Sodium flux during dialysis

1. Sodium flux during dialysis Sushrut S. Waikar, MD, MPH Renal Division Brigham and Women’s Hospital, Harvard Medical School

2. Background • Kidneys filter the blood, clearing it of waste products • 20% of heart’s output is directed to the kidneys, which filter ~180L plasma per day • Kidneys also regulate water and salt balance

3. Background • Loss of kidney function leads to death within days • Excessive buildup of nitrogenous waste, acid, potassium, sodium, water • Kidney function can be partially replaced by hemodialysis (~300,000 patients in United States)

4. Hemodialysis • Kidney function can be partially replaced by hemodialysis • First performed by Wilhelm Kolff in early 1940s • Procedure is typically performed for 4 hours thrice weekly (e.g., Monday, Wednesday, Friday)

5. Hemodialysis procedure • Blood flows into tubing that divides into thousands of parallel hollow fibers • Each fiber is a semipermeable membrane • Outside of the fibers runs the “dialysate” solution

6. Clearance during dialysis • Convection • Negative pressure applied, water and dissolved small solutes (< 40 kDa) pass across membrane into the dialysate fluid which is then discarded • Diffusion • Solutes travel across membrane down concentration gradient • Blood and dialysate flow in opposite directions, maximizing concentration gradient

7. Goals of a dialysis procedure • Get rid of the water that was ingested and produced (during metabolism) since the last procedure – usually 3 liters • Done by convection • Get rid of salt (sodium chloride, potassium chloride) • Maintain acid-base balance • Get rid of nitrogenous waste products (urea)

8. Plasma versus dialysate

10. Urea 70 mg/dL Urea 30 mg/dL

11. Sodium 142 meq/L Sodium ? meq/L

12. Sodium in dialysate: 140 meq/L Sodium 142 meq/L Sodium ? meq/L

13. Sodium in dialysate: 140 meq/L Sodium 142 meq/L Sodium ? meq/L CONVECTIVE CLEARANCE: water and small solutes are removed by negative pressure across membrane DIFFUSIVE CLEARANCE: sodium moves down its concentration gradient (in either direction, depending on plasma concentration; dialysate sodium usually fixed)

14. Factors that influence sodium flux • Dialysate sodium concentration = 140 meq/L • Plasma sodium concentration = 142 meq/L, changes during procedure • Convection and diffusion occur simultaneously • Gibbs Donnan effect • Large negatively charged proteins NOT able to pass through membrane; electroneutrality must be maintained • Sodium and other cations less “permeable” than anions like chloride, bicarbonate

15. Sodium 142 meq/L Sodium ? meq/L

16. Factors that influence Na in plasma • Plasma sodium concentration itself has many determinants, not just mass balance of sodium and water • Also affected by potassium mass balance • Water and sodium flux in various body compartments

17. Distrbution of salt + water in body • Water in a 70 kg man • 60% water = 42 liters • Intracellular: 28 liters • Extracellular: 14 liters • Interstitial = 10 liters • PLASMA VOLUME = 4 liters • Sodium is the primary extracellular cation, 140 meq / liter • Intracellular sodium

18. Dialysis membranes • Hollow fibers ~12,000 in parallel • 20 – 24cm length, diameter 180 to 220 um, 6 to 15 um thickness • Pores: avg diameter 30 Angstroms, 10^9 in number • Old: Cellobiose (saccharide) • New: synthetic membranes (e.g., polysulfone, polyamide, polymethylmethacrylate) • Manufactured polymers classified as thermoplastics

19. Dialysis procedure • Blood flow ~ 400 ml/min • 40% red blood cells, 60% plasma • Plasma: 93% water, 7% protein and lipids • Dialysate flow ~ 800 ml/min • Typically 2-4 liters of “ultrafiltration” (volume removed during 4h procedure)