Organ Transplant Flashcards
What may cause episodes of hyper acute rejection?
ABO mismatch
IgG anti HLA Class I antibodies in recipient
Rarely seen due to HLA matching
Why does graft rejection occur?
allografts have allelic differences at genes that code immunohistocompatability complex genes
what are the main genes that give rise to rejection?
ABO blood group
Human leucocyte antigens (HLA)
Minor histocompatability antigens
what are the 4 most important HLA alleles?
HLA A
HLA B
HLA C
HLA DR
(DR>B>A)
Types of organ rejection?
hyperacute
acute
chronic
Features of hyper acute rejection?
- mins-hours
- preformed Ab which activates complement
- thrombosis and necrosis
- ABO incompatibility
- HLA class I incompatibility
-Renal transplants at greatest risk and liver transplants at least risk.
Features of acute rejection?
- Acute cellular:
CD4 gives type IV reaction
cellular infiltrate
T cell immunosuppression tx - Acute antibody mediated:
B cell activation
Antibody attacks vessels
Vasculitis C4D
Ab removal and B cell immunosuppression Tx
Usually due to mismatched HLA
Other causes include cytomegalovirus infection
Chronic rejection features?
- Previous acute rejections and other immunosensitising events all increase the risk
- ascular changes are most prominent with myointimal proliferation leading to organ ischaemia.
- loss of acinar cells in pancreas
- rapidly progressive coronary artery disease in cardiac
Chronic allograft nephropathy
Ureteric obstruction
Recurrence of original renal disease (MCGN > IgA > FSGS)
Why are right sided renal transplants rare?
because the vena cava precludes mobilisation of the right renal artery
Presenting features and treatment of renal artery thrombosis?
Sudden complete loss of urine output
Immediate surgery may salvage the graft, delays beyond 30 minutes are associated with a high rate of graft loss
Presenting features and treatment of renal artery stenosis?
Uncontrolled hypertension, allograft dysfunction and oedema
Angioplasty is the treatment of choice
Presenting features and treatment of renal vein thrombosis?
Pain and swelling over the graft site, haematuria and oliguria The graft is usually lost
Presenting features and treatment of urine leaks?
Diminished urine output, rising creatinine, fever and abdominal pain
USS shows perigraft collection, necrosis of ureter tip is the commonest cause and the anastomosis may need revision
Presenting features and treatment of lymphocele?
Common complication (occurs in 15%), may present as a mass, if large may compress ureter
May be drained with percutaneous technique and sclerotherapy, or intraperitoneal drainage
Actions of corticosteroids on the immune system?
- suppression of macrophage activation
- reduction in proliferation of lymphocytes
- reduction in expression of endothelial cell adhesion molecules
- reduction of expression of major histocompatibility complex antigens on the graft
Example immunosuppression regime after transplant?
Initial: ciclosporin/tacrolimus with a monoclonal antibody
Maintenance: ciclosporin/tacrolimus with MMF or sirolimus
Add steroids if more than one steroid responsive acute rejection episod3
Ciclosporin MOA/SE?
Inhibits calcineurin, a phosphatase involved in T cell activation
Nephrotoxic
Monitor levels
Azathioprine MOA/SE?
Metabolised to form 6 mercaptopurine which inhibits DNA synthesis and cell division
Side effects include myelosupression, alopecia and nausea
Tacrolimus MOA/SE?
Lower incidence of acute rejection compared to ciclosporin
Also less hypertension and hyperlipidaemia
However, high incidence of impaired glucose tolerance and diabetes
MMF MOA/SE?
Blocks purine synthesis by inhibition of IMPDH
Therefore inhibits proliferation of B and T cells
Side-effects: GI and marrow suppression
Sirolimus MOA/SE?
Blocks T cell proliferation by blocking the IL-2 receptor
Can cause hyperlipidaemia
To which of the following vessels should a transplanted kidney be anastomosed?
external iliac artery and vein
Class I HLA antigens?
A,B,C
Class II HLA antigens?
DP,DQ and DR
Graft survival %?
1 year = 90%, 10 years = 60% for cadaveric transplants
1 year = 95%, 10 years = 70% for living-donor transplants
What is the is the most common and important viral infection in solid organ transplant recipients?
CMV
CMV: 4 weeks to 6 months post transplant
EBV: post transplant lymphoproliferative disease. > 6 months post transplant
