CHAPTER 12- TRANSPLANTATION.txt

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CHAPTER 12- TRANSPLANTATION.txt
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2012-01-07 18:14:39
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  1. What is most important in recipient/donor matching?
    What is the most important overall?
    • 1) HLA-A, -B, and -DR
    • 2) Most important overall is HLA-DR
  2. ABO compatibility:
    generally required for all transplants (except liver)
  3. Crossmatch:
    1) detects preformed recipient antibodies by mixing recipient serum with donor lymphocytes--> would generally cause hyperacute rejection (except liver)
  4. Panel reactive antibody (PRA)
    • 1) technique identical to crossmatch; detects preformed recipient antibodies using panel of typing cells
    • 2) get a percentage of cells that the serum reacts with
    • 3) What can increase PRA:
    • 1- transfusions
    • 2- pregnancy
    • 3- previous transplant
    • 4- autoimmune diseases
  5. How do you treat a minor rejection?
    pulse steroids
  6. Severe or secondary rejection:
    OKT3 or other drugs
  7. What is the #1 malignancy following any transplant?
    Skin cancer is the #1 malignancy following any transplant (squamous cell Ca #1)
  8. Posttransplant lymphoproliferative disorder (PTLD):
    • 1) next most common malignancy following transplant- Epstein-Barr virus related
    • 2) Tx: withdrawal of immunosuppression; may need chemotherapy and XRT for aggressive tumor
  9. Drugs (following slides):
  10. Azathioprine (Imuran):
    • 1) inhibits de novo purine synthesis, which inhibits T cells
    • 2) 6-mercaptopurine is the active metabolite (formed in the liver)
    • 3) Side effects: myelosuppression
    • 4) Keeps WBCs >3
  11. Mycophenolate
    similar action to azathioprine
  12. steroids
    inhibit genes for cytokine synthesis (IL-1, IL-6) and macrophages
  13. Cyclosporin (CSA):
    • 1) binds cyclophilin protein and inhibits genes for cytokine synthesis (IL-2, IL-3, IL-4, INF-gamma)
    • 2) side effects:
    • 1- nephrotoxicity
    • 2- hepatotoxicity
    • 3- HUS
    • 4- tremors
    • 5- seizures
    • 3) keeps trough 200-300
    • 4) undergoes hepatic metabolism and biliary excretion
  14. FK-506 (prograf)
    • 1) binds FK-binding protein; actions similar to CSA but 10-100x more potent
    • 2) Side effects:
    • 1) nephrotoxicity
    • 2) mood changes
    • 3) more GI and neurologic changes than CSA
    • 4) keeps trough 10-15
  15. ATGAM
    • 1) equine polyclonal antibodies directed against antigens on T cells (CD2, CD3, CD4, CD8, CD11/18)
    • 2) used for induction therapy
    • 3) complement dependent
    • 4) keeps peripheral T-cell count >3
  16. Thymoglobulin
    • 1) rabbit polyclonal antibodies
    • 2) similar action as ATGAM
  17. OKT3
    • 1) monoclonal antibodies that block antigen recognition function of T cells by binding CD3, inhibiting T-cell receptor complex
    • 2) interferes with both class I and II MHC
    • 3) causes CD3 opsonization that is complement dependent
    • 4) used for severe rejection
    • 5) follows peripheral CD3 cells
    • 6) Side effects:
    • 1- fever
    • 2- chills
    • 3- pulmonary edema
    • 4- shock
  18. Zenapax
    • 1) human monoclonal antibody against IL-2 receptors
    • 2) used with induction and to treat rejection
  19. Types of rejection (following slides):
  20. Hyperacute rejection:
    • 1) occurs within minutes to hours
    • 2) caused by preformed antibodies that should have been picked up by the crossmatch
    • 3) activates the complement cascade and thrombosis of vessels occurs
    • 4) Tx: emergent retransplant
  21. Accelerated rejection:
    • 1) occurs <1 week
    • 2) caused by sensitized T cells to donor antigens
    • 3) produces a secondary immune response
    • 4) Tx:
    • 1- increased immunosuppression
    • 2- pulse steroids
    • 3- possibly OKT3
  22. Acute rejection:
    • 1) occurs 1 week to 1 month
    • 2) caused by T cells (cytotoxic and helper T cells)
    • 3) Tx: increased immunosuppression, pulse steroids, and possibly OKT3
  23. Chronic rejection
    • 1) months to years
    • 2) partially a type IV hypersensitivity reaction (sensitized T cells)
    • 2) antibody formation also plays a role; leads to graft fibrosis and vascular damage
    • 3) monocytes and cytotoxic T cells have a role
    • 4) Tx: increased immunosuppression or OKT3- not really effective treatment
  24. Kidney Transplantation
    • 1) can store kidney for 48 hours
    • 2) need ABO type and crossmatch
    • 3) UTI- can still use kidney
    • 4) Acute increase in creatinine (1-3)- can still use kidney
    • 5) mortality primarily from stroke and MI
    • 6) attach to iliac vessels
  25. Complications of kidney transplant:
    • 1) Urine leaks (#1)- Tx: drainage and stenting usually first; may need reoperation
    • 2) Renal artery stenosis- diagnosed with ultrasound
    • Tx: PTA with stent
    • 3) Lymphocele- most common cause of external compression
    • Tx: 1st percutaneous drainage; if that fails, then need intraperitoneal marsupialization
    • 4) Postop oliguria- usually due to ATN (pathology shows hydrophobic changes)
    • 5) Postop diuresis- usually due to urea and glucose
    • 6) New proteinuria- suggestive of renal vein thrombosis
    • 7) Postop diabetes- side effect of CSA, FK, steroids
    • 8) Viral infections-
    • CMV- Tx: ganciclovir
    • HSV- Tx: acyclovir
  26. Acute rejection:
    • 1)usually occurs in 1st 6 months
    • 2) pathology shows tubulitis or vasculitis with more severe form
  27. Kidney rejection workup:
    • 1) usually for increased creatinine
    • 2) ultrasound with duplex (to rule out vascular problem and ureteral obstruction) and biopsy; empiric decrease in CSA or FK (these can be nephrotoxic); pulse steroids
  28. Chronic Kidney transplant rejection:
    usually do not see until after 1 year; no good treatment
  29. 5 year graft survival overall (kidney):
    70% (cadaveric 65%, living donors 75%)
  30. Living Kidney Donors:
    • 1) Most common complication:wound infection (1%)
    • 2) Most common cause of death: fatal PE
    • 3) The remaining kidney hypertrophies
  31. Liver Transplantation (slides to follow):
  32. How long can you store liver for?
    24 hours
  33. Contraindications to liver TXP:
    • 1) current EtOH abuse
    • 2) acute ulcerative colitis
  34. What is the most common reason for liver TXP in adults?
    chronic hepatitis
  35. Criteria for emergent TXP:
    • 1) stage III (stupor)
    • 2) stage IV (coma)
  36. Treatment for hepatitis B antigenemia:
    Patients with hepatitis B antigenemia can be treated with HBIG (hepatitis B immunoglobulin) and lamivudine (protease inhibitor) postoperatively
  37. Hepatocellular Ca
    if single tumor <5cm or up to 3 tumors each <3cm, can still consider TXP
  38. Portal vein thrombosis:
    not a contraindication to TXP
  39. What is the best predictor of 1-year survival?
    APACHE score
  40. What disease is most likely to recur in new liver allograft?
    • 1) Hepatitis C- disease most likely to recur in the new liver allograft
    • 2) reinfects essentially all grafts
  41. Hepatitis B-
    reinfection rate has been reduced to 20% with the use of HBIG
  42. EtOH:
    20% will start drinking again (recidivism)
  43. Macrosteatosis:
    • 1) extracellular fat globules in the liver allograft
    • 2) #1 predictor of primary nonfunction
    • 3) if 50% of cross section is macrosteatatic in potential donor liver, there is a 50% chance of primary nonfunction
  44. 1) duct-to-duct anastomosis is performed
    2) hepaticojejunostomy in kids
    3) right subhepatic, right and left subdiaphragmatic drains
    4) Biliary system (ducts, etc.) depends on hepatic artery blood supply
    5) Most common arterial anomaly- right hepatic coming off SMA
  45. Complications of Liver Tx:
    • 1) Bile leak #1
    • Tx: PTC tube and stent
    • 2) Primary nonfunction: (usually requires retransplantation)
    • 1st 24 hrs-
    • 1- total bilirubin >10
    • 2- bile output <20cc/12h
    • 3- PT and PTT 1.5x normal
    • After 96 hours
    • 1- hyperkalemia
    • 2- mental status changes
    • 3- increased LFTs
    • 4- renal and respiratory failure
    • 3) Hepatic Artery Thrombosis:
    • Tx: angio (potentially treated with angiography and baloon dilatation +/- stent), surgery, retransplanation; hepatic vein thrombosis rare
    • 4) Abscesses- most common from chronic hepatic artery thrombosis
    • 5) IVC stenosis- edema, ascites, renal insufficiency
    • 6) Cholangitis- get PMNs around portal triad, not mixed infilatrate
  46. Acute rejection of liver txp:
    • 1) Usually occurs in 1st 12 months
    • 2) T cell mediated against blood vessels
    • 3) Clinical:
    • 1- fever, jaundice, decreased bile output, change in bile consistency
    • 2- Labs: leukocytosis, eosinophilia, increased LFTs, total bilirubin/and PT
    • 4) Pathology- shows portal lymphocytosis, endotheliitis (mixed infiltrate), and bile duct injury
  47. Chronic rejection of Liver txp:
    • 1) dissapearing bile ducts (antibody and cellular attack on bile ducts)
    • 2) gradually get bile duct obstruction with increase in alk phosphatase, portal fibrosis
    • 3)acute rejection most common predictor
  48. Retransplantation rate for livers:
    5 year survival rate:
    • Retransplantation rate for livers: 20%
    • 5 year survival rate:70%
  49. Pancreas Transplantation
    • 1) need donor celiac and SMA for arterial supply
    • 2) need donor portal vein for venous drainage
    • 3) Attach to iliac vessels
    • 4) most use enteric drainage for pancreatic duct. Take second portion of duodenum from donor along with ampulla of vatar and pancreas, then perform anastomosis of donor duodenum to recipient bowel
  50. Successful pancrease/kidney TXP results in:
    • 1) stabilization of retinopathy
    • 2) decreased neuropathy
    • 3) increased nerve conduction and velocity
    • 4) decrease autonomic dysfunction (gastroparesis)
    • 5) deceased orthostatic hypotension
    • 1- no reversal of vascular disease
  51. Complications of pancreas txp:
    • Thrombosis (#1): hard to treat
    • Rejection: hard to diagnose if patient does not also have a kidney transplant
    • 1) can see increased:
    • 1- glucoe
    • 2- amylase
    • 3- trypsinogen
    • 4- fever/leukocytosis
  52. Heart Txp:
    • 1) can store for 6 hours
    • 2) need ABO compatibility and crossmatch
    • 3) for patients with life expectancy <1 year
  53. Persistent pulmonary hypertension after heart transplantation:
    • 1) Tx:
    • 1- Flolan (PGI2)
    • 2- inhaled nitric oxide
    • 3- ECMO if severe

    2) Associated with increased morbidity and mortality after heart txp
  54. Acute rejection of heart txp:

    Chronic rejection of heart txp:
    • Acute rejection of heart txp:
    • shows perivascular infiltrate with increased grades of myocyte inflammation and necrosis

    • Chronic rejection of heart txp:
    • progressive diffuse coronary atherosclerosis
  55. Lung Transplantation
    • 1) can store for 6 hours
    • 2) need ABO compatibility and crossmatch
    • 3) for patients with life expectancy <1 year
  56. #1 cause of early mortality in lung txp:
    reperfusion injury
  57. Name an indication for double lung txp:
    cystic fibrosis
  58. Exclusion criteria for using lungs:
    • 1) aspiration
    • 2) moderate to large contusion
    • 3) infiltrate
    • 4) purulent sputum
    • 5) PO2 <350 on 100% FiO2 and PEEP 5
  59. Acute rejection of lung txp:
    perivascular lymphocytosis
  60. Chronic rejection of lung txp:
    bronchiolitis obliterans
  61. Opportunistic infections:

    Viral:
    Protozoan:
    Fungal:
    • Viral:
    • 1- CMV
    • 2- HSV
    • 3- VZV

    • Protozoan:
    • 1- pneumocystis jiroveci (P. carinii) pneumonia (reason for bactrim prophylaxis)

    • Fungal:
    • 1- aspergillus
    • 2- candida
    • 3- cryptococcus
  62. Hierarchy for permission for organ donation from next of kin:
    • 1) spouse
    • 2) adult son or daughter
    • 3) either parent
    • 4) adult brother or sister
    • 5) guardian
    • 6) another other person authorized to dispose of the body

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