Transplantation Flashcards
Hyperacute transplant rejection
Minutes/hours -> graft destruction within 24 hours
Usually seen in xenogenic transplants (different species) or ABO incompatibility in allogeneic grafts
Due to pre-existing antibodies in the recipient that is directed at the graft -> causes rapid activation of innate and adaptive immune system -> endothelial injury -> platelet adhesion and thrombosis -> graft never becomes vascularised
Acute transplant rejection
Most common type.
First 6 months after transplant.
T-cell mediated (more common) or antibody-mediated rejection
Treat with high dose IV methylprednisolone, or if severe plasma exchange and IVIG
Chronic transplant rejection
> 6months after rejection
Fibrosis and arteriosclerosis
Usually due to extensive proliferation of smooth muscle -> progressive decline in organ function
May require another transplant
How to diagnose transplant rejection
Tissue biopsy
Prevention of transplant rejection
Optimise immunosuppression
Minimise immune differences between donor and recipient - ABO matching, HLA matching, donor specific antibody (DSA) matching
Brainstem reflex testing
Fixed pupils, no pupillary light reflex (CN2,3)
No corneal reflex (CN5,7)
Absent oculo-vestibular reflex (CN8,3,6)
No response to pain (CN5,7)
No gag reflex on pharyngeal stimulation (CN9,10)
No cough reflex on bronchial stimulation (CN10)
Apnoea test
No observed respiratory effort in response to disconnecting the ventilator. Brainstem death = no observed resp effort in response to disconnecting the ventilator. Produces a respiratory acidosis without inducing hypoxia or cardiovascular instability
Criteria for brainstem death diagnosis
Deeply unconscious, positive apnoea test, positive brainstem reflex test, certainty that there is irreversible brain damage of known cause, exclusion of sedative drugs, endocrine abnormalities, metabolic abnormalities, hypothermia, cardiovascular instability
Process of diagnosing brainstem death
Brainstem reflex test and apnoea test should be performed by two experienced doctors (one consultant, neither can be part of transplant team), on two separate occasions
Definition of brainstem death
Absence of brainstem reflexes, motor responses, and respiratory drive in a deeply unconscious patient with an irreversible widespread brain lesion of a known cause and no contributing metabolic derangements
Types of organ donors
Donation after brainstem death (DBD) - most common
Donation after circulatory death (DCD)
Live related
Live unrelated
Kidneys from living donors have better long-term function than from cadaveric donors, and less likely to suffer from delayed graft rejection
Organ preservation
The time between organ retrieval and reperfusion in the recipient has a profound impact on the final outcome of the transplant
Warm ischaemia time (DBD patients) the time between cessation of organ perfusion by donor’s blood circulation and perfusion with the preservation fluid
Cold ischaemia time (DCD patients) the time between cardiac arrest and perfusion of preservation solution
Prolonged CIT and WIT increases the risk of delayed graft function
Induction immunosuppression in transplant patients
Monoclonal antibodies (basiliximab - IL2 inhibitor) selectively inhibits T cells activation, reduces risk of acute rejection and graft loss. Causes oedema, HTN and tremor.
Maintenance immunosuppression in transplant patients
Calcineurin inhibitors (tacrolimus/ciclosporin) blocks IL-2 and inhibits T cell activation, but is nephrotoxic so levels should be monitored.
Mycophenolate mofetil is anti-proliferative so blocks lymphocyte proliferation by blocking DNA formation. Causes myelosuppression.
Azathioprine is an alternative of MMF, and is also an anti-proliferative. Precursor of 6-mercaptopurine. Causes severe myelosuppression. Measure TPMT levels before giving azathioprine.
Prednisolone (induction and maintenance, and treats acute cellular rejection). Causes DM, HTN, infection, osteoporosis, hyperlipidaemia, delayed wound healing, psych problems
Side effects of long term maintenance therapies
Increased cardiovascular risk, nephrotoxicity, opportunistic infections, malignancies
Indications for renal transplant
End stage renal failure (eGFR <15) or those with CKD stage 4 who have progressive disease
Contraindications for renal transplant
Absolute - untreated malignancy, active infection, untreated HIV/AIDS, prognosis <2yrs, malignant melanoma in last 5 years
Relative - comorbidities (eg. DM), age >65, obesity, HBV/HCV, previous malignancy
Complications of renal transplant
Surgery - haemorrhage, thrombosis, infection, hernia, lymphocele
Graft rejection (hyperacute, acute, chronic)
Delayed graft function (needs dialysis within first week, due to prolonged Cold/warm ischaemia time)
Renal artery/vein thrombosis (US doppler -> urgent surgery). Give aspirin/LMWH post-op to reduce risk.
Renal artery stenosis (late complication) causes uncontrollable HTN and worsening graft function. Diagnose with angiography, and treat with angioplasty.
Ureteric leaks due to breakdown of ureteric-bladder anastamosis. Causes reduced UO and abdo pain. Requires surgery
Prognosis of renal transplantion
DBD one-year survival 97%, living-donor one-year survival 99%
Cadaveric kidney lasts about 9 years, a monozygotic twin live-donor transplantation may last as long as 25 years
Indications for liver transplant
End stage liver failure (HCV infection, alcoholic liver disease, non-alcoholic fatty liver disease) Acute liver failure Autoimmune hepatitis Primary biliary cirrhosis Primary sclerosing cholangitis Wilsons Alpha-1-antitrypsin deficiency hereditary haemochromatosis Primary malignancies of the liver Budd-chiari syndrome Drug-induce acute liver failure
Classifying the severity of end stage liver disease
UKELD model for en-stage lifer disease. Calculates the patient’s INR, bilirubin, creatinine and sodium.
Estimates patients survival and is used to prioritise patients on the waiting list
Definition of acute liver failure
Severe encephalopathy and coagulopathy in the absence of pre-existing liver disease
Contraindications of liver transplant
Absolute - uncontrolled sepsis, active alcohol/substance abuse, advanced cardiac/pulm disease, extra-hepatic malignancy
relative - multi-system organ failure with fulminant liver failure, active infection, advanced age, frailty, extensive co-morbidities, medication-resistant HBV cirrhosis
Complications of liver transplant
Post-op haemorrhage
Sepsis (gram neg, or CMV)
Hyperacute/acute/chronic rejection
Graft primary non-function - injury during preservation which prevents recovery of the graft after revascularisation (new transplant is only treatment option)
Hepatic artery thrombosis (typically at the anastomosis), presents with graft failure. Doppler US and CT arteriography required.
Biliary leaks may cause localised peritonitis or sepsis
Biliary strictures
Long term: HTN, DM< renal impairment, dissemination of undetected donor diseases, recurrence of primary liver disease, chronic rejection
