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Prismaflex
Principles of CRRT
Pre-Reading
DIFFUSION
The molecules of a gas mixture or a solution are never at rest, but vibrate, drift and collide.
This inherent movement, which requires no external force but is temperature dependant,
is called Brownian Movement.
As a consequence, a certain component of a solution that is abundant in one area will spread
towards other areas where its concentration is lower. There is simply a tendency for the
compound to spread as evenly as possible in the defined space. This phenomenon is referred to
as diffusion.
In solutions, the term diffusion is used to describe the physical process in which dissolved
solutes move from an area of high solute concentration to another area of lower solute
concentration in order to reach an eventual equilibrium. The driving force is the concentration
gradient, and the net transport continues until equilibrium is reached and the solute
concentration is the same everywhere.
The rate of diffusion is much dependent upon the size of the solute. Bigger molecules move
more slowly than smaller ones, and hence their diffusion rate is much slower. Therefore we can
conclude that the larger the solute, the longer it takes before equilibrium is reached.
Now consider that we create two separate fluid compartments by introducing a membrane which
presents no barrier to small molecules, but which excludes larger molecules. Such a selectively
permeable membrane is referred to as semipermeable.
We can then observe that small solutes move freely between the compartments, behaving as if
the membrane were not present at all. The process is analogous to diffusion in a solution without
a membrane, and the driving force is the concentration gradient. Medium sized molecules are
slowed down by the membrane and large solutes are entirely excluded from the other
compartment. For example Small Solutes with a molecular weight below 300, such as the
waste products urea (MW60) and creatinine (MW113), easily move across a membrane.
The movement of solutes will continue as long as the concentration gradient is maintained. If the fluid
on the low concentration side of the membrane is continuously replaced with fresh solution, the
process will go on indefinitely.
The solute removal rate by diffusion in hemodialysis is controlled by:
• Blood flow rate
• Dialysis Fluid Flow Rate
• Concentration gradient between blood and dialysis fluid
• Dialyzer characteristics, such as membrane type, thickness and surface area.
Diffusion:
The movement of solutes from a higher concentration to a lower concentration
Diffusion is defined as the movement of solutes from a higher to a lower solute concentration area.
A membrane when fully permeable to the solute has little impact on diffusion. These cups, where
the solutes are represented by black dots, schematically illustrate the principle. Observe how the
initial concentration gradient is gradually eliminated as the solutes spontaneously spread in the fluid.
ULTRAFILTRATION
Ultrafiltration is the physical process in which fluid is transported through a semipermeable
membrane. The driving force of this transport is a pressure gradient across the membrane. The
pressure gradient can be applied in three different ways.
A hydrostatic pressure, created e.g. by a piston or a pump, can either be positive or negative.
A positive hydrostatic pressure (1) is created when the fluid is pushed through the membrane,
and a negative hydrostatic pressure (2) is created when fluid is sucked through the membrane.
In hemodialysis the combination of both positive (on the blood side) and negative pressures (on
the dialysis fluid side) make up the total pressure gradient over the membrane. This pressure
gradient, referred to as transmembrane pressure (TMP), is used to remove excess water.
The third alternative is to create an osmotic pressure (3). By adding a solute of large
molecular weight, i.e. a non-permeable solute, to the “suction side” of the membrane, fluid will move
from the compartment with high water concentration to the one with lower water concentration. This
principle is used to remove fluid in peritoneal dialysis, where glucose is the solute giving osmotic
pressure.
Footnote:
1.
Positive Pressure: above atmospheric pressure
2.
Negative Pressure: below atmospheric pressure
ULTRAFILTRATION
Ultrafiltration:
The movement of fluid through a membrane caused by a pressure gradient.
a. positive pressure
b. negative pressure
c. osmotic pressure
Ultrafiltration is the process in which fluid is transported through a semipermeable membrane.
The driving force is a pressure gradient across the membrane which can be created in different
ways:
a)
Positive pressure on the left compartment, represented by the large arrow, will “push”
fluid through the membrane.
b)
A negative pressure on the right compartment, will “suck” fluid through the membrane.
c)
Non-permeable solutes create an osmotic pressure. Thus, water will move from the
area of high water concentration to the area of lower water concentration
CONVECTION
Assume that we put a lump of sugar in a cup of coffee where it dissolves on the bottom. If we
should wait for the sugar to spread in the cup by diffusion alone, the coffee would surely turn cold.
Thus, in order to quickly get an even sugar concentration in the cup, we use the coffee-spoon to
stir the coffee, making the fluid move in a turbulent manner. In this case the sugar molecules do
not move by diffusion; instead they are transported by the movement of the solvent, the water.
The same phenomenon can be observed when a solution is passing through a semipermeable
membrane, dragging dissolved substances along. Convection is the term used to describe the
movement of the solutes across the membrane caused by the passage of solvent; hence the term
“solvent drag”.
The solute transport is directly proportional to the solvent transport, and the solvent transport in turn
depends on the pressure gradient.
For the removal of very large solutes with a high molecular weight, such as beta 2 microglobulin
(MW 11,800) for which the diffusion rate is extremely slow, convection is the only transport
principle.
Depending on the size of the pores in the membrane, solutes of different molecular weight will
pass through to different extent. Small solutes, not inhibited by the membrane, will pass through
the membrane at a rate and thus a concentration equal to that in the original solution. However,
for larger solutes the membrane will act as a sieve, and certain large solutes will not pass through
the membrane at all.
The solute removal rate by convection is controlled by:
•
Ultrafiltration rate
•
Membrane sieving properties
Convection:
The movement of solutes with a water-flow, “solvent drag”, e.g. the movement of membrane
permeable solutes with ultrafiltered water.
When a solution is moving, the solutes dissolved in it will move along, a process referred to as
convection. This phenomenon can be observed during ultrafiltration, where membrane-permeable
solutes will follow the ultrafiltered water.
FLUID REMOVAL
To remove excess fluid from blood by ultrafiltration, a pressure gradient across the membrane is
needed. In the blood compartment of the dialyzer, a positive pressure is created by the blood
pump. In the dialysis fluid compartment there is usually a negative pressure created by a suction
pump in the dialysis machine.
The resulting hydrostatic pressure gradient across the membrane is called the Transmembrane
Pressure, TMP, normally measured in mmHg (millimeters of mercury). Note that the TMP is not a
pressure but a pressure difference. The TMP is the difference between the pressure in the blood
compartment and the pressure in the dialysis fluid.
TMP = Filter Pressure + Return Pressure
- Effluent Pressure
2
The pressure gradient is the driving force for fluid transport across the membrane, a process
referred to as ultrafiltration. Fluid moves from the higher to the lower pressure area, i.e. from the
blood into the dialysis fluid. The ultrafiltration rate, i.e. the amount of fluid removed per unit of time, is
decided by two factors: the pressure gradient across the membrane (TMP) and the membrane’s
permeability to water.
When estimating the total pressure gradient, osmotic pressures sometimes need to be considered. The
plasma proteins create a small osmotic pressure of 20-30mmHg which is necessary to
maintain the volume of the blood. It is referred to as the oncotic pressure. To obtain any
ultrafiltration, this oncotic pressure needs to be overcome by a higher hydrostatic pressure
gradient. If the hydrostatic pressures in the two chambers were equal, there would be a net flow of
water from the dialysis fluid into the blood caused by the oncotic pressure, Osmotic pressures
cannot be measured or controlled by the dialysis machine and are normally not taken into
consideration in standard hemodialysis.
Each membrane type has its own permeability properties. The more permeable a dialysis
membrane is to water, the higher the ultrafiltration rate obtained at a given TMP. Standard
hemodialysis membranes are called low flux membranes, whereas membranes that are highly
permeable to water and used in the ICU setting are referred to as high flux membranes.
In summary, the fluid removal rate in hemodialysis is controlled by:
•
Total pressure gradient across the membrane (expressed as TMP)
•
Water permeability characteristics of the specific dialyzer
ADSORPTION
A recently described mechanism of solute removal is adsorption.
This is the final way in which solutes may be removed from the blood.
Adsorption occurs in two different ways:
•
•
Surface adsorption where the molecules are too large to permeate and migrate
through the membrane; however can adhere to the membrane.
Bulk adsorption within the whole membrane when molecules can permeate it.
It must be noted that movement of fluid is required for adsorption to occur.
Molecules that can be effectively adsorbed include:
•
•
•
•
B2 Microglobulin
Cytokines
Coagulation factors
Anaphylatoxins
Note:
Not all membranes possess the capabilities of adsorption and it is necessary to identify the
specific properties of a membrane which predict whether adsorption is possible.
Adsorption:
Molecular adherence to the surface or interior of the membrane.
References
Daugirdas, J.T. & Blake, G. & Todd, S. Handbook of Dialysis. 3rd Ed. Lippincott Williams &
Wilkins, Philadelphia. 2001.
Gambro BASICS : Gambro 2002
Hospal Power Point Presentation: Continuous Renal Replacement Therapy. Kathy DiMuzio.
Tournier, M.D. & Delaunay M. (Hospal) “The AN69 Dialysis Membrane” 1995.
QUIZ
1. The main driving force for diffusive transport is:
Temperature
Pressure gradient
Concentration gradient
2. The primary determining factor that determines the ability of a molecule to pass through a semipermeable membrane is the:
Cellulose membrane
Rate of the convective transport
Size of the molecule
3. Trans Membrane Pressure (TMP) is the pressure exerted on the filter membrane. TMP reflects the
difference between the hemofilter:
Fluid and blood compartments
Effluent and return pressure
Effluent, return and filter pressures
4. A semi-permeable membrane is defined as a membrane that will:
Not allow molecules or ions to pass through
Allow all molecules or ions to pass through
Allow certain molecules or ions to pass through
5. The main driving force for Ultrafiltration to occur across a semipermeable membrane is:
Temperature
Pressure gradient
Concentration gradient
6. The transport mechanism that is defined as the movement of solutes across a membrane caused by
the passage of fluid or solvent is called:
Convection
Osmosis
Diffusion
7. Convective transport is commonly referred to as “solvent drag”
True
False
8. The type of dialysis membrane used in the ICU setting:
Flux Capacitor
High Flux
Low Flux
9. The TMP is not a pressure but a pressure difference:
True
False
10. Which of the following are types of CRRT membrane Adsorption (more than 1 may be correct):
Bulk adsorption
Skin adsorption
Surface adsorption