Fiser Chapter 12 TRANSPLANTATION Flashcards Preview

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Flashcards in Fiser Chapter 12 TRANSPLANTATION Deck (73):

Mycophenolate (MMF, CellCept)
- Side effects
- Use
- Drug with similar action

- Inhibits de novo purine synthesis, which inhibits growth of T cells
- Side effects: myelosuppression, need to keep WBC > 3
- Used as maintenance therapy to prevent rejection
- Azathioprine (Imuran) has similar action


Mild rejection tx

pulse steroids


Biliary system (ducts, etc.) depends on _____ artery blood supply.



1) What kind of biliary anastomosis is performed in adults during liver TXP?
2) What kind of biliary anastomosis is performed in children during liver TXP?

1) duct-to-duct
2) hepaticojejunostomy


ABO Blood compatibility

generally required for all transplants (except liver)


Disease most likely to recur in new liver allograft?

Hepatitis C; reinfects essentially all grafts


Is ____ a contraindication for liver TXP?
1) hepatocellular CA
2) portal vein thrombosis

1) if no vascular invasion or mets cans till consider TXP
2) not a contraindication to liver TXP


Can you use kidney with...
a) UTI?
b) acute increase in Cr (1.0-3.0)

a) yes, can still use kidney
b) yes, can still use kidney



detects preformed recipient antibodies to the donor organ by mixing recipient serum with donor lymphocytes --> if these antibodies are present, it is termed a positive cross-match and hyperacute rejection would be likely to occur with TXP


Liver TXP complications:
Late hepatic artery thrombosis
- sequelae

results in biliary strictures and abscesses (NOT fulminant hepatic failure)


- 2nd most common malignancy following transplant
- related virus
- treatment

- Post-transplant lymphoproliferative disorder (PTLD)
- Epstein-Barr virus related
- Tx: withdrawal of immunosuppression; may need chemo and XRT for aggressive tumor


Acute kidney rejection:
- timing
- pathology

- Timing: usually occurs in first 6 months
- Pathology: tubulitis (vasculitis with more severe form)


Kidney TXP complications:
Renal artery stenosis
- Dx
- Tx

- diagnose with ultrasound
- Tx: PTA with stent


Sirolimus (Rapamycin)
- Use

- Binds FK-binding protein like FK-506 but inhibits mammalian target of rapamycin (mTOR); result is inhibition of T and B cell response to IL-2
- Used as maintenance therapy


Living kidney donors
1) most common complications?
2) most common cause of death?
3) what happens to remaining kidney?

1) wound infection (1%)
2) fatal PE
3) remaining kidney hypertrophies


MELD Score
1) components
2) use
3) what MELD score predicts usefulness

1) Creatinine, INR, bilirubin
2) Predicts if patient with cirrhosis will benefit more from liver TXP than from medical therapy
3) MELD > 15 benefits from liver TXP


Zenapax (daclizumab)
- Use

- human monoclonal antibody against IL-2 receptors; not cytolytic
- Used for induction and acute rejection episodes


Cyclosporine (CSA)
- Side effects
- Use
- Metabolism

- binds cyclophilin protein and inhibits genes for cytokine synthesis (IL-2, IL-4, etc.)
- Side effects: nephrotoxicity, hepatotoxicity, tremors, seizures, hemolytic-uremic syndrome
- Used for maintenance therapy
- need to keep trough 200-300
- Hepatic metabolism and biliary excretion (reabsorbed in the gut, get entero-hepatic recirculation)


#1 complication with liver TXP and the treatment

- bile leak
- Tx: place drain, then ERCP with stent across leak


Liver TXP complications:
Primary nonfunction
1) clinical/lab signs in first 24 hrs
2) clinical signs after 96 hrs
3) Tx

1) 1st 24 hrs: total bilirubin > 10, bile output , 20 cc/12h, elevated PT and PTT
2) after 96 hrs: mental status changes, rising LFTs, renal failure, repiratory failure
3) Tx: usually requires re-transplantation


Kidney TXP complications:
1) Usual cause of post-op oliguria and pathology
2) Usual cause of post-op diuresis
3) New proteinuria
4) Postop diabetes

1) usually due to ATN (pathology shows hydrophobic changes)
2) usually due to urea and glucose
3) suggestive of renal vein thrombosis
4) side effect of CSA, FK, steroids


Anti-thymocyte globulin (ATG)
- Use
- Side-effects

- Equine (ATGAM) or rabbit (Thymoglobulin) polyclonal antibodies against T cell antigens (CD2, CD3, CD4); is cytolytic (complement dependent)
- Used for induction and acute rejection episodes
- Need to keep WBC > 3
- Side effects: cytokine release syndrome (fever, chills, pulmonary edema, shock); give steroids before giving drug to try and prevent this


5-year graft survival overall (kidneys)

70% (65% cadaveric, 75% living donors)


Pancreas TXP complications:
Most common is...

venous thrombosis; hard to treat


Persistent pulm HTN after heart TXP:
- prognostic implications
- Tx

- associated with early mortality after heart TXP
- inhaled nitric oxide, ECMO if severe


Chronic liver rejection
- pathology/presentation

- unusual after liver TXP
- disappearing bile ducts (antibody and cellular attacks on bile ducts)
- gradually get bile duct obstruction with increase in alkaline phosphatase, portal fibrosis


Kidney TXP complications:
Two most common viral infections and their respective treatments

1) CMV - Tx: ganciclovir
2) HSV - Tx: acyclovir


Two primary causes of mortality with kidney TXP?

stroke and MI


Liver TXP complications:
Abscesses- most common cause

late (chronic) hepatic artery thrombosis


#1 cause of early mortality after lung TXP and treatment

- reperfusion injury
- Tx: similar to ARDS


Most common hepatic arterial anomaly

R hepatic coming off SMA


HLA-A, -B, and -DR

Most important in recipient/donor matching


Indication for double lung TXP

cystic fibrosis


Pancreas TXP complications:
- diagnosis

- hard to diagnose if patient does not also have a kidney TXP
- can see increased glucose or amylase, fever, leukocytosis



Most important overall (HLA = human leukocyte antigen)


Liver TXP complications:
1) Most-common early vascular complication
2) clinical/lab signs
3) Tx

1) hepatic artery thrombosis
2) rising LFTs, decreased bile output, fulminant hepatic failure
3) Tx: MC will need emergent re-transplantation for ensuing fulminant hepatic failure (can try to stent or revise anastomosis)


Location of attachment of kidney

iliac vessels


Acute liver rejection
1) mechanism
2) clinical presentation
3) lab changes
4) pathology
5) timing

1) T cell mediated against blood vessels
2) fever, jaundice, decreased bile output
3) leukocytosis, eosinophilia, increased LFTs, increased T. bili, increased PT
4) portal triad lymphocytosis, endotheliitis (mixed infiltrate), and bile duct injury
5) usually occurs in 1st 2 months


Chronic kidney rejection:
- timing
- treatment

- Timing: usually do not see until after 1 year
- Tx: no good treatment


FK-506 (Tacrolimus, Prograf)
- Side effects
- benefit compared to cyclosporine

- Binds FK binding protein; actions similar to CSA but more potent
- Side effects: nephrotoxicity, more GI sx and mood changes than CSA, much less entero-hepatic recirculation than CSA
- less rejection episodes in kidney TXPs with FK-506 compared to CSA
- need to keep trough 10-15


Opportunistic infections in TXP patients
1) viral
2) protozoan
3) fungal

2) pneumocystis jirovecii pneumonia (reason for Bactrim prophylaxis)
3) aspergillus, candida, cryptococcus


Kidney rejection workup:
1) what typically prompts workup?
2) what are the initial steps in workup?
3) what are initial management steps during workup?

1) usually for increase in Cr or poor urine output
2) ultrasound with duplex (to rule out vascular problem and ureteral obstruction) and biopsy
3) empiric decrease in CSA or FK (these can be nephrotoxic) and empiric pulse steroids


Hepatitis B Antigenemia
- treatment
- purpose of treatment for above

- Tx: HBIG (hepatitis B immunoglobulin) and lamivudine (protease inhibitor)
- Purpose: tx given after liver TXP to prevent re-infection
- Hep B reinfection rate is reduced to 20% with use of HBIG and lamivudine


Where are drains placed during liver TXP? (hint, 3 spots)

1) R subhepatic
2) R subdiaphragmatic
3) L subdiaphragmatic


#1 complication from kidney TXP and the treatment

urine leaks; Tx with drainage and stenting


Liver TXP complications:
IVC stensosis/thrombosis (rare)
1) clinical presentation
2) Tx

1) edema, ascities, renal insufficiency
2) Tx: thrombolytics, IVC stent


Liver TXP complications:
Portal vein thrombosis (rare)
1) early presentation
2) late presentation
3) Tx

1) abdominal pain
2) UGI bleeding, ascites, may be asymptomatic
3) if early: tx with re-op thrombectomy and revise anastomosis


1) What is macrosteatosis?
2) what is it a risk factor for in liver TXP?

1) extracellular fat globules in the liver allograft
2) risk factor for primary non-function; if 50% of cross-section is macrosteatotic in potential donor liver, there is a 50% chance of primary non-function


Liver TXP complications:
- pathology

See PMNs around the portal triad (NOT mixed infiltrate)


Heart transplantation
1) storage time
2) requirements
3) patient selection

1) up to 6 hours
2) need ABO compatibility and crossmatch
3) heart TXP considered for patients with life expectancy < 1 yr


- general MOA
- Use

- inhibits inflammatory cells (macrophages) and genes for cytokine synthesis
- used for induction after TXP, maintenance, and acute rejection episodes


Panel reactive antibody (PRA)

- Technique identical to cross-match; detects preformed recipient antibodies using a panel of HLA typing cells
- Get a percentage of cells that the recipient serum reacts with --> a high PRA (>50%) is often a contraindication to TXP (increased risk of hyperacute rejection)
- Transfusions, pregnancy, previous transplant. and autoimmune diseases can all increase PRA


Accelerated rejection
- timeline
- cause
- treatment

- occurs < 1 week
- caused by sensitized T cells to donor Ag
- Tx: increase immunosuppression, pulse steroids, possibly antibody Tx


Criteria for urgent liver TXP

- fulminant hepatic failure (encephalopathy - stupor, coma)


Hierarchy for Permission for Organ Donation from Next of Kin

1) spouse
2) adult son or daughter
3) either parent
4) adult brother or sister
5) guardian
6) any other person authorized to dispose of the body


Successful panc/kidney TXP results in:

- stabilization of retinopathy
- decreased neuropathy
- increased nerve conduction velocity
- decreased autonomic dysfunction (gastroparesis)
- decreased orthostatic hypotension

DOES NOT reverse vascular disease


Hyperacute rejection
- timeline
- cause
- pathology
- treatment

- occurs within minutes to hours
- caused by preformed antibodies that should have been picked up by the cross-match
- activates the complement cascade and thrombosis of vessels occurs
- Tx: emergent re-transplant (or just removal of organ if kidney)


#1 malignancy following ANY transplant

skin cancer (squamous cell CA #1)


Liver Transplantation
1) storage time
2) contraindications
3) most common reason for liver TXP in adults

1) can store for 24 hrs
2) contraindications: current EtOH abuse, acute ulcerative colitis
3) chronic hepatitis C


Acute rejection
- timeline
- cause
- treatment

- occurs 1 week to 1 month
- caused by T cells (cytotoxic and helper T cells)
- Tx: increase immunosuppression, pulse steroids, possibly antibody Tx


Heart TXP complications:
Chronic allograft vasculopathy
- definition
- prevalence/prognostic

- progressive diffuse coronary atherosclerosis
- MCC of late death and death overall following heart TXP


Pancreas transplantation - vascular
1) arterial supply
2) important vein
3) vascular attachment

1) need both donor celiac artery and SMA for arterial supply
2) need donor portal vein for venous drainage
3) attach to iliac vessels


Chronic rejection
- timeline
- cause
- pathology
- treatment

- occurs over months to years
- partially a type IV hypersensitivity reaction (sensitized T cells)
- antibody formation also plays a role
- leads to graft fibrosis
- Tx: increase immunosuppression - no really effective Tx


Chronic lung rejection
- pathology
- prevalence/prognosis

- bronchiolitis obliterans
- MCC of late death and death overall following lung TXP


What percentage of patients with EtOH induced liver failure will start drinking again after liver TXP (recidivism)?

20% will start drinking again


Kidney TXP complications:
Most common cause of external ureter compression and treatment

- lymphocele
- Tx: first try percutaneous drainage; if that fails, then need peritoneal window (make hole in peritoneum, lymphatic fluid drains into peritoneum and is re-absorbed - 95% successful)


Kidney Transplantation
- storage time
- requirements

- can store up to 48 hrs
- need ABO type compatibility and cross-match


Lung transplantation
1) storage time
2) requirements
3) patient selection

1) up to 6 hrs
2) need ABO compatibility and crossmatch
3) for patients with life expectancy < 1 yr


Pancreas transplantation
1) drainage of pancreatic duct
2) procedure

1) most use enteric drainage for pancreatic duct
2) Take 2nd portion of duodenum from donor along with ampulla of Vater and pancreas, then perform anastomosis of donor duodenum to recipient bowel


Severe rejection tx

steroid and antibody therapy (ATG or daclizumab)


Liver TXP
1) retransplantation rate
2) 5-year survival rate

1) 20%
2) 70%


Acute lung rejection
- pathology

perivascular lymphocytosis


Acute heart rejection
- pathology

perivascular lymphocytic infiltrate with varying grades of myocyte inflammation and necrosis