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Flashcards in Transplantation Deck (31)
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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
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

2
Q
Describe the different types of transplants?
Autograft 
Isografts 
Allograft 
Xenograft 
Prothetic graft
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

3
Q

Give an example of an autograft.

What tissues can xenografts be used for?

A

Coronary artery bypass graft

Heart valves
Skin

4
Q

What are the two types of deceased donor?

A

Donor after brain death – brain dead but heart-beating (death is confirmed using neurological criteria)
Donor after cardiac death –non-heart beating donors (death is confirmed using cardio-respiratory criteria)

5
Q

What must be confirmed with DBD donors?

A
  • Irremediable structural brain damage of known cause
  • Apnoeic coma that is NOT due to CV instability or depressant drugs, hypothermia, neuromuscular blockers etc.
  • Must be able to demonstrate a lack of brain stem function (e.g. pupils both fixed to light)
6
Q

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

A

Viral infection
Malignancy
Drug abuse, overdose or poison

7
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

8
Q

What is the difference between transplant selection and transplant allocation?

A

Transplant selection: waiting list at a transplant centre after multidisciplinary assessment

Transplant allocation: how organs are allocated as they become available

9
Q

What is the nationwide system of transplant allocation based on?

A
  1. Equity/fairness:
    - Time on waiting list
    - Super-urgent transplant
  2. Efficiency – what is the best use of the organ in terms of patient and graft survival?
10
Q

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

A

Paediatric or adult

Highly sensitised or not

11
Q

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

A
Waiting time
HLA match and age combined
HLA-B homozygosity
HLA-DR homozygosity
Donor-recipient age difference
Location of patient relative to donor
Blood group match
12
Q

Describe some strategies for increasing transplantation activity.

A
  • Increase deceased donation
  • Look for other sources of organs (e.g. “marginal donors”, xenotransplantation, stem cell biology etc.)
  • Optimise use of currently available organs (improve the half-life of an allograft)
13
Q

What are the two most relevant protein variations in clinical transplantation?

A
  1. ABO blood group

2. HLA (human leukocyte antigens)

14
Q

On which chromosome is the HLA gene encoded?

A

Coded on Chromosome 6 by MHC

15
Q

Where are the A and B proteins/antigens with carbohydrate chains found?

A

On red blood cells but also endothelial lining of blood vessels in transplanted organ

16
Q

Recall the structural differences between A, B, and O.

Describe the 4 main blood groups in terms of the antibodies in the plasma and the antigens on red blood cells.

A
A = has N acetyl-galactosamine
B = has galactose instead
O = has neither
Blood groups:
A: has anti-B
B: has anti-A
AB: no antibodies
O: has anti-A and anti-B (no antigens on RBC)
17
Q

What is ABO-incompatible transplantation?

A
  • Remove the antibodies in the recipient
  • Good outcomes (even if the antibody comes back)
  • Kidney, heart, liver
18
Q

What are the two classes of HLA and which HLA subtypes are in each class? Describe the polymorphic nature of these genes.

A

HLA Class I – A, B and C = present on all cells
HLC Class II – DP, DQ, DR = present on specialised antigen-presenting cells

Highly polymorphic – lots of alleles for each locus (for example: A1, A2, …, A341… etc.)
Each individual has most often 2 types for each HLA molecule (for example: A3 and A21)

19
Q

What are the most important HLA subtypes in organ compatibility?

A

A
B
DR

20
Q

Describe how to convey the number of A/B/DR mismatches? State the percentage chance for different numbers of mis-matches between siblings.

A

See which two alleles the recipient has for each of HLA-A, HLA-B, and HLA-DR.
Do the same for the donor.
Add up the number of matches between the two (i.e. max. no. of total matches = 6)
e.g. MM = 1:2:0 = 3 mis-matches

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

Sibling transplant = 25% chance of 0MM,25% chance of 6MM, 50% chance of 3MM.

21
Q

What are the two types of organ rejection?

A

T cell-mediated rejection

Antibody-mediated rejection (B cells)

22
Q

How is rejection diagnosed?

A

Histological examination of graft biopsy

23
Q

How is rejection classified based on the time of onset?

A

Hyperacute rejection
Acute rejection
Chronic rejection

24
Q

How may organ rejection present?

A

Deteriorating graft function e.g. rise in creatinine with kidney transplant
Pain and tenderness over graft
Fever

25
Q

Describe what happens in T cell-mediated rejection.

A
  • The graft can be infiltrated by allo-reactive CD4+ cells.
  • CTL lymphocytes release toxins to kill target (Granzyme B), punch holes in target cells (Perforin), trigger apoptotic cell death (Fas-Ligand)
  • Macrophages can phagocytose, release proteases, cytokines and oxygen/nitrogen radicals.
26
Q

In antibody-mediated rejection, antibodies are made against graft HLA and AB antigens. In what two ways can these antibodies arise?

A

Antibodies arise:
Pre-transplantation – ‘sensitised’ i.e. patient already been exposed in pregnancy or previous transplants.
Post-transplantation – ‘de novo’.

You may see features of both forms of rejection in graft rejected patients.

27
Q

How can rejection be prevented?

A

Maximise HLA compatibility

Life-long immunosuppressive therapy

28
Q

List some treatments for Antibody-mediated rejection.

A
Anti-CD20 antibodies
Bortezomib (proteasome inhibitor)
Anti-complement antibodies
Intravenous immunoglobulin (IVIG)
Plasma exchange
Splenectomy
29
Q

What is normally used for baseline immunosuppression following transplantation?

A

HLA binding signal transduction blockade: usually a calcineurin inhibitor (tacrolimus or cyclosporin)
Antiproliferative agent (e.g. azathioprine targets T cell cycle)
Corticosteroids

30
Q

Describe the treatment of episodes of acute rejection.

A

T cell mediated: steroids and anti-T cell agents

Antibody mediated: IVIg, plasma exchange, anti-CD20, anti-complement

31
Q

What is a major risk of the extensive immunosuppressive therapy that is given to patients following transplantation?

A
  • Increased risk of infection (opportunistic or conventional infection)
  • Post-transplantation malignancy