Surgery

Question 1

In transplantation, what are the three most important HLA-types and what HMC classes do they belong to?

Answer 1

MHC I:
     - HLA A
     - HLA B
MHC II:
     - HLA DR

Question 2

What cells have MHC I on their surface?

Answer 2

All nucleated cells

Question 3

What cells have MHC II on their surface?

Answer 3

APCs

Question 4

How might a donor produce specific HLA antibodies?

Answer 4

Exposure to HLA antigen:

 - Blood transfusion
 - Placenta
 - Previous transplant

Question 5

Put the following steps in a possibel model for transplant rejection in order:

• CD4+ (Th) cells activate B cells, NK cells and complement + cytokines
• B cells produce antibodies
• CD4+ cell activated by HLA Ag presented to it on MHC
• HLA Ag is taken up by an APC
• Antibodies, NK cells and CD8+ (Tc) cells result in rejection
• APC presents HLA Ag via MHC

Answer 5

1. HLA Ag is taken up by an APC
2. APC presents HLA Ag via MHC
3. CD4+ cell activated by HLA Ag presented to it on MHC
4. CD4+ (Th) cells activate B cells, NK cells and complement + cytokines
5. B cells produce antibodies
6. Abs, NK cells and CD8+ (Tc) cells result in rejection

Question 6

What infections can result if there is too much immunosuppression?

Answer 6

BK virus
CMV
Recurrent UTIs
Pneumocystic jiroveci

Question 7

What cancers can arise if there is too much immunosuppression? What might predispose to these?

Answer 7

Non-melanome skin cancer:
- Squamous and fast growing (usually)
Lyphoma:
- Espeically if not EBV immune

Question 8

What can result if there is too little immunosuppression?

Answer 8

Graft dysfunction

Graft loss

Question 9

What is the first sign of graft dysfunction/loss?

Answer 9

Rise in serum creatinine

Question 10

What causes a hyperacute transplant rejection?

Answer 10

Due to a positive crossmatch:

 - Preformed Abs to transplant
           - > eg. Different blood types

Question 11

How is a hyperacute kidney rejection treated?

Answer 11

Immediate removal

Question 12

What mediates an acute transplant rejection?

Answer 12

T or B cells

Question 13

How can an acute transplant rejection be treated?

Answer 13

Immunosuppression

Question 14

What can cause a chronic transplant rejection?

Answer 14

Immunological and vascular deterioration of the transplant

Question 15

What are the two examples of calcineurin inhibitors?

Answer 15

Cyclosporin

Tacrolimus

Question 16

How do calcineurin inhibitors work?

Answer 16

Reduced NK cell activation
Reduce Tc activation
Reduce cytokine release -> Stops B cell proliferation -> Reduces Ab production

Question 17

Which of the following is not a side effect of calcineurin inhibitors:

• Renal dysfunction
• Hypertension
• Leukopaenia
• DM
• Tremors

Answer 17

Leukopaenia

Question 18

What metabolises calcineurin inhibitors and what implications does this have?

Answer 18

Cytochrome P450:

- Lots of drug interactions

Question 19

What type of drugs are Azathioprine and MMF?

Answer 19

Anti-metabolites:

- Block purine synthesis

Question 20

What do Azathioprine and MMF cause?

Answer 20

Reduced lymphocyte and B cell proliferation

Question 21

Which of the following is not a side effect of Azathioprine and MMF:

• Leukopaenia
• Anaemia
• Increased risk of TB reactivation
• Colitis (Diarrhoea and Oesophagitis)

Answer 21

Increased risk of TB reactivation

Question 22

What drug does Azathioprine interact with heavily? What effect does this have?

Answer 22

Allopurinol:

 - Hugely potentiates azathioprine's effects
           - > ++ Leukopaenia
           - > Aplastic anaemia

Question 23

What happens when a kidney is removed from a Deceased Brain Dead donor?

Answer 23

Flushed with cooling solution and carried on ice to recipient

Question 24

If a patient dies from cardiac arrest, how is the kidney removal carried out?

Answer 24

Femoral artery catheter -> Flushes cooling perfusant

Remove kidney ASAP

Question 25

Why is a donated kidney from a cardiac arrest patient more likely to be used locally?

Answer 25

Increased risk of ischaemia -> Reduced graft survival

Question 26

In what patients is a Kidney-Pancreas Dual Transplant indicated?

Answer 26

T1DM with kidney disease

Question 27

What should the life expectancy be of a patient who is receiving a transplant?

Answer 27

>5 years

Question 28

How is the allocation of an organ carried out in the UK?

Answer 28

1st -> Tissue typing | 2nd -> Time on list

Question 29

What infections must be treated prior to transplant?

Answer 29

HBV HCV HIV

Question 30

If a patient has a PMHx of a solid tumour, how long must they be in remission before they can receive a transplant?

Answer 30

2 years

Question 31

In what cancers is the waiting time for transplant 5 years?

Answer 31

Colorectal | Breast

Question 32

Which of the following is not an absolute contraindication for transplant: - Known and untreated malignancy - Untreated TB - Severe IHD not treatable by surgery - HIV - Severe airway disease - Acute vasculitis - Severe PVD

Answer 32

HIV

Question 33

What are the features of a kidney transplant surgery?

Answer 33

Extraperitoneal 3-4hrs Stent inserted between ureter and bladder 15-20cm wound in iliac fossa

Question 34

If a graft has immediate function, what clinical features should be expected?

Answer 34

Good urine output | Reducing plasma levels of creatinine and urea

Question 35

If a graft has delayed function, what clinical features should be expected?

Answer 35

Acute Tubular Necrosis: | - For 10-30 days -> Then it will work

Question 36

In delayed graft function, what can be given in the interim before it works?

Answer 36

Haemodialysis

Question 37

How do we assess blood flow to a non-functioning transplant?

Answer 37

USS | Renograms

Question 38

If we take a biopsy of a non-functioning kidney, what are we looking for?

Answer 38

Rejection Acute Tubular Necrosis Cortical necrosis