Principles of Transplantation by DJ

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Information about Principles of Transplantation by DJ

Published on October 24, 2016

Author: joshidharmendra9


1. Presented by: Dr. Dharmendra Joshi BSMMU PRINCIPLES OF TRANSPLANTATION

2. INTRODUCTION Definition of terms Transplant immunology Graft rejection PRINCIPLES Pre-operative Intra-operative Post-operative ETHICAL CONSIDERATIONS CONCLUSION OUTLINE

3. DEFINITION OF TERMS An organ transplant is a surgical procedure in which a failing organ is replaced by a functioning one from a donor with a compatible tissue type. • Autograft • Allograft • Isograft • Xenograft • Orthotopic graft • Heterotopic graft INTRODUCTION

4. ORGANS THAT CAN BE TRANSPLANTED  Heart  Kidneys  Liver Thymus  Pancreas Lungs  Intestine

5. TISSUE THAT CAN BE TRANSPLANTED  Bones  Tendons  Cornea  Vein Heart valves  Skin of leg

6. The immune system recognizes graft from someone else as foreign body and triggers response via immune cells and substances they produce - cytokines and antibodies (Responses are via; recognition, amplification and memory) • Immunity TRANSPLANT IMMUNOLOGY Humoral (Antibody mediated) Cell mediated

7. • IMMUNE CELLS  Lymphocytes : T-lymphocyte, B-lymphocyte, N-killer cells  Antigen presenting cells(APC) : macrophages, dendritic cells  The Effector Cells : Neutrophils , macrophages and T- lymphocytes TRANSPLANT IMMUNOLOGY (Contd…)

8. Cell-mediated immune response Defend against intracellular pathogens/rejection Active Cytotoxic T cells Memory Cytotoxic T cells Memory Helper T cells Antigen- presenting cell Antigen (2nd exposure) Helper T cell Engulfed by Antigen (1st exposure) Cytotoxic T cell Key Stimulates Gives rise to + + + + + + + T-CELLS - Helper T cells - Cytotoxic T cells - Memory T cells

9. Key Stimulates Gives rise to + Memory Helper T cells Antigen- presenting cell Helper T cell Engulfed by Antigen (1st exposure) + + + + + + Defend against extracellular pathogens/Transplant rejection Memory B cells Antigen (2nd exposure) Plasma cells B cell Secreted antibodies Humoral (antibody-mediated) immune response

10. Human leucocytes antigen (HLA): • a group of highly polymorphic cell surface molecules • They act as antigen recognition unit on T-lymphocytes and are the major trigger for graft rejection • Types : class1 – HLA- A,B,C present in all nucleated cells, • CD8+ recognizes class 1 HLA • class2 – HLA- DR, DP, DQ present only on APC • Class 2- HLA-DR are most important in rejection • CD4+ recognize class 2 HLA TRANSPLANT ANTIGENS

11. Major histocompatibility complex MHC: oThey are clusters of genes on the short arm of chromosome 6 expressed on the cell surface as HLA i.e. genes that encode HLA. ABO: oThese blood group antigen are expressed not only on red blood cells but by most cell types as well. oIncompatibility leads to hyperacute rejection

12. Rejection of transplanted organs is a bigger challenge than the technical expertise required to perform the surgery. It results mainly from HLA and ABO incompatibility. • Hyperacute • Acute • Chronic GRAFT REJECTION

13. Hyper acute rejection • Immediate graft destruction due to ABO or preformed anti- HLA antibodies. • Characterized by intravenous thrombosis and interstitial hemorrhage. • Risk factors are previous failed transplant and blood transfusions • Kidney transplant is vulnerable to hyperacute rejection GRAFT REJECTION (Contd…)

14. Acute rejection • Usually occurs during the first 6 months. • May be cell mediated (T-cell), antibody mediated or both • Characterized by cellular infiltration of the graft(cytotoxic, B- cells, NK cells and macrophages) GRAFT REJECTION (Contd…)

15. Chronic Rejection: • It occurs after 6 months. • Most common cause of graft failure • Antibodies play important role • Non- immunological factors contribute to the pathogenesis • Characterized by myointimal proliferation in graft arteries leading to ischemia and fibrosis GRAFT REJECTION (Contd…)

16. PRE-OPERATIVE Patient selection and Evaluation Counseling Informed written consent Optimization PRINCIPLES

17. 1. RECIPIENT Clinical evaluation; history and physical examination Immunological evaluation Infection screening – septic work-up Others ; CBC, clotting profile, FBS, ECG, LFT, RFT, tumour markers. PATIENT SELECTION & EVALUATION (Recipient)

18. I. Living donor : Donor remains alive and donates a renewable tissue/cell, or donates an organ or part of an organ in which the remaining organ can regenerate or take on the workload of the rest of the organ (single kidney donation, partial donation of liver). A living donor should be healthy • Living unrelated donor (LURD) • Living related donor. (LRD) Patient selection & evaluation (DONOR)

19.  Advantages of living donor Improved graft survival Less recipient morbidity Early function and easier to manage Avoidance of long waiting time for transplant Less aggressive immunosuppressive regimens Patient selection & evaluation (DONOR)

20.  Contra-indications for living donor oMental disease oDiseased organ oMorbidity and mortality risk oABO incompatibility oCross matching incompatibility oTransmissible disease Patient selection & evaluation (DONOR)

21. • Evaluation : to assess for suitability oCLINCAL - history of risk factors for infection, malignancy in the past 5 years. Presence of co- morbidities oABO typing, Serology tests. oInfection and malignant screening oCT-Angiogram, Intravenous urography. oHLA typing. Patient selection & evaluation (DONOR)

22. • II. Deceased donor - Brain dead donors: o Normothermic patient. o No respiratory effort by the patient. o The heart is still beating. o No depressant drugs intake should be there while evaluating the patient. o Individual should not have any sepsis, cancer (except brain tumour). o Not a HIV or hepatitis individual. Patient selection & evaluation (DONOR)

23. • II. Deceased donor - Cardiac Death Donors (formerly non-heart beating donors) to increase the potential pool of donors as demand for transplants continues to grow. These organs have inferior outcomes to organs from a brain-dead donor. Patient selection & evaluation (DONOR)


25. • The tissue typing laboratory carries out 3 tasks : To determine the HLA type of blood for both donor and recipient by PCR. Lymphocyte cross-matching. HLA antibody screening and specificity TISSUE TYPING

26. Positive cross matching; o Recipient antibodies attacks donor’s. o Not suitable for transplant Negative cross matching; o Recipient antibodies do not attack donor o Suitable for transplant Methods; o Micro-cytotoxic assay, mixed lymphocytes, flow cytometry, DNA analysis. CROSS MATCHING

27. • May involve professional counselors/ psychotherapist • Aimed at preventing / minimizing possible complication • Need for adherence to post-op maintenance medications • Regular follow-up thorough evaluation • Life style modification; smoking, alcohol, sedentary life style, excessive salt ingestion. COUNSELING

28. Living Donor: Education Willingly but not for any financial reason or under stress Most undergo extensive screening – medical, psychological Surgery and anesthetic complications outline to patients INFORMED WRITTEN CONSENT

29. • DECEASED DONOR • Some Factors influencing refusal to consent by relatives; non-acceptance of brain death. A delay in funeral Lack of consensus within family members Fear of social criticism Dissatisfaction with the hospital staff Various Superstitions & Religious beliefs INFORMED WRITTEN CONSENT (Contd…)

30. RECIPIENT Nature of disease and the need for transplant Outcome and complications Need for compliance to immunosuppressive therapy Other available options INFORMED WRITTEN CONSENT (Contd…)

31. Correction of derangements, getting patient ready for surgery Correction of anemia Uremia Dehydration Treatment of infection Central line Urethral catheter Loading dose immunosuppression 12hr pre-op Prophylactic antibiotics OPTIMIZATION OF RECEPIENT

32. • Organ procurement and preservation • LIVING DONORs a. Strict asepsis and hemostasis b. Adequate exposure c. Removal of the organ d. Preservation e. Organ packaging f. Transplantation/vascular reconstruction INTRA-OPERATIVE PRINCIPLE

33. After removal, the organ is flushed with chilled organ preservation solution e.g. • University of Wisconsin(UW), • Eurocolins, • Celsior, • Custodiol, • Citrate/Marshall solutions PRESERVATION


35. • Initiation of preservation in situ- for DCD donors- donation after circulatory death donors *** DCD – Donor after Cardiac Death DCD DONOR

36. • Warm ischemic time: time an organ remains at body temperature between which the blood supply is cut off before cold perfusion. (within 30min) • Cold ischemic time: the time between the chilling of the organ, after blood supply has been cut off and the time it is warmed by reconnection ISCHEMIC TIME

37. Maximum and optimal cold storage times (approximate) • Organ Optimal (hours ) Safe maximum(hours) • Kidney < 24 48 • Liver < 12 24 • Pancreas < 10 24 • Small intestine < 4 8 • Heart < 3 6 • Lung < 3 8 COLD STORAGE TIME

38. Post-operative assessment • Clinical – vital signs; fever, tachychardia, hypertension, pain at site of transplant, pedal edema (compression of external iliac vein), decrease urine volume- features of hyperacute rejection • Investigations: USG- increase in size, pelvicalyceal dilation, Biopsy: mononuclear infiltrates, fibrinoid necrosis, interstitial haemorrhage. etc. • Maintenance immunosuppression, DVT prophylaxis, Treatment of infection , Regular follow up POST-OPERATIVE PRINCIPLE

39. The principles are the same for all type of organ transplant; maximize graft protection and minimize side effect. The agents used to prevent rejection act predominantly on T cells. The need for immunosuppression is highest in the first 3 month but indefinite treatment is needed It increase the risk of infection and malignancy. Post-operative IMMUNOSUPRESSION

40. AGENT MODE OF ACTION SIDE FFECT CALCINEURINE INHIBITORS Cyclosporine Tacrolimus Block IL-2 gene transcription Nephrotoxicity, hypertension, dyslipidaemia, hirsutism, gingival hyperplasia, neurotoxicity and diabetes AZATHIOPRINE Prevents lymphocyte proliferation Leucopenia, thrombocytopenia, hepatotoxicity, gastrointestinal symptoms MYCOPHENOLIC ACID DERIVATIVES eg MMF – Mycofenolate mofetil Prevents lymphocyte proliferation Leucopenia, thrombocytopenia, gastrointestinal symptoms CORTICOSTEROIDS Widespread anti- inflammatory effects Hypertension, dyslipidaemia, diabetes, osteoporosis, avascular necrosis, cushingoid appearance mTOR-inhibitors Sirolimus, Everolimus Blocks IL-2 receptor signal transduction Thrombocytopenia, dyslipidaemia, pneumonitis, impaired wound healing

41. AGENT MODE OF ACTION SIDE EFFECT ANTIBODY THERAPIES a. OKT3 monoclonal antibody b. Anti-CD25 monoclonal antibody c. Polyclonal antibody [antilymphocyte globulin (ALG) or anti- lymphocyte serum (ALS)] Depletion and blockade of T Cells Targets activated T cells Depletion and blockade of lymphocytes a. Cytokine release syndrome, pulmonary oedema, leucopenia b. None described c. Leucopenia, thrombocytopenia

42. • Immunosuppressive agents are given as Induction: early post-op period Maintenance: given for life Rescue agents: to reverse acute rejection REGIMENS

43. • INTERNATIONAL PERSPECTIVES ON THE ETHICS AND REGULATION OF HUMAN CELLAND TISSUE TRANSPLANTATION o Consent for removal of human cells and tissues o Confidentiality of donor data o Unpaid donation o Fair procurement of cells and tissues o Quality and safety of HC/HT procurement and processing o Fair distribution of processed cells and tissues o Consent for HC/HT transplantation ETHICAL CONSIDERATION

44. Genetic engineering – Cloning Newer specific Immuno-suppressive therapy FUTURE TREND

45. Organ transplant is a successive therapeutic option for treatment of end-stage organ disease. Success depends on improved surgical technique, immunosuppression, organ preservation and follow-up . CONCLUSION

46. • Bailey and Love’s “Short Practice of Surgery” 26th edition CRC press Taylor and Francis group. 2013 • E.A Badoe et al, “Principles and Practice of surgery including pathology in the tropics” 4th edition, Assembly of God Literature Center ltd, 2009 • M.A.R Al-Fallouji; “Postgraduate Surgery the candidate guide”. 2nd Edition. Rced Educational and Professional Pub. Ltd 1998 • Sabiston texbook of surgery. 18th edition.2007 • Andrew C et al “Operative urology at the cleveland clinic” 2nd edition. 2006. • Pediatric Liver Transplantation Author: F Brian Boudi, MD, FACP; Chief Editor: Stuart M Greenstein, Medscape. REFERENCES

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