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 following
1) adhesion mlq (cell to cell and cell to extracellular
2) cell to cell occluding junctions (impermeable)
3) permeable jnc allow communication bw cells
1) desmisomes (cell-cell), hemidesmisomes (cell-matrix)
2) tight junctions
3) gap junctions
How do the following work
1) g-protein
2) ligand-triggered protein kinase
1) intramembrane, transduce signal from receptor to response enzyme
2) receptor and response enzyme are single transmembrane protein
What kind of cell surface receptors are:
1) ABO blood-type antigens
2) HLA-type antigens
1) glycolipids on cell membrane
2) glycoproteins (Gp) on cell membrane
Cell cycle:
1) which part determines cell cycle length
2) protein synthesis
3) chromosome duplication
4) mitosis
5) nucleus division
1) G1 most variable
2) S
3) S
4) M
5) M
What phase of mitosis do the following occur in:
1) chromosome alignment
2) separate nucleus reforms around each set of chromosomes
3) centromere attachment, spindle formation, nucleus disappears
4) chromosomes pulled apart
1) metaphase
2) telophase
3) prophase
4) 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 transcription Transcription factors: 2) where do steroid hormones bind 3) where do thyroid hormones bind 4) what are initiation factors
1) DNA-template for RNA polymerase-> makes mRNA
2) bind in cytoplasm then enter nucleus
3) bind receptor in nucleus
4) bind RNA polymerase to initiate transcription
uses oligonucleotides to amplify specific DNA sequences
DNA polymerase chain reaction
1) Purines
2) Pyrimidines
3) what has the strongest bond and why
1) Adenine, Guanine
2) 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 reticulum
2) smooth endoplasmic reticulum
3) golgi apparatus
4) phagosomes
5) 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 lysosomes
4) engulf large particles and take to lysosome
5) same but for small particles
Protein Kinase C
1) what activates it
2) 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_ Keratin
2_ desmin
3_ vimentin
1) hair/nails
2) muscle
3) 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 components
where does it form
X, V, Ca, platelet factor 3, prothrombin
forms 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 work
1) Vitamin K
2) FFP and what is 1/2 life
1) 6 hours
2) immediate, 1/2 life is 6 hr
Normal 1/2 life for:
1) RBC
2) platelets
3) PMNs
1) 120 days
2) 7 days
3) 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 for
1) PTT
2) ACT (activated clotting time)
1) PTT 60-90 sec
2) ACT 150-200sec (>460sec for cardiopulmonary bypass)
At what INR is
1) relative contraindication for surgery
2) relative CI for central line, biopsy of eye surgery
1) >1.5
2) >1.3
what is most common congenital bleeding disorder
vonWillibrands
VonWillibrands disease
1) inheritance pattern
2) role of vWF
3) affect on PT/PTT/INR
4) difference bw type 1-3
5) treatment
1) Types I and II are AD, type III is AR
2) links GpIb receptor on platelets to collagen
3) 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 deficiency
5) for all you can give cryoprecipitate and recombinant VIII-vWF, for type 1 you can also give DDAVP
Hemophilia A
1) inheritance
2) deficiency, coags
3) why don’t pts with dz always bleed at circumcision
4) how high does factor level need to be pre op, post op?
5) treatment
1) sex-linked recessive
2) factor VIII, prolonged PTT, nl PT
3) VIII can cross the placenta from mother
4) 100% preop, 80-100% for 10-14days postop
5) recombinant factor VIII or cryoprecipitate, if joint bleed DO NOT aspirate, also can give ice and keep mobile
Hemophilia B
1) inheritance
2) deficiency, coags
3) what factor level do you need preop, postop?
4) treatment
1) sex-linked recessive
2) IX, increased PTT, nl PT
3) 100% pre-op, 30-40% for 2-3days postop
4) recombinant factor IX or FFP
factor VII deficiency
1) coags
2) treatment
1) increased PT, nl PTT
2) recomb factor VII or FFP
1) causes of acquired thrombocytopenia
2) deficiency in glanzmann’s thrombocytopenia
3) deficiency in Bernard Soulier disease
4) treatment for the above
1) ranitidine (H2-blockers), heparin
2) GpIIb/IIIa receptor deficiency (platelets can’t bind each other)- rx with platelets
- -fibrin normally links receptors together
3) 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
HIT
1) cause of thrombocytopenia
2) what is HITT
3) treatment
4) is lovenox or heparin more likely to cause?
1) antiplatelet antibodies (IgG PF4 antibody) -> platelet destruction
2) when there is also platelet aggregation and thrombosis (white clot)
3) stop heparin/lovenox, start argatroban
4) risk of lovenox is less than heparin
DIC (disseminated intravascular coagulation)
1) what is decreased? increased
2) coags?
3) what initiates it
4) rx
1) platelets, fibrinogen are decreased; fibrin split products and D-dimer are increased
2) inc PT and PTT
3) tissue factor
4) treat underlying cause (ie- sepsis)
how far in advance prior to surgery to stop and what they inhibit:
1) ASA
2) Clopidogrel (Plavix)
3) coumadin
1, 2 and 3 are all 7 days
1) 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 mutation
1) mechanism of action
2) rx
1) causes resistance to activated protein C (defect in factor V)
2) heparin, warfarin
Hyperhomocysteinemia
1) effect on clotting
2) rx
1) hypercoagulability
2) folic acid and B12
Antithrombin III deficiency treatmetn
recombinant AT-III or FFP then heparin and warfarin. heparin alone won’t work
polycythemia vera
1) defect
2) what level to keep Hct and platelets before surgery
3) rx
1) platelet function defect–> thrombosis
2) Hct< 400 before surgery
3) phlebotomy, ASA
most common factor causing aquired hypercoagulability
tobacco
Anti-phospholipid antibody syndrome
1) coags
2) mechanism of hypercoagulability
3) Dx
4) rx
1) hypercoagulable but prolonged PTT
2) antibodies to cardiolipin and lupus anticoagulant (phospholipids), so seen in ppl with lupus but also others
3) false positive RPR, prolonged PTT (not corrected with FFP), positive Russel Viper venom time
4) 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 necrosis
1) cause
2) 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 state
2) pts with relative protein C deficiency
Key elements in developement of:
1) venous thrombus
2) arterial thrombus
1) virchow’s triad: venous stasis, endothelial injury and hypercoaguability
2) endothelial injury
Post-op DVT treatment
1_ 1st DVT
2_ 2nd DVT
3) 3rd DVT or significant PE
1) 6months
2) 1 year
3) 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 action
1) Warfarin
2) SCDs
3) Heparin vs. LMWH
4) Argatroban
5) Bivalirudin (Angiomax)
6) Hirudin (from leeches)
1) prevents vit K-dependent decarboxylation of glutamic residues on vit-K dep factors
2) improve venous return and induce fibrinolysis with compression via release of tPA from endothelium
3) Heparin binds AT-III, LMWH (enoxaparin and fondapariunx) binds AT-III and increases neutralization of Xa and thrombin
4 and 5)reversible direct thrombin inhibitor
6) irreversible direct thrombin inhibitor
AC reversal
1) Warfarin
2) heparin/ LMWH
1) Vit K, FFP
2) 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) cause
2) symptoms/signs
3) labs (haptoglobin, free hemoglobun, bilirubin)
4) treatment
5) how can it present in anesthetized patients
1) ABO incompatibility, antibody mediated
2) back pain, chills, tachycardia, fever, hemoglobinuria, can lead to ATN, DIC, shock
3) haptoglobin 5g/dL increase in unconjugated bilirubin
4) fluids, diuretics, HCO3-, pressors, histamine blockers (Benadryl)
5) diffuse bleeding
Delayed hemolysis
1) cause
2) rx
1) antibody-mediated against minor antigens
2) 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 cells
1) Which CD?
2) what IL do they release and effect
3) type of hypersensitivity reaction that they mediate
1) CD4
2) IL-2-> maturation of cytotoxic T cells
IL-4-> B-cell maturation into plasma cells
3) delayed type hypersensitivity (brings in inflam cells by chemokine secretion)
Suppressor T cells
1) which CD?
2) role
CD8, regulate CD4 and CD8 cells
cytotoxic t cells
1) which CD
2) 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 I
1) effect
2) where found
3) structure
1) CD8 cell activation, target or cytotoxic T cells
2) on all nucleated cells
3) single chain with 5 domains
MHC class II
1) effect
2) where found
3) structure
1) CD4 activation, activates helper T cells (binds T cell receptor), stimulates antibody formation after interaction with B cell surface
2) 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 Cells
how 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 wound
2) 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 type
1) type I
2) type II
3) type III
4) 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 release
2) 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) stomach
2) Proximal small bowel
3) Distal small bowel
4) Colon
1) virtually sterile, some GPCs and some yeast
2) 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 48hrs
2) 48hrs to 5 days
3) after 5 days
1) atelectasis
2) UTI
3) 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 sepsis
2) late gm-neg sepsis
3) 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 resistance
3) 100-120 mg/dL
C. diff treatment:
1) oral
2) IV
1) vanc/flagyl
2) 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 surgery
2) clean contaminated
3) Contaminated
4) 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) GNR
2)anaerobe (and if present what does it imply)
… in SSI
1) E. Coli
2) . 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 factor
2) organisms that cause it
3) labs/diagnostic study results
4) rx
5) prophylaxis
1) low protein (500 cells/cc
4) ceftriaxone or other 3rd generation cephalosporin
5) Flouroquinolones (Norfloxacin
Secondary bacterial peritonitis
1) source
2) organisms
3) rx
1) intra-abdominal ie-perf viscus
2) polymicrob (B. fragilis, E. coli, enterococcus)
3) laparotomy to find source
risk of contracting HIV from the following exposures:
1) HIV blood transfusion
2) Infant from positive mother
3) needle stick from positive patient
4) 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 pts
1) type
2) where
3) rx
1) non-Hodgkins
2) stomach most common, then rectum
3) rx- chemo. Surgery if significant bleeding or perforation
ddx for HIV +
1) UGIB
2) LGIB (more common)
1) kaposi’s sarcoma, lymphoma
2) CMV, bacterial, HSV
CD4 counts
1) normal
2) symptomatic HIV
3) opportunistic infections (AIDS)
1) 800-1200
2) 300-400
3) <200
Hepatitis C
1) chance of transmittion with blood transfusion
2) prevalence
3) rx
4) prevalence of sequelae
1) <0.0001%
2) 1-2%
3) interferon
4) 60% chronic infection, 15% cirrhosis, 1-5% HCC, fulminant hepatic failure is rare
brown recluse spider bite rx
Dapsone (possible graft later)
Acute septic arthritis
1) cause
2) rx
1) Gonococcus, staph, H. flu, strep
2) drainage, ceftriaxone (or 3rd gen cyclosporin) + vanc until cx returns
lerktlnea. dialysis cather infection
1) organism
2) rx
1) S> aureus and s. epidermidis
2) intra peritoneal vanc and gentamicin, removal of catheter if pritonitis >5day, fecal peritonitis-> ex-lap
Difference between:
1) Antiseptic
2) Disinfectant
3) Sterilization
1) Kills and inhibits organisms on body
2) kills and inhibits organisms on inanimate objects
3) all organisms killed
Common antiseptics in surgery- what are they and what are they good for
1) Iodophors
2) Chlorhexadine gluconate
1) Betadine- good for GPCs and GNRs, poor for fungi
2) 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) Vancomycin
2) Gentamicin
3) what to do if peak too high
4) what to do if trough too high
1) peak 20-40, trough 5-10
2) peak 6-10, trough <1
3) decrease amount of dose
4) 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 zosyn
1) what makes up the abx
2) coverage
3) side effects
4) zosyn dosing frequency
1) Timentin is ticarcillin/clavulanic acid and Zosyn is piperacillin/sulbactam
2) GPC (staph and strep), GNRs and anaerobes, enterococci, pseudomonas, acinetobacter, serratia
3) inhibits platelets and high salt load
4) QID dosing
First generation cephalosporins
1) abx
2) coverage
3) which is the best for prophylaxis and why
4) does it penetrate the CNS
1) cefazolin (ancef) and cephalexin
2) GPC- staph and strep. *not effective for enterococcus
3) ancef- longest T1/2
4) no
Second-generation cephalosporins
1) abx
2) coverage
3) which is best for prophylaxis
1) cefoxitin, cefotetan, cefuroxime
2) GPCs, community-acquired GNRs, some anaerobic coverage, lose some staph coverage. *not effective for enterococcus, pseudomonas, acinetobacter or serratia
3) cefotetan- longest T1/2
third-generation cephalosporins
1) abx
2) coverage
3) side effects
1) ceftriaxone, ceftazidime, cefepime, cefotaxime
2) 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) Coverage
2) 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 T1/2
3) seizures.
Bactrim (Trimethoprim/sulfamethaxazole)
1) coverage
2) 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
Quinolones
1) coverage
2) dosing of cipro
3) dosing of levofloxacin
4) MRSA sensitivity and IV vs. PO efficacy.
1) GNRs, +/-GPCs, pseudomonas, acinetobacter, serratia. *doen’t cover enterococcus
2) BID
3) QD
4) 40% MRSA sensitive (IV and PO same efficacy)
Aminoglycosides
1) abx
2) coverage
3) cause of resistance
4) what abx is it synergistic with
5) Side effects
1) gentamicin, tobramycin
2) GNRs, pseudomonas, acinetobacter, serratia. *doesn’t cover anaerobes
3) modifying enzymes lead to decreased active transport
4) beta-lactams (ampicillin, amoxicillin) facilitate aminoglycocide penetration. Good for enterococcus coverage
5) reversible nephrotoxicity, irreversible ototoxicity
Erythromycin (macrolides)
1) Coverage
2) Side effects
3) other action
1) GPCs- best for community-acquired pneumonia and atypical pneumonias
2) nausea (PO), cholestasis (IV)
3) also binds motilin receptor (prokinetic for bowel)
Vancomycin (glycopeptides)
1) coverage
2) mechanism of action
3) how resistance develops
4) side effects
1) GPCs, Enterococcus, C. diff (P.O. intake), MRSA
2) binds cell wall proteins
3) from a change in cell wall-binding protein
4) 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 def
Rifampin- inhibits RNA polymerase. SE- hepatotoxicity, GI symptoms, high resistance rate
Pyrazinamide- hepatotoxicity SE
Ethambutol- SE is retrobulbar neuritis
mech of action and what it rxs and SE for
1) acyclovir
2) Ganciclovir
both inhibit viral DNA polymerase
1) HSV and EBV
2) 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 systems
2) Phase I of drug metabolism
3) Phase II of drug metabolism
1) hepatocyte smooth endoplasmic reticulum, P-450system
2) 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-450
1) Inhibitors
2) Inducers
1) Cimetidine, isoniazid, ketoconazole, erythromycin, cipro, flagyl, allopurinol, verapamil, amiodarone, MAOIs, disulfiram
2) 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
Gout 1) what builds up 2) mechanism of the following treatments a-Colchicine b-indomethacin c-Allopurinol d-Probenecid
1) uric acid, end product of purine metabolism
2) a-anti-inflammatory, binds TUBULIN and inhibits migration of WBCs
b-NSAID, inhibits prostaglandin synthesis (reversible cyclooxygenase inhibitor)
c-xanthine oxidase inhibitor, blocks uric acid formation from xanthine
d-increases renal secretion of uric acid
Lipid lowering drugs- actions and side effects
1) Cholestyramine
2) Statins
3) 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 rhabdomyolysis
3) inhibits cholesterol synthesis. Can cause flushing (rx- ASA)
GI drugs- brand name, action, mechanism, S/E
1) promethazine
2) Metoclopramide
3) Odansetron
4) Octreotide
1) phenergan, antiemetic, inhibits dopamine receptors. S/E- tardive dyskinesia, rx with benadryl
2) Reglan, prokinetic, inhibits dopamine receptors, can increase gastric and gut motility
3) Zofran, antiemetic, central-acting serotonin receptor inhibitor
4) long-acting somatostatin analogue, decreases gut secretions
Anti-reflux medications
1) Omeprazole
2) Cimetidine/ranitidine
1) PPI, blockes H/K ATPase in stomach parietal cells
2) 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) symptoms
2) first metabolic abnormality
3) second metabolic abnormality
1) tinnitus, headaches, nausea, vomiting
2) respiratory alkalosis
3) metabolic acidosis
what is the MC side effect of Gadolinium
nausea
Iodine contrast
1) MC side effect
2) MC side effect requiring treatment
1) nausea
2) dyspnea
treatment of tylenol overdose
N-acetylcysteine
components of the standard airway exam for nonanesthesiologists and what is concerning
1) BMI
2) mouth opening
3) mallampati classification
4) mandibular protrusion
5) neck anatomy
6) cervical spine mobility
7) beard
1) BMI>31
2) Interincisor or intergingival distance >3cm
3) Class III-IV
4) inability to protrude lower incisors to meet or extend past upper incisors
5) radiation changes or thick obese neck
6) limited extension or possibly unstable cervical spine
7) 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/e
1) sodium thiopental
2) 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 bp
2) 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 cholinesterases
3) fast acting, fewer hemodynamic changes. s/e-continuous infusions can lead to adrenocortical suppression
IV induction agents: Ketamine
1) effect
2) major benefit
3) s/e
4) 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 depression
3) hallucinations, catecholamine release (inc CO2, tachycardia), inc airway secretions, and inc cerebral blood flow
4) pts with head injury
5) good for children
Rapid Sequence Intubation
1) when is it indicated
2) what do you give
1) recent oral intake, GERD, delayed gastric emptying, pregnancy, bowel obstruction
2) 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
succinylcholine
1) speed of action and effect
2) side effects
3) who can’t you use it in
1) fast, short acting paralytic
2) malignant hyperthermia, hyperkalemia (depolarization releases K), open-angle glaucoma, atypical pseudocholinesterases, prolonged paralysis in pts (asians) with atypical psudocholinesterases
3) pts with severe burns, neuro injury, neuromuscular disorders, spinal cord injury, massive trauma, or acute renal failure
Malignant hyperthermia
1) medication indicated
2) cause
3) symptoms
4) treatment
1) succinylcholine
2) caused by a defect in calcium metabolism, calcium released from sarcoplasmic reticulum causes muscle excitation-contraction syndrome
3) inc end-tidal CO2, fever, tachycardia, rigidity, acidosis, hyperkalemia
4) 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 gravis
examples are: cis-atricurium, rocuronium, pancuronium
Cis-atracurium
1) how is it degraded
2) good for what pts?
3) what is released 2/2 use?
1) Hoffman degradation
2) renal and liver failure pts
3) histamine
speed of onset, duration and site of metabolism for:
1) Rocuronium
2) Pancuronium (and most comon side effect)
1) fast onset, intermediate duration, hepatic metabolism
2) 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 anesthetics
1) how do they work
2) how much 1%lido can you use
3) why are infected tissues hard to anesthetize
4) what is the longest, shortest acting and which is in between
5) side effects
1) increase action potential threshold, preventing Na influx
2) 0.5cc/kg of 1% lido (4.5mg/kg) with epi it is 7mg/kg
3) they are acidotic
4) length of action: bupivacaine>lidocaine>procaine
5) 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)
Nacotics
1) drugs
2) mechanism of action
3) where are they metabolized/excreted
4) rx for overdose
5) what pts shouldn’t get
1) morphine, fentanyl, demerol, codeine
2) act on mu-opioid receptors-> profound analgesia, respiratory depression ( dec CO2 drive), no cardiac effects, blunt sympathetic response
3) metab in liver, excreted by kidney
4) 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 release
- can 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
benzodiazepines
1) uses, where it is metabolized, side effect
2) shortest acting to longest acting ones
3) 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 depression
2) Versed (midazolam)- shortest acting (C/I in pregnancy bc crosses the placenta); Valium(diazepam)- intermediate acting; ativan (lorazepam)- long acting
3) Flumazenil (comptetive inhibitor). May cause seizures and arrhythmias, C/I in pt with elevated ICP or status epilepticus
Epidural anesthesia
1) how it works
2) s/e if morphine used
3) s/e if lidocaine used
4) how is motor function spared
1) analgesia by sympathetic denervation
2) respiratory depression
3) decreased HR and BP
4) 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 classes describe class 1-6 and E
1)healthy
2) mild dz, no limitation
3) 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) Donor
E) 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 electrolytes
1) Na and Cl in 0.9% and 3% NS
2) LR electrolytes
3) 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 28
3) (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) stomach
2) biliary system
3) pancreas
4) duodenum
1) 1-2L
2,3,4) 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 composition
1) sweat
2) Saliva
3) stomach
4) pancreas
5) Bile
6) large intestine
7) 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 replace
1) gastric losses
2) pancreatic/biliary/small intestine losses
3) large intestine losses
4) repletion ratio for GI losses
5) fluid for dehydration resuscitation
6) minimal UOP and should you replace it
1) D5 1/2NS +20KCl
2) LR with HCO3-
3) LR with K+
4) 1:1
5) NS
6) 0.5 cc/kg/hr, don’t replace
1) normal K+ level
2) EKG changes of hyper and hypo K+
3) rx for hyperkalemia and when do you often see it
4) rx for hypokalemia
1) 3.5-5
2) hyper-peaked t-waves, hypo- T waves disappear
3) 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, dialysis
4) usually seen with overdiuresis. may need to replete Mg before K
1) normal Na
2) hypernatremia: cause, sx, and how to correct
3) hyponatremia: cause; sx and how to correct
4) how to correct for hyperglycemia when evaluating Na level
1) 135-145
2) cause-dehydration; sx- HA, restless, irritable, seizures. rx- D5W slowly to avoid brain swelling
3) 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 Ca
2) levels of Ca when symptoms of hyperCa noted
3) what fluids should you NOT give in hyperCa
4) What diuretics should you NOT give
5) causes of hyperCa
6) rx of hyperCa
1) 8.5-10 or iCa 4.4-5.5
2) Ca>13 (iCa>6-7), sx- lethargy
3) LR
4) Thiazide diuretics (retain Ca)
5) breast cancer ismost common malignant cause, hyperparathyroidism is most common benign cause
6) NS at 200-300cc/hr + lasix. If malignant give mithramycin, calcitonin, alendronic acid and dialysis
1) levels of Ca in hypoCa and sx
2) cause
3) rx
4) how to adjust Ca for protein (albumin level)
1) Cas sign (carpopedal spasm), prolonged QT
2) parathyroidectomy
3) replace Mg before you can correct Ca
4) for every 1g decrease in protein add 0.8 to Ca
1) Normal Magnesium level
2) hypermagnesemia sx and pt’s it is seen in. and rx
3) hypomagnesemia- when do you see it and sx
1) 2.0-2.7
2) renal failure pts taking magnesium containing products. sx-lethrgic. rx- Calcium
3) in pts with massive diuresis, chronic TPN without mineral replacement or ETOH abuse. similar sx to hypoCa
Metabolic acidosis
1) equation for calculating Anion Gap (what is nl)
2) causes of high anion gap acidosis
3) causes of nl anion gap acidosis
4) rx of acidosis
1) AG= Na - (HCO3+Cl), nl is 10-15
2) MUDPILES: methanol, uremia, DKA, par-aldehydes, Isoniazid, lactic acidosis, ethylene glycol, salicilates
3) 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 alkalosis
1) causes
2) 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 for
1) FeNa, urine Na and BUN/Cr ratio and urine osmolality if prerenal prbm
(urine Na/Cr)/ (plasma Na/Cr) best test for azotemia
1) 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 syndrome
1) what is released
2) effect on organ systems
3) rx
1) purines and pyrimidines-> inc PO4 and uric acid, dec Ca
2) inc BUN and Cr (renal damage), EKG changes
3) 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 how
2) where does it go from there and where is it converted into active form
3) effect of active form of vit D
4) effect of renal failure on levels
1) skin (UV sunlight converts 7-dehydrocholesterol to cholecalciferol
2) Goes to liver for (25-0H) and then to Kidney for (1-OH) which creates active form of vit D
3) increases Ca-binding protein-> inc intestinal Ca absorption
4) 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 in
1) fat
2) protein
3) oral carbohydrates
4) dextrose
1) 9cal/g
2) 4cal/g
3) 4cal/g
4) 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 required
2) 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) TPN
2) PPN
1) glucose
2) 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) Albumin
2) Transferrin
3) Prealbumin
4) nl protein level
5) nl albumin level
1) 18 days
2) 10days
3) 2 days
4) 6-8.5
5) 3.5-5.5
what are acute indicators of nutritional status
retinal binding protein, prealbumin, transferrin
Ideal body weight for
1) men
2) women
1) 106lb + 6lb for each inch over 5ft
2) 106lb + 5lb for each inch over 5 ft
preop signs of poor nutritional status
weight loss >10% in 6months
weight <3 (strong risk factor for morbidity and mortality after surgery)
1) what is the respiratory quotient
2) RQ>1 signifies what State and how to treat
3) RQ <0.7 signifies what state and how to treat?
4) RQ=0.7
5) RQ=0.8
6) RQ-1.0
1) CO2 produced/O2 consumed= measure of energy expenditure
2) lipogenesis (overfeeding). rx- decrease carbs and caloric intake bc high carbs intake can lead to CO2 buildup and ventilator problems
3) ketosis and fat oxidation (starving). rx- inc carbs and caloric intake
4) pure fat utilization
5) pure protein synthesis
6) pure carb utilization
Postoperative phases: when do they occur and nitrogen balance
1) Diuresis phase
2) catabolic phase
3) anabolic phase
1) POD 2-5
2) POD 0-3 (negative nitrogen balance)
3) POD 3-6 (positive nitrogen balance)
Metabolic Differences bw starvation / injury
1) basal metabolic rate
2) presence of mediators (ie-TNF-a and IL-1)
3) major fuel oxidized
4) Ketone body production
5) gluconeogenesis
6) Protein metabolism
7) negative nitrogen balance
8) hepatic ureagenesis
9) muscle proteolysis
10) 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 stores
1) how quickly are they depleted in starvation and what does body switch to after
2) 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 fat
2) only in liver (skeletal muscle lacks it)
3) stays in muscle after breakdown from glycogen and is utilized
1) gluconeogenesis precursors
2) which is the primary substrate and simplest aa precursor
3) which are the only aa’s to increase during times of stress
4) where does gluconeogenesis occur during late starvation
1) aa’s (esp alanine), lactate, pyruvate, glycerol
2) Alanine
3) kidney
starvation:
1) when do you not see protein-conserving mechanisms
2) when do you see protein conserving mechs?
3) main source of energy
4) how much weight loss can most pts tolerate without major complications? how many days?
1) trauma due to catecholamines and cortisole
2) starvation
3) fats, however in trauma also use protein
4) 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 syndrome
1) when does it occur
2) electrolyte inbalances and s/e’s
3) how to prevent
1) when feeding after prolonged starvation/malnutrition
2) results in decreased K, Mg, PO4-> cardiac dysfnc, profound weakness, encephalopathy
3) start to re-feed at low rate 10-15kcal/kg/day
Cachexia
1) definition
2) mediating factor
1) anorexia, weight loss, wasting. glycogen breakdown, lipolysis protein catbolism
2) TNF-alpha
1) Kwashiorkor
2) Marasmus
1) protein deficiency
2) starvation
Hemostatic adjustments initiated after injury
1) response of hypothalamus
2) pancreatic response
3) cardiac response
4) adrenal reponse
5) injured tissue and muscle results
6) kidney response
7) peripheral vessel response
1) elaboration of ACTH, ADH, GH
2) inc glucagon, dec insulin
3) inc stroke volume and HR
4) inc cortisol and catecholamine release
5) RELEASE of local infalmmatory mediators (cytokines, prostaglandins, platelet activating factor), and mobilization of aa’s from skeletal muscle
6) volume conserving mechs (aldosteronem ADH), humoral cascades-> complement and kinins
7) peripheral vasoconstriction to redistribute blood to vital organs
Nitrogen balance
1) equation
2) how much protein is needed for 1g Nitrogen
3) significance of positive/negative Nitrogen balance
4) total protein synthesis in nl healthy 70kg male per day
1) (Nin-Nout)=([protein/6.25]-[24hr urine N +4g])
2) 6.25gm protein
3) positive- more protein ingested than excreted (anabolism)
negative- catabolism, more protein excreted than taken in
4) 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 down
1) Triacylglycerides (TAGs)
2) cholesterol
3) lipids (and break down products)
1) pancreatic lipase
2) cholesterol esterase
3) phospholipase (breaks it down into micelles and free fatty acids)
FAT DIGESTION
1) what are micelles made of
2) how do they enter the enterocyte
3) purpose of bile salts
4) putpose of cholesterol
5) what are the fat-soluble vitamins and how are they absorbed
6) how are medium and short-chain fatty acids absorbed
1) aggregates of bile salts, long-chain free fatty acids and monoacylglycerides
2) fuse with enterocyte membrane
3) increase absorption area for fats, helping form micelles
4) used to synthesize bile salts
5) A, D, E, K- absorbed in micelles
6) simple diffusion
FAT Digestion
1) what happens after micelles and other fatty acids enter enterocytes
2) 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 lymphatics
3) portal system (same as aa’s and carbs)
lipoprotein lipase
1) where is it found
2) function
1) on endothelium in liver and adipose tissue
2) clears chilomicrons and TAGs from the blood, breaking them down to fatty acids and glycerol
Free fatty acid-binding protein
1) where is it found
2) function
1) on endothelium in liver and adipose tissue.
2) binds short- and medium- chain fatty acids
Saturated fatty acids
1) what are they used for
2) what cells are fatty acids the preferred source of energy for?
1) fuel by cardiac and skeletal muscles
2) (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 found
2) what does it do
3) what signaling factors is it sensitve to
1) fat cells
2) breaks down TAGs (storage form of fat) to fatty acids and glycerol, which are released into the bloodstream
3) 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 DIGESTION
1) 3 enzymes resonsible
2) how are glucose and galactose absorbed and where do they go after
3) how is fructose absorbed and where is it released after
4) what is sucrose
5) what is lactose
6) what is maltose
1) 1st- salivary amylase, then pancreatic amylase and disaccharidases
2) secondary active transport, released into portal vein
3) facilitated diffusion, released into portal vein
4) fructose+glucose
5) galactose +glucose
6) glucose+glucose
Protein digestion
1) 4 enzymes responsible and order of action
2) where is trypsinogen released from
3) what activates trypsinogen and where is it released from
4) role of Trypsin
5) what breaks down protein and breakdown products
6) how is protein absorbed and where is it released
1) 1st-stomach pepsin, then trypsin, chymotrypsin and carboxypeptidase
2) from pancreas
3) activated by enterokinase which is released from the duodenum
4) activates other pancreatic protein enzymes and can autoactivate other trypsinogen molecules
5) proteases-> aa’s, dipeptides and tripeptides
6) 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’s
2) where are they metabolized?
3) what are the essential amino acids?
1) leucine, isoleucine, valine (LIV)
2) muscle
3) all branched chain aa’s (leucine, isoleucine, valine) + argenine, histidine, lysine, methionine, phenylalanine, threonine and tryptophan
What is the general composition of TPN
1) % aa’s
2) % dextrose
3) electrolytes
4) other
5) amount of kcal/cc in 10% and 20% lipid solution
1) 10%
2) 50%
3) Na, Cl, K, Ca, Mg, PO4, acetate
4) mineral and vitamins and lipids (given ceperately from TPN
5) 10% has 1.1 Kcal/cc, 20% has 2kcal/cc
CORI cycle
1) what is it and where does it occur
1) glucose utilized and converted into lactate in MUSCLE
2) lactate goes to liver and converted back to pyruvate and eventually glucose via GLUCOneogenesis
3) Glucose then transported back to muscle
Mineral and vitamin deficiencies- name the one that correlates to the symptoms below
1) hyperglycemia, encephalopathy, neuropathy
2) cardiomyopathy, weakness
3) pancytopenia
4) poor wound healing
5) weakness (failure to wean off ventilator), encephalopathy, decreased phagocytosis
1) Chromium
2) selenium
3) Copper
4) Zinc
5) Phosphate
Mineral and vitamin deficiencies- name the one that correlates to the symptoms below
1) Wernicke’s encephalopathy, cardiomyopathy
2) sideroblastic anemia, glossitis, peripheral neuropathy
3) megaloblastic anemia, peripheral neuropathy, beefy tongue
4) megaloblastic anemia, glossitis
5) pellagra (diarrhea, dermatitis, dementia)
1) Thiamine (B1)
2) Pyridoxine (B6)
3) Vit B12 Cobalamin
4) folate
5) Niacin
Mineral and vitamin deficiencies- name the one that correlates to the symptoms below
1) dermatitis, hair loss, thrombocytopenia
2) night blindness
3) coagulopathy
4) Rickets, osteomalacia, osteoporosis
5) neuropathy
1) essential fatty acids
2) Vit A
3) Vit K
4) Vit D
5) Vit E
what is 2nd most common cause of death in US
CANCER
MC cancer in
1) women
2) cancer-related death in men and women
3) men
4) how does PET work
1) breast
2) lung
3) prostate
4) positron emission tomography identifies mets by detecting fluorodeoxyglucose molecules
1) difference in how cytotoxic T cells and natural killer cells attack tumor
2) T/F: tumor antigens are random only in viral induced tumors
3) diff bw hyperplasia, metaplasia, and dysplasia. use GERD for example
1) cytotoxic T cells need MHC complex to attack tumor. NK cells can indivudually attack
2) false- Ag are random in all tumors except viral induced
3)hyperplasia- increased # of cells
metaplasia- 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 cancer
1) CEA and T1/2
2) AFP and T1/2
3) CA 19-9
4) CA 125
5) Beta-HCG (2 cancers)
6) PSA and T 1/2
7) NSE (2 cancers)
8) Chomagranin A
9) Ret oncogene
1) Colon CA, 18 days
2) HCC (liver CA)- 5 days
3) pancreatic CA
4) ovarian CA
5) choriocarcinoma, testicular CA
6) prostate CA, 18days
7) small cell lung CA, neuroblastoma
8) carcinoid tumor
9) 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 tumor
2) stage in which carcinogen acts with DNA
3) stage that follows tumor initiation
4) stage in which cancer cell become clinically detectable tumor
1) latency period
2) initiation
3) promotion of cancer cells
4) 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 example
2) 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) cervical
2) Gastric
3) HCC
4) nasopharyngeal CA
5) Burkitt’s lymphoma
6) other lymphomas
1) HPV
2) H. pylori
3) HBV and HCV
4) EBV
5) EBV
6) HIV
radiation therapy (XRT)
1) what cell phase is most vulnerable
2) how is most damage done
3) main target (ie-what is damaged)
4) type of radiation associated with skin-preserving effect and why?
1) M phase
2) formation of oxygen radicals-> max effect with high O2 levels
3) DNA- O2 radicals and XRT itself damage
4) 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 tumors
2) very radioresistant tumors
1) seminomas, lymphomas
2) 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 disadvantage
2) effect of cell-cycle nonspecific agents
1) 5FU and methotrexate- exhibit plateau in cell-killing ability
2) have linear reponse to cell killing
CHEMO:
1) Tamoxifen- mechanism of action, what it treats, risk of using
2) Taxol- mechanism
3) Bleomycin and busulfan S/E
4) Cisplatin- mechanism and S/E’s
5) 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 rupture
3) pulmonary fibrosis
4) platinum alkylating agent- S/E: nephrotoxic, neurotoxic, ototoxic
5) platinum alkylating agent)- bone (myelo) suppression
CHEMO:
1) Vincristine mech and S/E
2) Vinblastine mech and S/E
3) Levamisole mech
4) alkylating agents- how they work, what drug is ex, S/E
5) what can you give to help with hemorrhagic cystitis 2/2 cyclophosphamide
1) microtubule inhibitor, peripheral neuropathy, neurotoxic
2) microtubule inhibitor, bone (myelosuppression): vinBlastine B=bone
3) anthelminthic drug though to stimulate immune system against cancer
4) transfer alkyl groups-> form covalent bonds to DNA. Ie- Cyclophosphamide (acrolein is active metabolite). S/E- gonadal dysfnc, SIADH, hemorrhagic cystitis
5) Mesna
Chemo:
1) methotrexate- mechanism, S/E and how to reverse
2) 5-FU mechanism
3) what increases toxicity of 5-FU
4) doxorubicin- mechanism and how does it cause heart toxicity
5) 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 folate
2) inhibits thymidylate syntehesis-> inhibit DNA/purine synthesis.
3) leucovorin
4) DNA intercalator. heart tox 2/2 O2 radicals at doses >500mg/m2
5) 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 13
2) p53
3) ras
4) APC
5) src
6) sis
1) tumor suppressor gene involved in cell-cycle regulation
2) tumor suppressor, chrom 17, nl induces cell cycle arrest and apoptosis
3) proto-oncogene- G protein defect
4) tumor suppressor, chrom 5, cell cycle regulation and movement
5) proto-oncogene- tyrosine kinase defect
6) proto-oncogene- platelet-derived growth factor receptor defect
Mineral and vitamin deficiencies- name the one that correlates to the symptoms below
1) erb B
2) myc
3) DCC
4) bcl
5) BRCA
1) proto-oncogene- epidermal growth factor receptor defect
2) proto-oncogenes (c-, n-, l-), transcription factors
3) tumor suppressor- chrom 18, involved in cell adhesion
4) tumor suppressor involved in apoptosis
5) tumor suppressor
What is Li-Fraumeni syndrome
1) defect
2) cancers
1) p53 gene
2) childhood sarcoma, breast CA, brain tumor, leukemia, adrenal CA
Colon cancer
1) initial step in evolution of colorectal CA
2) other genes involved
3) does it met to bone?
1) APC mutation
2) p53, DCC, K-ras
3) not usually
Carcinogens- what type of cancer risk
1) coal tar
2) Beta-naphthylamine
3) Benzene
4) asbestos
1) larynx, skin, bronchial CA
2) urinary tract CA (bladder CA)
3) leukemia
4) mesothelioma
what cancers may spread to
1) suspicious supraclavicular node
2) axillary node
3) periumbilical node
4) ovaries
5) bone
6) skin
7) small bowel
1) neck, breast, lung, stomach (Virchow’s node), pancreas
2) lymphoma (#1), breast, melanoma
3) pancreas (sister mary joseph node)
4) stomach (krukenberg tumor), colon
5) breast #1, prostate
6) breast, melanoma
7) melanoma #1, lung and breast
Clinical trials- what do the following phases evaluate
1) phase I
2) phase II
3) phase III
4) phase IV
1) is it safe and at what dose
2) is it effective
3) is it better than existing therapy
4) implementation and marketing
describe the various types of chemo
1) induction
2) primary (neoadjuvant)
3) Adjuvant
4) salvage
1) sole treatment, used for advanced disease or when no other treatment exists
2) chemo given first, followed by another (secondary) therapy
3) given after other therapy is used
4) 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 has
1) skin lesions
2) Sezary cells
1) HTLV-1
2) 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 immunology
1) most important immune marker in recipient/donor matching
2) 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 treatment
1) mild rejection
2) severe rejection
1) pulse steroids
2) 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 level
5) 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 10-15
5) FK has less rejection episodes in kidney TXPs
Transplant drugs:
6) Sirolimus
- mechanism and use
7) 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 therapy
7) 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
Transplant drugs:
8) Zenapax (Daclizumab)
- mechanism
- T/F- is cytolytic
- human monoclonal Ab against IL-2 receptors
- used for induction and acute rejection episodes
- false: Is NOT cytolytic
Types of rejection- when it occurs, cause and rx
1) Hyperacute
1) minutes to hours; caused by preformed Abs that should have been picked up by cross match-> activates compliment cascade-> vessel thrombosis. Rx- emergent re-transplant (if kidney just remove organ)
Types of rejection- when it occurs, cause and rx
2)Accelerated rejection
occurs in <1wk; caused by sensitized T cells to donor Ags. Rx- increase immunosuppression, pulse steroids, possible Ab Tx
Types of rejection- when it occurs, cause and rx
3) Acute rejection
1 wk to 1 month; Caused by T cells (cytotoxic and helper). Rx- increase immunosuppression, pulse steroids, possibly Ab tx
Types of rejection- when it occurs, cause and rx
4) Chronic rejection
months to years; partially a type IV hypersensitivity reaction (sensitized T cells) + Ab formation has a role-> graft fibrosis
Rx- increase immunosuppresion, but really no effective rx
Kidney transplant
1) how long can kidney be stored
2) what compatibility do you need
3) can you still use a kidney that had UTI
4) can you still use a kidney that had an acute increase in Creatinine (1.0-3.0)
5) what do you attach the kidney to
6) primary causes of mortality after TXP
1) 48hr
2) cross-match and ABO
3, 4) yes
5) Iliac vessels
6) Stroke and MI
Complications of kidney txp
1) MC complication and how to rx
2) renal artery stenosis- how to dx and rx
3) lymphocele- rx
1) urine leak- rx with drainage and stenting best
2) ultrasound to dx, rx with PTA (percutaneous transluminal angioplasty) with stent
3) MC cause of external ureter compression- 1st try percutaneous drainage. if that fails do peritoneal window so lymph fluid drains into peritoneum and is reabsorbed
complications of kidney txp
1) cause of postop oliguria
2) cause of postop diuresis
3) what does new proteinuria raise concern for
4) cause of postop diabetes
5) common viral infections and rx
1) ATN (path shows hydrophobic changes)
2) urea and glucose
3) renal vein thrombosis
4) side effect of cyclosporin, FK and steroids
5) CMV- rx with ganciclovir; HSV- rx with acyclovir
Kidney rejection workup
1) symptoms that make you start w/u
2) studies to rx
3) empiric treatments
4) path seen in acute rejection
5) chronic rejection- when do you see and rx
6) 5-year graft survival
1) inc Cr or poor UOP
2) US with duplex to r/o vascular prbm and ureteral obstruction; and bx
3) pulse steroids, and decrease in CSA (cyclosporin) or FK as they can be nephrotoxic
4) tubulitis (vasculitis with more severe form)
5) usually after 1 yr. no good rx
6) 70% (cadaveric 65%, living donors 75%)
Living kidney donors
1) MC complication
2) MC cause of death
3) what happens to remaining kidney
1) wound infection (1%)
2) fatal PE
3) hypertrophies
liver transplant
1) how long can you store liver
2) C/I to liver TXP
3) MC reason for liver TXP
4) components of MELD score
5) MELD at which pt benefits from liver TXP
1) 24hr
2) current ETOH abuse, acute ulcerative colitis
3) chronic hep C
4) creatinine, INR, bilirubin- used to predict if pts with cirrhosis will benefit more from TXP than from medical therapy
5) MELD>15
1) criteria for urgent TXP
2) what can you rx pts with Hep B antigenemia be treated with after liver txp to help prevent reinfection
3) how much is the hep B reinfection rate reduced
1) fulminant hepatic failure (encephalopathy- stupor, coma)
2) Lamivudine (protease inhibitor) and HBIG (heb B immunoglobulin)
3) reduced to 20%
1) disease most likely to recur in new liver allograft
2) when can you consider txp in pts with HCC
3) is portal vein thrombosis a C/I to liver TXP
4) percent of ETOH abusers who will start drinking again after txp
1) hep C
2) if no vascular invasion or mets
3) no
4) 20%
Macrosteatosis in liver txp
1) what is it
2) what is it a risk factor for
1) extracellular fat globules in the liver allograft
2) primary non-function if 50% of cross-section is macrosteatatic in potential donor liver, there is a 50% chance of primary non-function
liver txp surgery
1) when is duct to duct anastamosis performed in liver transplant
2) what drains are placed
3) most common arterial anomaly
4) what dose biliary system depend on for blood supply
1) hepaticojejunostomy in kids
2) right subhepatic, right and left subdiaphragmatic drains
3) right hepatic coming off of SMA
4) hepatic artery
Liver txp complications
1) MC complication and rx
2) what is going on in a pt with:
- sx/signs in 1st 24 hours-total bili >10, bile output
1) bile leak (#1)- Tx: place drain, then ERCP with stent across leak
2) Primary nonfunction. rx- usually requires retransplantation
liver txp complications:
1) MC early vascular complication
2) pt with inc LFTs, dec bile output, fulminant hepatic failure s/p txp
3) pt with biliary strictures and abscesses but no fulminant hepatic failure
4) treatment for early hepatic artery thrombosis
1, 2) Early hepatic artery thrombosis
3) late (chronic) hepatic artery thrombosis
4) MC will need emergent re-transplantation for ensuing fulminant hepatic failure but can try to stent or revise anastomosis
liver txp complications:
1) pt with edema, ascites, renal insufficiency s/p txp. complication and how to rx
2) portal vein thrombosis- early and late signs and rx
3) cholangitis- cause
1) IVC stenosis/thrombosis (rare)- rx with thrombolytics, IVC stent
2) early- abd pain; late- UGI bleed, ascites, asx. rx- if early do re-op thrombectomy and revise anastamosis
3) get PMNs around the portal triad (NOT mixed infiltrate)
liver txp rejection
1) acute rejection: a- what mediates it, b- clinical signs/labs, c-path, d-time of onset
2) Chronic rejection- how common is it, signs/sx
1) a- t-cell mediated against blood vessels; b-fever, jaundice, dec bile output, leukocytosis, eosinophilia, inc LFTs, inc total bili, and inc PT; c- portal triad lymphocytosis, endotheliitis (mixed infiltrate) and bile duct injury; d- 1st 1-2 months
2) unusual; get disappearing bile ducts 2/2 Ab and cellular attack-> bile duct obstruction with inc alk phos and portal fibrosis
liver txp
1) retransplantation rate
2) 5-year survival
1) 20%
2) 70%
Pancreas txp
1) what arteries and veins do you need from donor
2) where do you attach it to
3) where do you attach pancreatic duct and what do you need to take from donor to do this
4) benefits of successful pancreas/kidney and what does it not reverse
1) donor celiac artery and SMA for arterial supply and donor portal vein for venous drainage
2) iliac vessels
3) most use enteric drainage. Take second portion of duodenum from donor along with ampula of vater and pancreas, then perform anastamosis of donor duodenum to recipient bowel
4) stabilization of retinopathy, dec neuropathy, inc nerve conduction velocity, dec autonomic dysfnc (gastroparesis), dec orthostatic hypoTN
- no reversal of vascular disease
Complications of pancreas transplant
venous thrombosis (#1)- hard to treat rejection- can see inc glucose or amylase, fever and leukocytosis
heart transplant
1) how long can you store
2) what compatibility do you need
3) which pts do you do it in
4) rx for persistent pulm HTN after heart transplant
5) acute rejection path findings
6) what is the MCC of late death and death overall following heart txp
1) 6hours
2) ABO compatibility and cross match
3) life expectancy
lung txp:
1) how long can you store
2) compatibility testing required
3) in which pts
4) #1 cause of early mortality and how to rx
5) indication for double lung txp
6) exclusion criteria for using lungs
1) 6hr
2) ABO and crossmatch
3)
lung txp rejection
1) path in acute rejection
2) chronic rejection
3) what is MCC of late death and death overall
1) perivascular lymphocytosis
2) bronchiolitis obliterans
3) chronic lung rejection
Oportunistic infections in txp patients
1) viral
2) protozoan and ppx treatment
3) fungal
1) CMV, HSV, VZV
2) Pneumocystis jiroveci pneumonia (reason for Bactrim ppx)
3) Aspergillis, Candida, Cryptococcus
hierarchy for permission for organ donation from Next of Kin
1) Spouse
2) adult son or daughter
3) either parent
4) adult brother or sister
5) guardian
6) any other person authorized to dispose of body
