Transplantation Flashcards
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 possibleuse
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
What are the different types of transplants?
Autograft – within the same individual
Isografts – between genetically identical individuals of the same species (eg between identical twins)
Allograft – between different individuals of the same species
Xenograft – between individuals of different species
Prosthetic graft – artificial material e.g. plastic, metal
Give an example of an autograft.
Coronary artery bypass graft
What tissues can xenografts be used for?
Heart valves
Skin
What are the two types of deceased donor?
Donor after brain death – brain dead but heart-beating
Donor after cardiac death –non-heart beating donors
What must be confirmed with DBD donors?
Neurological criteria:
- Irremediable structural brain damage of known cause
- Apnoeic coma that is NOT due to neuromuscular blockers, depressant drugs etc.
- Must be able to demonstrate a lack of brain stem reflexes eg loss of pupillary reflex
What must be excluded before harvesting organs from a deceased donor?
Viral infection
Malignancy
Drug abuse, overdose or poison
disease of the transplanted organ
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?
Selection – process of deciding which patients are eligible for a transplant and putting these patients on the waiting list. This is normally discussed in MDT meetings
Allocation – How organs are allocated as they become available
What is the nationwide system of transplant allocation based on?
Equity – fairness
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?
- Waiting time
- donor recipient age difference
- HLA match and age combined (a kidney from a 70yo may not work well in a 20yo recipient)
above 3 are the most important, other factors:
- HLA-B homozygosity
- HLA-DR homozygosity
- Location of patient relative to donor
- Blood group match
What are the main obstacles to donation?
Contraindication for use of that organ
Family not approached for consent
Family declined consent
Describe some other strategies for increasing transplantationactivity.
1.Deceased donation (from dead body) or marginal donors (elderly with
comorbidities)
- increase Living donation by doing transplantation across tissue compatibility barriers (eg using advanced drugs/immunosuppressants to allow a person to accept an organ that would not have been compatible if without the drug)
- Future – xenotransplantation + stem cell research
What are the main antigens that must be considered when determining the compatibility of an organ for transplant?
ABO
HLA
On which chromosome is the HLA gene encoded?
Chromosome 6
What are the two classes of HLA and which HLA subtypes are in each class?
HLA Class I – A, B and C = present on all cells
HLC Class II – DP, DQ, DR = present on specialised immune cells
What are the most important HLA subtypes in organ compatibility?
A
B
DR
NOTE: the fewer the number of mismatches, the better the outcome for the recipient
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?
Hyperacute
Acute
Chronic
How may organ rejection present?
Deteriorating graft function e.g. rise in creatinine with kidney transplant
Pain and tenderness over graft
Fever
NB some may be subclinical which is bad because the immune system may be slowly eating away the organ without you noticing
How can rejection be prevented?
Maximise HLA compatibility
Life-long immunosuppressive therapy
List some treatments for Antibody-mediated rejection.
Anti-CD20 antibodies Bortezomib (proteasome inhibitor) Anti-complement antibodies Plasma exchange IVIg (intravenous immunoglobulin) Splenectomy
What is normally used for baseline immunosuppression following transplantation?
- Signal transduction blockade: usually a calcineurin inhibitor (eg cyclosporin)
- Antiproliferative agent (e.g. azathioprine- an immunosuppressive)
- Corticosteroids (steroids are immunosuppressive)
Describe the treatment of episodes of acute rejection.
T cell mediated: steroids and anti-T cell agents
Antibody mediated: IVIg, plasma exchange, anti-CD20, anti-complement
What is a major risk of the extensive immunosuppressive therapythat is given to patients following transplantation?
- Increased risk of infection (including opportunistic infection)
- post transplantation malignancy (especially skin cancer and virally driven cancers eg EBV)
What is given to patients before transplantation
an induction agent (causing T-cell depletion or cytokine blockade)
cold ischaemia definition
cold ischaemia:
the cooling of a tissue, organ, or body part after its blood supply has been reduced or cut off. This can occur while the organ is still in the body or after it is removed from the body if the organ is to be used for transplantation.
Cold ischemia time= the duration from when the thing is cooled until it is reconnected to blood supply and warmed up
warm ischaemia definition
Warm Ischaemia:
In surgery, keeping a tissue, organ, or body part at body temperature after its blood supply has been reduced or cut off.
Warm ischemia time= How long the thing is kept at body temperature for until it is cooled or reconnected to a blood supply
What is used to diagnose death in DCD donors
death is diagnosed and confirmed using cardio-respiratory criteria; 5 minutes observation of irreversible cardiorespiratory arrest
Advantage of DBD over DCD
DCD have Longer period of warm ischaemia time compared to extracting organs from Donor after brainstem death. Warm ischaemia time is the time between the point of ‘disconnection’ until it is cooled for storage. In DCD, Being ischaemic for a longer period of time at body temp (hence longer warm ischaemic time) would cause more organ damage
Outline the mechanisms of t cell mediated rejection
- New transplanted organ leaks donor HLA antigens
- Antigens taken up by APCs
- APC present these to t helper cells
- This leads to a type IV hypersensitivity response. The t helper cells:
A. Recruit and activate cytotoxic t cells
B. Recruit + activate inflammatory cells like macrophages and neutrophils
Nb also activate B cells which then leads to antibody mediated rejection.
These cells all enter the kidney organ via slide 60 (rolling etc) and cause damage via mechanisms described on slide 61
if you see antibodies againt the graft pre-transplantation, what does this suggest?
they have seen these antigens before eg they may have had grafts before so have antibodies against that or they may have had pregnancy
If antibodies are seen post-transplantation= de novo synthesis of new antibodies
