klinika chirurgii ogólnej i transplantacyjnej

Klinika Chirurgii Ogólnej Klinika Chirurgii Ogólnej i Transplantacyjneji Transplantacyjnej

TRANSPLANTATIONTRANSPLANTATION

Maciej RomanowskiMaciej Romanowski

21.04.2321.04.23 Klinika Chirurgii Ogólnej i TransplantacyjnejKlinika Chirurgii Ogólnej i Transplantacyjnej 22


HistoriaHistoria

1902 - Opracowanie techniki zespoleń naczyniowych i eksperymentalnego przeszczepiania nerek u zwierząt

1912 - Nagroda Nobla

Alexis Carrel


HistoriaHistoria

1933 – Pierwszy allogeniczny przeszczep nerki z zespoleniem do naczyń udowych

Jurij Voronoy


HistoriaHistoria

Joseph Murray

1953 - Pierwsze udane przeszczepienie nerki między dwoma jednojajowymi bliźniętami Peter Bend Brigham Hospital, Boston

1991 - Nagroda Nobla(wraz z J. Merrill)

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


HistoriaHistoria

Thomas Starzl

1963 – Zastosowanie steroidów i azatiopryny w leczeniu immunosupresyjnym


HistoriaHistoria

Prof. Jan Nielubowicz Prof. Tadeusz Orłowski


TransplantationTransplantationCurrently, the most frequently performed Currently, the most frequently performed

transplants artransplants aree::

• • kidneykidney

• • liverliver

• • heartheart

• • lung.lung.


TransplantationTransplantationVarious terms and definitions arVarious terms and definitions aree used in transplant technology. used in transplant technology. AllotransplantationAllotransplantation means transplantation from a non-identical donor means transplantation from a non-identical donor

to a recipient of the same species (i.e. an allograft). Almost all to a recipient of the same species (i.e. an allograft). Almost all human transplants arhuman transplants aree in this category. in this category.

XenotransplantationXenotransplantation,, transplanting between members of different transplanting between members of different species, is rare.species, is rare.

GraftsGrafts which arwhich aree implanted into a recipient ar implanted into a recipient aree termed termed orthotopicorthotopic if if they occupy their normal anatomical site (e.g. liver transplants) they occupy their normal anatomical site (e.g. liver transplants) or or heterotopicheterotopic if they occupy an ectopic site (e.g. renal if they occupy an ectopic site (e.g. renal transplants).transplants).


TransplantationTransplantationRejection and immunosuppressionRejection and immunosuppression

EarEarlly transplants inevitably failed because of y transplants inevitably failed because of a complex rejection process, which a complex rejection process, which involved cellular immunity (T and B celinvolved cellular immunity (T and B celll lymophocytes) and humoral immunity lymophocytes) and humoral immunity (circulating antibody) mechanisms.(circulating antibody) mechanisms.


TransplantationTransplantationThe host response to the donor graft The host response to the donor graft

depends upon the tissue matching. depends upon the tissue matching. The two most important compatibility The two most important compatibility systems arsystems aree::

• • ABO blood groupABO blood group

• • HLA (human leucocyte antigen) CHLA (human leucocyte antigen) Cllass I ass I and Cand Cllass IIass II systems.systems.


TransplantationTransplantationThe therapeutic goal of The therapeutic goal of

immunosuppressionimmunosuppression is to overide any is to overide any response of the immune system to response of the immune system to tissue histoincompatibility while at the tissue histoincompatibility while at the same time to preserve the remaining same time to preserve the remaining functions of the recipient's immune functions of the recipient's immune system to protect against infection.system to protect against infection.


TransplantationTransplantation

Three patterns of rejection arThree patterns of rejection are e recognised:recognised:

• • hyperacutehyperacute

• • acuteacute

• • chronichronicc


TransplantationTransplantationHyperacute rejection.Hyperacute rejection. This occurs within minutes This occurs within minutes

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


TransplantationTransplantationAcute rejection.Acute rejection. This develops within a few weeks/months This develops within a few weeks/months

of transplantation and is of rapid onset. The graft of transplantation and is of rapid onset. The graft becomes tender and swollen and there is a deterioration becomes tender and swollen and there is a deterioration in function. The rejection process is mediated by a in function. The rejection process is mediated by a combination of cellular and humoral (antibody) combination of cellular and humoral (antibody) mechanisms. Biopsy of the graft will reveal a mixed mechanisms. Biopsy of the graft will reveal a mixed cellular infiltrate (lymphocytes, monocytes and plasma cellular infiltrate (lymphocytes, monocytes and plasma cells) together with evidence of antibody-mediated cells) together with evidence of antibody-mediated vascular endothelial damage.vascular endothelial damage.


TransplantationTransplantation

ChroniChronicc rejection. rejection. This begins months/years This begins months/years after transplantation. It is characterised by after transplantation. It is characterised by a progressive deterioration of the a progressive deterioration of the transplanted organ, with a mononuclear transplanted organ, with a mononuclear cellular infiltration on graft biopsy.cellular infiltration on graft biopsy.


TransplantationTransplantationlmmunosuppressive drugs used in transplantationlmmunosuppressive drugs used in transplantation

Action Action Side effectsSide effectsCyclosporin A Cyclosporin A Inhibits immunoactiInhibits immunoactivve leucocytes e leucocytes Nephrotoxic, Nephrotoxic, hepatotoxic hepatotoxic Azathioprine Azathioprine Inhibits RNAInhibits RNA and DNAand DNA synthesis synthesis BonBonee marrow marrow depression depression Steroids Steroids Inhibits inflammation Inhibits inflammation Growth retardation, Growth retardation,

hypertension, hypertension, increased increased infection infection riskrisk

Antiiymphocyte globulinAntiiymphocyte globulin Reduces lymphocyte numbers Reduces lymphocyte numbers Antithymocyte globulinAntithymocyte globulin Reduces thymocyte numbersReduces thymocyte numbers


TransplantationTransplantation Legal criteria for diagnosis of brain death Legal criteria for diagnosis of brain death (UK)(UK)

1. There must be a positive diagnosis of severe structural brain damage1. There must be a positive diagnosis of severe structural brain damage

2. The condition causing brain damage must be irreversible2. The condition causing brain damage must be irreversible

3. There must be complete loss of brain stem function—evidenced by fixed 3. There must be complete loss of brain stem function—evidenced by fixed pupils, no spontaneous eye movements or response to caloric testing, pupils, no spontaneous eye movements or response to caloric testing, absent corneal, eyelash and blink reflexes, absent laryngeal and absent corneal, eyelash and blink reflexes, absent laryngeal and cough reflexes, and no response to deep painful stimuli (note: some cough reflexes, and no response to deep painful stimuli (note: some spinal reflexes may be retained despite brain death)spinal reflexes may be retained despite brain death)

4. On removal of ventilatory support, there must be no spontaneous 4. On removal of ventilatory support, there must be no spontaneous respiratory activity in the presence of a physiologically adequate respiratory activity in the presence of a physiologically adequate increase in PCOincrease in PCO22

5. Any possible effects of hypothermia and drugs (e.g. muscle relaxants, 5. Any possible effects of hypothermia and drugs (e.g. muscle relaxants, respiratory depressants, alcohol) must be excludedrespiratory depressants, alcohol) must be excluded


TransplantationTransplantationRenal transplantationRenal transplantation

The main indication for transplantation is The main indication for transplantation is irreversible renal failure. The three most irreversible renal failure. The three most frefreqquent causes aruent causes aree::

•• chronichronicc glomerulonephritis glomerulonephritis

•• chronichronicc pyelonephritis pyelonephritis

•• diabetic nephropathy.diabetic nephropathy.



Most patients who arMost patients who aree on a transplant on a transplant waiting list will rewaiting list will reqquire peritoneal or uire peritoneal or haemodialysis until a suitable kidney haemodialysis until a suitable kidney becomes available.becomes available.



Donor sourcesDonor sources

Kidneys for transplantation come from two Kidneys for transplantation come from two sources:sources:

• • brain-dead donors (cadaveric transplants)brain-dead donors (cadaveric transplants)

• • living donorsliving donors



Most donor kidneys come from patients who have Most donor kidneys come from patients who have recently died in hospital, following either a recently died in hospital, following either a stroke or a major head injury. Donors arstroke or a major head injury. Donors aree accepted provided there is no evidence of active accepted provided there is no evidence of active infection, extracerebral malignancy, hepatitis A, infection, extracerebral malignancy, hepatitis A, B or C infection or HIV infection.B or C infection or HIV infection.



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



Once brainstem death is confirmed and consent Once brainstem death is confirmed and consent obtained, the kidneys arobtained, the kidneys aree harvested as part of a harvested as part of a multiple organ donation involving liver, kidneys, multiple organ donation involving liver, kidneys, heart and lungs. Immediately the circulation is heart and lungs. Immediately the circulation is arrested, the intraabdominal organs ararrested, the intraabdominal organs aree perfused perfused with a cold preservation fluid in order to with a cold preservation fluid in order to minimise the period of warm ischaemic time and minimise the period of warm ischaemic time and thus prevent organ degeneration. thus prevent organ degeneration.


TransplantationTransplantationTwo basiTwo basicc methods ar methods aree used for preserving organs between donation used for preserving organs between donation

and transplantation:and transplantation:• • Simple cold storage.Simple cold storage. The organ is flushed with ice-cold preservation The organ is flushed with ice-cold preservation

solution and stored at 0-4°C on ice. Using specially formulated solution and stored at 0-4°C on ice. Using specially formulated preservation solutions with agents designed to counter preservation solutions with agents designed to counter hypothermic celhypothermic celll swelling, it is n swelling, it is noow possible to storw possible to storee kidneys in kidneys in this way for 24-36 hours, livers for 12-18 hours and hearts for 4-this way for 24-36 hours, livers for 12-18 hours and hearts for 4-6 hours6 hours

• • Continuous oxygenated hypothermic pulsatile perfusionContinuous oxygenated hypothermic pulsatile perfusion using using special colloid-based (starch, plasma or albumin) solutions. This special colloid-based (starch, plasma or albumin) solutions. This technitechniqque is morue is moree complex and expensive but enables kidneys to complex and expensive but enables kidneys to be stored for 2-3 days; the ebe stored for 2-3 days; the eqquipment is portable and can be used uipment is portable and can be used during transportation but the techniduring transportation but the techniqque has not been extended to ue has not been extended to clinical preservation of other organsclinical preservation of other organs


TransplantationTransplantationHypothermiaHypothermia reduces the metabolic demands reduces the metabolic demands

of the organ and is the mainstay of effective of the organ and is the mainstay of effective organ preservation. organ preservation.

The period of The period of warm ischaemiawarm ischaemia between between circulatory arrest and cooling by perfusion circulatory arrest and cooling by perfusion with ice-cold preservation fluid must be kept with ice-cold preservation fluid must be kept to a minimum if irreversible damage to the to a minimum if irreversible damage to the organ is to be avoided. organ is to be avoided.


TransplantationTransplantationTransplant surgeryTransplant surgery

The kidney is transplanted into a heterotopic site in The kidney is transplanted into a heterotopic site in either the left or right iliac fossa. An either the left or right iliac fossa. An extraperitoneal pouch is prepared to receive the extraperitoneal pouch is prepared to receive the kidney and the renal vessels arkidney and the renal vessels aree anastomosed to anastomosed to the adjacent external iliac artery and vein.the adjacent external iliac artery and vein.

The ureter is usually implanted into the recipient's The ureter is usually implanted into the recipient's bladderbladder using an intramural tunnel to prevent using an intramural tunnel to prevent reflux. reflux.


Step by step


TransplantationTransplantationLiver transplantationLiver transplantationThe main indications for transplantation in adults The main indications for transplantation in adults

araree::• • cirrhosis secondary to viral hepatitiscirrhosis secondary to viral hepatitis• • fulminant liver failure.fulminant liver failure.

Transplantation is performed less often for:Transplantation is performed less often for:• • hepatocellular cancerhepatocellular cancer• • alcoholic cirrhosis.alcoholic cirrhosis.

klinika chirurgii ogólnej i transplantacyjnej

Documents