Transplantation Flashcards

(35 cards)

1
Q

When are organs transplanted

A

when they are failing or have failed, or for reconstruction

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2
Q

Give examples of organs that can be transplanted

A
Cornea
Skin 
Heart 
Lungs 
Kidney 
Liver
Bone Marrow
Small bowel 
Pancreas
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3
Q

What are the 4 types of transplant

A

Autograft
Isograft
Allograft
Xenograft

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4
Q

What is an autograft

A

within the same individual e.g. skin from buttock to face

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5
Q

What is an isograft

A

between genetically identical individuals of the same species

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6
Q

What is an allograft

A

between different individuals of the same species

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7
Q

What is a xenograft

A

between individuals of different species e.g. pig or cow heart valves

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8
Q

What are the two types of decreased donor

A

After brain death (DBD)

After cardiac death (DCD)

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9
Q

Describe the DBDs

A

Brain injury has caused death before terminal apnoea has resulted in cardiac arrest and circulatory standstill

E.g. Intracranial haemorrhage; road traffic accident (catastrophic cerebral haemorrhage)

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10
Q

What must be done with DBDs before harvesting

A

Brain death must be confirmed before the organs are harvested and cooled
Confirm using neurological criteria
Circulation established through resuscitation

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11
Q

What is the criteria for DBDs

A

Irremediable structural brain damage from a known cause
Demonstrable lack of brainstem function

Apnoeic coma not due to:

  • depressant drugs
  • metabolic / endocrine disturbance
  • hypothermia
  • neuromuscular blockers
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12
Q

How is lack of brainstem function demonstrated for DBDs

A

Eyes unresponsive (pupillary light reflex, corneal reflex, and cold caloric reflex test)
Cranial nerve motor reflexes absent
Gag reflex absent
No respiratory movements on disconnection from ventilator

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13
Q

What are some reasons for exclusion of a DBD

A

Viral infection, especially HIV, HBV, HCV
Malignancy
Drug abuse, overdose, or poisoning
Disease of the organ itself

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14
Q

What is the number 1 obstacle to donation and what is the rate for this

A

A braindead person’s family refusing to consent for his/her organs to be transplanted
43% refusal rate

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15
Q

What are some potential strategies for increasing transplantation

A

including more marginal donors (i.e. slightly relaxing some criteria for the deceased’s organs)

Exchange programmes to acquire better tissue matches

Xenotransplantation and stem cell research for the future

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16
Q

Describe DCDs

A

death is diagnosed and confirmed using cardio-respiratory criteria; 5 minutes observation of irreversible cardiorespiratory arrest
Controlled or uncontrolled
Longer period of warm ischaemia time

17
Q

What re the 7 elements of organ allocation for the kidney

A
Waiting time
HLA match and age combined
Donor-recipient age difference
Location of patient relative to donor
HLA-DR homozygosity
HLA-B homozygosity
Blood group match
18
Q

What are the most relevant protein variations in clinical transplantation

A

ABO blood group

HLA (human leukocyte antigens) coded on chromosome 6 by Major Histocompatibility complex (MHC)

19
Q

What is the consequence of not ABO cross matching between donor and recipient

A

Hyperacute rejection occurs as the foreign cells are lysed by complement and/or phagocytosed all with massive inflammation, platelet activation etc..

20
Q

How is ABO-incompatible matching overcome in transplantation

A

remove the recipient’s A/B antibodies (plasma exchange) with good outcomes

21
Q

Where are class I and II HLA expressed

A
Class I (A, B, C)- all cells
Class II (DR, DQ, DP) - immune cells (can be unregulated on other cells)
22
Q

Describe HLA molecules

A

Highly polymorphic – lots of alleles for each locus

Each individual has most often 2 types for each HLA molecule (for example: A3 and A21)

23
Q

What does exposure to a foreign HLA molecule result in

A

Immune response mediated by both B cells and T cells.

The immune reaction can cause immune graft damage and failure = rejection

24
Q

How important is HLA matching in organ donation and what is the criteria for it

A

HLA does not have to be perfectly matched (as that’s impractical) but there must be <6 mismatches

25
How is organ rejection diagnosed
histological examination of a graft biopsy
26
How is organ rejection treated
Immunosuppressive drugs
27
Which organs' rejection can be tested clinically and how
Kidney - creatinine Pancreas - serum amylase/lipase/glucose Hearts cannot be
28
What does a standard immunosuppressive regime entail
An induction agent Basline immunosuppression Treatment of episodes of acute rejection
29
Give examples of induction agents
e.g. cytokine blockade, T cell depletion
30
Give examples of agents used for baseline immunosuppression
Signal transduction blockade e.g. calcineurin inhibitor (cyclosporin), mTOR inhibitor Antiproliferative agent e.g. azathioprine Corticosteroids
31
How are acute rejection episodes treatment
Cellular: steroids, anti-T cell agents | Antibody-mediated: IVIg (intravenous immunoglobulin), anti-C5, plasma exchange
32
Describe the T cell lymphocyte response to pathogens and to donor cells
Foreign bodies taken up by APCs and presented on the membrane. T lymphocytes only recognise foreign proteins in the context of self cells In donor cells, they shed their own HLA molecules which are presented on APCs
33
What are the mechanisms fo T-cell mediated rejection
Graft infiltration by alloreactive CD4+ cells “Cytotoxic” T cells Macrophages
34
Describe how cytotoxic T cells bring about T-cell mediated rejection
Release of toxins to kill target e.g. Granzyme B Punch holes in target cells via perforin Apoptotic cell death via Fas -Ligand
35
Describe how macrophages bring about T-cell mediated rejection
Phagocytosis Release of proteolytic enzymes Production of cytokines Production of oxygen radicals and nitrogen radicals