trapping by soluble VEGF receptor-3 blocks VEGF-C signaling, augments interstitial hypertonic volume retention, decreases endothelial nitric oxide synthase expression and elevates blood pressure in response to HSD. Extracellular volumeIntracellular volume Clondronate liposomes deplete MPS, PBS liposomes were controls

23. VEGF-C and Kidneys H van Goor,H Leuvenink, Kidney International (2009) 75, 767

24. New Paradigm Na + = Volume H 2 O = Tonicity TBW ICFECF Blood sequestered