majid sajeel university of gujrat. objectives provide a history of transplantation review organs...
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Organ Transplantation
Majid SajeelUniversity of Gujrat
BIOTECHNOLOGY
ObjectivesProvide a history of transplantationReview organs that are transplantableDefine types of transplantsIssues related to recipientsOverview of immunosuppressionIssues related to donorsOther considerations
The History of Organ TransplantPrehistoric transplantation exists in mythological
tales of chimeric beings1903-1905: 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 WWI1952: 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
Continued…1957: Azathioprine deveoped by Drs. Hitchings
and Elion1966: First successful pancreas transplant by Kelly
and Lillehei1967: 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
Transplantable Organs/Tissues
LiverKidneyPancreasHeart LungIntestineFaceBone MarrowCorneaBlood
Types of TransplantHeterotopic or Orthotopic
organ added organ replaced
Autograft same beingIsograft/Syngenetic graft identical
twinsAllograft/homograft same speciesXenograft/heterograft between
species
Statistics
All organs 7282
Kidney 5827
Liver 743
Pancreas 106
Kid/Panc 182
Heart 211
Lung 200
Heart/Lung 1
Intestine 12
All organs 2662
Kidney 1498
Liver 610
Pancreas 86
Kid/Panc 115
Heart 174
Lung 144
Heart/Lung 5
Intestine 30
On Waitlist as of 1/9/09 Transplanted in 2007
Transplant RegionsOrgans 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.
Pre-Transplantation EvaluationBlood Type (A, B, AB, and O)
Rh factor does not matterHuman Leukocyte Antigen (HLA);
antigens on WBCCrossmatch; if positive, then cannot
receive organ; done multiple times up to 48 hrs prior to transplant
Serology; for HIV, CMV, hepatitisCardiopulmonary, cancer screening
Types of donorliving
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
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.
Good SamaritanGood Samaritan or "altruistic" donationA donation to someone not well-known to
the donorChoice:
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
Compensated donation
Donors get money or other compensation in exchange for their organs
Common in some parts of the worldWhether legal or notIs one of the many factors driving medical
tourism
In Pakistan40 percent to 50 percent of the residents
of some villages have only one kidneyThey have sold the other for a transplant
into a wealthy personProbably from another countrySaid Dr. Farhat Moazam 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
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.oCreatnine, Bilirubin, and INR-international normalized ratio for prothrombin time
PELD:<12 y.o.Alb, Bili, INR, growth failure and age
Tools Used to Stratify Transplant Recipients
CPRA=calculated Panel Reactive Antibody
Used in allocation of kidney, pancreas
Developed in 2004Measure of antibody
sensitization; reflects % of donors not compatible with candidate secondary to candidate’s unacceptable antigens
POOLED HLA (100 DONORS)
Panel Reactive Antibodies
(PRA)
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.
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
When Etiology Determined and NOT Reversible
LACK OF CEREBRAL FUNCTION
___________________
Deep comaNo response to painful
stimuli
**Can have spinal cord reflexes
LACK OF BRAINSTEM FUNCTION
_______________________
Pupillary reflexesCorneal reflexesOcculocephalic reflexes Occulovestibular
reflexesGag reflexCough reflex
Key Elements in the Process of Donation after Cardiac Death
Withdrawal of life sustaining measuresPronouncement 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
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 interestUse of heart in cardiac transplantation
References1. http://www3.niaid.nih.gov/topics/transplant/histo
ry2. http://www.unos.org3. http://www.organdonor.gov4. http://en.wikipedia.org/wiki/Organ_transplantatio
n