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Dialysis

Early history: Graham and Abel

Middle history: Kolff

Modern history: Scribner

Dialysis, also called kidney dialysis and hemodialysis, is the medical process of filtering waste products that have accumulated in the blood of patients whose kidneys are functioning at low levels. Normally, the kidneys perform the vital function of filtering waste materials out of the blood. When the kidneys stop functioning, death due to waste buildup occurs quickly.

In the kidney machine, blood is removed from a persons arm, passed through a dialyzing system (what is called an artificial kidney, or dialyzer). Within the dialyzer, the blood flows through a semipermeable membrane where special fluid, on the other side of the membrane, removes the waste products. The blood is then returned to the patients body through a vein. The machine functions much as a natural kidney does with one important exception. A natural kidney has a mechanism known as reverse dialysis for returning to the body certain small molecules (primarily glucose) that should not be excreted. The kidney machine is unable to do so, and glucose that it removes must be replaced by intravenous injection.

Early history: Graham and Abel

The principle behind the process was discovered by Scottish chemist Thomas Graham (17481843) in about 1861. Graham found that the rate at which some substances, such as inorganic salts, pass through a semipermeable membrane is up to 50 times as great as the rate at which other substances, such as proteins, do so. Scientists now know that such rate differences depend on the fact that the openings in semipermeable membranes are very nearly the size of atoms, ions, and small molecules. That makes possible the passage of such small particles while greatly restricting the passage of large particles.

In a typical dialysis experiment, a bag made of a semipermeable membrane is filled with a solution to be dialyzed. The bag is then suspended in a stream of running water. Small particles in solution within the bag gradually diffuse across the semipermeable membrane and are carried away by the running water. Larger molecules are essentially retained within the bag. By this process, a highly efficient separation of substances can be achieved.

The kidney is a dialyzing organ. By the process described above, it filters waste products such as urea out of the blood and forces them into the urine,

through which they are excreted from the body. Proteins and other important large molecules are retained in the blood.

A person whose kidneys have been damaged by disease or physical injury requires some artificial method for cleansing her or his blood. A device for carrying out this taskthe artificial kidney machine was developed in the early 1910s largely through the efforts of John J. Abel and his colleagues at the Johns Hopkins University.

In 1912, Abel was investigating byproducts in the blood, and needed a device to filter out these substances. With colleagues Benjamin Turner and Leonard Rowntree, he built a machine that circulated blood through celloidin tubing immersed in a saline-dextrose solution and wrapped around a rotating drum. Urea and other toxins passed out into the solution, and oxygen passed into the blood. Abel tested this process, which he called vividiffusion, on rabbits and dogs, and published the findings in 1914. A major problem, however, was the tendency of the blood to clot while circulating through the tubes. Abel had used hirudin, an anticoagulant obtained from leeches, to prevent clotting. Once the effective anticlotting agent heparin became widely available, dialysis was ready for clinical use.

Middle history: Kolff

Several pioneers developed early versions of dialysis machines during World War II when many injured soldiers and civilians suffered kidney damage and died. In 1937, a young Dutch physician, Willem Kolff (1911), working in Groningen, Holland, had already put together a crude dialyzing machine and worked to refine it. After the Germans occupied the Netherlands in 1941, Kolff moved to Kampen where, in spite of wartime shortages, he constructed a dialysis machine using cellophane tubing and beer cans. He first used his device on a human patient in March 1943 and, although all but one of the 15 patients he treated from 1943 to 1944 died, he persevered. By the end of the war, Kolff had refined his machine and he began to promote its use, bringing dialyzers to The Hague, Amsterdam, and London. Meanwhile, with no knowledge of Kolffs work, Nils Alwall of Sweden and G. Murray of Canada were also developing a dialysis machine. In 1947, Kolff brought blueprints for his latest machine to doctors at Peter Bent Brigham Hospital, Harvard Medical School in Boston, Massachusetts. These doctors, along with John Merrell, Karl Walter, and George Thorn, developed kidney dialysis into a standard treatment, using it to support patients in their pioneering kidney transplantations in 1954.

Modern history: Scribner

Kidney transplants, the first organs ever to be transplanted, were made possible because of dialysis, which kept the patient alive until the transplanted kidney began functioning or by maintaining patients awaiting a donor organ. Long-term dialysis was not possible, however, until 1960, because each time a patient was attached to a dialysis machine, both an artery and a vein had to be punctured, leading to eventual vessel deterioration. Dr. Belding Scribner of Seattle, Washington, overcame this problem when he designed a Teflon® and Silastic® shunt (two parallel tubes with a U-connection) that could be inserted into a patients artery and vein and left in place for months or even years.

Today, hemodialysis, a refined version of this technique, allows the patient the option of home treatment with the aid of a family member or friend, or by specialists at a dialysis center. Patients also have the option of using peritoneal dialysis, in which the abdomen lining (peritoneal membrane) filters waste from the blood into a cleansing solution called dialystate. Continuous Ambulatory Peritoneal Dialysis, the most common of three types, requires no machine and can be done by the patient. The dialystate, contained in a plastic bag, is transported through a permanent catheter inserted into the abdomen. The catheter is then plugged and, after four to six hours, the patient removes the plug, draining the solution containing waste matter back into the bag, which is then disposed of. This process is repeated continuously. Continuous Cyclic Peritoneal Dialysis is a similar function done by a machine connected to the catheter and performed at night while the patient sleeps. This procedure lasts from 10 to 12 hours every night. Intermittent Peritoneal Dialysis can also be done at home with a similar machine, but is usually performed in hospital several times a week for a total of 36 to 42 hours. Some sessions may last 24 hours.

See also Osmosis.

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dialysis Failure of the kidneys, whether acute (rapid onset) or chronic (gradual onset), is life-threatening, since waste products accumulate in the body and there are disturbances of body fluid volume and composition. There are two possible treatment: dialysis, or kidney transplantation. A period of dialysis may enable the kidneys of a patient with acute renal failure to recover. In patients with chronic renal failure, dialysis is generally used until a suitable donor kidney becomes available for transplantation. However, many kidney patients have been maintained for over 20 years, with a reasonable quality of life, by dialysis.

Dialysis is a way of removing toxic substances from the blood, and restoring the body fluid volume and composition to close to normal. Two kinds of dialysis are now common, though both types have long histories. Haemodialysis, using dialysers which are sometimes called artificial kidneys, was pioneered by the Dutch physician Willem Kolff, initially at Gronigen University Hospital, and then at Kampen Hospital. Kolff treated his first patient with an experimental haemodialyser in 1943, and in 1956 introduced the first practical haemodialysis machine.

Peritoneal dialysis has a longer history but a shorter period of practical application. The first peritoneal dialysis of a patient was performed in 1923, but the procedure did not become accepted until 1959, when developments in tubing and catheters had made the technique safer.

Neither peritoneal dialysis nor haemodialysis bear much resemblance to the way the kidneys normally work. The kidneys have a filtration process which is essentially non-selective: with the exception of the proteins, all the constituents of the blood plasma are filtered, whether or not the body needs to excrete them or retain them. The selectivity comes after the filtration process, when the nephrons (kidney tubules) reabsorb some substances into the blood, secrete others, or simply allow the filtered substances to continue along the nephron to escape in the urine. No artificial kidney works like this.

Haemodialysis

The principle of haemodialysis is that blood from the patient passes over a ‘dialysis membrane’ of very large surface area, on the other side of which is a dialysing fluid. Hollow fibres are often used instead of a flat membrane. Molecules pass from the blood into the dialysis fluid (and vice versa) by diffusion. The dialysis membrane is permeable (porous) to all the plasma constituents, with the exception of plasma proteins. If the concentration of a substance (such as urea) is greater in the patient's blood plasma than in the dialysis fluid, there will be net transfer of the substance to the dialysis fluid. Conversely, it is possible to raise the concentration of substances in the patient's blood plasma by having a higher concentration of substances (e.g. glucose or bicarbonate) in the dialysis fluid.

The rate of movement of any individual solute across the dialysis membrane depends on four factors: (i) the permeability of the membrane to the solute; (ii) the surface area of the membrane; (iii) the concentration gradient for the solute across the membrane (the difference in concentration between plasma and dialysing fluid); (iv) the length of time that the plasma and dialysing fluid remain in contact with the membrane.

The maximum rate of solute transfer will occur when the concentration difference is greatest. For urea, for example, this will be when the dialysis is begun, because the patient's plasma concentration is high, but the difference becomes smaller as the solute moves from blood plasma to dialysis fluid. This dissipation of the concentration gradient can be minimized by having high flow rates for blood and/or dialysis fluid.

In modern dialysers, the dialysis membrane or hollow fibre has significant permeability to water, so that water (and solute) can be removed from the blood by ultrafiltration (also called bulk flow). The process of carrying solute across a membrane by bulk flow of solvent (water) is convection. The rate of ultrafiltration will depend on the four factors listed above, and on the hydrostatic pressure difference between the blood compartment and the dialysing fluid compartment of the apparatus. Some artificial kidneys do not use dialysing fluid, and rely on ultrafiltration and bulk flow to remove water and solute across a membrane. This process is termed haemofiltration.

For both haemodialysis and haemofiltration, easy access to the patient's blood supply is essential, and since access may be required every few days over a period of many years, special arrangements are necessary. In general this involves a ‘shunt’ — an artificial connection from an artery to a vein, usually in an arm or leg. One such shunt is shown in Fig. 1. It is then a simple matter to connect the ‘artificial kidney’ to the patient's blood supply.

The total volume of blood in the artificial kidney at any moment is small (about 500 ml), with a flow rate of about 300 ml/min, and a total dialyser membrane area of 1–3 m2; this means that the equivalent of the whole blood volume of about 5 litres in an adult circulates through the dialyser every 15–20 min.

Peritoneal dialysis

This is commonly termed CAPD — continuous ambulatory peritoneal dialysis — since most patients undergo the procedure while going about many of their normal activities. The principle of the method is that the peritoneal membrane, which lines the peritoneal cavity in the abdomen, is used as the dialysis membrane.

The patient has a tube (catheter) inserted through the abdominal wall into the peritoneal cavity, and this remains in place on a semi-permanent basis. Dialysis fluid (0.5–3 litres) is allowed to flow into the peritoneal cavity via the catheter, left in typically for several hours or overnight and then drained and replaced with fresh fluid. Movement of fluid and solute occurs across the peritoneal membrane by diffusion and solvent drag (convection), as described above.

The high urea content of the blood in renal failure creates an osmotic attraction across the peritoneal membrane, so that water would tend to move from the peritoneal cavity into the patient. To prevent this, and ensure that water moves from the patient's blood to the dialysis fluid, an osmotically active substance is incorporated in the dialysis fluid. This is usually dextrose, but amino acids and glucose polymers can also be used.

Chris Lote

Bibliography

Gabriel, R. (1990). A patient's guide to dialysis and transplantation, (4th edn). Kluwer Academic.


See also kidneys; organ donation.
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Dialysis

Dialysis is a process by which small molecules in a solution are separated from large molecules. Dialysis has a number of important commercial and industrial applications and plays a crucial role in maintaining the health of humans. For some people, in fact, the term dialysis refers to a specific kind of medical treatment in which a machine (the dialysis machine) takes on the functions of a human kidney. Dialysis machines have made possible the survival of thousands of people who would otherwise have died as a result of kidney failure.

Dialysis is a specific example of a more general process known as diffusion. Diffusion was first described by Scottish chemist Thomas Graham (18051869) around 1861. Graham studied the movement of molecules of different sizes through a semipermeable membrane. (A semipermeable membrane is a thin sheet of material that allows some substances to pass throughor diffusebut not others.) Many tissues in the human body are semipermeable membranes. Graham discovered that some substances, such as the sodium and chloride ions of which ordinary table salt is composed, diffuse through a semipermeable membrane up to 50 times as fast as other substances, such as ordinary table sugar.

Today we know the reason behind Graham's observation. Semipermeable membranes are not actually solid sheets of material. Instead, they contain tiny holes too small to be seen by the unaided eye. Those holes are just large enough to allow tiny particles like sodium and chloride ions to pass through, but they are too small to permit the passage of large molecules, such as those of sugar.

In a typical dialysis experiment, a bag made of a semipermeable membrane is filled with a solution to be dialyzed. The bag is then suspended in a stream of running water. Small particles in the solution within the bag gradually diffuse across the semipermeable membrane and are carried away by the running water. Larger molecules are essentially retained within the bag. By this process, a highly efficient separation of substances can be achieved.

Kidney dialysis

The kidney is a dialyzing organ. Blood that enters the kidney has a great variety of materials in it; some are essential (important, necessary) to human life, others are harmful to life. Proteins circulating in the blood, for example, have many critical bodily functions, such as protecting against disease and carrying "messages" from one part of the body to another. But other materials in blood are waste products of bodily functions that must be eliminated. If they remained in blood, they would cause illness or death. Urea, formed during the breakdown of proteins, is one such compound.

Blood that passes through the kidney is dialyzed to separate essential compounds from harmful compounds. Protein molecules are too large to go through semipermeable membranes in the kidney and are retained in the blood. Urea molecules are much smaller than protein molecules. They pass through those membranes and into urine, in which they are excreted from the body.

The dialysis machine. Sometimes a person's kidneys may be damaged by disease or physical injury. They are no longer able to dialyze blood properly. At one time, people in this situation died because of the accumulation of poisonous materials (such as urea) in their blood. Then, in the 1910s, scientists invented an artificial kidney machine that could be used to dialyze blood. A pioneer in this research was American biochemist John Jacob Abel (18571938).

In the kidney machine, blood is removed from a person's arm, passed through a dialyzing system, and then returned to the patient. The machine functions much as a natural kidney wouldwith one important exception. A natural kidney has a mechanism known as reverse dialysis for returning to the body certain small molecules (primarily glucose) that should not be excreted. The kidney machine is unable to do so, and glucose that it removes must be replaced by intravenous injection.

Electrodialysis

Another form of dialysis is known as electrodialysis. In electrodialysis, an electrical field is set up around a dialysis apparatus. The electrical field causes charged particles in a solution to pass through the semipermeable membrane more quickly than they would without the field. Any large molecules in the solution, though, remain where they are.

One possible application of electrodialysis is the desalination of water. In this procedure, sodium ions and chloride ions from the salt in seawater are forced out, leaving pure water behind.

[See also Diffusion ]

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Artificial kidney

The kidneys perform the vital function of filtering waste materials out of the blood. When the kidneys stop functioning, a person can die quickly from waste buildup. As early as 1861, Scottish chemist Thomas Graham (1748-1843) described a procedure he called dialysis to purify (clean) the blood in case of kidney failure. The blood was spread across a membrane (a thin covering that forms a layer over or between objects and organs) that allowed wastes to pass into a balanced fluid, while replenishing (restoring)substances would pass from the fluid into the blood.

Abel's Studies

Practical application of dialysis was developed by John Jacob Abel, the first professor of pharmacology (the study of drugs) at Johns Hopkins University School of Medicine in Baltimore, Maryland. In 1912 Abel was investigating byproducts in the blood. He needed a device to extract these materials from the blood. With his colleagues Benjamin Turner and Leonard Rowntree, Abel built the first functioning dialysis machine. This machine circulated blood through celloidin tubing immersed in a saline (salt)-dextrose (a type of naturally-occurring sugar) solution wrapped around a rotating drum. Urea (a solution found in urine) and other toxins passed out into the solution and oxygen passed into the blood. Abel called the process vividiffusion, and tested it on rabbits and dogs. Abel, Turner, and Rowntree published their findings in 1914.

The major problem with dialysis in its early days was the tendency of the blood to clot (thicken) while circulating in the machine's tubes. Abel used hirudin, an anticoagulant (anti-clotting agent) obtained from leeches, to prevent clotting. Once hirudin was widely available, dialysis became clinically useful. Several researchers developed more advanced dialysis machines during World War II (1939-1945). The need for such machines was urgent because injured soldiers, as well as civilians pulled from the wreckage of bombed buildings, often died from acute kidney failure.

A Functioning Machine

Willem Kolff, a Dutch physician, became interested in saving kidney-failure patients in 1937. Working in Groningen, Holland, Kolff soon put together a crude dialysis machine and worked to refine it. When German troops occupied the Netherlands in 1941, Kolff moved to Kampen. In spite of wartime shortages, he constructed a dialysis machine using cello-phane tubing and beer cans. Kolff first used his device on a human patient in March of 1943. Although only one of the 15 patients he treated from 1943 to 1944 survived, Kolff persevered. By the time World War II ended, Kolff had refined his machine. He began to promote its use, bringing dialyzers to The Hague, Amsterdam, and London, England.

Transplants

In 1947 Kolff traveled to the United States to promote the use of his machine. He gave the blueprints of his latest invention to doctors at the Peter Bent Brigham Hospital (attached to the Harvard Medical School in Boston, Massachusetts) and explained the technique he used. The doctors included John Merrell, Karl Walter, and George Thorn. The trio made kidney dialysis a standard treatment for kidney problems. They also used dialysis to support patients in their pioneering development of kidney transplantation in 1954. Dialysis made the transplanting of kidneys possible by keeping patients alive until their new kidneys started to function. Dialysis also maintained patients whose kidneys had failed until a donated organ became available.

Long-Term Dialysis

Long-term dialysis was not possible until 1960 because during dialysis, both an artery and a vein had to be punctured (poked). This continuous puncturing eventually lead to vessel deterioration (decay). Dr. Belding Scribner of Seattle, Washington, overcame the puncture problem when he designed a Teflon and Silastic shunt. The shunt consisted of two parallel tubes with a U-connection that could be inserted into a patient's artery and vein and left in place for months or years. In 1966 the fistula was developed. The fistula is an internal surgical connection of an artery with a vein.

[See also Kidney transplant ]

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Dialysis

Dialysis is a process by which small molecules in a solution are separated from large molecules. The principle behind the process was discovered by the Scottish chemist Thomas Graham in about 1861. Graham found that the rate at which some substances, such as inorganic salts, pass through a semipermeable membrane is up to 50 times as great as the rate at which other substances, such as proteins , do so. We now know that such rate differences depend on the fact that the openings in semipermeable membranes are very nearly the size of atoms , ions, and small molecules. That makes possible the passage of such small particles while greatly restricting the passage of large particles.

In a typical dialysis experiment, a bag made of a semi-permeable membrane is filled with a solution to be dialyzed. The bag is then suspended in a stream of running water . Small particles in solution within the bag gradually diffuse across the semipermeable membrane and are carried away by the running water. Larger molecules are essentially retained within the bag. By this process, a highly efficient separation of substances can be achieved.

The kidney is a dialyzing organ . By the process described above, it filters waste products such as urea out of the blood and forces them into the urine, in which they are excreted from the body. Proteins and other important large molecules are retained in the blood.

A person whose kidneys have been damaged by disease or physical injury requires some artificial method for cleansing her or his blood. A device for carrying out this task–the artificial kidney machine–was developed in the early 1910s largely through the efforts of John J. Abel and his colleagues at the Johns Hopkins University. In the kidney machine, blood is removed from a person's arm, passed through a dialyzing system, and then returned to the patient. The machine functions much as a natural kidney does with one important exception. A natural kidney has a mechanism known as reverse dialysis for returning to the body certain small molecules (primarily glucose) that should not be excreted. The kidney machine is unable to do so, and glucose that it removes must be replaced by intravenous injection.

Electrodialysis is a form of dialysis in which the separation of ions from larger molecules is accelerated by the presence of an electrical field. In one arrangement, the solution to be dialyzed is placed between two other solutions, each containing an electrode. Cations within the middle solution are attracted to one electrode and anions to the other. Any large molecules in the middle solution remain where they are.

One possible application of electrodialysis is the desalination of water. In this procedure, sodium ions from seawater migrate to the cathode and chloride ions to the anode of an electrodialysis apparatus. Relatively pure water is left behind in the central compartment.

See also Osmosis.

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di·al·y·sis / dīˈaləsis/ • n. (pl. -ses / -sēz/ ) Chem. the separation of particles in a liquid on the basis of differences in their ability to pass through a membrane. ∎  Med. the clinical purification of blood by this technique, as a substitute for the normal function of the kidney. DERIVATIVES: di·a·lyt·ic / ˌdīəˈlitik/ adj.

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dialysis A method by which large molecules (such as starch or protein) and small molecules (such as glucose or amino acids) in solution may be separated by selective diffusion through a semipermeable membrane. For example, if a mixed solution of starch and glucose is placed in a closed container made of a semipermeable substance (such as Cellophane), which is then immersed in a beaker of water, the smaller glucose molecules will pass through the membrane into the water while the starch molecules remain behind. The plasma membranes of living organisms are partially permeable, and dialysis takes place naturally in the kidneys for the excretion of nitrogenous waste. An artificial kidney (dialyser) utilizes the principle of dialysis by taking over the functions of diseased kidneys.

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dialysis (dy-al-i-sis) n. a method of separating particles of different dimensions in a liquid mixture, using a thin semipermeable membrane. A solution of the mixture is separated from distilled water by the membrane; the solutes pass through the membrane into the water while the proteins, etc., are retained. The principle of dialysis is used in treating kidney failure (see haemodialysis). peritoneal d. the use of the peritoneum as a semipermeable membrane by patients with kidney failure, either continuously or intermittently, employed when haemodialysis is not appropriate.

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dialysis The separation of dissolved crystalloids of low molecular weight from colloidal macromolecules of high molecular weight by means of a semi-permeable membrane that allows the passage of the former but not of the latter, separation being due to the difference in molecular weight of the substances.