Transplantation

Question 1

Hyperacute transplant rejection

Answer 1

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

Question 2

Acute transplant rejection

Answer 2

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

Question 3

Chronic transplant rejection

Answer 3

> 6months after rejection
Fibrosis and arteriosclerosis
Usually due to extensive proliferation of smooth muscle -> progressive decline in organ function
May require another transplant

Question 4

How to diagnose transplant rejection

Answer 4

Tissue biopsy

Question 5

Prevention of transplant rejection

Answer 5

Optimise immunosuppression
Minimise immune differences between donor and recipient - ABO matching, HLA matching, donor specific antibody (DSA) matching

Question 6

Brainstem reflex testing

Answer 6

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)

Question 7

Apnoea test

Answer 7

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

Question 8

Criteria for brainstem death diagnosis

Answer 8

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

Question 9

Process of diagnosing brainstem death

Answer 9

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

Question 10

Definition of brainstem death

Answer 10

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

Question 11

Types of organ donors

Answer 11

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

Question 12

Organ preservation

Answer 12

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

Question 13

Induction immunosuppression in transplant patients

Answer 13

Monoclonal antibodies (basiliximab - IL2 inhibitor) selectively inhibits T cells activation, reduces risk of acute rejection and graft loss. Causes oedema, HTN and tremor.

Question 14

Maintenance immunosuppression in transplant patients

Answer 14

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

Question 15

Side effects of long term maintenance therapies

Answer 15

Increased cardiovascular risk, nephrotoxicity, opportunistic infections, malignancies

Question 16

Indications for renal transplant

Answer 16

End stage renal failure (eGFR <15) or those with CKD stage 4 who have progressive disease

Question 17

Contraindications for renal transplant

Answer 17

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

Question 18

Complications of renal transplant

Answer 18

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

Question 19

Prognosis of renal transplantion

Answer 19

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

Question 20

Indications for liver transplant

Answer 20

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

Question 21

Classifying the severity of end stage liver disease

Answer 21

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

Question 22

Definition of acute liver failure

Answer 22

Severe encephalopathy and coagulopathy in the absence of pre-existing liver disease

Question 23

Contraindications of liver transplant

Answer 23

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

Question 24

Complications of liver transplant

Answer 24

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

Question 25

Pancreas transplantation indications

Answer 25

Patients with DM who have progressed to end stage renal failure (eGFR <15)
Patients with life-threatening DM-related complications

Question 26

Types of pancreas transplants

Answer 26

Simultaneous pancreas and kidney transplant (most common)
Pancreas after kidney transplant
Pancreas transplant alone (if no renal impairment)

Question 27

Contraindications of pancreas transplant

Answer 27

Absolute - active infection, active malignancy, active alcohol.substance abuse, persistent non-adherence to medical therapy, severe cardiovascular disease

Relative - increasing age, recurrent UTIs, severe gastroparesis, heavy smoker, high BMI

Question 28

Complications of pancreatic transplant

Answer 28

Rejection (monitor through creatinine or blood glucose levels, or renal biopsy)

Pancreatic leak (abdo pain, distension, vomiting, peritonitis, raised serum amylase). Monitor amylase/lipase levels in the drain, CT to check for collections. Abx and percutaneous drainage of collections

Thromboses (pancreas portal vein most common). typically within 48 hours. Attempt thrombectomy.

Allograft pancreatitis due to ischaemia-reperfusion injury. Abdo pain, tenderness over graft, fever, vomiting. Rise in amylase and inflamm markers. Imaging. Conservative Mx