deck_1522518 Flashcards
what increases cell membrane fluidity
cholesterol
What gradient is used for co-transport of glucose, proteins and other mlq?
Na+ gradient
Are cells more negative inside or outside and why?
negative inside compared to outside bc of Na/K ATPase (3Na+ out/ 2K+ in)
What are the following1) adhesion mlq (cell to cell and cell to extracellular2) cell to cell occluding junctions (impermeable)3)permeable jnc allow communication bw cells
1)desmisomes (cell-cell), hemidesmisomes (cell-matrix)2)tight junctions3) gap junctions
How do the following work1) g-protein2) ligand-triggered protein kinase
1) intramembrane, transduce signal from receptor to response enzyme2) receptor and response enzyme are single transmembrane protein
What kind of cell surface receptors are:1) ABO blood-type antigens2)HLA-type antigens
1) glycolipids on cell membrane2) glycoproteins (Gp) on cell membrane
Cell cycle:1) which part determines cell cycle length2) protein synthesis3) chromosome duplication4) mitosis5) nucleus division
1) G1 most variable2) S3) S4)M5) M
What phase of mitosis do the following occur in:1) chromosome alignment2) separate nucleus reforms around each set of chromosomes3) centromere attachment, spindle formation, nucleus disappears4) chromosomes pulled apart
1) metaphase2) telophase3) prophase4) anaphase
1) describe nucleus membrane
double, outer membranse continuous with rough endoplasmic reticulum
Where are ribosomes made
in nucleolus (within the nucleus, no membrane)
1_ what is used for transcriptionTranscription factors:2) where do steroid hormones bind3) where do thyroid hormones bind4) what are initiation factors
1) DNA-template for RNA polymerase-> makes mRNA2)bind in cytoplasm then enter nucleus3) bind receptor in nucleus4) bind RNA polymerase to initiate transcription
uses oligonucleotides to amplify specific DNA sequences
DNA polymerase chain reaction
1) Purines2) Pyrimidines3) what has the strongest bond and why
1) Adenine, Guanine2) cytosine, thymidine(DNA), uracil(RNA)3) Cytosine-Guanine (3 hydrogen bonds… T-A only has two)
Translation
mRNA used as template by ribosomes for protein synthesis
How ribosomes work
small and large subunits read mRNA then bind appropriate tRNAs that have amino acids and eventually make proteins
glycolysis
1 glucose -> 2ATP + 2 pyruvate
Where does Krebs cycle occur
mitochondria inner matrix
Krebs cycle
2 pyruvate (from 1 glucose) -> NADH and FADH2 -> electron transport chain -> 36 ATP from 1 glucose
Gluconeogenesis
lactic acid (Cori cycle- opposite of glycolysis) + aa => glucose
why can’t fat and lipids be used in gluconeogenesis
acetyl CoA (breakdown product of fat metabolism) can’t be converted back to pyruvate
Where does Cori cycle occur
in liver, pyruvate has key role, converts lactate into new glucose
Functions of 1) Rough endoplasmic reticulum2) smooth endoplasmic reticulum3) golgi apparatus4) phagosomes5) endosomes
1) makes proteins (increased in pancreatic acinar cells)2) lipid/steroid synthesis, detoxifies drugs (increased in liver and adrenal cortex)3) modifies proteins with carbs then transported to cell membrane, secreted or targeted to lysosomes4)engulf large particles and take to lysosome5) same but for small particles
Protein Kinase C1) what activates it2) what does it do
1) calcium and diacylglycerol (DAG)2) phosphorylates other enzymes and proteins
Protein Kinase A- what activates it and what does it do
activated by cAMP, same as PKC in action
muscle thick filaments
myosin, uses ATP to slide along actin
muscle thin filamints
actin
Where are the following found?1_ Keratin2_ desmin3_ vimentin
1) hair/nails2) muscle3) fibroblasts
microtubules
form specialized cellular structures such as cilia, neuronal axons and mitotic spindles, , also involved in transport organelles in the cell
centriole
specialized microtubule in cell division (forms spindle fibers which pull chromosome apart)
Intrinsic coagulation pathway
exposed collagen +prekallikrein +HMW kininogen+ factor XII->activates XI +VIII->activates X + V-> prothrombin (II) converted to thrombin-> fibrinogen to fibrin
Extrinsic coagulation pathway
Tissue factor from injured cells + factor VII-> activates X + V->prothrombin (II) to thrombin-> fibrinogen to fibrin
prothrombin complex componentswhere does it form
X, V, Ca, platelet factor 3, prothrombinforms on platelets and catalyzes formation of thrombin
where do intrinsic and extrinsic pathways converge
factor X
role of tissue factor pathway inhibitor
inhibits factor X
role of fibrin
links platelets together (binds Gpiib/iiia) to form platelet plug
role of factor XIII
crosslinks fibrin
role of thrombin
converts fibrinogen to fibrin and fibrin split products, activates factors V and VIII, activates platelets
role of antithrombin III
key to anticoagulation, binds and inhibits thrombin, also inhibits factors IX, X, XI,
how does heparin work
activates antithrombinIII-> up to 1000x nl activity
Role of protein C
degrades factors V and VIII, degrades fibrinogen
Role of protein S
protein C cofactor
Vit K-dependent factors
II, VII, IX, X, proteins C and S
Role of tissue plasminogen activator
released from endothelium and converts plasminogin to plasmin for fibrinolysis
Role of Plasmin
degrades factors V and VIII, fibrinogen and fibrin-> lose platelet plug
Alpha-2 antiplasmin role
released from endothelium, natural inhibitor of plasmin
which clotting factor has the shortest half life
VII
which factors activity is lost in stored blood? in what product is it not lost in?
Factors V and VIII. Not lost in FFP
which factor is not synthesized in the liver
VIII, synthesized in endothelium
how long do the following take to work1) Vitamin K2) FFP and what is 1/2 life
1) 6 hours2) immediate, 1/2 life is 6 hr
Normal 1/2 life for:1) RBC2)platelets3) PMNs
1)120 days2)7 days3) 1-2 days
actions of prostacyclin (PGI2) and where is it released from
from endothelium-> decreases platelet aggregation and promotes vasodilation (antagonist to TXA2)
Actions of thromboxane (TXA2) and where it is released from
from platelets->increases platelet aggregation and promotes vasoconstriction, Triggers release of Ca in platelets-> exposes Gpiib/iiia receptror-> platelet to platelet binding and platelet to collagen binding via Gp1b receptor
Cryoprecipitate-which factors and when to use
Factors VIII-vWF and fibrinogen, use in hemophilia A and von Willibrands disease
FFP- which factors
all coag factors+ proteins C and S + AT-III
how DDAVP and conjugates estrogens work
cause release of VIII and vWF from endothelium
What does PT measure
II, V, VII, X, fibrinogen
What does PTT measure
all factors except VII, also measures fibrinogen
Anticoagulation goals for1) PTT2) ACT (activated clotting time)
1) PTT 60-90 sec2) ACT 150-200sec (>460sec for cardiopulmonary bypass)
At what INR is 1) relative contraindication for surgery2) relative CI for central line, biopsy of eye surgery
1) >1.52) >1.3
what is most common congenital bleeding disorder
vonWillibrands
VonWillibrands disease1) inheritance pattern2) role of vWF3) affect on PT/PTT/INR4) difference bw type 1-35) treatment
1) Types I and II are AD, type III is AR2) links GpIb receptor on platelets to collagen3) PTT can be prolonged, otherwise nl, long bleeding time (ristocetin test)4) type 1- reduced vWF quantity, type 2- defect in vWF (wont work well), type 3- complete vWF deficiency5) for all you can give cryoprecipitate and recombinant VIII-vWF, for type 1 you can also give DDAVP
Hemophilia A1) inheritance2)deficiency, coags3) why don’t pts with dz always bleed at circumcision4) how high does factor level need to be pre op, post op?5) treatment
1) sex-linked recessive2) factor VIII, prolonged PTT, nl PT3) VIII can cross the placenta from mother 4) 100% preop, 80-100% for 10-14days postop5)recombinant factor VIII or cryoprecipitate, if joint bleed DO NOT aspirate, also can give ice and keep mobile
Hemophilia B1) inheritance2) deficiency, coags3)what factor level do you need preop, postop?4) treatment
1) sex-linked recessive2) IX, increased PTT, nl PT3) 100% pre-op, 30-40% for 2-3days postop4) recombinant factor IX or FFP
factor VII deficiency1) coags2) treatment
1) increased PT, nl PTT2) recomb factor VII or FFP
1) causes of acquired thrombocytopenia2) deficiency in glanzmann’s thrombocytopenia3) deficiency in Bernard Soulier disease4) treatment for the above
1)ranitidine (H2-blockers), heparin2) GpIIb/IIIa receptor deficiency (platelets can’t bind each other)- rx with platelets–fibrin normally links receptors together3) GpIb receptor def (plt can’t bind collagen), rx with platelets–vWF normally links GpIb to collagen
Platemet disorder in Uremia and rx
inhibits platelet function. rx- hemodialysis (1st), DDAVP, platelets
HIT1)cause of thrombocytopenia2) what is HITT3) treatment4) is lovenox or heparin more likely to cause?
1) antiplatelet antibodies (IgG PF4 antibody) -> platelet destruction2) when there is also platelet aggregation and thrombosis (white clot)3) stop heparin/lovenox, start argatroban4) risk of lovenox is less than heparin
DIC (disseminated intravascular coagulation)1) what is decreased? increased2) coags?3)what initiates it4) rx
1) platelets, fibrinogen are decreased; fibrin split products and D-dimer are increased2)inc PT and PTT3) tissue factor4) treat underlying cause (ie- sepsis)
how far in advance prior to surgery to stop and what they inhibit:1) ASA2) Clopidogrel (Plavix)3)coumadin
1, 2 and 3 are all 7 days1) inhibits cycloxygenase-> decreased TXA2 (platelets lack DNA so can’t regen cyclooxygenase)2)ADP receptor antagonist (tx with platelets)3) inhibits vit-K dep factors, consider starting heparin while awaiting surgery
level that you want platelets before and after surgery
> 50,000 before surgery, >20,000 after surgery
how does prostate surgery affect clotting and how to treat
can release urokinase which activates plasminogen-> thrombolysis. Treat with Amicar (E-aminocaproic acid)
Factor V leiden mutation1)mechanism of action2) rx
1) causes resistance to activated protein C (defect in factor V)2) heparin, warfarin
Hyperhomocysteinemia1) effect on clotting2) rx
1) hypercoagulability2) folic acid and B12
Antithrombin III deficiency treatmetn
recombinant AT-III or FFP then heparin and warfarin. heparin alone won’t work
polycythemia vera1) defect2) what level to keep Hct and platelets before surgery3) rx
1) platelet function defect–> thrombosis2) Hct< 400 before surgery3)phlebotomy, ASA
most common factor causing aquired hypercoagulability
tobacco
Anti-phospholipid antibody syndrome1) coags2) mechanism of hypercoagulability3)Dx4) rx
1) hypercoagulable but prolonged PTT2) antibodies to cardiolipin and lupus anticoagulant (phospholipids), so seen in ppl with lupus but also others3) false positive RPR, prolonged PTT (not corrected with FFP), positive Russel Viper venom time4) heparin, warfarin
effect of cardipulmonary bypass on coagulation and treatment
factor XII (Hageman factor) activated-> hypercoaguable state. rx with heparin to prevent
Warfarin-induced skin necrosis1) cause2) which pts are most susceptible
1) pt on coumadin without being heparinized first. bc proteins C and S have shortest half-lives, they decrease first->relative hyperthrombic state2) pts with relative protein C deficiency
Key elements in developement of:1) venous thrombus2) arterial thrombus
1) virchow’s triad: venous stasis, endothelial injury and hypercoaguability2) endothelial injury
Post-op DVT treatment1_ 1st DVT2_ 2nd DVT3) 3rd DVT or significant PE
1) 6months2) 1 year3) lifetime
When to put in IVC (Greenfield) filter
contraindication to AC, documented PE while on AC, free-floating IVC, ilio-femoral or deep femoral DVT, recent pulmonary embolectomy
most common site of origin for PE and rx
ileofemoral embolism, if pt in shock despite ionotropes in pressors go to OR, otherwise give heparin or suction catheter-based intervention
what is a procoagulant agent and when to use
E-aminocaproic acid (Amicar). inhibits plasmin_> inhibits fibrinolysis. used in DIC, persistent bleeding after CP bypass, thrombolytic overdose
AC mechanisms of action1) Warfarin2) SCDs3) Heparin vs. LMWH4) Argatroban5) Bivalirudin (Angiomax)6) Hirudin (from leeches)
1) prevents vit K-dependent decarboxylation of glutamic residues on vit-K dep factors2) improve venous return and induce fibrinolysis with compression via release of tPA from endothelium3) Heparin binds AT-III, LMWH (enoxaparin and fondapariunx) binds AT-III and increases neutralization of Xa and thrombin4 and 5)reversible direct thrombin inhibitor6) irreversible direct thrombin inhibitor
AC reversal1) Warfarin2) heparin/ LMWH
1) Vit K, FFP2) Protamine (doesn’t work for LMWH)
half life of heparin
60-90 minutes
how is heparin cleared?
by reticuloendothelial system
complications of long-term heparin
alopecia, osteoporosis
can Heparin or warfarin be used in pregnancy?
heparin can bc it doesn’t cross placental barrier, but warfarin crosses so can’t be used
Cross-recation of protamine
with NPH or previous protamine exposure. 1% get protamine reaction (hypotension, bradycardia, decreased heart function)
Where is argatroban metabolized and T1/2
liver, T1/2= 50minutes
Where is bivalirudin metabolized and T1/2
proteinase enzymes in blood, T1/2=25min
what is most potent direct inhibitor of thrombin
Hirudin
Ancrod
Malayan pit viper venom-> tPA release
what are thrombolytics and mechanism of action and reversal
streptokinase, urokinase, tPA-> activate plasminogen (follow fibrinogen levels); fibrinogen <100 worry about bleed. reverse with Amicar (E-aminocaproic acid)
absolute contraindications to thrombolytic use
active internal bleed, recent CVA or neurosurg (<3mo), intracranial pathology or recent GI bleed
major but not absolute CI to thrombolytic use
surgery <10d ago, organ biopsy or obstetric delivery, L heart thrombus, active PUD, recent major trauma, uncontrolled HTN, recent eye surgery
which blood products don’t carry risk of HIV and hepatitis? why?
albumin and serum globulins (they are heat treated)
What is donated blood screened for
HIV, Hep B and C, HTLV, Syphilis, West Nile virus
who should you give CMV-negative blood too
low-birth-weight infants, bone marrow transplant patients, other transplant patients
1 cause of death from transfusion
ABO incompatibility from clerical error
Acute hemolysis with transfusion:1) cause2) symptoms/signs3) labs (haptoglobin, free hemoglobun, bilirubin)4) treatment5)how can it present in anesthetized patients
1) ABO incompatibility, antibody mediated2) back pain, chills, tachycardia, fever, hemoglobinuria, can lead to ATN, DIC, shock3) haptoglobin 5g/dL increase in unconjugated bilirubin4)fluids, diuretics, HCO3-, pressors, histamine blockers (Benadryl)5) diffuse bleeding
Delayed hemolysis1)cause2)rx
1) antibody-mediated against minor antigens2) observe if stable
Nonimmune hemolysis- rx
fluids and diuretics (from squeezed blood)
what is the most common transfusion reaction and why does it occur and treatment
febrile nonhemolytic transfusion reaction (recipient antibody against donor WBC), rx- d/c transfusion and use WBC filters for subsequent transfusions
Cause of anaphylaxis with blood transfusion and treatment
recipient antibodies against donor IgA in IgA deficient patient, rx- fluids, lasix, pressors, steroids, epinephrine, histamine blockers (Benadryl)
Cause of urticaria from blood transfusions and treatment
recipient antibodies against donor plasma proteins or IgA in an IgA deficient patient, rx- histamine blockers (benadryl), supportive
Cause of TRALI (transfusion-related acute lung injury)
caused by donor antibodies to recipient’s WBC-> clot in pulmonary capillaries
when does dilutional thrombocytopenia occur?
after 10units of pRBCs
effect of Ca on clotting
required for clotting cascade, hypoCa-> poor clotting, see this with massive transfusion
most common bacterial contaminate and what type of blood product is most commonly affected
GNRs (E. Coli), affects platelets bc not refridgerated
Helper T cells1) Which CD?2) what IL do they release and effect3) type of hypersensitivity reaction that they mediate
1) CD42) IL-2-> maturation of cytotoxic T cellsIL-4-> B-cell maturation into plasma cells3) delayed type hypersensitivity (brings in inflam cells by chemokine secretion)
Suppressor T cells1) which CD?2) role
CD8, regulate CD4 and CD8 cells
cytotoxic t cells1) which CD2) job
CD8, recognize and attack non-self-antigens attached to MHC class I receptors (ie- viral gene products)
what does the intradermal skin test PPD measure?
cell-mediated immunity (T-cells)
which infections are associated with defects in cell-mediated immunity
intracellular pathogens (TB and viruses)
Humoral (antibody) mediated immunity- how are B cells stimulated to become plasma (antibody secreting) cells
IL-4 from helper T cells (CD4) stimulates B cells to become plasma cells
MHC class I1)effect2) where found3) structure
1) CD8 cell activation, target or cytotoxic T cells2) on all nucleated cells3) single chain with 5 domains
MHC class II1) effect2) where found3) structure
1) CD4 activation, activates helper T cells (binds T cell receptor), stimulates antibody formation after interaction with B cell surface2) on antigen-presenting cells (monocytes, dendrites)3) 2 chains with 4 domains each
basic sequence of events of immune response in viral infection:
endogenous viral proteins produced-> bound to MHC class I-> cell surface->recognized by CD8 cytotoxic T cells
basic sequence of events of immune response in bacterial infection:
endocytosis ->proteins bound to class II MHC-> cell surface->recognized by CD4 T helper cells-> B cell activation-> Ab production and memory B cell formation
Natural Killer Cellshow they work and why we have them
do not require MHC, Ag presentation or previous exposure, not T or B cells. They recognize cells that lack self-MHC which is part of the body’s natural immunosurveillance for cancer
what is the initial Ab made after exposure to antigen
IgM
what is the largest antibody
IgM (5 domains, 10 binding sites)
what Ab is most abundant in body
IgG
what Ab is resonsible for secondary immune response
IgG
what Ab can cross the placenta/provides protection in newborn period
IgG
Where is IgA found
in secretions, peyer’s patches in gut and in breast milk (additional source of immunity in newborn)
role of IgA
helps prevent microbial adherence and invasion in gut
IgE role
allergic reactions, parasite infections, immediate hypersensitivity reactions
Which Abs are opsonins
IgM and IgG
which Abs fix complement
requires 2 IgG or 1 IgM
which region of Ab recognizes Ag
variable region
which region of Ab is recognized by PMNs and macs
constant region (Fc fragment doesn’t carry variable region)
diff bw polyclonal antibodies and monoclonal antibodies
poly have multiple binding sites to the Ag at multiple epitopes, monoclonal Ab have only 1 binding site to 1 epitope
what cell is major source of histamine in blood
Basophils
what cell is major source of histamine in tissue
Mast cells
what are the primary lymphoid organs
liver, bone, thymus
what are the secondary lymphoid organs
spleen and lymph nodes
what does immunologic chimera mean
2 different cell lines in 1 individual (ie- bone marrow tx pts)
Role of IL-2 and what dz can it be used to treat?
converts lymphocytes to lymphokine-activated killer cells by enhancing their immune response to tumor and into tumor-infiltrating lymphocytes. Can be used with some success for melanoma. (causes maturation of cytotoxic t cells)
When to give tetanus toxoid:1) non-tetanus prone wound2)wounds >6hr old, obvious contamination, devitilized tissue, crush, burn, frosbite or missile injuries (all are tetanus prone)3)when to give tetanus immune globulin
1) give tetanus toxoid only if pt has received
Describe the 4 types of hypersensitivity reactions and diseases/reactions for each type1) type I2) type II3) type III4) type IV
1) immediate hypersensitivity reaction (allergy), eosinophils have IgE receptors for the Ag->release major basic protein-> mast cells converted to basophils-> histamine, serotonin and bradykinin release2) IgG or IgM reacts with cell-bound Ag (ABO blood incompatibility, Graves, Myasthenia Gravis)3) Immune complex depositions (serum sickness, SLE)4)Delayed-type hypersensitivity- Ag stim of previously sensitized T cells (PPD, contact dermatitis)
sterility of/microflora in:1)stomach2)Proximal small bowel3) Distal small bowel4) Colon
1)virtually sterile, some GPCs and some yeast2) 10^5 bacteria (GPCs)3) 10^7 bacteria (GPCs, GPRs, GNRs)4) 10^11 bacteria (almost all anaerobes, some GNR, GPCs)
most common immune deficiency
malnutrition
most common organisms in GI tract
Anaerobes (esp bacteroides fragilis) are 1000:1 times more common that aerobes
most common aerobic bacteria in the colon
E. Coli
MC fever source:1)within 48hrs2) 48hrs to 5 days3)after 5 days
1) atelectasis2) UTI3) wound infection
What part of E. Coli causes gm neg Sepsis and how
Endotoxin (lipopolysaccharide A) released->triggers TNF-a release->activates complement-> activates coagulation cascade
Insulin and glucose in 1)early gm-neg sepsis2) late gm-neg sepsis3) optimal glucose in septic pts
1) decreased insulin, increased glucose (impaired utilization causes hyperglycemia just before clinical signs of sepsis)2) increased insulin, increased glucose 2/2 insulin resistance3)100-120 mg/dL
C. diff treatment:1) oral2) IV
1) vanc/flagyl2)flagyl *lactobacillus can help
Most common type of organism in abscesses
90% have anaerobes, 80% have both anaerobic and aerobic bacteria
When do abscesses usually occur
7-10 days postop
When do you need to give abx for abscesses
DM, cellulitis, clinical signs of sepsis, fever, elevated WBC or bioprosthetic hardware (mechanical valves, hip replacements)
incidence of wound infection in surgery:1) clean surgery2) clean contaminated3) Contaminated4) gross contamination
1) 2% (ie-hernia)2) 3-5% (ie- elective colon resection with prepped bowel)3) 5-10% (ie-gunshot wound to colon with repair)4) 30% (ie-abscess)
What is the purpose of prophylactic abx and how long to give
prevent surgical site infection, stop within 24hrs postop, except for cardiac surgery stop within 48hrs)
Most common organism in surgical wound infections
Staph aureus (coagulase-positive) is most common; Staph epidermidis is coagulase negative
what do staph organisms release
exoslime- a exopolysaccharide matrix
most common…1) GNR2)anaerobe (and if present what does it imply)… in SSI
1) E. Coli2). B. fragilis (implies translocation from gut
how much bacteria is needed to create SSI
10^5 (less if foreign body present)
risk factors for SSI
long operation, hematoma/seroma, old age, chronic disease (COPD, renal failure, liver failure, DM), malnutrition, immunosuppresive drugs
What should you think about if there is a surgical infection within 48hrs of procedure
Injury to bowel with leak, invasive soft tissue infection with Clostridium Perfringens and beta-hemolytic strept infections (bc they produce exotoxins).
most common infection in surgery pts, risk factor and orgnaism
UTI, foley, E. Coli
leading cause of infectious death after surgery and risk factors
nosocomial pneumonia, risk factors are length of ventilation, aspiration from duodenum
most common organisms in ICU pneumonia
1) S. aureus; 2)Pseudomonas; (GNR is most common class of organism)
most common organisms in line infection
1) S. epidermidis, 2) S. aureus, 3) yeast
most dirty line and line salvage rate with abx
femoral line; salvage rate is 50% with abx except less likely for yeast infection
what constitutes a positive central line culture and actions
> 15 colony forming units=line infection-> move line, also move if line site has signs of infection, never forget to dc line and place PIVs if line no longer needed
Signs/symptoms of necrotizing fasciitis
pain our of proportion to skin findings, WBC>20, thin gray drainage, skin blistering/necrosis, induration and edema, crepitus or soft tissue gas on x-ray
most common cause of nec fasciitis and treatment
Beta-hemolytic (group B) strep (exotoxin). rx- early debridement, high-dose PCN vs. broad spectrum if suspect polymicrobial
toxic part of C. perfingins and where it sets up and rx
alpha toxin, sets up in necrotic tissue bc decreases oxidation-redux potential, rx- early debridement and high-dose PCN
Fornier’s Gangrene0 cause and rx
mixed organisms (GPCs, GNRs, anaerobes) in DM or immunocompromised. rx- early debridement, try to preserve testicles, abx
when do you need fungal coverage for suspected infection
positive blood cultures, 2 sites other than blood, 1 site with severe sx, endophthalmitis, or pts on prolonged bacterial antibiotics with failure to improve
Actinomyces- what does it cause and rx
pulmonary sx (not a true fungus), tortuous abscesses in cervical, thoracic and abdominal areas. rx- drainage of PCN G
Nocardia- what does it cause and rx
pulmonary and CNS symptoms most common. rx- drainage and sulfonamides
what is the most common fungal inhabitant of the respiratory tract and rx
Candida- rx with fluconazole or anidulafungin for severe infections
Apergillosis rx
Voriconazole
Histoplasmosis- what does it cause, what regions is it found in, and rx
pulm sx- Missisippi and Ohio River valleys. rx- liposomal amphotericin if severe
cryptococcus- sx and rx
CNS sx most common (often in AIDs pt). rx- amphotericin
coccidioidomycosis- sx and rx and region
pulm sx, found in southwest, rx with amphotericin
Spontaneous Bacterial Peritonitis (SBP, primary)1) what is a risk factor2) organisms that cause it3) labs/diagnostic study results4) rx5) prophylaxis
1) low protein (500 cells/cc4)ceftriaxone or other 3rd generation cephalosporin5) Flouroquinolones (Norfloxacin
Secondary bacterial peritonitis1)source2) organisms3)rx
1) intra-abdominal ie-perf viscus2) polymicrob (B. fragilis, E. coli, enterococcus)3) laparotomy to find source
risk of contracting HIV from the following exposures:1) HIV blood transfusion2) Infant from positive mother3)needle stick from positive patient4)mucous membrane exposure
1) 70%2)30%3)0.3%4) 0.1%
How long after exposure dose HIV seroconversion occur
6-12 weeks
What treatment regimen should you get after exposure
AZT (Zidovudine- reverse transcriptase inhibitor) and ritonavir( protease inhibitor), give within 1-2hr after exposure
most common cause for laparotomy in HIV-positive pt
opportunistic infections (esp CMV); 2nd most common is neoplastic disease
most common intestinal manifestation of AIDS
CMV colitis (presents as bleeding or perforation sometimes)
most common neoplasm in AIDS pt
Kaposi’s Sarcoma
Lymphoma in HIV pts1) type2) where3)rx
1) non-Hodgkins2) stomach most common, then rectum3) rx- chemo. Surgery if significant bleeding or perforation
ddx for HIV +1) UGIB2) LGIB (more common)
1) kaposi’s sarcoma, lymphoma2) CMV, bacterial, HSV
CD4 counts1) normal2) symptomatic HIV3) opportunistic infections (AIDS)
1) 800-12002) 300-4003) <200
Hepatitis C1) chance of transmittion with blood transfusion2) prevalence3) rx4) prevalence of sequelae
1) <0.0001%2)1-2%3) interferon4) 60% chronic infection, 15% cirrhosis, 1-5% HCC, fulminant hepatic failure is rare
brown recluse spider bite rx
Dapsone (possible graft later)
Acute septic arthritis1) cause2) rx
1) Gonococcus, staph, H. flu, strep2) drainage, ceftriaxone (or 3rd gen cyclosporin) + vanc until cx returns
lerktlnea. dialysis cather infection1) organism2) rx
1) S> aureus and s. epidermidis2) intra peritoneal vanc and gentamicin, removal of catheter if pritonitis >5day, fecal peritonitis-> ex-lap
Difference between:1) Antiseptic2) Disinfectant3) Sterilization
1) Kills and inhibits organisms on body2) kills and inhibits organisms on inanimate objects3) all organisms killed
Common antiseptics in surgery- what are they and what are they good for1)Iodophors2)Chlorhexadine gluconate
1) Betadine- good for GPCs and GNRs, poor for fungi2)Hibiclens- good for GPCs, GNR and fungi
Mechanism of Action of Penicillins
inhibit cell wall synthesis
Mechanism of Action of Cephalosporins
inhibit cell wall synthesis
Mechanism of Action of carbapenems
inhibit cell wall synthesis
Mechanism of Action of monobactams (aztreonam)
inhibit cell wall synthesis
Mechanism of Action of vancomycin
inhibit cell wall synthesis
Mechanism of Action of tetracycline
inhibitor of the 30s ribosome and protein synthesis
Mechanism of Action of Aminoglycosides (tobramycin, gentamycin)
inhibitor of the 30s ribosome and protein synthesis
Mechanism of Action of linezolid
inhibitor of the 30s ribosome and protein synthesis
Mechanism of action of erythromycin and clindamycin and synercid
Inhibitors of 50s ribosome and protein synthesis
mechanism of action of quinolones
inhibitor of DNA helicase (gyrase)
mechanism of action of rifampin
inhibitor of RNA polymerase
mechanism of action of metronidazole
produces oxygen free radicals that breakup DNA
mechanism of action of sulfonamides
inhibits purine synthesis (PABA analogue)
mechanism of action of Trimethoprim
inhibits dihydrofolate reductase-> inhibits purine synthesis
What antibiotics are bacteriostatic
tetracycline, clindamycin, erythromycin (all have reversible ribosomal binding), bactrim
what abx have irreversible binding to 30s ribosome and are considered bactericidal
aminoglycosides
Mechanism of action of PCN resistance
plasmids for beta-lactamase
most common method of antibiotic resistence
transfer of plasmids
Cause of MRSA resistance
mutation of cell wall-binding protein
Cause of VRE (vanc-resist-enterococcus) resistance
mutation of cell wall-binding protein
Gentamicin resistance cause
modifying enzymes lead to a decrease in active transport of gentamicin into the bacteria
Appropriate drug level:1) Vancomycin2) Gentamicin3) what to do if peak too high4) what to do if trough too high
1) peak 20-40, trough 5-102) peak 6-10, trough <13) decrease amount of dose4) decrease dose frequency
PCN coverage
GPCs (strept, syphilis, Neisseria meningitides (GPR), Clostridium perfringens (GPR), beta-hemolytic strept, anthrax)***doesn’t work on Staph or Enterococcus
Oxacillin and naphcillin coverage
cover staph only
Ampicillin coverage
same as PCN + enterococci
Unasyn and Augmentin-what abx make them and coverage
Unasyn is ampicillin/sulbactam; Augmentin is amoxicillin/clavulanic acid. Sulbactam and clavulanic acid are beta-lactamase inhibitors. These are broad spectrum and cover GPCs (staph and strep), GNRs, enterococci and some anaerobes. * not effective for Psudomonas, Acinetobacter or Serratia
Ticarcillin and piperacillin coverage and side effects
GNRs- enterics, Pseudomonas, Acinetobacter, Serratia. S/E- inhibit platelets and high salt load.
Timentin and zosyn1) what makes up the abx2) coverage3) side effects4) zosyn dosing frequency
1)Timentin is ticarcillin/clavulanic acid and Zosyn is piperacillin/sulbactam2)GPC (staph and strep), GNRs and anaerobes, enterococci, pseudomonas, acinetobacter, serratia3) inhibits platelets and high salt load4) QID dosing
First generation cephalosporins1) abx2) coverage3) which is the best for prophylaxis and why4) does it penetrate the CNS
1) cefazolin (ancef) and cephalexin2) GPC- staph and strep. *not effective for enterococcus3) ancef- longest T1/24) no
Second-generation cephalosporins1)abx2)coverage3) which is best for prophylaxis
1) cefoxitin, cefotetan, cefuroxime2)GPCs, community-acquired GNRs, some anaerobic coverage, lose some staph coverage. *not effective for enterococcus, pseudomonas, acinetobacter or serratia3) cefotetan- longest T1/2
third-generation cephalosporins1) abx2) coverage3) side effects
1) ceftriaxone, ceftazidime, cefepime, cefotaxime2) GNRs mostly + some anaerobic coverage. Covers Pseudomonas, Acinetobacter, Serratia. *doesn’t cover enterococcus.3) cholestatic jaundice, sludging in gallbladder (Ceftriaxone)
Aztreonam (monobactam) coverage
GNRs, picks up Pseudomonas, Acinetobacter and Serratia
Carbapenems (meropenem and imipenem)1) Coverage2) what do you give it with and why?3) side effects
1) broad spectrum- GPCs, GNRs, anaerobes. *not effective for MEP (Mrsa, Enterococcus, Proteus)2) Cilastatin- prevents renal hydrolysis of the drug and increases T1/23) seizures.
Bactrim (Trimethoprim/sulfamethaxazole)1) coverage2) side effects
1) GNRs with some GPC coverage. Not effective for Enterococcus, Pseudomonas, Acinetobacter and Serratia, but does cover staph.2) teratogenic, allergic reactions, renal damage, Stevens-Johnson syndrome (erythema multiforme), hemolysis in G6PD-deficient pt
Quinolones1) coverage2)dosing of cipro3) dosing of levofloxacin4) MRSA sensitivity and IV vs. PO efficacy.
1) GNRs, +/-GPCs, pseudomonas, acinetobacter, serratia. *doen’t cover enterococcus2)BID3) QD4) 40% MRSA sensitive (IV and PO same efficacy)
Aminoglycosides1) abx2) coverage3) cause of resistance4) what abx is it synergistic with5) Side effects
1) gentamicin, tobramycin2) GNRs, pseudomonas, acinetobacter, serratia. *doesn’t cover anaerobes3) modifying enzymes lead to decreased active transport4) beta-lactams (ampicillin, amoxicillin) facilitate aminoglycocide penetration. Good for enterococcus coverage5) reversible nephrotoxicity, irreversible ototoxicity
Erythromycin (macrolides)1) Coverage2) Side effects3) other action
1) GPCs- best for community-acquired pneumonia and atypical pneumonias2)nausea (PO), cholestasis (IV)3) also binds motilin receptor (prokinetic for bowel)
Vancomycin (glycopeptides)1) coverage2) mechanism of action3)how resistance develops4) side effects
1) GPCs, Enterococcus, C. diff (P.O. intake), MRSA2) binds cell wall proteins3) from a change in cell wall-binding protein4) HTN, Redman syndrome (from histamine release), nephrotoxicity, ototoxicity
Synercid coverage (streptogramin-quinupristin-dalfopristin)
GPCs including MRSA and VRE
Linezolid coverage
GPCs including MRSA and VRE (oxazolidinones)
Tetracycline coverage and side effects
GPCs, GNRs, syphilis. S/E- tooth discoloration in children
Clindamycin coverage and side effects
anaerobes, some GPCs including C. perfringens, good for aspiration pneumonia. side effects- pseudomembranous colitis
Metronidazole coverage and side effects
anaerobes, disulfiram-like reaction, peripheral neuropathy from long-term use
Amphotericin- coverage and mechanism
antifungal, binds sterols in wall and alters membrane permeability. S/E- nephrotoxic, fever, hypokalemia, hypotension, anemia. The liposomal type has fewer side effects
Voriconazole and itraconazole coverage and mechanism
antifungals, inhibit ergosterol synthesis needed for cell membrane
Anidulafungin (Eraxis)- coverage and mech
antifungal, inhibits synthesis of cell wall glucan
what to give if pt has prolonged broad-spectrum abx and fever
itraconazole
rx for invasive aspergillosis
voriconazole
rx for Candidemia
anidulafungin
rx for fungal sepsis other than candida and aspergillosis
liposomal amphotericin
Name the anti-tuberculosis drugs, mechanisms of action and side effects
Isoniazid- inhibits mycolic acids (give with pyridoxine). SE- hepatotoxicity, B6 defRifampin- inhibits RNA polymerase. SE- hepatotoxicity, GI symptoms, high resistance ratePyrazinamide- hepatotoxicity SEEthambutol- SE is retrobulbar neuritis
mech of action and what it rxs and SE for1) acyclovir2) Ganciclovir
both inhibit viral DNA polymerase1) HSV and EBV2) CMV. SE- decreased bone marrow, CNS toxicity
complication of broad-spectrum abx
superinfection
Abx effective for enterococcus
vanc, Timentin/Zosyn, ampicillin/amoxicillin, or gent with ampicillin
Abx effective for psuedomonal, Acinetobacter and Serratia-
ticarcillin/piperacillin, Timentin/Zosyn, third-gen cephalosporins, aminoglycosides (Gentamicin and tobramycin), meropenem/imipenem, floroquinolones
how to rx pseudomonas
double cover
when should perioperative abx be given and what they prevent
give within 1 hr before incision. prevent SSI.
what medication routes avoid first-pass liver metabolism
sublingual and rectal
What is skin absorption for drugs based on
lipid solubility through the epidermis
what drugs are absorbed in the CNS (properties)?
nonionized, lipid-soluble drugs
what mlq binds drugs
albumin (PCNs and warfarin are 90% bound)
why can’t you give newborns sulfonamides?
will displace unconjugated bilirubin from albumin in newborn-> hyperbilirubinemia
Where are tetracyclines and heavy metals stored?
bone
0 order kinetics
constant amount of drug is eliminated regardless of dose
1st order kinetics
drug eliminated proportional to dose
how many T1/2 does it take for a drug to reach its steady state?
five T1/2’s
volume of distribution of a drug
amount of drug in the body divided by the amount of drug in plasma/blood. high volume of distribution means higher [] in extravascular compartment (ie- fat tissue) compared with intravascular compartment
bioavailability
fraction of unchanged drug reaching the systemic circulation (100% for IV drugs, less for other routes)
ED50
Drug level at which desired effect occurs in 50% of pts
LD50
drug level at which death occurs in 50% of pts
hyperactive drug rx
effect at an unusually low dose of drug
Tachyphylaxis
drug tolerance after only a few doses
Drug metabolism:1) 2 systems2) Phase I of drug metabolism3) Phase II of drug metabolism
1) hepatocyte smooth endoplasmic reticulum, P-450system2) demethylation, oxidation, reduction, hydrolysis reactions (mixed fnc oxidases, requires NADPH/ oxygen)3) glucuronic acid (#1) and sulfates attached (forms water-soluble metabolite); usually inactive and ready for excretion. Biliary excreted drugs may become deconjugated in intestines with reabsorption, some in active form (called enter-hepatic recirculation, ie-cyclosporin)
Cytochrome P-4501) Inhibitors2) Inducers
1) Cimetidine, isoniazid, ketoconazole, erythromycin, cipro, flagyl, allopurinol, verapamil, amiodarone, MAOIs, disulfiram2) cruciform veggies, ETOH, insecticides, cigarette smoke, phenobarbital (barbituates), Dilantin, theophylline, warfarin
what is most important organ for eliminating most drugs
kidney (glomerular filtration and tubular secretion)
Polar drugs and how they are excreted
water soluble drugs; more likely to be eliminated in an unaltered form
nonpolar drugs and how excreted
non-ionized, fat soluble; more likely metabolized before excretion
Gout1) what builds up2) mechanism of the following treatmentsa-Colchicineb-indomethacinc-Allopurinold-Probenecid
1) uric acid, end product of purine metabolism2) a-anti-inflammatory, binds TUBULIN and inhibits migration of WBCsb-NSAID, inhibits prostaglandin synthesis (reversible cyclooxygenase inhibitor)c-xanthine oxidase inhibitor, blocks uric acid formation from xanthined-increases renal secretion of uric acid
Lipid lowering drugs- actions and side effects1) Cholestyramine2) Statins3) Niacin
1) binds bile acids in gut so body has to resynthesize bile acids from cholesterol-> lowers body cholesterol. can bind vit. K and cause bleeding.2)HMG-CoA reductase inhibitors. Can cause liver dysfunction and rhabdomyolysis3) inhibits cholesterol synthesis. Can cause flushing (rx- ASA)
GI drugs- brand name, action, mechanism, S/E1) promethazine2) Metoclopramide3)Odansetron4) Octreotide
1) phenergan, antiemetic, inhibits dopamine receptors. S/E- tardive dyskinesia, rx with benadryl2) Reglan, prokinetic, inhibits dopamine receptors, can increase gastric and gut motility3) Zofran, antiemetic, central-acting serotonin receptor inhibitor4) long-acting somatostatin analogue, decreases gut secretions
Anti-reflux medications1)Omeprazole2) Cimetidine/ranitidine
1) PPI, blockes H/K ATPase in stomach parietal cells2) blocks H2 histamine receptors, decrease acid in stomach
Digoxin-mechanism-action-S/E’s
-inhibits Na/K ATPase and increases myocardial Ca-slows AV conduction, inotrope-can decrease blood flow to intestines-> mesenteric ischemia, visual changes (yellow hue), fatigue, arrhythmias
what increases sensitivity of heart to digitalis and can precipitate arrhythmias or AV block
hypokalemia
is digoxin cleared with dialysis
NO
Amiodarone-what does it treat-S/Es
-acute atrial and ventricular arrhythmias-pulm fibrosis with prolonged use, hypo- and hyperthyroidism
what cardiac condition is magnesium used to treat
Ventricular tachycaria/ torsades de pointes
ACE-inhibitors-Mechanism-Uses-S/E
-antiotensin-converting enzyme inhibitors-can prevent CHF after myocardial infarction, can prevent progression of renal dysfunction in pts with HTN and DM-S/E- can precipitate renal failure in pts with renal artery stenosis
what is the best single agent shown to improve survival in patients with CHF
ACE-inhibitors
what medication may prolong life in pts with severe LV failure, and reduce risk of MI and a-fib post op
beta-blocker
what is the best single agent shown to improve survival after and MI
beta-blocker
Atropine mechanism and action
acetylcholine antagonist, increases heart rate
metyaprone and aminoglutethimide-action-used for?
-inhibit adrenal steroid synthesis-used in pts with adrenocortical CA
Lueprolide-mechanism-should it be given continuously or intermittently?-use
- analogue of GnRH and LHRH-don’t give continuously bc will get paradoxic inhibition of LH and FSH-used in pts with metastatic prostate CA
NSAIDS-mechanisms and se
inhibit prostaglandin synthesis and lead to decreased mucus and HCO3- secretion and increased acid production (mech of ulcer formation)
Misoprostol- mechanism and use
PGE1 derivative, protective prostaglandin used to prevent peptic ulcer disease (consider use in pts on chronic NSAIDs)
Haldol- meachnism, use and S/E (and how to rx)
antipsychotic, inhibits dopamine receptors, can cause extrapyramidal manifestations (rx with Benadryl)
ASA poisoning 1) symptoms2) first metabolic abnormality3) second metabolic abnormality
1) tinnitus, headaches, nausea, vomiting2) respiratory alkalosis3) metabolic acidosis
what is the MC side effect of Gadolinium
nausea
Iodine contrast1) MC side effect2) MC side effect requiring treatment
1) nausea2) dyspnea
treatment of tylenol overdose
N-acetylcysteine
components of the standard airway exam for nonanesthesiologists and what is concerning1)BMI2) mouth opening3) mallampati classification4) mandibular protrusion5) neck anatomy6) cervical spine mobility7)beard
1) BMI>312) Interincisor or intergingival distance >3cm3) Class III-IV4) inability to protrude lower incisors to meet or extend past upper incisors5) radiation changes or thick obese neck6) limited extension or possibly unstable cervical spine7) full beard
MAC (minimum alveolar concentration)
smallest concentration of inhalational agent at which 50% of patients will not move with incision
Small MAC-lipid solubility and potency
more lipid soluble=more potent
relation of speed of induction to solubility
inversely proportional
what inhalation agent has the fastest onset and what is the relative MAC
Nitrous oxide- high MAC (low potency)
result of inhalational agents
unconsciousness, amnesia and some analgesia- most have some myocaridal depression-increase cerebral blood flow-decrease renal blood flow
Pros of using nitrous oxide
fast, minimal myocardial depression, tremors at induction
Halothane pros and cons and who it is good for
slow onset/offset with highest degree of cardiac depression and arrhythmias; least pungent= good for children
Sevoflurane- pros and who to use it for
fast, less laryngospasm and less pungent, good for mask induction
Isoflurane- what it is good for and why?
good for neurosurgery (lowers brain O2 consumption, no increase in ICP)
s/e of enflurane
seizures
IV induction agents- speed of action and s/e1)sodium thiopental2) propofol (and what pts can’t have it and where ist it metabolized)3)Etomidate
1) fast acting barbituate. s/e- decreases cerebral blood flow and metabolic rate, decrease bp2)rapid distribution and on/off. gives amnesia/sedative but no analgesia. s/e- hypotension, respiratory depression. can’t use if egg allergy. metabolized in liver and by plasma cholinesterases3) fast acting, fewer hemodynamic changes. s/e-continuous infusions can lead to adrenocortical suppression
IV induction agents: Ketamine1) effect2) major benefit3) s/e4) C/I in what pts?5)who is it good for
1) dissociation of thalamic/limbic systems; places pt in cataleptic state (amnesia, analgesia)2) no respiratory depression3) hallucinations, catecholamine release (inc CO2, tachycardia), inc airway secretions, and inc cerebral blood flow4)pts with head injury5) good for children
Rapid Sequence Intubation1) when is it indicated2) what do you give
1) recent oral intake, GERD, delayed gastric emptying, pregnancy, bowel obstruction2) pre-oxygenate, etomidate, syccinylcholine typical sequence
what is the last muscle to go down and the 1st muscle to recover from paralytics
diaphragm
what are the 1st mucles to go down and last to recover from paralytics
neck and face muscles
what is the only depolarizing agent of the muscle relaxants
succinylcholine
succinylcholine1) speed of action and effect2) side effects3) who can’t you use it in
1) fast, short acting paralytic2) malignant hyperthermia, hyperkalemia (depolarization releases K), open-angle glaucoma, atypical pseudocholinesterases, prolonged paralysis in pts (asians) with atypical psudocholinesterases3) pts with severe burns, neuro injury, neuromuscular disorders, spinal cord injury, massive trauma, or acute renal failure
Malignant hyperthermia1) medication indicated2) cause3) symptoms4) treatment
1)succinylcholine2) caused by a defect in calcium metabolism, calcium released from sarcoplasmic reticulum causes muscle excitation-contraction syndrome3) inc end-tidal CO2, fever, tachycardia, rigidity, acidosis, hyperkalemia4) dantrolene (10mg/kg) inhibits Ca release and decouples excitation complex, cooling blankets, HCO3, glucose, supportive care
How do nondepolarizing muscle relaxants/paralytics work and in what pts may their effect be prolonged.- what drugs are in this category
inhibit neuromuscular jnc by competing with acetylcholine; prolonged effect in myasthenia gravisexamples are: cis-atricurium, rocuronium, pancuronium
Cis-atracurium1) how is it degraded2) good for what pts?3) what is released 2/2 use?
1) Hoffman degradation2) renal and liver failure pts3) histamine
speed of onset, duration and site of metabolism for:1) Rocuronium2) Pancuronium (and most comon side effect)
1) fast onset, intermediate duration, hepatic metabolism2) slow onset, long duration, renal metabolism, s/e-tachycardia
Reversing drugs for nondepolarizing agents (Cis-atracurium, rocuronium, pancuronium) and mechanism of action-what should you give with them
neostigmine and edrophonium- block acetylcholinesterase increasing acetylcholine*give atropine and glycopyrrolate in addition to counteract effects of generalized acetylcholine overdose
local anesthetics1) how do they work2) how much 1%lido can you use3) why are infected tissues hard to anesthetize4) what is the longest, shortest acting and which is in between5) side effects
1) increase action potential threshold, preventing Na influx2)0.5cc/kg of 1% lido (4.5mg/kg) with epi it is 7mg/kg3)they are acidotic4) length of action: bupivacaine>lidocaine>procaine5)tremors, seizures, tinnitus, arrhythmias (CNS symptoms occur before cardiac)
benefit of adding epi to local and what pts can’t you use them in
allows higher doses to be used, don’t give epi to pts with arrhythmias, unstable angina, uncontrolled HTN, poor collaterals (penis and ear), uteroplacental insufficiency
which class of local rarely causes allergic reactions
amides- lidocaine, bupivacaine, mepivacaine
which class of local anesthetics has increased incidence of allergic reactions
Esters-tetracaine, procaine, cocaine (inc allergic rx due to PABA analogue)
Nacotics1) drugs2) mechanism of action3) where are they metabolized/excreted4) rx for overdose5) what pts shouldn’t get
1) morphine, fentanyl, demerol, codeine2) act on mu-opioid receptors-> profound analgesia, respiratory depression ( dec CO2 drive), no cardiac effects, blunt sympathetic response3)metab in liver, excreted by kidney4) Narcan (naloxone)5) avoid in pts on MAOIs bc can cause hyperpyrexic coma
morphine side effects
analgesia, euphoria, respiratory depression, miosis, constipation, histamine release-> hypoTN, dec cough
Demerol side effects and what pts to avoid using it in
analgesia, euphoria, respiratory depression, miosis, tremors, fasciculations, convulsions no histamine releasecan cause seizures (avoid in pts with renal failure and careful with total amount) 2/2 buildup of normeperidine
methadone- action
simulates morphine, less euphoria
fentanyl- onset time, strength, histamine released?
fast acting, 80x strength of morphine, but no cross reaction in pt with morphine allergy. no histamine release
Sufentanil and remifentanil- onset and half-life
very fast acting, short half-lives.
what is most potent narcotic
sufentanil
benzodiazepines1)uses, where it is metabolized, side effect2) shortest acting to longest acting ones3) rx of overdose (how it works, adverse effects, and who this rx is contraindicated in)
1) anticonvulsant, amnesic, anxiolytic. metabolized in liver. s/e-respiratory depression2)Versed (midazolam)- shortest acting (C/I in pregnancy bc crosses the placenta); Valium(diazepam)- intermediate acting; ativan (lorazepam)- long acting3) Flumazenil (comptetive inhibitor). May cause seizures and arrhythmias, C/I in pt with elevated ICP or status epilepticus
Epidural anesthesia1) how it works2) s/e if morphine used3) s/e if lidocaine used4) how is motor function spared
1) analgesia by sympathetic denervation2) respiratory depression3) decreased HR and BP4) use dilute concentrations
rx for acute hypotension and bradycardia in epidural/spinal anesthesia
turn epidural down, IVF, phenylephrine, atropine
S/e of T5 epidural
can affect cardiac accelerator nerves
In what pts are epidurals and spinal anesthesia contraindicated in
hypertrophic cardiomyopathy or cyanotic heart disease bc sympathetic denervation decreases afterload which worsens these conditions
what space is injected in spinal anesthesia
1) subarachnoid space- spread determined by patient position and baricity. Neurologic blockade> motor blockade
what is a caudal block used for
through sacrum, good for pediatric hernias and perianal surgery
epidural and spinal complications
hypotension, headache, urinary retention, abscess/hematoma formation, respiratory depresion (with high spinal)
spinal headaches- cause and symptoms and treatmetn
caused by CSF leak, HA that is worse with sitting up. rx- fluids, rest, caffeine, analgesics, blood patch to site if persists >24hours
what surgical pre-op risk factors/comorbidities are associated with the most postop hospital mortality
renal failure (#1) and CHF
what pts need a cardiology workup preop:
angina, previous MI, SOB, CHF, walks 5/min, high grade heart block, age>70, DM, renal insufficiency, patients undergoing major vascular surgery
what surgeries are considered high risk
aortic, major vascular and peripheral vvascular surgeries
what risk category is carotid endarterectomy
moderate
what are the biggest risk factors for postop MI
age>70, DM, previous MI, CHF, unstable angina
ASA classesdescribe class 1-6 and E
1)healthy2) mild dz, no limitation3) severe disease (angina, prev MI, poorly controlled HTN or DM, mod COPD)4) severe constant threat to life (unstable angina, CHF, renal failure, liver failure, severe COPD)5) Moribound (ruptured AAA, saddle pulm embolus)6) DonorE) emergency
what non cardiac surgical procedures are considered high risk (>5%)
emergent (esp in elderly), aortic, peripheral and other major vascular (except carotid endarterectomy), long procedure with large fluid shift
what noncard procedures are intermediate cardiac risk (<5%)
CEA, head and neck surgery, intraperitoneal and thoracic surgery, orthopedic and prostate surgery
what is the best determinant of esophageal vs tracheal intubation
end-tidal CO2 (ETCO2)
cause and rx of intubated pt undergoing surgery with sudden transient rise in ETCO2
hypoventilation, rx- inc tidal volume or respiratory rate
Cause of intubated pt with sudden drop in ETCO2
disconnected from vent, pulmonary embolism is also has hypotension
correct ET tube position
2cm above the carina
MC PACU complication
nausea and vomiting
what procedures are higher volume hospitals associated with lower mortality for?
abdominal aortic aneurysm repair and pancreatic resection
total body water-% of weight and how has a little more water and a little less water
2/3 of total body weight, more in infants, less in women
how much of water is intracellular (where) and extracellular (where)
2/3 intracell *muscle, 1/3 extracell (2/3 interstitial, 1/3 plasma)
what determines plasma/intersitial compartment osmotic pressures
proteins
what determines intracellular/extracelluar osmotic pressure
Na
MC cause of volume overload and sign
iatrogenic (weight gain)
cellular catabolism- what is released
H2O
fluids and electrolytes1) Na and Cl in 0.9% and 3% NS2) LR electrolytes3) plasma osmolality- how to calculate and what is normal osmolality
1) 0.9% (154, 154), 3% (513 and 513)2) has the ionic composition of plasma Na 130, K 4, Ca 2.7, Cl 109, bicarb 283) (2xNa) + (glucose/18) + (BUN/2.8); nl is 280-295
quick maintenance IVF calculation
40 + weight in Kg (from 4/2/1 rule)
what is the best indicator of adequate volume replacement
urine output
what is the fluid loss during open abdominal operations
0.5-1 L/hr
when should you replace blood loss
> 500cc
Insensible fluid losses- how much from where
10cc/kg/day 75% skin, 25%respiratory
what fluids to use in 1st 24hr postop? after that?
LR/NS/p-lyte, then switch to D5 1/2NS with 20KCL
what is the purpose of D5 in IVF
stimulates insulin release-> aa uptake and protein syntesis (also prevents protein catabolism
How much fluid is excreted daily by 1) stomach2) biliary system3) pancreas4) duodenum
1) 1-2L2,3,4) 0.5-1L
normal K+ requirement per day
0.5-1mEq/kg
normal Na+ requirement per day
1-2 mEq/kg
GI electrolyte loses- describe electrolyte composition1) sweat2) Saliva3) stomach4) pancreas5) Bile6) large intestine7) small intestine
1) hypotonic (Na [] 35-65)2)K+ (highest concentration of K in body)3) H+ and Cl-4) HCO3-5) HCO3-6) K+7) HCO3-, K+
best IVF to replace1) gastric losses2) pancreatic/biliary/small intestine losses3) large intestine losses4) repletion ratio for GI losses5) fluid for dehydration resuscitation6) minimal UOP and should you replace it
1) D5 1/2NS +20KCl2) LR with HCO3-3) LR with K+4) 1:15) NS6) 0.5 cc/kg/hr, don’t replace
1) normal K+ level2) EKG changes of hyper and hypo K+3)rx for hyperkalemia and when do you often see it4) rx for hypokalemia
1) 3.5-52) hyper-peaked t-waves, hypo- T waves disappear3) renal failure. rx- Ca gluconate- stabilizes heart membrane; Sodium bicarb (alkalosis-> K+ enters cell in exchange for H+); 10u insulin and 1 ampule of 50% dextrose (K driven into cells); Kayexalate, lasix, dialysis4) usually seen with overdiuresis. may need to replete Mg before K
1) normal Na2) hypernatremia: cause, sx, and how to correct3) hyponatremia: cause; sx and how to correct4) how to correct for hyperglycemia when evaluating Na level
1) 135-1452) cause-dehydration; sx- HA, restless, irritable, seizures. rx- D5W slowly to avoid brain swelling3)fluid overload; sx-HA, N/V, seizures. rx- 1st water restriction then diuresis. Correct slowly to avoid central pontine myelinosis (no more than 1mEq/hr)4) can cause psuedohyponatremia, for each 100increment of glucose over normal add 2 points to the Na value
electrolyte abnormality in SIADH
hyponatremia
1) normal Ca and ionized Ca2) levels of Ca when symptoms of hyperCa noted3) what fluids should you NOT give in hyperCa4) What diuretics should you NOT give5) causes of hyperCa6) rx of hyperCa
1) 8.5-10 or iCa 4.4-5.52) Ca>13 (iCa>6-7), sx- lethargy3) LR4) Thiazide diuretics (retain Ca)5) breast cancer ismost common malignant cause, hyperparathyroidism is most common benign cause6) NS at 200-300cc/hr + lasix. If malignant give mithramycin, calcitonin, alendronic acid and dialysis
1) levels of Ca in hypoCa and sx2) cause3) rx4) how to adjust Ca for protein (albumin level)
1) Cas sign (carpopedal spasm), prolonged QT2) parathyroidectomy3) replace Mg before you can correct Ca4) for every 1g decrease in protein add 0.8 to Ca
1) Normal Magnesium level2) hypermagnesemia sx and pt’s it is seen in. and rx3) hypomagnesemia- when do you see it and sx
1) 2.0-2.72) renal failure pts taking magnesium containing products. sx-lethrgic. rx- Calcium3) in pts with massive diuresis, chronic TPN without mineral replacement or ETOH abuse. similar sx to hypoCa
Metabolic acidosis1) equation for calculating Anion Gap (what is nl)2) causes of high anion gap acidosis3) causes of nl anion gap acidosis4) rx of acidosis
1) AG= Na - (HCO3+Cl), nl is 10-152) MUDPILES: methanol, uremia, DKA, par-aldehydes, Isoniazid, lactic acidosis, ethylene glycol, salicilates3) usually Na/HCO3 loss (ileostomies, small bowel fistula, massive bile leak)4) rx underlying cause, keep pH>7.2 with bicarb, severely decreased pH can affect myocardial contractility
metabolic alkalosis1) causes2) NG suction electrolyte effects and Rx
1) usually contraction (diarrhea, vomiting, NG suction)2) hypochloremic, hypokalemic metabolic alkalosis with paradoxical aciduria-lose Cl and H from stomach 2/2 NGT-> hypoCl and alkalosis-lose water-> kidney reabsorbs Na in exchange for K via Na/K ATPase exchanger (hypokalemia)-Na/H- exchanger activated in an effor to reabsorb water and K/H exchanger in effor to reabsorb K -> paradoxical aciduria-Rx- Normal saline to correct the Cl- deficit
how long does it take for respiratory compensation of metabolic abnormalities
minutes
how long does it take for renal compensation of metabolic abnormalties
HCO3- regulation takes hours to days
how to calculate FeNa and what is it the best test for1) FeNa, urine Na and BUN/Cr ratio and urine osmolality if prerenal prbm
(urine Na/Cr)/ (plasma Na/Cr) best test for azotemia1) FeNa20, urine osmolality >500mOsm)
how to preven renal damage from contrast dyes
prehydration is best, aso HCO3- and n-acetylcysteine
Myoglobin- why is it toxic to kidney and how to rx
converted to ferrihemate in acidic environment-> toxic to renal cells. rx- alkalinize urine.
Tumor lysis syndrome1) what is released2) effect on organ systems3) rx
1) purines and pyrimidines-> inc PO4 and uric acid, dec Ca2) inc BUN and Cr (renal damage), EKG changes3) hydration (best), rasburicase (converts uric acid in inactive metabolite allantoin), allopurinol ( dec uric acid production), diuretics, alkalinization of urine
Vitamin D (cholecalciferol)1) where is it made and how2) where does it go from there and where is it converted into active form3) effect of active form of vit D4) effect of renal failure on levels
1) skin (UV sunlight converts 7-dehydrocholesterol to cholecalciferol2) Goes to liver for (25-0H) and then to Kidney for (1-OH) which creates active form of vit D3) increases Ca-binding protein-> inc intestinal Ca absorption4) decreased active vitamin D (dec 1-OH hydroxylation)-> decreased Ca reabsorption from gut
why do pts with CKD have anemia
decreased erythropoeitin
difference of transferrin and ferritin
transferrin= transporter of iron; ferritin= stored iron
average caloric need
20-25 calories/kg/day
Calories in1) fat2) protein3) oral carbohydrates4) dextrose
1) 9cal/g2) 4cal/g3) 4cal/g4) 3.4 cal/g
nutritional req for average healthy adult make% protein, fat and carbs
20% protein (1gprotein/kg/day 20% should be essential aa’s), 30% fat (imp for essential fatty acids), 50% carbohydrates
how much do trauma/surgery/sepsis increase caloric requirements
20-40%
how much does pregnancy increase the caloric requirement and lactation?
pregnancy- 300kcal/day, lactation 500kcal/day (protein requirement also increases)
Burns:1) calories required2) protein required
1) 25kcal/kg/day + (30kcal/day x %burn)2) 1-1.5 g/kg/day + (3g x %burn)
what is most of energy expenditure used for
heat production
how much does fever increase basal metabolic rate
10% for each degree above 38.0 C
how to calculate caloric need for overweight patients
[(actual body weight- ideal body weight) x 2.5] + ideal body weight
what does the harris-benedict equation use to calculate basal energy expenditure
weight, height, age, and gender)
maximum glucose administration in central line TPN
3gm/kg/hr
what is the base of 1) TPN2) PPN
1) glucose2) fat
what is the fuel for colonocytes
short-chain fatty acids (ie- butyric acid)
what is the feul for small bowel enterocytes
Glutamine
what is the most common aa in blood stream and tissue
Glutamine
role of glutamine
releases NH4 in kidney to help with nitogen excretion, can be used for gluconeogenesis
what is the primary fuel for most neoplastic cells
Glutamine
T 1/2 of:1) Albumin2) Transferrin3) Prealbumin4) nl protein level5) nl albumin level
1) 18 days2) 10days3) 2 days4) 6-8.55) 3.5-5.5
what are acute indicators of nutritional status
retinal binding protein, prealbumin, transferrin
Ideal body weight for1) men2) women
1) 106lb + 6lb for each inch over 5ft2) 106lb + 5lb for each inch over 5 ft
preop signs of poor nutritional status
weight loss >10% in 6monthsweight <3 (strong risk factor for morbidity and mortality after surgery)
1) what is the respiratory quotient2) RQ>1 signifies what State and how to treat3) RQ <0.7 signifies what state and how to treat?4) RQ=0.75) RQ=0.86) RQ-1.0
1) CO2 produced/O2 consumed= measure of energy expenditure2) lipogenesis (overfeeding). rx- decrease carbs and caloric intake bc high carbs intake can lead to CO2 buildup and ventilator problems3) ketosis and fat oxidation (starving). rx- inc carbs and caloric intake4)pure fat utilization5) pure protein synthesis6) pure carb utilization
Postoperative phases: when do they occur and nitrogen balance1) Diuresis phase2) catabolic phase3) anabolic phase
1) POD 2-52) POD 0-3 (negative nitrogen balance)3) POD 3-6 (positive nitrogen balance)
Metabolic Differences bw starvation / injury1) basal metabolic rate2) presence of mediators (ie-TNF-a and IL-1)3) major fuel oxidized4) Ketone body production5) gluconeogenesis6) Protein metabolism7) negative nitrogen balance8) hepatic ureagenesis9) muscle proteolysis10) hepatic protein synthesis
1) - / ++2) - / +++3) fat/ mixed (fat and proteins)4) +++ / can be + or -5, 6, 7, 8, 9, 10) +/ +++
true/false: the magnitude of metabolic response is proportional to the degree of injury
true
Glycogen stores1) how quickly are they depleted in starvation and what does body switch to after2) where is glucose-6-phosphatase found?3) where is glucose-6-phosphate?
1) 24-36hours (2/3 skeletal muscle, 1/3 liver)-> body then switches to fat2) only in liver (skeletal muscle lacks it)3) stays in muscle after breakdown from glycogen and is utilized
1) gluconeogenesis precursors2)which is the primary substrate and simplest aa precursor3) which are the only aa’s to increase during times of stress4) where does gluconeogenesis occur during late starvation
1) aa’s (esp alanine), lactate, pyruvate, glycerol2) Alanine3) kidney
starvation:1) when do you not see protein-conserving mechanisms2) when do you see protein conserving mechs?3) main source of energy4) how much weight loss can most pts tolerate without major complications? how many days?
1) trauma due to catecholamines and cortisole2) starvation3) fats, however in trauma also use protein4) 15%, 7 days. If longer need to start TPN or Dobbhoff tube
what are the benefits of feeding via the gut
avoid bacterial translocation (bacterial overgrowth, increased permeability due to starved enterocytes, bacteremia) and TPN complications
Indications for PEG
when regular feeding not possible (CVA) or predicted not to occur for >4wk
Source of energy for brain normally and during starvation?what about peripheral nerves, adrenal medulla, RBCs and WBCs
brain- glucose normally but can use ketones with progressive starvation. The others are obligate glucose users
refeeding syndrome1) when does it occur2) electrolyte inbalances and s/e’s3) how to prevent
1) when feeding after prolonged starvation/malnutrition2) results in decreased K, Mg, PO4-> cardiac dysfnc, profound weakness, encephalopathy3) start to re-feed at low rate 10-15kcal/kg/day
Cachexia1) definition2) mediating factor
1) anorexia, weight loss, wasting. glycogen breakdown, lipolysis protein catbolism2)TNF-alpha
1) Kwashiorkor2) Marasmus
1) protein deficiency2) starvation
Hemostatic adjustments initiated after injury1) response of hypothalamus2) pancreatic response3) cardiac response4) adrenal reponse5) injured tissue and muscle results6) kidney response7) peripheral vessel response
1) elaboration of ACTH, ADH, GH2) inc glucagon, dec insulin3) inc stroke volume and HR4) inc cortisol and catecholamine release5) RELEASE of local infalmmatory mediators (cytokines, prostaglandins, platelet activating factor), and mobilization of aa’s from skeletal muscle6) volume conserving mechs (aldosteronem ADH), humoral cascades-> complement and kinins7) peripheral vasoconstriction to redistribute blood to vital organs
Nitrogen balance1) equation2) how much protein is needed for 1g Nitrogen3) significance of positive/negative Nitrogen balance4) total protein synthesis in nl healthy 70kg male per day
1) (Nin-Nout)=([protein/6.25]-[24hr urine N +4g])2) 6.25gm protein3) positive- more protein ingested than excreted (anabolism)negative- catabolism, more protein excreted than taken in4) 250g/day
what organ is responsible for aa production and breakdown
liver
what is majroity of protein breakdown from skeletal muscle
glutamine and alanine
purpose of urea production
used to get rid of ammonia from amino acid breakdown in liver
What enzyme breaks down1) Triacylglycerides (TAGs)2) cholesterol3) lipids (and break down products)
1) pancreatic lipase2) cholesterol esterase3) phospholipase (breaks it down into micelles and free fatty acids)
FAT DIGESTION1) what are micelles made of2) how do they enter the enterocyte3) purpose of bile salts4) putpose of cholesterol5) what are the fat-soluble vitamins and how are they absorbed6) how are medium and short-chain fatty acids absorbed
1) aggregates of bile salts, long-chain free fatty acids and monoacylglycerides2) fuse with enterocyte membrane3) increase absorption area for fats, helping form micelles4) used to synthesize bile salts5) A, D, E, K- absorbed in micelles6) simple diffusion
FAT Digestion1) what happens after micelles and other fatty acids enter enterocytes2) where do chylomicrons and long-chain fatty acids go?3) where do medium and short-chain fatty acids go? what other nutrients go to the same place?
1) chylomicrons formed (90%TAG, 10%phospholipid/proteins/cholesterol)2) thoracic duct to lymphatics3) portal system (same as aa’s and carbs)
lipoprotein lipase1) where is it found2) function
1) on endothelium in liver and adipose tissue2) clears chilomicrons and TAGs from the blood, breaking them down to fatty acids and glycerol
Free fatty acid-binding protein1) where is it found2) function
1) on endothelium in liver and adipose tissue.2) binds short- and medium- chain fatty acids
Saturated fatty acids1) what are they used for2) what cells are fatty acids the preferred source of energy for?
1) fuel by cardiac and skeletal muscles2) (ketones- acetoacetate and beta-hydroxybutyrate) are preferred nrg source for colonocytes, liver, heart and skeletal muscle
what are unsaturated fatty acids used for
structural components for cells
Hormone-sensitive lipase (HSL)1) where is it found2) what does it do3) what signaling factors is it sensitve to
1) fat cells2) breaks down TAGs (storage form of fat) to fatty acids and glycerol, which are released into the bloodstream3) growth hormone, catecholamines, glucocorticoids
What are the essential fatty acids, what are they needed for
linolenic, linoleic. needed for prostaglandin synthesis (long-chain fatty acids). Imp for immune cells.
CARBOHYDRATE DIGESTION1) 3 enzymes resonsible2) how are glucose and galactose absorbed and where do they go after3) how is fructose absorbed and where is it released after4) what is sucrose5) what is lactose6) what is maltose
1) 1st- salivary amylase, then pancreatic amylase and disaccharidases2) secondary active transport, released into portal vein3) facilitated diffusion, released into portal vein4) fructose+glucose5) galactose +glucose6) glucose+glucose
Protein digestion1) 4 enzymes responsible and order of action2) where is trypsinogen released from3) what activates trypsinogen and where is it released from4) role of Trypsin5) what breaks down protein and breakdown products6) how is protein absorbed and where is it released
1) 1st-stomach pepsin, then trypsin, chymotrypsin and carboxypeptidase2) from pancreas3) activated by enterokinase which is released from the duodenum4) activates other pancreatic protein enzymes and can autoactivate other trypsinogen molecules5) proteases-> aa’s, dipeptides and tripeptides6) secondary active transport, then released as free aa’s into the portal vein.
In which patients should you limit protein intake and why
liver and renal failure to avoid ammonia buildup and possible worsening encephalopathy
1)What are the branched chain aa’s2) where are they metabolized?3) what are the essential amino acids?
1) leucine, isoleucine, valine (LIV)2) muscle3) all branched chain aa’s (leucine, isoleucine, valine) + argenine, histidine, lysine, methionine, phenylalanine, threonine and tryptophan
What is the general composition of TPN1) % aa’s2) % dextrose3) electrolytes4) other5) amount of kcal/cc in 10% and 20% lipid solution
1) 10%2) 50%3) Na, Cl, K, Ca, Mg, PO4, acetate4) mineral and vitamins and lipids (given ceperately from TPN5) 10% has 1.1 Kcal/cc, 20% has 2kcal/cc
CORI cycle1) what is it and where does it occur
1) glucose utilized and converted into lactate in MUSCLE2) lactate goes to liver and converted back to pyruvate and eventually glucose via GLUCOneogenesis3) Glucose then transported back to muscle
Mineral and vitamin deficiencies- name the one that correlates to the symptoms below1) hyperglycemia, encephalopathy, neuropathy2) cardiomyopathy, weakness3) pancytopenia4) poor wound healing5) weakness (failure to wean off ventilator), encephalopathy, decreased phagocytosis
1) Chromium2) selenium3) Copper4) Zinc5) Phosphate
Mineral and vitamin deficiencies- name the one that correlates to the symptoms below1) Wernicke’s encephalopathy, cardiomyopathy2) sideroblastic anemia, glossitis, peripheral neuropathy3) megaloblastic anemia, peripheral neuropathy, beefy tongue4) megaloblastic anemia, glossitis5) pellagra (diarrhea, dermatitis, dementia)
1) Thiamine (B1)2) Pyridoxine (B6)3)Vit B12 Cobalamin4) folate5) Niacin
Mineral and vitamin deficiencies- name the one that correlates to the symptoms below1) dermatitis, hair loss, thrombocytopenia2) night blindness3) coagulopathy4) Rickets, osteomalacia, osteoporosis5) neuropathy
1) essential fatty acids2) Vit A3) Vit K4) Vit D5) Vit E
what is 2nd most common cause of death in US
CANCER
MC cancer in1) women2) cancer-related death in men and women3) men4) how does PET work
1) breast2) lung3) prostate4) positron emission tomography identifies mets by detecting fluorodeoxyglucose molecules
1) difference in how cytotoxic T cells and natural killer cells attack tumor2) T/F: tumor antigens are random only in viral induced tumors3) diff bw hyperplasia, metaplasia, and dysplasia. use GERD for example
1) cytotoxic T cells need MHC complex to attack tumor. NK cells can indivudually attack2) false- Ag are random in all tumors except viral induced3)hyperplasia- increased # of cellsmetaplasia- replaccement of one tissue with another (ie- GERD squamous epithelium in esophagus changed to columnar gastric tissue in Barret;s esophagus)dysplasia- altered size, shape and organization (ie- Barrett’s dysplasia
tumor markers: name the cancer1) CEA and T1/22) AFP and T1/23) CA 19-94) CA 1255) Beta-HCG (2 cancers)6) PSA and T 1/27) NSE (2 cancers)8) Chomagranin A9) Ret oncogene
1) Colon CA, 18 days2) HCC (liver CA)- 5 days3) pancreatic CA4) ovarian CA5) choriocarcinoma, testicular CA6) prostate CA, 18days7) small cell lung CA, neuroblastoma8) carcinoid tumor9) thyroid medullary CA
2 steps necessary for cancer transformation
1) heritable alteration in genome 2) loss of growth regulation
define the following stages of tumor growth:1) time between exposure and formation of clinically detectable tumor2) stage in which carcinogen acts with DNA3) stage that follows tumor initiation4) stage in which cancer cell become clinically detectable tumor
1) latency period2) initiation3) promotion of cancer cells4) progression
3 mechanisms from which cancer can arise
carcinogenesis (ie-smoking), viruses (ie-EBV) or immunodeficiency (ie-HIV)
1) what are oncogenes, where are they found and give an example2) what are proto-oncogenes
1) contained in retroviruses like EBV- associated with Burkitt’s lymphoma (8:14 translocation) and nasopharyngeal CA (c-myc)2) human genes with malignant potential
Viruses associated as the infectious agent in the following cancers:1) cervical2) Gastric3) HCC4) nasopharyngeal CA5) Burkitt’s lymphoma6) other lymphomas
1) HPV2) H. pylori3) HBV and HCV4) EBV5) EBV6) HIV
radiation therapy (XRT)1) what cell phase is most vulnerable2) how is most damage done3) main target (ie-what is damaged)4) type of radiation associated with skin-preserving effect and why?
1) M phase2) formation of oxygen radicals-> max effect with high O2 levels3) DNA- O2 radicals and XRT itself damage4) high-energy radiation bc maximal ionizing potential not reached until deeper structures
why do we fractionate XRT doses
allows repair of normal cells, allows re-oxygenation of tumor, allows redistribution of tumor cells in cell cycle
1) very radiosensitive tumors2) very radioresistant tumors
1) seminomas, lymphomas2) epithelial, sarcomas
why are large tumors less responsive to XRT
lack of O2 in tumor
how does brachytherapy work
source of radiation in or next to tumor delivers high, concentrated doses of radiation
CHEMO:1) what are cell-cycle specific agents and disadvantage2) effect of cell-cycle nonspecific agents
1) 5FU and methotrexate- exhibit plateau in cell-killing ability2) have linear reponse to cell killing
CHEMO:1) Tamoxifen- mechanism of action, what it treats, risk of using2) Taxol- mechanism3) Bleomycin and busulfan S/E4) Cisplatin- mechanism and S/E’s5) Carboplatin- mechanism and S/E’s
1) blocks estrogen receptor-> decreases short term (5-yr) risk of breast CA 45% (1% risk of clot, 0.1% risk of endometrial CA)2) promotes microtubule formation and stabilization that cannot be broken down-> cells rupture3) pulmonary fibrosis4) platinum alkylating agent- S/E: nephrotoxic, neurotoxic, ototoxic5) platinum alkylating agent)- bone (myelo) suppression
CHEMO:1) Vincristine mech and S/E2) Vinblastine mech and S/E3) Levamisole mech4) alkylating agents- how they work, what drug is ex, S/E5) what can you give to help with hemorrhagic cystitis 2/2 cyclophosphamide
1) microtubule inhibitor, peripheral neuropathy, neurotoxic2) microtubule inhibitor, bone (myelosuppression): vinBlastine B=bone3) anthelminthic drug though to stimulate immune system against cancer4) transfer alkyl groups-> form covalent bonds to DNA. Ie- Cyclophosphamide (acrolein is active metabolite). S/E- gonadal dysfnc, SIADH, hemorrhagic cystitis5) Mesna
Chemo:1) methotrexate- mechanism, S/E and how to reverse2) 5-FU mechanism3) what increases toxicity of 5-FU4) doxorubicin- mechanism and how does it cause heart toxicity5) Etoposide mechanism
1) inhibits dihydrofolate reductase (DHFR)-> inhibits purine and DNA synthesis. S/e- nephrotoxic, radiation recall. Leucovorin rescue (foloinic acid) reverses effects by re-supplying folate2) inhibits thymidylate syntehesis-> inhibit DNA/purine synthesis.3) leucovorin4) DNA intercalator. heart tox 2/2 O2 radicals at doses >500mg/m25) inhibits topoisomerase (which normally unwinds DNA)
which chemo agents are the least myelosuppressive
bleomycin, vincristine, busulfan and cisplatin
Why do we use GCSF (granulocyte colony-stimulating factor) after chemo and what are the S/E’s
1) used for neutrophil recovery after chemo. S/E- Sweet’s syndrome (acute febrile neutropenic dermatitis)
When do we resect a normal organ to prevent cancer
breast with BRCA I/II or strong fam hx; Thyroid with RET proto-oncogene and fam h/o thyroid CA
Are the following tumor suppressor genes or proto-oncogenes and what is the defect associated with CA:1) Rb1 (Retinoblastoma) on chromosome 132) p533) ras4) APC5) src6) sis
1) tumor suppressor gene involved in cell-cycle regulation2) tumor suppressor, chrom 17, nl induces cell cycle arrest and apoptosis3) proto-oncogene- G protein defect4) tumor suppressor, chrom 5, cell cycle regulation and movement5) proto-oncogene- tyrosine kinase defect6) proto-oncogene- platelet-derived growth factor receptor defect
Mineral and vitamin deficiencies- name the one that correlates to the symptoms below1)erb B2) myc3) DCC4) bcl5) BRCA
1) proto-oncogene- epidermal growth factor receptor defect2) proto-oncogenes (c-, n-, l-), transcription factors3) tumor suppressor- chrom 18, involved in cell adhesion4) tumor suppressor involved in apoptosis5) tumor suppressor
What is Li-Fraumeni syndrome1) defect2) cancers
1) p53 gene2) childhood sarcoma, breast CA, brain tumor, leukemia, adrenal CA
Colon cancer1) initial step in evolution of colorectal CA2)other genes involved3) does it met to bone?
1) APC mutation2) p53, DCC, K-ras3) not usually
Carcinogens- what type of cancer risk1) coal tar2) Beta-naphthylamine3) Benzene4) asbestos
1)larynx, skin, bronchial CA2) urinary tract CA (bladder CA)3) leukemia4) mesothelioma
what cancers may spread to 1) suspicious supraclavicular node2) axillary node3) periumbilical node4) ovaries5) bone6) skin7) small bowel
1) neck, breast, lung, stomach (Virchow’s node), pancreas2) lymphoma (#1), breast, melanoma3) pancreas (sister mary joseph node)4) stomach (krukenberg tumor), colon5) breast #1, prostate6) breast, melanoma7) melanoma #1, lung and breast
Clinical trials- what do the following phases evaluate1) phase I2) phase II3) phase III4) phase IV
1) is it safe and at what dose2) is it effective3) is it better than existing therapy4) implementation and marketing
describe the various types of chemo1) induction2) primary (neoadjuvant)3) Adjuvant4) salvage
1) sole treatment, used for advanced disease or when no other treatment exists2) chemo given first, followed by another (secondary) therapy3) given after other therapy is used4) for tumors that fail to respond to initial therapy
T/F: lymphnodes have good barrier function and should not be viewed as signs of metastasis
False- poor barriers, view as signs of met
When to use en bloc multiorgan resection
aggressive local invasivenes (not metastatic disease) ie- colon into uterus, adrenal into liver, gastric into spleen
when to use palliative cancer surgery
tumors of hollow viscus causing obstruction or bleeding (ie-colon CA), breast CA with skin or chest wall involvement
when should you not do sentinel LN bx
when clinically palpable nodes- for these pts go after and sample these nodes
survival rate for colon mets to liver
35% 5-year survival if completely resected
good prognostic indicators after resection of heaptic colorectal mets
tumor number 12mo
most successfully cured metastases with surgery
colon to liver, sarcoma to lung, but still low overall survival
for which tumor does surgical debulking improve chemotherapy
ovarian CA
which tumors are curable solid tumors with chemo only
hodgkin’s and non-Hodgkin’s lymphoma
T cell lymphomas- which type has1) skin lesions2) Sezary cells
1) HTLV-12) mycosis fungoides
HIV-related malignancies
Kaposi’s sarcoma, non-Hodgkin’s lymphoma
V-EGF- role in cancer
vascular epidermal growth factor- causes angiogenesis, involved in tumor metastasis
transplant immunology1) most important immune marker in recipient/donor matching2)which type of transplant does not require ABO blood compatibility?
1)HLA-DR is most important overall, but HLA-A and -B also v. imp (human leukocyte antigen)2)liver transplant
purpose of cross-match for transplant- what does it detect and how is it done (what is mixed together), what is likely to occur with TXP if positive-cross match
detects preformed recipient antibodies to the donor organ by mixing recipient serum with donor lymphocytes. If Abs are present-> positive cross match and hyperacute rejection
what is panel reactive antibody-what result is a C/I to transplant-what H&P factors can increase PRA
-identical technique to cross-match, but detects preformed recipient Abs using a panel of HLA typing cells and gives a percentage of cells that the recipient serum reacts with-high PRA (>50%) is C/I to transplant due to risk of hyperacute rejection-transfusions, pregnancy, previous transplant and autoimmune diseases
Transplant rejection treatment1) mild rejection2) severe rejection
1) pulse steroids2) steroid and Ab therapy (ATG=anti-thymocyte globulin or daclizumab)
1 malignancy following transplant
squamous cell skin cancer
2 malignancy following transplant-what virus is it related to-how to treat
post-transplant lympho-proliferative disorder (PTLD)-EBV related-withdrawal of immunosuppression, may need chemo and XRT for aggressive tumor
Transplant drugs:1) Mycophenolate (MMF, Cellcept)-mechanism-S/E-when is it used-what other drug has similar action
1)- inhibits de novo purine synthesis-> inhibits growth of T cells-S/E-myelosuppression, must keep WBC>3-maintenance therapy to prevent rejection-Azathioprine (Imuran) has similar action
Transplant drugs:2) Steroids-mechanism-when is it used
-inhibit inflammatory cells (macrophages) and genes for cytokine synthesis (IL-1 and IL-6)-used for induction after transplant, maintenance and acute rejection episodes
Transplant drugs:3) Cyclosporin (CSA)-mechanism-when is it used-side effects-what trough level do you want-where is it metabolized/excreted
calcineurin inhibitor-binds cyclophilin protein and inhibits genes for cytokine synthesis (IL-2, IL-4, etc)-used for maintenance therapy-S/E- nephrotoxicity, hepatotoxicity, tremors, seizures, hemolytic-uremic syndrome-trough 200-300-hepatic metabolism with biliary excretion (reabsorbed in gut, get entero-hepatic recirculation)
Transplant drugs:4) FK-506 (Prograf, tacrolimus)-mechanism-when is it used-S/E- what is goal tough level5) does FK-506 or cyclosporin have less rejection episodes in kidney transplants
4)calcineurin inhibitor -Binds FK-binding protein and inhibits genes for cytokine synth (like CSA)-maintenance therapy-nephrotoxicity, more GI sx and mood changes than CSA but less enterohepatic recirculation than CSA-trough 10-155) FK has less rejection episodes in kidney TXPs
Transplant drugs:6) Sirolimus-mechanism and use7) Anti-thymocyte globulin (ATG)-mechanism-use-T/F: is cytolytic so depends on complement-S/E and how to prevent
6) binds FK-binding protein like FK-506 but inhibits mammalian target of rapamycin (mTOR)-> inhibits T and B-cell response to IL-2-used as maintenance therapy7) Equine (ATGAM) or rabbit (Thymoglobulin) polyclonal Ab against T cell Ags (CD2, CD3, CD4)- used for induction and acute rejection episodes-True-cytokine release syndrome (fever, chills, pulm edema, shock). Give steroids and benadryl before drug to try to prevent
