Chapter 12 - Transplant Flashcards
Which HLA antigens are most important in recipient/donor matching?
HLA -A, -B, -DR (-DR most important overall)
ABO blood compatibility is not required for which transplant?
Liver
How is a crossmatch performed?
By mixing recipient serum with donor lymphocytes
What does a crossmatch detect?
Detects preformed antibodies; would generally cause hyperacute rejection
What is a panel reactive antibody (PRA)?
Technique identical to crossmatch; detects preformed recipient antibodies using a panel of typing cells
What can increase PRA?
Transfusions, pregnancy, previous transplant, autoimmune diseases
Treatment for mild rejection?
Pulse steroids
Treatment for severe or secondary rejection?
OKT3 or other drugs
1 malignancy following any transplant?
Skin cancer (squamous cell CA #1)
2 most common malignancy following transplant?
Posttransplant lymphoproliferative disorder (EBV-related)
Treatment for PTLD?
Withdrawal of immunosuppression; may need chemo/XRT for aggressive tumor
Mechanism of action of Azathioprine (Imuran)?
Inhibits de novo purine synthesis (which inhibits T cells); active metabolite is 6-mercaptopurine
Side effects of Azathioprine?
Myelosuppression; keeps WBC >3
Mechanism of action of steroids in anti-rejection?
Inhibit genes for cytokine synthesis (IL-1, IL-6) and macrophages
Mechanism of cyclosporin (CSA)?
Binds cyclophilin protein and inhibits genes for cytokine synthesis (IL-2, IL-3, IL-4, INF-gamma)
Side effects of CSA?
Nephrotoxicity, hepatotoxicity, HUS, tremors, seizures
Mechanism of action of FK-506 (Prograf)?
Binds FK-binding protein; similar to CSA but 10-100x more potent
Side effects of Prograf?
Nephrotoxicity, mood changes, more GI and neurological side effects than CSA
Mechanism of action of ATGAM?
Equine polyclonal antibodies directed against antigens on T cells (CD2, CD3, CD4, CD8, CD11/18)
What is ATGAM used for?
Induction therapy
ATGAM is dependent on what to work?
Complement dependent
Mechanism of action of thymoglobulin?
Rabbit polyclonal antibody; similary action as ATGAM
Mechanism of action of OKT3?
Monoclonal abs that block antigen recognition function of T cells by binding CD3, inhibiting T cell receptor complex; causes CD3 opsonization that is complement dependent
What is OKT3 used for?
Severe rejection
Side effects of OKT3?
Fever, chills, pulmonary edema, shock
Mechanism of action of Zenapax?
Human monoclonal ab againsst IL-2 receptors
When is Zenapax used?
Used with induction and to treat rejection
What is hyperacute rejection?
Within minutes to hours; caused by preformed antibodies that should have been picked up by the crossmatch; activates complement cascade and thrombosis of vessels occurs
Treatment of hyperacute rejection?
Emergent retransplant
What is accelerated rejection?
(<1 wk) Caused by sensitized T cells to donor antigens; produces secondary immune response
Treatment for accelerated rejection?
Increased immunosuppression, pulse steroids, possibly OKT3
What is acute rejection?
(1wk to 1month) Caused by T cells (cytotoxic and helper T cells)
Treatment of acute rejection?
Increased immunosuppression, pulse steroids, possibly OKT3
What is chrnoic rejection?
(months to years) Type IV hypersensitivity reaction (sensitized T cells); Ab formation also plays a role, leads to graft fibrosis and vascular damage
Treatment of chronic rejection?
Increased immunosuppression, OKT3 - no really effective treatment
How long can a kidney be stored?
48 hours
What is the mortality following kidney transplant from?
Stroke and MI
Can a kidney from a patient with a UTI or acute increase in Cr (1.0-3.0) still be used?
YES
Transplanted kidney is attached to what?
Iliac vessels
1 complication following kidney transplant?
Urine leak
Treatment for urine leaks following kidney transplant?
Drainage and stenting usually first; may need reoperation
Other complications of kidney transplant?
Renal arthery stenosis, lymphocele, postop oliguria, postop diuresis, new proteinuria, postop diabetes, viral infections
How is the diagnosis of renal artery stenosis made? Treatment?
Ultrasound; PTA with stent
What is the most common cause of external compression following kidney transplant? Treatment?
Lymphocele; perc drainage, then intraperitoneal marsupialization
What is postop oliguria caused by after kidney transplant?
ATN; path shows hydrophobic changes
What is post-op diuresis caused by following a kidney transplant?
Urea and glucose
What is new proteinuria caused by following a kidney transplant?
Renal vein thrombosis
What causes postop diabetes following kidney transplant?
Side effect of CSA, FK, steroids
What makes up a kidney rejection workup?
Usually done for increase in Cr; US with duplex and biopsy; empiric decrease in CSA or FK; pulse steroids
What is the most common complication for living kidney donors?
Wound infection
What is the most common cause of death in living kidney donors?
Fatal PE
What happens to the remaining kidney in living kidney donors?
Hypertrophies
How long can a liver be stored?
24 hours
What are contraindications to liver transplant?
Current EtOH abuse, acute UC
What is the most common reason for liver transplant in adults?
Chronic hepatitis
What are the criteria for emergent transplant?
Stage III (stupor), stage IV (coma)
What is the best predictor of 1-yr survival following liver transplant?
APACHE score
How can patients with hepatitis B angigenemia be treated following liver transplant?
HBIG and lamivudine (protease inhibitor)
Is portal vein thrombosis a contraindication to transplant?
NO
Is hepatocellular CA a contraindication to transplant?
NO: if single tumor <3cm
What disease is most likely to recur in the new liver allograft?
Hepatitis C; reinfects essentially all grafts
What is the reinfection rate of Hepatitis B?
20% with use of HBIG
What % will start using EtOH again?
20% (recidivism)
What is the #1 predictor of primary nonfunction of liver transplant?
Macrosteatosis; extracellular fat globules in the liver allograft
Where are drains placed following liver transplant?
Right subhepatic, right and left subdiaphragmatic
Biliary system depends on what blood supply?
Hepatic artery
What is the most common arterial anomaly in liver transplant?
Right hepatic off of SMA
1 complication following liver transplant?
Bile leak
Treatment for bile leak?
PTC tube and stent
What are indications of primary nonfunction of liver transplant?
Total bili >10, bile output <20cc/hr, PT and PTT 1.5x normal; after 96 hours: hyperkalemia, mental status changes, inc. LFTs, renal failure, repsiratory failure
Treatment for primary nonfunction of liver transplant?
Retransplantation
Treatment for hepatic artery thrombosis?
Angio (balloon dilation, +/- stent), surgery, retransplantation
What are signsof IVC stenosis following liver transplant?
Edema, ascites, renal insufficiency
Signs of cholangitis on pathology?
PMNs around portal triad, NOT a mixed infiltrate
Signs of acute rejection of liver transplant?
Fever, jaundice, dec. bile output, change in bile consistency; leukocytosis, eosinophilia, inc. LFTs, inc. total bili, inc. PT
Pathology findings in acute rejection of liver transplant?
Portal lympocytosis, endothliitis (mixed infiltrate) and bile duct injury
Most common predictor of chronic rejection?
Acute rejection
Signs of chronic rejection of liver transplant?
Disappearing bile ducts (Ab and cellular attack on bile ducts), gradually get bile duct obstruction in inc. in alk phos, portal fibrosis
Liver retransplantation rate?
20%
5-yr survival rate following liver transplant?
70%
What is the arterial supply for pancreas transplant?
Donor celiac and SMA
What is the venous supply for pancreas transplant?
Donor portal vein
What is the donor pancreas attached to?
Recipient iliac vessels
How is the pancreatic duct drained in pancreas transplant?
Enteric drainage; 2nd portion of duodenum from donor along with ampulla of Vater and pancreas, then perform anastomosis of donor duodenum to recipient bowel
Successful kidney/pancreas transplant results?
Stabilization of retinopathy, dec. neuropathy, inc. nerve conduction velocity, dec. autonomic dysfunction (gastroparesis), inc. orthostatic hypotension
1 complication of pancreas transplant?
Thrombosis - hard to treat
How is rejection of pancreas transplant diagnosed?
Difficulty if pt does not also have a kidney transplant; inc. glucose, amylase or trypsinogen; fever, leukocytosis
How long can a heart be stored?
6 hours
Complications following heart transplantation?
Persistent pulmonary hypertension
Treatment of persistent pulmonary hypertension following heart transplant?
Flolan (PGI2); inhaled NO, ECMO if severe; associated with inc. morbidity and mortality after transplant
Pathologic findings of acute rejection following heart transplant?
Perivascular infiltrate with inc. grades of myocyte inflammation and necrosis
Pathologic findings of chronic rejection following heart transplant?
Progressive diffuse coronary atherosclerosis
How long can lungs be stored for?
6 hours
1 cause of early mortality following lung transplant?
Reperfusion injury
Indication for double lung tranplant?
Cystic fibrosis
Exclusion criteria for using lungs?
Aspiration, moderate to large contusion, infiltrate, purulent sputum, PO2 <350 on 100% FiO2, PEEP 5
Pathologic findings of acute rejection following lung transplant?
Perivascular lymphocytosis
Pathologic findings of chrnoic rejection after lung transplant?
Bronchiolitis obliterans
What is the hierarchy for permission for organ donation from next of kin?
Spouse –> adult son or daughter –> either parent –> adult brother or sister –> guardian –> any other person authorized to dispse of the body
What is bactrim prophylaxis used against?
Pneumocystis jiroveci pneumonia