Transplantation Flashcards
Why is transplantation done?
Save life:
- Other life-support methods not fully developed
- Other methods at the end of their lives
Enhance life:
- Other methods are less good – e.g. kidney dialysis
- Organ is nor vital but enhances life – e.g. cornea
What are the different types of transplantation?
- Autograft - within the same individual – e.g. coronary artery bypass
- Isografts - between genetically identical individuals of the same species.
- Allografts - between different individuals of the same species
> Solid organs – kidney into the RIF
> Small bowel
> Free cells – bone marrow transplant
> Temporary – blood
> Privileged sites – cornea
> Framework – tendons
> Composite – face - Xenografts - between individuals of different species – e.g. heart valves and skin
- Prosthetic graft plastic, metal
What are the types of donors for allografts?
Deceased donor:
- DBD – Deceased Brain-Death (heart is beating):
> Cool to minimise ischaemic damage.
> There is irremediable structural brain damage of a KNOWN cause
> The apnoeic coma is NOT due to – depressant drugs, hypothermia, NM-blockers, metabolic or endocrine disturbances
> There is a demonstrateable lack of brain-stem function – e.g. no gag reflex
- DCD – Deceased Cardiac-Death (heart not beating):
> Long period of warn ischaemic time
> Suitable for kidney transplants
Living donor
What must be excluded from deceased donors?
- Viral infection
- malignancy
- drug abuse/overdose/poison
- disease of the transplanted organ
What is the max cold ischaemia for organs?
- for kidneys is 60 hours (ideally <24h) – much shorter for other organs
- Cornea is an exception at 96 hours’ cold ischaemia time
How do patients access the transplant waiting list?
Referral for assessment -> MDT assess eligibility -> NHS transplant list AND inspect contraindications (too early to be placed on list, co-morbidities, patient wishes)
How is transplantation allocated?
NHSBT (NHS Blood and Transplant) monitors allocation – using national guidelines and algorithms.
Organ allocation – Kidney: - 5 tiers of patient – paediatric/adult, sensitised/not-sensitised. - 7 elements: > Waiting time > HLA-matching + age > Donor-recipient age difference > Location > HLA-DR homozygosity > HLA-B homozygosity > ABO blood group matching
How can the number of donors be raised?
- UK Gov. Dept. of Health initiatives
- Public engagement
- Improved quality of organ retrieval and transplantation
- Donor transplant co-ordinators – critical care nurses and carry out family interviews to gain consent
Other strategies to increase transplantation activity:
- Increased deceased donation – from marginal donors including the elderly
- Increased living donation – the UK has a VERY GOOD living donator record
- Xenotransplantation and stem cell research opportunities
What are the most important variations in clinical transplantation?
- ABO blood group
- HLA coded on Chr6 by MHC
What are the ABO blood groups made of?
O+ = 1x fructose, 1x n-acetyl-glucosamine, 2x galactose
A+ = 1x fructose, 1x n-acetyl-glucosamine, 2x galactose, 1x n-acetyl-galactosamine
B+ = 1x fructose, 1x n-acetyl-glucosamine, 3x galactose
What causes antibody mediated rejection?
Circulating pre-formed anti-antibodies will bind to the donor endothelium
What do antibodies activate?
complement classical pathway
macrophages
What are the classes of HLA?
Class 1 – A, B, C – expressed on ALL cells
Class 2 – DR, DQ, DP – expressed by APCs
- individuals most often have 2 types of each HLA molecule due to 2 chromosomes (mum and dad)
How is HLA matching done in transplantation?
MM 1: 2: 0 = 3 miss-matches
- 0-6 is acceptable – more miss-match equals more chance of death later down the road
- Sibling -> sibling transplant = 25% chance of 0MM, 6MM, 50% chance of 3MM
What happens in T-cell mediated rejection?
- Lymphocytes infiltrate the interstitial area
- Lymphocytes rupture the tubular BM and cause tubulitis and local organ damage
- The graft can be infiltrated by allo-reactive CD4+ cells
- CTL lymphocytes can release – granzyme B, perforin and FasL
- Macrophages can – phagocytose, release proteases, produce cytokines and oxygen/nitrogen radicals
