Page 166 - Biomedical Engineering and Design Handbook Volume 2, Applications

DESIGN OF ARTIFICIAL KIDNEYS 145

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clinical condition called amyloidosis. The molecular weight of β -microglobulin is around
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11,800 Da. The molecular weight of albumin is 66,400 Da. Simply increasing the membrane
size to remove the β -microglobulin can lead to the removal of essential molecules like the
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blood serum albumin, which is close in molecular weight to the toxic molecules. Removal of
β -microglobulin has been shown to reduce morbidity in end-state renal disease (ESRD)
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patients. In addition, the interaction of blood with the dialyzer membrane often results in
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human complement activation. This immunological reaction may result in undesirable effects
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or even in morbidity in ESRD patients. In high flux dialysis, although a positive pressure gra-
dient exists across the hollow fiber tube, the large axial pressure drop may result in lower pres-
sure in certain portion of the distal (venous) end of the fiber. Thus in these regions of the fiber,
the pressure could be lesser than that in the dialysate fluid causing back filtration of dialysate
fluid in these high flux dialyzers. 11,12 This may result in complement-activating factors (cytokine-
inducing substances) to be back transported into the blood, causing significant complement acti-
vation and the associated immunological reactions. 11
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Reliable vascular access is essential for repeated hemodialysis. A fistula is constructed by joining
a major artery in the wrist (e.g., radial artery) with an adjacent vein such that a portion of the arterial
blood takes a shortcut directly into the vein. Woven tubes of synthetic materials such as Dacron, and
expanded polyterofluoroethylene (PTFE, Gortex, Impra) as synthetic grafts should be biocompatible
and blood compatible and should not cause clotting. Transcutaneous vascular access device should
also be blood compatible and biocompatible and should not cause clotting. The transcutaneous access
device should allow easy and quick connections. These access devices should not cause infection. The
National Kidney Foundation has issued clinical guidelines for vascular access. 13
Chemical Safety. Water quality, for dialysate fluid, is a major safety concern. 14 The patient’s
blood is exposed to approximately 20,000 L of dialysate fluid each year. Consequently, impurities
which are considered insignificant for drinking water may be potentially harmful for the dialysis
patient and can create long-term toxic effects. Substances present in the dialysate fluid, even in low
concentrations, can enter the blood stream and cause damage. For example, chloramine can cause
hemolytic anemia. Special attention should be paid to substances that bind to the plasma proteins.
For example, aluminum in small quantities can cause severe brain and bone damage in long-term
dialysis patients. Lead, cadmium, mercury, and selenium, etc., have similar toxic effects. The
Association for the Advancement of Medical Instrumentation (AAMI) has set up standards for
hemodialyzers and water quality for hemodialysis (Table 5.1). In addition, the water used to
makeup the dialysate fluid should not have excess microbial content. Improper water treatment or
inadequate design can lead to biofilm growth on various conduits of the artificial kidney machine.
Bacteria at these biofilm sites may release pyrogen or cytokine-inducing substances and other
endotoxins into the dialysate fluid. Although the microorganisms cannot cross the dialysis mem-
brane, the pyrogen lipids and cytokine-inducing substances produced by these organisms can cross
the dialysis membrane and can lead to infection. 15–17
Proper sterilization of the device (cartridge, etc.) is important. All membranes are not compati-
ble with all types of sterilization. For instance, ethylene oxide (EtO), when conjugated with human
blood serum albumin, may lead to anaphylactic reactions observed in some patients on EtO-sterilized
hemodialyzers.
Mechanical Safety. The dialysis membrane should have high shear strength (resistance to tearing)
and high ultimate strength. The membrane should maintain adequate strength and dimensional sta-
bility while wet. The membrane often loses water-soluble components and often adsorbs components
of the surrounding medium, which can lead to changes in dimensions and mechanical properties.
The blood side flow resistance should be low enough to maintain adequate blood flow with
minimal pumping. Artificial pumping of blood may cause hemolysis (destruction of red blood
cells). Therefore, pressure developed by patient’s own heart should be able to pump the blood
through the dialyzer machine back to the heart. The normal blood pressure in the adult is pulsatile
with 120 mmHg systolic (upper peak of the wave) and 70 mmHg diastolic (lower peak of the
waveform), with an average pressure of 100 mmHg. Blood pressure in children is even lower.
Usually, a roller-type blood pump is used to pump blood. This blood pump is placed in between
the arterial access line and the blood inlet manifold of the artificial kidney device.