Every day otherwise fit people are dying in hospital as a result of accidental head injury or spontaneous bleeding into the brain. These people can often be resuscitated and temporarily placed on breathing machines. Because the machines are keeping their respiration going – usually a function of the brain – the heart receives oxygen and can keep beating. In this situation the subject’s body tissues may remain alive, although the brain does not function anymore and he or she has stopped life as a human being. Many people carry donor cards, stating they wish their organs to be used in the case of their death. As soon as brain death occurs it is possible to remove organs for transplantation.
But before this is performed there are two extremely important matters to be dealt with. First, is the patient really dead? To make absolutely sure, two physicians who are not on the transplant team independently carry out a set of neurological (brain and nerve) function tests to check the patient’s brain stem, from where the vital functions such as breathing are controlled. All the tests are repeated again to double check. If the tests prove that there is brain stem death, then there is no doubt that the patient is clinically and legally dead. The other important matter is to check the feelings of the patient’s family, relatives or friends, usually whoever is next of kin. Although most people agree to the use of their relative’s organs, there is a substantial minority who find the subject too upsetting to consider such a proposal. Most countries have organizations which are responsible for co-ordinating tissue matching and finding the most urgent recipients. However, no matter how good the tissue match and how willing the relatives, no donor organ can be used if he or she suffered from a severe infection or a malignant tumour, for fear of spreading these to the recipient.
The process of rejection
Autografting usually presents the least problems, v v even though technically the procedure can be complex. Why is this? The answer lies in the body’s defence mechanism, the immune system. Because this is designed to reject any foreign material that is not part of that body, it is efficient not only in combating infection by microbes but also in trying to rid the body of potentially helpful, but still foreign, structures. By a double attack from antibodies and killer white blood cells the immune system invades foreign living tissue, kills its cells and slowly cuts off the blood supply, and thereby the oxygen. This process is called rejection. But how does the immune system recognize a ‘foreign’ organ? The answer lies in the specialized proteins lying on the surface of all body cells, with the exception of the red blood cells. This is called the HLA (Human Lymphocyte Antigen) system and it is genetically determined. A baby will inherit from its parents its own unique set of HLA proteins from the thousands of different combinations possible. This determines ‘tissue type’ of that individual. Any cells carrying an HLA set not identical to that unique set will be attacked. Because of this system the best chance of avoiding rejection is found in an autograft. Next comes an allograft transplant between identical twins, followed by one between close family members. The main way around the problem of rejection is to use drugs that damp down the body’s immune system; the immunosuppressive drugs .
A simple form of allograft is blood transfusion, in which millions of cells are donated by one individual for another’s use. Because the HLA system is not carried on red blood cells, detailed tissue matching does not have to be performed prior to transfusion; although blood groups must be matched.
Possibilities and limitations
Virtually every tissue and organ in the body has been transplanted at one time or another. However, in practice only a dozen or so organs are transferred on a regular basis, and with worthwile success rates. Skin grafting, for example, is required to cover raw areas caused by ulceration, burning or congenital defects. A full skin thickness defect only heals by scarring, which is not only ugly but contracts and does not feel like normal skin. If these areas are covered by skin grafting then the skin’s function, if not the full cosmetic appearance, can be partly recovered. In large burns, the amount of unscathed skin is not always enough to provide ‘split-thickness grafts’ in which a thin layer of healthy skin is taken from another part of the body and grafted onto the wound site. One of the alternatives is to use donor skin. Skin, unfortunately, strongly resists transplantation onto other individuals, and almost never ‘takes’. It does, however, provide important temporary functional cover. For this purpose large burns units keep a bank of frozen donor skin for temporary transplantation. (Skin is one of the few tissues that can be frozen in this manner.) In addition to cadaver human skin, pig skin is commercially available as a temporary graft.
Blood vessels are at present only rarely used as allografts to replace diseased arteries. Autotransplanta-tion of vessels is much more satisfactory, and long saphenous veins from the leg are often used to replace diseased leg arteries. The other major application is in the heart. If the coronary arteries supplying the heart are in poor condition this may lead to angina pectoris, heart attacks and death. By replacing the diseased coronary vessels with saphenous vein -coronary by-pass grafting – autotransplantation can offer patients the chance of a longer and pain-free life. v
In contrast to skin, which has a rich regeneration capacity, nervous tissue heals only very poorly. Occasionally a vital nerve is damaged by tumour growth and needs to be excised: for example, the facial nerve controlling the facial muscles can be affected by a tumour of the parotid salivary gland. No nerve ever grows again completely, but if a segment of less important nerve from another part of the body is sutured in its place, the nerve fibres may regrow and connect to restore at least some of its workings. Bone marrow, however, is a substance which is technically easy to transplant. Unlike most of the organs discussed above, this is not obtained from someone who has died but from a donor who is very much alive and well. The difficulty lies in finding the right donor. It must not be just a close tissue match but an exact match, and because of the number of tissue variables this often presents considerable problems. Marrow transplantation is needed when a child is born without the capacity to fight infection, often as a result of a lack of one or more types of white blood cells. This can also happen after vigorous treatment for leukaemia, which may kill off marrow cells. If a suitable donor is found, bone marrow is aspirated (sucked out) by needle and syringe and injected into the recipient’s bloodstream, where it finds its way to the bone marrow. The procedure can be very successful. One possible complication, apart from rejection, is when the new white cells and their progeny regard the new host as ‘foreign’ and begin their own widespread attack on all the body tissues. This is called graft-versus-host disease (GVHD), as opposed to the usual host-versus-graft rejection. The kidney is the organ most people associate with transplantation. If renal failure is serious, and dialysis is necessary to sustain life, a kidney transplant may give a new dimension oflife to the recipient, who is henceforth independent of the dialysis apparatus. The technique of this operation has much improved during recent years and the results are on average good. Kidneys may be donated by living related donors -one kidney is enough to sustain a person’s life – but the majority of renal transplants are cadaveric. As soon as the kidney is taken from the donor’s body, it is flushed through with an ice-cold preservation fluid. It is then stored in this fluid on ice (or in a special preservation machine) until the recipient is ready to receive it. Providing that the kidney is implanted within approximately 24 hours there is about an 80 per cent chance of it working. The new kidney is not usually placed in the normal kidney position but in the lower part of the abdomen. When the operation goes well, the new kidney starts producing urine while the patient is still on the operating table, soon after receiving a blood supply.
Of all transplants, the heart transplant carries the most charisma. The donor must have been a fit young person and the recipient must be near to death as a result of heart muscle failure, otherwise the risk of the operation would not be worthwhile. In the years following Barnard’s pioneering work the success rate was low but now the relatively few centres performing the operation achieve good results. The heart is not usually transplanted whole but divided through the atria (upper chambers) so as to minimize the number of connections that need to be performed. While the heart is being transplanted the circulation is maintained by a heart bypass machine which pumps oxygenated blood around the body. At the end of the operation the heart is restarted with an electric shock. Liver transplantation is a relatively new procedure, performed for either liver tumours or severe and potentially fatal liver disease, such as cirrhosis of the liver. Unlike the kidney, there is no artificial liver machine available, so liver transplants rely entirely on donor organs becoming available at a time compatible with the recipient’s condition.
The biggest problem in all transplant operations is by rejection of the transplanted organ by the recipient’s body. In itself the defence system is highly efficient in combating foreign material, but in this special and in fact unnatural case it has to be prevented from rejecting the new organ. An exception to this is the transplantation of the cornea. Most cases of blindness worldwide are the result of the clear part at the front of the eye, the cornea, becoming opaque, usually as a result of infection. In most of these cases the treatment is relatively simple: removing a section of the diseased cornea and replacing it with a transplanted healthy cornea. Rejection is extremely rare and cross-matching and tissue-typing are not required because the cornea is a ‘privileged site’. This is because it does not have a blood supply (nutrients and oxygen reach it by diffusion) and so the blood-borne rejection system cannot reach it. ‘Eye banks’ have been established, using a variety of short -or long-term storage methods. The results of corneal grafting are good, with up to a 90 per cent success rate for certain conditions.
All the organ and marrow allografts mentioned above (apart from corneas) would tend to be rejected, however good the tissue matching, if it were not for immunosuppressive drugs. This group of drugs allow a certain amount of control over the immune system. These drugs are always used with great caution because they suppress the entire immune system, not just the process of transplant rejection. If too much immunosuppression is used, or if the patient is too susceptible, the immune system is unable to react against even trivial everyday infections and the patient may die. On the other hand, too little immunosuppression may cause the body to partly reject the organ with the result that the graft function deteriorates, which, if left untreated, may lead to total rejection, graft loss and in some cases, death. The balance is precarious and important for the eventual success of the transplant.