H2i / H3ii / 21B20: Describe the physical principles of haemodialysis and haemofiltration, including the factors affecting clearance (80% marks). Outline the key components of renal replacement fluids (20% marks).

21B20: Exam Report

Describe the physical principles of haemodialysis and haemofiltration, including the factors affecting clearance (80% marks). Outline the key components of renal replacement fluids (20% marks).

28% of candidates passed this question.

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.

H2i / 21B20: Describe the physical principles of haemodialysis and haemofiltration, including the factors affecting clearance (80% marks). Outline the key components of renal replacement fluids (20% marks)

Definition

Clearance =  volume of blood completely purified of a solute per unit time (ml/min)

Haemodialysis

  • Composition of patient’s blood is altered by exposure to dialysate through a semi-permeable membrane.
    • Small molecules are cleared via diffusion
      • Diffusion = movement of solute down it’s concentration gradient, across the semipermeable membrane.
  • Rate of diffusion (and thus clearance) is outlined by the Fick equation
  • MAIN factor = concentration gradient (dc), which is influenced by
    • Blood concentration of solute – dialysate concentration
    • Counter-current mechanism maintains the concentration gradient along the length of the filter
  • Filter membrane characteristics:
    • dx = Thickness
    • A = surface area
  • Temperature (warmed)
  • Diffusivity coefficient for the solute, influenced by:-
    • the gas constant
    • size of the solute particles (larger size = lower coefficient)
  • Diffusivity coefficient for the solute
    • Particle size (increased molecular weight decreases diffusivity)
    • viscosity of the solvent

Haemofiltration

  • Composition of patient’s blood is altered by creating a transmembrane pressure (TMP)
  • TMP is the pressure gradient from a chamber containing the patient’s blood, across a semipermeable membrane, into an effluent chamber (filtrate).
    • Water moves due to ultrafiltration
    • Small and middle sized molecules via convection (solvent drag)
  • Filtrate is replaced with a replacement fluid.

Factors affecting clearance

  • Clearance of water by ultrafiltration depends on:
    • TMP, which is generated by the rate of flow into and out of the filter, and the rate of flow of effluent out of the filter
      • TMP = (Pf+Pr)/2 – Pe
        • Pf = pre-filter pressure
        • Pr = return pressure
        • Pe = effluent pressure
      • Plasma oncotic pressure, which opposes TMP, and which can be reduced by adding pre filter fluid.
  • Clearance (Cl) of solutes by convection is described by:
    • Cl = Qf × Cb × S
      • Qf = ultrafiltration rate,
      • Cb = solute concentration in plasma water
      • S = sieving coefficient:
        • measure of how easily a substance passes through the filter, from the blood compartment, to the effluent compartment

Factors Affecting Both

  • Adsorption: large molecules (cytokines, coagulation factors) adhere to the membrane
  • Protein binding: small or middle sized molecules bound to large proteins cannot be dialysed or filtered. e.g. aspirin binds 80-90% to albumin, therefore clearance rate lower in high protein states
  • Volume distribution: only molecules in the vascular compartment can be cleared: barbiturates have large Vd, whereby fat compartment acts a store.
  • The Gibbs-Donnan effect:
    • Impermeant charged ions in the blood create an electrical gradient that influences movement of permeant charged ions

Renal Replacement Fluids

  • 5000ml bag, warmed to body temp, containing:-
    • Electrolytes
      • Na generally isotonic
      • K variable: absent in many, can be added to physiological levels
      • Mg variable, but generally low-normal cf. physiological level
      • Phos variable (present in Phoxillium, absent in others)
      • Ca variable (absent in Prismocal, supraphysiological Hemsol B0, physiological in phoxillium)
      • Osmolarity = generally close to physiological (282-289mosm/L)
    • Buffer (increases strong ion difference (alkalinises)
      • Bicarbonate
      • Lactate
      • Acetate
      • Citrate
    • Sterile water

References

  1. Derranged physiology ‘Theoretical Foundations of Renal Replacement Therapy’ was heavily plagiarised for this
  2. Nomenclature for renal replacement therapy in acute kidney injury: basic principles
  3. Taken from the various product info sheets or direct from the bags in the unit:

Author: Freddie Hopkinson