Learning question : What are the pros and cons of transplant surgery ?

1. Title: Transplant surgery 05 January 2020 Learning question: What are the pros and cons of transplant surgery? Homework: Read and make notes on spreads from pp206-209. Answer textbook questions and complete last paper questions. Mark all questions using the mark schemes provided. Face transplant patient http://www.bbc.co.uk/news/world-us-canada-17534646 BBC documentary on the first recipient of a face transplant

2. Learning Objectives (a) explain the significance of genetic compatibility in transplant surgery with reference to the major histocompatibility (MHC) system (b) State the potential sources of donated organs and outline the advantages and disadvantages of each source (c) Outline the potential of genetic engineering in the use of non-human organs for transplant surgery

3. Key words • Donor • Recipient • Immune response • Tissue rejection • Compatibility • Blood group • Tissue typing • Human leucocyte antigen system (HLA) • Major histocompatibility complex (MHC) • Haplotype • Xenotransplantation

4. Genetic compatibility

5. Genetic compatibility • Tissue transplanted from one person into another will bring about an immune response to the foreign tissue and be destroyed – this is called tissue rejection. • This will always occur between to individuals, even from the same family, unless they are identical twins. • The ability to accept a transplanted organs, without tissue rejection is called compatibility. • This includes looking at the degree of genetic similarity at a particular locusof two individuals

6. Genetic compatibility • Initially, a blood test is carried out to see if the patient and the recipient’s blood types match • Tissue typing is next: with the exception of RBCs, all cells carry antigens other than A and B in their cell surface membranes. • The human leucocyte antigen system (HLA) is of particular interest. • HLA genes are found on chromosome 6. • 6 gene loci are involved, known as the Major Histocompatibility Complex (MHC)

7. Genetic compatibility • HLA genes are so close together, they are linked (transmitted into the same gamete together) • Each set of HLA antigens from chromosome 6 is referred to as a haplotype. We get 2 copies – one from each parent. • The loci of these antigens are given letters to identify them. • Each of the six loci has a large number of alleles. • This means that you could have an HLA-A1, B8, DR17!

9. Questions • How many haplotypes will you have in each liver cell? • What does the term compatibility mean in the field of transplant surgery? • What does MHC stand for? • What chromosome would you find MHC? • What do the genes in the MHC region code for?

10. Answers • 2 • Compatibility is the ability to accept transplanted tissue. • Major histocompatibility complex • Chromosome 6 • HLA antigens

11. Genetic compatibility • More precise tissue matching is being carried out with the advent of DNA technology. • Polymerase chain reaction (PCR) is replacing traditional serological techniques • More accurate and specific HLA typing, which means more precise HLA matching between donors and transplant patients.

13. Sources of donated organs • Cadaversused to be a good source of organ harvesting, but with a lower mortality rate, other options are being explored. • Why are more people surviving? • Road safety • Medical advances • Prevention of strokes

14. Sources of donated organs – extended criteria • Older donors being considered (e.g. livers over 70 years old) • Unsuitable hearts being used as a “bridge” until a suitable one is found • Livers can be split into two for two patients • One kidney may be donated by a living relative • “Domino” transplants – patients needs a new set of lungs, but gets a new heart and lungs because this operation is easier to perform. The patient’s heart is then given to someone else who needs the healthy heart

15. Success of donated organs • Living donors have a better outcome than cadavers (95% to 86% success rate respectively for kidney donation) • Ideal donor is an identical twin, then a sibling. Failing that, a blood relative are more likely to match than a stranger • Living donors can donate bone marrow, liver lobes, lung lobes and kidneys

16. Ethics of organ donation - Is it wrong to sell organs?

17. Ethics of organ donation - Is it wrong to sell organs? • Senior NHS doctors have complained about botched transplant surgeries done abroad • Doctors in India see poor donors dying after selling one of their kidneys • In March 2007, China published new rules governing human organ transplants – buying and selling organs is forbidden. Written permission from doctors is required before operation is carried out

18. Xenotransplantation • Animal – human transplantations are being studied by some transplant centres. • Pigs may be a possible source of transplant organs….what do you think? • What are the implications of this?

19. Question • Name four different sources of donated organs for transplant surgery. Which would be likely to have the best outcome? State one problem associated with each source.

20. Answer • Cadavers – establishing brain death, permission • Living donors – need a good tissue match • Xenotransplantation – immunological rejection, transfer of disease, sale of organs, monetary pressure, poorly executed operations to remove the wanted organ