Transplantation Flashcards
When are organs transplanted
when they are failing or have failed, or for reconstruction
Give examples of organs that can be transplanted
Cornea Skin Heart Lungs Kidney Liver Bone Marrow Small bowel Pancreas
What are the 4 types of transplant
Autograft
Isograft
Allograft
Xenograft
What is an autograft
within the same individual e.g. skin from buttock to face
What is an isograft
between genetically identical individuals of the same species
What is an allograft
between different individuals of the same species
What is a xenograft
between individuals of different species e.g. pig or cow heart valves
What are the two types of decreased donor
After brain death (DBD)
After cardiac death (DCD)
Describe the DBDs
Brain injury has caused death before terminal apnoea has resulted in cardiac arrest and circulatory standstill
E.g. Intracranial haemorrhage; road traffic accident (catastrophic cerebral haemorrhage)
What must be done with DBDs before harvesting
Brain death must be confirmed before the organs are harvested and cooled
Confirm using neurological criteria
Circulation established through resuscitation
What is the criteria for DBDs
Irremediable structural brain damage from a known cause
Demonstrable lack of brainstem function
Apnoeic coma not due to:
- depressant drugs
- metabolic / endocrine disturbance
- hypothermia
- neuromuscular blockers
How is lack of brainstem function demonstrated for DBDs
Eyes unresponsive (pupillary light reflex, corneal reflex, and cold caloric reflex test)
Cranial nerve motor reflexes absent
Gag reflex absent
No respiratory movements on disconnection from ventilator
What are some reasons for exclusion of a DBD
Viral infection, especially HIV, HBV, HCV
Malignancy
Drug abuse, overdose, or poisoning
Disease of the organ itself
What is the number 1 obstacle to donation and what is the rate for this
A braindead person’s family refusing to consent for his/her organs to be transplanted
43% refusal rate
What are some potential strategies for increasing transplantation
including more marginal donors (i.e. slightly relaxing some criteria for the deceased’s organs)
Exchange programmes to acquire better tissue matches
Xenotransplantation and stem cell research for the future
Describe DCDs
death is diagnosed and confirmed using cardio-respiratory criteria; 5 minutes observation of irreversible cardiorespiratory arrest
Controlled or uncontrolled
Longer period of warm ischaemia time
What re the 7 elements of organ allocation for the kidney
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 are the most relevant protein variations in clinical transplantation
ABO blood group
HLA (human leukocyte antigens) coded on chromosome 6 by Major Histocompatibility complex (MHC)
What is the consequence of not ABO cross matching between donor and recipient
Hyperacute rejection occurs as the foreign cells are lysed by complement and/or phagocytosed all with massive inflammation, platelet activation etc..
How is ABO-incompatible matching overcome in transplantation
remove the recipient’s A/B antibodies (plasma exchange) with good outcomes
Where are class I and II HLA expressed
Class I (A, B, C)- all cells Class II (DR, DQ, DP) - immune cells (can be unregulated on other cells)
Describe HLA molecules
Highly polymorphic – lots of alleles for each locus
Each individual has most often 2 types for each HLA molecule (for example: A3 and A21)
What does exposure to a foreign HLA molecule result in
Immune response mediated by both B cells and T cells.
The immune reaction can cause immune graft damage and failure = rejection
How important is HLA matching in organ donation and what is the criteria for it
HLA does not have to be perfectly matched (as that’s impractical) but there must be <6 mismatches
How is organ rejection diagnosed
histological examination of a graft biopsy
How is organ rejection treated
Immunosuppressive drugs
Which organs’ rejection can be tested clinically and how
Kidney - creatinine
Pancreas - serum amylase/lipase/glucose
Hearts cannot be
What does a standard immunosuppressive regime entail
An induction agent
Basline immunosuppression
Treatment of episodes of acute rejection
Give examples of induction agents
e.g. cytokine blockade, T cell depletion
Give examples of agents used for baseline immunosuppression
Signal transduction blockade e.g. calcineurin inhibitor (cyclosporin), mTOR inhibitor
Antiproliferative agent e.g. azathioprine
Corticosteroids
How are acute rejection episodes treatment
Cellular: steroids, anti-T cell agents
Antibody-mediated: IVIg (intravenous immunoglobulin), anti-C5, plasma exchange
Describe the T cell lymphocyte response to pathogens and to donor cells
Foreign bodies taken up by APCs and presented on the membrane. T lymphocytes only recognise foreign proteins in the context of self cells
In donor cells, they shed their own HLA molecules which are presented on APCs
What are the mechanisms fo T-cell mediated rejection
Graft infiltration by alloreactive CD4+ cells
“Cytotoxic” T cells
Macrophages
Describe how cytotoxic T cells bring about T-cell mediated rejection
Release of toxins to kill target e.g. Granzyme B
Punch holes in target cells via perforin
Apoptotic cell death via Fas -Ligand
Describe how macrophages bring about T-cell mediated rejection
Phagocytosis
Release of proteolytic enzymes
Production of cytokines
Production of oxygen radicals and nitrogen radicals
