medical

medical

[med-i-kuhl]
transplantation, medical, surgical procedure by which a tissue or organ is removed and replaced by a corresponding part, either from another part of the body or from another individual. A life-saving medical technique, transplantation also is an important tool in experimental biology; it is used to investigate endocrine gland functions, to study the interactions of cells in developing embryos, and to culture malignant tissue in cancer research.

Types of Transplanted Tissues and Organs

Transplantation to replace such diseased or defective tissue as corneas and hearts necessarily requires a dead donor; paired organs such as kidneys, or large or regenerating organs or tissues such as skin, bowel, lung, liver, or blood, can be donated by live donors (see blood transfusion). Skin autografts, employing skin from the patient's own body, are used to replace lost skin; autograft transplants are also done with bowel, bone, cartilage and other connective tissue, and ovarian tissue. Replacement skin for autografts is now also grown in laboratories, and autograft bladders have been laboratory grown and implanted. In 2008 Spanish surgeons implanted a trachea in which autograft tracheal and adult stem cells had grown over the connective tissue scaffold from a donated trachea. Bone marrow transplants can come either from a donor or from stored host bone marrow. Controversial fetal tissue implants have been used for some neurodegenerative diseases and experimentally for fetus-to-fetus transplants in certain genetic disorders. In addition to transplanted human tissues and organs, artificial parts ranging from heart valves to hip sockets are routinely implanted. See also heart, artificial.

Immunological Rejection of Transplanted Tissue

In transplanting complex organs (but not small tissue grafts), the larger blood vessels of the organ are surgically connected to those of the recipient. Connective tissue cells gradually link together the graft and host tissue. The main obstacle to successful transplantation is the rejection of foreign tissue by the host (see immunity). Transplanted tissue from another individual (i.e., homograft, or allograft, tissue) contains antigens that stimulate an immune response from the host's lymphocytes. Homograft tissue is normally destroyed within a few weeks; the rejection mechanism is similar to that by which the body resists infection. The greater the number of foreign antigens on the donor organ, the more rapid and severe the rejection reactions.

Organs donated from one identical twin to another are usually viable because such organs are antigenically identical, but even organs transplanted between individuals who are fairly closely matched antigenically, such as siblings, have a good chance of being rejected. An antigenic typing system based on human lymphocyte antigens (HLA typing), pioneered by Jean Dausset in Paris and Rose Payne at Stanford Univ., has made it possible to identify histocompatibility and minimize rejection.

Today, most recipients of transplants are maintained on immunosuppressive drugs. The side-effects of such antirejection drugs, which can themselves be life threatening, include increased risk of infection, cancer, diabetes, and other conditions. In time, however, many patients develop a tolerance to the implanted organs, and some can eventually be weaned off the drugs.

Researchers continue to study various ways to fool the immune system into accepting foreign tissues or to take advantage of the immune response. A new technique for nerve transplant begins with the patient taking immunosuppressive drugs, but after the patient's damaged nerves begin to grow and connect along the transplant, the drugs are discontinued and the immune system is allowed to destroy the transplanted nerve.

Noncellular tissues or tissues where the donor cells are not important to the graft (e.g., bone and cartilage) can usually be successfully transplanted without rejection. In these transplants the grafts provide nonliving structural support within which the recipient's living cells gradually become established. Corneal transplants have a high success rate largely because there are so few blood vessels in the cornea that corneal antigens may never enter the host's system to stimulate an immune reaction. Bone-marrow transplants effectively bring their own immune system with them, often rejecting the new host, instead of the other way around, in a reaction known as graft-versus-host disease.

Implantation of artificial organs, such as artificial bone, is successful because such organs (prostheses) do not produce antigenic substances. Artificial joints made of stainless steel have been developed; newer implants have used nonrusting titanium joints with the midsection of bone substitute composed of lightweight polyethylene.

Organ transplants from animals to humans are subject to hyperacute rejection, and transplantation of tissues from animals has been attempted for almost a century without much success. Some progress has been made, however, in circumventing the immune reaction. In one experimental approach, the tissues and organs of transgenic pigs, genetically engineered animals that have had human genes inserted, are combined with newly developed immunosuppressive drugs. In a potential step toward a different approach to developing swine that could be used as a source of organs, researchers have cloned pigs in which a gene that causes rejection by the human immune system has been genetically disrupted. The endangered species status of chimpanzees, genetically closest animals to humans, has eliminated their use as donors. Although transplants from animals to humans, called xenotransplants, might benefit the thousands of patients waiting for human organs, the possibility that they could spread some unknown animal virus into the human population has caused concern and delayed research experimentation.

History

Human tissue grafting was first performed in 1870 by a Swiss surgeon, Jacques Reverdin. In 1912 the French surgeon Alexis Carrel developed methods of joining blood vessels that made the transplantation of organs feasible. He advanced this technique further and stimulated the use of transplantation in experimental biology. He also developed fluids and the means of circulating them so that transplanted tissues could be kept alive outside a living body in artificial media. Theoretical work by Jean Dausset, George Davis Snell and Baruj Benacerraf on the genetic basis of histocompatibility paved the way for practical applications. In the 1940s, Sir Peter Brian Medawar and Sir Macfarlane Burnet described foreign tissue rejection and acquired immunological tolerance, opening the way for transplant operations. The first successful identical twin transplant of a human kidney was made by Joseph E. Murray in 1954. The first human heart transplant was performed by the South African surgeon Christiaan Barnard in 1967; in 1968, Edward D. Thomas performed the first successful bone-marrow transplant between people who were not twins. In the following decades liver, kidney, heart, pancreas, bone-marrow, small intestines, and multiple organ transplants became more and more routine.

As transplantation has become more common and more successful, the demand for organs has risen dramatically. The development of heart transplantation has produced an ongoing reexamination of the traditional biological and legal definitions of death, because obtaining a healthy organ for transplantation depends in large part on the earliest possible establishment of the donor's death. More than 2,000 heart transplants per year were being performed in the United States by the late 1990s, with thousands of patients waiting for available hearts. In all, more than 64,000 people were waiting to receive new organs, including hearts, kidneys, livers, lungs, and pancreases. Many people carry organ donor cards, which indicate their wish to donate if they are killed in an accident, and many states require hospitals to request donation from the families of eligible donors. A side effect of the demand for donated organs has been the increasing use of lung and liver tissue, as well as kidneys, from live donors.

In the late 1990s surprising successes were achieved in transplanting body parts other than organs. Surgeons in France and the United States were able to transplant hands that became partly functional without rejection crises. In 2005 a French surgical team achieved a partial face transplant, replacing damage areas (nose, lips, and chin) of a woman's face with skin and underlying tissues from a dead donor. A nearly total face transplant was performed in the United States three years later, and a total face transplant was performed in France the year after that. Although receiving less attention, successful transplants of knees, the trachea (windpipe), and the larynx (voice box) have also been achieved. Such operations, called nonvital transplants, have become possible owing to improved surgical techniques, monitoring of rejection, and drug therapy. Still largely experimental, they must be approved by ethics committees before being undertaken, especially as the risk of taking immunosuppressive drugs may outweigh the benefits of the operation.

Bibliography

See studies by R. Simmons et al. (1987) and M. Dowie (1988). See also L. Gutkind, Many Sleepless Nights: The World of Organ Transplantation (1988) and publications of the United Network for Organ Sharing.

or medical imaging

Use of electromagnetic radiation to produce images of internal body structures for diagnosis. X-rays have been used since 1895. Denser tissues, such as bones, absorb more X-rays and show as lighter areas on X-ray film. A contrast medium can be used to highlight soft tissues in still X-ray pictures or can be followed on X-ray motion-picture films as it moves through the body or part of the body to record body processes. In computerized axial tomography, X-rays are focused on specific tissue planes, and a series of such parallel “slices” of the body are processed by computer to produce a 3-D image. The risks of X-ray exposure are reduced by more precise techniques using lower doses and by use of other imaging techniques. Seealso angiocardiography; angiography; magnetic resonance imaging; nuclear medicine; positron emission tomography; ultrasound.

Learn more about diagnostic imaging with a free trial on Britannica.com.

Organization of U.S. physicians. It was founded in 1847 “to promote the science and art of medicine and the betterment of public health.” It has about 250,000 members, about half of all practicing U.S. physicians. It disseminates information to its members and the public, operates as a lobbying group, and helps set medical education standards. Its publications include Journal of the American Medical Association, American Medical News, and journals on medical specialties.

Learn more about American Medical Association (AMA) with a free trial on Britannica.com.

Chronic Hypoxia is a pathological condition in which the body as a whole (generalized hypoxia) or region of the body (tissue hypoxia) is deprived of adequate oxygen supply. However variations in arterial oxygen concentration can be part of normal physiology eg during strenuous physical exercise due to mismatch between supply and demand for oxygen at the cellular level. Hypoxia in which there is complete deprivation of oxygen supply is referred to as anoxia.

Hypoxia is distinguished from apoxemia, which is an abnormally low concentration of oxygen in arterial blood. A frequent error is to use the term hypoxia to mean low oxygen content in arterial blood. The correct term for low oxygen content in arterial blood is hypoxemia. It is possible to have a low oxygen content (e.g., due to anemia) but a high PO2. Incorrect use of these terms can lead to confusion.

Generalized hypoxia occurs in healthy people when they ascend to high altitude, where it causes altitude sickness and its potentially fatal complications, high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). Hypoxia also occurs in healthy individuals when breathing mixtures of gases with a low oxygen content, such as while diving underwater, especially when using closed-circuit rebreather systems that control the amount of oxygen in the supplied air. Altitude training intentionally uses mild, non-damaging intermittent hypoxia in order to produce beneficial effects for athletic performance adaptations that are evident at both systemic and cellular level.

Symptoms

Symptoms of generalized hypoxia depend on its severity and acceleration of onset. In the case of altitude sickness, where hypoxia develops gradually, the symptoms include headaches, fatigue, shortness of breath, a feeling of euphoria and nausea. In severe hypoxia, or hypoxia of very rapid onset, changes in levels of consciousness, seizures, coma, priapism, and death occur. Severe hypoxia induces a blue discolouration of the skin, called cyanosis. Because haemoglobin is a darker red when it is not bound to oxygen (deoxyhemoglobin), as opposed to the rich red colour that it has when bound to oxygen (oxyhaemoglobin), when seen through the skin it has an increased tendency to reflect blue light back to the eye. In cases where the oxygen is displaced by another molecule, such as carbon monoxide, the skin may appear 'cherry red' instead of cyanotic.

Types of hypoxia

  • Hypoxemic hypoxia is a generalized hypoxia, an inadequate supply of oxygen to the body as a whole. The term "hypoxemic hypoxia" specifies hypoxia caused by low partial pressure of oxygen in arterial blood. In the other causes of hypoxia that follow, the partial pressure of oxygen in arterial blood is normal. Hypoxemic hypoxia may be due to:
    • Low partial pressure of atmospheric oxygen such as found at high altitude or by replacement of oxygen in the breathing mix either accidentally as in the modified atmosphere of a sewer or intentionally as in the recreational use of nitrous oxide.
    • A decrease in oxygen saturation of the blood caused by sleep apnea or hypopnea
    • Inadequate pulmonary ventilation (e.g., in chronic obstructive pulmonary disease or respiratory arrest).
    • Shunts in the pulmonary circulation or a right-to-left shunt in the heart. Shunts can be caused by collapsed alveoli that are still perfused or a block in ventilation to an area of the lung. Whatever the mechanism, blood meant for the pulmonary system is not ventilated and so no gas exchange occurs (the ventilation/perfusion ratio is zero). Normal anatomical shunt occurs in everyone, because of the Thebesian vessels which empty into the left ventricle and the bronchial circulation which supplies the bronchi with oxygen.
  • Anemic hypoxia in which arterial oxygen pressure is normal, but total oxygen content of the blood is reduced.
  • Hypoxemic hypoxia when the blood fails to deliver oxygen to target tissues.
  • Histotoxic hypoxia in which quantity of oxygen reaching the cells is normal, but the cells are unable to effectively use the oxygen due to disabled oxidative phosphorylation enzymes. The effects of drinking alcoholic beverages is a common example.
  • Ischemic, or stagnant hypoxia in which there is a local restriction in the flow of otherwise well-oxygenated blood. The oxygen supplied to the region of the body is then insufficient for its needs. Examples are cerebral ischemia, ischemic heart disease and Intrauterine hypoxia, which is an unchallenged cause of perinatal death.

Pathophysiology

After mixing with water vapour and expired CO2 in the lungs, oxygen diffuses down a pressure gradient to enter arterial blood around where its partial pressure is 100mmHg (13.3kPa). Arterial blood flow delivers oxygen to the peripheral tissues, where it again diffuses down a pressure gradient into the cells and into their mitochondria. These bacteria-like cytoplasmic structures strip hydrogen from fuels (glucose, fats and some amino acids) to burn with oxygen to form water. Released energy (originally from the sun and photosynthesis) is stored as ATP, to be later used for energy requiring metabolism. The fuel's carbon is oxidized to CO2, which diffuses down its partial pressure gradient out of the cells into venous blood to finally be exhaled by the lungs. Experimentally, oxygen diffusion becomes rate limiting (and lethal) when arterial oxygen partial pressure falls to 40mmHg or below.

If oxygen delivery to cells is insufficient for the demand (hypoxia), hydrogen will be shifted to pyruvic acid converting it to lactic acid. This temporary measure (anaerobic metabolism) allows small amounts of energy to be produced. Lactic acid build up in tissues and blood is a sign of inadequate mitochondrial oxygenation, which may be due to hypoxemia, poor blood flow (e.g., shock) or a combination of both. If severe or prolonged it could lead to cell death.

Vasoconstriction and vasodilation

In most tissues of the body, the response to hypoxia is vasodilation. By widening the blood vessels, the tissue allows greater perfusion.

By contrast, in the lungs, the response to hypoxia is vasoconstriction. This is known as "Hypoxic pulmonary vasoconstriction", or "HPV".

Treatment

To counter the effects of high-altitude diseases, the body must return arterial PO2 toward normal. Acclimatization, the means by which the body adapts to higher altitudes, only partially restores PO2 to standard levels. Hyperventilation, the body’s most common response to high-altitude conditions, increases alveolar PO2 by raising the depth and rate of breathing. However, while PO2 does improve with hyperventilation, it does not return to normal. Studies of miners and astronomers working at 3000 meters and above show improved alveolar PO2 with full acclimatization, yet the PO2 level remains equal to or even below the threshold for continuous oxygen therapy for patients with chronic obstructive pulmonary disease (COPD). In addition, there are complications involved with acclimatization. Polycythemia, in which the body increases the number of red blood cells in circulation, thickens the blood, raising the danger that the heart can’t pump it.

In high-altitude conditions, only oxygen enrichment can counteract the effects of hypoxia. By increasing the concentration of oxygen in the air, the effects of lower barometric pressure are countered and the level of arterial PO2 is restored toward normal capacity. A small amount of supplemental oxygen reduces the equivalent altitude in climate-controlled rooms. At 4000 m, raising the oxygen concentration level by 5 percent via an oxygen concentrator and an existing ventilation system provides an altitude equivalent of 3000 m, which is much more tolerable for the increasing number of low-landers who work in high altitude. In a study of astronomers working in Chile at 5050 m, oxygen concentrators increased the level of oxygen concentration by 6 percent (that is, from 21 percent to 27 percent). This resulted in increased worker productivity, less fatigue, and improved sleep.

Oxygen concentrators are uniquely suited for this purpose. They require little maintenance and electricity, provide a constant source of oxygen, and eliminate the expensive, and often dangerous, task of transporting oxygen cylinders to remote areas. Offices and housing already have climate-controlled rooms, in which temperature and humidity are kept at a constant level. Oxygen can be added to this system easily and relatively cheaply.

See also

For aircraft decompression incidents at altitude see:

Footnotes

Bibliography

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