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188 Cards in this Set

  • Front
  • Back
Three most important HLAs for recipient/donor matching?

Most important overall?
HLA-A, -B, -DR

-DR
ABO blood compatibility required for all transplants except ___
liver
Crossmatch detects preformed recipient antibodies by mixing recipient serum with donor lymphocytes that would generally cause ___ (except liver)
hyperacute rejection
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)
Tx for mild rejection.
Pulse steroids
What is the number one malignancy following any transplant?
skin CA (squamous cell CA #1)
What is the second most common malignancy following transplant?
Posttransplant lymphoproliferative disorder (PTLD)
What virus is associated with Posttransplant lymphoproliferative disorder (PTLD)?
epstein-barr
What is the tx for posttransplant lymphoproliferative disorder (PTLD)?
Withdrawal of immunosuppression; may need chemotherapy and XRT for aggressive tumor
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
What antirejection drug works by inhibiting genes for cytokine synthesis (IL-1, IL-6) and macrophages.
steroids
What antirejection drug works by binding cyclophilin protein and inhibits genes for cytokine synthesis (IL-2, IL-3, IL-4, INF-gamma).
Cyclosporin (CSA)
What are the side effects of cyclosporin?

And what is the metabolism and excretion?
nephrotoxicity, hepatotoxicity, HUS, tremors, seizures

hepatic metabolism and biliary excretion
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
FK-506 (Prograf)
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
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
OKT3
What antirejection drug is human monoclonal antibody against IL-2 receptors. Used with induction to treat rejection.
Zenepax
What type of rejection occurs within minutes to hours?
Hyperacute rejection
What is hyperacute rejection caused by?
preformed antibodies that should have been picked up on crossmatch
What is the tx for hyperacute rejection.
Emergent retransplant
What type of rejection occurs <1 week?
accelerated rejection
What is accelerated rejection caused by?
sensitized T cells to donor antigens
What is the tx for accelerated rejection?
increase immunosuppression, pulse steroids, and possibly OKT3
What type of rejection occurs in 1 week to 1 month?
acute rejection
What is acute rejection caused by?
cytotoxic and helper T cells
What is the treatment for acute rejection?
increase immunosuppression, pulse steroids and possibly OKT3
What type of rejection occurs in months to years?
chronic rejection
What type of hypersensitivity reaction is chronic rejection? (Antibodies, monocytes and cytotoxic t cells also play a role)
Type IV
What is the tx for chronic rejection?
increase immunosuppression or OKT3 - no really effective tx
How long can you store a kidney?
48 hours
Can you still use a kidney with UTI or acute increase in Cr (1.0-3.0)
yes
2 main causes of mortality in kidney transplant?
stroke and MI
What vessels are donor kidney attached to?
external iliac
Number one complication of kidney transplant? tx?
urine leaks

drainage and stenting; may need reoperation
Most common cause of external compression after kidney transplant?

Tx 1st and if that fails
lymphocele

percutaneous drainage, intraperitoneal marsupialization (90% successful)
After kidney transplant, postop oliguria is usually due to ___ (pathology shows hyrophobic changes)
ATN
After kidney transplant, postop diuresis is usually due to ___ and ___
urea and glucose
New proteinuria after kidney transplant is usually suggestive of what?
renal vein thrombosis
Postop diabetes after kidney transplant is usually due to what?
side effects of rejection meds: CSA, FK, steroids
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
What is the 5-year graft survival for kidney transplant?
70% (65 cadaveric, 75 living)
Living kidney donors: most common complication? most common cause of death?
wound infection (1%)

fatal PE
How long can you store a liver for transplantation?
24 hours
2 contraindications to liver TXP
current ETOH abuse, acute ulcerative colitis
What is the most common reason for liver TXP in adults?
chronic hepatitis
Criteria for emergent liver TXP - stage III (___), stage IV (___)
stupor, coma
What are two postoperative tx for pts with Hep B after TXP?
HBIG (hep B immunoglobulin) and lamivudine (protease inhibitor)
What are the tumor size limitations on considering TXP with hepatocellular carcinoma
single tumor < 5 cm or up to 3 tumors each < 3 cm
Is portal vein thrombosis a contraindication to liver TXP?
no
What is the best predictor of 1 year survival after liver TXP?
APACHE score
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)
What percentage of liver TXP pts will start drinking again?
20%
What is the #1 predictor of primary nonfunction in liver TXP?
Macrosteatosis (extracellular fat globules in allograft)
(if 50% of cross section is macrosteatatic, there is 50% chance of primary nonfunction)
What is the difference in liver TXP procedure in adults vs. kids?
Duct-to-Duct in adults
Hepatico jejunostomy in kids
Location of drains after liver TXP
Right subhepatic, Right and Left subdiaphragmatic
What is the most common hepatic arterial anomaly?
right hepatic coming off SMA
#1 complication of liver TXP? Tx?
Bile leak

PTC tube and stent
What are the signs and sx of primary nonfunction after liver TXP in the 1st 24 hrs
total bilirubin > 10, bile output < 20 cc/12 hr, PT and PTT 1.5x normal
What are the signs and sx of primary nonfunction after liver TXP after 96 hours?
hyperkalemia, mental status changes, increased LFTs, renal failure, respiratory failure
What is the tx of primary nonfunction after liver TXP?
usually requires retransplantation
Most common cause of liver abscesses after TXP?
chronic hepatic artery thrombosis
Tx for hepatic artery thrombosis after liver TXP?
angio, surgery, retransplantation
Edema, acites, renal insufficiency after liver TXP could be due to what?
IVC stenosis
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
After liver TXP: disappearing bile ducts, gradual bile obstruction with increased alk phos, portal fibrosis. Dx?
chronic rejection
What is the most common predictor of chronic rejection in liver TXP?
acute rejection
Liver TXP retransplantation rate?
20%
LIver TXP 5 year survival rate?
70%
What is the arterial supply and venous drainage needed for pancreas transplant and what are they attached to?
donor celiac and SMA, donor portal vein, iliac vessels
What is the enteric drainage for pancreas TXP?
Second portion of duodenum is taken from donor along with ampulla of Vater and pancreas, anastomosis of donor duodenum to recipient bowel
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?
vascular disease
What is the number one complication of pancreas TXP
thrombosis (hard to treat)
After pancreas TXP: increase in glucose, amylase, or trypsinogen; fever; leukocytosis. Dx?
rejection
How long can a heart for TXP be stored?
6 hours
What is the life expectancy needed for a heart TXP?
< 1 year
What is the tx for persistant pulmonary hypertension after heart transplant?
Flolan (PGI2); inhaled nitric oxide, ECMO if severe
After heart TXP: perivascular infiltrate with increasing grades of myocyte inflammation and necrosis. Dx?
acute rejection
After heart TXP: progressive diffuse coronary atherosclerosis. Dx?
Chronic rejection
How long can a lung for transplantation be stored?
6 hours
What is the life expectancy needed for a lung TXP?
< 1 year
What is the number one cause of early mortality after lung TXP?
reperfusion injury
What is the indication for double-lung TXP?
cystic fibrosis
Exclusion criteria for using lungs for TXP includes: aspiration, moderate to large contusion, infiltrate, purulent sputum, PO2 < ___ on 100% FiO2 and PEEP 5
350
What is the sign of acute lung rejection? chronic?
perivasculare lymphocytosis

bronchiolitis obliterans
Inflammation phases: injury leads to exposed ___; ____ release, tissue factor release from ____
collagen, platelet-activating factor, endothelium
In inflammation platelets bind and release ___ which leads to PMN and macrophage recruitment.
PDGF
Play a dominant role in wound healing, release important growth factors (PDGF) and cytokines IL-1 and TNF-a.
Macrophages
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.
PDGF

(EGF and FGF also help chemotaxis, angiogenesis and epithelialization)
Stimulates angiogenesis and is involved in tumor metastasis.
V-EGF
Not stored, generated by phospholipase in endothelium and other cells. Stimulates many types of inflammatory cells; chemotactic; increased adhesion molecules
Platelet activating factor (PAF)
PMNs last ____ days in tissues, ___ days in blood
1-2, 7
Platelets last ___ days
7-10
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
Name the cell type involved in type I hypersensitivity reactions:

Have IgE receptors. Main source of histamine in blood. Not found in tissue.
Basophils
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
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
Name the cell type involved in type I hypersensitivity reactions:

Vasodilation, increased permeability, pain contraction of pulmonary arterioles. ACE inactivates.
Bradykinin
Has arginine percursor. Activates guanylate cyclase and increases cGMP, resulting in vascular smooth muscle dilation. Also called endotheliu-derived relaxing factor (EDRF).
Nitric Oxide
What does endothelin do?
vascular smooth muscle constriction
Main initial cytokine response to injury and infection is release of ___ and ____
TNF-alpha and IL-1
What is the largest producer of TNF?
macrophage
What cytokine is responsible for cachexia in cancer patients?
TNF-alpha
What is the main source of IL-1
macrophage
IL-1 effects are similar to ___ and synergizes with it.
TNF
Alveolar macrophages cause fever with atelectasis by releasing ___
IL-1
IL-1 also increases what other IL production?
IL-6
IL-1 responsible for fever which is mediated by ___ in hypothalamus.
PGE2 (NSAIDs decrease)
Which IL increases hepatic acute phase proteins (CRP, amyloid A) and lymphocyte activation.
IL-6
Released by lymphocytes in response to viral infection or other stimulates. Active macrophages, natural killer cells and cytotoxic T cells. Inhibit viral replication.
Interferon
Name 2 proteins decreased as result of hepatic acute phase response.
albumin, transferrin
Provides rolling adhesion. Located on leukocytes, bind to ones on endothelial and platelets
Selectins (L-selectins, E- and P- respectively)
On leukocytes; bind ICAMs; anchoring adhesion.
Beta 2 Integrins
ICAM, VCAM, PECAM, ELAM on endothelial cells, bind beta-2 integrin molecules located on leukocytes and platelets. These are also involved in ___
endothelial migration
In the classic complement pathway, antigen-antibody complexes activate. Which 2 abx? And which 3 factors are found only in the classic pathway?
IgG, IgM

Factors C1, C2, and C4
The alternative complement pathway, endotoxin, bacteria, other stimuli activate. What 3 factors are found only in this pathway?
B, D and P (properdin)
What is the common convergence point for classic and alternative complement pathways?
C3
What electrolyte is required for both complement pathways?
Mg
What are the 3 anaphylatoxins in the complement pathway that increase vascular permeability, smooth muscle contraction (bronchi); activate mast cells and basophils
C3a, C4a, C5a
What forms the membrane attack complex?
C5b-9b
What part of the complement cascade functions in opsonization?
C3b
What 2 parts of the complement cascade functions in chemotaxis?
C3a and C5a
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
What are the slow-reaching substances of anaphylaxis; bronchoconstriction; vasoconstriction followed by increased permeability (wheal and flare)
Leukotrienes
Which leukotriene is chemotactic?
LTB4
Catecholamines peak how many hours after injury?
24-48
What is the primary mediator of reperfusion injury?
PMNs
NADPH-oxidase system enzyme defect in PMNs. Results in decreased superoxide radical (O2-) formation.
Chronic granulomatous disease
What are the 3 wound healing phases?
Inflammation, Proliferation, Remodeling
What is the timeframe for the inflammation phase of wound healing?
days 1-10
What is the timeframe for the proliferation phase of wound healing?
5 days - 3 weeks
What is the timeframe for the remodeling phase of wound healing?
3 weeks - 1 year
Which phase of wound healing?:

PMNs, macrophages, epithelialization 1-2 mm/day
Inflammation
Which phase of wound healing?:

fibroblasts, neovascularization, production of collagen, granulation tissue
Proliferation
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
Peripheral nerves regenerate at ___ mm/day
1
Fibroblasts replace fibronectin-fibrin with ___
collagen
Chemotactic for macrophages also anchors fibroblasts.
Fibronectin
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
Which type of platelet granules contain: Platelet factor for aggregation. Beta-thrombomomdulin to bind thrombin and PDGF a chemoattractant.
Alpha granules
Which type of platelet granule contains adenosine, serotonin and calcium.
Dense granules
Name 3 platelet aggregation factors.
TXA2, thrombin, platelet factor 4
The most important factor in healing open wounds (secondary intention).
epithelial integrity
Epithelial migration occurs from what three places in wound healing?
wound edges, sweat glands, and hair follicles
Unepithelialized wounds leak ___ and protein, promote bacterial
serum
What is the most important factor in healing closed incisions (primary intention).
tensile strength
Tensile strengh depends on what?
collagen deposition and cross-linking
What is the strength layer of the bowel?
submucosa
What is the weakest time point for small bowel anastomosis?
3-5 days
Myofibroblasts communicate by ___
gap junctions
What part of wound healing are myofibroblasts involved in?
wound contraction and healing by secondary intention
What is the most common type of collagen
Type I
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
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
Collagen has ___ every 3rd amino acid; also has abundant lysine
proline
Wound tensile strength is never equal to prewound, only ___%
80%
What is the predominant collagen type synthesized for days 1-2?
Type III
What is the predominant collagen type synthesized by days 3-4?
Type I
Type III collagen is replaced by type I by ___ weeks
3
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
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
What is the transcutaneous oxygen measurement essential for wound healing?
> 25 mmHg
bacteria amount > ___ is an impediment to wound healing
10^5/cm2
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
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.