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188 Cards in this Set
- Front
- Back
Three most important HLAs for recipient/donor matching? |
HLA-A, -B, -DR
-DR |
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ABO blood compatibility required for all transplants except ___
|
liver
|
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Crossmatch detects preformed recipient antibodies by mixing recipient serum with donor lymphocytes that would generally cause ___ (except liver)
|
hyperacute rejection
|
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Technique identical to crossmatch; detects preformed recipient antibodies using a panel of typing cells. Transfusions, pregnancy, pervious transplant, and autoimmune diseases can all increase.
|
Panel reactive antibody (PRA)
|
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Tx for mild rejection.
|
Pulse steroids
|
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What is the number one malignancy following any transplant?
|
skin CA (squamous cell CA #1)
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What is the second most common malignancy following transplant?
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Posttransplant lymphoproliferative disorder (PTLD)
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What virus is associated with Posttransplant lymphoproliferative disorder (PTLD)?
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epstein-barr
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What is the tx for posttransplant lymphoproliferative disorder (PTLD)?
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Withdrawal of immunosuppression; may need chemotherapy and XRT for aggressive tumor
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Antirejection drug that inhibits de novo purine synthesis, which inhibits T cells. 6-Mercaptopurine is the active metabolite (formed in the liver). Side effects: myelosuppression. Keeps WBCs > 3.
Also, there is another drug with similar action. |
Azathioprine (Imuran)
Mycophenolate |
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What antirejection drug works by inhibiting genes for cytokine synthesis (IL-1, IL-6) and macrophages.
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steroids
|
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What antirejection drug works by binding cyclophilin protein and inhibits genes for cytokine synthesis (IL-2, IL-3, IL-4, INF-gamma).
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Cyclosporin (CSA)
|
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What are the side effects of cyclosporin?
And what is the metabolism and excretion? |
nephrotoxicity, hepatotoxicity, HUS, tremors, seizures
hepatic metabolism and biliary excretion |
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What antirejection drug binds FK-binding protein; actions similar to CSA but 10-100x more potent. Side effects include: nephrotoxicity, mood changes, more GI and neurologic changes than CSA
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FK-506 (Prograf)
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What antirejection drug is equine polyclonal antibodies direct against antigens on T cells (CD2, CD3, CD4, CD8, CD11/18). Used for induction therapy. Complement dependent. Keeps peripheral T-cell count >3?
Also there is another drug that has similar action but is rabbit polyclonal antibodies. |
ATGAM
Thymoglobulin |
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What antirejection drug is monoclonal antibodies that block antigen recognition function of T cells by binding CD3, inhibiting T-cell receptor complex. Used for severe rejection. Side effects include: fever, chills, pulmonary edema, shock
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OKT3
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What antirejection drug is human monoclonal antibody against IL-2 receptors. Used with induction to treat rejection.
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Zenepax
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What type of rejection occurs within minutes to hours?
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Hyperacute rejection
|
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What is hyperacute rejection caused by?
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preformed antibodies that should have been picked up on crossmatch
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What is the tx for hyperacute rejection.
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Emergent retransplant
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What type of rejection occurs <1 week?
|
accelerated rejection
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What is accelerated rejection caused by?
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sensitized T cells to donor antigens
|
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What is the tx for accelerated rejection?
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increase immunosuppression, pulse steroids, and possibly OKT3
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What type of rejection occurs in 1 week to 1 month?
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acute rejection
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What is acute rejection caused by?
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cytotoxic and helper T cells
|
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What is the treatment for acute rejection?
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increase immunosuppression, pulse steroids and possibly OKT3
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What type of rejection occurs in months to years?
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chronic rejection
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What type of hypersensitivity reaction is chronic rejection? (Antibodies, monocytes and cytotoxic t cells also play a role)
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Type IV
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What is the tx for chronic rejection?
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increase immunosuppression or OKT3 - no really effective tx
|
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How long can you store a kidney?
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48 hours
|
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Can you still use a kidney with UTI or acute increase in Cr (1.0-3.0)
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yes
|
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2 main causes of mortality in kidney transplant?
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stroke and MI
|
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What vessels are donor kidney attached to?
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external iliac
|
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Number one complication of kidney transplant? tx?
|
urine leaks
drainage and stenting; may need reoperation |
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Most common cause of external compression after kidney transplant?
Tx 1st and if that fails |
lymphocele
percutaneous drainage, intraperitoneal marsupialization (90% successful) |
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After kidney transplant, postop oliguria is usually due to ___ (pathology shows hyrophobic changes)
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ATN
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After kidney transplant, postop diuresis is usually due to ___ and ___
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urea and glucose
|
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New proteinuria after kidney transplant is usually suggestive of what?
|
renal vein thrombosis
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Postop diabetes after kidney transplant is usually due to what?
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side effects of rejection meds: CSA, FK, steroids
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Kidney rejection workup (usually for increase in Cr): ___ to rule out vascular problem and ureteral obstruction; bx; empiric decrease in CSA or FK because they can be nephrotoxic; what tx?
|
US with duplex
pulse steroids |
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What is the 5-year graft survival for kidney transplant?
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70% (65 cadaveric, 75 living)
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Living kidney donors: most common complication? most common cause of death?
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wound infection (1%)
fatal PE |
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How long can you store a liver for transplantation?
|
24 hours
|
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2 contraindications to liver TXP
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current ETOH abuse, acute ulcerative colitis
|
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What is the most common reason for liver TXP in adults?
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chronic hepatitis
|
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Criteria for emergent liver TXP - stage III (___), stage IV (___)
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stupor, coma
|
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What are two postoperative tx for pts with Hep B after TXP?
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HBIG (hep B immunoglobulin) and lamivudine (protease inhibitor)
|
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What are the tumor size limitations on considering TXP with hepatocellular carcinoma
|
single tumor < 5 cm or up to 3 tumors each < 3 cm
|
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Is portal vein thrombosis a contraindication to liver TXP?
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no
|
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What is the best predictor of 1 year survival after liver TXP?
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APACHE score
|
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What is more likely to occur in liver allograft, Hep B or C
|
Hep C (Hep B reduced to 20% with the use of HBIG)
|
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What percentage of liver TXP pts will start drinking again?
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20%
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What is the #1 predictor of primary nonfunction in liver TXP?
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Macrosteatosis (extracellular fat globules in allograft)
(if 50% of cross section is macrosteatatic, there is 50% chance of primary nonfunction) |
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What is the difference in liver TXP procedure in adults vs. kids?
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Duct-to-Duct in adults
Hepatico jejunostomy in kids |
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Location of drains after liver TXP
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Right subhepatic, Right and Left subdiaphragmatic
|
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What is the most common hepatic arterial anomaly?
|
right hepatic coming off SMA
|
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#1 complication of liver TXP? Tx?
|
Bile leak
PTC tube and stent |
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What are the signs and sx of primary nonfunction after liver TXP in the 1st 24 hrs
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total bilirubin > 10, bile output < 20 cc/12 hr, PT and PTT 1.5x normal
|
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What are the signs and sx of primary nonfunction after liver TXP after 96 hours?
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hyperkalemia, mental status changes, increased LFTs, renal failure, respiratory failure
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What is the tx of primary nonfunction after liver TXP?
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usually requires retransplantation
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Most common cause of liver abscesses after TXP?
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chronic hepatic artery thrombosis
|
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Tx for hepatic artery thrombosis after liver TXP?
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angio, surgery, retransplantation
|
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Edema, acites, renal insufficiency after liver TXP could be due to what?
|
IVC stenosis
|
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After liver TXP: fever, jaundice, decreased bile output, change in bile consistency. leukocytosis, eosinophilia, increased LFTs, total bilirubin, PT. Pathology shows portal lymphocytosis, endotheliitis, bile duct injury. Dx?
|
acute rejection
|
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After liver TXP: disappearing bile ducts, gradual bile obstruction with increased alk phos, portal fibrosis. Dx?
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chronic rejection
|
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What is the most common predictor of chronic rejection in liver TXP?
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acute rejection
|
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Liver TXP retransplantation rate?
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20%
|
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LIver TXP 5 year survival rate?
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70%
|
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What is the arterial supply and venous drainage needed for pancreas transplant and what are they attached to?
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donor celiac and SMA, donor portal vein, iliac vessels
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What is the enteric drainage for pancreas TXP?
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Second portion of duodenum is taken from donor along with ampulla of Vater and pancreas, anastomosis of donor duodenum to recipient bowel
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Successful pancreas/kidney TXP results in stabilization of retinopathy, decreased neuropathy, increased nerve conduction velocity, decreased autonomic dysfunction (gastroparesis), decreased orthostatic hypotension. But there is no reversal of what?
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vascular disease
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What is the number one complication of pancreas TXP
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thrombosis (hard to treat)
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After pancreas TXP: increase in glucose, amylase, or trypsinogen; fever; leukocytosis. Dx?
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rejection
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How long can a heart for TXP be stored?
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6 hours
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What is the life expectancy needed for a heart TXP?
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< 1 year
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What is the tx for persistant pulmonary hypertension after heart transplant?
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Flolan (PGI2); inhaled nitric oxide, ECMO if severe
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After heart TXP: perivascular infiltrate with increasing grades of myocyte inflammation and necrosis. Dx?
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acute rejection
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After heart TXP: progressive diffuse coronary atherosclerosis. Dx?
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Chronic rejection
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How long can a lung for transplantation be stored?
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6 hours
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What is the life expectancy needed for a lung TXP?
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< 1 year
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What is the number one cause of early mortality after lung TXP?
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reperfusion injury
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What is the indication for double-lung TXP?
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cystic fibrosis
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Exclusion criteria for using lungs for TXP includes: aspiration, moderate to large contusion, infiltrate, purulent sputum, PO2 < ___ on 100% FiO2 and PEEP 5
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350
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What is the sign of acute lung rejection? chronic?
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perivasculare lymphocytosis
bronchiolitis obliterans |
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Inflammation phases: injury leads to exposed ___; ____ release, tissue factor release from ____
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collagen, platelet-activating factor, endothelium
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In inflammation platelets bind and release ___ which leads to PMN and macrophage recruitment.
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PDGF
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Play a dominant role in wound healing, release important growth factors (PDGF) and cytokines IL-1 and TNF-a.
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Macrophages
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Similar effect as TGF-beta. Chemotactic and activates inflammatory cells (PMNs and macrophages). Chemotactic and activates fibroblasts -> collagen and ECM proteins. Angiogenesis. Epithelialization. Chemotactic for smooth muscle cells. Has been shown to accelerate wound healing.
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PDGF
(EGF and FGF also help chemotaxis, angiogenesis and epithelialization) |
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Stimulates angiogenesis and is involved in tumor metastasis.
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V-EGF
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Not stored, generated by phospholipase in endothelium and other cells. Stimulates many types of inflammatory cells; chemotactic; increased adhesion molecules
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Platelet activating factor (PAF)
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PMNs last ____ days in tissues, ___ days in blood
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1-2, 7
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Platelets last ___ days
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7-10
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Name the cell type involved in type I hypersensitivity reactions:
Have IgE receptors that bind allergen. Release major basic protein which stimulates basophils and mast cells to release histamine. Increased in parasitic infections. |
Eosinophils
|
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Name the cell type involved in type I hypersensitivity reactions:
Have IgE receptors. Main source of histamine in blood. Not found in tissue. |
Basophils
|
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Name the cell type involved in type I hypersensitivity reactions:
Primary cell type in type I reactions. Main source of histamine in tissues other than stomach. |
Mast cells
|
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Name the cell type involved in type I hypersensitivity reactions:
Vasodilation, tissue edema, postcapillary leakage. Primary effectors in type I hypersensitivity reactions (allergic reactions) |
Histamine
|
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Name the cell type involved in type I hypersensitivity reactions:
Vasodilation, increased permeability, pain contraction of pulmonary arterioles. ACE inactivates. |
Bradykinin
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Has arginine percursor. Activates guanylate cyclase and increases cGMP, resulting in vascular smooth muscle dilation. Also called endotheliu-derived relaxing factor (EDRF).
|
Nitric Oxide
|
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What does endothelin do?
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vascular smooth muscle constriction
|
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Main initial cytokine response to injury and infection is release of ___ and ____
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TNF-alpha and IL-1
|
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What is the largest producer of TNF?
|
macrophage
|
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What cytokine is responsible for cachexia in cancer patients?
|
TNF-alpha
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What is the main source of IL-1
|
macrophage
|
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IL-1 effects are similar to ___ and synergizes with it.
|
TNF
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Alveolar macrophages cause fever with atelectasis by releasing ___
|
IL-1
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IL-1 also increases what other IL production?
|
IL-6
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IL-1 responsible for fever which is mediated by ___ in hypothalamus.
|
PGE2 (NSAIDs decrease)
|
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Which IL increases hepatic acute phase proteins (CRP, amyloid A) and lymphocyte activation.
|
IL-6
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Released by lymphocytes in response to viral infection or other stimulates. Active macrophages, natural killer cells and cytotoxic T cells. Inhibit viral replication.
|
Interferon
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Name 2 proteins decreased as result of hepatic acute phase response.
|
albumin, transferrin
|
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Provides rolling adhesion. Located on leukocytes, bind to ones on endothelial and platelets
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Selectins (L-selectins, E- and P- respectively)
|
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On leukocytes; bind ICAMs; anchoring adhesion.
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Beta 2 Integrins
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ICAM, VCAM, PECAM, ELAM on endothelial cells, bind beta-2 integrin molecules located on leukocytes and platelets. These are also involved in ___
|
endothelial migration
|
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In the classic complement pathway, antigen-antibody complexes activate. Which 2 abx? And which 3 factors are found only in the classic pathway?
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IgG, IgM
Factors C1, C2, and C4 |
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The alternative complement pathway, endotoxin, bacteria, other stimuli activate. What 3 factors are found only in this pathway?
|
B, D and P (properdin)
|
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What is the common convergence point for classic and alternative complement pathways?
|
C3
|
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What electrolyte is required for both complement pathways?
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Mg
|
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What are the 3 anaphylatoxins in the complement pathway that increase vascular permeability, smooth muscle contraction (bronchi); activate mast cells and basophils
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C3a, C4a, C5a
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What forms the membrane attack complex?
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C5b-9b
|
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What part of the complement cascade functions in opsonization?
|
C3b
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What 2 parts of the complement cascade functions in chemotaxis?
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C3a and C5a
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Prostaglandins:
___ and ___ - vasodilation, bronchodilation, increased permeability; inhibit platelets ___ - vasodilation, bronchoconstriction, increased permeability |
PGI2 and PGE2
PGD2 |
|
___ inhibit cycloxygenase reversibly
___ inhibits cycloxygenase irreversibly, inhibits platelets adhesion by decreaseing ___ |
NSAIDs
Aspirin, TXA2 |
|
Inhibit phospholipase, which converts phospholipids to arachidonic acid -> inhibits inflammation
|
Steroids
|
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What are the slow-reaching substances of anaphylaxis; bronchoconstriction; vasoconstriction followed by increased permeability (wheal and flare)
|
Leukotrienes
|
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Which leukotriene is chemotactic?
|
LTB4
|
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Catecholamines peak how many hours after injury?
|
24-48
|
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What is the primary mediator of reperfusion injury?
|
PMNs
|
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NADPH-oxidase system enzyme defect in PMNs. Results in decreased superoxide radical (O2-) formation.
|
Chronic granulomatous disease
|
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What are the 3 wound healing phases?
|
Inflammation, Proliferation, Remodeling
|
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What is the timeframe for the inflammation phase of wound healing?
|
days 1-10
|
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What is the timeframe for the proliferation phase of wound healing?
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5 days - 3 weeks
|
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What is the timeframe for the remodeling phase of wound healing?
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3 weeks - 1 year
|
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Which phase of wound healing?:
PMNs, macrophages, epithelialization 1-2 mm/day |
Inflammation
|
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Which phase of wound healing?:
fibroblasts, neovascularization, production of collagen, granulation tissue |
Proliferation
|
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Which phase of wound healing?:
Type III collagen replaced with type I; decreased vascularity. Net amount of collagen does not change, although significant production and degradation occur. Collagen cross-linking occurs. |
Remodeling
|
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Peripheral nerves regenerate at ___ mm/day
|
1
|
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Fibroblasts replace fibronectin-fibrin with ___
|
collagen
|
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Chemotactic for macrophages also anchors fibroblasts.
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Fibronectin
|
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Name the predominant cell type by wound healing day:
Days 0-2 ___ Days 3-4 ___ Days 5 and on ___ |
PMNs,
macrophages, fibroblasts |
|
Platelet plug is made of platelets and ___
Provisional matrix is made of platelets, ___ and ___ |
fibrin
fibrin, fibronectin |
|
Accelerated wound healing is quicker healing that occurs when reopening a wound the 2nd time. Why does this occur?
|
healing cells are already present
|
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Which type of platelet granules contain: Platelet factor for aggregation. Beta-thrombomomdulin to bind thrombin and PDGF a chemoattractant.
|
Alpha granules
|
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Which type of platelet granule contains adenosine, serotonin and calcium.
|
Dense granules
|
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Name 3 platelet aggregation factors.
|
TXA2, thrombin, platelet factor 4
|
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The most important factor in healing open wounds (secondary intention).
|
epithelial integrity
|
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Epithelial migration occurs from what three places in wound healing?
|
wound edges, sweat glands, and hair follicles
|
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Unepithelialized wounds leak ___ and protein, promote bacterial
|
serum
|
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What is the most important factor in healing closed incisions (primary intention).
|
tensile strength
|
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Tensile strengh depends on what?
|
collagen deposition and cross-linking
|
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What is the strength layer of the bowel?
|
submucosa
|
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What is the weakest time point for small bowel anastomosis?
|
3-5 days
|
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Myofibroblasts communicate by ___
|
gap junctions
|
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What part of wound healing are myofibroblasts involved in?
|
wound contraction and healing by secondary intention
|
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What is the most common type of collagen
|
Type I
|
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Name the type of collagen:
skin, bone and tendons |
I
|
|
Name the type of collagen:
Cartilage |
II
|
|
Name the type of collagen:
increased in wound healing, also in blood vessels and skin |
III
|
|
Name the type of collagen:
basement membranes |
IV
|
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Name the type of collagen:
widespread, particularly found in the cornea |
V
|
|
Alpha-ketoglutarate, vitamin C, oxygen and iron are required for what part of wound healing?
|
hydroxylation of proline and subsequent cross-linking of proline residues
|
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Collagen has ___ every 3rd amino acid; also has abundant lysine
|
proline
|
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Wound tensile strength is never equal to prewound, only ___%
|
80%
|
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What is the predominant collagen type synthesized for days 1-2?
|
Type III
|
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What is the predominant collagen type synthesized by days 3-4?
|
Type I
|
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Type III collagen is replaced by type I by ___ weeks
|
3
|
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At ___ weeks wound is at 80% of its final strength and 60% of its original strength.
At ___ weeks, wound reaches maximum tensile strength, which is 80% of its original strength |
6
8 |
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Maximum collage accumulation at ___ weeks after that -> the amount of collagen stays the same but continued cross-linking improves strength
|
2-3
|
|
d-Penicillamine is used to treat RA, what does it do to wound healing
|
inhibits collagen cross linking
|
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What is the transcutaneous oxygen measurement essential for wound healing?
|
> 25 mmHg
|
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bacteria amount > ___ is an impediment to wound healing
|
10^5/cm2
|
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Albumin < ___ is a risk factor for poor wound healing
|
3.0
|
|
Steroids prevent wound healing by inhibiting macrophages, PMNs and collagen synthesis by ___; decreased wound tensile strength as well.
|
fibroblasts
|
|
What vitamin (24,000 IU qd) counteracts effects of steroids on wound healing?
|
Vitamin A
|
|
Name the disease associated with abnormal wound healing:
Type I collagen defect. |
osteogenesis imperfecta
|
|
Name the disease associated with abnormal wound healing:
10 types identified, all collagen disorders |
Ehlers-Danlos syndrome
|
|
Name the disease associated with abnormal wound healing:
fibrillin (collagen) defect |
Marfan's syndrome
|
|
Name the disease associated with abnormal wound healing:
Excessive firbroblasts. Tx: phenytoin |
Epidermolysis bullosa
|
|
90% of leg ulcers due to ___. Tx?
|
venous insufficiency. Unna boot, elastic wrap
|
|
Scar revisions, wait for ___ to allow maturation; may improve with age
|
1 year
|
|
What pts heal with little or no scarring?
|
infants
|
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What type of tissue contains no blood vessels
|
cartilage
|
|
Does denervation have an effect on wound healing?
|
no
|
|
Chemotherapy has no effect on wound healing after ___ days
|
14
|
|
What is the inheritance for keloids?
|
autosomal dominant
|
|
Tx for keloids?
|
XRT, steroids, silicone, pressure garments
|
|
What is the difference between a Keloid and hypertrophic scar tissue.
|
Keloids extend beyond original scar
|
|
Hypertrophic scar tissue often occurs in what type of wounds and what is the tx?
|
flexor surfaces of upper torso, burns or wounds that take a long time to heal.
Steroids, silicone, pressure garments. |