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A. the binding of the solute to protein: Diffusible substance may bind to proteins forming dialysis membrane impermeable complex. Such solutes are no longer available for diffusion (40-50% of measured calcium in patient blood is available for diffusion). The percentage of the total concentration of a diffusible solute (actually free to diffuse) is described as “solute activity”. B. the Gibbs-Donnan effect: Blood proteins are dialysis membrane impermeable, negatively charged and tend to accumulate at the membrane surface during dialysis. Coresponding numbers of membrane permeable cations such as sodium, calcium, magnesium must then retain in the blood to preserve elecroneutrality. This results in imbalance in the concentration of ions across the dialysis membrane. The protein-induced ion transport asymmetry is called the “Gibbs-Donnan effect”. It indirectly affects the magnitude of the concentration gradients required to drive diffusion across dialysis membrane. As solute movement continues over a peroid of time, the concentration falls in the solution of higher concentration, rises in the solution with the lower concentration, and the two solutions approach each other in composition i.e Equilibrium. As a result of this dissipation of the concentration gradient, the transfer of solute slows with the time.The maximum rate of solute transfer occurs initially when the concentration gradient is greatest.
Schematic diagram of diffusion No hydrostatic pressure is applied [Van Stone et al 1994, Physiology of peritoneal dialysis in handbook of dialysis 2nd edition]
The dissipation of the concentration gradient can be minimized and the transfer of solute optimized by increasing the volume of the fluids. a) In a static system (comparable to peritoneal dialysis) this is accomplished by replacing the recipient fluid with fresh solution at periodic intervals. b) In a flowing system (comparable to hemodialysis) this accomplished by increasing the flow rate of parent fluid (blood) or recipient fluid (dialysate). Both artificial and natural membranes are more permeable to small solutes than large solutes. Thus, dialysis is most effective in removing small solutes and less effective in removing larger solutes, particularly those over 1000 daltons.The surface area of the membrane available for diffusion affects the amount of solute transferred.
Mechnisms of solute removal in intermittent hemodialysis and continuous renal replacement therapy
UltrafiltrationThe process of water removal from the blood stream is called ultrafiltration; the fluid removed is the ultrafitrate. The UF during dialysis is performed for the purpose of removing water accumulated by ingestion of fluid or by metabolism of food during the interdialytic period. It is essential to prescribe and control the fluid removal rate so that total fluid removed during dialysis will be equal to the total fluid gained since the previous dialysis or from the dry weight.
Schematic diagram of osmotic ultrafiltration No hydrostatic pressure is applied. Triangles represent osmotic agent introduced to right compartment. This causes an early water shift to the right (ultrafitration), but this is later reversed if the osmotic agent is also small enough to diffuse along the concentration gradient from right to left. Thus only solutes of such size that they do not easily permeate the semipermeable membrane are capable of exerting a sustained osmotic force. [Sorkin MI et al 1994, Physiology of peritoneal dialysis in handbook of dialysis 2nd edition]
Schematic diagram of hydrostatic ultrafiltration The application of external pressure forces movement of water from left to right. Low molecular weight constituents will be swept through the membrane with this water (solvent drag.). In dialysis setting the pressure gradient is generated by manipulation if dialysis fluid parameters such as pressure volume or flow. [Von Stone MI et al 1994, Physiology of peritoneal dialysis in handbook of dialysis 2nd edition] Mechanism of UltrafiltrationA) In Hemodialysis: 1-Hydrostatic pressure The primary driving force for ultrafiltration is the hydrostatic pressure difference across the membrane, which is the Transmembrane Pressure (TMP), expressed in millimeters mercury (mmHg). The TMP is determined by the average or mean pressure in the blood compartment minus the mean dialysate compartment pressure.The relationship of ultrafiltrate to TMP is entirely dependent on the membrane (Dialyzer) properties. The permeability of dialyzer membranes to water is high, varies consonsiderably, and is a function of membrane thickness and pore size.The total capacity of the dialyzer for ultrafiltration is given by the Ultrafiltration Coefficient (KUF). The KUF is defined as the number of milliliters of fluid per hour that will be transferred across the membrane per mmHg pressure gradient across the membrane The KUF of most dialyzer ranges from 2 to 6 ml/hour. The relationship between ultrafiltration, KUF and TMP is expressed as: Ultrafiltration rate (ml/hr) = KUF X TMP How do you calculate UF rate from KUF? If one needs to remove 2 kg during a period of 4 hours 1- Add the volume of saline that will be given at the end of dialysis (usually 300 ml) and the amount of ingested fluid during dialysis (e.g., 100ml). 2- This means that 2.4 L will have to be removed during 4 hours dialysis i.e.2.4 X 1000 /4 = 600 ml/hour. 3- When using a dialyzer with KUF value of 4.0 ml/hour, the TMP will need to be set at 600/4 =150 mm Hg. N.B. (If the dialyzer KUF is 6 the TMP should be = 100 mm Hg). 2-Osmotic Ultrafiltration: Osmotic ultrafiltration does play an indirect role in total ultrafiltration; water shifts from intracellular to the extracellular compartment which occur during hemodialysis (so-called plasma refilling) can be optimized by introduction of an effective concentration of an osmotic agent into the extracellular space. Sodium is employed in some dialysis practice especially during sodium profiling B) In peritoneal dialysis: 1-Osmotic Ultrafiltration The primary driving force for ultrafiltraion in peritoneal dialysis is the Osmotic gradient (Osmotic Ultrafiltration). Osmosis is the movement of the solvent (eg water) from the side of low concentration to the side of higher concentration through a semipermeable membrane.The result of this movement of water will be equalization of total solute concentration on both sides of the membrane. Osmotic ultrafiltraion during peritoneal dialysis is achieved by adding large amount of glucose to dialysis solution. Peritoneal dialysis solution ordinarily contain 1.36 % (1.5), 2.27 % (2.5), 3.86 % (4.25). The osmotic pressure generated by glucose will draw water from the blood and tissues into the dialysate. 2-Hydrostatic pressure The hydrostatic ultrafiltraion effect is of minor importance |
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