Historical background
Thomas Graham, a London chemist, reported the principles of the semipermeable membrane in 1861 and gave the process of selective diffusion the name dialysis. Then, in 1913, Abel, Rowntree, and Turner devised an apparatus for the dialysis of blood, using a number of collodion tubes, through which flowed blood while a saline solution bathed the outsides of the tubes (Fig. 7-1). This device was used successfully to treat animals with uremia. Later, Kolff and Berk developed the first clinically successful artificial kidney, after the development of heparin for anticoagulation and the ready availability of cellulose in the form of cellophane tubing. They employed a rotating drum of wood slats around which a spiral of cellophane tubing was wrapped. The lower portion of the drum was immersed in a bath of dialysis fluid, while the blood was propelled along the tubing by rotating the drum. In 1948 Skeggs and Leonards developed a parallel plate dialyzer; the first disposable dialyzer was the Travenol twin-coil unit, marketed in 1956. About 1965 Gambro began production of disposable parallel plate devices, while at the same time hollow-fiber artificial kidneys were developed in the U.S.
Figure 7-1 Vividiffusion apparatus of Abel, Rowntree, and Turner.
(Adapted from Nosé Y: Manual on artificial organs, vol 1, The artificial kidney, St. Louis, 1969, Mosby.)
Solute transfer
What does hemodialysis mean?
Hemo, of course, means blood. Dialysis connotes a separation or filtration process. Metabolic wastes or toxins are filtered from the blood by a semipermeable membrane and carried away by the dialysis fluid. The goals of hemodialysis are to manage the uremia, fluid overload, and electrolyte imbalances that occur as a result of chronic kidney disease.
What waste products are removed by dialysis?
A large number of substances accumulate in uremia (see Chapter 4). The molecular size of many of these substances is less than 500 daltons (Da). A dalton is a unit of mass and is sometimes called atomic mass unit (amu). Daltons diffuse readily across cellulosic membranes. Particles in the range of 500 to 2000 Da, sometimes called middle molecules, diffuse poorly across such membranes. Polypeptides in this size range have been suspected of causing some uremic symptoms, although this has never been proven. Molecules larger than 3000 Da are not generally regarded as toxic, with the exception of β2-microglobulin (11,800 Da) and its relation to amyloidosis, bone disease, and anemia. See Table 7-1 for the molecular weight of some common substances.
Table 7-1 Molecular Weights of Some Common Substances
|
Substance |
Molecular weight (Da) |
|
Acetylsalicylic acid (aspirin) |
180 |
|
Albumin |
68,000 |
|
β2-microglobulin |
11,600 |
|
Cholesterol |
386 |
|
Creatinine |
113 |
|
Dextrose |
198 |
|
Glucose |
180 |
|
Hemoglobin |
68,800 |
|
Urea |
60 |
|
Vancomycin |
1486 |
Adapted from Daugirdas, JT: Handbook of dialysis, Philadelphia, 2007, Lippincott.
What factors affect the diffusion or removal of toxins in dialysis?
• Dialysate temperature: The higher the temperature, the greater the solute removal.
• Dialysate flow rate: The greater the dialysate flow rate, the greater the removal of solutes.
• Blood flow rate: The greater the blood flow rate, the greater the removal of solutes.
• Molecular weight of solutes: The smaller the molecular weight, the greater the removal of solutes.
• Concentration gradient: The greater the concentration gradient, the greater the amount of diffusion.
• Membrane permeability: The more permeable the membrane, the greater the removal of solutes.
What is a semipermeable membrane?
The semipermeable membrane is a selective membrane and acts as a sieve. The semipermeable membrane used in dialysis allows passage of some substances and fluid, but not all. It may be thought of as having submicroscopic openings or pores. Solute particles larger than these openings cannot pass through and are retained. Those particles small enough to pass through do so at a rate inverse to their size: very small particles traverse more rapidly than those somewhat larger.
How does the semipermeable membrane function in hemodialysis?
The patient’s blood is passed through a compartment formed by the semipermeable membrane. Dialyzing fluid surrounds this compartment. Red blood cells, white blood cells, platelets, and most plasma proteins are too large to pass through the pores of the membrane. Water and small particles, such as electrolytes, cross by diffusion (Fig. 7-2), as do urea (60 Da), creatinine (113 Da), and glucose (184 Da).
Figure 7-2 Semipermeable membrane.
What is diffusion?
Diffusion, or conductive transport, may be defined as the movement of solutes from an area of greater concentration of solutes to an area of lesser concentration of solutes. Molecules in solution are in constant motion and seek to spread uniformly throughout the solution. The rate of spread depends on the concentration, size, and electric charge of the particles. Diffusion of particles across a semipermeable membrane is the basis of dialysis. Diffusion will occur until equilibrium is reached (Fig. 7-3).
Figure 7-3 Typical hemodialysis system. Toxin-laden blood from the patient diffuses across the membrane within the dialyzer into the dialysis fluid. Clean blood is returned to the patient.
(From Black JM, Hawks JH, Keene AM: Medical-surgical nursing: clinical management for positive outcomes, ed 7, Philadelphia, 2005, Saunders.)
Why are all solutes and water in blood not removed by the dialyzer?
The dialysis fluid is an electrolyte solution similar in composition to normal plasma water. Water molecules cross the membrane in both directions, as do electrolytes and other small particles. Only if the concentration of a particular kind of particle is greater on one side than on the other will there be a net flow from the side of high concentration to the side of lower concentration. Solutes and waste products of a small molecular size diffuse from the blood side concentration (high) to the dialysate side concentration (low). This is the concentration gradient, which simply means a difference in concentration. A concentration gradient is necessary to accomplish solute removal in dialysis.
Are membranes permeable to middle-size and large molecules?
Several synthetic materials are used for high-flux dialysis. These include polyacrylonitrile (PAN), polycarbonate, polysulfone, polyamide, polymethyl methacrylate (PMMA), and other membrane materials.
What is mass transfer rate, or solute flux?
Artificial kidneys, or dialyzers, are designed to remove metabolic wastes from the body, restore water and electrolyte balance, and correct acid-base disturbances. The dialysis process involves transport of unwanted or excess solute and excess water from the blood across a semipermeable membrane. The engineering term for such transport is mass transfer, and the rate of movement is the mass transfer rate, or solute flux.
What factors affect mass transfer rate?
Flux, at a constant temperature, is governed by the solute concentration gradient and the physical characteristics of the dialyzer. The latter include effective membrane surface area, membrane permeability, blood and fluid flow rates, and flow geometry. The mass transfer rate varies continually throughout the course of a clinical dialysis procedure.
What is meant by flow geometry?
Flow geometry refers to the direction of the flow of blood and dialysate. Countercurrent flow occurs when the blood and dialysate flow in opposite directions, creating an optimal concentration gradient. Concurrent flow occurs when the blood and dialysate both flow in the same direction, creating a much smaller concentration gradient (Fig. 7-4).
Figure 7-4 Examples of blood and dialysate flow in the hollow-fiber dialyzer.
Transport
What is meant by diffusive transport?
As noted, solute particles diffuse through the dialysis membrane from the side of higher concentration to the side of lower concentration. This movement is termed diffusive transport or, less commonly, conductive transport.
What determines the rate of diffusive transport?
The rate of transfer depends on the following:
• The concentration gradient across the membrane for each solute.
• The surface area of the membrane. The greater the area, the more solute moved per unit of time.
• The mass transfer coefficient for the solute of interest for the particular membrane. The mass transfer coefficient increases for thinner or more porous membranes. It also is affected by the flow rates of both blood and dialysis fluid.
What is the sieving coefficient?
The amount of solute convected across a membrane in proportion to the quantity of fluid ultrafiltrated depends on particle size relative to pore size. If the pore-to-particle ratio is high, there is no restriction of solute transfer and the sieving coefficient is said to be 1. If none of the particles can be squeezed through, the sieving coefficient is zero.
What is convective transport?
When water moves across a membrane because of a pressure gradient (ultrafiltration), there is a friction effect on solute molecules. Low molecular weight molecules or particles can be swept through the membrane, along with the ultrafiltate. This associated solute movement is termed convective transport (from the Latin word convectus, meaning “carried together”) or solute drag.
What is the importance of convective transport?
Solute particles larger than 500 Da may have a low sieving coefficient but, because of their low diffusive transport, the convective component becomes a major fraction of their total transfer. Convective transport is of prime importance in high-flux hemodialysis and in the techniques of continuous arteriovenous hemofiltration, hemodialysis, and diafiltration.
What is meant by clearance?
Clearance is an empirical measure indicating a calculated volume of blood completely cleared of a substance in a given time. Clearance is expressed in milliliters per minute (mL/min). It is a theoretic, not a real, volume.
Controlled fluid removal at dialysis is essential. Ultrafiltration occurs in hemodialysis when fluid is removed under pressure. Most current dialyzers use elements of both positive blood compartment pressure and negative fluid compartment pressure (Fig. 7-5).
Figure 7-5 Ultrafiltration.
How does ultrafiltration occur?
Hydrostatic pressure is the pressure that forces plasma fluid out of the blood compartment and into the dialysate compartment of the dialyzer. The rate of fluid removal is influenced by the difference in hydrostatic pressure of the blood and dialysate compartments. The difference in the hydrostatic pressure of the blood and the dialysate represents the transmembrane pressure (TMP). The TMP reflects both positive and negative pressures in the dialyzer. Positive pressure is applied to the blood side of the dialyzer, which pushes the plasma fluid out. Negative pressure is applied to the dialysate side of the dialyzer to pull the plasma fluid out of the blood compartment to the dialysate compartment. It is very important that the dialysate compartment never exert a pressure more positive than the blood compartment. This is referred to as reverse filtration.
What is reverse filtration?
Reverse filtration, or backfiltration, occurs when the dialysate pressure is greater than the pressure on the blood side of the dialyzer. During high-flux dialysis the ultrafiltration control system prevents excessive net fluid removal. The process generates a blood–dialysis fluid profile within the dialyzer that is positive (blood-to-fluid) near the blood inlet but that may, under some circumstances, become negative (fluid-to-blood) toward the outlet. The movement of dialysis fluid into the blood is termed reverse filtration.
What is the significance of reverse filtration?
The water used in the preparation of dialysis fluid is not sterile. Addition of bicarbonate concentrate encourages and supports bacterial proliferation. Endotoxins and breakdown products form and may be carried across the high-flux membrane into the bloodstream when reverse filtration occurs. Pyrogen reactions as well as other adverse effects may occur.
How can the effects of reverse filtration be countered?
A molecular filter (ultrafilter) can be placed in the fluid delivery line just ahead of the dialyzer. This device uses ultrafiltration membranes to remove suspended particles of molecular size, but not dissolved solutes. Bacteria and pyrogen or pyrogen fragments are rejected by the ultrafilter (see Chapter 8).
What is the relationship between the hydrostatic pressure and the ultrafiltration rate?
For a particular dialyzer, at any given TMP, a certain amount of fluid will be removed per unit of time at specific blood and fluid flow rates. During the investigational phase of a new dialyzer, an average ultrafiltration rate per mm Hg TMP is calculated. This is the ultrafiltration coefficient (kUF) and it is unique to each dialyzer. The kUF is expressed as milliliters per hour (mL/h) of fluid removed for each mm Hg. The higher the kUF, the greater the amount of fluid that can be removed with less pressure being applied to the semipermeable membrane. (See Chapter 13 for information on how to calculate the TMP for a patient treatment.)
What affects the resistance in the blood circuit?
The two major components affecting resistance in the blood circuit are (1) the viscosity of the blood and (2) the geometry of the blood pathway.
Viscosity is largely a matter of hematocrit. The viscosity of blood of 30% hematocrit is approximately 2.3 to 2.5 centipoise, about 2 to 2.5 times that of water.
Several aspects are important to the geometry of the blood pathway:
• Length of the pathway. Hollow-fiber dialyzers have low resistance because of the short (15 to 50 cm) pathways.
• Number of pathways. With a large number of pathways, the divided resistance is lower. Hollow-fiber dialyzers have several thousand pathways and have low resistance.
• Cross-sectional area of the pathway. A large cross-sectional pathway has low resistance; a small cross-sectional pathway has high resistance. For hollow-fiber dialyzers, the control factor is the internal radius of the fiber.
How is the amount of ultrafiltration controlled during hemodialysis?
In the past, control of ultrafiltration was sought by manipulating the TMP. Blood outlet and fluid inlet pressures, critical variables in the calculation, are often inexact. The kUF information provided by manufacturer is most often based on in vitro studies and may differ from actual patient experience by as much as plus or minus 30%. Even with conventional cellulosic membranes and blood flow rates of 200 to 300 mL/min, wide discrepancies between planned and actual fluid removal may occur. With the use of high-efficiency or high-flux dialysis, precision in ultrafiltration management became crucial, leading to the development of equipment that directly controls ultrafiltration on a minute-to-minute basis. Most dialysis equipment in use today provide fairly precise ultrafiltration control.
How do ultrafiltration controls function?
There are two basic systems used to control ultrafiltration: (1) volumetric or balancing type and (2) servo-feedback or flow sensor type (see Chapter 6).
In the volumetric system, inflow and outflow through the fluid compartment are exactly balanced by special pumps. A separate pump removes fluid from this closed loop at a rate set by the operator. This creates negative pressure in the fluid loop, causing ultrafiltration across the membrane to match the rate of fluid removal.
The servo-feedback system uses very sensitive flowmeters to constantly monitor dialysis fluid inflow and outflow. This information feeds into a microprocessor that subtracts dialysate inflow (Qdi) from dialysate outflow (Qdo) to determine rate of ultrafiltration (Quf) continuously. The desired ultrafiltration rate is programmed by the operator; the microprocessor adjusts TMP so that measured Quf matches desired Quf.
Direct ultrafiltration control systems, when operating correctly, achieve a plus or minus 10% accuracy in volume of fluid removal.
What is ultrafiltration profiling?
Normal ultrafiltration provides fluid removal at a constant rate throughout the dialysis treatment. Ultrafiltration profiling is a technology available on some dialysis machines to vary the volume of fluid removal during the course of the dialysis treatment. Normally the dialysis nurse or technician will enter the volume of fluid to be removed or the patient’s goal for that dialysis treatment. The machine will automatically divide the total volume to be removed by the length of the treatment. With ultrafiltration profiling, fluid removal is varied based on what profile is chosen. For example, the machine may be set to remove the greatest volume of fluid in the first half of the treatment, when most of the fluid is available to be removed. The rate of removal will then be decreased for the remainder of the treatment when there is less fluid available to refill the vascular space. Other profiles are available and can be selected based on the types of symptoms the patient experiences predialysis, intradialytically, and postdialysis. All of the profiles will remove the required total volume during the patient’s treatment, but at different intervals and rates, thus increasing treatment tolerance and decreasing complications related to fluid removal.
What shifts occur between intracellular and extracellular fluid compartments during hemodialysis?
The removal of accumulated body water from the patient is achieved with ultrafiltration. Ultrafiltrate from the circulating blood volume or vascular compartment is first removed and the vascular compartment is then refilled with fluid from the extravascular compartment. When ultrafiltration occurs too rapidly, the rate of removal may exceed the repletion rate from the extravascular space, and hypovolemia and hypotension will occur. Inadequate refilling, that is, moving fluid from the tissues back into the vascular space during the dialysis treatment, is suspected to be a major cause of hemodialysis-related hypotension.
Infusion of hypertonic saline will increase osmolality in both the vascular and the extravascular spaces. This in turn attracts fluid from the much longer intracellular pool and avoids the hypovolemia that causes the low blood pressure.
What is sodium modeling?
Sodium modeling or sodium variation is a tool that may be used to minimize some of the complications associated with the hemodialysis treatment. The specific treatment complications that can be prevented with the use of this therapy are dialysis-associated hypotension and cramping. An understanding of how these complications occur is essential in order to understand this technology. As the hemodialysis patient is ultrafiltrated, the plasma fluid is being removed from the intravascular space. With rapid dialysis, the intravascular space is depleted of fluid and the “refill” from the extravascular space does not occur quickly enough. When the plasma volume is depleted or decreased, hypotension results. Cramping in the extremities may occur because their perfusion is also compromised with a decreased vascular volume. Hypoalbuminemia and right-sided heart failure may also contribute to the vascular refilling being delayed.
The sodium variation system helps maximize the refilling of the vascular space during ultrafiltration. This procedure involves the development of a computer model of sodium and water movement between compartments during dialysis. Sodium content of the dialysis fluid is varied during the procedure according to the preprogrammed plan. The sodium concentration of the dialysate being delivered to the dialyzer is increased to a level that is higher than the sodium concentration in the blood. The sodium in the dialysate is ramped up to approximately 150 to 160 mEq/L early in the course of the treatment, and is ramped down over the course of the treatment to approximately 140 mEq/L. This may be done in either of two ways: (1) addition of a special sodium chloride (NaCl) concentrate to the dialysis fluid by an infusion pump or, more commonly, (2) varying the proportion of the usual concentrate as the treatment progresses, thus changing the final sodium concentration. For example, a commonly used proportioning yields a dialysis fluid sodium of 140 mEq/L; a 10% increase in the amount of concentrate as it is mixed increases the final fluid sodium to 154 mEq/L, with only minor quantitative changes in other electrolyte concentrations, such as potassium and calcium. The sodium level can be raised to as much as 160 mEq/L. The sodium level is slowly returned to normal by the end of the dialysis treatment with no adverse effects on the patient, such as hypertension or increased thirst.
How is acid-base balance achieved during hemodialysis?
When continuous fluid proportioning systems were introduced in 1963, bicarbonate could not be used in the concentrate because the calcium and magnesium precipitated. Sodium acetate, which the body metabolizes to bicarbonate, was substituted to avoid the precipitation problem. Acetate-based concentrate became standard for many years. It had several disadvantages, particularly the production of cardiovascular instability.
The introduction of short, rapid dialysis and high-flux dialysis made the return to bicarbonate-based fluid mandatory for these procedures. Bicarbonate dialysate is now the standard of practice at most facilities. One of the goals of hemodialysis is to correct the acidosis associated with renal failure. During the dialysis treatment there is a transfer of bicarbonate from the dialysate to the blood. The diffusion of bicarbonate helps the patient to achieve acid-base balance by buffering the hydrogen ions.
How is bicarbonate used in dialysis fluid production?
The concentrate to be used is packaged in two parts. The “acid concentrate” contains chemicals other than sodium bicarbonate, plus a small amount of acid. The “bicarbonate concentrate” contains the sodium bicarbonate and some sodium chloride (necessary to increase conductivity for monitoring purposes). Three streams of fluid are blended by the proportioning equipment: water (34 parts), acid concentrate (1 part), and bicarbonate concentrate (1.8 parts).
Different types of equipment use concentrates of different composition and different mixing proportions. Each proportioning ratio requires its own particular acid and bicarbonate concentrates. Use of an incorrect concentrate can lead to a dialysate preparation of the correct conductivity but of the incorrect compositon. Accidental use of mismatched concentrate is a potentially fatal error. The End-Stage Renal Disease Conditions for Coverage 2008 suggest restricting the use of all machines in a facility to one proportioning ratio. If different ratios are used in the same facility, the supplies for the different ratios must be segregated and labeled clearly to avoid mismatch. Additionally, all staff should be aware and understand that there is more than one ratio in the facility.