Question 20

College Answer

A brief description of the underlying mechanisms of dialysis and hemofiltration was required. Diffusion, the predominant mechanism in haemodialysis, involves movement of solute down the concentration gradient across the semipermeable membrane. This concentration gradient is generated and maintained by counter current movement of dialysate and blood. In hemofiltration the predominant mechanism is convection and solvent drag of the solute across the semipermeable membrane by application of transmembrane pressure. The filtrate is then replaced by replacement fluid. Small molecules are effectively removed by dialysis whereas hemofiltration can remove small and middle molecules. Various factors that impact clearance in haemodialysis and haemofiltration were expected separately. Constituents of replacement fluid should have included three broad headings of electrolytes, buffer and sterile water. Many answers lacked the details of how counter current mechanisms help, the difference in the two modalities in regard to clearance of molecules, how clearance is impacted by protein binding and volume distribution, sieving coefficient of the membrane and flow rates of blood and dialysate (or effluent) flow. The constituents of replacement fluid lacked details of various types of electrolytes, the common buffers and the strong ion difference.

Discussion

Key principles of dialysis and factors affecting clearance

• Dialysis is a diffusional clearance strategy, and depends on:
  • Counter-current mechanism (an essential design feature)
  • Factors that influence the passive diffusion of molecules across membranes, which include:
    • Concentration gradient, which is influenced by
      • Blood concentration of the specific solute, and
      • The composition of the dialysate fluid
    • Filter membrane characteristics (thickness, porosity, surface area)
    • Temperature of the solution
    • Diffusivity coefficient for the solute
    • Solute properties, eg. particle size
    • Gibbs-Donnan effect
• Ultrafiltration is a convectional clearance strategy;
  • Clearance of water by ultrafiltration depends on:
    • Transmembrane Pressure (TMP), =  (Pf+Pr)/2 - Pe,  where
      • Pf = pre-filter pressure
      • Pr = return pressure
      • Pe = effluent pressure
    • Plasma oncotic pressure, which opposes TMP, and which can be altered by pre or post-replacement fluid
  • Clearance of solutes by ultrafiltration (convection), or the "convective flux" (Jc),  is described by the relationship Jc = Qf × Cb × S,  where
    • Qf = ultrafiltration rate,
    • Cb = solute concentration in plasma water, and
    • S = sieving coefficient: the ratio of a specific solute concentration in the ultrafiltrate (removed only by a convective mechanism), divided by the mean plasma concentration in the filter.

Replacement fluids:

• Dialysate is the fluid medium used to exchange solutes with the blood in a dialysis filter
• Replacement fluid is the fluid used to dilute the post-filter blood in haemofiltration, restoring volume and buffering the blood as it returns to the patient.
• In CRRT, these fluids are usually supplied as 5000ml bags, pre-packed and sterilised.
• The composition of these fluids is close to the composition of extracellular fluid
• The major difference is that these fluids are usually free from potassium and phosphate
• Most often the buffer used is bicarbonate, but lactate acetate and citrate are other options.
• Other major characteristics expected of dialysate and replacement fluid are that they are sterile and warmed to body temeperature.

Aucella, Filippo, Salvatore Di Paolo, and Loreto Gesualdo. "Dialysate and replacement fluid composition for CRRT." Acute kidney injury. Vol. 156. Karger Publishers, 2007. 287-296.