Discuss the Principle of Organ Transplant.pptx

Including types, immunological basis of rejection, pre , intra and post operative principles

1. Discuss The Principle Of Organ transplant By DR MOSES CLETUS GALADIMA

2. OUTLINE INTRODUCTION PRINCIPLES COMPLICATIONS ETHICAL CONSIDERATIONS CONCLUSION REFERENCES

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

4. History 1954-joe murray -first successful kidney transplant 1963-tom starzi -first human liver 1967-Christian barnard -first human heart transplant First kidney transplant in Nigeria march 2000 st Nicholas in lagos but by indigenous surgeons was in may 2002 inOAUTH

5. Transplant immunology Immune system recognizes graft as foreign body and trigger response via immune cells or substances they produce –cytokines and antibodies Cells- B and T lymphocytes, nk -cells APC- Effector cells-neutrophil, Macroph and T-LYPH Response is via recognition, amplification and memory

6. TRANSPLANT ANTIGEN HLA-Polymorphic cell surface antigen act as antigen recognition unit And are the major trigger for rejection HLA Types- class 1 and 2 Class 1- ABC, present in all nucleated cells Class 2 HLA DR,DP, DQ present only on APC HLA DR are most important in rejection

7. Cd8 and cd4 recognizes class 1 and 2 receptors respectively MHC-Clusters of genes on short arm of chromosomes 6 expressed on cell surface as HLA i.e genes that encode HLA ABO-Blood group antigen are expressed not only by RBCs but also by most cell types as well. Incompatibility leads to hyperacute rejection

8. Graft rejection Is a bigger challenge than expertise needed to performe the surgery result mainly from HLA and ABO incompatibility Types HYPERACUTE ACUTE CHRONIC

9. HYPERACUTE-Immediate due to ABO or preformed anti HLA antibodies characterised by intravenous thrombosis and interstitial hemorrhage Risk factors are previous failed transplant and blood transfusion Kidney is vulnerable to hyperacute rejection

10. ACUTE GR During the first 6months Cell mediated(t-cell), antibody mediated or both characterised by cellular infiltrations e.g cytotoxic, b cell, nk -cell, macrophages

11. Chronic After 6months Most common cause of GR Antibodies play important role Non-immunological factors contribute to the pathogenesis characterised myointimal proliferation in graft ateries leading to ischemia and fibrosis

12. Principles PRE-OPERATIVE Patient selection and evaluation Counseling Informed consent optimization

13. Patient selection -Recipient Pt who met indication Clinical evaluation, hx an exam r/o other dx and comorbidities Immunological evaluation,serology,hiv,hep,cmv,vdrl , tissue typing and cross matching, blood group Infection,septic workup, Mantoux Others fbc , clotting profile,fbs,ecg,uecr , tumor markers stool microscopy

14. Donor Cadaveric-pt with severe brain death Other criteria, Normothermic, no resp effort, heart still beating, no depressant drugs should be there while evaluating patient, pt should not have sepsis or cancer(except brain tumor), not a hiv or hep individual Living donor, should be healthy, can be living unrelated or related donor

15. Contra-indication for living donors-mental dix, disease organ, morbidity and mortality risk, ABO incompatibility, crossmatching incompatibility, transmissible disease Evaluation- hx -of risk factors for infection, malignancy in the past 5yrs or presence of comorbidity, abo incompat , serological,infection and malignancy screen,CT -angiogram, IV Urography, HLA typing

16. Factors that determine organ function after transplant Donor factors-extreme age or presence of dx in transplanted organ Procurement related factors-warm ischeamic time,cold ischeamic time and the preservation solution Recepient factor -immunologic factors,hemodynamic or metabolic stability,technical factors relating to the implantation, presence of drugs that impair transplant function

17. Tissue typing- laboratories carry out 3task 1determine the hla type of blood for both donor and recipient Lymphocyte crossmatching to exclude circulating antibodies in recipient against hla expressed by donor Hla antibody screening and specificity in recipient before and after transplant to guide immunosuppressive therapy

18. Positive cross matching- recipient antibodies attacks donors-not suitable Negative-do not attack donors-suitable Method – microcytotic assays, mixed lymphocytes, flow cytometry, DNA analysis

19. Counselling- professional counsellors, psychotherapist Aimed at preventing minimizing possible complications Need for adherence to post op maintenance meds Regular follow up thorough evaluation Life style modification-smoking alcohol, sedentary life style, junks, excessive salt,

20. Informed consent- Living donor- education, willingness not financial reason or duress,, extensive screening and medical psychological, involve family, surgery and anaesthetic complications outline to pt Decease donor- factors influencing refusal to donate by relative -non acceptance of brain death, superstition to been reborn with a missing organ, lack of consensus between family members, fear of social critic, disatification with hospital staff, religious believe, delay in funeral

21. Recepient -nature of disease and need for transplant,outcome and compliocations,need for compliance to immnunosupressive therapy and other valuable options

22. Optimization of recipient Correction of anemia,uremia,dehydration,treatment if infection, malaria,, deworming of patient, central line,urethral catheter, loading dose of immunosuppression 12hrs pre-op Prophylactic antibiotics

23. INTRA-OPERATIVE organ procurement and preservation -living donors strict asepsis and hemostasis adequate exposure control of the vessels above and below the organ to be removed is done and cross-clamping then removal of the organ

24. Preservation- After removal ,its flushed with chilled organ preservation solutions e.g university of Wisconsin( uw ) , eurocolins , custodiol , citrate/ marshall solutions Flush out blood ,cool storage cool at 0-4 degree Nonheart beating kidney donation- preservation insitu for DCD donors donation after circulatory death

25. Transplantation and vascular reconstruction Warm ischemic time- time an organ remain at the body temperature between which the blood supply is cut off before cold perfusion(within 30min) Cold ischemic time-time between chilling of the organ after blood supply has been cut off and the time its warmed by reconnection

26. Cold storage time Kidney- <24hrs Liver<12hr Pancrease <10hr Small intestine<4hr Heart<3hr lung <3hr

27. POST OPERATIVE Clinically-vitals-fever, tachy , htn , pain at site of transplant, pedal oedema(compress external iliac vein)decrease urine vol(signs of hyperacute rejection Invest- eucr , uss -increase size , plvicalyceal dila , biopsy- interstial hemorrages,intravenous thrombosis,mononuclear infiltrates,fibrinoid necrosis Maintainance immunosuppression,dvt prophylasis,treatment of infection,regular follow up

28. Clinical Immunosuppression Maximize graft,protection and minimize side effect, Act predominantly on t-cells Need is highest in the first 3months but needed indefinitely Increase risk of infection and malignancy

29. Calcineurine inhibitors e.g cyclosporine and tacrolimusb - block IL2gene transcription- nephrotoxicity,htn and dm Azathioprine-prevent lymphocyte proliferation- leukopenia throbopeni hepototoxic Corticosteroids-widespread antinflamatory-htn,dm osteoporosis

30. mTOR inhibitors e.g sirolimus, everolimus -block IL2 receptor signal transduction, throbocytpen , dyslipedemia Mycophenolic acid dervat e.g mycofenolate mofetil-prevent lymph proliferation Antibodies therapy e.g ok3 monoclonal,anti,ok3 monoclonal anti, anti cd25,polyclonal antib , antilymphocyte globulin alg,anti lymphocyte serum ALS target T-CELLS-leukopenia,

31. Regimen Induction-early post op Maintainance -for life Rescue-to reverse acute rejection

32. Induction—(most currently used)CNI+anti-cd25 monoclonal antibody Triple therapy; cni , mmf and steroids Dual- cni mmf or steroids Poly antibodies( alg / als ) Mainatanance - Mtor inhibitors esp in kidney transplant- bcos they are non-nephrotoxic substitute to cni Multidrug therapy- steroids,cni ,

33. Complications of immunossupression Infection Maligancy-Kaposi,scc of skin, post transplant lymphoproliferative dx(PTLPD) 1-3% of kidney trnansplant with50% mortality, bsc and malignant melanoma

34. Ethical consideration International perspectives on the ethics and regulation of human cell and tissue transplantation -consent for removal of human cell and tissue Confidentiality of donor data Fair procurement of cells and tissues Stewardship for donated cells and tissue Quality and safety of procurement and processing Fair distribution of processed cells and tissues Consent for transplantation

35. Future trend Genetic engineering-cloning Newer specific immunosuppressive E.g therapy Anti Pyrimidine Brequinar sodium (BQR) FK506 (Tacrolimus) is amacrolide antibiotics it specifically reduce IL2 production

36. conclusion Organ transplant is a successive therapeiutic option for treatment of end stage organ dieaseas . Success depends on improved surgical technique, immunosuppression, organ preservation and follow up

37. Reference E.A Badoe et al. “ Principles and aparactice of Surgery including pathology in the tropics” 4 th edition, Assembly of God Literature Centre ltd.2009 M.A.R Al-Fall uji;”Postgraduate Surgery the candidate guide” 2 nd Edition. Rced Educational and Professional Pub . LTD 1998 Baily and Love’s “Short Practice of Surgery” 26 th Edition CRC press Taylor and Francis group 2013 Sabiston Textbook of Surgery 18 th edition.2007

38. THANKS FOR LISTENING