Majid Sajeel
University of Gujrat
Objectives
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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
The History of Organ Transplant
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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
Continued…
1957: Azathioprine deveoped 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
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Transplantable Organs/Tissues
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Liver
Kidney
Pancreas
Heart
Lung
Intestine
Face
Bone Marrow
Cornea
Blood
Types of Transplant
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Heterotopic
organ added
or
Orthotopic
organ replaced
Autograft  same being
Isograft/Syngenetic graft  identical
twins
 Allograft/homograft  same species
 Xenograft/heterograft  between
species
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Statistics
On Waitlist as of 1/9/09
Transplanted in 2007
All organs
7282
All organs
2662
Kidney
5827
Kidney
1498
Liver
743
Liver
610
Pancreas
106
Pancreas
86
Kid/Panc
182
Kid/Panc
115
Heart
211
Heart
174
Lung
200
Lung
144
Heart/Lung
1
Heart/Lung
5
Intestine
12
Intestine
30
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.
Pre-Transplantation Evaluation
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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
Types of donor
Organ donors may be
living
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
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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.
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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
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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
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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. 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
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Tools Used to Stratify Transplant
Recipients
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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 INRinternational 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 2004
 Measure of antibody
sensitization; reflects
% of donors not
compatible with
candidate secondary
to candidate’s
unacceptable
antigens
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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
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 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:
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 Intoxication
}- perform tox screen
 NM blockade
 Shock
 Hypothermia (<90 deg F)warming blanket
When Etiology Determined and NOT
Reversible
LACK OF CEREBRAL
FUNCTION
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Deep coma
No response to painful
stimuli
**Can have spinal cord
reflexes
LACK OF BRAINSTEM
FUNCTION
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Pupillary reflexes
Corneal reflexes
Occulocephalic reflexes
Occulovestibular
reflexes
Gag reflex
Cough reflex
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
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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
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References
1.
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4.
http://www3.niaid.nih.gov/topics/transplant/hist
ory
http://www.unos.org
http://www.organdonor.gov
http://en.wikipedia.org/wiki/Organ_transplantati
on