Klinika Chirurgii Ogólnej i Transplantacyjnej

Klinika Chirurgii Ogólnej i Transplantacyjnej TRANSPLANTATION Maciej Romanowski

Klinika Chirurgii Ogólnej i Transplantacyjnej

Historia 1902- Opracowanie techniki zespoleń naczyniowych i eksperymentalnego przeszczepiania nerek u zwierząt 1912- Nagroda Nobla Alexis Carrel Klinika Chirurgii Ogólnej i Transplantacyjnej

Historia Jurij Voronoy 1933– Pierwszy allogeniczny przeszczep nerki z zespoleniem do naczyń udowych Klinika Chirurgii Ogólnej i Transplantacyjnej

Historia 1953 - Pierwsze udane przeszczepienie nerki między dwoma jednojajowymi bliźniętami Peter Bend Brigham Hospital, Boston 1991- Nagroda Nobla(wraz z J. Merrill) Joseph Murray Klinika Chirurgii Ogólnej i Transplantacyjnej

1954 Chirurdzy : J.E. Murray & J.H.Harrison we współpracy z nefrologiem J.P. Merill przeprowadzili pierwszy udany przeszczep nerki The Peter Bent Brigham Hospital in Boston, USA

Historia 1963– Zastosowanie steroidów i azatiopryny w leczeniu immunosupresyjnym Thomas Starzl Klinika Chirurgii Ogólnej i Transplantacyjnej

Historia Prof. Jan Nielubowicz Prof. Tadeusz Orłowski Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Currently, the most frequently performed transplants are: • kidney • liver • heart • lung. Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Various terms and definitions are used in transplant technology. Allotransplantation means transplantation from a non-identical donor to a recipient of the same species (i.e. an allograft). Almost all human transplants are in this category. Xenotransplantation, transplanting between members of different species, is rare. Graftswhich are implanted into a recipient are termed orthotopic if they occupy their normal anatomical site (e.g. liver transplants) or heterotopic if they occupy an ectopic site (e.g. renal transplants). Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Rejection and immunosuppression Early transplants inevitably failed because of a complex rejection process, which involved cellular immunity (T and B cell lymophocytes) and humoral immunity (circulating antibody) mechanisms. Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation The host response to the donor graft depends upon the tissue matching. The two most important compatibility systems are: • ABO blood group • HLA (human leucocyte antigen) Class I and Class IIsystems. Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation The therapeutic goal of immunosuppression is to overide any response of the immune system to tissue histoincompatibility while at the same time to preserve the remaining functions of the recipient's immune system to protect against infection. Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Three patterns of rejection are recognised: • hyperacute • acute • chronic Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Hyperacute rejection. This occurs within minutes to hours after transplantation. The transplanted organ becomes swollen and tender and there is severe vascular damage, with thrombosis and endothelial damage. There is an abrupt cessation of graft function. This injury is medi-ated by circulating recipient antibodies and is usually caused by a major ABO or HLA system incompatibility. Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Acute rejection. This develops within a few weeks/months of transplantation and is of rapid onset. The graft becomes tender and swollen and there is a deterioration in function. The rejection process is mediated by a combination of cellular and humoral (antibody) mechanisms. Biopsy of the graft will reveal a mixed cellular infiltrate (lymphocytes, monocytes and plasma cells) together with evidence of antibody-mediated vascular endothelial damage. Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Chronic rejection. This begins months/years after transplantation. It is characterised by a progressive deterioration of the transplanted organ, with a mononuclear cellular infiltration on graft biopsy. Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation lmmunosuppressive drugs used in transplantation Action Side effects Cyclosporin A Inhibits immunoactive leucocytes Nephrotoxic, hepatotoxic Azathioprine Inhibits RNAand DNAsynthesis Bone marrow depression Steroids Inhibits inflammation Growth retardation, hypertension, increased infection risk Antiiymphocyte globulin Reduces lymphocyte numbers Antithymocyte globulinReduces thymocyte numbers Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Legal criteria for diagnosis of brain death (UK) 1. There must be a positive diagnosis of severe structural brain damage 2. The condition causing brain damage must be irreversible 3. There must be complete loss of brain stem function—evidenced by fixed pupils, no spontaneous eye movements or response to caloric testing, absent corneal, eyelash and blink reflexes, absent laryngeal and cough reflexes, and no response to deep painful stimuli (note: some spinal reflexes may be retained despite brain death) 4. On removal of ventilatory support, there must be no spontaneous respiratory activity in the presence of a physiologically adequate increase in PCO2 5. Any possible effects of hypothermia and drugs (e.g. muscle relaxants, respiratory depressants, alcohol) must be excluded Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Renal transplantation The main indication for transplantation is irreversible renal failure. The three most frequent causes are: • chronic glomerulonephritis • chronic pyelonephritis • diabetic nephropathy. Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Renal transplantation Most patients who are on a transplant waiting list will require peritoneal or haemodialysis until a suitable kidney becomes available. Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Renal transplantation Donor sources Kidneys for transplantation come from two sources: • brain-dead donors (cadaveric transplants) • living donors Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Renal transplantation Most donor kidneys come from patients who have recently died in hospital, following either a stroke or a major head injury. Donors are accepted provided there is no evidence of active infection, extracerebral malignancy, hepatitis A, B or C infection or HIV infection. Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Renal transplantation Live donation is usually reserved for related donors who wish to help a family member with renal disease. Transplantation between unrelated individuals is less common and is fraught with ethical problems. Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Renal transplantation Once brainstem death is confirmed and consent obtained, the kidneys are harvested as part of a multiple organ donation involving liver, kidneys, heart and lungs. Immediately the circulation is arrested, the intraabdominal organs are perfused with a cold preservation fluid in order to minimise the period of warm ischaemic time and thus prevent organ degeneration. Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Two basic methods are used for preserving organs between donation and transplantation: • Simple cold storage. The organ is flushed with ice-cold preservation solution and stored at 0-4°C on ice. Using specially formulated preservation solutions with agents designed to counter hypothermic cell swelling, it is now possible to store kidneys in this way for 24-36 hours, livers for 12-18 hours and hearts for 4-6 hours • Continuous oxygenated hypothermic pulsatile perfusion using special colloid-based (starch, plasma or albumin) solutions. This technique is more complex and expensive but enables kidneys to be stored for 2-3 days; the equipment is portable and can be used during transportation but the technique has not been extended to clinical preservation of other organs Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Hypothermiareduces the metabolic demands of the organ and is the mainstay of effective organ preservation. The period of warm ischaemiabetween circulatory arrest and cooling by perfusion with ice-cold preservation fluid must be kept to a minimum if irreversible damage to the organ is to be avoided. Klinika Chirurgii Ogólnej i Transplantacyjnej

Transplantation Transplant surgery The kidney is transplanted into a heterotopic site in either the left or right iliac fossa. An extraperitoneal pouch is prepared to receive the kidney and the renal vessels are anastomosed to the adjacent external iliac artery and vein. The ureter is usually implanted into the recipient's bladderusing an intramural tunnel to prevent reflux. Klinika Chirurgii Ogólnej i Transplantacyjnej

Klinika Chirurgii Ogólnej i Transplantacyjnej

Klinika Chirurgii Ogólnej i Transplantacyjnej

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