Applied Renal – Dialysis

Master answer

Physical Principles and factors affecting clearance

• Haemodialysis:
  • Uses diffusion: “the movement of solutes from a high to a low solute concentration across a semipermeable membrane”
    • Convection (see below) occurs during diffusion
  • Blood is pumped through an extracorporeal circuit that contains a dialyser
  • Dialysate flow is countercurrent, with maximizes the gradient for diffusion
  • Solutes move across a membrane between blood and dialysate as per Fick’s Law
  • Flow across the circuit is determined by:
    • Set flow rate of centrifugal dialysis pump
    • parts of the circuit:
      • access port of vascular access (catheter / fistula / graft)
      • from patient (pre-membrane)
      • across membrane (trans-membrane)
      • to patient (post-membrane)
      • return port of vascular access (catheter / fistula / graft)
  • Assuming that machine delivers the flow which is set and the flow remains laminar and constant, the pressure across the various components varies based on the resistance.
  • The pressure gradient across the circuit depends upon:
    • characteristics of patient:
      • Blood viscosity
        • hematocrit
        • Blood protein and lipid content
        • Temperature changes changes flow and viscosity
        • Fåhræus–Lindqvist effect: Viscosity reduces in smaller diameter – because erythrocytes move over to the centre of the vessel/circuit, leaving only plasma near the wall of the vessel.
      • variable resistance during breathing or movement
      • collapsing vessels due to decreased vessel size / hypovolemia
      • antivoagulation used
    • characteristics of vascular access:
      • gauge and length of access
      • resistance from physical obstruction
      • resistance position
      • resistance from clots, fibrin
    • characetristics of circuit:
      • Age of circuit, presence of clots, fibrin
      • radius
      • length (usually constant ~3.5m)
      • surface coating of circuit
      • anticoagulation used
    • characteristics of membrane:
      • resistance worsens with clot, fibrin, lipid deposition
• Haemofiltration:
  • Uses ultrafiltration: “the movement of fluid through a membrane caused by a pressure gradient (hydrostatic or osmotic pressure)”
    • Convection (see below) occurs during ultrafiltration
  • Positive hydrostatic pressure in blood and a negative hydrostatic pressure in dialysate is generated → causing ultrafiltration and removal of solutes via solvent drag
  • Elimination via bulk flow is independent of solute concentration gradients across the membrane
  • Transport is dependent on starling forces
    • The transmembrane pressure generated: blood flow to the membrane; oncotic pressure gradient
    • Porosity of the membrane
  • Additionally, a high filtration fraction will cause excessive haemoconcentration, and clotting of the filter
  • The filtered fluid (ultrafiltrate) is discarded, and replaced with another fluid depending on the desired fluid balance

Other Mechanisms involved:

• Osmosis:
  • the movement of a pure solvent such as water, through a differentially permeable membrane, from a solution that has a lower solute (particle) concentration to one that has a higher solute concentration
  • The rate of osmosis depends on the concentration of solute, the temperature of the solution, the electrical charge of the solute and the difference between the osmotic pressures exerted by the solutions.
  • Movement across the membrane continues until the concentrations of the solutions equalise.
• Convection:
  • The movement of solutes with a water-flow “solvent drag” across a membrane during osmosis or ultrafiltration
  • Important for movement of small solute (urea, creatinine).
• Adsorption:
  • when the molecules (solutes) adhere to the surface or interior of the membrane.
  • with the movement of fluid across the membrane, if no fluid is moving then adsorption can not occur.
  • in 2 manners:
    • surface adsorption where the molecules are too large to permeate and migrate through the membrane; however they can adhere to the membrane.
    • bulk adsorption occurs within the whole membrane where molecules can permeate it.
  • Molecules that can be effectively adsorbed include:
    • B2 microglobulin
    • Cytokines
    • Coagulation factors
    • Anaphylatoxins

Renal Replacement Fluids

• Typically pre-packaged in 5L bags of sterile water
• contain sterile water, electrolytes and buffer
• Vary slightly in composition, but all are balanced salt solutions with either a lactate, bicarbonate or citrate buffer
  • Bicarbonate-based solutions: most commonly used two-compartment systems. 25-35mmol/L and used as both dialysate and replacement fluids
  • Lactate-based solutions: stable, cheaper, practical. But buffering capacity depends on conversion of lactate to bicarbonate. So not commonly used in CRRT
  • Citrate-based solutions: new generation, administered prefilter. Advantage that additional anticoagulation is not required.
    • Calcium-free solutions: When citrate-based fluids are used prefilter, these are used as dialysate and replacement fluids
• At present, there is no evidence to suggest that the choice of replacement fluid has an impact on survival or renal recovery.
• Replacement fluid can be added pre- or postfilter in varying ratios.
  • The benefit of adding some of the replacement fluid prefilter is that it lowers the hematocrit of the blood, which reduces the likelihood of the filter clotting.
  • The downside is that predilution reduces solute clearance and a compensatory increase in flow rates should be considered (15% for ultrafiltration rates of 2 L/h and up to 40% for rates of 4.5 L/h).

Source: Mishra, Rajesh Chandra. ISCCM Manual Of RRT And ECMO In ICU A Reference Book For Practicing Intensivists (p. 25). Jaypee Brothers Medical Publishers.
Kerr’s notes

JC / Kerr 2022

Answer by JC, Kerr