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MCD: Immunology > Transplantation > Flashcards

Transplantation Flashcards

1
Q

When may organs be transplanted?

A

When they are failing or have failed, or for reconstruction.

Life-saving or life-enhancing/changing.

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2
Q

When is an organ transplant life-saving?

A

Other life-supportive methods not fully developed (e.g. liver, heart (LVAD)).

Other life-supportive methods have reached the end of their possible use (e.g. small bowel- total parenteral nutrition/ venous access problems).

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3
Q

When is an organ transplant life-enhancing?

A

Other life-supportive methods less good, e.g. kidneys (dialysis) or pancreas (in selected cases, tx better than insulin injections).

Organ not vital but improved quality of life, e.g. cornea, reconstructive surgery.

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4
Q

What are the different types of transplantation?

A

Autografts: within the same individual

Isografts: between genetically identical individuals of the same species

Allografts: between different individuals of the same species

Xenografts: between individuals of different species, e.g. heart valves (pig/cow), skin

Prosthetic graft: plastic, metal

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5
Q

What are allografts used for?

A

Solid organs (kidney, liver, heart, lung, pancreas)

Small bowel

Free cells (bone marrow, pancreas islets)

Temporary: blood, skin (burns)

Privileged sites: cornea

Framework: bone, cartilage, tendons, nerves

Composite: hands, face, larynx

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6
Q

What are the different types of allograft donor?

A

Deceased donor

Living donor

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7
Q

When may a living allograft donor be used?

A

Bone marrow, kidney, liver

Genetically related or unrelated (spouse; altruistic)

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8
Q

What are the different types of deceased organ donors?

A

DBD- donor after brain death (brain dead, heart-beating):

  • road traffic accident, massive cerebral haemorrhage
  • confirm brain death
  • harvest organs and cool to minimise ischaemic damage

DCD- donor after cardiac death (non-heart beating donors):

  • heart stopped before organ harvest
  • longer period of warm ischaemia time
  • suitable for kidney
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9
Q

How is a lack of brain stem function demonstrated?

A

Pupils both fixed to light

Corneal reflex absent

No eye movements with cold caloric test

No cranial nerve motor responses

No gag reflex

No respiratory movements on disconnection (with PaCO2 > 50mmHg)

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10
Q

What are the requirements for deceased donors (DBD, heart beating)?

A

Irremediable structural brain damage of known cause.

Apnoeic coma.

Demonstrate lack of brain stem function.

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11
Q

In a deceased donor (DBD, heart beating), what must their apnoeic coma not be due to?

A

Depressant drugs

Metabolic or endocrine disturbance

Hypothermia

Neuromuscular blockers

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12
Q

What must be excluded in deceased donors?

A

Viral infection (HIV, HBV, HCV)

Malignancy

Drug abuse, overdose or poison

Disease of the transplanted organ- USS potential donor

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13
Q

What is the absolute maximum cold ischaemia time for kidneys?

A

60 hours (ideally less than 24 hours, much shorter for other organs).

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14
Q

How are organs allocated?

A

5 tiers of patients depending on:

  • paediatric or adult
  • highly sensitised or not

7 elements:

  • 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
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15
Q

What are the most relevant protein variations in clinical transplantation?

A

ABO blood group

HLA (human leukocyte antigens) coded on chromosome 6 by MHC (major histocompatibility complex)

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16
Q

What is transplant selection?

A

Access to waiting list.

Referral of patients to transplantation centres for assessment.

Multidisciplinary teams assess suitability for transplantation- eligibility criteria.

Patient is placed on the NHS Transplant List.

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17
Q

What is transplant allocation?

A

Access to organ.

National guidelines.

Evidence based computer algorithm.

Equity- what is fair?

  • time on waiting list
  • super-urgent transplant- imminent death (liver, heart)

Efficiency- what is best use for the organs in terms of patients survival and graft survival?

18
Q

What are the contraindications for transplant selection?

A

Too early to be placed on waiting list.

Comorbidity- medical, psychiatric, surgical (e.g. CV disease, malignancy, compliance).

Patient does not want a transplant.

19
Q

What is NHSBT?

A

NHS Blood and Transplant.

Provision of a reliable, efficient supply of blood, organs and associated services to the NHS.

Rules for organ allocation are established by medical community/health professionals/advisory groups/DH.

NHSBT monitors allocation.

20
Q

What is the main obstacle to organ donation?

A

Family approached but declined consent to donation.

21
Q

How many people are on the organ donor register?

A

20 million

22
Q

How many people die on average every day in need of an organ?

A

3 people.

23
Q

How many people may an organ donor help?

A

As many as 9.

24
Q

How many organ transplants are there annually?

A

4,500

25
Q

How many people died in circumstances making them eligible for organ donation?

A

Around 6000

26
Q

Who can be a donor transplant coordinator, and what is their role?

A

Registered nurses with experience in critical care.

Employment to shift from transplant centres to NHSBT.

Potential donors A&E/ICU.

Carry out family interviews- part of bereavement services.

27
Q

What are some strategies to increase transplantation activity?

A

Deceased donation:
-marginal donors- DCD, elderly, sick

Living donation:

  • transplantation across tissue compatibility barriers
  • exchange programmes: organ swaps for better tissue matching

The future?

  • xenotransplantation
  • stem cell research
28
Q

What is the mechanism of graft rejection?

A

Antibody activates complement and macrophages.

Secretion of cytokines, proteolytic enzymes, and tissue injury.

29
Q

What is rejection?

A

Exposure to foreign HLA molecules results in an immune reaction to the foreign epitopes.

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

Most common cause of graft failure.

30
Q

How is organ rejection diagnosed?

A

Histological examination of a graft biopsy.

31
Q

How is organ rejection treated?

A

Immunosuppressive drugs.

32
Q

What are the different types of organ rejection?

A

Hyperacute
Acute
Chronic

T-cell mediated
Antibody-mediated

33
Q

What is the role of cytotoxic T cells in T cell mediated rejection?

A

Release of toxins to kill target (granzyme B).

Punch holes in target cells (perforin).

Apoptotic cell death (Fas-ligand).

34
Q

What is the role of macrophages in T cell mediated rejection?

A

Phagocytosis

Release of proteolytic enzymes

Production of cytokines

Production of oxygen radicals and nitrogen radicals

35
Q

What is antibody mediated rejection?

A

Antibody against graft HLA and AB antigen.
Antibodies arise pre-transplantation (‘sensitised’) or post-transplantation (‘de novo’).

Antibodies bind on antigens (AB or HLA) present on donor endothelium. Recruit and activate complement, leading to cell lysis and creation of membrane attack complex.

Directly recruit inflammatory cells such as mononuclear cells and neutrophils, which cause injury to endothelium.

Intravascular process.

36
Q

How are patients monitored for post-transplant rejection?

A

Deteriorating graft function:
-kidney transplant: rise in creatinine, fluid retention, hypertension
liver transplant: rise in LFTs, coagulopathy
lung transplant: breathlessness, pulmonary infiltrate

Subclinical:

  • kidney
  • heart (no good test for dysfunction, regular biopsies)
37
Q

How is rejection prevented?

A

Maximise HLA compatibility

Life-long immunosuppressive drugs

38
Q

What are the targets of immunosuppressive drugs?

A

Targeting T cell activation and proliferation

Targeting B cell activation and proliferation, and antibody production

39
Q

What is the standard immunosuppressive regime?

A

Pre-transplantation- induction agent (T-cell depletion or cytokine blockade).

From time of implantation- base-line immunosuppression:

  • signal transduction blockage, usually a CNI inhibitor: tacrolimus or cyclosporin, sometimes mTOR inhibitor (rapamycin)
  • antiproliferative agent: MMF or azathioprine
  • corticosteroids

If needed- treatment of episodes of acute rejection:

  • T-cell mediated: steroids, anti-T cell agents
  • antibody-mediated: IVIG, plasma exchange, anti-CD20, anti-complement
40
Q

What are the most common opportunistic infections post-transplantation?

A

Normally relatively harmless infectious agents give severe infections because of immune compromise.

Cytomegalovirus

BK virus

Pneumocytis carinii

41
Q

What are some possible post-transplantation malignancies?

A

Skin cancer

Post-transplant lymphoproliferative disorder- Epstein Barr virus driven

MCD: Immunology (5 decks)

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