(See also grafting; transplant surgery.)
The Department of Health has drawn up a list of suitable eye-banks to which people can apply to bequeath their eyes, and an o?cial form is now available for the bequest of eyes. (See also DONORS; TRANSPLANTATION.)... corneal graft
The pioneering success was achieved with transplantation of the kidney in the 1970s; this has been most successful when the transplanted kidney has come from an identical twin. Less successful have been live transplants from other blood relatives, while least successful have been transplants from other live donors and cadaver donors. The results, however, are steadily improving. Thus the one-year functional survival of kidneys transplanted from unrelated dead donors has risen from around 50 per cent to over 80 per cent, and survival rates of 80 per cent after three years are not uncommon. For a well-matched transplant from a live related donor, the survival rate after ?ve years is around 90 per cent. And, of course, if a transplanted kidney fails to function, the patient can always be switched on to some form of DIALYSIS. In the United Kingdom the supply of cadaveric (dead) kidneys for transplantation is only about half that necessary to meet the demand.
Other organs that have been transplanted with increasing success are the heart, the lungs, the liver, bone marrow, and the cornea of the eye. Heart, lung, liver and pancreas transplantations are now carried out in specialist centres. It is estimated that in the United Kingdom, approximately 200 patients a year between the ages of 15 and 55 would bene?t from a liver transplant if an adequate number of donors were available. More than 100 liver transplants are carried out annually in the United Kingdom and one-year-survival rates of up to 80 per cent have been achieved.
The major outstanding problem is how to prevent the recipient’s body from rejecting and destroying the transplanted organ. Such rejection is part of the normal protective mechanism of the body (see IMMUNITY). Good progress has been made in techniques of tissue-typing and immunosuppression to overcome the problem. Drugs are now available that can suppress the immune reactions of the recipient, which are responsible for the rejection of the transplanted organ. Notable among these are CICLOSPORIN A, which revolutionised the success rate, and TACROLIMUS, a macrolide immunosuppressant.
Another promising development is antilymphocytic serum (ALS), which reduces the activity of the lymphocytes (see LYMPHOCYTE) cells which play an important part in maintaining the integrity of the body against foreign bodies.
Donor cards are now available in all general practitioners’ surgeries and pharmacies but, of the millions of cards distributed since 1972, too few have been used. The reasons are complex but include the reluctance of the public and doctors to consider organ donation; poor organisation for recovery of donor kidneys; and worries about the diagnosis of death. A code of practice for procedures relating to the removal of organs for transplantation was produced in 1978, and this code has been revised in the light of further views expressed by the Conference of Medical Royal Colleges and Faculties of the United Kingdom on the Diagnosis of Brain Death. Under the Human Tissue Act 1961, only the person lawfully in possession of the body or his or her designate can authorise the removal of organs from a body. This authorisation may be given orally.
Patients who may become suitable donors after death are those who have suffered severe and irreversible brain damage – since such patients will be dependent upon arti?cial ventilation. Patients with malignant disease or systemic infection, and patients with renal disease, including chronic hypertension, are unsuitable.
If a patient carries a signed donor card or has otherwise recorded his or her wishes, there is no legal requirement to establish lack of objection on the part of relatives – although it is good practice to take account of the views of close relatives. If a relative objects, despite the known request by the patient, sta? will need to judge, according to the circumstances of the case, whether it is wise to proceed with organ removal. If a patient who has died is not known to have requested that his or her organs be removed for transplantation after death, the designated person may only authorise the removal if, having made such reasonable enquiry as may be practical, he or she has no reason to believe (a) that the deceased had expressed an objection to his or her body being so dealt with after death, or (b) that the surviving spouse or any surviving relative of the deceased objects to the body being so dealt with. Sta? will need to decide who is best quali?ed to approach the relatives. This should be someone with appropriate experience who is aware how much the relative already knows about the patient’s condition. Relatives should not normally be approached before death has occurred, but sometimes a relative approaches the hospital sta? and suggests some time in advance that the patient’s organs might be used for transplantation after death. The sta? of hospitals and organ exchange organisations must respect the wishes of the donor, the recipient and their families with respect to anonymity.
Relatives who enquire should be told that some post-mortem treatment of the donor’s body will be necessary if the organs are to be removed in good condition. It is ethical (see ETHICS) to maintain arti?cial ventilation and heartbeat until removal of organs has been completed. This is essential in the case of heart and liver transplants, and many doctors think it is desirable when removing kidneys. O?cial criteria have been issued in Britain to recognise when BRAIN-STEM DEATH has occurred. This is an important protection for patients and relatives when someone with a terminal condition
– usually as a result of an accident – is considered as a possible organ donor.... transplantation
Composition The cellular components are red cells or corpuscles (ERYTHROCYTES), white cells (LEUCOCYTES and lymphocytes – see LYMPHOCYTE), and platelets.
The red cells are biconcave discs with a diameter of 7.5µm. They contain haemoglobin
– an iron-containing porphyrin compound, which takes up oxygen in the lungs and releases it to the tissue.
The white cells are of various types, named according to their appearance. They can leave the circulation to wander through the tissues. They are involved in combating infection, wound healing, and rejection of foreign bodies. Pus consists of the bodies of dead white cells.
Platelets are the smallest cellular components and play an important role in blood clotting (see COAGULATION).
Erythrocytes are produced by the bone marrow in adults and have a life span of about 120 days. White cells are produced by the bone
marrow and lymphoid tissue. Plasma consists of water, ELECTROLYTES and plasma proteins; it comprises 48–58 per cent of blood volume. Plasma proteins are produced mainly by the liver and by certain types of white cells. Blood volume and electrolyte composition are closely regulated by complex mechanisms involving the KIDNEYS, ADRENAL GLANDS and HYPOTHALAMUS.... blood
There are strict regulations about how death should be diagnosed before organs can be removed for transplantation, and potential donors must satisfy the BRAIN-STEM DEATH criteria, performed twice by two doctors who are independent of the transplant team. There is a great shortage of suitable organs for donation – partly because they must be in excellent condition if the operation is to be a success. Some medical conditions or modes of death make people unsuitable as organ donors; this makes it all the more important that people should be encouraged to donate their organs. People who wish to do so can carry a special card indicating their willingness to become donors in the event of their death. These cards can be obtained from various sources, including hospitals, GPs’ surgeries and many public buildings such as libraries. In the UK, informed positive approval from the patient, or relatives, is required.
Information about becoming a blood donor can be obtained by telephoning 0845–7 711
711. Those who wish to bequeath their bodies for dissection purposes should get in touch with HM Inspector of Anatomy. Other would-be organ donors may contact the British Organ Donor Society.... donors
Medical ethics are embedded in cultural values which evolve. Acceptance of abortion within well-de?ned legal parameters in some jurisdictions is an example of how society in?uences the way in which perceptions about ethical obligations change. Because they are often linked to the moral views predominating in society, medical ethics cannot be seen as embodying uniform standards independent of cultural context. Some countries which permit capital punishment or female genital mutilation (FGM – see CIRCUMCISION), for example, expect doctors to carry out such procedures. Some doctors would argue that their ethical obligation to minimise pain and suffering obliges them to comply, whereas others would deem their ethical obligations to be the complete opposite. The medical community attempts to address such variations by establish-ing globally applicable ethical principles through debate within bodies such as the World Medical Association (WMA) or World Psychiatric Association (WPA). Norm-setting bodies increasingly re?ect accepted concepts of human rights and patient rights within professional ethical codes.
Practical changes within society may affect the perceived balance of power within the doctor-patient relationship, and therefore have an impact on ethics. In developed societies, for example, patients are increasingly well informed about treatment options: media such as the Internet provide them with access to specialised knowledge. Social measures such as a well-established complaints system, procedures for legal redress, and guarantees of rights such as those set out in the NHS’s Patient’s Charter appear to reduce the perceived imbalance in the relationship. Law as well as ethics emphasises the importance of informed patient consent and the often legally binding nature of informed patient refusal of treatment. Ethics re?ect the changing relationship by emphasising skills such as e?ective communication and generation of mutual trust within a doctor-patient partnership.
A widely known modern code is the WMA’s International Code of Medical Ethics which seeks to provide a modern restatement of the Hippocratic principles.
Traditionally, ethical codes have sought to establish absolutist positions. The WMA code, for example, imposes an apparently absolute duty of con?dentiality which extends beyond the patient’s death. Increasingly, however, ethics are perceived as a tool for making morally appropriate decisions in a sphere where there is rarely one ‘right’ answer. Many factors – such as current emphasis on autonomy and the individual values of patients; awareness of social and cultural diversity; and the phenomenal advance of new technology which has blurred some moral distinctions about what constitutes a ‘person’ – have contributed to the perception that ethical dilemmas have to be resolved on a case-by-case basis.
An approach adopted by American ethicists has been moral analysis of cases using four fundamental principles: autonomy, bene?cence, non-male?cence and justice. The ‘four principles’ provide a useful framework within which ethical dilemmas can be teased out, but they are criticised for their apparent simplicity in the face of complex problems and for the fact that the moral imperatives implicit in each principle often con?ict with some or all of the other three. As with any other approach to problem-solving, the ‘four principles’ require interpretation. Enduring ethical precepts such as the obligation to bene?t patients and avoid harm (bene?cence and non-male?cence) may be differently interpreted in cases where prolongation of life is contrary to a patient’s wishes or where sentience has been irrevocably lost. In such cases, treatment may be seen as constituting a ‘harm’ rather than a ‘bene?t’.
The importance accorded to ethics in daily practice has undergone considerable development in the latter half of the 20th century. From being seen mainly as a set of values passed on from experienced practitioners to their students at the bedside, medical ethics have increasingly become the domain of lawyers, academic philosophers and professional ethicists, although the role of experienced practitioners is still considered central. In the UK, law and medical ethics increasingly interact. Judges resolve cases on the basis of established medical ethical guidance, and new ethical guidance draws in turn on common-law judgements in individual cases. The rapid increase in specialised journals, conferences and postgraduate courses focused on ethics is testimony to the ever-increasing emphasis accorded to this area of study. Multidisciplinary practice has stimulated the growth of the new discipline of ‘health-care ethics’ which seeks to provide uniformity across long-established professional boundaries. The trend is to set common standards for a range of health professionals and others who may have a duty of care, such as hospital chaplains and ancillary workers. Since a primary function of ethics is to ?nd reasonable answers in situations where di?erent interests or priorities con?ict, managers and health-care purchasers are increasingly seen as potential partners in the e?ort to establish a common approach. Widely accepted ethical values are increasingly applied to the previously unacknowledged dilemmas of rationing scarce resources.
In modern debate about ethics, two important trends can be identi?ed. As a result of the increasingly high pro?le accorded to applied ethics, there is a trend for professions not previously subject to widely agreed standards of behaviour to adopt codes of ethical practice. Business ethics or the ethics of management are comparatively new. At the same time, there is some debate about whether professionals, such as doctors, traditionally subject to special ethical duties, should be seen as simply doing a job for payment like any other worker. As some doctors perceive their power and prestige eroded by health-care managers deciding on how and when to ration care and pressure for patients to exercise autonomy about treatment decisions, it is sometimes argued that realistic limits must be set on medical obligations. A logical implication of patient choice and rejection of medical paternalism would appear to be a concomitant reduction in the freedom of doctors to carry out their own ethical obligations. The concept of conscientious objection, incorporated to some extent in law (e.g. in relation to abortion) ensures that doctors are not obliged to act contrary to their own personal or professional values.... ethics
Heart transplant Replacement of a person’s unhealthy heart with a normal heart from a healthy donor. The donor’s heart needs to be removed immediately after death and kept chilled in saline before rapid transport to the recipient. Heart transplants are technically demanding operations used to treat patients with progressive untreatable heart disease but whose other body systems are in good shape. They usually have advanced coronary artery disease and damaged heart muscle (CARDIOMYOPATHY). Apart from the technical diffculties of the operation, preventing rejection of the transplanted heart by the recipient’s immune system requires complex drug treatment. But once the patient has passed the immediate postoperative phase, the chances of ?ve-year survival is as high as 80 per cent in some cardiac centres. A key di?culty in doing heart transplants is a serious shortage of donor organs.... heart surgery
HLA incompatibility causes the immune response, or rejection reaction, that occurs with unmatched tissue grafts. Strong associations between HLA and susceptibility to certain diseases – notably the AUTOIMMUNE DISORDERS such as rheumatoid arthritis, insulin-dependent diabetes, and thyrotoxicosis – have been described. Certain HLA antigens occur together more frequently than would be expected by chance (linkage disequilibrium), and may have a protective e?ect, conferring resistance to a disease. (See IMMUNITY.)... hla system
There has been a rapid introduction in recent years of monoclonal antibodies which prevent T-cells from proliferating. They can be recognised by the su?x ‘mab’ (standing for monoclonal antibody) and include rituximab and alemtuzumab. In?iximab, used in CROHN’S DISEASE and RHEUMATOID ARTHRITIS, inhibits tumour necrosis factor alpha.... immunosuppression
Habitat: Throughout India and the Andamans.
English: Senega.Folk: Meradu, Maraad, Negali (Maharashtra). Maraad (Nepal).Action: Root—antiasthmatic; used as a substitute for Senega obtained from the American plant Polygala senega. (In Chinese medicine Senega refers to P. tenuifolia Willd.)
Key application: Senega Root— in productive cough, catarrh of the respiratory tract and chronic bronchitis. (German Commission E, ESCOP, WHO.)Senega yielded lactonic lignans, their glycosides and flavonol glycosides. The root gave arctiin, afzelin, myricitrin and rutin. A triterpenic saponin was also obtained from the plant. The root contains salicylic acid, methyl salicylate and senegin (a sapo- nin mixture).Senega is used for chronic bronchitis, catarrh, asthma and croup, as an infusion.Related species are: P. chinesis Linn., synonym P. glomerata Lour; P. tele- phioides Willd., synonym P. brachys- tachya DC. non-Bl., found throughout the plains of India. Both the plants are used as expectorant, antiasthmatic and anticatarrhal.Toxic constituents of Polygala senega root are: triterpene saponins—6- 16% senegasaponins A-D with agly- cone presenegenin or senegin. Sapo- nins irritate GI tract mucosa and cause reflex secretion of mucous in the bronchioles.A French patent is used against graft rejection, eczema and multiple sclerosis as an anti-inflammatory drug.... polygala chinensisInappropriate or excessive formation of antibodies may lead to illness, as in an allergy.
Antibodies against antigens in organ transplants may result in rejection of the transplanted organ.
In some disorders, antibodies are formed against the body’s own tissues, resulting in an autoimmune disorder.... antibody
Before transplantation, all of the recipient’s marrow is destroyed by cytotoxic drugs or radiation in order to prevent rejection of the donated cells and to kill any cancer cells present. The donor bone marrow is transfused into the circulation from where cells find their way to the bone marrow cavities and start to grow. In autologous , the patient’s bone marrow is stored by cryopreservation. Before being frozen, the marrow is usually treated to eliminate any undetected cancerous cells. If the patient’s disease recurs, the stored marrow can then be reinfused.
The major risks with are infection during the recovery period and rejection (known as graft-versus-host disease, or ).
Immunosuppressant drugs are used to prevent and treat rejection.
The risk of may be reduced by removing the T-cells from the bone marrow using monoclonal antibodies (see antibody, monoclonal) before reinfusion. does not occur with allogeneic or stem-cell transplantation.... bone marrow transplant
Side effects are uncommon when corticosteroids are given as a cream or by inhaler, but tablets taken in high doses for long periods may cause oedema, hypertension, diabetes mellitus, peptic ulcer, Cushing’s syndrome, inhibited growth in children, and, in rare cases, cataract or psychosis. High doses also impair the body’s immune system. Long-term treatment suppresses production of corticosteroid hormones by the adrenal glands, and sudden withdrawal may lead to adrenal failure.... corticosteroid drugs
Grafting is used to repair or replace diseased, damaged, or defective tissues or organs. The most common operations of this type are skin graft, bone graft, bone marrow transplant, corneal graft, kidney transplant, heart transplant, liver transplant, heart–lung transplant, heartvalve surgery, and microsurgery on blood vessels and nerves.
With autografting, the grafted tissue is usually assimilated well into the surrounding tissue at the new site.
The general risks of tissue rejection following other forms of grafting are discussed in transplant surgery.... grafting
The drugs work by suppressing the production and activity of white blood cells called lymphocytes. Side effects vary, but all the drugs increase the risk of infection and of the development of certain cancers.... immunosuppressant drugs
Transfusion of blood is a technique that has been used since the 17th century – although, until the 20th century, with a subsequent high mortality rate. It was only when incompatibility of BLOOD GROUPS was considered as a potential cause of this high mortality that routine blood-testing became standard practice. Since the National Blood Transfusion Service was started in the United Kingdom (in 1946), blood for transfusion has been collected from voluntary, unpaid donors: this is screened for infections such as SYPHILIS, HIV, HEPATITIS and nvCJD (see CREUTZFELDT-JAKOB DISEASE (CJD)), sorted by group, and stored in blood-banks throughout the country.
In the UK in 2004, the National Blood Authority – today’s transfusion service – announced that it would no longer accept donations from anyone who had received a blood transfusion since 1980 – because of the remote possibility that they might have been infected with the PRION which causes nvCJD.
A standard transfusion bottle has been developed, and whole blood may be stored at 2–6 °C for three weeks before use. Transfusions may then be given of whole blood, plasma, blood cells, or PLATELETS, as appropriate. Stored in the dried form at 4–21 °C, away from direct sunlight, human plasma is stable for ?ve years and is easily reconstituted by adding sterile distilled water.
The National Blood Authority prepares several components from each donated unit of blood: whole blood is rarely used in adults. This permits each product, whether plasma or various red-cell concentrates, to be stored under ideal conditions and used in appropriate clinical circumstances – say, to restore blood loss or to treat haemostatic disorders.
Transfusion of blood products can cause complications. Around 5 per cent of transfused patients suffer from a reaction; most are mild, but they can be severe and occasionally fatal. It can be di?cult to distinguish a transfusion reaction from symptoms of the condition being treated, but the safe course is to stop the transfusion and start appropriate investigation.
In the developed world, clinicians can expect to have access to high-quality blood products, with the responsibility of providing blood resting with a specially organised transfusion service. The cause of most fatal haemolytic transfusion reactions is a clerical error due to faulty labelling and/or failure to identify the recipient correctly. Hospitals should have a strict protocol to prevent such errors.
Arti?cial blood Transfusion with blood from donors is facing increasing problems. Demand is rising; suitable blood donors are becoming harder to attract; the processes of taking, storing and cross-matching donor blood are time-consuming and expensive; the shelf-life is six weeks; and the risk of adverse reactions or infection from transfused blood, although small, is always present. Arti?cial blood would largely overcome these drawbacks. Several companies in North America are now preparing this: one product uses puri?ed HAEMOGLOBIN from humans and another from cows. These provide oxygen-carrying capacity, are unlikely to be infectious and do not provoke immunological rejections. Yet another product, called Oxygene®, does not contain any animal or human blood products; it comprises salt water and a substance called per?ubron, the molecules of which store oxygen and absorb carbon dioxide more e?ectively than does haemoglobin. Within 24 hours of being transfused into a person’s bloodstream, per?ubron evaporates and is harmlessly breathed out by the recipient. Arti?cial blood is especially valuable in that it contains no unwanted proteins that can provoke adverse immunological reactions. Furthermore, it is disease-free, lasts for up to three years and is no more expensive than donor blood. It could well take the place of donor blood within a few years.
Autologous transfusion is the use of an individual’s own blood, provided in advance, for transfusion during or after a surgical operation. This is a valuable procedure for operations that may require large transfusions or where a person has a rare blood group. Its use has increased for several reasons:
fear of infection such as HIV and hepatitis.
shortages of donor blood and the rising cost of units of blood.
substantial reduction of risk of incompatible transfusions. In practice, blood transfusion in the UK is
remarkably safe, but there is always room for improvement. So, in the 1990s, a UK inquiry on the Serious Hazards of Transfusion (SHOT) was launched. It established (1998) that of 169 recently reported serious hazards following blood transfusion, 81 had involved a blood component being given to the wrong patient, while only eight were the result of viral or bacterial infections.
There are three ways to use a patient’s own blood in transfusion:
(1) predeposit autologous donation (PAD) – taking blood from a patient before operation and transfusing this blood back into the patient as required during and after operation.
(2) acute normovalaemic haemodilution (ANH) – diluting previously withdrawn blood and thus increasing the volume before transfusion.
(3) perioperative cell salvage (PCS) – the use of centrifugal cell separation on blood saved during an operation, particularly spinal surgery where blood loss may be considerable.
The government has urged NHS trusts to consider the introduction of PCS as a possible adjunct or alternative to banked-blood transfusion. In one centre (Nottingham), PCS has been used in the form of continuous autologous transfusion for several years with success.
Exchange transfusion is the method of treatment in severe cases of HAEMOLYTIC DISEASE OF THE NEWBORN. It consists of replacing the whole of the baby’s blood with Rh-negative blood of the correct blood group for the baby.... transfusion
The term innate immunity is given to the protection that we are born with, such as the skin and the mucous membranes that line the mouth, nose, throat, intestines, and vagina. It also includes antibodies, or immunoglobulins (protective proteins), that have been passed to the child from the mother. If microorganisms penetrate these defences, they encounter “cell-devouring” white blood cells called phagocytes, and other types of white cells, such as natural cellkilling (cytotoxic) cells. Microorganisms may also meet naturally produced substances (such as interferon) or a group of blood proteins called the complement system, which act to destroy the invading microorganisms.The 2nd part of the immune system, adaptive immunity, comes into play when the body encounters organisms that overcome the innate defences. The adaptive immune system responds specifically to each type of invading organism, and retains a memory of the invader so that defences can be rallied instantly in the future.
The adaptive immune system first must recognize part of an invading organism or tumour cell as an antigen (a protein that is foreign to the body). One of 2 types of response – humoral or cellular – is then mounted against the antigen.
Humoral immunity is important in the defence against bacteria. After a complex recognition process, certain B-lymphocytes multiply and produce vast numbers of antibodies that bind to antigens. The organisms bearing the antigens are then engulfed by phagocytes. Binding of antibody and antigen may activate the complement system, which increases the efficiency of the phagocytes.
Cellular immunity is particularly important in the defence against viruses, some types of parasites that hide within cells, and, possibly, cancer cells. It involves 2 types of T-lymphocyte: helper cells, which play a role in the recognition of antigens and activate the killer cells (the 2nd type of T-lymphocyte), which destroy the cells that have been invaded.
Disorders of the immune system include immunodeficiency disorders and allergy, in which the immune system has an inappropriate response to usually innocuous antigens such as pollen.
In certain circumstances, such as after tissue transplants, immunosuppressant drugs are used to suppress the immune system and thus prevent rejection of the donor tissue as a foreign organism.... immune system
A person’s tissue type is classified in terms of their histocompatibility antigens, the most important of which are the human leukocyte antigens (HLAs), on the surface of cells. A person’s set of HLAs is inherited and unique (except for identical twins, who have the same set). Nevertheless, close relatives often have closely matching types. A person’s tissue-type is established by laboratory tests on cells from a blood sample. In one method, an antiserum containing antibodies to a particular is added to the test specimen. If the is present, it is detected by an observable colour or other change.... tissue-typing
Rejection is a major problem. However, a combination of a corticosteroid drug and ciclosporin are given in order to suppress this response.
Every patient who undergoes an organ transplant operation must take immunosuppressant drugs indefinitely. (See also heart transplant; heart–lung transplant; liver transplant; kidney transplant.)... transplant surgery
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