HD overview - Information Package

The following document provides an overview of Hemodialysis. I will cover the principles of HD as a medical treatment as well as information about HD devices and the market from a very basic standpoint. Although very basic, I hope this gives you an idea about Hemodialysis. Should there be any questions or if there is something you would like to know in deeper detail, please dont hesitate to ask me.

Kidney failure Normal kidneys perform two main functions; elimination of metabolic wastes and other toxins substances (1) and maintaining a stable composition of internal fluid environments (2). Kidneys also have several endocrine functions; among which are the production of renin, which affects sodium, blood pressure and fluid volume and erythropoietin (EPO), which controls red blood cell production. What happens in kidney failure? Renal failure can be either chronic or acute. In both cases there is enough loss of kidney function as to disturb the bodys internal environment. Waste products and protein metabolic wastes accumulate. In acute renal failure (ARF) is a severe and sudden kidney failure due to a variety of reasons (accidents, surgery, etc). Usually kidneys will get back to work and dialysis is needed until so. Most intrinsic renal failures are recoverable. Chronic renal failure is a progressive and irreversible kidney function loss. This is referred as to end-stage renal disease (ESRD). As kidney function falls 10-15% of normal function, dialysis is needed. Main causes of chronic renal failure are diabetes (about 45%) and hypertension (about 26%).

Basic principles of hemodialysis Dialysis is the passage of molecules, which are in a solution, by diffusion across a semipermeable membrane (a membrane with pores). The kinetics of diffusion are dependent on the solute (molecules contained in a solution) and the membranes characteristics. The solute characteristics that affect movement of particles through a semipermeable membrane include molecular weight, size, charge, shape and lipid solubility. The membranes characteristics that determine its permeability include the number, geometry and distribution of pores, membrane surface area and thickness and membrane surface characteristics (such as charge and hydrophilicity). Molecular diffusion across a semipermeable membrane occurs basically because of the different concentrations in the solutions on each side of the membrane. Solutes can also pass across the membrane by filtration, through the process of convection. In this case it is a difference in pressure between both sides of the membrane what causes the solvent (the fluid in which solutes are dissolved) to cross the membrane because of difference in pressures between both sides of the membrane and in doing so, it will drag solutes across it.

Yeray Llabrs

-For Internal use only-

HD overview - Information Package

Diffusion across a semipermeable membrane (figure 1): Solutes in higher concentration in the blood compartment (like potassium and uremic toxins represented as open circles) diffuse through the membrane into the dialysate compartment. Conversely, solutes in higher concentration in the dialysate (green triangles) will diffuse through the membrane to the blood compartment. In short, we can manage what should go from blood to dialysate and vice versa, so that we can clean blood of uremic wastes and other things and give blood needed substances. That is the essence of hemodialysis. That is how blood is cleaned.

Convection across a semipermeable membrane (figure 2): Applying Hydrostatic pressure to the blood compartment will cause solute to cross the membrane dragging solutes to the dialysate side.

Yeray Llabrs

-For Internal use only-

HD overview - Information Package

Ultrafiltration (UF) UF is controlled fluid removal. During the HD session, some fluid (usually 1.5 3 liters) has to be removed from the patient. Given that there is little or no urine production, this excess fluid has to be removed by the HD machine. Before the treatment, the patients weight is measured and the doctor will decide how much fluid to remove. At the end of treatment patients weight will be taken again.

The dialysis filter The dialysis filter (dialyzer) is the heart of the treatment. It is the place where blood is cleared from toxic wastes and other substances, and where water can be removed from the patient. There are a great variety of filters, depending on material of the membrane, membrane area and pore sizes. There are other factors that also influence the quality of the filter that are related to the way (the quality) the dialyzer is manufactured. The vast majority of filters look like this one:

Yeray Llabrs

-For Internal use only-

HD overview - Information Package

Note that the filter is filled with hundreds of really thin fibers (called fiber bundles, figure 4). Blood flows inside the fibers, while dialysate bathes the outside. The fibers walls are the semipermeable membranes across which diffusion and convection occurs. There is no direct contact between blood and dialysate. If this occurs, it is called a blood leak and is detected by the machine. This could happen if a fiber brakes or if there is a defect in the dialyzer. Figure 5 shows an electronic microscopes picture of a single fiber. There you can see the membrane.

What is the dialysate and how is it made? As we have seen, the dialysate is the solution that will be separated from the blood through the semipermeable membrane and it will carry waste and fluid removed from blood away. This solution has to be as similar as possible to the bloods plasma. In this way, blood plasma will tend to have a similar composition, through diffusion, to that of the dialysate (getting rid of undesired substances). A wrong dialysate, due to an erroneous prescription or mixture, could be fatal. This solution can have several different compositions, and it will be up to the doctor to decide which is best for each patient (though these compositions are fairly standard), and this constitutes part of the dialysis prescription. The dialysate is composed of three main parts: high purity water, an acid part (A) and a basic (B, usually bicarbonate) part (each of them containing different electrolytes and other substances). The Hemodialysis device will mix and deliver the final dialysate to the filter according to the prescription.

Yeray Llabrs

-For Internal use only-

HD overview - Information Package

The extracorporeal blood circuit (EBC) The EBC is the circuit (mainly composed of blood lines, heparin syringe and filter all of which are disposables) through which blood flows. Blood never enters any part of the machine! The following picture represents a standard blood circuit:

1. Usually, double-needle treatment modality is performed. This simply means there is a needle for blood to go to the blood circuit of the machine and a second needle through which blood returns to the patient once it has gone through the filter. This needle site is referred to as the patients dialysis access (we will come back to that later on). 2. This is the blood pump. The blood pump creates a negative pressure (before the pump) for blood to be sucked out of the patients access and a positive pressure (after the pump) to pump the blood into the rest of the circuit and back to the patient. 3. Heparin pump. Heparin is the most widely used anticoagulant drug. Because blood is in contact with foreign materials when outside the patient, we need to use anticoagulant to avoid blood clots in the circuit. When clots are formed in the filter, its effectiveness decreases and we can have other more serious problems. Usually heparin is administered continuously throughout the treatment by an automatic pump. 4. The dialyzer (filter). This is where it all happens. As you can see in the picture, blood is flowing in one direction and dialysate (the mixture made by the HD machine) in the opposite direction. Keep in mind both blood and dialysate are always separated by the semipermeable membrane. Here at the filter the exchange between blood and dialysate takes place. In average blood flows at 200-300mm/min. and dialysate anywhere from 200 to 800 or even a 1000mm/min. Blood flows depend on patients access and dialysate flows depend on the doctors prescription. The higher both flows

Yeray Llabrs

-For Internal use only-

HD overview - Information Package

are the better clearance of blood! After the filter, blood goes back to the patient and dirty dialysis fluid goes to the drain. The following picture shows a real extracorporeal blood circuit (EBC). I will also mention some important features which are standard in any machine and crucial for the treatment: Note: this picture corresponds to a particular treatment type (only use in particular cases; when there is only one needle) and involves the upper pump and the chamber to the left filled halfway through with blood.

1. 2.

This is the blood coming from the patient which is sucked by the blood pump (2) The blood pump. This is a so-called occlusion pump (widely used). As it rotates, it squeezes the blood line and in doing so it pushes blood on one half of the pump (positive pressure) and it sucks on the other half (negative pressure). Heparin pump. A simple system which pumps heparin from the syringe located in the pump (standard syringes). The heparin is injected directly into the blood line (difficult to appreciate in the picture). In the picture you can see part of the filter, hanging from the left side of the machine. There are two wide hoses connected to it. One (red cap) brings in fresh dialysate fluid and the other (blue cap) drains the used dialysate. In the filter there is also a blood inlet and outlet (not seen in the picture) After leaving the filter, blood must pass through a venous chamber. If there are any air bubbles in the blood, this air will be expelled out through this chamber. At this point the level of the chamber is also detected. There has to be particular

3.

4.

5.

Yeray Llabrs

-For Internal use only-

HD overview - Information Package

level in the chamber for optimal effectiveness. Some machines incorporate the level detection of the venous chamber together with the air detection. In this particular device these are separated (5, 6). 6. Air bubble detector. As you can imagine, its important to detect any possible air bubbles heading to the patient. If air is detected (via ultrasound) pumps stop and a clamp (7) will close to make sure blood flow into the patient completely stops. Venous clamp. The clamps main purpose is to block the blood line if any air is detected. It is also used in some machines for running pressure tests before the treatment. You can see in the photo that there is also an arterial clamp (in red). This is mostly used for tests, not so much as a security feature. This is where bloods temperature can be monitored and changed. Arterial/venous pressure measurement. This is to measure the pressure at which blood is being drawn out of the patient (arterial) and the pressure at which blood is going back in the patient (venous). It measures blood pressure in the blood circuit, NOT the patients blood pressure. Some machines have an extra module for this purpose or it is done manually. This module is used for ONLINE treatment. We will come back to that later on. Basically it means that the machine can use the dialysate as infusion for the patient, without the need to use saline bags.

7.

8. 9.

10.

The dialysis machine

This is how new conventional machines look. Basically it is composed of three main parts: 1. Monitor/user interface; Newer machines are equipped with a touch screen and easy-to-use applications. Through this screen, the user enters all needed data and parameters for the treatment and all treatment data and results are displayed in the screen. As we have seen before, this is the extracorporeal blood circuit The hydraulics mix the water, part A and part B to create fresh dialysate which will be sent to the filter (through one of the white hoses you can see hanging from the side of the machine. It also takes care of discharging the used dialysate.

2.

3.

Yeray Llabrs

-For Internal use only-

HD overview - Information Package

The patients dialysis access As mentioned previously, the dialysis access is the needle puncture site from where the blood will leave the patient to enter the blood circuit and go back to the patient. Although it varies from patient to patient, needle punctures can be somehow traumatic. Good and proper location of punctures is essential to fistula conservation. There are three major used accesses; Arterio-venous fistula; this is the most commonly used dialysis access. The needles will be inserted always in a vein (never arteries!). Through surgery, a vein will be attached to an artery. Arteries have higher blood flows than veins. As a result, after a short period of time (called maturation period, 3-8weeks) the size of the vein attached to the artery will increase and we will achieve a higher flow in that vein which will allow us to dialyze at a good blood flow. During the maturation period, an alternative puncture site will be prepared. When surgery is good and fistula well taken care of, it can last years. When it doesnt work properly, surgery is needed to create a new one.

Loop graft; this is an option for patients for which the fistula cannot be constructed by directly joining a vein and an artery. An artery and a vein will be connected through an artificial tube (the graft). The graft can be made of different materials (e.g. Teflon). The needles will be inserted in the graft itself:

Yeray Llabrs

-For Internal use only-

HD overview - Information Package

Catheters; these are used usually for acute dialysis or in cases where the patient does not have a fixed dialysis access (e.g.: if the fistula is maturing). Catheters can be placed at different sites, being the most common of those the subclavian, jugularis and femoral. This type of access is more delicate than others and requires a very careful manipulation (high infection risk).

Main treatment modalities for chronic patients Hemodialysis; in hemodialysis there is basically movement across the membrane by diffusion. There is also some convective transport when we ultrafiltrate to remove fluid from the patient. Hemofiltration; this treatment is based on convective transport across the membrane. Fluid is infused to the patient at the same rate it is ultra-filtrated. This is very effective for removal of medium and large size molecules. The fluids to be infused in the patient used to be available only as premixed bags. Nowadays, machines can produce so pure dialysate that it can be infused to the patient! So there is no need for extra bags hanging on top of the machine. Patients are usually very stable during this type of treatments because there lower volumetric changes in the vascular system (less hypotension episodes, which are common during HD) Hemodiafiltration; combines both dialysis and hemofiltration and it is being used quite often as it seems to be the best treatment. Machines that have the online option can create replacement fluid (the dialysate) pure enough to be used as infusion, and it makes hemodiafiltration easy to perform.

Yeray Llabrs

-For Internal use only-

HD overview - Information Package

History and home hemodialysis (HHD) Nowadays, more than 99% of the dialysis population is treated at dialysis centers, which can be public, private or owned by big dialysis products makers and HD service providers companies. Patients are treated 3 times a week and treatments last an average of 4 - 4.5 hours. Dialysis units usually run 2 or 3 shifts a day and require an average of 1 nurse per 4 patients as well as 1 helper per 2 nurses and a Nephrologist present at all times. Besides the medical staff, a technician is usually also present at the clinic. Back in the 60s, when technology made dialysis more available, patients where treated mostly at home because there were no dialysis units. Patients had to pay for their own treatments or sometimes they were sponsored with, for example, research funds. At the beginning of the 70s, Medicare came out with a program through which all dialysis patients were entitled to dialysis. It was then that dialysis units proliferated. Nephrologists and staffs little experience, the aging and diabetic dialysis population and the difficulty to operate HD machines, made ambulatory dialysis the first choice and its spread. Obviously nephrologists realized the business opportunity as well! In the last years there has been a growing interest in HHD. Many studies have proven that dialyzing at home has several medical advantages due to a lower stress and to the fact that at home patients have the choice to dialyze every day (with treatments of 1.5 2.5 hours), which is not possible in-center because of lacking infrastructure to do so; too many patients, too expensive. Studies have also shown considerable reduce expenditure with HHD. This savings come mainly from medical staff, less drugs needed (because of better treatment outcomes), transportation and fewer hospitalizations. Although big dialysis companies and service providers are developing HHD as the treatment of the future, it hasnt really flown yet for several reasons; private practitioners fear loosing part of their business, few training programs to prepare patients to run their treatments at home, difficulty to find companions to help patient during treatments, fear of patients to do it on their own (due to lack of information), etc

Yeray Llabrs

-For Internal use only-