Transplantation Flashcards
What is an Autograft
Within the same individual (one part of the body to the other
What is an Isografts
Between genetically identical individuals of the same species
What is an Allografts
Between different individuals of the same species
What is an Xenografts
Between individuals of different species
What is an Prosthetic graft
Plastic, metal
Examples of areas of xenografts? (3)
- Heart valves (pig/cow)
- Skin
Examples of areas of autografts? (3)
- Reconstructive surgeries, coronary artery bypass surgery etc.
- The future of autografts lies in the use of STEM CELLS to make full organs which function as they should
Examples of areas of allografts? (3)
Solid organs (kidney, liver, heart, lung, pancreas)
- Small bowel
- Free cells (bone marrow, pancreas islets)
- Temporary blood, skin (burns)
- Privileged sites cornea
- Framework bone, cartilage, tendons, nerves
- Composite hands, face, larynx, uterus
Difference between orthotopic and heterotopic transplantation?
ORTHOTOPIC transplantation Organ put in the place where it should be (this is the most common and done for heart, lungs and liver)
HETEROTOPIC transplantation Organ not put in the place where it should be (kidneys and pancreas)
What organ is suitable for donor after cardiac death
- Suitable for kidney
What organ is suitable for donor after brain death
Most
What do you do to organs once harvested and why?
- Harvest organs and cool to minimise ischaemic damage
How to demonstrate brain death? (6)
pupils both fixed to light corneal reflex absent no eye movements with cold caloric test no cranial nerve motor responses no gag reflex no respiratory movements on disconnection (with PaCO2 >50 mmHg)
Cold time for kidney?
- absolute maximum cold ischaemia time for kidney 60h (ideally <24h
2 things that must be considered before allocating an organ? Explain both
- Equity – what is fair?
Time on waiting list
Super-urgent transplant - imminent death (liver, heart)
Efficiency – what is the best use for the organ in terms of patients’ survival and graft survival?
7 elements of prioritising an organ recipient?
- Waiting time
- HLA match and age combined
- Donor-recipient age difference
- Location of patient relative to donor
- HLA-DR homozygosity
- HLA-B homozygosity
- Blood group match
How is organ donation made fair and who regulates it?
- Rules for organ allocation are established by medical community/health professionals/advisory groups/DH
- NHSBT monitors allocation
What is the main obstacle to organ donation post brain death?
Family decline consent for donation (43%)
Ways government has tried to increase organ donation?
Organ Donation Taskforce (2008-2013)
Making a donor transplant coordinator
Improving public engagement
Improving quality of organ retrieval and organ transplantation standards, guidelines, training and resources
What do donor transplant nurses do
- Employment to shift from transplant centres to NHSBT
- Seek out potential donors in A&E /ICU
- They carry out family interviews - part of bereavement services
Strategies to increase transplantation? (3)
- increased donation
Marginal donors – DCD, elderly, sick with co-mobidities - Living donation
transplantation across tissue compatibility barriers
Exchange programmes: organ swaps for better tissue matching - The future?
Xenotransplantation
Stem cell research
Half life of a kidney transplant?
10-14 years
2 main things you have to match during organ transplantation?
- ABO blood group (however we have developed techniques to avoid this so it’s a bit of a historical problem)
- HLA (human leukocyte antigens) coded on chromosome 6 by Major Histocompatibility complex (MHC)
How do we get around ABO-incompatible transplantations?
- Remove the antibodies in the recipient (plasma exchange)
- We do see good outcomes (even if the antibody comes back)
What happens if you incorrectly match blood groups?
If you give a blood group A person a blood group B heart:
- Circulating, pre-formed, recipient anti-B antibody binds to B blood group antigens on donor endothelium = antibody-mediated rejection
- Antibody activates complement and macrophages
What are the MHC Class I subgroups?
- Class I (A, B, C)– expressed on all cells
What are the MHC Class II subgroups?
- Class II (DR, DQ, DP) – expressed antigen-presenting cells but also can be upregulated on other cells
Which cells have MHC class II
- Class II (DR, DQ, DP) – expressed antigen-presenting cells but also can be upregulated on other cells
Which cells have MHC class I
- Class I (A, B, C)– expressed on all cells
Each individual has how many types of each HLA molecule and why?
- Each individual has most often 2 types for each HLA molecule (one from mummy and one from daddy)
How many of which alpha and beta chains are in MHC class 1 and 2
A1, 2 and 3 and B2microglobulin in class 1
A1, 2 and B1, 2
Which three different HLA isotopes do we match
HLA-A, HLA-B and HLA-DR
How do represent the number of mismatches of different isotopes
MM X:Y:Z meaning X number of mismatches at HLA-A, Y number at B and Z number at DR
most common cause of graft failure is…?
Rejection
How to diagnose graft rejection?
- Diagnosis = histological examination of a graft biopsy
How to treat graft rejection?
immunosuppressive drugs
2 ways of splitting the type of rejection and the subcategories of each?
Rejection can be divided by how quickly it develops:
- HYPERACUTE (immediate/days)
- ACUTE (weeks/months)
- CHRONIC (years)
It can also be divided into:
- T-CELL MEDIATED
- ANTIBODY-MEDIATED
Explain T cell mediated transplant rejection
- When an organ is transplanted, both recipient and donor antigen presenting cells will take up fragments of the donated organ’s HLA antigens
- These will then circulate to the local lymph nodes where T-cells will circulate through
- Some T-(helper) cells which are able to mount an allospecific response will come into contact with the APCs
- These alloreactive T cells will then re-circulate until they reach the transplanted organ, infiltrate it
Recruit T killer and cause cell apoptosis
Then macrophages come along and finish the job
What toxin do cytotoxic T cells release to damage cells? how do they cause apoptosis?
Granzyme B and perforin
Stimulate apoptosis by activating the fas ligand
What is a defining feature of renal allograft rejection
Tubulitis
Describe the antibody mediated mechanism of transplant rejection
- Antibodies bind on antigens (AB or HLA) present on the donor’s endothelium
- They recruit complement and activate it
- This can lead to cell lysis (creation of membrane attack complex)
- Antibodies can also directly recruit inflammatory cells which can cause injury to the endothelium
How to differentiate between antibody and T cell mediated graft rejection histologically
WE CAN SEE THE DIFFERENCE BETWEEN ANTIBODY-MEDIATED AND T-CELL MEDIATED HISTOLOGICALLY BECAUSE THEY LOOK DIFFERENCE, ONE IS TUBULAR ONE IS A VASCULAR LOOKING THING
What 3 signs indicate a deterioration in kidney transplant function
Rise in creatinine, fluid retention, hypertension
What 2 signs indicate a deterioration in liver transplant function
Rise in LFTs, coagulopathy
What 2 signs indicate a deterioration in lung transplant function
breathlessness, pulmonary infiltrate
2 ways of preventing rejection
- Maximise HLA compatibility (very difficult however)
- Life-long immunosuppressive drugs
2 general targets of immunosuppressants?
- Targeting T cell activation and proliferation
- Targeting B cell activation and proliferation, and antibody production
3 ways of targeting T cell activation and proliferation with immunosuppressants?
Target the initial interaction between an APC and a T cell – target presentation of a peptide and binding to MHC, or can tarfet co-stimulation between APCs and T cells, or can target paracrine effect of cytokines
5 ways of targeting B cell activation and proliferation and antibody function with immunosuppressants?
I.V. immunoglobulins (IVIG) and plasma exchange, anti-CD20 drugs, proteasome inhibitors, anti-C5 and finally, splenectomy
What immunosuppressive regime is used pre-implantation? (2)
Induction agent (T-cell depletion or cytokine blockade)
What immunosuppressive regime is used post-implantation? (4)
- line immunosuppression for the rest of their life:
- Signal transduction blockade, usually a CNI inhibitor: Tacrolimus or Cyclosporin; sometimes mTOR inhibitor (Rapamycin)
- Antiproliferative agent: MMF or Azathioprine
- Corticosteroids
What opportunistic infections must you watch out for post-transplantation?
Cytomegalovirus, BK virus, Pneumocytis carinii