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Organ Transplantation

Biotechnology. Majid Sajeel University of Gujrat. Organ Transplantation. Objectives. Provide a history of transplantation Review organs that are transplantable Define types of transplants Issues related to recipients Overview of immunosuppression Issues related to donors

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Organ Transplantation

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  1. Biotechnology MajidSajeel University of Gujrat Organ Transplantation

  2. Objectives • Provide a history of transplantation • Review organs that are transplantable • Define types of transplants • Issues related to recipients • Overview of immunosuppression • Issues related to donors • Other considerations

  3. The History of Organ Transplant • Prehistoric transplantation exists in mythological tales of chimeric beings • 1903-1905: Modern transplantation began with the work of Alexis Carrel who refined vascular anastomoses as well as transplanted organs within animals • 1914-1918: Skin grafting in WWI • 1952: Dr. Hume at Peter Bent Bringham Hospital in Boston attempted allograft kidney from unrelated donor • 1954: Dr. Joseph E. Murray transplanted kidney from Ronald Herrick to his identical twin, Richard Herrick, to allow him to survive another 8 years despite his ESRD • 1956: First successful BMT by Dr. Donnall Thomas, the recipient twin received whole body radiation prior to transplant

  4. Continued… • 1957: Azathioprinedeveoped by Drs. Hitchings and Elion • 1966: First successful pancreas transplant by Kelly and Lillehei • 1967: First successful heart transplant by Christiaan Barnard in South Africa, That same yr., first successful liver transplant performed by Thomas Starzl • 1981: First successful heart/lung transplant by Dr. Reitz at Standford • 1983: First successful lung transplant by Dr. Joel Cooper; cyclosporin approved • 1984: Congress passed the National Organ Transplant Act (NOTA • 1999: pancreatic islet cell transplant by Dr. Shapiro • 2008: face transplant

  5. Transplantable Organs/Tissues • Liver • Kidney • Pancreas • Heart • Lung • Intestine • Face • Bone Marrow • Cornea • Blood

  6. Types of Transplant • Heterotopic or Orthotopic organ added organ replaced • Autograft same being • Isograft/Syngeneticgraft  identical twins • Allograft/homograft same species • Xenograft/heterograft  between species

  7. Statistics On Waitlist as of 1/9/09 Transplanted in 2007

  8. Transplant Regions • Organs are first offered to patients within the area in which they were donated* before being offered to other parts of the country in order to: • reduce organ preservation time • improve organ quality and survival outcomes • reduce costs incurred by the transplant patient • increase access to transplantation *With the exception of perfectly matched donor kidneys.

  9. Pre-Transplantation Evaluation • Blood Type (A, B, AB, and O) Rh factor does not matter • Human Leukocyte Antigen (HLA); antigens on WBC • Crossmatch; if positive, then cannot receive organ; done multiple times up to 48 hrs prior to transplant • Serology; for HIV, CMV, hepatitis • Cardiopulmonary, cancer screening

  10. Types of donor living Organ donors may be brain dead • Brain dead means the donor must have received an injury (either traumatic or pathological) to the part of the brain that controls heartbeat and breathing • In "living donors", the donor remains alive and donates a renewable tissue, cell, or fluid

  11. Reasons for donation and ethical issues • Living related donors: donate to family members or friends in whom they have an emotional investment. • The risk of surgery is offset by the psychological benefit of not losing someone related to them, or not seeing them suffer the ill effects of waiting on a list.

  12. Good Samaritan • Good Samaritan or "altruistic" donation • A donation to someone not well-known to the donor • Choice:  out of a need to donate  Some donate to the next person on the list  others use some method of choosing a criteria important to them  Web sites are being developed that facilitate such donation

  13. Compensated donation • Donors get money or other compensation in exchange for their organs • Common in some parts of the world • Whether legal or not • Is one of the many factors driving medical tourism

  14. In Pakistan • 40 percent to 50 percent of the residents of some villages have only one kidney • They have sold the other for a transplant into a wealthy person • Probably from another country • Said Dr. FarhatMoazam of Pakistan, at a “World Health Organization” conference Pakistani donors are offered $2,500 for a kidney but receive only about half of that because middlemen take so much

  15. Tools Used to Stratify Transplant Recipients • MELD/PELD= model for end stage liver disease and pediatric end stage liver disease • MELD developed in 2002 to account for objective findings rather than subjective findings; range is 6-40 • MELD:>12y.o Creatnine, Bilirubin, and INR-international normalized ratio for prothrombin time • PELD:<12 y.o. Alb, Bili, INR, growth failure and age

  16. Tools Used to Stratify Transplant Recipients • CPRA=calculated Panel Reactive Antibody • Used in allocation of kidney, pancreas • Developed in 2004 • Measure of antibody sensitization; reflects % of donors not compatible with candidate secondary to candidate’s unacceptable antigens POOLED HLA (100 DONORS) Panel Reactive Antibodies (PRA)

  17. Determination of Brain Death • Defined formally in 1968 by ad Hoc committee at Harvard headed by Beecher • Defined by government in Office of the President with Uniform Determination of Death Act in 1981 • Individual who has sustained either 1. irreversible cessation of circulatory or respiratory functions or 2. irreversible cessation of all functions of the entire brain, including brainstem, is dead. A determination of death must be made in accordance with accepted medical standards.

  18. Diagnosis of Brain Death • Pt suffered irreversible loss of brain function (either cerebral hemisphere or brainstem) • Establish cause that accounts for loss of function • Exclude reversible etiology: • Intoxication }- perform tox screen • NM blockade • Shock • Hypothermia (<90 deg F)warming blanket

  19. When Etiology Determined and NOT Reversible • LACK OF CEREBRAL FUNCTION ___________________ Deep coma No response to painful stimuli **Can have spinal cord reflexes • LACK OF BRAINSTEM FUNCTION _______________________ Pupillary reflexes Corneal reflexes Occulocephalic reflexes Occulovestibular reflexes Gag reflex Cough reflex

  20. Key Elements in the Process of Donation after Cardiac Death • Withdrawal of life sustaining measures • Pronouncement of death from time of onset of asystole (usually btwn 2-5 minutes) • To avoid conflicts of interest transplantation team physicians are not a member of the end-of-life care or declaration of death • Liver within 30 min and kidney within 60 min • If time to asystole exceeds 5 min, then recovery of organs is canceled

  21. Drawbacks to Transplantation after Cardiac Death • Healthcare workers may be uncomfortable recommending withdrawal of care for one pt to obtain organ for a second • Interval between withdrawal of care and death may be shortened and family relationship may be altered • Conflict of interest • Use of heart in cardiac transplantation

  22. References • http://www3.niaid.nih.gov/topics/transplant/history • http://www.unos.org • http://www.organdonor.gov • http://en.wikipedia.org/wiki/Organ_transplantation

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