BME355 Lab Listing: Dialysis
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Dialysis


Preparation

Lab Outline

Procedure

Learning more


Dialysis: Passive diffusion through a membrane
  • Objective:
    • Understanding the kidney as a part of the excretory system
    • Understanding the mass transfer process
    • Illustrating an artificial organ
    • Getting acquainted with techniques for chemical concentration measurement
  • Introduction to Dialysis
    The goal of this lab session is to understand dialysis and the factors effecting performance. Hemodialysis is the most frequently prescribed type of dialysis treatment in the United States for severe kidney disease and involves circulating the patient's blood outside of the body through a dialysis machine.

    Dialysis treatment replaces the function of the kidneys, which normally serve as the body's filtration system. Through the use of a blood filter and a dialysate solution, the treatment removes waste products and excess fluids from the bloodstream, while maintaining the proper chemical balance of the blood. The blood is filtered and cleansed inside the hemodialyzer and returned to the body.

    Kidneys
    Kidneys are the most important organs of the excretory system. The function of the kidney is to clean from the blood substances not needed in the body. The kidney is a complex filter, where active and passive mechanisms are involved as well as several complex control mechanisms. For a more complete anatomical and physiological description of the kidneys, see for example Human Physiology by L. Sherwood or other physiology books.

    Nephrons

    Figure 1: Nephron

    The basic component of the kidney is the nephron (see Figure 1). There are about one million nephrons per kidney. Dialysis becomes necessary if more than 90% of the nephrons are not functioning.

    The nephron is divided in 4 sections:

    • Glomerulus
    • Proximal Convoluted Tubule (PCT)
    • Loop of Henle
    • Distal Convoluted Tubule (DCT)

    The glomerulus is composed of a network of capillaries which sit over the Bowman's capsule. When blood come from the afferent arteriole, 10% of the circulating plasma and ions are absorbed. Considering that cardiac output is 5 liters per minute, and that 20 to 25% of the blood circulates through the kidneys, nearly 180 liters are absorbed per day by the Bowman's capsule. Each of the nephron sections is responsible for absorption, secretion, and reabsorption of plasma and ions (see Figure 2).


    Figure 2: Concentrations in the nephron depends on relative reabsorption versus water. Substances that need to be eliminated, such as creatinine and urea (metabolic end products), become highly concentrated while those that need to be conserved are strongly reabsorbed by the tubules.

    The mass transfer in the nephron is complex: it includes filtration, osmosis, diffusion convection and active transport (see Figure 3).
    Figure 3: Mass transfer in the nephron

    Urine
         Upon reaching the collecting tube, the end product is urine. Human adults urinate approximately 1 liter a day. This means that nearly 179 liters are reabsorbed before leaving the nephron (see Figure 4).


    Figure 4: Volume flow in each segment of the tubular system

         Urine is composed of water, end products of protein metabolism and other waste, and excess ions and other components of metabolic processes. By controlling ion reabsorption, the kidneys have an important role in acid-base regulation ( H+ and COH-) and also play a role in vasoconstriction (through Na+ concentration regulation).

    Solute Urine conc. Plasma conc. Ratio U/P
    glucose (mg/100ml) 0 100 0
    Na+ (mEq/100ml) 150 150 1
    Urea (mg/100ml) 900 15 60
    Creatinine (mg/100ml) 150 1 150
    Table 1: Solute concentrations in plasma and urine.

    Kidney Function
         Kidney function is measured by clearance and glomerular filtration rate.
    Clearance is the volumetric rate, usually expressed in ml/min, at which a solute is removed from the blood. It expresses the amount of blood that will be cleaned of a given substance in a given amount of time.
         Glomerular filtration rate (GFT) is the rate at which all nephrons filter plasma. A typical value is 120ml/min and values under 80ml/min are considered pathological.

    The Artificial Kidney
    The artificial kidney serves two major functions: solute and water removal. The core of the artificial kidney is the semi-permeable membrane. If blood is in contact with the membrane and dialysate is on the other side, solutes will be removed from the blood and pass to the dialysate side. See Figure 5.


    Figure 5: Solutes passing through porous membrane.

    When in contact with a porous membrane, the smallest solutes pass from the blood compartment to the other compartment. Thus, making blood flow between layers of this membrane or inside hollow fibers, with dialysate flowing on the outside, the blood can be cleaned of some solutes. This effect is enhanced using a counter current system where the blood flows in one direction and the dialysate flows in the other. The average concentration difference across the membrane is larger this way.

    The majority of hemodialysis treatments in the United States use hollow fiber dialyzers. A hollow fiber dialyzer such as you will use in this lab is composed of thousands of tube-like hollow fiber strands encased in a clear plastic cylinder several inches in diameter. There are two compartments within the dialyzer: the blood compartment and the dialysate compartment. The membrane that acts as a barrier that separates these two compartments is semipermeable: in general smaller molecules pass through it but larger molecules do not. Several factors such as hydrostatic pressures, solute size and concentration, and type of membrane play an important role in regulating exchange between the compartments. See Figure 6.

    As blood is pushed through the blood compartment in one direction, suction or vacuum pressure pulls the dialysate through the dialysate compartment in a countercurrent, or opposite direction. These opposing pressures drain excess fluids out of the bloodstream and into the dialysate, a process called ultrafiltration.

    Diffusion moves waste products in the blood across the membrane into the dialysate compartment. Electrolytes and other chemicals in the dialysate solution can cross the membrane into the blood compartment.

    Figure 6: Large surfaces, such as in this hollow fiber dialyzer, are needed to clean a person's blood.

    Substance MW radius (nm)
    Cl- 35 0.12
    H2O 39 0.12
    Na+ 23 0.18
    Urea 60 0.23
    Glucose 180 0.38
    Hemoglobin 64,450 ~7
    Albumin 69,000 7.5
    Red Cell   3750
    Table 2: Blood Components





    Mass transfer and Clearance
    In the dialysis process, water and solutes are removed.

    Overall Mass Transfer
    Overall Mass Transfer is the fractional depletion of a given solute in the blood as it passes through the dialyzer. For now, we will assume there is no water filtration. Under steady state conditions, the mass transfer rate is given by:

    N = QBo (CBi - CBo) = QDo (CDo - CDi)

    where CBi, CBo, CDi and CDo (mol/ml) are blood input, blood output, dialysate input and dialysate output concentrations respectively.

    QBo and QDo (ml/min) are the blood and dialysate output flow rates, respectively.

    Solute Removal
    Solute Removal for the artificial kidney can be characterized by the clearance K (ml/min). Again, assuming no water filtration, clearance is defined as the mass transfer rate divided by the initial concentration difference:

    K = N / ( CBi - CDi)

    This can be written two ways:

    K1 = QBo (CBi - CBo) / (CBi - CDi)

    K2 = QDo (CDo - CDi) / (CBi - CDi)

    Clearance is a function of blood flow. It varies only between 0 and the blood flow. We therefore define extraction fraction as the normalized clearance with respect to blood flow:

    K/ QBo = (CBi - CBo) / (CBi - CDi)

    Filtration
    Typically, water is removed from the blood by ultrafiltration. It is clinically desirable to remove accumulated water from the patients blood. In clinical situations, the blood is usually subject to higher pressure than the dialysate resulting in ultrafiltration. Ultrafiltration can be enhanced by increasing the resistance to blood flow at the dialyzer output, subjecting the dialysate to negative pressure or using membranes that are more permeable to water. Ultrafiltration (ml/min) is defined as the difference between the blood flow entering the dialyser and the blood flow leaving, corresponding to the water removed from the patient per minute:

    F = QBi - QBo

    When there is ultrafiltration, clearance can now be written as:

    K1 = QBi (CBi - (QBo/QBi)CBo) / (CBi - CDi)

    or

    K2 = QDi ((QDo/QDi)CDo - CDi) / (CBi - CDi)

    Hemodialysis system
    Pumps, heaters, temperature controls, pressure and flow meters and bubble detectors are included to help blood circulate avoiding blood cell destruction. Figure 7 shows a complete hemodialysis system.

    Figure 7: Hemodialysis system

    Clinical Issues
    Dialysis is typically for patients with temporary or permanent kidney failure. It can also be used in the treatment of patients suffering from poisoning or overdose, in order to quickly remove drugs from the bloodstream.

    In order to circulate the patient's blood outside of the body, two needles are inserted into the patient's vein, or access site, and are attached to tubing connected to the dialyzer and dialysis machine that monitors and maintains blood flow and administers dialysate. For patients with temporary treatment needs, access to the bloodstream is gained by inserting a catheter into the subclavian vein near the patient's collarbone. Patients in long-term dialysis require fistulas or grafts for stronger and more durable access.

    An alternative to hemodialysis is peritoneal dialysis where the patient's peritoneum acts as a blood filter. A catheter is surgically inserted into the patient's abdomen. During treatment, the catheter is used to fill the abdominal cavity with dialysate. Waste products and excess fluids move from the patient's bloodstream into the dialysate solution. After a waiting period, the waste-filled dialysate is drained from the abdomen, and replaced with clean dialysate.

    Conductimeter - Wheatstone bridge
    As part of the experiment, you will need to measure salt concentration. For this purpose, you will need to implement a Wheatstone bridge circuit.

    A Wheatstone bridge is basically two voltage dividers connected in parallel, where the output signal comes from the difference in their individual outputs. The Wheatstone bridge has good sensitivity and helps to get useful values when the part of the signal changing due to the input change is a small percentage of the output signal.

    History
    The Early Development of Dialysis and Transplantation
    History of Dialysis Bottom navigation banner.