Transplantation Flashcards
When was the first transplant of an organ done?
Technically first was a vascular anastamoses in 1912 by Alexis Carrel, a french surgeon.
First real organ was by Joe Murray in 1954, the kidney, in identical twins.
Both won Nobel prizes.
Extended Criteria donors (ECD)?
Olderthan 60, not in the best shape. Have 2 of the following
- Long history of HTN
- Terminal serum Cr of >1.5
- Cerebrovascular accident cause of death
Deceased Cardiac Death donor?
- Donor does not meet criteria for brain death but their heart stops
- Similar outcome to a standard criteria donor but 42-51% risk for delayed graft function compared to 24% in the standard donor. You need a week of dialysis treatment after transplanatation
What defines the KAS (Kidney allocation score
- Dialysis time - Longer time on dialysis means you’ll get new kidneys sooner (justice)
- Life Years for Transplant - How many years would you get with the transplant?
- Donor profile index - Quality of the organ being given
What must we rule out to do a transplant?
- Infection (immunosuppressants will kill them)
- Sensitization (basic organ matching)
- Malignancy (immunosuppressants, other issues)
Make sure to confirm vascular integrity and bladder capacity
When do we do a pancreas transplant?
- Type 1 DM with a c-peptide deficiency (let’s get those islet cells back)
Discuss hyperacute rejection
This doesn’t happen anymore really since we do proper matching.
- Preformed antibodies bind recipient complement, indicating a cross match with rapid and irreversible organ destruction
Discuss maturation of a T cell (long card, but this is important!)
T cell begins double negative (no CD8 no CD4, no TCR). It then gains all three (now has CD4, CD8, and low TCR levels).
Upon hitting a thymic epithelial cell presenting self MHC, the T cell will die unless it binds. This entire process is known as positive selection.
Next up is negative selection. Interaction of the T cell with the thymic epithelial cell favored CD4 or CD8. Whichever one was best is what that T cell becomes (so CD4/MHC II or CD8/MHC I). This cell binds to a thymic dendrite. High affinity for self antigen gets you apoptosed, but mid affinity allows you to mature.
Role of CTLA4?
Negative regulator of T cell (mice that get this knocked out get huge lymph nodes due to rampant T cell proliferation)
How do we induce immunosuppression?
- Deplete lymphocytes with Thymoglobulin (polyclonal antibodies from rabbits, acts like a shotgun against the whites, drops them down to close to zero) and Campath (Alemtuzumab, monoclonal antibody that is Anti CD-52, works similarly as thymoglobulin)
- Anti-IL2R (basiliximab, dacliximab)
- Glucocorticosteroids
How do we maintain immunosuppression?
- Calcineurin inhibitors (Cyclosporine, tacrolimus)
- Antimetabolites (Azathioprine, mycophenolate mofetil)
- Glucocorticosteroids
- TOR inhibitors (Sirloimus, Everolimus)
- Costimulation (Belatacept, Abatacept)
How do we due rescue immunosuppression?
In cellular rejection, we use steroids, Thymoglobulin, Campath, but these are not great
In humoral or antibody mediated rejection, we use steroids, IVIG + plasmapheresis, Rituximab (Anti-CD20), and thymoglobulin
Top 10 answers on the boards~
- Positive T cell cross match = don’t transplant
- IL-2 = Most drugs target this type of pathway
- CMV PNA after transplant, be careful
- Don’t treat chronic rejection
- Treat acute rejection
- Cyclosporine is great
- T cells is usually the answer
- Chromosome 6
- Reduce the cold ischemic time
- When in doubt pick c.
