3. Transplantation Flashcards
When is a ‘life enhancing’ transplantation done?
Occur in organs where other-life support methods aren’t as good e.g. dialysis
Why do the following organs fail: • Cornea • Skin • Bone marrow • Kidney • Liver • Heart • Lungs • Pancreas • Small bowel
- Cornea - degenerative disease, infection, trauma
- Skin - burn, trauma, tumour
- Bone marrow - tumour, hereditary disease
- Kidney - diabetes, HT, glomerulonephritis
- Liver - cirrhosis
- Heart - CAD, cardiomyopathy, congenital defects
- Lungs - COPD, CF, pulmonary HT
- Pancreas - T1DM
- Small bowel - hereditary conditions or related to prematurity
What is an autograft?
Transplantation within the same individual
What is an isograft?
Transplantation between genetically identical individuals of the same species
What is an allograft?
Transplantation between different individuals of the same species
What is an xenograft?
Transplantation between different species (e.g. heart valves and surgical skin plasters)
What is a prosthetic graft?
Using plastic or metal
Give examples of future autograft surgery
- Using stem cells to make full organs
- At the moment they can be transferred into various cell lineages - hard to organise them into 3D structures
- Can use scaffolds to form 3D structures
Give examples of the following types of allografts: • Free cells • Temporary • Privileged sites • Framework • Composite
- Free cells - bone marrow, pancreas islets
- Temporary - blood
- Privileged sites - cornea
- Framework - cartilage, nerves
- Composite - hands, face, larynx
What is a composite graft?
A graft involving several tissues e.g. face transplant involve skeletal muscle, skin and blood vessels
What is an orthotopic and heterotopic transplant?
- Orthotopic - organ placed where it should be e.g. liver
* Heterotopic - organs placed elsewhere in the body e.g. kidneys and pancreas
Where are transplanted kidneys often placed?
- In the iliac fossa
* Attached to the iliac vessels
What is the pancreas plumbed onto and transplanted with?
- Plumbed onto the iliac arteries
* Transplanted with a segment of bowel
What type of organ can be transplanted from a living donor?
- Bone marrow
- Kidney
- Liver
Describe the 2 main types of deceased donation
- DBD (donor after brain death) - need to confirm brain death, mainly road accident and cerebral haemorrhage, harvest organs and cool
- DCD (donor after cardiac death) - suitable for kidney transplant, long period of warm ischaemia time can cause damage
What potentially reversible things can cause apnoeic coma?
- Depressant drugs
- Metabolic or endocrine disturbance
- Hypothermia
- Neuromuscular blockers
How can a lack of brain stem function be demonstrated?
- 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)
What has to be excluded before using a DBD/DCD patient before transplantation?
- Viral infection e.g. HIV, HBV
- Malignancy
- Drug abuse
- Overdose
- Poison
- Disease of the organ to be transplanted
What is the absolute maximum and ideal cold ischaemia time for the kidney?
60 hours (ideally <24h)
What does transplant selection and allocation refer to?
- Selection - access to waiting list
* Allocation - access to organ
What are the contraindications to being placed on the transplant selection list?
- Too early - still has some organ function
- Co-morbidity - medical, psychiatric, surgical e.g. CV disease, malignancy, compliance
- Patient does not want a transplant
What is considered in transplant allocation?
Equity
• What is fair?
• Time on waiting list
• Urgent? imminent death
Efficiency
• What is the best use for the organ in terms of survival
What does it mean by kidney transplants being highly sensitised?
Likely to develop rejection if they receive a transplant
How many tiers are there in kidney allocation and what do they depend on?
- 5 tiers
* Depends on age and sensitivity
What are the 7 elements for receiving a donation?
- 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
What is the main obstacle to donation?
Familial consent
What is a donor transplant coordinator?
- Registered nurse with experience in critical care
- Employment to shift from transplant centres to NHS BT (blood + transplant)
- Potential donors a+e/ICU
- Carry out family interviews - part of bereavement servicea
What is the half life of a kidney from a deceased and living donor?
- Deceased - 10 years
* Living - 13/14 years
Does a transplant kidney last forever (lifetime)?
No, down to the immunology of transplantation
HLA coded on which chromosome by HLA is relevant (in transplantation)?
Chr6
Where are A and B carbohydrates found apart from red blood cells?
Endothelial lining of blood vessels in transplanted organs
What happens if you transplant an organ from a donor that has a different blood type?
- Recipients antibodies bind to the antigen on the endothelial cells of the donor organ
- Activation of complement and thrombosis
- Immediate, acute rejection
How can we remove antibodies to prevent acute rejection by ABO-incompatible transplant?
Plasma exchange
What does the recipient’s APC present in the context of a transplant and what cells does this activate?
- APC presents donor’s HLA peptide
* T cell activation for T cells that are allo-specific
What are the 6 different types of HLA?
- Class I - A, B, C
* Class II - DP, DQ, DR
Where are Class I and II HLA expressed?
- Class I - all cells
* Class II - DR, DQ, DP - APCs but also upregulated on other cells
How polymorphic is HLA?
- Highly
* Lots of alleles for each locus
How many types for each HLA molecule does each individual most often have?
- 2 types for each HLA
* One maternal and one paternal
Briefly describe the structure of HLA class I and II?
- Class I - contains α (1, 2, 3) chain and β-microglobulin – the peptide binding grove is only comprised of α
- Class II - contains α (1, 2) and β (1, 2) chain - peptide binding groove comprises both α and β
Are all HLA antigens immunogenic?
No
What range of HLA mismatches can you have with a potential donor?
0 to 6
Describe T cell mediated rejection
• APCs take up fragments from the donated organ antigen
• Circulate to the lymph nodes and present antigen
• T cells that can mount an allo-specific response come into contact
- initially through CD4+
• CD4+ infiltrates the organ
• Recruit inflammatory cells - organ damage e.g. CD8+ and macrophages
(occurs in tubules and interstitium)
Describe antibody-mediated rejection
• There are antibodies against graft HLA and AB antigen
• Antibodies can arise:
- pre-transplantation (sensitised) e.g. blood transfusions, previous grafts, pregnancy
- post-transplantation (de novo) i.e. most patients
• Endothelium is the main target
(intravascular process)
What can be used for detecting a deteriorating graft function in:
• Kidney transplant
• Liver transplant
• Lung transplant
- Kidney transplant - rise in creatinine, fluid retention, HT
- Liver transplant - rise in LFTs, coagulopathy
- Lung transplant - breathlessness, pulmonary infiltrate
How can a heart transplant be monitored for rejection?
Regular biopsies
What do immunosuppressive drugs target, with reference to transplant rejection?
• T cell and B cell activation and proliferation
- initial interaction between APC and T cell
- TCR interaction and co-stimulatory mechanisms
- nucleotide synthesis
• Cytokine production
• Antibody production
What antibodies can be used before the organ is implanted to reduce the risk of rejection?
- Anti-CD52 antibodies
- Causes CD52 depletion
- Kills off a lot of T-cells
- Rituximab (anti-CD20)
- Depletes B cells
- Blocks the effect of complement
- Bortezomib
- Kills off plasma cells producing antibodies
What immunosuppressants are used from time of implantation?
- Signal transduction blockade - CNI inhibitor
- Sometimes mTOR inhibitor
- Antiproliferative agent
- Corticosteroids
What immunosuppressants can be used in episodes of acute rejection?
- T-cell mediated: steroids, anti-T cell agents
* Antibody-mediated: IVIG, plasma exchange, anti-CD20, anti-complement
Outline the changed risk of infection post-transplant?
- Increased risk for conventional infections
- Opportunistic infection - normally harmless e.g. CMV
- Vulnerable to skin cancers
- Post-transplant lymphoproliferative disorder - EBV driven
- Other e.g. Kaposi’s sarcoma
