Transplantation Flashcards

1
Q

What is the difference between life-saving and life-enhancing transplantation?

A

Life-saving – other life-supportive methods are not fully developed or other life-supportive methods have reached the end of their possible use e.g. liver

Life-enhancing – other life-supportive methods are less good e.g. Kidneys and dialysis – the organ is not vital but it improves the quality of life e.g. cornea

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2
Q

What are the different types of transplants?

A

Autograft – within the same individual

Isografts – between genetically identical individuals of the same species

Allograft – between different individuals of the same species

Xenograft – between individuals of different species

Prothetic graft – artificial material e.g. plastic, metal

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3
Q

Give an example of an autograft.

A

Coronary artery bypass graft

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4
Q

What tissues can xenografts be used for?

A

Heart valves

Skin

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5
Q

What are the two types of deceased donor?

A

Donor after brain death – brain dead but heart-beating

Donor after cardiac death –non-heart beating donors

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6
Q

What must be confirmed with DBD donors?

A

Irremediable structural brain damage of known cause

Apnoeic coma that is NOT due to depressant drugs, hypothermia, neuromuscular blockers etc.

Must be able to demonstrate a lack of brain stem function (e.g. pupils both fixed to light)

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7
Q

What must be excluded before harvesting organs from a deceased donor?

A

Viral infection
Malignancy
Drug abuse, overdose or poison

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8
Q

How are the organs maintained once they’ve been removed?

A

They are rapidly cooled and perfused

NOTE: absolute maximum cold ischaemia time for the kidneys is 60 hours

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9
Q

What is the difference between transplant selection and transplant allocation?

A

Selection – access to the waiting list

Allocation – access to the organ

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10
Q

What is the nationwide system of transplant allocation based on?

A

Equity – fairness

Efficiency – what is the best use of the organ in terms of patient and graft survival?

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11
Q

What are the 5 tiers of patients on the organ transplant waiting list based on?

A

Paediatric or adult

Highly sensitised or not

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12
Q

What are the 7 elements that are used to decide upon organ allocation?

A

Main 3:
Waiting time

HLA match and age combined

HLA-B homozygosity

Other 4:

HLA-DR homozygosity

Donor-recipient age difference

Location of patient relative to donor

Blood group match

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13
Q

What are the main obstacles to donation?

A

Contraindication for use of that organ

Family not approached for consent

Family declined consent

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14
Q

Describe some other strategies for increasing transplantationactivity.

A

Use marginal donors e.g. elderly and sick

Transplantation across compatibility barriers

Exchange programmes – organ swaps for better tissue matching

Future – xenotransplantation + stem cell research

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15
Q

What are the main antigens that must be considered when determining the compatibility of an organ for transplant?

A

ABO blood group

HLA

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16
Q

On which chromosome is the HLA gene encoded?

A

Chromosome 6

17
Q

What are the two classes of HLA and which HLA subtypes are in each class?

A

HLA Class I – A, B and C = present on all cells

HLC Class II – DP, DQ, DR = present on specialised immune cells

18
Q

What are the most important HLA subtypes in organ compatibility?

A

A
B
DR
NOTE: the fewer the number of mismatches, the better the outcome for the recipient

19
Q

What are the two types of organ rejection?

A

T cell-mediated rejection

Antibody-mediated rejection (B cells)

20
Q

How is rejection diagnosed?

A

Histological examination of graft biopsy

21
Q

How is rejection classified based on the time of onset?

A

Hyperacute
Acute
Chronic

22
Q

How may organ rejection present?

A

Deteriorating graft function e.g. rise in creatinine with kidney transplant

Pain and tenderness over graft

Fever

23
Q

How can rejection be prevented?

A

Maximise HLA compatibility

Life-long immunosuppressive therapy

24
Q

List some treatments for Antibody-mediated rejection.

A

Anti-CD20 antibodies

Bortezomib (proteasome inhibitor)

Anti-complement antibodies

Plasma exchange

IVIg

Splenectomy

25
What is normally used for baseline immunosuppression following transplantation?
Signal transduction blockade: usually a calcineurin inhibitor (tacrolimus or cyclosporin) Antiproliferative agent (e.g. azathioprine) Corticosteroids
26
Describe the treatment of episodes of acute rejection.
T cell mediated: steroids and anti-T cell agents Antibody mediated: IVIg, plasma exchange, anti-CD20, anti-complement
27
What are the risks of the extensive immunosuppressive therapy that is given to patients following transplantation?
Increased risk of infection (including opportunistic infection) Malignancy Drug toxicity
28
What can be translplanted from a living donor?
bone marrow, kidney, liver
29
Why are transplantations required?
rgans are transplanted when they are failing or have failed, or for reconstruction
30
How does blood group effect transplantation rejection?
A and B proteins with carbohydrate chains on red blood cells but also endothelial lining of blood vessels in transplanted organ O has neither A or B Antibodies are produced to all blood group antigens not expressed If receive organ with other antigens on then your antibodies will attack it
31
How can ABO-incompatible transplantation be overcome?
Remove the antibodies in the recipient (plasma exchange) Good outcomes (even if the antibody comes back)
32
What's the mechanism of t cell mediated rejection?
T cell activation by APC Graft infiltration by alloreactive CD4+ cells Cytotoxic t cells: Release of toxins to kill target Granzyme B Punch holes in target cells Perforin Apoptotic cell death Fas -Ligand Macrophages: Phagocytosis Release of proteolytic enzymes Production of cytokines Production of oxygen radicals and nitrogen radicals
33
What's the mechanism of antibody mediated rejection?
Antibody against graft HLA and AB antigen Antibody activates complement and macrophages
34
What are the 2 ways of antibody production against a transplant?
Pre-transplantation (“sensitised”) Post-transplantation (“de novo”)
35
What is the stadard immunosupressive regime pre-implantation?
Induction agent for T-cell depletion or cytokine blockade.