Final: Organ Transplant Part 1

What occurs in a hyper acute rejection?

Antibody mediated, causes irreversible damage from ischemia Can be life threatening

What does someone who has had a transplant have to do the rest of their life?

Be on immunosuppressants (unless 0 mismatches)

What is sirolimus used in combination with?

Cyclosporine and corticosteroids

When do acute rejections occur?

Days to months

What should you teach a patient on immunosuppressants?

Do not skip doses

If corticosteroids are used for transplant therapy, how should be they used?

Doses are reduced over time and may be weaned off after a few years (used for induction therapy then wean off)

What three things should you be monitoring for a patient on calcineurin inhibitors?

Drug levels, renal function (nephrotoxicity), and neurostatus (neurotoxicity)

With which three types of transplant are calcineurni inhibitors used?

Heart, liver, and kidney transplants

What organs can a brain death donor donate?

Heart, lungs, pancreas, intestine, liver

How long can organs last (transplant window) without preservation measures? Heart, lungs: Liver: Pancreas: Kidney: Intestines:

Heart, lungs: 4-6 hours Liver: 8-12 hours Pancreas: 12-18 hours Kidney: 24-36 hours Intestines: 8-16 hours

What does HLA stand for?

Human leukocyte antigen

What is Sirolimus?

Immunosuppressant for renal transplants

What are polyclonal antibody-lymphocyte immune globulin used for?

Induction therapy or to prevent acute infection

Using immunosuppressants places the patient at risk for which two things?

Infection and malignancy

What are four AE of calcineurin inhibitors?

Infections, malignancy, nephrotoxicity, neurotoxicity

Why is use of mycophenolate mofitel limited?

It is limited by GI toxicities

How does chronic rejection progress?

It is progressive, the patient never really improves

What is the most common transplant?

Kidney

Which organ are hyper-acute rejections most commonly seen with?

Kidney

What can a living donor donate?

Kidney, bone marrow/stem cell, one or two lobes of liver, lung or part of a lung, part of a pancreas, part of the intestines

What are the most commonly transplanted organs?

Kidney, liver, and heart

With which two types of donations is HLA matching most important?

Kidneys and bone marrow; 5-6 matches needed

Which donor organs can be used in parts?

Liver, lungs, pancreas, and intestines can be used in parts Liver has lobes, portions of small intestines, kidneys (have two), typically do double lung (but can do single)

What is often the result of chronic rejection?

Lose the graft (tissue)

When does chronic rejection occur?

Months to years

Are calcineurin inhibitors effective?

Most effective immunosuppressant

How is a hyper acute rejection treated?

Must remove the graft or they will not survive

What would put someone at the top of the list for donation?

Near death, perfect match, current condition- doing better this month then last month?, size

What are hand and face transplants called?

New, VCAs- vascularized composite allografts because they are surgeries composed of grafting many kinds of tissue: bone, muscle, nerves, skin, and blood vessels.

Are hyper acute reactions common? Why?

No due to the final crossmatch before transplant that will determine whether the recipient is sensitized to any of the donor HLAs (rarely does the crossmatch fail to detect it)

Is chronic rejection reversible?

No, irreversible, increased fibrosis and scarring

What prognosis is chronic rejection associated with?

Not associated with the optimistic prognosis of acute rejection- poor

When are the organs retrieved from a brain death donor?

OR team but retrieves organ before letting the patient pass away

When are organs retrieved when DCD?

OR team extubates, etc. until the patient dies, if the patient dies within an hour then they can retrieve the organs

What organs can be donated after cardiac death (DCD)?

Organs- heart, lungs, pancreas, intestine, liver

The Uniform Anatomical Gift Act (UAGA or the Act)

Passed in the US in 1968 and has since been revised in 1987 and in 2006. Sets a regulatory framework for the donation of organs, tissues, and other human body parts in the US. The UAGA helps regulate body donations to science, medicine, and education.

What occurs if chronic rejection occurs with a kidney transplant?

Patient will be followed (BUN, Cr, symptoms, etc.) to look for infection response Patients ends up back on dialysis and needs a new kidney

Why does body size matter?

Pediatric organ vs adult, may or may not work depending on the organ

What is the role of calcineurin inhibitors?

Prevent cell mediated attack against transplanted organ

What is the goal of using immunosuppressants for transplants?

Prevent rejection while maintaining sufficient immunity to prevent overwhelming infections

What are monoclonal antibodies used for?

Prevention and treatment of acute rejection episodes

What is the treatment for acute rejection?

Reversal with immunosuppressants, start immediately

What tissues can be transplanted?

Skin Bone Heart valves Connective tissues

Which part of the intestines would likely be transplanted?

Small intestines, probably the lower end

What is the treatment for chronic rejection?

Supportive care and back on the donor list

What is the effect of mycophenolate mofetil?

Suppressive effects on both T and B lymphocytes

What mediates an acute rejection?

T-cytotoxic lymphocytes

Which two calcineurin inhibitors are used?

Tacrolimus and Cyclosporine

Which act regulates organ/tissue donation?

The Anatomical Gift Act

What occurs in chronic rejection?

The organ is infiltrated with T and B cells (they injury the tissue) The organ will function at first then lose its function and eventually is completely lost

What are five considerations when matching donors and recipients?

1. ABO group 2. HLA 3. Geographic location 4. Body size 5. Severity of condition

What is the graft?

The transplantable tissue

What is matching HLA called?

Tissue typing

What is the current trend regarding medication in transplant centers? Why?

To use immunosuppression protocols that do not use corticosteroids because of their many side effects

What type of transplant therapy are most patients on?

Triple therapy: calcineurin inhibitor, a corticosteroid, and mycophenolate mofetil

When is LOPA contacted? OPA?

When a patient is expected to die or death has occurred OPA: organ procurement agency

When is mycophenolate mofetil most effective?

With tacrolimus or cyclosporine (synergistic effect)

When will a hyper acute reaction occur?

Within minutes to hours

Is donating your body to science different from life tissue donation?

Yes

Are acute rejections common?

Yes, it is not uncommon to have at least one episode

Why is geographic location considered?

You need to be able to get the organ transplanted within 72 hours

What is a HLA?

a gene complex encoding the major histocompatibility complex (MHC) proteins in humans. These cell-surface proteins are responsible for the regulation of the immune system in humans.

Crossmatching

a test done just before transplant. A crossmatch determines if your body already has antibodies formed against the donor's antigens. It is very important to know if you have antibodies against a possible donor, because if you are incompatible with that donor you would not be able to safely receive a transplant from him/her.

What would knock a patient off the donation list?

abuse and non-compliance, malignancies, infection/ sepsis

In heart transplants it manifests as

accelerated coronary artery disease

What does ABO group refer to?

Blood type and Rh factor

What occurs to cause an acute rejection?

Body reacts to the foreign tissue (response mediated) T-cells attack it

What is the foundation for most transplant regimens?

Calcineurin inhibitors

What does donation after death or cadaver donor refer to?

Cardiac or brain death Tissue- heart valve, bone, skin (can be retrieved up to 24 hours after death)

What are T and B cells characteristic of?

Chronic, low-drags immune mediated injury

Organs must be used within a certain time frame · A person joins the transplant list every ______ minutes

10 130 listed every day

What % chance is there that an identical sibling would be a HLA match?

100%

· ________ people on donor list

121, 076 LA: 2,107 [Kidney 1808, liver 194, heart 50, kid/ pan 35]

What occurs in tissue typing?

Closer the histology matches, the better chance for success (decreased chance for rejection)

In which type of transplant is chronic rejection common? rare?

Common in the lung, rare in the liver

If a patient on mycophenolate mofetil is experiencing NV and diarrhea, how should you respond?

Contact HCP to lower dose or give smaller doses more frequently

What besides organs can be donated?

Cornea Tissues Hands Face Bone marrow, blood steam cells, cord stem cells Blood and blood products

Tissue donation must be initiated within ____ hours of death. However, tissue can be processed and stored for an extended period of time. Each year, about 30,000 donors provide lifesaving and life-enhancing tissue

24

What % chance is there that a sibling would be a HLA match?

25%

How many HLAs are important for organ transplant?

6

Organs must be used within _____ hours

72

_____ people receive an organ each day ____-____ people die each day waiting for an organ

74 15-18

Who is usually the living donor?

A family member

What are the HLAs important for organ transplant?

A,B and DR antigens 3 from mother and 3 from father Example: A2, A30 B8, B70 DR3, DR8

What are the three types of rejections?

Acute Hyperacute Chronic

In kidney transplants it manifests as

fibrosis and glomerulopathy.

Chronic rejection results in

fibrosis and scarring

The local tissue bank (a tissue recovery organization) will be notified by the

hospital, medical examiner or funeral home

If person rejects the organ, if it is within the time period of viability—

it can be re-transplanted in another recipient

Tendons, the elastic-like cords that attach bones and muscles to each other, can be donated to help rebuild damaged

joints.

The more HLA matches the _____ likely the patient is to have an immune response

less

In liver transplants it is characterized by

loss of bile ducts

What is mycophenolate mofetil?

lymphocyte specific inhibitor of Purine synthesis

If there are 0 antigen mismatches for a kidney donor and recipient what does this mean? What will be done?

one kidney must be sent to that recipient It does not matter where they are on the list or where they are located (brings them high up on the list)

2,553 organs transplanted to date this year 1,193 donors used to be called _________ ________________

organ harvesting (less sensitive, more barbaric)

Skin can be used as a natural dressing for people with

serious burns. It can even save lives by stopping infections.

Most people can be _________ donors when they die.

tissue

What are three symptoms of neurotoxicity?

tremors, HA, parathesia

Monoclonal antibodies-

antiantigen receptor antibody that interferes with the function of the T lymphocytes, the pivotal cell in the response to graft rejection

In lung transplants it manifests as

bronchiolitis obliterans.