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Organ transplantation

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					Organ transplantation
    Rajeev Suryavanshi
   Dept of General Surgery
            Transplantation:
 Process  of taking a graft – cell, tissue or
  organs – from one individual – the donor-
  and placing into another individual – the
  recipient.
 Orthotopic – graft at normal anatomical
  location ( liver, heart)
 Heterotopic – graft located in different
  location ( kidney, pancreas)
      Transplant terminology-
 Allograft: transplant among same species.
 Isograft : transplant among monozygotic
             twins.
 Xenograft : transplant between different
             species.
 Auto transplant: moving graft with in same
            body from one site to another.
           Historical facts:
 1stsuccessful kidney transplant was
  isograft.
 Starzl in Denver 1963 –performed 1st liver
  transplant.
 1966 –Kelly & Merkel performed the first
  pancreatic transplant in Minneapolis.
 Christiaan Barnard – Cape Town , S.A –
  performed the first heart transplant.
                History-
 Rejection – major obstacle till 1970’s
 Jean Borel – discovery of cyclosporin A
  revolutionized transplant program.
 1985 -1995 – was newer
  immunosuppressant coming .
      Transplant immunology-
 Histocompatibility- degree to which an allograft,
  shares regulatory components of the immune
  system with the recipient.
 MHC (Major Histocompatibility Complex)-
 * Short arm Ch 6.
 * Cluster of genes.
 * Called HLA.
 * Produce 2 class of products – classI & Class II
 * Polymorphic.
             Immunology-
    HLA System- 7 loci on HLA gene
     complex.
    HLA-A, HLA-B, HLA-C, HLA-D, HLA-DR,
     HLA-DQ & HLA-DP.
    Function & Biochemistry divided
     Histocompatibility antigens as –
1.    Class I antigen.
2.    Class II antigen.
              Immunology-
1. MHC-Class I
   antigen-
 A, B, C Loci
 Targets of cytotoxic
   T cells
 Present on all
   nucleated cells.
  ( T, B- Lymphocytes
   & platelets)
                Immunology-
2. MHC Class II antigen-
 D & DR Loci
 Function antigen
   presentation.
 Present – B.lymphocyte,
   monocytes,macrophages,
   endothelial cells,
   activated T lymphocytes.
 (absent on platelets &
   unactivated T lympocyte)
             Lymphocytes-
1. T-Lymphocytes-       2. B Lymphocytes-
Three types-             Antibodies
 Helper T cells –       Plasma cells.
   class II antigen
 Cytotoxic T cell –
   class I antigen.
 Suppressor T cells.
Transplant antigen recognition &
          destruction-

      MHC Antigen molecule
               +                          T Cell activation
      TCR ( T Cell Receptor)




    T Cell mediated Cytotoxicity.      T Cell Amplification
            CD+8 Cells                    (Recruitment
    Both CD4& CD8 can destroy          Clonal expansion)
                                    CD+4 cells- IL2, Interferon γ
  Transplant antigen recognition &
            destruction-
2. B lymphocytes –
 Recognize antigen without need for
    presenting or MHC.
 Antibodies.
 Humoral response important in class 1
    antigen.
 Cytotoxic (Anti HLA) Ab, if present in the
    recipient at the time of transplant – cause
    hyperacute rejection.
Antibody mediated cytotoxicity-
 Ab bound to antigen
 ADCC- antibody
  depended cellular
  cytotoxicity.
 Compliment
  mediated.
                  Rejection-
    Host response to donor graft depends on
     histocompatibility.
    Incompatible-rejection 3 types

A.   Hyperacute
B.   Acute
C.   chronic
    A. Hyper acute Rejection-
 Anti HLA cytotoxic antibodies .
 Starts – once anastomosis is complete.
 Immediate thrombosis.
 Destruction in 24-48 hours.
 No treatment .
 Prevention – pretransplant cross match.
       B. Acute Rejection-
T  Cell mediated
 Most commonly seen
 Day 5 to 6 months.
 Immune cellular reaction
 Supressed by immunosuppressant
        c. Chronic Rejection-
 Unclear
 Humoral  factors mediated
 Insidious (months- years)
 Untreatable
 Histology- gradual fibrosis of the graft.
 No effect of immunosupression
     Immunosupressive drugs-
Induction, Maintance and Rescue.
1. Corticosteroids.
2. Antiproliferative agents – Azathioprine.
3. Calcineurin inhibitors - Cyclosporin.
                            - Tacrolimus (FK 506)
4. Antilymphocyte prep - ALG, OKT3.
5. Newer drugs              - Rapamycin.
                            - Spergualin.
        Immunosupressants
1. Corticosteroids-
 Inhibit inflammatory part of rejection
 For induction , maintance & rescue.
 Prednisone.
2. Azathioprine-
 Mercaptopurine class of drug
 Inhibit nucleic acid synthesis.
 Dose adjustment needed – WBC count.
 Depress marrow, hepatotoxic.
        Immunosupressants-
3. Cyclosporin-
 Inhibits production & release of IL2 by T-
   Helper cells.
 Nephrotoxic, hepatotoxic.
 ↑ Neoplasia- Lymphomas.
4. Tacrolimus (FK 506)-
 Prevents cytokine transcription and prevents T
   cell activation
 T Cell spesific
 Drug of choice in liver transplants.
     Immunosupressant drugs.
5. ALG (Antilymphocyte globulin)-
 acute rejection ,
 Targets T cells
 Coats antigens and clears by cell lysis.
6. OKT3-
 Monoclonal antibody
 T cell , site of work , prevents amplification.
7. Rapamycin-
 Macrolide antibiotic
 Works on IL 2 receptor.
        Organ transplantation-
A.   Kidney
B.   Heart
C.   Combined Heart & Lung
D.   Lung
E.   Liver
F.   Pancreas.
           Renal Transplant-
 Most common organ transplant.
 Age 1 – 70 years
 Indications – ESRD.
-Ch. Glomerulonephritis.
-Diabetic nephropathy
-Ch. Pyelonephritis.
-Polycystic Kidneys.
 Patients unsuitable for transplant-mx by
  hemodialysis or CAPD.
        Contraindications to renal
               transplant-
A.   Absolute:               B. Relative:
    Cancer                   Ischemic cardiac dis.
    HIV                      Aorto ileac occlusive
    Active T.B                vascular disease.
    Ch. Active hepatitis.    Obesity

    Active drug abuse.       Hyperoxaluria.
          Kidney transplant-
A. Recipient           B. Renal donors-
  Histocompatibility
  testing-              Living related
 Blood group comp.
                        Cadaver
 HLA typing
                        Living non related
 Anti HLA antibody
  cross match.
    Evaluation – live kidney donor.
   History & Physical
   Lab- CBC, biochem, HIV, Hepatitis screening ,
    CMV serology, ABO compatability.
   GTT if diabetes in family
   Urine- micro & culture.
   24 hour urinary clearance for cret, protein.
   CXR, ECG,
   Angiography or CT Scan
   IVU.
Contraindications – cadaver donor.
A.   Absolute:           B. Relative:
    Age > 70 yrs.        Age >60 &<6 years.
    Renal disease        Mild hypertension
    Malignancy           Early diabetes
    Long standing HTN    Hepatitis C Positive
    Sepsis.
    Iv drug abuser
    HIV seropositive
    HbsAg- positive
         Operative technique-
 Donor surgery – live
  or cadaver
 Recipient surgery- R
  or L iliac fossa.
* Renal A. – In. Iliac A.
* Renal V. – Int. Iliac V
* Ureter – Bladder
 Patient need
  induction
  immunosupression
               Complications-
   Lymphocele                Rejection-
   Ureteric necrosis.       -Elevating BUN, Cret.
   Rejection                -Renal USG-
   Immunosupression          *Prominent pyramids
    related                   *loss of renal sinus fat.
   Renal artery stenosis.   -MRI
                             -Renal bx
           Heart Transplant-
 Recipient-   Indication:
 ESCD
 Severe Cardiac disability despite max
  medical treatment.
 Symptomatic cardiac ischemia refractory
  to conventional treatment.
-cardiomyopathy ischemic & idiopathic
  comprise the bulk of the patients.
       Contraindiactions - heart
              transplant.
   Age >65 years
   Significant irreversible pulmonary ,
    hepatic or renal dysfunction.
   Severe pulmonary hypertension
   Unresolved , recent malignancy.
   Severe peripheral and cerebral vascular
    disease.
   Diabetes with end organ dysfunction.
        Cardiac donor-criteria
 Age < 40 years
 HIV, Hepatitis B negative serology.
 No active severe infection , malignancy.
 ABO compatable with recipient.
 No significant cardiac disease or trauma.
- ABO & HLA match if performed between
  donor and recipient.
        Operative technique
 Recipient   heart is removed, R & L atria
  trimmed .
 Left atria anastomosed first followed by
  right .
 Aorta followed by pulmonary artery is
  anastomosed .
 Heart rate supported by atrial pacing .
              Heart transplant-
A. Immunosupression-
 Triple therapy –
   Azathioprine,
   Corticosteroids , and
   Cyclosporin.
B. Follow up-
 Monitor for infection &
   rejection.
endomyocardial bx-
  monthly x 1 year,
 3monthly there after.
            Liver transplant-
Indication-
 Treatment of irreversible liver failure- from
  acute or fulminant disease or more
  commonly chronic disease.
 Prognosis better in chronic disease then
  acute failure.
          Causes of liver failure-
   Laennec’s cirrhosis.
   Sclerosing cholangitis.
   Primary biliary cirrhosis.
   HepatitisA,B,C
   Autoimmune hepatitis.
   Cholangiocarcinoma.
   Wilson disease.
   Biliary atresia.
   Hemochromatosis.
   Cystic fibrosis.
 Contraindications liver transplant.
 Severe  cardiopulmonary disease.
 Disseminated cancer.
 Multisystem organ failure.
 Non compliance with medical therapy.
 Severe neurological impairment.
          Donor selection-
 Braindead.
 Negative serology for HIV
 No systemic infection.
 No evidence of cancer.
 No massive hepatic injury.
 Blood group match required but not
  absolutely necessary.
 HLA matching not routinely done.
       Operative technique-
 Orthotopic   transplant.
3 phases-
 Dissection phase- liver attachments are
  dissected
 An hepatic phase- time when there is no
  liver in circuit.
 Reperfusion phase-after revascularization.
                Complications-
               Liver transplant-
A.   Technical –           B. Immunosupression
    Bleeding                 related-
    Hepatic A stenosis.    Rejection

    Pul. Vein             ( commonest)
     thrombosis.            Infection
    Biliary stenosis.      Nephrotoxicity
    Intraabdominal         Bone marrow
     infection.               supression.
        Pancreatic transplant
 Non essential organ
  transplant for mx of
  diabetes.
 Pancreas with
  duodenum is taken &
  transplanted.
 1 year survival is
  65%.
     Survival after transplant-
                       1year   5years.
 Kidney transplant-     94%     76%
           cadaver      86%      60%.
 Heart Transplant-      63%     38%
 Liver Transplant-      79%     40%
Thank you

				
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