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Z.Fiser > Fiser.12.Transplantation > Flashcards

Fiser.12.Transplantation Flashcards

1
Q

What is HLA?

A

human leukocyte antigen

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2
Q

what are the three HLAs that are the most important in recipient/donor matching in transplant? Which is the most important?

A

HLA-DR (most important); HLA-A, and HLA-B

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3
Q

which type of transplant is ABO blood compatibility not required?

A

Required for all transplants except liver

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4
Q

How do you perform a cross match?

A

mixes recipient serum with donor lymphocytes

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5
Q

What does a cross match detect in transplant?

A

detects preformed recipient antibodies to the donor organ.

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6
Q

what does a “positive cross match” in a transplant evaluation indicate?

A

indicates preformed recipient antibodies to the donor organ, therefore hyperacute rejection will likely occur with transplant

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7
Q

How is the panel reactive antibody (PRA) performed?

A

combining recipient serum to a panel of HLA specific to the country the transplant is occurring in to detect what percentage of the population the patient has preformed antibodies to

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8
Q

How do you interpret the PRA (panel reactive antibody) percentage? What is the cutoff that is a contraindication to transplant?

A

PRA percentage is the percent of cells that the recipient serum reacts with. A high PRA (>50%) is a contraindication to transplant 2/2 increased risk of hyperacute rejection

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9
Q

What four PMH can increase panel reactive antibody (PRA) in a potential transplant recipient?

A

transfusions, pregnancy, previous transplant, autoimmune diseases

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10
Q

What is the treatment for mild rejection?

A

pulse steroids

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11
Q

what is the treatment for severe rejection (2)

A

steroid + antibody therapy

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12
Q

name two potential antibody therapies for severe rejection

A

ATG (anti thymocyte globulin) or daclizumab

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13
Q

what is the MC malignancy following any transplant?

A

squamous cell carcinoma of the skin

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14
Q

What is the second most common malignancy following any transplant?

A

post-transplant lymphoproliferative disorder

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15
Q

Describe the pathophysiology of post-transplant lymphproliferative disorder (PTLD)

A

uncontrolled proliferation of B-cell lymphocytes infected with epstein-barr virus

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16
Q

how do you treat PTLD (post transplant lymphoproliferative disorder)?

A

withdraw immunosupppression, may need chemo and XRT for aggressive tumor

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17
Q

what is the trade name of mycophenolate mofetil?

A

MMF, Cellcept

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18
Q

what is the MOA of mycophenolate mofetil?

A

inhibits de novo purine synthesis, which inhibits growth of T-cells

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19
Q

name one side effect of mycophenolate mofetil

A

myelosuppression

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20
Q

what is the goal WBC count with mycophenolate mofetil?

A

WBC > 3

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21
Q

when is the use of mycophenolate mofetil indicated in transplant patients?

A

used as maintenance therapy to prevent rejection

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22
Q

what is the trade name of azathioprine?

A

imuran

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23
Q

what is the MOA of azathioprine?

A

prodrug that is converted to 6-mercaptopurine and 6-thioguanine that inhibits purine biosynthesis, causing myelosuppression

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24
Q

what are the three indications for steroid use in transplant patients?

A

induction after transplant, maintenance, and acute rejection episodes

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25
Q

what is the MOA of steroids in transplant patient immunosuppression (2)

A

inhibit inflammatory cells (macrophages) and genes for cytokine synthesis (IL-1, IL-6).

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26
Q

what is the MOA of cyclosporine?

A

binds cyclophilin protein and inhibits genes for cytokine synthesis

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27
Q

what phase of immunosuppression is cyclosporine used for in transplant patients?

A

maintenance therapy

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28
Q

name five adverse effects of cyclosporine

A

nephrotoxicity, hepatotoxicity, tremors, seizures, hemolytic-uremic syndrome

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29
Q

what is the goal trough level for cyclosporine?

A

200-300

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30
Q

which organ metabolizes cyclosporine?

A

hepatic metabolism

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31
Q

how is cyclosporine excreted? Which cycle does it undergo?

A

biliary excretion, reabsorbed in the gut, undergoes enterohepatic circulation

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32
Q

what are the two other names for FK-506?

A

tacrolimus and prograf

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33
Q

what is the MOA of tacrolimus?

A

binds FK-binding protein, inhibits genes for cytokine synthesis and inhibits inflammatory cells

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34
Q

which is more potent: tacrolimus or cyclosporin?

A

tacrolimus

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35
Q

name three AEs of tacrolimus and how it compares to cyclosporine

A

nephrotoxicity; more GI sx and mood changes than cyclosporine

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36
Q

how much enterohepatic circulation occurs with cyclosporine compared to tacrolimus?

A

tacrolimus undergoes much less enterohepatic circulation compared to cyclosporine

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37
Q

how does tacrolimus compare to cyclosporine in preventing renal transplant rejection?

A

tacrolimus has less kidney transplant rejection episodes compared to cyclosporine

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38
Q

what is your goal trough with tacrolimus?

A

10-15

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39
Q

what is the trade name of sirolimus?

A

Rapamycin

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40
Q

what is the MOA of sirolimus and how is it different from tacrolimus?

A

binds to FK-binding protein like tacrolimus but also inhibits mamallian target of rapamycin (mTOR) which inhibits T and B cell response to IL2

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41
Q

what phase of immunosuppression is sirolimus used for in transplant patients?

A

used for maintenance therapy

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42
Q

what type of antibodies are in “anti-thymocyte globulin” (ATG)

A

equine (ATGAM) or rabbit (thymogloulin) polyclonal antibodies against T-cell antigens

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43
Q

which T-cell antigens are targeted by anti-thymocyte globulin? (3)

A

CD2, CD3, CD4

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44
Q

what phases of immunosuppression is anti-thymocyte globulin (2)

A

used for induction and acute rejection episodes

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45
Q

what is the mechanism of cell lysis a/w antithymocyte globulin?

A

it is cytolytic by using complement

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46
Q

what is the goal WBC count when using antithymocyte globulin?

A

goal WBC > 3

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47
Q

what AEs are a/w antithymocyte globulin?

A

cytokine release syndrome

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48
Q

what are the S/Sx of cytokine release syndrome (4)

A

fever, chills, pulmonary edema, shock

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49
Q

how do you prevent cytokine release syndrome a/w antithymocyte globulin use?

A

administer antithymocyte globulin with steroids and benadryl

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50
Q

what is the trade name for daclizumab?

A

Zenapax

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51
Q

What type of Ab is used in daclizumab?

A

human monoclonal Ab against IL2 receptors

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52
Q

what phase of immunosuppression is daclizumab used for in transplant patients (2)

A

induction and acute rejection

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53
Q

what is the mechanism of cell lysis a/w daclizumab?

A

none - it is NOT cytolytic :)

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54
Q

how long does it take for hyperacute rejection to occur?

A

occurs within minutes to hours

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55
Q

what is the MOA of hyperacute rejection?

A

preformed antibodies that SHOULD have been picked up by crossmatch –> activate complement cascade –> thrombosis of vessels

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56
Q

how do you treat hyperacute rejection?

A

emergent retransplant (or just removal of organ if kidney)

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57
Q

how long does it take for accelerated rejection to occur?

A

occurs < 1 week

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58
Q

what is the MOA of accelerated rejection?

A

caused by sensitized T-cells to donor antigens

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59
Q

how do you treat accelerated rejection?

A

increase immunosuppression, pulse steroids, and possibly antibody tx

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60
Q

how long does it take for acute rejection to occur?

A

1 week to 1 month

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61
Q

what is the MOA of acute rejection?

A

caused by T cels (cytotoxic and helper T cells)

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62
Q

how do you treat acute rejection?

A

increase immunosuppression, pulse steroids, and possibly antibody Tx

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63
Q

how long does it take for chronic rejection to occur?

A

months to years

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64
Q

what is the MOA of chronic rejection

A

partially a type IV hypersensitivity reaction (2/2 sensitized T cells) and Ab formation also plays a role

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65
Q

what happens to the graft with chronic rejection?

A

graft fibrosis

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66
Q

how do you treat chronic rejection?

A

increase immunosuppression, no really effective treatment

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67
Q

how long can you store a donor kidney?

A

can store up to 48 hours

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68
Q

what two pre-transplant tests do you need for renal transplant on donor and recipient?

A

ABO type compatibility and cross-match

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69
Q

what do you do if the donor for the kidney prior to transplant had a UTI?

A

you can still use the kidney

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70
Q

what do you do if the donor had an acute increase in creatinine prior to donation? What range of Cr is considered acceptable?

A

can still use the kidney, Cr 1.0-3.0 acceptable

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71
Q

what are the 2 MCC of mortality s/p renal transplant/

A

stroke & MI

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72
Q

which vessels do you attach the kidney to in renal transplant?

A

iliac vessels

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73
Q

what is the #1 complication s/p renal transplant?

A

urine leak

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74
Q

how do you treat a urine leak s/p renal transplant?

A

drainage and stenting

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75
Q

how do you diagnose renal artery stenosis s/p renal transplant?

A

diagnose with ultrasound

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76
Q

how do you treat renal artery stenosis

A

PTA with stent

77
Q

what is the MCC of external ureteral compression s/p renal transplant?

A

lymphocele

78
Q

how do you treat lymphocele s/p renal transplant? (first and second line)

A

first line: perc drainage. If that fails, peritoneal window (make hole in peritoneum, lymphatic fluid drains ito peritoneum and is reabsorbed)

79
Q

What percentage of lymphoceles are resolved with percutaneous drainage or peritoneal window s/p renal transplant?

A

95% are resolved with one of these two interventions

80
Q

what should you suspect with postop oliguria s/p renal transplant?

A

acute tubular necrosis

81
Q

what are the pathological findings in a renal transplant with ATN?

A

pathology shows hydrophobic changes

82
Q

what are the two causes of postop diuresis s/p renal transplant?

A

urea and glucose

83
Q

what should you suspect in a post-renal transplant patient with new onset proteinuria?

A

suspect renal vein thrombosis

84
Q

why would a post-renal transplant patient develop postop diabetes?

A

side effect of CSA, tacrolimus, or steroids

85
Q

name two viral infections post-renal transplant patients are at risk for

A

CMV and HSV

86
Q

how do you treat CMV in a post-renal transplant patient?

A

ganciclovir

87
Q

how do you treat HSV in a post-renal transplant patient?

A

acyclovir

88
Q

what is the timeline for acute rejection s/p renal transplant?

A

occurs within 6 months

89
Q

what does the pathology show in acute rejection in a renal transplant patient?

A

shows tubulitis (vasculitis with a more severe form)

90
Q

what two S/Sx would prompt a kidney rejection workup s/p transplant?

A

elevated Cr or poor UOP

91
Q

what imaging should you get to workup possible kidney rejection and why?

A

ultrasound with duplex to rule out vascular problems and ureteral obstruction

92
Q

should you biopsy the transplanted kidney when evaluating for rejection?

A

yes

93
Q

what should you do to your doses of cyclosporine or tacrolimus and why?

A

reduce the doses empirically of either of these drugs since they can be nephrotoxic

94
Q

what should you use to treat suspected renal transplant rejection?

A

empiric pulse steroids

95
Q

when do you usually see chronic rejection in renal transplants/

A

at 1 year post transplant

96
Q

what is the treatment for chronic rejection?

A

no good treatment

97
Q

what is the rate of 5-year graft survival s/p renal transplant? what is the difference between cadaveric vs living donors?

A

70% overall: 65% cadeveric, 75% living donors

98
Q

what is the MCC s/p living donor nephrectomy?

A

wound infection

99
Q

what is the rate of wound infection s/p living donor nephrectomy?

A

1% rate of SSI

100
Q

what is the MCC of death s/p living donor nephrectomy?

A

PE

101
Q

what happens to the remaining kidney s/p living donor nephrectomy?

A

the remaining kidney hypertrophies

102
Q

how long can you store a donated liver prior to transplant?

A

24 hours

103
Q

name two contraindications to liver transplant

A

current EtOH abuse, acute ulcerative colitis

104
Q

what is the most common reason for liver transplant in adults?

A

chronic hep C

105
Q

what three lab values are used to calculate MELD?

A

creatinine, INR, and bilirubin

106
Q

what does the MELD score predict and what is its cutoff?

A

predicts whether a cirrhotic patient will benefit more from liver transplant than medical management (MELD > 15 indicates benefit from liver transplant)

107
Q

name the one indication for urgent liver transplant

A

fulminant hepatic failure

108
Q

name three S/Sx of fulminant hepatic failure

A

encephalopathy with stupor / coma

109
Q

how can you treat hepatitis B patients after liver transplant to prevent reinfection

A

patients with hep B antigenemia can be treated with HBIG (hepatitis B immunogloublin) and lamivudine( protease inhibitor) after liver transplant to prevent reinfection

110
Q

what is the HepB reinfection rate with HBIG + lamivudine s/p liver transplant?

A

reduce reinfection rate to 20%

111
Q

how can you prevent Hep C reinfection s/p liver transplant

A

no way to prevent, is likely to recur in liver allograft, reinfects essentially all grafts

112
Q

when can you consider liver transplant in a patient with hepatocellular carcinoma?

A

if no vascular invasion or metastases, can consider liver transplant

113
Q

can you perform liver transplant in a patient with portal vein thrombosis

A

yes, PVT is not a contraindication to liver transplant

114
Q

what percent of alcoholics will start drinking again s/p liver transplant?

A

20% recidivism rate

115
Q

what are the pathologic findings of macrosteatosis in a transplanted liver?

A

extracellular fat globules in the liver allograft

116
Q

what does macrosteatosis of a potential liver transplant indicate? How can you use the pathologic findings to predict outcome?

A

macrosteatosis is a risk factor for primary non-function. If 50% cross section is macrosteatic in a potential donor liver, there is a 50% chance of primary non-function

117
Q

what kind of biliary anastomosis do you perform in liver transplant in adults?

A

duct to duct

118
Q

what kind of biliary anasotmosis do you perform in liver transplants in kids?

A

hepaticojejunostomy

119
Q

where do you place surgical drains s/p liver transplant and how many?

A

3 drains, one right subhepatic, one right subdiaphragmatic, one left subdiaphragmatic

120
Q

which blood supply determines the biliary system anatomy?

A

hepatic artery blood supply determines biliary system

121
Q

what is the most common arterial anomaly seen in liver transplant?

A

right hepatic coming off SMA

122
Q

what is the MC complication s/p liver transplant?

A

bile leak

123
Q

how do you treat bile leak s/p liver transplant (first and second line)?

A

first line: place drain. second line: ERCP with stent across leak

124
Q

How does primary nonfunction of the liver transplant present in the first 24 hours postop? (4 lab findings)

A

Tbili > 10; bile output < 20cc/12 hours; elevated PT; elevated PTT

125
Q

how does primary nonfunction of a liver transplant present after 96 hours postop? (3 S/Sx, 1 lab finding)

A

mental status changes, elevated LFTs, renal failure, respiratory failure

126
Q

what is the treatment for primary nonfunction of a liver transplant?

A

usually requires retransplantation

127
Q

what is the MC early vascular complication s/p liver transplant?

A

early hepatic artery thrombosis

128
Q

how does early hepatic artery thrombosis present s/p liver transplant (3 findings)

A

elevated LFTs, low bile output, fulminant hepatic failure

129
Q

how do you treat early hepatic artery thrombosis s/p liver transplant

A

most commonly require emergent retransplantation. Sometimes can treat with stent or revision of anastomosis

130
Q

what are two complications that result from late hepatic artery thrombosis s/p liver transplant?

A

results in biliary strictures and abscesses (not fulminant hepatic failure)

131
Q

what is the MCC of abscesses s/p liver transplant

A

MCC = late (chronic) hepatic artery thrombosis

132
Q

name 3 S/Sx a/w IVC stenosis/thrombosis s/p liver transplant

A

rare complication: p/w edema, ascites, and renal insufficiency

133
Q

how do you treat IVC stenosis / thrombosis s/p liver transplant?

A

thrombolytics, IVC stent

134
Q

how does early portal vein thrombosis present s/p liver transplant?

A

abdominal pain

135
Q

how does late portal vein thrombosis present s/p liver transplant (2)

A

UGI bleeding, ascites, qqf asymptomatic

136
Q

how do you treat early portal vein thrombosis s/p liver transplant?

A

reop thrombectomy and revise anastomosis

137
Q

what pathologic findings do you see with cholangitis s/p liver transplant?

A

PMNs around the portal triad (not mixed infiltrate)

138
Q

what is the mechanism of acute rejection of liver transplant?

A

T-cell mediated against blood vessels

139
Q

what are 3 clinical findings a/w acute rejection of liver transplant?

A

fever, jaundice, reduced bile output

140
Q

what are 5 lab findings a/w acute rejection of liver transplant?

A

leuckocytosis, eosinophilia, elevated LFTs, elevated Tbili, prolonged PT

141
Q

what pathologic findings do you see with acute rejection of liver transplant? (3)

A

portal triad lymphocytosis, endotheliitis (mixed infiltrate), and bile duct injury

142
Q

when does acute rejection of liver transplant occur?

A

within the first 2 months postop

143
Q

how common is chronic rejection s/p liver transplant?

A

its unusual

144
Q

what are the pathologic findings a/w chronic rejection s/p liver transplant?

A

“disappearing bile ducts”

145
Q

what is the pathophysiology of chronic rejection of a liver transplant?

A

antibody and cellular attack on bile ducts –> bile duct obstruction and portal fibrosis

146
Q

what lab abnormality is a/w chronic rejection of a liver transplant and why?

A

bile duct obstruction causes elevated alk phos

147
Q

what is the retransplantation rate s/p liver transplant?

A

20%

148
Q

what is the 5 year survival rate s/p liver transplant?

A

70%

149
Q

what two arteries do you need in the donor pancreas for successful pancreatic transplant?

A

need donor celiac artery and SMA

150
Q

what donor vein do you need for successful pancreatic transplant?

A

need donor portal vein for drainage

151
Q

where do you anastomose the vessels for pancreatic transplant?

A

to the iliac vessels

152
Q

which portion of the donor small intestine is required for pancreatic transplant?

A

need the second portion of the duodenum and the ampulla of vater for pancreatic transplant

153
Q

what kind of bowel anastomosis is performed with pancreatic transplant?

A

require enteric drainage for the pancreatic duct, so anastamose the donor duodenum to the recipient small bowel

154
Q

how does a successful panc/kidney transplant affect vascular disease?

A

does NOT reverse vascular disease

155
Q

how does a successful panc/kidney transplant affect retinopathy?

A

stabilization of retinopathy

156
Q

how does a successful panc/kidney transplant affect neuropathy?

A

reduce neuropathy

157
Q

how does a successful panc/kidney transplant affect nerve conduction velocity?

A

increases nerve conduction velocity

158
Q

how does a successful panc/kidney transplant affect autonomic dysfunction?

A

reduced autonomic dysfunction

159
Q

how does a successful panc/kidney transplant affect gastroparesis?

A

reduces gastroparesis

160
Q

how does a successful panc/kidney transplant affect orthostatic hypotension?

A

reduces orthostatic hypotension

161
Q

what is the MC complication s/p pancreatic transplant?

A

venous thrombosis

162
Q

how do you treat venous thrombosis s/p pancreatic transplant?

A

hard to treat

163
Q

name 4 S/Sx of pancreas transplant rejection

A

increased glucose, increased amylase, fever, leukocytosis

164
Q

how does the presence of a kidney transplant affect the presentation of rejection of a concurrent pancreatic transplant?

A

the kidney/panc makes it easier to diangose rejection

165
Q

how long can you store a donor heart prior to transplant?

A

6 hours

166
Q

what two tests do you need to perform on donor and recipient prior to heart transplant?

A

need ABO compatibility and crossmatch

167
Q

what life expectancy does a patient require to qualify for a heart transplant?

A

life expectancy < 1 year

168
Q

what is the prognosis of patients with persistent pulmonary HTN s/p heart transplant?

A

poor prognosis, a/w early mortality

169
Q

how do you treat persistent pulmonary HTN s/p heart transplant

A

inhaled NO, ECMO if severe

170
Q

what are the pathologic findings a/w acute cardiac transplant rejection?

A

perivascular lymphocytic infiltrate with varying grades of myocyte inflammation and necrosis

171
Q

what is the pathophysiology of chronic allograft vasculopathy s/p liver transplant

A

progressive diffuse coronary atherosclerosis

172
Q

what is the MCC of late death s/p cardiac transplant

A

chronic allograft vasculopathy

173
Q

what is the MCC of overall death s/p cardiac transplant?

A

chronic allograft vasculopathy

174
Q

how long can you store donor lungs prior to lung transplant?

A

6 hours

175
Q

what two tests need to be performed on donor and recipient s/p lung transplant

A

ABO compatibility and crossmatch

176
Q

what life expectancy is required for a patient to be considered for lung transplant?

A

life expectancy < 1 year

177
Q

what is the #1 cause of early mortality s/p lung transplantation?

A

reperfusion injury

178
Q

what is the pathophysiology of reperfusion injury s/p lung transplant?

A

similar to ARDS

179
Q

name one indication for double lung transplant

A

cystic fibrosis

180
Q

name 5 contraindications for using donor lungs

A

aspiration; moderate to large contusion; infiltrates; puruletn sputum; PO2 < 350 on 100% FiO2 + PEEP 5

181
Q

what are the pathologic findings a/w acute rejection s/p lung transplant?

A

perivascular lymphocytosis

182
Q

what is the disease a/w chronic rejection s/p lung transplant?

A

bronchiolitis obliterans

183
Q

what is the MCC of late death s/p lung transplant?

A

bronchiolitis obliterans

184
Q

what is the MCC of death overall s/p lung transplant?

A

bronchiolitis obliterans

185
Q

name three opportunistic viral infections in transplant patients

A

CMV, HSV, VZV

186
Q

name one opportunistic protozoan infection in transplant patients

A

pneumocystitis jiroveci pneumonia

187
Q

why do transplant patients require Bactrim prophylaxis

A

to prevent pneumocystitis jiroveci pneumonia

188
Q

name three opportunistic fungal infections

A

aspergillus, candida, cryptococcus

189
Q

what is the herarchy of permission for organ donation from next of kin (6)

A

1) spouse; 2) adult son / daughter; 3) either parent; 4) adult brother/sister; 5) guardian; 6) any other person authorized to dispose of the body

Z.Fiser (22 decks)

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