Hemodialysis (HD): overview

Basic setup

Blood from the patient perfuses an extracorporeal circuit and enters the tiny capillaries of the hollow fiber dialyzers
Dialysate passes on opposite side of membrane
High efficiency system: blood and dialysate move at rapid speeds, so particles move quickly
Particle removal is mostly by diffusion
Fluid removal by
(hydrostatic pressure across the dialyzer membrane)
- Small particles are also forced across the membrane by hydrostatic pressure

Small and middle sized (based on molecular weight) molecules tend to traverse the membrane fairly easily
- “Small” molecules are <500 Da
- “Middle” molecules are 500-60,000 Da
- “Large” molecules >60,000 Da
Small molecules may be bound to larger molecules such as albumin
- When this is the case, the small molecules will behave like the larger molecules they are bound to

The removal of plasma water from whole blood across a semipermeable membrane (the dialysis filter) down a pressure gradient
- There is positive pressure in the blood compartment and negative pressure in the dialysate compartment; the difference between these two is the transmembrane pressure (TMP)
- To increase the UF rate in HD, we decrease the pressure of the dialysate, which increases the hydrostatic pressure gradient (TMP)
  - When moving down this pressure gradient, the movement of water “drags” the dissolved solutes along with it (this “solvent drag” is called convective mass transfer)
    - Ultrafiltrated water is isotonic
      - Contrast this with loop diuretics, which produce a hypotonic urine
    - Solids and large molecules are left behind; the exact composition of the ultrafiltrated fluid depends on the TMP and on the characteristics of the filter membrane
In dialysis, we use the term ultrafiltration to quantify the net removal of water

In dialysis, convection refers to the mass transfer of solutes down a pressure gradient in ultrafiltrated fluid
- Pressure is applied to one side of the semipermeable membrane, forcing water and the dissolved molecules across the membrane
  - To establish this pressure gradient, one can apply positive pressure on one side of the membrane or negative pressure to the other side; in dialysis, we apply negative pressure on the dialysate side of the membrane to force water and solutes over from the blood side of the membrane
- Unlike diffusion, particle movement is not dependent on size: if molecules can fit through the pores of the membrane, they will flow equally well
  - Membrane pore size limits the convective transfer of molecules larger than 20-50 kDa

Given the same dose of dialysis, diffusion and convection are similarly effective at removing small solutes, but convection is better at clearing large molecules

K₀A (“K-O-A”) is a property of the dialyzer
Product of permeability (K₀) & surface area (A): K₀A = K₀ & A
- Permeability (K₀) = transfer coefficient of the membrane for a given solute
  - Dependent upon pores per surface area, thickness of the membrane, and design of the dialyzer (i.e., degree of contact between blood and dialysate columns across the membrane)
Describes maximum ability of dialyzer to “clear” a given substance (how well the filter allows molecules to move from the blood into the dialysate)
The in vitro K₀A is specified by the manufacturer of the dialyzer
In vitro K₀A is often 20-30% higher than in vivo measurements
K₀A urea is the maximum possible urea clearance (mL/min) at infinite Q_B and Q_D
High efficiency dialyzers have a urea K₀A >600 mL/min, whereas conventional dialyzers have a urea K₀A of <500

Clearance (K_D) describes ability of a dialyzer to remove a substance from the blood under a given set of circumstances (the dialysis prescription)
- Some define high efficiency dialyzers as having a K_urea of >210 mL/min
Clearance is a function:
- Size and permeability of the filter selected (K₀A)
- Blood flow rate (Q_B)
- Dialysate flow rate (Q_D)
At higher blood flow rates, larger dialyzers are able to achieve better clearance (greater efficiency) than smaller dialyzers at the same blood flow rates
At lower blood flow rates (<100 mL/min), there is no advantage to using a large dialyzer
- In children, we may not be able to achieve a high blood flow rate, so a smaller dialyzer may be more appropriate
  - Smaller dialyzers require smaller extracorporeal blood volume - less blood outside of the patient that is liable to clot
Smaller molecules (e.g., urea) diffuse easily, and clearance (K_D) increases with Q_B and Q_D
Larger molecules (e.g., vitamin B12) diffuse slowly, and clearance does not increase as much as blood or dialysate flow rates increase
- In other words, large molecules have a lower K_D (relative to small molecules) for a given Q_B and Q_D