Surgery Flashcards
In transplantation, what are the three most important HLA-types and what HMC classes do they belong to?
MHC I: - HLA A - HLA B MHC II: - HLA DR
What cells have MHC I on their surface?
All nucleated cells
What cells have MHC II on their surface?
APCs
How might a donor produce specific HLA antibodies?
Exposure to HLA antigen:
- Blood transfusion - Placenta - Previous transplant
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
- HLA Ag is taken up by an APC
- APC presents HLA Ag via MHC
- CD4+ cell activated by HLA Ag presented to it on MHC
- CD4+ (Th) cells activate B cells, NK cells and complement + cytokines
- B cells produce antibodies
- Abs, NK cells and CD8+ (Tc) cells result in rejection
What infections can result if there is too much immunosuppression?
BK virus
CMV
Recurrent UTIs
Pneumocystic jiroveci
What cancers can arise if there is too much immunosuppression? What might predispose to these?
Non-melanome skin cancer:
- Squamous and fast growing (usually)
Lyphoma:
- Espeically if not EBV immune
What can result if there is too little immunosuppression?
Graft dysfunction
Graft loss
What is the first sign of graft dysfunction/loss?
Rise in serum creatinine
What causes a hyperacute transplant rejection?
Due to a positive crossmatch:
- Preformed Abs to transplant - > eg. Different blood types
How is a hyperacute kidney rejection treated?
Immediate removal
What mediates an acute transplant rejection?
T or B cells
How can an acute transplant rejection be treated?
Immunosuppression
What can cause a chronic transplant rejection?
Immunological and vascular deterioration of the transplant
What are the two examples of calcineurin inhibitors?
Cyclosporin
Tacrolimus
How do calcineurin inhibitors work?
Reduced NK cell activation
Reduce Tc activation
Reduce cytokine release -> Stops B cell proliferation -> Reduces Ab production
Which of the following is not a side effect of calcineurin inhibitors:
- Renal dysfunction
- Hypertension
- Leukopaenia
- DM
- Tremors
Leukopaenia
What metabolises calcineurin inhibitors and what implications does this have?
Cytochrome P450:
- Lots of drug interactions
What type of drugs are Azathioprine and MMF?
Anti-metabolites:
- Block purine synthesis
What do Azathioprine and MMF cause?
Reduced lymphocyte and B cell proliferation
Which of the following is not a side effect of Azathioprine and MMF:
- Leukopaenia
- Anaemia
- Increased risk of TB reactivation
- Colitis (Diarrhoea and Oesophagitis)
Increased risk of TB reactivation
What drug does Azathioprine interact with heavily? What effect does this have?
Allopurinol:
- Hugely potentiates azathioprine's effects - > ++ Leukopaenia - > Aplastic anaemia
What happens when a kidney is removed from a Deceased Brain Dead donor?
Flushed with cooling solution and carried on ice to recipient
If a patient dies from cardiac arrest, how is the kidney removal carried out?
Femoral artery catheter -> Flushes cooling perfusant
Remove kidney ASAP
Why is a donated kidney from a cardiac arrest patient more likely to be used locally?
Increased risk of ischaemia -> Reduced graft survival
In what patients is a Kidney-Pancreas Dual Transplant indicated?
T1DM with kidney disease
What should the life expectancy be of a patient who is receiving a transplant?
> 5 years
How is the allocation of an organ carried out in the UK?
1st -> Tissue typing
2nd -> Time on list
What infections must be treated prior to transplant?
HBV
HCV
HIV
If a patient has a PMHx of a solid tumour, how long must they be in remission before they can receive a transplant?
2 years
In what cancers is the waiting time for transplant 5 years?
Colorectal
Breast
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
HIV
What are the features of a kidney transplant surgery?
Extraperitoneal
3-4hrs
Stent inserted between ureter and bladder
15-20cm wound in iliac fossa
If a graft has immediate function, what clinical features should be expected?
Good urine output
Reducing plasma levels of creatinine and urea
If a graft has delayed function, what clinical features should be expected?
Acute Tubular Necrosis:
- For 10-30 days -> Then it will work
In delayed graft function, what can be given in the interim before it works?
Haemodialysis
How do we assess blood flow to a non-functioning transplant?
USS
Renograms
If we take a biopsy of a non-functioning kidney, what are we looking for?
Rejection
Acute Tubular Necrosis
Cortical necrosis