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53 Cards in this Set

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What type of rejection?
Foreign MHC Ag's on graft cells stimulate cytotoxic + helper T cells
Acute rejection:
-2/2 foreign MHC antigens of graft cells (mediated by cytotoxic and helper T cells)
-Bx: lymphocytic infiltrate
-Tx: OKT3, increase immunosupression, pulse steroids
(1 week-1 month p/ transplant)
_-type rejection is 2/2 ongoing production of Ab against donor Ag
Occurs @ timepoint _
ANTIBODY-MEDIATED rejection is 2/2 ongoing production of Ab against donor Ag
Occurs anytime (depends on pt's amnestic response)
Highly presensitized cases can be treated c/ plasmapheresis, IV Ig
_-type rejection of kidney allograft ->
margination of neutrophils, diffuse CD4 staining in peritubular capillaries
ANTIBODY-MEDIATED rejection of kidney allograft ->
margination of neutrophils, diffuse CD4 staining in peritubular capillaries
Drug is metabolized in liver to 6-mercaptopurine -> inhibits purine synthesis -> inhibits T cells
Azathioprine = Imuran = purine analog that acts as antimetabolite
-Inhibits de novo PURINE synthesis -> inhibits T CELLS
-6-MERCAPTOPURINE = active metabolite formed in liver
-SE: myelosupression
-Keep WBCs > 3
After liver tx, delayed hepatic artery thrombosis can cause _
After liver tx, delayed hepatic artery thrombosis can cause BILE DUCT NECROSIS
-Biliary anastomosis receives its blood supply from hepatic artery
Pt presents c/ biliary stricture p/ liver transplant:
-Check __ b/c may be 2/2 __
Biliary stricture p/ liver transplant:
-check hepatic artery flow b/c may be 2/2 ischemia
RARELY s/p liver tx, hepatic vein thrombosis + IVC stenosis can cause _
-Tx = _
RARELY s/p liver tx, hepatic vein thrombosis + IVC stenosis can cause BUDD CHIARI
-Tx = surgery (IVC stenosis may be dilated + stented sometimes)
what kinds of cells lack mycophenolic acid?
Cellcept = myfortic:
-active metabolite = MPA
-inhibits purine synthesis
-all cells have MPA except WBC
2 wks after transplant, pt develops resp insufficiency.
CXR: diffuse infiltrates
Bronchial washings: cells c/ inclusion bodies

What is the diagnosis, tx?
CMV Pneumonia
CXR: diffuse infiltrates
Bronchial washings: ALVEOLAR MACROPHAGES (c/ inclusion bodies)
Tx: GANCYCLOVIR
What is a postive cross-match?
Cross match;
-Mix donor lymphocytes + recipient serum
-Postive cross-match =
recipient has preformed Ab's against donor Ag's
-Hyperacute rejection likely
Cross match is performed by mixing _ from donor with _ from recipient
Cross match;
-Mix donor lymphocytes + recipient serum
-Postive cross-match =
recipient has preformed Ab's against donor Ag's
-Hyperacute rejection likely
Mechanism of drug _ =
binding to cyclophilin protein ->
inhibit genes for synthesis of cytokines IL-2, IL-3, IL-4, INF-gamma
Cyclopsporin (CSA)
-Binds cyclophilin protein ->
inhibits genes for synthesis of IL-2 (also IL-3, IL-4, INF-gamma)
-Rotamase inhibitor
-SE: NEPHROTOXIC, hepatotoxic, HUS, tremors, seizures
-Trough level 200-300
-Hepatic metabolism, Biliary excretion
Cyclopsporin (CSA)
Metabolized by the _
Excreted by the _
Cyclopsporin (CSA)
-Binds cyclophilin protein ->
inhibits genes for synthesis of IL-2 (also IL-3, IL-4, INF-gamma)
-Rotamase inhibitor
-SE: NEPHROTOXIC, hepatotoxic, HUS, tremors, seizures
-Trough level 200-300
-Hepatic metabolism, Biliary excretion
55 year-old male with history of an orthotopic kidney transplant 5 years ago develops cholangitis due to choledocholithiasis and requires a common bile duct exploration. Seven days post-op the patient develops acute rejection. The most likely cause is:
Cyclopsporin (Hepatic metabolism, Biliary excretion) being secreted via T tube
Recall that cyclosporin is excreted in its active form into the bowel. If you have a T-tube after any choledochotomy you will be draining out all the cyclosporin, thus causing rejection.
what types of drugs require revison of Prograf, Cya, or Rapamycin dosing 2/2 cytochrome p450
interact c/ antifungals, abx, Ca channel blockers
what is the mechanism of FK-506
FK-506 = Prograf:
-binds FK-binding protein -> blocks IL-2 production/expression from T cells
-SE: nephrotoxic (Mg, K, BP problems) mood changes, more GI and neuro changes (e.g. tremor) than cytosporine
-Keep trough 10-15
-10% of heart tx, liver tx pts develop renal failure
Graft vs. Host disease:
-mediated by _ type lymphocytes
Graft vs. Host Disease:
T cell mediated
Heart transplant => _% 1-yr survival
Heart transplant:
-84% 1-yr survival. Candidates for transplant have life expectancy < 1 yr.
-if persistant pulm HTN p/ transplant => Flolan (PGI2). ECMO if severe.
-Acute rejection: perivasc. infiltrate, myocyte inflamm and necrosis
-Chronic rejection: progressive diffuse coronary atherosclerosis
Fulminant hepatic failure POD2 s/p orthotopic liver tx.
Most likely cause = _
HEPATIC ARTERY THROMBOSIS
= most likely cause of fulminant hepatic failure POD2 s/p orthotopic liver tx.
Tx = angiography + nalloon dilatation +- stent -> retransplantation
_-type rejection is 2/2 preformed donor-specific Ab's
Occurs @ timepoint _
Tx = _
HYPERACUTE rejection: type 2 hypersensitivity
-2/2 preformed donor-specific Ab's
Occurs @ reperfusion
Tx = graft removal
(avoid by not transplanting when crossmatch is positive)
_-type rejection of kidney allograft ->
widespread glomerular capillary thrombosis, necrosis, +/- areas of interstitial hemorrhage
HYPERACUTE rejection of kidney allograft -> donor-specific Ab's -> widespread glomerular capillary thrombosis, necrosis, +/- areas of interstitial hemorrhage
What rejection type:
Pre-formed recipient Ab's to donor Ag's -> complement cascade
= a type _ hypersensitivity rxn
Most commonly due to _
Tx = _
Hyperacute rejection:
Type 2 hypersensitivity
Pre-formed recipient Ab's to donor Ag's -> complement cascade -> vascular thrombosis
Most commonly due to ABO incompatibility (postiive crossmatch)
Tx = remove organ
Pt 1 wk s/p renal tx has increased Cr. US shows flow acceleration, narrowing @ arterial anastomosis
-Tx =_
Tight arterial anastomosis following kidney tx:
-Increase in Cr soon after surgery
US: flow acceleration, narrowing @ arterial anastomosis
-Tx: angiogram c/ angioplasty + stent
how are monoclonal Ab's used in transplant?
Induction: high immuo risk => ned for potent induction, e.g. c/ anti-T cell agents
-esp in 2nd transplant, Af Am, high PRA
-less effect in pts c/ low immuno risk
_ = #1 cause of oliguria p/ renal tx
ATN = #1 cause of oliguria p/ renal tx
#1 complication after renal tx = _
Tx = _
URINE LEAK = #1 complication s/p renal tx
-Tx: percutaneous drainage of fluid collection, place ureteral stent across anastomosis
-Redo the anastomosis if it totally fell apart on POD 1
New proteinuria in pt s/p renal tx.
Suspect _
Renal vein thrombosis:
-New proteinutia in pt s/p renal transplant
#1 cause of death in living related kidney donor = _
PE = #1 cause of death in living related kidney donor
#1 cause of death following kidney transplant = _
MI = #1 cause of death following kidney transplant
(some say stroke)
Liver tx => _% 1 yr survival
best predictor = __
Liver tx:
-70% 1-yr survival (APACHE score = best predictor). 20% retransplantation rate.
-Indications: chronic hepatitis #1 (emergent if stage 3=stupor or stage 4 =coma), hepatocellular ca if single tumor <5cm or up to 3 tumors <3cm
-Contraindications: current EtOH, active UC
-HepC ~100% reinfection; use HBIG (+ lamivudine = protease inhibitor) to reduce HepB reinfection to ~20%.
-Macrosteatosis = #1 predictor of primary graft nonfunction
-Duct-to-duct anastomosis. Hepatico-jej in kids.
-Hepatic artery feeds bilary system.
-Complications: bile leal #1 , primary nonfunction, hep artery thrombosis +/- abscess following, IVC stenosis, cholangitis
#1 complication of liver tx = __
LIver tx complications:
-Bile leak #1 => PTC tube + stent
-Primary nonfunction => usually needs re-tx
-Hepatic artery thrombosis => angio + balloon dilation +/- stent (hepatic vein thrombosis rare)
-Abscess (usually 2/2 hepatic artery thrombosis)
-IVC stenosis (have edema, ascites, renal insuff)
-Cholangitis (PMNs around portal triad - not mixed infiltrate)
Liver tz:
-#1 cause of early mortality = _
-exclusion criteria for donating lungs
Lung t:
-Candidates have life expectancy <1 yr
-Reperfusion injury = #1 cause of early mortality
-Exlusion criteria for lungs: PO2 <350 on FiO2 1 and PEEP 5, aspiration, mod-large contusion, infiltrate, purulent sputum
-Acute rejection: perivascular lymphocytosis
-Chronic rejection: bronchiolitis obliterans
mechanism of mycophenolate
Mycophenolate = Cellcept:
-blocks purine synthesis-> decreases T and B cell proliferation
(similar mechanism to azathioprine)
What drug? -
Bind CD3 molecule on lymphocytes -> inhibits formation of T-cell receptor complex -> opsonization of T cell
-Can be used to treat rejection resistant to pulse steroids
OKT3: -
Monoclonal Ab's block CD3 molecule on lymphocytes -> inhibits formation of T-cell receptor complex = block T cell Ag recognition-> complement-dependent CD3 opsonization of T cell
-Interferes c/ MHC class I, II
-Treats ACUTE REJECTION resistant to pulse steroids
what drug is used to treat acute rejection that is resistant to pulse steroids?
OKT3 = monoclonal Ab
-Blocks CD3 molecule on lymphocytes -> inhibits formation of T-cell receptor complex = block T cell Ag recognition -> complement-dependent CD3 opsonization of T cell
-Interferes c/ MHC class I, II
-Treats ACUTE REJECTION resistant to pulse steroids
Portal vein thrombosis s/p liver tx (much less common than hepatic artery thrombosis)
-Early PVT causes _, Tx is _
Late PVT causes _, Tx is _
Portal vein thrombosis s/p liver tx
-Early thrombosis: -> liver dysfx, Tx = re-op + thrombectomy
-Late thrombosis/stenosis: -> portal venous HTN (ascites, variceal bleeding, splenomegaly), Tx surgery for thrombosis, angioplasty for stenosis
#1 virus post-transplant = _
CMV = #1 virus post-transplant (others: HSV, VZV)
-Since immunosupression is mostly cellular, not humoral, viral infections > bacterial
#1 protozoal infection post-transplant = _
Pneumocystis carinii (AKA jeroveci) pneumonia => need Bactrim ppx
#1 malignancy following transplant = _
(3 other common malignancies are...)
SKIN CANCER = #1 malignancy following transplant
-Others: leukemia, lymphoma, cervical
-b/c immunosupression is mostly cellular, not humoral.
Post-transplant lymphoproliferative disorder:
-Main RF = _
Tx: _ -> _ if that does not work
Post-transplant lymphoproliferative disorder:
-Most commonly ass'd c/ EBV
Tx: decrease immunosupression -> chemo-XRT if tumor does not regress
2 major targets of Ab-mediated graft rejection
3 major targets of Ab-mediated graft rejection =
HLA class 1 Ag's
endothelium-ass'd donor Ag's
Principal cells in acute rejection are _
Acute rejection
-1 week to 1 month post-op
-T cell mediated (cytotoxic, helper T cells )
-Tx: increase immunosupression, pulse steroids, +/- OKT3
Pt 1 wk s/p renal tx has increased Cr. US is normal.
Next step = _
Pt 1 wk s/p renal tx has increased Cr. US is normal.
Next step = renal bx to r/o acute rejection
Pt 1 wk s/p renal tx has increased Cr -> US normal -> Bx shows acute tubulitis +/- vasculitis
Next step = _
Acute rejection of renal allograft:
Increased Cr 1 week s/p tx, US normal, Bx (+) for acute tubulitis (+ vasculitis if severe)
-PULSE STEROIDS
-Follow Cr, re-Bx kidney in 5-7 days
_ = #1 cause of urinary obstruction 2/2 ureter compression
Lymphocele = #1 cause of urinary obstruction 2/2 ureter compression
-Forms in retroperitoneal space @ iliac fossa developed for implantation of the allograft (disrupts the tiny lymphatics that surround the recipeint's eternal iliac artery + vein)
Lymph collects post-op in perinephric space -> mashes the ureter -> low UOP.
US shows hypoechoic mass, hydronephrosis.
May have temporary decrease in Cr if pressure in renal pelvis overcomes pressure in the ureter
-Tx: percutaneous drainage -> laparoscopic peritoneal window if not successful
What is wrong?
Months-years s/p renal tx, pt has oliguria, hypertension, rising Cr
Renal artery stenosis s/p renal tx:
-usually occurs months-years after tx
-presents c/ oliguria, hypertension, rising serum Cr
3 causes of vascular compromise of graft s/p renal tx
Vascular compromise:
Occurs w/in hrs-days of renal tx
-Brought on bt renal artery/vein thrombosis, arterial dissection, pseudoaneurysm formation
New proteinuria in pt s/p renal tx.
Suspect _
New proteinuria in pt s/p renal tx.
Suspect renal vein thrombosis
what immunosupression drug?
-blocks IL-2 R's @ nuclear level.
-same transport binding protein as Prograf but different mechanism
-bad for wound healing
Sirolimus (rapamycin):
-blocks IL-2 R's @ nuclear level
-same transport binding protein as Prograf but different mechanism
-bad for wound healing
-increases cholesterol and triglycerides
Drug that inhibits IL-1 production by macrophages
Steroids:
-inhibit genes for synthesis of cytokies (IL-1, IL-6) form macrophages
what 3 HLAs are most important in recipient/donor matching?
which is most important overall?
Tissue types: HLA-A, B, C, DP, DQ, DR
HLA-A, B, DR most important in matching
HLA-DR most important overall
When does ureteroneocystostomy stenosis occur in post-op course following renal tx?
-Amything that can be done to prevent it?
Ureteroneocystosomy stenosis = stenosis @ ureterovesical anastomosis
Occus EARLY in post-op course
-May be prevented c/ intraop stent placement through anastomosis
What drug?
Human monoclonal Ab against IL-2 receptors
Zenepax:
-Human monoclonal Ab against IL-2 receptors
-Uses: induction, rejection tx