Chapter 12: Transplantation Flashcards
1
Q
Most important in recipient/donor matching
A
HLA-A, -B, and -DR
2
Q
HLA: most important overall
A
HLA-DR
3
Q
Generally required for all transplants (except liver)
A
ABO blood compatibility
4
Q
Cross-match
A
Detects preformed recipient antibodies to the donor organ by mixing recipient serum with donor lymphocytes
5
Q
What does a positive cross-match mean?
A
If antibodies are present, the cross-match is positive and a hyper acute rejection would likely occur with TXP.
6
Q
Panel reactive antibody (PRA)
A
Technique identical to cross-match; detects performed recipient antibodies use a panel of HLA typing cells
7
Q
Panel reactive antibody (PRA) which is a contraindication to transplant
A
> 50% (% of cell that the recipient serum reacts with) - > increased risk of hyper-acute rejection
8
Q
What can increase the panel reactive antibody (PRA)?
A
Transfusion
Pregnancy
Previous transplant
Autoimmune diseases
9
Q
Tx: mild rejection
A
Pulse steroids
10
Q
Tx: severe rejection
A
Steroid and antibody therapy (ATG or daclizumab)
11
Q
1 malignancy following any transplant
A
Skin cancer (squamous cell CA #1)
12
Q
2 Next most common malignancy following transplant (Epstein-Barr virus related)
A
Post-transplant lympho-proliferative disorder (PTLD)
13
Q
Tx: post-transplant lympho-proliferative disorder (PTLD)
A
Withdrawal of immunosuppression; may need chemotherapy and XRT for aggressive tumor
14
Q
Mycophenolate (MMF, CellCept)
A
- Inhibits de novo purine synthesis, which inhibits growth of T cells
- Side effects: myelosuppression (need to keep WBC>3)
- Used as maintenance therapy to prevent rejection
15
Q
Steroids
A
Inhibit inflammatory cells (macrophages) and genes for cytokine synthesis (IL-1, IL-6); used of induction after TXP, maintenance, and acute rejection episodes
16
Q
Cyclosporin (CSA)
A
Binds cyclophilin protein and inhibits genes for cytokine synthesis (IL-2, IL-4,etc); used for maintenance therapy Side effects: Nephrotoxicity Hepatotoxicity Tremors Seizures Hemolytic-uremic syndrome
17
Q
Trough: cyclosporin (CSA)
A
200-300
18
Q
Cyclosporin (CSA): metabolism
A
Undergoes hepatic metabolism and biliary excretion (reabsorbed in the gut, get enter-hepatic recirculation)
19
Q
Sirolimus (Rapamycin)
A
- Binds FK-binding protein like FK-506 but inhibits mammalian target of rapamycin (mTOR); result is that it inhibits T and B cell response to IL-2
- Used as maintenance therapy
20
Q
Anti-thymocyte globulin (ATG)
A
- Equine (ATGAM) or rabbit (Thymoglobulin) polyclonal antibodies against T cell antigens (CD2, CD3, CD4)
- Used for induction and acute rejection episodes
- Is cytolytic (complement dependent)
Side effects:Cytokine release syndrome (Fevers, chills, pulmonary edema, shock)
21
Q
What can prevent cytokine release syndrome from anti-thymocyte globulin (ATG)?
A
Steroids and benadryl
22
Q
Zenapax (daclizumab)
A
Human monoclonal antibody against IL-2 receptors
- Used for induction and acute rejection episodes
- Is not cytolytic
23
Q
Hyperacute rejection
A
- Occurs within minutes to hours
- Caused by preformed antibodies that should have been picked up by the cross-match
- Activates the complement cascade and thrombosis of vessels occurs
24
Q
Tx: hyperacute rejection
A
Emergent re-transplant (or just removal of organ if kidney)
25
Tx: accelerated rejection
Increase immunosuppression, pulse steroids, and possible antibody treatment
26
Acute rejection
- Occurs 1 week to 1 month
| - Caused by T cells (cytotoxic and helper T cells
27
Tx: acute rejection
Increased immunosuppression, pulse steroids, and possibly antibody treatment
28
Chronic rejection
- Months to years
- Partially and type 4 hypersensitivity rejection (sensitized T cells)
- Antibody formation also plays a role
- Leads to graft fibrosis
29
Tx: chronic rejection
Increase immunosuppression - no really effective treatment
30
How long can a kidney be stored?
48 hours
31
Can you still use a kidney with a UTI?
Yes
32
Can you use a kidney with an acute increase in creatinine (1.0-3.0)?
Yes
33
Kidney transplant: what is mortality most likely from?
Stroke and MI
34
What do you attach the kidney to?
Attach to iliac vessels
35
Complications kidney transplant
Urine leaks, renal artery stenosis, lymphocele, postop oliguria, postop diuresis, new proteinuria, postop diabetes, viral infection, acute / chronic rejection
36
#1 cause complication with kidney transplant
Urine leaks
37
Tx: urine leaks s/p kidney transplant
Drainage and stenting
38
Dx / Tx: renal artery stenosis s/p kidney transplant
Dx: US
Tx: PTA with stent
39
MCC external ureter compression s/p kidney transplant
Lymphocele
40
Tx: lymphocele s/p kidney transplant
1st try percutaneous drainage; if that fails, then need peritoneal window (make hole in peritoneum, lymphatic fluid drains into peritoneum and is reabsorbed - 95% successful)
41
Usually due to ATN (pathology shows hydrophobic changes) s/p kidney transplant
Postop oliguria
42
Usually due to urea and glucose s/p kidney transplant
Postop diuresis
43
Suggestive of renal vein thrombosis s/p kidney transplant
New proteinuria
44
Side effect of CSA, FK, steroids s/p kidney transplant
Postop diabetes
45
Viral infections s/p kidney transplant
CMV - Tx: ganciclovir
| HSV - Tx: acyclovir
46
Time / path: acute rejection s/p kidney transplant
- Time: usually occurs in first 6 months
| - Path: tubulitis (vasculitis with more severe form)
47
Kidney rejection workup (usually for increase in creatinine or poor urine output)
- US with duplex (r/o vascular problem and ureteral obstruction) and biopsy
- Empiric decrease in CSA or FK (can be nephrotoxic)
- Empiric pulse steroids
48
When do you see chronic rejection s/p kidney transplant?
Usually do not see until after 1 year; no good treatment
49
5-year graft survival overall: kidney transplant
70% (cadaveric 65%, living donors 75%)
50
Living kidney donors: MC complication
Wound infection (1%)
51
Living kidney donors: MCC death
fatal PE
52
How long can a liver be stored?
24 hours
53
Contraindications for liver transplant
Current EtOH abuse, acute ulcerative colitis
54
MC reason for liver transplant in adults
Chronic hepatitis C
55
Uses creatinine, INR, and bilirubin to predict if patients with cirrhosis will benefit more from liver transplant than from medical therapy
MELD score
56
MELD score: benefits from liver transplant
MELD score > 15
57
Criteria for urgent liver transplant
Fulminant hepatic failure (encephalopathy - stupor coma)
58
Tx: patients with hepatitis B antigenemia after liver transplant to help prevent reinfection
HBIG (hepatitis B immunoglobulin) and lamivudine (protease inhibitor)
Reinfection rate is reduced to 20% with use of HBIG and lamivudine s/p liver transplant
59
Disease most likely to recur in the new liver allograft; reinfects essentially all grafts s/p liver transplant
Hepatitis C
60
Is portal vein thrombosis a contraindication to liver transplant?
no
61
Definition: recidivism
20% will start drinking again s/p liver transplant
62
Macrosteatosis: risk-factor for primary non-function
If 50% of cross-section is macrosteatatic in potential donor liver, there is a 50% chance of primary non-function.
63
Surgery: liver transplant
Duct to duct anastomosis is performed. Hepaticojejunostomy in kids. Right sub hepatic, right, and left sub diaphragmatic drains are placed.
64
Liver transplant: depends on hepatic artery blood supply
Biliary system (ducts, etc)
65
Liver transplant: MC arterial anomaly
Right hepatic coming off SMA
66
Complications liver transplant
Bile leak, primary nonfunction, early / late hepatic artery thrombosis, abscesses, IVC stenosis/thrombosis, portal vein thrombosis, cholangitis, acute rejection
67
#1 complication liver transplant
Bile leak
| - Tx: place drain, then ERCP with stent across leak
68
DX: s/p Liver transplant:
| - 1st 24 hours: total bili > 10, bile output
DX: primary non-function
69
Tx: primary non-function s/p liver transplant
Re-transplantation
70
MC early vascular complication s/p liver transplant
Early hepatic artery thrombosis
71
Dx: s/p liver transplant:
| - Increased LFTs, decreased bile output, fulminant hepatic failure
Dx: early hepatic artery thrombosis
72
Tx: early hepatic artery thrombosis
MC will need emergent re-transplantation for ensuing fulminant hepatic failure (can try to stent or revise anastomosis)
73
Complication s/p liver TXP: results in biliary strictures and abscesses (not fulminant hepatic failure)
late hepatic artery thrombosis
74
Hepatic abscesses s/p transplant
MC'y from late (chronic) hepatic artery thrombosis
75
Dx: s/p liver transplant
- (rare) edema, ascites, renal insufficiency
- Tx: thrombolytics, IVC stent
IVC stenosis / thrombosis
76
Dx: s/p liver transplant
- (rare) Early - abdominal pain. Late - UGIB, ascites, may be asymptomatic
- Tx: if early, re-op thrombectomy and revise anastomosis
Portal vein thrombosis (rare)
77
Dx: s/p liver transplant - get PMNs around portal triad (not mixed infiltrate)
Cholangitis
78
Dx: s/p liver transplant - T cell mediated against blood vessels.
- Clinical: fever, jaundice, decreased bile output
- Labs: leukocytosis, eosinophilia, increased LFTs, increased total bilirubin, and increasedPT
- usually occurs in 1st 2 months.
Acute rejection s/p liver transplant
79
Pathology: acute rejection liver transplants
Shows portal triad lymphocytosis, endotheliitis (mixed infiltrate) and bile duct injury
80
Chronic rejection: liver
Unusual after liver transplant; get disappearing bile ducts (antibody and cellular attack on bile ducts); gradually get bile duct obstruction with increase in alkaline phosphatase, portal fibrosis
81
Liver TXP: Retransplantation rate
20%
82
Liver TXP: 5-year survival rate
70%
83
Pancreas TXP: donor arterial supply
Need both donor celiac artery and SMA for arterial supply
84
Pancreas TXP: donor venous drainage
Need donor portal vein for venous drainage
85
Where do you attach pancreas TXP?
Attach to iliac vessels
86
How do you drain pancreatic duct s/p pancreas TXP?
Most use enteric drainage for pancreatic duct. Take 2nd portion of duodenum from donor along with ampulla of Vater and pancreas, then perform anastomosis of donor duodenum to recipient bowel.
87
Successful pancreas/kidney TXP results in..
Stabilization of retinopathy, decreased neuropathy, increased nerve conduction velocity, decreased autonomic dysfunction (gastroparesis), decreased orthostatic hypotension. No reversal of vascular disease.
88
Complications: pancreas TXP
- Venous thrombosis (#1) - hard to treat
- Rejection - hard to diagnosis if pt does not also have a kidney transplant. (Can see increased glucose or amylase; fever, leukocytosis)
89
How long can a heart store for TXP?
Can store for 6 hours
90
Persistent pulmonary hypertension after heart transplantation
- Associated with early mortality after heart TXP
| - Tx: inhaled nitric oxide, ECMO if severe
91
Chronic allograft vasculopathy (progressive diffuse coronary atherosclerosis)
MCC of late death and death overall following heart TXP
92
How long can you store a lung?
Can store for 6 hours
93
Lung TXP:
| - #1 cause of early mortality
Reperfusion injury (Tx: similar to ARDS)
94
Indication for double-lung TXP
Cystic fibrosis
95
Lung TXP: exclusion criteria for using lungs
Aspiration, moderate to large contusion, infiltrate, purulent sputum, PO2
96
Lung TXP: chronic rejection
bronchiolitis obliterans
| MCC of late death and death overall following lung TXP
97
Opportunistic infections:
- Viral?
- Protozoan?
- Fungal?
- Viral: CMV, HSV, VZV
- Protozoan: Pneumocystis jiroveci pneumonia (reason for Bactrim prophylaxis)
- Fungal: Aspergillus, Candida, Cryptococcus
