Fiser.12.Transplantation Flashcards
1
Q
What is HLA?
A
human leukocyte antigen
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
3
Q
which type of transplant is ABO blood compatibility not required?
A
Required for all transplants except liver
4
Q
How do you perform a cross match?
A
mixes recipient serum with donor lymphocytes
5
Q
What does a cross match detect in transplant?
A
detects preformed recipient antibodies to the donor organ.
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
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
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
9
Q
What four PMH can increase panel reactive antibody (PRA) in a potential transplant recipient?
A
transfusions, pregnancy, previous transplant, autoimmune diseases
10
Q
What is the treatment for mild rejection?
A
pulse steroids
11
Q
what is the treatment for severe rejection (2)
A
steroid + antibody therapy
12
Q
name two potential antibody therapies for severe rejection
A
ATG (anti thymocyte globulin) or daclizumab
13
Q
what is the MC malignancy following any transplant?
A
squamous cell carcinoma of the skin
14
Q
What is the second most common malignancy following any transplant?
A
post-transplant lymphoproliferative disorder
15
Q
Describe the pathophysiology of post-transplant lymphproliferative disorder (PTLD)
A
uncontrolled proliferation of B-cell lymphocytes infected with epstein-barr virus
16
Q
how do you treat PTLD (post transplant lymphoproliferative disorder)?
A
withdraw immunosupppression, may need chemo and XRT for aggressive tumor
17
Q
what is the trade name of mycophenolate mofetil?
A
MMF, Cellcept
18
Q
what is the MOA of mycophenolate mofetil?
A
inhibits de novo purine synthesis, which inhibits growth of T-cells
19
Q
name one side effect of mycophenolate mofetil
A
myelosuppression
20
Q
what is the goal WBC count with mycophenolate mofetil?
A
WBC > 3
21
Q
when is the use of mycophenolate mofetil indicated in transplant patients?
A
used as maintenance therapy to prevent rejection
22
Q
what is the trade name of azathioprine?
A
imuran
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
24
Q
what are the three indications for steroid use in transplant patients?
A
induction after transplant, maintenance, and acute rejection episodes
25
what is the MOA of steroids in transplant patient immunosuppression (2)
inhibit inflammatory cells (macrophages) and genes for cytokine synthesis (IL-1, IL-6).
26
what is the MOA of cyclosporine?
binds cyclophilin protein and inhibits genes for cytokine synthesis
27
what phase of immunosuppression is cyclosporine used for in transplant patients?
maintenance therapy
28
name five adverse effects of cyclosporine
nephrotoxicity, hepatotoxicity, tremors, seizures, hemolytic-uremic syndrome
29
what is the goal trough level for cyclosporine?
200-300
30
which organ metabolizes cyclosporine?
hepatic metabolism
31
how is cyclosporine excreted? Which cycle does it undergo?
biliary excretion, reabsorbed in the gut, undergoes enterohepatic circulation
32
what are the two other names for FK-506?
tacrolimus and prograf
33
what is the MOA of tacrolimus?
binds FK-binding protein, inhibits genes for cytokine synthesis and inhibits inflammatory cells
34
which is more potent: tacrolimus or cyclosporin?
tacrolimus
35
name three AEs of tacrolimus and how it compares to cyclosporine
nephrotoxicity; more GI sx and mood changes than cyclosporine
36
how much enterohepatic circulation occurs with cyclosporine compared to tacrolimus?
tacrolimus undergoes much less enterohepatic circulation compared to cyclosporine
37
how does tacrolimus compare to cyclosporine in preventing renal transplant rejection?
tacrolimus has less kidney transplant rejection episodes compared to cyclosporine
38
what is your goal trough with tacrolimus?
10-15
39
what is the trade name of sirolimus?
Rapamycin
40
what is the MOA of sirolimus and how is it different from tacrolimus?
binds to FK-binding protein like tacrolimus but also inhibits mamallian target of rapamycin (mTOR) which inhibits T and B cell response to IL2
41
what phase of immunosuppression is sirolimus used for in transplant patients?
used for maintenance therapy
42
what type of antibodies are in "anti-thymocyte globulin" (ATG)
equine (ATGAM) or rabbit (thymogloulin) polyclonal antibodies against T-cell antigens
43
which T-cell antigens are targeted by anti-thymocyte globulin? (3)
CD2, CD3, CD4
44
what phases of immunosuppression is anti-thymocyte globulin (2)
used for induction and acute rejection episodes
45
what is the mechanism of cell lysis a/w antithymocyte globulin?
it is cytolytic by using complement
46
what is the goal WBC count when using antithymocyte globulin?
goal WBC \> 3
47
what AEs are a/w antithymocyte globulin?
cytokine release syndrome
48
what are the S/Sx of cytokine release syndrome (4)
fever, chills, pulmonary edema, shock
49
how do you prevent cytokine release syndrome a/w antithymocyte globulin use?
administer antithymocyte globulin with steroids and benadryl
50
what is the trade name for daclizumab?
Zenapax
51
What type of Ab is used in daclizumab?
human monoclonal Ab against IL2 receptors
52
what phase of immunosuppression is daclizumab used for in transplant patients (2)
induction and acute rejection
53
what is the mechanism of cell lysis a/w daclizumab?
none - it is NOT cytolytic :)
54
how long does it take for hyperacute rejection to occur?
occurs within minutes to hours
55
what is the MOA of hyperacute rejection?
preformed antibodies that SHOULD have been picked up by crossmatch --\> activate complement cascade --\> thrombosis of vessels
56
how do you treat hyperacute rejection?
emergent retransplant (or just removal of organ if kidney)
57
how long does it take for accelerated rejection to occur?
occurs \< 1 week
58
what is the MOA of accelerated rejection?
caused by sensitized T-cells to donor antigens
59
how do you treat accelerated rejection?
increase immunosuppression, pulse steroids, and possibly antibody tx
60
how long does it take for acute rejection to occur?
1 week to 1 month
61
what is the MOA of acute rejection?
caused by T cels (cytotoxic and helper T cells)
62
how do you treat acute rejection?
increase immunosuppression, pulse steroids, and possibly antibody Tx
63
how long does it take for chronic rejection to occur?
months to years
64
what is the MOA of chronic rejection
partially a type IV hypersensitivity reaction (2/2 sensitized T cells) and Ab formation also plays a role
65
what happens to the graft with chronic rejection?
graft fibrosis
66
how do you treat chronic rejection?
increase immunosuppression, no really effective treatment
67
how long can you store a donor kidney?
can store up to 48 hours
68
what two pre-transplant tests do you need for renal transplant on donor and recipient?
ABO type compatibility and cross-match
69
what do you do if the donor for the kidney prior to transplant had a UTI?
you can still use the kidney
70
what do you do if the donor had an acute increase in creatinine prior to donation? What range of Cr is considered acceptable?
can still use the kidney, Cr 1.0-3.0 acceptable
71
what are the 2 MCC of mortality s/p renal transplant/
stroke & MI
72
which vessels do you attach the kidney to in renal transplant?
iliac vessels
73
what is the #1 complication s/p renal transplant?
urine leak
74
how do you treat a urine leak s/p renal transplant?
drainage and stenting
75
how do you diagnose renal artery stenosis s/p renal transplant?
diagnose with ultrasound
76
how do you treat renal artery stenosis
PTA with stent
77
what is the MCC of external ureteral compression s/p renal transplant?
lymphocele
78
how do you treat lymphocele s/p renal transplant? (first and second line)
first line: perc drainage. If that fails, peritoneal window (make hole in peritoneum, lymphatic fluid drains ito peritoneum and is reabsorbed)
79
What percentage of lymphoceles are resolved with percutaneous drainage or peritoneal window s/p renal transplant?
95% are resolved with one of these two interventions
80
what should you suspect with postop oliguria s/p renal transplant?
acute tubular necrosis
81
what are the pathological findings in a renal transplant with ATN?
pathology shows hydrophobic changes
82
what are the two causes of postop diuresis s/p renal transplant?
urea and glucose
83
what should you suspect in a post-renal transplant patient with new onset proteinuria?
suspect renal vein thrombosis
84
why would a post-renal transplant patient develop postop diabetes?
side effect of CSA, tacrolimus, or steroids
85
name two viral infections post-renal transplant patients are at risk for
CMV and HSV
86
how do you treat CMV in a post-renal transplant patient?
ganciclovir
87
how do you treat HSV in a post-renal transplant patient?
acyclovir
88
what is the timeline for acute rejection s/p renal transplant?
occurs within 6 months
89
what does the pathology show in acute rejection in a renal transplant patient?
shows tubulitis (vasculitis with a more severe form)
90
what two S/Sx would prompt a kidney rejection workup s/p transplant?
elevated Cr or poor UOP
91
what imaging should you get to workup possible kidney rejection and why?
ultrasound with duplex to rule out vascular problems and ureteral obstruction
92
should you biopsy the transplanted kidney when evaluating for rejection?
yes
93
what should you do to your doses of cyclosporine or tacrolimus and why?
reduce the doses empirically of either of these drugs since they can be nephrotoxic
94
what should you use to treat suspected renal transplant rejection?
empiric pulse steroids
95
when do you usually see chronic rejection in renal transplants/
at 1 year post transplant
96
what is the treatment for chronic rejection?
no good treatment
97
what is the rate of 5-year graft survival s/p renal transplant? what is the difference between cadaveric vs living donors?
70% overall: 65% cadeveric, 75% living donors
98
what is the MCC s/p living donor nephrectomy?
wound infection
99
what is the rate of wound infection s/p living donor nephrectomy?
1% rate of SSI
100
what is the MCC of death s/p living donor nephrectomy?
PE
101
what happens to the remaining kidney s/p living donor nephrectomy?
the remaining kidney hypertrophies
102
how long can you store a donated liver prior to transplant?
24 hours
103
name two contraindications to liver transplant
current EtOH abuse, acute ulcerative colitis
104
what is the most common reason for liver transplant in adults?
chronic hep C
105
what three lab values are used to calculate MELD?
creatinine, INR, and bilirubin
106
what does the MELD score predict and what is its cutoff?
predicts whether a cirrhotic patient will benefit more from liver transplant than medical management (MELD \> 15 indicates benefit from liver transplant)
107
name the one indication for urgent liver transplant
fulminant hepatic failure
108
name three S/Sx of fulminant hepatic failure
encephalopathy with stupor / coma
109
how can you treat hepatitis B patients after liver transplant to prevent reinfection
patients with hep B antigenemia can be treated with HBIG (hepatitis B immunogloublin) and lamivudine( protease inhibitor) after liver transplant to prevent reinfection
110
what is the HepB reinfection rate with HBIG + lamivudine s/p liver transplant?
reduce reinfection rate to 20%
111
how can you prevent Hep C reinfection s/p liver transplant
no way to prevent, is likely to recur in liver allograft, reinfects essentially all grafts
112
when can you consider liver transplant in a patient with hepatocellular carcinoma?
if no vascular invasion or metastases, can consider liver transplant
113
can you perform liver transplant in a patient with portal vein thrombosis
yes, PVT is not a contraindication to liver transplant
114
what percent of alcoholics will start drinking again s/p liver transplant?
20% recidivism rate
115
what are the pathologic findings of macrosteatosis in a transplanted liver?
extracellular fat globules in the liver allograft
116
what does macrosteatosis of a potential liver transplant indicate? How can you use the pathologic findings to predict outcome?
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
what kind of biliary anastomosis do you perform in liver transplant in adults?
duct to duct
118
what kind of biliary anasotmosis do you perform in liver transplants in kids?
hepaticojejunostomy
119
where do you place surgical drains s/p liver transplant and how many?
3 drains, one right subhepatic, one right subdiaphragmatic, one left subdiaphragmatic
120
which blood supply determines the biliary system anatomy?
hepatic artery blood supply determines biliary system
121
what is the most common arterial anomaly seen in liver transplant?
right hepatic coming off SMA
122
what is the MC complication s/p liver transplant?
bile leak
123
how do you treat bile leak s/p liver transplant (first and second line)?
first line: place drain. second line: ERCP with stent across leak
124
How does primary nonfunction of the liver transplant present in the first 24 hours postop? (4 lab findings)
Tbili \> 10; bile output \< 20cc/12 hours; elevated PT; elevated PTT
125
how does primary nonfunction of a liver transplant present after 96 hours postop? (3 S/Sx, 1 lab finding)
mental status changes, elevated LFTs, renal failure, respiratory failure
126
what is the treatment for primary nonfunction of a liver transplant?
usually requires retransplantation
127
what is the MC early vascular complication s/p liver transplant?
early hepatic artery thrombosis
128
how does early hepatic artery thrombosis present s/p liver transplant (3 findings)
elevated LFTs, low bile output, fulminant hepatic failure
129
how do you treat early hepatic artery thrombosis s/p liver transplant
most commonly require emergent retransplantation. Sometimes can treat with stent or revision of anastomosis
130
what are two complications that result from late hepatic artery thrombosis s/p liver transplant?
results in biliary strictures and abscesses (not fulminant hepatic failure)
131
what is the MCC of abscesses s/p liver transplant
MCC = late (chronic) hepatic artery thrombosis
132
name 3 S/Sx a/w IVC stenosis/thrombosis s/p liver transplant
rare complication: p/w edema, ascites, and renal insufficiency
133
how do you treat IVC stenosis / thrombosis s/p liver transplant?
thrombolytics, IVC stent
134
how does early portal vein thrombosis present s/p liver transplant?
abdominal pain
135
how does late portal vein thrombosis present s/p liver transplant (2)
UGI bleeding, ascites, qqf asymptomatic
136
how do you treat early portal vein thrombosis s/p liver transplant?
reop thrombectomy and revise anastomosis
137
what pathologic findings do you see with cholangitis s/p liver transplant?
PMNs around the portal triad (not mixed infiltrate)
138
what is the mechanism of acute rejection of liver transplant?
T-cell mediated against blood vessels
139
what are 3 clinical findings a/w acute rejection of liver transplant?
fever, jaundice, reduced bile output
140
what are 5 lab findings a/w acute rejection of liver transplant?
leuckocytosis, eosinophilia, elevated LFTs, elevated Tbili, prolonged PT
141
what pathologic findings do you see with acute rejection of liver transplant? (3)
portal triad lymphocytosis, endotheliitis (mixed infiltrate), and bile duct injury
142
when does acute rejection of liver transplant occur?
within the first 2 months postop
143
how common is chronic rejection s/p liver transplant?
its unusual
144
what are the pathologic findings a/w chronic rejection s/p liver transplant?
"disappearing bile ducts"
145
what is the pathophysiology of chronic rejection of a liver transplant?
antibody and cellular attack on bile ducts --\> bile duct obstruction and portal fibrosis
146
what lab abnormality is a/w chronic rejection of a liver transplant and why?
bile duct obstruction causes elevated alk phos
147
what is the retransplantation rate s/p liver transplant?
20%
148
what is the 5 year survival rate s/p liver transplant?
70%
149
what two arteries do you need in the donor pancreas for successful pancreatic transplant?
need donor celiac artery and SMA
150
what donor vein do you need for successful pancreatic transplant?
need donor portal vein for drainage
151
where do you anastomose the vessels for pancreatic transplant?
to the iliac vessels
152
which portion of the donor small intestine is required for pancreatic transplant?
need the second portion of the duodenum and the ampulla of vater for pancreatic transplant
153
what kind of bowel anastomosis is performed with pancreatic transplant?
require enteric drainage for the pancreatic duct, so anastamose the donor duodenum to the recipient small bowel
154
how does a successful panc/kidney transplant affect vascular disease?
does NOT reverse vascular disease
155
how does a successful panc/kidney transplant affect retinopathy?
stabilization of retinopathy
156
how does a successful panc/kidney transplant affect neuropathy?
reduce neuropathy
157
how does a successful panc/kidney transplant affect nerve conduction velocity?
increases nerve conduction velocity
158
how does a successful panc/kidney transplant affect autonomic dysfunction?
reduced autonomic dysfunction
159
how does a successful panc/kidney transplant affect gastroparesis?
reduces gastroparesis
160
how does a successful panc/kidney transplant affect orthostatic hypotension?
reduces orthostatic hypotension
161
what is the MC complication s/p pancreatic transplant?
venous thrombosis
162
how do you treat venous thrombosis s/p pancreatic transplant?
hard to treat
163
name 4 S/Sx of pancreas transplant rejection
increased glucose, increased amylase, fever, leukocytosis
164
how does the presence of a kidney transplant affect the presentation of rejection of a concurrent pancreatic transplant?
the kidney/panc makes it easier to diangose rejection
165
how long can you store a donor heart prior to transplant?
6 hours
166
what two tests do you need to perform on donor and recipient prior to heart transplant?
need ABO compatibility and crossmatch
167
what life expectancy does a patient require to qualify for a heart transplant?
life expectancy \< 1 year
168
what is the prognosis of patients with persistent pulmonary HTN s/p heart transplant?
poor prognosis, a/w early mortality
169
how do you treat persistent pulmonary HTN s/p heart transplant
inhaled NO, ECMO if severe
170
what are the pathologic findings a/w acute cardiac transplant rejection?
perivascular lymphocytic infiltrate with varying grades of myocyte inflammation and necrosis
171
what is the pathophysiology of chronic allograft vasculopathy s/p liver transplant
progressive diffuse coronary atherosclerosis
172
what is the MCC of late death s/p cardiac transplant
chronic allograft vasculopathy
173
what is the MCC of overall death s/p cardiac transplant?
chronic allograft vasculopathy
174
how long can you store donor lungs prior to lung transplant?
6 hours
175
what two tests need to be performed on donor and recipient s/p lung transplant
ABO compatibility and crossmatch
176
what life expectancy is required for a patient to be considered for lung transplant?
life expectancy \< 1 year
177
what is the #1 cause of early mortality s/p lung transplantation?
reperfusion injury
178
what is the pathophysiology of reperfusion injury s/p lung transplant?
similar to ARDS
179
name one indication for double lung transplant
cystic fibrosis
180
name 5 contraindications for using donor lungs
aspiration; moderate to large contusion; infiltrates; puruletn sputum; PO2 \< 350 on 100% FiO2 + PEEP 5
181
what are the pathologic findings a/w acute rejection s/p lung transplant?
perivascular lymphocytosis
182
what is the disease a/w chronic rejection s/p lung transplant?
bronchiolitis obliterans
183
what is the MCC of late death s/p lung transplant?
bronchiolitis obliterans
184
what is the MCC of death overall s/p lung transplant?
bronchiolitis obliterans
185
name three opportunistic viral infections in transplant patients
CMV, HSV, VZV
186
name one opportunistic protozoan infection in transplant patients
pneumocystitis jiroveci pneumonia
187
why do transplant patients require Bactrim prophylaxis
to prevent pneumocystitis jiroveci pneumonia
188
name three opportunistic fungal infections
aspergillus, candida, cryptococcus
189
what is the herarchy of permission for organ donation from next of kin (6)
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
