Module 2- Organ Transplants Flashcards
A successful transplant is the most satisfactory treatment for ___
End-stage organ failure
Why are ethical aspects of organ transplantation particularly difficult?
Because viable organs are a scarce resource with demand far outstripping supply — issues of allocation ultimately become a decision of who shall live and who shall die
Increasing demand faced with limited supply
- A new person is added to
the organ transplant waiting
list every 9 minutes - Only 3 in 1000 people die in
a way that allows for organ
donation - 17 people die each day
waiting for an organ
transplant
Organ transplants are a fundamentally human idea - timeline of transplants
Graphic- how the national organ transplant system works
Waiting list
- Once a person is diagnosed with a failing organ, they can be placed on the national transplant waiting list to receive a donor organ
- Every 10 minutes, someone in the US is added to the list
- Each year, the number of people on the waiting list is much larger than both the number of donors and the number of transplants, which grows slowly
Organ donors
- A donor dies at a hospital. The person may have registered to be an organ donor or their family may give permission
- Some kidney and liver recipients have living donors
- A donor can supply up to eight organs
What are the four types of transplants?
- Autologous
- Isogenic
- Allogeneic
- Xenogeneic
Diagram explaining the four types of transplant
Diagram showing what body parts can be donated
Autologous transplant
Uses the person’s own stem cells (within an individual)
Isogenic transplant
Graft (transplant) between genetically-identical individuals (identical twins)
Allogeneic transplant
Graft between genetically disparate individuals of the same species (non-identical)
Xenogeneic transplant
Graft between different species (human to animal)
What is standing in the way of cadaveric organ donation?
- Of the 6,200 hospitals in the US, over 5,000 fail to produce a single organ donor in any given year
Why might this be?
- Organs can only be harvested from a small subset of dying individuals
- The traditional criteria for a diagnosis of death was irreversible cessation of circulatory and respiratory function
- In the late 60s, the criteria was expanded to include irreversible cessation of the brain stem
- The ethics behind brain death
Addressing Barriers to Cadaveric Organ Donation
- In 1968, the Uniform Anatomical Gift Act was passed, establishing a uniform organ donor card as a legal document
- In 1986 came the introduction of Required Request Laws, under which hospitals must notify the local Organ Procurement Organization of all patient deaths and have a conversation with the next of kin regarding the donation
How does organ donation work with living donors?
- First, it is important to keep in mind that close relatives provide the best immunological match
- Because one can function well with only one kidney, renal grafting is widely accepted
- However, living donation of partial livers is controversial. Around 500-1,000 of these procedures were done in the US last year
- Aside from kidneys, a majority of donors are deceased
What lasts longer- living donor kidneys or deceased donor kidneys?
Living donor kidneys last longer than deceased donor kidneys (~27 vs. ~15 years)
Kidney paired donation
- This pilot program works to match donors
and candidates with other pairs who do not
match - Their vision is for every kidney transplant
candidate with an incompatible but willing
and approved living donor to receive a living
donor kidney transplant - Their mission is to develop a successful
KPD program with universal access to all
OPTN members and prioritizing the safety of
donors and candidates
The matching process- waiting
- The wait for an acceptable organ can vary
- Many factors are considered while on the waiting list, including:
-Blood type
-Distance from donor
-Body size
-Severity of illness
-Time on list
-Tissue type
Transplant Evaluation Process
- The goal is to find a histocompatible recipient
-2 rounds of lab test are done here, primary and secondary analyses
- Primary analysis refers to blood type and tissue type testing
- Secondary analysis refers to serological cross matching
Blood type testing- table of blood types
Table showing which blood type is compatible with which donor blood type
Tissue type testing
- Major Histocompatibility Complex (MHC) antigens - principle markers of “self” in the immune system – located on all nucleated cells
- Human Leukocyte HLA antigens - a
subset of six MHC antigens which are
used in tissue typing
-Many additional minor antigens are present so that even a perfect “six antigen match” requires
immunosuppression and may eventually be rejected
Why do we need to look beyond immunology to decide which eligible recipient gets an organ? And what secondary issues are evaluated?
- Because several histocompatible recipients will typically be identified for a single organ
Secondary issues evaluated include:
- Longest on the list first - how long a patient has been on the waiting list
- Youngest first - likely duration of benefit
- Sickest first - urgency of patient’s condition
- Sickest last - likelihood of benefit to the patient
-These considerations are not mutually
consistent, and sometimes contradictory
Commonly transplanted organs and the factors affecting their transplantation
Ethical questions to consider
- Should someone imprisoned for life be entitled to a liver or heart transplant? How
about a prisoner on death row? - Should a prisoner about to be executed be allowed to donate his or her organs?
- Should an alcoholic receive a liver transplant? If no, how long does someone have
to be sober before receiving a transplant? - Some patients have rare HLA profiles. Should matching criteria be dropped or
relaxed for these patients, who otherwise will never get grafts?
Transportation of organs
- Quick transport can be critical to the success of the surgery
Typical maximum organ preservation times
- Heart or lung: 4-6 hours
- Liver: 8-12 hours
- Pancreas: 12-18 hours
- Kidney: 24-36 hours
Diagram of how UNOS controls organ distribution
Explain how organs are transported
- Grafts are immediately perfused with preservative solutions.
- In addition, kidneys are usually frozen.
The maximum time between recovery and implantation varies with organ
type:
- Heart 4-6 hours
- Liver 8-12 hours
- Kidney 24-26 hours
- This is where helicopters come in handy!
How has technology progressed in transporting organs?
- The breakthrough is WARM Perfusion, which preserves organs better than when they are frozen
- More than 815 successful human organ transplants have been performed using TransMedics perfusion devices so far in other countries. And the company is currently sponsoring five U.S. clinical trials for its devices and is developing a perfusion device for kidney transplants.
Lung in a box
- On March 22, 2018, FDA approval was granted to the Organ Care System (OCS) Lung System, also known as a “lung-in-a-box”
- The OCS Lung System is a revolutionary system that preserves donor organs
Surgery
If all goes well with the surgery, the patient can live with the transplanted organ for years
What are the two types of living donor surgery?
- Open
- Laproscopic
Open surgery for living donors
- Donor must undergo an operation
where the kidney is removed through a large incision in the side of the body. - Results in pain and a long recovery period.
Laparoscopic surgery for living donors
- Tiny incisions are used and the kidney is removed using a scope/camera and special, miniaturized surgical tools.
- Shorter recovery period and lower complication rate.
Survival rates, 1 year after transplant
Starting in 2007: Medicare evaluates transplant centers based on 1 year survival rates - can you think of any issues with this process?
Diagram of different types of corneal graft rejection
What is transplant rejection?
This occurs when a recipient’s immune system attacks the transplanted organ or tissue
How can we prevent rejection?
- The purpose of immunosuppression is to prevent graft rejection
- Initial immunosuppression is aggressive and patient-specific
- Maintenance immunosuppression generally
consists of a combination of 3 classes of compounds
Table showing types of graft/transplant rejection
Hyperacute immune reaction
In hyperacute rejection, preformed antibodies react with:
- alloantigens on the vascular endothelium of the graft,
- active complement, and
- trigger rapid intravascular thrombosis and necrosis of the vessel wall
Acute rejection response
- In acute cellular rejection, CD8 T Lymphocytes reactive with alloantigens on graft endothelial cells and parenchymal cells cause damage to these cell types.
- Endothelium inflammation is called “endothelialitis”.
- Alloreactive antibodies may also contribute to vascular injury.
Chronic rejection (delayed type hypersensitivity)
- In chronic rejection with graft arteriosclerosis, T cells reactive with graft alloys produce
cytokines that induce endothelial & intimal smooth muscle cell proliferation, leading to
luminal occlusion. - This is probably a chronic DTH reaction to alloantigens in the vessel
wall.
Graft rejection- graft vs. host
First-set vs. second-set rejection
Diagram showing what transplants from pigs are imminent and which ones are years away
What organs could be harvested from a pig?
Organ transplants from pigs- iPS cells
Cloning pigs for organ transplantation diagram (xenotransplantation)
Timeline for organ transplant from pig
When was the first pig-to-human kidney transplant?
2021
