Transplant Flashcards
Orthotopic vs heterotopic transplant
Orthotopic: transplant graft placed in its anatomic position. Heterotopic: graft placed at different site
Brain death declaration criteria for adults
No cerebral function (in coma); no brainstem function (no CN functions, no CN reflexes such as papillary, conreal, cold water calorics, Doll’s eyes, or gag); no spontaneous breathing (as shown by apnea test)
Brain death criteria for peds
TWO exams/apnea tests/EEGs 12-48 hrs apart (depending on age, younger needs longer time in between exams)
What are the MHC alleles?
MHC I: A, B, C. MHC II: DR, DQ, DP
Which of the MHC alleles are used for tissue typing?
A, B, and DR. DR is the most important to match
Why does matching paradoxically result in worse outcomes in liver transplant?
HLA presents viral peptides to T cells, and compatibility may potentiate the inflammatory phase of viral reinfection after transplant, increasing chance of recurrence of original disease
Steroids
Medium dose for maintenance, high dose for rejection
Cyclosporine (CsA)
Calcineurin inhibitor, used for maintenance only. P450 metabolism. Side effects include: nephrotoxicity, HTN, hypertricosis, gingival hyperplasia, hepatoxicity
Mycophenolate mofetil (MMF)
Aka Cellcept, used for maintenance or rejection. Works by inhibiting purine metabolism. Side effects: diarrhea, nausea.
Azathioprine
Inhibits DNA synthesis. Used for maintenance only. Side effects: leukopenia, hepatotoxicity (don’t use in liver tx)
FK-506, aka tacrolimus
Used for maintenance, preferred drug in liver transplant. Calcineurin inhibitor, way more potent than cyclosporine. Side effects: nephrotoxicity, neurotoxicity, diabetogenic
Rapamycin
Calcineurin inhibitor. Side effects: hyperTG
Antibodies used in transplant management
Antithymocyte globulin (ATG), OKT3 (antibody to CD3). Usually used for rescue in steroid-resistant rejection but also can be used for induction and maintenance.
Post-transplant lymphoproliferative disorder
Caused by EBV -> monoclonal B-cell lymphoma. Tx: stop or lower immunosupression, and it can be reversible (not always)
Hyperacute rejection
Immediately following graft reperfusion. Caused by pre-existing host antibody binding to donor tissue, initiating complement mediated lysis -> thrombosis of graft. No treatment, graft will be lost. Prevent by ABO typing and negative crossmatch.
Delayed vascular rejection
A variant of hyperacute rejection in which the level of host antibodies is too low to be detected by usual assays. Rejection occurs around POD 3
Acute rejection
Occurs between POD 5 and 6 months, occurs to some degree in all transplants unless btw identical twins. Due to normal T cell activity. Dx: biopsy. Tx: steroids, immune globulins if refractory. Over 90% of transplants salvaged with treatment.
Chronic rejection
Occurs over months to years. Due to cumulative effect of recognition of donor MHC by recipient immune system, likely antibody AND cell mediated.
Histology of chronic rejection
Chronic rejection in heart grafts is felt to be manifest by accelerated graft atherosclerosis. Kidneys with chronic rejection have fibrosis (scarring) and damage to the microvasculature. Livers: decreased number of bile ducts on biopsy, “vanishing bile duct syndrome”. Transplanted lungs: “bronchiolitis obilterans” a scarring problem in the substance of the lung.
Most common causes of ESRD, adults
- DM
- HTN
- Glomerulonephritis
Peds: congenital uro/renal stuff
Complications specific to kidney transplant, early
Delayed graft function (must operate), graft thrombosis (must repair), urine leak (usu at VUJ, must repair), bleeding
Complications specific to kidney transplant, late
Lymphocele (perinephric fluid collection compressing iliac vein and ureter, may have to drain), ureteral stricture (rising creatinine, balloon dilate or surgery), renal artery stenosis (HTN, fluid retention, angioplasty or surgery)
Delayed graft function
Delayed graft function is a form of acute renal failure resulting in post-transplantation oliguria, increased allograft immunogenicity and risk of acute rejection episodes, and decreased long-term survival.
Indication for pancreatic transplant
Type I insulini dependent diabetes,
Two types of drainage for pancreatic transplant
Bladder (can measure urinary amylase, if decreased it is sign of rejection) or enteric (pro is no need for bicarb replacement). Equal efficacy, mortality, etc.
Preferred immunosuppresive drug in liver transplant
Tacrolimus (remember, nephrotoxic). Also, steroids, azathioprine, cyclosporine. May have steroid + 1-2 calcineurin inhibitor(s), or wean down to just 1 calcineuron inhibitor.
Small bowel transplant
This is a thing apparently
Most common cause of perioperative death in cardiac transplant?
Infection (PNA, mediastinitis, CLABSI, UTI)
Calcineurin inhibitors MOA
Ultimately inhibits release of IL-2, which is necessary for stimulating T cell expansion and differentiation
OKT3 side effects
Fevers and headaches from cytokine release. Noncardiogenic pulmonary edema, encephalitis, nephrotoxicity, aseptic meningitis