principles of organ transplant and renal transplant

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PRINCIPLES INVOLVED IN ORGAN TRANSPLANTBy - Dr NAVIL SHARMAGuide Dr BALCHANDRA KASHYAPI

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CONTENTSINTRODUCTIONDefinition of termsTransplant immunologyGraft rejectionPRINCIPLESPre-operatives Intra-operatives Post-operative COMPLICATIONSRENAL TRANSPLATATION

ETHICAL CONSIDERATIONS

CONCLUSION

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INTRODUCTIONDEFINITION 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 - Transfer of organ from one part to another in the same individual. E.g skin graft, vuscular graft.Allograft - from one individual to another of the same speciesIsograft - transfer of organ from one individual to his or her monozygotic twinsXenograft - transfer of organ from one individual to another of different species

Autograft the transfer of organ from one part to another in the same individualAllograft from one individual to another of the same specieIsograft transfer of organ from one individual to his or her identical twinXenograft the transfer of organ from one individual to another of different specieOrthotopic graft a graft placed in it normal anatomical positionHeterotopic graft a graft placed at a site different from the organ is normally located.

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INTRODUCTIONDEFINITION OF TERMS Orthotopic graft- graft placed in it normal anatomical position

Heterotopic graft - graft placed at a site different from the organ is normally located

Autograft the transfer of organ from one part to another in the same individualAllograft from one individual to another of the same specieIsograft transfer of organ from one individual to his or her identical twinXenograft the transfer of organ from one individual to another of different specieOrthotopic graft a graft placed in it normal anatomical positionHeterotopic graft a graft placed at a site different from the organ is normally located.

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Organs that can be transplanted are:Heart KidneysLiverThymusPancreasLungsIntestine

Tissues that can be transplanted are:BonesTendonsCorneaVeinHeart valvesSkin of leg

TRANSPLANT IMMUNOLOGYThe 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

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

Humoral (Antibody mediated)Cell mediated

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LYMPHOCYTES T-LYMPHOCYTES Mediator of cell mediated immunityThey recognizes MHC antigen on transplant tissuesCytotoxic T-cells produces cytotoxic factors (perforins, granzymes) implicated in transplant rejection B-LYMPHOCYTES Mediators of humoral immunity by antibody production.There activation is aided by cytokine and the T-helper cellsClonal selection generates plasma cells secreting antibodies.There are 5 major classes of antibodies or immunoglobulin; IgG, IgM, IgA, IgE and IgD the 1st 3 are involve in graft rejectionN-KILLER CELLS Cells of innate immunity, capable of killing foreign targets without prior sensitization

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Cell-mediated immune responseDefend against intracellular pathogens/rejectionActiveCytotoxic T cellsMemoryCytotoxic T cellsMemoryHelper T cellsAntigen-presenting cellAntigen (2nd exposure)Helper T cellEngulfed byAntigen (1st exposure)Cytotoxic T cellKeyStimulatesGives rise to+++++++T-CELLSHelper T cellsCytotoxic T cellsMemory T cells

9Figure 43.16 An overview of the acquired immune response

Cytotoxic T cell

Perforin

Granzymes

TCR

CD8

Class I MHCmolecule

TargetcellPeptideantigen

Pore

Released cytotoxic T cell

Dying target cell

10Figure 43.18 The killing action of cytotoxic T cellsFor the Discovery Video Fighting Cancer, go to Animation and Video Files.

KeyStimulatesGives rise to+MemoryHelper T cellsAntigen-presenting cellHelper T cellEngulfed byAntigen (1st exposure)++++++Defend against extracellular pathogens/Transplant rejectionMemoryB cellsAntigen (2nd exposure)Plasma cellsB cellSecretedantibodiesHumoral (antibody-mediated) immune response10/19/2015bbinyunus2002@gmail.com11

11Figure 43.16 An overview of the acquired immune response

ANTIGEN PRESENTING CELLS(APC)They capture antigens and display to lymphocytes e.g. Macrophages, dendritic cells and follicular dendritic cells.Dendritic cells : initiate T-cells response Macrophages : Initiate effector phase of cell mediated immunityFollicular dendritic cells : display antigens to B-lymphocytes in humeral response.

EFFECTOR CELLSThey eliminate antigens by phagocytosis E.g neutrophils, macrophage and T-lymphocytes

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TRANSPLANT ANTIGENS

Human leucocytes antigen (HLA) ;a group of highly polymorphic cell surface moleculesThey act as antigen recognition unit on T-lymphocytes and are the major trigger for graft rejectionTypes : class1 HLA- A,B,C present in all nucleated cells,CD8+ recognizes class 1 HLA class2 HLA- DR, DP, DQ present only on APCClass 2- HLA-DR are most important in rejectionCD4+ recognize class 2 HLA

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Major histocompatibility complex MHC;They are clusters of genes on the short arm of chromosome 6 expressed on the cell surface as HLA i.e. genes that encode HLA. ABOThese blood group antigen are expressed not only on red blood cells but by most cell types as well.Incompatibility leads to hyperacute rejection

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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.Types of Graft RejectionHyperacute : 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 transfusionsKidney transplant is vulnerable to hyperacute rejection . Hyperacutly rejecting kidney rapidly becomes cyanotic, mottled, and flaccid and may excrete few drops of bloody urine.This form of rejection is rarely seen in today's practiceGRAFT REJECTION

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Steps in the hyperacute rejection of a kidney graft.Hyperacute Rejection

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Acute :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).Histologically, humoral rejection is associated with vasculitis, whereas cellular rejection is marked by an interstitial mononuclear cell infiltrate, edema, and tissue injury as well as mild interstitial haemorrhage.

Chronic :It occurs after 6 month .Most common cause of graft failure. Non- immunological factors contribute to the pathogenesis characterized by myo-intimal proliferation in graft arteries leading to ischemia and fibrosis

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PRINCIPLESPRE-OPERATIVE Patient selection and EvaluationCounselingInformed consentOptimization

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PATIENT SELECTION AND EVALUATION1. RECIPIENTPatient who met the indication for transplant ORGAN FAILURE Clinical evaluation; history and physical examination to rule out other diseases and co-morbiditiesImmunological evaluationBlood groupTissue typing & cross matchingSerology; HIV, Hepatitis, CMV, VDRLInfection screening septic work-upOthers ; CBC, clotting profile, FBS, ECG, LFT, RFT, tumour markers.

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2. DONOR

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 healthyLiving unrelated donor (LURD)Living related donor. (LRD)Advantages of living donorImproved graft survivalLess recipient morbidityEarly function and easier to manage Avoidance long waiting time for transplantLess aggressive immunosuppressive regimen

Absence of spontaneous respiration. Absence of cranial reflexes. Absence of response to stimuli. Irreversible causes. Absence of cerebral blood flow. Isoelectric EEG. Sustained apnoea with elevated CO2

Clinical testing for brainstem deathAbsence of cranial nerve reflexes Pupillary reflex Corneal reflex Pharyngeal (gag) and tracheal (cough) reflex Oculovestibular (caloric) reflexAbsence of motor response The absence of a motor response to painful stimuli appliedto the head/face and the absence of a motor responsewithin the cranial nerve distribution to adequatestimulation of any somatic area is an indicator ofbrainstem death The presence of spinal reflexes does not precludebrainstem deathAbsence of spontaneous respiration After pre-ventilation with 100% oxygen for at least 5 min,the patient is disconnected from the ventilator for 10 minto confirm absence of respiratory effort, during which timethe arterial Pco2 level should be > 8 kPa (60 mmHg) toensure adequate respiratory stimulation. To prevent hypoxia during the apnoeic period, oxygen(6 l min-1) is delivered via an endotracheal catheter

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Contra-indications for living donorMental diseaseDisease organMorbidity and mortality riskABO incompatibility Crossmatching incompatibilityTransmissible disease Evaluation : to assess for suitability CLINCAL - history of risk factors for infection, malignancy in the past 5 years. Presence of co-morbidities ABO typing, Serology tests.Infection and malignant screeningCT-Angiogram, Intravenous urography.HLA typing.

II. Deceased donor- Brain dead donors: Donors who have been declared