Flashcards in Transplant Surgery Deck (153):
What is an autograft?
Same individual is both donor and recipient
What is an isograft?
Donor and recipient are genetically identical
What is an allograft?
Donor and recipient are genetically dissimilar, but of the same species
What is a xenograft?
Donor and recipient belong to different species
What is an orthotopic transplant?
Donor organ is placed in normal anatomic position
What is a heterotopic transplant?
Donor organ is placed in a different site than the normal anatomic position
What is a paratopic transplant?
Donor organ is placed close to original organ
What is chimerism?
Sharing cells between the graft and donor
What are histocompatibility antigens?
Distinct (genetically inherited) cell surface proteins of the human leukocyte antigen (HLA) system
Why are histocompatibility antigens important?
They are targets (class I antigens) and initiators (class II antigens) of immune response to donor tissue
Which cells have class I antigens?
All nucleated cells
Which cells have class II antigens?
Macrophages, monocytes, B cells, activated T cells, endothelial cells
What are the gene products of MHC called in humans?
What is the location of the MHC complex?
Short arm of chromosome 6
What is a haplotype?
Combination of HLA genes on a chromosome inherited from one parent (thus, two siblings have a 25% chance of being haploidentical)
Does HLA matching matter in organ transplantation?
With recent improvement in immunosuppression, the effect is largely obscured, but it still does matter.
The most important ones to match in order to improve renal allograft survival are HLA-B and HLA-DR.
What is the source of T cells?
What is the function of T cells?
Cell-mediated immunity and rejection
What are the types of T cells?
Th (CD4): helper T cells (help B cells become plasma cells).
Ts (CD8): suppressor T cells (regulate immune response).
Tc (CD8): cytotoxic T cells (kill cell by direct contact).
What is the function of B cells?
What is the cell type that produces antibodies?
B cells differentiate into plasma cells
What is a macrophage?
Monocyte in parenchymal tissue
What is the function of macrophages?
Process foreign protein and present it to lymphocytes
What is an APC?
What is the sequence of events leading to antibody production?
1. Macrophage engulfs antigen and presents it to Th cells. The macrophage produces IL-1.
2. Th cells then produce IL-2, and the Th cells proliferate.
3. Th cells then activate (via IL-4) B cells that differentiate into plasma cells, which produce antibodies against the antigen presented.
Who needs to be immunosuppressed?
All recipients (except autograft or isograft)
What are the major drugs used for immunosuppression?
Triple therapy: corticosteroids, azathioprine, cyclosporine/tacrolimus.
Also, OKT3, ATGAM, mycophenolate.
What is the advantage of triple therapy immunosuppression?
Employs three immunosuppressive drugs, therefore, a lower dose of each can be used, decreasing the toxic side effects of each
What is induction therapy?
High doses of immunosuppressive drugs to induce immunosuppression
Which corticosteroid is most commonly used in transplants?
How does prednisone function?
Primarily blocks production of IL-1 by macrophages and stabilizes lysosomal membrane of macrophages
What is the associated toxicity with corticosteroids?
Cushing's syndrome, alopecia, striae, HTN, diabetes, pancreatitis, ulcer disease, osteomalacia, aseptic necrosis (especially of the femoral head)
What is the relative potency of the commonly used corticosteroids?
How does azathioprine (Muran) function?
Prodrug that is cleaved into mercaptopurine.
Inhibits synthesis of DNA and RNA, leading to decreased cellular (T/B) production.
What is the associated toxicity with azathioprine?
Toxic to bone marrow (leukopenia and thrombocytopenia), hepatotoxic, associated with pancreatitis
When should a lower dose of azathioprine be administered?
When WBC is < 4
What is the associated drug interaction involving azathioprine?
Decrease dose if patient is also on allopurinol, because allopurinol inhibits the enzyme xanthine oxidase, which is necessary for the breakdown of azathioprine
What is the function of cyclosporine?
Inhibits production of IL-2 by Th cells
What is the associated toxicity with cyclosporine?
11 H's and 3 N's:
Hepatitis, Hypertrichosis, gingival Hyperplasia, Hyperlipidemia, Hyperglycemia, Hypertension, HUS, Hyperkalemia, Hypercalcemia, Hypomagnesemia, Hyperuricemia.
Nephrotoxicity, Neurotoxicity (headache, tremor), Neoplasia (lymphoma, KS, SCC).
What drugs increase cyclosporine levels?
Diltiazema, ketoconazole, erythromycin, fluconazole, ranitidine
What drugs decrease cyclosporine levels?
Dilantin, Tegretol, rifampin, isoniazid, barbiturates
What are the drugs of choice for hypertension from cyclosporine?
How does ATGAM function?
Antibody against thymocytes, lymphocytes (polyclonal)
What is ATGAM?
When is ATGAM typically used?
What is the associated toxicity with ATGAM?
Thrombocytopenia, leukopenia, serum sickness, rigors, fever, anaphylaxis, increased risk of viral infection, arthralgia
How does OKT3 function?
Monoclonal antibody that binds CD3 receptor (on T cells)
What is a major problem with multiple doses of OKT3?
Blocking antibodies develop, and OKT3 is less effective each time it's used
What are basiliximab and daclizumab?
Anti-CD25 monoclonal antibodies
What is tacrolimus also known as?
How does tacrolimus work?
Blocks IL-2 receptor expression, inhibits T cells
What is the potency of tacrolimus compared to cyclosporine?
What are the side effects of tacrolimus?
Nephrotoxicity and CNS toxicity (tremor, seizure, parasthesia, coma), hyperkalemia, alopecia, diabetes
What is sirolimus also known as?
How does sirolimus work?
Blocks T-cell signaling
What is the associated toxicity with sirolimus?
Hypertriglyceridemia, thrombocytopenia, wound-healing problems, anemia, oral ulcers
What is MMF?
Mycophenolate MoFetil (CellCept)
How does MMF work?
Inhibitor of inosine monophosphate dehydrogenase required for de novo purine synthesis which expanding T and B cells depend on.
Also inhibits adhesion molecule and antibody production.
How is ABO crossmatching performed?
Same procedure as in blood typing
What is the purpose of lymphocytotoxic crossmatching?
Tests for HLA antibodies in serum.
Most important in kidney and pancreas transplants.
How is HLA crossmatching performed?
Mix recipient serum with donor lymphocyte and rabbit complement
Is HLA crossmatching important?
Yes, for kidney and pancreas transplants
How many methods of rejection are there?
2: humoral and cell-mediated
What are the 4 types of rejection and their associated time courses?
1. Hyperacute (immediate in OR)
2. Accelerated acute (7-10 days post-transplant)
3. Acute (weeks-months post-transplant)
4. Chronic (months-years post-transplant)
What happens in hyperacute rejection?
Anti-graft antibodies in recipient recognize foreign antigen immediately after blood perfuses transplanted organ
What happens in acute rejection?
T cell-mediated rejection
What type of rejection is responsible for chronic rejection?
Cellular, antibody (humoral), or both
What is the treatment for hyperacute rejection?
Remove transplanted organ
What is the treatment for acute rejection?
What is the treatment for chronic rejection?
Not much (irreversible) or re-transplant
What is the optimal storage temperature of an organ?
4 C (keep on ice in a cooler)
Why should the transplant organ be kept cold?
Cold decreases the rate of chemical reactions.
Decreased energy use minimizes effects of hypoxia and ischemia.
What is U-W solution?
University of Wisconsin solution, containing potassium phosphate, buffers, starch, steroids, insulin, electrolytes, adenosine.
Used to perfuse an organ prior to removal from the donor.
Why should U-W solution be used?
Lengthens organ preservation time
What is the maximum time between heart harvest and transplant?
What is the maximum time between lung harvest and transplant?
What is the maximum time between pancreas harvest and transplant?
What is the maximum time between liver harvest and transplant?
What is the maximum time between kidney harvest and transplant?
In what year was the first kidney transplant performed in man?
Who performed the first human kidney transplant?
Joseph E. Murray
What are the indications for kidney transplant?
Glomerulonephritis, pyelonephritis, polycystic kidney disease, malignant HTN, reflux pyelonephritis, Goodpasture's syndrome, congenital renal hyperplasia, Fabry's disease, Alport's syndrome, renal cortical necrosis
What is renal failure?
GFR < 20-25% of normal.
As GFR drops to 5-10% of normal, uremic symptoms begin (e.g. lethargy, seizures, neuropathy, electrolyte disorders).
What is the most common cause for kidney transplants?
What are the sources of donor kidneys?
Deceased donor (70%), living related donor
What survival rate is associated with kidney transplant from deceased donor source?
1-year patient survival: 90% if HLA-matched, 80% if not.
3-year graft survival: 75%.
What survival rate is associated with kidney transplant from living related donor source?
1-year patient survival: 95%
3-year graft survival: 85%
What are the tests for kidney compatibility?
ABO, HLA typing
If a choice of left or right donor kidney is available, which is preferred?
Left (longer renal vein allows for easier anastomosis)
Should the placement of the transplanted kidney be heterotopic or orthotopic? Why?
Heterotopic (retroperitoneal in the RLQ or LLQ above the inguinal ligament).
Preserves native kidneys, allows easy access to iliac vessels, places ureter close to the bladder, easy to biopsy kidney.
What anastomoses are formed with a heterotopic kidney transplant?
1. Renal artery to iliac artery
2. Renal vein to iliac vein
3. Ureter to bladder
What is the correct placement of the ureter in a heterotopic kidney transplant?
Submucosally through the bladder wall (decreases reflux)
What is the differential diagnosis of post-renal transplant fluid collection?
Hematoma, Abscess, Urinoma, Lymphocele
What is the indication for removal of native kidneys in a kidney transplant?
Uncontrollable HTN, ongoing renal sepsis
What is the red flag that indicates kidney rejection?
How is U/S with Doppler used in the workup for kidney rejection?
Look at flow in portal vein, hepatic artery.
Rule out thrombosis, leaky anastomosis, infection (abscess).
How is a cholangiogram used in the workup for kidney rejection?
Look at bile ducts
How is a biopsy used in the workup for kidney rejection?
Especially important 3-6 weeks post-op, when CMV is of greatest concern
Does hepatorenal syndrome renal function improve after liver transplant?
What percentage of kidney transplant patients requires re-transplant?
What are the reason for kidney re-transplant?
Primary graft dysfunction, rejection, infection, vascular thrombosis, recurrence of primary disease
Who performed the first pancreas transplant?
Richard C. Lillehei and William D. Kelly (1966)
What are the indications for pancreas transplant?
Type I (juvenile) diabetes associated with severe complications (renal failure, blindness, neuropathy) or very poor glucose control
What are the tests for pancreas compatibility?
ABO, HLA-DR matching (class II)
What is the placement of a pancreas transplant?
Heterotopic, in iliac fossa, or paratopic
Where is anastomosis of the exocrine duct in heterotopic pancreas placement? Why?
To the bladder.
Measures the amount of amylase in urine, gives an indication of pancreatic function.
What is the associated electrolyte complication with pancreas transplants?
Loss of bicarbonate
Where is anastomosis of the exocrine duct in paratopic pancreas placement?
To the jejunum
What is the advantage of paratopic pancreas placement?
Endocrine function drains to the portal vein directly to the liver, and pancreatic contents stay within the GI tract (no need to replace bicarbonate)
What are the red flags indicating pancreas rejection?
Hyperamylasemia, hyperglycemia, hypoamylasuria, graft tenderness
Why should the kidney and pancreas be transplanted together?
Kidney function is a better indicator of rejection.
Also better survival of graft is associated with kidney-pancreas transplant than pancreas alone.
Why is hyperglycemia not a good indicator for pancreas rejection surveillance?
Appears relatively late with pancreatic rejection
Who performed the first heart transplant?
Christiaan Barnard (1967)
What are the indications for heart transplant?
< 65 years with terminal acquired heart disease
What are the contraindications to heart transplant?
Active infection, poor pulmonary function, increased pulmonary artery resistance
What are the tests for heart compatibility?
What is the placement for a heart transplant?
Orthotopic anastomosis of atria, aorta, pulmonary artery
What is sewn together in a heart transplant?
Donar heart atria, pulmonary artery, aorta are sewn to the recipient heart atria, pulmonary artery, aorta
What are the red flags of heart rejection?
Fever, hypotension or hypertension, increased T4/T8 ratio
What is coronary artery vasculopathy?
Small vessel occlusion from chronic rejection of heart transplant.
Often requires re-transplant.
What are the tests for heart rejection?
What are survival statistics for heart transplants?
1 year: 85%
5 years: 65%
What is the anastomosis in a living donor intestinal transplantation?
Ileocolic artery and vein
What is the anastomosis in a deceased donor intestinal transplantation?
What are the indications for an intestinal transplantation?
Short gut syndrome, motility disorders, inability to sustain TPN (liver failure, lack of venous access, etc.)
What is a common postoperative problem with intestinal transplantations other than rejection?
GVHD from lymphoid tissue in transplanted intestines
What is GVHD?
What is the most common cause of death after intestinal transplantation?
How is intestinal rejection surveillance conducted?
What is the clinical clue to intestinal rejection?
Who performed the first lung transplant?
James Hardy (1963)
What are the indications for lung transplant?
Pulmonary fibrosis, COPD, eosinophilic granuloma, primary pulmonary HTN, Eisenmenger's syndrome, CF
What are the contraindications to lung transplant?
Current smoking, active infection
What tests comprise the pre-transplant assessment of a lung recipient?
1. Pulmonary: PFTs, VQ scan
2. Cardiac: echo, cath, angiogram
3. Exercise tolerance test
What are the lung donor requirements?
< 55 years; clear CXR; PA O2 tension of 300 on 100% O2 and 5 cm PEEP; no purulent secretions on bronchoscopy
What are necessary anastomoses in a lung transplant?
Bronchi, PA, pulmonary veins (bronchial artery not necessary)
What are the postoperative complications with lung transplant?
Bronchial necrosis or stricture, reperfusion, pulmonary edema, rejection
What are the red flags of lung rejection?
Decreased arterial O2 tension; fever; increased fatigability; infiltrate on CXR
What is chronic lung rejection called?
What are the survival rates for lung transplant?
1 year: 80%
3 years: 70%
What are 4 major complications of transplants?
3. Post-transplant lymphoproliferative disease
4. Complications of steroids
What are the usual agents of infection post-transplant?
DNA viruses (CMV, HSV, VZV)
When should CMV infection be suspected post-transplant?
> 21 days
What is the time of peak incidence of CMV infections post-transplant?
What are the signs and symptoms of post-transplant CMV infection?
Fever, neutropenia, signs of transplant rejection.
Also can present as viral pneumonitis, hepatitis, colitis.
How is post-transplant CMV infection diagnosed?
Biopsy of transplant to differentiate rejection; cultures of blood, urine
What is the treatment for post-transplant CMV infection?
Ganciclovir +/- immunoglobulin
What are the complications of ganciclovir?
Bone marrow suppression
What are the signs and symptoms of post-transplant HSV infection?
Herpetic lesions, shingles, fever, neutropenia, rejection of transplant
What is the treatment for post-transplant HSV infection?
Acyclovir until patient is asymptomatic
What are the most common types of post-transplant malignancies?
Skin/lip cancer, B-cell cancer, cervical cancer, T-cell lymphoma, Kaposi's sarcoma
What is post-transplant lymphoma associated with?
Multiple doses of OKT3; EBV; youth