Transplant Surgery Flashcards
What is an autograft?
Same individual is both donor and recipient
What is an isograft?
Donor and recipient are genetically identical
What is an allograft?
Donor and recipient are genetically dissimilar, but of the same species
What is a xenograft?
Donor and recipient belong to different species
What is an orthotopic transplant?
Donor organ is placed in normal anatomic position
What is a heterotopic transplant?
Donor organ is placed in a different site than the normal anatomic position
What is a paratopic transplant?
Donor organ is placed close to original organ
What is chimerism?
Sharing cells between the graft and donor
What are histocompatibility antigens?
Distinct (genetically inherited) cell surface proteins of the human leukocyte antigen (HLA) system
Why are histocompatibility antigens important?
They are targets (class I antigens) and initiators (class II antigens) of immune response to donor tissue
Which cells have class I antigens?
All nucleated cells
Which cells have class II antigens?
Macrophages, monocytes, B cells, activated T cells, endothelial cells
What are the gene products of MHC called in humans?
HLA
What is the location of the MHC complex?
Short arm of chromosome 6
What is a haplotype?
Combination of HLA genes on a chromosome inherited from one parent (thus, two siblings have a 25% chance of being haploidentical)
Does HLA matching matter in organ transplantation?
With recent improvement in immunosuppression, the effect is largely obscured, but it still does matter.
The most important ones to match in order to improve renal allograft survival are HLA-B and HLA-DR.
What is the source of T cells?
Thymus
What is the function of T cells?
Cell-mediated immunity and rejection
What are the types of T cells?
Th (CD4): helper T cells (help B cells become plasma cells).
Ts (CD8): suppressor T cells (regulate immune response).
Tc (CD8): cytotoxic T cells (kill cell by direct contact).
What is the function of B cells?
Humoral immunity
What is the cell type that produces antibodies?
B cells differentiate into plasma cells
What is a macrophage?
Monocyte in parenchymal tissue
What is the function of macrophages?
Process foreign protein and present it to lymphocytes
What is an APC?
Antigen-Presenting Cell
What is the sequence of events leading to antibody production?
- Macrophage engulfs antigen and presents it to Th cells. The macrophage produces IL-1.
- Th cells then produce IL-2, and the Th cells proliferate.
- Th cells then activate (via IL-4) B cells that differentiate into plasma cells, which produce antibodies against the antigen presented.
Who needs to be immunosuppressed?
All recipients (except autograft or isograft)
What are the major drugs used for immunosuppression?
Triple therapy: corticosteroids, azathioprine, cyclosporine/tacrolimus.
Also, OKT3, ATGAM, mycophenolate.
What is the advantage of triple therapy immunosuppression?
Employs three immunosuppressive drugs, therefore, a lower dose of each can be used, decreasing the toxic side effects of each
What is induction therapy?
High doses of immunosuppressive drugs to induce immunosuppression
Which corticosteroid is most commonly used in transplants?
Prednisone
How does prednisone function?
Primarily blocks production of IL-1 by macrophages and stabilizes lysosomal membrane of macrophages
What is the associated toxicity with corticosteroids?
Cushing’s syndrome, alopecia, striae, HTN, diabetes, pancreatitis, ulcer disease, osteomalacia, aseptic necrosis (especially of the femoral head)
What is the relative potency of the commonly used corticosteroids?
Cortisol: 1
Prednisone: 4
Methylprednisone: 5
Dexamethasone: 25
How does azathioprine (Muran) function?
Prodrug that is cleaved into mercaptopurine.
Inhibits synthesis of DNA and RNA, leading to decreased cellular (T/B) production.
What is the associated toxicity with azathioprine?
Toxic to bone marrow (leukopenia and thrombocytopenia), hepatotoxic, associated with pancreatitis
When should a lower dose of azathioprine be administered?
When WBC is < 4
What is the associated drug interaction involving azathioprine?
Decrease dose if patient is also on allopurinol, because allopurinol inhibits the enzyme xanthine oxidase, which is necessary for the breakdown of azathioprine
What is the function of cyclosporine?
Inhibits production of IL-2 by Th cells
What is the associated toxicity with cyclosporine?
11 H’s and 3 N’s:
Hepatitis, Hypertrichosis, gingival Hyperplasia, Hyperlipidemia, Hyperglycemia, Hypertension, HUS, Hyperkalemia, Hypercalcemia, Hypomagnesemia, Hyperuricemia.
Nephrotoxicity, Neurotoxicity (headache, tremor), Neoplasia (lymphoma, KS, SCC).
What drugs increase cyclosporine levels?
Diltiazema, ketoconazole, erythromycin, fluconazole, ranitidine
What drugs decrease cyclosporine levels?
Dilantin, Tegretol, rifampin, isoniazid, barbiturates
What are the drugs of choice for hypertension from cyclosporine?
Clonidine, CCBs
How does ATGAM function?
Antibody against thymocytes, lymphocytes (polyclonal)
What is ATGAM?
Anti-thymocyte globulin
When is ATGAM typically used?
Induction
What is the associated toxicity with ATGAM?
Thrombocytopenia, leukopenia, serum sickness, rigors, fever, anaphylaxis, increased risk of viral infection, arthralgia
How does OKT3 function?
Monoclonal antibody that binds CD3 receptor (on T cells)
What is a major problem with multiple doses of OKT3?
Blocking antibodies develop, and OKT3 is less effective each time it’s used
What are basiliximab and daclizumab?
Anti-CD25 monoclonal antibodies
What is tacrolimus also known as?
Prograf (FK506)
How does tacrolimus work?
Blocks IL-2 receptor expression, inhibits T cells
What is the potency of tacrolimus compared to cyclosporine?
100-fold
What are the side effects of tacrolimus?
Nephrotoxicity and CNS toxicity (tremor, seizure, parasthesia, coma), hyperkalemia, alopecia, diabetes
What is sirolimus also known as?
Rapamycin, Rapamune
How does sirolimus work?
Blocks T-cell signaling
What is the associated toxicity with sirolimus?
Hypertriglyceridemia, thrombocytopenia, wound-healing problems, anemia, oral ulcers
What is MMF?
Mycophenolate MoFetil (CellCept)
How does MMF work?
Inhibitor of inosine monophosphate dehydrogenase required for de novo purine synthesis which expanding T and B cells depend on.
Also inhibits adhesion molecule and antibody production.
How is ABO crossmatching performed?
Same procedure as in blood typing
What is the purpose of lymphocytotoxic crossmatching?
Tests for HLA antibodies in serum.
Most important in kidney and pancreas transplants.
How is HLA crossmatching performed?
Mix recipient serum with donor lymphocyte and rabbit complement