Surgical Recall Ch 73: Transplant Surgery

Front 1

Define autograft.

Back 1

same individual is both donor and recipient

Front 2

Define isograft.

Back 2

donor and recipient are genetically identical (identical twins)

Front 3

Define allograft.

Back 3

donor and recipent are genetically dissimilar, but of the same species.

Front 4

Define xenograft.

Back 4

donor and recipent are of different species.

Front 5

Define orthotopic.

Back 5

Donor organ is placed in normal anatomic position (liver, heart)

Front 6

Define heterotopic.

Back 6

donor organ is placed in different site than the normal anatomic position (kidney, pancreas)

Front 7

Define paratopic.

Back 7

donor organ is placed close to orginal organ.

Front 8

Define chimerism.

Back 8

sharing cells between the graft and donor.

Front 9

What are histocompatibilty antigens?

Back 9

dinstict (genetically inherited) cell surface proteins of the human leukocyte antigen (HLA) system

Front 10

Why are histocomatibity antigens important?

Back 10

They are targets (class I antigens) and initiators (class II antigens) of immune response to donor tissue (i.e., distinguishing self from nonself)

Front 11

Which cells have class I antigens?

Back 11

all nucleated cells (think: class 1 = all cells = "one for all"

Front 12

Which cells have class II antigens?

Back 12

macrophages
monocyes
B cells
activated Tcells
endothelial cells

Front 13

What are the gene products of MHC called in humans?

Back 13

HLA (human leukocyte antigens)

Front 14

What is the location of the MHC complex?

Back 14

short arm of chromosome 6

Front 15

What is a haplotype?

Back 15

the combinantion of HLA genes on a chromosome inherited from one parent

Thus two siblings have a 25% changce of being haploidentical

Front 16

Does HLA matching matter for organ transplantation?

Back 16

With recent improvements in immunosuppression (i.e. cyclosprine) the effect is largey obscured, but it still does matter.

The most important ones to match to improve renal allograft survival are HLA-B and HLA-DR.

Front 17

What is the function of Tcells?

Back 17

cell mediated immunity

rejection

Front 18

What are the types of Tcells?

Back 18

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

Front 19

What is the function of Bcells?

Back 19

humoral immunity

Front 20

What is the cell type that produces antibodies?

Back 20

Bcells differentiate into plasma cells

Front 21

What is a macrophage?

Back 21

a monocyte in parechymal tissue

Front 22

What is the function of macrophages?

Back 22

process foreign protein and present it to lymphocytes

Front 23

Descibe the events leading to antibody production/

Back 23

1)macrophage engulfs antigen and presents it to Th cells; the macrophage produces IL-1

2) The Th cells then produce IL-2, and the Th cells proliferate

3) The Th cells then activate (via IL-4) B cells that differentiate into plasma cells, which produce antibodies against the antigen presented

Front 24

Who needs to be immunosuppressed?

Back 24

all recipients (except autograft and isograft)

Front 25

What is the most commonly used corticosteroid for transplants?

Back 25

prednisone

Front 26

How does prednisone function?

Back 26

primarily blocks production of IL-1 by macrophage and stabilizes lysosomal membrane of macrophage

Front 27

What is the toxicity associated with prednisone?

Back 27

"cushingoid" alopecia, striae, HTN, diabetes, pancreatitis, ulcer disease, osteomalacia, aseptic necrosis (esp of the femoral head)

Front 28

What is the MOA of azothioprine (imuran)?

Back 28

prodrug that is cleaved into mercaptopurine; inhibits the synthesis of DNA and RNA, leading to decreased cellular (T/B cells) production

Front 29

What is the toxicity associated with azathioprine?

Back 29

toxic to bone marrow (leukopenia + thrombocytopenia), hepatotoxic, associated with pancreatitis

Front 30

When should a lower dose of AZA be administered?

Back 30

when WNC is less than 4

Front 31

What is the drug interaction associated with azathioprine (imuran)?

Back 31

decrease the dose if the patient is also on ALLOPURINOL

because allopurinol inhibits xanthine oxidase, which is necessary for the breakdown of azathioprine

Front 32

What is the function of cyclosporine (CSA)?

Back 32

"Calcineurin inhibitor" inhibits the production of IL-2 by Th cells

Front 33

What is the toxicity associated with cyclosporine (CSA)?

Back 33

Toxicity includes the 1 H's:
1) Hepatitis
2) Hypertrichosis
3) gingival Hyperplasia
4) Hyperlipidemia (worse than FK)
5) Hyperglycemia
6) Hypertension (worse than (FK)
7) HUS
8) Hyperkalemia
9) Hypercalcemia
10) Hypomagnesemia
11) Hyperuricemia

and 3 N's:
1) Nephrotoxicity
2) Neurotoxicity (headache, tremor)
3) Neoplasia (lymphoma, KS, squamous cell skin cancer)

Front 34

What is the toxicity associated with ATGAM?

Back 34

thrombocytopenia
leukopenia
serum sickness
rigors
fever
anaphylaxis
increased risk of viral infection
arthralgia

Front 35

How does OKT3 work?

Back 35

MONOclonal antibody that binds CD3 receptor on Tcells

Front 36

What is a major problem with multiple doses of OKT3?

Back 36

blocking antibodies develop and OKT3 is less effective each time it is used

Front 37

What are basiliximab and daclizumab?

Back 37

anti-CD25 monoclonal antibodies

Front 38

What is tacromilus also known as?

Back 38

Progaf (FK506)

Front 39

How does tacromilus work?

Back 39

similar to CSA - "calcineurin inhibitor" blocks IL-2 receptor expression, inhibits Tcells

Front 40

What is the potency of tacromilus compared CSA?

Back 40

100 times more potent than CSA

Front 41

What are the side effects of tacromilus?

Back 41

nephrotoxicity and CNS toxicity (tremor, seizure, parasthesia, coma) , hyperkalemia, alopecia, diabetes

Front 42

What is sirolimus also known as?

Back 42

rapamycin, rapamune

Front 43

How does sirolimus work?

Back 43

Like CSA and tacromilus, but it does not inhibit calcineurin, rahter it blocks Tcell signalling

Front 44

What is the toxicity of sirolimus?

Back 44

hypertriglyceridemia
thrombocytopenia
wound/healing problems
anemia
oral ulcers

Front 45

What is mycophenolate mofetil (mmf) also known as?

Back 45

CellCept

Front 46

How does MMF (mycophenylate mofetil) work?

Back 46

inhibitor of insosine monophosphate dehydrogenase (required for de novo purine synthesis which expanding T and B cells depend on)

also inhibits adhesion molecules and antibody production