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Flashcards in Transplant Surgery Deck (153):
1

What is an autograft?

Same individual is both donor and recipient

2

What is an isograft?

Donor and recipient are genetically identical

3

What is an allograft?

Donor and recipient are genetically dissimilar, but of the same species

4

What is a xenograft?

Donor and recipient belong to different species

5

What is an orthotopic transplant?

Donor organ is placed in normal anatomic position

6

What is a heterotopic transplant?

Donor organ is placed in a different site than the normal anatomic position

7

What is a paratopic transplant?

Donor organ is placed close to original organ

8

What is chimerism?

Sharing cells between the graft and donor

9

What are histocompatibility antigens?

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

10

Why are histocompatibility antigens important?

They are targets (class I antigens) and initiators (class II antigens) of immune response to donor tissue

11

Which cells have class I antigens?

All nucleated cells

12

Which cells have class II antigens?

Macrophages, monocytes, B cells, activated T cells, endothelial cells

13

What are the gene products of MHC called in humans?

HLA

14

What is the location of the MHC complex?

Short arm of chromosome 6

15

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)

16

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.

17

What is the source of T cells?

Thymus

18

What is the function of T cells?

Cell-mediated immunity and rejection

19

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).

20

What is the function of B cells?

Humoral immunity

21

What is the cell type that produces antibodies?

B cells differentiate into plasma cells

22

What is a macrophage?

Monocyte in parenchymal tissue

23

What is the function of macrophages?

Process foreign protein and present it to lymphocytes

24

What is an APC?

Antigen-Presenting Cell

25

What is the sequence of events leading to antibody production?

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.

26

Who needs to be immunosuppressed?

All recipients (except autograft or isograft)

27

What are the major drugs used for immunosuppression?

Triple therapy: corticosteroids, azathioprine, cyclosporine/tacrolimus.
Also, OKT3, ATGAM, mycophenolate.

28

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

29

What is induction therapy?

High doses of immunosuppressive drugs to induce immunosuppression

30

Which corticosteroid is most commonly used in transplants?

Prednisone

31

How does prednisone function?

Primarily blocks production of IL-1 by macrophages and stabilizes lysosomal membrane of macrophages

32

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)

33

What is the relative potency of the commonly used corticosteroids?

Cortisol: 1
Prednisone: 4
Methylprednisone: 5
Dexamethasone: 25

34

How does azathioprine (Muran) function?

Prodrug that is cleaved into mercaptopurine.
Inhibits synthesis of DNA and RNA, leading to decreased cellular (T/B) production.

35

What is the associated toxicity with azathioprine?

Toxic to bone marrow (leukopenia and thrombocytopenia), hepatotoxic, associated with pancreatitis

36

When should a lower dose of azathioprine be administered?

When WBC is

37

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

38

What is the function of cyclosporine?

Inhibits production of IL-2 by Th cells

39

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).

40

What drugs increase cyclosporine levels?

Diltiazema, ketoconazole, erythromycin, fluconazole, ranitidine

41

What drugs decrease cyclosporine levels?

Dilantin, Tegretol, rifampin, isoniazid, barbiturates

42

What are the drugs of choice for hypertension from cyclosporine?

Clonidine, CCBs

43

How does ATGAM function?

Antibody against thymocytes, lymphocytes (polyclonal)

44

What is ATGAM?

Anti-thymocyte globulin

45

When is ATGAM typically used?

Induction

46

What is the associated toxicity with ATGAM?

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

47

How does OKT3 function?

Monoclonal antibody that binds CD3 receptor (on T cells)

48

What is a major problem with multiple doses of OKT3?

Blocking antibodies develop, and OKT3 is less effective each time it's used

49

What are basiliximab and daclizumab?

Anti-CD25 monoclonal antibodies

50

What is tacrolimus also known as?

Prograf (FK506)

51

How does tacrolimus work?

Blocks IL-2 receptor expression, inhibits T cells

52

What is the potency of tacrolimus compared to cyclosporine?

100-fold

53

What are the side effects of tacrolimus?

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

54

What is sirolimus also known as?

Rapamycin, Rapamune

55

How does sirolimus work?

Blocks T-cell signaling

56

What is the associated toxicity with sirolimus?

Hypertriglyceridemia, thrombocytopenia, wound-healing problems, anemia, oral ulcers

57

What is MMF?

Mycophenolate MoFetil (CellCept)

58

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.

59

How is ABO crossmatching performed?

Same procedure as in blood typing

60

What is the purpose of lymphocytotoxic crossmatching?

Tests for HLA antibodies in serum.
Most important in kidney and pancreas transplants.

61

How is HLA crossmatching performed?

Mix recipient serum with donor lymphocyte and rabbit complement

62

Is HLA crossmatching important?

Yes, for kidney and pancreas transplants

63

How many methods of rejection are there?

2: humoral and cell-mediated

64

What are the 4 types of rejection and their associated time courses?

1. Hyperacute (immediate in OR)
2. Accelerated acute (7-10 days post-transplant)
3. Acute (weeks-months post-transplant)
4. Chronic (months-years post-transplant)

65

What happens in hyperacute rejection?

Anti-graft antibodies in recipient recognize foreign antigen immediately after blood perfuses transplanted organ

66

What happens in acute rejection?

T cell-mediated rejection

67

What type of rejection is responsible for chronic rejection?

Cellular, antibody (humoral), or both

68

What is the treatment for hyperacute rejection?

Remove transplanted organ

69

What is the treatment for acute rejection?

High-dose steroid/OKT3

70

What is the treatment for chronic rejection?

Not much (irreversible) or re-transplant

71

What is the optimal storage temperature of an organ?

4 C (keep on ice in a cooler)

72

Why should the transplant organ be kept cold?

Cold decreases the rate of chemical reactions.
Decreased energy use minimizes effects of hypoxia and ischemia.

73

What is U-W solution?

University of Wisconsin solution, containing potassium phosphate, buffers, starch, steroids, insulin, electrolytes, adenosine.
Used to perfuse an organ prior to removal from the donor.

74

Why should U-W solution be used?

Lengthens organ preservation time

75

What is the maximum time between heart harvest and transplant?

6 hours

76

What is the maximum time between lung harvest and transplant?

6 hours

77

What is the maximum time between pancreas harvest and transplant?

24 hours

78

What is the maximum time between liver harvest and transplant?

24 hours

79

What is the maximum time between kidney harvest and transplant?

72 hours

80

In what year was the first kidney transplant performed in man?

1954

81

Who performed the first human kidney transplant?

Joseph E. Murray

82

What are the indications for kidney transplant?

Glomerulonephritis, pyelonephritis, polycystic kidney disease, malignant HTN, reflux pyelonephritis, Goodpasture's syndrome, congenital renal hyperplasia, Fabry's disease, Alport's syndrome, renal cortical necrosis

83

What is renal failure?

GFR

84

What is the most common cause for kidney transplants?

Diabetes

85

What are the sources of donor kidneys?

Deceased donor (70%), living related donor

86

What survival rate is associated with kidney transplant from deceased donor source?

1-year patient survival: 90% if HLA-matched, 80% if not.
3-year graft survival: 75%.

87

What survival rate is associated with kidney transplant from living related donor source?

1-year patient survival: 95%
3-year graft survival: 85%

88

What are the tests for kidney compatibility?

ABO, HLA typing

89

If a choice of left or right donor kidney is available, which is preferred?

Left (longer renal vein allows for easier anastomosis)

90

Should the placement of the transplanted kidney be heterotopic or orthotopic? Why?

Heterotopic (retroperitoneal in the RLQ or LLQ above the inguinal ligament).
Preserves native kidneys, allows easy access to iliac vessels, places ureter close to the bladder, easy to biopsy kidney.

91

What anastomoses are formed with a heterotopic kidney transplant?

1. Renal artery to iliac artery
2. Renal vein to iliac vein
3. Ureter to bladder

92

What is the correct placement of the ureter in a heterotopic kidney transplant?

Submucosally through the bladder wall (decreases reflux)

93

What is the differential diagnosis of post-renal transplant fluid collection?

HAUL:
Hematoma, Abscess, Urinoma, Lymphocele

94

What is the indication for removal of native kidneys in a kidney transplant?

Uncontrollable HTN, ongoing renal sepsis

95

What is the red flag that indicates kidney rejection?

Increased creatinine

96

How is U/S with Doppler used in the workup for kidney rejection?

Look at flow in portal vein, hepatic artery.
Rule out thrombosis, leaky anastomosis, infection (abscess).

97

How is a cholangiogram used in the workup for kidney rejection?

Look at bile ducts

98

How is a biopsy used in the workup for kidney rejection?

Especially important 3-6 weeks post-op, when CMV is of greatest concern

99

Does hepatorenal syndrome renal function improve after liver transplant?

Yes

100

What percentage of kidney transplant patients requires re-transplant?

20%

101

What are the reason for kidney re-transplant?

Primary graft dysfunction, rejection, infection, vascular thrombosis, recurrence of primary disease

102

Who performed the first pancreas transplant?

Richard C. Lillehei and William D. Kelly (1966)

103

What are the indications for pancreas transplant?

Type I (juvenile) diabetes associated with severe complications (renal failure, blindness, neuropathy) or very poor glucose control

104

What are the tests for pancreas compatibility?

ABO, HLA-DR matching (class II)

105

What is the placement of a pancreas transplant?

Heterotopic, in iliac fossa, or paratopic

106

Where is anastomosis of the exocrine duct in heterotopic pancreas placement? Why?

To the bladder.
Measures the amount of amylase in urine, gives an indication of pancreatic function.

107

What is the associated electrolyte complication with pancreas transplants?

Loss of bicarbonate

108

Where is anastomosis of the exocrine duct in paratopic pancreas placement?

To the jejunum

109

What is the advantage of paratopic pancreas placement?

Endocrine function drains to the portal vein directly to the liver, and pancreatic contents stay within the GI tract (no need to replace bicarbonate)

110

What are the red flags indicating pancreas rejection?

Hyperamylasemia, hyperglycemia, hypoamylasuria, graft tenderness

111

Why should the kidney and pancreas be transplanted together?

Kidney function is a better indicator of rejection.
Also better survival of graft is associated with kidney-pancreas transplant than pancreas alone.

112

Why is hyperglycemia not a good indicator for pancreas rejection surveillance?

Appears relatively late with pancreatic rejection

113

Who performed the first heart transplant?

Christiaan Barnard (1967)

114

What are the indications for heart transplant?

115

What are the contraindications to heart transplant?

Active infection, poor pulmonary function, increased pulmonary artery resistance

116

What are the tests for heart compatibility?

ABO, size

117

What is the placement for a heart transplant?

Orthotopic anastomosis of atria, aorta, pulmonary artery

118

What is sewn together in a heart transplant?

Donar heart atria, pulmonary artery, aorta are sewn to the recipient heart atria, pulmonary artery, aorta

119

What are the red flags of heart rejection?

Fever, hypotension or hypertension, increased T4/T8 ratio

120

What is coronary artery vasculopathy?

Small vessel occlusion from chronic rejection of heart transplant.
Often requires re-transplant.

121

What are the tests for heart rejection?

Endomyocardial biopsy

122

What are survival statistics for heart transplants?

1 year: 85%
5 years: 65%

123

What is the anastomosis in a living donor intestinal transplantation?

Ileocolic artery and vein

124

What is the anastomosis in a deceased donor intestinal transplantation?

SMA, SMV

125

What are the indications for an intestinal transplantation?

Short gut syndrome, motility disorders, inability to sustain TPN (liver failure, lack of venous access, etc.)

126

What is a common postoperative problem with intestinal transplantations other than rejection?

GVHD from lymphoid tissue in transplanted intestines

127

What is GVHD?

Graft-Versus-Host Disease

128

What is the most common cause of death after intestinal transplantation?

Sepsis

129

How is intestinal rejection surveillance conducted?

Endoscopic biopsies

130

What is the clinical clue to intestinal rejection?

Watery diarrhea

131

Who performed the first lung transplant?

James Hardy (1963)

132

What are the indications for lung transplant?

Pulmonary fibrosis, COPD, eosinophilic granuloma, primary pulmonary HTN, Eisenmenger's syndrome, CF

133

What are the contraindications to lung transplant?

Current smoking, active infection

134

What tests comprise the pre-transplant assessment of a lung recipient?

1. Pulmonary: PFTs, VQ scan
2. Cardiac: echo, cath, angiogram
3. Exercise tolerance test

135

What are the lung donor requirements?

136

What are necessary anastomoses in a lung transplant?

Bronchi, PA, pulmonary veins (bronchial artery not necessary)

137

What are the postoperative complications with lung transplant?

Bronchial necrosis or stricture, reperfusion, pulmonary edema, rejection

138

What are the red flags of lung rejection?

Decreased arterial O2 tension; fever; increased fatigability; infiltrate on CXR

139

What is chronic lung rejection called?

Obliterative bronchiolitis

140

What are the survival rates for lung transplant?

1 year: 80%
3 years: 70%

141

What are 4 major complications of transplants?

1. Infection
2. Rejection
3. Post-transplant lymphoproliferative disease
4. Complications of steroids

142

What are the usual agents of infection post-transplant?

DNA viruses (CMV, HSV, VZV)

143

When should CMV infection be suspected post-transplant?

> 21 days

144

What is the time of peak incidence of CMV infections post-transplant?

4-6 weeks

145

What are the signs and symptoms of post-transplant CMV infection?

Fever, neutropenia, signs of transplant rejection.
Also can present as viral pneumonitis, hepatitis, colitis.

146

How is post-transplant CMV infection diagnosed?

Biopsy of transplant to differentiate rejection; cultures of blood, urine

147

What is the treatment for post-transplant CMV infection?

Ganciclovir +/- immunoglobulin

148

What are the complications of ganciclovir?

Bone marrow suppression

149

What are the signs and symptoms of post-transplant HSV infection?

Herpetic lesions, shingles, fever, neutropenia, rejection of transplant

150

What is the treatment for post-transplant HSV infection?

Acyclovir until patient is asymptomatic

151

What are the most common types of post-transplant malignancies?

Skin/lip cancer, B-cell cancer, cervical cancer, T-cell lymphoma, Kaposi's sarcoma

152

What is post-transplant lymphoma associated with?

Multiple doses of OKT3; EBV; youth

153

What is the treatment for post-transplant lymphoproliferative disease?

Drastically reduce immunosuppression, +/- XRT, +/- chemotherapy