Physical and chemical characteristics of dialysis membranes

This chapter is related to the aims of Section H3(i) from the 2017 CICM Primary Syllabus, which expects the exam candidate to "describe the principles of dialysis and renal replacement fluid". Among the principles of dialysis, the properties of the membrane are particularly important, and it is worth knowing a little about them. Having said this, it is also important to acknowledge that the CICM examiners have never asked the trainees anything about this, in either the fellowship or the primary exams. It is possible to go through one's entire fifty year career in Intensive Care neither knowing nor caring about these matters, and the effective use of dialysis in ICU does not rely on the user's indepth understanding of filter membrane composition. The minimum level of understanding for this topic is therefore actually less than the contents of the summary box below.

In summary:

• Dialysis filters contain about 10,000 hollow fibres with a total surface area around 1-2m². 
• Desirable membrane properties are low cost, minimal thickness, maximal strength and biological compatibility
• Most membranes these days are synthetic, highly biocompatible and approximately 100-200 μm thick  with an internal diameter of 200-500 100-200 μm

In the event that one needs or wants to know more, the best references for this topic is probably the article by Yamashita et al (2015) and the older review by Sakai (2000). 

Anatomy of the dialysis filter

The dialysis filter is essentially a cylinder of inert plastic which is designed to separate the blood compartment from the dialysate compartment by means of numerous tiny hollow tubes. This sort of arrangement took over from rotating drums in 1969 (Gotch et al, 1969) and became commercially available in 1972.

The key features of this design are:

• An enclosed plastic jacket which contains the dialysate
• Dialysate inlet and outlet ports, the distance between which is the effective length of the dialyser
• Blood inlets and header caps which contain the flow of blood in and out of the filter
• "Tube sheets" which stabilise the open ends of the hollow fibres
• Hollow fibres which carry blood though the dialyser compartment

In one of the pictures above, the header cap has been removed and the polyurethane tube sheet can be seen. The surface appears rough because of the thousands of little openings, allowing blood into the hollow fibres. The blood, entering the top of the filter, is forced through these tiny openings.

The fibres merit a closer look. They are, after all, where the magic happens.

Each filter may have several thousand (usually around 10,000) such hollow fibres and their length is usually 15-20cm, Up close, one can see that their walls are relatively thin, and their crossection is flat (which allows more of them to be packed in together, increasing the surface area). They become more round in crossection and the walls swell somewhat when they are wet, leaving a working internal diameter of 500-200 micrometers and  giving a total surface area in a range between 0.8 m² to up to 2.5 m².

Membrane materials

The characteristics of an ideal membrane must be:

• Cheap - according to Sakai (2000) over 70 million m² of membrane are used per year, worldwide
• As thin as possible
• As strong as possible, including when it is wet
• Chemically, or at least biologically inert
• Non-thrombogenic
• Selectively permeable, allowing diffusion only for specific undesirable molecules

Biological membranes have it easy. The cellular lipid bilayer can afford to be a nanometer thick because it needs to span only the diameter of the cell, which is tiny. Comparatively, the dialysis filter is a million times larger, and therefore the membrane is a  hundred thousand times times thicker (i.e. in the order of 10-100 microns or so, i.e. 0.01-0.1 mm thick). In order for a clinically significant amount of mass transport to take place, the dialysis filter needs to compensate for the membrane thickness by maximising other variable in Fick's equation susceptible to our control, which is surface area.  This is increased by having multiple hollow fibres which are long enough and numerous enough to have a large combined surface area. Additionally, it is possible to create membrane materials where the filtration membrane - a relatively thin and fragile layer - is deposited on to a relatively thick and porous substrate which acts as a support  structure. The SEM images below are of polyvinylpyrrolidone on poly(vinylidene fluoride) hollow fibres, modified from Zhang et al (2015)

Historically, a variety of materials had been used for dialysis. Abel Rowntree and Turner used nitrogenated cellulose ("celloidin") which was prepared painstakingly by deposition onto glass tubes, using an ether solution. When cellophane became available, that was used instead in the early rotating drum dialysers. Cuprophane came next, which was the trade name for cuprammonium rayon - made from some natural cellulose dissolved in cuprammonium solution. The biocompatibility of these membranes left much to be desired, largely because of the numerous charged (OH) groups on the surface of the molecules. Acetylating the cellulose (replacing the OH groups with acetate groups) resulted in an increased biocompatibility. Generally, cellulose-based membranes were hydrophilic, which favours good interaction with blood components (in contrast, blood clots rather readily when in contact with hydrophobic materials because of their tendency to adsorb protein). 

Modern membranes are entirely synthetic (usually polyarylethersulfones or polyethersulfones) and have a chemical compositions which are carefully guarded industry secrets, like the eleven herbs and spices. These are petrochemicals and therefore are generally hydrophobic, but blending them with something hydrophilic (eg. polyvinylpyrrolidone, PVP) can create the desirable combination of good biocompatibility and high tensile strength. PVP ends up being used as a pore-forming agent, and is then washed out of the membrane, leaving behind the cavities of the "finger" layer.