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