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Bench to bedside and beyond > 14. Transplantation and Rejection > Flashcards

14. Transplantation and Rejection Flashcards

1
Q

What is transfusion?

A

The transfer of blood or blood products from donor to recipient

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2
Q

What is transplantation?

A

The transfer of organs/tissues/cells from donor to recipient

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3
Q

What does NHS blood and transplant do?

A
  1. Manages blood transfusion and transplantation services
  2. includes donation, storage and transplantation of blood/blood components, organs, tissues, bone marrow and stem cells
  3. research
  4. 1.6 million units of blood a year
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4
Q

Why is there a push to increase black and ethnic minority donors?

A
  1. they are more likely to have certain blood types like Rh0 or B+
  2. This is very important for sickle cell patients
  3. important for people who need to have regular transfusions as they need to have an almost perfect match.
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5
Q

Who can receive a blood transfusion?

A
  1. potentially anyone
  2. people with severe blood loss through trauma
  3. neonates
  4. Pregnancy
  5. Surgical patients
  6. chronic anaemia
  7. cancer patients
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6
Q

Who can be a transfusion donor and what can they donate?

A
  1. potentially anyone
  2. Whole blood products
  3. Apheresis to separate blood products into platelets, plasma, granulocytes, concentrated RBC
  4. Stem Cells
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7
Q

What health checks do donors have to go through?

A
  1. All done to check out the infection risk
  2. Travel, Tattoos, recent infections, chronic conditions
  3. Screening for infections
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8
Q

What microbiological screening does blood go through?

A

Mandatory: HIV, HBV, HVC, HTLV, HEV and syphilis
Discretionary: Malaria, WNV, CMV, extra HBV (done if donor health checks bought up questions )
Bacterial screening: done for platelets only as they are stored at room temp so have a better chance of developing bacterial growth

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9
Q

What is a transfusion transmitted infection?

A
  1. An agent present in the bloodstream in an infectious form at a sufficient dose for infectivity.
  2. AND can withstand storage conditions for the blood products prior to transfusion
  3. viruses, bacteria and parasites but not all infectious agents
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10
Q

What are the bloodgroup antigens?

A
  1. A+/-
  2. B+/-
  3. AB+/-
  4. O+/-
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11
Q

Why do we need to consider blood group when doing a transfusion?

A
  1. The antigen on the surface of RBC can elicit an immune response
  2. There are 36 blood groups but we mainly worry about the main 8
  3. Alloantibodies form in response to antigens not present on the persons own RBC
  4. clinically significant alloantibodies cause problems in transfusion and transplantation
  5. We always consider donor and recipient ABO and RhD blood group
  6. Extended blood grouping is needed for people that need regular transfusions like sickle cell patients
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12
Q

Where are ABO antigens expressed?

A
  1. Red blood cells
  2. endothelial cells
  3. Epithelial cells
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13
Q

When do ABO antibodies arise?

A

most people have the naturally and are important for transfusion and transplants

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14
Q

When do anti-RhD antibodies arise?

A

AFTER exposure to incompatible blood including in pregnancy.
RhD incompatibility can cause immediate haemolytic transfusion reactions

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15
Q

Why do ABO alloantibodies arise naturally?

A

due to parts of the gut microbiome expressiing very similary carbohydrate antigens

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16
Q

When was the 1st organ transplant?

A

1905 - a cornea

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17
Q

When was the 1st liver transplant?

A

1963

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18
Q

When was the 1st kidney transplant?

A

1954

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19
Q

When was the 1st heart/lung transplant?

A

1983

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20
Q

In the UK how many people die in circumstances where transplantation available?

A

~5000

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21
Q

How many people die every day due to the shortage of donor?

A

3

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22
Q

What tissues/organs can be transplanted?

A
  1. Heart
  2. Kidney
  3. Liver
  4. Lungs
  5. cornea
  6. Heart valves
  7. bone
  8. skin
  9. hand
  10. face
  11. uterus
  12. small bowel
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23
Q

What cells can be transplanted?

A
  1. haemopoietic stem cells for leukaemia
  2. pancreatic islets
  3. other stem cell populations
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24
Q

Why would you need a transplant? - kidneys

A

chronic kidney disease leading to end stage renal failure
caused by
- diabetes
- nephritis
- polycystic kidney disease

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25
Q

Why would you need a transplant? - heart

A
  1. congenital heart disease
  2. coronary artery disease
  3. heart failure
  4. cardiomyopathy
  5. Valvular heart disease
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26
Q

Why would you need a transplant? - lungs

A
  1. Cystic fibrosis
  2. pulmonary oedema
  3. emphysema
  4. pulmonary hypertension
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27
Q

Why would you need a transplant? - liver

A

end-stage liver failure caused by:
1. congenital liver defects
2. chronic liver disease - cirrhosis and fibrosis

28
Q

Why would you need a transplant? - blood

A

Cancers
1. leukaemia
2. lymphoma
3. myeloma
Immune system/ metabolic disorders
1. sickle cell anaemia
2. thalassaemia
3. severe combined immunodeficiency

29
Q

Why were the 1943 Gibson and Medawar skin graft experiments important?

A
  1. important to understand the role of the immune system in transplant rejection.
  2. including donor-specific response, systemic immunity, immunological memory
30
Q

Why is the immune system a major barrier to successful transplantation?

A
  1. HLA class 1 are on all nucleated cells so can affect any transplant
  2. lymphocyte recognition of mismatched HLA is a major cause of rejection
  3. HLA genes are highly polymorphic so exact matching is very hard
31
Q

What are autologous transplants?

A

transplant from one part of the body to another part within the same person

32
Q

What are syngeneic transplants?

A

transplants between genetically identical people like identical twins

33
Q

What are allogeneic transplants?

A

Transplants between non-identical people of the same species

34
Q

What are Xenogeneic transplants?

A

Transplants between animals of different species.
This has the biggest risk of rejection.

35
Q

Why is HLA-matching important?

A
  1. in an ideal world every transplant will be a 100% match, not it is not possible
  2. HLA-matching is essential for haematopoietic stem cell transplants to avoid graft versus host disease
  3. HLA-matching is carefully considered for kidney transplants as they have more time to match them up due to dialysis and the length of storage of kidneys
36
Q

When is HLA-matching not considered?

A
  1. For heart and liver transplants
  2. organ preservation is a lot harder
  3. recipients are often critically ill
  4. ABO and anatomical matching is considered
  5. immunosuppression overcomes HLA mismatches
37
Q

HLA matching: tissue typing

A

PCR/NGS and serological techniques to determine HLA compatibility

38
Q

HLA matching: cross-matching

A

tests performed for anti-HLA alloantibodies in the recipient.
Called the complement-dependent cytotoxicity test

39
Q

HLA matching: other tests

A
  1. Serum from recipient screened pre-transplant
  2. Serum screened post-transplant to help detect rejection
40
Q

Why is it important to encourage black and minority ethnic donors?

A
  1. organ donation rates are a lot lower due to cultural differences, lack of trust, religion
  2. most minority ethnic patients wait longer for a transplant
  3. it is important to have a large pool of ethnically diverse donors
41
Q

Why is immunosuppression important in transplantation?

A
  1. developed in the 1960s
  2. allowed for non-HLA-identical transplants like heart
  3. cyclosporin inhibits proliferation and differentiation of T cells
  4. before cyclosporin most hearts and livers were rejected
  5. downsides of every drug like kidney damage
42
Q

what is a draw back of long-term immunosuppression?

A
  1. vulnerable to infection
  2. increase the risk of cancer
43
Q

What is a possible future of transplantation?

A

using enzymes to remove blood group antigens to get over the matching problem

44
Q

What needs to be considered for organ donation?

A
  1. type of donor - living or deceased
  2. consent for donation
  3. how the organs/cells are obtained
  4. how the organs/cells are processed
  5. how the organs/cells transported and stored
  6. degenerative biochemical changes
45
Q

What are some of the problems with living donors?

A
  1. lack of organ availability leading to donation for financial gain
  2. black market organs that are very dangerous for both donor and recipient
46
Q

What can you donate while you are living?

A
  1. bone marrow
  2. 1 kidney
  3. lobe of the liver
47
Q

What are the 2 types of deceased donors?

A
  1. donation after brainstem death (DBD)
  2. Donation after circulatory death (DCD)
48
Q

What is the criteria for brainstem death?

A
  1. catastrophic brain injury
  2. on a mechanical ventilator without which they wouldn’t survive
  3. 2 doctors must agree
  4. highly regulated
  5. Hard for families as they can still look alive
49
Q

What is uncontrolled circulatory death?

A

organ retrieval happens after unexpected cardiac arrest and the patient can’t/shouldn’t be resuscitated

50
Q

What is controlled circulatory death?

A

organ retrieval happens after a planned withdrawal of life-sustaining treatment

51
Q

How many organs can you get from each donor?

A

DCD = 2.8 organs
DBD = 3.2 organs

52
Q

Why is there lower donation potential for DCD donors?

A
  1. Ischaemic injury can occur in solid organs in the time between treatment withdrawal and cold perfusion
  2. the liver and pancreas are vulnerable but it is very problematic for heart transplants
  3. BUT DCD donors may be better for lung transplants to avoid a sympathetic storm
53
Q

What is a sympathetic storm?

A

An acute response of the sympathetic nervous system and produces lots of adrenaline.
Can dramatically affect the lungs

54
Q

What is a big barrier to donor consent and organ donation?

A
  1. families not talking about what they want to refusing donation on behalf of someone that wanted to donate
  2. living donors cannot financially benefit at all
55
Q

What is considered with donor status?

A
  1. cause of death
  2. age
  3. Co-morbidities
  4. smoker status
  5. active malignancy
  6. graft quality
  7. ischaemic time
56
Q

What is warm ischaemia?

A

When the donor organ is still in the body but cut off from the blood flow.
AND
When the organ is reattached in the recipient but blood flow hasn’t been restored

57
Q

What is cold ischaemia?

A

when the organ is in cold perfusion after retrieval

58
Q

What is reperfusion injury?

A

Reoxygenation causes dysregulated cellular metabolism which leads to a build up of ROS and cell injury

59
Q

What happens in organ processing and transport?

A
  1. need to prevent tissue deterioration and contamination
  2. organs must be retrieved immediately from decreased donors
  3. Organ retrieval service is 24/7
  4. degenerative change can occur during transport
60
Q

What causes degenerative changes during organs transport?

A
  1. enzymes
  2. oxidation
  3. free radicals
  4. microbial growth
61
Q

How can we limit degenerative changes?

A
  1. freezing of non-living tissue (-40–80) bone, cartilage
  2. cryopreservation of living tissue (-135) heart valves, arteries, skin
  3. storage of living tissue above 0 to support cell metabolism, proliferation, protein synthesis and cell repair
  4. Hypothermic storage (0-4) reduces metabolism and bacterial growth and increases tolerance to ischemia
62
Q

How long can organs last in hypothermic conditions?

A
  1. kidneys <2 days
  2. liver <24 hours
  3. Heart <6 hours
  4. Cartilage <28 days
63
Q

What is normothermic perfusion?

A
  1. deliver oxygen and nutrients
  2. removes waste products
  3. maintains blood vessels
  4. viability testing
  5. but it is complex and costly
64
Q

What microbiological screening do organ donors undergo?

A
  1. done to avoid donor-derived infection
  2. similar to transfusion tests
  3. additional CMV and EBV tests
  4. the majority of the adult population are infected with CMV and EBV
    Mandatory: HIV, HBV, HCV
    Recommended: HTLV, HEV, syphilis, CMV, EBV,
65
Q

How is organ offering done?

A
  1. which patient needs organs most urgently
  2. which patient is most likely to benefit
  3. A computer program matches patients to organs with agreed prioritisation
  4. decisions vary by organ type but considerations include: blood type, clinically significant antibodies, tissue type, geography, likelihood of being offered another organ, time on transplant list
66
Q

What are some surgical complications of transplants?

A
  1. infection
  2. rejection
  3. immunosuppression
  4. non-function of transplanted organ
  5. recurrence of disease
    6, quality of life
67
Q

What is the future of transplantation?

A

regenerative medicine
1. regenerate and repair damaged tissue
2. stem cells
3. gene editing
4. 3D printing
5. need graft vascularisation and innervation

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