WHAT IS DIALYZER?

What is a dialyzer? How it works?

The dialyzer has semipermeable membrane – thousands of hollow fibers each thinner than a hair- is housed in a housing material made up of polycarbonate case. The case holds the hollow fiber membranes together and has ports for blood and dialysate to flow in and out.  Both the header sides of the dialyzer are sealed with polyurethane compound by just allowing open ends of the membranes to expose to the blood & allow it to get in and out from the other open end.

Classification of artificial membrane used for blood purification therapy 

Artificial membranes are classified based on the following categories:

a) Biocompatibility

b) Membrane Surface Area

c) Molecular weight cutoff

d) Ultrafiltration Coefficient

e) Mass transfer Coefficient

f) Clearance

a) Biocompatibility:   

Something that is biocompatible will not trigger a response from the body’s immune system. When blood touches a foreign substance, immune cells rush to defend the body. This response is meant to help us, but it can cause harm. The blood may clot to prevent blood loss but this can cut off blood flow. Or, an allergy may occur.

All dialyzers are made of foreign substances. They all react to some degree with immune cells in the patient’s blood. These effects may be so subtle that patients do not notice them. They may cause minor symptoms during treatment. Or, rare but severe allergies (anaphylaxis) can occur that could lead to death. It is vital to use a membrane the patient can tolerate.

We can test a membrane against a patient’s blood. The body releases certain proteins and chemicals when blood meets a foreign substance. Their levels can tell the doctor how biocompatible a membrane is for that patient.

How well a membrane adsorbs (attracts and holds) proteins are key to whether it is biocompatible. Adsorbed proteins coat the inside of each fiber so blood touches the protein – not the “foreign” membrane.

Bio incompatibility is not quantifiable hence it depends on evidence of activation of the following processes.

1)Thrombogenesis: Is a degree of activation of platelets causing clotting of the dialyzers.  synthetic membranes activate platelets less than cellulosic membranes. 

2)Complement activation:  The complement system of proteins is an important non-specific component of the body’s reaction to and defense against foreign-substance attack.    Activation of the complement system is a marker of bio incompatibility. 

3)Leukocyte activation Leucocytes, when coming in contact with bio incompatible surfaces, becomes “sticky”.  These Leukocytes lose their stickiness over time and re-appear in the circulation as dialysis progresses.

4) Cytokine induction:  Cytokines are “the words in the language that cells use to talk to each other”. Activation of the immune cells causes the release of cytokines that in turn activate other cells and mediators of the inflammatory response. Cytokines also have various adverse effects on nutrition and metabolism.  

b) Membrane Surface Area:   

The surface area is the maximum available area of the membrane for diffusion to occur in a better way.  The surface area is key to how well a dialyzer removes solutes. If all else stays the same, dialyzers with more surface area expose more blood to the dialysate. This means we can remove more solutes. The total dialyzer surface area can range from 0.5-2.5 square meters.

c) Molecular cut-off:   

Molecular weight cutoff is the largest molecule that can pass through a membrane (see Figure 3). It is measured in daltons (Da). Larger molecules have higher molecular weights. Smaller molecules have lower ones (see Table 1). Doctors choose membranes that will remove certain molecules from the blood.

A group of small molecules has urea and creatinine with molecular weights 60 & 113 daltons respectively.  The other group of middle molecules has Vitamin B12 and B2-microglobulin with molecular weights 1355 & 11818.  The third group of large molecules has some protein-bound substances such as myoglobin, cytokines & leptin, etc.

d) Ultrafiltration Coefficient:    

Water permeability is a function of pore size - dialyzers are classified according to their KUF values printed on a dialyzer brochure.  This value shows the rate of flow across the membrane per unit of effective transmembrane pressure.  For instance,

KUF value for low flux dialyzers will be < 10ml/hr/mmHg/m2 whereas for High flux dialyzers KUF will be 20ml/hr/mmHg/m2.

For example. A patient is using a dialyzer with Kuf of 10.  The dialysis machine’s TMP reads 100 mmHg. The patient would lose 1000ml of water per hour of treatment (10ml/hr/mmHg × 100 mmHg = 1000 ml/Hr) 

e) Mass Transfer Coefficient: KоA

Kо (membrane clearance) × A (surface area) = KоA, or mass transfer coefficient. KоA measures how well a given solute will pass through a membrane. It is the highest possible clearance of that solute through a membrane at certain blood and dialysate flow rates. A higher KоA means a more permeable membrane

A KоA can be used with any blood and dialysate flow rates to estimate how well a membrane will clear a certain solute. The most common read the section of measuring dialyzer effectiveness.

f) Clearance:

Dialyzers vary in how well they remove solutes from the blood. The amount of blood that can be cleared of a solute in a given time is clearance (K). Dialyzer makers give clearance rates for molecules at certain blood and dialysate flow rates.

There are three main ways to remove solutes that affect a dialyzer’s clearance:

A)Diffusion

B)Convection

C)Adsorption

Membrane Materials

Like a nephron in a kidney, a dialyzer membrane is selective. It allows only certain solutes and water to pass through. Large substances, like protein and blood cells, won’t fit through the small pores.

A membrane’s material and clearance will affect how it works (see Figure 4).

What a membrane is made of can affect diffusion and UF. The material can also affect the efficiency of the treatment and the patient’s comfort.

Cellulose Membranes

Early dialyzer membranes were made from cellulose, a plant fiber. These membranes were thin and strong, but they were not biocompatible. Experts were concerned that the dialyzer membranes were causing poor clinical outcomes. This type of membranes is no longer in use.

Cellobiose (a glucose dimer) is the repeating unit in a basic cellulose (e.g., Cuprophane) polymer membrane. The basic molecular structure is unsubstituted resulting in frequent and repeatedly exposed -OH (hydroxyl) groups on the surface of the membrane. As we will see later this -OH group has implications for blood-membrane interactions.

Modified Cellulose Membranes

Starting in the 1970’s, cellulose membranes were chemically changed (some of the hydroxyl groups were replaced with other molecules). These changes made the membranes more biocompatible. To avoid confusion, they are called “modified cellulose membranes.”

They use convection, diffusion, and adsorption to remove solutes.  These membranes do a good job with solutes up to 15000 Da, so they clear β2M(11800 Da) to some extent. Biocompatibility ranges from good to very good.

Synthetic Membranes

Synthetic membranes are made from these polymers (long strings of plastic).

      Polycarbonate

      Polyacrylonitrile (PAN)

      Polysulfone (PSF)

      Polyethersulfone (PES)

      Polymethylmethacrylate (PMMA)

Solutes are removed by diffusion, adsorption, and a bit of convection.  Clearance of solutes depends mainly on UF rates. Synthetic membranes do a good job of removing solutes up to 15000 Da, so they clear some β2M (11800 Da). Their biocompatibility is very good. They are highly adsorptive, so they can quickly keep the blood from touching the membrane. Dialyzer membranes have improved over time. Today, they are more consistent and tightly controlled. This means we can better control diffusion and solute removal. With better membranes–like high flux membranes–came the need for more control over UF. Volumetrically controlled machines came on the market in the early 1980s.