Transplant Surgery, C73 P671-690 Flashcards
Define the following terms:
Autograft
P671
Same individual is both donor and
recipient
Define the following terms:
Isograft
P671
Donor and recipient are genetically
identical (identical twins)
Define the following terms:
Allograft
P672
Donor and recipient are genetically
dissimilar, but of the same species
Define the following terms:
Xenograft
P672
Donor and recipient belong to different
species
Define the following terms:
Orthotopic
P672
Donor organ is placed in normal anatomic position (liver, heart)
Define the following terms:
Heterotopic
P672
Donor organ is placed in a different site
than the normal anatomic position
(kidney, pancreas)
Define the following terms:
Paratopic
P672
Donor organ is placed close to original
organ
Define the following terms:
Chimerism
P672
Sharing cells between the graft and donor
BASIC IMMUNOLOGY
What are histocompatibility
antigens?
P672
Distinct (genetically inherited) cell
surface proteins of the human leukocyte
antigen system (HLA)
BASIC IMMUNOLOGY
Why are they important?
P672
They are targets (class I antigens) and initiators (class II antigens) of immune response to donor tissue (i.e., distinguishing self from nonself)
BASIC IMMUNOLOGY
Which cells have class I
antigens?
P672
All nucleated cells (Think: class 1 = ALL cells and thus “ONE for ALL”)
BASIC IMMUNOLOGY
Which cells have class II
antigens?
P672
Macrophages, monocytes, B cells,
activated T cells, endothelial cells
BASIC IMMUNOLOGY
What are the gene products
of MHC called in humans?
P672
HLA (Human Leukocyte Antigen)
BASIC IMMUNOLOGY
What is the location of the
MHC complex?
P672
Short arm of chromosome 6
BASIC IMMUNOLOGY
What is a haplotype?
P672
Combination of HLA genes on a
chromosome inherited from one parent;
therefore, two siblings have a 25%
chance of being “haploidentical”
BASIC IMMUNOLOGY
Does HLA matching matter
in organ transplantation?
P673
With recent improvements in
immunosuppression (i.e., cyclosporine),
the effect is largely obscured, but it still
does matter; the most important ones to
match in order to improve renal allograft
survival are HAL-B and HLA-DR
CELLS
T CELLS
What is the source?
P673
Thymus
CELLS
T CELLS
What is the function?
P673
Cell-mediated immunity/rejection
CELLS
T CELLS
What are the types?
P673
Th (CD4): helper T—help B cells become plasma cells Ts (CD8): suppressor T—regulate immune response Tc (CD8): cytotoxic T—kill cell by direct contact
B CELLS
What is the function?
P673
Humoral immunity
B CELLS
What is the cell type that
produces antibodies?
P673
B cells differentiate into plasma cells
MACROPHAGE
What is it?
P673
Monocyte in parenchymal tissue
MACROPHAGE
What is its function?
P673
Processes foreign protein and presents it
to lymphocytes
MACROPHAGE
What is it also known as?
P673
Antigen-Presenting Cell (APC)
MACROPHAGE Briefly describe the events leading to antibody production. P673
1. Macrophage engulfs antigen and presents it to Th cells; the macrophage produces IL-1 2. Th cells then produce IL-2, and the Th cells proliferate 3. Th cells then activate (via IL-4) B cells that differentiate into plasma cells, which produce antibodies against the antigen presented
IMMUNOSUPPRESSION
Who needs to be
immunosuppressed?
P674
All recipients (except autograft or isograft)
IMMUNOSUPPRESSION
What are the major drugs
used for immunosuppression?
P674
Triple therapy: corticosteroids,
azathioprine, cyclosporine/tacrolimus
IMMUNOSUPPRESSION
What are the other drugs?
P674
OKT3, ATGAM, mycophenolate
IMMUNOSUPPRESSION
What is the advantage of
“triple therapy”?
P674
Employs three immunosuppressive drugs;
therefore, a lower dose of each can be used,
decreasing the toxic side effects of each
IMMUNOSUPPRESSION
What is “induction therapy”?
P674
High doses of immunosuppressive drugs
to “induce” immunosuppression
IMMUNOSUPPRESSION CORTICOSTEROIDS Which is most commonly used in transplants? P674
Prednisone
IMMUNOSUPPRESSION
CORTICOSTEROIDS
How does it function?
P674
Primarily blocks production of IL-1 by
macrophage and stabilizes lysosomal
membrane of macrophage
IMMUNOSUPPRESSION CORTICOSTEROIDS What is the associated toxicity? P674
“Cushingoid,” alopecia, striae, HTN,
diabetes, pancreatitis, ulcer disease,
osteomalacia, aseptic necrosis (especially
of the femoral head)
IMMUNOSUPPRESSION CORTICOSTEROIDS What is the relative potency of the following corticosteroids: Cortisol? P674
1
IMMUNOSUPPRESSION CORTICOSTEROIDS What is the relative potency of the following corticosteroids: Prednisone? P674
4
IMMUNOSUPPRESSION CORTICOSTEROIDS What is the relative potency of the following corticosteroids: Methylprednisolone? P674
5
IMMUNOSUPPRESSION CORTICOSTEROIDS What is the relative potency of the following corticosteroids: Dexamethasone? P674
25
IMMUNOSUPPRESSION
AZATHIOPRINE (AZA [IMURAN®])
How does it function?
P674
Prodrug that is cleaved into
mercaptopurine; inhibits synthesis of DNA
and RNA, leading to decreased cellular
(T/B cells) production
IMMUNOSUPPRESSION AZATHIOPRINE (AZA [IMURAN®]) What is the associated toxicity? P675
Toxic to bone marrow (leukopenia
thrombocytopenia), hepatotoxic,
associated with pancreatitis
IMMUNOSUPPRESSION AZATHIOPRINE (AZA [IMURAN®]) When should a lower dose of AZA be administered? P675
When WBC is <4
IMMUNOSUPPRESSION AZATHIOPRINE (AZA [IMURAN®]) What is the associated drug interaction? P675
Decrease dose if patient is also on allopurinol, because allopurinol inhibits the enzyme xanthine oxidase, which is necessary for the breakdown of azathioprine
IMMUNOSUPPRESSION
CYCLOSPORINE (CSA)
What is its function?
P675
“Calcineurin inhibitor” inhibits
production of IL-2 by Th cells
IMMUNOSUPPRESSION CYCLOSPORINE (CSA) What is the associated toxicity? P675
Toxicity for cyclosporine includes the 11 “H’s” and three “N’s”: Hepatitis, Hypertrichosis, gingival Hyperplasia, Hyperlipidemia (worse than FK), Hyperglycemia, Hypertension (worse than FK), Hemolytic uremic syndrome, Hyperkalemia, Hypercalcemia, Hypomagnesemia, Hyperuricemia, Nephrotoxicity, Neurotoxicity (headache, tremor), Neoplasia (lymphoma, KS, squamous cell skin cancers)
IMMUNOSUPPRESSION CYCLOSPORINE (CSA) What drugs increase CSA levels? P675
Diltiazem
Ketoconazole
Erythromycin, fluconazole, ranitidine
IMMUNOSUPPRESSION CYCLOSPORINE (CSA) What drugs decrease CSA levels? P675
By inducing the p450 system: dilantin,
Tegretol®, rifampin, isoniazid, barbiturates
IMMUNOSUPPRESSION CYCLOSPORINE (CSA) What are the drugs of choice for HTN from CSA? P675
Clonidine, calcium channel blockers
IMMUNOSUPPRESSION CYCLOSPORINE (CSA) ATGAM/ANTITHYMOCYTE GLOBULIN How does it function? P675
Antibody against thymocytes,
lymphocytes (polyclonal)
IMMUNOSUPPRESSION
ATGAM/ANTITHYMOCYTE GLOBULIN
When is it typically used?
P675
For induction
IMMUNOSUPPRESSION ATGAM/ANTITHYMOCYTE GLOBULIN What is the associated toxicity? P676
Thrombocytopenia, leukopenia, serum
sickness, rigors, fever, anaphylaxis,
increased risk of viral infection, arthralgia
IMMUNOSUPPRESSION
OKT3
How does it work?
P676
MONOclonal antibody that binds CD3
receptor (on T cells)
IMMUNOSUPPRESSION OKT3 What is a major problem with multiple doses? P676
Blocking antibodies develop, and OKT3
is less effective each time it is used
IMMUNOSUPPRESSION OKT3 What are basiliximab and daclizumab? P676
Anti-CD25 monoclonal antibodies
IMMUNOSUPPRESSION TACROLIMUS What is tacrolimus also known as? P676
Prograf®(FK506)
IMMUNOSUPPRESSION
TACROLIMUS
How does it work?
P676
Similar to CSA—“calcineurin inhibitor,”
blocks IL-2 receptor expression, inhibits
T cells
IMMUNOSUPPRESSION TACROLIMUS What is its potency compared to CSA? P676
100x more potent than CSA
IMMUNOSUPPRESSION
TACROLIMUS
What are its side effects?
P676
Nephrotoxicity and CNS toxicity
(tremor, seizure, parasthesia, coma),
hyperkalemia, alopecia, diabetes
IMMUNOSUPPRESSION SIROLIMUS What is sirolimus also known as? P676
Rapamycin, Rapamune®
IMMUNOSUPPRESSION
SIROLIMUS
How does it work?
P676
Like CSA and tacrolimus, it does not
bind to and inhibit calcineurin; rather, it
blocks T-cell signaling
IMMUNOSUPPRESSION
SIROLIMUS
Toxicity?
P676
Hypertriglyceridemia, thrombocytopenia,
wound/healing problems, anemia, oral
ulcers
IMMUNOSUPPRESSION
MYCOPHENOLATE MOFETIL (MMF)
What is MMF also known as?
P676
CellCept®
IMMUNOSUPPRESSION
MYCOPHENOLATE MOFETIL (MMF)
How does it work?
P677
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
OVERVIEW OF IMMUNOSUPPRESSION MECHANISMS What drug acts at the following sites: A? P677 (picture)
Corticosteroids
OVERVIEW OF IMMUNOSUPPRESSION MECHANISMS What drug acts at the following sites: B? P677 (picture)
CSA/tacrolimus
OVERVIEW OF IMMUNOSUPPRESSION MECHANISMS What drug acts at the following sites: C? P677 (picture)
AZA/MMF
OVERVIEW OF IMMUNOSUPPRESSION MECHANISMS What drug acts at the following sites: D? P677 (picture)
OKT3/ATGAM
MATCHING OF DONOR AND RECIPIENT
How is ABO crossmatching
performed?
P678
Same procedure as in blood typing
MATCHING OF DONOR AND RECIPIENT What is the purpose of lymphocytotoxic cross-matching? P678
Tests for HLA antibodies in serum;
most important in kidney and pancreas
transplants
MATCHING OF DONOR AND RECIPIENT
How is the test performed?
P678
Mix recipient serum with donor
lymphocyte and rabbit complement
MATCHING OF DONOR AND RECIPIENT
Is HLA crossmatching
important?
P678
Yes, for kidney and pancreas transplants
REJECTION
How many methods of
rejection are there?
P678
Two: humoral and cell-mediated
REJECTION Name the four types of rejection and their associated time courses. P678
- Hyperacute—immediate in O.R.
- Accelerated acute—7 to 10 days
post-transplant - Acute—weeks to months post-transplant
- Chronic—months to years
post-transplant
REJECTION
What happens in hyperacute
rejection?
P678
Antigraft antibodies in recipient
recognize foreign antigen immediately
after blood perfuses transplanted organ
REJECTION
What happens in acute
rejection?
P678
T cell–mediated rejection
REJECTION What type of rejection is responsible for chronic rejection? P678
Cellular, antibody (humoral), or both
REJECTION
What is the treatment of
hyperacute rejection?
P678
Remove transplanted organ