Dialyzing membranes

Three primary processes are utilized for the removal of substances from the blood. Diffusion is the movement of a solute across the dialyzer membrane from an area of higher concentration (usually the blood) to a lower concentration (usually the dialysate). This process is the primary means for small molecules to be removed from the bloodstream, such as electrolytes. At times, solutes can be added to the dialysate that are diffused into the bloodstream. Changing the composition of the dialysate allows for control of the amount of electrolytes... 

A process similar to osmosis is dialysis. In dialysis, a dialyzing membrane allows both solvent and minute solute particles of a certain size to pass. The passage of these particles, like osmosis, is from a region of high concentration to a region of low concentration. Our kidneys are a dialysis system responsible for the removal of toxic wastes from the blood. In artificial dialysis, blood is circulated through dialysis tubes made of membranes, which are immersed in a clean solution that lacks the wastes in the blood. The impurities are filtered out of the blood as they move across the walls of the dialyzing tubes. 

Figure 8.1 shows, in graphical terms, the concentration gradients of a diffusing solute in the close vicinity and inside of the dialyzer membrane. As discussed in Chapter 6, the sharp concentration gradients in liquids close to the surfaces of the membrane are caused by the hquid film resistances. The solute concentration within the membrane depends on the solubility of the solute in the membrane, or in the liquid in the minute pores of the membrane. The overall mass transfer flux of the solute J(kmol h m" ) is given as... 

Hollow Fiber with Sorbent Walls. A cellulose sorbent and dialyzing membrane hollow fiber was reported in 1977 by Enka GlanzstolT AG. This hollow fiber, with an inside diameter of about A00 p m. has a double-layer wall The inner wall consists of Cuprophan cellulose and is very-thin. approximately 8 pm. The outer wall, which is ca 40-prn thick, consists mainly of sorbent substance bonded by cellulose. The advantage of such a fiber is that it combines the principles of hemodialysis w ith those of hernoperfusion. Two such fibers have been made one with activated carbon in the liber wall, and one with aluminum oxide, which is a phosphate binder. 

As mentioned earlier, a simple dilution effect may not be achieved by increasing the solution volume. The increase in flow rate on one side of the dialyzing membrane may effect an increased efficiency of dialysis. In this case, part of the diluent effect would be negated by obtaining a larger proportion of the test material in the recipient stream. On the other hand, increased flow rate might decrease the dialysis efficiency and the result obtained would be out of proportion to the simple dilution to be expected. 

As blood circulates along the dialyzer membrane, uremic toxins diffuse into the dialysate that is discarded, under the action of the concentration gradient (Figure 18.3). 

In this equation./ A is the surface area X is the thickness of the dialyzing membrane/ and D is the diffusivity of a given solute in the dialyzing membrane. Solute diffusivity is primarily determined by molecular weight. 

Victims of kidney disease rely upon artificial kidney machines to remove waste products from their blood. Such machines use a process called dialysis, which is similar to osmosis. The difference is that the dialyzing membrane permits not just water, but also salts and other small molecules dissolved in the blood to pass through. These move out into a surrounding tank of distilled water. The red blood cells are too large to pass through the dialyzing membrane, so they return to the patient s body. 

An example of a hemodialyzer is shown in Figure 45-17. The most important fimctional part is the dialyzer membrane. Biocompatibihty of the dialyzer membrane is an essential requirement because of high surface areas and long contact times with blood. The most important physiological interactions that occur, apart from protein fouling of tubing and membranes, are complement activation and induction of cytokine release. 

Another cause of dialysis-induced hypoxemia is the use of bioincompatible dialyzer membranes, which activate complement (C3 and C5). This causes the formation of C3a and C5a, which are chemotactic for neutrophils and are ana-phylatoxic, thereby causing pulmonary sequestration of neutrophils and platelets (hence neutropenia and thrombocytopenia), with resultant ventilation-perfusion (V/Q) mismatch and hypoxemia. This is evidenced by the simultaneous development 15 minutes after the start of dialysis of hypoxemia, neutropenia, and high circulating levels of C3a and C5a (C2). 

Dialyzer membrane bioincompatibility, hence complement activation, is maximal with the first use of cuprophane membranes, is considerably less with cellulose acetate, and is negligible or absent with polyacrylonitrile and polymethacrylate membranes. With dialyzer reuse, complement activation is greatly attenuated (C2). The effects of dialysate and dialyzer on the induction of hypoxemia are additive, so that hypoxemia is greatest during the first use of a cuprophane membrane and acetate bath, but is much improved by the substitution of a bicarbonate bath. The use of a polyacrylonitrile or polymethacrylate membrane with a bicarbonate bath will not cause hypoxemia (D3). 

Vs we have seen in Section 7.8, blood is the medium for exchange of both nutrients and waste products. The membranes of the kidneys remove waste materials such as urea and uric acid (Chapter 22) and excess salts and large quantities of water. This process of waste removal is termed dialysis, a process similar in function to osmosis (Section 7.6). Semipermeable membranes in the kidneys, dialyzing membranes, allow small molecules (principally water and urea) and ions in solution to pass through and ultimately collect in the bladder. From there they can be eliminated from the body. 

This binding was not affected by high micromolar concentrations of either its precursor, NAD+, or its breakdown product, ADP-ribose, although it could be totally inhibited by 0.3 (xM unlabeled cADPR. Scat-chard analysis indicated a of 25 fmol/mg protein and a of around 17 nM. However, the presence of dialyzable endogenous cADPR in the microsomal preparations may obscure the determination, since in dialyzed membranes considerably lower Kj values have been obtained (Lee et al, 1994c). 

The commercial article is yellowish-hro NTn sp. gr. 0.919 to 0.943 soft, flexible almost impermeable, but still capable of acting as a dialyzing membrane when used in sufficiently thin layers. It is insoluble in HsO and alcohol, both of which, however, it absorbs by long immersion, the former to the extent of 35 per cent., and the latter of 20 per cent., of its own weight it is soluble in ether, petroleum, fatty and essential oils its best solvent is carbon disul-fld, either alone, or, better, mixed with 5 parts of absolute alcohol. 

The excellent sorption capacity of the hypercrosslinked mesoporous poly-DVB with respect to selective removal of P2M from its mixtures with albumin and other semm proteins, combined with superior hemocompat-ibility of the beads surface modified with poly(N-vinyl)pyrrolidone, justified the manufacturing of an experimental batch of the material for initial clinical studies. The polymer was named BetaSorb (RenalTech International, USA) and was used in 300 mL cylindrical polysrdfone devices that were steam-sterilized and filled with normal saline containing 1000 lU heparin. The device was placed in line with the dialysis circuit, upstream of the dialyzer, in order to not affect the pressure drop across the dialyzer membrane. The blood flow was maintained at the customary value of 400 mL/ min, again the optimal flow rate for the dialyzer. The complete setup of the combined hemoperfusion-hemodialysis treatment [361] is displayed in Fig. 15.2. 

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