Power point presentation Slides Presented in Lectures at Services institute of Medical Sciences Lahore

1. ORGAN
TRANSPLANTATION

2. HISTORICAL BACKGROUND
• Failed initially due to lack of appreciation of
immune response
• 1954 – renal transplant between identical
twins
• 1960 – first immunosuppressive drugs were
used
• 1980s – more powerful ciclosporin permitted
transplantation of liver, heart, lungs, pancreas

3. CLASSIFICATION OF GRAFTS
• AUTOGRAFT – from one part of the body to
another e.g. skin
• ALLOGRAFT – between members of the same
species e.g. human to human
• ISOGRAFT – between identical twins
• XENOGRAFT – between different species e.g. pig
to human
• STRUCTURAL GRAFTS – biological (arterial and
heart valve grafts) or synthetic (Dacron)

4. • ORTHOTOPIC – diseased organ is removed and
replaced by the transplanted organ in the
normal anatomical position e.g. heart, lung,
liver
• HETEROTOPIC – the transplanted organ is
placed in a different position to the normal
anatomical position e.g. kidney and pancreas

5. ORGAN DONORS
• 2 sources:
– LIVING – Applies mainly to kidney transplantation,
where the donor can maintain adequate renal
function with only one kidney
– DECEASED – those who have sustained lethal
brainstem injury following a head injury,
intracranial haemorrhage or primary brain tumour

6. • ASYSTOLIC DONATION – organs are removed
from the donor after cardiac arrest; possible
for kidney and liver

7. EXCLUSIONS TO ORGAN DONATION
There are three main reasons why a potential
donor may be unsuitable:
1. Potential transmission of infection – hepatitis
B, C and HIV
2. Malignancy – except low-grade primary brain
tumours
3. Impaired function of donor organ – e.g. heart
with severe coronary artery disease

8. ORGAN PRESERVATION
• Organ must be maintained in its optimum
state
• Achieved by combination of
– cooling the organ to 4°C to reduce metabolic
activity and
– Perfusing it with and storing it in a preservation
solution that acts as a buffer and prevents cell
swelling by osmosis

9. ISCHEMIA TIMES - TERMINOLOGY
• WARM ISCHEMIA
– Donor warm ischemia – starts from the time of
asystole until cold perfusion begins
– Recipient warm ischemia – starts from the
removal of the organ from ice until reperfusion
• COLD ISCHEMIA – time between the end of
donor warm ischemia until the onset of
recipient warm ischemia

10. ORGAN RECIPIENTS
• No one should undergo transplantation unless
fit enough to withstand the operative
procedure

11. IMMUNOLOGY
• Major histocompatibility complex (MHC)
– When an organ is transplanted, it is recognized as
foreign by the host’s immune system and the
rejection response is initiated
– This recognition is initiated by an interaction
between T cells and histocompatibility antigens on
the surface of the donor organ
– The MHC is a group of genes that encode
molecules (antigens) expressed on the surface of
cells

12. • Human leucocyte antigen system
– This system describes the locus on chrmosome 6
containing the genes encoding the MHC antigens

13. ORGAN MATCHING
• 3 LEVELS:
1. ABO matching
2. Lymphocytotoxic cross-matching
3. MHC matching

14. ABO MATCHING
• Required for all transplants
• Presence of preformed ABO antibodies means
that the transplanted organs must be ABO
compatible
• Crossing the ABO barrier results in hyperacute
rejection

15. LYMPHOCYTOTOXIC CROSS-MATCH
• To detect circulating antibodies in the
recipient against donor HLA antigens, a direct
lymphocytotoxic cross-match is performed
• Donor cells (lymphocytes) mixed with
recipient sera in the presence of complement
and observing for cytolysis

16. MHC MATCHING
• In order to minimize the immune response to
an organ allograft, the recipient’s MHC
antigens can be matched to the donor
• Perfect matching comes from an identical twin

17. REJECTION
• Hyperacute rejection
• Acute rejection
• Chronic rejection
• Graft versus host disease

18. HYPERACUTE REJECTION
• Occurs immediately
• Preformed antibodies to donor HLA I antigens
• Intravascular thrombosis and interstitial
haemorrhage
• Is prevented by ensuring compatibility

19. ACUTE REJECTION
• Occurs within 6 months
• T-cell dependent
• May be cell-mediated, antibody mediated or
both
• Mononuclear cell infiltration of graft
• Treated by increasing immunosuppressive
therapy

20. CHRONIC REJECTION
• Occurs after months to years
• Antibodies
• Risk factor – recurrent acute rejection
• Myointimal proliferation – ischemia and
fibrosis

21. GRAFT VERSUS HOST DISEASE
• Some donor organs (liver and small bowel)
contain large numbers of lymphocytes
• These may react against HLA antigens
expressed by recipient tissues
• Characteristic rash on palms and soles

22. IMMUNOSUPPRESSIVE THERAPY
• Is a balance between giving enough drug to
prevent rejection, but not too much to cause
infection
• Usually consists of a steroid (e.g.
prednisolone), an antinucleotide such as
azathioprine and an inhibitor of T-cell
activation such as ciclosporin

23. COMPLICATIONS
• EARLY: may be related to the four components
of transplant surgery:
1. The surgical operation – wound infection,
anastomotic breakdown
2. The quality of the organ – long cold ishemia
time, less well performance
3. The immunological response
4. The effects of immunosupression – infective
complications (wound, chest, viral)

24. • LATE:
1. Immunological complications – acute and
chronic rejection
2. Immunosuppressive complications – drug side-
effects, infection, malignancy
3. Recurrent disease – e.g. hepatitis B and C may
re-infect a transplanted liver