Transplant Flashcards

1
Q

Acute phase proteins made by liver (9)

A
  1. fibrinogen
  2. haptoglobin
  3. CRP
  4. C3
  5. ceruloplasmin
  6. alpha-antitrypsin
  7. alpha-antichymotrypsin
  8. alpha-acid glycoprotein
  9. amyloid A
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2
Q

Lab findings with hepatocellular injury

A

Increased AST/ALT

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3
Q

Lab findings with liver obstruction (5)

A

Increased ALP, GGT, Bili (D), 5-nucletidase, leucine amino peptidase

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4
Q

Lab findings of decreased liver function (5)

A

Decreased albumin, transferrin, coag factors (=Increased INR)
Hypoglycemia
Altered glucose metabolism

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5
Q

What are MHC antigens?

A

Surface antigens, aka HLA (human leukocyte antigens)
Reason for organ rejection as molecules involved in antigen presentation to Tcells

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6
Q

What are class I MHC?

A

HLA-A,B,C
ALL CELLS have these on surface
same internal contents of cell and bring to surface for presentation
Recognized by CD8 = cell death
Expression increased by cytokines and interferons

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7
Q

What are Class II MHC?

A

Expression of HLA DR, DQ, DP, DM
Only on antigen presenting cells - present to CD4 cells
Leads to B-cell antibody development and presenting cell damage
Leads to macrophage activation

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8
Q

What is indirect antigen recognition?

A

Conventional antigen presentation. Antigens taken up and then presented in MHC to t-cells

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9
Q

What is direct antigen recognition?

A

In solid organ transplant, antigen presenting cells present themselves = rejection

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10
Q

Role of antibodies? (4)

A

Target for phagocytosis
Activate complement
Neutralize toxins
Block attachments of pathogens to cells or tissue

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11
Q

5 classes of immunoglobulins

A

Ig A,D,E,G,M

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12
Q

What is the structure of immunoglobulins?

A

4 peptide chains
heavy x 2
light x 2

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13
Q

What does IgD do?

A

On surface of B cells, function unknown

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14
Q

What does IgA do?

A

low levels blood, most abundant at mucosal surfaces (i.e. gut)

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15
Q

What does IgM do?

A

Surface of B cells. Secreted as pentamer (5 molecules).
Activates complement
First antibody produced at time of infection

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16
Q

What does IgE do?

A

Low amount in blood. Bound to mast cells and basophils.
Responsible for type I hypersensitivity.
Increased in parasitic infections

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17
Q

What does IgG do?

A

Most abundant AB
Production depends on cytokines
Leaves bloodstream and enters tissues
ACTIVELY TRANSPORTED ACROSS PLACENTA (the only one)
Activates complement
neutralizes toxins

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18
Q

Contraindications to transplant donation (4)

A

Sepsis - start abx before taking
Viral infection (HTLV1, HIV, HBV, HCV, EBV, CMV, HSV)
Cancer
No consent

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19
Q

What are contraindications to receiving transplant? (7)

A

HIV (actually not an absolute indication if lvls are controlled)
Malignancy
Irreversible brain damage
Irreversible infxn
Irrreversible multiple organ faiilure
Irreversible significant cardiopulmonary dz
Inability to comply with medical therapy

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20
Q

Contraindications specific to liver transplant? (8)

A

Inability to have procedure
Recent intracranial hemorrhage
Irreversible neurologic impairment
Active substance abuse
Intractable hypotension
Evidence of systemic infection
Extrahepatic malignancy
Inability to comply with followup/meds

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21
Q

Contraindications specific to renal transplant (3)

A

Recurrent renal dz (FSGS, hemolytic uremia syndrome, MPGN)
Liver transplant contraindications
psychosocial

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22
Q

What does blood transfusion effect refer to in context of organ rejection?

A

Improved graft survival believed to be secondary to suppression of rejection mechanisms in patients who receive blood before their transplant

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23
Q

What is hyper acute rejection?

A

Minutes to hours
can happen across ABO groups
preformed IgG antibodies
TYPE AND SCREEN

24
Q

What is acute rejection?

A

1-3 weeks but most common 3-6 months
T cells
2 types - vascular and cellular
Treat with methylprednisolone –> taper

25
What is chronic rejection?
All organs: Atherosclerosis Obliteration FIbrosis
26
Risk factors for chronic organ rejection (6)
Donor issues (age, HTN, etc) Poor organ harvest Delayed graft function Recipient issues (HTN, diabetes, infection) Inadequate immunosuppression Previous acute rejection episodes
27
What is the typical immunosuppressive regime for low-risk pts?
Induction: IL2 inhibitor (intra-op), steroids (first 4 days) Maintenance: Calcineurin inhibitor OR sirolimus... AND antimetabolite +/- steroids All patients on CCB to decrease nephrotoxicity of calcineurin Valganciclovir for CMV ppx
28
What is the typical immunosuppressive regime for high-risk patients?
Same as low risk PLUS thymoglobulin OR OKT3 to induction drugs and definitly on steroids for maintenance
29
What are induction agents for immunosuppression for transplant?
anti-lymphocytic globulin monoclonal antibody OKT3 (4) IL2 receptor inhibitor Radiation
30
How does anti-lymphocytic globulin work for immunosuppression?
Targets Tcells Can be given ppx, early transplant, or to reverse rejection most common complication is allergic rxn Anemia and TCP can also occur
31
How does OKT3 work for immunosuppression?
Blocks Tcells can elicit immune reactions Cytokine release = chills, rigours, fever Increased incidence of lymph proliferative disorders
32
How do IL2 receptor inhibitors work for immunosuppression?
Basiliximab and daclizumab Prevents IL2 from binding and propagating immune responses. IL2 is powerful cytokine
33
How does radiation work for immunosuppression?
Decreases response of immune system More often done before bone marrow transplant
34
What are immunosuppression maintenance agents? (6)
Steroids Azathioprine (imuran) MMF Cyclosporin Tacrolimus Sirolimus
35
What is the MOA of adrenal corticosteroids?
Decreases lymphocyte counts Decreases macrophage activity Inhibits cytokines Suppresses prostaglandin synthesis
36
What are the side effects of adrenal corticosteroids? (11)
HTN Weight gain GI bleeding peptic ulcers Euphoric personality changes Cataracts Hyperglycemia Pancreatitis Muscle wasting Osteoporosis Avascular necrosis
37
What is the MOA of azathioprine?
Blocks DNA, RNA synthesis Inhibits humeral and cellular immunity Decreases neutrophil production Decreases macrophage activation
38
What are the side effects of azathioprine (3)
Marrow suppression --> leukopenia Hepatotoxicity and leukopenia GI upset
39
What is the MOA of cyclosporine?
Inhibits IL-1 Inhibits IL2 production Inhibits mitogen activation Inhibits T cell activation ** T-cell inhibition big part of it
40
What are the side effects of cyclosporine? (3N 7H)
Nephrotoxicity (dose dependent) Neoplasia Neurotoxic Hyperuricemia HTN Hyperglycemia HyperK Hyperplasia of gingiva Hepatotoxic Hirsutism
41
What is the MOA of mycophenolate mofetil?
Inhibits purine metabolism Inhibits T and B lymphocytes **similar to azathioprine, but preferred
42
What are the side effects of mycophenolate mofetil? (2)
Leukopenia GI upset (diarrhea)
43
What is the MOA of tacrolimus?
Calcineurin inhibitor Leads to decreased IL2 production Inhibits T helper and killer cells
44
What are side effects of tacrolimus? (7)
Nephrotoxic Neurotoxic Hyperglycemia HyperK HTN Hepatotoxic Alopecia
45
What is the MOA of sirolimus?
Binds same receptor as tacrolimus Does NOT block T cell cytokine gene expression Inhibits transduction of signals from IL2R to nucleus calcium-independent pathway
46
What drugs interact with cyclosporin?
Rifampin (decrease) Steroids (increase) CCBs (decrease) Nephrotoxins (additive effect)
47
What drugs increase cyclosporin levels?
H2 antagonists Cephalosporins Thiazides Lasix Androgenic roids Acyclovir Warfarin
48
Which drugs decrease cyclosporine levels?
Rifampin Anticonnvulsants Sulfinpyrazone
49
Which drugs increase nephrotoxicity of cyclosporine?
NSAIDs Cipro
50
What are post-transplant complications?
Infection Neoplasia Post-renal transplant HTN
51
What ppx drugs are used to prevent post-transplant infection?
Acyclovir/Ganciclovir (CMV) Septra (pneumocystis) Nystatin/clotrimazole/fluconazole (fungus)
52
Post-trransplant opportunistic infections (bugs)
Aspergilis Blastomycosis Nocardiosis Toxoplasmosis Cryptococcosis Pneumocystis
53
Causes of post-renal transplant hypertension
Graft rejection Renal transplant artery stenosis Native nephrectomy Corticosteroids Cyclosporine
54
What cause renal transplant artery stenosis?
Improper anastomotic technique Kinking of vessel Damage of artery Atherosclerotic disease Fibrosis
55
How is renal transplant artery stenosis diagnosed?
Imaging (MRA or angiogram) Peripheral renin (elevated) Captopril stimulation test (BP falls more and renin rises more) Differential renal vein renin sampling
56
What is the treatment for renal artery transplant stenosis?
Perc. angioplasty #1 Open surgical correction #2