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Transplant Flashcards

1
Q

What are the criteria for brainstem death (6)?

A
  • Fixed unresponsive pupils
  • Absent corneal reflex
  • Absent ouculovestibular/caloric reflexes
  • No response to supraorbital pressure
  • No cough/gag reflex
  • No respiratory efforts to hypercapnia (PaCO2 >6kPa or 6.5kPa if retainer)

Must also be normothermic, not sedated, all reversible circulatory, metabolic and endocrine disturbances excluded and reversible causes of apnoea exclude - in a patient who is comatosed with a known aetiology of irreversible brain damage

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2
Q

What is the most common complication after renal transplant?

A

Lymphocele - up to 50%

RAS 10% (thrombosis <1%)
Renal vein thrmobosis similar
Urine leak 10% (distinguish by measuring collection creatinine:serum creatinine)
Haemorrhage 1%

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3
Q

What is the most common side effect of cyclosporin?

A

Nephrotoxicity

Calcineurin inhibitor inhibits IL-2 and IFN-G – inhibits T cell activation

Also; hirsutism, gingival hyperplasia, tremor and hyperplasia

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4
Q

What mediates hyper acute rejection?

A

Preformed antibiodies within host

  • Complement system activated by antigens
  • neutrophils, endothelial and platelet activation
  • inflammation scarring and ischaemia

Type 3 hypersensitivity reaction

Acute - type 2 hypersensitivity mediated by B cells
Chronic - Type 4 hypersensitivity mediated by humoral and cellular mechanisms

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5
Q

What is the most common side effect of azathioprine?

A

Pancytopenia (esp leukopenia)

Others include alopecia, <1% pancreatitis/hepatotoxicity

Prodrug of 6-mercaptopurine - inhibits purine synthesis
MMF is similar - but has less bone marrow suppression and lower rejection rates

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6
Q

What are the indications for pancreas organ transplantation?

A

Usually IDDM, 6% NIDDM

  • ESRF
  • Hypoglycaemic unawareness
  • IDDM with uncontrolled ketoacidosis

Others

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7
Q

What are absolute contraindications to renal transplant (7)?

A
  • Predicted survival < 5 years
  • Incurable malignancy
  • HIV (?not true)
  • Severe CVS disease
  • Predicted graft loss >50% at 1 year
  • Anti-GBM antibody disease with circulating antibody
  • Inability to comply with immunosuppressants
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8
Q

What proportion of patients are insulin independent at 1 year post pancreatic transplant?

A

82%

cf 14% after islet transplantation (injected into portal vein percutaneously)

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9
Q

How much liver can be removed from a healthy donor?

A

55-70% (regenerates to almost 100% function within 4-6 weeks)

Complications 10%, mortality 0-1%

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10
Q

What are the Milan Criteria for liver transplant?

A

For HCC

  • Single tumour <5cm
  • Up to 5 tumours all ≤3cm
  • Single tumour 5-7cm stable over 6months

without major vessel or extra hepatic involvement

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11
Q

Which type of pancreas transplant has the best 1 year survival?

A

SPK 86%
PAK 80%
PTA 78%

Although complications and mortality higher with SPK

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12
Q

How is delayed graft function related to cold ischaemic time?

A

For every 6 hours, increases by 23%

Synergistic effect with Acute rejection - if both than 35% 5 year survival rate
Acute rejection more likely with DGF (37% vs 20%)

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13
Q

What are expanded criteria donors?

A

Donors with age >60 or

50-59 with vascular cormorbidities (hypertension, creatinine >133, death by ICH)

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14
Q

What is sirolimus?

A

Non-calcineurin (i.e. ciclosporin, tacrolimus) inhibitor immunosuppressant.

mammalian target of rapamycin (mTOR) inhibitor

also everolimus

lower nephrotoxicity/hypertension

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15
Q

What is Alemtuzumab?

A

anti-CD52 (all immune cells)

Often used with lyphmocyte depleting antibiodies in acute phase

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16
Q

What is the usual anti rejection protocol for renal transplants?

A

A Calcineurin inhibitor (Ciclosporin, Tacrolimus) or Sirolimus if intolerant
An anti proliferative drug (MMF, AZT)
Steroids

Probably should also have IL-2RA - Basiliximab, recently licensed and maybe anti-thymocyte globulin)

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17
Q

Which T-cell receptor binds to MHC-Class 1?

A

CD8- MHC Class 1 (A, B,C)

CD4 - MHC Class 2 (DP,DQ,DR)

Most important HLAs are DR > B >A, C

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18
Q

What are orthotopic and heterotopic transplants?

A

Orthotopic - normal anatomical site

Heterotopic - different

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19
Q

What are isograft, allograft and autografts?

A

Isograft - genetically identical (also syngeneic)
Allograft - same species, different genetically
Autograft - same individual

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20
Q

Which solid organ transplant is most commonly affected by vascular thrombosis?

A

Pancreas alone - 5-8%

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21
Q

In patients with blood group AB, what are the most important criteria for transplant?

A

Can receive any ABO,

therefore:

Living>DBD>DCD
then HLA

Rhesus is irrelevant

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22
Q

How frequently does acute rejection occur after a liver transplant?

A

Up to 40%, normally 7-10 days

Non specific features, obstructive jaundice, Banff schema

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23
Q

When might haematuria occur after a pancreatic transplant?

A

If there is a pancreaticoduodenocystostomy and Venus thrombosis occurs

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24
Q

What is the most common infection after a renal transplant?

A

UTI (30% in 3 months) - standard pathogens

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25
Q

What is the incidence of non melanomatous skin cancer after solid transplant?

A

45-75% at 20 years

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26
Q

Which virus is associated with Kaposi’s sarcoma?

A

HHV8

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27
Q

How is a renal transplant preserved after removal prior to transplantation?

A

Using University of Winsconsin solution at 4 degrees C

Cold ischaemic times of up to 20hours are well tolerated. Warm >20mins problematic

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28
Q

What is Encapsulating peritoneal sclerosis?

A

Intra-peritoneal fibrosis after PD

RF include duration, peritonitis and hypertonic glucose dialysate
If obstructive symptoms may need peritonectomy

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29
Q

What is the most common cause of a sudden loss of urine output after renal transplant?

A

Renal artery thrombosis

Renal vein thrombosis is more insidious with haematuria and pain

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30
Q

What is the histopathological finding of chronic liver rejection?

A

Paucity of bile ducts

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31
Q

How is acute rejection of liver transplant treated?

A

Steroids +/- polyclonal anti-T cell antibodies

Occurs in 30-50%

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32
Q

What is the characteristic complication of Tacrolimus treatment?

A

Diabetes (up to 50%)

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33
Q

What are the key factors in preventing rejection and improving liver graft survival?

A

-Short cold ischaemia
-Minimal size mismatch
-ABO matching (but may be overcome with rituximab!)
Avoid steatotic liver donors

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34
Q

What is the most common cause of liver transplantation in the UK?

A

Alcoholic liver disease
(?Hep C worlwide)

In children its primary biliary atresia

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35
Q

What are the most common causes of renal transplant?

A

Diabetes and Chronic Glomerulonephritis

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36
Q

What are the absolute and relative contraindications to organ donation?

A

Absolute

  • nvCJD
  • HIV

Relative

  • disseminated malignancy
  • melanoma (unless local and >5 yrs)
  • treated malignancy <3 years (except NMSC)
  • age >60
  • Active TB
  • active sepsis
  • Hep B/C
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37
Q

What is the threshold for vessel diameter and creating of AV fistulae?

A

2mm - 16% 3 month patency below this, 76% above.

Start radiocephalic then brachiocephalic probably.

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38
Q

What are the advantages of a brachiocephalic over radiocephalic fistula?

A

Higher flow rates, easier to cannulate, quicker to mature

but lower long term patency, higher swelling and steal and arch stenosis

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39
Q

In patients with chronic liver disease, what are some cause of decompensation (6)?

A 
Infection (UTI, pneumonia, SBP)
Hepatitis Flare
HCC
Portal vein thrombosis
Alcohol
Drug induced

(Cholangitis, Cancer)

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40
Q

What is the MELD score?

A

Composite score of 6-40 based on creatinine, bilirubin and INR predicts 3 month mortality

Can be used to triage transplant (?>16)

UKELD also used adds sodium - score above 49 (9% 1 year mortality) –> transplant

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41
Q

What criteria must be met before undertaking testing for brainstem death?

A
  • in apnoeic coma, unconscious and dependent on ventilation
  • known cause that could lead to brainstem death
  • all possibilities of drug intoxication, temperature aberration and metabolic imbalances excluded

If ICH, SAH can be performed within 6 hours
If hypoxic brain injury 24 hours

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42
Q

How is testing for brainstem death conducted 1+5?

A

By two experienced clinicians, at least 1 consultant, not involved in transplant.

1) Apnoea testing - preoxygenate for 10 mins, disconnect vent until PaCO2>6.65 and observe for absence of respiratory efforts

2) CN testing
-Check for pupillary reflex
Afferent/direct (II - optic)
Efferent/consensual (III - oculomotor)
-Corneal reflex
Afferent (V - trigeminal/ophthlamic)
Efferent (VII - facial)
- Vestibulo-ocular reflex (irrigate with cold water - eyes should move away)
Afferent (VIII - vestibular)
Efferent (VI - abducens)
-Supraorbital pressure
Afferent (V - trigeminal)
Efferent (VII Facial)
- Gag reflex
Afferent (IX Glossopharyngeal)
Efferent (VII Facial)
- Dolls eye reflex (move side to side and see if eyes move - not mandatory)
Afferent (VIII vestibular)
Efferent (VI Abducens)

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43
Q

What are the criteria for withdrawal of tacrolimus/calcineurin inhibitors?

A

> 12 months post transplant
no episodes of acute rejection in last 3 months
no contraindications to MMF or antiproliferatives

biopsy demonstrating absence of cell/antibody mediate rejection

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44
Q

What are the causes of chronic transplant dysfunction (CTD)?

A 
Prexisting - donor disease, injury at retrieval, ischaemia-reperfusion
Post transplant
-Immune mediated injury, rejection (acute/chronic)
-Recurrent GN
-Obstruction
-UTI
-Renal vascular stenosis
-Atheromatous disease
-Hypertension
-Calcineurin inhibitor toxicity
-BK virus nephropathy
-DM
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45
Q

What is the Childs Pugh score?

A

Combination of:

1) Encephalopathy
2) Ascites
3) Bilirubin
4) Albumin
5) PT

Childs Pugh A 5-6 points = least severe - 1 year survival 100%
Childs Pugh B 7-9 points = moderate severity - 80%
Childs Pugh C 10-15 points = most severe - 45%

Can only be A if only 1 mild abnormality - bili>34, alb<35, INR >1.7, ascites or encephalopathy

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46
Q

In whom should CMV prophylaxis be given?

A
  • CMV neg, donor CMV positive
  • if having T cell depleting antibodies for induction if either donor or recipient positive

Usually Valganciclovir within 10 days for 100 days.

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47
Q

What are optimal tacrolimus levels?

48
Q

What are the outcomes for liver transplant in the UK?

A

90% graft survival at 1 year

70-75% at 6 years - Cholestatic disease > HCV/malignant disease

49
Q

What is the most common anatomic variants of liver anatomy?

A

Hiatt group 2: Replaced Left hepatic artery from LGA (9.7%)
Hiatt group 3: Replaced right hepatic artery from SMA (10.6%)

Traditional 75.7%

50
Q

What is the most common cause of acute liver failure in the UK?

A

Paracetamol > Non-A-to-E-Hepatitis > other drugs >Viral

<10% of transplants

51
Q

Which patients with paracetamol induced liver failure should be discussed with the liver unit? (6)

A
  • pH<7.3 or HCO3<18
  • INR>3 on D2 or >4 after
  • Oliguria/AKI
  • Altered level of consciousness
  • Hypoglycaemia
  • Lactate >4 unresponsive to fluids
52
Q

What features of decompensation of CLD should warrant consideration of liver transplant?

A
  • Jaundice
  • Ascites
  • Variceal haemorrhage
  • Hepatic encephalopathy
53
Q

What UKELD score suggests a survival benefit to transplantation?

A

≥49

Some others also benefit e.g. PBC with intractable pruritus

54
Q

In which situation can a non Milan criteria HCC be transplanted?

A
  • 5-7cm if no progression over 6 months

- HCCs downstaged with TACE etc

55
Q

What are absolute contraindications to Liver Transplant?

A
  • Predicted extra hepatic mortality >50% at 5 years
  • Severe irreversible pulmonary disease
  • Alcohol/drug misuse
  • Active or previousextra-hepatic malignancy (exc neuroendocrine)
    • Extrahepatic sepsis, untreated HIV, Liver cancer outside criteria
56
Q

What proportion of patients added to the Liver transplant waiting list are transplanted within 1 year?

57
Q

How are liver transplants post DBD allocated?

A

Transplant benefit score

58
Q

In which order is the liver usually plumbed in at transplant?

A

1) IVC
2) PV
3) HA
4) CBD

59
Q

If used, when should sirolimus be started after liver transplant?

A

At least 3 months due to risk of hepatic artery thrombosis and impaired wound healing

60
Q

When should steroids be avoided following liver transplant?

A

If for Hep C

61
Q

What are the leading causes of death post liver transplant (after 1 year)

A

Malignancy (22%)
CVD (11%)
Infection (9%)

62
Q

What is the rate of recurrence of PBC and PSC following liver transplant?

A

50% and 70% at 5 years

63
Q

How does a urine leak post transplant present?

A

Perigraft collection
Rising creatitine
Falling urine output

64
Q

How frequently should HLA status be reassessed in patients on the transplant list?

A

At least once every 3 months

If sensitising event then 2-4 weeks after this

65
Q

Which subtype of Blood group A is least antigenic?

66
Q

What is the mortality at 5 years after elective liver transplant?

67
Q

What is the BANFF Classification?

A 
Assessing for chronic rejection
Grade 1 - interstitial Inflammation with tubulitis (A/B)
A: Moderate tubulitis
B: Severe tubulitis
Grade 2 - Intimal arteritis
A: Mild/moderate
B: Severe
Grade 3 - Transmural arteritis
68
Q

When is CD3/OKT mostly used?

A

In acute rejection where other measures have failed

Muromonomab OKT

69
Q

Which class of antibodies mediate hyper acute rejection?

70
Q

What agents might be useful for treatment of CMV infection?

A

Valganciclovir
Ganciclovir
Foscarnet
Cidofovir

71
Q

How often should renal transplant criteria be reassessed if still on the list?

72
Q

In patients with detectable HBV DNA, what antivirals are helpful pretransplant?

A

Entecavir and Tenofovir

73
Q

Which immunosuppressant is specifically contraindicated in pregnancy?

A

Myocphenolate

74
Q

Which immunosuppressant should be withdrawn when chronic rejection is suspected?

A

Tacrolimus

75
Q

Which agent can be given to reduce the risk of non melanoma skin cancer in renal transplant patients?

A

Acitretin

Also favour sirolimus

76
Q

At what GFR is retransplant offered?

A

10-15ml/min

77
Q

Where does the most severe reperfusion injury occur?

A

At time of transplant

78
Q

How does MMF work?

A

Inhibition of ionisine monophosphate dehydrogenase

79
Q

How should fistula associated steal be treated?

A

Banding initially

80
Q

What is often the mechanism of prolonged bleeding post fistula needling?

A

Venous outflow stenosis (ix fistulogram)

81
Q

How should early problems with a pancreatic transplant be investigated?

A

Probably CT

82
Q

What is the role of HLA matching in liver transplant?

A

It is not useful and not measured

83
Q

how should bk virus detection be managed?

A

decrease immunosuppression

84
Q

What are the Maastricht criteria?

A

1 to 5

3/4 controlled/suitable

85
Q

How does Alemtuzumab work?

A

Anti-CD52

Campath

86
Q

What diabetes complication is characteristically not reversed by transplant?

A

Peripheral neuropathy

86
Q

What diabetes complication is characteristically not reversed by transplant?

A

Peripheral neuropathy

87
Q

What is the incidence of wound complications in patients undergoing surgery on Sirolimus?

A

25-50% poor wound healing/seroma

88
Q

how should a post transplant urine leak be managed?

A

decompress bladder
if no better –> surgery
if delayed consider nephrostomy

88
Q

how should a post transplant urine leak be managed?

A

decompress bladder
if no better –> surgery
if delayed consider nephrostomy

89
Q

what criteria indicate renal transplant?

A
  • eGFR<15

- Or expected within 6 months and will convey survival benefit

90
Q

When is the earliest a renal transplant biopsy might be performed?

91
Q

How often is reoperation required for SPK?

A

25% bleeding!

92
Q

what is a key factor differentiating renal vein from artery thrombosis?

A

Swelling of wound/kidney 3% vs 1%

93
Q

What is the most common cause of late failure of AV fistulas?

A

Stenosis - reduction in vessel lumen by >50%

Neointimal proliferation –> angioplasty

94
Q

How frequently are there accessory renal arteries?

94
Q

How frequently are there accessory renal arteries?

95
Q

What is the orientation of the renal hilum?

A

Vein Anteriorly then artery then ureter posteriorly

96
Q

What is the 5 year survival of renal, liver and sb transplants?

A

80-90%
60-79%
<40%

97
Q

What is the definitive treatment of choice for symptomatic lymphocoele post renal transplant?

A

Laparoscopic fenestration

98
Q

Which immunosuppressant is associated with tremor?

A

Tacrolimus

99
Q

What threshold should be used for vein diameter when making an AVF?

A

> 2cmm (patency at 3 months of 76% vs 16%)

100
Q

What are the pros/cons of an elbow vs wrist fistula?

A 
Pros - higher flow, easier to cannulate
Cons 
-- lower long term patency
-- increased steal
-- more arm swelling
-- shorter vein for needling
101
Q

What is the first line treatment for steal in an AVF?

A

Banding - praline suture around a balloon catheter to narrow venous outflow

then ?bypass (DRIL)

102
Q

How does renal failure increase the risk of CVS disease?

A

Volume overload due to excess fluid and anaemia –> LVH
Arterial medial calcification (hyperparathyroidism)
Cardiac myocyte injury due to uraemia, PTH and ATII
Oxidant stress
Hyperhomocysteinaemia

103
Q

How should a patient with suspected chronic renal transplant rejection be investigated?

A 
History of symptoms, compliance
Examination fro fluid overload
Tests
- U&E, HbA1c, Tacrolimus levels
- Virology (CMV EBV, BK/JC)
- Urinalysis/culture
- USS kidney (RAS)
- Biopsy sometimes
104
Q

When can calcineurin inhibitors be withdrawn?

A

> 12 months post transplant
No acute rejection in last 3 months
Biopsy demonstrating absence of cell/antibody mediating rejection
No contraindication to MMF

105
Q

How can hepatic encephalopathy be classified?

A

World congress of gastroenterology classification system (minimal, episodic, persistent)

West Haven criteria

106
Q

How is a fistula clinically assessed?

A

Palpable thrill (loss –> stenosis/thrombosis)
Aneurysmal dilatation
Redness/pain (infection)

Dopple flow rate (should be more than 300ml/min for AVF)

107
Q

What are the Maastricht criteria?

A

I - DOA - uncontrolled
2 - Failed resuscitation - uncontrolled
3 - Awaiting Cardiac arrest - controlled
4 - Cardiac arrest in brainstem dead - controlled
5 - unexpected cardiac arrest in critically ill patient

108
Q

When may organ donation be considered in patients awaiting cardiac death?

A

<30 mins of hypotension <50mmHg + SpO2<70% (Liver and Pancreas)
<4 hours of asystole (Kidneys)

5 minute standoff time, <15minutes to cold perfusion

109
Q

What is the mechanism of anti-rejection of steroids?

A

Upregulate IL-10

Down regulate IL2, IL6 and IFN Gamma

110
Q

What are the risk factors for primary non-function of a liver transplant?

A 
--Donor
Increasing donor age
Steatosis
Elevated Sodium
DCD

–Recipient
Prolonged cold ischaemic and warm ischaemic time
haemodynamic instability

111
Q

What are the biopsy characteristics of acute rejection (liver)?

A

Cellular (occurs in 20-80% at D5-30)
Portal inflammation
Bile duct inflammation
Venous inflammation

Banff criteria - indeterminate, mild, moderate, severe

Antibody

  • Portal oedema
  • ductular reaction
  • neutrophil rich inflammatory infiltrate
112
Q

When does Post Transplant Lymphoproliferative disease tend to present?

A

Most within 1 year, corresponding to aggressive immunosuppression. Late presenters tend to have aggressive tumors and worse prognosis

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