Flashcards in Transplantation Deck (31)
What is the difference between life-saving and life-enhancing transplantation?
Life-saving – other life-supportive methods are not fully developed or other life-supportive methods have reached the end of their possible use
Life-enhancing – other life-supportive methods are less good e.g. Kidneys and dialysis – the organ is not vital but it improves the quality of life
Describe the different types of transplants?
Autograft – within the same individual
Isografts – between genetically identical individuals of the same species
Allograft – between different individuals of the same species
Xenograft – between individuals of different species
Prothetic graft – artificial material e.g. plastic, metal
Give an example of an autograft.
What tissues can xenografts be used for?
Coronary artery bypass graft
What are the two types of deceased donor?
Donor after brain death – brain dead but heart-beating (death is confirmed using neurological criteria)
Donor after cardiac death –non-heart beating donors (death is confirmed using cardio-respiratory criteria)
What must be confirmed with DBD donors?
- Irremediable structural brain damage of known cause
- Apnoeic coma that is NOT due to CV instability or depressant drugs, hypothermia, neuromuscular blockers etc.
- Must be able to demonstrate a lack of brain stem function (e.g. pupils both fixed to light)
What must be excluded before harvesting organs from a deceased donor?
Drug abuse, overdose or poison
How are the organs maintained once they’ve been removed?
They are rapidly cooled and perfused
NOTE: absolute maximum cold ischaemia time for the kidneys is 60 hours
What is the difference between transplant selection and transplant allocation?
Transplant selection: waiting list at a transplant centre after multidisciplinary assessment
Transplant allocation: how organs are allocated as they become available
What is the nationwide system of transplant allocation based on?
- Time on waiting list
- Super-urgent transplant
2. Efficiency – what is the best use of the organ in terms of patient and graft survival?
What are the 5 tiers of patients on the organ transplant waiting list based on?
Paediatric or adult
Highly sensitised or not
What are the 7 elements that are used to decide upon organ allocation?
HLA match and age combined
Donor-recipient age difference
Location of patient relative to donor
Blood group match
Describe some strategies for increasing transplantation activity.
- Increase deceased donation
- Look for other sources of organs (e.g. “marginal donors”, xenotransplantation, stem cell biology etc.)
- Optimise use of currently available organs (improve the half-life of an allograft)
What are the two most relevant protein variations in clinical transplantation?
1. ABO blood group
2. HLA (human leukocyte antigens)
On which chromosome is the HLA gene encoded?
Coded on Chromosome 6 by MHC
Where are the A and B proteins/antigens with carbohydrate chains found?
On red blood cells but also endothelial lining of blood vessels in transplanted organ
Recall the structural differences between A, B, and O.
Describe the 4 main blood groups in terms of the antibodies in the plasma and the antigens on red blood cells.
A = has N acetyl-galactosamine
B = has galactose instead
O = has neither
A: has anti-B
B: has anti-A
AB: no antibodies
O: has anti-A and anti-B (no antigens on RBC)
What is ABO-incompatible transplantation?
- Remove the antibodies in the recipient
- Good outcomes (even if the antibody comes back)
- Kidney, heart, liver
What are the two classes of HLA and which HLA subtypes are in each class? Describe the polymorphic nature of these genes.
HLA Class I – A, B and C = present on all cells
HLC Class II – DP, DQ, DR = present on specialised antigen-presenting cells
Highly polymorphic – lots of alleles for each locus (for example: A1, A2, …, A341… etc.)
Each individual has most often 2 types for each HLA molecule (for example: A3 and A21)
What are the most important HLA subtypes in organ compatibility?
Describe how to convey the number of A/B/DR mismatches? State the percentage chance for different numbers of mis-matches between siblings.
See which two alleles the recipient has for each of HLA-A, HLA-B, and HLA-DR.
Do the same for the donor.
Add up the number of matches between the two (i.e. max. no. of total matches = 6)
e.g. MM = 1:2:0 = 3 mis-matches
NOTE: the fewer the number of mismatches, the better the outcome for the recipient
Sibling transplant = 25% chance of 0MM,25% chance of 6MM, 50% chance of 3MM.
What are the two types of organ rejection?
T cell-mediated rejection
Antibody-mediated rejection (B cells)
How is rejection diagnosed?
Histological examination of graft biopsy
How is rejection classified based on the time of onset?
How may organ rejection present?
Deteriorating graft function e.g. rise in creatinine with kidney transplant
Pain and tenderness over graft
Describe what happens in T cell-mediated rejection.
- The graft can be infiltrated by allo-reactive CD4+ cells.
- CTL lymphocytes release toxins to kill target (Granzyme B), punch holes in target cells (Perforin), trigger apoptotic cell death (Fas-Ligand)
- Macrophages can phagocytose, release proteases, cytokines and oxygen/nitrogen radicals.
In antibody-mediated rejection, antibodies are made against graft HLA and AB antigens. In what two ways can these antibodies arise?
Pre-transplantation – ‘sensitised’ i.e. patient already been exposed in pregnancy or previous transplants.
Post-transplantation – ‘de novo’.
You may see features of both forms of rejection in graft rejected patients.
How can rejection be prevented?
Maximise HLA compatibility
Life-long immunosuppressive therapy
List some treatments for Antibody-mediated rejection.
Bortezomib (proteasome inhibitor)
Intravenous immunoglobulin (IVIG)
What is normally used for baseline immunosuppression following transplantation?
HLA binding signal transduction blockade: usually a calcineurin inhibitor (tacrolimus or cyclosporin)
Antiproliferative agent (e.g. azathioprine targets T cell cycle)