Solid organ transplant Flashcards
List classes of transplant organ complications
Anatomy
Rejection
Infection
Drug toxicity
Discuss anatomical complications of organ transplant
Vascular
- Thrombosis
- stenosis
- AV fistula
- pseudoaneurysms formation - can lead to life threatening bleeding if they rupture
Acute thrombosis of arteries may lead to fulminant organ failure
Non vascular - anastomoses may include bile ducts, bronchi and ureter
- anastomotic leaks and obstructions from scarring
- migration of stents or stone development that may lead to acute graft dysfunction
- infection
- abcess formation
Discuss rejection as a complications of organ transplant
Rejection involves a complex set of t-cell receptor mediator pathways that lead to cytotoxic activity, B-cell memory and antibody formation and cell death of the transplant allograft.
Rejection typically occurs in three phases
1) hyperacute - rejection occurs with preformed antibodies against the major histocompatability complex or ABO blood type antigens - rare with current matching techniques and occurs in the peri-operative period.
2) Acute rejection occurs days to weeks after transplantation. The patient presents with constitutional symptoms and sings of transplant organ insuffiecieny. If immunosuprression is stopped acute rejection can occur at any time
3) chronic - months to years and results in the gradual failure of the transplanted organ over time. Each organ present slightly differently with interstitial fibrosis and tubular atrophy causing dysfunction in kidneys, inflammation causing airway obstruction lung and fibrosis of bile ducts veins and arteries in the liver.
Discuss infection as a complications
Primary cause of mortality after transplantations. Deaths from infection occur in 13-16% of kidney and heart transplants, 15% of liver and 21% in lungs.
All transplant patients with fever should be aggressively investigated
Can occur in 3 distinct time periods
Discuss infection in the first month after transplatn
Majority are pre-exisiting, donor derived or nosocomoial. Both patient and donor are screened extensively but pre-existing viraln infection like HIV and HCV no longer preclude transplant.
Pre-exisiting in patient
- bacterial colinisation (pseudomonas, TB)
- Viral (HIV, HBV, HCV, EBV, CMV, HSV, VZV)
Discuss infection 1-6 months post transplant
Very high risk period for the transplant patient.
CMV is the most important and prevalent immunomodulating viral infection during this period.
Causes CMV pneumoniits , hepatitis and reduces immune function in the patient.
Most are given prophylaxis with valganciclovir for high risk patients.
EBV is another common immunomoduating virus
BK virus is common and asymptmatic in healthy patients but pathological in transplant
Pirmary Varicella infection can be life threatening with penumonia, pancreaittis, hepatitis and encpehalitis + DIC - treatment with IV varicella zoster immune globulin and IV aciclovir.
As this period is the highest level of immunosupression nosocomial infection are common.
- Listeria
- Norcardia
- TB
- Invasive candidiasis
- PCP
- Toxoplasmosis
- Cryptococcus
Discuss the 6 motnhs and beyond for infection in transplant patients
Can be split into three groups
1) healthy transplant patients
- nil chronic immunomodulating viral infection and a functioning allograft
- maintained with low doses of imunosupressant medications
- mild increase in normal community acquired infeciton
2) Chornic viral infection
- Progressive disease may develop as a result of the combination of viral immunomodulating infection and long term immunosuppression.
- Hep B and C can place the patient at risk for HCC
3)Chronic rejection
0 aggressive immunosuppressive treatment and are at high risk of late infection.
Discuss Immunosupressive regime in general
Regimens are transplant centre specific but most include a calcineurin inhibitor an antimetabolite and varying dosages of steroids.
Discuss Calcineurin inhibtors
1) Cyclosproine
- prevents both cellular and humoral immunity by binding to a family of proteins called cyclophilins which inhibit lymphocyte signal transudction.
- Side effects can be severe
- Nephrotoxicity is important - cyclosporine causes renal tubular injury and direct renal artery vasospasm in a dose dependant manner leading to HTN in patients
- They are also hepatotoxic, lead to hyperlipidaemia, hyperuricema, hyperkalaemia, hirsutism remor and gingival hyperplasia.
2) Tacro
- Macrolide compound that binds to lymphocyte proteins and inhibits cytokine synthesis.
- improved side effect profile and more effective immunosupression is used more frequently as either primary or rescue therapy for allograft rejection.
- Causes nephrotoxicity as well as neurotoxicity
- in combination with steroids can lead to hyperglycaemia
- Macrolide antibiotics should not be prescribed to tacro patients as it augments there levels.
Discuss antimetabolites
1) Azathiopine
- inhibits both deoxyribonucleic acid and ribonucleic acid synthesis resulting in suppression of lymphocyte proliferation.
- Works as a bone marrow toxin so patients may exhibit dose related neutropenia
2) Mycophenolate mofetil (MMF)
- more potent and selective inhibition of lymphocyte proliferation so it has largely replaced azathriprine.
- Low side effect profile.
Discuss heart transplant
1,5 and 10 year survival - 88.6%,73.1% , 53%
The transplanted heart is denervated which causes clinically important physiological chagnes
- Without parasympathetic tone the resting HR is between 95-110
Drug consideration
- Atropine will have non effect on trasnplanted heart.
- Avoid B blockers in transplant patients as can worsen autonomic dysfucntion.
- Is sensitive to adenosine and requires dose reduction by half
ECG:
-Incomplete RBBB and repol abnormalities
REJECTION
- ACute- medication non compliance, drug-drug interaction or concurrent CMV infeciton.
- CAV (cardiac allograft vasculopathy) is asscoiated with chronic rejection - retransplant is the only definitive treatment.
Discuss liver transplant
1, 5 and 10 year surivical - 85%, 67% and 51%
HAT (hepatic artery thrombosis) is the most common vascular complications and is devastating becuase it is the only artieral blood supply to the transplanted liver.
Hepatic artery rupture is uncommon and is usually a result of bacterial arteritis - patient will present with haemorrhagic shock
Describe Kings college criteria - for paracetamol OD
Arterial Ph <7.30
INR >6.5
Creatinine 300
Grade 3-4 encpehaloapthy
OTHER
Lactate >3.5mmol after fluid resus
phosphate >3.75
Discuss kindey transplant
1, 5 and 10 year survival rates - 92%, 70% and 43% most successful.
The location of the transplanted kidney is most commonly in the iliac fossa. Donor renal vessels are anastomesed to recipient iliac vessels, and the donor ureter can be anastomosed directly to the recepient bladder or native ureter with J stents
Vascular complications such as bleeding and thrombosis can occur
A haematoma can occur up to a week afger the procedure and cause urinary osbturction.
Late vascular complciations are due to stricutre and stneosis.
Discuss lung transplant
Rare
Surivial rates lag behind other solid organ transplant with 1 year survival being 80% for the graft
