Transplant Flashcards
1
Q
HLA-A, -B, -DR
A
most important in recipient / donor matching
2
Q
HLA-DR
A
most important overall
3
Q
ABO blood compatibility
A
generally required for all transplants (except liver)
4
Q
Crossmatch
A
detects preformed recipient antibodies by mixing recipient serum with donor lymphocytes; would generally cause hyperacute rejection (except liver)
5
Q
Panel reactive antibody
A
technique identical to crossmatch; detects preformed recipient antibodies using a panel of typing cells; get a percentage of cells that the serum reacts with; transfusions, pregnancy, previous transplant, and autoimmune diseases can all increase PRA
6
Q
Mild rejection
A
pulse steroids
7
Q
Severe or secondary rejection
A
OKT3 or other drugs
8
Q
Skin cancer
A
1 malignancy following any transplant (squamous cell CA #1)
9
Q
Posttransplant lymphoproliferative disorder (PTLD)
A
next most common malignancy following transplant (EBV related)
*tx: withdrawal of immunosuppression; may need chemotherapy and XRT for aggressive tumor
10
Q
Azathioprine (imuran)
A
- inhibits de novo purine synthesis, which inhibits T cells
- 6-mercaptopurine is active metabolite (formed in liver)
- side effects: myelosuppression
- keeps WBCs > 3
11
Q
Mycophenolate (cellcept)
A
inhibits T and B cell proliferation as well as antibody production
12
Q
Cyclosporin (CSA)
A
- binds cyclophilin protein and inhibits genes for cytokine synthesis (IL-2, IL-3, IL-4, INF gamma)
- side effects: nephrotoxicity, hepatotoxicity, HUS, tremors, seizures
- keep trough 200-300
- undergoes hepatic metabolism and biliary excretion
13
Q
FK-506 (prograf)
A
- binds FK-binding protein; actions similar to CSA but 10-100x more potent
- side effects: nephrotoxicity, mood changes; more GI and neurologic changes than CSA
- keep trough 10-15
14
Q
ATGAM
A
- equine polyclonal antibodies directed against antigens on T cells (CD2, CD3, CD4, CD8, CD11/18)
- used for induction therapy
- complement dependent
- keeps peripheral T cell count > 3
15
Q
Thymoglobulin (antithymyocyte globulin rabbit)
A
rabbit polyclonal antibodies that cause immunosuppression by acting against human T cell surface antigens and depleting CD4 lymphocytes
16
Q
OKT3 (muromonab)
A
- monoclonal antibodies that block antigen recognition function of T cells by binding CD3, inhibiting T cell receptor complex
- interferes with both class I and II MHC
- causes CD3 opsonization that is complement dependent
- used for severe rejection
- follows peripheral CD3 cells
- side effects: fever, chills, pulmonary edema, shock
17
Q
zenapax
A
human monoclonal antibody against IL-2 receptors
*used with induction and to treat rejection
18
Q
Hyperacute rejection
A
- occurs within minutes to hours
- caused by preformed antibodies that should have been picked up by the crossmatch
- activates the complement cascade and thrombosis of vessels occurs
- tx: emergent retransplant
19
Q
Accelerated rejection
A
- occurs less than 1 week
- caused by sensitized T cells to donor antigens
- produces a secondary immune response
- tx: increase immunosuppression, pulse steroids, possibly OKT3
20
Q
Acute rejection
A
- occurs 1 week to 1 month
- caused by T cells (cytotoxic and helper T cells)
- tx: increase immunosuppression, pulse steroids, OKT3
21
Q
Chronic rejection
A
- months to years
- partially a type IV hypersensitivity reaction (sensitized T cells)
- antibody formation also plays a role; leads to graft fibrosis and vascular damage
- monocytes and cytotoxic T cells have a role
- tx: increase immunosuppression or OKT3, no really effective treatment
22
Q
kidney transplantation
A
- can store kidney for 48 hours
- need ABO type and crossmatch
- UTI - can still use kidney
- acute increase in creatinine (1.0-3.0), can still use kidney
- mortality primarily from stroke and MI
- attach to iliac vessels
23
Q
kidney transplant complications
A
- urine leaks #1; tx: drainage and stenting usually first, may need reop
- renal artery stenosis - dx with US; tx: PTA with stent
- lymphocele - most common cause of external compression; tx: 1st percutaneous drainage; if that fails, then need intraperitoneal marsupialization (90% successful)
- post op oliguria - usually due to ATN (path shows hydrophobic changes)
- post op diuresis - usually due to urea and glucose
- new proteinuria - suggestive of renal vein thrombosis
- post op diabetes - side effect of CSA, FK, steroids
- viral infections - CMV tx: ganciclovir; HSV tx: acyclovir
24
Q
Kidney transplant rejection
A
- acute rejection usually occurs in 1st 6 months; path shows tubulitis or vasculitis with more severe form
- work up - usually for increase in creatinine; US with duplex (to r/o vascular problem and ureteral obstruction) and biopsy; empiric decrease in CSA or FK (these can be nephrotoxic); pulse steroids
- chronic rejection - usually do not see until after 1 year; no good treatment
- 5 year graft survival overall - 70% (cadaveric 65%, living donors 75%)
25
Q
Living kidney donors
A
- most common complication - wound infection (1%)
- most common cause of death - fatal PE
- the remaining kidney hypertrophies
- kidneys transplanted from deceased pediatric donors aged 5 and below have lower graft survival rates than those from older pediatric and young adult donors; at older extreme of age, graft survival rates are also lower
26
Q
Liver transplantation
A
- can store for 24 hours
- contraindications to liver TXP - current ETOH abuse, acute UC
- chronic hepatitis - most common reason for liver TXP in adults
- criteria for emergent TXP - stage III (stupor), stage IV (coma)
- patients with hepatitis B antigenemia can be treated with HBIG (hepatitis B immunoglobulin) and lamivudine (protease inhibitor) postoperatively
- hepatocellular CA - if single tumor < 5 cm or up to 3 tumors each < 3 cm, can still consider TXP
- portal vein thrombosis - not a contraindication to TXP
- APACHE sore - best predictor of 1 year survival
- hepatitis C - disease most likely to recur in the new liver allograft; reinfects essentially all grafts
- hepatitis B - reinfection rate has been reduced to 20% with the use of HBIG
- ETOH - 20% will start drinking agin (recidivism)
- Macrosteatosis - extracellular fat globules in liver allograft; #1 predictor of primary nonfunction; if 50% of cross section is macrosteatatic in potential donor liver, there is a 50% chance of primary nonfunction
- duct to duct anastomosis is performed
- hepaticojejunostomy in kids
- biliary system depends on hepatic artery blood supply
- most common arterial anomaly - right hepatic coming off SMA
27
Q
Liver Transplant complications
A
- bile leak #1; tx: PTC tube and stent
- primary nonfunction: 1st 24 hours - total bilirubin > 10, bile output < 20 cc / 12h, PT and PTT 1.5 x normal; after 96 hours - hyperkalemia, mental status changes, increase LFTs, renal failure, respiratory failure; usually requires retransplantation
- hepatic artery thrombosis - tx: angio (potentially treated with angiography and balloon dilation +/- stent), surgery, retransplantation; hepatic vein thrombosis rare
- abscesses - most common from chronic hepatic artery thrombosis
- IVC stenosis - edema, ascites, renal insufficiency
- cholangitis - get PMNs around portal triad, not mixed infiltrate
28
Q
Liver transplant rejection
A
- acute rejection - T cell mediated against blood vessels; — clinical: fever, jaundice, decrease bile output, change in bile consistency
- labs: leukocytosis, eosinophilia, increase LFTs, total bili, and PT
- path: shows portal lymphocytosis, endotheliitis (mixed infiltrate), and bile duct injury
- usually occurs in 1st 2 months
- chronic rejection - disappearing bile ducts (antibody and cellular attack on bile ducts); gradually get bile duct obstruction with increase in alkaline phosphatase, portal fibrosis (acute rejection most common predictor)
- retransplantation rate 20%
- 5 year survival rate 70%
29
Q
Pancreas Transplantation
A
- need donor celiac and SMA for arterial supply
- need donor portal vein for venous drainage
- attach to iliac vessels
- most use enteric drainage for pancreatic duct; take second portion of duodenum from donor along with ampulla of Vater and pancreas, then perform anastomosis of donor duodenum to recipient bowel
- successful pancreas/kidney TXP results in stabilization of retinopathy, decrease neuropathy, increase nerve conduction velocity, decrease autonomic dysfunction (gastroparesis), decrease orthostatic hypotension
- no reversal of vascular disease
30
Q
Pancreas transplant comlications
A
- thrombosis #1 - hard to treat
- rejection - hard to diagnose if patient does not also have a kidney transplant; can see increase glucose, amylase, or trypsinogen; fever, leukocytosis
31
Q
Heart transplantation
A
- can store for 6 hours
- need ABO compatibility and crossmatch
- for patients with life expectancy < 1 year
- persistent pulmonary HTN after heart transplant; tx: Flolan (PGI2); inhaled nitric oxide, ECMO if severe; assoc with increase morbidity and mortality after heart TXP
32
Q
Heart TXP rejection
A
- acute rejection: shows perivascular infiltrate with increase grades of myocyte inflmmation and necrosis
- chronic rejection - progressive diffuse coronary atherosclerosis
33
Q
Lung transplant
A
- can store for 6 hours
- need ABO compatibility and crossmatch
- for patients with life expectancy < 1 year
- # 1 cause of early mortality - reperfusion injury
- indication for double lung TXP - cystic fibrosis
- exclusion criteria for using lungs - aspiration, mod to large contusion, infiltrate, purulent sputum, PO2 < 350 on 100% FiO2 and PEEP 5
- acute rejection - perivascular lymphocytosis
- chronic rejection - bronchiolitis obliterans
34
Q
Opportunistic Infection
A
- viral - CMV, HSV, VZV
- protozoan - Pneumocystis jiroveci (P carinii) pneumonia (reason for Bactrim for prophylaxis)
- fungal - Aspergillus, candida, cryptococcus
35
Q
Hierarchy for permission for organ donation from next of kin
A
- spouse
- adult son or daughter
- either parent
- adult brother or sister
- guardian
- any other person authorized to dispose of the body
